Induced interconversion of agonist affinity states in muscarinic receptor from mice brain: effects of temperature and sugars.
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Animals↗
Biomedical subjects
D Gurwitz
Publications and source records attributed to D Gurwitz.
Central muscarinic receptor degeneration following 6-hydroxydopamine lesion in mice.
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Animals↗
Hemoglobin desaturation: its occurrence during sleep in patients with cystic fibrosis.
Sleep studies were performed in 20 clinically stable cystic fibrosis (CF) patients (mean age, 18.2 years) to determine the magnitude of fall in hemoglobin saturation (Sao2) during sleep and to relate these changes to pulmonary function and echocardiographic findings. Five healthy young adults served as controls. In both groups, the maximum fall in Sao2 was seen during rapid eye movement (REM) sleep. The mean maximum fall in the control group during REM sleep was 2.0% (range, 1% to 3%), compared with 7.4% (range, 1% to 23%) in the CF group. Of the 11 patients in whom right ventricular systolic time intervals were obtained, eight of the nine patients with falls in Sao2 greater than 3% during REM sleep had echocardiographic evidence of pulmonary hypertension. Repeated episodes of desaturation during sleep may contribute to the development and progression of cor pulmonale in CF patients.
Adolescent↗
Corticosteroids in status asthmaticus.
Nineteen children who were not steroid dependent and were hospitalized in status asthmaticus were studied to evaluate the effect of corticosteroids. They were randomized into two groups. Each group received salbutamol inhalations and intravenous aminophylline therapy. One group received 7 mg/kg hydrocortisone intravenously every six hours; the other group served as a control. Each group showed significant improvement in clinical score and peak expiratory flow rate after 36 hours; there was no statistical difference in the degree of improvement. Six of ten steroid-treated children and six of nine controls achieved a PEFR of 50% predicted by 36 hours. The response to inhaled salbutamol was similar in each group. The results show that in the first 36 hours of therapy, corticosteroids have no additive effect on the bronchodilator response of aminophylline and salbutamol and do not hasten the recovery of nonsteroid-dependent children in status asthmaticus. Although the results show that an inhaled sympathomimetic drug is beneficial in status asthmaticus, corticosteroid therapy does not increase the responsiveness of the airways to these agents.
Adolescent↗
Mechanism of hemoglobin desaturation during rapid-eye-movement sleep in normal subjects and in patients with cystic fibrosis.
To assess the mechanism of the decrease in hemoglobin O2 saturation during rapid-eye-movement sleep, we studied 5 normal subjects 22 to 30 yr of age and 20 patients with cystic fibrosis 9 to 29 yr of age. The largest decrease in arterial O2 saturation, as monitored with an ear oximeter during sleep, occurred during rapid-eye-movement sleep, with a mean +/- SEM decrease of 2 +/- 0.31% in the normal subjects and 7.4 +/- 1.3% in the patients in both groups. Rapid-eye-movement sleep was associated with a significant loss of intercostal and diaphragmatic tonic muscle activity (p < 0.01), as monitored with surface electrodes, and a decrease in the baseline position of the rib cage and abdomen, as recorded by magnetometers (p < 0.01). This suggests a decrease in functional residual capacity, which was accompanied by a consistently lower arterial O2 saturation during rapid-eye-movement sleep. Short periods (< 20 s) of inhibition of phasic respiratory muscle activity during rapid-eye-movement sleep were followed by further decreases in arterial O2 saturation. We conclude that the desaturation during rapid-eye-movement sleep in all subjects was mainly due to a decrease in functional residual capacity, leading to airway closure in the dependent lung regions. The hemoglobin desaturation was further aggravated by transient periods of hypoventilation.
Adolescent↗
Pulmonary function and bronchial reactivity in children after croup.
Ninety-six children who were admitted into hospital with croup 8.5 yr previously were studied to assess lung function, atopic disease, and bronchial reactivity. Although absolute values in pulmonary function showed only small differences, children who have had croup are members of a population that is significantly different from normal children. Thirty-five per cent had heightened bronchial reactivity, as determined by methacholine challenge. There was no increased incidence of atopic disease in the children studied. One can speculate that these children who have had croup may be a population susceptible to developing chronic obstructive airway disease as adults.
Asthma↗
Dose-response study of oral fenoterol in asthmatic children.
To assess the dose of oral fenoterol, a beta 2-receptor stimulant, which provided optimal bronchodilation with minimal side effects, we studied 12 children using a double-blind crossover comparison of three dose levels, 2.5, 5 and 7.5 mg, and a placebo. ventilatory function, pulse rate, blood pressure and clinical examination were compared over a 3-hour period. Administration of fenoterol resulted in bronchodilation; a maximal effect was seen at 60--90 min lasting over the period of the study. 7.5 mg of fenoterol produced the maximal bronchodilation, but it was not significantly different from 5 mg. Side effects were minimal and no significant drug-response relationship was noted for blood pressure and pulse rate. 5 mg of fenoterol provided optimal bronchodilation with minimal side effects.
Administration, Oral↗
Perspectives in cystic fibrosis.
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Adolescent↗
Pulmonary function abnormalities in asymptomatic children after hydrocarbon pneumonitis.
To assess the effect of hydrocarbon pneumonitis on the developing lung, we studied the pulmonary function of 17 asymptomatic children, 8 to 14 years after the initial insult. Fourteen of the 17 subjects (82%) had one or more pulmonary function abnormalities, the most frequent being a high volume of isoflow. Volume of isoflow, ratio residual volume to total lung capacity, slope of phase III, flow rates at 50% and 25% of vital capacity and 60% of the total lung capacity, one-second forced expiratory volume, and maximum midexpiratory flow rate differed significantly (P less than .05) from values in control groups. Closing volume and closing capacity were not significantly different. Residual abnormalities present in children after hydrocarbon pneumonitis can be explained on the basis of small airway obstruction and/or loss of elastic recoil. These children may be at risk for the development of chronic lung disease as adults when they are exposed to exogenous factors such as air pollution or smoking.
Child, Preschool↗
Severe antithrombin III deficiency in an infant associated with multiple arterial and venous thromboses.
Inherited antithrombin III (AT-III, heparin cofactor) deficiency is a rare condition, presenting with thrombotic disease in adult life. This paper reports an 8 months old South African Black male infant with multiple large vessel venous and arterial thromboses, and E. coli septicaemia. This was associated with an extremely low plasma AT-III level. Micronodular cirrhosis and intracytoplasmic hyaline globules in the liver cells were present. These globules were eosinophilic, and PAS-positive after diastase. They measured approximately 5 mu to 30 muin diameter, occurred singly in the liver cells and were located mainly in the periportal areas. The histological findings in the liver are similar to those observed in alpha 1-antitrypsin (AAT) deficiency in which the intracytoplasmic globules represent accumulation of altered AAT. Immunochemical studies carried out on formalin fixed tissue failed to detect cross reaction material with anti-alpha 1 antitrypsin or anti-AT III antiserum. This is the first case report of AT-III deficiency presenting in infancy. It is also the first case associated with distinctive liver pathology. The available data presented are insufficient to distinguish between an inborn defect and acquired caused of the severely depressed AT-III plasma level and the distinctive liver pathology.
Alpha-Globulins↗
Agonist and antagonist binding to rat brain muscarinic receptors: influence of aging.
The objective of the present study was to determine the binding properties of muscarinic receptors in six brain regions in mature and old rats of both sexes by employing direct binding of [3H]-antagonist as well as of the labeled natural neurotransmitter, [3H]-acetylcholine [( 3H]-AcCh). In addition, age-related factors were evaluated in the modulation processes involved in agonist binding. The results indicate that as the rat ages the density of the muscarinic receptors is altered differently in the various brain regions: it is decreased in the cerebral cortex, hippocampus, striatum and olfactory bulb of both male and female rats, but is increased (58%) in the brain stem of senescent males while no significant change is observed for females. The use of the highly sensitive technique measuring direct binding of [3H]-AcCh facilitated the separate detection of age-related changes in the two classes (high- and low-affinity) of muscarinic agonist binding sites. In old female rats the density of high-affinity [3H]-AcCh binding sites was preserved in all tissues studied, indicating that the decreases in muscarinic receptor density observed with [3H]-antagonist represent a loss of low-affinity agonist binding sites. In contrast, [3H]-AcCh binding is decreased in the hypothalamus and increased in the brain stem of old male rats. These data imply sexual dimorphism of the aging process in central cholinergic mechanisms.
Acetylcholine↗
Selective neurotoxicity induced by the ionophore lasalocid in rat dissociated cerebral cultures, involvement of the NMDA receptor/channel.
An in vitro model of dissociated cerebral cultures, prepared from prenatal 15-16-days rat fetuses, was used to further characterize the neurotoxic effects caused by the antibiotic ionophore lasalocid-X-537A. The damage caused by lasalocid (1-2 microM, 2-4 hr) included swelling of perikarya, followed by cytolysis of most neurons present in the cultures. The neuronal damage was dose-dependent, noticeable at concentrations above 0.5 microM, and was more pronounced in established cultures (14 days in vitro-DIV) than in younger ones (7 DIV). Unlike neurons, no damage was observed in glia and other non-neuronal cells present in the cultures by exposure to 2 microM lasalocid. Moreover, the drug was not toxic for cultures of rat astrocytes and C6 glioma cells. Another calcium ionophore A-23187 (calcimycin, 1 microM), destroyed both neuronal and non-neuronal cells within 1 hr. Ca2+ influx was increased by 140% in cultures exposed to lasalocid (1.5 microM). The lasalocid neurotoxic effects were neither inhibited by 10 microM nimodipine (a calcium channel antagonist) nor by 10 microM 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX)(a non-N-methyl-D-aspartic acid (NMDA) receptor antagonist), but were exclusively blocked by 10 microM MK-801 (a non-competitive NMDA receptor/channel antagonist). The neurotoxicity induced by lasalocid was further confirmed by measurements of lactate dehydrogenase (LDH) released into the media. Lasalocid (1.5 microM) induced the release of both LDH and arachidonic acid (AA) (by 8 and 4 fold of control values, respectively), and this was blocked by MK-801 but not by CNQX. These results are in according with the observations that activation of calcium influx through the NMDA receptor leads to activation of phospholipase A2 (PLA2) and release of AA. In contrast, MK-801 did not block the release of either LDH or AA mediated by the calcium ionophore A-23187 (1 microM) in these cultures. [3H]-MK-801 binding to washed rat cortical membranes, a measure of direct interaction with the NMDA receptor/channel complex, was not affected by lasalocid either alone or in the presence of glutamate and glycine. [3H]-D-aspartate release, a measure of excitatory amino acid (EAA) secretion mediated by NMDA receptor activation, was increased by lasalocid and could be blocked by MK-801. These observations suggest that lasalocid induces selective neurotoxicity, which involves the NMDA receptor/channel complex, possibly indirectly, resulted in elevated intracellular Ca2+ levels and the subsequent glutamate or aspartate release.
Animals↗