Biomedical subjects

C D Kim

Publications and source records attributed to C D Kim.

At least 55 records · Page 3Linked to original sources

PubMed1998

The in vitro pharmacological profile of KR31080, a nonpeptide AT1 receptor antagonist.

KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol- 5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT1) receptors in rabbit aorta and human recombinant AT1 receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (AII) with decreased maximal response (pD'2 = 10.1 +/- 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [125I]AII binding to rabbit aortic membranes (AT1 receptors) and [125I][Sar1, Ile8]AII binding to human recombinant AT1 receptors in a concentration-dependent manner with IC50 values of 0.84 +/- 0.08 nM and 1.92 +/- 0.15 nM, respectively, but did not inhibit specific [125I]AII binding to bovine cerebellum membranes (AT2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT1 receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT1 selective angiotensin receptor antagonist which exerts a competitive antagonism in the [125I]AII binding assay and insurmountable AT1 receptor antagonism in the functional study.

1-Sarcosine-8-Isoleucine Angiotensin II↗

PubMed1998

Effects of levosulpiride in patients with functional dyspepsia accompanied by delayed gastric emptying.

OBJECTIVES: Levosulpiride is the levo-enantiomer of sulpiride, a well-known antiemetic, antidyspeptic and antipsychotic drug. This study was undertaken to investigate the effects of levosulpiride on dyspeptic symptoms and gastric motor function in a group of patients with functional dyspepsia showing delayed gastric emptying. METHOD: Forty two eligible patients were entered into a 3 week, double-blind randomized comparison of 25mg of levosulpiride or placebo t.i.d.. Symptom assessment and gastric scintigraphy following the intake of scrambled egg sandwich, were performed in each patient before and after treatment. RESULTS: The improvement of symptom score in levosulpiride group was higher than the placebo group (p < 0.05). We assessed global efficacy, which was excellent in 1 (6%), good 11 (65%), fair 4 (24%), nil 1 (6%) of those receiving levosulpiride, and fair 9 (60%), nil 5 (33%), poor 1 (6%) of those receiving placebo. Levosulpiride tended to be more effective than placebo in relieving the dyspeptic symptoms especially in the subgroups of dysmotility-like (p < 0.05) and nonspecific (p < 0.05) as compared to other subgroups (p = 0.16). The reduction of gastric emptying time after levosulpiride treatment was more marked than Placebo group (p < 0.05). We found a significant correlation between changes of symptom score and gastric emptying time (r = 0.47, p = 0.01). No serious adverse effects were reported after administration of either levosulpiride or placebo. Only two patients reported mild somnolence during levosulpiride administration. CONCLUSIONS: Levosulpiride is effective and well tolerated in patients with functional dyspepsia accompanied by delayed gastric emptying. Its efficacy may be related to its action on the gastric motor function by improving the delayed gastric emptying.

Adolescent↗

PubMed1998

Bone marrow immunoscintigraphy (BMIS): a new and important tool for the assessment of marrow fibrosis in renal osteodystrophy?

One of the classic histologic forms of renal osteodystrophy is osteitis fibrosa, and its distinguishing characteristic is bone marrow (BM) fibrosis, caused by the activation of marrow parenchymal cells. A bone biopsy must be performed in order to establish the diagnosis of renal osteodystrophy. The clinical use of bone biopsy is restricted, however, due to the invasiveness of the procedure. In recent studies, bone scans have provided information useful for the differential diagnosis between osteomalacia and osteitis fibrosa. However, bone scans can not provide information on the bone marrow status. Bone marrow immunoscintigraphy (BMIS) using Tc-99m anti-granulocyte antibody (AGA), a highly sensitive test for the detection of bone marrow abnormalities which is also a noninvasive method, has rarely been reported in chronic renal failure (CRF). BMIS can provide information in patients with myelofibrosis. The purpose of this study was to evaluate the usefulness of BMIS in CRF patients with special regards to biochemical parameters. Nineteen CRF patients (13 men, 6 women; mean age: 48 +/- 11 years) in whom bone scintigraphy using Tc-99m MDP (methylene diphosphonate) showed the so-called superscan pattern were included in the study. Their primary renal diseases were chronic glomerulonephritis (n = 14), diabetes (n = 4), and polycystic kidney disease (n = 1). Modes of therapies were continuous ambulatory peritoneal dialysis (CAPD) (n = 13; mean duration: 9.5 months), HD (n = 5; mean duration: 7.8 months), and conservative treatment (n = 1). BMIS using Tc-99m labeled anti-granulocyte monoclonal mouse antibody BW250/183 was performed, and the results were compared with the biochemical parameters of the patients. According to the presence of BM expansion, which may represent marrow fibrosis, the 19 patients were divided into two groups: Group I (n = 7) with BM expansion and Group II (n = 12) with normal marrow distribution. The biochemical parameters and bone markers of Group I were compared with those of Group II. There was no significant difference in biochemical parameters (blood hemoglobin, serum ferritin, erythropoietin, BUN, creatinine) between the two groups. There were no significants difference in serum calcium, phosphorus, tartate-resistant acid phosphatase (TRAP), and intact parathyroid hormone (iPTH) between the two groups. Serum alkaline phosphatase (ALP) and osteocalcin were significantly (P < 0.05) higher in Group I than in Group II. These results suggest that patients with bone marrow expansion in BMIS have increased levels of ALP and osteocalcin, indicating an increased osteoblastic activity. BMIS may be useful for the detection of bone marrow expansion due to marrow fibrosis in renal osteodystrophy, and for the evaluation of the extent of bone marrow fibrosis.

Biomarkers↗

PubMed1998

Effect of rebamipide on liver damage and increased tumor necrosis factor in a rat model of endotoxin shock.

We investigated the effect of rebamipide, a novel antiinflammatory agent, on liver damage in a rat model of circulatory shock induced by bacterial endotoxin (E. coli lipopolysaccharide, LPS). Endotoxemia for 6 hr resulted in a 5.9-fold rise in the serum levels of nitrite (P < 0.05) with a significant rise in the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactic dehydrogenase (LDH), suggestive of liver dysfunction. The increased activities of serum ALT, AST, and LDH, but not serum nitrite were significantly inhibited by rebamipide (100 mg/kg, orally for five days). Myeloperoxidase activity in the liver was significantly elevated in the rats with endotoxemia by 2.4-fold (P < 0.05), which was also significantly inhibited by rebamipide. Upon LPS injection, serum TNF-alpha levels peaked at 1 hr after LPS (from 167.4 +/- 20.0 to 1570.0 +/- 100.0 pg/ml) and thereafter rapidly declined. The increased TNF-alpha level measured at 1 hr was significantly inhibited by pretreatment with rebamipide (100 mg/kg for five days). It is suggested that rebamipide exerts a strong protective effect on the LPS-induced liver damage through inhibition of activation of neutrophils and TNF-alpha production.

Alanine↗

PubMed1997

Decreased CGRP level with increased sensitivity to CGRP in the pial arteries of spontaneously hypertensive rats.

It was aimed to investigate the importance of calcitonin gene-related peptide (CGRP) in maintenance of normal cerebral microcirculation. We examined both the functional (in vivo) and biochemical effects (in vitro) of CGRP on the pial arteries of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). When mock cerebrospinal fluid containing capsaicin (3 x 10(-7) M) was suffused over the cortical surface, the diameter of pial arteries of SHR was transiently increased and rapidly returned to the baseline level, while the capsaicin-induced increase in pial arterial diameters of WKY was large and sustained for a longer duration (> 10 min). Capsaicin-induced vasodilation was significantly attenuated by pretreatment with CGRP8-37, a CGRP1, receptor antagonist, in both WKY and SHR. On the other hand, cortical suffusion with CGRP (10(-9) approximately 10(-6) M) exerted a larger enhancement in the vasodilation of pial artery of SHR than WKY. The CGRP-induced vasodilation was significantly antagonized by CGRP8-37 in both WKY and SHR. The released level of CGRP-like immunoreactivity (CGRP-LI) from the pial artery was significantly lower in SHR (12.3 +/- 1.2 fmol/mm2/hr) than that in WKY (24.5 +/- 3.9 fmol/mm2/hr). CGRP (10(-6) M)-induced stimulation of cyclic AMP formation was rather larger in the pial arteries from SHR (50.2 +/- 5.8 fmol/mm2/30 min, p < 0.05) than those from WKY (34.5 +/- 3.8 fmol/mm2/30 min). These data suggest that, in the pial arteries of SHR, the transient vasodilation to capsaicin and enhanced vasodilation to CGRP are related to the decreased CGRP level in the cerebral microvascular beds, consequently leading to increased sensitivity of the CGRP receptors to CGRP.

Animals↗

PubMed1997

Endoscopic resection of submucosal tumor of the esophagus: results in 62 patients.

BACKGROUND AND STUDY AIMS: Although most submucosal tumors of the esophagus are benign, reliable exclusion of leiomyosarcoma requires histological analysis. However, this is rarely possible with an endoscopic forceps biopsy. In an attempt to establish the diagnosis, and as an alternative to surgery, we present here our experience with the endoscopic removal of submucosal tumors of the esophagus using two different techniques. PATIENTS AND METHODS: Sixty-two patients (38 men, 24 women, mean age 47) with submucosal tumors of the esophagus were treated endoscopically. If the tumor was less than 2 cm in diameter, polypoid, or showed a round protrusion with at least moderate elevation at endoscopy, a conventional snare polypectomy was performed. If the tumor was larger than 2 cm in diameter or only mildly elevated, the technique of modified endoscopic incisional enucleation was carried out, consisting of complete stripping of the overlying tissue followed by tumor enucleation using an electrocautery snare and a coagulation electrode. RESULTS: Based on these criteria, 36 patients underwent conventional snare polypectomy, and 25 received endoscopic incisional enucleation; complete resection of the tumor was possible in these 61 cases. In one patient, only partial removal was possible, due to firm and wide adhesions to the surrounding tissue. The tumor diameters ranged from 0.6 cm to 7.5 cm, with a mean value of 1.9 cm; 14 tumors measured more than 3 cm. At histopathology, the resected specimens were found to be 56 leiomyomas, four granular cell tumors, one neurogenic tumor, and one cyst. No serious complications such as perforation or massive bleeding occurred, and oozing bleeding, which was encountered in three patients, was easily managed by endoscopic electrocoagulation. During the follow-up period (mean 38.4 months, range 3-107 months) no recurrence was observed in any of the 61 patients who received complete resections. CONCLUSION: This method of endoscopic removal of submucosal tumors of the esophagus appears to be safe and effective in experienced hands. It allows complete histopathological workup, and at the same time complete removal of the tumor. The method can be considered as an alternative to surgery in symptomatic cases.

Adult↗

PubMed1997

Double-blind placebo-controlled study of cisapride in patients with nonspecific esophageal motility disorder accompanied by delayed esophageal transit.

BACKGROUND: Nonspecific esophageal motility disorder (NEMD) represents a difficult therapeutic challenge because of the heterogeneous nature of the esophageal motor functions. We studied the effects of cisapride on the esophageal symptoms and esophageal motor function in a group of patients with NEMD showing delayed esophageal transit. METHODS: Seventy eligible patients were entered into a 4-week, double-blind randomized comparison of 10 mg of cisapride or placebo, four times daily. Symptom assessment, esophageal manometry after wet swallows, and esophageal scintigraphy after intake of a liquid and solid bolus were performed in each patient before and after treatment. RESULTS: After 4 weeks of treatment cisapride significantly increased the prevalence of esophageal peristaltic contractions (percentage of total contractions, P < 0.05 versus base line and placebo) and significantly improved esophageal emptying of the solid bolus (P < 0.05 versus placebo) but not of the liquid bolus. Placebo did not have any significant effects versus base line on these variables. Both placebo and cisapride improved the distal esophageal amplitude versus base line (no significant intergroup differences). Symptom scores were significantly reduced after 4 weeks of treatment versus base line in both groups (no significant intergroup differences except for heartburn and regurgitation, P < 0.05). On global evaluation of treatment, significantly more patients in the cisapride group were rated as markedly or moderately improved, when compared with placebo. CONCLUSIONS: The results of the present study showed that cisapride is effective and well tolerated in patients with NEMD accompanied by delayed esophageal transit. Symptomatic improvement may possibly be related to its beneficial action on the esophageal body by increasing the number of peristaltic contractions and esophageal emptying of solids.

Adult↗

PubMed1997

Preventive effect of rebamipide on gastric mucosal cell damage evoked by activation of formyl-methionyl-leucyl-phenylalanine receptors of rabbit neutrophils.

We investigated the underlying mechanism by which rebamipide exerts a preventive effect on neutrophil-mediated gastric mucosal cell damage. The release of 2',7'-bis-(2-carboxyethyl)-5-(and -6)-carboxyfluorescein (an index of cytotoxicity) was significantly increased by 16.7% (P < .05) when 2',7'-bis-(2-carboxyethyl)-5-(and -6)-carboxyfluorescein-acetomethyl ester (5 microM) loaded gastric mucosal cells were incubated with neutrophils (5 x 10(6) cells/well) that were activated by cytochalasin B (5 microM) and formyl-methionyl-leucyl-phenylalanine (fMLP) (1 nM). In the in vitro study, upon application of cytochalasin B and fMLP, formation of superoxide anion and release of myeloperoxidase increased with increased neutrophil aggregation. These parameters were attenuated by pretreatment with rebamipide (100-1000 microM) in a concentration-dependent manner. In the Scatchard analysis, the maximum binding of [3H]fMLP to neutrophils decreased from 0.57 to 0.44 pmol/2 x 10(6) cells (P < .05) by application of rebamipide (300 microM) with little change in K(D). Neutrophils isolated from rabbits orally treated with rebamipide (100 mg/kg for 3 days) also showed a decrease in the production of superoxide anion upon stimulation with fMLP and a decrease in the binding of [3H]fMLP to its receptors on the neutrophil plasma membrane (0.59-0.45 pmol/2 x 10(6) cells, P < .05). Taken together, it is suggested that the inhibitory effect of rebamipide on the neutrophil-mediated gastric mucosal cell injury is due, in part, to alterations in the neutrophil membrane that ultimately result in a decrease in the number of binding sites for fMLP to its receptors.

Alanine↗

PubMed1997

Effect of cisapride and renzapride on gastrointestinal motility and plasma motilin concentration in dogs.

The effects of cisapride and renzapride (BRL 24924), on plasma concentration of motilin and gastroduodenal motility were studied in seven dogs with implanted force transducers in the antrum and duodenum. In the interdigestive state, the i.v. administration of cisapride (5 mg) or renzapride (5 mg) administered in phase I resulted in a prompt and marked increase in plasma motilin concentration and in gastroduodenal motility. Mean plasma motilin levels during the first 30 min after cisapride and after renzapride injection were 85.0 +/- 6.5 (+/- S.E.) and 96.1 +/- 6.3 pM., respectively. These values were significantly greater (P < .001) than those for the corresponding time period of the control cycle, 52.2 +/- 5.6 and 57.4 +/- 5.3 pM (mean phase III level, 120 +/- 8.1 pM), respectively. The increases in the motilin level after cisapride or renzapride coincided with significant increases in contractile activities of the antrum to 43.2 +/- 5.3% and 44.9 +/- 4.6% and of the duodenum to 28.4 +/- 3.1% and 34.2 +/- 2.2% of phase III activity (100%) from that in the corresponding control period, 0.7 +/- 0.4% and 0.2 +/- 0.1%, respectively. The changes in both plasma motilin and motility in response to the two drugs were abolished completely by the i.v. administration of atropine. The drugs also enhanced the meal-induced contractile activities of the antrum as well as the duodenum but failed to influence the postprandial plasma motilin concentration. We conclude that cisapride and renzapride have similar effects on plasma motilin and gastroduodenal motility: 1) the two drugs increase plasma motilin levels and stimulate gastroduodenal motility in the interdigestive state, and 2) in the digestive state, both drugs enhance motility without influencing the plasma motilin levels.

Animals↗

PubMed1996

Interleukin-1 alpha, interleukin-1 beta and interleukin-8 gene expression in human aural cholesteatomas.

Bone destruction is a common characteristic feature of chronic otitis media, especially aural cholesteatoma. A number of immunohistochemical studies have suggested that interleukin-1 (IL-1) may be responsible for cholesteatomatous bone destruction. We designed this study to present the mRNA expression patterns of IL-1 alpha, IL-1 beta, and IL-8, which can induce and activate the leukocyte, the major reservoir of potent proteolytic enzymes. Total RNAs were extracted from aural cholesteatomas, external auditory canal skin (EACS), postauricular skin (PAS), and granulation tissues and transcribed into cDNAs. cDNAs were amplified by using PCR technique with primers for IL-1 alpha, IL-1 beta, IL-8, and beta-actin. Amplified products were hybridized with each internal probe and the relative density was measured. In granulation tissues, the relative density of IL-1 alpha was greater than that of other tissues. The ratio of IL-1 beta and IL-8 of aural cholesteatoma was significantly higher than that of EACS and PAS. We suggest that both of IL-1 alpha and IL-1 beta may play a role in the pathological changes, and that IL-8, which is mainly produced from cholesteatomatous epithelium, may have an important role in the pathological changes of cholesteatomas.

Blotting, Southern↗

PubMed1996

Pseudoaneurysm and splenic infarction in chronic pancreatitis--a case report.

Peripancreatic pseudoaneurysm and splenic infarction are rare but life-threatening complications of chronic pancreatitis. The incidence of pseudoaneurysm in patients who undergo angiography for pancreatitis is about 10%. Clinically, pseudoaneurysm is hard to discover until rupture occurs. The authors have recently experienced a case of intact pseudoaneurysm and splenic infarction in chronic alcoholic pancreatitis. A bolus enhanced CT scan and angiography were essential to confirm these complications of pancreatitis. We managed these complications successfully by distal pancreatectomy and splenectomy.

Adult↗

PubMed1995

Negative feedback regulation of pancreatic exocrine secretion in guinea pigs.

We have investigated whether hormonally mediated negative feedback mechanisms regulate pancreatic exocrine secretion in guinea pigs. In anesthetized guinea pigs prepared with a tube in the proximal duodenum, pyloric ligation, and pancreatic duct cannulation with PE-10 tubing, diversion of pancreatic juice for as long as 4 h in fasting states failed to increase either pancreatic secretion or plasma levels of secretin or cholecystokinin (CCK). In the same animal preparation, intraduodenal (ID) infusion of sodium oleate (SO) resulted in significant increases in both pancreatic secretin and plasma levels of the two hormones that were significantly suppressed by ID infusion of pancreatic juice or a combination of trypsin and chymotrypsin. In another group of guinea pigs, this significant increase in pancreatic secretion was profoundly suppressed by a rabbit antisecretin serum (0.2 ml) or loxiglumide (10 mg.kg-1.h-1). Moreover, a combination of the antiserum and loxiglumide completely abolished the pancreatic secretion. The effect of atropine, 20 micrograms.kg-1.h-1 i.v., on SO-stimulated pancreatic secretion and hormone release was also studied. Atropine completely suppressed the pancreatic secretion of volume flow, bicarbonate, and protein stimulated by SO, whereas neither one of the two hormone levels was affected by intravenous atropine, indicating that atropine blocks the actions of both secretin and CCK on the pancreatic exocrine secretion. It is concluded that a negative feedback regulation of exocrine pancreatic secretion is operative in the intestinal phase of pancreatic secretion in guinea pigs and that this feedback mechanism is mediated by both secretin and CCK. Furthermore, in guinea pigs, cholinergic tone plays an important modulating role in the mechanism.

Animals↗

PubMed1995

Preventive effect of rebamipide on gastric lesions induced by ischemia-reperfusion in the rat.

Rebamipide (2-(4-chlorobenzoylamino)-3-[2-(1H)-quinolinon-4-yl] propionic acid), a novel antiulcer agent, has been reported to prevent various acute experimental gastric mucosal lesions and to accelerate the healing of chronic gastric ulcers. We investigated the effect of rebamipide on rat gastric mucosa damaged by exposure to 30 min of ischemia and 60 min of reperfusion (I/R) with continuous intragastric instillation of 0.1 N HCl (1 ml/100 g body weight) into the stomach. Rebamipide, at 30 and 100 mg/kg, i.p., reduced the mucosal damage score from 2.28 (I/R vehicle group) to 1.54 and 1.07, respectively. Pretreatment with rebamipide significantly reduced the activity of myeloperoxidase (an index of neutrophil infiltration) and preserved the activities of superoxide dismutase and nitric oxide synthase in the gastric mucosa with inhibition of malondialdehyde production. Thus, a negative correlation between the activities of nitric oxide synthase and myeloperoxidase (y = 4.35-9.45x, r = .67, P < .01) was observed. In an in vitro study, rebamipide inhibited N-formyl-met-leu-phe-induced chemotaxis of neutrophils and production of superoxide anion from opsonized zymosan-stimulated neutrophils. However, it did not affect the production of superoxide anion either by the xanthine-xanthine oxidase reaction or phorbol 12-myristate 13-acetate-stimulated neutrophils. Based on these results, it is suggested that rebamipide exerts a protective effect on the I/R-induced gastric mucosal damage through inhibition of mobilization and activation of neutrophils in association with an attenuation of the decreases in both superoxide dismutase and nitric oxide synthase activities, thereby preventing the gastric microcirculation from deterioration.

Alanine↗

PubMed1994

Mechanism of action of insulin on pancreatic exocrine secretion in perfused rat pancreas.

In conscious rats, we have previously shown that immunoneutralization of circulating insulin with a rabbit anti-insulin serum abolished the pancreatic exocrine secretion stimulated by a meal or a combination of exogenous secretin and cholecystokinin octapeptide (CCK-8). To investigate the mechanism of endogenous insulin action on the exocrine pancreas, isolated rat pancreata were perfused with intra-arterial infusion of Krebs-Henseleit solution (37 degrees C) at 1.2 ml/min, whereas both pancreatic juice and portal venous effluent were collected separately in 15-min samples. Simultaneous intra-arterial infusion of secretin and CCK-8 in doses of 0.75 and 4.2 pmol/h; respectively, significantly increased volume, bicarbonate, and protein output in 7 rat pancreata (P < 0.01). When a rabbit anti-insulin serum was administered intra-arterially (0.1-ml bolus followed by 0.1 ml for 10 min), pancreatic secretion of volume, bicarbonate, and protein output was profoundly suppressed (n = 7, P < 0.01), whereas a normal rabbit serum failed to influence pancreatic secretion. The decrease in pancreatic secretion by the antiserum coincided with a significant increase in somatostatin in portal venous effluent from 1.4 +/- 0.2 to 4.1 +/- 0.8 pM (n = 6, P < 0.05). The combined administration of a rabbit antisomatostatin serum (0.4 ml) and the anti-insulin serum partially reversed the effect of the anti-insulin serum alone. Thus the pancreatic secretion was significantly greater than that achieved by the anti-insulin serum alone (P < 0.05). These observations strongly suggest that the action of insulin on exocrine pancreas is mediated by its local or paracrine action.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Esophageal duplication cyst complicated with intramural hematoma--case report.

Esophageal duplication cysts account for a very small percentage of benign esophageal tumors and are infrequently symptomatic. Esophageal duplication cysts result from aberrant alignment of the normal vacuolization process that produce the esophageal lumen in the 5th to 8th week of embryonic life. Complications most often are bleeding into or infection of cysts. Recently, we experienced a case of esophageal duplication cyst complicated with intramural huge hematoma and the cause of hematoma could not be identified. We report it with a review of literatures.

Esophageal Cyst↗

PubMed1993

Effect of [(CH2NH)4,5]secretin on pancreatic exocrine secretion in guinea pigs and rats.

[psi 4,5]Secretin was shown to be a secretin receptor antagonist that inhibits secretin-stimulated increase in adenosine 3',5'-cyclic monophosphate in isolated pancreatic acini of the guinea pig. To determine whether it inhibits pancreatic exocrine secretion in vivo, we have studied the effect of [psi 4,5]secretin on the pancreatic secretion stimulated by secretin in anesthetized guinea pigs and rats. In basal state, [psi 4,5]secretin given intravenously for 2 or 3 h in varying doses of 1.6-32.7 nmol.kg-1.h-1 dose dependently increased pancreatic secretion of both fluid and bicarbonate during the 1st h, but it returned gradually to basal level within 2 or 3 h. On the other hand, [psi 4,5]secretin significantly inhibited the pancreatic secretion stimulated by either exogenous or endogenous secretin in a dose-related manner. The inhibitory effect of [psi 4,5]secretin in guinea pigs was greater than that in rats. However, it did not completely block the secretin-stimulated pancreatic secretion, whereas a rabbit antisecretin serum suppressed it completely. We conclude that 1) in the unstimulated state, [psi 4,5]secretin is a partial agonist of pancreatic exocrine secretion of both fluid and bicarbonate; and 2) when pancreatic secretion is stimulated by secretin, unlike an antisecretin serum, it is a partial inhibitor in intact guinea pigs and rats.

Animals↗

PubMed1992

Similarities between effects of superoxide-mediated endothelium-derived relaxing factor and cromakalim.

A stable endothelium-derived relaxing factor has been reported to be generated on exposure of endothelial cells to the superoxide anion. In this study, we first evaluated the effects of the relaxing factor and cromakalim on mechanical tone and, second, assessed their consequences on the 86Rb efflux rate. On application of hypoxanthine-xanthine oxidase to a bath for generating superoxide anion, the precontracted rabbit mesenteric artery exhibited another transient increase in contraction, followed by sustained relaxation. This relaxation was lost in the K(+)-physiological salt solution (PSS) (greater than 35 mM) and was inhibited by glibenclamide (10 microM) but not by N-methyl-L-arginine or methylene blue. Hypoxanthine-xanthine oxidase application did not increase either basal or stimulated synthesis of guanosine 3',5'-cyclic monophosphate. In the presence of 2 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and 10 mM MgCl2, the relaxing factor caused a significant increase in 86Rb efflux from the aortic and mesenteric arterial segments, as did the cromakalim. The increased 86Rb efflux, either by the relaxing factor or by cromakalim, was wholly inhibited by glibenclamide. These results suggest that superoxide-mediated endogenous relaxing factor may have a similar mechanism of action to cromakalim in vasodilatation.

Animals↗

PubMed1989

Release of superoxide-dependent relaxing factor(s) from endothelial cells.

In the present work, an experimental system was designed to study superoxide anion radical, implicated as the cause of vascular dilatation. To circumvent its direct effect, we employed a two-bath system. When the endothelial cells (EC) were exposed to electrical field stimulation (EFS) or to a hypoxanthine-xanthine oxidase system in bath A plus its physiological buffer solution suffused on a helical strip of cat basilar artery in bath B, the contraction to 5-hydroxytryptamine (5-HT) was depressed to approximately 40-50% of the control value. The reduction was not elicited on EFS in a state of calcium deficiency or in the absence of EC. The depression could be prevented by pretreatment with superoxide dismutase (SOD), but not with an effective dose of catalase, dimethyl sulfoxide (DMSO), mannitol, or indomethacin. The percent depression of contraction was paralleled by an increase in SOD-inhibitable cytochrome c reduction, which was not associated with cyclic guanosine 3',5'-monophosphate formation. These results suggest that superoxide-dependent relaxing factor is released from EC differently than the endothelium-derived relaxing factor mediated by acetylcholine.

Animals↗