Biochemical, histological and echocardiographic changes during experimental cardiomyopathy in STZ-induced diabetic rats.

Diabetes mellitus is associated with an increased susceptibility to cardiovascular disease and it has been suggested that alterations in myocardial function may contribute to the development of diabetic cardiovascular complications. The objective of the present study is to examine the left ventricular (LV) function in streptozotocin (STZ)-induced diabetic rats in a definite course of time by non-invasive methods, i.e. M-mode and Doppler echocardiography. From the results, it was found that treatment of animals with STZ resulted in increase in blood glucose, triglycerides, cholesterol, low density lipoproteins (LDL) and decrease in serum total protein levels.Echocardiographic studies revealed that LV internal dimension (mm) during systole was significantly increased after 12 weeks of diabetes when compared to base line data of the same animals and with control animals 6.50+/-0.13 versus 4.25+/-0.17, versus 4.34+/-0.25 (P<0.05), however there was no significant change after 4-8 weeks of diabetes. Also LV internal dimension (mm) during end diastole increased significantly only after 12 weeks of diabetes than to base line data of the same animals and with control animals 7.71+/-0.34 versus 6.18+/-0.25, versus 6.25+/-0.18 (P<0.05). Fractional shortening (%), 15.69+/-5.1 versus 31.22+/-1.7, versus 30.56+/-2.1 (P<0.05), and ejection fraction (%) 37+/-2.31 versus 68.18+/-2.8, versus 60.32+/-3.5 (P<0.05), differ significantly after 12 weeks of diabetes when compared to base line data of the same animals and with control animals. E-wave (cm/s) was significantly decreased after 12 weeks of diabetes 21.11+/-1.5 versus 35.19+/-4.5, versus 32.75+/-3.0 (P<0.05), and A-wave (cm/s) was significantly increased after 12 weeks of diabetes 34.88+/-4.2 versus 19.21+/-2.8, versus 20.59+/-2.1 (P<0.05); thus, diabetic animals after 12 weeks had an inversed E/A ratio. Histological studies revealed that after 8 weeks of diabetes, necrosis was minimal, but after 12 weeks of diabetes extensive focal endomyocardial necrosis was observed. From this study, we conclude that overt LV systolic and diastolic dysfunction was fully visible at 12 weeks of diabetes on echocardiography and this non-invasive technique of echocardiography is useful in diagnosing LV dysfunction in diabetic rats without the need of invasive histopathological procedures.     

The phenotype of a flavin-containing monooyxgenase knockout mouse implicates the drug-metabolizing enzyme FMO1 as a novel regulator of energy balance

Flavin-containing monooxygenases (FMOs) of mammals are thought to be involved exclusively in the metabolism of foreign chemicals. Here, we report the unexpected finding that mice lacking Fmos 1, 2 and 4 exhibit a lean phenotype and, despite similar food intake, weigh less and store less triglyceride in white adipose tissue (WAT) than wild-type mice. This is a consequence of enhanced whole-body energy expenditure, due mostly to increased resting energy expenditure (REE). This is fuelled, in part, by increased fatty acid β-oxidation in skeletal muscle, which would contribute to depletion of lipid stores in WAT. The enhanced energy expenditure is attributed, in part, to an increased capacity for exercise. There is no evidence that the enhanced REE is due to increased adaptive thermogenesis; instead, our results are consistent with the operation in WAT of a futile energy cycle. In contrast to FMO2 and FMO4, FMO1 is highly expressed in metabolic tissues, including liver, kidney, WAT and BAT. This and other evidence implicates FMO1 as underlying the phenotype. The identification of a novel, previously unsuspected, role for FMO1 as a regulator of energy homeostasis establishes, for the first time, a role for a mammalian FMO in endogenous metabolism. Thus, FMO1 can no longer be considered to function exclusively as a xenobiotic-metabolizing enzyme. Consequently, chronic administration of drugs that are substrates for FMO1 would be expected to affect energy homeostasis, via competition for endogenous substrates, and, thus, have important implications for the general health of patients and their response to drug therapy.     

Evaluation of Nutritional Status and Eating Pattern in First and Second-Time Denture Wearers: A Prospective 60 Days (2 Months) Pilot Study

Elderly individuals with extensive tooth loss preferentially consume soft, easier to chew foods which have a low nutrient density. The purpose of this study was to suggest that every complete denture wearer has to be periodically counseled by a registered Dietician and Dentist for check up to avoid malnutrition and disease. Fourteen patients were selected for this study. Seven of them with four or five teeth remaining without any functional units and seven patients who were known cases of complete denture wearers with ill-fitting or worn out dentures. The results of the study analyzed the change in eating pattern and hence the nutritional status of two groups of edentulous subjects; Group I (patients who underwent a recent transition from partially edentulous state to a completely edentulous state), and Group II (known complete denture wearers for five to ten years). Clinical examination of Group I showed an improvement, by, the decrease in percentages in both the paleness of the conjunctiva and nails of the selected patients. In Group II, there was a significant change in anthropometry and iron intake and the clinical examination showed positive changes in the patient's normal appearance, eyes and nails. Paired sample statistics between both the groups evaluated significant changes in energy, iron and vitamin C intakes in the dietary assessment chart. The general questionnaire assessment showed an improvement in the eating pattern of both the groups, which, may definitely account for a positive change in the nutritional status of the participants later. This study emphasizes that every complete denture wearer needs to be periodically counseled by a registered dietician and dentist for checkup to avoid malnutrition and disease.     

Metabolic remodeling precedes mitochondrial outer membrane permeabilization in human glioma xenograft cells

Glioma cancer cells adapt to changing microenvironment and shift from mitochondrial oxidative phosphorylation to aerobic glycolysis for their metabolic needs irrespective of oxygen availability. In the present study, we show that silencing MMP-9 in combination with uPAR/cathepsin B switch the glycolytic metabolism of glioma cells to oxidative phosphorylation (OXPHOS) and generate reactive oxygen species (ROS) to predispose glioma cells to mitochondrial outer membrane permeabilization. shRNA for MMP-9 and uPAR (pMU) as well as shRNA for MMP-9 and cathepsin B (pMC) activated complexes of mitochondria involved in OXPHOS and inhibited glycolytic hexokinase expression. The decreased interaction of hexokinase 2 with mitochondria in the treated cells indicated the inhibition of glycolysis activation. Overexpression of Akt reversed the pMU- and pMC-mediated OXPHOS to glycolysis switch. The OXPHOS un-coupler oligomycin A altered the expression levels of the Bcl-2 family of proteins; treatment with pMU or pMC reversed this effect and induced mitochondrial outer membrane permeabilization. In addition, our results show changes in mitochondrial pore transition to release cytochrome?c due to changes in the VDAC-Bcl-XL and BAX-BAK interaction with pMU and pMC treatments. Taken together, our results suggest that pMU and pMC treatments switch glioma cells from the glycolytic to the OXPHOS pathway through an inhibitory effect on Akt, ROS induction and an increase of cytosolic cytochrome c accumulation. These results demonstrate the potential of pMU and pMC as therapeutic candidates for the treatment of glioma.     

Itolizumab in combination with methotrexate modulates active rheumatoid arthritis: safety and efficacy from a phase 2, randomized,open-label,parallel-group,dose-ranging study

Clinical Rheumatology - The objective of this study was to assess the safety and efficacy of itolizumab with methotrexate in active rheumatoid arthritis (RA) patients who had inadequate response to...     

A Positional Analyzer for Measuring Centric Slide

Centric relation (CR) has been considered mainly as a position posterior to habitual occlusion or maximum intercuspation (MI). Awareness of the tooth contacts relationship in centric relation position of the mandible and diagnosing the case from this position is essential to consistently select treatment plans that will allow to treat to or very near to centric relation occlusion. Centric slide and other occlusal relationships are conceived of as positions, which can be studied in three dimensions. Clinically, the difference between the two occlusal positions namely CR and MI (centric slide) can easily be determined, but for a more precise evaluation of its length and directions, an occlusal analysis on articulator mounted casts is necessary. Study was under taken on the mounted casts of ten subjects on a semi adjustable articulator to which a stylus and recording table was devised and attached for measurement of CR-MI slide in the three planes namely anterior-posterior, medio-lateral and superior-inferior. It was found that there was a displacement from CR to MI (centric slide) in all the three planes and numerically the mean slide was 0.688 ± 0.623, 0.261 ± 0.627 and 0.127 ± 0.541 mm in the antero-posterior, medio- lateral and superior-inferior directions respectively. The stylus and table attachment may be an accurate indirect method to measure positional changes of the condyle in 3D.     

The many faces of glutathione in bacteria

Glutathione is one of the most abundant thiols present in cyanobacteria and proteobacteria, and in all mitochondria or chloroplast-bearing eukaryotes. In bacteria, in addition to its key role in maintaining the proper oxidation state of protein thiols, glutathione also serves a key function in protecting the cell from the action of low pH, chlorine compounds, and oxidative and osmotic stresses. Moreover, glutathione has emerged as a posttranslational regulator of protein function under conditions of oxidative stress, by the direct modification of proteins via glutathionylation. This review summarizes the biosynthesis and function of glutathione in bacteria from physiological and biotechnological standpoints.     

Studies on the signal cascade mechanism mediating the cardioprotective actions of bradykinin

The cardioprotective involvement of bradykinin was evaluated using the ACE inhibitor, lisinopril, and the APP inhibitor, 2-mercaptoethanol alone and in combination in rats with experimental myocardial infarction. The signal cascade mechanism mediating the cardioprotective actions of bradykinin was evaluated by administering aspirin and methylene blue prior to lisinopril and 2-mercaptoethanol combined treatment. Myocardial infarction was produced by occlusion of the left anterior descending coronary artery for 30 min followed by 4 h of reperfusion. Infarct size was measured by the TTC stain method. Serum free radical levels were estimated by the method developed by Yagi. A lead II electrocardiogram was monitored throughout the experiment. With the combined inhibition of both the enzymes ACE and APP, a better cardioprotection was observed. The observed cardioprotection was decreased with the prior administration of aspirin and methylene blue. The results suggest the cardioprotective role of bradykinin during experimental myocardial infarction. The results are further suggesting the involvement of both prostaglandins and nitric oxide pathways in the cardioprotective actions of bradykinin.