Cutaneous markers of coronary artery disease

Coronary artery disease (CAD) is rapidly increasing in prevalence across the world and particularly in south Asians at a relatively younger age. As atherosclerosis starts in early childhood, the process of risk evaluation must start quite early. The present review addresses the issue of cutaneous markers associated with atherosclerosis, and the strengths and weaknesses of the markers in identifying early coronary atherosclerosis. A diligent search for such clinical markers, namely xanthelasma, xanthoma, arcus juvenilis, acanthosis nigricans, skin tags, ear lobe crease, nicotine stains, premature graying in smokers, hyperpigmented hands in betel quid sellers, central obesity, and signs of peripheral vascular disease may prove to be a rewarding exercise in identifying asymptomatic CAD in high risk individuals.     

Adrenal glucocorticoids modulate [3H]cyclic AMP binding to protein kinase A (PKA), cyclic AMP-dependent PKA activity, and protein levels of selective regulatory and catalytic subunit isoforms of PKA in rat brain

Alterations in hypothalamic-pituitary-adrenal (HPA) function are associated with changes in mood and behavior. Protein kinase A (PKA), on activation, phosphorylates many important intracellular proteins and thereby plays a major role in mediating various physiological functions in brain. We systematically examined the relationship of altered HPA function with PKA modifications in rat brain after administering corticosterone to normal rats and by first adrenalectomizing rats and then simultaneously treating them with different doses of corticosterone. Rats were decapitated on day 1, 4, or 14. Subcutaneously implanted 50- or 100-mg corticosterone pellets in normal rats for 4 or 14 days significantly decreased PKA activity, B(max) of [3H]cyclic AMP binding, and protein levels of selective PKA regulatory (RIalpha, RIIbeta) and catalytic (Catbeta) subunit isoforms in cortex and hippocampus in a dose-dependent manner without any significant changes at day 1; these changes were more pronounced at day 14. However, adrenalectomy caused the opposite changes in these measures at day 4 or 14 in both cortex and hippocampus, and the magnitude of the changes was more pronounced at day 14. Simultaneous treatment with implanted corticosterone at 50- or 100-mg doses in adrenalectomized rats reversed the adrenalectomy-induced increases in PKA measures in a dose-dependent manner. These results suggest that endogenous glucocorticoid modifies the expression of RIalpha, RIIalpha, and Catbeta subunit isoforms of PKA, as well as the catalytic and regulatory activities of PKA, and that these alterations in PKA may in part explain HPA axis-mediated changes in mood and behavior.     

Antidepressants reduce phosphoinositide-specific phospholipase C (PI-PLC) activity and the mRNA and protein expression of selective PLC beta 1 isozyme in rat brain

In order to examine whether antidepressants mediate their action by interacting with one of the key components of the phosphoinositide (PI) signaling pathway, i.e. PI-specific phospholipase C (PLC), and whether this represents a common mechanism of action of antidepressants, we determined the effects of antidepressants of various classes on PI-PLC activity and on the expression of PLC isozymes in rat brain. It was observed that chronic (21-day) but not acute (1-day) administration with desipramine (DMI), fluoxetine (FLX) and phenelzine (PHLZ), decreased PI-PLC activity in membrane and cytosol fractions of cortex and hippocampus. Similar changes were observed with alprazolam (ALP) and buspirone (BUS), who possess anxiolytic and antidepressant properties. On the other hand, an anxiogenic drug, metachlorophenylpiperazine (MCPP), increased PI-PLC activity in both membrane and cytosol fractions of cortex and hippocampus. The immunolabeling studies showed that all the antidepressants and anxiolytics that caused a decrease in PI-PLC activity also selectively decreased the protein levels of a specific isozyme of PLC, i.e. PLCβ₁, in membrane and cytosol fractions of cortex and hippocampus, whereas MCPP increased the levels of this particular isozyme. These changes were accompained with changes in the mRNA levels of PLCβ₁, as determined by quantitative RT-PCR. These antidepressants and anxiolytics did not cause significant changes in the expression of PLC δ₁ or γ₁ isozyme. Our results thus suggest that modulation of PI-PLC may be common to all classes of antidepressants, which in turn, may be associated with their mechanisms of action.     

Increase in the Specific Surface Area of Budesonide During Storage Postmicronization

Purpose. To evaluate an anomalous increase in the specific surface area of budesonide during storage postmicronization. Methods. Budesonide was micronized using a conventional air-jet mill. Surface areas and total pore volumes were measured using nitrogen sorption. Porosity was measured using mercury intrusion porosimetry. Particle size was measured using laser diffraction. Results. Budesonide exhibited a surface area increase of 22 ± 2% when stored at 25°C following micronization. The rate of surface area increase was lower at 20°C, suggesting a temperature-dependent stress relaxation mechanism for the micronized particles. The increase in surface area was accompanied by: (a) an increase in total pore volume; (b) a shift of the pore size distribution to smaller pore sizes; (c) a decrease in size of particles above 1 m; and (d) an increase in rugosity/surface roughness. Conclusions. Freshly micronized budesonide exhibited an unusual and significant postmicronization increase in specific surface area upon storage under ambient conditions. Postmicronization stress-relief by intraparticle crack formation, crack propagation with time, and particle fracture seems to be the primary mechanism behind this surface area increase.     

Hyperhomocysteinemia,and low intakes of folic acid and vitamin B12 in urban North India

Summary Background and Aim An adverse coronary risk profile has been reported amongst rural-to-urban migrant population living in urban slums undergoing stressful socio-economic transition. These individuals are likely to have low intakes of folic acid and vitamin B12, which may have an adverse impact on serum levels of homocysteine (Hcy). To test this hypothesis, we studied serum levels of Hcy in subjects living in an urban slum of North India and healthy subjects from urban non-slum area. Methods Group I consisted of 46 subjects (22 males and 24 females) living in an urban slum, while group II consisted of healthy subjects (n = 26, 13 males and 13 females) living in the adjacent non-slum area. Anthropometric measurements, biochemical profile (fasting blood glucose, total cholesterol, serum triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) and fasting serum levels of Hcy were measured. Dietary intakes of folic acid, vitamin B12, vitamin B1, and iron were calculated by the 24-hour dietary recall method. Serum levels of Hcy were correlated with dietary intakes of nutrients, anthropometry, and metabolic variables. Results Sex-adjusted serum levels of Hcy in mmol/L (Mean ± SD) were high, though statistically comparable, in both the groups (group I: 20.8 ± 5.9 and group II: 23.2 ± 5.9). Overall, higher than normal serum levels of Hcy (> 15 μmol/L) were recorded in 84 % of the subjects. A substantial proportion of subjects in both groups had daily nutrient intakes below that recommended for the Asian Indian population (folic acid: 93.4 % in group I and 96.7 % in group II, vitamin B12: 76.1 % in group I and 88.4 % in group II). However, between the two groups, average daily dietary intakes of both the nutrients were statistically comparable. As compared to non-vegetarians, vegetarians showed lower intakes of folic acid (p < 0.01) and vitamin B12 (p < 0.01) in both groups. On multivariate linear regression analysis with serum Hcy as the response variable and vegetarian/non-vegetarian status and sex (male/female) as predictor variables, higher serum levels of Hcy were observed in vegetarians vs non-vegetarians (β = 4.6, p < 0.05) and males vs females (β = 5.3, p < 0.01). Conclusions Low intakes of folic acid and vitamin B12, and hyperhomocysteinemia, in both the healthy population living in urban slums and adjacent urban non-slum areas, are important observations for the prevention of nutritional and cardiovascular diseases in the Indian subcontinent. Received: 30 October 2001, Accepted: 14 January 2002     

Substituted acrylophenones and related mannich bases as possible spermicides and inhibitors of HIV envelope glycoprotein-CD4 interaction

Several appropriately substituted 4-(dialkylamino-alkyl)-substituted-styryl-alkyl ketones or acetophenones were prepared and subjected to the Mannich reaction to yield compounds that would incorporate both alpha,beta-unsaturated keto groups and a substituted aminomethyl function with or without another olefinic moiety at position 4. The spermicidal activity of the prepared compounds was evaluated. Several compounds 2d, 4a and 4e were found to possess spermicidal activity at 0.005% concentration, while compounds 2a, 2c, 2f, 3a and 4b were active at 0.01% concentration. Compounds 2a, 2c, 3a, 4a and 4e also inhibited the interaction between recombinant HIV Env and CD4. Out of these, compound 2c was found to be most active.     

Factors associated with severe asthma

OBJECTIVE:To study the role of various factors associated with development and severity of bronchial asthma in children between 5-15 years of age. SETTING: Tertiary Care Medical College Hospital. METHODS: A case control study was carried out during May 96 to April 98. Sixty children each suffering from mild (chronic) and severe asthma (chronic) and 60 controls were enrolled to study the association of various risk factors with development of asthma and for severe disease. RESULTS: On univariate analysis factors associated with significant risk for development of asthma included family history of asthma (p = 0.003), lack of exclusive breastfeeding (p = 0.05), past history of bronchiolitis (p = 0.02), associated allergic rhinitis (p = 0.04) and atopic dermatitis (p = 0.01). For development of severe asthma, associated factors were early onset of symptoms (p = 0.01), family history of asthma in grandparents (p = 0.04) and more than 10 cigarettes per day smoked by any family member. No significant effect of air pollution, overcrowding, pets and passive smoking were found on either development of asthma or it's severity. On multivariate analysis only age of onset below 48 months was associated with severe asthma (OR 2.13, 95% CI 1.00-4.54). Exclusive breastfeeding for more than 4 months was the most protective factor for development of asthma (OR 0.25, 95% CI 0.08-0.70). A strong association between development of asthma and past history of bronchiolitis or tuberculosis (OR 5.26, 95% CI 1.7-16.20) and presence of associated atopic dermatitis or rhinitis (OR 7.5, 95% CI 1.64-34.48) was observed. CONCLUSION: History of associated allergic diseases and past history of bronchiolitis were significantly associated with development of asthma. Exclusive breastfeeding for first 4 months of life was protective. The most significant factor associated with severe asthma was onset of illness before 48 months of age. There was no significant effect of air pollution, over crowding, pets at home or passive smoking on severity of asthma     

3'-deoxyribonucleosides and their derivatives as anti-amoebic agents

In general nucleoside analogues were found to possess in vitro amoebicidal property against trophozoites of Entamoeba histolytica. The acid-labile nature of these compounds completely destroyed their ability to cure caecal amoebiasis of rats. However the therapeutic efficacy of one of these compounds yielded most promising results, with 10% cures when it was administered as enteric coated formulation.     

Recurrent volvulus of the stomach

Summary A 3-month-old female child presenting with recurrent crying and vomiting since with was diagnosed radiologically to have recurrent volvulus of the stomach. She was successfuly treated by anterior gastropexy. From the departments of Pediatric Surgery and Radiology, M.Y. Hospital & M.G.M. Medical College, Indore.