Search

Introduction: We assessed the baseline knowledge and the improvement and retention of knowledge after attending diabetes self-management education (DSME) programs with respect to different socioeconomic status (SES). We also looked into the change in body mass index (BMI), blood pressure, and glycemic parameters after attending the DSME sessions., Materials and Methods: This was a retrospective, cohort study carried out via chart review based on data collected from manual or electronic medical records (EMR) and questionnaire responses of 160 adult patients with type 2 diabetes (T2D) who attended two DSME sessions with a gap of at least six months., Results: Baseline knowledge on diabetes was uniform ( P = 0.06), irrespective of differences in SES, and DSME sessions significantly improved the knowledge in all socioeconomic classes ( P value < 0.05 in each SES group). However, SES did have a significant influence on the finally acquired knowledge of diabetes as was evident from the final score after attending two DSME sessions. A significant number of patients (48.1%) from our cohort either improved or retained their knowledge of diabetes over a mean follow-up of 15.5 months. The BMI of our cohort was significantly reduced from baseline to final follow-up ( P = 0.016)., Conclusion: DSME sessions were effective in improving knowledge and awareness among T2D patients, irrespective of socioeconomic classes in Eastern India. The acquired knowledge from DSME sessions was retained over a long time., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Family Medicine and Primary Care.)

Idiopathic hirsutism (IH) is a common clinical condition with multiple diagnostic and therapeutic uncertainties. There are no clear recommendations for the diagnosis and management of the condition. This practice update was developed to guide the primary care physicians and the specialists in better and more systematic management of IH particularly in the Indian context. Twelve experienced members consisting of eminent endocrinologists, physicians, a dermatologist, a gynaecologist and a psychiatrist were invited by the Integrated Diabetes and Endocrine Academy (IDEA). A literature search was performed using online databases from PubMed, Cochrane Library and Google Scholar. Published articles from peer-reviewed indexed journals, with a preference for meta-analyses and randomized controlled trials, were selected. A meeting took place with all the 12 members individually giving their opinions on predetermined questions of interest. After the initial meeting during IDEACON 2023, two more meetings were held and the practice update was formulated after voting. Practice updates were made on important areas such as the cut-off for modified Ferriman-Gallwey Score for the Indian population, conditions to be excluded before diagnosing IH, when to refer to specialists, investigations in a suspected case of IH and choice of therapies for its management., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Endocrinology and Metabolism.)

Indomethacin, a known nonsteroidal anti-inflammatory drug (NSAID) induces gastric inflammation, causing degradation of the extracellular matrix by specific matrix metalloproteinases (MMPs). We investigated the antiulcer efficacy of 3-indolyl furanoids ( 3g and 3c , i.e., methoxy substitution at 4- and 5-positions of the indole ring, respectively), derived from indomethacin. Interestingly, 3g protected against indomethacin-induced gastropathy in vivo by inhibiting MMP-9. Our work established a chemical modification strategy for the development of safer NSAIDs. Moreover, in vitro and in silico studies confirmed that 3g inhibited MMP-9 activity with an IC 50 value of 50 μM by binding to the catalytic cleft of MMP-9, leading to ulcer prevention. Pharmacokinetics was presented as the mean concentration-time profile in the rat plasma, and the extraction efficiency was greater than 70%, showing a C max of 104.48 μg/mL after 6.0 h ( t max ) treatment with half-life and area under the curve being 7.0 h and 1273.8 h μg/mL, respectively, indicating the higher antiulcer potency of 3g .

The role of the intestine in human health and disease has historically been neglected and was mostly attributed to digestive and absorptive functions. In the past two decades, however, discoveries related to human nutrition and intestinal host-microbe reciprocal interaction have established the essential role of intestinal health in the pathogenesis of chronic diseases and the overall wellbeing. That transfer of gut microbiota could be a means of disease phenotype transfer has revolutionized our understanding of chronic disease pathogenesis. This narrative review highlights the major concepts related to intestinal microbiota, metabolism, and metabolome (3M) that have facilitated our fundamental understanding of the association between the intestine, and human health and disease. In line with increased interest of microbiota-dependent modulation of human health by dietary phytochemicals, we have also discussed the emerging concepts beyond the phytochemical bioactivities which emphasizes the integral role of microbial metabolites of parent phytochemicals at extraintestinal tissues. Finally, this review concludes with challenges and future prospects in defining the 3M interactions and has emphasized the fact that, it takes 'guts' to stay healthy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Community Health Worker (CHW) programs have long been used to provide acute care for children and women in healthcare shortage areas, but their provision of comprehensive longitudinal care for chronic problems is rare. The Village Health Worker (VHW) program, initiated in 2007, is an example of a long standing "horizontal" CHW program in rural Southwestern Uganda that has delivered village-level care for chronic disease based on a biannual village health census that identifies individual and family health risks. To facilitate continuity of care for problems identified, health census data were electronically transformed into family-specific Family Health Sheets (FHS) in 2016 which summarize the pertinent demographic and health data for each family, as well as health topics the family would like to learn more about. The FHS, evaluated and discussed here, serves as an epidemiologically-informed "bedside" tool to help VHWs provide longitudinal care in their villages., Methods: 48 VHWs in the program completed a survey on the utility of the FHS and 24 VHWs participated in small discussion groups. Responses were analyzed using both quantitative and standard conceptual content analysis models RESULTS: 46 out of 48 VHWs reported that the FHS made them a "much better VHW." In addition to helping target interventions in child health, women's health, and sanitation, the FHS assisted follow-up of non-communicable diseases in the community. In discussion groups, VHWs reported that the FHS helped them understand risks for future disease, facilitated earning stipends, and increased credibility and trust in the community. Limitations cited were the infrequent updates of the FHS, only biannually with the census, and the lack of cross-reference capability by health problem., Discussion: The FHS supports VHWs in providing longitudinal and comprehensive healthcare of chronic diseases in their villages. Limitations, potential solutions, and future directions are discussed., (© 2021. The Author(s).)

Context: Gender incongruent individuals are exposed to unique stressors as a result of their minority social position. Poor social support has a further adverse impact on the lives and wellbeing of gender incongruent individuals. There is a paucity of scientific data from India on the socioeconomic status (SES) of gender incongruent community., Aims: Aim of the study is to understand and estimate the social support, wellbeing, and SES of gender incongruent individuals in Eastern India., Subjects and Methods: Data of 120 gender incongruent patients from the endocrinology outpatient department of a tertiary care hospital in eastern India were collected. We looked at demographic characteristics, social support, underlying psychiatric comorbidities, and SES. SES was calculated by the Kuppuswamy's socioeconomic status (KSS) scale based on occupation, education, and income., Statistical Analysis Used: Microsoft Word and Excel were used to generate tables., Results: Most of the gender incongruent individuals were transfeminine. Almost half of them had no history of addiction. Most of them had good support from family and friends and very few (only 3%) had mental health problems. Calculation by KSS scale showed most of the study population lay in the upper middle or lower middle socioeconomic class., Conclusions: Strong support from friends and family appears a key factor for protection against psychiatric comorbidities and an all-round impact on the lives and wellbeing of the study population., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Indian Journal of Endocrinology and Metabolism.)

Microbes develop several strategies to survive in the adverse condition such as biofilm formation, attaining non-dividing state, altering drug target or drug, thereby increases the burden of drug dosage. To combat these issues, nanoparticles have shown an alternative approach for new treatment strategy but synthesis via chemical synthetic route limits their application in biomedical field. Here, green method for the synthesis of gold nanoparticles using sophorolipid (SL) is discussed that is characterized by various techniques. Initially, the antimicrobial activity was checked against metabolically active state of microbes; Gram-positive Staphylococcus aureus and Gram-negative Vibrio cholerae using XTT assay and growth kinetics assay. Results suggested higher efficacy of nanoparticles for Gram-negative, therefore further analyzed against Escherichia coli that confirmed its potency for the same. AuNPs-SL also signifies its efficiency at least metabolically active state; non dividing cells and biofilm of these microbes. Induced morphological changes were studied by SEM that revealed AuNPs-SL led to disruption of cell membrane and leakage of intracellular fluid to the surroundings. Inhibition of respiratory enzymes activity also plays a crucial role in bactericidal action as indicated by LDH assay. Synergy of AuNPs-SL with different antibiotics was also analyzed using checkerboard assay. These results suggested the possible use of AuNPs-SL as an antimicrobial therapy in the field of nanomedicine.

Polychlorinated biphenyls (PCBs) are one of the most widely studied group of persistent organic pollutants (POPs). There are 209 different PCBs, however not all 209 can currently be individually quantified in one analytical run. This means that a subset of PCBs congeners are often determined and reported. Some of the most commonly reported subsets are the 7 indicator PCBs (28, 52, 101, 118, 138, 153 and 180) and the WHO 12 PCBs (77, 81, 105, 114, 118, 123, 126, 156, 157, 167, 169 and 189). The WHO 12 congeners are co-planar 'dioxin like' PCBs that are effective for establishing health risks. The 7 indicator PCBs were selected as some of the most common PCBs across the compositional range of the most common technical mixtures (such as Aroclors), and are used to give an indication of the total PCB concentrations. These groups of indicator PCBs were established several decades ago. However, in the environment commercial mixtures are subject to weathering and fractionation processes, and additional sources of non-Aroclor PCBs are also becoming more important. In this manuscript we use existing large scale comprehensive congener specific datasets to evaluate the effectiveness of indicator PCBs to predict total concentrations and establish if they are still fit for purpose. The results indicate that while these traditional indicators are a useful tool to estimate total concentrations in humans with background exposure there are many instances where they are not fit for purpose and can lead to significant under predictions in total PCB concentrations in environmental matrices., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Ovarian cancer (OC) is the fourth most common gynecological malignancy due to its highly aggressive, recurrent, and drug-resistant nature. The last two features are rendered by the presence of cancer stem cells (CSCs). Factors like TGFβ1 and their downstream signaling pathways are upregulated in most cancers and are known to induce EMT and stemness, but the exact mechanisms underlying the process remain unelucidated. In our study, TGFβ1 induced enhanced stem-like properties like high expression of the pluripotent markers SOX2, OCT4a, and NANOG, along with CD44, and CD117 in the OC cells. In addition, increased activity of the aldehyde dehydrogenase enzyme, formation of compact spheroids, and a quiescent phenotype were observed. In deciphering the mechanism behind it, our data propose ZEB1 transcription factor to play a substantial role in inducing the EMT-mediated stemness and chemoresistance. Further, in our study, we elucidated the significant contribution of both Smad and non-Smad pathways like ERK, JNK, and P38 MAPK pathways in the induction of stem-like characteristics. The novelty of the study also resides with the fact in the expression of different lineage-specific markers, like CD31, CD45, and CD117 along with CD44 in the TGFβ1-induced epithelial ovarian cancer spheroids. This suggests a tendency of the spheroidal cells towards differentiating into heterogenic populations, which is a distinctive feature of a stem cell. Taken together, the present study provides an insight to the molecular cues involved in the acquisition of stemness and chemoresistance along with tumor heterogeneity in TGFβ1-induced OC cells., (© 2018 Wiley Periodicals, Inc.)

Protein kinase C (PKC) isozymes play major roles in human diseases, including cancer. Yet, the poor understanding of isozymes-specific functions and the limited availability of selective pharmacological modulators of PKC isozymes have limited the clinical translation of PKC-targeting agents. Here, we report the first small-molecule PKCδ-selective activator, the 7α-acetoxy-6β-benzoyloxy-12-O-benzoylroyleanone (Roy-Bz), which binds to the PKCδ-C1-domain. Roy-Bz potently inhibited the proliferation of colon cancer cells by inducing a PKCδ-dependent mitochondrial apoptotic pathway involving caspase-3 activation. In HCT116 colon cancer cells, Roy-Bz specifically triggered the translocation of PKCδ but not other phorbol ester responsive PKCs. Roy-Bz caused a marked inhibition in migration of HCT116 cells in a PKCδ-dependent manner. Additionally, the impairment of colonosphere growth and formation, associated with depletion of stemness markers, indicate that Roy-Bz also targets drug-resistant cancer stem cells, preventing tumor dissemination and recurrence. Notably, in xenograft mouse models, Roy-Bz showed a PKCδ-dependent antitumor effect, through anti-proliferative, pro-apoptotic, and anti-angiogenic activities. Besides, Roy-Bz was non-genotoxic, and in vivo it had no apparent toxic side effects. Collectively, our findings reveal a novel promising anticancer drug candidate. Most importantly, Roy-Bz opens the way to a new era on PKC biology and pharmacology, contributing to the potential redefinition of the structural requirements of isozyme-selective agents, and to the re-establishment of PKC isozymes as feasible therapeutic targets in human diseases.

Probiotic industries strive for new, efficient and promising probiotic strains that impart a positive impact on consumer health. Challenges are persisting in isolation, screening, and selection of the new indigenous probiotic strains. In the present research, we explored the probiotic potential of 17 lactic acid bacteria isolated from Yak milk in a series of in vitro tests. We also demonstrated their health benefits, i.e., cholesterol degradation, lactose digestion, antimicrobial activity, antioxidant, and anticancer activities. Principal component analysis revealed that more than 50% of the strains fulfilled the examined criteria, e.g., survival in acidic pH, bile concentrations, and adherent property. Approximately all the strains produced antimicrobial substances against the maximum number of tested strains including clinical strains. Most strains degraded cholesterol in comparison to the reference probiotic strain whereas strain Yc showed 1.5 times higher the degradation efficiency of the control strain. Lan4 strain exhibited remarkable anticancer activity and induced the maximum apoptosis (87%) in the Hela cells and was non-toxic to the non-cancerous HEK293 cells. Around ten strains showed positive lactose digestion. Overall, this can be concluded that selected lactic acid bacteria revealed excellent probiotic properties along with desirable health benefits. These strains need to be further investigated in details for their application in the development of novel probiotic preparations for the improvement of public health.

Context: There has been a rise in the incidence of type 1 diabetes mellitus (T1DM) in India. The prevalence of thyroid autoantibodies and thyroid dysfunction is common in T1DM., Aims: The aim of this study is to determine the incidence of thyroid dysfunction and thyroid autoantibodies in T1DM subjects, without any history of thyroid disease, and the prevalence of glutamic acid decarboxylase (GAD) antibody, Islet antigen-2 antibody (IA2), thyroid peroxidase (TPO), and thyroglobulin autoantibodies (Tg-AB) in T1DM subjects., Settings and Design: This was a cross-sectional clinical-based study., Subjects and Methods: Fifty subjects (29 males, 31 females) with T1DM and without any history of thyroid dysfunction were included in the study. All subjects were tested for GAD antibody, IA2 antibody, TPO antibody, thyroglobulin antibody, free thyroxine, and thyroid-stimulating hormone., Statistical Analysis Used: A Chi-square/pooled Chi-square test was used to assess the trends in the prevalence of hypothyroidism. A two-tailed P < 0.05 was considered statistically significant., Results: The mean age of the subjects was 23.50 years. 9.8% of subjects were below the age of 12 years, 27.45% of subjects were of age 12-18 years, 37.25% of subjects were of age 19-30 years, and 25.49% of subjects were above 30 years. 78% were positive autoantibody for GAD, 30% for IA-2, 24% for TPO, and 16% were positive for Tg-AB. A total of 6.0% of T1DM subjects had evidence of clinical hypothyroidism, but the prevalence of subclinical hyperthyroidism (SCH) varied from 32% to 68.0% for we considered different definitions of SCH as advocated by different guidelines. All subjects with overt hypothyroidism had positive GAD and thyroid autoantibodies. One (2%) subject had clinical hyperthyroidism with strongly positive GAD, TPO, and Tg-AB., Conclusions: We found a high prevalence of GAD, IA2, TPO, and Tg-AB in our T1DM subjects. A substantial proportion of our subjects had undiagnosed thyroid dysfunction with a preponderance of subclinical hypothyroidism. All T1DM subjects with overt hypothyroidism or hyperthyroidism had positive GAD and thyroid autoantibodies. The high prevalence of undiagnosed thyroid dysfunction highlights the importance of regular thyroid screening in T1DM subjects., Competing Interests: There are no conflicts of interest.

Background: With the increased number of cholera outbreaks and emergence of multidrug resistance in Vibrio cholerae strains it has become necessary for the scientific community to devise and develop novel therapeutic approaches against cholera. Recent studies have indicated plausibility of therapeutic application of metal nano-materials. Among these, silver nanoparticles (AgNPs) have emerged as a potential antimicrobial agent to combat infectious diseases. At present nanoparticles are mostly produced using physical or chemical techniques which are toxic and hazardous. Thus exploitation of microbial systems could be a green eco-friendly approach for the synthesis of nanoparticles having similar or even better antimicrobial activity and biocompatibility. Hence, it would be worth to explore the possibility of utilization of microbial silver nanoparticles and their conjugates as potential novel therapeutic agent against infectious diseases like cholera., Results: The present study attempted utilization of Ochrobactrum rhizosphaerae for the production of AgNPs and focused on investigating their role as antimicrobial agents against cholera. Later the exopolymer, purified from the culture supernatant, was used for the synthesis of spherical shaped AgNPs of around 10 nm size. Further the exopolymer was characterized as glycolipoprotein (GLP). Antibacterial activity of the novel GLP-AgNPs conjugate was evaluated by minimum inhibitory concentration, XTT reduction assay, scanning electron microscopy (SEM) and growth curve analysis. SEM studies revealed that AgNPs treatment resulted in intracellular contents leakage and cell lysis., Conclusion: The potential of microbially synthesized nanoparticles, as novel therapeutic agents, is still relatively less explored. In fact, the present study first time demonstrated that a glycolipoprotein secreted by the O. rhizosphaerae strain can be exploited for production of AgNPs which can further be employed to treat infectious diseases. Although this type of polymer has been obtained earlier from marine fungi and bacteria, none of these reports have studied the role of this polymer in AgNPs synthesis and its application in cholera therapy. Interestingly, the microbial GLP-capped AgNPs exhibited antibacterial activity against V. cholerae comparable to ciprofloxacin. Thus the present study may open up new avenues for development of novel therapeutic agents for treatment of infectious diseases. Graphical abstract Development of novel therapeutic agents for treatment of cholera.

Chewing betel quid may release chemical carcinogens including xenobiotics resulting in oral malignancy cases preceded by potential malignant lesions and conditions - Oral Submucous Fibrosis (OSF) being one of them. The cytochrome P4501A1 (CYP1A1) enzyme is central to the metabolic activation of these xenobiotics, whereas CYP2E1 metabolizes the nitrosamines and tannins. The present study investigated the association of polymorphisms at CYP1A1m1 (T3801C), m2 (A2455G), and CYP2E1 PstI site (nucleotide 21259) with the risk of OSF. The study was conducted on 75 OSF patients and 150 controls from an eastern Indian population. The above polymorphisms were analyzed by PCR-RFLP method. Analyses of data show that polymorphisms in CYP1A1m2 [OR=8.25 (4.31-15.80)]; CYP1A1m1 [OR=2.88 (1.57-5.24)] and CYP2E1 PstI site [OR=3.16 (1.10-9.04)] revealed significant association with OSF. Our results suggest that polymorphism in CYP1A1 and CYP2E1 may confer an increased risk for Oral Submucous Fibrosis., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The interest in gelatinases is increased because of their association in diverse human diseases, though the relationship between MMP expression and disease progression is very complex and varies in cell to cell. Targeting gelatinases in disease treatment is complicated by the fact that gelatinases are indispensable for normal development and physiology due to their multifunctionality, possible functional redundancy, context-dependent expression, and activity. They are secreted as inactive zymogens which are processed to become active by removal of N-terminal propeptide. The folded conformation of zymogen is required to keep the gelatinases in its latency. Acting on a broad spectrum of extracellular substrates, the gelatinases (both MMP-2 and MMP-9) are critical to the biological processes. Three-dimensional structures of gelatinase-inhibitor complexes and inhibition profiles of compounds screened on them provide an invaluable source to gain insight into the structural determinants as well as functional selectivity. The quest for selective MMP inhibitors (MMPIs) still remains a challenge in search of successful clinical candidates. An increased understanding of the structure, regulation, and function of the individual MMPs will likely lead to more effective strategies in the development of highly selective inhibitors for any given MMP that can then be exploited to achieve the desired drugs.

Pelvic girdle pain (PGP) is a term used specifically to pregnancy-related pain in the lumbosacral, sacroiliac and symphysis pubis joints. Pregnancy-induced hormonal and physical changes increase the risk of musculoskeletal problems in pregnancy. The severity of these conditions varies from mild self-limiting pain to a severe disabling condition. PGP is common in pregnancy and while most can be managed as outpatients, a few patients require inpatient admission for further investigations and management. Prompt identification of these conditions is essential to avoid serious disability. Lack of awareness and failure of recognition not only results in women feeling isolated, but may also result in long-term morbidity. In this review, we explore the aetiology, presentation, risk factors, risk of recurrence, differential diagnosis and multidisciplinary management of these conditions. We also enclose obstetric guidelines to increase the awareness of the health professionals.

Lipomannan (LM) is one of the domains of lipoarabinomannan (LAM) glycolipids, the latter being one of several cell surface organic molecules that fortify mycobacterial species against external attack. Some members of mycobacterial families are pathogenic, most notably Mycobacterium tuberculosis and Mycobacterium leprae, while others are nonpathogenic, and used in the clinic, such as Mycobacterium smegmatis. Additional biological significance arises from the fact that LM has been implicated in several health disorders outside of those associated with mycobacterial pathogens, notably for treatment of bladder cancer. LM is comprised of a heavily lipidated phosphoinositide dimannoside headgroup, from which a mannan array, of varied complexity, extends. The latter consists of a 1,6-alpha-linked backbone flanked at position O2, not necessarily regularly, with alpha-linked mannosides. This paper gives an example of lipomannan synthesis in which all of the sugar components, whether functioning as donors or acceptors, are obtained from n-pentenyl orthoesters, themselves in turn prepared in three easy steps from D-mannose. Assembly of the mannan array is facilitated by the exquisite regioselectivity occasioned by the use of ytterbium triflate/N-iodosuccinimide as the trigger for reaction of n-pentenyl orthoesters.

Oral submucous fibrosis (OSF) is a precancerous condition of the oral cavity and oropharynx and a significant number of such cases transform into oral squamous cell carcinoma (OSCC). Presently, diagnosis of OSF is done mainly through qualitative histopathological techniques and in the level of diagnostic molecular biology no specific genetic marker is evident. Keeping these facts in mind this study evaluates histopathological changes in the epithelium and subepithelial connective tissue of OSF through quantitative digital image analysis in respect to specific candidate features and analyses null mutations in the GSTM1 and GSTT1 by PCR amplification. The analysis revealed that there are subtle quantitative differences in the histological images of OSF compared to NOM. The thickness of the epithelium and cell population in its different zones, radius of curvature of rete-ridges and connective tissue papillae were decreased but length of rete-ridges and connective tissue papillae, fibrocity and the number of cellular components (predominantly inflammatory cells) in the subepithelial connective tissue were increased in OSF. The PCR study revealed that there is no significant difference in the allelic variants in GSTM1 between OSF and normal, while GSTT1 null gene showed significantly higher frequencies in this precancerous condition. This study establishes a distinct quantitative difference between normal oral mucosa (NOM) and OSF in respect to their histological features and GST null gene frequencies.

Background: Arsenic is ubiquitous in the environment, and chronic or acute exposure through food and water as well as occupational sources can contribute to a well-defined spectrum of disease. Despite arsenic being a health hazard and a well-documented human carcinogen, a safe, effective and specific preventive or therapeutic measure for treating arsenic induced toxicity still eludes us., Objective: This study was undertaken to evaluate the therapeutic efficacy of aqueous garlic (Allium sativum L.) extract (AGE) in terms of normalization of altered biochemical parameters particularly indicative of oxidative stress following sodium arsenite (NaAsO(2)) exposure and depletion of inorganic arsenic burden, in vitro and in vivo., Results: AGE (2mg/ml) co-administered with 10 microM NaAsO(2) attenuated arsenite induced cytotoxicity, reduced intracellular reactive oxygen species (ROS) level in human malignant melanoma cells (A375), human keratinocyte cells (HaCaT) and in cultured human normal dermal fibroblast cells. Moreover, AGE application in NaAsO(2) intoxicated Sprague-Dawley rats resulted in a marked inhibition of tissue lipid peroxide generation; enhanced level of total tissue sulfhydryl groups and glutathione; and also increased the activities of antioxidant enzymes, superoxide dismutase and catalase to near normal. An increase in blood ROS level and myeloperoxidase activity in arsenic-intoxicated rats was effectively prevented by AGE administration. AGE was also able to counter arsenic mediated incongruity in blood hematological variables and glucose level., Conclusions: The restorative property of AGE was attributed to its antioxidant activity, chelating efficacy, and/or oxidizing capability of trivalent arsenic to its less toxic pentavalent form. Taken together, evidences indicate that AGE can be a potential protective regimen for arsenic mediated toxicity.

The healing activity of the ethanol extracts of Piper betel, Emblica officinalis, Terminalia bellerica, and Terminalia chebula against the indomethacin-induced stomach ulceration has been studied and compared with that of misoprostol. Compared to autohealing, all the drugs accelerated the healing process, albeit to different extents. The relative healing activities of the extracts was P. betel>E. officinalis>T. bellerica~T. chebula, that correlated well with their in vivo antioxidant and mucin augmenting activities. The excellent healing activity of the extracts of P. betel and E. officinalis indicated a major role of mucin protection and regeneration in the healing of nonsteroidal anti-inflammatory drugs mediated stomach ulceration.

Readily prepared mannosyl n-pentenylorthoesters (NPOEs) serve as donors in themselves and as convenient intermediates for other glycosyl donors, such as n-pentenyl glycosides (NPGs), thioglycosides, and trichloroacetimidates. These various donors are activated by different reagents, and are therefore amenable to versatile, discriminate use. Scandium and ytterbium triflates respond very differently to these donors, with the result that chemoselective discrimination between NPOEs, NPGs, trichloroacetimidates as well as ethyl and phenyl thioglycosides can be achieved. Appropriate NPOEs are also able to provide 2,6 and 3,6 diol acceptors via rearrangement or glycoside formation, and these can be used for one-pot, sequential glycosidations based on orthogonal donors, and in situ double differential glycosidations. Thus NPOEs activated by iodonium ion, specifically generated from ytterbium triflate/N-iodosuccinimide, can be used to monoglycosidate the diols rapidly, with exquisite regio, and sometimes chemo, selectivity. The residual NPOE is converted into disarmed NPG, which is refractory to the reaction conditions, and so poses no threat to the free-OH of the monoglycosidation product. Further glycosidation of the latter can then achieved by direct addition of a trichloroacetimidate or ethyl thioglycoside. This basic strategy has been used to prepare a branched chain pentadecamannan. The success is an example of the efficiency of donor/acceptor MATCH concept for regioselective glycosylation.

Adenovirus infection is a significant cause of ocular, respiratory, and gastrointestinal illness and can spread rapidly. Morbidity is considerable in immune-suppressed individuals and there is significant mortality. There are no effective therapies. During preclinical studies of adenoviral-mediated gene therapy for ocular disorders, we noticed a significant increase in transduction when the target cells were exposed to adenovirus in the presence of ocular vitreous. The vitreous is mainly comprised of water, collagen, and the large polysaccharide hyaluronan. In this paper, we report data that implicate hyaluronan in the adenoviral infectious process and show that interference with the interaction between hyaluronan and its cellular receptor CD44 can block adenovirus transduction in vitro and in vivo.

Films composed in whole or in part of organic compounds represent an important atmospheric interface. Urban surfaces are now known to be coated with a film ("grime") whose chemical composition somewhat resembles that of urban atmospheric aerosols. Such films may act as media in which atmospheric trace gases may be sequestered (leading to their removal from the gas phase); they may also act as reactive media, either as a "solvent" or as a source of reagents. Organic coatings on aqueous surfaces are also important, not just on ocean and lake surfaces ("biofilms") but also on the surfaces of fogwaters and atmospheric aerosol particles. We have initiated experimental uptake studies of trace gases into simple proxies for urban organic films using two techniques: a Knudsen cell effusion reactor and a laser-induced fluorescence method. We will discuss our first results on non-reactive uptake of organic compounds by organic films we use as proxies for urban grime coatings. In general, the measured uptake coefficients appear to track the octanol-air partition coefficients, at least qualitiatively. We have also measured the kinetics of reactions between gas-phase ozone and small polycyclic aromatic hydrocarbons (PAHs), when these are adsorbed at the air-aqueous interface or incorporated into an organic film. Reactions at the "clean" air-water interface and at a coated interface consisting of a monolayer of various amphiphilic organic compounds all follow a Langmuir-Hinshelwood mechanism, in which ozone first adsorbs to the air-aqueous interface, then reacts with already adsorbed PAH. By contrast, the reaction in the pure organic film occurs in the bulk phase. Under some circumstances, heterogeneous oxidation of PAHs by ozone may be as important in the atmosphere as their gas phase oxidation by OH.

Molecular mechanisms of multidrug resistance in Vibrio cholerae belonging to non-O1, non-O139 serogroups isolated during 1997 to 1998 in Calcutta, India, were investigated. Out of the 94 strains examined, 22 strains were found to have class I integrons. The gene cassettes identified were dfrA1, dfrA15, dfrA5, and dfrA12 for trimethoprim; aac(6')-Ib for amikacin and tobramycin; aadA1 and aadA2 for streptomycin and spectinomycin; and ereA2 for erythromycin resistance. To our knowledge, this is the first report of the presence of dfrA5, dfrA12, aac(6')-Ib, and ereA2 cassettes in class I integrons of V. cholerae. Forty-three of 94 strains also had plasmids, and out of these, 14 contained both class I integrons and plasmids. Pulsed-field gel electrophoresis followed by Southern hybridization revealed that in the 14 plasmid-bearing strains, class I integrons resided either on chromosomes, on plasmids, or on both. Our results indicated that besides class I integrons and plasmids, a conjugative transposon element, SXT, possibly contributed to the multiple antibiotic resistance.

The antipsychotic drug, prochlorperazine (Pcp), was tested for its antimicrobial efficacy against 103 strains belonging to both gram positive and gram negative bacteria. The drug was found to possess maximum activity against Staphylococcus aureus, Vibrio cholerae and Shigella spp. Pcp was moderately active against E. coli but most of the strains belonging to Bacillus spp, Klebsiella spp, Salmonella spp and Lactobacillus spp were found to be resistant to this drug. The drug was tested for its mode of antibacterial activity against Shigella dysenteriae 1 and it was found to be bacteriostatic in action. In in vivo studies, Pcp offered significant protection to Swiss albino mice at concentrations of 0.75 micro g/g (P < 0.01) and 1.5 microg/g (P < 0.001) body weight when challenged with 50 median lethal dose of Salmonella typhimurium NCTC 74. Thus the result depicts that prochlorperazine may emerge as a strong antimicrobial drug to replace the conventional antibiotics and to overcome the problem of drug resistance.

Oral administration of ethanol extract of the rhizome ofPirorhiza kurroa at a dose of 20mg/kg body weight, for 10 consecutive days, was found to enhance the rate of healing on Indomethacin-induced gastric ulcer in rats, compared to the ulcerated group without treatment. The level of peroxidised lipid, in terms of thiobarbituric acid reactive species (TBARS), in gastric tissue, was increased in ulcerated rats which was restored to near normalcy on treatment with ethanol extract. The specific activity ofin vivo antioxidant enzymes, viz SOD and catalase and total tissue sulfhydryl (thiol) group, which were markedly decreased in ulcerated group, were found to be significantly elevated (p<0.05), on treatment with the above extract, at the specified dose, compared to the indomethacin-induced ulcerated group without any supporting treatment. The present study thus suggests that the ethanol extract of rhizome ofPicrorhiza kurroa, at the dose of 20mg/kg body weight, accelerated the healing of stomach wall of indomethacin induced gastric ulcerated rats by anin vivo free radical scavenging action.

Pretreatment of an ethanolic extract of leaf ofPiper betle linn at a dose of 200mg/kg body weight, orally administered to rats for ten consecutive days, was found to possess a significant protective action against gastric lesions induced by indomethacin. The extract pretreatment resulted in significant increase in superoxide dismutase (SOD) and catalase (CAT) activity, increase in mucus, hexosamine and total thiol group content, but marked reduction in oxidatively damaged protein and peroxidised lipid levels as compared to untreated ulcerated control. The extract was also found to possess both superoxide and hydroxyl free radical scavenging action. The present observations establish the efficacy of the extract in prevention of experimentally induced peptic ulcer by indomethacin and antioxidant property appears to be predominantly responsible for such cytoprotective activity in the experimental model.