The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by quinolinic acid in the rat striatum.

The ability of CB(1) receptors to regulate the release of glutamate in the striatum, together with the finding that, in experimental models of Huntington disease (HD), both endocannabinoid levels and CB(1) receptor densities are reduced, has prompted the investigation on the neuroprotective role of the cannabinoids in HD. Quinolinic acid (QA) is an excitotoxin that, when injected in the rat striatum reproduces many features of HD and that acts by stimulating glutamate outflow. The aim of the present study was to test the ability of the cannabinoid receptor agonist WIN 55,212-2 to prevent the effects induced by QA in the rat striatum. In microdialysis experiments, probe perfusion with WIN 55,212-2 significantly and dose-dependently prevented the increase in extracellular glutamate induced by QA. In electrophysiological recordings in corticostriatal slices, the application of WIN 55,212-2 prevented QA-induced reduction of the field potential amplitude. Both effects of WIN 55,212-2 were prevented by the CB(1) receptor antagonist AM 251. In in vivo experiments, intrastriatal WIN 55,212-2 significantly attenuated the striatal damage induced by QA, although no significant effects were observed on a behavioural ground. These data demonstrate that the stimulation of CB(1) receptors might lead to neuroprotective effects against excitotoxic striatal toxicity.

Adenosine A 2A receptor antagonists prevent the increase in striatal glutamate levels induced by glutamate uptake inhibitors.

Active uptake by neurons and glial cells is the main mechanism for maintaining extracellular glutamate at low, non-toxic concentrations. Activation of adenosine A(2A) receptors increases extracellular glutamate levels, while A(2A) receptor antagonists reduce stimulated glutamate outflow. Whether a modulation of the glutamate uptake system is involved in the effects elicited by A(2A) receptor blockers has never been investigated. This study examined the ability of adenosine A(2A) receptor antagonists to prevent the increase in glutamate levels induced by blockade of the glutamate uptake. In rats implanted with a microdialysis probe in the dorsal striatum, perfusion with 4 mm l-trans-pyrrolidine-2,4-dicarboxylic acid (PDC, a transportable competitive inhibitor of glutamate uptake), or 10 mm dihydrokainic acid (DHK, a non-transportable competitive inhibitor that mainly blocks the glial glutamate transporter GLT-1), significantly increased extracellular glutamate levels. The effects of PDC and DHK were completely prevented by the adenosine A(2A) receptor antagonists SCH 58261 (0.01 mg/kg i.p.) and/or ZM 241385 (5 nm via probe). Since an impairment in glutamate transporter function is thought to play a major role in neurodegenerative disorders, the regulation of glutamate uptake may be one of the mechanisms of the neuroprotective effects of A(2A) receptor antagonists.

Influence of patients' representations and beliefs about diabetes and its treatment on their adherence to therapy.

Research in the last 25 years has shown that diabetic patients' adhesion to medical advice is a multi-factor phenomenon. Most recent research has focused on a patient-centred approach, on the representations that the patient has with respect to medicine, health and disease (with particular regard to the perceived self-efficiency in managing the disease, trust in conventional medicine, treatment, drugs, etc) and on the level of agreement between the patient's representations and those of the health care provider. These representations can potentially act as barriers/facilitators on patients' adhesion to treatment; the best adherence can only be obtained if the real needs of the patient are met, matching therapy with his/her representations and expectations, and acknowledging the constraints that everyday life puts on the individual. The indication is therefore to avoid exclusively considering the physical burdens of the disease, while ignoring the personal and social significance of the experience that the patient is having. It will take time for this to become routine in health care, since it requires a complex change from a traditional, bio-medical approach to an integrated bio-psycho-social approach. The aim of this review is to show how those disease representations of diabetes, and the treatment having considerable impact on patients' adhesion, are being considered in recent literature, and how this nonetheless still constitutes a little explored aspect in medical consultation and research.

Primary peritonitis due to group A streptococcus.

Primary peritonitis is a rare condition occurring, by definition, in patients without underlying causes, such as perforated viscus, pre-existing ascites, or nephrosis. We report a case of primary peritonitis and shock due to group A beta-hemolytic streptococcus, a rare etiology. A review of the world's literature shows a predilection for women to have this condition. The entry site is obscure in most cases. Asymptomatic genital tract colonization may be a portal of entry in some women. Shock or toxic shock syndrome often accompany the abdominal findings. Laparotomy to exclude a perforated viscus may be unavoidable. Despite the significant morbidity, expeditious and appropriate antibiotic therapy is curative.