Gender difference in the interaction of smoking and monoamine oxidase B intron 13 genotype in Parkinson's disease

We tested for gender-specific interactions between smoking and genetic polymorphisms of monoamine oxidase B (MAO-B) intron 13 (G or A allele), monoamine oxidase A (MAO-A) EcoRV (Yor N allele), and dopamine D2 recepor (DRD2) Taq1B (B1 or B2 allele) in a case-control study of 186 incident idiopathic Parkinson's disease (PD) cases and 296 age- and gender-matched controls. The odds ratios (ORs) for PD risk for ever smokers versus never smokers were 0.27 (95% CI: 0.13-0.58) for men of genotype G, and 1.26 (0.60-2.63) for men of genotype A (interaction chi2 = 8.14, P = 0.004). In contrast, for women, the OR for ever smokers versus never smokers were 0.62 (95% CI: 0.25-1.34) and 0.64 (95% CI: 0.18-2.21) for women of genotype GG/GA and AA, respectively (interaction chi2 = 0.001, P = 0.975). No interactions were detected between smoking and either MAO-A EcoRV or DRD2 Taq1B genotypes. These results suggest that a strong gender difference exists with respect to the modifying effect of MAO-B genotype on the smoking association with PD.     

Inhibition of muscarinic receptor-induced proliferation of astroglial cells by ethanol: mechanisms and implications for the fetal alcohol syndrome

In utero exposure to ethanol is deleterious to fetal brain development. Children born with the fetal alcohol syndrome (FAS) display a number of abnormalities, the most significant of which are central nervous system (CNS) dysfunctions, such as microencephaly and mental retardation. An interaction of ethanol with glial cells, particularly astrocytes, has been suggested to contribute to the developmental neurotoxicity of this alcohol. At low concentrations (10-100 mM) ethanol inhibits the proliferation of astroglial cells in vitro, particularly when stimulated by acetycholine through muscarinic M3 receptors. Of the several signal transduction pathways activated by these receptors in astrocytes or astrocytoma cells, which are involved in mitogenic signaling, only some (e.g. protein kinase C (PKC) zeta, p70S6 kinase) appear to be targeted by ethanol at the same low concentrations which effectively inhibit proliferation. Inhibition of astroglial proliferation by ethanol may contribute to the microencephaly seen in FAS.     

Idiopathic generalized epilepsies misdiagnosed as partial epilepsies

Idiopathic generalized epilepsy (IGE) is often not recognized with serious consequences on the sufferers. We examined factors contributing to the missed diagnosis of IGE in 41 adults attending our epilepsy clinic with diagnosis of partial epilepsy who had semiology or EEG findings suggesting a possible differential diagnosis. After careful re-evaluation, the diagnosis of IGE was established in 25 patients: 22 (88%) with JME, one with juvenile absence, one with perioral myoclonia with absences, one with eyelid myoclonia with typical absences. Myoclonic jerks, the hallmark of the JME and other IGE, were not usually reported by patients or misdiagnosed as focal motor seizures. Brief and infrequent absence seizures and focal EEG abnormalities were other factors contributing to not recognizing JME. All 25 patients did not achieve seizure control before re-evaluation of diagnosis. After appropriate diagnosis of IGE and change of AED to valproate or valproic acid, 19 (76%) became seizure free and six (24%) had a significant improvement on seizure control. Association with lamotrigine provided further improvement in three of these patients. An appropriate questioning to identify myoclonic and absence seizures and a proper interpretation in the context of whole clinical constellation are essential for a correct seizure classification and diagnosis of IGE in adults.     

Reversible posterior encephalopathy syndrome: case report

The posterior reversible leukoencephalopathy syndrome (PRES) is a recently proposed cliniconeuroradiologic entity.The most common causes of PRES are hypertensive encephalopathy, eclampsia, cyclosporin A neurotoxicity and the uremic encephalopathies.Most patients are markedly hypertensive at presentation, although some have only mildly elevated or even normal blood pressure. Symptoms may include headache, nausea, vomiting, altered mental status, seizures,stupor, and visual disturbances. On CT and MR studies, edema has been reported in a relatively symmetrical pattern, typically in the subcortical white matter and occasionally in the cortex of the occipital and parietal lobes. These often striking imaging findings usually are resolved on follow-up studies obtained after appropriate therapy. Diffusion-weighted images would not show hyperintense signal because of the presence of interstitial rather than cytotoxic edema. We report a case of PRES due to hypertensive encephalopathy studied by CT and MRI.     

Long-term angiotensin II inhibition increases mitochondrial nitric oxide synthase and not antioxidant enzyme activities in rat heart

OBJECTIVE: To provide insight into the subcellular mechanisms involved in the improvement of cardiovascular structure and function by long-term inhibition of the renin-angiotensin system. DESIGN: The activities of antioxidant enzymes and mitochondrial free radical production were determined in the heart of control (C), enalapril-treated (E), and losartan-treated (L) rats to test the hypothesis of increased antioxidant enzyme activities and participation of mitochondria in the effects of chronic treatments with angiotensin II inhibitors. METHODS: At 6 and 18 months of treatment, superoxide dismutases (SOD), Se-glutathione peroxidase, and catalase activities were determined in left ventricle homogenates by spectrophotometric methods and nitric oxide (NO) production in submitochondrial membranes by the oxyhemoglobin oxidation assay. The maximal rate of hydrogen peroxide (H2O2) production by submitochondrial membranes was also evaluated at 18 months by the scopoletin-horseradish peroxidase method. RESULTS: No significant increase was found in the antioxidant enzymes measured. At 6 months, Mn-SOD was actually decreased in E and catalase in both E and L, whereas at 18 months Se-glutathione peroxidase was decreased in L. Production of NO by submitochondrial particles was 64% higher at 6 months in E and 105% higher at 18 months in E and L. Maximal hydrogen peroxide production was lower at 18 months in both groups. CONCLUSIONS: Results do not support the hypothesis of an increase in antioxidant enzyme activity by long-term treatment with angiotensin II inhibitors as previously suggested and point towards a role for the NO produced by mitochondrial nitric oxide synthase (mtNOS) in the protective effect of these drugs.     

Cr（V）involvementin the toxicity pathway of testicular damage

AIM: The functional integrity of the blood-testis barrier (BTB) in male mice exposed to Cr(V) was studied in order to clarify the mechanism underlying testicular injury. METHODS: Adult male mice were subcutaneously injected repeated doses of 8.02 micromol (0.5 ml) of Cr/mouse.day for 5 days. Animals receiving a similar volume of bis(hydroxyethyl)-aminotris(hydroxymethyl)methane buffer (BT) were used as controls. The animals were sacrificed on day 6 and small fragments of seminiferous tubules, approximately 8-10 mm length, were incised and sutured at both ends. They were exposed in vitro to horseradish peroxidase-containing culture medium for 10 minutes. Tissues were then fixed and processed for ultrastructural studies. RESULTS: Controls and Cr(V)-treated group resulted in the uptake of the tracer by Sertoli cells. However, the major finding consisted in the permeability of the BTB only in the Cr(V)-group, as evidenced by the presence of the tracer within the junctions between the neighbouring Sertoli cells. CONCLUSION: The BTB is disrupted in mice submitted to Cr(V). The permeability of the BTB is a crucial feature to be investigated for the understanding of lesions within the seminiferous tubule.