Τρίτη, 8 Νοεμβρίου 2016

Process Development for the Care of the Person Under Investigation for Ebola Virus Disease: a Collaboration of Biocontainment Unit and Emergency Medicine Personnel

Opinion Statement

Patients presenting with epidemiological risk factors for Ebola virus disease (EVD) and symptoms consistent with the disease require screening with a molecular assay. If the initial test is negative, but the patient has been symptomatic for less than 3 days, a follow-up test is required to reliably exclude the disease. During this time, persons under investigation (PUI) for EVD may have illnesses other than EVD that require further evaluation and management and well-defined processes are essential to the delivery of consistent, high-quality care for these patients while preserving the safety of healthcare providers.



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IJERPH, Vol. 13, Pages 1100: Multilevel Safety Climate and Safety Performance in the Construction Industry: Development and Validation of a Top-Down Mechanism

The character of construction projects exposes front-line workers to dangers and accidents. Safety climate has been confirmed to be a predictor of safety performance in the construction industry. This study aims to explore the underlying mechanisms of the relationship between multilevel safety climate and safety performance. An integrated model was developed to study how particular safety climate factors of one level affect those of other levels, and then affect safety performance from the top down. A questionnaire survey was administered on six construction sites in Vietnam. A total of 1030 valid questionnaires were collected from this survey. Approximately half of the data were used to conduct exploratory factor analysis (EFA) and the remaining data were submitted to structural equation modeling (SEM). Top management commitment (TMC) and supervisors’ expectation (SE) were identified as factors to represent organizational safety climate (OSC) and supervisor safety climate (SSC), respectively, and coworkers’ caring and communication (CCC) and coworkers’ role models (CRM) were identified as factors to denote coworker safety climate (CSC). SEM results show that OSC factor is positively related to SSC factor and CSC factors significantly. SSC factor could partially mediate the relationship between OSC factor and CSC factors, as well as the relationship between OSC factor and safety performance. CSC factors partially mediate the relationship between OSC factor and safety performance, and the relationship between SSC factor and safety performance. The findings imply that a positive safety culture should be established both at the organizational level and the group level. Efforts from all top management, supervisors, and coworkers should be provided to improve safety performance in the construction industry.

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IJERPH, Vol. 13, Pages 1101: Association between Secondhand Smoke in Hospitality Venues and Urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol Concentrations in Non-Smoking Staff

The purpose of this study was to determine the relationship between urinary cotinine and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) concentrations in non-smoking staff and the indoor levels of fine particles (PM2.5) in hospitality venues that allow smoking, with respect to demographic and indoor environmental factors. We evaluated 62 hospitality venues that allowed smoking in Seoul, Korea. A real-time aerosol monitor was used to measure indoor PM2.5 concentrations. Field technicians recorded indoor environmental characteristics. One non-smoking staff member in each hospitality venue was tested for urinary cotinine and total NNAL concentrations. Demographic characteristics were obtained from self-reported staff questionnaires. Natural-log (ln)-transformed PM2.5 concentrations were significantly correlated with the ln-transformed cotinine (r = 0.31) and the total NNAL concentrations (r = 0.32). In multivariable regression analysis, the urinary cotinine concentrations of the staff members were significantly correlated with indoor PM2.5 concentrations; those with the highest concentrations were more likely to be women or staff members that worked in venues with a volume <375 m3. Total NNAL concentrations were significantly correlated only with indoor PM2.5 concentrations. Indoor PM2.5 may be used as an indicator for urinary cotinine and total NNAL concentrations in non-smoking staff members in hospitality venues that allow smoking.

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IJERPH, Vol. 13, Pages 1103: Independent Factors of Changes of Ankle-Brachial Index in Peripheral Arterial Occlusive Disease in Elderly Patients with or without Diabetes

Peripheral arterial disease (PAD) belongs to the commonly-occurring pathologies associated with elderly age. A simple tool for defining the severity of PAD is the ankle-brachial index (ABI). The purpose of this research was to determine independent factors of changes of ABI in elderly patients with occlusive PAD disease (PAOD) with and without diabetes. The research was carried out on 49 elderly patients with PAOD, including 29 patients with type 2 diabetes, and 20 patients without diabetes. The concentration of interleukin-6 (IL-6), E-selectin, fibrinogen, and C-reactive protein (CRP) in the blood serum was marked. In all patients, the independent factors of changes of ABI were determined with the use of the multiple logistic regression analysis. Our results show that in the group of patients with PAOD suffering from diabetes, it was demonstrated that the ABI was related to age, the duration of the symptoms of PAD, body mass index (BMI), low-density lipoprotein cholesterol, fibrinogen, and sex (determination coefficient R2 = 0.699). In patients with PAOD without diabetes, the ABI was related to age, the duration of the symptoms of PAD, the levels of CRP, E-selectin, high-density lipoprotein cholesterol, and the glomerular filtration rate(determination coefficient R2 = 0.844). We conclude that in elderly patients with PAOD with and without diabetes, the participation of independent factors related to the ABI is diversified; in patients with diabetes, the concentration of IL-6 and fibrinogen is lower, and the concentration of E-selectin is higher than in patients without diabetes.

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A Case of False-Positive Mycobacterium tuberculosis Caused by Mycobacterium celatum

Mycobacterium celatum is a nontuberculous mycobacterium shown to cause symptoms similar to pulmonary M. tuberculosis. Certain strains have been shown to cross-react with the probes used to detect M. tuberculosis, making this a diagnostic challenge. We present a 56-year-old gentleman who developed signs and symptoms of lung infection with computed tomography scan of the chest showing right lung apex cavitation. Serial sputum samples were positive for acid-fast bacilli and nucleic acid amplification testing identified M. tuberculosis ribosomal RNA, resulting in treatment initiation. Further testing with high performance liquid chromatography showed a pattern consistent with M. celatum. This case illustrates the potential for M. celatum to mimic M. tuberculosis in both its clinical history and laboratory testing due to the identical oligonucleotide sequence contained in both. An increasing number of case reports suggest that early reliable differentiation could reduce unnecessary treatment and public health intervention associated with misdiagnosed tuberculosis.

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Accuracy of Approximation for Discrete Distributions

The paper is a contribution to the problem of estimating the deviation of two discrete probability distributions in terms of the supremum distance between their generating functions over the interval . Deviation can be measured by the difference of the th terms or by total variation distance. Our new bounds have better order of magnitude than those proved previously, and they are even sharp in certain cases.

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Congenital Unilateral Agenesis of the Parotid Gland: A Case Report and Review of the Literature

Congenital unilateral agenesis of the parotid gland is a rare condition with only few cases reported in the literature. A review of 21 cases in the available literature is presented in this article. We report on a further case of a 34-year-old woman with agenesis of the left parotid gland and lipoma of the right cheek. Clinicopathological characteristics of described cases in the literature were discussed.

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Phase II Trial of Angiotensin-(1-7) for the Treatment of Patients with Metastatic Sarcoma

Background. Angiotensin-(1-7) [Ang-(1-7)] is an endogenous antiangiogenic hormone with anticancer activity. In a phase I study of Ang-(1-7), two of three patients with metastatic sarcoma experienced disease stabilization. This phase II study examined clinical and biomarker outcomes for patients with metastatic sarcoma. Methods. Ang-(1-7) was administered by subcutaneous injection at a dose of 20 mg daily. If excessive toxicities occurred in the first cohort, a dose deescalation cohort was allowed. Blood samples were obtained to measure changes in biomarkers. Results. Treatment was well-tolerated and the dose deescalation cohort was not required. Plasma PlGF concentrations following treatment were not statistically significantly changed. A significant increase in plasma Ang-(1-7) was observed at 4 hours after injection. The median progression-free survival was 2.7 months (95% CI; 1.4 to 4.1 months), and the median overall survival was 10.2 months (95% CI; 5.3 to 18.3 months). Two patients with vascular sarcomas demonstrated prolonged disease stabilization of 10 months (hemangiopericytoma) and 19 months (epithelioid hemangioendothelioma). Conclusions. Ang-(1-7) at a dose of 20 mg daily was well-tolerated. This prospective phase II study failed to confirm the PlGF biomarker effect identified in the prior phase I study. Prolonged disease stabilization in hemangiopericytoma and epithelioid hemangioendothelioma may warrant further investigation.

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An Improved Version of Discrete Particle Swarm Optimization for Flexible Job Shop Scheduling Problem with Fuzzy Processing Time

The fuzzy processing time occasionally exists in job shop scheduling problem of flexible manufacturing system. To deal with fuzzy processing time, fuzzy flexible job shop model was established in several papers and has attracted numerous researchers’ attention recently. In our research, an improved version of discrete particle swarm optimization (IDPSO) is designed to solve flexible job shop scheduling problem with fuzzy processing time (FJSPF). In IDPSO, heuristic initial methods based on triangular fuzzy number are developed, and a combination of six initial methods is applied to initialize machine assignment and random method is used to initialize operation sequence. Then, some simple and effective discrete operators are employed to update particle’s position and generate new particles. In order to guide the particles effectively, we extend global best position to a set with several global best positions. Finally, experiments are designed to investigate the impact of four parameters in IDPSO by Taguchi method, and IDPSO is tested on five instances and compared with some state-of-the-art algorithms. The experimental results show that the proposed algorithm can obtain better solutions for FJSPF and is more competitive than the compared algorithms.

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The Efficacy of Infliximab Monotherapy versus Infliximab-Azathioprine Sequential Treatment in Crohn’s Disease: Experience from a Tertiary Medical Center in China

Objective. To evaluate the efficacy of infliximab (IFX) monotherapy versus infliximab-azathioprine sequential treatment in Crohn’s disease (CD) patients. Methods. Patients newly diagnosed with CD using IFX as induction therapy were enrolled. After 6 times of IFX infusions, they were divided into IFX monotherapy group and IFX-AZA sequential therapy group. Clinical remission rates were assessed at weeks 57, 84, 111, and 138 while endoscopic remission rates were assessed at weeks 84 and 138 to evaluate the efficacy of these two groups. Results. A total of seventy-nine patients had accomplished 138-week follow-up. At weeks 84 and 138, the deep remission rate (18/22 and 17/22) of IFX monotherapy group was significantly higher compared to IFX-AZA sequential therapy group (26/57 and 21/57) ( and 0.001, resp.). Similar findings were found in complete endoscopic remission rate. The clinical remission rates of IFX monotherapy group were similar to that of IFX-AZA sequential therapy group (). At weeks 84 and 138, the endoscopic remission rate and the endoscopic improvement rate between these two groups displayed no significant difference (). Conclusion. IFX monotherapy provides higher deep remission rate compared with IFX-AZA sequential therapy in two-year maintenance therapy. For patients who could not receive prolonged IFX therapy, IFX-AZA sequential therapy is acceptable, though long-term efficacy remains to be seen.

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Myeloproliferative Disease: An Unusual Cause of Raynaud’s Phenomenon and Digital Ischaemia

We describe a 59-year-old female who presented with ischaemic digits, preceded by a 6-month history of Raynaud’s phenomenon affecting her fingers and toes. There were no clinical or laboratory features of primary vasculitis or connective tissue disease, Doppler imaging was normal, and bloods were unremarkable aside from a platelet count of 786 × 109/L (150–400) and white cells of 16 × 109/L (4–11). In view of the thrombocytosis a JAK2 mutation assay was requested which confirmed a JAK2 V617F mutation, suggesting essential thrombocytosis (ET) as the cause. She received treatment with hydroxycarbamide which normalised her platelet count and led to a complete resolution of her Raynaud’s symptoms. Raynaud’s phenomenon is a rare manifestation of ET. Myeloproliferative disorders such as ET should be considered in the differential diagnosis of Raynaud’s phenomenon and vasculitis.

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Midbrain Frequency Representation following Moderately Intense Neonatal Sound Exposure in a Precocious Animal Model (Chinchilla laniger)

Auditory brain areas undergo reorganization resulting from abnormal sensory input during early postnatal development. This is evident from studies at the cortical level but it remains unclear whether there is reorganization in the auditory midbrain in a species similar to the human, that is, with early hearing onset. We have explored midbrain plasticity in the chinchilla, a precocious species that matches the human in terms of hearing development. Neonatal chinchillas were chronically exposed to a 2 kHz narrowband sound at 70 dB SPL for 4 weeks. Tonotopic maps in inferior colliculus (central nucleus) were defined based on single neuron characteristic frequency. We hypothesized an overrepresentation of the 2 kHz region of the maps. However, we observed a significant decrease in the proportion of neurons dedicated to the 2 kHz octave band and also away from the exposure frequency at 8 kHz. In addition, we report a significant increase in low frequency representation (

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Dynamics Analysis of Unbalanced Motorized Spindles Supported on Ball Bearings

This paper presents an improved dynamic model for unbalanced high speed motorized spindles. The proposed model includes a Hertz contact force model which takes into the internal clearance and an unbalanced electromagnetic force model based on the energy of the air magnetic field. The nonlinear characteristic of the model is analysed by Lyapunov stability theory and numerical analysis to study the dynamic properties of the spindle system. Finally, a dynamic operating test is carried out on a DX100A-24000/20-type motorized spindle. The good agreement between the numerical solutions and the experimental data indicates that the proposed model is capable of accurately predicting the dynamic properties of motorized spindles. The influence of the unbalanced magnetic force on the system is studied, and the sensitivities of the system parameters to the critical speed of the system are obtained. These conclusions are useful for the dynamic design of high speed motorized spindles.

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Congenital Renal Fusion and Ectopia in the Trauma Patient

We present two separate cases of young male patients with congenital kidney anomalies (horseshoe and crossed fused renal ectopia) identified following blunt abdominal trauma. Despite being rare, ectopic and fusion anomalies of the kidneys are occasionally noted in a trauma patient during imaging or upon exploration of the abdomen. Incidental renal findings may influence the management of traumatic injuries to preserve and protect the patient’s renal function. Renal anomalies may be asymptomatic or present with hematuria, flank or abdominal pain, hypotension, or shock, even following minor blunt trauma or low velocity impact. It is important for the trauma clinician to recognize that this group of congenital anomalies may contribute to unusual symptoms such as gross hematuria after minor trauma, are readily identifiable during CT imaging, and may affect operative management. These patients should be informed of their anatomical findings and encouraged to return for long-term follow-up.

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Endobronchial Carcinoid and Concurrent Carcinoid Syndrome in an Adolescent Female

Endobronchial carcinoid tumors are the most common intrabronchial tumors in children and adolescents. Common signs and symptoms include persistent cough and wheezing not responsive to bronchodilators, hemoptysis, and recurrent fever. Diagnosis is frequently made by imaging and direct visualization with flexible bronchoscopy; surgery remains the gold standard treatment, and lung-sparing resections should be performed whenever possible. Though carcinoid syndrome—characterized by flushing, palpitations, wheezing, shortness of breath, and diarrhea—has been found in association with adult bronchial carcinoid tumors, to our knowledge only one previous study has reported the presence of carcinoid syndrome in a pediatric patient with an endobronchial carcinoid. Here, we report a case of a 14-year-old girl with chronic cough found to have an endobronchial carcinoid tumor and signs and symptoms consistent with carcinoid syndrome.

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Expression and Clinical Significance of the Novel Long Noncoding RNA ZNF674-AS1 in Human Hepatocellular Carcinoma

Long noncoding RNAs (lncRNAs) play crucial roles in cancer occurrence and progression. However, the relationship between the expression levels of lncRNAs and the hepatocellular carcinoma (HCC) process is unclear. The goal of this study was to determine the expression level of ZNF674-AS1, a newly found lncRNA, in HCC and its clinical association. The expression of ZNF674-AS1 in 137 pairs of tumorous and adjacent normal tissues from patients with HCC was detected by quantitative real-time reverse transcription polymerase chain reaction. Additionally, the potential associations between its level in HCC tissue and clinicopathological features were analyzed. The expression of ZNF674-AS1 in the HCC cell lines HepG2, HCCLM3, SK-Hep1, HuH7, Hep3B, and MHCC97H was significantly downregulated compared with that in the normal liver cell line QSG-7701. The expression of ZNF674-AS1 was downregulated in 72% (99/137) of HCC tissues compared with that in paired adjacent normal tissues (). The results showed that the ZNF674-AS1 expression level was significantly correlated with metastasis (), clinical stage (), and histopathologic grading (). In addition, the Kaplan–Meier survival curves revealed that low ZNF674-AS1 expression was associated with poor prognosis in patients with HCC. Our data suggest that ZNF674-AS1 may play some role during cancer occurrence and progression and may be a new biomarker for HCC.

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P(3HB) Based Magnetic Nanocomposites: Smart Materials for Bone Tissue Engineering

The objective of this work was to investigate the potential application of Poly(3-hydroxybutyrate)/magnetic nanoparticles, P(3HB)/MNP, and Poly(3-hydroxybutyrate)/ferrofluid (P(3HB)/FF) nanocomposites as a smart material for bone tissue repair. The composite films, produced using conventional solvent casting technique, exhibited a good uniform dispersion of magnetic nanoparticles and ferrofluid and their aggregates within the P(3HB) matrix. The result of the static test performed on the samples showed that there was a 277% and 327% increase in Young’s modulus of the composite due to the incorporation of MNP and ferrofluid, respectively. The storage modulus of the P(3HB)MNP and P(3HB)/FF was found to have increased to 186% and 103%, respectively, when compared to neat P(3HB). The introduction of MNP and ferrofluid positively increased the crystallinity of the composite scaffolds which has been suggested to be useful in bone regeneration. The total amount of protein absorbed by the P(3HB)/MNP and P(3HB)/FF composite scaffolds also increased by 91% and 83%, respectively, with respect to neat P(3HB). Cell attachment and proliferation were found to be optimal on the P(HB)/MNP and P(3HB)/FF composites compared to the tissue culture plate (TCP) and neat P(3HB), indicating a highly compatible surface for the adhesion and proliferation of the MG-63 cells. Overall, this work confirmed the potential of using P(3HB)/MNP and P(3HB)/FF composite scaffolds in bone tissue engineering.

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Detection of Surface Defects on Steel Strips Based on Singular Value Decomposition of Digital Image

Image segmentation technology has been widely used to detect the surface defects in metal industries effectively. In some fields of the manufacturing industry, the determination of defects is more concerned than the accurate location and shape of defects. However, most of current image segmentation algorithms are complex or have difficulty determining the defect. This paper presents a novel method for determining and roughly locating the surface defects of steel strips based on Singular Value Decomposition. The method has no need of image segmentation. The gray level matrix of a digital image is projected on its singular vectors obtained by Singular Value Decomposition. A defect is reflected as a sudden change on the projections. Therefore, the defects can be determined and roughly located according to the sudden changes. The experimental results suggest that this method is valid and convenient for determining the surface defects directly.

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IJMS, Vol. 17, Pages 1860: Focal Adhesion Kinase-Dependent Role of the Soluble Form of Neurotensin Receptor-3/Sortilin in Colorectal Cancer Cell Dissociation

The aim of the present review is to unravel the mechanisms of action of the soluble form of the neurotensin (NT) receptor-3 (NTSR3), also called Sortilin, in numerous physiopathological processes including cancer development, cardiovascular diseases and depression. Sortilin/NTSR3 is a transmembrane protein thought to exert multiple functions both intracellularly and at the level of the plasma membrane. The Sortilin/NTSR3 extracellular domain is released by shedding from all the cells expressing the protein. Although the existence of the soluble form of Sortilin/NTSR3 (sSortilin/NTSR3) has been evidenced for more than 10 years, the studies focusing on the role of this soluble protein at the mechanistic level remain rare. Numerous cancer cells, including colonic cancer cells, express the receptor family of neurotensin (NT), and particularly Sortilin/NTSR3. This review aims to summarize the functional role of sSortilin/NTSR3 characterized in the colonic cancer cell line HT29. This includes mechanisms involving signaling cascades through focal adhesion kinase (FAK), a key pathway leading to the weakening of cell–cell and cell–extracellular matrix adhesions, a series of events which could be responsible for cancer metastasis. Finally, some future approaches targeting the release of sNTSR3 through the inhibition of matrix metalloproteases (MMPs) are suggested.

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IJMS, Vol. 17, Pages 1852: X-Linked miRNAs Associated with Gender Differences in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune disease that predominantly affects women. MicroRNAs have emerged as crucial regulators of the immune system, whose expression is deregulated in RA. We aimed at quantifying the expression level of 14 miRNAs located on the X chromosome and at identifying whether differences are associated with disease and/or sex. A case–control study of 21 RA patients and 22 age- and sex-matched healthy controls was performed on peripheral blood mononuclear cells. The expression level of five miRNAs (miR-221, miR-222, miR-532, miR-106a, and miR-98) was significantly different between RA and controls when stratifying by sex, and the expression level of four miRNAs (miR-222, miR-532, miR-98, and miR-92a) was significantly different between RA females and males. The expression quantitative trait loci (eQTL) analysis revealed a significant gender effect of the FoxP3 promoter polymorphism rs3761548A/C on miR-221, miR-222 and miR-532 expression levels, and of the FoxP3 polymorphism rs2232365A/G on miR-221 expression levels in PBMC of RA patients. These data further support the involvement of the X chromosome in RA susceptibility. X-linked miRNAs, in the context of sex differences, might provide novel insight into new molecular mechanisms and potential therapeutic targets in RA for disease treatment and prevention.

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Phase II clinical trial using novel peptide cocktail vaccine as a postoperative adjuvant treatment for surgically resected pancreatic cancer patients

Abstract

We investigated peptide cocktail vaccine OCV-C01 containing epitope peptides derived from KIF20A, vascular endothelial growth factor receptor (VEGFR)1, and VEGFR2 combined with gemcitabine in the adjuvant treatment for resected pancreatic cancer patients. A single-arm multicenter phase II study was performed on 30 patients with pancreatic ductal carcinoma who underwent pancreatectomy. At each 28-day treatment cycle, patients received weekly subcutaneous injection of OCV-C01 for 48 weeks, and gemcitabine was administered intravenously at 1,000 mg/m2 on days 1, 8, and 15 for 24 weeks. Patients were followed for 18 months. The primary endpoint was disease-free survival (DFS) and secondary endpoints included safety, overall survival (OS) and immunological assays on peptide-specific cytotoxic T lymphocyte (CTL) activity and KIF20A expression in resected pancreatic cancer. The median DFS was 15.8 months (95% confidence interval (CI), 11.1-20.6), and the DFS rate at 18 months was 34.6% (95% CI, 18.3-51.6). The median OS was not reached and the OS rate at 18 months was 69.0% (95% CI, 48.8-82.5). The administration of OCV-C01 was well tolerated. In the per protocol set, there were significant differences in DFS between patients with KIF20A-specific CTL responses and without (p=0.027), and between patients with KIF20A expression and without (p=0.014). In addition, all four patients who underwent R0 resection with KIF20A expression had no recurrence of pancreatic cancer with KIF20A-specific CTL responses. OCV-C01 combined with gemcitabine was tolerable with a median DFS of 15.8 months, which was favorable compared with previous data for resected pancreatic cancer. This article is protected by copyright. All rights reserved.



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Gamma-glutamyltransferase and risk of prostate cancer: Findings from the KIHD prospective cohort study

Abstract

Increased circulating serum gamma-glutamyltransferase (GGT) has been linked with an increased risk of chronic disease outcomes, including overall and several site-specific cancers. However, the relationship of GGT with prostate cancer risk is uncertain. We aimed to assess the prospective association of GGT with risk of prostate cancer. Serum GGT activity was assessed at baseline in the Finnish Kuopio Ischemic Heart Disease prospective cohort of 2,390 men aged 42-61 years without a history of cancer at baseline. We corrected for within-person variability in GGT values using data from repeat measurements taken several years apart. During a median follow-up of 24.6 years, 230 cases of prostate cancer occurred. The age-adjusted regression dilution ratio for loge GGT was 0.69 [95% confidence interval (CI): 0.63-0.74]. Serum GGT was nonlinearly associated with risk of prostate cancer. In age-adjusted Cox regression analysis, the hazard ratio (HR) (95% CIs) for prostate cancer in a comparison of the top quartile versus bottom quartiles 1-3 of GGT values was 1.43 (1.07 to 1.93; P=0.017), which persisted on adjustment for several established cancer risk factors 1.46 (1.06 to 2.02; P=0.020). The association remained unchanged on further adjustment for total energy intake, socioeconomic status, physical activity, and C-reactive protein. The association did not importantly vary across several clinical subgroups. Gamma-glutamyltransferase is positively and independently associated with future risk of prostate cancer in a middle-aged Finnish male population over long-term follow-up. Further research is needed to understand the mechanistic pathways involved and if GGT may have potential relevance in prostate cancer prevention. This article is protected by copyright. All rights reserved.



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KRAS driven expression signature has prognostic power superior to mutation status in non-small cell lung cancer

Abstract

KRAS is the most frequently mutated oncogene in non–small cell lung cancer (NSCLC). However, the prognostic role of KRAS mutation status in NSCLC still remains controversial. We hypothesize that the expression changes of genes affected by KRAS mutation status will have the most prominent effect and could be used as a prognostic signature in lung cancer.

We divided NSCLC patients with mutation and RNA-seq data into KRAS mutated and wild type groups. Mann-Whitney test was used to identify genes showing altered expression between these cohorts. Mean expression of the top five genes was designated as a “transcriptomic fingerprint” of the mutation. We evaluated the effect of this signature on clinical outcome in 2,437 NSCLC patients using uni- and multivariate Cox regression analysis.

Mutation of KRAS was most common in adenocarcinoma. Mutation status and KRAS expression were not correlated to prognosis. The transcriptomic fingerprint of KRAS include FOXRED2, KRAS, TOP1, PEX3, and ABL2. The KRAS signature had a high prognostic power. Similar results were achieved when using the second and third set of strongest genes. Moreover, all cutoff values delivered significant prognostic power (p<0.01). The KRAS signature also remained significant (p<0.01) in a multivariate analysis including age, gender, smoking history and tumor stage.

We generated a “surrogate signature” of KRAS mutation status in NSCLC patients by computationally linking genotype and gene expression. We show that secondary effects of a mutation can have a higher prognostic relevance than the primary genetic alteration itself. This article is protected by copyright. All rights reserved.



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FORMULATION OF BIOADHESIVE CHITOSAN/PLURONIC THERMOSENSITIVE IN-SITU GEL FOR MODIFIED RELEASE OF GATIFLOXACIN

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
Shah Hirva*, Shah Dhiren, Vashi Jenisha.
Bacterial conjunctivitis requires treatment of antibiotics for almost a week. It may result in poor patient compliance with conventional dosage forms due to greater frequency of drug administration. Some dosage regimens are 2-3 drops every 2-3 hours. The excessive drug loss is exhibited by conventional formulations in the cul-de-sac upon instillation. The thermosensitive Chitosan/Pluronic in-situ gel loaded with Gatifloxacin, used for bacterial conjunctivitis, exhibited sol-gel transition upon instillation. The formulation prepared by polymer mixing exhibited bioadhesive and gelling properties. The selected independent variables were percentage of Pluronic F127 (A) and percentage of Chitosan (B) and dependent variables were gelling temperature and bioadhesive strength. This temperature triggered gelling system was prepared with the objectives of increasing contact time, achieving controlled release, reducing the frequency of administration and obtaining greater therapeutic efficacy of the drug. The characterization showed that all formulations had clarity, variation in gelling capacity. Other physical properties like pH, viscosity and drug content were found to be varying from 7.1-7.7, 240-410 cps, and 84.62-96.83% respectively. Therefore, the formulation having 0.3%w/v chitosan and 20% w/v Pluronic F127 exhibited the critical gelling temperature at 37°C and bioadhesion strength of 4.0 g/cm2. This formulation showed better sustained drug release i.e. 75.10% drug release for period of 10 hours.


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PHYSICOCHEMICAL CHARACTERIZATION, IN-VITRO STUDIES AND IN-VIVO ASSESSMENT OF DRUG CYCLODEXTRIN INCLUSION COMPLEX FOR ORAL BIOAVAILABILITY ENHANCEMENT OF FEBUXOSTAT

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
Abhishek Pathak*, Sadhana J Rajput.
The objective of this research was to enhance the oral bioavailability of Febuxostat (FBX) by preparing the Febuxostat/cyclodextrin inclusion complex. The β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, Methyl-β-cyclodextrin and γ-cyclodextrin were used to prepare inclusion complex with FBX by physical mixing, kneading method and freeze drying method. And 2-hydroxypropyl-β-cyclodextrin was selected as a best fit carrier for inclusion of FBX in (1:1) molar ratio on the basis of phase solubility and inclusion efficiency study. Freeze drying method was found most effective method in terms of solubilization and dissolution of FBX. The physicochemical characterization of prepared inclusion complexes was performed by Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD) and Infra-red spectroscopy (IR) analysis indicated the perfect inclusion of FBX in 2-hydroxypropyl-β-cyclodextrin. Adequate dissolution was achieved in distilled water and phosphate buffer pH-6.8. In-vitro Cell Cytotoxicity Studies (MTT Assay) using Caco-2 cell line model confirmed the bio-tolerability of FBX-inclusion complexes. In vivo assessment demonstrated that freeze dried inclusion complex of FBX with 2-hydroxypropyl-β-cyclodextrin exhibited better pharmacokinetic properties compared to plain FBX and commercial formulation. The relative oral bioavailability of FBX in Albino rabbits resulted from Freeze dried inclusion complex was found 3.08 fold and 2.29 fold greater than plain FBX and marketed formulation, respectively.


http://ift.tt/2fc7sY1

SIMULTANEOUS DETERMINATION OF FLURBIPROFEN AND PANTOPRAZOLE IN BULK AND PHARMACEUTICAL DOSAGE FORM BY RP-HPLC

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
Varaprasad Adepu*, K.E.V Nagoji, V.Girijasastry.
RP-HPLC method is developed for determination of pantoprazole and flurbiprofen in binary combination. Pantoprazole and flurbiprofen were detected at 270 nm using a BDS Hypersil C8 (250 X 4.6 mm, 5 μm) column and mixture of 0.02M phosphate buffer (pH 3.0) and acetonitrile 30:70 v/v as mobile phase.The flowrate was 1ml/min and effluent was detected at 270nm. Response was linear over the range of 10-100 mcg/ml for pantoprazole and of 5-50 mcg/ml for flurbiprofen. The retention time of flubiprofen was 2.407 min and pantoprazole was 5.441 min.The developed method efficiently separated the analytical peaks from mixture. The method was validated according to ICH guidelines with respect to specificity, linearity, accuracy, precision, LOD and LOQ. The method developed can be applied successfully for determination of pantoprazole and flurbiprofen in dosage form.


http://ift.tt/2fyQr8Y

MULTIPLE DISEASES AND POLYPHARMACY IN THE ELDERLY CARDIOVASCULAR DISEASE PATIENTS: CHALLENGES FOR THE INTERNIST WITH A NEED FOR AN EFFECTIVE SOLUTION

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
Battu Rakesh*, Emilda .T. Joy, Jaladi Himaja, Dr.B.S.Suresha.
Polypharmacy is arguably one of the most pressing prescribing issues. There is no formally accepted definition, but it is usually considered as concurrent prescribing of at least four or five drugs. Multiple diseases and multimorbidity inevitably lead to the use of multiple drugs, a condition known as polypharmacy. Polypharmacy, a preventable and significant contributor to morbidity and mortality in geriatrics of cardiovascular disease. Aging seldom comes alone, often being accompanied by chronic diseases, co-morbidity, disability and frailty. Older people are particularly prone to adverse consequences due to age related physiological changes altering the pharmacokinetic and pharmacodynamics characteristics of many medicines. Over the last 2030 years, problems related to aging, multimorbidity, and polypharmacy have become a prominent issue in global healthcare. Therapy in Intensive Care Unit (ICU) often involves poly pharmacy and patients require close therapy monitoring. Polypharmacy also has the potential to influence many aspects of safe prescribing, including adverse drug reactions, risk of medication interactions, and adherence. Clinical pharmacists need to challenge the current culture of ratcheting up numbers of medications, and to increase awareness of the consequences of polypharmacy. This can be addressed, in part, through continued medical education, and also through clinical guidelines, particularly for common conditions affecting older patients. Proactively addressing the problem has significant potential to maximise quality of life for patients, help patients to manage their own medicines, reduce adverse effects, and encourage more rational and efficacious drug use. When individualization of therapy is warranted, the role of pharmacist can prove to be the best in achieving the therapeutic goals and improve the treatment outcomes of the patients. The main objectives of the study are to assess the prevalence of polypharmacy in cardiovascular disease patients ≥ 65 years and to assess the various causes for polypharmacy and to reduce and manage polypharmacy. This Cross Sectional study was carried out in the Department of General Medicine, MIMS Teaching Hospital, Mandya, Karnataka, using a well-designed patient data collection form. Among 114 cardiovascular disease patients analysed 65 patients were males (57.01%) and 49 (42.99%) were females. Among all admitted patients in ICCU, RICU, MICU and medical wards (male and female) for cardiac problems, patients were suffering mostly from co-morbid conditions and commonly found co-morbid condition was hypertension and diabetes mellitus, which supports the study that polypharmacy is extremely high in Hypertensive and Diabetic patients are more prone to high risk of complications (Drug-Drug Interactions and Adverse drug reactions). Polypharmacy was identified in 86 patients (75.43%) which include 51 (59.30%) males and 35 (40.70%) females. The study highlights the emergency department as a place where potential drug interactions can be identified in high-risk elderly patients. The presence of a Clinical Pharmacist would be of potential benefit to the process of identification of Polypharmacy and drug interactions. Furthermore, rational prescribing for the elderly should essentially involve listing potentially inappropriate medications, where the risks of administration may outweigh the benefits of administration. Polypharmacy places geriatric patients at risk of adverse events, functional decline, and geriatric syndromes. The strategies such as use of a risk stratification tool and application of palliative care principles represent initial steps forward to reduce polypharmacy.


http://ift.tt/2fbYSZi

PHYTOCHEMICAL SCREENING AND BIOPESTICIDAL EFFICACY OF SOME PLANTS OF EAST SINGHBHUM, JHARKHAND

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
Namrata Kumari, Kiran Shukla, Hanuman Prasad Sharma.
Preliminary phytochemical studies have been carried out on 5 plant species, growing wildly in East Singhbhum,district of Jharkhand. The leaf extracts were prepared using organic solvent in soxlet apparatus. Three insect pests viz. storage pest, mealybugs and cut worm/caterpillar were used in the study. All the five plants studied exhibited pesticidal properties which are dose dependent. Annona squamosa and Cleistanthus collinus contains highest amount of the phytochemical and are most effective in these pest. It can be used as bio-pesticides. Blumea balsamifera was least effective as pesticides.


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EFFECT OF MIXING ESSENTIAL OILS CONTENTS OF ARTEMESIA HERBA ALBA ASSO. AND ARTEMISIA MONOSPERMA DELILE ON PATHOGENIC BACTERIA OF URINARY TRACT

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
Heba Ibrahim Abd EI-Moaty, Rehab A. Lotfy.
The objective of the study is to assess antibacterial activities of essential oil and its mixture of two Artemesia species against four bacterial strains isolated from urine (Escherichia coli, Pseudomonas aeruginosa, Proteus spp. and Klebsiella spp.). The essential oils percentages of the aerial parts of Artemesia herba alba and Artemesia monosperma were 0.83 % and 0.22 %, respectively as clear yellowish liquid oil. Mixing essential oil of both plants with ratio (1:2 v: v), respectively, gave highest antibacterial activity, then the mixture were investigated using GC MS, beside investigation the essential oil of each plant alone. The obtained results showed that, the major constituents of the essential oil of Artemesia herba alba were Geraniol (28.27 %), Artemesia alcohol (24.92 %), Yomogi alcohol (13.05 %) and αˈ-Ionol (11.66 %), which resembled monoterpene alcohol compounds. Meanwhile the major constituents of the essential oil of Artemesia monosperma were Naphthalene 2-ethenyl (Aromatic hydrocarbon) (35.20 %), Imidazolidine (Heterocyclic compound) (19.27 %), and 2αˈ-pinene (Monoterpenes) (10.89 %). On other-hand the obtained major components of the mixture (1: 2, v: v) were Naphthalene 2-ethenyl (31.78 %), Imidazolidine (14.84%) and 2αˈ-pinene (12.93 %). Meanwhile the mixture of Artemesia herba alba and Artemesia monosperma with ratio (1: 2 v: v, respectively) showed highest antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Proteus spp. and Klebsiella spp. isolated from urine. The present study scientifically proved that the mixture of essential oil of Artemesia herba alba and Artemesia monosperma is antimicrobial agent that can be used to treat urinary tract infectious diseases.


http://ift.tt/2fc5PK2

SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF N-HETEROCYCLIC SUBSTITUTED HYDRAZONE SCHIFF’S BASES

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
Vrushali T. Kale*, Archana S. Burghate, Shrikant A. Wadhal.
The present research deals with the synthesis, spectral studies and biological evolution of substituted hydrazone schiffs bases derivatives of benzothiazolyl and benzimidazolyl for antimicrobial activity. the compounds were synthesized by green chemistry technique which includes synthesis series of 2-[1-(Benzothiazole-2-yl hydrazono)-ethyl]-4-methyl phenol 3, 2-(Benzothiazole-2-yl hydrazono)-methyl)- phenol, N-Benzothiazole-2-yl-N-(1-4-chloro-phenyl)-ethylidene]-hydrazine ,2-[1-H-Benzimidazole-2-yl hydrazono)-methyl]-4-methyl phenol and implemented for their antibacterial activity study. The antimicrobial activities of these synthesized compounds are done by agar disc diffusion method at two different concentrations in DMSO against gram positive bacteria Staphylococcus aureus and gram negative bacteria Escherichia coli. Structures of all the newly synthesized compounds were confirmed by their IR, 1H-NMR and CHN analysis .From the synthesized compounds 3a,3b,3c biologically active Escherichia.coli and Staphylococcus. Aureus.


http://ift.tt/2fyMuRS

NIOSOMES- A NOVEL TOOL FOR ANTI-AGEING COSMECEUTICALS

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
Prabha Singh*, Huda Ansari, Shalan Dabre.
Aging is a complex biological process that has not yet been completely elucidated. Human aging and longevity are affected by multiple reasons like genetic factors, environmental factors such as diseases, lifestyle, and social factors. Ageing gives rise to different age related diseases like cognitive impairment, diabetes mellitus, and frailty. Also people around the world have always been looking for better health and appearance. Therefore, the ideal anti-ageing formulation should be applicable for both maintaining the healthful appearance as a cosmetic product as well as preventing the development of degenerative diseases. With increasing advancement in the field of science and technology and also with increase in the information about products available through the use of social media, formulating new products and advertising them have become quite easy. Nowadays formulation containing nanotechnology combined with cosmeceuticals is growing on a larger scale. Thus, we can say that novel cosmetic delivery systems have enormous potential and are next generation carrier systems. Novel drug delivery systems like liposomes, were discovered in 1960s and since then they have been used effectively. However, due to their stability issues, new delivery systems like niosomes were discovered with improved stability. Niosomes are used in the field of cosmetics since the early 1970s. They are stable with good penetrating power and less irritating as compared to other colloidal carrier systems. This review article focuses on the role of niosomes as a carrier for anti-aging topical products.


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MIXED HYDROTROPY: A RISING TOOL FOR SOLUBILITY ENHANCEMENT OF TRANSDERMAL DRUG DELIVERY AND COSMECEUTICAL APPLICATIONS

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
Satish Polshettiwar, Snehal Shivaji Khorate*.
Solubility is the important phenomenon in pharmaceutical formulation, which plays very effective and significant role in the designing of various dosage forms. It is important characteristics of a drug for its oral bioavailability, formation and development of different dosage form of different drugs and for quantitative analysis. There are many techniques which are used to enhance the aqueous solubility, hydrotropy is one of them which is simple, advance, cost effective, eco-friendly and novel method. Hydrotropy is defined as a solubilization process whereby addition of a large amount of second solutes results in an increase in the aqueous solubility of another solute and chemicals which are used in the hydrotropy are called hydrotropes like sodium benzoate, sodium citrate, urea, niacinamide etc. To achieve highest degree of solubility hydrotropes can be combined with polymers or cosolvents as in mixed hydrotropy. Mixed hydrotropic solubilization technique is the phenomenon to increase the solubility of poorly water-soluble drugs in the blends of hydrotropic agents which gives synergistic enhancement in solubility. Based on advantages of certain properties like the high selectivity, independent of pH and cheap, easy availability makes this technique more powerful than other Solubilization methods. In the present review attempt has been made to provide detailed information on the novel applications of hydrotropy with respect to Cosmeceutical and transdermal formulations as well the mechanism of hydrotropes, hydrotropic agents, classification and Solubilization of hydrotropes, several hydrotropes used in tablet formulation are discussed.


http://ift.tt/2fyRR3s

3 H-QUINAZOLIN-4-ONES AS ANTICANCER AGENTS: A REVIEW

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
Nilesh S. Khairnar*, Jogendra C. Hundiwale, Avinash V. Patil.
Heterocyclic chemistry composed of at least fifty percent of all organic chemistry research worldwide which contains heterocyclic moieties. 4(3H)-Quinazolinone is nothing but the 3H-Quinazolin-4-one which play a prominent role in the field of Pharmaceutical Medicinal Chemistry for to invent or discover the new potent moiety. It is strongly showing evidence as active chemical agents in all human being or in animals by their pharmacological activity. 4(3H)-Quinazolinone and their entire derivatives having very good pharmaceutical utility among the influential classes of heterocyclic moieties by synthesizing it through various synthetic avenues. It shows some of the Pharmaceutical or Biochemical activities like anticancer, analgesic & anti-inflammatory, anti HIV, antimicrobial, anticonvulsant, antimalerial & antifungal etc. from the literature survey. Cancer is very crucial or critical health problem now a day in developing as well as undeveloped countries. It has achieved first position as killer by surpassing the heart disease also from all over the world. It is quiet difficult task to design novel antitumor agent in lab level but it is critically very important. The purpose of this review was to follow literature work reported by researchers on 3H-Quinazolin-4-ones for only anticancer activity. This review might be helpful in the development of novel lead molecules which is having heterocyclic nucleus to potential drug profile for future prospect as anticancer agent and become prospective part in fulfillment of pharmaceutical world. Epidermal Growth Factor Receptor (EGFR) is made from one of the erbB members which come from Tyrosine Kinase Receptor (TKR). It is cellular transmemberane glycoprotein.


http://ift.tt/2fc1A16

THIAZOLES AS AN ANTICANCER AGENT: AN OVERVIEW

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
Prabodh V. Sapkale, Avinash V. Patil.
Cancer is a potentially major disease caused mainly by many surrounding factors that mutate genes encoding critical cell-regulatory proteins. The resultant aberrant cell behaviour leads to expansive masses of abnormal cells that destroy surrounding normal tissue and can spread to vital organs resulting in disseminated disease, commonly patient death is occurred. Structurally diverse thiazoles with electron-donating and electron-withdrawing groups were conveniently synthesized through various methods which are explained in this review. The effect of substitution at the 2- and 4-positions was investigated. Thiazole is also showing various biological activities but recently it shows major activity as anticancer with minimizing side effect and adverse effect. It also has large area for research with same biological activity.


http://ift.tt/2fyJLb2

STUDIES ON THE FORMULATION AND EVALUATION OF FAST DISSOLVING DOSAGE FORMS OF LORATADINE

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
Ramesh KVRNS*, Maha Hammad Sitta, Omar Sarheed, Shahnaz Usman, Hemant Yadav, Fasiha Shah, Quamrul Islam.
Loratadine is a anti allergic drug (NSAID) used in the management of the symptomatic relief of allergy such as hay fever (allergic rhinitis), urticarial (hives), chronic idiopathic urticaria. Loratadine is a poorly water-soluble drug and for such drugs, dissolution plays an important role in their absorption. In the present investigation, an approach of solvent deposited systems of the dispersions of loratadine in Gelucire 50/13 (G) and Hydroxypropyl cellulose (HPC) on Neusilin (N) were prepared to enhance the dissolution of loratadine. Dispersions were prepared employing different proportions of the carriers. The prepared dispersions were characterized by infra-red spectroscopy, x ray diffraction and differential scanning calorimetry. The results of the XRD and DSC study indicated that the drug existed in amorphous form in the dispersions. The dispersions exhibited higher dissolution compared to the pure drug and there were no interactions with the carriers. Dispersion in gelucire showed much higher dissolution than the dispersion in hydroxypropyl cellulose. There was 10 to 12 fold increase in dissolution rate with various dispersions when compared with the pure drug. Dispersions on neusilin resulted in products which had good flow properties enabling direct compression of the dispersion into tablets. The Kawakita constants calculated for the various products are suggestive of good flow character. All the tablets showed good pharmaceutical characteristics and exhibited rapid dissolution. From the results of the investigation in may be concluded that employing solvent deposited systems of the solid dispersions is a useful approach to prepare the fast dissolving tablets of loratadine.


http://ift.tt/2fc7HTd

SYNTHESIS AND ANTIMICROBIAL SCREENING OF SOME NEW N-ACETYL PYRAZOLINES FROM SUBSTITUTED CHALCONES

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
Abdulkareem Ali Hussein,*, Bushra Ahmed Kateb,, P.A. Kulkarni.
In the present study, a novel series of N-acetyl pyrazolines (4a-j) were synthesized from different chalcones (3a-j) with hydrazine hydrate and glacial acetic acid. The compounds were synthesized and characterizes by TLC, melting points, IR, and 1H-NMR spectra. All the synthesized compounds have been screened and evaluated for antibacterial activity against Staphylococcus aureus gr +ve, Escherichia coli gr ve, Bacillus subtilis gr +ve, Salmonella typhi gr ve , and antifungal activity against Aspergillus oryzoe, Aspergillus niger, using disc diffusion method. The compounds show the moderate to good activity against bacteria. The new structural classes of compounds may prove as lead molecules and good candidates for the future investigations.


http://ift.tt/2fyRPIS

RUNNING MORTALITY SYNDROME (RMS) IN FARM-REARED SHRIMP, LITOPENAEUS VANNAMEI CULTURE SYSTEMS IN ANDHRA PRADESH, INDIA

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
S. A. Mastan, Md. Osman Ahmed*.
Since 2011, a new syndrome has struck the shrimp industry in India. The syndrome was such that, the farmed shrimp in the affected ponds show different mortality patterns which results in unusual symptoms with no co-relation to any other reported diseases. In running mortality syndrome affected farms mortality percentage reaching upto 50-70% and as a result of this several farmers have partially harvested in the middle of crop and some farmers were closed down their farming operations for two or three seasons. The symptoms includes cut antennae, uropods turn red in colour and later the hepatopancreas begins will turn reddish yellow; finally entire body turns dark red in colour. A continuous internal mortality of shrimp was observed in affected ponds. The dead shrimp settle down in the bottom of the affected ponds and do not come surface. Mortality was observed only during inter- moult stage. Mortality rate is relatively more in low saline ponds. White or yellow faecal matter was noticed in the gut of affected shrimps. This condition is known as Running Mortality Syndrome (RMS).The present paper reports the incidences of Running Mortality Syndrome (RMS) in Litopenaeus vannamei culture systems in Andhra Pradesh.


http://ift.tt/2fc90Bv

STUDY OF PONGAMIA PINNATA FLOWER AND SEED EXTRACTS FOR THEIR ANTIOXIDANT AND ANTIBACTERIAL ACTIVITY

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
R. S. A. Sorna Kumar*, R. Rajeswari, M. Selvakumar, N. Karthick raja, N. Hariharan.
Various plants that have rich medicinal properties have been used to cure many diseases for several thousand years. Pongamia pinnata is widely used as a traditional medicine commonly known as Pungai in tamil which has been distributed throughout the India.P. pinnata is a source of biomedicines have been used as a crude drug for the treatment of tumours, piles, skin diseases, itches, abscess, painful rheumatic joints wounds, ulcers, diarrhoea etc. In this study,it was found that flower extract possess good antioxidant activity wherein seed extracts gave good antimicrobial activity.it was also found that kernel is less toxic to haemocytes than flower. Methanolic flower extracts also showed higher free phenolic content, Aqueous flower extract had maximum antioxidant activity. Aqueous flower extract was found to be active against Brucella melitensis and P.fluroscens. Based on the study it was found that flower extract possess good antioxidant activity wherein seed extracts gave good antimicrobial activity.


http://ift.tt/2fyNo0F

ANTIBACTERIAL, ANTIFUNGAL AND CYTOTOXICITY ACTIVITY OF METHANOLIC EXTRACT OF EUPHORBIA HITRA AGAINST PC-3 AND MCF-7 CELL LINES

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
Perumal .R, Selvamaleeswaran .P, Maheswaran .S, Sureshkumar .M.
Plants are considered to be a perennial source of medicine from time immemovial. The phytochemical screening was carried on the leaves extracts of Euphorbia hitra, divulged the presence of some active ingredients namely alkaloids, tannins, saponnins, phenols, steroids, flavanoids and terpenoids. The antibacterial activities of methanol extract of Euphorbia hitra aganist some pathogens; Proteus vulgaris Enterococcus faecalis and Pseudomonas aeruginosa .The well diffusion method was used to determine the antibacterial activity. The antifungal activities of methanol extract of Euphorbia hitra aganist some fungus; Trichophyton rubrum, Trichophyton mentagarophytes and Alternaria solan the disc diffusion method was used to regulate the antifungal activity. The prostate cancer is the most important form of cancer in males and the second leading cause of cancer related death.MCF-7 and PC-3 cell lines was derived from adinocarcinoma of human prostate this was assayed for MTT assay on treatment with Methanolic leaf extract of Euphorbia hitra where in inhibition of the cell growth was noticed.


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FORMULATION AND EVALUATION OF EXTENDED RELEASE MATRIX TABLETS OF TENATOPRAZOLE SODIUM USING NATURAL POLYMERS

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
B. Divya*, J. Sreekanth, D. Satyavati.
Delayed release dosage forms are the best formulations which are used for drugs that are destroyed in the gastric fluids, or cause gastric irritation, and are absorbed preferentially in the intestine. The stability of Proton pump inhibitors is a function of pH; these are rapidly degraded in acid media, and are stable under alkaline conditions. Therefore exposure of Tenatoprazole sodium to the acidic content of the stomach would lead to significant degradation of the drug and hence, reduced bioavailability. The present investigation is aimed to formulate the matrix tablets of Tenatoprazole sodium with cashew nut tree gum, Okra gum and Xanthum gum and during formulation of the matrix tablets, granules are prepared with drug and polymers and dried and sieved well and were finally enteric coated with AQOAT AS-MF to prevent the tablets from acidic environment. Then the granules are compressed in to tablets. The tablets were evaluated for preformulation studies like angle of repose, bulk density, compressibility index and physical characteristics like hardness, weight variation, friability and drug content. In-vitro release of drug was performed in phosphate buffer solution pH 6.8 for twelve hours. All the physical characters of the fabricated tablet were within acceptable limits. It is cleared through the dissolution profile of Tenatoprazole sodium matrix tablets prepared using different polymers were indicated an increase in the polymer ratio retarded the drug release to a greater extent as evident from the in vitro drug release profile of batches A-3, B-3 & C-3. Therefore, 50% polymer level was found to be ideal for the matrix system. A better sustained drug release i.e 89.7±0.32 % drug release was obtained with the matrix tablet (Batch B-3) made-up of the Okra gum (Drug: polymer ratio=1:1) than with the cashew nut tree gum and Xanthum gum.


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A STUDY ON SEVERITY OF POTENTIAL DRUG DRUG INTERACTIONS IN COMMUNITY PHARMACIES OF MYSORE CITY

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
Patel Jaskumar Nileshkumar, Ansu Anie Sunny, Jaidev Kumar*, Mit Kaushikbhai Suthar, Umesh.
Pharmacoepidemiologic studies, carried out in Europe and the Americas, have found varying rates of potential drug-drug interactions, ranging from 5% to 80%. Risk factors that have showed closer association with the presence of potential drug-drug interactions in previous studies includes Polypharmacy, age, gender, clinical conditions, medications and the number of physicians that a patient visits. By applying computerized DDI screening programs research investigators can significantly improve the identification of potentially harmful DDIs, beyond what can be achieved with manual review alone and the main objective of the study is to assess the potential drug-drug interactions in prescriptions of patients with chronic diseases in community setting and to evaluate the severity of drug-drug interaction. Among 500 potential drug-drug interactions, majority of PDDIs were moderate in severity (n=354, 71%) followed by major PDDIs (n=126, 25.4%) and minor PDDIs (n=20, 4%). This finding was similar to that found in another study performed by Anna Chatsisvili et al in community pharmacies in Greece where majority of PDDIs were moderate in severity. PDDIs involving beta adrenergic blockers and oral hypoglycemic agent (glimepiride+metformin) were the highest recorded (22.4%) followed by beta blockers and dihydropyridine calcium channel blockers (10.6%), ACE inhibitors and thiazide diuretics (8.2%). Our research study was only observational study; as a result investigators could not be able to evaluate the health care outcomes of the patients which remains as one of the biggest limitations of this research study.


http://ift.tt/2fc79wC

DIACEREIN NANOSUSPENSION: PROCESS OPTIMIZATION, PHYSICOCHEMICAL CHARACTERIZATION, CYTOTOXICITY ASSESSMENT AND IN-VIVO EVALUATION FOR ORAL BIOAVAILABILITY ENHANCEMENT

2016-11-08T01-11-23Z
Source: Indo American Journal of Pharmaceutical Research
Abhishek Pathak*, Sadhana J Rajput.
The present research was focused on bioavailability enhancement of Diacerein (DAR) by formulating an efficient Diacerein nanosuspension (DAR-NS) through wet media milling using Poloxamer-407 (P-407) and zirconium oxide beads. A 33 factorial design was employed to evaluate the combinatorial effect of P-407 concentration, DAR concentration and milling time on the particle size (PS) and saturation solubility (SS) of DAR-NS. The morphology of DAR-NS was examined by Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). The loss of crystalline nature of DAR was confirmed by Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD). The in-vitro studies revealed significant increment in SS and dissolution efficiency of drug in DAR-NS. The MTT assay and in-vitro permeability studies using Caco-2 cells described the reduction in cytotoxicity and improved permeation. The in-vivo studies illustrated the enhancement in oral bioavailability of drug from DAR-NS by 3.93 and 2.41 fold compared to plain DAR and commercial formulation, respectively. The DAR-NS was found to be stable at 5°C±3°C and room temperature for 6 months. These results concise that prepared nanosuspension significantly improved the oral bioavailability of DAR which could minimize the drug side effects by reducing dose frequency and thus will lead to improved patient compliance.


http://ift.tt/2fyNG7G

Dependence of descriptors of co-localization on microscope spatiotemporal resolution and the choice of regions of interest

Abstract

The advent and increasing availability of super-resolution microscopies has prompted re-searchers to re-investigate questions of co-localization and co-clustering in the hope of providing more precise and relevant data. Here, we focus on the problem of studying inter-organelle interfaces, a topic of growing interest in cell biology. We sought to identify mitochondria-associated membrane (MAM) candidate sites from dual-colour large-field super-resolution images. MAMs are specialized lipid microdomains of the endoplasmic reticulum (ER) in close apposition with mitochondria. Using total internal reflection fluorescence structured-illumination microscopy (TIRF-SIM, Brunstein et al., Optics Express, 2013), we achieved a three-dimensional spatial resolution down to ∼100 nm. Based on experimental and simulated data, we studied how the spatio-temporal resolution affects common descriptors of co-localization. The apparent overlap scaled inversely with spatial resolution (as expected for objects that are in close apposition and do not merge), independently of the precise metrics used. Important for live-cell imaging, organelle motility made measurements more uncertain, rendering statements of how physiological stimulations or pharmacologic manipulations affect co-localization less robust. Organelle density, or equivalent, the choice of different subcellular regions of interest (ROIs) had a marked effect on the amount of co-localization, as had the size of the ROI chosen. Our study calls for prudence when interpreting co-localization data and suggests that cell and organelle motility, the choice of the ROI analysed, the effective spatiotemporal resolution all impact on the result and hence should systematically be stated, particularly when co-localization arguments are used to assess the effect of drug application on cellular signalling pathways.



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Genotyping



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Study of blood pressure profile and correlation of hypertension with age, sex, anthropometric measurements (weight, height, body mass index), socio economic status and hereditary factors in school going children

2016-11-08T00-20-56Z
Source: International Journal of Contemporary Pediatrics
Kamatham Madhusudhan, Rajendra Betham, Venkateswara Rao Jampana.
Background: Pre hypertension in childhood is a precursor of hypertension in adulthood. Weight, height and body mass index (BMI) can be taken as surrogate marker of prevalence of hypertension and hence measurement of these parameters can help in early detection of children at risk of hypertension. The present study was done to determine the correlation of hypertension with age, gender, anthropometric measurements, socioeconomic status, and hereditary factors and to estimate the prevalence of hypertension and pre hypertension. Methods: It is an observational study involving 1009 healthy urban school children of 5 to 15 years of age. Height and weight were taken according to standard techniques (Jelliffee 1966). In order to exclude age as a confounding factor; BMI was plotted on percentile charts. Results: There was a linear increase of mean blood pressure with increasing age, height and weight. The mean systolic and diastolic blood pressures of children with BMI 85th to 95th percentile (overweight group) and with BMI ≥95th percentile (obese group) were higher than the lower BMI groups. The children belonging to high socio economic status (class I) and those with family history of hypertension were having higher mean values of systolic and diastolic blood pressure. Equal number of children belonged to pre hypertension (65) and hypertension (67) category. Conclusions: The mean systolic and diagnostic blood pressure was equal in both sexes. Children with overweight/obesity, family history of hypertension and class I socioeconomic status had increased mean values of systolic and diastolic blood pressure. Prevalence of high blood pressure was 13.1% (pre hypertension: 6.44% and hypertension: 6.64%).


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Prevalence and correlation of soil transmitted helminth infection to the degree of anemia and nutritional status among pediatric patients of age group 6-14 years in Kishanganj, Bihar, India

2016-11-08T00-20-56Z
Source: International Journal of Contemporary Pediatrics
Santosh Kumar, Jasninder Singh, Abhay Kumar.
Background: Intestinal parasites are a major public health problem in tropical and sub­tropical countries, affecting the physical growth and cognitive development in school age children. This study was conducted to estimate the prevalence of various helminthes, the symptomatology and clinical manifestations of various helminthes and to correlate the nutritional status with the type of helminthic infestation. Methods: Cross-sectional study involving children aged 6­14 years attending pediatric outpatient department in MGM Medical College, Kishanganj who were screened to estimate the prevalence of soil transmitted helminthes. Results: Out of the 500 children examined, 275 children were positive for one or other helminthic ova in the stool samples giving overall incidence of 55 %. Ascariasis was most common with 58.2% among all the positive cases, hookworm 7.3%, trichuris trichura 14.5%, hymenolepsis nana 3.6%, taenia saginata 1.8% while mixed infestations constitute 14.5%. There was no significant association of gender and infestation (p value >0.05). Patients on non-vegetarian diet were more prone to get infested (Chi- square value = 19.48, p value


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Numerical Study of Single Well Vapor Extraction Process

Vapor extraction (Vapex) is an emerging technology to produce heavy oil and bitumen from subsurface formations. Single well (SW) Vapex technique uses the same concept of Vapex process but only with one horizontal well. In this process solvent is injected from the toe of the horizontal well with oil production at the heel section. The main advantage of SW-Vapex process lies in the economic saving and applicability in problematic reservoirs, where drilling of two horizontal wells is impractical. The performance of SW-Vapex seems to be comparable with dual horizontal Vapex process using proper optimization schemes. This study is grouped into two sections: (i) a screening study of early time operating performance of SW-Vapex and (ii) a sensitivity analysis of the effect of the reservoir and well completion parameters. Simulation results show that solvent injection rate can be optimized to improve oil production rate. Higher injection rates may not necessarily lead to increase in production. This study confirms that SW-Vapex process is very ineffective in reservoirs with high oil viscosity (more than 1,500 cp) and thin formations (less than 10 m).

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Dual Solutions of Non-Newtonian Casson Fluid Flow and Heat Transfer over an Exponentially Permeable Shrinking Sheet with Viscous Dissipation

The two-dimensional boundary layer flow of a non-Newtonian Casson fluid and heat transfer due to an exponentially permeable shrinking sheet with viscous dissipation is investigated. Using similarity transformations, the governing momentum and energy equations are transformed to self-similar nonlinear ODEs and then those are solved numerically by very efficient shooting method. The analysis explores many important aspects of flow and heat transfer of the aforesaid non-Newtonian fluid flow dynamics. For the steady flow of non-Newtonian Casson fluid, more amount of wall mass suction through the porous sheet is required in comparison to that of Newtonian fluid flow. Dual similarity solutions are obtained for velocity and temperature. The viscous dissipation effect has major impact on the heat transfer characteristic. In fact, heat absorption at the surface occurs and it increases due to viscous dissipation. For higher Prandtl number, the temperature inside the boundary layer reduces, but with larger Eckert number (viscous dissipation) it is enhanced.

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Lack of Association between SLC30A8 Variants and Type 2 Diabetes in Mexican American Families

SLC30A8 encodes zinc transporter 8 which is involved in packaging and release of insulin. Evidence for the association of SLC30A8 variants with type 2 diabetes (T2D) is inconclusive. We interrogated single nucleotide polymorphisms (SNPs) around SLC30A8 for association with T2D in high-risk, pedigreed individuals from extended Mexican American families. This study of 118 SNPs within 50 kb of the SLC30A8 locus tested the association with eight T2D-related traits at four levels: (i) each SNP using measured genotype approach (MGA); (ii) interaction of SNPs with age and sex; (iii) combinations of SNPs using Bayesian Quantitative Trait Nucleotide (BQTN) analyses; and (iv) entire gene locus using the gene burden test. Only one SNP (rs7817754) was significantly associated with incident T2D but a summary statistic based on all T2D-related traits identified 11 novel SNPs. Three SNPs and one SNP were weakly but interactively associated with age and sex, respectively. BQTN analyses could not demonstrate any informative combination of SNPs over MGA. Lastly, gene burden test results showed that at best the SLC30A8 locus could account for only 1-2% of the variability in T2D-related traits. Our results indicate a lack of association of the SLC30A8 SNPs with T2D in Mexican American families.

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The Order Classes of 2-Generator -Groups

In order to classify a finite group using its elements orders, the order classes are defined. This partition determines the number of elements for each order. The aim of this paper is to find the order classes of 2-generator -groups of class 2. The results obtained here are supported by Groups, Algorithm and Programming (GAP).

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Relationships between Muscle Architecture of Rectus Femoris and Functional Parameters of Knee Motion in Adults with Down Syndrome

This study was designed to measure in vivo muscle architecture of the rectus femoris in adults with Down syndrome, testing possible relationships with functional parameters of the knee motion. Ten adults with Down syndrome and ten typically developed participated in the study. Pennation angle and thickness of the rectus femoris and subcutaneous layer of the thigh were measured via ultrasound imaging. Knee kinematics and electromyographic activity of the rectus femoris were recorded during free leg dropping. Muscle thickness was reduced and subcutaneous layer was thicker in persons with Down syndrome with respect to typically developed adults, but there were no differences in the pennation angle. The area of the rectus femoris EMG activity during the leg flexion was greater in Down syndrome with respect to typically developed adults. The leg movement velocity was lower in Down people than in controls, but the knee excursion was similar between the groups. Functional parameters correlated with pennation angle in the persons with Down syndrome and with muscle thickness in typically developed persons. The description of muscle architecture and the relationships between morphological and functional parameters may provide insights on the limits and the opportunities to overcome the inherent biomechanical instability in Down syndrome.

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Sugammadex-Enhanced Neuronal Apoptosis following Neonatal Sevoflurane Exposure in Mice

In rodents, neonatal sevoflurane exposure induces neonatal apoptosis in the brain and results in learning deficits. Sugammadex is a new selective neuromuscular blockade (NMB) binding agent that anesthesiologists can use to achieve immediate reversal of an NMB with few side effects. Given its molecular weight of 2178, sugammadex is thought to be unable to pass through the blood brain barrier (BBB). Volatile anesthetics can influence BBB opening and integrity. Therefore, we investigated whether the intraperitoneal administration of sugammadex could exacerbate neuronal damage following neonatal 2% sevoflurane exposure via changes in BBB integrity. Cleaved caspase-3 immunoblotting was used to detect apoptosis, and the ultrastructure of the BBB was examined by transmission electron microscopy. Exposure to 2% sevoflurane for 6 h resulted in BBB ultrastructural abnormalities in the hippocampus of neonatal mice. Sugammadex alone without sevoflurane did not induce apoptosis. The coadministration of sugammadex with sevoflurane to neonatal mice caused a significant increase (150%) in neuroapoptosis in the brain compared with 2% sevoflurane. In neonatal anesthesia, sugammadex could influence neurotoxicity together with sevoflurane. Exposure to 2% sevoflurane for 6 h resulted in BBB ultrastructural abnormalities in the hippocampus of neonatal mice.

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