In addition to anxiolytic and anticonvulsant properties, benzodiazepines (BDZ) produce sedation, ataxia, and muscular relaxation. In general, it was difficult to separate these properties within this ...chemical class during the search for clinically useful anxiolytics; and when BDZ's were used to characterize 3H-BDZ binding sites they indicated only a single homogenous class of receptors. A new chemical series was discovered, triazolopyridazines (TPZ, prototype CL 218,872), which showed anticonflict activity in rats and monkeys without sedation or ataxia and inhibited 3H-BDZ binding in brain membranes with kinetic characteristics suggesting the presence of multiple BDZ receptors. High affinity and low affinity sites for the TPZ were demonstrated, the former designated at Type 1 and the latter as Type 2. Anatomical and in vivo studies have supported different distributions of each receptor in brain. Lately, the physical separation of discrete proteins which bind 3H-BDZ has been reported. The multiple receptors and the variety of endogenous substances which have been proposed as modulators and ligands of the receptors might explain variability as well as selectivity in pharmacological properties in these drugs.
Changes in metabolic and functional activity of platelets stored as platelet concentrates in plastic bags highly permeable to gases were investigated. The following parameters were measured daily: ...pH, pO2, pCO2, HCO3, glucose, lactic acid, lactic dehydrogenase, cellular ATP and platelet aggregation induced by different agents (collagen and ADP). As indexes of lipid peroxidative damage, the cellular levels of conjugated dienes, malonyldialdehyde and some antioxidant molecules such as coenzyme Q10 and vitamin E were determined. A marked increase in pO2, conjugated dienes, malonyldialdehyde, lactic acid and lactic dehydrogenase activity was observed during the preservation. Platelet ATP content was unmodified and a remarkable decrease in platelet aggregability was found. pCO2, cyclooxygenase activity, vitamin E, coenzyme Q10, bicarbonate and glucose showed a rapid fall. Our data seem to indicate a preservation of platelet metabolic activity and a correlation between increased lipid peroxidation and functional impairement.
Synaptosomes from rat cerebral cortex incubated with 3H-S-adenosyl-L-methionine (3H-SAM) displayed an increase in chloroform- extractable tritium when norepinephrine was added to the reaction ...mixture. The products of this mixture were maximally generated from intact synaptosomes, only partially inhibited by propranolol, and not enhanced by exogenous phospholipids. Thin layer chromatographic analysis of these chloroform extracts in three solvent systems yielded large norepinephrine- stimulated peaks of radioactivity that did not consistently co-chromatograph with authentic methylated phospholipid standards: phosphatidylmonomethylethanolamine (PME), phosphatidyldimethylethanolamine (PDE), and phosphatidylcholine (PC). Further, attempts to identify these peaks of radioactivity using as standards several putative methylated products of varied chemical classes, failed to elucidate likely candidates. It appears that while norepinephrine markedly stimulates the amount of tritium extracted into the chloroform phase, careful and positive structural elucidation of formed products is required before it can be concluded that these are indeed methylated phospholipids.
To determine the relationship between vascular beta-amyloid (beta A4) and senile plaques (SPs) and neurofibrillary tangles (NFTs).
We counted vascular amyloid deposition with SP and NFT density in ...the medial temporal lobe (CA1 plus the subiculum) and the cerebellum.
The brains of seven patients with Alzheimer's disease and of three age-matched nondemented control subjects were studied.
In Alzheimer's disease, the density of beta A4-laden blood vessels was significantly higher in the cerebellum than in CA1 plus the subiculum. Conversely, the densities of SPs and NFTs were much greater in the CA1 plus the subiculum than in the cerebellum.
This study indicates that local vascular beta A4 deposition is not directly correlated with SP and NFT densities. Deposition of beta A4 in blood vessel walls may not be instrumental in the formation of SPs and/or NFTs in the brain.
A protocol for the biochemical study of platelet stored for transfusional use at 22 degrees C and under continuous shaking in a plastic bag highly permeable to gases and with a suitable area/volume ...ratio, is described. Plasmatic dextrose, lactic acid, lactic dehydrogenase activity, cellular ATP and malonyldialdehyde were monitored during the storage, as well as some acid-base indexes namely: pH, pCO2, HCO3-, pO2. The platelet functional status was checked as aggregating power induced by ADP and collagen and by beta-thromboglobulin release. The results obtained are indicative of a discrete maintenance of aerobic metabolism by platelets which are able to give up CO2 and take up O2 so that the plasmatic pH is constant during the storage. However, the malonyldialdehyde increase suggests that platelets become increasingly susceptible to peroxidative attacks. The aggregating response was dramatically reduced even on the third day of storage. The data obtained point out that, under the conditions reported, platelets can be transfused up to the third day of storage.
A field test of a lens opacity rating system was run. Findings were graded in 7 categories: Cortex: (1) Waterclefts, Vacuoles, & Flakes (WVF, 4 grades), (2) Wedges & Spokes graded by number of ...Quadrants affected (WS-Q), and (3) Inward extent of Wedges & Spokes (WS-I, 3 grades); Nucleus: (4) Opacification (NUC-O) and (5) Coloration (NUC-C), each using 4 grades; and Subcapsular areas: (6) Anterior (SUB-A) and (7) Posterior (SUB-P) opacification, each using 5 grades. An instruction booklet with corresponding guidelines, sketches, and photographs was developed. Reproducibility of grading was tested in 3 clinics using 16 ophthalmologist-examiners. At each clinic, examiners were randomly paired. They independently performed slit-lamp exams of assigned patients (9 on average) on the same day (inter-examiner) and 1-2 weeks later (intra-examiner). To test intra-examiner reliability, examiners were divided into two groups (one from each pair), with gradings analyzed by group. For each group, 53 to 58 patients had evaluable examinations. Intra-examiner concordance for each lens category (defined as at most one grade difference in one lens) was as follows (for examiner groups 1 and 2, resp.): WVF: 98% & 97%; WS-Q: 96% & 100%; WS-I: 100% & 100%; NUC-O: 98% & 100%; NUC-C: 100% & 98%; SUB-A: 90% & 100%; and, SUB-P: 92% & 100%. Inter-examiner concordances were slightly lower than those found for intra-examiner. Grading lens findings in the manner described above appears to have potential utility in large scale studies.
We investigated metabolic, blood gas and acid-base balance modifications of erythrocyte concentrates resuspended in PAGGS-sorbitol solution during 6 weeks of storage. Glucose utilization was impaired ...during the last 2 weeks, while the intraerythrocytic ATP level decreased only 50% from the 1st to the 6th week. The K+ and Hb concentration in the medium showed a progressive increase which was more pronounced during the last 2 weeks. The decrease in pH progressed to reach 6.27 at the 6th week of storage. Intraerythrocytic 2,3-DPG dropped rapidly in the course of the 1st week and the percentage of oxyhemoglobin showed a remarkable increase after the 1st week (90%). Our data suggest that erythrocyte concentrates in PAGGS-sorbitol should be transfused, for optimal efficacy, within 4 weeks.
Coenzyme Q10 in dilated cardiomyopathy Manzoli, U; Rossi, E; Littarru, G P ...
International journal on tissue reactions,
1990, Letnik:
12, Številka:
3
Journal Article
Recenzirano
The authors have tried to study the therapeutic efficacy of coenzyme Q10 (CoQ10) in patients with dilated cardiomyopathy (DCM). In fact, CoQ10 has been shown to be deficient in myocardial tissue ...biopsies taken from DCM hearts, compared to normal hearts. Thirty patients with histological diagnosis of DCM were orally treated with CoQ10 (100 mg/die) for 2 months. Before and after treatment a clinical examination with determination of NYHA class and an echocardiographic examination with determination of ejection fraction (EF) and of telediastolic (TDV) and telesystolic (TSV) volumes were performed, and blood was drawn for plasma CoQ10 determination. In seven patients the pretreatment endomyocardial level of CoQ10 was also assayed. Seven patients left the study because of poor therapeutic compliance. In 47% of patients the clinical symptomatology regressed, with improvement of NYHA class. The EF improved from 0.31 +/- 0.09 to 0.37 +/- 0.11 (p less than 0.001). The TDV passed from 262.2 +/- 85 ml to 203.3 +/- 83 ml (p less than 0.05), and the TSV from 166.13 +/- 75 ml to 126.9 +/- 56 ml (ns). The CoQ10 plasmatic levels improved in 95% of the patients: from 0.74 +/- 0.37 micrograms/ml to 2.27 +/- 0.99 micrograms/ml (p +/- 0.0001). The CoQ10 myocardial levels did not show univocal values, but the patients with lower myocardial levels seemed to have a better therapeutic response. These data suggest that the CoQ10 deficiency in DCM may be reversible and that the therapeutic effects depend on the basal plasmatic and myocardial levels. Therapy with coenzyme Q10 may be considered to be an efficacious aid in the traditional treatment of chronic cardiac failure.
Auditory event-related potential (ERP) components have been anatomically linked to temporal lobe structures and functionally related to attentional and memory processes. We recorded auditory ERPs ...using an "oddball" paradigm from two patients with amnestic syndromes secondary to medial temporal lobe encephalitic infections. The oddball paradigm elicits the exogenous N1 and P2 components, and the endogenous N2 and P3 components. Electrical source analysis was used to test for alterations in source strength and orientation in these patients compared to control subjects. Symmetric dipoles placed in the temporal lobe region were used to measure ERP component activity. In the patient with a lesion confined to the left, medial temporal lobe, including the posterior hippocampus, dipole orientation was displaced anteriorally. In the patient with lesions to the anterior medial temporal lobe, temporal poles, and orbital frontal cortex, the negative components of the ERP (N1 and N2) were reduced in the right hemisphere, accompanied by disturbed orientation. These findings are consistent with other evidence that the different components of the auditory ERP can be dissociated on the basis of lesion effects, and that the antero-posterior extent of encephalitic lesions may play an important role in modulating ERP abnormalities.
Specific 3H-diazepam binding and 3H-GABA binding were measured in cortical membranes of untreated rats and rats which had been administered unlabeled diazepam (5.0 mg/kg, IP) thirty minutes prior to ...sacrifice. Washed and unwashed membranes from control animals showed identical levels of 3H-diazepam binding. Unwashed membranes of diazepam-treated animals showed consistently and significantly lower binding of 3H-diazepam than membranes derived from control animals and treated similarly. 3H-GABA was almost non-existent in unwashed membranes of either group of animals. The binding capability of membranes of treated animals for 3H-diazepam returned to control levels upon washing with buffer prior to the binding assay. The specific binding of 3H-GABA in membranes derived from either group of animals also improved after the buffer washes. However, no difference could be detected in 3H-GABA binding between control and diazepam-treated animals. The failure of diazepam to modulate 3H-GABA binding in unwashed membranes and the participation of an endogenous inhibitory material repressing 3H-GABA binding are discussed.
