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Biomedical subjects

T Hamaguchi

Publications and source records attributed to T Hamaguchi.

At least 91 records · Page 5Linked to original sources

Effects of food intake on the bioavailability of sulpiride from AEA film-coated tablet having a pH-dependent dissolution characteristic in normal or drug-induced achlorhydric subjects.

The effect of food intake on the bioavailability of sulpiride from a commercial film-coated tablet (100 mg/T) treated with polyvinylacetal diethylaminoacetate (AEA), which remains undissolved at pH above 4 approximately 5, were investigated in four healthy male subjects in the normal state or in a drug-induced achlorhydric state. The drug was administered as a single oral 100 mg dose of sulpiride under the fasting and nonfasting state using a crossover study design. Fifteen urine samples were collected over a 48 h period following sulpiride administration to determine sulpiride concentrations by HPLC. The bioavailability was estimated from the cumulative amount excreted unchanged in urine over 48 h (Du48). When AEA film-coated tablet was taken by subjects in the normal state, the bioavailability under the fasting state differed markedly among the four subjects due to differences in gastric acidity. The effect of food intake on the bioavailability also differed markedly among the individuals, being lower in high gastric acidity subject and higher in those with low gastric acidity subjects. When AEA film-coated tablet was taken by subjects in a simulated achlorhydric state, the bioavailability under the fasting state was very poor for all four subjects and did not show inter-subject variation. With food intake, the bioavailability increased 6-fold, probably due to the more vigorous movement of the formulation in the gastrointestinal tract, since both the basal and the meal-stimulated gastric acid secretion were markedly inhibited in the simulated achlorhydric state.

Achlorhydria↗

Tissue specificity in expression and alternative RNA splicing of human phosphofructokinase-M and -L genes.

Mode of the expression of phosphofructokinase (PFK) -M and -L genes was examined in various human tissues including muscle, placenta, liver, kidney, pancreas, stomach and reticulocytes. The gross level of mRNA expression of PFK-M and -L genes was estimated by Northern analysis. Polymerase chain reaction was used to detect mRNA expressed at low levels in these tissues. Tissue-specific expression of alternatively spliced PFK-M gene transcripts was also determined by polymerase chain reaction. The results indicated that alternative splicing of PFK-M gene transcripts was controlled in a tissue-specific manner.

Base Sequence↗

Taurine deficiency and doxorubicin: interaction with the cardiac sarcolemmal calcium pump.

An anticancer drug, doxorubicin, and a naturally occurring beta-amino acid, taurine, exert opposing actions on myocardial calcium content and lipid peroxidation. Thus, we tested the hypothesis that the two agents may interact to modify cardiac calcium metabolism and indices of lipid peroxidation. Cardiac taurine levels were reduced by half in rats given tap water containing a beta-amino transport inhibitor, beta-alanine. Taurine deficiency was associated with an increased susceptibility of the heart to doxorubicin-mediated calcium accumulation, a phenomenon commonly associated with doxorubicin cardiotoxicity. Taurine deficiency also predisposed the heart to enhanced formation of malondialdehyde caused by doxorubicin administration. While increases in malondialdehyde levels are often associated with lipid peroxidation, the failure of doxorubicin to cause changes in oxidized glutathione content makes peroxidative mechanisms a less likely explanation for the potentiation of doxorubicin-mediated myocardial calcium accumulation in taurine-deficient rats. A more likely possibility is the interaction between taurine deficiency and doxorubicin to inhibit the sarcolemmal calcium pump. The data also suggest that the interaction between doxorubicin and taurine deficiency does not involve alterations in the pharmacokinetics of doxorubicin or the cardiotoxic metabolite, doxorubicinol. It is concluded that reduction in sarcolemmal calcium pump activity by taurine deficiency may contribute to myocardial calcium accumulation in hearts whose calcium homeostasis has been compromised by doxorubicin.

Animals↗

Glucose infusion abolishes the excessive ATP degradation in working muscles of a patient with McArdle's disease.

A 23-year-old woman with McArdle's disease performed mild leg exercise on a bicycle ergometer. Saline or 10% glucose solution was infused throughout exercise. After exercise with saline infusion, her plasma concentrations of ammonia, hypoxanthine and creatine kinase increased greatly. Conversely, after exercise with glucose infusion, there were no appreciable changes in these plasma substances. In addition, she noticed that glucose infusion relieved her from muscle symptoms during exercise. These findings suggest that glucose infusion to patients with McArdle's disease ameliorates excessive ATP degradation in exercising muscles.

Adenosine Triphosphate↗

[Clinical study of extracorporeal shock wave lithotripsy for 1000 patients with renal and ureteral stones].

Using a Dornier HM3 lithotripter, we treated 1,000 patients with renal and ureteral stones from April, 1986 to July, 1989. They consisted of 612 solitary stones (pelvic stones, 152; calyceal stones, 167; ureteral stones, 293), 265 multiple stones and 123 staghorn calculi (complete, 48; partial, 75). The overall rate of the auxiliary procedure was 59.3% (pre-operative, 47.9%; post-operative, 11.4%). Pre-operative procedure included 430 catheterizations, 26 percutaneous nephrostomies (PNSs) and 23 pyelograms . Post-operative procedure included 69 transurethral lithotripsy , 21 PNSs, 26 percutaneous nephrolithotripsy (PNLs), 6 meatotomy , 5 chemolysis and 1 open surgery. 484 (68.3%) in 709 good follow-up cases were stone-free at the time of 3 months since the first extracorporeal shock-wave lithotripsy (ESWL). Complications were pain (34.8%), fever (4.3%), pain & fever (8.5%), subcapsular hematoma (0.1%) and ureteral obstruction (0.1%). Thus, ESWL is considered to be a useful means for renal and ureteral stones and in the case of large stone the combination therapy with PNL is more effective than ESWL-monotherapy.

Adult↗

Effects of food intake and meal size on the bioavailability of sulpiride in two dosage forms.

This study examined the influences of food intake on sulpiride (100 mg) bioavailability from a commercial film-coated tablet and of the meal size (small, medium or large) on sulpiride bioavailability from an aqueous solution in three healthy male volunteers. The cumulative urinary excretions of sulpiride for 48 h (Du48) from two dosage forms following oral administration were decreased approximately 30% by food intake. Also, a good correlation was found between the bioavailability of sulpiride from the solution and size of meals with the same dietary components. These results suggest that food intake and meal size before dosing significantly affect the gastrointestinal absorption of sulpiride.

Administration, Oral↗

Autoantibodies to the insulin receptor impair clearance of plasma endogenous insulin.

Plasma insulin clearance was studied in a patient with autoantibodies to the insulin receptor, manifesting persistent hyperinsulinemia associated with alternating hyper- and hypoglycemia. In the postabsorptive period, the plasma glucose level gradually decreased. To prevent the development of hypoglycemia, glucose was infused and the glycemic level was clamped at 50 mg/dl without insulin infusion. The plasma C-peptide level was below the detectable range during the clamp, indicating no appreciable secretion of insulin. The plasma insulin level declined exponentially with a markedly prolonged disappearance rate (half-time: 3.0 h) during the study. These results indicate that hyperinsulinemia in the postabsorptive period in this patient is attributable to the impairment of plasma insulin clearance through receptor-mediated mechanisms, and also confirm that the receptor plays the principal role in plasma insulin removal.

Acanthosis Nigricans↗

Hyperinsulinemia due to impaired insulin clearance associated with fasting hypoglycemia and postprandial hyperglycemia: an analysis of a patient with antiinsulin receptor antibodies.

Antiinsulin receptor antibodies were detected in the serum of a patient with insulin-resistant diabetes. Fasting hypoglycemia and postprandial hyperglycemia recurred every day. The plasma insulin level was 553 +/- 359 pmol/L [77 +/- 50 microU/mL (mean +/- SD)] in the fasting state and rose above 7500 pmol/L postprandially. The glycemic clamp at 2.8 mmol/L (50 mg/dL) without insulin infusion revealed that the half-life of plasma endogenous insulin was 173 min, indicating severely impaired plasma insulin clearance. During the clamp the glucose infusion rate was almost constant (0.9-1.2 mg/kg.min) despite an exponential decline in the plasma insulin level from 460 pmol/L (65 microU/mL) to 129 pmol/L (18 microU/mL). Intravenous insulin administration did not appreciably accelerate the basal constant decrease in the plasma glucose level during the postabsorptive period. These results indicate the coexistence of marked insulin resistance and constant ability to decrease plasma glucose level. In in vitro experiments, antireceptor immunoglobulin G from this patient increased the fructose 2,6-bisphosphate concentration in the presence of glucagon (less than 0.1 nmol/L) in primary cultured rat hepatocytes. The antireceptor immunoglobulin G stimulated autophosphorylation of rat liver insulin receptor. We conclude that antiinsulin receptor antibodies could impair plasma insulin clearance, resulting in persistent hyperinsulinemia, and that continuous receptor stimulation by the antibodies was responsible for the development of hypoglycemia.

Animals↗

The bioavailability of sulpiride taken as a film-coated tablet with sodium bicarbonate, cimetidine, natural orange juice or hydrochloric acid.

The bioavailability of sulpiride taken in film-coated tablet form with sodium bicarbonate or cimetidine or with natural orange juice or diluted hydrochloric acid was studied. A commercial sulpiride film-coated tablet (100 mg/T) treated with polyvinylacetal diethylaminoacetate (AEA), which remain undissolved at pH above 4-5, was given to four healthy volunteers who had fasted overnight. The subjects were divided into two groups, those showing high and low bioavailability of sulpiride from an AEA film-coated tablet. The two high bioavailability subjects took one tablet (100 mg) with 100 ml of water (1) alone, (2) together with 1 g of sodium bicarbonate or (3) during concurrent dosing with cimetidine, 200 mg three times a day. The two low bioavailability subjects swallowed one tablet with 100 ml of (1) water, (2) natural orange juice, or (3) diluted hydrochloric acid. Urine samples were collected over a 48-h period following sulpiride administration to determine sulpiride concentrations by HPLC. The bioavailability was estimated from the cumulative amount excreted unchanged in urine over 48 h (Du48). In the high bioavailability subjects, the bioavailability of sulpiride markedly decreased with the coadministration of sodium bicarbonate or cimetidine compared to when the tablet was taken alone. In the low bioavailability subjects, the bioavailability remarkably increased with the concomitant intake of orange juice or diluted hydrochloric acid over that with only water. These results suggest that the bioavailability of sulpiride from AEA film-coated tablet is influenced by the individual's gastric acidity and by coadministered drug and drink which affect gastric acidity.

Adult↗

[4 cases of paraquat poisoning].

A clinical study was performed on 4 patients with paraquat poisoning treated between 1985 and 1987. The survival rate was 0% in our hospital.

Adult↗

[Successful surgical treatment of a patient with tension pneumopericardium and left hemothorax caused by multiple rib fractures].

A 62-year-old man underwent operation for tension pneumopericardium and left hemothorax caused by multiple rib fractures. He sustained other multiple injuries, such as acute subdural hematoma, compound fractures of the left leg. At left thoracotomy, massive hemorrhage from the left apical lung disrupted by the first and second fractured ribs was encountered and pericardium was seen to be bulging and tensely inflated. Incision of the pericardial sac resulted in expulsion of air with a subsequent fall in central venous pressure and heart rate. And after repair of the tear of the laceration of the left lung, the chest was closed with underwater seal drainages of the left pleural cavity. He was successfully weaned off the ventilator after 12 days. After extubation, repeated bronchoscopy was done, but the tracheobronchial injury was not able to be found out.

Hemothorax↗

Cellular oncogene expression in the idiopathic cardiomyopathic hamster heart during the growing process.

The expression of various proto-oncogenes was evaluated in the Syrian hamster with hereditary idiopathic cardiomyopathy. mRNA from the heart and aorta of controls (BIO-RB) and cardiomyopathic hamsters (UM-X7.1 strain, BIO 14.6 line) was tested using RNA hybridization techniques. Of the 19 different v-oncogene probes used in the study, only the v-myc probe revealed a substantially greater expression of oncogene in the 30th day of cardiomyopathic hamster heart than in control hamster heart. The amplified expression of c-myc was also observed in the heart of 1-year-old, but not of 7-day-old cardiomyopathic hamster. Overexpression of c-myc, otherwise associated with the regulation of cell differentiation or rapid growth, may relate to the pathological state or pathogenesis of the hereditary cardiomyopathy.

Age Factors↗

Mechanism of the protective action of taurine against isoprenaline induced myocardial damage.

The effect of the sulphur amino acid, taurine, on the biochemical changes induced by a toxic dose of isoprenaline was examined in chick hearts. Isoprenaline treatment (80 and 240 mg.kg-1 subcutaneously twice a day for four days) caused a dose dependent increase in heart to body weight ratio. Isoprenaline administration induced a substantial accumulation of calcium and caused a profound decrease of adenosine triphosphate content and creatine phosphokinase activity in the myocardium. A pronounced increase in lipoperoxide and decrease in phospholipid and reduced glutathione concentrations were also seen. Oral administration of taurine (200 mg.kg-1 for seven days) partially protected against these changes induced by isoprenaline. It is suggested that the beneficial effect of taurine may be due in part to inhibition of lipoperoxide formation and calcium accumulation and to protection against the deterioration of membrane phospholipids.

Adenosine Triphosphate↗

Further studies on the resolution of human mercapt- and nonmercaptalbumin and on human serum albumin in the elderly by high-performance liquid chromatography.

High-performance liquid chromatographic (HPLC) analysis of human serum albumin (HSA) on Asahipak GS-520 showed at least two peaks, the principal component corresponding to human mercaptalbumin (HMA) and the secondary one to nonmercaptalbumin (HNA). HPLC analysis of HSA on Asahipak ES-520 N showed three peaks, the principal component corresponding to HMA, the secondary one to HNA having mixed disulfide with cysteine or glutathione and the tertiary one to HNA oxidized higher than mixed disulfide. Two kinds of rapid HPLC for the resolution of HSA into HMA and HNA were developed by the present authors. Using these HPLC, the present authors found a significant decrease in the fraction of HMA in the elderly.

Aged↗

[A case of a complete paraplegic fathering a girl following artificial insemination after an intrathecal neostigmine injection].

A case of a 32-year-old paraplegic male who fathered a girl following artificial insemination after an intrathecal neostigmine injection is described. The patient became a complete paraplegic after injury to the spinal cord caused by a traffic accident in 1971, resulting in ejaculatory disturbance. In June, 1984 the first intrathecal neostigmine injection was tried and 2.7 ml of semen was collected and offered to artificial insemination. However, the first to ninth attempt did not result in fertilization. The tenth attempt was made in March 7, 1986, and 3 ml of semen presenting 240 X 10(6) spermatozoa per ml with 5% of motile sperms was collected. This resulted in pregnancy, and the patient's wife delivered a healthy girl weighing 2552 g by cesarean section on November 19, 1986. This is the fourth case of a paraplegic who fathered a child following artificial insemination after an intrathecal neostigmine injection in the Japanese literature.

Adult↗

[Male infertility with chromosomal abnormalities. III. 46, XYq-].

A deletion of the long arm of the Y chromosome (46,XYq-) was found in two cases with normal male habitus but with azoospermia. The first case was of a 28-year-old married man, an office worker, complaining of infertility. His height was 153 cm, weight 57 kg and distance of extended hand 152 cm. Both testes were 13 ml in size. The second case was a 32-year-old married man, a fireman, complaining of infertility. His height was 160 cm, weight 64 kg and distance of extended hand 161 cm. Both testes were 10 ml in size. In each case, the external genitalia showed a normal male type, but azoospermia was identified in semen analysis. The testicular biopsy specimens revealed spermatogenic arrest with thickening of basement membrane. Chromosomal analysis showed 46,XYq- karyotype. Basal serum levels of luteinizing hormone and follicle-stimulating hormone were slightly elevated and the serum testosterone level was within normal limits. Eight cases of 46,XYq- karyotype in the Japanese literature including our cases were reviewed.

Adult↗

[Problems in evaluating male fertility: valuable factors in evaluating male fertility and normal values of seminal parameters].

To determine the valuable factor for evaluating male fertility, a comparative study was done as to various seminal parameters between fertile and infertile groups. The fertile group consists of 57 proven fertile males and the infertile group consists of randomly chosen 67 infertile patients. Seminal parameters assessed were sperm concentration, motility, mean velocity, total sperm output, total motile sperm output, sperm morphology, acrosin activity and sperm penetration rate on zona-free hamster egg penetration assay (SPA). The infertile group was significantly different from the fertile group in every parameter except acrosin activity. However, the range of each parameter in the two groups overlapped each other. The diagnostic rate of each parameter, which is the percentage of an infertile male correctly diagnosed as infertile, was calculated by using 95% specificity threshold value of fertile males. The 95% specificity threshold values of sperm concentration, motility and % normal shaped sperm were 24.9 x 10(6)/ml, 34.9% and 55%, respectively, and they could be acceptable for the normal limit of seminal parameters. The diagnostic rate was highest in penetration rate (72.4%). In other words, penetration rate is the most valuable factor in various parameters for making a distinction between fertile and infertile males. Sperm motility and mean velocity showed the next highest diagnostic rate. On the other hand, sperm concentration showed a poor diagnostic rate (36.8%). In addition, there was no significant correlation between penetration rate and any other seminal parameters. These results suggest that the SPA will be an essential test for evaluating male fertility and penetration rate may be a marker of male fertility in the treatment of male infertility.

Adult↗

Reduction of doxorubicin-induced cardiotoxicity in mice by taurine.

The effect of taurine on doxorubicin-induced cardiotoxicity was examined in mice. A single intraperitoneal injection of doxorubicin (15 mg/kg) produced a significant elevation of calcium and lipoperoxide content at 72 hr, as well as a significant depletion of creatine phosphokinase, glutamic oxaloacetic transaminase and lactate dehydrogenase activities at 48 hr and glutathione peroxidase activity at 24 hr in the myocardium. These results suggest that a substantial myocardial damage had occurred. All biochemical alterations except depletion of glutathione peroxidase, were markedly attenuated by the combined oral and intraperitoneal administration of taurine. Taurine significantly improved the survival rate of the mice treated with doxorubicin. These results demonstrate that taurine antagonized doxorubicin-induced cardiotoxicity.

Animals↗