Isoproterenol fails to produce myocardial necrosis in streptozotocin-induced diabetic rats.

Biochemical alterations in the hearts of non-diabetic and 5 weeks of streptozotocin-induced diabetic rats following isoproterenol (ISO) administration were compared. Serum lactate dehydrogenase (LDH) and myocardial adenosine triphosphate (ATP), creatine phosphate (CP), lactate and glycogen were used as indices of myocardial injury. Hearts from diabetic rats (blood glucose greater than 350 mg/dl), before ISO administration, had normal lactate levels but significantly low high-energy phosphate (HEP) levels and high glycogen levels in comparison to non-diabetic rats. No difference was observed in serum LDH levels between these two groups. ISO administration to non-diabetic rats caused myocardial necrosis as evidenced by a significant depletion of myocardial glycogen and HEPs along with significant myocardial lactate accumulation and an increase in serum LDH. However, the hearts from diabetic rats failed to show any significant HEP depletion, accumulation of lactate and leakage of LDH into serum following ISO-administration, though myocardial glycogen level was significantly lowered. These observations, in conjunction with earlier reports, point to the hypothesis that, in diabetes, there are certain alterations in the sarcolemma which hamper the process by which ISO causes myocardial necrosis.     

Role of Cholesterol in APP Metabolism and Its Significance in Alzheimer’s Disease Pathogenesis

Alzheimer’s disease (AD) is a complex multifactorial neurodegenerative disorder believed to be initiated by accumulation of amyloid β (Aβ)-related peptides derived from proteolytic processing of amyloid precursor protein (APP). Research over the past two decades provided a mechanistic link between cholesterol and AD pathogenesis. Genetic polymorphisms in genes regulating the pivotal points in cholesterol metabolism have been suggested to enhance the risk of developing AD. Altered neuronal membrane cholesterol level and/or subcellular distribution have been implicated in aberrant formation, aggregation, toxicity, and degradation of Aβ-related peptides. However, the results are somewhat contradictory and we still do not have a complete understanding on how cholesterol can influence AD pathogenesis. In this review, we summarize our current understanding on the role of cholesterol in regulating the production/function of Aβ-related peptides and also examine the therapeutic potential of regulating cholesterol homeostasis in the treatment of AD pathology.     

A multifaceted strategy using mobile technology to assist rural primary healthcare doctors and frontline health workers in cardiovascular disease risk management: protocol for the SMARTHealth India cluster randomised controlled trial

Background

Blood Pressure related disease affected 118 million people in India in the year 2000; this figure will double by 2025. Around one in four adults in rural India have hypertension, and of those, only a minority are accessing appropriate care. Health systems in India face substantial challenges to meet these gaps in care, and innovative solutions are needed.

Methods

We hypothesise that a multifaceted intervention involving capacity strengthening of primary healthcare doctors and non-physician healthcare workers through use of a mobile device-based clinical decision support system will result in improved blood pressure control for individuals at high risk of a cardiovascular disease event when compared with usual healthcare. This intervention will be implemented as a stepped wedge, cluster randomised controlled trial in 18 primary health centres and 54 villages in rural Andhra Pradesh involving adults aged ≥40 years at high cardiovascular disease event risk (approximately 15,000 people). Cardiovascular disease event risk will be calculated based on World Health Organisation/International Society of Hypertension’s region-specific risk charts. Cluster randomisation will occur at the level of the primary health centres. Outcome analyses will be conducted blinded to intervention allocation.

Expected outcomes

The primary study outcome is the difference in the proportion of people meeting guideline-recommended blood pressure targets in the intervention period vs. the control period. Secondary outcomes include mean reduction in blood pressure levels; change in other cardiovascular disease risk factors, including body mass index, current smoking, reported healthy eating habits, and reported physical activity levels; self-reported use of blood pressure and other cardiovascular medicines; quality of life (using the EQ-5D); and cardiovascular disease events (using hospitalisation data). Trial outcomes will be accompanied by detailed process and economic evaluations.

Significance

The findings are likely to inform policy on a scalable strategy to overcome entrenched inequities in access to effective healthcare for under-served populations in low and middle income country settings.

Trial registration

Clinical Trial Registry India CTRI/2013/06/003753.

     

Effect of culturing parameters on the vegetative growth of Haematococcus alpinus (strain lcr‐cc‐261f) and modeling of its growth kinetics

The present study investigated the effect of different culture conditions on the vegetative growth of a new species, Haematococcus alpinus (strain LCR‐CC‐261f) using airlift photobioreactors. The influence of culture medium, aeration rates, CO₂ concentration in air‐gas mixture, temperature, light intensities, and wavelengths were investigated to achieve sustainable high cell density cultures. Growth parameters were determined by fitting the data to a form of the logistic equation that included a lag phase. The shear‐sensitive vegetative cells favored lower aeration rates in the photobioreactors. MLA medium increased to 40 mM nitrate produced high density cultures. Temperatures between 12°C and 18°C, 3% (v/v) CO₂ concentration and a narrow photon flux density ranging between 37 and 48 μmol photons · m^?2 · s^?1 were best suited for growth. The wavelength of the light source also impacted growth and a high cell density of 9.6 × 10⁵ cells · mL^?1 was achieved using a mixture of red and blue compared to warm white, red, or blue LEDs.     

Reactive oxygen species function as second messenger during ischemic preconditioning of heart

The mechanisms involved in the hypolipidemic effects of fish oil have not been clearly established. This study shows that supplementation of 10% menhaden oil to the chick diet for 7 days produced a significant hypocholesterolemia and hypotriglyceridemia. Fatty acid composition of chick plasma drastically changed by the same dietary manipulation. Percentages of 20:5 and 22:6 n-3 fatty acids strongly increased, while percentages of 20:4 n-6, 18:2 n-6, and 18:1 n-9 significantly decreased. Changes observed in the relative percentages were parallel to those obtained in the amount of each fatty acid. Ratio of n-3/n-6 clearly decreased in plasma by fish oil feeding. Total cholesterol and triacylglycerol contents decreased in high density lipoprotein (HDL) but did not change in low density lipoprotein (LDL). All chemical constituents of very low density lipoprotein (VLDL) significantly decreased after the first week of menhaden oil supplementation to the diet. Similar modifications in fatty acid composition of the three lipoprotein fractions were also found. Our results suggest that the hypocholesterolemic effects of fish oil may be mediated by the depletion in VLDL synthesis and secretion into the chick plasma. On the other hand, the strong decrease found in the arachidonic acid (AA) content of chick plasma and lipoproteins may contribute to the beneficial effects of fish oil consumption by lowering the production of its derived eicosanoids.     

Pharmacological preconditioning with resveratrol: an insight with iNOS knockout mice

Resveratrol, a natural antioxidant and polyphenol found in grapes and wine, has been found to pharmacologically precondition the heart through the upregulation of nitric oxide (NO). To gain further insight of the role of NO in resveratrol preconditioning, mouse hearts devoid of any copies of inhibitory NO synthase (iNOS) (iNOS knockout) and corresponding wild-type hearts were perfused with 10 microM resveratrol for 15 min followed by 25 min of ischemia and 2 h of reperfusion. Control experiments were performed with wild-type and iNOS knockout hearts that were not treated with resveratrol. Resveratrol-treated wild-type mouse hearts displayed significant improvement in postischemic ventricular functional recovery compared with those of nontreated hearts. Both resveratrol-treated and nontreated iNOS knockout mouse hearts resulted in relatively poor recovery in ventricular function compared with wild-type resveratrol-treated hearts. Myocardial infarct size was lower in the resveratrol-treated wild-type mouse hearts compared with other group of hearts. In concert, a number of apoptotic cardiomyocytes was lower in the wild-type mouse hearts treated with resveratrol. Cardioprotective effects of resveratrol was abolished when the wild-type mouse hearts were simultaneously perfused with aminoguanidine, an iNOS inhibitor. Resveratrol induced the expression of iNOS in the wild-type mouse hearts, but not in the iNOS knockout hearts, after only 30 min of reperfusion. Expression of iNOS remained high even after 2 h of reperfusion. Resveratrol-treated wild-type mouse hearts were subjected to a lower amount of oxidative stress as evidenced by reduced amount of malonaldehyde content in these hearts compared with iNOS knockout and untreated hearts. The results of this study demonstrated that resveratrol was unable to precondition iNOS knockout mouse hearts, whereas it could successfully precondition the wild-type mouse hearts, indicating an essential role of iNOS in resveratrol preconditioning of the heart.