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Biomedical subjects

M Nakashima

Publications and source records attributed to M Nakashima.

At least 451 records · Page 25Linked to original sources
PubMed1990

[Myocardial lesions after snake bites by the Crotalus durissus terrificus species (rattlesnake). A case report].

Extensive and severe myocardial lesions are reported in a patient who died due to snakebite (Crotalus Durissus Terrificus). These lesions are documented by clinical, electrocardiographic, enzymatic and histological evidences. The main pathological features are represented by sarcoplasmatic vacuoles, densely clumped myofibrils and amorphous acidophilic mass into the cardiac fibers. These lesions are identical to those which have already been described in skeletal muscle after snakebite. This seems to be the first case report that shows undoubt myocardial lesions due to snakebite with anatomopathological documentation.

Adult↗
PubMed1990

[MR imaging of bone and soft tissue tumors].

One hundred sixty-one patients with tumors of bone or soft tissues underwent MRI. We believe to be able to differentiate benign from malignant lesions on the basis of imagings at internal, marginal, and peripheral properties. MR imagings demonstrated specific morphologic features that suggest the correct tissue diagnosis. MR imagings with STIR method or Gd-DTPA were more valuable. Because of the high contrast between the tumors and normal tissue, especially by STIR method, MRI provides improved detection and delineation of bone soft tissue tumors when compared to other diagnostic modalities.

Bone Neoplasms↗
PubMed1990

[Basic and clinical evaluation of rapid diagnosis of tuberculosis by detecting tuberculostearic acid].

Tuberculostearic acid (TSA) is known to be one of the characteristic lipid in the limited species of the order Actinomycetale, including Mycobacterium tuberculosis. We studied the significance of detecting TSA in the diagnosis of tuberculosis from clinical specimens collected from 791 patients with various respiratory diseases by using gas--chromatography/mass--spectrometry. By our method, the detectable limit of TSA was around 10(2)-10(3) bacilli of Mycobacterium tuberculosis, and our method is as sensitive as culture examination for tuberculosis. In sputa collected from patients with active pulmonary tuberculosis (n=169), TSA positively was around 90%, while less than 10% false positive ws also recognized. In pleural effusion (n=81) and bronchial washing (n=91) collected from patients with active tuberculosis, the positivity of TSA was around 70%. We could also detect TSA in about 30% of clinical specimens collected from patients suspected of tuberculosis. The diagnostic sensitivity of TSA for tuberculosis was similar to that of adenosine deaminase activity (ADA), while TSA was slightly superior to ADA in specificity. These findings indicate that detection of TSA from clinical specimens is useful to make rapid diagnosis of pulmonary tuberculosis.

Bronchoalveolar Lavage Fluid↗
PubMed1990

Beneficial effects of a new 5-lipoxygenase inhibitor on occlusion- and occlusion-reperfusion-induced myocardial injury.

Effects of a new 5-lipoxygenase inhibitor TZI-41127 (2-(4-hydroxy-3,5-dimethylphenyl)-5-methoxy-3-methylindole) on occlusion- and occlusion-reperfusion-induced myocardial injury were examined in rats and dogs. The occlusion-reperfusion-induced myocardial injury was produced by the occlusion of the left anterior descending (LAD) coronary artery for 90 min following 22 h reperfusion in Beagle dogs. The drug was orally administered twice in a dose of 30 mg/kg. The first administration was 2 h before the occlusion and the second one was 1 h after the start of the occlusion. Eighteen dogs were divided into two groups. Nine were for control which were administered the vehicle, and the other were for the drug treatment. One animal of each group died because of ventricular fibrillation. The risk area and the infarct area were measured 22 h after reperfusion. The risk area as percent of total ventricle was not different between the two groups. However, the infarct area as percent of the risk area was significantly less in the drug-treated group. Although the ventricular arrhythmias immediately after the reperfusion were not prevented by the drug treatment, the ventricular arrhythmias 22 h after the reperfusion were significantly less in the drug-treated group. The arterial blood pressure, the heart rate and the double product were not significantly different between the two groups. The infarct size induced by LAD occlusion in rats was also reduced by the pretreatment with TZI-41127. Thus, TZI-41127 has beneficial effects on occlusion- and occlusion-reperfusion-induced myocardial injury.

Animals↗
PubMed1989

Delta-sleep-inducing peptide (DSIP) stimulates the release of immunoreactive Met-enkephalin from rat lower brainstem slices in vitro.

We studied whether delta-sleep-inducing peptide (DSIP) acted on opioid receptor directly or indirectly. DSIP did not have binding activity to any subtype of opioid receptors. DSIP at doses of 1 pM-1 nM significantly stimulated the release of immunoreactive Met-enkephalin (iME) from superfused slices of the rat lower brainstem. The DSIP-induced release of iME was calcium-dependent. These results show that DSIP acts on opioid receptor indirectly by stimulating the release of iME in producing antinociceptive effects.

Animals↗
PubMed1989

Inhibition of inflammatory proteinase, medullasin, by alpha 2-macroglobulin and ovomacroglobulin.

The in vitro activity of inflammatory proteinase, medullasin, was stoichiometrically inhibited by a serum proteinase inhibitor, alpha 2-macroglobulin, and its homolog, chicken ovomacroglobulin. The two inhibitors were cleaved by medullasin only in the bait region. The effectiveness of alpha 2-macroglobulin to inhibit medullasin in competition with alpha -1-proteinase inhibitor was measured under a simulated in vivo condition and an estimation was made that about 60-70% medullasin is inhibited by alpha-1-inhibitor and 30-40% by alpha 2-macroglobulin.

Binding, Competitive↗
PubMed1989

Reduction of rat striatal thyrotropin-releasing hormone receptors produced by repeated methamphetamine administration.

It has been reported previously that repeated, but not continuous, administration of methamphetamine (MAP) to animals produces progressive and sustained enhancement of MAP-induced behavior (behavioral sensitization), which may be related to functional changes in central dopamine (DA) systems. To investigate the possible involvement of thyrotropin-releasing hormone (TRH), a neuromodulator of DA, both immunoreactive TRH (IR-TRH) levels and specific TRH binding were examined in rat brain regions after MAP administration either repeatedly (4 mg/kg intraperitoneally once a day for 14 consecutive days) or continuously (about 4 mg/kg/day for 13 consecutive days). Although no significant changes were observed in IR-TRH levels in any regions of the brain following repeated MAP injections, specific TRH binding in the striatum significantly decreased. Scatchard analysis revealed that the decrease was due to a reduction in the maximum number of binding sites (Bmax). Pretreatment with haloperidol prior to each MAP injection prevented this decrease. Continuous MAP administration had no effect on regional specific TRH binding. These results suggest that repeated MAP administration caused lasting dysfunction in the brain TRH system, which may be implicated in the behavioral sensitization.

Animals↗
PubMed1989

Phase I study of E1040, a new parenteral cephem antibiotic.

The safety and pharmacokinetics of E1040, a new injectable cephem antibiotic, were evaluated in healthy volunteers. In single-dose studies, 125, 250, 500, 1000 and 2000 mg of E1040 were administered by I.V. infusion over 1 hour. Results of 5 minutes I.V. infusions of 500, 1000 and 2000 mg of the drug were also studied. Plasma concentration-time profiles were well suited to a two-compartment open model. The half-life of elimination from plasma was 1.85 +/- 0.16 hours, and the Cmax and AUC paralleled the doses given. The mean urinary recovery within the first 24 hours was 85.7 +/- 6.43% of the dose. In a multiple-dose study, 2000 mg of E1040 (I.V. over 1 hour) was administered every 12 hours (total 9 times) and no abnormal accumulation of the drug in plasma was observed. There were no significant differences in plasma levels or in urinary recoveries between single- and multiple-dose regimens. There were no subjective or objective abnormal findings definitely attributable to the drug except that one subject given 250 mg over 1 hour reported diarrhea, and another complained of nausea during the infusion of 2000 mg over 5 minutes. From these results E1040 was concluded to be safe and well tolerated.

Adult↗
PubMed1989

Phase I study of Y-20811, a new long-acting thromboxane synthetase inhibitor by intravenous administration.

The safety, pharmacological action and pharmacokinetics of Y-20811, a thromboxane (TX) synthetase inhibitor, were investigated by single intravenous administration of 5, 10, and 25 mg each to six healthy adult male volunteers. Throughout the entire test period, no abnormality attributable to the test drug was found in subjective and objective symptoms, routine laboratory tests, physical tests, or bleeding time; and the drug was well tolerated by subjects. Inhibition of serum TXB2 production and an increase in 6-keto-prostaglandin (PG) F1 alpha production during whole-blood coagulation exhibited a dose-dependent change from 0.5 hours after administration. In addition, arachidonic acid (AA)-induced platelet aggregation was inhibited, and adenosine diphosphate (ADP)-induced secondary aggregation was also inhibited. The duration of these actions was long; inhibition of serum TXB2 production and the increase in 6-keto-PGF1 alpha production lasted for 168 hours after administration , and inhibition of platelet aggregation lasted for more than 48 h after administration. The initial phase half-life (t1/2 alpha) and final phase half-life (t1/2 beta) of Y-20811, calculated from the change in plasma concentration, were 0.1-0.3 hours and 1.9-3.1 hours, respectively. The area under the plasma concentration-time curve (AUC) increased in a dose-dependent manner, but the values of volume of distribution (Vss) and total clearance (CLt) were almost constant in any dose group. At each of the three doses, 60-64% of the dose was excreted in unchanged form, and 8-10% in conjugated form in the urine, within 48 hours after administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1989

Phase I study of Y-20811, a new long-acting thromboxane synthetase inhibitor by oral administration.

The safety, pharmacological action and pharmacokinetics of the thromboxane (TX) synthetase inhibitor Y-20811, a prospective medication for ischemic vascular disorder, were investigated in Phase I clinical trials in which single and repeated doses were administered orally to 32 healthy adult male volunteers. In the single-dose study, subjects were given single doses of 2.5, 5, 10, 25, 50, and 100 mg; in the repeated-dose study, a single dose of 50 mg was administered daily for 5 days. In the repeated-dose study, slight elevation of liver function test parameters in 1 subject was observed, but throughout the trials, no abnormality attributable to the test drug was found in other routine laboratory tests, subjective and objective findings, vital signs (blood pressure, pulse rate, body temperature, respiration rate), ECG, or bleeding time; nor did any finding indicate a problem concerning the safety of Y-20811. In both single- and repeated-dose studies, inhibition of the serum TXB2 production and an increase in the 6-keto-prostaglandin F1 alpha production during whole-blood coagulation, and inhibition of arachidonic acid-induced platelet aggregation were observed from 1 hour after administration of Y-20811. The duration of these actions was long, the former two lasting 168 hours (1 week) and the latter 48-72 hours or more. Slight inhibition of adenosine diphosphate-induced secondary platelet aggregation was also observed. The maximum plasma concentration time (tmax) of Y-20811 was 0.5-1.1 hours. The initial-phase half-life (t1/2 alpha) was 0.8-1.1 hours and the final-phase half-life (t1/2 beta) was 4.7-9.2 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Gas chromatographic assay and disposition of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, in healthy volunteers.

Quantitative determinations of plasma concentrations of 6-chloro-2-pyridylmethyl nitrate, a new antianginal drug, and its urinary metabolite, 6-chloro-2-pyridinecarboxylic acid (metabolite 1), were obtained using GC with a 63Ni electron-capture detector. 6-Chloro-2-pyridylmethyl nitrate was extracted from plasma with n-pentane. Metabolite 1 was extracted from acidic urine with ethylacetate, back extracted with 0.1 M NaHCO3, and methylated with boron trifluoride methanol reagent. The internal standard for metabolite 1 determination was prepared by propylation of metabolite 1 with boron trifluoride n-propanol reagent. The formation of the esters was confirmed by the GC-MS results. These methods proved to be sensitive and reproducible. A single dose of 6-chloro-2-pyridylmethyl nitrate (5, 10, 20, 40, or 60 mg) was given perorally to healthy volunteers. From the data, a large interindividual variability in the apparent plasma clearance was apparent (85.5 +/- 123 L/min; CV 144%). However, metabolite 1 was the main metabolite in human urine, and the interindividual variation was slight (CV 13%).

Administration, Oral↗
PubMed1989

Involvement of thromboxane and leukotriene in arachidonate induced coronary constriction in diabetic rats.

Vascular responsiveness to sodium arachidonate was examined in isolated perfused hearts from rats with streptozotocin-induced diabetes. In diabetic rats arachidonate induced a biphasic coronary vascular response characterized by initial vasoconstriction followed by prolonged vasodilation. Non-diabetic rats showed only a vasodilator response. The vasoconstrictor phase found in diabetic rats was abolished by ONO-3708, a selective thromboxane A2 antagonist. Indomethacin partly inhibited the vasoconstrictor response, the residual response being abolished by a leukotriene antagonist, ONO-1078. The vasodilator response, however, was completely abolished by indomethacin in both diabetic and nondiabetic rats. Furthermore, the coronary constrictor response to leukotriene D4 was enhanced in diabetic compared to nondiabetic rats. These results suggest an involvement of leukotriene in the vasoconstrictor response to arachidonate in diabetic rats, especially when cyclooxygenase is inhibited.

Animals↗
PubMed1989

Human scalp hair as evidence of individual dosage history of haloperidol: method and retrospective study.

Hair samples and morning pre-dose plasma were collected from 40 patients who had received fixed daily doses of haloperidol for more than four months and whose compliance was good. After washing, 1 to 2 cm-long portions nearest to the roots of 2 to 3 strands of hair were completely dissolved in 2.5N NaOH. Haloperidol in that sample or alkalinised plasma was extracted and measured by RIA. Haloperidol concentrations in hair correlated well both with the trough concentration in plasma at steady-state (r = 0.772, n = 39) and with the daily dose (r = 0.555, n = 40). Another keratinized tissue, nail, was also collected from 20 of the 40 patients and the haloperidol level was compared with that in hair. The former was only about 4.3% of the latter and was significantly correlated only with the daily dose (r = 0.525, n = 20). Hair from 10 other patients in whom the dosage of haloperidol had been changed within a few months prior to sampling the hair was cut into 0.5 or 1 cm-long portions from the roots and the drug concentration in each portion was measured. If hairs were assumed to grow at 1 cm/month, a history of individual dosage could be deduced in 9 of the 10 patients from the distribution of drug level along the length of the hair. The results suggest that human scalp hair could serve as a useful tool for monitoring individual dosage history over several months, or in demonstrating exposure or non-exposure of a patient to a drug.

Adult↗
PubMed1989

A simple method for producing graded aortic insufficiencies in rats and subsequent development of cardiac hypertrophy.

Selective perforation of the right cusp of the aortic valve alone (1V) or in combination with that of the left valve cusp (2V) by a plastic rod inserted from the right common carotid artery was performed to cause aortic insufficiency (AI) in rats. The development of cardiac hypertrophies subsequent to these interventions to cause graded cardiac volume overloads was followed up every week till the end of week 4 after the operations by radiographic measurement of the cardiothoracic ratio (CTR). Rats were killed 2 and 4 weeks after the operations, and the density of beta-adrenoceptors in hypertrophied cardiac muscle membranes was determined by radioligand binding assay and compared with sham-operated (sham) rats. Production of AI resulted in an enlargement of the cardiac shadow in 1VAI and 2VAI rats, with significant graded increases in the CTR at the end of week 3. The occurrence of graded cardiac hypertrophies was well revealed in graded increases of the heart weight/body weight ratio among the sham, 1VAI, and 2VAI rats at the end of both week 2 and week 4. There was a tendency to stepwise increases due to graded AI in the density of binding sites for 3H-dihydroalprenolol, with a significant increase in 2VAI rats at the end of week 2. At the end of week 4, plasma norepinephrine levels of 2VAI rats was raised significantly as compared with the sham rats. Selective perforation of either one or two cusps of the aortic valve can be performed with ease using touch alone and provides us with a simple method for producing graded cardiac hypertrophies in rats due to pure volume overload.

Animals↗
PubMed1989

Prediction of individual dosage requirements for lignocaine: a validation study for Bayesian forecasting in Japanese patients.

The performance of the Bayesian feedback method for predicting lignocaine dosage developed by Vozeh et al. was evaluated in 53 Japanese patients, treated for either suppression or prophylaxis of ventricular arrhythmias, with respect to accuracy, precision, efficiency, and safety. The lignocaine serum concentrations at 12 h (C12) and 24 h (C24) after continuous infusion was started were predicted and compared retrospectively using the early concentration at 2-4 h (C2-4). The mean of the prediction error (PE) and the root mean-squared error (RMSE) were used as a measure of accuracy and precision. The 95% confidence interval of PE for C12 included zero, but those of PE for C24, whether C2-4 was used alone or in combination with C12, were less than zero, meaning that the prediction of C24 was significantly biased. The RMSE for C12 (13.2%) was less than that for C24 (16.2%), but the difference was not statistically significant. The fraction of measurements lying within the statistically approximate 68% prediction interval (+/- 1 SD) was used to evaluate the estimate of the SD of prediction. The fraction of measurements inside the prediction interval was significantly larger than the expected 68% for both C12 and C24 (p less than 0.05), showing that the estimate of the size of the PE is biased on the safer side. The clinical effects of lignocaine were also evaluated from the viewpoints of suppression of number of ventricular premature beats, prevention of more severe grades of arrhythmias, and toxicity. At least the appearance of toxicity, which four patients exhibited, was related to the lignocaine serum concentration (greater than 6 micrograms/ml).

Adult↗
PubMed1989

Determination of caffeine in saliva by high-performance liquid chromatography: new sampling method for saliva using filter paper.

We report an assay method for the determination of salivary caffeine concentrations by high-performance liquid chromatography. A simple, new method for collecting mixed saliva using a piece of filter paper has been developed. An arbitrary amount of saliva is absorbed and a fixed amount of internal standard is added. The mean coefficient of variation of measurements repeated by changing both volumes absorbed and caffeine concentrations of saliva was 5.6% with this method. The detection limit was determined to be 0.5 microgram/ml. Precision of measurements and recoveries did not depend upon the volume of saliva absorbed. Four volunteers were given a capsule of 230 mg caffeine, and saliva was collected by the ordinary method using chemical stimulation with citric acid and by our filter paper absorption methods; the methods were compared. Salivary caffeine concentrations were always lower than plasma concentrations, and there were no big differences between two methods, although salivary concentrations measured by our method was higher, with a significant difference at 1.5 h after dosing. From the practical viewpoint this method would be convenient and sufficiently accurate.

Adult↗
PubMed1989

Human scalp hair as evidence of individual dosage history of haloperidol: prospective study.

The concentration of haloperidol in hair was measured by radioimmunoassay after hairs were dissolved in 2.5 N NaOH solution and the drug was extracted. In patients to whom haloperidol had been administered at fixed daily doses for more than 1 month, and in whom therapy had been just discontinued (group A, n = 5) or the doses cut to half (group B, n = 3), hairs were collected when the dose was changed and at 1 and 2 or 3 months thereafter. A few strands of hair collected on each occasion were cut into 1-cm-long portions from the roots, and the haloperidol concentration was measured in each portion. When hairs were assumed to grow at a rate of 1-1.5 cm/month, the portion of hair that reflected the change of dose was observed to move upward along the hair length in all patients of group A. However, these phenomena were less obvious in group B. These results indicate that at the least, hair could serve as an indicator of individual exposure or nonexposure to haloperidol and could yield retrospective information. In rats whose hairs had been removed by plucking from an area on the back, either saline or 1 mg/kg of haloperidol (i.p., b.i.d.) was administered for 2 weeks (first period), followed by 0, 0.5, 1, or 2 mg/kg b.i.d. for the subsequent 2 weeks (second period). At the end of each period, hairs that had grown in the plucked area were collected. Within-groups, haloperidol levels in hairs collected at the end of each period corresponded to the doses given.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗