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Biomedical subjects

A Fujimura

Publications and source records attributed to A Fujimura.

At least 91 records · Page 5Linked to original sources
PubMed1998

Changes in immune-endocrine response after surgery.

The authors evaluated the relationship between hormonal and cytokine responses after surgery. Patients who underwent thoracic oesophagectomy (O group; n = 7), pulmonary lobectomy (P group; n = 5), modified mastectomy (M group; n = 5) and laparoscopic cholecystectomy (LC group; n = 7), were randomly selected. Circulating neutrophil and lymphocyte numbers were assayed. Changes in the concentration of the hormones [adrenocorticotrophic hormone (ACTH), cortisol, and antidiuretic hormone (ADH)] and cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), IL-6, and IL-10] were analysed. In O and P groups, neutrophils were still seen on post-operative day (POD) 3, while the leukocyte counts of M and LC groups returned to normal. The number of lymphocytes significantly decreased on POD1 and POD3 only after oesophagectomy. The pattern of hormonal levels was consistent in all groups. While TNF-alpha and IL-1 beta were undetectable in the peripheral blood, the concentration of IL-6 and IL-10 increased in O and P groups, but not in M and LC groups. The degree of lymphocytepenia and neutrophilia correlated well with the extent of surgical trauma.

Adrenocorticotropic Hormone↗
PubMed1998

Timing of lymphocyte transfusion and portal clamping for the development of lethal graft-versus-host disease in the rat.

The effects of surgical intervention on the incidence and augmentation of graft-versus-host disease (GVHD) were studied in the rat. To elicit GVHD, splenocytes from parental LEW rats at a dose of 4 x 10(8) or 1.5 x 10(8) cells/350g body weight were injected via the tail vein into (LEW x BN)F1 rats. The injection of 4 x 10(8) of LEW rat splenocytes induced lethal GVHD in all nontreated F1 rats, while 1.5 x 10(8) of LEW splenocytes did not induce any signs of GVHD. However, when the F1 rats had received the same dose of parental LEW lymphocytes in combination with portal clamping, 14 recipients out of the 15 rats (93%) suffered GVHD and 10 rats (67%) died from GVHD. Interestingly, portal clamping 7 days after the injection enhanced the incidence of GVHD, whereas no GVHD was observed in the intervention group either 3 or 7 days prior to the cell transfusion. When 1.5 x 10(8) of allogeneic lymphocytes were injected intravenously together with 0.1-1.0 mg/kg of endotoxin instead of portal clamping, the injection led the early death by GVHD, while the injection of methylpredonisolone did not enhance GVHD. These results thus indicate that either simultaneous or delayed surgical intervention has the potential to trigger a dormant state in transferred alloreactive lymphocytes.

Animals↗
PubMed1998

Comparison of venodilatory effect of nicardipine, diltiazem, and verapamil in human subjects.

OBJECTIVE: Venodilatory effects of calcium antagonists have not been fully investigated, especially in human subjects. The present study was undertaken to compare the direct venodilatory effects of nicardipine, diltiazem and verapamil using the dorsal hand-vein technique. METHODS: In eight healthy male subjects, increasing doses (0.001, 0.01, 0.1, 1 and 10 microg x min(-1)) of these drugs and saline alone were infused, on four separate occasions, into the dorsal hand vein preconstricted with noradrenaline, and its diameter was measured by a linear-variable differential transformer. RESULT AND CONCLUSIONS: Diltiazem caused significant venodilation at a dose of 0.01 microg x min(-1) or more, while verapamil and nicardipine only caused this effect at 1 microg x min(-1) or more. The potency of the effect was diltiazem > verapamil > nicardipine. The venodilation at a dose of 1 microg x min(-1) was 41.7%, 16.2% and 8.5%, respectively, for each drug. These findings indicate that the venodilatory effect of diltiazem is larger than that of verapamil and nicardipine in human subjects.

Adult↗
PubMed1998

Effects of dopamine on veins in humans: comparison with noradrenaline and influence of age.

OBJECTIVE: To compare the venoconstricting effect of dopamine with that of noradrenaline and to investigate the influence of age on the responsiveness to dopamine in human subjects. METHODS: In eight young and eight elderly male subjects, increasing doses of dopamine or noradrenaline were infused into a dorsal hand vein and its diameter was measured using a linear variable differential transformer. RESULTS: There was no significant difference between the maximum venoconstriction (Emax) for dopamine and that for noradrenaline. The infusion rate to induce 50% of Emax (ED50) for dopamine in the young and elderly subjects was 363 ng x min(-1) and 352 ng min(-1), and the ED50 for noradrenaline was 40.7 ng min(-1) and 43.8 ng x min(-1), respectively. Neither in the Emax nor in the ED50 for these drugs were there significant differences between the young and elderly subjects. CONCLUSION: The venoconstricting effect of dopamine is 5-20 times less than that of noradrenaline, and aging does not influence the responsiveness to dopamine and noradrenaline in human subjects.

Adult↗
PubMed1998

Effect of omeprazole and cimetidine on plasma aldosterone response to angiotensin II.

OBJECTIVE: The Effect of omeprazole, a proton pump inhibitor, and cimetidine, and H 2-receptor antagonist, on plasma aldosterone (PA) response to angiotensin II (AII) were evaluated. METHODS: Furosemide (a loop diuretic agent, 20 mg) was given intravenously to eight healthy subjects during a control period, and after pretreatment with omeprazole (20 mg daily) or cimetidine (800 mg daily) for 6 days. Blood samples for determination of plasma renin activity (PRA), AII, PA, adrenotorticotropic hormone (ACTH) and potassium were obtained just before, and 30, 60 min and 120 min after furosemide administration. RESULTS: PRA, AII and PA increased significantly after furosemide administration whereas ACTH and potassium did not. Significant correlations between plasma AII and PA were obtained in the control and omeprazole trial, but not in the cimetidine trial. The slope of the regression lines of the control and omeprazole trails did not differ significantly. CONCLUSION: These results suggest that, in contrast to cimetidine, the inhibitory effect of omeprazole on AII-stimulated aldosterone production following dosing with furosemide is negligible.

Adrenocorticotropic Hormone↗
PubMed1998

Pharmacokinetic alterations of quinapril during repeated treatment in elderly subjects.

OBJECTIVE: To examine whether the pharmacokinetics of quinaprilat, an active metabolite, change during repeated treatment with quinapril, an ACE inhibitor, in elderly subjects. METHODS: Quinapril (10 mg) was given once daily for 8 days in eight elderly hypertensive subjects (76 years old). Blood samples were obtained for a 24-h period after the first and eighth doses. RESULTS: Plasma concentrations of quinaprilat after the eighth dose significantly higher than those after the first dose. The maximum plasma concentration (Cmax) tended to be greater, and the area under the plasma concentration-time curve (AUC) was significantly greater after the eighth dose. CONCLUSIONS: The study showed an increase in quinaprilat concentrations and subsequent increase in AUC, during repeated treatment with quinapril in elderly subjects. However, the differences observed were very small and of no clinical significance.

Aged↗
PubMed1998

Endoscopic findings in transplanted allo-intestine of rats after discontinuance of immunosuppressive agent.

In clinical practice, graft rejection in small-bowel transplantation should be diagnosed before irreversible condition of the graft. We have already reported the usefulness of endoscopic examination for the early detection of acute rejection in a rat model. Here we evaluated rejection after discontinuance of methyl-deoxyspergualin by endoscopy. Heterotopic small-bowel transplantation was performed by the cuff method from a DA to a LEW rat. Endoscopic and histological examinations were performed through the stomas. Two-week administration of methyl-deoxyspergualin significantly prolonged graft survival. Graft rejection after discontinuance of the agent occurred much more slowly than rejection without the immunosuppressive drug. Erosive mucosal changes were endoscopically observed in the early phase of rejection in rats that did not receive the immunosuppressant. However, endoscopic findings after discontinuance of methyl-deoxyspergualin indicated edematous changes and thickening of the wall without erosion, and, histologically, the grafted intestine showed slowly-progressing rejection with flattened villi. If we pay attention to edematous changes and hardening of intestinal wall, and take selective biopsies, endoscopic examination may improve the early diagnosis of slowly progressive rejection in the clinical setting.

Animals↗
PubMed1998

Platelet protective effect of TAK-029, a novel glycoprotein IIb/IIIa antagonist: an in vitro study.

Previous studies have indicated that exposure of fibrinogen receptors associated with the glycoprotein IIb/IIIa complex contributes to platelet loss during cardiopulmonary bypass. TAK-029 is a newly developed reversible, nonpeptide inhibitor of platelet glycoprotein IIb/IIIa receptors. In this study, we tested the platelet preserving effect of TAK-029 in an in vitro model. The methods included the comparison of the release of beta-thromboglobulin (beta-TG) between a TAK-029 group (n = 5) and a control group (n = 5) in a mock circulation under a shear force generated by a centrifugal pump. To evaluate the degree of beta-TG release, deltabeta-TG/deltaT was calculated where deltabeta-TG is the increase in beta-TG and deltaT is the time. The results showed that the value of deltabeta-TG/deltaT in the TAK-029 group was significantly lower than it was in the control group (4.22 +/- 0.27 x 10(2) ng/ml vs. 7.33 +/- 0.66 x 10(2) ng/ml, respectively). In conclusion, TAK-029 reduced the platelet activation under the shear forces of an in vitro model, suggesting that TAK-029 is a potential candidate for platelet protection during cardiopulmonary bypass.

Blood Platelets↗
PubMed1998

Drug-induced Cushing syndrome in a patient with ulcerative colitis after betamethasone enema: evaluation of plasma drug concentration.

The authors report the induction of Cushing syndrome by daily betamethasone enema in a patient with ulcerative colitis, and they determine for the first time the pharmacokinetic profile of betamethasone after rectal dosing. The authors found high plasma concentrations of betamethasone, which could have been enough to cause Cushing syndrome. Suppression of the hypothalamus-pituitary-adrenal axis disappeared after the dose schedule was changed from every day to three times a week. These findings suggest that a considerable amount of betamethasone is absorbed after rectal dosing.

Administration, Rectal↗
PubMed1998

Panipenem-betamipron and decreases in serum valproic acid concentration.

Serum concentrations of valproic acid (VPA) were reduced to 0% to 40% of the original levels by concomitant use with panipenem-betamipron (PAM-BP) in three patients. The serum VPA level began to decrease 2 days after the administration of PAPM-BP, and it began to increase within 24 hours of the last dose. The rapid change in the serum VPA level suggests the existence of unique and as yet unknown mechanisms of interaction between VPA and PAPM-BP. Epileptic seizures developed in two of the three patients during PAPM-BP use, which signaled the dangers of PAPM-BP administration to patients concomitantly administered VPA. PAPM-BP should not be used in patients administered VPA.

Adult↗
PubMed1998

Time-dependent cyclosporine A-induced nephrotoxicity in rats.

1. We investigated the toxicity of cyclosporine A (CsA) with reference to the timing of its administration in rats. 2. To elucidate the time-dependent effects of CsA on renal function and survival rate, CsA (75 mg/kg per day) or vehicle was orally administered once daily at four different times (3, 9, 15 and 21 h after lights on; HALO) over a period of 21 days to male Wistar rats (n = 56) kept in rooms with a 12 h light-dark cycle. 3. On the 7th day after treatment, creatinine clearances (Ccr) of groups dosed at 3 and 9 HALO (inactive period) were not reduced in comparison with clearances of time-matched control rats, whereas Ccr significantly decreased in rats dosed at 15 and 21 HALO (active period). Cyclosporine A markedly increased urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion in all dosed groups at the 7th day after treatment, except for rats dosed at 3 HALO. In rats dosed at 3 HALO, Ccr decreased progressively; however, it did not decrease progressively in rats dosed at 9 HALO. In surviving rats treated during the inactive period, urine NAG subsequently returned to control levels. Survival rates were greater in animals dosed during inactive periods than those in groups dosed during active periods. 4. Significant differences in CsA-induced toxicity were obvious as a result of the timing of its administration. A different time course between Ccr and urine NAG excretion was observed during repeated CsA administration. Degenerative changes in proximal tubules were demonstrated after chronic administration of CsA, suggesting that severe and persistent tubular damage cannot be assessed by urinary NAG excretion.

Acetylglucosaminidase↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗