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Biomedical subjects

Shogo Tokudome

Publications and source records attributed to Shogo Tokudome.

32 records · Page 2Linked to original sources
PubMed2004

Analysis of fatal injuries to motorcyclists by helmet type.

To clarify the characteristics of injuries of motorcyclists dying in accidents in relation to helmet type, we retrospectively analyzed forensic autopsies of 36 helmeted motorcycle riders. The presence of major injuries and injury severity were evaluated with the injury severity score and the 1990 revision of the Abbreviated Injury Scale. Persons with open-face helmets (19 cases) were significantly more likely to have sustained severe head and neck injuries, especially brain contusions, than were persons with full-face helmets (17 cases). Furthermore, major injuries of the chest or abdomen, rib fractures, lung injuries, and liver injuries were each present in more than one quarter of all cases (26.3% to 70.6%), but their prevalences did not differ significantly between riders with different types of helmet. Because many types of head and neck injuries cannot be prevented and fatal chest and abdominal injuries occur despite the use of full-face helmets, more effective helmets and devices for protecting the chest and abdomen are needed to decrease deaths from motorcycle accidents.

Accidents, Traffic↗
PubMed2004

Bioactivation of capecitabine in human liver: involvement of the cytosolic enzyme on 5'-deoxy-5-fluorocytidine formation.

Capecitabine, an anticancer prodrug, is thought to be biotransformed into active 5-fluorouracil (5-FU) by three enzymes. After oral administration, capecitabine is first metabolized to 5'-deoxy-5-fluorocytidine (5'-DFCR) by carboxylesterase (CES), then 5'-DFCR is converted to 5'-deoxy-5-fluorouridine (5'-DFUR) by cytidine deaminase. 5'-DFUR is activated to 5-FU by thymidine phosphorylase. Although high activities of drug metabolizing enzymes are expressed in human liver, the involvement of the liver in capecitabine metabolism is not fully understood. In this study, the metabolism of capecitabine in human liver was investigated in vitro. 5'-DFCR, 5'-DFUR, and 5-FU formation from capecitabine were investigated in human liver S9, microsomes, and cytosol in the presence of the inhibitor of dihydropyrimidine dehydrogenase, 5-chloro-2,4-dihydroxypyridine. 5'-DFCR, 5'-DFUR, and 5-FU were formed from capecitabine in cytosol and in the combination of microsomes and cytosol. Only 5'-DFCR formation was detected in microsomes. The apparent K(m) and V(max) values of 5-FU formation catalyzed by cytosol alone and in combination with microsomes were 8.1 mM and 106.5 pmol/min/mg protein, and 4.0 mM and 64.0 pmol/min/mg protein, respectively. The interindividual variability in 5'-DFCR formation in microsomes and cytosol among 14 human liver samples was 8.3- and 12.3-fold, respectively. Capecitabine seems to be metabolized to 5-FU in human liver. 5'-DFCR formation was exhibited in cytosol with large interindividual variability, although CES is located in microsomes in human liver. In the present study, it has been clarified that the cytosolic enzyme would be important in 5'-DFCR formation, as is CES.

Antimetabolites, Antineoplastic↗
PubMed2004

Changes in blood viscosity with mucopolysaccharide polysulfate.

We examined the dose-dependent effects of mucopolysaccharide polysulfate (MPS) on coagulation variables and whole-blood viscosity in human blood. Both 0.01% and 0.1% MPS significantly reduced levels of both fibrin monomer and thrombin-antithrombin III complex in a manner similar to that of 2.0 IU/ml heparin sodium. Furthermore, MPS dose-dependently decreased whole-blood viscosity, as measured with an oscillation viscometer. Because MPS can be applied in creams and gels, percutaneous application of MPS may effectively reduce whole-blood viscosity in local veins.

Adult↗
PubMed2004

Changes in blood viscosity with heavy and light exercise.

To clarify the relationship of the intensity of acute exercise to sudden cardiac death, we examined the effects of short-term heavy and light exercise on whole blood viscosity. Nine healthy sedentary male volunteers performed ten minutes of heavy (more than 95% of maximum oxygen consumption) or light (60% to 65% of maximum oxygen consumption) exercise. Blood samples were obtained before, immediately after, and one hour after exercise. The whole blood viscosity was immediately examined with an oscillation-type viscometer and was found to increase significantly after exercise and subsequently return to baseline levels within one hour after exercise. The whole blood viscosity increased by a similar degree after heavy or light exercise. Therefore, our results suggest that there is a similar risk of sudden cardiac death, due to increased whole blood viscosity, after short-term heavy or light exercise.

Adult↗
PubMed2004

An autopsy case of fatal anaphylactic shock following fluorescein angiography: a case report.

We present a rare autopsy case of fatal anaphylactic shock following fluorescein angiography. A 71-year-old Japanese woman undergoing retinal angiography to evaluate diabetic retinopathy died immediately after an injection of sodium fluorescein. Forensic autopsy and post-mortem biochemical analyses revealed an elevated serum level of tryptase which, in the absence of morphologic changes suggesting injury or disease, confirmed the diagnosis of fatal anaphylactic shock. Although serious adverse effects are rare after fluorescein angiography, patients should be observed, with appropriate resuscitation equipment available, for several hours after the administration of fluorescein.

Aged↗
PubMed2003

Effects of polymorphism in promoter region of human CYP2A6 gene (CYP2A6*9) on expression level of messenger ribonucleic acid and enzymatic activity in vivo and in vitro.

Cytochrome P450 (CYP) 2A6 catalyzes nicotine C-oxidation, leading to cotinine formation, a major metabolic pathway of nicotine in humans. There are genetic polymorphisms in the human CYP2A6 gene. Previously, we demonstrated that in vivo nicotine metabolism is impaired with the CYP2A6*4, CYP2A6*7, and CYP2A6*10 alleles in Japanese subjects and Korean subjects. An allele possessing a point mutation in the TATA box termed CYP2A6*9 (T-48G) has been reported to decrease the transcriptional activity in vitro as assessed by luciferase assay. In this study we investigated the effects of the CYP2A6*9 allele on in vivo enzymatic activity by evaluating nicotine metabolism. The mutation of T-48G was found only on the CYP2A6*1A allele but not on the CYP2A6*1B allele. Allele frequencies of CYP2A6*9 in Japanese subjects (n = 92) and Korean subjects (n = 209) were 21.3% and 22.3%, respectively. In Korean subjects the cotinine/nicotine ratios as an index of nicotine metabolism in the subjects with CYP2A6*9/CYP2A6*9 (4.3 +/- 2.4) were significantly lower than those in the subjects with CYP2A6*1A/CYP2A6*9 (7.7 +/- 5.6) and CYP2A6*1A/CYP2A6*1A (10.4 +/- 9.2) (P <.05 and P <.005, respectively). In Japanese subjects a similar result was observed, although it was not significant. Thus it is suggested that the mutation in the TATA box (CYP2A6*9 allele) caused the decreased in vivo enzymatic activity. With an in vitro study, it was shown that the expression levels of CYP2A6 messenger ribonucleic acid and coumarin 7-hydroxylase activity in human livers genotyped as CYP2A6*1/CYP2A6*9 and CYP2A6*9/CYP2A6*9 tended to be lower than those in human livers genotyped as CYP2A6*1/CYP2A6*1, although there was no significant difference because of the small number of samples. These in vitro data supported the in vivo data demonstrating that the CYP2A6*9 allele caused the decreased expression level and enzymatic activity of CYP2A6.

Alleles↗
PubMed2003

Changes in blood viscosity with synthetic protease inhibitors.

We examined the effects on whole blood viscosity and coagulation time of various dosages of the synthetic low-molecular protease inhibitors gabexate mesilate and nafamostat mesilate with an oscillation-type viscometer. When either agent was added, blood viscosity decreased dose-dependently along a sigmoid-like curve. Furthermore, coagulation time was shorter with gabexate mesilate than with nafamostat mesilate owing to the differences of half-life in human blood. Thrombin generation, which results from the activation of coagulation factors, is inhibited by synthetic protease inhibitors and subsequently decreases blood viscosity dose-dependently.

Adult↗
PubMed2003

Microscopic measurement of the facial nerve root exit zone from central glial myelin to peripheral Schwann cell myelin.

OBJECT: The authors have attempted to define the exact borders of the root exit zone (RExZ) of the facial nerve, measure the distribution of myelin histologically, and examine the relationship between contact vessels and the RExZ. METHODS: Seventy-five facial nerves were obtained from brainstems excised from 44 adult patients at autopsy. The arteries and veins associated with the facial nerve were counted and measured. The facial nerves, associated vasculature, and adjoining portions of the brainstem were then removed en bloc. These tissues were serially sectioned and stained, and a photomicrograph of each section was obtained. The distribution of myelin on each section was measured from the upper edge of the supraolivary fossette, and the relationship between contact vessels and the RExZ examined. The lateral transitional zone of the facial nerve began 8 mm distal to the upper edge of the supraolivary fossette (root exit point [RExP]) and had a mean length of 1.9 mm. The root detachment point (RDP) of the facial nerve at the medial side was located very close to the beginning of the medial transitional zone. In more than 80% of the nerves that were examined, vascular structures compressed the central glial myelin of the nerve. CONCLUSIONS: The authors propose the use of the terms "RExP," "RDP," and "transitional zone," instead of RExZ, which cannot be well defined. The RDP appears to be a good landmark for use during microvascular decompression.

Adolescent↗
PubMed2002

Enantiomer analysis of a new street drug, 3,4-methylenedioxy-N-methyl-butanamine, in rat urine.

A new street drug, 3,4-methylenedioxy-N-methyl-butanamine (MBDB), has been found in Japan recently. The stereoisomer monitoring and the urinary excretion kinetics are not determined in biological fluids even though abused MBDB is a racemic form [enantiomer ratio (-/+) = 1.00]. The present studies were done by high-performance liquid chromatography (HPLC) equipped with a chiral activity column at 40 degrees C using urine specimens from five Wistar rats. Urine samples were collected over six time intervals after a single oral administration of racemic MBDB (30 mg/kg). Unchanged MBDB and 3,4-methylenedioxybutanamine (BDB), an N-demethylated metabolite, were found in the rats' urine. Each enantiomer of MBDB and BDB was monitored (peak resolution > 1.00) by HPLC analysis within 30 min. For both MBDB and BDB, the (+)-isomers were excreted a little more than the (-)-isomers. The stereoselective disposition of BDB was more remarkable than that of MBDB and was observed in the urine throughout the study (p < 0.05). The urinary excretion of MBDB showed significant difference between the two enantiomers from 4 to 20 h (p < 0.05). The amount of MBDB excreted up to 24 h was 34.7+/-2.8% of the administered dose: 17.6+/-1.4% for (+)-isomer and 17.1+/-1.5% for (-)-isomer. The amount of BDB was 4.9+/-1.0%; 2.9+/-0.6% for (+)-isomer and 2.0+/-0.4% for (-)-isomer. The enantiomer ratio (-/+) of MBDB and BDB was 1.00 or a little smaller. The ratio (-/+) of MBDB changed from 1.00+/-0.02 to 0.88+/-0.09 by 24 h, and that of BDB from 0.68+/-0.03 to 0.78+/-0.02. The ratio (-/+) for MBDB and BDB accumulated up to 24 h was 0.97+/-0.01 and 0.70+/-0.06, respectively, and the total ratio (-/+) of the two substances was 0.93+/-0.02 (p < 0.05). These findings suggested that the stereoselective disposition of racemic MBDB was different from that of 3,4-dimethylenedioxyamphetamine and 3,4-dimethylenedioxymethamphetamine and was similar to that of methamphetamine.

3,4-Methylenedioxyamphetamine↗