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961.
962.
Molecular determinants of benzodiazepine receptor affinities and anticonvulsant activities 总被引:2,自引:0,他引:2
In vivo convulsant activities profiles and receptor binding studies together with the techniques of theoretical chemistry were used to characterize 15 compounds, from five different chemical families, known to bind to the BDZ receptor. The experimental goals of this study were to determine the affinity of these analogs for this receptor, the effect of gamma-aminobutyric acid on the affinity, and, in a self-consistent manner, the nature of the activity, agonist (anticonvulsant), antagonist, or inverse agonist (proconvulsant, convulsant), elicited by binding to this receptor. To these ends, in vivo studies were made to determine the proconvulsant, convulsant, and anticonvulsant activities and antagonism to anticonvulsant activities of the 15 analogs. Their receptor affinities at 25 degrees were also determined by competitive inhibition of [3H] flunitrazepam and [3H]Ro 15-1788 in the absence and presence of gamma-aminobutyric acid. The goal of the theoretical studies was to identify and calculate molecular properties that modulate these affinities and types of activities and from them to develop a model of receptor recognition and activation that could consistently explain observed behavior and predict new results. Thus, molecular orbital calculations were carried out for all analogs, using semiempirical quantum mechanical methods. In addition to the optimization of structures, a number of electronic properties, such as polarizations, partition coefficients, and proton and electron affinities were computed and examined for their ability to modulate relative affinities and modes of activation of the receptor. From these studies, a model for receptor recognition involving two anchoring hydrogen bond-acceptor sites and for activation involving interaction of the most lipophilic aromatic region of each compound with the receptor was developed, which could systematically account for the three different types of behavior, agonist, antagonist, and inverse agonist, observed for these analogs. Electronic rather than structural properties were found to be the principal modulator of both recognition and activation. A possible mechanism of agonist activation of the receptor involving electron transfer to the agonist, as well as a possible induced conformational change in the receptor, is also suggested by these results. Finally, by complementarity, some steric and electronic characteristics of the receptor binding site could be deduced. 相似文献
963.
964.
965.
Measurements of lactic acid concentration and gas analysis were performed in lumbar cerebrospinal fluid from 36 patients without malignant central nervous system involvement and four patients with meningeal dissemination of non-Hodgkin lymphoma. The upper lactic acid concentration in controls of 2.48 mmol/l was exceeded in all four patients, also in cases with low blast counts and normal protein and glucose content. The pH, pCO2, pO2 and standard bicarbonate concentration in spinal fluid of patients with meningeal dissemination in non-Hodgkin lymphoma did not show significant differences compared with other patients and controls. Determination of the lactic acid concentration in cerebrospinal fluid add information, relevant to the diagnosis of meningeal involvement in non-Hodgkin lymphoma. 相似文献
966.
967.
Barrett's oesophagus: a clinical study of 52 patients 总被引:4,自引:0,他引:4
This paper reports a series of 52 patients with Barrett's (or columnar-lined) oesophagus from one medical unit diagnosed over a six-year period. The commonest associated symptoms were heartburn, regurgitation and dysphagia but 10 patients had no oesophageal symptoms and two had no symptoms at all. Gastrointestinal bleeding (overt or occult) was observed in almost one-third of patients. At diagnosis, 26 patients had oesophagitis, 23 had oesophageal ulceration and 10 had benign oesophageal strictures. An association between oesophageal ulceration and non-steroidal anti-inflammatory drug ingestion was suggested by the data and patients with oesophageal ulceration were significantly older than patients with uncomplicated Barrett's oesophagus. No patient had adenocarcinoma of the oesophagus at diagnosis and neither carcinoma nor dysplasia were seen during a mean period of 16.4 months. However, 17 per cent of patients in the series had malignancies in other sites. Most patients did well on medical treatment and only two were referred for anti-reflux surgery (both for non-healing oesophageal ulcers). Barrett's oesophagus was seen in 10 per cent of patients with gastro-oesophageal reflux at endoscopy. Oesophageal ulceration in patients with Barrett's oesophagus made up 21 per cent of oesophageal ulcers seen and benign oesophageal stricture in patients with Barrett's oesophagus constituted 13 per cent of all benign strictures seen. Barrett's oesophagus is common in our population and despite complications, it can be managed successfully, at least in the short term, by conservative means. 相似文献
968.
Effects of herbal medicine Dai-Kenchu-to on anorectal function in children with severe constipation.
AIM: We administered the herbal medicine Dai-Kenchu-To (DKT) to children with severe chronic constipation or with severe constipation after surgery for anorectal malformations. We then objectively assessed the effect of DKT on anorectal function by manometric study in addition to using a clinical scoring system. PATIENTS AND METHODS: Ten children with severe chronic constipation and 5 children with severe constipation after surgery for anorectal malformations were assessed. These 15 children received 0.3 g/kg/day of DKT for periods ranging from 3 months to 1 year. We objectively assessed their bowel function, sphincter function and rectal reservoir function by anorectal manometry and clinical scoring. RESULTS: In 10 children with severe chronic constipation, the clinical score after administration of DKT (7.2 +/- 0.8) improved significantly compared with that before administration of DKT (4.6 +/- 2.9) (p < 0.02). The threshold sensation volume and the maximum tolerable volume after administration of DKT significantly (p < 0.05; p < 0.01) decreased (128 +/- 63 ml vs. 69 +/- 18 ml; 229 +/- 99 ml vs. 144 +/- 47 ml), and rectal compliance after administration of DKT also significantly (p < 0.05) decreased (12.4 +/- 10.9 ml/cmH(2)O vs. 4.7 +/- 3.9 ml/cmH(2)O). CONCLUSION: The present study demonstrated that DKT had a favorable clinical effect on severe constipation in children, and anorectal manometry showed an improvement in their rectal reservoir functions. It appears that the results were secondary to DKT-stimulated peristalsis of the intestine, which promoted regular bowel habits. 相似文献
969.
A O Adefule-Ositelu 《Acta ophthalmologica》1989,67(4):396-400
Ocular complications as severe as blindness are encountered as a result of drug abuse in the eye patients seen at the Lagos University Teaching Hospital, Nigeria. They are due to self-administered medications, ignorance, social and economic factors and malpractice. There is an acute need for the Nigerian general practitioners to be trained on the management of ocular problems with demarcation as to when references to the ophthalmologists are imperative. Traditional healers still see a lot of the patients before they come to the hospitals. An understanding between the Western trained doctors and the traditional healers is necessary to curb the unnecessary complications and blindness. Public enlightenment programmes in the national medias should be implemented in order to dissuade patients from self-administration of medications and from consulting the unspecialized. 相似文献
970.