Phosphoinositide 3-kinase is involved in the induction of the human sperm acrosome reaction downstream of tyrosine phosphorylation

In somatic cells phosphoinositide 3-kinase (PI 3-kinase) is activated upon interaction with both receptor tyrosine kinases (RTK) and G- proteins resulting in the production of moieties involved in the inositol phospholipid signalling pathway. As G proteins, RTK and the inositol phospholipids have all been implicated in the human sperm acrosome reaction, experiments were carried out to determine whether PI 3-kinase was also involved in this phenomenon. Wortmannin is a selective inhibitor of PI 3-kinase and was shown to significantly inhibit the acrosome reaction induced by both mannose-bovine serum albumin (mannose-BSA) (10, 50 and 100 nM) and a polyclonal antibody raised against an extracellular region of the sperm zona receptor kinase (ZRK, at 100 nM only). Wortmannin did not inhibit the A23187- or progesterone-induced acrosome reaction. These results suggest that PI 3- kinase is involved in the human sperm acrosome reaction. The levels of tyrosine phosphorylation of sperm proteins as detected by Western blotting using antiphosphotyrosine antibodies was not affected by wortmannin in agonist (A23187 and mannose-BSA)-stimulated spermatozoa. This indicated that PI 3-kinase operates downstream of tyrosine phosphorylation in the signal transduction cascade which leads to the human sperm acrosome reaction.      

Po gene expression in cultured Schwann cells

Summary This study examines the expression of the major myelin protein gene Po in cultured Schwann cells, grown on their own or in association with neurons. Many freshly dissociated Scwhann cells from actively myelinating nerves express Po mRNA in high abundance. If neurons are not present, signal intensity falls markedly with time so that by 7 days in culture only a basal expression is evident which is negligible compared to the levelin vivo. Dorsal root ganglia from embryo day 16 (E16) rats contain no significant levels of Po mRNA but when grown in full myelinating medium (containing serum and embryo extract) increasing expression is seen from 4 to 5 days onward even though myelination does not occur until after the second week. In this intervening period the intensity of Po mRNA expression is lower than that found in the actively myelinating cell. Neurons from sympathetic ganglia are also capable of inducing Po mRNA expression. Schwann cells in dorsal root ganglia explants grown in serum-free defined medium do not assemble a basal lamina and will not wrap or myelinate axons. Nevertheless Po mRNA, but not protein, is expressed in levels similar to those found in full myelinating medium prior to myelination. Such Schwann cells also exhibit galactocerebroside and the sulphatide recognised by the 04 antibody. It appears that in defined medium or in myelinating medium prior to myelination axonal signals can induce Po mRNA expression to a certain degree. However, full up-regulation is usually associated with the rapid membrane expansion accompanying myelination. Whether this augmented up-regulation is due to further axonal signalling or events in the Schwann cell is unknown, but the results suggest that Po expression can be regulated at several stages of synthesis.     

A mobile screening programme for the cardiovascular and microvascular complications of Type 2 diabetes in primary care.

The Diabetes National Service framework (NSF), and the quality payments in the new contract for UK General Practitioners, promote regular screening for diabetes complications. The new contract also includes immediate incentives to meet screening and quality targets, but it will be difficult to meet these targets in primary care. We have developed a mobile 'annual review' programme for patients with Type 2 diabetes managed solely in primary care, that screens for cardiovascular disease, hypertension, retinopathy and neuropathy at the patient's general practice, and gives written foot care, dietary advice and level 1 smoking cessation advice to all patients.     

Does regional anaesthesia improve outcome after surgery?

There is conclusive evidence that regional anaesthesia provides better postoperative analgesia than systemic opioid techniques. Regional anaesthesia also has the potential to improve the functional outcome from surgery, although proving this in a clinically relevant way is challenging; many studies are inconclusive with methodological weaknesses making comparison difficult and offering conflicting evidence. Systematic reviews offer better evidence that regional anaesthesia improves outcome but both anaesthetic and surgical practice have evolved over time, so older data may not be relevant to current practice. Regional anaesthesia improves outcome only when incorporated into a structured postoperative rehabilitation and recovery programme (Enhanced Recovery), using the effective analgesia provided to achieve specific targets. These targets include early mobilization, active physiotherapy and early return to enteral nutrition. Other benefits of regional anaesthesia (reduced blood loss, lower risk of thromboembolic events and duration of ileus) also contribute to a reduction in postoperative morbidity. However, unless the postoperative recovery programme is modified to incorporate these benefits into a patient's recovery, the full impact of regional anaesthesia on surgical outcome will not be realized.