Πέμπτη, 7 Μαρτίου 2019

Traditional Chinese Medicine

Integrated network pharmacology and antioxidant activity-guided screen system to exploring antioxidants and quality markers of Shunaoxin pills against chronic cerebral ischemia
Nian-Wei Chang, Dan-Dan Cheng, Jia-Nan Ni, Ying-Ying Guo, Guang-Cui Chu, Unchol Kim, Min Jiang, Gang Bai

World Journal of Traditional Chinese Medicine 2019 5(1):1-8

Objective: The main objective of the study is to screen the quality markers (Q-markers) for relieving oxidative stress damage and against chronic cerebral ischemia in Shunaoxin pills (SNX). Methods: The benefit effect of SNX was evaluated by a rat chronic cerebral ischemia model. The main ingredients of SNX were identified by ultra-performance liquid chromatography-quadrupole time-of-flight, whereas its core targets and pathways around antioxidative stress were predicted by PharmMapper and kyoto encyclopedia of genes and genomes (KEGG) analysis. Moreover, the antioxidants were screened by high-performance liquid chromatography with postcolumn derivatization system and then representative ingredients were verified by cell experiments. Results: SNX could increase expression of catalase and superoxide dismutase (SOD) as well as antagonize oxidative damage in the brain. The effects may be related to three types of antioxidant pathways, including nitrogen metabolism, arachidonic acid metabolism, and the cyclic guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway by multiple active components regulate targets. Among them, ferulic acid and ligustilide were shown the key scavenging ability for reactive oxygen free radicals and significantly increased the contents of nitric oxide (NO), NO synthase, and SOD as well as decreased malonaldehyde. Conclusion: The oxidation resistances of biological and chemical processes in SNX to protect against cerebral oxidative stress injury were preliminary revealed by an integrated network pharmacology and antioxidant activity-guided screen system. Ferulic acid and ligustilide played a major antioxidant role that could be used as Q-markers to control the quality of SNX. 


Research on characteristic manifestations of Xiaochaihu decoction based on association rules mining
Li-Ying Zhu, Chun-Hua Jia, Eunhee Park

World Journal of Traditional Chinese Medicine 2019 5(1):9-17

Objective: The aim of this study is to explore the characteristic manifestations and contraindications of Xiaochaihu decoction (XD [It also stands for all the seven herbs in XD]) syndrome and to clarify the principle of using XD. Methods: By searching on the Encyclopedia of Traditional Chinese Medicine, 254 cases whose symptoms were relieved by XD and 48 cases who misused XD in ancient time were selected. Moreover, they are divided into two groups. Microsoft Excel 2016 was used as a storage tool. These two groups of cases were all treated with XD because of their similar manifestations, but therapeutic efficacies are reverse. The manifestations mislead doctors should be selected out to clarify the indications of using XD. Thus, the professional data mining software RapidMiner was used as a platform to do the frequent statistic and to create association rules between manifestations and herbs of both groups, respectively. After comparing the results of two groups, we can make a conclusion. Results: The characteristics of XD syndrome are alternative chills and fever, hypochondriac pain, and inflammatory swelling and pain (ear or breast). When any of these manifestations occur, XD can be used. Wiry pulse paired with alternative chills and fever, headache, thirst, or hypochondriac pain is also regarded as the indications of using XD. XD should not treat for fever paired with other manifestations, such as headache, delirium, or aversion to cold. In addition, the manifestations with high concurrence frequency do not mean the high correlation. Moreover, only according to the frequency, statistics cannot make correct conclusions. Conclusions: (1) XD is more fit for the excess syndrome such as excess fire in the liver or gallbladder meridians. (2) The medical records in which the XD is misused are also worth analyzing. (3) Association rules cannot be substituted with frequency statistics. 


Traditional Chinese medicine based on Zheng differentiation versus angiotensin receptor blocker/angiotensin-converting enzyme antagonist in efficacy of treating diabetic kidney disease: A meta-analysis of randomized clinical trials
Wei-Jun Huang, Tao Yang, Chuan-Jiang Liu, Yong-Hua Xiao, Qiang Fu, Qing Gong, Hua Zhang, Fan Shao, Hong Yue, Shi-Dong Wang, Jin-Xi Zhao

World Journal of Traditional Chinese Medicine 2019 5(1):18-28

Objective: To compare the efficacy of traditional Chinese medicine (TCM) based on Zheng differentiation with angiotensin receptor blocker/angiotensin-converting enzyme inhibitor (ARB/ACEI) in treating diabetic kidney disease (DKD) from the aspects of decreasing urinary microalbumin, declining 24-h urinary protein, reducing endpoint events, and renal function protection. Methods: The Chinese Biomedical Literature Database (CBM), the Chinese Academy of Sciences database (CNKI), the VIP Chinese journal database, Wanfang DATA, Medline database, Cochrane library, excerpt medical database (Embase), and Web of science were used for literature searching. The reviewer manager 5.3 software was utilized to analyze the data. Results: Twenty-four studies including 1956 participants were involved in this review. Results showed that TCM had a better effect (mean difference [MD], −23.20, 95% confidence interval [CI], −30.60 to −15.79, P < 0.00001) than ARB/ACEI on lowering urinary albumin excretion rate (UAER) and urine albumin-to-creatinine ratio (MD −4.56 mg/mmol, 95% CI, −5.76 to −3.36, P < 0.00001). Moreover, the advantage of decreasing UAER was greater as the follow-up period become longer (P = 0.04). TCM also had a better effect in 24-h urinal protein, decreasing 0.36 g/24 h (95% CI, −0.45 to −0.27, P < 0.00001) more than the control in shorter follow-up period (ranged from 12 to 24 weeks) subgroup but only 0.08 g/24 h (95% CI, −0.13 to −0.03, P = 0.0006) in the longer follow-up period (>24 weeks) subgroup. TCM worked as well as ACEI/ARB in reducing endpoint events (relative risk, 0.67, 95% CI, 0.20–2.224, P = 0.51) and decreasing urinary albumin concentration (UAC) (MD, −16.50, 95% CI, −46.28–13.28, P = 0.28). As for protecting renal function, TCM had an equal effect to AECI/ARB in improving creatinine clearance ratio (MD, −3.30, 95% CI, −6.66–0.03, P = 0.05) or estimated glomerular filtration rate (MD, 1.00, 95% CI, −0.59–2.58, P = 0.22). However, TCM had a better effect in releasing the glomerular hyperfiltration state (MD, −9.64, 95% CI, −14.45 to −4.84, P < 0.0001). Conclusions: TCM based on Zheng differentiation can work as well as ACEI/ARB in treating DKD and even better in decreasing urinary microalbumin and releasing glomerular hyperfiltration. It is a good alternative treatment of DKD. 


Effect of Yinqi ointment on wound morphology and growth factor in treating diabetic foot ulcer
Ya-Li Liu, You-Shan Li, Yu-Qing Du, Shuang Dai

World Journal of Traditional Chinese Medicine 2019 5(1):29-35

Objective: To investigate the effect of Yinqi ointment on wound morphology and growth factor in treating diabetic foot ulcer (DFU). Methods: From December 2016 to December 2017, 92 cases of DFU with deficiency of both Qi and Yin syndrome were randomly divided into treatment group and control group (44 cases in each group). The treatment group was treated with Yinqi ointment, while the control group was treated with mupirocin ointment. After 4 weeks of treatment, the ulcer healing effect, ulcer area, granulation tissue, epithelial tissue coverage, pain score, and dynamic analysis of vascular endothelial growth factor (VEGF), epidermis growth factor (EGF), and basic fibroblast growth factor (bFGF) in local granulation tissue were statistically analyzed before and after treatment in both groups. Results: The total effective rate was 88.37% in the treatment group and 74.42% in the control group. The wound reduction rate, epithelial tissue coverage rate, granulation tissue growth rate, and local pain relief rate in the treatment group were significantly superior to those in the control group (P < 0.05). Through the local granulation detection, the treatment group and the control group have increased VEGF, EGF, and bFGF, but the treatment group increased the role of growth factor than the control group. Conclusion: Yinqi ointment can promote the healing of DFU, and its mechanism may be related to the increase of the content of growth factor in granulation tissue. 


Effects of peiyuan tongnao capsule on working memory and the expression of glutamic acid and receptor in hippocampal area in rats with cerebral ischemia
Jing Bai, Ying Gao, Yong-Hong Gao, Wang Li

World Journal of Traditional Chinese Medicine 2019 5(1):36-41

Objective: To explore the effects of Peiyuan Tongnao (PYTN) Capsule on working memory, the content of glutamic acid, and the expression of NMDA receptor 2B (NR2B) in rats with cerebral ischemia. Materials and Methods: 52 Sprague-Dawley rats were randomly divided into sham group, model group, nimodipine group, and PYTN group. The bilateral common carotid artery occlusion (BCAO) was performed to establish rat model with cerebral ischemia in the model, nimodipine, and PYTN groups. Gastric lavage with some drug based on body weight conversion was performed daily for 4 weeks in the nimodipine and PYTN groups. The working memory of the rats was tested by Morris water maze. The expression of Nissl body in hippocampus tissue was observed by Nissl staining. The determination of Glu content in hippocampus was detected by high-performance liquid chromatography. The expression level of NR2B in hippocampus area was determined using Western blot. Results: Morris water maze test on working memory escape latency. In the model group, day 1 versus day 4, there was a statistical difference (P < 0.05). In the nimodipine group, day 1 vs. day 4 displayed a statistical difference (P < 0.05). In the PYTN group, day 1 versus day 3 and day 1 versus day 4 were in significant differences (P < 0.05). The Glu content in hippocampus of the sham group was significantly different from that of model group (P < 0.05). The Glu content in the PYTN group was significantly different from that of the model group (P < 0.05). With regard to the expression of NMDA 2B in hippocampus between the sham group and the model, nimodipine, and PYTN groups, all were displayed statistical significance (P < 0.01). As the same, the expression of NMDA 2B in the model group was significant from that of the nimodipine group (P < 0.05) and PYTN group (P < 0.01). Conclusion: PYTN capsule was beneficial for improving working memory and protect neural cells in rats of cerebral ischemia, which may be associated with upregulation of the expression of Glu and NMDAR2B in hippocampus. 


Effects of ginsenoside Rb1 on skeletal muscle insulin resistance and adenosine monophosphate-activated protein kinase signaling pathway in obese mice
Dan-Dan Zhao, Ying Bai, Rui Wu, Fang-Fang Mo, Chen-Yue Liu, Ru-Yuan Zhu, Guang-Jian Jiang, Jia-Xian Liu, Dong-Wei Zhang, Si-Hua Gao

World Journal of Traditional Chinese Medicine 2019 5(1):42-49

Objectives: The objective of the study is to observe the effects of ginsenoside Rb1 on indexes of body weight, body composition, blood lipid, skeletal muscle endurance, and insulin sensitivity in obese mice, probe into its pharmacological action, and further explore its effects on adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in skeletal muscle. Materials and Methods: Eight-week-old C57BL/6J mice were fed with high-fat diet for 12 weeks to establish obese mouse model. The model-establishment obese mice were randomly divided into three groups including model control group, metformin group, and ginsenoside Rb1 group. In the normal control group, normal diet was administered. The intervention period was 8 weeks. Body weight and food intake of the mice were measured regularly every week. The treadmill test was performed at weeks 3 and 7, and the oral glucose tolerance test was carried out at weeks 4 and 8. Body composition of the mice was detected by applying NMR Animal Body Composition Analyzer at week 8. Four parameters of blood lipids and free fatty acid (FFA) levels were detected. The mRNA expression of AMPKα and proliferator-activated receptor gamma coactivator-1α (PGC-1α) in skeletal muscle was examined by real-time fluorescence quantitative polymerase chain reaction, and the influence of ginsenoside Rb1 on protein expression of AMPKα, p-AMPKα, and PGC-1α was observed by western blotting. Results: The body weight (since the 5th week of drug administration) and food intake of the mice in the ginsenoside Rb1 group were significantly lower than those in the model control group (P < 0.05) in a time-dependent manner. Ginsenoside Rb1 could significantly reduce the levels of triglyceride and low-density lipoprotein cholesterol, while increase the high-density lipoprotein cholesterol level (P < 0.05). In addition, ginsenoside Rb1 could reduce the serum FFA level (P < 0.05). After the administration of ginsenoside Rb1 for 8 weeks, the body fat mass of obese mice decreased and the lean mass increased (P < 0.05). The skeletal muscle endurance and the oral glucose tolerance of the obese mice improved using ginsenoside Rb1. At the molecular level, ginsenoside Rb1 could up-regulate the mRNA and protein expression of AMPKα in skeletal muscle, and increase the content of p-AMPK protein significantly (P < 0.01). At the same time, the mRNA and protein level of PGC-1α was also un-regulated, correspondingly (P < 0.01). Conclusion: Ginsenoside Rb1 exerts effects on reducing body weight, decreasing blood lipid levels, enhancing the skeletal muscle endurance, and increasing the insulin sensitivity in obese mice by activating the related proteins in AMPK signaling pathway in skeletal muscle. 


Investigation of radix achyranthis bidentatae phytochemistry and pharmacology
Liu Yang, A-Jiao Hou, Mei-Ling Yan, Xu-Dong Xing, Xin-Yue Guo, Hai Jiang, Bing-You Yang, Kelvin Chan, Qiu-Hong Wang, Hai-Xue Kuang

World Journal of Traditional Chinese Medicine 2019 5(1):50-60

Radix achyranthis bidentatae (RAB), a member of the Amaranthaceae family, has been widely used in Traditional Chinese Medicine for 1000s of years. Increasing interest in RAB-derived medicinal has led to the discovery of additional triterpenoid saponins, phytoecdysones, polysaccharides, and many other compounds, as well as investigations into their pharmacology. A large number of pharmacological studies have shown RAB and its active components possess a range of pharmacological activities, including anti-tumor, anti-fertility, anti-senile, and anti-inflammatory effects. This review is an up-to-date summary and synthesis of the uses of RAB from phytochemical and pharmacological perspectives. 


Effects of the clearing the lung and dissipating phlegm method in the treatment of acute exacerbation of chronic obstructive pulmonary disease: A systematic review and meta-analysis
Tao Zhang, Yao-Hui Li, Gai-Xia Liu, Xiu-Lin Tang

World Journal of Traditional Chinese Medicine 2019 5(1):61-69

Objective: The objective of this study is to evaluate the efficacy and safety of the clearing the lung and dissipating phlegm method in the treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD) and to provide evidence for the treatment of the disease. Materials and Methods: Literature was searched from the United States National Library of Medicine (PubMed), Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database (Wanfang), and the Full-Text Database of Chinese Scientific and Technical Periodicals (VIP). A comprehensive collection was made of randomized controlled trials (RCTs) before June 2018, in which the treatment groups used either the clearing the lung and dissipating phlegm formulas only or combined it with routine Western medicine therapy, and the control group adopted routine Western medicine therapy only for the acute exacerbation of COPD. The Cochrane risk of bias method was used to evaluate the quality of the literature. The data were analyzed and retrieved independently by two reviewers before meta-analysis was carried out with RevMan 5.3 software to evaluate the primary outcome measures, including the total clinical effective rate, and the secondary outcome measures such as the pulmonary function (forced vital capacity [FVC], forced expiratory volume in the 1 s [FEV1], percentage of FEV1 [FEV1%], and FEV1/FVC) and blood gases (PaO2 and PaCo2). Results: A total of 13 RCTs involving 990 patients (496 in the treatment group and 494 in the control group) were included in this study. Meta-analysis revealed significant difference in the efficacy of the group that adopted solely the routine Western medicine method and the group that combined the Western medicine with the clearing the lung and dissipating phlegm method. Outcome measures including the pulmonary function (FVC, FEV1, FEV1%, and FEV1/FVC) and the blood gases (PaO2 and PaCo2) were significantly improved as compared to the control group (P < 0.00001). However, adverse effects in the treatment group using combined traditional Chinese medicine were not reported due to the short observation time of the study. Conclusion: The clearing the lung and dissipating phlegm method can improve the efficacy in the treatment of acute exacerbation of COPD, the outcome measures of the pulmonary function and the blood gases, as well as the life quality of the patients. However, due to the fact that the existing studies are generally of poor quality in which randomization and its implementation were not properly carried out, more high-quality RCTs are necessary to confirm the findings of this study. 


Molecular Immunology

Both knock-down and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-κB activity and inflammatory gene expression

Publication date: May 2019

Source: Molecular Immunology, Volume 109

Author(s): Brener C. Carvalho, Leonardo C. Oliveira, Carolina D. Rocha, Heliana B. Fernandes, Isadora M. Oliveira, Felipe B. Leão, Thalita M. Valverde, Igor M.G. Rego, Sankar Ghosh, Aristóbolo M. Silva

Abstract

Small Ras GTPases are key molecules that regulate a variety of cellular responses in different cell types. Rap1 plays important functions in the regulation of macrophage biology during inflammation triggered by toll-like receptors (TLRs). However, despite sharing a relatively high degree of similarity with Rap1, no studies concerning Rap2 in macrophages and innate immunity have been reported yet. In this work, we show that either way alterations in the levels of Rap2a hampers proper macrophages response to TLR stimulation. Rap2a is activated by LPS in macrophages, and although putative activator TLR-inducible Ras guanine exchange factor RasGEF1b was sufficient to induce, it was not fully required for Rap2a activation. Silencing of Rap2a impaired LPS-induced production of IL-6 cytokine and KC/Cxcl1 chemokine, and also NF-κB activity as measured by reporter gene studies. Surprisingly, overexpression of Rap2a did also lead to marked inhibition of NF-κB activation induced by LPS, Pam3CSK4 and downstream TLR signaling molecules. We also found that Rap2a can inhibit the LPS-induced phosphorylation of the NF-κB subunit p65 at serine 536. Collectively, our data suggest that expression levels of Rap2a in macrophages might be tightly regulated to avoid unbalanced immune response. Our results implicate Rap2a in TLR-mediated responses by contributing to balanced NF-κB activity status in macrophages.



PD-1-expressing B cells suppress CD4+ and CD8+ T cells via PD-1/PD-L1-dependent pathway

Publication date: May 2019

Source: Molecular Immunology, Volume 109

Author(s): Xufu Wang, Guoqiang Wang, Zenghua Wang, Bin Liu, Na Han, Jiao Li, Chenghui Lu, Xinfeng Liu, Qin Zhang, Qingbo Yang, Guoming Wang

Abstract

B cell-mediated regulatory function is instrumental to the maintenance of tolerance, but may also contribute to immune dysfunction during infectious diseases and malignancies. In this study, we investigated a subset of B cells characterized by PD-1 expression. Data showed that these PD-1+ B cells were rare in peripheral blood, but were significantly upregulated in differentiated thyroid tumors. The PD-1+ B cells also expressed significantly higher level of PD-L1. Continuous, but not short-term, anti-Ig/CD40 L stimulation could upregulate the expression of PD-1 and PD-L1 in B cells. In in vitro experiments, PD-1+ B cells significantly suppressed the proliferation of CD4+ and CD8+ T cells and reduced their viability upon CD3/CD28 stimulation, thus suggesting that these PD-1+ B cells presented regulatory functions. However, unlike other IL-10-secreting Breg cell subsets, the PD-1+B cells did not express high level of IL-10. Instead, it seemed that PD-L1 was instrumental to the suppressive effects mediated by PD-1+ B cells, since the blockade of PD-L1 significantly increased the proliferation and viability of T cells in the coculture. Interestingly, compared to untreated patients with differentiated thyroid tumor, the thyroidectomy and 131I-treated patients presented significantly lower frequencies of PD-1+ B cells. Together, our investigation demonstrated that the PD-1+ B cells possessed regulatory capacity toward T cell responses, and although rare in peripheral blood, they were significantly enriched in thyroid tumors.



Dust mite-derived Der f 3 activates a pro-inflammatory program in airway epithelial cells via PAR-1 and PAR-2

Publication date: May 2019

Source: Molecular Immunology, Volume 109

Author(s): Bizhou Li, Zehong Zou, Fanmei Meng, Eyal Raz, Yuye Huang, Ailin Tao, Yuncan Ai

Abstract

Protease activity of allergens has been suggested to be involved in the pathogenesis of allergic diseases. The major allergen Der f 3 from Dermatophagoides farinae harbors serine protease activity, but its immunopathogenesis remains unclear. This study aims to explore the effect of Der f 3 on the airway epithelial barrier and on the molecular pathways by which Der f 3 induces inflammation. RNA-seq was performed to identify differentially expressed genes in bronchial airway epithelial cells (AEC) between native Der f 3 and heat-inactivated (H) Der f 3, coupled with real-time PCR (RT-PCR) and ELISA for validation. Unlike other protease allergens such as that induce Th2-promoting alarmins (IL-25, IL-33, TSLP) in AECs, Der f 3 induced pro-inflammatory cytokines and chemokines including IL-6, IL-8 and GM-CSF, which are known to promote Th17 response. These pro-inflammatory mediators were induced by Der f 3 via the MAPK and NF-κB pathways as well as the store-operated calcium signaling. Gene silencing with small interfering RNA in A549 and BEAS-2B cells indicated that activation of AECs by Der f 3 was mainly dependent on protease-activated receptor 2 (PAR-2), while PAR-1 was also required for the full activation of AECs. Double knock-down of PAR-1 and PAR-2 largely impaired Der f 3-inducecd IL-8 production and subsequent signaling pathways. Our data suggest that Der f 3 induces pro-inflammatory mediators in human epithelial cell lines via the PARs-MAPK-NF-κB axis. Our results provide a molecular mechanism by which Der f 3 may trigger the Th17-skewed allergic response toward house dust mites.



Nanobody against the E7 oncoprotein of human papillomavirus 16

Publication date: May 2019

Source: Molecular Immunology, Volume 109

Author(s): Shufeng Li, Wei Zhang, Kunpeng Jiang, Haitao Shan, Minke Shi, Baojun Chen, Zichun Hua

Abstract

The persistent infection of high-risk human papillomavirus (HPV) is one of the most common causes of cervical cancer. It is well documented that expression of two oncogenes (E6/E7) plays a key role in tumor progression. HPV16E7 -targeting via nanobody (Nb) therefore could be beneficial for HPV16-associated cancer diagnosis and therapy. In this work, phage-display approach was employed to select the high affinity HPV16E7-specific Nb. Firstly; a high-quality immune library was constructed. After three round of biopanning, high-affinity HPV16 E7-specific nanobodies were retrieved. By phage ELISA and sequencing, four different sequences of anti- HPV16E7 nanobodies were selected. Then recombinant nanobody Nb2 was cloned and expressed in E. coli, and the specificity and thermal stability of purified Nb2 was evaluated. To examine the potential of Nb2 as an inhibitor of E7 function, Nb2 was expressed within HPV16 positive cells. Proliferation assay showed that the intracellular expressed Nb2 as an intrabody can decrease the growth of HPV16-positive cells. The results indicate that Nb2 as an intracellular antibody directed towards HPV oncoprotein E7 has great promise in applications for the therapy of HPV16-associated disease.



Fli-1 transcription factor regulates the expression of caspase-1 in lung pericytes

Publication date: April 2019

Source: Molecular Immunology, Volume 108

Author(s): Pengfei Li, Andrew J. Goodwin, James A. Cook, Perry V. Halushka, Xian K. Zhang, Hongkuan Fan

Abstract

Our previous data demonstrated that Friend leukemia virus integration 1 (Fli-1), an ETS transcription factor, governs pericyte loss and vascular dysfunction in cecal ligation and puncture-induced murine sepsis by regulating essential pyroptosis markers including caspase-1. However, whether Fli-1 regulates caspase-1 expression levels in vitro and how Fli-1 regulates caspase-1 remain unknown. Our present work further demonstrated that overexpressed Fli-1 significantly increased caspase-1 and IL-18 expression levels in cultured mouse lung pericytes. Bacterial outer membrane vesicles (OMVs) have been found to induce cell pyroptosis through transferring LPS intracellularly. Using OMVs to induce an in vitro model of pyroptosis, we observed that OMVs significantly increased protein levels of Fli-1 in mouse lung pericytes. Furthermore, knockdown of Fli-1 by siRNA blocked OMVs-induced caspase-1, caspase-11 and IL-18 expression levels. As caspase-1 was predicted as a potential target of Fli-1, we cloned murine caspase-1 promoter into a luciferase construct. Our data demonstrate for the first time that Fli-1 regulates caspase-1 expression by directly binding to its promoter regions measured by chromatin immunoprecipitation (ChIP) assay and luciferase reporter system. In summary, our findings demonstrated a novel role and mechanism of Fli-1 in regulating caspase-1 expression in lung pericytes.



The ficolin response to LPS challenge in mice

Publication date: April 2019

Source: Molecular Immunology, Volume 108

Author(s): Ida Jarlhelt, Ninette Genster, Nikolaj Kirketerp-Møller, Mikkel-Ole Skjoedt, Peter Garred

Abstract

The ficolins belong to an important family of pattern recognition molecules, which contributes to complement activation via the lectin pathway. How the ficolins respond to inflammatory stimuli remains only partly understood. In the present study, we investigated the ficolin A and ficolin B expression and protein distribution patterns in a mouse model of LPS-induced inflammation. The time- and tissue-specific expression of ficolin A and B was determined by real time PCR. Furthermore, ficolin protein levels in serum and bone marrow extracts from LPS challenged mice were determined by novel in-house developed sandwich ELISAs. Ficolin A was mainly expressed in liver and spleen. However, our data also suggested that ficolin A is expressed in bone marrow, which is the main site of ficolin B expression. The level of ficolin A and B expression was increased after stimulation with LPS in the investigated tissues. This was followed by a downregulation of expression, causing mRNA levels to return to baseline 24 h post LPS challenge. Protein levels appeared to follow the same pattern as the expression profiles, with an exception of ficolin B levels in serum, which kept increasing for 24 h. Ficolin A was likewise significantly increased in bronchoalveolar lavage fluid from mice infected with the fungi A. fumigatus, pointing towards a similar effect of the ficolins in non-sterile mouse models of inflammation. The results demonstrate that LPS-induced inflammation can induce a significant ficolin response, suggesting that the murine ficolins are acute phase reactants with increase in both mRNA expression and protein levels during systemic inflammation.



Modified DCs and MSCs with HPV E7 antigen and small Hsps: Which one is the most potent strategy for eradication of tumors?

Publication date: April 2019

Source: Molecular Immunology, Volume 108

Author(s): Azam Bolhassani, Sepideh Shahbazi, Elnaz Agi, Nooshin Haghighipour, Amin Hadi, Fatemeh Asgari

Abstract

Immunotherapy with DCs as antigen-presenting vehicles have already improved patients' outcome against a variety of tumors. Moreover, MSCs were recently used to develop anti-cancer therapeutic or anti-microbial prophylactic vaccines. The current study evaluated immune responses and anti-tumor effects generated by DCs and MSCs derived from mouse bone marrow which were modified with small heat shock proteins 27 and 20 (sHsp27 and sHsp20) and also E7 oncoprotein in tumor mouse model. Two vaccination strategies were utilized including homologous DC or MSC prime/ DC or MSC boost, and heterologous MSC or DC prime/ protein boost vaccinations. Our data revealed that DCs pulsed with E7+Hsp27 and/or E7+Hsp20 in homologous and heterologous prime/ boost vaccinations could stimulate high levels of IgG2a, IgG2b, IFN-γ and IL-10 directed toward Th1 responses. Moreover, these regimens induced an increased level of Granzyme B, and displayed complete protection more than 60 days after treatment. On the other hand, MSCs transfected with E7+Hsp27 DNA in homologous and heterologous prime/ boost vaccinations could significantly enhance the E7-specific T-cell responses and suppress tumor growth in mice. However, MSCs transfected with E7+Hsp20 DNA did not induce a complete protection against TC-1 tumor compared to DCs pulsed with E7+Hsp20 protein complexes. These results indicated that DC- and MSC-based vaccinations with specific modalities will be a useful approach for immunotherapy and protection against HPV-associated cancers.



Modulation of antiviral immunity by the ichnovirus HdIV in Spodoptera frugiperda

Publication date: April 2019

Source: Molecular Immunology, Volume 108

Author(s): Vincent Visconti, Magali Eychenne, Isabelle Darboux

Abstract

Polydnaviruses (PDVs) are obligatory symbionts found in thousands of endoparasitoid species and essential for successful parasitism. The two genera of PDVs, ichnovirus (IV) and bracovirus (BV), use different sets of virulence factors to ensure successful parasitization of the host. Previous studies have shown that PDVs target apoptosis, one of the innate antiviral responses in many host organisms. However, IV and BV have been shown to have opposite effects on this process. BV induces apoptosis in host cells, whereas some IV proteins have been shown to have anti-apoptotic activity. The different biological contexts in which the assays were performed may account for this difference. In this study, we evaluated the interplay between apoptosis and the ichnovirus HdIV from the parasitoid Hyposoter didymator, in the HdIV-infected hemocytes and fat bodies of S. frugiperda larvae, and in the Sf9 insect cell line challenged with HdIV. We found that HdIV induced cell death in hemocytes and fat bodies, whereas anti-apoptotic activity was observed in HdIV-infected Sf9 cells, with and without stimulation with viral PAMPs or chemical inducers. We also used an RT-qPCR approach to determine the expression profiles of a set of genes known to encode key components of the other main antiviral immune pathways described in insects. The analysis of immune gene transcription highlighted differences in antiviral responses to HdIV as a function of host cell type. However, all these antiviral pathways appeared to be neutralized by low levels of expression for the genes encoding the key components of these pathways, in all biological contexts. Finally, we investigated the effect of HdIV on the general antiviral defenses of the lepidopteran larvae in more detail, by studying the survival of S. frugiperda co-infected with HdIV and the entomopathogenic densovirus JcDV. Coinfected S. frugiperda larvae have increased resistance to JcDV at an early phase of infection, whereas HdIV effects enhance the virulence of the virus at later stages of infection. Overall, these results reveal complex interactions between HdIV and its cellular environment.



Phenylethanoid glycosides of Phlomis younghusbandii Mukerjee ameliorate acute hypobaric hypoxia-induced brain impairment in rats

Publication date: April 2019

Source: Molecular Immunology, Volume 108

Author(s): Fei Luan, Maoxing Li, Keqing Han, Qiang Ma, Jian Wang, Yan Qiu, Linhong Yu, Xirui He, Daoheng Liu, Haizhen Lv

Abstract

High altitude cerebral edema (HACE), whose development process is associated with oxidative stress and inflammatory response, is a life-threatening condition caused by rapid ascent speed to high altitudes. Phenylethanoid glycosides (PhGCs) are primary active constituents isolated from Phlomis younghusbandii Mukerjee that reportedly exhibit potent anti-oxidant and anti-inflammatory activities. The present study aims to investigate the protective effect of phenylethanoid glycosides (PhGCs) from P. younghusbandii in acute hypobaric hypoxia (AHH) – stimulated HACE rats and its underlying mechanisms. The expression of pro-inflammatory cytokine levels (IL-1β, TNF-α, and IL-6) was detected by RT-PCR and ELISA at mRNA and protein levels in brain tissues. Western blotting was carried out to measure the major protein levels (IL-1β, TNF-α, and NF-κB) in brain tissues. The oxidative stress biomarkers (MDA, SOD, and GSH) were evaluated using kits. Results demonstrate that PhGCs significantly improved pathological changes in brain tissues, reduced the brain's water content, and attenuated the production and mRNA expression of pro-inflammatory cytokines. Furthermore, the increased oxidative stress and the decrease in anti-oxidant stress system under the AHH condition were also abrogated reversely through PhGCs treatment by elevating the levels of SOD and GSH and suppressing the accumulation of MDA. Simultaneously, there was also a significant reduction in NF-κB, IL-1β, and TNF-α protein expression levels in brain tissues, suggesting that blocking the NF-κB signaling pathway activation prevented the production of pro-inflammatory cytokines. Taken together, these findings indicate that PhGCs may afford a protectively intervene in HACE through the suppression of oxidative stress and inflammatory response via the inhibition of the NF-κB signaling pathway, indicating that PhGCs are promising agents for the treatment of acute HACE.



Tumor suppressor p53 inhibits porcine epidemic diarrhea virus infection via interferon-mediated antiviral immunity

Publication date: April 2019

Source: Molecular Immunology, Volume 108

Author(s): Zhichao Hao, Fang Fu, Liyan Cao, Longjun Guo, Jianbo Liu, Mei Xue, Li Feng

Abstract

p53 is a tumor suppressor gene that can be activated in many contexts, such as DNA damage or stressful conditions. p53 has also been shown to be important for responses to certain viral infections. Porcine epidemic diarrhea virus (PEDV) is a major enteric pathogen of the coronavirus family that causes extensive mortality among piglets. The involvement of p53 during PEDV infection has not previously been investigated. In this study, we detected p53 upregulation in response to PEDV infection. Treatment with a p53 specific activator or p53 overexpression markedly decreased viral replication, and we showed that there was more viral progeny produced in p53 knock-out cells than in p53 wild-type cells. Finally, we demonstrated that inhibition of viral infection by p53 was mediated via p53-dependent IFN signaling, leading to IFN-stimulated response element (ISRE) activation, as well as the upregulation of IFN-stimulated genes (ISGs) and IFN-β released from infected cells. These findings demonstrate that p53 suppresses PEDV infection, offering a novel therapeutic strategy for combatting this deadly disease in piglets.



Ophthalmology

Complicated lower lid ectropions presenting to tertiary care hospital in Sub-Himalayan Region of Himachal Pradesh and their management
Gaurav Sharma, Sushma Sawaraj

Sudanese Journal of Ophthalmology 2018 10(2):39-43

Introduction: Ectropions of the lower lid area are of diverse etiology. They may be involutional, mechanical, paralytic, or cicatricial. The patients have lot of discomfort due to exposure and epiphora. Some of them also develop complications like infectious keratitis that are vision threatening as well. Cicatricial ectropions, severe ectropions with tissue laxity are sometimes difficult to manage. In this study, we intend to describe techniques we have used for the management of selected complicated cases of Ectropions. Aim and Objectives: The aim of the study is to describe the complicated cases of ectropions presenting to a tertiary care hospital in Sub-Himalayan region of Himachal Pradesh, India, and the various techniques used in their management. Materials and Methods: Cases of complicated ectropions fulfilling the inclusion and exclusion criterion which presented to the department of ophthalmology were included in the study. The patients were subjected to detailed history and clinical examination according to a predesigned pro forma. They were divided into four subtypes and managed surgically. Results: Horizontal lid shortening with or without blepharoplasty was performed in the cases of involutional ectropions and showed good outcome in all cases. There was no significant lid notching postoperatively. The cicatricial ectropion cases were managed surgically using Z plasty in all but one case of generalized cicatricial ectropion where skin grafting using postauricular graft was used. Postoperatively, the patients improved symptomatically, and cosmetic outcome was also acceptable. Conclusions: Horizontal shortening with or without blepharoplasty if performed meticulously is a good procedure providing excellent results; however, the site for pentagon excision and the amount of resection required needs to be decided, along with any medial or lateral canthal tendon stabilization. Cicatricial ectropions unless are generalized or very severe managed well with Z plasty, however, it is very important to understand the dynamics of the scar before deciding the site and dimensions of the Z plasty. Full-thickness skin graft is sometimes the only option for generalized cicatricial ectropions. 


Donor factors influencing corneal tissue utilization in North India
Anuradha Raj, Garima Mittal, Harsh Bahadur

Sudanese Journal of Ophthalmology 2018 10(2):44-49

Purpose: The study aimed to determine the effect of various donor factors on utilization pattern of donor corneal tissue. Methods: This was a cross-sectional, retrospective study. Data of 509 donors with 1007 eyes details from eye bank (EB) were reviewed from December 2012 to June 2017. Donor data was analyzed including the age, sex of the donor, cause of death, source of tissue, death to enucleation time (DET), death to preservation time (DPT), type of tissue collected, grades of the tissue, serology reports and various utilization parameters. Results: Tissue utilization of EB was 356 out of 1007 which made 35.35% with cumulative utilization to the tune of 512 out of 1007 (50.84%). 82.50% tissues utilized for surgical use were from donor>65 years of age. Type and grading of tissue influenced the utilization of the tissues significantly (P = 0.00) each. Maximum keratoplasties 179 (50.28%), 202 (56.74%) were done with DET>3 hrs and DPT ≤4 respectively. DET, DPT and serology showed significant influence on the utility of the tissue (P = 0.00) each. Major cause of exclusion of the tissue for utilization was poor quality of the tissue which was C grade. Grading of tissue was significantly affected by DET, DPT and mode of tissue procured. Donor age >65 years showed higher surgical utility. Conclusion: Various donor factors like DET, DPT, tissue grade and type and serology results affects the utility of harvested corneal tissue. Potential modifiable donor factors needs to be addressed such as attention must be paid to the cause of death, contraindications and time factors related to donor. 


Ocular injuries associated with traumatic hyphema in a tertiary hospital
Olusola Joseph Omotoye, Iyiade Adeseye Ajayi, Emmanuel Chinwedu Abah

Sudanese Journal of Ophthalmology 2018 10(2):50-53

Introduction: Traumatic hyphema is one of the most challenging clinical problems frequently encountered by ophthalmologists. Aim: The aim of this study is to determine the prevalence of ocular injuries in patients being managed for traumatic hyphema in this center to have a strategic plan to reduce consequential visual sequelae from the injury. Materials and Methods: This was a cross-sectional study conducted based on the data obtained from an eye clinic from January 2010 to July 2017. Information on demographic characteristics, chief presenting complaints and duration of symptoms before presentation, laterality, presenting visual acuity, grade of hyphema, intraocular pressure, associated ocular injury, and treatment offered were obtained. Results: Traumatic hyphema constituted 4.2% of all ocular emergencies seen in this center. There were 37 (82.2%) males and 8 (17.8%) females with a male-to-female ratio of 4.6:1.0. Of the 45 cases, 32 (71.1%) patients presented with blindness in the affected eye with the worst presentation occurring in Grade 4 hyphema. Thirty-three patients (73.3%) presented more than 24 h to the eye facility, age, and eye pain significantly affected the duration of presentation. The prevalence of ocular injuries in patients that had traumatic hyphema was 34 (75.6%). Fourteen (31.1%) patients presented with corneal injury ranging from corneal abrasions to corneal laceration. Conclusion: The prevalence of associated ocular injuries in patients with traumatic hyphema was high with corneal injuries as the most ranked complications. Reduction of consequential poor visual prognosis would include counseling on early presentation, meticulous examination of the injured eye, and quick and appropriate surgical intervention as indicated to prevent corneal staining. 


Comparison of eye patching with cyanoacrylate glue application for anterior chamber reformation in infected perforated corneal ulcers
Rini Saha, Gautam Singh Parmar, Ashok Kumar

Sudanese Journal of Ophthalmology 2018 10(2):54-59

Objectives: This study was designed with the primary objective to compare between eye patching and cyanoacrylate glue application for anterior chamber (AC) reformation in infected perforated corneal ulcers. Subjects and Methods: This is a nonrandomized prospective comparative study conducted in a tertiary eye hospital. Patients with perforated keratitis were offered either eye patching (Group 1) or cyanoacrylate gluing (Group 2) under hospital admission and medical treatment to reform the AC. Success was defined as a formed AC at the time of discharge from the hospital. Patients were followed up to 1 month after discharge. Normally distributed data were expressed as mean ± standard deviation and skewed data as median. Nominal data between the two groups were compared using Chi-square test or Fisher's exact test. Results: Forty eyes underwent eye patching and 38 eyes cyanoacrylate gluing to reform the AC. The number of eyes with formed AC was more in Group 2 (92%) compared to Group 1 (70%) (P = 0.020). Subgroup analysis on the basis of the size of perforation and size of ulcer showed that AC reformation was better in Group 2 compared to Group 1 in all aspects [Table 1]. In intragroup analysis, success in Group 1 was significantly better in small perforations (P = 0.001) and in small ulcers (P = 0.032) and ulcer in central location (P = 0.004). In Group 2, there was no significant difference in AC reformation between small and large perforation or ulcer. In both groups, AC reformation in peripheral perforations was poor compared to central and paracentral perforations (P = 0.004, 0.032). Conclusions: Cyanoacrylate glue is better than eye patching to restore ocular integrity. However, eye patching showed promising results in subgroup of patients with small perforated ulcers.{Table 1} 


Impact of cataract surgery on visual functions and quality of life in Azare, North-Eastern Nigeria
Mohammed Dantani Adamu, Ahmed Saidu, Mahmud Alhassan Babanini, Ahmadu Shehu Mohammed

Sudanese Journal of Ophthalmology 2018 10(2):60-63

Purpose: The purpose of this study is to assess the impact of cataract surgery on the subjective visual functions (VFs) and quality of life (QoL) of patients who had cataract surgery at the Federal Medical Centre Azare, Bauchi State, Nigeria. Materials and Methods: This was a hospital-based prospective observational study which used the VF and QoL questionnaires. These were administered to the patients preoperatively and also 6 weeks' postoperatively. The visual acuity, VF, and QoL scores of the pre- and post-operative period were compared. A paired t-test was used for comparison. Results: A total of 181 patients were recruited. The mean age of the patients was 60.5 years, and 110 (60.8%) were males. The mean preoperative VF and QoL scores were 55.1 (Standard deviation [SD] ± 19.7) and 39.5 (SD ± 17.8), respectively. The mean postoperative VF and QOL scores were 31.5 (SD ± 9.9, t = 18.79, P = <0.001) and 25.4 (SD ± 2.4, t = 10.87, P ≤ 0.001) respectively. Conclusion: This study shows that both VFs and QoL of cataract patients can be greatly improved with cataract surgery. 


Distribution of xerophthalmia among children in the traditional quranic schools in Al-Gezira State of Sudan
Zoelfigar Dafalla Mohamed, Saif Hassan Alrasheed

Sudanese Journal of Ophthalmology 2018 10(2):64-67

Background: Vitamin A deficiency is considered a serious public health issue in poor nations, which leads to corneal opacity and results in childhood blindness in most of the low-income countries. Aim: To determine the prevalence of xerophthalmia among children at traditional Quranic schools in Al-Gezira state of Sudan. Materials and Methods: This was a quantitative cross-sectional study conducted on 822 children aged from 5 to 15 years, living in traditional Quranic schools. The clinical examinations for all children in this study include the demographics of patients (name, gender, age, and duration of students in schools), symptoms (vision during the day and night), and then outer eye checked for all children by lope and magnifier and visual acuity using Snellen's chart. Results: The prevalence of night blindness, conjunctival xerosis, corneal xerosis, and Bitot's spots was 17.3%, 20.3%, 0.2%, and 0.7%, respectively. There was a significant association between the duration of staying the children at the schools and the development of night blindness (P ≤ 0.02). Conclusion: Children of this community are susceptible to xerophthalmia because food is inadequate of Vitamin A. The governmental and nongovernmental organization should supply this community by the diet rich of Vitamin A and Vitamin A supplementation orally for affected children as well as annually comprehensive eye examinations. 


A 28-Year-old male with anterior ectopic cilia and hypermetropic anisometropic amblyopia
Hina Kauser, Monica Kapoor

Sudanese Journal of Ophthalmology 2018 10(2):68-70

Only few cases of Eptopic cilia have been reported in literature. Anterior ectopic cilia cause no apparent ocular symptoms and can be surgically excised for cosmetic improvement. We report a case of a 28-year-old male with anterior ectopic cilia in association with hypermetropic anisometropic amblyopia. Only 15 cases of anterior ectopic cilia have been reported in literature. Few of them were associated with some conditions such as choristoma, aberrant lacrimal glands, atopic eczema, nail–patella syndrome, and hypochromic nevus. To the best of our knowledge, this is the first reported case of anterior ectopic cilia associated with hypermetropic anisometropic amblyopia. No underlying common causative disorder became evident. The observed association was considered as coincidental. 


Anaesthesia

Specific reversal agents: Fast and fearless – A new era in anticoagulation care
Abhay Bhave

Indian Journal of Anaesthesia 2019 63(3):167-168



Novel reversal agents and laboratory evaluation for direct-acting oral anticoagulants (DOAC): An update
Shagun B Shah, Akhilesh Pahade, Rajiv Chawla

Indian Journal of Anaesthesia 2019 63(3):169-181

Novel oral anticoagulants (NOACs) are no longer “novel” but their reversal agents definitely are. Although NOACs enjoy high clinical efficacy, monitoring and reversal of their effect is a challenge which this review attempts to surmount. Ideally, for NOAC activity measurement, specific anti-Factor IIa levels and anti -Factor Xa levels should be monitored (chromogenic assays), but such tests are not readily available. Modifications of the existing coagulation tests catering to this unmet need for quantification of DOAC activity have been reviewed. The available United States Food and Drug Administration (FDA) approved reversal agents, idarucizumab for dabigatrin and andexanet alfa for anti-Xa direct acting oral anticoagulants have given promising results but are prohibitively priced. Medline, Embase, and Scopus databases were thoroughly searched for clinical trials on laboratory investigations and specific as well as non-specific reversal-agents for DOACs. 


Efficacy of local wound infiltration analgesia with ropivacaine and dexmedetomidine in tubercular spine surgery – A pilot randomised double-blind controlled trial
Medha Mohta, Anju Rani, Ashok Kumar Sethi, Anil Kumar Jain

Indian Journal of Anaesthesia 2019 63(3):182-187

Background and Aims: Regional analgesic techniques are difficult to use in tubercular spine patients due to distorted spinal anatomy and presence of infection. This study was conducted with the aim to evaluate analgesic efficacy of local wound infiltration before wound closure in tubercular spine patients. Methods: This pilot randomised double-blind controlled study was conducted in 32 American Society of Anesthesiologists I-III patients, age ≥15 years, undergoing elective surgery for spinal tuberculosis. All the patients received general anaesthesia using standard technique and intravenous morphine for intraoperative analgesia. They received wound infiltration with either normal saline (group C) or local infiltration analgesia with 0.375% ropivacaine 3 mg/kg, adrenaline 5 μg/mL and dexmedetomidine 1 μg/kg in a total volume of 0.8 mL/kg (group LIA) before wound closure. Patient-controlled analgesia using intravenous morphine provided postoperative analgesia. The primary objective was to study 24-h morphine consumption, whereas the secondary objectives included pain scores, complications and patient satisfaction. Repeated measures analysis of variance, Chi-square test and Mann–Whitney U test were used for statistical analysis. Results: Morphine requirement was lower in group LIA (6.7 ± 2.7 mg) than in group C (27.7 ± 7.9 mg);P < 0.001. Group LIA also had lower pain scores (P < 0.001), longer time to rescue analgesic (P < 0.001), better patient satisfaction to pain relief (P = 0.001) and lower incidence of postoperative nausea and vomiting than group C. Conclusion: Wound infiltration with ropivacaine, adrenaline and dexmedetomidine before wound closure provided good postoperative analgesia with lower morphine requirement. 


A randomised controlled comparison of video versus instructor-based compression only life support training
Shahna Ali, Manazir Athar, Syed Moied Ahmed

Indian Journal of Anaesthesia 2019 63(3):188-193

Background and Aims: Sudden cardiac deaths remain a major health problem worldwide. Most of these cases generally involve out of hospital cardiac arrest, making the role of bystander resuscitation very crucial. In the developing countries, illiteracy and scarcity of health professionals is a great barrier to cardiopulmonary resuscitation (CPR) training. Video-based CPR training can offer an easily accessible modality in these situations. Hence, this study was conducted with an aim to assess the efficacy of video-based training in comparison to the traditional instructor-based CPR training in layman. Methods: This prospective cross-over observational study included 109 undergraduate university students attending voluntary resuscitation training and were randomly divided into two groups of video-based demonstration (VBD) and instructor-based demonstration (IBD) of compression only life support (COLS). They were then assessed for psychomotor skill development (Laerdal Simpad Plus Q-CPR) and perception about the quality of training methodology as primary and secondary objectives, respectively. Results: Population characteristics were similar in both the groups. In the VBD, scene safety was performed by 95.2% and call for help by 97.6%, and by 76.1% each in the IBD group (P < 0.05). Response to compression time (RCT) was significantly shorter in VBD (35 ± 9 sec) as compared to IBD (54 ± 14 sec) (P < 0.001). However, the proportion of participants performing response check, correct site identification, and other parameters were comparable. Conclusion: Video-based COLS training significantly decreased the RCT by 35% compared to traditional instructor-based training. However, other features of high-quality CPR remain comparable. 


Prediction of outcomes in chest trauma patients using chest trauma scoring system: A prospective observational study
Minal Harde, G Aditya, Sona Dave

Indian Journal of Anaesthesia 2019 63(3):194-199

Background and Aims: Prognostication of chest trauma patients by scoring systems is of vital importance to predict morbidity and mortality. We aimed to predict outcomes in chest trauma patients using chest trauma scoring system (CTS) in Indian patients. Methods: This was a prospective observational study done in a trauma care centre at a tertiary care teaching public hospital. CTS was calculated by scores of age, severity of pulmonary contusion, number of rib fractures and presence of bilateral rib fractures. Final CTS ranges from 2 to 12. We evaluated CTS to predict outcome that is mortality as primary objective and development of complications like pneumonia and need for ventilator support as secondary objective in Indian population. Results: Data were collected from 30 patients and they were divided into two groups, CTS <5 (15) and CTS ≥5 (15). High CTS ≥5 was statistically significantly associated with high incidence of pneumonia (P = 0.046), increased requirement of mechanical ventilation (P = 0.025) and mortality (P = 0.035) in chest trauma. Area under the ROC for mortality shows that the test is acceptable (0.75) and at CTS score 5.5 maximum sensitivity is 87.5% and specificity is 68%. Conclusion: This study concludes that a CTS ≥5 is associated with poor outcomes. This scoring system may be used to identify patients at risk of complications and institute early intensive focussed care. 


Ultrasound-guided erector spinae plane block for postoperative analgesia in modified radical mastectomy: A randomised control study
Swati Singh, Gunjan Kumar, Akhileshwar 

Indian Journal of Anaesthesia 2019 63(3):200-204

Background and Aims: Several locoregional techniques have been described for providing postoperative analgesia after breast surgery. The optimal technique should be easy to perform, reproducible and provide good analgesia. This randomised control study was designed to evaluate the postoperative analgesic effect of ultrasound-guided erector spinae plane (US-guided ESP) block for modified radical mastectomy (MRM) surgery. Methods: A total of 40 females belonging to American Society of Anesthesiologists' 1 or 2 posted for MRM were randomly allocated into Group 1 (control group) and group 2 (ESP group). Patients in Group 1 received only general anaesthesia (GA) and were managed for pain postoperatively according to routine protocol, while group 2 (ESP group) patients received unilateral US-guided ESP block preoperatively (20 mL 0.5% bupivacaine to the operating side) followed by GA. The primary objective of study was to record postoperative 24 h cumulative morphine requirement. Differences between the two groups were analyzed using the Mann–Whitney U-test or a two-tailed Student's t-test. Results: Postoperative morphine consumption was found to be significantly less in patients receiving US-guided ESP block compared to control group (1.95 ± 2.01 mg required in ESP group vs 9.3 ± 2. 36 mg required in control group, P value = 0.01)). All the patients in control group required supplemental morphine postoperatively compared to only two patients requiring that in US-guided ESP block group (P < 0.01). Conclusion: US-guided ESP block when given prior to MRM surgery provided effective postoperative analgesia. CTRI registration no. - CTRI/2018/03/012712 registered in the clinical trial registry, India. 


A comparative evaluation of pre-emptive versus post-surgery intraperitoneal local anaesthetic instillation for postoperative pain relief after laparoscopic cholecystectomy: A prospective, randomised, double blind and placebo controlled study
Prabhu Gnapika Putta, Hemalatha Pasupuleti, Aloka Samantaray, Hemanth Natham, Mangu Hanumantha Rao

Indian Journal of Anaesthesia 2019 63(3):205-211

Background and Aims: Intraperitoneal local anaesthetic instillation (IPLAI) reduces postoperative pain and analgesic consumption effectively but the timing of instillation remains debatable. This study aims at comparing pre-emptive versus post-surgery IPLA in controlling postoperative pain after elective laparoscopic cholecystectomy. Methods: Ninety patients belonging to American Society of Anesthesiologists physical status I or II were randomly assigned to receive IPLAI of either 30 ml of normal saline (C) or 30 ml of 0.5% bupivacaine at the beginning (PE) or at the end of the surgery (PS) using a double-dummy technique. The primary outcome was the intensity of postoperative pain by visual analogue scale score (VAS) at 30 minute, 1, 2, 4, 6, 24 hours after surgery and time to the first request for analgesia. The secondary outcomes were analgesic request rate in 24 hours; duration of hospital stay and time to return to normal activity. Data were compared using analysis of variance, Kruskal-Wallis or Chi-square test. Results: For all predefined time points, VAS in group PE was significantly lower than that in groups C (P < 0.05). The time to first analgesic request was shortest in group C (238.0 ± 103.2 minutes) compared to intervention group (PE, 409.2 ± 115.5 minutes; PS, 337.5 ± 97.5 minutes;P < 0.001). Time to attain discharge criteria was not statistically different among groups. Conclusion: Pre-emptive intraperitoneal local anaesthetic instillation resulted in better postoperative pain control along with reduced incidence of shoulder pain and early resumption of normal activity in comparison to post surgery IPLAI and control. 


Haemodynamic changes during prone positioning in anaesthetised chronic cervical myelopathy patients
Nitin Manohar, Venkatapura J Ramesh, Muthuchellappan Radhakrishnan, Dhritiman Chakraborti

Indian Journal of Anaesthesia 2019 63(3):212-217

Background and Aims: Anaesthetised patients, when positioned prone, experience hypotension and reduction in cardiac output. Associated autonomic dysfunction in cervical myelopathy patients predisposes them to haemodynamic changes. The combined effect of prone positioning and autonomic dysfunction in anaesthetised patients remains unknown. Methods: Thirty adult chronic cervical myelopathy patients, aged 18-65 years with Nurick grade ≥2 were recruited in this prospective observational study. Heart rate, mean blood pressure, cardiac output, stroke volume, total peripheral resistance and stroke volume variation were measured using NICOM®monitor. Data were collected in supine before anaesthetic induction (baseline), 2 minutes after induction, 2 minutes after intubation, before and after prone positioning and every 5 minutes thereafter until skin incision. Repeated measures analysis of variance (ANOVA) was used to analyse the haemodynamic parameters across the time points. Bivariate Spearman's correlation was used to find factors associated with blood pressure changes. A P value <0.05 was kept significant. Results: Cardiac output during the entire study period remained stable (P = 0.186). Sixty percent of the patients experienced hypotension. At 15 and 20 minutes after prone positioning, mean blood pressure decreased (P = 0.001), stroke volume increased (P = 0.001), and heart rate and total peripheral resistance decreased (P < 0.001, P= 0.001, respectively). These changes were significant when compared to pre-prone position values. Number of levels of spinal cord compression positively correlated with the incidence of hypotension. Conclusion: Cervical myelopathy patients experienced hypotension with preserved cardiac output in prone position due to a reduction in total peripheral resistance. Hypotension correlated with the number of levels of spinal cord compression. 


I-Gel as an intubation conduit: Comparison of three different types of endotracheal tubes
Nitin Choudhary, Abhijit Kumar, Amit Kohli, Sonia Wadhawan, Poonam Bhadoria

Indian Journal of Anaesthesia 2019 63(3):218-224

Background and Aims: I-Gel®, a novel SAD has been introduced as a ventilating device but has widely gained popularity as conduit for intubation. Unlike intubating laryngeal mask airway (ILMA), I-Gel® does not have an endotracheal tube specially designed for it. Hence the aim of this study was to compare the rate of successful intubation via I-Gel®using three different types of endotracheal tubes. Methods: We randomised 75 American Society of Anesthesiologists (ASA) physical status I and II patients, between the age group 18-60 years of either sex undergoing elective surgery under general anaesthesia into three groups on the basis of endotracheal tube (ETT), used for intubation via I-Gel®: Group P (Polyvinyl chloride ETT), Group I (Intubating laryngeal mask airway ETT), Group F (flexometallic ETT). After following the standard induction protocol, appropriate size I Gel®was inserted in all patients. Thereafter group specific ETT was inserted via I-Gel®. We recorded and compared the time taken for successful intubation, the success rate, number of attempts taken, manoeuvres used, and complications among three different types of ETT. Quantitative variables were compared using Kruskal Wallis test and the qualitative variables were compared using Chi-square test. Results: The time taken for successful intubation was least in group P (10.51 ± 3.82 seconds). Group P also had the highest first attempt (68%) and overall rate of successful intubation (88%). Conclusion: PVC ETT had highest first attempt success rate and required minimum time for endotracheal intubation via I-Gel®when compared to ILMA ETT and Flexible ETT. 


Comparison of bispectral index targeted end-tidal concentration of desflurane during three phases of orthotopic liver transplantation
Gyanendra Kumar, Nitin Sethi, Deepanjali Pant, Jayashree Sood, Amarjeet Singh, Shashank Pandey, Amitabh Dutta

Indian Journal of Anaesthesia 2019 63(3):225-230

Background and Aims: Reduced inhalational anaesthetic requirement in end-stage liver disease during living donor orthotopic liver transplantation (LD-OLT) is due to increased endogenous opioids. This study evaluated the changes in bi-spectral index (BIS) monitored end-tidal desflurane (ETDes) requirements during ‘dissection’, ‘anhepatic’, and ‘neohepatic’ phases of LD-OLT. Methods: This prospective, cohort study included 40 adults undergoing LD-OLT under general anaesthesia (GA). All patients received BIS-guided desflurane GA. ETDesrequirements in three phases of LD-OLT (primary objective); relationship between inhalational anaesthetic requirements and severity of liver disease; and effect of changes in mean arterial pressure (MAP) and body temperature on ETDesconcentration for all three phases were also evaluated. Results: ETDesduring the ‘dissection’ phase (2.92 ± 0.65%) was > ‘anhepatic’ (2.68 ± 0.85%, P= 0.049) and ‘neohepatic’ phases (2.58 ± 0.71%, P= 0.005). Patients with model of end-stage liver disease (MELD) score < 20 returned significantly greater ETDesthan those with MELD score ≥20 during the ‘dissection’ (MELD <20: 3.11 ± 0.49%; MELD ≥20: 2.58 ± 0.77%, P= 0.01) and ‘anhepatic’(MELD <20: 2.96 ± 0.76%; MELD ≥20: 2.17 ± 0.79%, P= 0.003) phases. A positive correlation was observed between ETDes(r = 0.584, P= 0.001) and temperature in the ‘dissection’ phase only. Conclusion: In patients undergoing LD-OLT, BIS monitoring guidance of depth of desflurane GA suggests lower desflurane requirements during ‘anhepatic’ and the ‘neohepatic’ phase of surgery. Also, the desflurane requirement is greater in patients with lesser severity of liver disease. 


Plastic Surgery

A transilience? Or a natural progression?!
Dinesh Kadam

Indian Journal of Plastic Surgery 2018 51(3):263-263



Tony Watson Eulogy
Ravin Thatte

Indian Journal of Plastic Surgery 2018 51(3):264-265



Intraoperative partial pressure of oxygen measurement to predict flap survival
Ankit Gupta, Akhil Kumar, Shyam Gupta, Sameek Bhattacharaya, Manoj Kumar Jha, Vinay Kumar Tiwari, R Pradeep Kulal, Shobhit Gupta, Sahil Niyazi

Indian Journal of Plastic Surgery 2018 51(3):266-273

Introduction: Flap monitoring using partial pressure of oxygen (pO2) is a proven modality. Instruments needed are expensive and are not readily available to a clinician. Here, pO2of flap has been determined using readily available and cheap methods, and a cut-off value is calculated which helps in predicting flap outcome. Methods and Results: Total 235 points on 84 skin flaps were studied. Capillary blood was collected from flap and fingertip using 1-ml syringes after at least 30 min of flap inset, and pO2analysed using blood gas analyser. Fall/change of pO2(difference of mean of pO2[diff-pO2]) was also calculated by subtracting the flap pO2from the finger pO2. Flap was monitored clinically in post-operative period and divided into two groups depending on its survival with Group 1 – dead points and Group 2 – alive points. pO2and diff-pO2amongst both the groups were compared and found to be statistically different (P = 0.0001). Cut-off value calculated for pO2was found to be <86.3 mmHg with a sensitivity of 100% and specificity of 89.05%. The difference of >68.503 mmHg of flap pO2compared from finger pO2was calculated as a cut-off with sensitivity of 94.12 and specificity of 79.60%. Conclusions: Flap areas having intra-operative pO2value <86.3 mmHG have higher chances (60.71%) of getting necrosis later. Similarly, if diff-pO2compared to fingertip is >68.5 mmHg, chances of those points getting necrosed in post-operative period are high.


Free fibula flap for lower limb salvage after tumour resection
Vinay Kant Shankhdhar, Prabha S Yadav, Ajay Puri, Ashish Kasat, Jaiswal Dushyant, Ram Badari Narayan Raghu, Ashish Gulia

Indian Journal of Plastic Surgery 2018 51(3):274-282

Context: Post-tumour resection lower limb salvage. Aim/Introduction: Resection of tumours of the femur and tibia around the knee and ankle joints results in large bony defects. Often arthrodesis is an alternative; in case, adequate functional motors cannot be preserved or due to economic constraints. Thus, in an immunocompromised patient, the vascularised fibula is the best form of reconstruction. The vascularised fibular flap (pedicled/free) can be used in combination with an allograft. We refer to such a combination reconstruction as ‘allocombo’. The vascularised fibular graft hypertrophies in due course of time, and till that period, the allograft provides the required mechanical strength to allow early ambulation. Subjects and Methods: A retrospective study of 24 cases of vascularised fibular graft for lower limb reconstruction was conducted from February 2003 to March 2014. The average defect size was 15.5 cm and the average length of fibula harvested was 24.35 cm. A total of 19 free fibular flaps and 5 pedicled fibula were done. Mean age was 26 years. Fibula was nestled in the allograft obtained from the tissue bank. Results: The mean follow-up time was 52 months. Free flap success rate was 96%. Successful healing was achieved at 45 ends (97.8%). Radiological evidence of union at osteotomy sites occurred at an average of 6.8 months. Eight patients eventually succumbed to disease. At the final follow-up, the mean Musculoskeletal Tumour Society functional score of the evaluable patients was 26 (range 20–30). Conclusions: Pedicled fibula is a good option if the defect is within 14 cm of the knee joint at the femoral end. The vessels have to curve around the fibular head, thus its removal improves the reach of the pedicle. The flap is easy to harvest with predictable vascular anatomy and it can provide a large amount of vascularised bone and skin paddle. It results in early ambulation, rehabilitation and reduced morbidity. We realised that fixation is easier and chances of vascular injury are less in free as compared to pedicled fibula.


Reconstruction with free flaps in robotic head-and-neck onco-surgeries
Rajan Arora, Vinay Kumar Verma, Kripa Shanker Mishra, Hemant Bhoye, Rahul Kapoor

Indian Journal of Plastic Surgery 2018 51(3):283-289

Aims and Objective: The aim of the present article is to highlight how reconstruction with free flaps is different and difficult in cases with robotic head-and-neck cancer surgery. It also highlights the technical guidelines on how to manage the difficulties. Materials and Methods: Eleven patients with oropharyngeal cancer having undergone tumour excision followed by free-flap reconstruction been reviewed here. Nine patients had tumour excision done robotically through intraoral route while neck dissection done with transverse neck crease incision. There is a problem of difficult flap inset in this group of patient. Two patients had intraoral excision of tumour followed by robotic neck dissection via retroauricular incision. With no incision directly on the neck, microvascular anastomosis is challenging in this set of patients. Free flap was used in all the cases to reconstruct the defect. Results: Successful reconstruction with free flap was done in all the cases with good outcome both functionally and aesthetically. Conclusion: Free-flap reconstruction is possible in robotic head-and-neck cancer surgery despite small and difficult access, but it does need practice and some technical modifications for good outcome.


Management of cleft lip and palate in Egypt: A National survey
Tarek Abdelhameed Abulezz, Ahmed K Elsherbiny, Ahmed S Mazeed

Indian Journal of Plastic Surgery 2018 51(3):290-295

Background: Variable protocols for the management of cleft lip and/or palate (CLP) patients are currently used. However, to our knowledge, there are no previously published data about cleft management and practice in Egypt. Materials and Methods: One-hundred questionnaires were distributed to cleft surgeons attending the annual meeting of the Egyptian Society of Plastic and Reconstructive Surgeons in March 2016 to investigate timing, techniques and complications of cleft surgery. Seventy-two colleagues returned the questionnaire, and the data were analysed using Microsoft Excel software. Results: The majority of cleft lip cases are repaired between 3 and 6 months. Millard and Tennison repairs for unilateral cleft lip, while Millard and Manchester techniques for bilateral cleft lip are the most commonly performed. Cleft palate is usually repaired between 9 and 12 months with the two-flap push-back technique being the most commonly used. The average palatal fistula rate is 20%. Pharyngeal flap is the method of choice to correct velopharyngeal incompetence. Polyglactin 910 is the most commonly used suture material in cleft surgery in the country. Multidisciplinary cleft management is reported only by 16.5% of participants. Conclusion: Management of CLP in Egypt is mainly dependent on personal preference, not on constitutional protocols. There is a lack of multidisciplinary approach and patients’ registration systems in the majority of centres. The establishment of cleft teams from the concerned medical specialties is highly recommended for a more efficient care of cleft patients.


Commentary on: Management of cleft lip and palate in Egypt – A national survey
Jyotsna Murthy

Indian Journal of Plastic Surgery 2018 51(3):296-297



A retrospective analysis of incidence and management of palatal fistula
Ravi Kumar Mahajan, Amreen Kaur, Sardar Mahipal Singh, Prakash Kumar

Indian Journal of Plastic Surgery 2018 51(3):298-305

Background: Cleft palate repair may be compromised by a number of complications, most commonly the development of a fistula. Fistulas may cause hypernasal speech, articulation problems and food or liquid regurgitation from the nose. Objective: The study determines the incidence and management of cleft palatal fistulas in a series of primary cleft palate repair surgeries. It is a retrospective analysis of total 185 palatal fistula cases operated at our hospital from the year 2004 to 2016. Subjects and Methods: Of 185 palatal fistulas, 132 cases had been operated at our institute for primary palatoplasty, and the rest 53 were the outside-operated cases. The patients with bilateral as well as unilateral cleft lip and palate were included. Isolated cleft palate patients were also included in the study. Palatal fistulas were subdivided into three types depending on their size. Anterior palatal fistulas were mostly treated by using tongue flap (65.57%), followed by local flaps (34.43%). Middle and posterior palatal fistulas were mostly treated by von Langenbeck Palatoplasty. One patient (>5 mm fistula) was treated using free radial forearm flap. Results: Anterior palatal fistulas (65.57%) were most commonly reported, followed by middle (24.86%) and posterior (9.18%). Most commonly, the size of the fistulas ranged from 2 mm to 5 mm. The complication rate was reported to be 3.75% in case of tongue flap and 11.9% complications were reported in case of local flaps. Conclusion: Tongue flap remains the flap of choice for managing very difficult and challenging anterior palatal fistulas compared to local flaps.


Extended adipofascial wrap around radial forearm flap for hard palate reconstruction
BC Ashok, Pradeep Kumar Nagaraj, Srikanth Vasudevan, Anantheshwar Y.N. Rao, Sudarshan Reddy Nagireddy, Ritu Singh Batth

Indian Journal of Plastic Surgery 2018 51(3):306-308

Background: While using radial forearm free flap in palate reconstruction, the pedicle lies in the nasal floor, constantly exposed to the nasal secretions and turbulent air current. To overcome this problem, we have designed a procedure which utilises the adipofascial extension to wrap the pedicle and nasal side of the flap. Materials and Methods: The study was done during 2017 and 2018, 2 years’ period. Totally 13 consecutive patients with defect in the palate status post-oncological resection and those in whom local flaps were not enough to cover the defect were included into the study. These patients were divided into two groups. First group in whom adipofascial extension was not used to cover the pedicle and second group in whom adipofascial extension was used to cover the pedicle. The incidence of nasal crusting, secondary haemorrage, blow out and flap necrosis were analysed and compared. Results: In Group 1, we had 2 among 6 (33%) patients with secondary haemorrage. One patient had partial flap loss. On exploring, we noticed thrombosis of cephalic vein. We did not had any incidence of blow out of the pedicle. In Group 2, none of the patients had any secondary haemorrage. All flaps healed well. On doing nasal endoscopy at 6 months of follow-up, all flaps showed complete mucosalisation at the nasal side. Conclusion: Use of adipofascial extension while planning a radial forearm free flap to cover the nasal side of the flap and pedicle in the nasal floor helps to reduce the nasal crusting and secondary haemorrhage.


The characteristics of private plastic surgery practice in developing country: An epidemiological study
Irena Sakura Rini, Made Ananda Krisna, Adi Basuki, Kasih Rahardjo Djarot

Indian Journal of Plastic Surgery 2018 51(3):309-315

Background: With the rise in working-age population, there has been notable economic growth in Indonesia. Along with it, there is an increase in expenditure for non-food items such as health-care service, without exception to plastic surgery practice. Aesthetic plastic surgery practice has gained its popularity in several other developing countries such as Brazil, Russia, India and China. Epidemiology report of private plastic surgery practice in Jakarta, the capital of Indonesia, will provide the evidence of increasing need for aesthetic plastic surgery practices as the basis for further improvement. Methods: This is a single-centre descriptive cross-sectional study with a total sampling method which included all patients registered at a private plastic surgery clinic between January 2008 and December 2016. Results: There were 1457 medical procedures. The majority (93.4%) of patients were female. More than 80% were surgical procedures, the most common ones were breast implant and blepharoplasty with the latter being similarly popular in both gender. The majority of the patients fell into 20–45-year-old group. Patients <20-year-old had undergone a more minor surgical procedure such as skin tumour and nevus excision or scar treatment while patients >45-year-old had more procedures with rejuvenation purpose. Conclusion: The epidemiology of private plastic surgery practice in an urban area of developing country resembles those in either developed or developing countries with a similar socio-demographic profile. This data can be further utilised for a more focused private plastic surgery practice improvement. The limitation however is that, the study is based on a single centre data.


Anesthesia

Peritubal infiltration of fentanyl compared to dexmedetomidine with ropivacaine in percutaneous nephrolithotomy: A randomized comparative analysis
Sumit Soni, Kalpesh Parmar, Shyam Meena Charan, Sameer Sethi, Naveen B Naik

Anesthesia: Essays and Researches 2019 13(1):1-6

Context: Dexmedetomidine has been found as an effective adjuvant in various nerve blocks. Despite several studies on dexmedetomidine with ropivacaine, there is no study on comparing with fentanyl in peritubal infiltration in percutaneous nephrolithotomy (PCNL). Aims: The aim of this study was to compare the effect of the addition of dexmedetomidine or fentanyl in peritubal local anesthetic infiltration on pain scores and analgesic consumption in patients who underwent PCNL. Settings and Design: This was a prospective, randomized, double-blind, tertiary care center-based study. Subjects and Methods: A total of 60 American Society of Anesthesiologists Class I, II, and III patients were selected and randomly divided into two groups: Group RF ropivacaine and fentanyl (n = 30) and Group RD ropivacaine and dexmedetomidine (n = 30). Balanced general anesthesia was given. After completion of the surgery, peritubal infiltration was given at 6 and 12 O'clock positions under fluoroscopic guidance. Postoperative pain was assessed using the visual analog scale and dynamic visual analog scale rating 0–10 for initial 48 h. Postoperative sedation was assessed using five-point sedation score. Time to first rescue analgesic, number of doses of tramadol, and total consumption of tramadol required in 48 h were noted. Statistical Analysis Used: Descriptive data were expressed in mean and standard deviation for between-group comparisons; the Chi-square and Fisher's exact tests were used for categorical variables, whereas t-test and Mann–Whitney U-test were used to compare continuous variables between two groups. Results: Duration of analgesia in group RD (12.87 ± 3.85) is more prolonged than group RF (8.13 ± 3.28) h. Total dose of rescue analgesia required in 48 h in group RF was higher as compared to group RD. Conclusions: Addition of dexmedetomidine to ropivacaine is more effective than fentanyl in terms of prolongation of analgesic efficacy of local anesthetic in peritubal block along with short-lived mild sedation.


Intra-articular morphine versus dexmedetomedine for knee arthroscopy under local anesthesia
Doaa Galal Diab, Alaaeldin Adel Elmaddawy, Abdelrahman Elganainy

Anesthesia: Essays and Researches 2019 13(1):7-12

Background: Knee arthroscopy has both diagnostic and therapeutic applications which can be performed under general, regional, or local anesthesia. Morphine is used as an additive to local anesthetics. Dexmedetomedine, the highly selective alpha-2 (α2)-adrenoceptor agonist with the sedative and analgesic effect can be used also to augment local anesthetic effect. Patients and Methods: Sixty patients submitted for elective knee arthroscopy whose age between 25 and 45 years, of either sex, the American society of anethesiologists physical status Classes I and II at a university hospital were enrolled in this study. Patients were classified into two groups. Morphine Group (M) (n = 30): Patients received 20 ml of 0.5% bupivacaine plus 5 ml of 0.2% lidocaine with epinephrine 1:200,000 plus 1 mg morphine. Dexmedetomedine Group (D) (n = 30): Patients received 20 ml of 0.5% bupivacaine plus 5 ml of 0.2% lidocaine with epinephrine 1:200,000 plus 1 μg/kg dexmedetomedine. Results: Demographic data of patients showed no significant difference among the studied groups. Heart rate (HR) was significantly lower in (D) Group compared to that of (M) Group 5 min from the start of procedure to immediately postoperatively. Moreover, (D) Group showed a significant decrease in HR 10 min up to 35 min intraoperatively compared to the basal value. Furthermore, mean arterial blood pressure (MBP) was significantly lower in (D) Group compared to that of (M) Group 15 min from the start of surgery up to 1 h postoperatively. Furthermore, (D) Group showed a significant decrease in MBP 15 min intraoperative up to 2 h postoperatively compared to the basal value. While there was no significant difference in (visual analogue score [VAS], onset and total consumption of ketorolac, surgeon and patients' satisfaction, side effects in (D) Group compared to (M) Group, respectively. Conclusion: Addition of either morphine or dexmedetomidine to bupivacaine intraarticularly improved both intraoperative anesthesia and postoperative analgesia with minimal side effects or complications in knee arthroscopy, with superiority of dexmedetomidine compared to morphine on hemodynamic stability.


A comparison of stress response between insertion of gastro-laryngeal tube and endotracheal intubation in patients undergoing upper gastrointestinal endoscopic procedures for endoscopic retrograde cholangiopancreatography
Josemine Davis, Deepak Kumar Sreevastava, Deepak Dwivedi, Siddaramesh Gadgi, Saurabh Sud, Puja Dudeja

Anesthesia: Essays and Researches 2019 13(1):13-18

Background: Complex gastrointestinal (GI) endoscopic procedures like endoscopic retrograde cholangiopancreatography (ERCP) require deep sedation or general anesthesia. Comorbidities with the poor physiological condition warrant endotracheal intubation to prevent hypoxia and aspiration. The gastro-laryngeal tube (GLT), a new supraglottic airway device with a separate channel for endoscope looks promising. Aims: The aim of the study is to compare the stress response during insertion of GLT and endotracheal intubation (ETT) in patients undergoing upper GI endoscopic procedures like ERCP. Subjects and Methods: This control versus comparison study comprised two groups with 30 patients each who underwent ETT and GLT insertion. The standard general anesthesia technique was used. In GLT group, the device was inserted without neuromuscular blocker. In ETT group, injection atracurium 0.5 mg/kg intravenous was administered as muscle relaxant for aiding endotracheal intubation. Hemodynamic parameters and time taken for the insertion of GLT/ETT were recorded. Statistical Analysis: Data were analyzed using SPSS version 20. Student's t-test was used to compare quantitative data between the groups. ANOVA test was applied for intragroup comparisons between GLT and ETT groups. Categorical variables were analyzed using the Chi-square test. Results: Heart rate and mean arterial pressure increased from baseline in ETT group, following laryngoscopy and endotracheal intubation as well as with GLT insertion. However, the stress response caused by endotracheal intubation was significantly greater than that caused by GLT insertion. Conclusion: GLT as an airway device is a safe alternative with decreased stress response compared to endotracheal intubation for upper GI endoscopy procedures.


The effect of forced-air warmer, ondansetron or their combination on shivering in pregnant women coming for elective cesarean section under spinal anesthesia: A prospective, randomized controlled comparative study
KS Ram Kiran, Kalyani Surya Dhana Lakshmi Sangineni

Anesthesia: Essays and Researches 2019 13(1):19-24

Context: Perioperative shivering can occur in up to 85% of patients undergoing cesarean section under spinal anesthesia. It has many detrimental effects and disrupts early mother-child bonding. Therefore, it should ideally be prevented by either pharmacologic or nonpharmacological means. Aims: The primary aim of this study was to evaluate the efficacy of intraoperative forced-air warming, ondansetron or their combination in preventing perioperative shivering in patients undergoing elective cesarean section under spinal anesthesia. Settings and Design: A prospective randomized controlled comparative study done at the tertiary care center. Subjects and Methods: A total of 120 patients undergoing elective cesarean section under spinal anesthesia were randomly assigned to three groups. Group O received ondansetron 4 mg intravenously (i.v.) after giving block with no forced air warming. Group W received forced-air warming intraoperatively. Group C received ondansetron 4 mg i.v. after giving block plus intraoperative forced-air warming. Core temperature (tympanic membrane) and the arm skin temperature were measured and shivering was graded simultaneously. Statistical Analysis Used: Parametric data were analyzed using one-way ANOVA and Student's paired t-test where ever appropriate. Nonparametric data were analyzed using the Kruskal–Wallis and the Chi-square test. Values of P < 0.05 were considered statistically significant. Results: Shivering incidence was higher in Group O and Group W being 17.5% and 20%, respectively, and least in Group C being 5%. The incidence of Grade ≥3 shivering requiring rescue drug was lower in Group C (2.5%) compared to that of the Groups W (5%) and O (10%) but was not statistically significant (P = 0.21). Conclusions: Combined use of ondansetron and forced- air warmer was more effective in reducing the incidence of shivering in pregnant women during elective cesarean section than when used individually.


Efficacy of dexmedetomidine as an adjunct in aiding video laryngoscope-assisted assessment of vocal cord movements at extubation following total thyroidectomy
Santhosh Djearadjane, Sunil Rajan, Jerry Paul, Lakshmi Kumar

Anesthesia: Essays and Researches 2019 13(1):25-30

Background: Assessment of vocal cord movements following total thyroidectomy diagnoses recurrent laryngeal nerve injury. Use of videoscope along with sedatives may blunt hemodynamic responses seen with the conduct of direct laryngoscopy for assessing vocal cord mobility. Aims: The primary objective of this study was to assess changes in mean arterial pressure (MAP) during vocal cord assessment following total thyroidectomy using video laryngoscope, with and without the use of dexmedetomidine as an adjunct. Secondary objectives included assessment of changes in heart rate (HR), patient reactivity score along with ease of laryngoscopy and vocal cord visibility. Settings and Design: This randomized, prospective, unblinded study was conducted in 54 patients at a tertiary care center. Materials and Methods: Group D received dexmedetomidine 0.5 μg/kg, once the thyroid was removed. Group S did not receive dexmedetomidine. Hemodynamic response at extubation, patient reactivity, ease of laryngoscopy, and ease of vocal cord assessment were noted. Statistical Analysis Used: Chi-square test and Independent t-test. Results: Baseline HR, systolic blood pressure (SBP), and MAP were comparable between the groups. However subsequently, Group D had significantly lower HR and SBP at the time of extubation and at 3 and 6 min later. MAP at extubation and at 3 min later was comparable, but at 6 min, Group D had significantly lower values. In both groups, patient reactivity scores, ease of laryngoscopy, and vocal cord visibility were comparable (P > 0.05). Conclusion: Dexmedetomidine 0.5 μg/kg when used as an adjunct clinically improved conditions for assessing vocal cord mobility with significant attenuation of associated hemodynamic responses. 


A prospective study of comparison of analgesic efficacy of dexamethasone as an adjuvant in supraclavicular block with intravenous dexamethasone after supraclavicular block in patients undergoing forearm surgeries
Madhavi Rahul Godbole, Seema Shreepad Karhade, Priya P Parihar

Anesthesia: Essays and Researches 2019 13(1):31-35

Context: Brachial plexus block is a preferred anesthesia technique for upper limb surgeries below the shoulder joint. Drugs used as adjuvants in block enhance the postoperative analgesia significantly. Aim: We aimed to evaluate the analgesic efficacy, of perineural dexamethasone used as an adjuvant to supraclavicular block as against systemic dexamethasone after supraclavicular block. Time for rescue analgesia was also noted in both groups. Subjects and Methods: In our randomized study, 60 patients belonging to the American Society of Anesthesiologist physical status Classes I and II were randomly allocated in two groups of thirty. Group BD received supraclavicular block with local anesthetic and dexamethasone 0.05 mg/kg as an adjuvant. Group BI received supraclavicular block with local anesthetic and intravenous (IV) dexamethasone 0.05 mg/kg after the block. In both groups, the comparison of postoperative analgesia and time for first rescue analgesic was noted. Statistical Analysis Used: Data analysis was done using SPSS version 20.0. Demographic data and continuous variables were analyzed by independent sample t-test. Categorical data were analyzed by unpaired t-test. Results: Group BD showed significantly prolonged postoperative analgesia as compared to Group BI. Time for rescue analgesic in Group BD was (15.8 ± 2.6) H as compared to Group BI (10.3 ± 1.07) H. Conclusions: Dexamethasone, when used in supraclavicular block significantly, prolongs the duration of analgesia as against IV dexamethasone after supraclavicular block. 


A prospective crossover study evaluating the efficacy of king vision video laryngoscope in patients requiring general anesthesia with endotracheal intubation
Ramachandra R Avula, Nagendra Nath Vemuri, Rambabu Tallapragada

Anesthesia: Essays and Researches 2019 13(1):36-39

Background: Direct laryngoscopy used for tracheal intubation requires aligning the pharyngeal, laryngeal and oral axes to achieve a line of sight. Video laryngoscopy provides a better view of the glottis without the need for aligning the three axes. Aims: To evaluate the effectiveness of King vision laryngoscope over Macintosh laryngoscope in visualizing the glottis and intubating the trachea, when used on a same patient as in a cross over manner. Settings and Design: Department of Anaesthesia, Mediciti Institute of Medical Sciences, prospective crossover study conducted over a period of six months. Subjects and Methods: Sixty adult patients belonging to ASA physical status class I-II, requiring tracheal intubation were randomly assigned to intubation by King vision or Macintosh laryngoscope. Improvement, if any, in the Cormack-Lehane grading using the King vision scope, following initial grading with the Macintosh blade in the same patient was analyzed. Statistical Analysis: Mean and Standard deviation were calculated for different parameters under the study. Where appropriate, results were analyzed using the Mc Nemar χ2 test. A ‘p’ value less than 0.05 was considered statistically significant. Results: In the King Vision group, Cormack and Lehane grade improved in the majority (9/12) of patients in whom the initial Cormack and Lehane grade was >1 using the Macintosh blade. Conclusions: The use of the King vision blade significantly improved the laryngoscopic view over the Macintosh blade but the time for intubation was prolonged.


A comparative study between the efficacy of fentanyl, antihistamines, and dexmedetomidine in suppressing photic sneeze reflex during peribulbar block
Karim YK Hakim, Mohammed Awad Alsaeid

Anesthesia: Essays and Researches 2019 13(1):40-43

Background: The photic sneeze reflex (autosomal dominant) is a condition that causes sneezing in response to numerous stimuli, such as looking at bright lights or periocular (surrounding the eyeball) injection. Unexpected or sudden sneezing during injection can be a dangerous side effect in periocular injection, in which abrupt head movement may cause globe injury. Aims: We intended to evaluate the efficacy of adding fentanyl, dexmedetomidine, and antihistamines on the incidence of the sneeze reflex associated with propofol sedation during periocular local anesthesia injections. Settings and Design: Our study was a randomized, prospective, double-blinded and controlled clinical study. Patients and Methods: This study was conducted in Ain Shams and Fayoum university hospitals at the ophthalmic surgery department. After obtaining approval from our universities ethical committee and written informed valid consents from the patients, 90 patients were included in this study. The study population included patients of both sex, ASA grade 1 and 2, in the age ranging from 18-65 years. Patients were scheduled for cataract extraction surgeries and received peribulbar block. Then patients were randomly divided into three groups (30 patients each) using a computer- generated table of random numbers. Patients were preoxygenated with supplemental oxygen by nasal cannula, all 90 patients received intravenous propofol 1mg.kg- 1 bolus for sedation and were randomized to receive adjunctive drug 2 to 4 minutes prior to propofol injection: 30 patients received intravenous fentanyl 1 μmg.kg-1 (Group F), 30 patients received dexmedetomidine 1μmg.kg-1 (Group D), and 30 patients received antihistamine (pheniramine 22.75 mg) (Group H). The same local anesthetic admixture, consisting of 5 mL 2% lidocaine with 90 IU hyaluronidase, combined with 5 mL 0.5% plain bupivacaine in a 10-mL syringe at room temperature was administered to all patients using peribulbar block technique. A masked observer (surgeon or anesthesia assistant) recorded whether the patient had a sneezing event. Continuous cardiorespiratory monitoring was performed intraoperatively. Intraoperative and postoperative medication side effects were recorded including bradycardia (HR <55 beats/min), hypotension (MAP <50 mmHg sustained for >10 min), oxygen desaturation (SpO2<90%), nausea, vomiting and prolonged sedation using Ramsay Sedation Score (RSS). Statistical Analysis Used: Student's t-test and Chi-square test were used for analysis. Results: The demographic data of the three study groups revealed non-significant differences between the three study groups as regards age, sex distribution, and the duration of surgery. No patient was excluded after inclusion to the study. All patients were able to complete the entire study and their data were included in the final analysis. Five events of sneezing had occurred in 90 patients. Two in (D) group and three in (H) group with is no statistically significant difference between the three groups as regard sneezing. Bradycardia, hypotension and sedation had occurred significantly in group (D) compared to group (F) and group (D). No patient suffered from nausea, vomiting or oxygen desaturation in all studied groups. No statistically significant difference as regards patient satisfaction between the three studied groups. Conclusion: Fentanyl, dexmedetomidine and antihistamines with propofol sedation suppress photic sneeze reflex during peribulbar block.


Evaluation of neuromuscular blockade with vecuronium during general anesthesia with oxygen, nitrous oxide, isoflurane versus oxygen, air, isoflurane: A randomized controlled study
Vishanth Boddu, Srinivasan Swaminathan, Hemavathy Balachander, Ranjith Kumar Sivakumar

Anesthesia: Essays and Researches 2019 13(1):44-49

Background: The use of air oxygen mixture with isoflurane has become more common in the place of nitrous oxide, especially in laparoscopic and abdominal surgeries. With a varied mixture of gases and isoflurane used in general anesthesia, the exact dosing requirement and time duration of action have not been precisely studied with vecuronium when given as a bolus, as is given routinely. Purpose: This study was undertaken to evaluate and compare the neuromuscular effect of vecuronium during anesthesia with oxygen, nitrous oxide and isoflurane versus oxygen, air and isoflurane. Methodology: The study was a prospective, randomized controlled trial on 70 patients allocated into two groups as follows: Group N (nitrous oxide group) and Group A (medical air group). The primary objective was to measure and compare the posttetanic count (PTC1) – train of four (TOF1) interval, to evaluate the time taken for recovery from the intense blockade in both groups. The secondary objectives were to compare time duration for twitch height depression to be 30% of baseline after administering vecuronium, time duration from vecuronium administration to appearance of the first PTC1, PTC (n) at the reappearance of the 1st twitch, time interval between TOF1 and TOF3 and time from vecuronium administration to appearance of TOF3 in both the groups. Results: There is no significant difference between both the groups with reference to the block onset time using 30% depression of single twitch and recovery time from neuromuscular blockade using PTC, PTC1-TOF1 and TOF1-TOF3 time intervals. Conclusion: Measuring and comparing neuromuscular transmission monitoring parameters such as the onset time(ST depression to 30%), and recovery using PTC, PTC1-TOF1 and TOF1-TOF3 time intervals, it is concluded that the character of neuromuscular block with vecuronium is unaffected and not prolonged with or without nitrous oxide when used with isoflurane.


Evaluation of ultrasound-guided erector spinae plane block and oblique subcostal transversus abdominis plane block in laparoscopic cholecystectomy: Randomized, controlled, prospective study
Serkan Tulgar, Mahmut Sertan Kapakli, Halil Cihan Kose, Ozgur Senturk, Onur Selvi, Talat Ercan Serifsoy, David Terence Thomas, Zeliha Ozer

Anesthesia: Essays and Researches 2019 13(1):50-56

Background: Oblique subcostal transversus abdominis plane block (OSTAP) is a recently described regional anesthetic technique used in upper abdominal surgeries such as laparoscopic cholecystectomy (LC). Erector spinae plane block (ESPB) has also been reported for postoperative analgesia in LC. Aim: We aimed to compare the effectiveness of OSTAP and ESPB in providing postoperative analgesia in patients undergoing these surgeries. Setting and Design: This study was designed as a double-blinded, prospective, randomized, efficiency study in a tertiary university hospital, postoperative recovery room, and ward. Materials and Methods: A total of 72 patients were recruited and 60 patients were randomized into three equal groups (ESPB, OSTAP, and control group). Pain intensity between groups was compared using Numeric Rating Scale (NRS) scores. In addition, consumption of paracetamol and tramadol and additional rescue analgesic requirement were measured. Standard multimodal analgesia was performed in all groups, while ESPB block was also performed in Group ESPB and OSTAP block was also performed in group OSTAP. Statistical Analysis Used: Descriptive statistics were expressed as mean ± standard deviation. Independent t-test, Mann–Whitney U-test, Chi-square test, Fisher's exact test, Shapiro–Wilk test, one-way ANOVA, and post hoc Tukey's analysis were used for statistical analysis. Results: NRS was lower in block groups during the first 3 h. There was no difference in NRS scores at other hours. Analgesic consumption and rescue analgesic requirement were lower in groups ESPB and OSTAP when compared to those of control group. Block groups were similar. Conclusion: Bilateral ultrasound-guided ESPB and OSTAP performed at the end of LC lead to akin analgesia requirement and improve the quality of multimodal analgesia.


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