Possible involvement of dopaminergic mechanisms in the antimigraine action of flunarizine

Flunarizine, a calcium antagonist widely used in the prophylactic treatment of migraine, may interfere with dopaminergic systems. Flunarizine therapy can in fact induce extrapyramidal side effects and can increase basal as well as stimulated prolactin levels. To better define the mechanism of flunarizine action in migraine, we studied prolactin and growth hormone responses to thyrotropin releasing hormone and sulpiride in 13 female migraineurs before and after 60 days of flunarizine therapy. The treatment did not modify basal prolactin and growth hormone levels, but prolactin response to thyrotropin releasing hormone was enhanced. A paradoxical increase of growth hormone to thyrotropin releasing hormone observed before therapy was blunted after flunarizine treatment. These data indicate a modulatory action of flunarizine on dopaminergic systems which might to some extent explain the antimigraine action of this drug.     

Hemoglobin Sabine [beta 91 (F7) Leu-->Pro]: occurrence in a Sardinian individual with hemolytic anemia and inclusion bodies.

BACKGROUND. Hemoglobin (Hb) Sabine (beta 91 Leu-->Pro) is an unstable variant detected for the first time in a 16-year-old Scottish-English-German girl affected by moderately severe hemolytic anemia. A second case was described in a patient of Yugoslavian descent. We report another case of this Hb variant arising as a de novo mutation in a Sardinian patient. METHODS. Definition of the mutation was obtained by DNA direct sequencing on amplified beta-globin gene, as well as by structural analysis of the hemoglobin variant. RESULTS AND CONCLUSION. The patient presented a moderately severe hemolytic anemia with red blood cell inclusion bodies. Hemoglobin electrophoresis showed that quantitatively the abnormal fraction represented 9% of the total Hb amount. beta globin gene analysis revealed a single nucleotide substitution, T-->C, at codon 91, which gives rise to a leucine-->proline substitution. Structural analysis of the variant confirmed the amino acid substitution (Leu-->Pro) predicted by DNA sequencing.     

Diffuse lymphoid tissue associated with the human bulbourethral gland. An immunohistologic characterization.

This study investigates the presence and distribution of immunocompetent cells in bulbourethral glands obtained from four multiorgan transplant donors. Monoclonal antibodies reacting with B (Leu 12+) and T (Leu 4+) cells, suppressor-cytotoxic cells (Leu 2+), helper-inducer (Leu 3a+) and natural killer (Leu7+) phenotypes, monocyte-macrophages, (LeuM3+), and cells expressing interleukin-2 receptor and HLA-DR antigen were tested in all specimens using an indirect immunoperoxidase staining procedure. T lymphocytes were estimated to represent 10% of the mucosal cell population. Almost all intraepithelial lymphocytes were suppressor-cytotoxic (CD8+) cells. The results demonstrate the presence of a defined distribution of immunocompetent cells in these sex accessory glands. Their role in combatting infections or other chronic genitourinary diseases is still undefined.     

Liver transplant rejection: value of the resistive index in Doppler US of hepatic arteries

The authors prospectively evaluated the accuracy of the resistive index (RI) in Doppler ultrasound (US) for the detection of the increased vascular resistance that theoretically occurs with acute liver transplant rejection. RIs were calculated for the proximal hepatic artery and a more distal hepatic artery branch in 67 liver transplant recipients. Biopsies were performed within 24 hours of transplantation, with no intervening therapy. Examination of biopsy specimens by a single pathologist revealed findings of no, minimal, or moderate to severe rejection. RIs in hepatic arteries showed no significant differences among the three pathologic groups. No correlation was found between the RI and improved or worsened rejection in 11 patients who underwent biopsy and US more than once. RIs in hepatic arteries are of no value in the prediction of liver transplant rejection.     

Long-term neurological assessment of the post-resuscitative effects of flunarizine, verapamil and nimodipine in a new model of global complete ischaemia

In anesthetized rats, global complete ischaemia lasting for 9 min was induced by controlled hydraulic compression of the chest. A neurological score, based on cranial and spinal reflexes, postural tone, gait, movement and limb placement, was determined at 2 hr and 1, 2, 3, 7, 14, 21 and 28 days after resuscitation. Three doses of three calcium antagonists, flunarizine, verapamil and nimodipine and their respective solvents, were given intravenously during the resuscitation. The total neurological score was significantly better than solvent with 0.16 and 0.63 mg/kg of flunarizine and 0.04 and 0.16 mg/kg of verapamil; it was significantly better with solvent (10% ethanol) than with 0.04 and 0.16 mg/kg of nimodipine. The deficiency in tactile placing reactions of the hindpaws was the most resistant to therapy. This non-invasive model of global ischaemia in rats seems useful for the evaluation of drugs, since it requires minimal anesthesia and allows assessment of neurological recovery over an extended period of time.     

Neuroendocrine evaluation in catamenial epilepsy

The hypothesis that catamenial epilepsy depends on abnormal rhythmic hormone activity in the hypothalamus-pituitary-gonadal axis has never been critically tested. No significant modifications in the secretory pattern of pituitary hormones, both basally and in response to stimulatory tests, were found in a group of catamenial epileptic women. On the contrary, our data showed a reduction of luteal phase progesterone secretion. These findings indicate that an imbalanced secretion of ovarian steroids plays a role in the catamenial exacerbation of epilepsy.     

Improved short-term neurological recovery with flunarizine in a canine model of cardiac arrest

A 10-minute cardiac arrest was produced in dogs by electrical fibrillation of the heart. Recovery of cerebral function was monitored by estimating the cerebral metabolic rate of oxygen consumption (CMRO2), cerebral blood flow (CBF), electroencephalograph (EEG) and extent of neurological deficit. The study group received flunarizine (0.1 mg/kg intravenously) at the beginning of resuscitation, while control animals were given the drug vehicle. By four hours after resuscitation, CMRO2 in flunarizine-treated dogs was 121 +/- 43% of pre-arrest baseline, as compared with 37 +/- 9% in control animals (P less than 0.02). In the flunarizine group, CBF was 83 +/- 21% of baseline, while it was only 31 +/- 8% in controls (P less than 0.01). As compared with the control group, no other significant changes were detected in electrocardiographic, hemodynamic, or biochemical parameters in the flunarizine-treated dogs. A significant improvement in the visual EEG score (P less than 0.001) and neurological deficit (P less than 0.05) was seen in flunarizine-treated dogs six hours after ischemic insult.