dl-alpha-lipoic acid ameliorates cyclophosphamide induced cardiac mitochondrial injury

Mitochondria play a central role in heart metabolism and function. Administration of antineoplastic drug cyclophosphamide (CP) adversely affects the heart mitochondria which may result in cardiotoxicity. The present study is aimed at evaluating the role of lipoic acid (LA) in CP induced myocardial injury. Male albino rats of Wistar strain were used for the study. CP was administered as a single intraperitoneal injection (200 mg/kg BW). A decrease in the activities of TCA cycle enzymes such as succinate dehydrogenase, malate dehydrogenase and isocitrate dehydrogenase was noted in CP treated rats. Simultaneously there was a decrease in the activities of mitochondrial complexes of electron transport chain. Decrease in the activities of these enzymes suggests a loss in mitochondrial function and integrity. Ultrastuctural observations were also in agreement with the above abnormal changes. Loss of myofilaments and damage of mitochondrial cristae revealed the cytotoxic effect of CP. The supplementation of LA (25 mg/kg BW) restored the above abnormalities to near normalcy. The study brings out the importance of LA in improving the mitochondrial function in cardiac cells after CP administration.     

Role of lupeol and its ester on cyclophosphamide-induced hyperlipidaemic cardiomyopathy in rats

Cyclophosphamide, an alkylating agent widely used in cancer chemotherapy, causes fatal cardiotoxicity. In this study, lupeol, a pentacyclic triterpene isolated from Crataeva nurvala stem bark, and its ester, lupeol linoleate, were investigated for their possible hypocholesterolaemic effects against cyclophosphamide-induced lipidaemic instabilities. Male albino Wistar rats were categorized into 6 groups. Group I served as control. Rats in groups II, V and VI were injected intraperitoneally with a single dose of cyclophosphamide (200 mg kg(-1)) dissolved in saline. Cyclophosphamide-treated groups V and VI respectively received lupeol and lupeol linoleate (50 mg kg(-1)), dissolved in olive oil, for 10 days by oral gavage. Groups III and IV served as drug controls and were administered lupeol and lupeol linoleate, respectively. Cyclophosphamide administration induced abnormal changes in serum lipoproteins and lipid fractions in both serum and cardiac tissue. The activity of lipid metabolizing enzymes was distorted significantly in the cyclophosphamide-treated rats. The cyclophosphamide-treated rats also showed extensive intermuscular haemorrhage in histology. Lupeol and its ester reversed the above alterations induced by cyclophosphamide. This study encapsulates the early lipaemic abnormalities in the heart tissue of cyclophosphamide-treated rats. Treatment with lupeol linoleate was more effective than lupeol in rendering protection to the cardiac tissue challenged by cyclophosphamide.     

Evaluation of memory in abacus learners

Abacus is a method used by Chinese, Japanese and Koreans to improve mathematical skills. This system has now invaded our country. The improvement in mathematical skills is said to be due to a coordinated functioning of both right and left hemisphere. As learning and memory in any field is achieved by coordinating and analyzing the different sensory inputs, whether an abacus trainee would also improve the short-term memory as a whole was evaluated in our study. 50 children of average IQ between 5 and 12 years from 2 regular schools and 50 from an abacus institute were evaluated for short-term memory before and after a period of one and two years. The memory tests were taken from Wechsler memory scale, Mini mental state examination, Mann - Buitar visual memory screen for objects. The results showed that the abacus learners at the end of one and two years had a better visual and auditory memory when compared to non-abacus learners.     

Obesity, polycystic ovarian syndrome and thyroid dysfunction in women with epilepsy

Introduction:

Women with epilepsy (WWE) have an increased risk for several endocrine disorders. Obesity and Polycystic Ovarian Syndrome (PCOS) are common side-effects of anticonvulsant drugs.

Aim:

To study the prevalence of Obesity, PCOS, Thyroid dysfunction in WWE on monotherapy with Carbamazepine (CBZ), Sodium Valproate (VAL) and Phenytoin (DPH)

Material and Methods:

Sixty WWE in the reproductive age group (13 – 45 yr) who are on atleast 6 months of monotherapy with either CBZ (20) or VAL (20) or DPH (20) are subjects of the study. Their Anthropometric data is recorded. They are interviewed and investigated for PCOS and thyroid dysfunction. Twenty healthy women in the reproductive age group served as controls. BMI>25 is taken as cut-off for Obesity. PCOS is defined as menstrual irregularity and/or clinical /biochemical hyperandrogenism with ultrasound evidence of PCO as per the Rotterdam criteria. TSH <0.1 and >4 is taken as evidence of thyroid dysfunction. Women are grouped according to the anticonvulsant drug received and the data analyzed in each group.

Results:

The mean BMI among VAL and CBZ users is significantly higher than among DPH users (23.3 & 23.4 vs 20.4). There is no significant difference in incidence of PCOS among WWE using either DPH or VAL or CBZ. Elevated TSH>4 is seen more often in WWE on VAL (9/20) compared to CBZ (6/20) and DPH (3/20). WWE on CBZ, VAL and DPH did not differ in mean BMI, Obesity, PCOS compared to healthy controls. As compared to healthy controls, more WWE on drug therapy had significantly elevated TSH (1/20 vs20/60).

Conclusions:

WWE on VAL and CBZ had significant weight gain compared to DPH users. Despite weight gain, there was no difference in the incidence of PCOS between the users of VAL, CBZ and DPH. As compared to healthy controls, more WWE on drug therapy had significantly elevated TSH, more so in the VAL group.     

Remedial effect of lupeol and its ester derivative on hypercholesterolemia-induced oxidative and inflammatory stresses

In the hypercholesterolemic condition, the net result of combined lipemic-oxidative and inflammatory aberrations is manifested as an increase in adhesion molecule expression, increased vascular permeability, and the progress of atherogenesis. The aim of the present work is to evaluate the role of lupeol and its ester derivative on oxidative and inflammatory abnormalities in hypercholesterolemic condition. Hypercholesterolemia was induced in male albino rats of Wistar strain by feeding them a high-cholesterol diet (HCD) containing normal rat chow supplemented with 4% cholesterol and 1% cholic acid for 30 days. The pentacyclic triterpene, lupeol, and the ester derivative of lupeol, lupeol linoleate, were supplemented (50 mg/kg body weight per day, PO) during the last 15 days. Oxidative stress in HCD-fed animals was characterized by a significant increase in reactive oxygen species with concomitant decrease in the thiol levels in heart. Cardiac nuclear factor-κB nuclear translocation was confirmed by immunohistochemisty in HCD-fed rats. The tumor necrosis factor- levels showed an increase in hypercholesterolemic condition, whereas a departure toward control values and decreased nuclear translocation of nuclear factor-κB and oxidative stress were notable in supplementation with triterpenes. The nitric oxide levels and mRNA expression for inducible nitric oxide synthase was also significantly increased in HCD-fed animals. Treatment with lupeol and lupeol linoleate reversed the nitrosative stress to near normalcy. These observations highlight the beneficial effects of the triterpene, lupeol, and linoleate ester in ameliorating the oxidative and inflammatory abnormalities in the hypercholesterolemic conditions.     

Nucleosomes on linear duplex DNA allow homologous pairing but prevent strand exchange promoted by RecA protein.

To understand the molecular basis of gene targeting, we have studied interactions of nucleoprotein filaments comprised of single-stranded DNA and RecA protein with chromatin templates reconstituted from linear duplex DNA and histones. We observed that for the chromatin templates with histone/DNA mass ratios of 0.8 and 1.6, the efficiency of homologous pairing was indistinguishable from that of naked duplex DNA but strand exchange was repressed. In contrast, the chromatin templates with a histone/DNA mass ratio of 9.0 supported neither homologous pairing nor strand exchange. The addition of histone H1, in stoichiometric amounts, to chromatin templates quells homologous pairing. The pairing of chromatin templates with nucleoprotein filaments of RecA protein-single-stranded DNA proceeded without the production of detectable networks of DNA, suggesting that coaggregates are unlikely to be the intermediates in homologous pairing. The application of these observations to strategies for gene targeting and their implications for models of genetic recombination are discussed.     

Detecting reflux: does ureteric jet Doppler waveform have a role?

Background

Vesicoureteral reflux (VUR) has a prevalence of 30–40 % post-febrile urinary tract infection (UTI). If not detected early and treated, renal scarring, hypertension, and renal failure may occur. Micturating cystourethrography (MCU) is an invasive procedure associated with radiation exposure. Hence, this study aimed at evaluating the utility of ureteric jet Doppler waveform (UJDW) as a screening tool in detecting VUR, and at assessing the feasibility of performing it in children aged 2–4 years.

Methods

Any child 2–18 years old who needed an MCU was included. Exclusion criteria were active UTI, indwelling catheter, and inability to drink the required amount of fluid. The UJDW was performed prior to the MCU.

Results

One hundred eighty-two ureteric units were analyzed. Sensitivity and specificity of UJDW in detecting VUR was 80.3 and 87.9 %. Twenty-three children (45 ureteric units), aged 2–4 years were compared with 73 children (137 ureteric units), aged 5–18 years. Sensitivity and specificity of UJDW in detecting VUR in 2–4 years was 77.3 and 91.3 %, respectively; while in children ≥5 years, it was 81.8 and 87.1 %, respectively.

Conclusions

UJDW has a uniformly high specificity regardless of age or etiological groups, making it a good tool for follow-up. UJDW is a feasible technique, even in children aged 2–4 years.     

Preparation and evaluation of [Ho] holmium-dimethyl diethylenetriaminepentaaceticacid (DMDTPA) as potential radiopharmaceutical for endovascular radiation therapy (EVRT)

Holmium-166 with its favorable radiation characteristics could be used in endovascular radionuclide therapy (EVRT) technique in liquid filled low-pressure balloon angioplasty. ¹⁶⁶Ho-dimethyl di ethylene triamine penta acetic acid (DMDTPA) was prepared and its biodistribution carried out to evaluate its suitability as an EVRT formulation. DMDTPA was synthesized, characterized and was complexed with ¹⁶⁶Ho. The complex was stable at 37°C in human serum environment and at room temperature for 48 h. Biodistribution studies in mice revealed rapid renal clearance (90% of the injected dose in 30 min p.i.) with insignificant retention in any of the major organs including bone. The studies show that ¹⁶⁶Ho-DMDTPA is a good formulation which can be explored as an EVRT source.     

Self-management practices of type 1 diabetes mellitus

International Journal of Diabetes in Developing Countries - The effective management of Type 1 Diabetes (T1D) involves self-management practices and education about self-monitoring of blood glucose...