Glucocrinology of Modern Sulfonylureas: Clinical Evidence and Practice-Based Opinion from an International Expert Group.

AIM: The primary objective of this document is to develop practice-based expert group opinion on certain important but less discussed endocrine and metabolic effects of modern sulfonylureas (SUs) and their usage in the management of diabetes mellitus (DM). BACKGROUND: Modern SUs may be considered a panacea in DM care with their beneficial extra-pancreatic, pleiotropic, and cardiovascular effects. Safe glycemic control with SUs could be achieved with appropriate patient selection, drug and dosage selection, and patient empowerment. Additionally, sulfonylureas also exhibit certain endocrine and metabolic effects, which could be considered beneficial in the management of DM. In this regard, a group of international clinical experts discussed the less known beneficial aspects of SUs and safe and smart prescription of modern SUs in DM care. RESULTS: The concept of glucocrinology or the relationship of glycemia with the endocrine system was emphasized during the meetings. Clinical experts arrived at a consensus for the usage of modern SUs in the presence of other endocrine dysfunction and the impact of these drugs on endocrine health. The beneficial pleiotropic and cardiovascular effects of modern SUs were also discussed. The key discussion points were considered to develop clinical expert opinions for the use of modern SUs in persons with DM. Clinical expert opinions were developed for indications, pleiotropic benefits, cardiovascular outcomes, adherence, and safe use of modern SUs. CONCLUSIONS: Appropriate clinical judgement coupled with a patient-centered approach is crucial to achieve the best outcome in persons with DM. Owing to their safety, efficacy, extra-pancreatic benefits including effects on endocrine and metabolic aspects, and low cost of therapy, modern SUs could be considered as drugs/agents of choice for the treatment of diabetes. FUNDING: Sanofi India.

Euthymia in Diabetes: Clinical Evidence and Practice-Based Opinion from an International Expert Group.

AIM: To develop an evidence-based expert group opinion on various types of euthymia associated with diabetes mellitus (DM) and its management. BACKGROUND: Diabetes mellitus is a metabolic syndrome characterized by diverse biomedical and psychosocial features. Emotional health disturbances may lead to psychological and psychiatric dysfunction and may negatively influence glycemic control. Patients with DM may experience diabetes distress (DD) associated with burden of self-care, interpersonal issues, and emotional worries regarding the ability to cope with the illness. Euthymia or a state of positive mental health and psychological well-being should be considered a key outcome of diabetes care. Therefore, to achieve optimal outcomes, the consideration and measurement of psychological and psychiatric aspects along with glycemic levels are very important. A group of multidisciplinary clinical experts came together in an international meeting held in India to develop a workable concept for euthymia in diabetes care. A multidisciplinary approach was suggested to enhance the clinical outcomes and facilitate patient-centered care. During the meeting emphasis was given to the concept of a euthymia model in diabetes care. This model focuses on enhancement of self-care skills in diabetic patients and preventative health awareness among diabetes care providers. Euthymia also encompasses patient-provider communication to aid enhancement of coping skills. RESULTS: After due discussions and extensive deliberations, the expert group provided several recommendations on implementing the concept of euthymia in DM care. CONCLUSIONS: Introduction of the concept of euthymia in routine clinical practice is important to improve the quality of life and coping skills in patients with DM. A timely clinical assessment of psychological and psychiatric aspects along with patient-reported outcomes of diabetes contributes to overall health and well-being of affected individuals. FUNDING: Sanofi India.

The microRNA signatures: aberrantly expressed miRNAs in prostate cancer.

MicroRNAs (miRNAs) are short, non-coding, conserved, oligonucleotides that are regulatory in nature and are often dysregulated in many cancers including prostate cancer. Depending on the level of complementarity between the miRNA and mRNA target, they can either inhibit translation or degrade the target mRNA. MiRNAs expression is specific to the type of cancer, its stage and level of metastasis, making miRNAs potential stage-specific biomarkers of cancer. Recent research has shown that these miRNAs have the potential to be a diagnostic and prognostic non-invasive biomarker for various cancers including prostate cancer. Various miRNAs have been reported as novel biomarkers for prostate cancer therapy. However, there is inconsistency in the data reported and no overlapping expression pattern could be found. In this review, we have highlighted the most consistently reported dysregulated miRNAs in prostate cancer from the existing literature and discussed the currently available data on their role in regulating the hallmarks of prostate cancer. These four most consistently reported dysregulated miRNAs viz. miRNA-141, miRNA-375, miRNA-221 and miRNA-21 need to be further validated in terms of their regulatory potential in regulating various pathways important for prostate cancer management.

Noncatheter-related bacteraemia due to Chryseobacterium indologenes in an immunocompetent patient.

Chryseobacterium indologenes belongs to a group of nonfermentative Gram-negative bacilli and is an uncommon human pathogen. It causes severe infections such as septicaemia and ventilator-associated pneumonia in immunocompromised patients or after prolonged hospitalisation. We report a case of a noncatheter-related bacteraemia in a 22-year-old immunocompetent female whose blood culture showed the growth of C. indologenes, identified by Vitek GNI system (bioMerieux, France). The patient responded to treatment with ciprofloxacin. The pathogenicity and virulence factors of C. indologenes remain unclear. This case indicates that C. indologenes might cause symptomatic disease in immunocompetent persons with otherwise no associated underlying risk factors.

Regional and seasonal variations in ultraviolet B irradiation and vitamin D synthesis in India.

UNLABELLED: Evaluation of ultraviolet B index (UVBI) and its impact on vitamin D synthesis is important. We observed the maximum UVBI between 11 am and 1 pm. There was no increase in serum 25(OH)D levels following sun exposure during winter as the UVBI was significantly low, emphasizing the need for vitamin D supplementation during these months. INTRODUCTION: The amount of vitamin D3 synthesizing UVB irradiation (290-320 nm) reaching the earth's surface at different altitudes and seasons in different parts of India and it's impact on vitamin D synthesis has not been well studied. METHODS: The hourly UVB index (UVBI) from 10 am to 3 pm everyday for 12 months was measured by a solar meter in 4 different zones (North, Northeast, West and South) of the country. To study the impact of sun light exposure on vitamin D synthesis during winter, healthy school children aged 10-15 years were exposed to sunlight for a period of 30 min per day, between 11 am to 12 noon with 10 % body surface area, for 4 weeks. The main outcome measures were serum 25(OH)D, PTH, calcium, phosphate, and alkaline phosphatase levels before and after sun exposure. RESULTS: The mean UVBI was highest between 11 am and 1 pm throughout the year in all locations. The highest UVBI was recorded from the North zone (4.5 ± 2.7 µW/Cm(2)), while the least was recorded in the Northeast zone (2.1 ± 1.2 µW/Cm(2)). UVBI readings in the Northeast zone were consistently low throughout the year, while all the other three zones showed significant seasonal fluctuations. Surprisingly, we observed a significant decrease in serum 25(OH)D levels from baseline (6.3 ± 4.6 to 5.1 ± 2.7 ng/mL; p < 0.001) despite sun exposure. CONCLUSION: The mean UVBI was highest between 11 am and 1 pm throughout the year in all locations. No increase in the serum 25(OH)D levels was observed following sun exposure in winter, emphasizing the need for vitamin D supplementation during these months.

Variations in the spatial distribution of gall bladder cancer: a call for collaborative action.

BACKGROUND: The incidence of gall bladder cancers in this part of the world is high and the spatial variation in occurrence of gall bladder cancers can be identified by using geographical information system. MATERIALS AND METHODS: Data set containing the address information of gall bladder cancer patients from the District of Kamrup, India was obtained from cancer registry of a regional cancer center. The data set consisted of patients registered during the period of January 2010 to December 2012. The ArcGIS 10.0 used for the present analysis and the population density map of the District was prepared by using LandScan, 2008™. RESULTS: There were isolated areas with very high density of cases and low population density termed as "hot spots". Alternatively there were areas with very high population density and lesser number of cases with gall bladder cancers. CONCLUSION: This type of an analysis using GIS provides evidence to conduct joint research by epidemiologists and specialists from environmental and geological sciences in tandem.

Addressing barriers to effective basal insulin therapy.

Diabetes has reached epidemic proportions worldwide. It is a major health hazard particularly in developing countries like India due to the genetic susceptibility and changes in lifestyle. Glycaemic control is very poor in India as reflected by recent studies showing average HbA1c of > 9%. Insulin therapy is the mainstay of diabetes management. Currently available insulins have certain limitations. Modern insulin therapy needs to overcome these limitations to effectively achieve the optimal glycemic control. Hypoglycaemia is one of the important barrier which limits the use of insulin therapy and incidence of hypoglycaemia increases with increased variability in glucose lowering effects of Insulin when one tries to achieve stricter glycaemic targets. Fixed time administration is another important barrier, particularly for basal insulin administration that may affect the quality of life. Also the available basal insulins do not provide complete 24 hours control of fasting hyperglycaemia. Insulin degludec is designed to have a flat and stable glucose-lowering effect for more than 42 hours with less risk of hypoglycaemia. And it overcomes most of the issues with currently available basal insulins.

Recommendations for insulin initiation based on ethnicity.

Even in a developed country like USA, substantial number of subjects with type 2 diabetes fail to achieve adequate glycemic control despite the availability of several groups of anti-diabetic medications targeting multiple pathophysiological features of type 2 diabetes. Are we treating our type 2 diabetes subjects appropriately? To aid practicing clinicians various professional bodies like American Diabetes Association (ADA), European Association for Study of Diabetes (EASD), Canadian Diabetes Association (CDA), etc. regularly publish clinical practice guidelines and consensus statements. Since racial and ethnic differences in insulin resistance, dietary pattern, glucose metabolism, genetic variation are known phenomena, it would be interesting to evaluate the aptness of these guidelines from ethnopharmacy perspective. We postulate that certain ethnic characteristics of populations will decide the best form of insulin therapy rather than blanket recommendations on starting every patient on basal insulin.

Baseline characteristics of the Indian cohort from the IMPROVE study: a multinational, observational study of biphasic insulin aspart 30 treatment for type 2 diabetes.

INTRODUCTION: The IMPROVE study is an openlabel, nonrandomized, observational study aimed at determining the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) treatment in subjects with type 2 diabetes from 11 countries. Here, we report the baseline data of the Indian cohort. METHODS: All subjects with type 2 diabetes requiring insulin and considered suitable for BIAsp 30 therapy based on their physician's clinical judgment were eligible to enter the study. The data recorded at baseline included demographic characteristics, detailed medical histories, physician-cited reasons for starting BIAsp 30 treatment, and the chosen dosage regimens. RESULTS: The Indian cohort included 17,995 subjects with diabetes. Poor glycemic control (glycated hemoglobin [HbA(1c)], 8.7%-9.6%) was observed at baseline in all four geographical zones (North, South, East, and West) and prestudy treatment groups (no therapy, only oral antidiabetic drug [OAD], OAD +/- insulin, and OAD +/- insulin +/- BIAsp 30). Prevalence of both micro- and macrovascular complications was high, also reflecting poor glycemic control. Improving HbA(1c) and fasting and postprandial blood glucose levels were the most common reasons for starting BIAsp 30 therapy. The subjects were prescribed a mean BIAsp 30 dose of approximately 24 IU, and a twice-daily regimen was employed in almost 80% of subjects. CONCLUSION: The baseline results of the IMPROVE study Indian cohort confirm the poor glycemic control and the delayed initiation and/or inadequacy of treatment in subjects with type 2 diabetes. These results also highlight the need for timely and appropriately intensive insulin-based therapy.

Fluorescence lifetime fluctuations of single molecules probe the local environment of oligomers around the glass transition temperature.

Single molecule fluorescence experiments have been performed on a BODIPY-based dye embedded in oligo(styrene) matrices to probe the density fluctuations and the relaxation dynamics of chain segments surrounding the dye molecules. The time-dependent fluorescence lifetime of the BODIPY probe was recorded as an observable for the local density fluctuations. At room temperature, the mean fraction of holes surrounding the probes is shown to be unaffected by the molecular weight in the glassy state. In contrast, the free volume increases significantly in the supercooled regime. These observations are discussed in the framework of the entropic theories of the glass transition.

The practice of telepathology in India.

Telepathology in India is still in the evolving stages. Although, much progress has been made around the world specially in the field of digital imaging and virtual slides, the practice of telepathology in India still revolves around static telepathology, be it in telelearning or distance learning, or in remote diagnosis. Websites such as telepathology.org.in have been very successful in popularizing telepathology through quizzes of interesting and rare cases. The only study of teleconsultation from India, has shown that a good concordance with glass slide and static telepathology images. The reasons for the relative delay in acceptance of telepathology in India are manifold.

Nail changes in alopecia areata: incidence and pattern.

One hundred consecutive patients with alopecia areata were examined for presence of nail abnormalities. Nail changes were seen in 44/100 (44%) of patients with most frequent occurrence in multifocal variety (30/44=68%). The commonest abnormality observed was superficial pits seen in 28 (64%) patients. Presence and severity of nail changes may indicate a more severe and recalcitrant disease.

Hypopigmented pityriasis versicolor developing on a pre-existing Becker's Naevus.

A 24-year-old male presenting with pityriasis versicolor developing on a pre-existing lesion of Becker's naevus is being reported for its rare occurrence.

Pattern of childhood STDs in a major hospital of East Delhi.

Of the 1418 patients with STDs, who attended the STD clinic between January 1996 to December 2000, 50 (3.4%) were children below 14 years of age. Boys (29) were more than girls (21). Syphilis was the most common STD found in these children (46.8%), followed by vulvo-vaginal candidiasis (19.2%), condylomata acuminata (10.6%), gonorrhoea (8.5%), herpes progenitalis (6.4%), chancroid (4.3%), perianal candidosis and perianal molluscum contagiosum (2.1 % each). Three children had more than one STD. A history of sexual abuse could be elicited in 30 children (60%), none of the children were positive of HIV. All children with symptoms pertaining to their genitourinary system should be evaluated thoroughtly for sexual abuse.

Glibenclamide induced photosensitivity.

A 54 - year-old man with diabetes mellitus developed photodermatitis following ingestion of second generation sulphonylurea, glibenclamide. The case is being reported to highlight the infrequently reported side effect of glibenclamide.

Comparative efficacy of ketoconazole and fluconazole in the treatment of pityriasis versicolor: a one year follow-up study.

Pityriasis versicolor can be treated by a single or multiple dosage regime of ketoconazole as well as by fluconazole. The therapeutic efficacy of these two drugs has not been compared. One hundred and eighty patients with moderate to extensive pityriasis versicolor confirmed by KOH and Wood's lamp examination were randomly assigned to one of the four oral antifungal regimes: Ketoconazole 400 mg single dose (Category I), Ketoconazole 200 mg daily for 10 days (Category II), Fluconazole 400 mg single dose (Category III) or Fluconazole 150 mg per week for 4 weeks (Category IV). Follow up was done at 2 and 4 weeks and then at 3, 6 and 12 months after the treatment in each group. KOH and Wood's lamp examinations were repeated each time. After four weeks of treatment, clinical cure was observed in 66.6% (Category I), 73.3% (Category II), 80% (Category III) and 59.9% (Category IV) of patients. Mycological cure after four weeks of treatment was observed in 53.3% (Category I), 73.3% (Category II), 82.2% (Category III) and 64.4% (Category IV) of patients. After twelve months of follow-up, maximum relapses were observed with Category I. No relapse was seen in Category III patients. The time period of relapse varied from three to ten months. In conclusion, single dose 400 mg oral fluconazole provided the best clinical as well as mycological cure rate with no relapse during twelve months of follow-up.

Clinico-myocological profile of tinea capitis in North India and response to griseofulvin.

There is a paucity of literature on tinea capitis from North India. The response to griseofulvin has not been studied as well. We studied 153 consecutive patients of tinea capitis for clinical patterns, causative dermatophytic species, clinico-etiological correlation, and response to griseofulvin. Culture and sensitivity were done on all patients. All patients were treated with griseofulvin for 6-8 weeks; non-responders were further treated with fluconazole. Ninety percent of the patients were less than 15 years of age, 75% belonged to poor socioeconomic groups and 19% had a family history of tinea capitis. The seborrheic variant was the commonest clinical pattern seen in 47.8% of patients, followed by grey patch, black dot, kerion, and alopecia-areata-like tinea capitis in 35.9%, 8.5%, 6.5% and 1.3% of patients, respectively. Only 66% of patients had a positive culture. T. violaceum was the commonest dermatophytic species isolated in 38% patients. M. audouinii, T. schoenleinii, T. tonsurans, M. gypseum, T. verrucosum and T. mentagrophytes were isolated in 34%, 10%, 9%, 3%, 3% and 3% of patients, respectively. Of the isolates 94% were susceptible to griseofulvin, and 100% were susceptible to fluconazole. By using griseofulvin for 6-8 weeks 97.4% of the patients were cured; nonresponders required therapy with fluconazole for cure. To conclude, tinea capitis is still a disease of younger people of poor socioeconomic status. T. violaceum and M. audouinii are the most common responsible dermatophytes. The response to griseofulvin was excellent, and it should be used as a first line therapy.

Food and feeding of Amphiesma stolatum (Linnaeus 1758).

The food and feeding behaviour of Amphiesma stolatum was studied. A total of 117 snakes were examined to analyse the diet composition. Ten live snakes were maintained in enclosure for evaluating the feeding habit, choice of food and rate of assimilation. The anurans constituted the major diet of the food spectrum. In captivity, fishes (fry), amphibians and reptiles were consumed by the snakes. A. stolatum exihibited Elaphe type of hunting behaviour. In most cases the snake struck the prey at its head. The assimilation rate with frog was highest.