Chronic treatment with scopolamine and physostigmine changes nerve growth factor (NGF) receptor density and NGF content in rat brain

Nerve growth factor (NGF) and NGF receptors were measured in cortex and hippocampus of rats treated with drugs affecting cholinergic neurotransmission. High (K_d= 0.045nM) and low (K_d= 21nM) affinity¹²⁵I-NGF binding sites were present in both cortical and hippocampal membranes with hippocampus containing higher numbers of both sites than cortex. Chronic treatment of rats with the muscarinic receptor antagonist scopolamine (5 mg/kg, twice daily) decreased the density of high- and low-affinity sites by 50–90% in cortical and hippocampal membranes. These changes were seen after 7 days, but not 3 days, of scopolamine treatment. Chronic infusion of physostigmine (1 mg/kg/day) using minipumps increased the number of high- and low-affinity sites in cortex 3- and 6-fold, respectively. The changes in receptor-binding parameters induced by physostigmine were transient as they were evident after 3 days of treatment, but returned to control levels after 7 days. NGF content in cortex and hippocampus was reduced by about 50% following 7, but not 3, days of chronic physostigmine infusion. In contrast, scopolamine treatment failed to change NGF levels in the cholinergic neuronal target regions but it decreased NGF content in the septal area. The content of NGF mRNA in the cortex measured by Northern blot analysis failed to change following either scopolamine or physostigmine treatment. The results suggest that levels of NGF and NGF receptors in the target regions of cholinergic neurons are regulated by the extent of cholinergic neurotransmitter activity.     

Causes of Death and Risk Factors for Mortality in Patients With Severe Chronic Obstructive Pulmonary Disease

ObjectiveThe objective of this study was to assess the causes of death and risk factors for mortality in a cohort of patients with severe chronic obstructive pulmonary disease (COPD).Patients and methodsWe studied 203 patients with severe COPD (forced expiratory volume in 1 second [FEV₁] <50%), who were attended in our respiratory department day hospital (2001-2006). Clinical variables were recorded on inclusion, and clinical course and causes of death were retrospectively reviewed.ResultsThe mean (SD) age of patients was 69 (8) years and the mean FEV₁ was 30.8% (8.2%). One-hundred and nine patients died (53.7%); death was attributed to respiratory causes in 72 (80.9%), with COPD exacerbation being the most frequent specific cause within this category (48.3%). During follow-up, 18.7% required admission to the intensive care unit (ICU). Survival at 1, 3, and 5 years was 80%, 53%, and 26%, respectively. The multivariate analysis showed that mortality was associated with age, stage IV classification according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD), cor pulmonale, and hospital admission during the year prior to inclusion. Need for admission to the ICU during follow-up was a factor independently associated with higher mortality.ConclusionsMortality in patients with severe COPD was high and exacerbation of the disease was one of the most frequent causes of death. Age, GOLD stage, cor pulmonale, prior admission to hospital, and need for admission to the ICU during follow-up were independent predictors of mortality.     

Lindane inhibition of [35S]TBPS binding to the GABAA receptor in rat brain.

The inhibition of [³⁵S]t-butylbicyclophosphorothionate ([³⁵S]TBPS) binding to the GABA_A receptor by the insecticide γ-hexachlorocyclohexane, lindane, was studied in several brain regions and using different membrane preparation methods, both in vitro and after dosing the animals with the chemical. In the latter studies, the amount of lindane remaining in the membrane suspensions used for binding assays was determined. In vitro data showed values of IC₅₀ from 150 to 1675 nM, varying in function of the membrane preparation method used. This may account for the discrepancies in IC₅₀ values found in the literature. IC₅₀ values within the range of 150–250 nM were determined using extensively washed membranes from several brain regions, so no evidence arose for brain regional differences in the affinity of lindane for the TBPS binding site. After different schedules of acute treatment with lindane, we found a manifest relationship between the extent of the observable inhibition of [³⁵S]TBPS binding and the lindane amount remaining in the membrane suspensions used for binding assays. This relationship was in good agreement with the in vitro data, so no support for an in vivo acute regulation of the binding site was obtained.     

Regulation of glucose homeostasis in pre-obese Zucker rats before and after weaning

This study was undertaken to determine the changes which could occur in glucose homeostatis during the suckling-weaning transition in the genetically obese Zucker (fa/fa) rat. Glucose kinetics and glucose utilization in individual tissues were determined in 15-day-old suckling and 30-day-old weaned obese Zucker rats either in the post-absorptive state or during a glucose infusion. During suckling, glucose turnover rates in the basal state as well as glucose production and utilization during the glucose infusion were identical in lean and obese rats. Furthermore, individual tissue glucose utilizations were similar in the two groups of rats, except in brown adipose tissue where utilization was lower in obese than in lean rats during the glucose challenge. After weaning, glucose turnover rates and glucose utilization in individual tissues were identical in the two genotypes in the basal state. During the glucose infusion, hepatic glucose production was less suppressed in the obese. Furthermore, glucose utilization was significantly lower in muscles (extensor digitorum longus, tibialis anterior, diaphragm) and higher in white adipose tissue of obese rats. These data show that, before weaning, pre-obese Zucker rats present a perturbation only in the uptake of glucose in brown adipose tissue. Major defects in the regulation of glucose homeostatis occur after weaning.     

Cervical pregnancy complicated with group B streptococcal meningitis.

Maternal group B streptococcal infection is an uncommon entity. Herein we describe a case of a 27-year-old-woman who presented life-threateniing group B streptococcus meningitis with an ectopic cervical pregnancy. No other infectious focus have been found. To our knowledge this is the first time that this association has been reported.     

Movement disorders in patients with peripheral facial palsy.

Acute unilateral facial paralysis is usually a benign neurological condition that resolves in a few weeks. However, it can also be the source of a transient or long-lasting severe motor dysfunction, featuring disorders of automatic and voluntary movement. This review is organized according to the two most easily recognizable phases in the evolution of facial paralysis: (1). Just after presentation of facial palsy, patients may exhibit an increase in their spontaneous blinking rate as well as a sustained low-level contraction of the muscles of the nonparalyzed side, occasionally leading to blepharospasm-like muscle activity. This finding may be due to an increase in the excitability of facial motoneurons and brainstem interneurons mediating trigeminofacial reflexes. (2). If axonal damage has occurred, axonal regeneration beginning at approximately 3 months after the lesion leads inevitably to clinically evident or subclinical hyperactivity of the previously paralyzed hemifacial muscles. The full-blown postparalytic facial syndrome consists of synkinesis, myokymia, and unwanted hemifacial mass contractions accompanying normal facial movements. The syndrome has probably multiple pathophysiological mechanisms, including abnormal axonal branching after aberrant axonal regeneration and enhanced facial motoneuronal excitability. Although the syndrome is relieved with local injections of botulinum toxin, fear of such uncomfortable contractions may lead the patients to avoid certain facial movements, with the implications that this behavior might have on their emotional expressions.