Loss of glutamic acid decarboxylase (Gad67) in striatal neurons expressing the Drdr1a dopamine receptor prevents L-DOPA-induced dyskinesia in 6-hydroxydopamine-lesioned mice.

The objective in this study was to test the hypothesis that the GABA-synthesizing enzyme, glutamic acid decarboxylase (Gad67), expressed in striatal neurons plays a key role in dyskinesia induced by L-DOPA (LID) in a rodent model of Parkinson's disease. In light of evidence that the dopamine Drd1a receptor is densely expressed in striatal direct pathway striatal neurons while the orphan G-protein-coupled receptor Gpr88 is densely expressed in striatal direct and indirect pathway striatal neurons, we used a cre-lox strategy to produce two lines of mice that were Gad1 (Gad1 is the gene encoding for Gad67)-deficient in neurons expressing the Drd1a or the Gpr88 receptor. Gad67 loss in Gpr88-expressing neurons mice did not result in gross motor abnormalities while mice with Gad67 loss in Drd1a-expressing neurons were impaired on the Rotarod and the pole test. Knockout and control littermate mice were unilaterally injected into the medial forebrain bundle with 6-hydroxydopamine (6-OHDA) in order to lesion dopamine neurons on one side of the brain. 6-OHDA-lesioned mice were then injected once daily for 10 days with L-DOPA. Mice with a Gad67 loss in Gpr88-expressing neurons and control littermates developed abnormal involuntary movements (AIM), a measure of dyskinesia. In contrast, mice with a Gad67 loss in Drd1a-expressing did not develop AIM. The results demonstrate that Gad67 in Drd1a-expressing neurons plays a key role in the development of LID and they support the hypothesis that altered GABAergic neurotransmission in the direct pathway is involved in dyskinesia.

A study of platelet functions with a new analyzer using high shear stress (PFA 100) in patients undergoing coronary artery bypass graft.

Platelet dysfunction can be a major factor in excessive bleeding following cardiopulmonary bypass (CBP). A rapid, specific and sensitive method to identify platelet dysfunction would be a useful tool for identifying patients at an increased risk of bleeding. The ability of PFA100, an in vitro bleeding test, to predict increased bleeding risk linked to platelet dysfunction was tested in 146 patients undergoing primary coronary artery bypass graft. Blood samples were taken the day before surgery, and 15 min and 5 h after heparin neutralization. The preoperative closure times (CT), i.e. the time required for platelets in citrated whole blood to occlude an aperture cut into a membrane coated with collagen plus either epinephrine (CTEPI) or adenosine diphosphate (CTADP) were longer in blood-group-O patients than in patients with other groups. The 15 min postoperative values were significantly longer from preoperative values essentially owing to CBP-induced hemodilution. Interestingly, 5 h after CBP, a significant reduction in CT values probably reflected platelet hyperaggregability. No correlation was found between calculated blood loss (CBL) and either preoperative or postoperative PFA values.

Severe mental retardation with marfanoid habitus in a young Lebanese male. A diagnostic challenge.

A severely mentally retarded 20-year-old male adult with a marfanoid habitus reported since birth and dysmorphic features is described. A younger brother presented the same appearance at birth but died at 2 months of age following a cardiopathy. Despite some clinical differences, his features are very close to the Lujan-Fryns syndrome and to two unrelated girls described by de Die-Smulders et al. (1). This case shows the challenge that clinicians could have while investigating patients with mental retardation and marfanoid habitus for diagnosis and genetic counseling.