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Biomedical subjects

A Kawaguchi

Publications and source records attributed to A Kawaguchi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effect of angiotensin II on venodilator response to nitroglycerin.

OBJECTIVE: An enhanced circulatory angiotensin II level that results from the administration of nitroglycerin may contribute to the development of nitrate tolerance. Using human hand veins, we investigated whether a subconstricting dose of angiotensin II attenuates the venodilator effect of nitroglycerin, whether pretreatment with losartan influences this effect, and whether angiotensin II also attenuates the venodilator effect of diltiazem. METHODS: In 9 healthy male subjects, increasing doses (0.5-128 ng/min) of nitroglycerin were infused into the dorsal hand vein pretreated with 0 (control), 0.3, or 1 ng/min of angiotensin II. In 8 healthy male subjects, angiotensin II (0.3 and 1 ng/min) was infused into the vein dilated by nitroglycerin with and without pretreatment with losartan and with diltiazem. The diameter of the vein was measured with a linear variable differential transformer. RESULTS: The venodilator response of nitroglycerin was significantly suppressed by the pretreatment with angiotensin II; The maximum venodilator effect was dose-dependently decreased, and the infusion rate producing half-maximum response was dose-dependently increased. The venodilation caused by nitroglycerin was decreased by angiotensin II, and this effect was attenuated by pretreatment with losartan. The venodilation caused by diltiazem was also attenuated by angiotensin II, but this attenuating effect was smaller compared with that caused by nitroglycerin. CONCLUSIONS: These findings suggest that an enhanced angiotensin II level might attenuate the venodilation caused by nitroglycerin and diltiazem, and pretreatment with losartan might decrease the attenuating effect of angiotensin II.

Adult↗
PubMed2001

Furosemide-probenecid interaction as a laboratory exercise for undergraduate education in clinical pharmacology.

OBJECTIVE: The aim of this study was to determine the easiness, reproducibility, and safety of a laboratory exercise for a drug interaction between furosemide and probenecid. METHODS: From 1995 to 1999 approximately 100 medical students participated in the exercise each year after they gave written informed consent. The students were randomly assigned to one of the three groups in a double-blind fashion: group 1, placebo plus 20 mg of furosemide; group 2, 250 mg of probenecid plus 20 mg of furosemide; and group 3, 1000 mg of probenecid plus 20 mg of furosemide. The students took probenecid or its placebo 1 hour before furosemide. Urine volume and urinary sodium excretion were measured for 3 hours after furosemide. At the end of the exercise in 1999, students responded to several questionnaires concerning the utility of furosemide. RESULTS: The entire course of the exercise was completed within half a day. The following findings were obtained every year. (1) Probenecid dose dependently blunted the diuretic effects of furosemide. (2) Time courses of the diuretic effects were altered by probenecid. Ten to twenty percent of the students had slight complaints but completed the exercise without any medications. Finally, more than 80% of the students considered the exercise to be useful. CONCLUSIONS: The data suggest that the exercise of the drug interaction between furosemide and probenecid is easy to perform, reproducible, and safe. Through the experience of the laboratory exercise, students will develop an attitude to assess and estimate potential drug interactions before they prescribe drugs.

Diuresis↗
PubMed2001

Removal of digoxin by column for specific adsorption of beta(2)-microglobulin: a potential use for digoxin intoxication.

BACKGROUND: A beta(2)-microglobulin adsorption column used for the treatment of dialysis-related amyloidosis removes serum beta(2)-microglobulin by recognition of lipophilic residue in the protein. No data are available for the adsorption of the highly lipophilic drug digoxin. METHODS: In vivo clearance of digoxin with the beta(2)-microglobulin column was measured by a single use of the column in 8 patients receiving hemodialysis with a therapeutic level of digoxin. In vitro adsorption was evaluated by use of incubation with adsorbent of the column and digoxin or ranitidine, a hydrophilic drug. Clearance with the beta(2)-microglobulin column was further compared with that obtained by use of activated charcoal in the dogs intoxicated with digoxin. RESULTS: Digoxin concentration was reduced from 1.11 +/- 0.25 ng/mL to 0.57 +/- 0.15 ng/mL at 240 minutes after initiation of hemoperfusion with the column in the patients. Digoxin clearance with the beta(2)-microglobulin column was about 145 +/- 20 mL/min, with a blood flow rate of 160 to 220 mL/min (80% of plasma flow rate). Eighty-five percent of digoxin was adsorbed in vitro, and the capacity of the beta(2)-microglobulin column was not saturated until a toxic level was reached (50 ng/mL). This value was higher than that obtained with use of charcoal. In dogs with digoxin intoxication, digoxin clearance was 38.9 +/- 1.5 mL/min, with a blood flow rate of 50 mL/min (95% of plasma flow rate), which was almost twice as that achieved with charcoal. The degree of thrombocytopenia and leukopenia was small with use of the beta(2)-microglobulin column. CONCLUSION: These data suggested that the beta(2)-microglobulin column selectively adsorbs digoxin. This column is a promising tool for the treatment of digoxin intoxication, especially in patients undergoing hemodialysis.

Adsorption↗
PubMed2001

Different effects of St John's wort on the pharmacokinetics of simvastatin and pravastatin.

OBJECTIVE: St John's Wort, a widely used herbal product, is an inducer of CYP3A4 and it decreases blood concentrations of CYP3A4 substrates. The effects of St John's Wort on the pharmacokinetics of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors simvastatin (an inactive lactone pro-drug) and pravastatin were determined in this study. METHODS: Sixteen healthy male subjects (n = 8 in group 1 and n = 8 in group 2) took a St John's Wort caplet (300 mg) or matching placebo three times a day for 14 days in a double-blind, crossover study. On day 14, a single oral dose of 10 mg simvastatin and 20 mg pravastatin was given to subjects in group 1 and group 2, respectively. Blood samples were obtained during a 24-hour period after the administration of each drug. RESULTS: Repeated St John's Wort treatment tended to lower plasma simvastatin concentration and significantly (P <.05) lowered concentrations of simvastatin hydroxy acid, its active metabolite. The peak concentration in plasma (ratio, 0.72 of placebo) of simvastatin hydroxy acid tended to be decreased and its area under the plasma concentration-time curve between time zero and 24 hours after administration (ratio, 0.48 of placebo) was significantly decreased (P <.05) by St John's Wort. On the other hand, St John's Wort did not influence plasma pravastatin concentration. No significant differences were observed in the elimination half-life of simvastatin or pravastatin between the placebo and St John's Wort trials. CONCLUSIONS: This study showed that St John's Wort decreases plasma concentrations of simvastatin but not of pravastatin. Because simvastatin is extensively metabolized by CYP3A4 in the intestinal wall and liver, which are induced by St John's Wort, it is likely that this interaction is partly caused by the enhancement of the CYP3A4-mediated first-pass metabolism of simvastatin in the small intestine and liver.

Adult↗
PubMed2001

Mitogenomic exploration of higher teleostean phylogenies: a case study for moderate-scale evolutionary genomics with 38 newly determined complete mitochondrial DNA sequences.

Although adequate resolution of higher-level relationships of organisms apparently requires longer DNA sequences than those currently being analyzed, limitations of time and resources present difficulties in obtaining such sequences from many taxa. For fishes, these difficulties have been overcome by the development of a PCR-based approach for sequencing the complete mitochondrial genome (mitogenome), which employs a long PCR technique and many fish-versatile PCR primers. In addition, recent studies have demonstrated that such mitogenomic data are useful and decisive in resolving persistent controversies over higher-level relationships of teleosts. As a first step toward resolution of higher teleostean relationships, which have been described as the "(unresolved) bush at the top of the tree," we investigated relationships using mitogenomic data from 48 purposefully chosen teleosts, of which those from 38 were newly determined during the present study (a total of 632,315 bp), using the above method. Maximum-parsimony and maximum-likelihood analyses were conducted with the data set that comprised concatenated nucleotide sequences from 12 protein-coding genes (excluding the ND6 gene and third codon positions) and 22 transfer RNA (tRNA) genes (stem regions only) from the 48 species. The resultant two trees from the two methods were well resolved and largely congruent, with many internal branches supported by high statistical values. The tree topologies themselves, however, exhibited considerable variation from the previous morphology-based cladistic hypotheses, with most of the latter being confidently rejected by the mitogenomic data. Such incongruence resulted largely from the phylogenetic positions or limits of long-standing problematic taxa, which were quite unexpected from previous morphological and molecular analyses. We concluded that the present study provided a basis of and guidelines for future investigations of teleostean evolutionary mitogenomics and that purposeful higher-density taxonomic sampling, subsequent sequencing efforts, and phylogenetic analyses of their mitogenomes may be decisive in resolving persistent controversies over higher-level relationships of teleosts, the most diversified group of all vertebrates, comprising over 23,500 extant species.

Animals↗
PubMed2001

Robotically assisted video-enhanced-endoscopic coronary artery bypass graft surgery.

Since 1988, through fierce industry-driven competition and patients' preference for minimally invasive procedures, widely diffused through the media, laparoscopic cholecystectomy was universally adopted and rapidly became the "gold standard" for symptomatic cholelithiasis. Robotically assisted video enhanced-endoscopic coronary artery bypass surgery (RAVE-CABG) will most likely follow suit with its similar developmental processes for symptomatic coronary artery disease. Since 1998, there are currently two surgical robotic systems that have been used in a clinical setting for endoscopic coronary artery bypass (ECABG): the da Vinci and the ZEUS system. Although each has separate learning curves to overcome, as with any new technology, both offer the promise to contribute in the interests of reduced hospital days, earlier return to normal activity, less pain, better cosmesis, and the rethinking of surgical dogma such as wide exposure.

Coronary Artery Bypass↗
PubMed2001

Bioactive constituents of chinese natural medicines. VI. Moutan cortex. (2): structures and radical scavenging effects of suffruticosides A, B, C, D, and E and galloyl-oxypaeoniflorin.

Five paeonol glycosides, suffruticosides A, B, C, D, and E, and a monoterpene glucoside, galloyl-oxypaeoniflorin, were isolated from the glycosidic fraction of Chinese Moutan Cortex, the root cortex of Paeonia suffruticosa Andrews, together with paeonolide, apiopaeonoside, galloyl-paeoniflorin, oxypaeoniflorin, and paeoniflorin. The structures of five suffruticosides and galloyl-oxypaeoniflorin were elucidated on the basis of chemical and physicochemical evidence. Suffruticosides A, B, C, and D, galloyl-oxypaeoniflorin, and galloyl-paeoniflorin exhibited more potent radical scavenging effects than alpha-tocopherol.

Carbohydrate Conformation↗
PubMed2001

Dosing time-dependent effect of trandolapril on the prevention of cardiac hypertrophy in rats with aortic banding.

Trandolapril was given to male Wistar rats with aortic banding at 10 AM or 10 PM for 6 weeks to examine the influence of dosing time on the development of left ventricular mass (LVM). Aortic banding increased the LVM compared with the sham-operated animals (P<0.01). Trandolapril (1 mg/kg) at 10 AM reduced LVM (1.74+/-0.04 [S.E.M.] mg/g) more than the dosing at 10 PM (1.92+/-0.04 mg/g, P<0.05), suggesting that trandolapril has a dosing time-dependent effect in the prevention of cardiac hypertrophy in rats with aortic banding.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

Myocardial revascularization on the beating heart after recent onset of acute myocardial infarction.

OBJECTIVE: Coronary artery bypass grafting (CABG) after the recent onset of acute myocardial infarction (AMI) is associated with high morbidity and mortality. Myocardial revascularization without cardiopulmonary bypass (CPB) has been proposed as an alternative technique to treat these patients in an attempt to decrease the operative risks. METHODS: From January 1995 to June 1999, 518 patients underwent CABG after the recent onset of AMI (1-20 days): 421 patients were revascularized on-CPB and 97 patients off-CPB. Preoperative risk factors (redo operations, congestive heart failure, stroke, extensive calcification of the aorta, and dialysis) were significantly higher in the off-CPB group (p-value < 0.05). Preoperative use of intra-aortic balloon pump (IABP) (off-CPB 5.2% versus on-CPB 2.4%, p-value = NS) and emergent operations (off-CPB 5.2% versus on-CPB 2.6%, p-value = NS) were similar in both groups. Mean number of grafts per patient was 3.46 in the on-CPB group versus 1.82 in the off-CPB group (p-value < 0.005). RESULTS: Actual mortality was 2.9% in the on-CPB group versus 6.2% in the off-CPB group (p-value = NS). Morbidity was comparable in the two groups. Multivariate analysis showed that advanced age, preoperative hemodynamic instability, and left ventricular hypertrophy were independent risk factors for death. Global ischemic time and preoperative hypertension were independently related to postoperative AMI. At univariate and multivariate analysis, CPB was not related to mortality or major postoperative complications. CONCLUSION: Multivariate analysis demonstrates that CABG can be performed safely with or without CPB in patients with recent AMI. CPB is not independently related to mortality or major adverse outcomes.

Aged↗
PubMed2001

Coronary artery exposure in off-pump cabg: a word of caution.

Coronary exposure and stabilization have focal importance in off-pump coronary surgery. Off-pump complete myocardial revascularization can be performed safely in the majority of the patients whenever strict surgical protocols are followed. Although new devices may be used to facilitate the performance of this demanding operation, technical pitfalls should be recognized to ensure the success of the procedure. We herein report our timely experience with the Xpose device (Guidant Corp., Cupertino, CA).

Aged↗
PubMed2001

[Tumor ablation with MRI navigation--a novel method of microwave coagulation therapy for hepatic tumor].

Fifty-eight patients with hepatic tumor which consisted of 22 hepatocellular carcinomas and 36 metastatic liver tumors were treated by microwave coagulation therapy with MRI navigation. The tumors were located in all segments of liver except S1. In 24 cases among them, the abdominal approach was difficult, because the tumors were located just below the diaphragm. These cases were selected for thoracoscope-assisted microwave ablation under MR-guidance across the diaphragm. All MR data were collected on a vertically oriented open MRI system (0.5 T SIGNA SP/i system: GE Medical Systems). The microwave electrode was introduced into the liver through a 14G needle via a percutaneous puncture with real-time MR image navigation. Microwave ablations at 60 W for 60 seconds were repeated several times depending on the tumor size. MR imaging may be employed as a reliable guide for percutaneous puncture. Moreover, sufficient safety margin could be obtained for hepatic tumor ablation. MR-guided microwave thermoablation therapy is a feasible method of treatment for hepatic tumors.

Carcinoma, Hepatocellular↗
PubMed2001

[A remarkably improved multimetastatic gastric cancer with the use of TS-1 and CDDP].

A 62-year-old male presented to our hospital with jaundice. On the abdominal ultrasound and abdominal CT, there was evidence of multiple, massive liver metastases with dilatation of intrahepatic bile ducts, thickened wall of the stomach from the body to the antrum, direct invasion to the pancreas, multiple lymph node metastases, and ascites. We believed it was Stage IV and too far advanced for surgery. Therefore, ST-1 60 mg bid was started, and CDDP 50 mg was infused in the seventh week. On the follow-up CT and ultrasound three months later, the thickening of the gastric wall and the lymph node metastasis had improved and the border between the stomach and the pancreas had become clearer. The liver metastases seen on both lobes had decreased significantly both in size and number. The dilatation of the intrahepatic bile ducts disappeared, and the liver function normalized. No side effects were evident during the treatment with the medications.

Antimetabolites, Antineoplastic↗
PubMed2000

The effect of a Rho kinase inhibitor Y-27632 on superoxide production, aggregation and adhesion in human polymorphonuclear leukocytes.

We investigated the involvement of p160ROCK (a Rho-associated coiled coil-forming protein kinase), one of Rho kinases on superoxide anion production (O(2)(-) production), aggregation and adhesion of human polymorphonuclear leukocytes under physiological condition, using a selective p160ROCK inhibitor, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide (Y-27632). Y-27632 inhibited the O(2)(-) production stimulated by phorbol-12-myristate-13-acetate (PMA) in a dose-dependent manner. Stauroprorine blocked the PMA-induced O(2)(-) production while wortmannin did not. Y-27632 also inhibited the O(2)(-) production by guanosine 5'-O-(3-thiotriphosphate) (GTP(gamma)S) 100 microM. N-formyl-Met-Leu-Phe (fMLP)-induced O(2)(-) production was not influenced by Y-27632, but was inhibited by wortmannin. The enhanced O(2)(-) production by Ca-ionophore A23817 and thapsigargin was not inhibited by Y-27632. Y-27632 did not change the basal intracellular Ca(2+) concentration nor its elevation stimulated by fMLP. Polymorphonuclear leukocytes aggregation induced by PMA was dose-dependently decreased by Y-27632 while their aggregation stimulated by fMLP was enhanced by the agent. Polymorphonuclear leukocytes adhesion induced by PMA or fMLP was not influenced by Y-27632.These results suggest that p160ROCK is involved in the PMA-induced O(2)(-) production and aggregation in human polymorphonuclear leukocytes. This kinase might locate in downstream of protein kinase C in polymorphonuclear leukocytes.

Adult↗
PubMed2000

Promoter-targeted selection and isolation of neural progenitor cells from the adult human ventricular zone.

Adult humans, like their nonhuman mammalian counterparts, harbor persistent neural progenitor cells in the forebrain ventricular lining. In the absence of adequate surface markers, however, these cells have proven difficult to isolate for study. We have previously identified and selected neural progenitor cells from both the fetal and adult rodent ventricular zone (VZ), by sorting forebrain cells transfected with plasmid DNA encoding the gene for green fluorescent protein driven by the early neuronal promoter for Talpha1 tubulin (P/Talpha1:hGFP). We have now extended this approach by purifying both P/Talpha1:hGFP tubulin-defined neuronal progenitors, as well as potentially less committed E/nestin:hGFP-defined neural progenitor cells, from the adult human VZ. The ventricular wall of the temporal horn of the lateral ventricle was dissected from temporal lobes obtained from four adult patients undergoing therapeutic lobectomy. These samples were dissociated, and the cultured cells transduced with either P/Talpha1:hGFP or E/nestin:EGFP plasmid DNA. A week later, the cells were redissociated, selected via fluorescence-activated cell sorting (FACS) on the basis of neural promoter-driven GFP expression, and replated. The majority of these cells expressed the early neuronal protein betaIII-tubulin upon FACS; within the week thereafter, most matured as morphologically evident neurons that coexpressed betaIII-tubulin and microtubule-associated protein (MAP)-2. Many of these neurons had incorporated bromodeoxyuridine in vitro in the days before FACS, indicating their mitogenesis in vitro. Thus, the use of fluorescent transgenes under the control of early neural promoters permits the enrichment of neuronal progenitor cells from the adult human ventricular zone. The specific acquisition, in both purity and number, of residual neural progenitor cells from the adult human brain may now permit hitherto unfeasible studies of both their biology and practical application.

Adult↗