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Biomedical subjects

C Tanaka

Publications and source records attributed to C Tanaka.

At least 397 records · Page 22Linked to original sources
PubMed1982

Evidence for the presence of D2 and 5-HT2 receptors in the human prefrontal cortex.

The D2 receptor and two distinct affinity 5-HT2 receptors in the human prefrontal cortex were labeled with 3H-spiperone. In the Scatchard analysis of stereoselective binding defined by (+)- and (-)-butaclamol, two high affinity binding sites were clearly demonstrated. Apparent KD values of these higher and lower affinity sites determined in this manner were 0.028 and 0.64 nM, respectively. However, drug displacement studies of 3H-spiperone binding at these sites, using different concentrations of 3H-spiperone (0.05 nM for higher affinity sites and 0.5 nM for lower affinity sites), indicated that 70-80% of the higher affinity sites and almost all of the lower affinity sites showed characteristics of the 5-HT2 receptor and that 20-30% of the higher affinity sites showed characteristics of the D2 dopamine receptor. An additional saturation experiment related to the specific binding of 3H-spiperone to 5-HT2 receptors confirmed the existence of two distinct populations of 5-HT2 receptors that had different affinities for spiperone. Apparent KD values for higher and lower affinity 5-HT2 receptors were 0.091 and 1.27 nM, respectively. As the D2 receptor is a possible site of antipsychotic action of neuroleptics, these receptors, especially the D2 receptor in the human prefrontal cortex, seem to play an important role in psychotic disorders.

Binding, Competitive↗
PubMed1982

Proton nuclear magnetic resonance studies on brain edema.

The water in normal and edematous brain tissues of rats was studied by the pulse nuclear magnetic resonance (NMR) technique, measuring the longitudinal relaxation time (T1) and the transverse relaxation time (T2). In the normal brain, T1 and T2 were single components, both shorter than in pure water. Prolongation and separation of T2 into two components, one fast and one slow, were the characteristic findings in brain edema induced by both cold injury and triethyl tin (TET), although some differences between the two types of edema existed in the content of the lesion and in the degree of changes in T1 and T2 values. Quantitative analysis of T1 and T2 values in their time course relating to water content demonstrated that prolongation of T1 referred to the volume of increased water in tissues examined, and that two phases of T2 reflected the distribution and the content of the edema fluid. From the analysis of the slow component of T2 versus water content during edema formation, it was demonstrated that the increase in edema fluid was steady, and its content was constant during formation of TET-induced edema. On the contrary, during the formation of cold-injury edema, water-rich edema fluid increased during the initial few hours, and protein-rich edema fluid increased thereafter. It was concluded that proton NMR relaxation time measurements may provide new understanding in the field of brain edema research.

Animals↗
PubMed1982

[Laboratory and clinical studies of cefmetazole in serious infection by Staphylococcus (author's transl)].

Cefmetazole (CMZ) is an antibiotic agent belonging to the cephamycin group, which is resistant to beta-lactamase and has a broad antibacterial spectrum covering from Gram-negative to -positive organisms. Although this agent has been proved to have an antibacterial activity against Staphylococcus spp., it has not been used for treatment of the infections caused by the organism. Thus, 62 strains of S. aureus isolated clinically were compared for their sensitivity to CMZ, cefoxitin (CFX), cefuroxime (CXM), cefazolin (CEZ), and ampicillin (ABPC). In addition, 5 children suffering from septicemia due to S. aureus were treated with CMZ 158 mg/kg at a mean daily dose for a mean period of 14 days. The dose was used after dividing into 3 and 4 equal parts in 1 and 4 children, respectively. One old patient with septicemia was given 2,000 mg of CMZ twice daily for 4 days and once daily for subsequent 3 days. Another child with bacterial meningitis was treated with 50 mg/kg of CMZ 4 times daily for 63 days. The drug was given intravenous injection by one-shot or drip infusion in all cases under observation of clinical effects, bacteriological effects and side effects. The MIC of CMZ against S. aureus at inoculum sizes of 10(6) and 10(8) cells/ml was 1.56 mcg/ml in 72.6 and 56.5% of the strains, respectively. When 5 drugs were compared on the basis of the MIC to which the largest number of strains were sensitive, CEZ was most active, and CMZ was ranked in the next place and similar to CXM in activity. However, when the whole range of the MIC was considered, CMZ was more excellent than CXM, its MIC was lower than those of CEZ, CFX and ABPC in a greater number of strains. It was considered from the results that the serum level of CMZ was effective against 100 and 93.5% of strains at an inoculum size of 10(6) cells/ml and against 100 and 83.9% of strains at an inoculum size of 10(8) cells/ml until 4 and 6 hours after a one-shot intravenous injection of 50 mg/kg of Moni-trol I standard, respectively in the children. Thus, CMZ is expected to manifest a sufficient effect on septicemia caused by S. aureus in children who receive a one-shot intravenous injection of 50 mg/kg of it 4 times daily. Treatment with CMZ was clinically evaluated to be excellent in 3, good in 3 and poor in none of 6 patients with septicemia due to S. aureus, and fair in the 1 with Staphylococcal meningitis. The bacteriological result was excellent, since the causal organisms were eradicated in all cases. With regard to side effects, abnormal eosinophilia was found in 2 cases, but it was no ascribable to this drug in 1 of them. GOT showed an abnormal rise in 1 case and both GOT and GPT in 1, although they were considered not to be related to this drug in either case. It is considered from these results that CMZ is a valuable drug in treatment of septicemia due to S. aureus.

Aged↗
PubMed1982

[Nuclear magnetic resonance studies of effects of glycerol on brain edema].

Effects of glycerol on the state of water in edematous brain tissues were studied by the pulse FT NMR technique. Brain edemas were induced experimentally by cold injury and triethyl tin (TET) intoxication in Wistar rats. Ten percent w/v glycerol (1 g/kg body weight) were injected intravenously at 30 minutes before decapitation for the NMR measurements. Transverse relaxation times (T2) in the cerebral gray and white matter were measured by Meiboom-Gill pulse sequence at the resonant frequency of 100 MHz. Water content was calculated from the difference between wet and dry weight after heating in an oven at 95-100 degrees C for 72 hours after the NMR measurements. In the normal brain T2 value was 76.4 msec and 75.4 msec in the gray and white matter respectively. In the edematous brain, T2 separated into two components, one slow and one fast, corresponding with the increase of water content. Values of the slow component (slow T2) were characteristic of both types of brain edema. In the cold injury edema, slow T2 values became 105 msec in the gray matter and 96 msec in the white matter, while in the TET induced edema, it became 450 msec in the white matter. After glycerol infusion, slow T2 became faster in these regions in both types of brain edema, showing 92.1 msec in the gray matter and 88.1 msec in the white matter of the cold injury edema, and 388 msec in the white matter of TET induced edema. The degree of the changes of slow T2 values per unit change of water content was greater in the cold injury edema than in the TET induced edema. Serum osmolality elevated 23.8 mOsmol greater than the control value after glycerol infusion in this experiment. It is concluded from these findings that glycerol retracts free mobile water molecules from the edema fluid by osmotic pressure gradient.

Animals↗
PubMed1982

Antihypertensive effects of the calcium antagonistic agent nifedipine.

The calcium antagonist nifedipine (Adalat) was administered to 60 patients with essential hypertension and investigations were performed on acute and chronic hypotensive effects. The following results were obtained: 1. Acute hypotensive effects: Nifedipine (20 mg) was either orally or sublingually administered. Following oral administration, significant hypotensive effect was attained 20 min after administration and the maximum hypotensive response was obtained 2-4 h after administration. In cases of sublingual administration, significant hypotensive effect was notable 5 min after administration and blood pressure reached the lowest level 2-3 h after administration. The hypotensive effects lasted for a relatively longer period and significantly lower blood pressure than the control level was observed even 3 h after administration. 2. Chronic hypotensive effects: Nifedipine (30-60 mg/d) was orally administered consecutively. Significant hypotensive effect was attained in and after the 4th week of administration. The yearly changes in the long-term administration cases over 3 years demonstrated significant hypotensive effects. The cases who did not respond to single administration of thiazides or beta-blockers exhibited significant hypotensive response by the combined use of nifedipine. 3. Change in heart rate: In the acute study, heart rate increased after nifedipine administration and lasted for several hours. In the long-term administration cases, the changes in heart rate were not significant. 4. Side effects attributable to nifedipine such as headache in 2 cases, facial flushing, palpitation, warm sensation and nausea in 1 case each were observed early after the administration but there were no cases in whom administration was discontinued due to these side effects.

Administration, Oral↗
PubMed1981

Identification of the D-1 dopamine receptor subunit in rat striatum after photoaffinity labeling.

When rat striatal membranes, photolabeled with [3H]dopamine under assay conditions similar to those used for dopamine-sensitive adenylate cyclase, were subjected to sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, several radioactively labeled bands appeared. Labeling of these bands was reduced in the presence of non-radioactive dopamine during photolysis, but was unaffected by the presence of sulpiride. Haloperidol preferentially reduced the labeling of the main band which had a molecular weight of about 57,000 rather than the other weakly labeled bands. Labeling of this 57,000 dalton protein was not apparent when rat cerebellar membranes were used and was markedly eliminated by kainic acid-induced lesions that destroyed the intrastriatal nerve cell bodies. These results indicate that this 57,000 dalton protein is the binding subunit of the D-1 dopamine receptor.

Animals↗
PubMed1981

Stimulation of the rat dorsal raphe in vivo releases labeled serotonin from the parietal cortex.

In vivo release of labeled serotonin ([3H]5-HT) from the parietal cortex was investigated by cortical cup technique and electrical stimulation of midbrain raphe in rats anesthetized with pentobarbital sodium. The spontaneous efflux of tritium from the parietal cortex preload with [3H]5-HT followed a multiphasic exponential course. After 120 min, the rate of efflux appeared to fit the single exponential function (slow phase). Imipramine (10(-6)-10(-3) M) produced a dose-dependent increase in the spontaneous release. When pargyline in concentrations ranging from 10(-4) to 10(-3) M were added to the medium in the cup, the unchanged [3H]5-HT significantly increased in a dose-dependent manner and the slow declining coefficient of tritium efflux significantly decreased in the presence of 10(-4) pargyline. Stimulation of the rostral two-thirds of the dorsal raphe and the lateral 5-HT bundle originating from the dorsal raphe significantly increased the release of [3H]5-HT and its metabolites while stimulation of the caudal one-third of the dorsal raphe did not produce a significant increase in the release of [3H]5-HT and its metabolites. Stimulation of the medium raphe produced no or only a slight increase in the release of [3H]5-HT and its metabolites. These findings are a direct demonstration of the in vivo release of [3H]5-HT from the parietal cortex with stimulation of the dorsal raphe, particularly the rostral two-thirds of the nucleus and provide the neurochemical evidence for the dorsal raphe-cortical 5-HT pathway via the lateral 5-HT bundle.

Animals↗
PubMed1981

Pressor effect of L-threo-3,4-dihydroxyphenylserine in rats.

The pressor effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) in rats and its decarboxylation in vivo have been examined. On i.v. administration, it produces a slow-onset and long-lasting pressor response, but no significant change in heart rate or e.c.g. The pressor effect was markedly reduced by inhibition of peripheral decarboxylase and by blockade of alpha-adrenoceptors. The slow-onset and long-acting pressor effect was also evident when the drug was given orally, while intracerebroventricular administration produced a long-lasting decrease in blood pressure. Noradrenaline (NA) concentrations in the plasma were significantly increased by both i.v. and oral administration of L-threo-DOPS. Elevation of plasma NA concentration by L-threo-DOPS given i.v. was suppressed by inhibition of decarboxylase. The plasma concentration of the drug was highest immediately after its i.v. administration. Its pressor effect was enhanced in rats made hypotensive by chemical sympathectomy with 6-hydroxydopamine (6-OHDA), compared with control rats, nevertheless, L-threo-DOPS produced the same increase in plasma NA concentrations in sympathectomized rats as in the controls. These results indicate that L-threo-DOPS is gradually converted to NA by L-aromatic amino acid decarboxylase in vivo. These findings suggest that L-threo-DOPS may be clinically useful as an oral pressor agent for the treatment of certain disorders related to hypotension.

Administration, Oral↗
PubMed1981

Age-related changes in the chronotropic effect and the enzymic decarboxylation of L-threo-3,4-dihydroxphenylserine in the rat heart.

The cardiac effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) and the enzymatic decarboxylation of the drug by L-aromatic amino acid decarboxylase (AADC) were studied in atria isolated from rats ranging in age from newborn to adults and the findings compared with the cardiac effect of noradrenaline (NA). L-threo-DOPS produced dose-dependent, slow-onset and positive chronotropic effects in atria from rats of different ages. Its effect was inhibited in atria from benserazide-treated rats, suggesting that the effects are due to NA formed from L-threo-DOPS by enzymic decarboxylation rather than to the compound itself. Chronotropic sensitivity to L-threo-DOPS was highest in the newborn and decreased with age during the first 3 weeks of life. The development of cardiac response to it correlated well with the development of enzymic decarboxylation of the drug that did not correlated with the developments of chronotropic sensitivity to NA and of NA concentrations in the heart. These findings suggest that in newborn rats, L-threo-DOPS is effectively converted by AADC to NA which in turn acts on beta-receptors in the pacemaker cell membrane.

Age Factors↗