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Biomedical subjects

A Fujimura

Publications and source records attributed to A Fujimura.

At least 109 records · Page 6Linked to original sources

Effect of fibrin glue on small and large bowel anastomoses in the rat.

Fibrin glue has been used as a hemostatic and adhesive agent for many years, but its efficacy in digestive surgery is still controversial. In this study, we evaluated the effect of fibrin glue on the healing of the small and large bowel anastomotic portions by measurement of the anastomotic bursting pressure. Further, the efficacy of fibrin glue in preventing intra-abdominal adhesion formation was assessed. Our results indicated that fibrin glue enhanced the resistance towards an elevation of intraluminal pressure in small bowel, but not in large bowel. Concomitantly, the glue did not significantly attenuate postoperative adhesion formation. A sealing action of fibrin glue might protect against bleeding and microleakage, resulting in beneficial effects on small bowel anastomosis.

Anastomosis, Surgical↗

Effect of amezinium metilsulfate on the finger skin vasoconstrictor response to cold stimulation and venoconstrictor response to noradrenaline.

Orthostatic hypotension can be caused by an inadequate vasoconstrictor response. The effects of amezinium on vasoconstrictor response to sympathetic stimulation and to exogenous noradrenaline were investigated and compared with those of midodrine. In 8 healthy men, the following experiments were performed after a single oral dose of 10mg of amezinium, 2mg of midodrine or a placebo. First, finger-tip blood flow (FTBF) was recorded using a laser Doppler flowmeter before and during the contralateral hand cooling and a reduction ratio of FTBF was calculated as an index of the vasoconstrictor response. Second, dose-response curves to increasing doses (1-512ng/min) of noradrenaline infused locally to the dorsal hand vein were determined using a linear variable differential transformer. The reduction ratio of FTBF was significantly increased (p<0.05) by amezimium [placebo, 75.9 +/- 9.8(mean +/- SD)%; amezinium, 85.1 +/- 7.9%; midodrine, 78.1 +/- 9.3%]. The infusion rate of noradrenaline producing a half-maximum venoconstriction was significantly decreased (p<0.05) by amezinium (placebo, 40.6 +/- 33.9 ng/min; amezinium, 21.0 +/- 21.3 ng/min; midodrine, 33.2 +/- 31.5 ng/min). These findings indicate that amezinium increases the vasoconstrictor response to sympathetic stimulation and to noradrenaline in normal subjects, and this mechanism might contribute to the improvement by amezinium of the symptoms of orthostatic hypotension.

Adrenergic alpha-Agonists↗

Role of bradykinin in the reduction of left ventricular hypertrophy induced by angiotensin-converting enzyme inhibitors in spontaneously hypertensive rats.

We examined the effects of icatibant, a specific bradykinin B2-receptor antagonist, on the regression of left ventricular mass (LVM) induced by angiotensin converting enzyme (ACE) inhibitors, ramipril and imidapril, in spontaneously hypertensive rats. Both ramipril and imidapril lowered blood pressure equally, which were not influenced by icatibant. Icatibant did not alter the regressive effect of imidapril, while it showed a tendency to increase LVM in the ramipril-treated rats. The changes of LVM induced by icatibant were significantly different between the ramipril- and the imidapril-treated rats, suggesting that the role of bradykinin in the antihypertrophic effect might differ among ACE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗

Effects of renin-angiotensin system blockade and dietary salt intake on left ventricular hypertrophy in Dahl salt-sensitive rats.

We studied the effects of chronic blockade of the renin-angiotensin system on hypertension and cardiac left ventricular hypertrophy (LVH) in Dahl salt-sensitive (DS) rats given a high-salt or low-salt diet. [Experiment 1] Twelve-week-old male DS rats were fed an 8% NaCl diet and received the angiotensin II receptor (AT1) antagonist, candesartan (3 mg/kg/d), the angiotensin converting enzyme inhibitor enalapril (30 mg/kg/d), or vehicle for 6 wk after 3 wk of 8% salt-loading. Neither candesartan nor enalapril with concomitant high salt-loading attenuated the blood pressure (BP) elevation. LVH was also not attenuated significantly by these treatments. [Experiment 2] After 8 wk of 8% salt-loading, the rats were given a 0.3% NaCl diet and concurrently received candesartan, enalapril, or vehicle for 5 wk. Switching from the high-salt to low-salt diet significantly decreased BP and left ventricular mass in the vehicle-treated animals. Both candesartan and enalapril normalized BP during salt-depletion; the blockade of the renin-angiotensin system produced an additive reduction in LVH. These findings suggest that sodium intake and hemodynamic load, but not the renin-angiotensin system, may be major determinants of the development of LVH in DS rats.

Angiotensin II↗

Effect of captopril on the time-dependent variation of kaolin-induced writhing reaction.

Effect of captopril, an angiotensin-converting enzyme (ACE) inhibitor, on the time-dependent variation of kaolin-induced writhing reactions was examined in mice kept under conditions of light from 07:00 to 19:00 and dark from 19:00 to 07:00. The number of writhes was counted for 60 minutes after a single intraperitoneal injection of kaolin at 01:00, 07:00, 13:00, and 19:00. The number of writhes showed a time-dependent variation, with a peak at 19:00 and a trough at 07:00 in the control group. Captopril significantly increased the number of writhes after dosing at 01:00 and 07:00 (during the active period). The ACE activity following captopril dosing was significantly lower in the 07:00 than the 19:00 trial. These results suggest that the pharmacological effect of captopril varies with the dosing time, and the enhancement of the kaolin-induced writhing reaction is greater following dosing of the agent at nighttime in mice.

Angiotensin-Converting Enzyme Inhibitors↗

Bifid ribs observed in the third and the fourth ribs.

Three cases of bifid ribs were found in two cadavers during routine dissections at the Iwate Medical University School of Dentistry. All of the cases were found in the third or the fourth rib. The distal parts of the osseous rib bifurcated with an angle of 60 degrees and both of the branches had their own costal cartilage. The costal cartilage fused again to form the trunk which was connected to the sternum. The space between the two branches was filled with presumably normal intercostal muscles. Blood supply was maintained by a small branch from the interthoracic artery to the upper branches. However, the intercostal nerves did not branch toward the upper branch but only ran along the lower margins of the lower branches of the bifid ribs.

Aged↗

Introduction of DNA into rat liver with a hand-held gene gun: distribution of the expressed enzyme, [32P]DNA, and Ca2+ flux.

DNA-coated Au particles were accelerated by pressurized He gas to supersonic velocities for introduction of a gene into cells. Experimental and theoretical analyses both revealed a heterogeneous distribution of the particles per shot (1 mg Au = 2.4 x 10(7) particles with 2 microg [32P] DNA = 2.5 x 10(11) moles). For introduction of genes into the liver of living rats, the best results were obtained with a newly developed hand-held gene delivery system. The beta-galactosidase gene introduced into rat liver with Au particles by He at 250 psi was expressed (1.2 microunits/microg protein) in a limited area of the liver surface (8 x 8 mm, depth 0.5 mm). When the same gene gun was used on a monolayer of cultured COS7 cells (about 5 microm thick), cells were lost in the central area of heavy bombardment. Cell death caused by influx of Ca2+ was prevented by the use of the cytosol-type culture medium.

Animals↗

Hormone-cytokine response. Pneumoperitoneum vs abdominal wall-lifting in laparoscopic cholecystectomy.

BACKGROUND: Changes in blood hormone and cytokine were investigated in patients who underwent laparoscopic cholecystectomy via insufflation (CO2 group) vs those who had abdominal wall-lifting (Air group). METHODS: Seventeen female patients with cholecystolithiasis were randomly divided into two groups. Peripheral blood samples were obtained during perioperative period, and plasma hormone levels (ACTH, cortisol) and serum cytokine levels (TNFalpha, IL-1beta, IL-6, IL-10) were measured. RESULTS: The number of circulating lymphocytes significantly decreased at 1 h after surgery in both groups, but the decrease in the CO2 group was significantly smaller than that in the Air group. There was no significant difference in hormone elevation between groups. Serum concentrations of IL-6 and IL-10 in the Air group were significantly higher than in the CO2 group. CONCLUSIONS: CO2 insufflation may reduce cytokine production in laparoscopic cholecystectomy.

Abdominal Muscles↗

Decrease in oral bioavailability of cyclosporin A by coadministration of probucol in rats.

To assess the pharmacokinetic interaction of cyclosporin A with probucol, we administered cyclosporin A (10 mg/kg body weight) to rats orally or intravenously with or without pretreatment of probucol (10 mg/animal, daily for 8 days). The whole blood cyclosporin A concentration-time curves after oral administration showed a 34% reduction in peak concentration and a 30% decrease in area under the blood concentration-time curve (AUC) by administration of probucol. No apparent change in elimination half-life or volume of the central compartment was observed with the treatment of probucol. After intravenous administration of cyclosporin A, the blood levels could be described by a two-compartment open model. No differences were observed in the AUC, elimination half-life or total clearance of cyclosporin A by the pretreatment of probucol. Calculated bioavailability following oral administration of cyclosporin A decreased by 33% with the treatment of probucol. These results suggest that probucol may not profoundly influence the disposition of cyclosporin A. Coadministration of probucol could decrease the fraction of absorbed cyclosporin A after oral administration.

Administration, Oral↗

Daily variation in an intensity of kaolin-induced writhing reaction in mice.

The daily variation in an intensity of kaolin-induced writhing reaction was examined in mice kept under conditions of light; 07:00 - 19:00 and dark; 19:00 - 07:00. The number of writhes was counted for 30 minutes after a single intraperitoneal injection of kaolin at 00:00, 02:00, 04:00, 06:00, 08:00, 10:00, 12:00, 14:00, 16:00, 18:00, 20:00 and 22:00. The number of writhes showed a daily variation with a peak at 18:00 and a trough at 06:00. The intensity of writhing reaction was significantly reduced by pretreatment with the bradykinin B1 (Des-Arg9-[Leu8]-BK) and B2 (icatibant) receptor antagonists. Significant daily variation in this parameter was still observed in the group with the B1 antagonist, but disappeared in the B2 antagonist-treated group. These results suggest that the kaolin-induced writhing reaction shows the daily variation with a peak at the end of the resting period and a trough at the end of the active period. The B2 receptor mediated stimuli appears to be involved in this phenomenon.

Analgesia↗

[Application of gene gun for local-regional cancer].

We studied the in vivo gene transfusion using a gene gun, formerly used in plants and culture cells. The hand-held type gene gun (Helios Gene Gun System) is simple and convenient for effective gene transfection in living animals. This method has some advantages in that there is no need for use of viral vector, independence on the cell cycle and local inducement of plural genes. There is a great possibility for application to local-regional cancer.

Animals↗

Lack of diurnal variation in glomerular filtration rates in the elderly.

The present study was undertaken to examine the effect of age on diurnal variation in glomerular filtration rate (GFR). The GFR, as estimated by creatinine clearance (Clcr), was determined during a 24-hour period in 10 younger (mean +/- SD age 42 +/- 9 years) and 10 older (mean age 75 +/- 4 years) patients with hypertension. Significant diurnal variations in Clcr were observed in the younger patients, with a peak during the day and trough during the night. Such were not observed in the older patients, however. These results suggest that diurnal variation in GFR is affected by age. Chronopharmacologic profiles of drugs, which are mainly excreted in urine by glomerular filtration, might be altered in these patients.

Adult↗

No evidence of a direct venodilatory effect of furosemide in healthy human subjects.

The present study was undertaken to examine whether furosemide, a loop diuretic, has a direct venodilatory effect in healthy male subjects. Furosemide, or amrinone, an inotropic agent with a vasodilatory action, was infused into a dorsal hand vein that had been preconstricted by phenylephrine. The diameter of the vein was measured by a linear variable differential transformer. Venodilation was observed during the infusion of amrinone, but such a response was not detected with furosemide. These findings do not support the hypothesis that furosemide has a direct venodilatory effect in healthy human subjects.

Adult↗

Influences of bathing and hot weather on the pharmacokinetics of a new transdermal clonidine, M-5041T.

The influences of bathing and hot weather on plasma concentrations of clonidine were examined during application of a new transdermal clonidine system, M-5041T, in eight healthy volunteers. An M-5041T patch containing 6 mg of clonidine was applied on the right chest for 96 hours during winter with or without bathing (40 degrees C for 5 minutes) and also during summer without bathing. Plasma concentrations and urinary excretion of clonidine were determined for a 160-hour period after application. Plasma concentrations of clonidine in the winter trials did not differ significantly with or without bathing. Plasma drug concentration as a whole was significantly higher in the summer trial than in the winter trial, however. The maximum plasma concentration (Cmax), area under the plasma concentration-time curve (AUC), and urinary excretion (Ae) of clonidine also tended to be higher in the summer trial. These results suggest that plasma levels of clonidine are higher after application of M-5041T during hot weather. Although the period of bathing used in this study was short, the influence of bathing seems to be negligible.

Administration, Cutaneous↗

Clinical pharmacology of multiple-dose losartan, an angiotensin II receptor antagonist, in patients with essential hypertension.

The pharmacokinetic and pharmacodynamic alterations of multiple doses of losartan, an angiotensin II receptor antagonist, were examined in nine patients with essential hypertension. Participants were given placebo once daily for the first 7 days (from day -7 to day -1), and then 50 mg of losartan for the next 9 days (from day 1 to day 9). The 24-hour blood pressure was measured on days -1, 1, and 7 and blood samples for measurement of losartan and its active metabolite, E-3174, were obtained on days 1 and 7. Plasma concentrations of uric acid and plasma clearance were determined before and during treatment with losartan, and at the end of the study. Pharmacokinetic parameters after the seventh dose, including maximum plasma concentration (Cmax) and time to Cmax (tmax) of losartan and E-3174, did not differ significantly from those after the first dose. The blood pressure lowering effect of losartan, however, was significantly greater after the seventh dose than after the first dose. Plasma uric acid decreased and its plasma clearance (ClUA) increased significantly during repeated administration with losartan. These values returned to pretreatment levels after the end of treatment. These results suggest that although the pharmacokinetic profiles of losartan and E-3174 do not change during repeated administration, the blood pressure lowering effect in hypertensive patients is greater after multiple doses than after a single dose.

Adult↗

Pharmacokinetics of a new thromboxane A2 receptor antagonist, S-1452, and its effect on platelet aggregation in healthy volunteers.

To study the pharmacokinetics of a new thromboxane A2 (TXA2) receptor antagonist, S-1452, eight healthy volunteers were given placebo or S-1452 orally on four occasions in step-wise increasing doses of 10 mg, 25 mg, and 50 mg separated by 2-week intervals. Blood samples for measurement of plasma concentrations of the drug and of its inhibitory effect on platelet aggregation were obtained for 24 hours after administration. Bleeding time after administration was measured. S-1452 was rapidly absorbed, with a peak plasma concentration at 30 minutes after administration. Thereafter, the drug was rapidly eliminated (elimination half-life, 0.4-0.5 hours), and no drug was detected at 6 hours. The inhibitory effect of S-1452 on platelet aggregation, which was stimulated by the TXA2 receptor agonist U-46619, persisted more than 6 hours after drug administration. Bleeding time was slightly prolonged after a single dose of S-1452. These results suggest that although S-1452 is rapidly eliminated in plasma, its inhibitory effects on platelet aggregation persist for a longer period. Careful observations are needed to prevent potential bleeding episodes during repeated treatment with the drug.

Administration, Oral↗