Biomedical subjects

C H Cho

Publications and source records attributed to C H Cho.

At least 127 records · Page 7Linked to original sources

PubMed1995

Role of dorsal motor nucleus of vagus in gastric function and mucosal damage induced by ethanol in rats.

Experimental evidence indicates that the autonomic nervous system, especially the cholinergic pathway modulates the mucosal defensive mechanism and affects mucosal damage in the stomach. The present study investigated the role of the dorsal motor nucleus of vagus (DMV) in gastric function and its influences on ethanol-induced mucosal damage in pentobarbitone-anesthetized rats. Electrolytic lesion of the DMV as compared with sham operation and lesions of other brain areas, eg, nucleus reticular gigantocellularis and cuneate nucleus, reduced the basal gastric mucosal blood flow (GMBF) and also the blood flow after ethanol administration. The same operation did not affect the acid secretion either in the basal state or during the ethanol treatment period. Lesions at the caudal half of the DMV produced a bigger depression of GMBF when compared with lesion at the rostral half. In the sham-operated rats, ethanol induced severe hemorrhagic lesions in the gastric glandular mucosa, and this was significantly potentiated by lesions at the DMV, especially in the caudal half. The present findings indicate that acute DMV damage at the caudal half markedly affects the GMBF but not the acid secretion. The action on GMBF may contribute to the aggravation of ethanol-induced gastric damage in rats. These data reinforce the idea that the central vagal pathway, especially the caudal half of the DMV, plays a significant role in the modulation of GMBF, which in turn affects the integrity of gastric mucosal barrier.

Animals↗

PubMed1995

Endogenous mediators in adaptive cytoprotection against ethanol-induced gastric gland damage in rabbits.

The present study determined the participation of different endogenous mediators in adaptive cytoprotection against gastric gland damage caused by ethanol in rabbits. Using the isolated gland preparation, pretreatment with 10(-5)M of either indomethacin, Nw-nitro-L-arginine methyl ester (L-NAME) or N-ethylmaleimide (NEM), but not of substance P antagonist, intensified the 10% (v/v) ethanol-induced gastric gland damage and lessened the degree of cytoprotection evoked by 2% (v/v) ethanol to a significant level. Co-administration with 10(-4)M of prostaglandin E2, L-arginine or glutathione to the respective groups completely reversed the above adverse effects. These results demonstrate the involvement of endogenous prostaglandins, nitric oxide and glutathione in gastric adaptive cytoprotection against the damaging action of ethanol in the rabbit gastric glands.

Adaptation, Physiological↗

PubMed1995

Contributions of physical and chemical properties of mild irritants to gastric cytoprotection in rats.

The present study demonstrated the cytoprotective abilities of low concentrations of ethanol, NaCl and HCl, against the gastric mucosal damage caused by 100% ethanol, and the contributions of the physical and chemical properties of these mild irritants to their protective actions. The results have shown the differential protective effects of ethanol (10-40%), NaCl (2.5-12.5%) and HCl (0.15-0.45M), with the optimal cytoprotective concentrations being 20% ethanol, 5% NaCl and 0.3M HCl, respectively. Solutions of KCl and NaCl with similar osmolarity, and H2SO4 and HCl of similar acidity and osmolarity, all showed similar protective protective potentials as compared to the osmotic agent mannitol, which possessed a concentration- and tonicity-dependent protective action against 100% ethanol-induced mucosal damage. Some concentration of methanol, propan-2-ol and ethanol, having similar osmolarity with deionized water, exerted indifferent protective effects. It is therefore concluded that adaptive cytoprotection induced by low concentrations of NaCl and HCl could depend on their physical properties, while that of ethanol could act through its unique chemical property.

Animals↗

PubMed1995

Differential antiarrhythmic potency of adenosine in normotensive and spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) have functional defects in purinergic neurotransmission. Because adenosine is antiaarrhythmic, the adenosine probably has lesser antiarrhythmic potency in SHR. We tested this hypothesis by comparing the antiarrhythmic effects of adenosine against arrhythmias induced by global myocardial ischemia/reperfusion in isolated perfused heart of SHR and its normotensive counterparts: Wistar Kyoto rats (WKY) and Sprague-Dawley rats (SD). The Langendorff isolated perfused heart preparation was used. Ventricular fibrillation (VF) was induced by global myocardial ischemia/reperfusion. Ischemia/reperfusion-induced VF was most severe in SD. The severity of VF in WKY was similar to that in SHR. Adenosine 75 micrograms/heart had significant antiarrhythmic effect in both types of normotensive rats; a much higher dose of adenosine (150 micrograms/heart) was required to attenuate cardiac arrhythmias in SHR, suggesting reduced responsiveness to adenosine in genetically hypertensive rats. The mechanisms of action responsible for reduced responsiveness to adenosine in SHR require further study.

Adenosine↗

PubMed1995

The mechanistic pathway of gastric adaptive cytoprotection: a study on different components of the autonomic nervous system.

1. The involvement of different components of the autonomic nervous system in the pathogenesis of ethanol-induced damage and the adaptive cytoprotection of mild irritants were studied in the gastric mucosa of male rats. 2. Capsaicin, yohimbine, and domperidone aggravated the 100% ethanol-induced gastric mucosal damage and attenuated the cytoprotective action of 20% ethanol, but not of 5% NaCl and 0.3 M HCl. Butoxamine and prazosin blocked the adverse actions of yohimbine and domperidone respectively. 3. Atropine, pirenzepine, and lidocaine lessened the severity of 100% ethanol-induced mucosal injury and further increased the cytoprotective action of 5% NaCl and 0.3 M HCl, but not of 20% ethanol. 4. Our results demonstrated that sensory afferent neurones, alpha 2-adrenoceptors and D2-dopaminergic receptors all play a significant role in the defensive mechanism of the gastric mucosa and the adaptive cytoprotection of 20% ethanol, while the M1- and M2-muscarinic receptors and sensory chemoreceptors on the gastric mucosa contribute only to the former action. The adverse effect of yohimbine and domperidone on lesion formation is probably mediated through the release of catecholamines, which subsequently act on the beta 2- and alpha 1-adrenoceptors respectively.

Adaptation, Physiological↗

PubMed1995

The effect of nicotine and its interaction with carbon tetrachloride in the rat liver.

In order to study the effects of nicotine on liver, groups of rats were given nicotine doses that simulated those seen in chronic smoking (54 and 108 mumol/l of nicotine) for 10 days. A subgroup was also given a single subcutaneous injection of 6 g/kg of carbon tetrachloride (CCl4) shortly before the animals of the group were killed. Histology demonstrated a significant hepatotoxic effect in the group receiving 108 mumol/l of nicotine when compared with the control group in the form of fatty change, focal or confluent necrosis and dark-cell change. The effects in pregnant rats were less severe. Carbon tetrachloride alone induced significant fatty change and focal necrosis in non-pregnant rats but not in pregnant rats. Nicotine also aggravated the CCl4 induced pathological changes in livers of both non-pregnant and pregnant animals. Thus nicotine alone, when given at a concentration of 108 mumol/l, exerted hepatotoxic effects; the alkaloid also aggravated the hepatotoxicity of CCl4. Pregnant rats were more resistant to the hepatotoxic effects produced by nicotine and CCl4.

Animals↗

PubMed1995

Different pharmacological actions of adenosine on gastric function and mucosal damage in normotensive and spontaneously hypertensive rats.

It has been reported that there are functional defects in the purinergic system in spontaneously hypertensive rats (SHR). The following experiments examined the gastric effects of adenosine in these animals. SHR had a significantly higher gastric mucosal blood flow (GMBF), but the secretion of acid and pepsin was not different from that of normotensive counterparts. In SHR, adenosine (s.c. 3.75 or 7.5 mg/kg) time- and dose-dependently decreased gastric acid secretion and GMBF. The nucleoside, however, did not affect the pepsin secretion. In normotensive rats, gastric acid secretion was also reduced, but not to the extent of SHR. The GMBF was increased instead. Adenosine potentiated ethanol-induced mucosal damage in SHR, which was likely caused by GMBF reduction. It is concluded that adenosine produces a greater depressive action on the stomach in SHR. These differential actions are probably due to the genetic difference between the two types of animals.

Adenosine↗

PubMed1995

Felodipine- and ethanol-induced gastric mucosal damage in rats.

Calcium channel blockers like verapamil have been shown to potentiate ethanol-induced gastric mucosal damage. However, the exact mechanism for this adverse drug interaction is still unknown. We used felodipine to study the ulcerogenic mechanisms of calcium channel blockers and the pathogenesis of ethanol-induced ulceration. The experiment was conducted in an ex vivo gastric chamber prepared in anesthetized animals. Felodipine (0.25, 0.5, 1.0, or 2.0 mg/kg s.c.) dose-dependently reduced the systemic blood pressure which was accompanied by a decrease in gastric mucosal blood flow (GMBF), with an insignificant change in heart rate. Ethanol lowered the GMBF and produced gastric mucosal lesions, and these actions were potentiated by felodipine. Preincubation with calcium gluconate but not the sodium salt attenuated the adverse effects of ethanol on GMBF and lesion formation; it also significantly prevented the gastric effects of felodipine but not the decrease of the systemic blood pressure. It is concluded that felodipine aggravates ethanol ulceration through a depressive action on the GMBF. These actions were attenuated by the supplementation with calcium ions in the gastric mucosa. Therefore, maintenance of calcium homeostasis in the gastric wall could play a significant role in the prevention of ethanol ulceration in rats.

Analysis of Variance↗

PubMed1994

The intraperitoneal effects of 5-hydroxytryptamine on haemodynamics, gastric mucosal blood flow and platelet aggregation.

The effects of 5-hydroxytryptamine (5-HT) on gastric mucosal blood flow and lesion formation have been established. However, the mechanisms accounting for the reduction of gastric mucosal blood flow have not been defined. The current study aimed to test the hypothesis that decrease of gastric mucosal blood flow in rats is the result of changes of systemic blood pressure and/or platelet aggregation. 5-HT (given i.p. 5 or 10 mg/kg) time and dose dependently reduced gastric mucosal blood flow and systemic arterial blood pressure; it also potentiated ethanol-induced mucosal damage. Methysergide (a 5-HT2-receptor blocker) pretreatment alleviated the decrease of gastric mucosal blood flow and lesion formation but not the systemic blood pressure. Also in the 5-HT-treated animals, the mucosal oxygen (O2) and haemoglobin levels as well as the systemic blood CO2 were reduced, but the blood O2 was increased. The latter two parameters correlated with an elevation of the respiratory rate. The blood platelet count was not affected by 5-HT pretreatment. Adenosine diphosphate (ADP) dose dependently induced a similar degree of platelet aggregation in platelet rich plasma fractions in the saline and 5-HT-treated rats in vitro. 5-HT in the concentrations of 1 or 10 microM, promoted the platelet aggregation produced by ADP. However, this action was attenuated in the 5-HT-pretreated rats, indicating that tachyphylaxis of 5-HT action on platelet aggregation could occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

PubMed1994

The gastric cytoprotective action of adenosine and prostaglandin E2 in rabbits.

The direct protective action of adenosine and prostaglandin E2 (PGE2) was examined in an isolated gastric gland preparation in rabbits. Ethanol (8%, v/v) incubation markedly increased the release of lactate dehydrogenase (LDH) and number of non-viable glands in the preparation. Both effects were prevented by PGE2 preincubation in a concentration (10(-6), 1.4 x 10(-5) or 2.8 x 10(-5) M)-dependent manner. The protective action was smaller in adenosine-treated groups, and yet the highest concentration (10(-4) M) of the compound also significantly inhibited the cytotoxic effects of ethanol. These findings indicate that both adenosine and PGE2 possess cytoprotective action on gastric glands in rabbits, but the former compound exerts its action beyond physiological concentrations. It is concluded that endogenous PGE2, but not adenosine may act as an ulcer modulator in the stomach.

Adenosine↗

PubMed1994

The role of endogenous ulcerogenic mediators in the pathogenesis of peptic ulcer.

The pathogenetic mechanisms of different types of peptic ulcer are still unclear. Extensive investigations have been focused on the identification of potential endogenous ulcerogenic mediators in animals and men. These studies are important in the development of a better therapeutic agent, either to prevent or to cure peptic ulcer in humans. Several endogenous substances have been identified and are reported to be involved in the production of gastrointestinal lesions in animals. Also these substances were increased during inflammatory responses and their actions were reported as vascular dependent and possibly free radicals related. Reports related to the types of these mediators have been extensive. The more important ones include some of the lipid metabolites, neuropeptides, biogenic amines, and also Helicobacter pylori and reactive free radicals. The present study summarizes the ulcerogenic mechanisms of these substances and the types of ulcer involved. More current information may enable us to understand better the etiology of peptic ulcer and possibly its prevention and cure in man. Any particular types of ulceration will not be specifically discussed in this article, because they have been extensively studied and reviewed.

Animals↗

PubMed1994

The differential mechanisms of mild irritants on adaptive cytoprotection.

The protective action of mild irritants has been established. However, the mechanisms as to how they antagonize the injurious action produced by the subsequent challenge with an ulcerogenic stimulus are still unclear. The present study examined the different protective mechanisms of an oral administration of the three mild irritants, 20% ethanol, 0.3 mol/L HCl or 5% NaCl against the gastric injurious actions of absolute ethanol in rats. In an attempt to clarify the pathways and mediators involved in the adaptive cytoprotection, [D-Pro2, D-Trp7,9]-substance P (substance P antagonist), Nw-nitro-L-arginine methyl ester (L-NAME), indomethacin, capsaicin, lidocaine, atropine or hexamethonium was given. The protective action of 20% ethanol but not the other two mild irritants, was antagonized by L-NAME, indomethacin and capsaicin, which are the inhibitors of nitric oxide (NO) and prostaglandins (PG) synthesis, and afferent sensory neuron blocker, respectively. Substance P antagonist, lidocaine or atropine given alone, prevented mucosal damage; however, only substance P antagonist enhanced the anti-lesion action of 20% ethanol, while atropine and lidocaine increased the protective effect of NaCl and HCl. The three mild irritants increased the residual gastric secretion. Only 20% ethanol and 5% NaCl but not 0.3% HCl significantly increased the basal adherent mucus and also attenuated the mucus depletion by absolute ethanol. It is concluded that the cytoprotective action of either ethanol or NaCl seems to be mediated through the increase of residual gastric secretion and adherent mucus. In the ethanol-treated group, these actions could act through the afferent sensory fibres, with NO and PG as the possible mediators.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

PubMed1994

The vagus nerve and its non-cholinergic mechanism in the modulation of ethanol-induced gastric mucosal damage in rats.

The role of the cholinergic pathway in the vagus nerve in modulating gastric lesion formation by ethanol was examined, using an ex-vivo stomach chamber preparation. Subdiaphragmatic vagotomy significantly increased the lesion areas but lowered acid secretion and gastric mucosal blood flow (GMBF). Atropine had no effect, whereas pirenzepine antagonized ethanol-induced mucosal damage. All three procedures showed similar potencies in depressing acid secretion, but only pirenzepine reversed the fall in the GMBF produced by ethanol. These differential effects of vagotomy, atropine and pirenzepine on gastric function suggest that the cholinergic component in the vagus nerve may not be important in the formation of ethanol-induced gastric damage. The persistent protective action as well as the restoration of ethanol-induced GMBF drop by pirenzepine in vagotomized animals further support this hypothesis. The worsening effect of vagotomy is probably modulated by a non-cholinergic mechanism, the abolition of which makes the gastric mucosa more susceptible to damage by ethanol. The acid-independent protective action of pirenzepine and its influence on the GMBF, which were not exhibited by atropine, are indeed unique and perhaps may be attributed to this non-cholinergic pathway.

Animals↗

PubMed1994

Effects of beta-adrenoceptor antagonists on portal vein hypertension and ethanol-induced gastric mucosal damage in rats.

The effects of various beta-adrenoceptor antagonists, with different pharmacological properties, on systemic and portal vein blood pressure and on ethanol-induced gastric mucosal damage were examined in surgically-induced portal hypertensive rats. Propranolol (5, 10 or 20 mg kg-1), nadolol (5 or 10 mg kg-1), metoprolol (10 or 20 mg kg-1), labetalol (20 or 40 mg kg-1) and pindolol (3 or 6 mg kg-1) reduced systemic blood pressure to a similar degree in both portal vein-ligated and sham-operated rats. All beta-adrenoceptor antagonists, except for pindolol, significantly reduced portal venous pressure and ethanol-induced macroscopic gastric mucosal damage in portal hypertensive animals. Sham-operated rats had lower portal venous pressure and less gastric damage compared with portal hypertensive rats, but both were unaffected by beta-adrenoceptor antagonist pretreatment. We conclude that: propranolol, nadolol, metoprolol and labetalol are effective in reducing the portal venous pressure and ethanol-induced gastric mucosal damage in portal hypertensive rats, but not in portal normotensive animals; there was no direct relationship between the reduction of portal vein and systemic blood pressure; and local anaesthetic action is probably important in reducing the portal vein pressure and ethanol-induced gastric mucosal lesions, while the intrinsic sympathomimetic effect can counteract the actions of the beta-adrenoceptor antagonists on portal venous pressure and gastric mucosa.

Adrenergic beta-Antagonists↗

PubMed1994

Modulatory role of 5-HT3 receptors in gastric function and ethanol-induced mucosal damage in rat stomachs.

The involvement of 5-hydroxytryptamine (5-HT) in gastric function and mucosal damage has been defined. 5-HT also potentiates lesion formation in animals. The current study investigated further whether these actions are mediated through 5-HT3 receptors in rats. Ondansetron, a 5-HT3 receptor antagonist, was given subcutaneously, 2 or 4 mg/kg, 30 min before the gastric parameters were measured. The higher dose of ondansetron, 4 mg/kg, significantly increased gastric mucosal blood flow (GMBF) and also basal acid and Na+ secretion. However, it did not affect pepsin output. 5-HT time dependently reduced GMBF and pepsin secretion, but not that of acid and Na+. These actions were not altered by ondansetron pretreatment. The drug, however, dose dependently reduced ethanol-induced gastric mucosal lesions in the 5-HT-treated animals. These findings indicate that 5-HT3 receptors regulate not only basal GMBF, but also acid and Na+ secretion in stomachs. However, the depressive action of 5-HT on GMBF and pepsin secretion is most likely not mediated through 5-HT3 receptors. Ondansetron also modulates the toxicities of ethanol in the stomach and this action is likely to be mediated through the preservation of GMBF.

Animals↗

PubMed1994

Assessment of hemodynamic changes in rat stomachs by laser Doppler velocimetry and reflectance spectrophotometry. Effects of ethanol and prostaglandin E2 under ischemic and congestive conditions.

One of the ulcerogenic mechanisms by which ethanol induces mucosal lesions in the stomach is the depression of gastric mucosal blood flow (GMBF). The goal of this study was to determine whether lesion formation is the result of vascular ischemia alone or ischemia combined with congestion. The aims of this study were to answer this question by evaluating the relationship between GMBF, oxygen saturation (ISO2) and hemoglobin volume (IHb) in the gastric mucosa under the influences of ethanol and prostaglandin E2 (PGE2) in the ischemic and congestive states, using a laser Doppler flowmeter and tissue spectrum analyzer. Ligation of the gastric celiac artery or vein markedly decreased the GMBF and the ISO2 level. The former procedure also reduced but the latter increased the IHb level. Ethanol administration produced effects similar to venous ligation, i.e. vascular stasis with ischemia. There was a negative correlation between GMBF and severity of lesion formation after ethanol administration. However, at the lesion site all the hemodynamic parameters were significantly reduced, indicating that a necrotic condition had occurred. PGE2 preincubation (25 micrograms) elevated GMBF, ISO2 and IHb levels. It also alleviated the reduction of blood flow induced by ethanol and increased the recovery rate of GMBF and ISO2 after the release of arterial or venous ligation. It is concluded that the decrease in blood flow due to ethanol is probably caused by constriction of venules rather than arterioles inside the mucosa, and this effect could lead to vascular congestion. PGE2 probably dilates both arterioles and venules in the gastric mucosa and thereby increases the blood flow in the gastric mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Influence of chronic nicotine intake and acute ethanol challenge on gastric mucus level and blood flow in rabbits.

The effects of nicotine pretreatment on ethanol-induced gastric mucosal lesions and changes of gastric mucosal mucus levels and blood flow (GBF) were studied in anaesthetized rabbits. Nicotine treatment 25 or 50 micrograms/ml drinking water did not affect the volume of water consumption during the 10-day experimental period. It did not produce gastric mucosal lesions or affect the superficial adherent mucus content. The length of mucus-containing cells and the basal GBF were also unaffected. Intragastric administration of absolute ethanol reduced GBF, this effect was not altered by nicotine. However, the alkaloid potentiated the ulcerogenic actions of ethanol both on lesion formation and mucus depletion evoked by graded oral doses of ethanol (50 or 100%, v/v). Ultrastructurally, the mucous cells were more degenerated in the animals co-treated with nicotine and ethanol. It is concluded that reductions of mucus-containing cells and adherent mucus on the gastric mucosa are likely to be the contributory factors involved in the aggravating action of nicotine on ethanol-induced gastric mucosal lesions in rabbits.

Animals↗

PubMed1994

Adenosine deaminase and carcinoembryonic antigen in pericardial effusion diagnosis, especially in suspected tuberculous pericarditis.

BACKGROUND: Adenosine deaminase (ADA) and carcinoembryonic antigen (CEA) have been measured in pleural fluid to help distinguish malignant from benign effusions, especially in tuberculous pleurisy. We investigated ADA and CEA levels in patients with moderate to large pericardial effusions of different etiologies. METHODS AND RESULTS: We performed diagnostic and therapeutic pericardiostomy with drainage and biopsy. We measured ADA and CEA levels in the pericardial fluid in 26 patients with moderate to large pericardial effusion and 19 control patients. Patients were included in a prospective protocol from August 1991 to August 1993. Patients were grouped as follows: group 1, 9 patients with tuberculous pericarditis (TP) confirmed by bacteriologic culture or histology of pericardial biopsy; group 2, 5 patients with clinically strongly suspected TP; group 3, 12 patients with malignancy (8) and acute pericarditis (4); group 4, 19 control patients without pericardial disease. We treated patients with TP with isoniazid, rifampin, and either streptomycin or ethambutol for 12 months and pyrazinamide for 2 months. We observed for symptoms and signs of recurrent pericarditis or constrictive pericarditis on follow-up. In group 1 the ADA activity was significantly higher (101 +/- 14 U/L) than that in group 3 (22 +/- 5 U/L) or that in group 4 (17 +/- 2 U/L) (P < .05). There was no significant difference between ADA activity in group 1 (101 +/- 14 U/L) and that in group 2 (100 +/- 26 U/L). With a cutoff value for ADA activity of 40 U/L, sensitivity was 93% and specificity 97% in the diagnosis of TP. In benign diseases, the CEA level was significantly lower (1.0 +/- 0.3 ng/mL) than that in malignant diseases (135.1 +/- 79.7 ng/mL) (P < .05). With a cutoff value for CEA level of 5 ng/mL, sensitivity was 75% and specificity 100% in the diagnosis of malignant pericarditis. Follow-up study (mean, 12.9, 19.8, and 11.8 months in groups 1, 2, and 3, respectively, showed no symptoms or signs of constrictive pericarditis, except for 1 patient. CONCLUSIONS: Pericardial fluid ADA and CEA are useful for the differential diagnosis of pericardial effusion of various causes. They also have great value in early diagnosis of TP, particularly when the results of other clinical and laboratory tests are negative.

Adenosine Deaminase↗