Hyperhomocysteinemia alters sinoatrial and atrioventricular nodal function : role of the cardiac NMDA receptor.

Introduction: Hyperhomocysteinemia (HHcy) is a pathological condition characterized by excessive levels of plasma homocysteine (Hcy). Patients with HHcy are reported to be at risk for arrhythmias like atrial fibrillation and sudden cardiac death (SCD); however, the causative mechanisms remain unknown. The effects of HHcy on sinus node function, atrioventricular conduction and ventricular vulnerability were investigated by in vivo electrophysiological (EP) analysis, and the role of the cardiac N-methyl-D-aspartate receptor (NMDA-R) in promoting Hcy-induced conduction abnormalities was explored. Materials and Methods: Anesthetized wild-type control mice (WT), mice receiving Hcy in the drinking water for 12 weeks (DW), and heterozygous cystathionine-ß-synthase knockout mice (CBS+/-) were subjected to electrocardiographic (ECG) analysis and programmed electrophysiological (EP) studies. To examine the role of the NMDA-R in eliciting conduction changes in HHcy, animals from the three groups were subjected to paired-design repeat EP studies before and after intraperitoneal injection of magnesium sulfate (MgS04, 20mg/kg), an endogenous blocker of NMDA-R. Another set of studies utilized a specific NMDA-receptor antagonist, dizocilpine (MK-801), in similarly paired-design studies in an acute, intraperitoneal infusion model of HHcy. Expression levels of cardic NMDA-R in all three groups of animals were quantified by immunoblotting, and immunohistochemical identification of cardiac NMDA-Rs at the mouse atrioventricular (A V) junction was undertaken. Results: DW compared to WT had significantly shorter RR, PR, QT, and HV intervals, corrected sinus node recovery times (CSNRT), Wenckebach periodicity (WP), AV nodal effective refractory periods (A VNERP), and right ventricular effective refractory periods (RVERP). No ventricular arrhythmias were induced in either WT or DW. In the paired-design studies, blockade of cardiac NMDA-R with MgS04 had no effect on any ECG or EP variables in WT but significantly prolonged RR, QT, HV, CSNRT, WP, and AVNERP in DW and CBS+/- animals. Immunopositive staining for cardiac NMDA-R at the mouse A V junction was detected. Conclusions: Significant changes in conduction were observed between wild-type mice and mice with diet-induced or genetically-induced hyperhomocysteinemia (HHcy). Low-dose magnesium administration did not alter ECG or EP conduction variables in wildtype mice, but had a profound effect on mice with HHcy. These results suggest that shortened sinoatrial and atrioventricular conduction time in mild HHcy may involve cardiac NMDA-Rs

Split hand/split-foot malformations: a report of four cases in a family with variable presentations

Split hand/split-foot malformation is a congenital anomaly with failure of development of the central digital rays of hand or foot to a variable extent. It is characterized by hypoplasia/aplasia of the phalanges, toes, metacarpals and metatarsals. The presentation may be an isolated anomaly or may be associated with syndrome and thus have variable pattern of inheritance. We report a family of 10 members; four of which are affected with autosomal recessive pattern of inheritance. We discuss here the clinical presentation, genetic inheritance, prenatal diagnosis and treatment for the malformation

Effect of atenolol on hemoglobin level in mild to moderate hypertension

Background: Hypertension is the most common cardiovascular disease and a major cardiovascular risk factor that causes significant morbidity and mortality worldwide. Most common type is primary (essential) hypertension and is genetically determined. It affects many systems of the body and can also alter various hematological parameters. The study was undertaken to check the effect of atenolol on hemoglobin (Hb) level in mild to moderate hypertension.Methods: The study was prospective and non-randomized. Thirty newly diagnosed hypertensives selected for atenolol therapy by medicine personnel were enrolled in the study based on inclusion and exclusion criteria. Patients were divided into pre-treatment (before starting atenolol therapy) and post-treatment group. Red blood cell (RBC) count, Hb, packed cell volume (PCV) and red cell indices were measured at the time of enrolment and then monthly after starting atenolol for next 3 months.Result: Results were analyzed by repeated measure analysis of variance. Atenolol treatment was found to increase Hb and PCV significantly, whereas no significant change in RBC count and red cell indices.Conclusions: Treatment with atenolol for mild to moderate hypertension has shown a significant increase in Hb and PCV level. This positive effect may be because of the decrease in sodium and water reabsorption by decrease in sympathetic overactivity and excretion of sodium and water by improvement in kidney functions. Atenolol has no any direct effect on Hb synthesis and erythropoiesis

Utilization of Amul Dairy effluent for agriculture practices

ABSTRACT Pot experiments were conducted to evaluate the impact of Amul dairy effluent on certain physico-chemical properties of soil and on growth, and quality of Lady's finger (Abelomoschus esculentus) and Guar (Cymopsis tetragonoloba.). The effluent used in different concentration 20%, 40%, 60%, 80% and 100%. The pH of the waste water was near about neutral but it contained an enough amount of nitrogen, phosphate, chloride, calcium, carbonates, bicarbonates and suspended and dissolved solids when compared with fresh water. Soil receiving the waste water showed no significant changes in water soluble salts, electrical conductivity, cation exchange capacity, pH, total organic carbon etc. Moreover, waste water irrigation resulted in increased growth and nutrients of both the crops

Cell Membrane Modification for Rapid Display of Bi-Functional Peptides: A Novel Approach to Reduce Complement Activation

Ischemia and reperfusion of organs is an unavoidable consequence of transplantation. Inflammatory events associated with reperfusion injury are in part attributed to excessive complement activation. Systemic administration of complement inhibitors reduces reperfusion injury but leaves patients vulnerable to infection. Here, we report a novel therapeutic strategy that decorates cells with an anti-complement peptide. An analog of the C3 convertase inhibitor Compstatin (C) was synthesized with a hexahistidine (His6) tag to create C-His6. To decorate cell membranes with C-His6, fusogenic lipid vesicles (FLVs) were used to incorporate lipids with nickel (Ni2+) tethers into cell membranes, and these could then couple with C-His6. Ni2+ tether levels to display C-His6 were modulated by changing FLV formulation, FLV incubation time and FLV levels. SKOV-3 cells decorated with C-His6 effectively reduced complement deposition in a classical complement activation assay. We conclude that our therapeutic approach appears promising for local ex vivo treatment of transplanted organs to reduce complement-mediated reperfusion injury

Fracture Mechanics Analysis and Strength Prediction of Carbon Fiber Composite Laminate with a Delamination

The use of advanced carbon fibre-reinforced composites in aircraft primary structures has been steadily increasing over past two decades due to their high specific strength and stiffness, and their tailoring as per the need. The composite panels used in primary structures of aircraft are liable to be buckling during its service periods. It is observed that structures can withstand substantial amount of loads after they have buckled. Therefore, an approach to efficiently design the postbuckled composite structures is required to be developed. The designers of the next generation of aircraft are looking into the aspect of postbuckling composite structures to achieve substantial improvements in aircraft structural efficiency. In this work, the postbuckling response and growth of circular delamination in flat and curved composite plates are investigated for different delamination sizes and their locations through the laminate thickness. The prediction of delamination initiation and growth is carried out using the strain energy release rates obtained from the finite element analysis and comparing them to B-K's mixed-mode fracture criterion. The failure load is thus predicted. Predicted results for onset of delamination growth compared well with experimental results. Its variation with different delamination sizes and their locations across panel thickness was also investigated. It is observed that the failure loads are influenced by the delamination sizes depending on their locations across the laminate thickness. The different delamination sizes at H/3 laminate thickness did not have significant effects on the variations of compressive strengths of the delaminated composite panel. But, the compressive strengths of the panels having different delamination sizes at H/2 laminate thickness are more than that at H/3 and increase linearly with increase in delamination sizes

Chondroid syringoma of the toe: A rare pedal tumor

Chondroid syringoma is a rare tumor of sweat gland origin. Usually benign, malignant transformation is more commonly seen in tumors of pedal origin, making this a concerning clinical finding. This case study reviews the identification, diagnosis and treatment of a benign chondroid syringoma in the right second toe of a patient

Primary transfer of extensor hallucis brevis tendon for repair of extensor hallucis longus tendon rupture

Extensor hallucis longus tendon rupture can have a detrimental effect on gait and stability if not treated appropriately. While an end to end anastomosis is the preferred surgical technique, this is not always possible in neglected injuries due to tendon retraction. We present the primary transfer of the extensor hallucis brevis tendon as a viable alternative in cases of neglected extensor hallucis longus tendon ruptures. Due to the close proximity of the extensor hallucis brevis tendon and the preservation of its intended function in the foot, this allows for ease of repair of a difficult defect while maintaining tensile strength of the extensor hallucis longus tendon. Clinically, the patient was able to return to 100% pain free function within 5 months

The Roles of Platelet-Activating Factor and Magnesium in Pathophysiology of Hypertension, Atherogenesis, Cardiovascular Disease, Stroke and Aging

Hypertension and atherosclerosis are debilitating diseases that affect millions each year. Long-term consequences include but are not limited to stroke, myocardial infarction, and kidney failure. Platelet-activating factor (PAF) is a proinflammatory mediator synthesized from a subclass of phosphatidylcholines that increases platelet activation, leukocyte adhesion, infiltration of macrophages, and intracellular lipid accumulation, thereby contributing to atherosclerosis. Magnesium, a key micronutrient and free radical scavenger, is a water-soluble mineral that regulates peripheral vasodilation and calcium, phosphate, and hydroxyapatite homeostasis. Magnesium’s antihypertensive ability stems from its role as a natural calcium antagonist and promoter of vasodilatory mediators, such as nitric oxide. Platelet-activating factor and magnesium share an inverse relationship, and elevated magnesium levels have been shown to have protective effects against plaque formation as well as antihypertensive and antiarrhythmic effects, all of which allow for healthier aging. The purpose of this literature review is to investigate the role of platelet-activating factor and magnesium in the pathophysiology of hypertension, atherosclerosis, cardiovascular disease, stroke, and aging. Since the pathophysiology of the platelet-activating factor biomolecule is underexplored, further research studies are warranted in order to navigate the putative signaling pathways involved in the cardioprotective effects of dietary magnesium as a natural anti-PAF agent