Benzydamine hydrochloride buccal bioadhesive gels designed for oral ulcers: Preparation,rheological, textural,mucoadhesive and release properties

This study developed and examined the characterization of Benzidamine hydrochloride (BNZ) bioadhesive gels as platforms for oral ulcer treatments. Bioadhesive gels were prepared with four different hydroxypropylmethylcellulose (HPMC) types (E5, E15, E50 and K100M) with different ratios. Each formulation was characterized in terms of drug release, rheological, mechanical properties and adhesion to a buccal bovine mucosa. Drug release was significantly decreased as the concentration and individual viscosity of each polymeric component increased due to improved viscosity of the gel formulations. The amount of drug released for the formulations ranged from 0.76?±?0.07 and 1.14?±?0.01 (mg/cm²?±?SD). Formulations exhibited pseudoplastic flow and all formulations, increasing the concentration of HPMC content significantly raised storage modulus (G′), loss modulus (G″), dynamic viscosity (?′) at 37°C. Increasing concentration of each polymeric component also significantly improved the hardness, compressibility, adhesiveness, cohesiveness and mucoadhesion but decreased the elasticity of the gel formulations. All formulations showed non-Fickian diffusion due to the relaxation and swelling of the polymers with water. In conclusion, the formulations studied showed a wide range of mechanical and drug diffusion characteristics. On the basis of the obtained data, the bioadhesive gel formulation which was prepared with 2.5% HPMC K 100M was determined as the most appropriate formulation for buccal application in means of possessing suitable mechanical properties, exhibiting high cohesion and bioadhesion.     

Health and Ecological Effects of Adiponitrile

Adiponitrile (ADN) has moderate acute toxicity with an oral LD₅₀ in rats of 100 to 500 mg/kg and a 4‐hr LC₅₀ in rats of 1.71 mg/L (vapor plus aerosol). ADN produced slight eye but no skin irritation in rabbits. Repeated exposures by inhalation produced changes in the hematologic profile with effects seen at 100 or 300 mg/m³. The hematologic changes were reversible upon cessation of further inhalation exposures. Dogs fed up to 500 ppm (equivalent to 12–15 mg/kg) showed no effects but 1,000 ppm produced vomiting and nausea which limited further testing at that concentration. ADN was not a genetic toxin, developmental toxin, reproductive toxin nor did it produce an increase in tumors in a 2‐yr drinking water study in rats. Human experience reports are limited to one accidental poisoning case and a few skin exposures resulting in transient irritation and inflammation. ADN is rapidly absorbed and excreted by mammals, and is metabolized to some extent although unchanged ADN is readily detected in urine, and does not bioaccumulate.     

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Validation of a novel method for determination of low-density lipoprotein cholesterol levels in Indian patients with type 2 diabetes

Background and aimsLDL-cholesterol (LDL-C), being the primary predictor of cardiovascular disease in Type 2 diabetes (T2D), is associated with cardiovascular risk stratification and requires to be estimated with better accuracy with minimal bias. Different formulae have been devised to calculate the LDL-C from the measured lipid profile parameters.MethodsIn this analytical cross-sectional study, a total of 150 patients with T2D were studied, and blood samples were subjected for lipid profile analysis at the Central Biochemistry laboratory. Different formulae assessed calculated LDL-C.ResultsWe observed that all formulae, except Ahmadi, underestimated the LDL-C compared to direct assay. A significant difference was observed between all calculated LDL-C and directly measured LDL-C. On linear regression analysis, the newer formula Martin's has a better approximation with direct assay (slope: 0.9708) than Friedewald (slope: 0.9477). Similarly, Martin's formula exhibited lesser bias (?13.56) in calculating LDL-C in patients with T2D compared with Friedewald's formula.ConclusionsThe study demonstrated that in patients with T2D, all formulae except Ahmadi significantly underestimated the LDL-C when compared with the direct assay. The newer Martin's formula appeared to more precisely calculate LDL-C in T2D when compared with the traditional Friedewald's formula.     

Integrating gene expression profiling into NCCN high-risk cutaneous squamous cell carcinoma management recommendations: impact on patient management

Abstract

Objective: To integrate gene expression profiling into the management of high-risk cutaneous squamous cell carcinoma (cSCC) within the National Comprehensive Cancer Network (NCCN) guidelines to improve risk-aligned management recommendations.

Methods: A cohort of 300 NCCN-defined high-risk cSCC patients, along with the American Joint Committee on Cancer (AJCC) T stage, Brigham and Women’s Hospital (BWH) T stage, and known patient outcomes were analyzed. Risk classifications using a validated 40-gene expression profile (40-GEP) test and T stage were applied to NCCN patient management guidelines. Risk-directed patient management recommendations within the NCCN guidelines framework were aligned based on risk for metastasis.

Results: Of the 300 NCCN high-risk cSCC patients, 159 (53.0%) were 40-GEP Class 1 and AJCC T1-T2, and 173 (57.7%) were Class 1 and BWH T1-2a, indicating low risk for metastasis and, thereby, suggesting low management intensity. The 40-GEP integration suggested high intensity management for only 24 (8.0%) patients (all Class 2B), and moderate intensity management for the remainder of the cohort.

Conclusions: The 40-GEP test can be integrated within existing NCCN guideline recommendations for managing cSCC patients to help refine risk-directed management decisions. Integration of the 40-GEP test would allow >50% of this NCCN-defined high-risk cohort to be managed with the lowest intensity recommendations within the broad NCCN guidelines. High intensity management was deemed risk-appropriate for a small subpopulation (8.0%). This study demonstrates that the 40-GEP test, in combination with T stage, has clinical utility to impact patient management decisions in NCCN high-risk cSCC for improving risk-aligned management within the NCCN guidelines framework.     

Carotid intima-media thickness,lipid profile,serum amyloid A and vitamin D status in children with familial Mediterranean fever

Aim of the workIt was to estimate the carotid intima-media thickness (CIMT), lipid profile, serum amyloid A and vitamin D in Familial Mediterranean Fever (FMF) patients and to explore the relationship between CIMT and FMF.Patients and methodsThe study comprised forty-five FMF patients diagnosed during the attack free period and 40 healthy children with similar demographic features as control. The diagnosis of the FMF cases was confirmed by clinical, laboratory assessments and confirmed by the molecular diagnosis. The CIMT, lipid profile, complete blood picture, serum amyloid A (SAA) levels, vitamin D and the growth pattern were investigated.ResultsThe study showed no significant difference of CIMT among patients and controls, significant decrease of vitamin D levels, while lipid profile parameters, triglyceride (TG) to HDL-Cholesterol (HDL-C) ratio, serum amyloid A were significantly increased. A significant correlation was present between the CIMT with the serum cholesterol, low density lipoprotein and triglycerides as well as between SAA and the number of attacks. In addition, vitamin D levels showed significant negative correlation with colchicine. M694I mutation was the most prevalent among FMF patients. Growth parameters were normal in FMF cases.ConclusionThis study sheds light that the normal CIMT in the FMF patients makes it difficult to describe the children as having subclinical atherosclerosis although the higher TG/HDL ratio reflects their risk of atherosclerosis. Moreover, significant decrease of vitamin D in FMF patients was observed. The growth parameters of the FMF patients on regular treatment of colchicine were not affected.     

Assessing possible DSM-5 ASD subtypes in a sample of victims meeting caseness for DSM-5 ASD based on self-report following multiple forms of traumatic exposure

Acute stress disorder (ASD) was introduced into the DSM-IV to recognize early traumatic responses and as a precursor of PTSD. Although the diagnostic criteria for ASD were altered and structured more similarly to the PTSD definition in DSM-5, only the PTSD diagnosis includes a dissociative subtype. Emerging research has indicated that there also appears to be a highly symptomatic subtype for ASD. However, the specific nature of the subtype is currently unclear. The present study investigates the possible presence of ASD subtypes in a mixed sample of victims meeting caseness for DSM-5 ASD based on self-report following four different types of traumatic exposure (N = 472). The results of latent profile analysis revealed a 5-class solution. The highly symptomatic class was marked by high endorsement on avoidance and dissociation compared to the other classes. Findings are discussed in regard to its clinical implications including the implications for the pending the ICD-11 and the recently released DSM-5.     

Review of a 7-Year Record of the Bacteriological Profile of Airway Secretions of Children with Cystic Fibrosis in North India

Background: Cystic fibrosis (CF) is now a recognised entity in India, with prevalence rates between 1/10,000 and 1/50,000. However, no data were available with regard to the profile of respiratory pathogens in the Indian setting. Materials and Methods: The records of respiratory secretion bacterial cultures of children with CF in a tertiary care hospital in North India from January 2010 to December 2016 were reviewed. Culture data were evaluated; the organisms were noted and their antimicrobial susceptibilities were analysed. The microbiological profile and antimicrobial susceptibility pattern of CF patients were evaluated. Results: A total of 445 samples from 146 children were processed, of which 246 (55%) samples showed bacterial growth. Mixed infections 48 (19.5%) were common in older children. Children aged 3–6 months (62.5%) showed the highest culture positivity. The most commonly isolated organisms were Pseudomonas aeruginosa (52.6%) and Staphylococcus aureus. Children with initial cultures positive for P. aeruginosa had 55% of their subsequent cultures showing polymicrobial infections. P. aeruginosa was most susceptible to ciprofloxacin (89%) and piperacillin-tazobactum (88%). Among the staphylococcal isolates, 38% were methicillin-resistant S. aureus (MRSA). The percentage of MRSA increased from 66% in 2010 to 75% in 2012, followed by a decline to 24% in 2016. Conclusions: The pattern of airway colonisation in the Indian setting is different from the Caucasian population, and P. aeruginosa and Burkholderia cepacia complex appear early. Colonisation with P. aeruginosa benefits from therapy. In case of infection, care must be taken while initiating empiric therapy. It should be based on local antibiograms to prevent the emergence of resistant microbes.     

Effects of upper-body resistance exercise training on serum nesfatin-1 level,insulin resistance,and body composition in obese paraplegic men

Background

As a recently discovered adipokine, nesfatin-1 is conducive to insulin sensitivity, lipid profile, energy balance, and probably obesity.