pH responsive cylindrical MSN for oral delivery of insulin-design,fabrication and evaluation

Objective: The objective of the present study was to develop novel PMV [poly (methacrylic acid-co-vinyl triethoxylsilane)]-coated mesoporous silica nanoparticles (MSN) with improved hypoglycemic effect for oral insulin (INS) delivery.

Methods: MSN was synthesized under acidic condition using Pluronic® P 123 and Tetra ethoxy orthosilane. Surfactant was removed by calcination. Calcined MSN was coated with pH sensitive polymer PMV. Cytotoxicity of this coated MSN was evaluated by MTT assay using CHO-K1 cell line. Different MSN samples were characterized with BET surface area analyzer, FESEM, TEM, FT-IR, XRD, TG-DTA. In vivo study was performed using male rats. Pharmacokinetic study was conducted using HPLC.

Results and discussion: Highest surface area (304.3921 m²/g) was observed in case of calcined sample. Adsorption pore width of final coated sample was highest (64.7844?nm) compared with others. No noticeable cytotoxicity was observed for this coated support. The entrapment efficiency of insulin was found to be 39.39%. In vitro studies were done at different pH using Franz-diffusion cell. Results showed significant release at pH 7.4. Cumulative drug release over a period of 6?h was more than 48% at this systemic pH. Effect of this MSN-PMV-INS on blood glucose level was retained for 16?h. This novel formulation has shown 73.10% relative bioavailability of insulin.

Conclusion: A novel-coated mesoporous silica support was successfully developed for delivery of insulin through oral route.     

Identification and phylogenetic characterization of bovine ephemeral fever virus (BEFV) of Middle Eastern lineage associated with 2018–2019 outbreaks in India

Bovine ephemeral fever virus (BEFV) is an evolving arbovirus reported across tropical, subtropical and temperate climatic zones globally. This study reveals prominent BEFV outbreaks in India, emerging annually during monsoons in subtropical areas accompanied by a congenial abundance of the vector population. PCR‐based detection of viral genomic RNA in the blood samples collected during outbreaks of 2018–2019 for the first time confirmed the presence of BEFV in India. Phylogenetic analysis based on the glycoprotein gene of BEFV showed the current isolates to have high sequence homology with Middle Eastern lineage with nearly 97%, identity to Turkey (BEFV Ad12/TUR) and Israel (Israel 2006) isolates.     

An analysis of the standard curve parameters of cytomegalovirus,BK virus and hepatitis B virus quantitative polymerase chain reaction from a clinical virology laboratory in eastern India

PurposeQuantitative real-time polymerase chain reactions (qPCRs) are important for accurate detection of nucleic acid target including that for viral load determination. Assessment of the quality of a PCR run is essential for quality control, diagnostics and research. In order to reduce subjectivity qPCR standard curves are accompanied with parametric values for slope, Y- intercept, correlation coefficient (R²) and PCR efficiency. In this study the performance of three qPCR assays-cytomegalovirus, hepatitis B virus and BK virus-with respect to standard curve parameters-slope, Y intercept, R² and efficiency were examined.MethodsUsing ideal values (Slope (minus 3.32); Y intercept ?= ?the number of PCR cycles; R2 ?= ?1 and efficiency ?= ?100%) we estimated the intra-assay variability (range) and deviation from ideal parameters (Δ). We also calculated the standard deviation (SD) and coefficient of variation (CV) for each of these parameters. We have evaluated the quality of each of the three viral load assays (CMV, HBV, BKV) using these statistical approach.ResultsWe found lab developed tests (CMV) to have least deviation from ideal Y intercept (limit of detection); however, commercial kit based assays had better linearity (scatter plot correlation between amplification factor and PCR efficiency). Using a scatter plot for the three assays we found the correlation with calculated amplification factor and PCR efficiency was most linear in case of BKV (0.9974), closely followed by the HBV assay (R² ?= ?0.9968). Although the CMV quantitative standards were least linear (0.868), the CV (coefficient of variation) was also the least in case of the CMV assay.ConclusionThe study highlights an objective way of assessing qPCR assay quality and demonstrates a method to compare assays, validate tests and perform quality control.     

Sickle cell trait is not associated with chronic kidney disease in adult Congolese patients: a clinic-based,cross-sectional study

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are associated with significant cardiovascular (CV) and renal morbidity and mortality rates, with substantial economic burden.1,2 Therefore, early identification of CKD patients at high risk of progression is urgently needed for early and targeted treatment to improve patient care.1-3 Diabetes and hypertension are the primary risk factors for CKD and ESRD but do not fully account for CKD and ESRD risk.1-3 Marked variability in the incidence of CKD suggests that factors other than diabetes and hypertension contribute to its aetiology.4Family studies have suggested a genetic component to the aetiology of CKD and ESRD.5 In African Americans, high-risk common variants in the Apol1/MYH9 locus may explain up to 70% of the differences in ESRD rates between European and African Americans.5 While this finding has great implications for ESRD, the identification of additional risk factors for CKD, including genetic loci in association with estimated glomerular filtration rate (eGFR), may help to advance our understanding of the underpinnings of CKD in African Americans.5 In this era of identifying genetic risk factors for kidney disease, it may be appropriate to revisit one of the most common genetic disorders: sickle cell haemoglobinopathies.5In this regard, sickle cell trait (SCT), present in approximately 7–9% of African Americans, has been reported to be a potential candidate gene.6 However, conflicting reports exist as to whether SCT is a risk factor for the progression of nephropathy.6,7 Haemoglobin S (HbS) was selected for in Africa because of the protection it affords from malarial infection, a scenario similar to the protection from trypanosomal infection provided by heterozygosity for APOL1 nephropathy risk variants.6Whereas APOL1 contributes to risk for nephropathy in an autosomal recessive inheritance pattern, HbS reportedly had a dominant effect on risk, with SCT being associated with ESRD.6 In line with this finding, a few small studies on African Americans reported HbS as an independent risk factor for CKD and ESRD.8 However, other studies using a large sample of African Americans stated that SCT was not independently associated with susceptibility to ESRD in African Americans,6 highlighting the need for further studies in other populations such as those of sub-Saharan Africa where SCT is prevalent.Although SCT is very prevalent in black Africans,9 few studies have been conducted to assess the association between SCT and CKD.10 In Democratic Republic of Congo (DRC), the prevalence of CKD and SCT has been reported to be 12% and 17–24%, respectively.11-13 No study has evaluated the frequency of SCT among CKD patients to assess its association with reduced kidney function. Therefore, the aim of this clinic-based, cross-sectional study was to assess the potential association between SCT and CKD among adult Congolese patients.     

Role of split calvarial graft in reconstruction of craniofacial defects

The aim of this study was to evaluate the clinical applications, graft uptake, and complications of split-thickness calvarial graft for the reconstruction of craniofacial defects.This retrospective study included 26 patients with craniofacial defects treated between January 2008 and December 2009. This included 17 male and 09 female patients between 9 and 45 years. Depending on the treatment provided, the patients were divided into 3 groups. Group 1 included 11 patients with cranial defect operated on for cranioplasty. Group 2 included 7 patients with orbital floor defect operated on for orbital floor reconstruction, and group 3 included 8 patients with alveolar cleft defect operated on for secondary alveolar grafting. Clinicoradiologic follow-up ranged from 18 to 24 months.In group 1, the symmetry of the calvarium was restored with good cosmesis. Improvement in neurologic function was observed in 7 patients. In group 2, the orbital volume and ocular function was maintained. In group 3, graft uptake was satisfactory with increase in bone density, and continuity of the alveolar bone was maintained. Cuspid eruption was aided orthodontically.Split calvarial grafts are suitable materials for craniofacial reconstruction. Their embryological origin, thickness, and shape are ideal for the restoration of craniomaxillofacial defects.