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Biomedical subjects

K Kido

Publications and source records attributed to K Kido.

At least 55 records · Page 3Linked to original sources

Effects of N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) on insulin and glucagon secretion in isolated perfused rat pancreas.

N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) has a structure which differs from those of other known blood glucose-lowering agents including sulfonylureas. It has been shown that oral administration of A-4166 exerts blood glucose-lowering effects in animal in vivo studies. In the present study, we investigated the effects of A-4166 on insulin and glucagon secretion at several glucose concentrations using isolated perfused rat pancreas preparations. Both 3.0 and 30 mumol/l A-4166 significantly stimulated insulin secretion as compared with basal levels at glucose concentrations of 8.0 and 11.0 mmol (p < 0.01 and p < 0.05, respectively). In contrast, glucagon secretion was not affected by administration of A-4166 up to 30 mumol/l at these glucose concentrations. At a glucose concentration of 5.6 mmol/l, neither 0.3 nor 3.0 mumol/l A-4166 produced significant changes in insulin and glucagon secretion. However, A-4166 at 30 mumol/l significantly stimulated insulin secretion and inhibited glucagon secretion as compared with basal levels (p < 0.01 and p < 0.01, respectively). We conclude that A-4166 at 3.0 and 30 mumol/l directly stimulates insulin secretion but has little effect on glucagon secretion in isolated perfused rat pancreas at glucose concentrations of 8.0 and 11.0 mmol/l. these results, taken together with previously published data, suggest that oral administration of A-4166 could be a useful strategy for stimulating endogenous insulin secretion in non-insulin-dependent diabetic patients.

Animals↗

[Research trend for pathogenesis of sarcoidosis--streptococcal cell wall component (SCW)].

In search for the pathogenetic factors, we have found the following: 1) Chronic bacterial foci in the upper airway is showing adverse effect on clinical course of sarcoidosis. Alpha-streptococcus is mainly detected. 2) The prevalence of chronic tonsillitis in sarcoidosis is high if compared with that among Japanese adults examined by rhinolaryngologists. 3) The development of noncaseating epithelioid granulomas is reported after injections of an aqueous suspension of alpha-streptococcal cell wall (SCW) fragments into susceptible Lewis female rats. 4) Both protracted clinical course in sarcoidosis and higher responsiveness to SCW antigen are related to HLA-DR4, DR9 and DRw8. These results suggest that in sarcoidosis significance of persistence of antigen in upper respiratory tract and the significant correlation between SCW binding to Ia and immunogenicity, implicated by Schaeffer's, are seen.

Adult↗

[The prediction of blood pressure after adrenalectomy in primary aldosteronism].

In 30-40% of patients with primary aldosteronism owing to adenoma, hypertension is not relieved even though a hyper-functioning adenoma has been completely removed. The purpose of this study is to determine whether the prognosis of hypertension can be evaluated pre-operatively in patients with primary aldosteronism. Thirteen patients (6 men, 7 women; 47 +/- 9 years old) with primary aldosteronism were studied and adrenalectomy was performed in all cases. The success of the operation was confirmed by the normalization of plasma renin activity (PRA), plasma aldosterone concentration (PAC) and serum potassium. Eight patients, 3 men and 5 women, whose blood pressure (BP) was reduced to below 140mmHg systolic and 90mmHg diastolic at one year after the operation were classified as "group N" and the other 5 cases, 3 men and 2 women, remained hypertensive and were classified as "group H". There were no significant differences in the age of the patients, duration of hypertension, pretreatment mean BP and severity of hypertension between the two groups. Thus, it is doubtful that the lack of improvement of hypertension is due to the irreversible damage of the small arteries. Although pretreatment BP was similar in the two groups, systolic BP after the administration of 200mg per day of spironolactone for one week was significantly reduced in group N, but not in group H. Moreover, a significant correlation was found between mean BP after treatment with spironolactone and post-operative mean BP in all subjects. Pretreatment PRA was significantly lower in group H.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

Protective effect of the calcium channel blocker diltiazem on hepatic function following warm ischemia.

The purpose of this study was to investigate the protective effect of a calcium channel blocker diltiazem (DTZ) on hepatic ischemic injury using a canine model. Hepatic ischemia was induced by temporary clamping of hepatic afferent blood vessels for 60 min with establishment of a portojugular bypass. The administration of DTZ at a dose of 70 micrograms/kg bolus i.v. injection before hepatic ischemia and thereafter via the portal vein at a dose of 10 micrograms/kg/min well restored the hepatic blood flow (HBF, 92 +/- 5%; P < 0.01) and arterial ketone body ratio (AKBR, 1.15 +/- 0.16; P < 0.01) 1 hr after interruption compared with untreated controls (HBF, 61 +/- 7%; AKBR, 0.53 +/- 0.09). In addition, the increase of plasma lactate level and the decrease of mean arterial pressure were significantly suppressed after ischemia (P < 0.05). We concluded that DTZ has a protective effect on ischemia-induced hepatic damage and might be useful in the prevention of primary graft failure caused by warm ischemia in liver transplantation.

Animals↗

Effects of alpha 2- and beta-adrenergic agonism on glucagon secretion from perfused pancreata of normal and streptozocin-induced diabetic rats.

Insulin secretion is known to be inhibited by alpha 2-adrenergic agonism and stimulated by beta-adrenergic agonism in both experimental animals and humans. In contrast, adrenergic regulation of glucagon secretion remains controversial. This study was designed to determine the effects of alpha 2- and beta-adrenergic agonism on islet alpha cells, using isolated perfused pancreata of normal and streptozocin-induced diabetic (STZ-D) rats. The alpha 2-adrenoceptor agonist clonidine at a concentration of 10(-7) mol/L significantly stimulated glucagon secretion as compared with basal levels in both normal (1,286 +/- 90 v 417 +/- 53 ng/L, P < .01) and STZ-D rats (551 +/- 86 v 130 +/- 19 ng/L, P < .01). Also, the beta-adrenoceptor agonist isoproterenol at a concentration of 10(-7) mol/L significantly stimulated glucagon secretion as compared with basal levels in both normal (751 +/- 130 v 347 +/- 41 ng/L, P < .05) and STZ-D rats (182 +/- 22 v 92 +/- 20 ng/L, P < .01). Furthermore, these alpha 2- and beta-agonistic effects were almost completely inhibited in the presence of the alpha 2-adrenoceptor antagonist yohimbine and the beta-adrenoceptor antagonist propranolol at a concentration of 10(-6) mol/L, respectively. Insulin secretion was markedly reduced in STZ-D rats. These results suggest that even in a severely diabetic state, not only beta- but also also alpha 2-adrenergic agonism stimulates glucagon secretion from rat pancreatic alpha cells.

Adrenergic alpha-Agonists↗

Development of an artificial placenta: survival of isolated goat fetuses for three weeks with umbilical arteriovenous extracorporeal membrane oxygenation.

The purpose of our study was to examine the feasibility of long-term extrauterine incubation of an isolated premature fetus in artificial amniotic fluid with arteriovenous extracorporeal circulation. Two premature goat fetuses (age 120 and 128 days) were incubated in an isothermal artificial amniotic fluid incubator with arteriovenous extracorporeal membrane oxygenation via the umbilical vessels. We administered pancuronium bromide to suppress fetal movement and swallowing because movement and swallowing have been implicated in fetal deterioration during extrauterine fetal incubation. The fetuses maintained stable circulatory and respiratory parameters. The total incubation time was 494 and 543 h. The animals were then removed from the incubator and stimulated to initiate lung respiration. With ventilator support, both animals maintained stable blood-gas exchange and survived for more than 1 week. These results clearly indicate that umbilical arteriovenous extracorporeal membrane can effectively support extended extrauterine incubation of an isolated premature fetus.

Amniotic Fluid↗

[Clinical evaluation of the long-term treatment with chlormadinone acetate in patients with benign prostatic hypertrophy].

Fifty patients with benign prostatic hypertrophy were treated with chlormadinone acetate (CMA) at the dose of 50 mg/day for 12 months. Subjective symptoms and objective findings were evaluated before, and after 4 and 12 months of treatment. Better improvement was observed in all of the subjective symptoms and in almost all the parameters of objective findings, in proportion to the period of CMA treatment. Generally speaking, 12 months of treatment was more effective than 4 months of treatment. Two patients had impotence (4.0%). Both of them complained of side effects within 4 months after treatment, but they were not severe. In conclusion, long-term treatment of benign prostatic hypertrophy with CMA was useful.

Aged↗

Glucose-induced insulin secretion and alpha 2-adrenergic receptor subtypes.

alpha 2-Adrenoceptor antagonists have been investigated in human in vivo studies as new oral antihyperglycemic agents. alpha 2-Adrenoceptors are subdivided into alpha 2A and alpha 2B subtypes by using receptor-binding methods or cloning methods. This study was designed to determine the alpha 2-adrenergic receptor subtype(s) involved in glucose-induced insulin and glucagon secretion from the isolated perfused rat pancreas at a glucose concentration of 16.7 mmol/L. Both the alpha 2A-preferential agonist oxymetazoline and the non-subtype-selective alpha 2-agonist p-aminoclonidine, at concentrations above 10(-9) mol/L, significantly inhibited glucose-induced insulin secretion (p < 0.05 and p < 0.01, respectively) and stimulated glucagon secretion from 10(-7) mol/L, as compared with basal levels (p < 0.01, respectively). In contrast, the alpha 1-selective agonist phenylephrine, at concentrations up to 10(-6) mol/L, affected neither insulin nor glucagon secretion as compared with basal levels. Furthermore, the non-subtype-selective alpha 2-antagonist rauwolscine, at concentrations above 10(-6) mol/L, and the alpha 2A-preferential antagonist WB-4101, at 10(-5) mol/L, significantly antagonized the effects of 10(-7) mol/L p-aminoclonidine on both insulin and glucagon secretion (p < 0.01 and p < 0.05, respectively). In contrast, neither the alpha 1- and alpha 2B-selective antagonist prazosin nor the alpha 2B-preferential antagonist chlorpromazine, at concentrations up to 10(-5) mol/L, antagonized the effects of p-aminoclonidine. These results suggest that alpha 2A rather than alpha 2B-adrenergic agonism inhibits glucose-induced insulin secretion and stimulates glucagon secretion in the isolated perfused rat pancreas.

Adrenergic alpha-Agonists↗

[Experimental study of multi-visceral transplantation in dogs].

The purpose of the present study was to examine the technical, functional and immunologic aspects in the multivisceral transplantation using canine model. After removal of upper abdominal organs en bloc, the composite graft including the liver, pancreas, spleen and duodenum was orthotopically transplanted in 35 dogs. Ten recipients survived more than 3 days, and 6 more than 6 days. Cause of early death was massive lymphatic leakage, and late death was due to acute rejection or other complications. As technical considerations, perfusion of the graft should be only via aorta to prevent pancreatic edema, and reperfusion should be at first with arterial blood flow to minimize the ischemic damage of the graft. Hepatic and pancrease-endocrine functions were recovered by 3 days, after grafting, and 2-3 days later pancreas-exocrine function was restored. Thereafter the hepatic function was progressively deteriorated again from 6 to 8th day, although the pancreatic function was well maintained until death. At autopsy this hepatic dysfunction was histologically confirmed to be caused by severe acute rejection. On the other hand, the pancreas and duodenum were morphologically almost normal. The results demonstrated the dissociation in functional recovery after grafting and extent of rejection reaction among each grafted organ in the multivisceral transplantation.

Animals↗

[Clinical significance of flow cytometric DNA analysis in patients with rectal cancer].

DNA content was measured by flow cytometry using paraffin-embedded material from 148 primary rectal cancers and 10 distant metastatic lesions. DNA ploidy pattern was classified into the following three groups in terms of the DNA index: 1.00 was defined as the diploid group (DP), 1.00 < DNA index < 1.60 as the low-aneuploid group (LAP) and > or = 1.60 as the high-aneuploid group (HAP). Primary carcinomas were DP in 26.4%, LAP in 36.5% and HAP in 37.1%. The DNA ploidy pattern of the primary tumor correlated well with clinicopathological findings such as depth of invasion, lymphatic invasion, pathological stage, metastasis to distant organs and curability of the tumor. In patients with HAP tumor after curative operation, the recurrence rate (21.6%) in distant organs was significantly higher than those with DP tumor (2.8%) and LAP tumor (6.4%) [p < 0.05]. Two LAP patients and 8 HAP patients with distant metastatic disease had the same DNA ploidy pattern HAP in the metastatic lesions. These data indicate that tumor DNA ploidy patterns classified into three groups in rectal cancer may play an important role in predicting prognosis, including distant metastasis.

DNA, Neoplasm↗

Sequence-dependent cleavage of DNA by alkylation with antisense oligodeoxyribonucleotides containing a 2-(N-iodoacetylaminoethyl)thio-adenine.

Antisense oligodeoxyribonucleotides (15mers), containing a 2-(N-iodoacetylaminoethyl)thio-adenine, were synthesized and tested for their ability to cleave complementary DNAs (21mers). Cleavage of the target DNAs was done by alkylation followed by treatment with piperidine, and the positions of the alkylated sites were estimated by identification of the cleaved products. By using several combinations of the modified strands and their target DNAs, it was determined that alkylation occurred at adenine or guanine, depending on the torsion angle of the modified nucleoside.

Adenine↗

Initial hepatic metabolic function in canine liver and pancreas cluster transplantation.

In this study, initial hepatic metabolic function was evaluated by determining the arterial ketone body ratio (AKBR) and plasma amino acid concentrations in an experimental orthotopic combined hepatopancreatic transplantation (OHPT), and comparing the same values in orthotopic liver transplantation (OLT). In OHPT, AKBR decreased in the anhepatic phase and recovered to the preoperative value just 1 h after reperfusion. On the other hand, in OLT, the recovery of AKBR took 3 h after reperfusion with a significant difference compared to OHPT (P less than 0.05). Plasma amino acid levels, especially alanine and total free plasma amino acids increased in the anhepatic phase and recovered within 1 h of reperfusion in OHPT. However, they did not recover until 3 h after reperfusion in OLT. This rapid recovery of hepatic metabolic function in OHPT should be attributed to the order of reperfusion in which the reconstruction of arterial blood flow precedes that of portal blood flow. This model is useful for assessing the best way by which the grafted liver can for assessing the best way by which the grafted liver can control the timing, order, rate, and volume of blood that should be released.

Amino Acids↗

Arachidonic acid metabolites and alpha 2-adrenoceptor-mediated glucagon secretion in rats.

Effects of phospholipase A2 inhibitor, cyclooxygenase inhibitor and lipoxygenase inhibitor on glucagon secretion induced by the alpha 2-adrenergic agonist clonidine were studied in the isolated perfused rat pancreas. The phospholipase A2 inhibitor mepacrine at 25 and 50 mumol/l significantly inhibited glucagon secretion induced by 0.1 mumol/l clonidine (P less than 0.01, respectively), whereas 5 mumol/l mepacrine did not affect clonidine-induced glucagon secretion. Also, both 100 mumol/l acetylsalicylic acid (cyclooxygenase inhibitor) and 100 mumol/l caffeic acid (lipoxygenase inhibitor) significantly inhibited clonidine-induced glucagon secretion (P less than 0.01, respectively), whereas neither 10 mumol/l acetylsalicylic acid nor 10 mumol/l caffeic acid affected clonidine-induced glucagon secretion. None of the drugs at the tested concentrations affected insulin secretion at a glucose concentration of 5.5 mmol/l. These results suggest that not only cyclooxygenase metabolites but also lipoxygenase metabolites are involved in the stimulation of glucagon secretion mediated through the alpha 2-adrenergic receptors in perfused rat pancreas.

Animals↗