[Correlation between in vitro dissolution characteristics of macrolide antibiotic tablets and bioavailability in man].
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Biomedical subjects
Publications and source records attributed to S Kitazawa.
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Catecholaminergic synaptic input to neurons containing corticotropin-releasing factor (CRF) in the parvocellular portion of the paraventricular nucleus (PVN) in the rat hypothalamus was observed. The experimental techniques used combine autoradiography after 3H-noradrenaline (3H-NA) injection or uptake of 5-hydroxydopamine (5-OHDA) with immunocytochemistry using CRF antiserum. CRF-like immunoreactive cell bodies and fibers in the PVN received synaptic inputs from the axon terminals in which a selective accumulation of 3H-NA or 5-OHDA was found. This finding suggests that the secretion of CRF neurons may be regulated via synapses by catecholaminergic neurons.
Primary malignant lymphoma is an extremely rare neoplasm in the liver, with only 10 cases having been reported in the English literature. An autopsy case of primary hepatic lymphoma is presented herein. Although a few lymph nodes were slightly involved, large involvement of lymphoma was apparent in the liver. This lymphoma was classified as a diffuse large-cell (histiocytic) type. Microscopically, the PAP method for immunoglobulin showed positive staining of IgG and lambda in the lymphoma cells.
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An exsorption technique which can assess the transport of a drug from blood to the intestinal lumen was used to study the effects of glucose and to determine the presence of segmental differences in drug transport across the rat small intestinal membrane following intravenous drug administration. The drugs used in the study were un-ionized (sulfanilamide) or ionized (metoclopramide and sulfisoxazole) at the physiological pH (6.5) of rat small intestine. An intestinal segment of 20 cm from the ligament of Treitz to the distal part was used as the jejunum and the same length from the ileocecal junction to the proximal part was regarded as the ileal segment. Isotonic NaCl or glucose was used as the intraluminal perfusate. In the case of sulfanilamide, the exsorption rate remained almost constant during the perfusion of NaCl or glucose and no segmental differences in the exsorption rates were observed. For the weakly basic drug (metoclopramide) the exsorption rate in the jejunum was significantly decreased by glucose. Conversely, for the weakly acidic drug (sulfisoxazole), the exsorption rate in the jejunum was increased during glucose perfusion. In contrast to the effects observed in the jejunum, glucose did not have any significant effect on the exsorption rate of drugs studied in the ileum. These observations might be explained by the intraluminal pH in the respective segments and changes in the pH mediated by glucose perfusion.
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Synapses between neurons with corticotropin-releasing-factor-(CRF)-like immunoreactivities and other immunonegative neurons in the hypothalamus of colchicine-treated rats, especially in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) were observed by immunocytochemistry using CRF antiserum. The immunoreactive nerve cell bodies and fibers were numerous in both the PVN and the SON. The CRF-containing neurons had synaptic contacts with immunonegative axon terminals containing a large number of clear synaptic vesicles alone or combined with a few dense-cored vesicles. We also found CRF-like immunoreactive axon terminals making synaptic contacts with other immunonegative neuronal cell bodies and fibers. And since some postsynaptic immunonegative neurons contained many large neurosecretory granules, they are considered to be magnocellular neurosecretory cells. These findings suggest that CRF functions as a neurotransmitter and/or modulator in addition to its function as a hormone.
Apical membrane vesicles were isolated from the confluent LLC-PK1 cells by nitrogen cavitation and Mg/EGTA precipitation methods. The specific activities of marker enzymes for apical membranes were enriched 8- to 18-fold relative to those in the homogenate. D-[3H]Glucose uptake into the vesicles was stimulated in the presence of Na+ gradient (overshoot phenomenon), and the values of apparent Km and Vmax for Na+-dependent component of D-glucose uptake were 0.3 mM and 5.8 nmol/mg protein per min, respectively.
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Theophylline binding to plasma protein was studied with seven bronchial asthmatic inpatients. The extent of protein binding was monitored using an ultrafiltration device, EMIT FreeLevelTM System 1, whose performance is pH independent between 7.5 and 8.5 and concentration independent between 2 and 10 mcg/ml. When protein-free theophylline solutions are used a linear pH dependency was observed between 7.0 and 8.3. With theophylline-spiked human plasma using the same samples, the binding was found to be concentration-independent in the range 5 to 40 mcg/ml. The intra- and inter-individual variations in theophylline binding to plasma proteins were relatively large. A calculation procedure for predicting free fractions at normal physiological plasma pH, 7.4, using the observed free fraction at a given plasma pH is proposed. A good correlation was obtained between plasma and salivary theophylline concentrations. Salivary levels alone, however, are unreliable for monitoring theophylline therapy.
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In order to explore the effects of metals upon the subsequent onset of several clinical events in SMON, a retrospective cohort study was attempted. Study subjects were 216 "exposed" patients and 149 "unexposed" patients. "Exposure" was defined as the simultaneous ingestion of metal-containing drugs with clioquinol before the onset of neurological disorders. These two cohorts were identified from 531 patients among 832 patients, collected by the nationwide survey in 1975 and 1976. Effects provoked by ingestion of five metals (alminum, calcium, magnesium, copper and bismuth) were evaluated by relative risks with and without adjustment of the total amount of clioquinol ingested. Adjusted relative risks were estimated by maximum likelihood method. Significance of relative risk was determined by its 95% confidence interval. Following major findings emerged from the present analysis. (1) Simultaneous ingestion of Al-, Ca-, Mg-, Cu- or Bi-containing drugs with clioquinol significantly reduced the risk of developing motor disturbances. (2) Risk of developing visual disturbances were favorably modified by Al-containing drugs. (3) Clinical severity was significantly reduced by ingestion of Al-, Ca-, Mg- or Bi-containing drugs. (4) About 2-fold increase in risk of unfavorable clinical course was demonstrated by Al-containing drugs. (5) Onset of both green-fur on the tongue and relapse appeared unrelated to the metal-containing drugs ingested. (6) Combined ingestion of two kinds of metal-containing drugs with clioquinol appeared to yield more favorable effects than single ingestion of metal-containing drugs. (7) Al- or Bi-containing drugs demonstrated the strongest association with clinical features of SMON, followed by the drugs containing Mg or Ca. Cu-containing drugs had little association.
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The uptake of cephalosporin antibiotics by brush border membrane vesicles isolated from rat renal cortex has been studied by a rapid filtration technique, demonstrating a carrier-mediated transport system for amino-cephalosporins such as cephalexin and cephradine. The antibiotics were taken up into an osmotically reactive intravesicular space. The uptake of cephalexin was saturable (apparent Km2.2 mM), was inhibited by structural analogues and sulfhydryl reagents, and was stimulated by the countertransport effect, although the Na+ gradient did not affect the uptake. This transport system was essentially different from the transport system for p-aminohippurate in brush border membranes. The uptake properties for cephradine in brush border membrane vesicles appeared to be similar to those for cephalexin. The present results suggest the existence of a carrier-mediated transport system for amino-cephalosporins in brush border membranes. This system may be a part of the mechanism of tubular reabsorption of these antibiotics.
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The uptake of [3H]-labeled p-aminohippurate by brush-border and basolateral membrane vesicles isolated from rat renal cortex has been studied by a rapid filtration technique. Some characteristics of carrier-mediated transport for p-aminohippurate were demonstrated in basolateral membrane vesicles: the uptake was inhibited by probenecid or 4,4'-diisothiocyano-2,2'-disulfonic stilbene (DIDS), was saturable, was stimulated by the countertransport effect, and showed discontinuity in the Arrhenius plot. In contrast, brush-border membrane vesicles failed to display saturability of p-aminohippurate uptake and stimulation by the countertransport effect, although probenecid and DIDS reduced the uptake. Furthermore, p-aminohippurate uptake by brush-border membrane vesicles was influenced more sensitively by alteration in the membrane potential compared with that by basolateral membrane vesicles.