Distribution of purinergic P2X receptors in the equine digit, cervical spinal cord and dorsal root ganglia

Purinergic pathways are considered important in pain transmission, and P2X receptors are a key part of this system which has received little attention in the horse. The aim of this study was to identify and characterise the distribution of P2X receptor subtypes in the equine digit and associated vasculature and nervous tissue, including peripheral nerves, dorsal root ganglia and cervical spinal cord, using PCR, Western blot analysis and immunohistochemistry. mRNA signal for most of the tested P2X receptor subunits (P2X_{1–5, 7}) was detected in all sampled equine tissues, whereas P2X₆ receptor subunit was predominantly expressed in the dorsal root ganglia and spinal cord. Western blot analysis validated the specificity of P2X_{1–3, 7} antibodies, and these were used in immunohistochemistry studies. P2X_{1–3, 7} receptor subunits were found in smooth muscle cells in the palmar digital artery and vein with the exception of the P2X₃ subunit that was present only in the vein. However, endothelial cells in the palmar digital artery and vein were positive only for P2X₂ and P2X₃ receptor subunits. Neurons and nerve fibres in the peripheral and central nervous system were positive for P2X_1–3 receptor subunits, whereas glial cells were positive for P2X₇ and P2X_{1 and 2} receptor subunits. This previously unreported distribution of P2X subtypes may suggest important tissue specific roles in physiological and pathological processes.     

DGK1-encoded diacylglycerol kinase activity is required for phospholipid synthesis during growth resumption from stationary phase in Saccharomyces cerevisiae

In the yeast Saccharomyces cerevisiae, triacylglycerol mobilization for phospholipid synthesis occurs during growth resumption from stationary phase, and this metabolism is essential in the absence of de novo fatty acid synthesis. In this work, we provide evidence that DGK1-encoded diacylglycerol kinase activity is required to convert triacylglycerol-derived diacylglycerol to phosphatidate for phospholipid synthesis. Cells lacking diacylglycerol kinase activity (e.g. dgk1Δ mutation) failed to resume growth in the presence of the fatty acid synthesis inhibitor cerulenin. Lipid analysis data showed that dgk1Δ mutant cells did not mobilize triacylglycerol for membrane phospholipid synthesis and accumulated diacylglycerol. The dgk1Δ phenotypes were partially complemented by preventing the formation of diacylglycerol by the PAH1-encoded phosphatidate phosphatase and by channeling diacylglycerol to phosphatidylcholine via the Kennedy pathway. These observations, coupled to an inhibitory effect of dioctanoyl-diacylglycerol on the growth of wild type cells, indicated that diacylglycerol kinase also functions to alleviate diacylglycerol toxicity.     

The interaction of vasoactive substances during exercise modulates platelet aggregation in hypertension and coronary artery disease

Background

In Shanghai there are 1.2 million people with hypertension, many of whom have difficulty in affording medical treatment. Community based, anti-hypertensive clubs have been created to provide health education but education alone is often ineffective. Lifestyle change programmes have shown some potential for reducing blood pressure but in previous trials have required specialist staff and extensive contact. We have previously demonstrated that self-management programmes delivered by health professionals, such as a nurse who has had short training in self-management techniques can change health behaviour and reduce symptoms. This study was designed to evaluate the benefits of a simple, cognitive-behavioural, self-management programme for hypertension based around a hypertension manual and delivered in the setting of a community anti-hypertensive club in Shanghai.

Method

The method was a pragmatic randomised controlled trial with an intention-to-treat analysis. Adult patients with mild-to-moderate primary hypertension, waiting to join a neighbourhood anti-hypertension club, were randomised to the self-management programme or to an information only control procedure. They attended the group treatment sessions on 4 occasions over 5 weeks for education combined with goal setting for lifestyle change and an introduction to exercise. The main outcome measures were: changes in blood pressure; blood total cholesterol; diet; activity level and health related quality of life 1 month and 4 months after the end of treatment.

Results

A total of 140 adults with mild-to-moderate primary hypertension took part. All of the main outcomes showed beneficial changes. Four months after the end of treatment the mean blood pressure differences between groups were systolic 10.15 mm Hg (P < 0.001, 95% CI 7.25–13.05), and diastolic 8.29 mmHg (P < 0.001, 95% CI 6.71–9.88). Patients in the intervention group also had significantly reduced weight, lowered blood total cholesterol, increased physical activity and improved quality of life.

Conclusion

Patients with mild-to-moderate primary hypertension attending a 5 week, group and manual based, cognitive-behavioural self-management programme, delivered through a voluntary club in Shanghai experienced a significant reduction in blood pressure.

Trial registration

Current Controlled Trials ISRCTN73114566