STABILITY INDICATING ANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF MEMANTINE HCl AND DONEPEZIL HCl USING RP-HPLC

Objective: To develop and validate stability indicating method for the analysis of Memantine HCl and Donepezil HCl.Methods: The chromatographic separation was performed on Hypersil BDS (4.6 x 150 mm, 5m) using Sodium dihydrogen ortho phosphate: Acetonitrile (30:70v/v) at a flow rate of 1 ml/min and detection of both the eluents was carried out by UV Detector.Results: The Retention time of Memantine HCl and Donepezil HCl were found to be 2.833 min. and 4.777 min respectively. Method was found to be linear over the range of 40-120μg/ml for Memantine HCl and 20-60μg/ml for Donepezil HCl. Percentage recovery of Memantine HCl and Donepezil HCl was found to be 99.62% and 99.45% respectively. The percentage purity thus found is 98.5% and 98.6% for Memantine HCl and Donepezil HCl. The Limit of Detection of Memantine HCl and Donepezil HCl is 3.69 mg/ml and 2.72 mg/ml. and Limit of Quantification of Memantine HCl and Donepezil HCl is 11.13 mg/ml and 8.25 mg/ml respectively. In the stress degradation studies, it was found that Memantine HCl and Donepezil HCl showed no degradation in acid (0.1M HCl), base (0.1M NaOH), peroxide, heat and sunlight.Conclusion: A new sensitive, simple, and stability indicating high performance layer chromatographic (HPLC) method has been developed and validated for determination of Memantine HCl and Donepezil HCl. The proposed method can be used for routine determination of Memantine HCl and Donepezil HCl stability.Â

Relationship Between Applied Load and Clearance in Suture Knots

Ethicon Coated Vicryl absorbable sutures of different diameters were studied in order to determine if a relationship exists between the load and measured clearance. A prototype was designed to simulate knot location. Tensile tests were conducted on the suture knots followed by clearance measurements after each load level was applied. From the results it was concluded that the measured clearance was directly proportional to the amount of load applied to the suture knot. Also, based on the diameter of the suture, the smaller the diameter, the lower was the total displacement of the knot or the clearance

Circulating Mucosal Associated Invariant T Cells Are Activated in Vibrio cholerae O1 Infection and Associated with Lipopolysaccharide Antibody Responses

Background: Mucosal Associated Invariant T (MAIT) cells are innate-like T cells found in abundance in the intestinal mucosa, and are thought to play a role in bridging the innate-adaptive interface. Methods: We measured MAIT cell frequencies and antibody responses in blood from patients presenting with culture-confirmed severe cholera to a hospital in Dhaka, Bangladesh at days 2, 7, 30, and 90 of illness. Results: We found that MAIT (CD3+CD4−CD161hiVα7.2+) cells were maximally activated at day 7 after onset of cholera. In adult patients, MAIT frequencies did not change over time, whereas in child patients, MAITs were significantly decreased at day 7, and this decrease persisted to day 90. Fold changes in MAIT frequency correlated with increases in LPS IgA and IgG, but not LPS IgM nor antibody responses to cholera toxin B subunit. Conclusions: In the acute phase of cholera, MAIT cells are activated, depleted from the periphery, and as part of the innate response against V. cholerae infection, are possibly involved in mechanisms underlying class switching of antibody responses to T cell-independent antigens

Live Attenuated B. pertussis as a Single-Dose Nasal Vaccine against Whooping Cough

Pertussis is still among the principal causes of death worldwide, and its incidence is increasing even in countries with high vaccine coverage. Although all age groups are susceptible, it is most severe in infants too young to be protected by currently available vaccines. To induce strong protective immunity in neonates, we have developed BPZE1, a live attenuated Bordetella pertussis strain to be given as a single-dose nasal vaccine in early life. BPZE1 was developed by the genetic inactivation or removal of three major toxins. In mice, BPZE1 was highly attenuated, yet able to colonize the respiratory tract and to induce strong protective immunity after a single nasal administration. Protection against B. pertussis was comparable to that induced by two injections of acellular vaccine (aPV) in adult mice, but was significantly better than two administrations of aPV in infant mice. Moreover, BPZE1 protected against Bordetella parapertussis infection, whereas aPV did not. BPZE1 is thus an attractive vaccine candidate to protect against whooping cough by nasal, needle-free administration early in life, possibly at birth

Diasporic virginities: social representations of virginity and identity formation amongst British arab muslim women

This study compares how practising and non-practising British Arab Muslim women position themselves in relation to representations of virginity. Overall, in our qualitative study, we found that representations of culture and religion influenced social practices and social beliefs in different ways: non-practising Muslim women felt bound by culture to remain virgins, while practising Muslim women saw it as a religious obligation but were still governed by culture regarding the consequences of engaging in premarital sex. Interestingly, some practising Muslim participants used Mut’a (a form of temporary ‘marriage’) to justify premarital sex. This, however, did not diminish the importance of virginity in their understanding and identification as Arab women. In fact, this study found that virginity, for the British Arabs interviewed, embodied a sense of ‘Arabness’ in British society. Positioning themselves as virgins went beyond simply honour; it was a significant cultural symbol that secured their sense of cultural identity. In fact this cultural identity was often so powerful that it overrode their Islamic identities, prescribing their behaviour even if religion was seen as more ‘forgiving’

Opioid medication use and blood DNA methylation:epigenome-wide association meta-analysis

Aim: To identify differential methylation related to prescribed opioid use. Methods: This study examined whether blood DNA methylation, measured using Illumina arrays, differs by recent opioid medication use in four population-based cohorts. We meta-analyzed results (282 users; 10,560 nonusers) using inverse-variance weighting. Results: Differential methylation (false discovery rate \u3c0.05) was observed at six CpGs annotated to the following genes: KIAA0226, CPLX2, TDRP, RNF38, TTC23 and GPR179. Integrative epigenomic analyses linked implicated loci to regulatory elements in blood and/or brain. Additionally, 74 CpGs were differentially methylated in males or females. Methylation at significant CpGs correlated with gene expression in blood and/or brain. Conclusion: This study identified DNA methylation related to opioid medication use in general populations. The results could inform the development of blood methylation biomarkers of opioid use

Preferential Solvation Study of the Synthesized Aldose Reductase Inhibitor (SE415) in the {PEG 400 (1) + Water (2)} Cosolvent Mixture and GastroPlus-Based Prediction

This article presents evidence that the binary cosolvent system can be a promising approach for enhanced oral absorption in controlling diabetes mellitus (DM) and associated complications in humans

A Key Role of Dendritic Cells in Probiotic Functionality

BACKGROUND: Disruption of the intestinal homeostasis and tolerance towards the resident microbiota is a major mechanism involved in the development of inflammatory bowel disease. While some bacteria are inducers of disease, others, known as probiotics, are able to reduce inflammation. Because dendritic cells (DCs) play a central role in regulating immune responses and in inducing tolerance, we investigated their role in the anti-inflammatory potential of probiotic lactic acid bacteria. METHODOLOGY/PRINCIPAL FINDINGS: Selected LAB strains, while efficiently taken up by DCs in vitro, induced a partial maturation of the cells. Transfer of probiotic-treated DCs conferred protection against 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. Protection was associated with a reduction of inflammatory scores and colonic expression of pro-inflammatory genes, while a high local expression of the immunoregulatory enzyme indolamine 2, 3 dioxgenase (IDO) was observed. The preventive effect of probiotic-pulsed DCs required not only MyD88-, TLR2- and NOD2-dependent signaling but also the induction of CD4+ CD25+ regulatory cells in an IL-10-independent pathway. CONCLUSIONS/SIGNIFICANCE: Altogether, these results suggest that selected probiotics can stimulate DC regulatory functions by targeting specific pattern-recognition receptors and pathways. The results not only emphasize the role of DCs in probiotic immune interactions, but indicate a possible role in immune-intervention therapy for IBD