Study of propranolol and its related adrenoceptor antagonists on changes of gastric electrical parameters induced by ethanol in rats.

The actions of different adrenoceptor antagonists on gastric potential difference (PD), electrical current (I) and resistance (R) were studied, using the voltage clamp technique. In an isolated gastric mucosal tissue, 5% ethanol was able to reduce the PD and I across the gastric mucosa. Direct incubation with propranolol 10(-4) mol/l either from the mucosal or submucosal sides attenuated such effects. Intraperitoneal administration of propranolol (2.5-10 mg/kg), a nonselective beta-adrenoceptor blocker with significant membrane-stabilizing activity, given 30 min before the preparation of the gastric tissue, not only alleviated the fall in PD and I across the gastric mucosa, but also increased the R of the stomach tissue. Butoxamine, a selective beta2-antagonist, produced the similar but less significant effects in the same experimental setting. Metroprolol, a beta1-adrenoceptor blocker, given by the similar doses did not produce significant effects. Nonselective beta-adrenoceptor blocker, nadolol but not the beta- and alpha-adrenoceptor blocker, labetalol, also significantly preserved the decrease of PD induced by ethanol, but to a lesser extent. These findings suggest that blockade of the beta2-receptors in the gastric mucosa together with membrane-stabilizing activity could improve the integrity of the gastric mucosa, and these effects are probably acting through its direct action on the tissue.

Effects of selective beta-adrenoceptor antagonists on gastric ulceration in the rat.

Metoprolol and butoxamine, beta-adrenoceptor antagonists which act selectively at the beta 1- and beta 2-adrenoceptors, respectively, have been investigated for their actions on the ethanol, indomethacin and cold-restraint stress ulcer models. Oral administration of butoxamine but not metoprolol significantly attenuated gastric mucosal damage in the three types of ulcer model. Intraperitoneal injection of butoxamine reduced indomethacin ulceration but not that of the other two models. The stimulatory effect of butoxamine on the gastric mucosal potential difference and intramucosal mucus level correlated positively with its anti-ulcer action. Only oral administration of butoxamine significantly increased the mucosal prostaglandin E2 (PGE2) level but not after intraperitoneal injection. Oral administration of butoxamine also significantly increased the mucosal PGE2 level in the three types of ulcer model but this drug was only effective in the indomethacin ulcer model after intraperitoneal injection. Gastric acid and pepsin output were not affected by either drug. Metoprolol significantly reduced systemic blood pressure; this could be attributed to a reduction in gastric mucosal blood flow. These results imply that beta 2-adrenoceptors play a significant role in the pathogenesis of gastric ulceration. We suggest that the anti-ulcer effect of butoxamine was in part a result of strengthening of the mucosal barrier but that this was not effected by modification of acid or pepsin secretions in the stomach. Stimulation of PGE2 in the gastric mucosa could contribute in part to the anti-ulcer action of the drug, especially when given by the oral route.

A mechanistic study of beta-adrenoceptor antagonists on ethanol-induced gastric damage.

The beta-adrenoceptor subtypes and the roles of myeloperoxidase and prostaglandin E2 in the anti-ulcer effect of beta-adrenoceptor antagonists were studied. A non-selective beta-adrenoceptor antagonist, propranolol, or selective beta-adrenoceptor antagonists, metoprolol (a beta 1-adrenoceptor antagonist) or butoxamine (a beta 2-adrenoceptor antagonist) were used. Propranolol given either intraperitoneally or orally reduced ethanol-induced mucosal damage and myeloperoxidase activity. Oral administration of butoxamine produced similar effects. The blood neutrophil count was increased after ethanol administration and this was reversed by the two drugs. Metoprolol did not affect myeloperoxidase activity, neutrophil count and mucosal damage under these experimental conditions. Oral administration of propranolol or butoxamine increased mucosal prostaglandin E2 level. It is concluded that the inflammatory responses to ethanol, as indicated by neutrophil infiltration in gastric mucosa, can be specifically inhibited by drugs that block beta 2-adrenoceptors. This action would explain in part why propranolol and butoxamine but not metoprolol lessened gastric damage. In addition, oral administration of propranolol and butoxamine increased the mucosal prostaglandin E2 level, which could partially contribute to their anti-ulcer effects.

A study of the antiulcer mechanisms of propranolol in rats.

Although propranolol has been shown to protect against ethanol and stress ulceration, the antiulcer mechanisms are still unclear. The present study examined the antiulcer mechanisms of propranolol in three different types of ulceration induced respectively by ethanol (60%), indomethacin (30 mg/kg) and stress (cold-restraint). Propranolol pretreatment in the highest dose (10 mg/kg) given either intraperitoneally (i.p.) or orally (p.o.) prevented gastric mucosal damage in these three ulcer models. The three doses of the drug (2.5, 5 or 10 mg/kg) dose-dependently decreased systemic blood pressure which was accompanied by a reduction of gastric mucosal blood flow. These findings suggest that the protection was unrelated to an improvement of local circulation in the stomach. However, propranolol preserved the mucus levels in the three types of ulcer models. The beta-adrenoceptor blocker also increased the basal gastric mucosal potential difference. These findings indicate that propranolol strengthens the mucosal barrier by the preservation of mucosal mucus and enhancement of the mucosal integrity in the stomach.

Evidence for potential application of zinc as an antidote to acetaminophen-induced hepatotoxicity.

The therapeutic application of zinc sulphate as an antidote to acetaminophen overdose was examined in ICR mice. Hepatotoxicity was induced by a single oral dose of acetaminophen (750 mg/kg). Various treatments (normal saline, 15 or 30 mg/kg zinc sulphate, 150 mg/kg N-acetylcysteine, 15 mg/kg zinc sulphate + 150 mg/kg N-acetylcysteine) were given i.p. 1 h after acetaminophen overdose. Serum alanine aminotransferase, hepatic glutathione and malondialdehyde levels were measured before experiments and at various intervals after the administration of acetaminophen. Serum acetaminophen levels were also measured at different different intervals. Zinc sulphate showed protection by dose-dependently reducing alanine aminotransferase and malondialdehyde levels. The drug also partially prevented the depletion of hepatic glutathione. These effects were not as good as those of N-acetylcysteine. However, the combination of zinc sulphate with N-acetylcysteine produced even better protective effects. Furthermore, drug treatments did not affect serum acetaminophen levels. It is concluded that both drugs attenuate acetaminophen-induced hepatic toxicity, and the action is likely to be mediated through replenishment of hepatic glutathione levels. The use of zinc sulphate alone or in combination with N-acetylcysteine could be another alternative for the treatment of acetaminophen overdose in view of possible side effects produced by N-acetylcysteine.

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.

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)

Experiences with unerupted anterior and posterior teeth.

The causes of tooth impaction are as numerous as are ways to manage the problem. Treatment is usually instituted only after an unfavourable eruption prognosis of the impacted tooth has been established from radiographic and clinical examination. Advantages of guided eruption and surgical removal have to be weighed. Fifteen cases of various degrees of impaction, difficulty of treatment, complications and failures of eruption are discussed.

Dentofacial orthopaedic correction of maxillary retrusion with the protraction facemask--a literature review.

The retruded maxilla in the Class III skeletal pattern could be effectively corrected with the protraction facemask in selected cases. A review of the different types of orthopaedic appliances used in Class III treatment, the rationale for facemask therapy, the effect of this treatment and the factors affecting stability is presented.

A procedure for attachment of gold chain for traction of impacted teeth.

There is a need to improve the strength of the attachment of the gold chain to impacted teeth. Dislodgement of the gold chain requires a second surgery for reattachment. Failures have been observed to occur at two interfaces. The authors have devised a method of attaching the gold chain to the mesh pad securely, by ligating them together. This article describes the method and discusses other factors which enhance the retention of the gold chain to the impacted tooth.