Common variants of IL6, LEPR, and PBEF1 are associated with obesity in Indian children

The increasing prevalence of obesity in urban Indian children is indicative of an impending crisis of metabolic disorders. Although perturbations in the secretion of adipokines and inflammatory molecules in childhood obesity are well documented, the contribution of common variants of genes encoding them is not well investigated. We assessed the association of 125 common variants from 21 genes, encoding adipocytokines and inflammatory markers in 1,325 urban Indian children (862 normal weight [NW group] and 463 overweight/obese [OW/OB group]) and replicated top loci in 1,843 Indian children (1,399 NW children and 444 OW/OB children). Variants of four genes (PBEF1 [rs3801266] [P = 4.5 × 10(-4)], IL6 [rs2069845] [P = 8.7 × 10(-4)], LEPR [rs1137100] [P = 1.8 × 10(-3)], and IL6R [rs7514452] [P = 2.1 × 10(-3)]) were top signals in the discovery sample. Associations of rs2069845, rs1137100, and rs3801266 were replicated (P = 7.9 × 10(-4), 8.3 × 10(-3), and 0.036, respectively) and corroborated in meta-analysis (P = 2.3 × 10(-6), 3.9 × 10(-5), and 4.3 × 10(-4), respectively) that remained significant after multiple testing corrections. These variants also were associated with quantitative measures of adiposity (weight, BMI, and waist and hip circumferences). Allele dosage analysis of rs2069845, rs1137100, and rs3801266 revealed that children with five to six risk alleles had an approximately four times increased risk of obesity than children with less than two risk alleles (P = 1.2 × 10(-7)). In conclusion, our results demonstrate the association of the common variants of IL6, LEPR, and PBEF1 with obesity in Indian children.     

Herbal enema: At the cost of colon

Various colonic side-effects of herbal enema have been reported in literature ranging from mild abdominal discomfort to self-limiting haemorrhagic colitis. It rarely requires blood transfusion or subtotal colectomy. We report a 57-year-old male patient developing severe ileo-colitis with persistent massive rectal bleeding immediately after herbal enema administration for the treatment of chronic constipation and was resistant to conservative management. Patient was managed successfully with emergency total laparoscopic colectomy. Post-operative recovery of the patient was excellent.     

Isolation and Characterization of Ammonia Secreting Cyanobacterium Nostoc sp. NDUPC007 from Agriculture Fields of Varanasi

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Nostoc sp. NDUPC007 was isolated from agricultural fields of Varanasi, U.P., India. Cyanobacterium was...     

Visceral leishmaniasis elimination targets in India,strategies for preventing resurgence

ABSTRACT

Introduction: Visceral leishmaniasis (VL) is a fatal parasitic disease caused by a parasite belonging to the Leishmania donovani complex and transmitted by infected female Phlebotomous argentipes sand flies. The VL elimination strategy in the Indian subcontinent (ISC), which has a current goal of reducing the incidence of VL to below 1/10,000 of population by the year 2020, consists of rapid detection and treatment of VL to reduce the number of human reservoirs as well as vector control using indoor residual spraying (IRS). However, as the incidence of VL declines toward the elimination goal, greater targeting of control methods will be required to ensure appropriate early action to prevent the resurgence of VL.

Area covered: We discuss the current progress and challenges in the VL elimination program and strategies to be employed to ensure sustained elimination of VL.

Expert commentary: The VL elimination initiative has saved many human lives; however, for VL elimination to become a reality in a sustained way, an intense effort is needed, as substantial numbers of endemic subdistricts (primary health centers (PHCs) blocks level) are yet to reach the elimination target. In addition to effective epidemiological surveillance, appropriate diagnostic and treatment services for VL at PHCs will be needed to ensure long-term sustainability and prevent reemergence of VL.     

Myocardial cell membrane stress ionic dyskinesia reversal by diltiazem

Based on previous observations of cardioplegic ionic myocardial distress, myocardial stress dyskinesia was investigated as another possible cause of exercise stress testing-induced silent myocardial ischemia by analyzing the efficacy of the myocytic calcium channel blocker diltiazem in normalizing the results of patients who previously tested positive.From October 2004 to February 2006, 25 patients (13 women [52%]; aged between 28 and 71 years; mean age 56.9 years) complaining of precordial pain, with no coronary artery obstruction detected by scintigraphy and coronary cineangiography studies, presenting with positive ergometric testing, defined by ST segment depression, with no precordial pain or arrhythmia during testing, were treated with diltiazem in three daily doses of 90 mg, and were restudied five or seven days after the first examination. Treadmill electrocardiography exercise testing was performed using the standard Bruce protocol, analyzing the following parameters: the J point and Y point of the ST segment depression, maximum oxygen uptake reached, heart rate, double product and exercise performance measured in metabolic equivalents.The administration of diltiazem abolished patients' complaints of atypical precordial pain in all cases and blocked ST segment depression, both J point (control: mean 2.3+/-0.5 mm; with treatment: 0.4+/-0.5 mm; P<0.001) and Y point (control: mean 1.9+/-0.7 mm; with treatment: 0.1+/-0.3 mm; P<0.001). The heart rate variations were not significant (P>0.05), with mean values of 156.2+/-12.0 beats/min for the control and 149.0+/-19.2 beats/min with treatment. There was significant (P<0.01) improvement in the functional classification of the heart with treatment (mean 2.7+/-0.9 for the control and 2.0+/-0.7 with treatment), without significant variations (P>0.05) in maximum oxygen uptake and double product results.The administration of the myocytic calcium channel blocker diltiazem impeded the occurrence of the silent ST segment depression, previously induced by exercise stress testing in patients without confirmed obstructive coronary artery disease, supporting the involvement of calcium-dependent myocardial contraction ionic dyskinesia in the genesis of silent ST segment depression.     

Biphasic Testosterone Delivery Profile Observed with Two Different Transdermal Formulations

Purpose. Our long-term goal is to develop formulations for pulsatile testosterone (T) delivery. T has been reported earlier to show biphasic pharmacokinetics in humans by Mazer et al, as well as biphasic permeation across excised rat skin by our group. We examined two kinds of formulations to evaluate their delivery profiles and to assess whether differences in the formulation approach affect pharmacokinetics in animal models. Methods. One formulation consisted of T and a polymer blend dissolved in isopropanol; administered by dispensing the solution on the skin to cast a film in situ. The other was an adhesive-dispersion patch. In vitro release from the patch was evaluated using a flow-through cell interfaced with an HPLC pump and UV detector. Single dose pharmacokinetics were evaluated in castrated Wistar rats and bonnet monkeys immunized against gonadotropin-releasing hormone to deplete endogenous T. Results. Two maximas were observed in the T release profile from the patch and in serum concentration versus time profiles in both animal models on application of either formulation. The relative magnitudes of the two maximas and the time interval separating them were different in the case of each formulation. Conclusions. Both formulations result in biphasic pharmacokinetics of T in the animal models studied. Discrete maximas presumably correlate with 'burst' and 'sustained' phases of drug release.     

Corneal thickness measurements in normal and keratoconic eyes: Pentacam comprehensive eye scanner versus noncontact specular microscopy and ultrasound pachymetry

PURPOSE: To compare central corneal thickness (CCT) measurements taken with the Pentacam comprehensive eye scanner (CES), noncontact specular microscopy (SM), and ultrasound pachymetry (UP) in normal and keratoconic corneas. SETTING: Department of Ophthalmology, Ankara University School of Medicine, Ankara, Turkey. METHODS: In a prospective study, 3 CCT measurements were taken with the Pentacam CES, SM, and UP in that sequence from 1 eye of 45 consecutive patients with myopia (group A) and 62 consecutive patients with keratoconus (group B). Eyes with keratoconus were further divided into 3 subgroups, mild, moderate, and severe, according to the mean keratometry readings. RESULTS: Pentacam CES (r = 0.994) and UP (r = 0.993) demonstrated very high and comparable reproducibility in group A. In group B, Pentacam CES displayed better reproducibility (r = 0.988) than UP (r = 0.969) and SM (r = 0.901). The mean CCT measurements of Pentacam CES and UP were not significantly different in group A (P = .37) and in eyes with mild keratoconus (P = .29), whereas significant differences between all instrument pairs were evident in group B and in moderate and severely keratoconic eyes (P<.05). Noncontact SM measurements were significantly smaller than those of Pentacam CES and UP in all groups (P<.05) when a measurement could be obtained. There were significant linear correlations between CCT measurements of Pentacam CES, UP, and noncontact SM in groups A, B, and mildly keratoconic eyes (P<.001). CONCLUSIONS: Results suggest that whereas Pentacam CES and UP may be used interchangeably in normal eyes in the clinical setting for the measurement of CCT, one should be cautious interpreting corneal thickness data from Pentacam CES, UP, and particularly SM in eyes with keratoconus. Whereas, in normal and mildly keratoconic eyes, Pentacam CES and UP demonstrated very high and comparable reproducibility, in moderately keratoconic eyes, Pentacam CES readings showed better reproducibility than UP.     

Purification and properties of a protein from bovine lens which inhibits trypsin and two endogenous lens proteinases

An inhibitor of trypsin-like proteinases was isolated from the water-soluble proteins of bovine lens cortex. The inhibitor was purified by four simple procedures: the separation of the inhibitor fraction by Agarose A-1·5 m gel filtration, extraction with 2·5% TCA at 70°C, ammonium sulfate precipitation of the TCA-soluble proteins and a final separation by gel filtration chromatography. This preparation was found to be homogeneous by SDS-PAGE with an approximate subunit molecular weight of 5500 daltons. Gel filtration separated the ammonium sulfate precipitate into an inactive high-molecular-weight peak which eluted in the void volume, and two peaks of approximately 40 000 daltons and 10 000 daltons. Both low-molecular-weight peaks gave a single 5500 dalton band on SDS-PAGE, but only the 40 000 dalton peak was active when concentrated and assayed with bovine trypsin. These data suggest that the inhibitor is present in multimeric forms in solution, but only the octamer appears to be active. Antibodies prepared against the purified inhibitor showed a single precipitin line, while no reaction was seen with an α-crystallin antiserum. Upon storage in solution all of the inhibitor became converted into a high-molecular-weight form which was completely inactive. SDS-PAGE dissociated the inhibitor aggregate into a major 44000 dalton band along with several minor bands. Amino acid analysis showed that the purified inhibitor contains a very high content of hydrophobic residues.The lens inhibitor was effective in reducing the activity of trypsin, but complete inhibition was not seen even at high inhibitor levels. A rapid and complete inhibition was observed, however, with two endogenous trypsin-like proteinases isolated from the α-crystallin region.