N-Acetylaspartate synthase is bimodally expressed in microsomes and mitochondria of brain

N-Acetylaspartate (NAA) is an abundant amino acid derivative of the central nervous system that is localized primarily in neurons and has found widespread use in clinical NMR spectroscopy (MRS) as a non-invasive indicator of neuronal survival and/or viability. Its function, although still obscure, is thought to reflect its unusual metabolic compartmentalization wherein NAA synthase occurs in the neuron and aspartoacylase, the hydrolytic enzyme that removes the acetyl moiety, occurs in myelin and glia. The NAA synthase enzyme, acetyl-CoA/l-aspartate N-acetyltransferase (ANAT), was previously shown to function in mitochondria (MIT), although other subcellular fractions were apparently not examined. In this study we confirmed its presence in MIT but also found significant activity in rat brain microsomes (MIC). The reaction mixture, consisting of [(14)C]aspartate plus acetyl-CoA in Na-phosphate buffer (pH 7), gave rise to [(14)C]NAA that was separated and quantified by TLC. Reaction rates were 29.0+/-0.46 and 6.27+/-0.27 nmol/h/mg for MIC and MIT, respectively. K(m) values and pH optima were similar, and both fractions showed modest enhancement of ANAT activity with the detergents Triton CF-54 and CHAPS. Our tentative conclusion is that ANAT is bimodally targeted to MIT and a component of MIC-likely endoplasmic reticulum. ANAT activity increased in both MIC and MIT between 29 and 60 days of age but differed thereafter in that only MIT ANAT showed a decrease after 1 year.     

A novel neurotrophic peptide: APP63-73

The objective of this study was to find out which N-terminal segment/s of amyloid precursor protein (APP) has any neurotrophic properties, since soluble APP-alpha (sAPP-alpha) has neurotrophic effects. We investigated neurotrophic properties of eight peptide segments of N-terminal APP. The APP63-73 was able to enhance neuronal growth; augment axonal and cell body growth in human neuroblastoma cell line, SH-SY5Y. Neurotrophic effects of chronic APP63-73 treatment were assessed in vivo using streptozotocin-induced diabetes and ovariectomized rats. Thus, this study demonstrated that APP63-73 peptide has neurotrophic effects both in vivo and in vitro.     

An outbreak of sheep pox on a sheep breeding farm in Jammu, India

An outbreak of sheep pox occurred in December 2001 on a sheep breeding farm in Jammu, India. The farm maintains three exotic breeds of sheep, i.e. American Merino, Rambouillet and Australian cross. The disease agent was confirmed as sheep pox virus by clinical and post-mortem examination as well as laboratory testing. Typical pock lesions were dispersed over the body of the affected animals with nodular lesions observed in the lung tissue of the dead animals. Sheep pox virus antigen and antibody were detected in infected tissue and convalescent sera, respectively, with serological tests. Viral deoxyribonucleic acid was extracted from the infected tissue and amplified using a diagnostic polymerase chain reaction. Sheep of the Rambouillet breed were found to be most susceptible to infection with morbidity and mortality rates of 26.9% and 8.3%, respectively. Morbidity and mortality rates in the entire flock were 18.4% and 6.3%, respectively. The grazing and migration pattern indicates that the disease was probably introduced to the farm by local sheep.     

Repeated treatment with S. aureus superantigens expands the survival rate of Ehrlich ascites tumor bearing mice

The bacterial superantigen Staphylococcal enterotoxin-A (SEA), produced by some strains of Staphylococcus aureus, causes proliferation of cytotoxic T-lymphocytes and cytokine production in vivo. SEA has been shown to be highly efficient for antibody-targeted superantegen immunotherapy for different tumor models. A candidate B-cell superantigen that has received considerable attention these days is staphylococcal protein-A (PA). It has been shown to possess multiple immunological responses. The anti-tumor property of PA is well documented in the literature in various transplantable tumors of rats and mice. In the present study, we have shown that the T-cell superantigen SEA and B-cell superantigen PA induce immunomodulatory and anti-tumor activity which is strongly protentiated by PA + SEA co-administration. Combination treatment with PA and SEA prolongs the immune response in vivo, limits the development of immunological unresponsiveness and promotes maximum anti-tumor effects to tumor carrying animals, as compared with PA or SEA alone. The immune response after combined therapy is characterized by substantially augmented IFN-gamma, TNF-alpha, Nitric oxide and strong CTL activity. Our data demonstrate that combined PA + SEA therapy induces long-term survival of the animals, carrying the Ehrlich ascites tumor.     

Prominence of symptoms and level of stigma among depressed patients in Calcutta

A pilot study of 29 patients for research on clinical depression employed the framework of cultural epidemiology to examine illness-related experience, meaning, behaviour with a Bengali version of the explanatory Model Interview Catalogue (EMIC). This report examined patterns of distress and stigma with reference to the most troubling patient-specified symptom. All subjects were psychiatric outpatients in the Institute of Psychiatry, Calcutta, and met Diagnostic and Statistical Manual (DSM)-IV criteria for a major depressive episode. Only 5 patients (17.2%) identified sadness as the most troubling problem, and 48.3% specified pains and other somatic symptoms instead. An internally consistent stigma scale with Cronbach's alpha of .67, comprised 13 items, was used to assess stigma. In addition to the scale score for each subject, the contribution of each item was reported and compared. A suggestive, though not significantly lower value of the stigma score for patients reporting somatic symptoms as most troubling, compared with sadness, was consistent with findings from prior studies showing a positive relationship between the magnitude of depression and stigma. These findings are discussed with reference to their impact on recognition and help seeking among patients, and recognition and management of depression by general practitioner. Culturally distinctive presentations and social contexts of depression and other mental illnesses should be addressed in professional training and public health communications.     

Safe motherhood--a long way to achieve

Maternal mortality ratio (MMR) is the most important index for monitoring the progress of safe motherhood programmes. A retrospective analysis of all maternal deaths at RG Kar Medical College and Hospital, Calcutta from 1st January, 1995 to 31st December, 1997 was carried out. There were 29,563 live births and 203 maternal deaths giving cumulative MMR of 686.67 per 100,000 live births. Among the victims 25.6% were < or = 20 years of age, majority (73.4%) were unbooked, mostly from rural (59.6%) or urban slum (20.2%) and from low socio-economic status (59.6%). Most (60.10%) were multiparous and 50.74% patients died within 24 hours of hospital admission. Direct causes were responsible for 83.25%, indirect causes for 14.78% and unrelated causes for 1.97% of maternal deaths. Toxaemia was the leading cause (53.20%) of maternal mortality. Other important causes were haemorrhage (16.75%), sepsis (12.31%), severe anaemia (6.4%), infective hepatitis (1.47%) and heart disease (3.44%). In comparison to previous years no significant changes in MMR had been found though there were temporary decline in some years. The contribution of toxaemia in maternal deaths is significantly high and is on the rise. The other national and global pictures were reviewed. India is among the countries of high MMR and far away from achieving safe motherhood. Majority of deaths are preventable. The medical causes of maternal deaths are in fact, the end point of a longer chain of many underlying factors like low socio-economic status, poverty, illiteracy, high parity and inadequate or no health care. An active community-based health care system accessible to every mother with strong referral system is the most effective approach to achieve safe motherhood.     

Risk factors of diarrhoea among flood victims: a controlled epidemiological study

The concept and practice of 'disaster preparedness and response', instead of traditional casualty relief, is relatively new. Vulnerability analysis and health risks assessment of disaster prone communities are important prerequisites of meaningful preparedness and effective response against any calamity. In this community based study, the risk of diarrhoeal disease and its related epidemiological factors were analysed by collecting data from two selected flood prone block of Midnapur district of West Bengal. The information was compared with that of another population living in two non-flood prone blocks of the same district. The study showed that diarrhoeal disease was the commonest morbidity in flood prone population. Some behaviours, like use of pond water for utensil wash and kitchen purpose, hand washing after defecation without soap, improper hand washing before eating, open field defecation, storage of drinking water in wide mouth vessels etc. were found to be associated with high attack rate of diarrhoea, in both study and control population during flood season compared to pre-flood season. Attack rates were also significantly higher in flood prone population than that of population in non-flood prone area during the same season. Necessity of both community education for proper water use behaviour and personal hygiene along with ensuring safe water and sanitation facilities of flood affected communities were emphasized.     

Spinocerebellar ataxia type 6 in eastern India: Some new observations

Introduction:Spinocerebellar ataxias (SCAs) are hereditary, autosomal dominant progressive neurodegenerative disorders showing clinical and genetic heterogeneity. They are usually manifested clinically in the third to fifth decade of life although there is a wide variability in the age of onset. More than 36 different types of SCAs have been reported so far and about half of them are caused by pathological expansion of the trinucleotide, Cytosine Alanine Guanine (CAG) repeat. The global prevalence of SCA is 0.3-2 per 100,000 population, SCA3 being the commonest variety worldwide, accounting for 20-50 per cent of all cases, though SCA 2 is generally considered as the commonest one in India. However, SCA6 has not been addressed adequately from India though it is common in the eastern Asian countries like, Japan, Korea and Thailand.Objective:The present study was undertaken to identify the prevalence of SCA6 in the city of Kolkata and the eastern part of India.Results:6 of the 83 subjects turned out positive for SCA6, constituting therefore, 13.33% of the patient pool.Discussion:SCA6 is prevalent in the eastern part of India, though not as frequent as the other common varieties.Conclusions:Further community based studies are required in order to understand the magnitude of SCA6 in the eastern part, as well as in other regions of India.     

Sitagliptin, an dipeptidyl peptidase-4 inhibitor, does not alter the pharmacokinetics of the sulphonylurea, glyburide, in healthy subjects

AIMS

Sitagliptin, a dipeptidyl peptidase-4 inhibitor, is an incretin enhancer that is approved for the treatment of Type 2 diabetes. Sitagliptin is mainly renally eliminated and not an inhibitor of CYP450 enzymes in vitro. Glyburide, a sulphonylurea, is an insulin sensitizer and mainly metabolized by CYP2C9. Since both agents may potentially be co-administered, the purpose of this study was to examine the effects of sitagliptin on glyburide pharmacokinetics.

METHODS

In this open-label, randomized, two-period crossover study, eight healthy normoglycaemic subjects, 22–44 years old, received single 1.25-mg doses of glyburide alone in one period and co-administered with sitagliptin on day 5 following a multiple-dose regimen for sitagliptin (200-mg q.d. ×6 days) in the other period.

RESULTS

The geometric mean ratios and 90% confidence intervals [(glyburide + sitagliptin)/glyburide] for AUC_0–∞ and C_max were 1.09 (0.96, 1.24) and 1.01 (0.84, 1.23), respectively.

CONCLUSION

Sitagliptin does not alter the pharmacokinetics of glyburide in healthy subjects.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• No data are available on the potential drug interaction of sitagliptin and glyburide.
• Sitagliptin belongs to a new class of drugs called DPP-4 inhibitors recently approved for the treatment of Type 2 diabetes.

WHAT THIS STUDY ADDS

• Glyburide is a commonly used sulphonylurea medication to treat Type 2 diabetes.
• Combination therapy is often required to achieve adequate glucose control in Type 2 diabetes.
• Sitagliptin does not appear to interfere with glyburide pharmacokinetics and therefore may be potentially co-administered with glyburide for the treatment of Type 2 diabetes.