EVALUATION OFANTI-OXIDANT AND ANTI-ACNE ACTIVITIES (IN-VITRO) OF THE FORMULATED HERBAL GELS

Objective: The objective of the present study was to evaluate the anti-oxidant and anti-acne activities (in-vitro) of the formulated herbal gels. Methods: Herbal extracts and volatile oils were prepared and procured. Preliminary screenings for the anti-oxidant and anti-acne activities (in-vitro) were carried out to select the suitable candidates for the preparation of anti-acne herbal gels. Gels were further evaluated for the activities. Results: The herbal gel (F2) containing the herbal extracts (Azadirachtaindica, Ocmium sanctum, Curcuma longa) each (1%) and volatile oils (Melaleucaalternifoliae, Salviaesclareae and Citrus sinensis) each (0.05%) showed maximum anti-oxidant activity (IC50 value 0.407 mg) amongst all four gels. Significant anti-acne activity against P. acne and S. epidermidis was showed by F2 when compared with the marketed synthetic gel (Clindac gel). Conclusion: The study proves that the herbal actives used in the formulation have promising anti-oxidant and anti-acne activity

Parasites found in surgical pathology: the institutional experience

Background: Parasitic infestation has a worldwide prevalence and it affects almost all age groups and both the sexes. The incidence of these infections is slowly rising in today’s era. Parasites are mainly found in stool samples but due to increase in a immunocompromised state now a days, tissue parasitaemia has increased globally necessitating more such type of studies. Parasite found in surgical pathology either incidentally or in clinically suspicious cases not only improves morbidity but also saves clinician’s time and patient’s money.Methods: A retrospective-cross sectional study is done based on histomorphological and cytomorphological evaluation of 25 cases diagnosed at The Department of pathology, New Civil Hospital Surat from January 2015 to January 2017.Results: Most common parasite seen was Echinococcus presenting as hydatid cyst in liver followed by filariasis. Most common age group affected was 0-20 years of age. Most common intestinal parasite found in our study was Entamoeba histolytica. Patients presented with variety of symptoms.Conclusions: Distribution of parasite in tissue section in relation to frequency, age, sex, various system involvements and its correlation with clinical symptoms are analyzed in our study

Targeting species specific amino acid residues: Design, synthesis and biological evaluation of 6-substituted pyrrolo[2,3-d]pyrimidines as dihydrofolate reductase inhibitors and potential anti-opportunistic infection agents

To combine the potency of trimetrexate (TMQ) or piritrexim (PTX) with the species selectivity of trimethoprim (TMP), target based design was carried out with the X-ray crystal structure of human dihydrofolate reductase (hDHFR) and the homology model of Pneumocystis jirovecii DHFR (pjDHFR). Using variation of amino acids such as Met33/Phe31 (in pjDHFR/hDHFR) that affect the binding of inhibitors due to their distinct positive or negative steric effect at the active binding site of the inhibitor, we designed a series of substituted-pyrrolo[2,3-d]pyrimidines. The best analogs displayed better potency (IC50) than PTX and high selectivity for pjDHFR versus hDHFR, with 4 exhibiting a selectivity for pjDHFR of 24-fold

Development and Evaluation of Active Case Detection Methods to Support Visceral Leishmaniasis Elimination in India.

As India moves toward the elimination of visceral leishmaniasis (VL) as a public health problem, comprehensive timely case detection has become increasingly important, in order to reduce the period of infectivity and control outbreaks. During the 2000s, localized research studies suggested that a large percentage of VL cases were never reported in government data. However, assessments conducted from 2013 to 2015 indicated that 85% or more of confirmed cases were eventually captured and reported in surveillance data, albeit with significant delays before diagnosis. Based on methods developed during these assessments, the CARE India team evolved new strategies for active case detection (ACD), applicable at large scale while being sufficiently effective in reducing time to diagnosis. Active case searches are triggered by the report of a confirmed VL case, and comprise two major search mechanisms: 1) case identification based on the index case's knowledge of other known VL cases and searches in nearby houses (snowballing); and 2) sustained contact over time with a range of private providers, both formal and informal. Simultaneously, house-to-house searches were conducted in 142 villages of 47 blocks during this period. We analyzed data from 5030 VL patients reported in Bihar from January 2018 through July 2019. Of these 3033 were detected passively and 1997 via ACD (15 (0.8%) via house-to-house and 1982 (99.2%) by light touch ACD methods). We constructed multinomial logistic regression models comparing time intervals to diagnosis (30-59, 60-89 and ≥90 days with =90 days compared to the referent of <30 days for ACD vs PCD were 0.88, 0.56 and 0.42 respectively. These ACD strategies not only reduce time to diagnosis, and thus risk of transmission, but also ensure that there is a double check on the proportion of cases actually getting captured. Such a process can supplement passive case detection efforts that must go on, possibly perpetually, even after elimination as a public health problem is achieved

Target Based Design and Synthesis of Fused Pyrimidines in the Potential Treatment of Cancer and Opportunistic Infection

This dissertation describes an introduction, background and research progress in the areas of agents designed as (a) selective Pneumocystis jirovecii dihydrofolate reductase (pjDHFR) inhibitors for pneumocystis pneumonia (PCP) infection; (b) inhibitors of microtubule polymerization and multiple receptor tyrosine kinase (RTK) for potential treatment of cancer; and (c) substrates for tumor-targeted therapy for cancer. PCP is a host species-specific infection. Most of the drugs, synthesized and evaluated so far, have been tested against Pneumocystis carinii dihydrofolate reductase (the causative organism in rats), which would not necessarily be effective against pjDHFR (the causative organism in humans). Trimethoprim-sulfamethoxazole (TMP-SMX) combination, which has been used for PCP for decades, has major limitations due to low inhibitory potency of TMP, side-effects of SMX and emergence of resistant strains expressing mutated dihydropteroate synthase enzyme (target of SMX). For patients unresponsive or resistant to this treatment, newer drugs are critically needed. The absence of an X-ray crystal structure of pjDHFR poses a large gap in drug discovery efforts. The status quo, as it pertains to designing selective inhibitors for an enzyme, is to exploit the amino acid differences between the active sites of the desired and undesired target enzyme. Structure based design, using a pjDHFR homology model and through identification of amino acid differences between pjDHFR and hDHFR active sites, has been presented in the text. Novel synthetic strategies were developed for efficient synthesis of 6- and 7-substituted 5-methyl-pyrrolo[2,3-d]pyrimidine-2,4-diamines, N6-substituted pyrido[3,2-d]pyrimidine-2,4,6-triamines, 6-(arylthio)pyrido[3,2-d]pyrimidine-2,4-diamines and 7-(arylthio)pyrido[3,2-d]pyrimidine-2,4-diamines. In cancer chemotherapy, the two major limitations are the dose-limiting toxicities of clinically used agents and development of resistant to the treatment. Combination chemotherapy with antiangiogenic agents and microtubule targeting agents has shown an advantage against both these drawbacks. Single agents with both antiangiogenic activity and cytotoxicity would afford a therapy that circumvents pharmacokinetic problems of multiple agents, avoids drug-drug interactions, lowers the drug dose, decrease overlapping toxicities, and delays or prevents tumor cell resistance. The work in this dissertation discusses the development of fused pyrimidines, aimed to inhibit tubulin polymerization as well as act as antiangiogenic agents which inhibit one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), platelet derived growth factor receptor-β (PDGFRβ) and epidermal growth factor receptor (EGFR), using molecular modeling studies. This work also reviews the synthesis pyrrolo[3,2-d]pyrimidines and thieno[3,2-d]pyrimidines and discusses novel synthetic strategies for substituted pyrrolo[3,2-d]pyrimidines and thieno[3,2-d]pyrimidines. Cancer cells transport folates through reduced folate carrier (RFC), Proton-Coupled Folate Transporter (PCFT) and/or Folate receptors (FR). Among several targeting strategies for cancer cells, selectively targeting through PCFT and FRs, over RFC have been successfully investigated. The next valid step in the field is to carry out a structure based design of agents to gain selectivity for PCFT and/or FRs transport over RFC and thus avoid dose-limiting toxicities. Absence of X-ray crystal structures for PCFT and RFC make this step impossible. The work in this dissertation discusses our efforts to fulfil this gap in the literature by developing a 3D QSAR pharmacophore for PCFT and RFC. PMX, the most widely used antifolate has three disadvantages: (i) transport by RFC; (ii) dependence on its polyglutamylation for potency; and (iii) development of resistance due to mutagenesis in the target enzyme (thymidylate synthase). This dissertation focuses on development of substituted-pyrrolo[3,2-d]pyrimidines to combat the above-mentioned drawbacks of PMX, using the X-ray crystal structures of intracellular targets and transporters and using the basic principles of scaffold hopping and bioisosteric replacements. The work described herein discusses our efforts to obtain agents with inhibition of two or more intracellular targets to inhibit de novo purine biosynthesis. Synthetic efforts for the development of pyrrolo[3,2-d]pyrimidines with different linkers and aryl substitutions have been discussed

An impact of gap acceptance on road safety: A critical systematic review

An uncontrolled intersection is a critical area for crashes that depends on macroscopic traffic parameters. While the intersection is the potential of the center of crashes due to inappropriate decision of driver. Therefore, the study focuses on the effect of the gap acceptance parameter for the safety of drivers at an uncontrolled intersection. To examine, a systematic review of the literature is implemented to understand the different parameters, their impact, and models developed by the researchers. Additionally, it is demonstrated that the crashes are highly affected by the gap acceptance and the different models are formed to estimate the critical gap for different road sections under homogeneous and heterogeneous traffic conditions. However, it is not possible to definitively conclude the best model to evaluate the gap acceptance factor but can be preferred to reduce the severity of crashes. Nonetheless, most studies remain inconclusive, there is an emerging trend in the literature suggesting the increase of the crash risk at an uncontrolled intersection. Lastly, it is most important to mention the model suitability based on empirical studies commenced under the strong limitations. Consequently, there is a need for research in this area to correlate the gap acceptance with road safety to reduce the severity of accidents to improve the existing transportation system

RAPID COMMUNICATION Increased prevalence of symptoms of gastroesophageal reflux diseases in type 2 diabetics with neuropathy

AIM: To analyze the prevalence of gastroesophageal reflux disease (GERD) related symptoms in patients with diabetes mellitus (DM) and to find out the relationship between diabetic neuropathy and the prevalence of GERD symptoms. METHODS: In this prospective questionnaire study, 150 consecutive type 2 diabetic patients attending the endocrine clinic were enrolled. A junior physician helped the patients to understand the questions. Patients were asked about the presence of five most frequent symptoms of GERD that included heartburn (at least 1/wk), regurgitation, chest pain, hoarseness of voice and chronic cough. Patients with past medical history of angina, COPD, asthma, cough due to ACEI or preexistin

Development of substituted pyrido[3,2-d]pyrimidines as potent and selective dihydrofolate reductase inhibitors for pneumocystis pneumonia infection

Pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii (pj) can lead to serious health consequences in patients with an immunocompromised system. Trimethoprim (TMP), used as first-line therapy in combination with sulfamethoxazole, is a selective but only moderately potent pj dihydrofolate reductase (pjDHFR) inhibitor, whereas non-clinical pjDHFR inhibitors, such as, piritrexim and trimetrexate are potent but non-selective pjDHFR inhibitors. To meet the clinical needs for a potent and selective pjDHFR inhibitor for PCP treatment, fourteen 6-substituted pyrido[3,2-d]pyrimidines were developed. Comparison of the amino acid residues in the active site of pjDHFR and human DHFR (hDHFR) revealed prominent amino acid differences which could be exploited to structurally design potent and selective pjDHFR inhibitors. Molecular modeling followed by enzyme assays of the compounds revealed 15 as the best compound of the series with an IC50 of 80 nM and 28-fold selectivity for inhibiting pjDHFR over hDHFR. Compound 15 serves as the lead analog for further structural variations to afford more potent and selective pjDHFR inhibitors