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Biomedical subjects

J K Ko

Publications and source records attributed to J K Ko.

At least 37 records · Page 2Linked to original sources
PubMed1997

Co-regulation of mucosal prostanoids and substance P by indomethacin in rat stomachs.

The present investigation examined the correlation between the regulation of mucosal prostaglandin (PG) biosynthesis and the release of the neuropeptide substance P (SP) in rat stomachs by indomethacin, a cyclooxygenase inhibitor. When given subcutaneously at the dose of 5 mg/kg, indomethacin reduced mucosal biosynthesis of PGE2 and concurrently lowered mucosal SP level. The inter-relationship between mucosal generation of PG and SP was further demonstrated by using [D-Pro2, D-Trp7,9]-SP, which also inhibited PGE2 production besides its suppression on SP release. Co-administration of either arachidonic acid, the PGE2 precursor, or SP reversed the inhibitory actions of indomethacin and [D-Pro2, D-Trp7,9]-SP, respectively, on mucosal levels of PGE2 and SP. Our findings suggest that indomethacin, aside from its depletion of endogenous PG, also exerts a secondary action in regulating the release of SP, which is mediated indirectly through PG in the gastric mucosa. These actions may play a role in the modulation of gastric mucosal integrity.

Animals↗
PubMed1997

The vascular and glandular organoprotective properties of metronidazole in the rodent stomach.

BACKGROUND: The gastroprotective action of metronidazole, an antimicrobial used in the therapy against Helicobacter pylori infection, is unclear. Thus, the aim of the present investigation was to study the organoprotective action and antiulcer mechanisms of this drug in rodents. METHODS AND RESULTS: Metronidazole (10 mg/kg), given either per os or intraperitoneally, 30 min beforehand, reduced ethanol (40%, 10 mL/kg, p.o.)-induced gastric mucosal damage in male rats. Likewise, oral administration of metronidazole dose-dependently attenuated the indomethacin (30 mg/kg, p.o.)-induced gastric lesion formation and the concurrent depletion of mucosal mucus. However, metronidazole did not affect the basal mucosal prostaglandin E2 content. In an ex vivo gastric chamber preparation, 40% ethanol incubation markedly lowered transmucosal potential difference and increased mucosal vascular permeability in rat stomachs. Incubation with all doses of metronidazole did not modulate gastric mucosal blood flow nor transmucosal potential difference, either before or after ethanol treatment. Nevertheless, the increase in vascular permeability by 40% ethanol was significantly alleviated by either p.o. or i.p. metronidazole pretreatment. In addition, exposure of the isolated rabbit gastric gland preparation to metronidazole (10(-5) and 10(-4) M) significantly attenuated the damaging action of 10% ethanol. CONCLUSION: It is concluded that metronidazole possesses a direct vascular and glandular organoprotective property in the rodent stomach. However, the anti-ulcer action does not appear to involve prostaglandins nor act through the improvement of gastric mucosal blood flow. Preservation of intramucosal mucus may partly contribute to the prevention of indomethacin-induced ulceration in rats.

Animals↗
PubMed1996

Adaptive gastric mucosal cytoprotection in rats: different modes of action by three mild irritants.

The mechanisms of adaptive mucosal cytoprotection by mild irritants were investigated in rats. In an ex vivo chamber preparation, application of 20% ethanol, 5% NaCl or 0.3 M HCl to the posterior side of the mucosa significantly protected that side of the stomach against mucosal damage caused by subsequent exposure to 100% ethanol, with contralateral transmission of protection to the anterior side by 20% ethanol and 0.3 M HCl. Atropine or lidocaine significantly reversed the cytoprotection of 20% ethanol. Bilateral vagotomy partially prevented the antilesion action of 20% ethanol, and completely prevented the action of 0.3 M HCl. However, the three mild irritants did not affect gastric mucosal blood flow, but restored the ion transport mechanism which was depressed by ethanol. It is therefore concluded that the three mild irritants have their own distinctive cytoprotective mechanisms against ethanol ulceration, which is predominantly not mediated by effects on the vascular system of the gastric mucosa.

Animals↗
PubMed1996

The antilesion actions of anticholinergic agents on ethanol-induced injury in rat stomachs: the importance of gastric vascular integrity and tonicity.

1. The antilesion actions of two antimuscarinic drugs on ethanol-induced gastric injury and mucosal integrity were examined in male rats. Histological examinations were made and gastric emptying rates determined after in vivo administration of the drugs to conscious rats. In anaesthetized rats, with an ex vivo gastric chamber, effects on gastric transmucosal potential difference, Evan's blue leakage and Na+ output were examined. 2. In conscious animals, atropine (1 mgkg-1, i.p.) and pirenzepine (1 mgkg-1, i.p.) both significantly reduced macroscopic lesion formation, but not microscopic damage and functional alterations, caused by orally administered absolute ethanol. Moreover, these drugs did not show any effect on the basal gastric adherent mucus level, nor the depleting action of ethanol on both adherent mucus and the mucosal mucus layer. Nevertheless, both atropine and pirenzepine significantly reduced gastric emptying rate. 3. In anaesthetized animals, pirenzepine but not atropine increased the basal transmucosal potential difference (PD); however, it could not prevent the ethanol-induced drop in PD. Furthermore, the inhibitory action of ethanol on sodium ion output from the gastric mucosa was not attenuated by these drugs. Pirenzepine, however, significantly lessened the increase in vascular permeability caused by 100% ethanol. This action was not shared by atropine. 4. These findings indicate that both atropine and pirenzepine exert their antilesion actions through the relaxation of the stomach. Pirenzepine also preserves the integrity of the gastric mucosal vasculature, which is distinct from the action of atropine. The protective action of these drugs occurs only at the macroscopic level.

Animals↗
PubMed1995

The importance of gastric emptying and mucosal folds in the adaptive cytoprotection of mild irritants in rats.

This study examines the involvement of gastric emptying and mucosal folds in the adaptive cytoprotection of different mild irritants against 100% ethanol-induced gastric mucosal damage. Pre-exposure to either 20% ethanol, 5% NaCl or 0.3M HCl significantly reduced the gastric mucosal damage caused by 100% ethanol in rats. Administration of either one of the three mild irritants increased the basal gastric residual volume and decreased the area occupied by gastric mucosal folds, but only 20% ethanol reduced the gastric emptying rate. Indomethacin (5 mg/kg, s.c.) pretreatment did not affect ethanol ulceration and gastric emptying rate when given by itself, but reversed the flattening of mucosal folds produced by the three mild irritants, and abolished the protective effect of 20% ethanol. These results suggest that the gastric adaptive cytoprotection induced by the three mild irritants acts through luminal dilution of the noxious agent, possibly caused by gastric retention. The reduction of mucosal folds could also contribute to the anti-lesion action of 20% ethanol. It is therefore suggested that the protective actions of the three mild irritants act through different mechanisms.

Adaptation, Physiological↗
PubMed1995

The role of non-protein sulfhydryl compounds in gastric adaptive cytoprotection against ethanol-induced mucosal damage in rats.

The contribution of the endogenous nonprotein sulfhydryl compounds (SH) in gastric adaptive cytoprotection was investigated in rats. N-ethylmaleimide (NEM) treatment significantly reduced mucosal SH level, and aggravated the mucosal injury induced by absolute ethanol. Oral administration of the mild irritants, 20% ethanol, 5% NaCl or 0.3 M HCl, significantly increased the basal mucosal SH level. These agents also showed a cytoprotective action against the necrotizing effect of absolute ethanol. Administration of NEM did not alleviate this cytoprotective potential, although it abolished the increased SH level evoked by these mild irritants. Thus, it is concluded that modulation of endogenous SH by mild irritants perhaps only plays a minor role in the gastric adaptive cytoprotection.

Administration, Oral↗
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

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

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 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

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↗
PubMed1992

Supraventricular tachycardia mechanisms and their age distribution in pediatric patients.

To better define the natural history of supraventricular tachycardia (SVT) in young patients, age distribution of SVT mechanisms was examined in 137 infants, children and adolescents. Patients with a history of cardiac surgery or neuromuscular diseases were excluded. An electrophysiologic study was performed in each patient: transesophageal (110 patients) or transvenous (14 patients) or both (13 patients). Mechanisms were classified as SVT using accessory atrioventricular (AV) connection (SVT using accessory connection, including orthodromic and antidromic reciprocating tachycardia), primary atrial tachycardia (including chaotic, automatic and reentrant atrial tachycardia), and tachycardia due to reentry within the AV node. SVT using accessory connection occurred in 100 of 137 patients (73%) and was the most prevalent mechanism. Primary atrial tachycardia and reentry within the AV node were present in 19 of 137 (14%) and 18 of 137 (13%) patients, respectively. Using a multinomial logit model, relative probabilities for tachycardia mechanisms for 5 age groups--prenatal, less than 1, 1 to 5, 6 to 10 and greater than 10 years--were determined. Primary atrial tachycardia (11 to 16%) and SVT using accessory connection (58 to 84%) appeared throughout infancy, childhood and adolescence. On the other hand, tachycardia due to reentry within the AV node (0 to 31%) rarely appeared before age 2 years. Mechanisms of SVT appear to have age-dependent distributions. SVT using accessory connection is the most common mechanism in young patients. We speculate that the propensity to tachycardia due to reentry within the AV node occurs during postnatal development.

Adolescent↗
PubMed1991

Predictors of early mortality in patients with angiographically documented left main coronary artery disease.

To determine predictors of early death after coronary angiography in patients with significant left main coronary artery disease (greater than or equal to 60% diameter narrowing, LMCAD), we reviewed the clinical records of patients with LMCAD who died after angiography. Of 1,288 patients with LMCAD studied between January 1978 and October 1989, 21 died within 2 days after angiography (group 1). As a control group, 85 patients were randomly sampled from 1,196 patients who survived at least 30 days after angiography (group 2). The predictors of early death after angiography in patients with LMCAD were older age (P less than 0.05), New York Heart Association Class III or IV (P less than 0.005), shorter duration of unstable angina (P less than 0.005), higher left ventricular end-diastolic pressure (P less than 0.006), lower ejection fraction (P less than 0.005), and significant left circumflex artery disease (P less than 0.006). The use of heparin infusion after angiography did not appear to be a significant factor. It is suggested that earlier operation or more aggressive management be undertaken in patients who, at cardiac catheterization, have significant LMCAD associated with the above-listed variables.

Aged↗