Differential ontogenesis of type I and II benzodiazepine receptors in mouse cerebellum

The ontogeny of type I and type II benzodiazepine binding sites was studied in mouse cerebellum by displacement of [3H]flunitrazepam binding by zolpidem, a ligand specific for the type I sites. Type I binding sites predominate throughout development and in the adult while type II sites account for 25% of total cerebellar benzodiazepine binding sites at birth and, during development, decrease to 10% or less in the adult. On a per cerebellum basis type II sites increase during the first postnatal week and then remain at a steady level while type I sites increase until adulthood. These results may indicate a specific localization of the type II sites (and of the corresponding alpha-protein subunits in the GABA/benzodiazepine receptor complex) in structures already present at birth and developing during a short early postnatal period. The affinity of zolpidem for its high affinity (type I) binding sites increases during cerebellar ontogeny, this increase possibly indicates an epigenetic (post-translational) 'maturation' process of the corresponding receptor molecule. Hill numbers indicate the existence of an additional binding site heterogeneity greater during development but still present in the adult; probably this is to be related to the simultaneous presence of different 'maturation' stages during development and with a certain variety of the final products.     

Effects of isometric exercise on blood cell adrenoceptors in essential hypertension

The effect of handgrip (HG) isometric exercise on plasma catecholamines, alpha 2-adrenoceptors on platelets and beta 2-adrenoceptors on lymphocytes was studied in normotensive subjects (NT) and essential hypertensive subjects (HT). Whereas systolic blood pressure (SBP) increases were similar in NT and HT subjects, diastolic blood pressure (DBP) and heart rate (HR) increased more in the former group. Baseline values and changes in plasma epinephrine (E) and norepinephrine (NE) did not differ between both groups. No differences were apparent in alpha 2-adrenoceptor density and affinity between NT and HT subjects before or after the test. HG isometric exercise induced a similar increase in beta 2-adrenoceptors on lymphocytes of 22 +/- 7 and 13 +/- 5% in NT and HT subjects, respectively. Affinity to the beta 2-adrenoceptors under baseline conditions was somewhat lower in HT (8.1 +/- 0.4 pM) than in NT subjects (6.5 +/- 0.5 pM), and this difference persisted during the test. Our results indicate that there are no differences in alpha 2- and beta 2-adrenoceptor densities either at baseline conditions or after HG isometric exercise between NT and HT subjects. Small differences noted in affinity to the beta 2-adrenoceptors require further investigation.     

Neuropeptide levels in the basal ganglia of aged common marmosets following prolonged treatment with MPTP

Summary Aged common marmosets were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 0.5–2.0 mg/kg/week i.p.) for 16 or 24 weeks, observed for a total of 30 weeks and then killed for measurement of biochemical pramaters in basal ganglia. The MPTP treatment induced a marked depletion in dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels in the caudate nucleus and putamen. In contrast, the concentrations of five neuropeptides: [Met⁵]-enkephalin, [Leu⁵]-enkephalin, cholecystokinin, substance P and neurotensin as measured by a combined HPLC/RIA method, remained unaltered in all basal ganglia regions examined. Enkephalin precursor levels, as reflected by cryptic [Met⁵]-enkephalin content, were increased in the putamen, but not in the caudate nucleus, as a consequence of MPTP administration. Cryptic [Leu⁵]-enkephalin content remained unchanged in the striatum of MPTP treated marmosets. Overall, these results suggest an increase in striatal [Met⁵]-enkephalin release following chronic MPTP treatment of aged marmosets. However, the chronic treatment of aged marmosets with MPTP does not reproduce the neuropeptide alterations characteristic of Parkinson's disease.     

Evidence that the serotonin agonist, DOI, increases renin secretion and blood pressure through both central and peripheral 5-HT2 receptors

DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCI] is a serotonin (5-HT1C/5-HT2) agonist, with potent cardiovascular effects. The purpose of the present studies was to determine the identity and location of the 5-HT receptor subtype(s) mediating the renin and blood pressure responses to DOI. Injection (i.p.) of DOI to conscious male rats elevated plasma renin activity in a dose-dependent manner. The 5-HT1C/5-HT2 antagonist ritanserin completely blocked the DOI-induced increase in plasma renin activity. In order to distinguish the 5-HT2- from the 5-HT1C- mediated effect of DOI, spiperone was administered before DOI. Low doses of spiperone (0.01 and 0.1 mg/kg, s.c.) significantly reduced the renin response to DOI. Because spiperone has a higher affinity for 5-HT2 than 5-HT1C receptors, these data suggest that DOI stimulates renin secretion through 5-HT2 receptors. To separate central from peripheral 5-HT receptors, we injected DOI into rats pretreated with saline or xylamidine, a 5-HT2 antagonist which does not cross the blood-brain barrier. Xylamidine produced a shift to the right and suppression of the maximal effect of DOI on plasma renin activity, suggesting a role for peripheral 5-HT2 receptors in the effect of DOI. On the other hand, i.c.v. administration of DOI, using doses lower than the peripherally effective doses, caused a significant elevation of plasma renin activity at 200 micrograms/kg. These experiments suggest that DOI's elevation of plasma renin activity has both peripheral and central sites of action.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nuclear estrogen receptor beta in lung cancer: expression and survival differences by sex.

PURPOSE: A role for estrogens in determining lung cancer risk and prognosis is suggested by reported sex differences in susceptibility and survival. Archival lung tissue was evaluated for the presence of nuclear estrogen receptor (ER)-alpha and ER-beta and the relationship between ER status, subject characteristics, and survival. EXPERIMENTAL DESIGN: Paraffin-embedded lung tumor samples were obtained from 214 women and 64 men from two population-based, case-control studies as were 10 normal lung autopsy samples from patients without cancer. Nuclear ER-alpha and ER-beta expression was determined by immunohistochemistry. Logistic regression was used to identify factors associated with ER positivity and Cox proportional hazards models were used to measure survival differences by ER status. RESULTS: Neither tumor (0 of 94) nor normal (0 of 10) lung tissue stained positive for ER-alpha. Nuclear ER-beta positivity was present in 61% of tumor tissue samples (170 of 278; 70.3% in men and 58.3% in women) and 20% of normal tissue samples (2 of 10; P = 0.01). In multivariate analyses, females were 46% less likely to have ER-beta-positive tumors than males (odds ratio, 0.54; 95% confidence interval, 0.27-1.08). This relationship was stronger and statistically significant in adenocarcinomas (odds ratio, 0.40; 95% confidence interval, 0.18-0.89). Women with ER-beta-positive tumors had a nonsignificant 73% (P = 0.1) increase in mortality, whereas men with ER-beta-positive tumors had a significant 55% (P = 0.04) reduction in mortality compared with those with ER-beta-negative tumors. CONCLUSIONS: This study suggests differential expression by sex and influence on survival in men of nuclear ER-beta in lung cancer, particularly in adenocarcinomas.     

Long-term Results of Primary Stent Placement to Treat Infrarenal Aortic Stenosis

OBJECTIVE: To determine the safety and the long-term results of primary stent placement for localized distal aortic occlusive disease. DESIGN: Retrospective observational study. PATIENTS AND METHODS: From July 1998 to July 2005 17 patients (14 female and 3 men, mean age 57 years (39-80)) were treated for intermittent claudication. Five of these patients underwent additional endovascular treatment of focal iliac lesions. RESULTS: Technical success defined as residual stenosis of less than 50% or a trans-stenotic systolic pressure gradient <10% was achieved in 14 of 17 (82%) patients. Major complications included dissection at the puncture site in one patient and thrombosis of additional iliac stents in another patient. Both of these complications were successfully treated. During a mean follow-up of 27 months (range 1-86), four patients had recurrence of symptoms due to in-stent restenoses (n=2), femoral (n=1) or iliac occlusion (n=1), respectively. By Kaplan-Meier analysis, primary aortic hemodynamic patency was 83% at 3 years. Secondary aortic hemodynamic patency was 100%. The primary clinical patency was 68% at 3 years. CONCLUSION: Primary stent placement for distal aortic stenoses is an alternative to surgical treatment because of its high patency and relatively low complication rates.     

Hearing impairment and cognitive development]

The study of the cognitive abilities of hearing-impaired children is important for both practical (e.g. to determine appropriate teaching strategies) and theoretical reasons (e.g. to examine the role of language in thought processes). The aim of this paper is to examine the cognitive function of hearing-impaired children from a review of the literature. If most studies show that deaf children are similar to normal children in virtually all aspects of cognitive function, many studies also emphasize pronounced differences in their academic achievement. Besides the degree of hearing loss and the age at onset of deafness, environmental factors (such as parental support and educational methods) seem to play an important role in the cognitive development and academic success of these children. This underlines the importance of the measures adopted for the deaf children as they may have a positive or negative impact on their development.