Biomedical subjects

H Oguchi

Publications and source records attributed to H Oguchi.

At least 73 records · Page 4Linked to original sources

PubMed1993

Pharmacokinetics of temocapril, an ACE inhibitor with preferential biliary excretion, in patients with impaired liver function.

Six subjects with normal liver function (Group 1) and 7 patients with liver dysfunction (Group 2; mean ICGR15 value 30.5 (5.2)%; range 16 to 56) received a single oral dose of 1 mg temocapril, a prodrug-type ACE inhibitor, with preferentially excreted by the biliary route. The plasma temocapril concentrations in Group 2 at 30 min and 1 h postdose were significantly higher than in Group 1, but the difference had disappeared 2 h postdosing. Although the half life of temocapril diacid in Group 2 was significantly longer than in Group 1, there was no significant difference between the two groups in AUC, Cmax or tmax. In Group 2, urinary recovery of temocapril was significantly increased, suggesting a possible delay in the bioactivation of temocapril into the diacid, but recovery of the diacid itself was not abnormal. ACE inhibitory action in Group 2 remained unchanged. Temocapril is regarded as an ACE inhibitor the disposition and efficacy of which are little affected in patients with impaired liver function.

Adult↗

PubMed1993

Stiffening of connective tissue in elderly diabetic patients: relevance to diabetic nephropathy and oxidative stress.

Limited joint mobility seen in diabetes mellitus is thought to be the result of stiffening of periarticular connective tissue, which is presumably derived from increased cross-linking of collagen related to advanced glycation end products. In this study the extent of the stiffening of connective tissue was measured by the passive extension angle of the metacarpophalangeal joints in 205 elderly diabetic patients. Association with diabetic nephropathy, with which advanced glycation end products have recently been demonstrated to increase, and metabolic abnormalities were also considered. The angle of the metacarpophalangeal joints was significantly correlated with age (r = -0.24, p < 0.01), and was significantly smaller in men than in women (p < 0.01). The angle demonstrated a decrease in association with diabetic retinopathy and nephropathy, and only the association with nephropathy was significant (p < 0.05). The angle was weakly, but significantly, correlated with serum thiobarbituric acid reactants as a measure of lipid peroxides (r = -0.15, p < 0.05), triglyceride (r = -0.20, p < 0.01) and HDL cholesterol (r = 0.19, p < 0.01), but not with blood glucose (r = 0.02), HbA1c (r = 0.06) or duration of diabetes (r = -0.05). In addition, the angle in 14 non-diabetic patients on haemodialysis was significantly (p < 0.05) smaller than that in age- and sex-matched normal subjects. Thus, it was indicated that the stiffening of connective tissue was associated with diabetic nephropathy, serum lipid peroxide and dyslipidaemia. Stiffening of connective tissue seems to be more affected by oxidative stress than non-enzymatic glycation per se.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗

PubMed1993

Pregnancy and successful delivery in a patient with triple heart valve prosthesis.

A 42-year-old patient had a history of rheumatic fever in childhood. At 37 years of age, she underwent a triple heart valve replacement; thereafter, she was followed with the administration of warfarin and methyldigoxin. Her third pregnancy occurred with the last menstruation on 12 March 1990. At the 30th gestational week, she was admitted to the Nagoya University Hospital for the control of anticoagulation and rest. She delivered by cesarean section a healthy male infant weighing 2070 g at 34 weeks of gestation. The post-operative course was uneventful. This report shows that a patient with a three heart valve prosthesis tolerated pregnancy well under intense medical supervision.

Adult↗

PubMed1993

Randomised study of immunotherapy with OK-432 in uterine cervical carcinoma.

OK-432, a streptococcal preparation, was administered to patients with stage Ib and II cervical carcinoma except for adeno- and adenosquamous carcinomas. To evaluate the efficacy of OK-432 precisely, 177 patients were stratified by clinical stage, radiotherapy, and lymph node metastasis after complete radical hysterectomy and pelvic lymphadenectomy. Within each stratum, patients were divided randomly into OK-432 and control groups. 85 patients received OK-432 and 92 patients did not. No significant difference was observed in overall 5-year disease free rates between the OK-432 and the control groups, although the mean diameter of erythema on SU-polysaccharide (SU-PS) skin test was larger in the OK-432 group than in the control group. In stage IIb, a significant difference was observed between the OK-432 and control groups. This difference, however, could be attributed in part to the different incidence of the lymph node metastasis. In stage II without lymph node metastasis, 5-year disease free rate was significantly higher in the OK-432 group.

Adult↗

PubMed1993

Pharmacokinetics of temocapril and enalapril in patients with various degrees of renal insufficiency.

Temocapril is a novel ACE inhibitor that is cleared via dual excretion routes in humans. Borderline or mildly hypertensive patients with normal renal function [group 1, creatinine clearance (CLCR) > 70 ml/min (4.2 L/h), n = 12], moderate renal impairment [group 2, CLCR 30 to 70 ml/min (1.8 to 4.2 L/h), n = 12] or severe renal impairment [group 3, CLCR < 30 ml/min (1.8 L/h), n = 12] received a single oral dose of either temocapril 1 mg (n = 6, each group) or enalapril 5mg (n = 6, each group). These 2 drugs gave similar values for the area under the plasma concentration-time curve (AUC) of the active diacids. The maximum plasma concentration of enalapril diacid was increased 2- and 6-fold in moderate and severe renal impairment, respectively, whereas that of temocapril diacid was not altered. The AUC of enalapril diacid increased 13-fold at CLCR values < 30 ml/min, but that of temocapril diacid increased only 2-fold. The duration of plasma ACE inhibition due to enalapril was greatly prolonged by the impairment of renal function, whereas that due to temocapril was affected very little. Urinary recovery of temocapril diacid was decreased markedly in patients with severe renal dysfunction, most probably because the diacid was excreted through the biliary route. On the other hand, urinary recovery of enalapril diacid remained fairly high even in patients with severe renal impairment, because of extremely high plasma diacid concentrations resulting from the lack of biliary excretion. These observations suggest that temocapril is beneficial in the treatment of hypertension in patients with severely impaired renal function.

Adult↗

PubMed1993

Expression of glycoconjugates in pancreatic, gastric, and colonic tissue by Bauhinia purpurea, Vicia villosa, and peanut lectins.

We have earlier prepared a pancreatic cancer-associated mucin, whose altered carbohydrate structure was recognized by Vicia villosa (VVA), Bauhinia purpurea (BPA), and peanut (PNA) lectins and which was found preferentially in the sera of patients with pancreatic or gastric cancer. Cancer-associated structures of the sugar chain on serum antigen may reflect those occurring in malignant tissues. Accordingly, we investigated the tissue distribution of carbohydrate structures reactive to these lectins by using lectin histochemistry in pancreatic cancer, gastric cancer, and colonic cancer tissue specimens and in their normal counterparts. VVA showed a higher affinity for pancreatic cancer (77.5%), gastric cancer (89%), and colonic cancer (87%) cells than for the cells of their normal counterparts, whose affinity was 0%, 41.7%, and 36.4%, respectively. PNA showed a higher affinity for pancreatic (70%) and colonic cancer cells (86.5%). BPA failed to show significant binding differences between neoplastic and normal cells in any of the pancreatic, gastric, or colonic tissue specimens. It did, however, bind to intraductal contents in most of the pancreatic cancer tissues but bound to intraductal contents in only a few chronic pancreatitis and normal pancreatic tissues. VVA and PNA did not bind to intraductal contents in any of the normal, chronic pancreatitis, or pancreatic cancer tissues. These results imply that, among the lectins used so far, VVA has the highest affinity for neoplastic cells, and it may provide a supplement for use in the pathologic diagnosis of malignant diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1992

Protective effect of vitamin E supplementation on increased thermal stability of collagen in diabetic rats.

Products similar to non-enzymatic glycation end products are known to arise from the interactions between proteins and lipid peroxides in vitro. In this study, we assessed the effect of vitamin E, which possibly modifies lipid peroxide, on advanced glycation end products or similar products in vivo by measuring the fluorescence and thermal rupture time of tail tendon collagen in streptozotocin-induced diabetic rats. The diabetic rats and non-diabetic rats were fed a vitamin E supplemented diet, and a control diet starting 3 days after the streptozotocin injection. After the 4-week treatment, the serum lipid peroxide levels expressed as thiobarbituric acid reactants in the diabetic rats on control diet (15.9 +/- 2.6 mumol/l[SEM]) were significantly (p less than 0.05) higher than in the non-diabetic rats (7.9 +/- 1.3 mumol/l on control diet and 3.3 +/- 0.4 mumol/l on supplemented diet), but the levels in the diabetic rats on supplemented diet (7.9 +/- 2.3 mumol/l) were reduced to the normal levels. No significant differences were found in serum glucose and glycated haemoglobin levels within the diabetic rats on control and supplemented diets. Both the fluorescence and thermal rupture time of collagen were significantly (p less than 0.05) increased in the diabetic rats on both diets compared with those in the corresponding non-diabetic rats. Although there was no significant difference in the collagen-linked fluorescence within the diabetic rats on control and supplemented diets, the thermal rupture time was significantly (p less than 0.01) shortened with supplemented diet (10.8 +/- 0.7 min on supplemented diet vs 15.0 +/- 0.7 min on control diet).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Ultrastructural study of the glomerular slit diaphragm in fresh unfixed kidneys by a quick-freezing method.

In normal kidneys fixed by perfusion with tannic acid and glutaraldehyde, glomerular slit diaphragms have been reported to consist of highly ordered and isoporous substructures with a zipper-like configuration. We have re-evaluated the ultrastructure of fixed or unfixed glomeruli using quick-freezing and deep-etching (QF-DE) and freeze-substitution (QF-FS) methods. In the fixed slit diaphragms, zipper-like substructures were often observed by the QF-DE method. In contrast, in fresh unfixed glomeruli the slit diaphragms mainly consisted of non-porous substructures. The slit diaphragms were more widely opened in the fixed glomeruli, as examined by the QF-FS method. These results suggest that the foot processes shrink during tissue preparation by conventional methods with chemical fixatives, and that the broadening of slit diaphragms and zipper-like substructures are formed by the pulling apart of adjacent foot processes due to shrinkage.

Animals↗

PubMed1992

Effects of the S2-serotonergic receptor antagonist, ketanserin, on cerulein-induced pancreatitis in the rat.

We investigated the effects of ketanserin, a S 2 (5-hydroxytryptamine 2; 5-HT 2)-serotonergic receptor antagonist, on cerulein-induced pancreatitis in the rat. Large pharmacological doses of cerulein induced acute pancreatitis in the rat. Ketanserin reduced the cerulein-induced increase in serum amylase concentration in a dose-dependent manner. Treatment with 10 mg/kg of ketanserin per os markedly improved cerulein-induced pancreatitis and was associated with a significant reduction of the increase in serum amylase concentration. In addition, a very specific serotonin S 2 antagonist, ritanserin which has no antihypertensive effect, also reduced the cerulein-induced increase in the serum amylase concentration. These results suggest that S 2 (5-HT 2) may play a role in pathophysiology of cerulein-induced pancreatitis in the rat.

Acute Disease↗

PubMed1992

No significant effect of vitamin E deficiency or supplementation on collagen-linked fluorescence in skin of diabetic rats.

It is speculated that oxidative stress in vivo may have some influence on advanced, nonenzymatic, glycosylation end products. However, this has not been demonstrated yet. We assessed changes in collagen-linked fluorescence in the skin of nondiabetic and streptozotocin-induced diabetic rats fed three different diets for 4 weeks that could modify oxidative stress: vitamin E-deficient (D), vitamin E-supplemented (S), and control (C). The serum lipid peroxide level expressed as thiobarbituric acid (TBA) activity in diabetic rats on the S diet (9.6 +/- 1.0 [SE] nmol/L/mL) was significantly (P less than .01) lower than that in rats on the D diet (111.4 +/- 22.4), and similar to that in nondiabetic rats on the C diet (12.4 +/- 2.2). The collagen-linked fluorescence level was significantly (P less than .01) higher in diabetic rats than in nondiabetic rats, which corresponded to the serum glucose and glycosylated hemoglobin levels. However, there were no significant differences in the fluorescence levels among three groups classified by three different diets in both nondiabetic and diabetic rats (21.7 +/- 1.7 arbitrary U/mg collagen for D, 22.3 +/- 2.0 for C, and 22.8 +/- 2.5 for S in nondiabetic rats v 41.2 +/- 4.1 for D, 40.1 +/- 4.7 for C, and 39.3 +/- 3.5 for S in diabetic rats), despite significant changes in serum lipid peroxide levels. Consequently, there were no significant changes found in collagen-linked fluorescence levels in diabetic rats wherein oxidative stress was modified by vitamin E deficiency and supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Seven tumor markers in benign and malignant germ cell tumors of the ovary.

Seven tumor markers were analyzed clinically in 135 patients with germ cell tumors of the ovary who were treated in Tokai Ovarian Tumor Study Group, an association comprising Nagoya University and its affiliated hospitals, between January 1979 and September 1990. Positive rate of AFP was 100% (36/36) in yolk sac tumor, 61.9% (13/21) in immature teratoma, and 11.8% (2/17) in dysgerminoma, but there were no positive cases of mature cystic teratoma with malignant transformation (0/7) and mature cystic teratoma (0/31). Positive rate of CA125 was over 50% in all tumor types except mature cystic teratoma, which showed a positive rate of 23.7%. CA125 was useful for the screening of malignant germ cell tumors. CA19-9 showed a high positive rate in teratomatous tumors, which were immature teratoma, mature cystic teratoma with malignant transformation, and mature cystic teratoma. Dysgerminoma and yolk sac tumor, especially dysgerminoma, had a high positive rate of LDH. TPA and CEA were not considered useful tumor markers for germ cell tumors of the ovary.

Biomarkers, Tumor↗

PubMed1992

Cytotoxicities of oxides, phosphates and sulphides of metals.

The cytotoxicities of oxides, phosphates and sulphides, which possibly form on dental alloys, were tested using the 'agar method'. The relative magnitudes of the cytotoxicities of these compounds exhibited tendencies similar to those of the metal components in the compounds. In correlation with dental amalgams, zinc oxide was the most cytotoxic, just as with metallic zinc, while tin oxides and mercury oxides exhibited no cytotoxicity. Zinc was the most influential element in the cytotoxicity of dental amalgams. On the other hand, in correlation with Ni-Cr alloys, Co-Cr alloys, and/or stainless steels a chromium oxide and a cobalt oxide showed serious cytotoxicity, whereas the iron oxides were non-cytotoxic. Sulphides, which possibly form on silver alloys, showed cytotoxicity. Oxides and phosphates of titanium and aluminium, and hydroxyapatite, were not cytotoxic, supporting the use of these materials for implants. Not only the valence of an element but also the chemical species combining with the element affect the cytotoxicity of the alloy containing it.

Biocompatible Materials↗

PubMed1992

Evaluation of a high-velocity flame-spraying technique for hydroxyapatite.

Titanium alloy sprayed with hydroxyapatite (HA) was developed by a high-velocity flame-spraying technique (HVFST). Biocompatible responses of bony tissues to high-velocity flame-sprayed HA (HVFS-HA) implanted into tibias of adult male rabbits was investigated 4 and 18 months after implantation by light and electron microscopy. Both light and electron microscope features in histological sections showed that inflammatory responses of tissues in situ were completely cleared and the interface between the bone and the implant was filled with newly formed bony substrate. This suggests that the HVFS-HA was sufficiently biocompatible to be adapted to the bone in situ.

Alloys↗

PubMed1992

Possible participation of a prostaglandin E1 analogue in the aggravation of diabetic nephropathy.

A relation between the progression of diabetic nephropathy and glomerular hyperfiltration has been speculated. We describe two cases of non-insulin-dependent diabetic males aged 55 and 59 years in whom diabetic nephropathy was aggravated during the administration of limaprost, a a prostaglandin E1 analogue with a vasodilatory action. We also observed a short-term effect of limaprost on renal hemodynamics in three cases with diabetic nephropathy. In case 1, one year after limaprost administration the serum albumin level fell from 3.6 to 2.6 g/dl and the serum creatinine level rose from 1.0 to 1.6 mg/dl. In case 2, 9 months after limaprost administration the serum albumin level fell from 3.6 to 2.9 g/dl and the serum creatinine level rose from 1.8 to 2.3 mg/dl. In the latter stages of limaprost administration, the downslopes of reciprocal serum creatinine against time appeared to be augmented in the two cases. After the 3-day administration of limaprost, the peripheral and renal blood flows, and the glomerular filtration rate (GFR) were observed to rise, but the filtration fraction (FF) and urinary protein output were elevated. Keeping in mind the pre-existing renal damage, the increases in GFR and FF suggested acceleration of compensatory glomerular hyperfiltration in less damaged surviving glomeruli. The sustained acceleration of hyperfiltration with long-term administration of limaprost as an exogenous vasodilatory prostaglandin was assumed to eventuate in the aggravation of diabetic nephropathy. Attention should be paid to drugs which increase GFR in patients with established diabetic nephropathy.

Alprostadil↗

PubMed1992

Accumulation of cis-diamminedichloroplatinum (II) and its analogues in sensitive and resistant human ovarian carcinoma cells.

Human ovarian carcinoma cell line (NOS2), established from a patient with serous cystadenocarcinoma of the ovary, has been exposed to a stepwise increase in cis-diamminedichloroplatinum (II) (CDDP) concentration to produce a CDDP-resistant cell line NOS2CR) as an experimental model for resistance to CDDP. NOS2CR cells showed a 7-fold resistance to CDDP and a lesser degree of cross-resistance to diammine (1,1-cyclobutanedicarboxylato)-platinum (II) (CBDCA) and (-)-(R)-2-aminomethylpyrrolidine (1,1-cyclobutanedicarboxylato) platinum (II) (DWA2114R). In the absence of CDDP, cross-resistance to DWA2114R was reduced to the original level by 2 months, although 83% resistance to CDDP remained up to 6 months. To investigate CDDP-resistant mechanisms, alterations in the intracellular accumulation of CDDP and analogues were assayed by atomic absorption. In both NOS2 and NOS2CR cells, accumulation of CDDP increased linearly with time and was concentration-dependent. NOS2CR cells demonstrated 71, 52 and 12% reduction in accumulation of CDDP, CBDCA, and DWA2114R, respectively. These reductions did not seem to be due to P-glycoprotein, because expression of multidrug-resistant 1 gene was not detected in either NOS2 or NOS2CR cells. These studies indicate that the mechanisms of resistance to CDDP and analogues in NOS2CR cells are related in the main to reduced intracellular accumulation of drugs. DWA2114R might be helpful to treat CDDP-resistant and recurrent tumors which were treated by CDDP.

Antineoplastic Agents↗

PubMed1992

Insulin-dependent diabetes mellitus showing microangiopathic hemolytic anemia and chronic disseminated intravascular coagulation.

It has been reported that microangiopathic hemolytic anemia occasionally occurs in patients with severe diabetic microangiopathy. We report a case of insulin-dependent diabetes mellitus in whom microangiopathic hemolytic anemia and chronic disseminated intravascular coagulation (DIC) were thought to be complicated. The patient showed fragmentation hemolytic anemia and progressive diabetic microangiopathy, together with a mild elevation of serum fibrin(ogen) degradation products. Considering the state of chronic DIC, heparin therapy was started, but mild hemolysis persisted. It is possible that microangiopathic hemolytic anemia and chronic DIC cause a vicious cycle in patients with severe diabetic microangiopathy, leading to rapid progression of diabetic microangiopathy.

Adult↗

PubMed1992

Clinical evaluation of pancreatic cancer-associated mucin expressing CA19-9, CA50, Span-1, sialyl SSEA-1, and Dupan-2.

We have previously described the purification and partial characterization of a new pancreatic cancer-associated antigen, a pancreatic cancer-associated mucin expressing CA19-9, CA50, Span-1, sialyl SSEA-1, and Dupan-2. This study describes the clinical evaluation of various assay systems for this antigen which depend on measuring respective serum levels. Elevated levels of antigen were detected in the sera from both patients with malignant and non-malignant diseases. However, elevated serum levels of CA19-9 and Lewisa and Lewisb epitopes on moieties were restricted to pancreatic and biliary tract cancers, although adequate sensitivity was not attained. Coordinate evaluation of these three markers improved the sensitivity to some extent without loss of specificity for the diagnosis of pancreatic and biliary tract cancers, because of the heterogeneity of the coexpression of these epitopes. We developed additional assay systems with a combination of this antigen and two lectins (Bauhinia purpurea (BPA) and Vicia villosa (VVA)). Elevated levels of BPA- and VVA-reactive antigens were detected in 41% and 31%, respectively, of pancreatic cancer sera samples. Few patients with chronic pancreatitis had an elevated serum level of either antigen, and higher elevated levels of these markers were restricted to the sera of patients with malignancies. Our results suggest that this antigen is found in the sera of patients with various conditions and in the sera of normal subjects but that antigens bearing CA19-9 or Lewisa or Lewisb epitopes and an altered carbohydrate structure recognized by BPA and VVA lectins are preferentially present in the sera of patients with pancreatic and other malignancies.

Antigens, Neoplasm↗

PubMed1992

Beneficial effect of dibutyryl cyclic AMP (DBcAMP) on ischemic acute renal failure in the rat.

To determine the effect of dibutyryl cyclic AMP (DBcAMP) on ischemic acute renal failure (IARF), that disorder was induced in male Wistar rats. After the animals were anesthetized with sodium pentobarbital (50 mg/kg, i.p.), the right kidney was removed and the left renal pedicle was clamped for 60 min. DBcAMP (5 mg/kg, i.p.) was given each 30 min before and after the renal pedicle clamping in half the dose each. Twenty-four hours after surgery, the levels of serum creatinine, BUN, serum potassium, and FENa% were significantly less elevated; and the total urine volume was significantly less decreased for 24 h in the group of IARF given DBcAMP than in the group of IARF alone. The elevation in Ca2+ content of the renal cortex was also significantly lower in the group of IARF given DBcAMP than in the group of IARF alone. These data indicate that DBcAMP can produce a beneficial effect on experimentally induced IARF. Since the intracellular accumulation of Ca2+ has been reported to be a potentially harmful factor in the development of IARF, it is suggested that the effect of DBcAMP on IARF can be in part due to an inhibition of the intracellular accumulation of Ca2+ in the kidney.

Acute Kidney Injury↗