Ethnopharmacology

Inhibitory effect of ethanol extract of Ampelopsis brevipedunculata rhizomes on atopic dermatitis-like skin inflammation Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Young-Ae Choi, Ju-Hee Yu, Hong Dae Jung, Soyoung Lee, Pil-Hoon Park, Hyun-Shik Lee, Taeg Kyu Kwon, Tae-Yong Shin, Seung Woong Lee, Mun-Chul Rho, Young Hyun Jang, Sang-Hyun Kim Abstract Ethnopharmacological relevance Extracts from various parts of Ampelopsis brevipedunculata has been used as anti-inflammatory agents in Asian folk medicine. Aim of the study: To demonstrate the medicinal effect of the A. brevipedunculata in skin inflammation, specifically atopic dermatitis (AD). Materials and methods The effect of ethanol extract of A. brevipedunculata rhizomes (ABE) on AD was examined using an AD-like skin inflammation model induced by repeated exposure to house dust mite (Dermatophagoides farinae extract, DFE) and 2,4-dinitrochlorobenzene (DNCB). The mechanism study was performed using tumor necrosis factor (TNF)-α and interferon (IFN)-γ-activated human keratinocytes (HaCaT). Serum histamine and immunoglobulin levels were quantified using enzymatic kits, while the gene expression of cytokines and chemokines was analyzed using quantitative real time polymerase chain reaction. The expression of signaling molecules was detected using Western blot. Results Oral administration of ABE alleviated DFE/DNCB-induced ear thickening and clinical symptoms, as well as immune cell infiltration (mast cells and eosinophils) into the dermal layer. Serum Immunoglobulin (Ig) E, DFE-specific IgE, IgG2a, and histamine levels were decreased after the administration of ABE. ABE also inhibited CD4+IFN-γ+ and CD4+IL-4+ lymphocyte polarization in lymph nodes and expression of TNF-α, IFN-γ, IL-4, IL-13, and IL-31 in the ear tissue. In TNF-α/INF-γ-stimulated keratinocytes, ABE inhibited the gene expression of TNF-α, IL-6, IL-1β, and CCL17. In addition, ABE decreased the nuclear localization of signal transducer and activator of transcription 1 and nuclear factor-κB, and the phosphorylation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. Conclusion Collectively, our data demonstrate the pharmacological role and signaling mechanism of ABE in the regulation of skin allergic inflammation, which supports our suggestion that ABE could be developed as a potential therapeutic agent for the treatment of AD. Graphical abstract

Anti-inflammatory activities of Canarium subulatum Guillaumin methanol extract operate by targeting Src and Syk in the NF-κB pathway Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Eunju Choi, Mi-Yeon Kim, Jae Youl Cho Abstract Ethnopharmacological relevance Canarium subulatum Guillaumin is an herbal medicinal plant native to Southeast Asia. Ethnopharmacological evidence suggests that plants of the genus Canarium cure a variety of inflammatory diseases. Aim of the study The pharmacological mechanisms of C. subulatum Guillaumin remain poorly understood. In this study, we investigate inflammatory mechanisms and target molecules using C. subulatum Guillaumin methanol extract (Cs-ME) in inflammatory reactions managed by macrophages. Materials and methods To identify the anti-inflammatory activities of Cs-ME, lipopolysaccharide (LPS)-stimulated macrophages and a murine HCl/EtOH-induced gastritis model were chosen. The luciferase reporter gene assay, Western blot analysis, overexpression strategy, and the cellular thermal shift assay (CETSA) were employed to investigate the molecular mechanisms and target enzymes of Cs-ME. The active ingredients of this extract were also determined by HPLC. Results Released levels of nitric oxide (NO) and mRNA expression levels of iNOS and IL-6 were downregulated by Cs-ME without exhibiting cytotoxicity. This extract inhibited MyD88-induced promoter activity and the nuclear translocation of nuclear factor (NF)-κB. Moreover, we found that Cs-ME reduced the phosphorylation of NF-κB upstream signaling molecules including IκBα, IKKα/β, Src, and Syk in LPS-stimulated macrophage-like RAW264.7 cells. The results of Western blot and CETSA confirmed that Src and Syk are anti-inflammatory targets of Cs-ME. In addition, orally injected Cs-ME alleviated HCl/EtOH-induced gastric ulcers in mice. HPLC analysis indicated that quercetin, luteolin, and kaempferol are major active components of this extract with anti-inflammatory activity. Conclusions Cs-ME exhibits anti-inflammatory effects in vitro and in vivo by targeting Src and Syk in the NF-κB signaling pathway. Consequently, Cs-ME could be developed as an anti-inflammatory herbal medicine. Graphical abstract

Anti-obesity effect of argel (Solenostemma argel) on obese rats fed a high fat diet Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Riham A. El-shiekh, Dalia A. Al-Mahdy, Samar M. Mouneir, Mohamed S. Hifnawy, Essam A. Abdel-Sattar Abstract Ethnopharmacological relevance Solenostemma argel (Argel) is a desert plant commonly used in Egyptian and Sudanese traditional medicine to suppress appetite, for treatment of diabetes, and as an antispasmodic and anti-inflammatory agent. Previously the anti-diabetic, hypolipidemic and lipase inhibitory activities of Argel were reported in animal studies and in-vitro assays. However, its specific mechanism of action as an anti-obesity agent has not been studied before. Aim of the study Assessment of the possible anti-obesity effect of Solenostemma argel on diet-induced obesity and elucidation of its mechanism of action, as well as, standardization of the active plant extract. Materials and methods The ethanolic extract (EtOH-E) and its fractions (CH2Cl2-F: methylene chloride and BuOH-F: n-butanol) were prepared from the aerial parts of S. argel and studied at two dose levels; 200 and 400 mg kg−1 in a model of high fat diet (HFD) fed rats. The animals (72 Male Wister rats) were assigned into 9 groups: group (i) fed with normal diet and groups (ii-iv) fed with high fat diet (HFD) for 16 weeks and treated with orlistat, EtOH-E, CH2Cl2-F and BuOH-F in the beginning of the 8th week. At the end of the experiment, blood samples were analysed for lipid and liver biomarkers, glucose and insulin levels, as well as, adipokines and inflammatory markers. Liver and adipose tissues were examined histopathologically and their homogenates were used to determine levels of oxidative stress markers and lipogenesis-related genes. Body weight was monitored weekly during the experiment. Results Our data showed that consumption of S. argel significantly controlled weight gain, attenuated liver steatosis, improved the lipid profile, modulated adipokines activities, increased β-oxidation gene expression, as well as, decreased the expression of lipogenesis-related genes and ameliorated inflammatory and lipid peroxidation derangement. The ethanolic extract was also standardized using LC–MS analysis for its content of stemmoside C. Conclusions The current study revealed that S. argel is a promising Egyptian natural drug, rich in pregnane glycosides, and could be considered a new therapeutic candidate targeting obesity. Graphical abstract

Evaluation of the schistosomicidal, antioxidant and anti-inflammatory activities of the ethyl acetate fraction from Ozoroa pulcherrima Schweinf. Roots on Schistosoma mansoni-induced liver pathology in mice and its phytochemical characterization Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Hermine Boukeng Jatsa, Nestor Gipwe Feussom, Ulrich Membe Femoe, Mérimé Christian Kenfack, Emilienne Tienga Nkondo, Joseph Bertin Kadji Fassi, Nadège Distele Simo, Cyriaque Moaboulou, Calvine Noumedem Dongmo, Christelle Dongmo Tsague, Etienne Dongo, Pierre Kamtchouing, Louis-Albert Tchuem Tchuente Abstract Ethnopharmacological relevance Ozoroa pulcherrima Schweinf. (syn.: Heeria pulcherrrima Schweinf.) is a small shrub belonging to the family Anacardiaceae. In Africa, the stem and the leaves are used to treat dystocia, hyperthermia, and conjunctivitis, while the root is used to treat dysmenorrhea and intestinal helminthiasis. Aim of the study The aim of this study was to assess the schistosomicidal, antioxidant and anti-inflammatory effects of the ethyl acetate fraction from O. pulcherrima roots methanolic extract (EAOp) on S. mansoni- induced liver pathology in mice. Additionally, its phytochemical composition was elucidated. Material and methods The phytochemical characterization of EAOp was carried out by High-Performance Liquid Chromatography-Mass spectrometry (HPLC-MS). Total phenolic and flavonoid contents were also quantified in the fraction. S. mansoni-infected mice received daily and per os, for 28 days, EAOp at 200 or 400 mg/kg, starting from the 36th day post-infection. Praziquantel was used as reference drug. Uninfected-untreated, uninfected-treated and infected-untreated mice served as controls. At the 65th day post-infection mice were sacrificed and parasitological burden monitored. Transaminases, total bilirubin, and total proteins levels were determined in the plasma. Malondialdehyde (MDA), nitrites, superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels were measured in the liver as biomarkers of the oxidative stress. Liver histology and morphometric analysis of granulomas were also conducted. Results The HPLC-MS analysis data of EAOp revealed the presence of four triterpenes namely oleaterminaloic acid, hydroxyoleanolic acid, moronic acid, and oleanolic acid; a flavonoid dipentoxybenzoic acid and two alkaloids. Its total phenolic content was 76.46 ± 0.01 mg GAE/g and total flavonoid content 6.26 ± 0.31 mg rutin equivalent/g. The reductions of worm burden (48.89 and 75.56%), fecal egg count (77.76 and 69.52%) and egg load in the liver (65.33 and 77.18%) and intestine (78.06 and 84.63%) were significant after EAOp treatment. EAOp at all doses significantly (p < 0.001) reversed the increasing transaminases activities and total bilirubin level induced by the infection. A normalization of total proteins concentration was also recorded. Treatment of S. mansoni-infected mice with EAOp at 200 or 400 mg/kg resulted in a significant reduction (p < 0.001) of MDA concentration by 73.20% and 67.78% respectively. The level of nitrites which was reduced by the infection significantly increased after the treatment. EAOp significantly increased by 4.67 and 5.69-fold the CAT activity and by 126.67% the GSH level. Histologically, a significant reduction of the number (66.39 and 57.82%) and the volume (52.25 and 34.81%) of liver inflammatory granulomas was recorded after EAOp treatment at all doses. Conclusions These results suggest that the liver pathology in S. mansoni infection is improved by EAOp which disclosed good schistosomicidal, antioxidant and anti-inflammatory activities. Its effects on the liver dysfunction and the hepatic oxidative stress were comparable to that of praziquantel. These findings justified the traditional use of O. pulcherrima for the treatment of intestinal helminthiasis. This fraction can be considered as a promising source for schistosomicidal agents. Graphical abstract

Preclinical study of safety of Dendropanax morbifera Leveille leaf extract: General and genetic toxicology Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Jun-Won Yun, Seung-Hyun Kim, Yun-Soon Kim, Eun Jin Choi, Ji-Ran You, Eun-Young Cho, Jung-Hee Yoon, Euna Kwon, Hyoung-Chin Kim, Ja-June Jang, Jin-Sung Park, Jeong-Hwan Che, Byeong-Cheol Kang Abstract Ethnopharmacology relevance Dendropanax morbifera Leveille (DM) has been used in traditional medicines for infectious and skin diseases, and dysmenorrhea. It exhibits a diverse therapeutic potential including anti-cancer, anti-thrombotic, anti-diabetic, anti-oxidant, and anti-inflammatory activities. Aim of the study Despite promising health benefits of DM, knowledge of its potential adverse effects is very limited. The current study focused on the investigation of subchronic toxicity and genotoxicity of extract obtained from DM according to the test guidelines published by the Organization for Economic Cooperation and Development. Materials and methods We conducted a toxicological evaluation of DM extracts using 14-day repeated-dose toxicity study and 13-week repeated-dose toxicity study in Sprague-Dawley rats administered orally at doses of 500, 1000, or 2000 mg/kg/day. The clastogenicity of DM extract was also evaluated by in vitro chromosome aberration assay and in vivo micronucleus assay. Results Assessment of subchronic toxicity of DM extract by oral administration in rats revealed unremarkable treatment-related findings with respect to food/water consumption, body weight, mortality, urinalysis, hematology, serum biochemistry, necropsy, organ weight and histopathology at doses of 500, 1000, and 2000 mg/kg. Accordingly, the level of no-observed-adverse-effect for DM extract in 13-week subchronic toxicity study was considered to be 2000 mg/kg/day in rats. The data observed from in vitro chromosome aberration assay and in vivo micronucleus assay exclude any clastogenicity of DM extract. Conclusion The results suggest that the oral consumption of DM extract has no adverse effects in humans and represents a safe traditional medicine. Graphical abstract

Curcuma longa L. ameliorates asthma control in children and adolescents: A randomized, double-blind, controlled trial Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Gabriel Manarin, Daniela Anderson, Jorgete Maria e Silva, Juliana da Silva Coppede, Persio Roxo-Junior, Ana Maria Soares Pereira, Fabio Carmona Abstract Ethnopharmacological relevance Roots of Curcuma longa L. are used as medicine for millennia. They possess several pharmacological properties, including anti-inflammatory action, and can be suitable for asthma treatment. Aim of the study We aimed to test the hypothesis that, in children and adolescents with persistent asthma, the administration of powdered roots of C. longa for 6 months, in addition to standard treatment, compared to placebo, will result in better disease control. Patients and methods We conducted a randomized, double-blind, placebo-controlled, phase II clinical trial. Patients were randomly assigned to receive 30 mg/kg/day of C. longa for 6 months, or placebo. Data were collected prospectively. All patients were categorized for asthma severity and control according to GINA-2016 and underwent pulmonary function tests. Results Overall, both groups experienced amelioration of their frequency of symptoms and interference with normal activity, but no differences were found between the two treatment groups. However, patients receiving C. longaexperienced less frequent nighttime awakenings, less frequent use of short-acting β-adrenergic agonists, and better disease control after 3 and 6 months. Conclusion The powdered roots of C. longa led to less frequent nighttime awakenings, less frequent use of short-acting β-adrenergic agonists, and better disease control after 3 and 6 months, when compared to placebo. Graphical abstract

Evaluation of the subacute toxicity of Yongdamsagan-tang, a traditional herbal formula, in Crl:CD Sprague Dawley rats Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Eunsook Park, Mee-Young Lee, Chang-Seob Seo, Hyeun-Kyoo Shin, Su-Cheol Han, Hyekyung Ha Abstract Ethnopharmacological relevance Yongdamsagan-tang, a traditional herbal formula, is used widely for the treatment of inflammatory and viral diseases. However, the safety of Yongdamsagan-tang has not been established. Aim of the study To evaluate the subacute toxicity of Yongdamsagan-tang water extract (YSTE) in Crl:CD Sprague Dawley rats. Materials and methods We evaluated the subacute toxicity of YSTE in male and female Crl:CD Sprague Dawley rats (n = 5 per group). Rats were treated with YSTE at doses of 0, 1000, 2000 and 5000 mg/kg administered once a day by oral gavage for 4 weeks. Results There were no significant changes in mortality, body weight, food intake, serum biochemistry, or results of hematology and urinalysis after YSTE administration. However, all rats treated with 5000 mg/kg/day YSTE exhibited excessive salivation and discolored urine. Necropsy findings showed discoloration in the liver of both male (n = 1) and female (n = 3) rats treated with 5000 mg/kg/day YSTE, and an increase in the relative weights of kidney and liver was also found in male rats treated with 5000 mg/kg/day. In addition, decreases in serum creatinine, total bilirubin, alanine transaminase, and alkaline phosphatase were observed in male rats treated with 2000 or 5000 mg/kg/day YSTE. Conclusions Abnormalities in some rats are considered to be independent of YSTE toxicity. Therefore, the results suggest that oral administration of YSTE in rats for 4 weeks is safe at doses of up to 5000 mg/kg/day. Graphical abstract

Huo Xue Tong Luo capsule ameliorates osteonecrosis of femoral head through inhibiting lncRNA-Miat Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Bin Fang, Ying Li, Chen Chen, Qiushi Wei, Jiaqian Zheng, Yamei Liu, Wei He, Dingkun Lin, Gang Li, Yonghui Hou, Liangliang Xu Abstract Ethnopharmacological relevance Traditional Chinese medicine has a long history of treating various bone diseases including osteoporosis and osteonecrosis etc. In clinical treatment, Huo Xue Tong Luo capsule (HXTL capsule) containing Peach kernel, Safflower carthamus, Angelica sinensis, Ligusticum wallichii etc, is one of the mostly used prescriptions for treating osteonecrosis of the femoral head (ONFH) with promising effects. Objectives This study aims to identify the underlying molecular mechanism of how HXTL capsule exerts its function to ameliorate ONFH. Materials and methods All femoral bone tissues were collected during surgeries. Rat bone marrow mesenchymal stem cells (rMSCs) were used. Quantitative real time PCR was used to check the relative expression levels of genes. ChIP assay was performed to evaluate the binding of H3K4me3 and H3K27me3 in Miat promoter. Results We showed that HXTL capsule promoted osteogenesis in rat MSCs as demonstrated by quantitative real time PCR and Alizarin Red S staining. Then we found silencing the endogenous lncRNA-Miat could promote osteogenesis of rMSCs. In addition, the ChIP assay showed that HXTL capsule significantly increased occupancy of H3K27me3 and decreased H3K4me3 in promoter regions of Miat, meaning HXTL capsule inhibited Miat expression through histone modifications. At last, by examining the femoral heads samples obtained from patients with ONFH during total hip arthroplasty surgery, we found the RNA level of hMiat in necrotic tissue was much higher than that of normal tissue. Conclusions Taken together, our study shows that lncRNA-Miat might play an important role in pathogenesis of ONFH, and HXTL capsule can promote osteogenesis to ameliorate ONFH through inhibiting the transcriptional expression of Miat, at least partially. Graphical abstract

Urginea indica attenuated rheumatoid arthritis and inflammatory paw edema in diverse animal models of acute and chronic inflammation Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Ghazala Akhtar, Arham Shabbir Abstract Ethnopharmacological relevance Urginea indica has been used in the traditional system of medicine to treat various inflammatory diseases. Aim of the study Present study investigates the effects of aqueous and ethanolic extracts of U. indica on joint inflammation using different models of acute and chronic inflammation. Materials and methods FCA-induced arthritic rat model, a model of chronic joint inflammation, was used to evaluate the anti-arthritic effects of plant extracts (500 mg/kg, each extract). Macroscopic arthritic scoring, digital water plethysmometery, and histopathological evaluation (H & E staining) were performed to measure the severity of arthritis. Acute inflammatory models like, carrageenan-, histamine- and serotonin-induced paw edema models were used to evaluate effects of U. indica, and supported by xylene-induced ear edema model. Results Both extracts significantly inhibited arthritic development, paw edema, bone erosion, pannus formation, and infiltration of inflammatory cells. Treatment with U. indica extracts resulted in almost normalization of altered counts of white blood cells (WBCs), platelets, and red blood cells (RBCs), along with Hb content. Both extracts were found safe in terms of hepatotoxicity and nephrotoxicity as determined by non-significant difference of alanine aminotransferase (ALT), aspartate transaminase (AST), urea, and creatinine levels among all groups. U. indica significantly attenuated carrageenan-induced paw edema. There are several mechanisms involved in the attenuation of carrageenan-induced paw edema; inhibition of autacoids is one of those important mechanisms. The autacoid inhibition was confirmed by reduction of histamine- and serotonin-induced paw edema found in plant extract treated groups. Suppression of xylene-induced ear edema by plant extract further validated the suggested mechanism of autacoid inhibition. GC-MS analysis showed the presence of isopropyl palmitate in the highest quantity (26.852%). Conclusions This study validated the folkloric uses of U. indica and showed that plant possessed anti-arthritic and anti-inflammatory properties which might be ascribed to inhibition of autacoids. Graphical abstract

Subchronic toxicity and concomitant toxicokinetics of long-term oral administration of total alkaloid extracts from seeds of Peganum harmala Linn: A 28-day study in rats Publication date: 28 June 2019 Source: Journal of Ethnopharmacology, Volume 238 Author(s): Youxu Wang, Hanxue Wang, Liuhong Zhang, Yunpeng Zhang, Yuchen Sheng, Gang Deng, Shuping Li, Ning Cao, Huida Guan, Xuemei Cheng, Changhong Wang Abstract Ethnopharmacological relevance The seeds of Peganum harmala Linn, in which the most abundant active compounds are harmaline and harmine, have been widely used as a traditional medicine in various countries to treat a broad spectrum of diseases including asthma, cough, depression, Parkinson's and Alzheimer's diseases. However, few studies on long-term or subchronic toxicity of seeds of P. harmala were reported after overdose. Aim of the study To investigate the subchronic toxicity and concomitant toxicokinetics of total alkaloid extracts from seeds of P. harmala (TAEP) after oral administration for four weeks in rats. Materials and methods The subchronic toxicity and concomitant toxicokinetics of TAEP were evaluated after 28-day oral administration in rats at daily dose levels of 15, 45, and 150 mg/kg. The signs of toxicity and mortality were monitored and recorded daily. The body weight and average food consumption were measured weekly. The analyses of hematology, biochemistry, urine, relative organ weights and histopathology were conducted at the termination of treatment and recovery phase. For concomitant toxicokinetics study, the plasma toxicokinetic parameters, tissue distribution, and excretion of predominant ingredients harmaline and harmine in TAEP and metabolites harmalol and harmol were tested. Results Following initial repeated exposure to high-dose (150 mg/kg/day) of TAEP excitotoxic reaction, such as tremor, was observed, but tolerated on the fourth day after multiple dosing. The significant alterations in blood glucose and lipid metabolism in liver were observed, but recovered after four weeks of drug withdrawal. The no-observed-adverse-effect level (NOAEL) of TAEP was considered to be 45 mg/kg/day under the present study conditions. There were no significant gender differences in most indexes of subchronic toxicity throughout the experimental period with the exception of food consumption and body weight. In concomitant toxicokinetics study, the alterations of dynamic characteristic for harmaline, harmine and metabolite harmol after multiple oral administration at three doses had been observed. Harmaline, harmine and metabolites harmalol and harmol were widely distributed in organs and there was no accumulation in the tissues examined. The reduction of harmaline and metabolite harmalol in brain after multiple dosing at dose of 150 mg/kg might be closely related to the tremor tolerance. The main excretory pathway for metabolites harmalol and harmol was urinary excretion via kidney. Conclusions The results revealed that TAEP at doses of 15 and 45 mg/kg/day in rats might be safe. Excitotoxic reaction such as tremor occurred initially at dose of 150 mg/kg/day, however, the toxicity was tolerant and reversible. In addition, harmaline and harmine in TAEP had a quick absorption into blood and metabolized to harmalol and harmol, and there was no drug accumulation in the detected tissues. Further studies should be investigated to clarify the mechanisms of tremor tolerance and neurotoxicity of TAEP. Graphical abstract

Kidney Diseases and Transplantation

Burden, access, and disparities in kidney disease Deidra C Crews, Aminu K Bello, Gamal Saadi, for the World Kidney Day Steering Committee  Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):281-290 Kidney disease is a global public health problem, affecting over 750 million persons worldwide. The burden of kidney disease varies substantially across the world, as does its detection and treatment. In many settings, rates of kidney disease and the provision of its care are defined by socio-economic, cultural, and political factors leading to significant disparities. World Kidney Day 2019 offers an opportunity to raise awareness of kidney disease and highlight disparities in its burden and current state of global capacity for prevention and management. Here, we highlight that many countries still lack access to basic diagnostics, a trained nephrology workforce, universal access to primary health care, and renal replacement therapies. We point to the need for strengthening basic infrastructure for kidney care services for early detection and management of acute kidney injury and chronic kidney disease across all countries and advocate for more pragmatic approaches to providing renal replacement therapies. Achieving universal health coverage world-wide by 2030 is one of the World Health Organization’s Sustainable Development Goals. While universal health coverage may not include all elements of kidney care in all countries, understanding what is feasible and important for a country or region with a focus on reducing the burden and consequences of kidney disease would be an important step towards achieving kidney health equity.

Therapeutic plasma exchange for children with kidney disorders: Definitions, prescription, indications, and complications Khalid A Alhasan Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):291-298 Therapeutic plasma exchange (TPE) is a procedure that involves the removal of a large volume of plasma that is replaced with a replacement fluid, which is usually 5% albumin or fresh-frozen plasma. This therapeutic modality presents several technical challenges in children but has become increasingly used in pediatric nephrology. Owing to advances in technology, scientists have gained substantial knowledge of the molecular pathogenesis underlying many pediatric renal diseases, supporting the use of TPE in treating these disorders. This review presents a synopsis of the literature as it relates to the accepted indications for TPE in children, the technical aspects of the procedure, and the associated complications. Increased collaboration between pediatric nephrologists will hopefully allow scientists to obtain more data in children to assess the benefits of TPE in various renal disorders and improve the quality of care provided in children with renal disorders.

Birth weight, gestational age, and blood pressure: Early life management strategy and population health perspective Issa Al Salmi, Faisal A M. Shaheen, Suad Hannawi Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):299-308 The incidence of hypertension (HTN) is rising worldwide with an estimated prevalence of 22%, 7.5 million deaths (12.8%). It is a major risk factor for coronary heart diseases and hemorrhagic strokes. In Oman, the crude prevalence of HTN was 33.1%, whereas the age-adjusted prevalence was 38.3%. Among Gulf Cooperation Countries, 47.2% of the individuals were hypertensive, and women were more likely to have HTN than men. Similarly, the prevalence of low-birth-weight (LBW) is also rising globally with the more prevalent incidence in developing countries reaching almost a rate just lower than 20.0/100 births. In Oman, the prevalence of LBW was 4.2% in 1980, which doubled (8.1%) in 2000 and has shown a slow but steady increase reaching 10.2% in 2013. LBW term is the most commonly used surrogate measure of intrauterine growth retardation and has been related to increased cardiovascular mortality, due to increased risk of cardiovascular risk factors, including blood pressure (BP), diabetes, cholesterol level, and other risk factors. The epidemiologic evidence clearly points to an inverse association between birth weight and many hemodynamic cardiovascular risk markers. Possible mechanisms operating in fetal life that might determine BP include the structural development of resistance arteries, the setting of hormone levels, and nephron endowment. Retarded fetal growth leads to permanently reduced cell numbers in the kidney. Patients with high BP had almost 50% less number of glomeruli compared to that of the normotensive individuals, and subsequent accelerated growth may lead to excessive metabolic demand on this limited cell mass. It is not merely a reduced nephron number that is responsible for HTN, but compensatory maladaptive changes that occur internally when nephrogenesis is compromised. The likelihood of an adverse outcome is greatly amplified in those born with LBW who later develop obesity or an increased ponderal index.

Chyluria in pregnancy: Etiology, diagnosis, and management perspective Bimalesh Purkait, Gaurav Garg, Manmeet Singh, Ashish Sharma, Siddharth Pandey, Satya Narayan Sankhwar Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):309-314 Chyluria is clinically described as passage of milky urine. Chyle is absorbed by intestinal lacteals and is composed of emulsified fats, few proteins, and fibrin in varying proportions. Parasitic chyluria is caused mainly by Wuchereria bancrofti infection. The incidence of chyluria in pregnancy is not uncommon in endemic regions. The literature pertaining tomedical management of chyluria in pregnancy is scant. The antifilarial drugs have potential teratogenic risk and are not recommended in pregnant patients. Hence, there is a management dilemma for managing patients with chyluria during pregnancy. In this review, we have tried to highlight the evidence-based diagnosis and management of chyluria in pregnancy.

Association of hepcidin and anemia in early chronic kidney disease Satyendra Kumar Sonkar, Neeraj Kumar Singh, Gyanendra Kumar Sonkar, Sant Pandey, Vivek Bhosale, Anil Kumar, Kauser Usman Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):315-324 Hepcidin is being extensively studied for anemia and inflammation in chronic kidney disease (CKD) patients. Hepcidin is thought to regulate iron metabolism by iron blockade through various mechanisms. Patients with CKD have early cardiac mortality due to anemia and subclinical inflammation; hence, we studied hepcidin as a biomarker in patients with early stage of CKD in relation to anemia and inflammation. In our cross-sectional study, a total of 80 patients were enrolled of whom, there were 25, 26, and 29 patients in CKD stages 1, 2, and 3, respectively. Patients were divided into normal iron level (39), functional iron deficiency (FID) (18), and absolute iron deficiency (AID) (23) based on transferrin saturation and ferritin. We found significantly high level of hepcidin (P <0.05) and high-sensitivity C-reactive protein (hsCRP) (P <0.05) in FID as compared to AID as well as normal iron level. We also found other inflammatory markers such as albumin, transferrin, and ferritin to be significantly associated with FID. In univariate analysis, hemoglobin (Hb) varied significantly with serum total iron-binding capacity (r = 0.40, P <0.001), log hsCRP (r = -0.32, P <0.01), and log ferritin (r = -0.23, P <0.05); however, Hb was not affected significantly with log hepcidin (r = -0.07, P >0.05). The study indicates that among early CKD patients with FID, there was high level of hepcidin along with other inflammatory parameters, which may be associated with poor cardiovascular disease outcome due to increased inflammation.

Acute cortical necrosis in pregnancy still an important cause for end-stage renal disease in developing countries Anupma Kaul, Hiral Lal, Prabhakar Mishra, Manoj Jain, Narayan Prasad, Mandakini Pradhan, Manas Ranjan Patel, Amit Gupta, Raj Kumar Sharma Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):325-333 Renal cortical necrosis (RCN) is a serious complication of acute kidney injury (AKI) and pregnancy is a clinical state closely associated with it with poor renal outcomes. The incidence is much higher in obstetrical AKI compared to other causes of RCN. Despite better medical care facilities available, this continues to be an important cause of morbidity and mortality in developing countries. This is a retrospective analysis among all pregnant females presenting with AKI from January 1999 to December 2014 at a tertiary care center in the northern part of India. We looked for the incidence of obstetrical-related RCN in our renal biopsies performed in the last 15 years and to evaluate precipitating factors responsible for RCN. RCN constituted 8.3% of pregnancy-related AKI cases in our institution. The overall incidence has been declining which was 9.09% from 1999 to 2008 to 7.8% from 2009 to 2014. The patient’s median age was 29.3 ± 5.2 years. The average time to presentation from the day of delivery was 8.7 ±2.1 days. The mortality was observed in 11.7% of them with sepsis and multiorgan dysfunction present in all of them. The most common etiology for RCN was found to be septic abortion and puerperal sepsis accounting for - 15.3% each. Postpartum hemorrhage was a cause in 9.09% of patients. The most important cause of RCN was postpartum thrombotic microangiopathy which was observed in 48.7% of patients. Kidney biopsy was helpful in diagnosis in 31 patients while computed tomography scan abdomen alone helped in diagnosis in five patients. Patchy cortical necrosis in histology was seen in 35.4% of patients and morbidity in terms of prolonged hospitalization was seen in 22.7% while dialysis dependency in 61.5% of the study population. In conclusion, strategies need to be implemented in reducing the preventable causes for RCN which is not only catastrophic in terms of renal outcomes but also for social and psychological perspectives as well.

Seroconversion following hepatitis B vaccination in children with chronic kidney disease Nivedita Kamath, Anil Vasudevan, Arpana Iyengar Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):334-338 Seroconversion following hepatitis B vaccination is low in children with chronic kidney disease (CKD). This study aimed to assess the seroconversion and persistence of protective immunity following hepatitis B vaccination in children with CKD. This prospective observational study was conducted in a tertiary pediatric nephrology centre to assess the seroconversion and maintenance of antibody titers (>10 mIU/mL) at one year following hepatitis B vaccination (10 μg at 0, 1, and 2 months) in children with CKD Stages II to V. Those who did not seroconvert after the schedule were re-vaccinated, and antibody titers were checked. Categorical data were expressed as proportions and analyzed using the Chi-square test. Pearson’s correlation test was used to determine the correlation of antibody titers with other continuous variables. Seroconversion was observed in 72% (n = 26/36) after vaccination. Only 60% (n = 6/10) had seroconversion after the second course of vaccination. Only 60% of children (n = 12/20) who seroconverted had protective antibody titers at one year. Seroconversion following three doses of hepatitis B vaccine is low in children with CKD. Antibody titers should be monitored periodically as the protective immunity wanes rapidly.

Status of fasting in Ramadan of chronic hemodialysis patients all over Egypt: A multicenter observational study Abir Farouk Megahed, Ghada El-Kannishy, Nagy Sayed-Ahmed Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):339-349 There is a paucity of data concerning safety of fasting in Ramadan in chronic kidney disease patients on hemodialysis (HD). The aim of the present study was to assess the frequency of fasting in Ramadan in HD patients in Egypt and the possible effect of fasting on clinical and biochemical variables. This observational multicentric study was carried out during 2016 when fasting duration was around 16 h.

A study of detection and comparison of immunofluorescence on formalin-fixed paraffin-embedded tissue with fresh frozen renal biopsy specimen Ranjana Solanki, Madan Kumar Solanki, Deepika Hemrajani, Jayesh Saha Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):350-358 Direct immunofluorescence on the fresh frozen tissue is established way of demonstrating of immunoglobulins and complement deposition in renal biopsies. IF studies can be done on paraffin-fixed tissue (IF-P) and give comparable results to those obtained on frozen tissue for most pathogenic immunoglobulins and immunoglobulin fragments; although, the detection of C3c may be more problematic. In our study, we used proteinase-K method for antigen retrieval. We aimed to detect immunoglobulins and complements in formalin-fixed paraffin-embedded (FFPE) tissue sections from renal biopsies and have comparison of IF staining intensity on FFPE sections with conventional IF on fresh frozen tissue. Based on our results, we conclude that IF-P can serve as salvage technique and has significant diagnostic utility.

Postoperative complications in living liver donors: A retrospective study, single-center experience in Saudi Arabia Nouf Abdulaziz Althonaian, Alanoud Saleh Alsaiari, Weaam Ahmed Almanea, Norah Jezaa Alsubaie, Awatif Ali Almuharimi, Alaa Althubaiti, Abdulrahman Rashed Altamimi, Khalid Omer Abdullah, Wael Abdulaziz Ohali Saudi Journal of Kidney Diseases and Transplantation 2019 30(2):359-364 Living donor liver transplantation (LDLT) offers life to patients with end-stage liver disease. The balance between the benefit to the recipient and the risk to the donor plays a central role in justifying LDLT. However, the incidence rates of complications posttransplant differ widely. This study is designed to identify postoperative complications in LDLT in a tertiary care center King Abdulaziz Medical City (KAMC). This was a retrospective cohort study. All donors at KAMC between January 2003 and December 2015 were reviewed through a hospital database and patient charts to determine the postoperative complications based on the modified Clavien classification system. All donors were relatives of the recipients and assessed before the surgery. A total of 101 donors underwent LDLT: 75 were male and 26 were female, with a mean age of 27.7 ± 6.6. The breakdown of specific surgical procedures was as follows: 65 (64.3%) donors underwent right hepatic lobectomy, 31 (30.6%) underwent left lateral hepatectomy, three (2.97%) underwent extended right hepatectomy with the inclusion of the middle hepatic vein, and two (1.98%) underwent left hepatectomy. Postoperative complications were determined in 20 patients (19.8%), but no mortality was observed. Complications were reported in 14 (21.5%) right and six (19.4%) left lateral hepatectomy donors. A total of 12 patients had Grade I complications, six patients had Grade II complications, and Grade III complications were reported in two cases. The most frequent complications were upper limb weakness to brachial plexus neuropathy and mild bile leak. Life-threatening complications in our center have not been reported in LDLT; however, some donors may experience postoperative morbidity, which usually were mild and had a good prognosis.

Andrology

Prostate cancer: molecular and cellular mechanisms and their implications in therapy resistance and disease progression Ninghan Feng, Jiaoti Huang Asian Journal of Andrology 2019 21(3):213-214

Transcriptional repression by androgen receptor: roles in castration-resistant prostate cancer Galina Gritsina, Wei-Qiang Gao, Jindan Yu Asian Journal of Andrology 2019 21(3):215-223 Androgen receptor (AR), a hormonal transcription factor, plays important roles during prostate cancer progression and is a key target for therapeutic interventions. While androgen-deprivation therapies are initially successful in regressing prostate tumors, the disease ultimately comes back as castration-resistant prostate cancer (CRPC) or at the late stage as neuroendocrine prostate cancer (NEPC). CRPC remains largely dependent on hyperactive AR signaling in the milieu of low androgen, while NEPC is negative of AR expression but positive of many AR-repressed genes. Recent technological advances in genome-wide analysis of transcription factor binding sites have revealed an unprecedented set of AR target genes. In addition to its well-known function in activating gene expression, AR is increasingly known to also act as a transcriptional repressor. Here, we review the molecular mechanisms by which AR represses gene expression. We also summarize AR-repressed genes that are aberrantly upregulated in CRPC and NEPC and represent promising targets for therapeutic intervention.

B lymphoma Moloney murine leukemia virus insertion region 1: An oncogenic mediator in prostate cancer Qipeng Liu, Qiaqia Li, Sen Zhu, Yang Yi, Qi Cao Asian Journal of Andrology 2019 21(3):224-232 B lymphoma Moloney murine leukemia virus insertion region 1 (BMI1), a core member of polycomb repressive complex 1 (PRC1), has been intensely investigated in the field of cancer epigenetics for decades. Widely known as a critical regulator in cellular physiology, BMI1 is essential in self-renewal and differentiation in different lineages of stem cells. BMI1 also plays a significant role in cancer etiology for its involvement in pathological progress such as epithelial–mesenchymal transition (EMT) and cancer stem cell maintenance, propagation, and differentiation. Importantly, overexpression of BMI1 is predictive for drug resistance, tumor recurrence, and eventual therapy failure of various cancer subtypes, which renders the pharmacological targeting at BMI1 as a novel and promising therapeutic approach. The study on prostate cancer, a prevalent hormone-related cancer among men, has promoted enormous research advancements in cancer genetics and epigenetics. This review summarizes the role of BMI1 as an oncogenic and epigenetic regulator in tumor initiation, progression, and relapse of prostate cancer.

The regulatory pathways leading to stem-like cells underlie prostate cancer progression Chun-Jung Lin, U-Ging Lo, Jer-Tsong Hsieh Asian Journal of Andrology 2019 21(3):233-240 Prostate cancer (PCa) is the most common cause of malignancy in males and the third leading cause of cancer mortality in the United States. The standard care for primary PCa with local invasive disease mainly is surgery and radiation. For patients with distant metastases, androgen deprivation therapy (ADT) is a gold standard. Regardless of a favorable outcome of ADT, patients inevitably relapse to an end-stage castration-resistant prostate cancer (CRPC) leading to mortality. Therefore, revealing the mechanism and identifying cellular components driving aggressive PCa is critical for prognosis and therapeutic intervention. Cancer stem cell (CSC) phenotypes characterized as poor differentiation, cancer initiation with self-renewal capabilities, and therapeutic resistance are proposed to contribute to the onset of CRPC. In this review, we discuss the role of CSC in CRPC with the evidence of CSC phenotypes and the possible underlying mechanisms.

Lineage plasticity-mediated therapy resistance in prostate cancer Alexandra M Blee, Haojie Huang Asian Journal of Andrology 2019 21(3):241-248 Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cells eventually evade these strategies through multiple mechanisms. Lineage reprogramming in response to hormone therapy represents a key mechanism that is increasingly observed. The studies in this area have revealed specific combinations of alterations present in adenocarcinomas that provide cells with the ability to transdifferentiate and perpetuate AR-independent tumor growth after androgen-based therapies. Interestingly, several master regulators have been identified that drive plasticity, some of which also play key roles during development and differentiation of the cell lineages in the normal prostate. Thus, further study of each AR-independent tumor type and understanding underlying mechanisms are warranted to develop combinational therapies that combat lineage plasticity in prostate cancer.

Impact of taxanes on androgen receptor signaling Shanshan Bai, Bryan Y Zhang, Yan Dong Asian Journal of Andrology 2019 21(3):249-252 The development and progression of metastatic castration-resistant prostate cancer is the major challenge in the treatment of advanced prostate cancer. The androgen receptor signaling pathway remains active in metastatic castration-resistant prostate cancer. Docetaxel and cabazitaxel are the first- and second-line chemotherapy, respectively, for patients with metastatic castration-resistant prostate cancer. These two taxanes, in general, function by (i) inhibiting mitosis and inducing apoptosis and (ii) preventing microtubule-dependent cargo trafficking. In prostate cancer, taxanes have been reported to inhibit the nuclear translocation and activity of the androgen receptor. However, whether this is attainable or not clinically remains controversial. In this review, we will provide a comprehensive view of the effects of taxanes on androgen receptor signaling in prostate cancer.

Beta-adrenergic signaling on neuroendocrine differentiation, angiogenesis, and metastasis in prostate cancer progression Yicheng Zhao, Wenliang Li Asian Journal of Andrology 2019 21(3):253-259 Prostate cancer is a complex, heterogeneous disease that mainly affects the older male population with a high-mortality rate. The mechanisms underlying prostate cancer progression are still incompletely understood. Beta-adrenergic signaling has been shown to regulate multiple cellular processes as a mediator of chronic stress. Recently, beta-adrenergic signaling has been reported to affect the development of aggressive prostate cancer by regulating neuroendocrine differentiation, angiogenesis, and metastasis. Here, we briefly summarize and discuss recent advances in these areas and their implications in prostate cancer therapeutics. We aim to provide a better understanding of the contribution of beta-adrenergic signaling to the progression of aggressive prostate cancer.

Battle of the sexes: contrasting roles of testis-specific protein Y-encoded (TSPY) and TSPX in human oncogenesis Yun-Fai Chris Lau, Yunmin Li, Tatsuo Kido Asian Journal of Andrology 2019 21(3):260-269 The Y-located testis-specific protein Y-encoded (TSPY) and its X-homologue TSPX originated from the same ancestral gene, but act as a proto-oncogene and a tumor suppressor gene, respectively. TSPY has specialized in male-specific functions, while TSPX has assumed the functions of the ancestral gene. Both TSPY and TSPX harbor a conserved SET/NAP domain, but are divergent at flanking structures. Specifically, TSPX contains a C-terminal acidic domain, absent in TSPY. They possess contrasting properties, in which TSPY and TSPX, respectively, accelerate and arrest cell proliferation, stimulate and inhibit cyclin B-CDK1 phosphorylation activities, have no effect and promote proteosomal degradation of the viral HBx oncoprotein, and exacerbate and repress androgen receptor (AR) and constitutively active AR variant, such as AR-V7, gene transactivation. The inhibitory domain has been mapped to the carboxyl acidic domain in TSPX, truncation of which results in an abbreviated TSPX exerting positive actions as TSPY. Transposition of the acidic domain to the C-terminus of TSPY results in an inhibitory protein as intact TSPX. Hence, genomic mutations/aberrant splicing events could generate TSPX proteins with truncated acidic domain and oncogenic properties as those for TSPY. Further, TSPY is upregulated by AR and AR-V7 in ligand-dependent and ligand-independent manners, respectively, suggesting the existence of a positive feedback loop between a Y-located proto-oncogene and male sex hormone/receptors, thereby amplifying the respective male oncogenic actions in human cancers and diseases. TSPX counteracts such positive feedback loop. Hence, TSPY and TSPX are homologues on the sex chromosomes that function at the two extremes of the human oncogenic spectrum.

Current opinion and mechanistic interpretation of combination therapy for castration-resistant prostate cancer Jin Xu, Yun Qiu Asian Journal of Andrology 2019 21(3):270-278 Recent advances in genomics technology have led to the massive discovery of new drug targets for prostate cancer; however, none of the currently available therapeutics is curative. One of the greatest challenges is drug resistance. Combinations of therapies with distinct mechanisms of action represent a promising strategy that has received renewed attention in recent years. Combination therapies exert cancer killing functions through either concomitant targeting of multiple pro-cancer factors or more effective inhibition of a single pathway. Theoretically, the combination therapy can improve efficacy and efficiency compared with monotherapy. Although increasing numbers of drug combinations are currently being tested in clinical trials, the mechanisms by which these combinations can overcome drug resistance have yet to be fully understood. The purpose of this review is to summarize recent work on therapeutic combinations in the treatment of castration-resistant prostate cancer and discuss emerging mechanisms underlying drug resistance. In addition, we provide an overview of the current preclinical mechanistic studies on potential therapeutic combinations to overcome drug resistance.

Epigenetic regulation of prostate cancer: the theories and the clinical implications Yiji Liao, Kexin Xu Asian Journal of Andrology 2019 21(3):279-290 Epigenetics is the main mechanism that controls transcription of specific genes with no changes in the underlying DNA sequences. Epigenetic alterations lead to abnormal gene expression patterns that contribute to carcinogenesis and persist throughout disease progression. Because of the reversible nature, epigenetic modifications emerge as promising anticancer drug targets. Several compounds have been developed to reverse the aberrant activities of enzymes involved in epigenetic regulation, and some of them show encouraging results in both preclinical and clinical studies. In this article, we comprehensively review the up-to-date roles of epigenetics in the development and progression of prostate cancer. We especially focus on three epigenetic mechanisms: DNA methylation, histone modifications, and noncoding RNAs. We elaborate on current models/theories that explain the necessity of these epigenetic programs in driving the malignant phenotypes of prostate cancer cells. In particular, we elucidate how certain epigenetic regulators crosstalk with critical biological pathways, such as androgen receptor (AR) signaling, and how the cooperation dynamically controls cancer-oriented transcriptional profiles. Restoration of a “normal” epigenetic landscape holds promise as a cure for prostate cancer, so we concluded by highlighting particular epigenetic modifications as diagnostic and prognostic biomarkers or new therapeutic targets for treatment of the disease.

Cardiovascular Medicine

Evaluation of the effect of heart failure reversal therapy on the exercise capacity in patients with chronic heart failure and their association with comorbidities Rohit Sane, Gurudatta Amin, Snehal Dongre, Rahul Mandole Research in Cardiovascular Medicine 2019 8(1):1-5 Background: New treatment modalities are needed to improve the aerobic capacity of patients with chronic heart failure (CHF) considering the increasing disease prevalence. This study was done to evaluate the effect of heart failure reversal therapy (HFRT) on exercise indices, namely VO2 max and metabolic equivalents (METs). Methodology: This retrospective study screened data of 147 patients who had visited Madhavbaug Clinics between July 2018 and December 2018. The mean VO2 max and METs on day 30 of HFRT initiation was compared with that at baseline. Regression analysis was used to calculate the odds for increase in VO2 max and METs by HFRT, in specific comorbidity. Results: Of the 64 patients who fit the study criteria, majority were males (n = 51) with mean age of 57.89 ± 8.14 years. The most common comorbidity was hypertension (n = 45) followed by diabetes mellitus (n = 36) and coronary artery disease (n = 27). Mean VO2 max and METs increased significantly at day 30 of HFRT initiation compared to the mean values on day 1 (P < 0.05). Odds for elevation in VO2 max and METs were maximum in patients with myocardial infarction (MI) (VO2 max: odds ratio [OR] = 4.95; confidence interval [CI] = 0.26–91.5. METs: OR = 3.46; CI = 0.18–65.54), ischemic heart disease (IHD) (VO2 max: OR = 2.85; CI = 0.32–24.7. METs: OR = 1.67; CI = 0.18–15.29), or obesity (VO2 max: OR = 2.57; CI = 0.29–22.4. METs: OR = 1.5; CI = 0.16–13.78). All odds were statistically insignificant (P > 0.05). Conclusion: HFRT leads to significant increase in the VO2 max and METs in CHF patients, indicating improved aerobic capacity. Odds for increased exercise indices with HFRT were maximum in CHF patients suffering from MI, IHD, and obesity.

Compliance of Iranian perfusionist with the American Society of extracorporeal technology standards Nooredin Mohammadi, Alireza Alizadeh Ghavidel, Mohammad Zirak, Mohammad Zia Toutounchi, Amir Faravan Research in Cardiovascular Medicine 2019 8(1):6-10 Background: Standards play an important role in representing the minimum favorable and acceptable performance and are used in determining the exact current status of a hospital and evaluating and monitoring its performances. Standards also play an important role in providing quality services by perfusionists to patients undergoing open heart surgery with heart–lung machine. Objectives: This study aimed to analyze the compliance with standards related to perfusionists in Iran by comparison with the American Society of Extracorporeal Technology Standards. Methods: In this descriptive cross-sectional study, a questionnaire developed by the American Society of Extracorporeal Technology Standards was used to collect data from 48 Iranian hospitals and educational medical centers. The level of compliance with perfusion standards related to perfusionists was analyzed and compared with the American Society of Extracorporeal Technology Standards. Results: The results showed that 45.52% of the centers were in compliance with factors related to standards of competence, qualification, and backup staffing for critical situation. Only 23% of the centers comply with standards of perfusionists' interaction with the medical team which indicates an unsatisfactory interaction between perfusionists and the medical team, and regarding the working hours, only 18.5% of the centers comply with the standards in this area. Conclusion: The comparison made between the compliance of Iranian perfusionists and the American Society of Extracorporeal Technology Standards reveals an unsatisfactory level. This suggests the need for the development of accreditation programs and standards of care on the one hand and conduction of a continuous evaluation of these standards on the other hand.

Clinical results of combined amiodarone and mexiletine therapy in refractory ventricular tachycardias Shabnam Madadi, Mehdi Nemati, Amirfarjam Fazelifar, Farzad Kamali, Majid Haghjoo Research in Cardiovascular Medicine 2019 8(1):11-13 Background: Refractory recurrent ventricular tachycardia is a difficult therapeutic problem. There are implantable cardioverter-defibrillator (ICD) patients with amiodarone-refractory of ventricular arrhythmia (VA) who are not eligible for catheter ablation. The aim of this cohort study was to assess the efficacy of mexiletine in combination with amiodarone in the reduction of VA in this group of patients. Methods: This was a retrospective study of all consecutive ICD patients who were treated by adding mexiletine to amiodarone in refractory electrical storm or frequent VA episodes. The enrolled patients were ineligible for catheter ablation. Results: Thirty-seven patients (32 males; mean age, 57 ± 14 years; range, 26–81 years) were studied. Adding mexiletine to amiodarone had no significant effect on QRS width, QTc interval, and PR interval (all P > 0.05). We observed a significant decrease in the number of total ICD shock and significant increase in appropriate antitachycardia pacing during follow-up after initiating mexiletine. Mexiletine therapy also significantly reduced the amiodarone dose during the follow-up. No mortality was observed in the present cohort during the study period. Conclusions: Mexiletine, when added in case of amiodarone failure, reduces VA episodes and appropriate therapies in patients with an implantable cardioverter defibrillator.

Pericardial effusion and outcome in children at a Tertiary Hospital in North-Western Nigeria: A 2-year retrospective review Igoche David Peter, Mustafa Ohikhena Asani, Ibrahim Aliyu Research in Cardiovascular Medicine 2019 8(1):14-18 Background: Pericardial effusion may culminate in cardiac tamponade which could be fatal. This study aims to describe the prevalence of cardiac tamponade, with the etiology, and outcome of childhood pericardial effusion at Aminu Kano Teaching Hospital, Kano, Nigeria. Materials and Methods: Hospital records of children with pericardial effusion were retrospectively analyzed from June 2016 to May 2018. Data were described via percentages, tables, and bar and pie charts. Results: Of the 5876 pediatric admissions during the study duration, 10 (0.2%) children presented with cardiac tamponade (9 boys and 1 girl) and had emergency echocardiography-guided percutaneous pericardiocentesis; 5 (50%) of them had purulent, 4 (40%) had serous, and 1 (10%) had hemorrhagic pericardial effusion. Seventeen children, aged 8 months to 13 years with a male: female ratio of 2.4:1, had pericardial effusion during the study period. Pericardial effusion of infectious origin (58.8%) was the most common followed by uremic (17.4%), rheumatic (11.8%), and trauma and idiopathic (5.9%). Tuberculosis (TB) was the most implicated cause of infectious pericardial effusion (70%), and also the most common cause of cardiac tamponade (50%). Mortality was recorded in two children (11.8%) with end-stage renal disease and decompensated rheumatic heart disease, both complicated by pericardial effusion. None of them were in tamponade and hence did not have pericardiocentesis. Emergency echocardiography-guided percutaneous pericardiocentesis was safe and successful in all those who had this procedure. Conclusion: Cardiac tamponade is common in children with pericardial effusion in Kano. TB is the leading cause of childhood pericardial effusion and cardiac tamponade. Mortality was reported in two children, with pericardial effusion of uremic and rheumatic etiology each.

Walking performance in the 6-min walk test and gait speed in patients undergoing open heart surgery: A preliminary cohort study Kornanong Yuenyongchaiwat, Sasipa Buranapuntalug, Khajonsak Pongpanit, Chitima Kulchanarat Research in Cardiovascular Medicine 2019 8(1):19-22 Context: The 6-minute walk test (6-MWT) has been commonly used to assess patients after open heart surgery. However, due to some situations, where patients could not perform the test for the duration of 6-minutes, a short walking distance test has been utilized to test the patients (i.e., 5-meter walk distance: 5-MWD). However, little is known whether fixed duration walking test, or fixed-distance walking test, regarding to the prediction of duration of hospital admission. Aims: The aim of the study was to evaluate the 6-MWT and 5-MWD in patients who had undergone open heart surgery, in order to predict hospital admission. Settings and Design: A prospective cohort study was designed at Thammasat University Hospital, Thailand. Methods and Material: Fifty-seven participants, who had open heart surgery were recruited and were asked to perform 6-MWT and 5-MWD pre and post-operative heart operation. Statistical Analysis Used: Regression analysis was used to test the prediction of the length of hospital admission and the walking performance.Results: A regression analyses indicated that after adjustment for age and gender, baseline 5-MWD and 6-MWT were associated with increased the hospital admission (ΔR2 = 0.112 and ΔR2 = 0.068, respectively). Conclusions: The 5-MWD might be an alternative to predict the length of hospital admission in patients who had undergone open heart surgery.

Effects of Magnesium Replacement Therapy in Patients with Chronic Stable Heart Failure and Normal Magnesium Level Ahmad Amin, Mitra Chitsazan, Mandana Chitsazan, Arezoo Haghighattalab, Sepideh Taghavi, Nasim Naderi Research in Cardiovascular Medicine 2019 8(1):23-28 Objectives: In the present study, we sought to assess the changes in functional, biochemical, and echocardiographic measurements of heart failure (HF) during a 12-week Mg2+ supplementation in chronic stable HF patients. Methods: Twenty patients with clinically stable New York Heart Association (NYHA) Class I–III systolic HF (echocardiography-derived left ventricular ejection fraction [LVEF] of <40%) and normal magnesium level (1.5–2 mg/dl) were recruited consecutively in this before and after study. The patients received oral Mg2+ (400 mg MgO b.i.d., for a total of 482.6 mg of elemental Mg2+) for a total of 12 weeks. Results: Twenty patients, including 10 (50%) men, with a mean ± standard deviation age of 53 ± 15 years were included. The 6-min walk distance significantly increased from 379 (348–440) m to 583 (506–604) m. High-sensitivity C-reactive protein significantly decreased from 12 (7–14) to 3 (2–4) mg/dL (P < 0.001). N-terminal pro-brain natriuretic peptide also declined from 653 (415–2660.75) to 189.5 (82.5–537.75) ng/dL (P < 0.001). The LVEF and systolic pulmonary artery pressure significantly improved (both P < 0.001). Conclusion: We demonstrated beneficial effects of Mg2+ supplementation in patients with normal magnesium level. We suggest routine Mg2+ supplementation to all HF patients with low-to-normal Mg2+ levels and normal kidney function.

Trial design: The effect of high-dose rosuvastatin on echocardiographic parameters in patients with intermediate- and high-risk pulmonary embolism – A randomized placebo-controlled trial Azin Alizadeh Asl, Mohamad Mehdi Peighambari, Jamal Moosavi, Omid Shafe, Moona Naghshbandi, Melody Farrashi, Nakisa Khansary, Hamid Reza Pouraliakbar, Kiara Rezaei Kalantari, Hooman Bakhshandeh, Hamed Talakoob, Maryam Mohseni Salehi, Sajjad Naderi, Ehsan Ghourchian, Farzaneh Mehrvarz, Nahid Rafiee, Parham Sadeghipour Research in Cardiovascular Medicine 2019 8(1):29-34 Background: It has been shown recently that a considerable burden of pulmonary embolism (PE) roots from an inflammatory response. The activated inflammatory cascade will be responsible for the final fibrotic response of pulmonary vascular bed, creating further mechanical obstruction which results in subsequent right ventricular (RV) dysfunction, influencing functional capacity and future prognosis. Although anticoagulants represent the cornerstone treatment of PE, the drug class has a minimal effect on the mentioned pathology. Study Design: The present study is a single-center randomized, double-blind, parallel group controlled trial with placebo which will evaluate the effect of high-intensity statin – rosuvastatin 20 mg daily on patients with intermediate-to-high-risk PE. Study population will be selected from patients for whom statin is not otherwise indicated. Primary end point of the present trial will be echocardiographic measures of RV function. We believe that the mentioned indexes represent an accurate surrogate for the functional capacity and prognosis. Our secondary end point will be the composites of PE recurrence and exertional capacity measured by 6-minute walk test. Conclusions: The result of the present trial might influence the complimentary treatment of acute PE.

Assessment of the effect of percutaneous coronary intervention on left ventricular function in patients with coronary artery disease using tissue doppler strain rate imaging Mohamed Elsayed Abou Ellail, Mahmoud Shawky Abd El Moneum, Hany Hassan Ebaid, Eman Said El-Kishk Research in Cardiovascular Medicine 2019 8(1):35-39 Objectives: this study aimed to assess the effects of percutaneous coronary intervention (PCI) on regional and global left ventricular (LV) functions (systolic and diastolic) in patients with coronary artery disease (CAD) using tissue Doppler strain rate (SR) imaging. Patients and Methods: in this study, we randomly assigned 100 Egyptian adult symptomatic patients with CAD that underwent coronary angiography and candidate for PCI on the left anterior descending artery. LV early diastolic and systolic SR were measured 24 h before and 48 h after PCI. Results: Most of the LV diastolic and systolic parameters (A, E', E/A, E/E', and isovolumic relaxation time [IVRT]) showed significant difference before and after elective PCI, while mitral E velocity, DT, and pulmonary vein flow before and after PCI did not show significant difference. SR imaging findings showed high significant difference mean peak systolic and mean early diastolic SR of ischemic regions after PCI; mean early diastolic SR before PCI was 1.86 ± 0.13 while after PCI was 2.57 ± 0.18 (P < 0.001) and mean peak systolic SR before PCI was 0.65 ± 0.18 while after PCI was 0.901 ± 0.15 (P < 0.001). Conclusion: Most of the LV diastolic and systolic parameters (A, E', E/A, E/E', and IVRT) improved after PCI in CAD patients. Furthermore, regional myocardial function as measured by mean peak systolic and mean early diastolic SR in the ischemic segments improved significantly compared with that in nonischemic segments.

Takayasu's Arteritis: Cardiac and Renal Involvement Vitorino Modesto dos Santos Research in Cardiovascular Medicine 2019 8(1):40-40

Oral Medicine and Radiology

A year of change and rejuvenate Ajay Parihar Journal of Indian Academy of Oral Medicine and Radiology 2019 31(1):1-1

Change has become a necessity: Curricular reforms and change management is what we need Vasanti Lagali-Jirge Journal of Indian Academy of Oral Medicine and Radiology 2019 31(1):2-3

Knowledge, attitudes, and practices regarding sterilization protocol among undergraduate dental students in Faridabad City: A questionnaire-based study Akshat Sachdeva, Aditi Sharma, Sumit Bhateja, Geetika Arora Journal of Indian Academy of Oral Medicine and Radiology 2019 31(1):4-10 Aim: To assess the level of knowledge, attitudes, and practices regarding sterilization/infection control measures among undergraduate dental students. Materials and Methods: A total of 300 dental students from Manav Rachna Dental College, Faridabad, Haryana participated in this study. A questionnaire survey comprising 24 questions regarding knowledge, attitudes, and practices was completed by the participants. Results: It was observed that a majority of the students were highly concerned regarding the sterilization and infection control protocol. 96.9% students dispose of their gloves after use. About 89% are aware of the exact specifications of sterilization via autoclave. Use of mouth masks and head caps as effective infection control measures was practiced among 82.4% students. A large fraction of students comprising about 85% believed that proper sterilization could not be achieved by simple boiling of instruments. Conclusion: The level of knowledge and attitude of sterilization measures were acceptable, although compliance and practice of the same needs to be more worked upon.

A comparative study of efficacy of intralesional corticosteroids and hyaluronidase therapy with and without ultrasound therapy in patients with oral submucous fibrosis Harika Guduru, Komali Garlapati, Raji Viola Solomon, Ancy V Ignatius, Mounika Yeladandi, Nithika Madireddy Journal of Indian Academy of Oral Medicine and Radiology 2019 31(1):11-16 Background: Oral submucous fibrosis (OSMF) is a potentially malignant disorder affecting any part of the oral cavity, sometimes pharynx associated with trismus and burning sensation. Physical therapies such as ultrasound therapy was found to have therapeutic benefits of decreasing inflammation and accelerating healing process in OSMF patients. Hence, this study was designed to evaluate the therapeutic benefit of ultrasound treatment when compared to empirical combination of intralesional dexamethasone and hyaluronidase treatment alone in OSMF patients. Objectives: To evaluate and compare the clinical efficacy of intralesional infiltration of 2 ml dexamethasone (4 mg/ml) + hyaluronidase 1500 IU, ultrasound therapy in combination with intralesional infiltration and only ultrasound therapy, in reducing the signs and symptoms in patients with OSMF. Materials and Methods: The present study was performed in the Department of Oral Medicine and Radiology, with a total sample of 33 participants grouped into Group A (intralesional infiltration of 2 ml dexamethasone 4 mg/ml + hyaluronidase 1500 IU dissolved in 0.5 ml of 2% lignocaine twice a week for 8 weeks), Group B (a combination treatment of intralesional infiltration twice a week for 8 weeks and ultrasound therapy for 15 days), and Group C (only ultrasound therapy for 15 days). The collected data were subjected to statistical analysis using SPSS 16 software. Results: Statistical analysis revealed that there was a significant difference in M.M.O in Group A (1.3 ± 0.48), Group B (2.55 ± 0.75), and Group C (1.65 ± 1.20) and also VAS score of 42% ± 0.10, 41% ± 0.13, and 15% ± 0.05, respectively, after treatment. Conclusion: The results revealed that therapeutic ultrasound can be used as an adjuvant treatment, as it can alleviate the signs and symptoms of patients suffering from OSMF, thus improving the quality of life.

Comparison between conventional radiograph and 3D volumetric radiograph for determining the morphology and morphometry of mental foramen Rakashree Chakraborty, Sourav Sen, Arati Panchbhai, Rahul R Bhowate, Aditya Dupare Journal of Indian Academy of Oral Medicine and Radiology 2019 31(1):17-23 Objective: Mental foramen is a vital anatomical structure in human mandible as they are important for dental surgeons for extraction, implant placement, osteotomy procedures, anesthetists in nerve block, and surgical procedures to avoid injury to neurovascular bundle in mental foramen area. The aim of this study was to compare the position, shape, size, and distinctness of mental foramen using orthopantomogram (OPG) and digitalized volumetric tomography (DVT). Materials and Method: This study was conducted on 25 individuals for both the genders. Position, shape, size, and distinctness of mental foramen were compared using OPG and DVT and were evaluated by Expert three-dimensional (3D) software in DVT and Annotation software in OPG. Results: Mental foramen was found to be on the vicinity of the second premolar region with respect to apices of premolars and molars and was more common in the middle third region of the jaw bone with respect to superoinferior cortex of the mandible in vertical plane. There was no significant difference in the position of the mental foramen using OPG and DVT. The commonest shape of mental foramen was found to be oval and was better defined in DVT. The size of the mental foramen was observed to be 0.49 ± 0.05 and 0.51 ± 0.06 cm in OPG and DVT, respectively, and more distinctly visible in DVT. There was no significant difference in the position, shape, size, and distinctness of the mental foramen among genders. Conclusion: Conventional radiography can be initially done for the position of the mental foramen but the details must be confirmed using 3D volumetric radiography to avoid any kind of procedural complications.

Role of immunological alterations in oral submucous fibrosis Sarada Malempati, Vamshi Krishna Guttikonda, Thejasri Vishnubhatla, Mahesh Neerupakam, Sridevi Koduri, Krishnaveni Buduru Journal of Indian Academy of Oral Medicine and Radiology 2019 31(1):24-28 Background: Oral Submucous fibrosis (OSMF) is a premalignant condition affecting the oral mucosa. It is observed to have a multifactorial etiology including genetic predisposition and autoimmune origin. This study aimed to study the etiological role of immunological factors in OSMF. Settings and Design: It was a prospective study carried out in the Department of Oral Medicine and Radiology at Lenora Institute of Dental Sciences, Rajahmundry. Aims and Objective: To estimate and compare the serum IgG and IgA between the OSMF subjects and controls. To assess the statistical significance of the difference in the levels of albumin, globulin, total protein, IgG and IgA between study group and control group if any. Materials and Methods: It was an observational study in which the serum albumin, serum globulin, total protein, IgG and IgA were evaluated in a total of 60 patients who gave consent to participate in the study. Results and Discussion: Increase of IgG was observed in 9 (30%) subjects of the OSMF group and in 4 (13.2%) of the control group. IgA level was increased in 2 (6.6%) subjects of OSMF group and in 5 (16.6%) subjects of the control group. However, this difference was not statistically significant. Conclusion: The findings from the study indicated an alteration in the immunoglobulin level in patients with OSMF. However, the association was not significant. Therefore, further and larger studies are advocated to verify the immunological association with OSMF. One important observation made in the study was a positive association between the duration of exposure and stage of OSMF. This implies that interventions which modify the arecanut chewing habits can bring about a reduction in OSMF and in turn oral cancer.

Comparison of conventional pharmacological therapy and holistic approaches (Naturopathy and Yoga) in the management of chronic orofacial pain: A randomized controlled study Khushboo Bhalla, Nagaraju Kamarthi, Sangeeta Singh Malik, Sumit Goel, Swati Gupta Journal of Indian Academy of Oral Medicine and Radiology 2019 31(1):29-35 Background: Orofacial pain disorders and their management forms an important and integral part of our oral medicine specialty. Only oral physicians are well-trained to provide non-surgical treatment of these complex disorders. Today, the escalating costs of drugs and several adverse effects associated with modern medicines have led to the search of alternative systems all over the world. Hence, this study is an effort to assess the efficacy of holistic approaches (naturopathy and yoga) alone as well as in combination with pharmacological therapy in the treatment of chronic orofacial pain of non-odontogenic origin. Materials and Methods: The present study was conducted on 60 patients who were randomized into three groups A, B and C, each group consisting of 20 patients (10 of myofascial pain and 10 of trigeminal neuralgia). In group A it was prescribed conventional medicines for their respective treatment. Holistic approaches (naturopathy and yoga) were added with conventional pharmacological therapy in group B and only holistic approaches were performed in group C. The duration of treatment was of 3 months a and the patients were analysed using pain scale, quality of life scale (QOL) and stress scale after every ten days follow-up. Results: The patients of trigeminal neuralgia showed best result when treated with pharmacological treatment. The holistic approaches showed significant results only when combined with pharmacological therapy for the treatment of trigeminal neuralgia. On the other hand, holistic approaches works best in myofascial pain both alone and in combination with pharmacological therapy. Acupuncture and facial massage along with yoga have a great impact on quality of life by reducing stress and anxiety of the patient. Conclusion: Holistic approaches are useful means in treating patients with chronic orofacial pain as it eliminates the risk of adverse effects associated with long term use of muscle relaxants and anti-convulsants.

Comparative evaluation of citric acid and TENS as means for salivary stimulation in adults: An Invivo study Mimansha Pandey, Vanaja Reddy, Panjab V Wanjari Journal of Indian Academy of Oral Medicine and Radiology 2019 31(1):36-39 Introduction: Xerostomia and salivary gland hypofunction are associated with advancing age, autoimmune diseases such as Sjφgren's syndrome, head and neck radiation, smoking and recreational drug usage. Palliative management of xerostomia included topical agents such as ice chips, saliva substitutes, increasing water intake, paraffin and systemic agents like pilocarpine had been used. The above mentioned agents had side-effects and have led to find newer modalities like electrical and chemical stimulation. Aim: The present study was undertaken to evaluate the effectiveness of citric acid and transcutaneous electric nerve stimulation (TENS) as a means of stimulating salivary function in healthy adult subjects. Materials and Methods: Hundred adult subjects, 50 males and 50 females between the age group of 18-45 years, with no history of salivary gland disorder were randomly enrolled in the study. During the first visit unstimulated whole saliva was collected in a graduated tube and aafter 1 hr stimulated saliva was collected using citric acid and obtained saliva was measured and recorded. At the second visit, unstimulated whole saliva was collected in a graduated tube and after 1 hr stimulated saliva was collected with TENS and obtained saliva was measured and recorded. Results: The obtained data of unstimulated and stimulated saliva of the subjects was tabulated and subjected to statistical analysis using paired and unpaired t-test. The results showed increased salivary flow rate with both the modalities. And comparative evaluation revealed greater salivary flow rate with citric acid when compared to TENS. Conclusion: The present study substantiated the fact that citric acid as well as TENS can be used as an effective and wholesome method in stimulation of whole salivary flow rate in patients with xerostomia and salivary gland hypofunction.

Prevalence of Stafne's Cyst – A retrospective analysis of 18,040 Orthopantomographs in Western India Sugandha Arya, Ashish Pilania, Jitender Kumar Journal of Indian Academy of Oral Medicine and Radiology 2019 31(1):40-44 Introduction: Stafne's cyst (SC) is a bone depression found on the lingual side of the mandible. It is a sharply demarcated osteolytic lesion of the mandible, caudal to the inferior alveolar nerve and restricted to the regions of the molars and mandibular angle. Purpose: Stafne's bone cyst is usually asymptomatic being diagnosed on the routine radiographs as an incidental finding hence, its actual prevalence is unknown. Moreover, the lesion simulates many odonogenic pathologies thereby, and the entity remains a diagnostic challenge. So, the present study was conducted to investigate the prevalence of SC in Jodhpur population of Western India. Materials and Methods: A retrospective analysis of 18040 OPGs was done on the basis of diagnostic criteria described by Stafne. Results: A total of 6 cases fulfilled diagnostic criteria of SC (0.03%), 4 cases were reported in men (66.6%), at a mean age of 50.75 years, and 2 cases in women (33.3%), at a mean age of 31.5 years. Involvement of SC on left and right side of the mandible was given as 4:2 in ratio. All 6 cases of SC was found in the body of mandible (100%). Rare case of double unilateral form of SC was reported in 1 patient. Conclusion: Orthopantomographs (OPGs) may ensure initial opinion regarding the diagnosis of SC and alert the clinicians to exclude other potential pathologies to avoid invasive procedures.

Efficacy of aloe vera and triamcinolone acetonide 0.1% in recurrent aphthous stomatitis: A preliminary comparative study Versha R Giroh, Manjula Hebbale, Amit Mhapuskar, Darshan Hiremutt, Priya Agarwal Journal of Indian Academy of Oral Medicine and Radiology 2019 31(1):45-50 Introduction: Aloe vera has various pharmacological actions due to which it has been selected as an alternative treatment modality in treating various oral diseases. It has antibacterial, antifungal, antiinflammatory, antioxidant, antitumor, and immune boosting. It has been used for the management of oral lesions such as oral lichen planus, oral submucous fibrosis, radiation-induced mucositis, burning mouth syndrome, xerostomia, recurrent aphthous ulcers. Aim: The aim of this study is to the compare the effects of the topical aloe vera gel and triamcinolone acetonide 0.1% in patients with minor ulcers of aphthous stomatitis. Materials and Methods: Thirty-four patients presenting with clinical signs and symptoms of aphthous stomatitis were included for the randomized single blinded study after informed consent. Group A patients received topical aloe vera gel (Forever Bright Aloe vera Gel), and Group B patients received topical triamcinolone acetonide 0.1% (kenacort oral paste) three times a day for 7 days or till the ulcer heals completely. The parameters such as the size of the ulcer, burning sensation, and pain were recorded at each visit. Results: In this study, kenacort oral paste was found to be effective than aloe vera in wound healing (measured by the diameter of ulcer). In contrast, aloe vera gel had a better response in terms of pain and burning sensation. Conclusion: Aloe vera has a wide spectrum of unique properties and uses. It is a promising agent in treating oral lesion in the field of oral medicine. It can be used as an alternative medicine and in patients who are allergic to steroid medication.

Microbiology

Flavobacterium edaphi sp. nov., isolated from soil from Jeju Island, Korea Abstract An aerobic, Gram-stain-negative, bright yellow-pigmented, oxidase and catalase-positive, non-motile, non-spore forming, rod-shaped strain designated DMN11T was isolated from the soil of crossroads of Jeju Island in South Korea. Colonies were circular, bright yellow-pigmented and smooth with regular edges and measured approximately 1–2 mm in diameter. Flexirubin-type pigments were absent. Phylogenetic tree analysis based on the 16SrRNA gene sequence revealed that the strain DMN11T formed a lineage within the family Flavobacteriaceae of the phylum Bacteroidetes, and it was the most closely related to Flavobacterium suzhouense XIN-1Tand Flavobacterium hauense BX12T (98.6% and 98.2% similarity, respectively). The major isoprenoid quinone was MK-6. The major fatty acids were summed feature 3 (comprising C16:1ω7c and/or C16:1ω6c), iso-C15:0and iso-C15:0 3OH. The polar lipid profile of the strain DMN11T showed the presence of phosphatidylethanolamine (PE) as major lipid. The DNA G+C content was 35.3 mol%, as determined by the thermal denaturation method. The mean levels of DNA–DNA relatedness of the strain DMN11T with F. suzhouense XIN-1T and F. hauense BX12T were 20.5% and 29.2%, respectively. Thus, the data accumulated in this study support the suggestion that the strain DMN11T is considered to represent a novel species of the genus Flavobacterieum, for which the name Flavobacterium edaphi sp. nov. is proposed. The type strain is DMN11T (= KCTC 62114T = JCM 32372T).

The rhizomicrobiomes of wild and cultivated crops react differently to fungicides Abstract The fungicides used to control diseases in cereal production can have adverse effects on non-target microbial communities, with possible consequences for plant health and productivity. Although we know that fungicides affect microbial community structure and soil activities, it is unclear how crop cultivars have altered the impact of fungicides on rhizomicrobiomes. In this study, the rhizosphere bacterial and fungal communities and structures of cultivated crops and their wild relatives were studied by Illumina MiSeq sequencing analysis. The results indicated that the rhizomicrobiome communities of wild crops reacted more strongly to fungicides than that of their cultivated relatives. Furthermore, fungal community composition was more affected by fungicides than bacterial community composition. Remarkably, the same trend was observed in both soybean and rice with regard to the influence of crop cultivar on the response of the rhizomicrobiome to fungicide application, although the level of the response was not similar. We report for the first time that the rhizomicrobiomes of wild crops reacted more strongly to fungicides than the rhizomicrobiomes of cultivated crops.

Caballeronia ginsengisoli sp. nov., isolated from ginseng cultivating soil Abstract A Gram-stain-negative, strictly aerobic, non-motile, ivory colored and rod-shaped bacterium (designated Gsoil 652T) isolated from ginseng cultivating soil, was characterized using a polyphasic approach to clarify its taxonomic position. Strain Gsoil 652T was observed to grow optimally at 30 °C and at pH 7.0 on R2A agar medium. Phylogenetic analysis, based on 16S rRNA gene sequences similarities, indicated that Gsoil 652T belongs to the genus Caballeronia of the family Burkholderiaceae and was most closely related to Caballeronia choica LMG 22940T (98.9%), Caballeronia udeis LMG 27134T (98.9%), Caballeronia sordidicola LMG 22029T (98.2%) and Caballeronia humi LMG 22934T (98.1%). The DNA G+C content was 62.1 mol% and Q-8 was the major isoprenoid quinone. The main polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, unidentified aminophospholipid, and unidentified phospholipid. The predominant fatty acids were C16:0, C17:0 cyclo and C19:0 cyclo ω8c. The DNA–DNA relatedness value between strain Gsoil 652Tand closely related type strains of Caballeronia species were less than 36.0%. Moreover, strain Gsoil 652T could be distinguished phenotypically from the recognized species of the genus Caballeronia. The novel isolate, therefore, represents a novel species, for which the name Caballeronia ginsengisoli sp. nov. is proposed, with the type strain Gsoil 652T (= KACC 19441T = LMG 30326T).

Cinnamaldehyde inhibit Escherichia coli associated with membrane disruption and oxidative damage Abstract In this study, the antimicrobial mechanism of cinnamaldehyde (CIN) against Gram-negative Escherichia coli ATCC 25922 (E. coli) based on membrane and gene regulation was investigated. Treatment with low concentration (0, 1/8, 1/4, 3/8 MIC) of CIN can effectively suppress the growth of E. coli by prolonging its lag phase and Raman spectroscopy showed obvious distinction of the E. coli after being treated with these concentration of CIN. The determination of relative conductivity indicated that CIN at relatively high concentration (0, 1, 2, 4 MIC) can increase the cell membrane permeability, causing the leakage of cellular content. Besides, the content of malondialdehyde (MDA) and the activity of total superoxide dismutase (SOD) of E. coli increased with increasing treatment concentration of CIN, implying that CIN can cause oxidative damage on E. coli cell membrane and induce the increase of total SOD activity to resist this oxidative harm. Moreover, quantitative real-time RT-PCR (qRT-PCR) analysis revealed the relationship between expression of antioxidant genes (SODa, SODb, SODc) and treatment CIN concentration, suggesting that SOD, especially SODc, played a significant role in resistance of E. coli to CIN. The underlying inactivation processing of CIN on E. coli was explored to support CIN as a potential and natural antimicrobial agent in food industry.

Endozoicomonas coralli sp. nov., isolated from the coral Acropora sp. Abstract A novel bacterium, designated strain Acr-12T, was isolated from the coral Acropora sp. off coast of Southern Taiwan. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain Acr-12T belonged to the genus Endozoicomonas and had closest phylogenetic identity to Endozoicomonas acroporae Acr-14T (98.7%) and Endozoicomonas atrinae WP70T (97.8%). Cells of strain Acr-12T were Gram-negative, aerobic, non-motile, poly-β-hydroxybutyrate-accumulating, rod-shaped and formed creamy white colonies. Optimal growth occurred at 30 °C, pH 7, and in the presence of 3% NaCl. Strain Acr-12T contained summed feature 3 (C16:1ω7c and/or C16:1ω6c), summed feature 8 (C18:1ω7c and/or C18:1ω6c) and C16:0 as the predominant fatty acids. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The predominant isoprenoid quinone was Q-9. The genomic DNA G + C content was 49.6 mol%. The DNA–DNA relatedness of strain Acr-12T with respect to the closest species of the genus Endozoicomonas was less than 30%. Phenotypic characteristics of the novel strain also differed from those of the closest related species of the genus Endozoicomonas. On the basis of the genotypic, chemotaxonomic, and phenotypic data, strain Acr-12Trepresents a novel species in the genus Endozoicomonas, for which the name Endozoicomonas coralli sp. nov. is proposed. The type strain is Acr-12T (= BCRC 80921T = KCTC 42900T).

Isolation and identification of Ammodendron bifolium endophytic bacteria and the action mechanism of selected isolates-induced seed germination and their effects on host osmotic-stress tolerance Abstract This study aimed to identify Ammodendron bifolium endophytic bacteria, and to evaluate promoting mechanism of selected isolates on seed germination and their effects on host osmotic-stress tolerance. Forty-five strains were isolated from A. bifolium and were classified into 13 different genera by 16S rDNA gene sequence analysis. AY3, AY9 and AG18, which were identified as Staphylococcus, Kocuria, Bacillus sp., promoted host seed ethylene release during germination. Ethrel and 1-aminocyclopropane-1-carboxylic acid (ACC) imitated the effect of AY3, AY9 and AG18 on seed germination. The data suggest that ethylene mediates AY3-, AY9-, AG18-induced A. bifolium seed germination. In addition, osmotic stress prevented seed germination and radicle elongation. However, the inhibitory effect of osmotic stress on seed germination and radicle elongation were rescued by AY3, AY9 and AG18. The results show that AY3, AY9 and AG18 increased osmotic-stress tolerance in A. bifolium. AY3, AY9, AG18 induced A. bifolium seed germination through promoting ethylene production during endophytic bacteria–plant interaction, and increase osmotic-stress tolerance in A. bifolium. AY3, AY9 and AG18 are potential candidates for the protection of A. bifolium.

Free radical stress induces DNA damage response in RAW264.7 macrophages during Mycobacterium smegmatis infection Abstract Genomic instability resulting from oxidative stress responses may be traced to chromosomal aberration. Oxidative stress suggests an imbalance between the systemic manifestation of reactive free radicals and biological system's ability to repair resulting DNA damage and chromosomal aberration. Bacterial infection associated insult is considered as one of the major factors leading to such stress conditions. To study free radical responses by host cells, RAW 264.7 macrophages were infected with non-pathogenic M. smegmatis mc2155 at different time points. The infection process was followed up with an assessment of free radical stress, cytokine, toll-like receptors (TLRs) and the resulting DNA damage profiles. Results of CFU count showed that maximum infection in macrophages was achieved after 9 h of infection. Host responses to the infection across different time periods were validated from nitric oxide quantification and expression of iNOS and were plotted at regular intervals. IL-10 and TNF-α expression profile at protein and mRNA level showed a heightened pro-inflammatory response by host macrophages to combat M. smegmatis infection. The expression of TLR4, a receptor for recognition of mycobacteria, in infected macrophages reached the highest level at 9 h of infection. Furthermore, comet tail length, micronuclei and γ-H2AX foci recorded the highest level at 9 h of infection, pointing to the fact that breakage in DNA double strands in macrophage reaches its peak at 9 h of infection. In contrast, treatment with ROS inhibitor N-acetyl-l-cysteine (NAC) prevented host cell death through reduction in oxidative stress and DNA damage response during M. smegmatis infection. Therefore, it can be concluded that enhanced oxidative stress response in M. smegmatis infected macrophages might be correlated with DNA damage response.

Modulation of nitrogen metabolism of maize plants inoculated with Azospirillum brasilense and Herbaspirillum seropedicae Abstract Maize is highly responsive to the application of nitrogen to achieve high productivity. Inoculation with diazotrophic bacteria can improve plant growth with low N fertilization. The objective was to evaluate the inoculation of two species of diazotrophs on N metabolism in maize plants, in the presence of two concentrations of nitrogen in a hydroponic system. A factorial arrangement composed of two N levels (3.0 and 0.3 mM), with the presence of Hs—Herbaspirillum seropedicae, and Ab—Azospirillum brasilense or not. The parameters used were dry mass; N, P, and K accumulation; nitrate reductase activity; soluble fractions in roots and leaves. The inoculation altered the N metabolism and promoted greater development of maize plants, as well as a higher accumulation of P and K in the shoots. A more intensive process of N assimilation was evidenced when the plants were inoculated with H. seropedicae, leading to increased levels of NO3− and reduced N-amino, sugars, and NH4+ in leaves associated with high N level, opposite of A. brasilense.

Chromosomal integration of heterologous oxalate decarboxylase in Lactobacillus plantarum WCFS1 using mobile genetic element Ll.LtrB Abstract Lactobacillus plantarum WCFS1 (L. plantarum WCFS1) is commonly used as a potential cell factory because of its 'generally recognized as safe' status. The plasmid instability and the presence of antibiotic selection marker complicate the application of genetically modified L. plantarum in human clinical trials. In the present study, we aimed to integrate oxalate decarboxylase (oxdC) gene of Bacillus subtilis origin by targeted chromosomal mutation in L. plantarum using mobile genetic element Ll.LtrB as a therapeutic tool against calcium oxalate stone disease. oxdC expression cassette was constructed and integrated into a targeted gene, thymidylate synthase (thyA) in the L. plantarum genome. The dependence on external thymidine for growth and survival was established by live dead population assay and SEM (scanning electron microscopy) analysis. The western blotting assay showed the secretion of 44 kDa OxdC protein in the culture supernatant of L. plantarum ∆thyA:OxdC. The biologically contained recombinant strain significantly reduced the oxalate concentration by 53% and exhibited a loss of viability when introduced to environmental samples. Biologically contained L. plantarum secreting OxdC constructed using group II intron has the ability to degrade oxalate present in the extracellular environment and could be used as a therapeutic tool for the calcium oxalate stone disease.

Pharmacological properties of marine macroalgae-associated heterotrophic bacteria Abstract The rich diversity of marine macroalgae and their associated bacterial flora represent a potential reservoir of bioactive compounds with valuable biotechnological and pharmaceutical use. Heterotrophic bacteria associated with the intertidal macroalgae were isolated and evaluated for their pharmacological properties using various in vitro models. Among 148 cultivable isolates, more than 50% were dominated by γ-Proteobacteria and Firmicutes, wherein 53 of them showed consistent antibacterial activity against a broad spectrum of clinically significant pathogens. The bacteria were characterized by extensive microbiological, molecular and chemical identification tools. The heterotrophs Bacillus amyloliquefaciens MTCC 12716 and Shewanella algae MTCC 12715 isolated from a red marine macroalga Hypnea valentiae exhibited potential anti-infective properties against multidrug-resistant pathogens, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis (minimum inhibitory concentration of 6.25–12.5 µg/mL). The organic extract of B. amyloliquefaciens displayed significantly greater antioxidative properties (IC90 < 1 mg/mL) and the activities showed considerable positive correlation (r2 > 0.8, P < 0.05) with the inhibitory activities against angiotensin converting enzyme-I, pro-inflammatory cyclooxygenases and 5-lipoxygenase, dipeptidyl peptidase-4 and hydroxymethylglutaryl coenzyme A reductase, which were associated with hypertension, inflammation, diabetes, and hypercholesterolemia, respectively. The applications of nuclear magnetic resonance-based fingerprinting to analyze the characteristic signals in the solvent extracts and to correlate them with the pharmaceutical properties were underlined. The heterotrophic bacterium B. amyloliquefaciens MTCC 12716 might, therefore, serve as a potential therapeutic candidate to develop products with wide pharmaceutical applications.