Association between type 2 diabetes mellitus and anthropometric measurements - a case control study in South India.

INTRODUCTION: Obesity is a major risk factor for type 2 diabetes mellitus (T2DM). Clinical evidence indicates a stronger association of diabetes with central obesity than general obesity. The present study aimed to compare the association between type 2 diabetes mellitus and different anthropometric measurements and evaluate the usefulness of these measurements in clinical practice. METHODS: A case-control study was done among 102 individuals; of whom 51 cases included diagnosed T2DM (≥ 20 years age) patients attending the Medicine out-patient consultation of a tertiary care hospital and 51 controls who were screen negative for T2DM and recruited from the local community. Various anthropometric measurements were used according to standard World Health Organization (WHO) protocols. Data was entered and analyzed using Statistical Package for Social Sciences (SPSS) version 15. RESULTS: The proportion of cases with Body Mass Index (BMI) ≥ 25 kg/m2 was 55% as compared to 22% of controls and this association was statistically significant (p < 0.05). The proportion of cases with high waist circumference cut-offs (WC) was 74.5% as compared to 45.1% healthy individuals and this association was also statistically significant (p < 0.05, OR = 3.56). A Receiver Operating Characteristic (ROC) curve for both gender revealed highest area under the curve for body mass index (area = 0.787). Body mass index had the best discriminatory power. Waist to hip ratio was not a sensitive marker especially for females. CONCLUSIONS: A strong association between obesity indices and diabetes was identified. BMI and WC could be used in clinical practice for suggesting life style modifications.

Aortic arch tortuosity with PHACE syndrome - a rare case scenario.

PHACE syndrome is a rare neurocutaneous disorder characterised by an association of infantile haemangiomas with structural anomalies of brain, cerebral vasculature, eye, aorta and chest wall.1 Coarctation of aorta (COA) is most the common cardiac anomaly reported in PHACE syndrome. COA or interrupted aortic arch in PHACE is unique and complex both in location and character compared to the typical coarctation anatomy. Arterial tortuosity of the cerebral vasculature has been well described in literature in PHACE syndrome. We present a rare case of tortuous aortic arch continuing as descending aorta in an infant with PHACE syndrome.

Evaluation of the toxic effect of star fruit on serum biochemical parameters in rats.

The objective of the present study was to evaluate the toxic effect of Averrhoa carambola (star fruit) juice at different storage conditions in Sprague Dawley (SD) rats. Twenty female rats weighing 180 +/- 20 g were randomly assigned into four groups with five rats per group (n = 5). First group served as the control group, fed with distilled water (vehicle). Second, third and fourth groups were orally treated with juice of A. carambola stored for 0, 1 and 3 h respectively for 14 days. Cage-side observations were done daily after each treatment. Body weight, food consumption and water intake were recorded on day-0, day-3, day-7 and day-14. All rats were fasted overnight prior to blood collection through cardiac puncture on day-15. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea and creatinine in blood serum were measured. Data were analyzed using Dunnett's test. From the results obtained, there was no lethality found and LD(50) could not be determined. Increment of ALT levels (P<0.05) was reported in those rats treated with A. carambola juice stored for 3 h. On the basis of these results, we can conclude that A. carambola juice stored for 0 hand 1 h are safe to be consumed. However, juice stored for 3 h exerts toxic effect on rat liver at hepatocellular level.

Mechanistic aspects of benzothiazepines: a class of antiarrhythmic drugs.

The authors have presented ab initio Hartree Fock calculations coupled with intermolecular interaction calculations to study mechanistic aspects of benzothiazepine class of calcium channel blockers. A channel model has been taken containing pore region glutamates and all three classes' sensing residues. Benzothiazepine drugs have been docked in and ternary complex (that is, drug ...Ca(2+)... channel model) stability has been studied and related to mechanistic aspects of these drugs.

An analog of the human albumin N-terminus (Asp-Ala-His-Lys) prevents formation of copper-induced reactive oxygen species.

Copper mobilization and redox activity form damaging reactive oxygen species (ROS) and are implicated in the pathogenesis of ischemia-reperfusion injury, chronic inflammation, Alzheimer's disease, aging, and cancer. Protein sequestration of Cu(II) ions has been shown to prevent ROS-generating reactions. The first four amino acids of the N-terminus of human albumin, Asp-Ala-His-Lys (DAHK), form a tight binding site for Cu(II) ions. We synthesized several analogs, including the enantiomer d-DAHK, to study their effects on copper-induced hydroxyl radical and superoxide formation in the presence of ascorbate. d-DAHK prevented thiobarbituric acid-reactive species (TBARS) formation within physiological and acidic pH ranges (7.5-6.5) and inhibited low-density lipoprotein lipid peroxidation. A d-DAHK/Cu complex exhibited superoxide dismutase-like activity by significantly inhibiting superoxide formation. These in vitro results suggest that d-DAHK may shift the Cu(II)-binding equilibrium from the exchangeable Cu(II) pool to the tightly-bound, nonexchangeable pool, prevent ROS formation, and potentially provide therapeutic benefit for ROS-related diseases.

Identification of a urokinase receptor-integrin interaction site. Promiscuous regulator of integrin function.

Adhesion and signaling by integrins require their dynamic association with nonintegrin membrane proteins. One such protein, the glycolipid-anchored urokinase receptor (uPAR), associates with and modifies the function of the beta(2)-integrin Mac-1 (CD11b/CD18). In this study, a critical non-I-domain binding site for uPAR on CD11b (M25; residues 424-440) is identified by homology with a phage display peptide known to bind uPAR. Recombinant soluble uPAR and cells expressing uPAR bound to immobilized M25, binding being promoted by urokinase and blocked by soluble M25, but not a scrambled control or homologous peptides from other beta(2)-associated alpha-chains. Mac-1, but not a mutated Mac-1 in which M25 was replaced with the homologous sequence of CD11c, co-precipitated with uPAR. In the beta-propeller model of alpha-chain folding, M25 spans an exposed loop on the ligand-binding, upper surface of alphaM, identifying uPAR as an atypical alphaM ligand. Although not blocking ligand binding to Mac-1, M25 (25-100 microM) inhibited leukocyte adhesion to fibrinogen, vitronectin, and cytokine-stimulated endothelial cells. M25 also blocked the association of uPAR with beta(1)-integrins and impaired beta(1)-integrin-dependent spreading and migration of human vascular smooth muscle cells on fibronectin and collagen. These observations indicate that uPAR associates with integrins directly and that disruption of this association broadly impairs integrin function, suggesting a novel strategy for regulation of integrins in the settings of inflammation and tumor progression.

7E3 monoclonal antibody directed against the platelet glycoprotein IIb/IIIa cross-reacts with the leukocyte integrin Mac-1 and blocks adhesion to fibrinogen and ICAM-1.

Recent clinical trials suggest that blockade of integrins is a promising strategy for the treatment of acute coronary syndromes. Administration of 7E3 monoclonal antibody (mAb) Fab fragment (c7E3 Fab) directed against platelet integrin IIb/IIIa (alpha IIb beta 3, CD41/CD61) reduces acute ischemic complications of coronary angioplasty and clinical restenosis at 6 months. However, 7E3 mAb is not selective for platelet IIb/IIIa but also cross-reacts with the leukocyte integrin Mac-1 (alpha M beta 2, CD11b/CD18) and the vitronectin receptor (alpha v beta 3, CD51/CD61). Information regarding how this mAb may affect other cells important in vascular repair is scant. Potential interactions of c7E3 Fab with inflammatory (i.e., monocytes and neutrophils), vascular smooth muscle, and endothelial cells may contribute to the in vivo actions of c7E3 Fab. In this study we explored the binding of 7E3 to monocytic cells and the functional effect of 7E3 and c7E3 Fab on Mac-1-mediated adhesion to fibrinogen (FGN) and intercellular adhesion molecule-1 (ICAM-1), ligands abundant in the injured vessel wall. Flow cytometry demonstrated that 7E3 bound to THP-1 monocytic cells and identified a subpopulation (approximately 10%) of Mac-1 that was qualitatively similar to that recognized by CBRM1/5, a mAb directed to an activation-specific neoepitope present on a subset of Mac-1 molecules. mAb 7E3 bound to K562 cells transfected with just the alpha subunit (CD11b) of Mac-1 but not to nontransfected cells, confirming a direct interaction between 7E3 and Mac-1. mAb 7E3 and c7E3 Fab blocked the adhesion of Mac-1-bearing cells to FGN (80 +/- 11% and 78 +/- 9% inhibition, respectively) and ICAM-1 (62 +/- 14% and 62 +/- 17%). Both 7E3 and c7E3 Fab significantly inhibited (70 +/- 6% and 62 +/- 26%) soluble FGN binding to human peripheral blood monocytes. Thus, c7E3 Fab cross-reacts with the CD11b subunit of Mac-1 and interrupts cell-extracellular matrix and cell-cell adhesive interactions and may thereby influence the recruitment of circulating monocytes to sites of vessel injury. Given the recent evidence that adherent and infiltrating monocyte number directly correlates with the extent of neointimal hyperplasia, inhibition of Mac-1-dependent adhesion and IIb/IIIa-dependent function by c7E3 Fab may jointly contribute to the regulation of vascular repair and to the sustained clinical benefits observed with c7E3 Fab after angioplasty.

Mac-1 (CD11b/CD18) and the urokinase receptor (CD87) form a functional unit on monocytic cells.

The leukocyte integrin Mac-1 (CD11b/CD18) and the urokinase receptor (uPAR, CD87) mediate complementary functions in myelomonocytic cells. Both receptors promote degradation of fibrin(ogen) and also confer adhesive properties on cells because Mac-1 and uPAR bind fibrin and vitronectin, respectively. Staining of lung biopsy specimens from patients with acute lung injury indicated that fibrin and vitronectin colocalize at exudative sites in which macrophages bearing these receptors accumulate. Because of the parallel roles and physical proximity of Mac-1 and uPAR, the capacity of these receptors to functionally interact was explored. Induction of Mac-1 and uPAR expression on monocytic cell lines by transforming growth factor- beta 1 and 1.25-(OH)2 vitamin D3 conferred urokinase and uPAR-dependent adhesion to vitronectin, which was further promoted by engagement of Mac-1. Vitronectin attachment promoted subsequent Mac-1-mediated fibrinogen degradation threefold to fourfold. In contrast, enhancement of uPAR occupancy by exogenous urokinase or receptor binding fragments thereof inhibited Mac-1 function. Addition of urokinase progressively inhibited Mac-1-mediated fibrinogen binding and degradation (maximal inhibition, 91% +/- 14% and 72% +/- 15%, respectively). Saturation of uPAR with urokinase also inhibited binding of the procoagulant Mac-1 ligand, Factor X. These inhibitory effects of uPAR were reproduced in fresh monocytes, cultured monocytic cells, and in Chinese hamster ovary (CHO) cells transfected with both human Mac-1 and human uPAR. These data show that the procoagulant and fibrinolytic potential of monocytic cells is co-ordinately regulated by ligand binding to both Mac-1 and uPAR and identify uPAR as a regulator of integrin function. Vitronectin-enhanced fibrin(ogen) turnover by Mac-1 may operate as a salvage pathway in the setting of urokinase and plasmin inhibitors to promote clearance of the provisional matrix and subsequent healing.

Mechanisms of pertussis toxin-induced myelomonocytic cell adhesion: role of Mac-1(CD11b/CD18) and urokinase receptor (CD87).

Stimulation of monoblastic U937 cells with transforming growth factor beta 1 and 1,25-(OH)2 vitamin D3 (TGF-beta 1/D3) upregulates urokinase receptor (uPAR) and confers urokinase-dependent adhesiveness to the cells for serum- or vitronectin-coated surfaces. Recent studies show that uPAR itself is a high-affinity adhesion receptor for vitronectin and that urokinase (uPA) is an activator of this adhesive function. In the course of exploring possible G-protein involvement in this adhesion it was observed that TGF-beta 1/D3-primed U937 cells became adhesive to vitronectin in an uPAR-dependent manner when exposed to pertussis toxin (PTX). The adherent response is concentration- and time-dependent, and was not due to the ADP-ribosyltransferase activity of the toxin because the purified B-subunit of PTX was equally effective. Although promoting adhesion to serum- or vitronectin-coated surfaces, PTX blocked spontaneous cell adhesion to fibrinogen, an endogenous ligand for the Mac-1 receptor (CD11b/CD18). Flow cytometry study showed that expression of the alpha-subunit of Mac-1 (CD11b) on primed cells was increased by nearly threefold. Monoclonal antibody to CD11b abolished the PTX-induced cell adhesion and the binding of the primed cells to PTX-coated plates. Activation of Mac-1 receptor by its endogenous ligand fibrinogen induced cell adherent response similar to PTX. PTX, but not uPA, triggered a rapid rise in [Ca2+]i in primed U937 cells, and PTX-induced adhesion was significantly attenuated by 1,2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxy-methyl ester (BAPTA/AM), a selective membrane-permeant [Ca2+]i chelator. PTX-induced cell adhesion was also prevented by antibodies to uPAR and by conditioned medium containing soluble uPAR. Together these data indicate that PTX B-subunit may bind to Mac-1 integrin, which leads to a rapid rise in [Ca2+]i and subsequent activation of uPAR for adherence to vitronectin, suggesting a functional link between Mac-1 and activation of uPAR important to cellular trafficking and host defence in response to Bordetella pertussis infection.

Urokinase receptor is a multifunctional protein: influence of receptor occupancy on macrophage gene expression.

Binding of urokinase to the glycolipid-anchored urokinase receptor (uPAR) has been implicated in macrophage differentiation. However, no biochemical markers of differentiation have yet been directly linked to uPAR occupancy. As extensive changes in proteolytic profile characterize monocytic differentiation, we have examined the role of uPAR occupancy on protease expression by differentiating phagocytes. Antibodies to either urokinase or to uPAR that prevent receptor binding inhibited induction of cathepsin B in cultured monocytes and both cathepsin B and 92-kD gelatinase mRNA and protein in phorbol diester-stimulated myeloid cells. Mannosamine, an inhibitor of glycolipid anchor assembly, also blocked protease expression. Anti-catalytic urokinase antibodies, excess inactive urokinase, or aprotinin had no effect, indicating that receptor occupancy per se regulated protease expression. Antibodies to the integrins CD11a and CD29 or to the glycolipid-anchored proteins CD14 and CD55 also had no effect. Protease induction was independent of matrix attachment. Antibodies to urokinase or uPAR affected neither the decrease in cathepsin G nor the increase in tumor necrosis factor-alpha in phorbol ester-stimulated cells. These data establish that uPAR is a multifunctional receptor, not only promoting pericellular proteolysis and matrix attachment, but also effecting cysteine- and metallo-protease expression during macrophage differentiation.

Early mobilization following anterior fixation with bone graft and metal plate in traumatic cervical fracture dislocations.

Eighteen cases of traumatic fracture dislocation were managed surgically using a technique which involved an anterior cervical approach followed by discectomy, bone graft, and insertion of a metal plate. The patients were mobilized early to prevent the usual complications of bedsores, deep vein thrombosis, pulmonary embolism, chest infection, and contractures. After more than two years of follow-up, no patient has had problems with local infection, screw loosening, neurological deterioration, dysphagia, or persistence of laryngeal nerve paresis. The benefits of this technique, already endorsed by some authors, include reduced morbidity and hospitalization as well as decreased demand on the staff, particularly as required by quadriplegic patients.

[Cerebral aspergilloma. Review of the literature apropos of a case]. / L'aspergillome cérébral. Revue de la littérature à propos d'un cas.

The incidence of mycotic infection of C.N.S. seems to have increased in the last few years and the diagnosis is being made more and more frequently. The authors are reporting a case of a 27 year old man, admitted with severe intracranial hypertension, very poor visual acuity and right motor weakness. The C.T. Scan showed a massive space occupying lesion in the left hemisphere. Only the biopsy, then the surgical removal of the lesion revealed the true histological nature. It turned out to be aspergilloma. The patient expired 13 hours later. Up to date, 25 cases of Aspergillus granulomas have been reported. This disease is included in the entity of neuromycosis. Its specificity compared to the other types of cerebral mycotic localization as for example abscess, meningitis, mycotic aneurysm, lies in the fact that it presents as granulomatous mass in the hemisphere, mimicking a brain tumor without any specific neuroradiological findings. In the light of so far published literature, the authors draw the attention to the fact of the difficulty of diagnosis of this dreadful benign disease due to the lack of specific clinical and radiological findings. They are stressing the necessity of early and vigorous diagnosis mainly in patients with a risk factor to try to reduce the high mortality that has been universally reported in almost all cases.

Induced autotetraploidy in chickpea (Cicer arietinum L.).

In chickpea, out of three colchicine concentrations and two treatment durations used (combinations of 0.25, 0.05, 0.025% colchicine and 4 and 6 h duration), seed treatment with 0.25% for 4 h proved to be the most effective in producing autotetraploids. Colchicine treatment on seedlings failed. The induced tetraploidy was accompanied by larger leaves, flowers, stomata, pollen grains and seeds. Mean percentage stainable pollen and podset were reduced, but some plants had relatively normal meiosis and produced as many pods as the diploid parent, indicating the potential of induced autotetraploids in chickpea improvement.

Acute hemorrhagic pancreatic necrosis in mice. Influence of the age and sex of the animals and of dietary ethionine, choline, methionine, and adenine sulfate.

The influence of several factors on the development of acute hemorrhagic pancreatitis (pancreatic necrosis) with fat necrosis in mice fed DL-ethionine with a choline-deficient diet has been investigated. The results showed that: a) the incidence of the induced disease is dependent upon the age and sex of the animals and the dietary level of ethionine; b) 100% of young female mice fed 0.5% ethionine develop acute hemorrhagic pancreatitis and die within 5 days; c) the incidence is only 10 to 20% when 0.5% ethionine is fed with either a choline-supplemented diet or with laboratory chow; and d) development of pancreatic pathology is completely prevented by the inclusion in the diet of 0.5% methionine but not by the inclusion of 0.5% adenine. Possible mechanisms whereby choline deficiency potentiates the pancreatotoxicity of ethionine in mice are discussed.