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Biomedical subjects

M Nakano

Publications and source records attributed to M Nakano.

At least 595 records · Page 33Linked to original sources

Disposition of enantiomers of sulpiride in humans and rats.

Pharmacokinetics of sulpiride enantiomers after intravenous administration of (+/-)-, (+)-, and (-)-sulpiride was examined in humans and rats. Pharmacokinetics profiles were similar in (+)- and (-)-enantiomers after intravenous administration of (+/-)-sulpiride. Metabolic inversion at a chiral centre was not observed after intravenous administration of each enantiomer in rats.

Administration, Oral↗

Effect of milk on absorption of norfloxacin in healthy volunteers.

The authors studied the effect of milk on the bioavailability of norfloxacin in six healthy male volunteers in a randomized crossover trial. After an overnight fast, 200 mg of norfloxacin was given with 200 mL of water or milk. Area under the curve (AUC) of norfloxacin with milk was significantly (P < 0.01) smaller than that with water. The mean peak serum concentration was decreased to 60% after oral administration of norfloxacin with milk (P < 0.01). The apparent volume of distribution at central compartment (Vc/f) value of norfloxacin was significantly (P < 0.05) increased with milk. Milk exhibits a clinically significant effect on norfloxacin absorption.

Adult↗

Inhibitory effects of procainamide and probenecid on renal excretion of sultopride enantiomers in rats.

The effects of the coadministration of procainamide and probenecid on the pharmacokinetic behavior of sultopride, an antipsychotic agent, after intravenous administration were studied with rats. The areas under the concentration-time curve for and renal clearances of (+)-sultopride and (-)-sultopride, which exist as organic cations under physiological pH conditions, were significantly decreased (p < 0.01) by the coadministration of procainamide, an organic cation under physiological pH conditions. The renal clearance of (-)-sultopride was partially decreased (p < 0.05) by the coadministration of probenecid, an organic anion under physiological pH conditions. The results suggest that drug-drug interactions between organic cations and organic anions occur to a certain extent during the tubular secretion process in rats.

Amisulpride↗

A case of renal cell carcinoma with metastasis to the thyroid gland and concomitant early gastric cancer.

Metastatic lesions from renal cell carcinoma are commonly recognized in the lung and bone, however, thyroid metastasis has rarely been reported in the literature. We present herein a case of a man with lung and thyroid metastatic tumors from renal cell carcinoma. Although making a preoperative diagnosis of thyroid metastasis is difficult because there is no established diagnostic criteria, we were able to identify this thyroid lesion as a metastatic tumor from renal cell carcinoma by the pathological findings. Interestingly, hypercalcemia was recognized in this patient whose serum parathyroid hormone (PTH) level was not increased. Moreover, this patient also had early gastric cancer simultaneously, being a so-called 'double cancer'. After surgical resection of the right kidney and stomach, interferon was administered without any efficacy against the metastatic lesions of the lung and thyroid gland.

Carcinoma, Renal Cell↗

The ability of polymorphonuclear leukocytes to produce active oxygen in a model of peritonitis in rats.

To elucidate the mechanism of enhancing survival in peritonitis rats treated with lentinan, a fully purified beta-1,3-glucan, we measured the active oxygen-producing ability of polymorphonuclear leukocytes (PMNs). Four groups of rats (group I, fecal peritonitis control; II, rats receiving 3 mg/kg lentinan intraperitoneally at the same time as peritonitis induction; III, rats receiving 1 mg/kg gentamicin intramuscularly; and IV, rats receiving combined lentinan-gentamicin treatment) were used. The survival period was significantly longer in group IV than in the other three groups. The ability of ascitic PMNs to produce active oxygen (superoxide, H2O2, myeloperoxidase) was significantly more than that of blood PMNs in each group at 20 h after peritonitis induction. The increase in active oxygen production in ascitic PMNs was higher in group IV compared with that in the other three groups. The concentration of lentinan in the blood was high at 24 h after administering lentinan intraperitoneally to both the normal and peritonitis rats. In the in vitro study, the superoxide production in normal rat blood PMNs was significantly higher in the presence of cytokines (IL-1 beta, IL-6, TNF-alpha) without dose-dependence but was not higher for the lentinan group than in the control. This study therefore suggests that lentinan activated the peritoneal macrophage secretory activity and produced cytokines which thus enhanced the ability of PMNs to produce active oxygen, which possesses a bactericidal ability in PMNs.

Animals↗

Stereoselective analysis of the disposition of tosufloxacin enantiomers in man.

The pharmacokinetics of tosufloxacin enantiomers after oral administration of racemic tosufloxacin were examined in healthy volunteers. Only small differences were observed in time to peak concentration (2.6 +/- 0.3 [mean +/- SEM] h for (+)-tosulfoxacin vs 2.4 +/- 0.2 h for (-)-tosufloxacin), elimination half-life (3.61 +/- 0.24 h vs 3.49 +/- 0.23 h), and area under the curve (2.78 +/- 0.19 h.micrograms/ml vs 2.87 +/- 0.19 h.micrograms/ml); however, peak concentration (0.40 +/- 0.03 microgram/ml vs 0.44 +/- 0.03 microgram/ml), renal clearance (226 +/- 10 ml/min vs 202 +/- 10 ml/min), and urinary recovery (35.4 +/- 2.2% vs 32.4 +/- 1.9%) differed significantly between enantiomers.

Administration, Oral↗

The pharmacokinetics of the beta 2-adrenoceptor agonist, tulobuterol, given transdermally and by inhalation.

We have studied the pharmacokinetics of tulobuterol given transdermally or by aerosol inhalation in healthy male volunteers. Tulobuterol was rapidly absorbed after inhalation, with a tmax of 0.8-1.5 h. The Cmax and the AUC increased linearly with dose. Tulobuterol was well absorbed after transdermal administration, with an absorption lag-time of about 4 h. The Cmax and AUC increased linearly with dose and the tmax was about 9-12 h. The mean percentage of drug absorbed during the application of a patch for 24 h was 82-90% after a single dose and 82-85% during repeated dosing. The mean urinary recoveries as unchanged drug after a single inhalation and patch application were 3-4% and 5-6% respectively. Tulobuterol did not accumulate during repeated inhalation or transdermal application. It was well tolerated, except for an increase in heart rate of 10-20 beats.min-1 after five repeated applications of a 4 mg patch.

Administration, Cutaneous↗

Pharmacological intervention for renal protection during cardiopulmonary bypass.

The possibility of minimizing organ damage following cardiopulmonary bypass (CPB) was examined. In the control group, n = 21, upon completion of CPB, elevation of the lysosomal enzyme beta-glucuronidase, which is a sensitive indicator of cellular damage, was affected by the concentration of granulocyte elastase (r = 0.59) or the endothelial-derived constricting factor, endothelin, (r = 0.8). Renal damage, which was detected by an increase in renal tubular enzymes (N-acetyl-beta-D-glucosaminidase and gamma-glutamyltranspeptidase) in urine, was also affected by endothelin (r = 0.79, r = 0.56), elastase (r = 0.6, r = 0.71), and by free hemoglobin levels (r = 0.76, r = 0.82). Next, the efficacy of pharmacological intervention for the prevention of renal damage was evaluated. During CPB, the administration of an elastase inhibitor (ulinastatin, 3 x 10(5) IU), n = 8, or a calcium antagonist (nicaldipine HCl, elastase release inhibitor; 5 gamma/kg per min), n = 8, significantly reduced the elevation of beta-glucuronidase and renal tubular enzymes (p < 0.05). Although the ulinastatin and nicardipine groups demonstrated low values of elastase in the Intensive Care Unit (ICU), only the values of the nicardipine group reached statistical significance (p < 0.05). A reduction in endothelin levels compared to the control group was observed in the nicardipine group. However, preventive and counteractive effects of nicardipine against vasoconstriction caused by endothelin were also considered to play an important role in the prevention of renal damage. The addition of haptoglobin (4,000 IU) to the priming solution of the CPB also reduced levels of renal tubular enzymes (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary Bypass↗

Decreased production of active oxygen species by neutrophils in patients with liver cirrhosis and hepatocellular carcinoma.

Adult respiratory distress syndrome (ARDS) following infection is one of the postoperative complications of hepatectomy of cirrhosis. In this study we focused on the anti-microbial activity of neutrophils. We measured production of active oxygen species by neutrophils, and simultaneously examined their nutritional status, immunity and ICG (K-ICG) disappearance ratio. When compared to the controls, the patients with cirrhosis had significantly lower production of O2- upon stimulation by N-formyl-Met-Leu-Phe (fMLP) or opsonic zymosan (OZ). The presence of cancer did not affect results for the groups studied. Overall H2O2 production was lower in cirrhotic patients than in controls. There was a positive correlation between O2- production and K-ICG, which was used to estimate the severity of cirrhosis. Indicators of nutrition and immunity were also lower in cirrhotic patients, but neither of these indicators correlated with the production of active oxygen species. From these results, we concluded that the production of active oxygen species by neutrophils is lower in cirrhotic patients than in controls. Moreover, this decline correlates with the severity of cirrhosis.

Carcinoma, Hepatocellular↗

Evaluation of the penetration depth of transdermally applied 3% GA MHPh 2Na-10% lidocaine gel in man.

In order to estimate the penetration depth of transdermal 3% GA MHPh 2Na-10% lidocaine gel mixture, the following physiological functions of the skin were examined before and after a 60 min occulusive application of the gel in 16 adult volunteers. Thermal sweat expulsins ceased completely on the gel-treated ventral surface of one forearm in all the firs 5 subjects, though it continued on the untreated contrast area of the other forearm. Sympathetic skin response (SSR) was also no longer induced on the gel-treated middle finger in 1 of another 3 subjects and was severely depressed in the other 2 subjects, while the SSR on the untreated index finger appeared constantly. Vasomotion of the skin circulation on another 3 subjects, remained unaffected on both the gel-treated and the untreated fingers. Extraction of a leg-hair in the treated area did not induce pain sensation in all the last 5 subjects. In addition to the transcellular main roots, some of the transcutaneously applied gel seems to penetrate deeply into the skin through the appendageal roots such as the eccrine sweat glands and the pilosebaceous glands.

Journal Article↗

Sacroperineal anorectoplasty using intraoperative ultrasonography: a preliminary report.

Intraoperative ultrasonography (US) was applied to sacroperineal anorectoplasty for the purpose of making a pull-through tunnel under visual guidance. Intraoperative US images the horizontal plane of the muscle complex and the tip of the forceps, which is placed at the entrance of the tunnel (ie, the space anterior to the puborectalis sling), ready to penetrate the muscle complex. A surgeon can thus penetrate the center of the muscle by confirming the relation between the muscle and forceps on the US screen. Postoperative computed tomography of four patients on whom this technique was applied demonstrated that the rectum was pulled through the exact center of the puborectalis and external sphincter muscles.

Anal Canal↗

Evaluation of three occlusal examination methods used to record tooth contacts in lateral excursive movements.

Accurate and repeatable methods for recording tooth contacts are required for the clinical management of problems related to occlusion. A thorough understanding of the materials and procedures used in these methods is important to achieve desirable results in the treatment of such problems. This study compared three occlusal examination methods to determine the influence of materials and procedures on the number of tooth contacts recorded. Tooth contacts were analyzed at two lateral mandibular positions with each method. It was found that the method that uses black silicone recorded the highest number of tooth contacts. Thus the most frequent type of occlusal pattern observed was full-balanced occlusion. This study suggested that the disparities of results reported in literature on occlusal contact patterns could be the result of the different materials and methods used for occlusal registration.

Adult↗

Accumulation of cardiac lipofuscin in crab-eating monkeys (Macaca fasicularis): the same rate of lipofuscin accumulation in several species of primates.

Previously, we have reported that the aging process begins at sexual maturation (Nakano, M. et al., Mech. Ageing Dev., 52 (1990) 93-106). In this paper, we reported the cardiac lipofuscin accumulation of crab-eating monkeys. The first appearance of cardiac lipofuscin was around sexual maturation, and the rate of accumulation in crab-eating monkey was 0.45. Several primates which have different life spans show the same rate of lipofuscin accumulation in the life stage. Namely, even in a different life span, the amount of lipofuscin accumulation in a given period of life such as puberty, middle age, old age was the same. From these results, it is suggested that the amount of lipofuscin accumulation is the same in the life span of primates having different life spans.

Aging↗

Non-specific resistance induced by a low-toxic lipid A analogue, DT-5461, in murine salmonellosis.

The ability of DT-5461, a chemically synthetic low-toxic lipid A analogue, to activate anti-Salmonella activity in C3H/HeN mice was examined. Previous intraperitoneal (i.p.) injection of DT-5461 (100 micrograms or more/mouse) significantly hindered the bacterial growth in the peritoneal cavities of the mice after the i.p. infection with Salmonella typhimurium LT2 strain. The effect was the maximum when DT-5461 was given 6 h before the challenge. The injection of DT-5461 6 h in advance could also confer protection against the infection. Bactericidal activity enhancement was also seen in mice that had been injected with a small amount of recombinant murine IFN-gamma (10(3) U per mouse) and non-effective dose (10 micrograms) of DT-5461 together 6 h before the challenge. Bactericidal effect enhancement was seen in mice that had been injected with IFN-gamma at 6 h and DT-5461 at 3 h before the challenge, while it could be hardly seen in mice injected with them in a reversed order. The i.p. injection of DT-5461 recruits the exudate cells into the peritoneal cavities, and the phagocytic and bactericidal abilities of the macrophages in the exudate cells are apparently elevated. The mechanisms of non-specific resistance enhancement induced by DT-5461 were discussed.

Adjuvants, Immunologic↗

Increased generation of reactive oxygen species in embryos cultured in vitro.

Previous studies have suggested that oxygen toxicity is closely related to the developmental blockage of embryos cultured in vitro. In this study, to obtain an actual proof of the increase in production of reactive oxygen species within embryos, we have measured the level of H2O2 in individual embryos using a fluorimetric method. Mouse (ICR) pronuclear stage embryos from the oviducts were cultured for a specified time under various conditions in a medium to which 2',7'-dichlorodihydrofluorescin diacetate was added. After washing the embryos, the fluorescence emissions of the H2O2-dependent oxidative product in embryos were measured. The fluorescent emissions were lowest in embryos cultured under 5% O2 and highest under 40% O2 (5% < 20% < 40%), just the inverse of the culture efficacy. The fluorescence emmissions of embryos cultured in Ham's F-10, which contains hypoxanthine and transition metals such as Cu and Fe, were higher than those cultured in BWW and alpha MEM, which do not contain these components (alpha MEM < BWW < Ham's F-10; again this is the inverse of the culture efficacy). The fluorescence emissions of embryos increased with the time of the exposure to visible light. L-cysteine and thioredoxin, both of which have been shown to promote embryo development, decreased the fluorescence emissions of embryos. All of these results would provide direct evidence for the hypothesis that oxygen radicals are involved in the developmental blockage.

Animals↗

Detection of Epstein-Barr virus DNA in cardiac and aortic tissues from chronic, active Epstein-Barr virus infection associated with Kawasaki disease-like coronary artery aneurysms.

We describe three patients with chronic, active Epstein-Barr virus infection associated with Kawasaki disease-like coronary artery aneurysms. The Epstein-Barr virus genome was detected in three cardiac tissue samples and one aortic tissue sample examined by means of the polymerase chain reaction. These findings suggest that chronic Epstein-Barr virus infection may play a pathogenic role in the development of coronary artery aneurysms.

Antibodies, Viral↗

Effects of carbohydrate intake on the blood ethanol level and alcoholic fatty liver damage in rats.

Effects of carbohydrate (CHO) intake on the blood ethyl alcohol (ethanol) level were studied in rats with a surgically placed gastric cannula. A basal diet (protein, 2.07; fat, 1.98; CHO, 5.76 g/day), a high-CHO diet (CHO, 4.39 g/day) + ethanol, a medium-CHO diet (CHO, 2.69 g/day) + ethanol or a low-CHO diet (CHO, 0.98 g/day) + ethanol was infused into the stomach for 4 weeks starting from the 2nd postoperative week. The basal diet and the test diets were isocaloric, and the ethanol (2.80 g/day) in the test diets accounted for 39% of the total calories. The liquid diets (50 kcal in 50 ml) were infused over 16 h from 16.00 to 08.00 h each day. The low-CHO diet group had significantly higher blood ethanol levels than the high-CHO diet group 4, 8 and 16 h after the start of infusion. These groups could be ranked by liver triglyceride content at autopsy as follows: low-CHO > medium-CHO > high-CHO > or = basal. Consistent with the triglyceride content, histological changes of the liver could be ranked by the degree of fatty changes in the same order: low-CHO > medium-CHO > high-CHO > basal. Thus, for a given amount of ethanol consumption, lower CHO intake was associated with higher blood ethanol levels and with more severe fatty changes of the liver.

Animals↗