Opposite effects of acute and chronic administration of alcohol on gastric emptying and small bowel transit in rat.

The effects of acute and chronic administration of a large dose of alcohol on gastric emptying and small bowel transit were studied in rats. The development of tolerance to the acute effect of alcohol on gastrointestinal motility during chronic alcohol administration was also investigated. Gastric emptying and small intestinal transit were assessed by the Phenol Red recovery method. Acutely, ethanol was given in a dose of 2.5 g/kg body wt by gavage 30 min before the test meal. Chronically, ethanol was administered by two different methods: (1) a dose of 2.5 g/kg body wt was administered by gavage daily for 10 days; (2) animals received 15% ethanol in their drinking water for 30 days. A single large dose of alcohol inhibited gastric emptying and small bowel transit. Treatment with a large dose of alcohol for 10 days did not change the gastric emptying significantly, but inhibited the small intestinal transit. Alcohol consumption in drinking water for 30 days accelerated gastric emptying and small bowel transit. Tolerance to the acute inhibitory effect of a single large dose of alcohol on gastrointestinal motility did not develop during chronic alcohol treatment.

Improvement of nitrergic relaxation by farnesol of the sphincter of Oddi from hypercholesterolaemic rabbits.

Field stimulation relaxed the rabbit sphincter of Oddi muscle rings after incubation with atropine (1 microM) and guanethidine (4 microM) with a threefold increase in tissue cyclic cGMP content, a response previously shown to be essentially nitrergic. Preparations from hypercholesterolaemic rabbits (1.5% dietary cholesterol load over 8 weeks increasing serum total cholesterol from pre-diet 1.4+/-0.3 to 22.6+/-3.8 mmol/l) exhibited contractions with no change in cyclic GMP content under the same conditions. The nitrergic relaxation was recaptured with a twofold increase in tissue cyclic GMP content in preparations from hypercholesterolaemic rabbits undergone a treatment with 30 microM/kg farnesol i.v. twice a day over the last 3 days of the dietary period. We conclude that farnesol treatment restores nitrergic relaxation of the sphincter of Oddi in hypercholesterolaemia.

Delayed cardiac protection against harmful consequences of stress can be induced in experimental atherosclerosis in rabbits.

Multiple brief periods of rapid ventricular pacing confer both short- and long-term protection on the ischaemic heart. The duration of the short-term protection does not exceed 2 h, whereas the long-term protective effect appears several hours after the inducing insults, with maximal protection 24-48 h later. Up to now, delayed cardiac protection by preceding ischaemic insults against harmful consequences of stress has been produced in the normal, healthy animal only. The purpose of this study was, therefore, to test whether delayed cardiac protection can be induced in experimental atherosclerosis in rabbits produced by feeding cholesterol-rich diet over 2 months. Repeated brief periods of rapid ventricular pacing were used to induce delayed protection of the heart. Moderation of post-pacing right intracavitary ST segment elevation and that of the left ventricular end-diastolic pressure (both produced by ventricular overpacing: 500 beats/min for 15 min) were found in normal animals as well as in those fed cholesterol-enriched diet. The short-lived protection induced by a single 'preconditioning' pacing was reproducible only in normal animals. As measured by means of radioimmunoassay, the protective effect of either short- or long-term protection appeared in parallel with an attenuation of ischaemia-induced increase in cardiac cyclic AMP content, in both normal and atherosclerotic rabbits. An increase in cardiac cyclic GMP content was characteristic of the short- but not long-term protection. These results suggest that the delayed cardiac protection by preceding multiple brief rapid pacings operates even in experimental atherosclerosis, but the short-term protection induced by a single preconditioning stimulus is lost.

The ursodeoxycholic acid-p-aminobenzoic acid deconjugation test, a new tool for the diagnosis of bacterial overgrowth syndrome.

OBJECTIVE: To determine the possible complementary role of the ursodeoxycholic acid-p-aminobenzoic acid (UDCA-PABA) loading test in the diagnosis of intestinal bacterial overgrowth. DESIGN: A prospective clinical study. PATIENTS AND METHODS: The hydrogen breath and UDCA-PABA tests were performed simultaneously in 68 patients with suspected contaminated small bowel syndrome (CSBS), and in 10 healthy control subjects. The hydrogen breath test was performed by oral loading of 25 g of lactose and/or 10 g of lactulose. The UDCA-PABA test was carried out by oral loading of 250 mg of UDCA-PABA conjugate, followed by measurement of the amount of PABA excreted in the urine. The diagnosis of bacterial overgrowth was considered to be established when either the hydrogen breath test or the UDCA-PABA test produced abnormal results. RESULTS: Thirty-five of the 68 patients proved to have CSBS. In 13 of these 35 patients, only the enhanced urinary PABA excretion (11.7 +/- 1.42 mg vs. 3.6 +/- 0.68 mg) indicated bacterial overgrowth, 15 of the 35 patients gave only a positive hydrogen breath test, and in the remaining seven cases the results of both tests were abnormal. In eight CSBS patients, the urinary excretion of PABA was decreased significantly following 10-day tinidazole treatment (5.5 +/- 1.29 mg vs. 13.1 +/- 2.07 mg). CONCLUSION: The UDCA-PABA test is a valuable clinical method for the detection of bacterial overgrowth, especially in cases where hydrogen production alone fails to reveal CSBS. It is also a useful procedure for evaluating the efficacy of antibacterial treatment.

[The ursodeoxycholic acid-p-aminobenzoic acid test in the diagnosis of small bowel bacterial overgrowth syndrome]. / Az ursodezoxikólsav-p-aminobenzoesav teszt a kontaminált vékonybélszindróma diagnosztikájában.

UNLABELLED: Contaminated small bowel syndrome is frequently associated with meteorism due to excessive gas formation, and diarrhoea as a result of bacterial fermentative processes, including splitting of carbohydrates or deconjugating and dehydroxylating bile salts. In addition to gas production, bacteria capable of metabolizing bile salts have been shown to release p-aminobenzoic acid (PABA) from and Ursodeoxycholic-acid-PABA substrate. Our aim was to determine the possible complementary role of the UDCA-PABA test in the diagnosis of bacterial overgrowth. PATIENTS AND METHODS: The H2 breath and UDCA-PABA tests were performed simultaneously on 46 patients with suspected contaminated small bowel syndrome, and on 7 healthy subjects. The H2 breath test was performed by oral loading of 25 g lactose and/or 10 g lactulose. The UDCA-PABA test was carried out by determining urinary excretion of PABA after oral loading with 250 mg UDCA-PABA conjugate. The diagnosis of bacterial overgrowth was established, when either H2 breath, or UDCA-PABA test proved to be pathological. RESULTS: Based upon the pathologic values of either the H2 breath test, or the UDCA-PABA test, 25 out of 46 patients proved to have contaminated small bowel syndrome. In 10 out of 25 patients only pathologic urinary PABA excretion (12.772 +/- 1.707 vs 4.1 +/- 0.58), indicated bacterial overgrowth, and in 9 out of the same group only positive H2 breath test (early rise of > 20 ppm of H2) indicated the same, while in 6 cases both tests proved to be pathological. In 7 CSBS patients the urinary excretion of PABA significantly decreased following a 10 day Tinidazole treatment (5.48 +/- 1.286 vs 13.068 +/- 2.068). CONCLUSION: The UDCA-PABA test proved to be a valuable complementary method to detect bacterial overgrowth, when H2 production failed to reveal bacterial overgrowth.

Impaired nitrergic relaxation of the sphincter of Oddi of hyperlipidaemic rabbits.

Field stimulation relaxed the sphincter of Oddi muscle rings of the rabbit after incubation with phentolamine, oxprenolol and atropine (all 1 microM). The relaxation was blocked by NG-nitro-L-arginine methyl ester (30 microM) and was reversed by 3 mM L-arginine but not D-arginine. Sphincter of Oddi preparations from hypercholesterolaemic rabbits exhibited contractions under the same conditions. We conclude that nitrergic relaxation is impaired in the sphincter of Oddi from hypercholesterolaemic rabbits.

Central effects of antiserum against human atrial natriuretic polypeptide on water and electrolyte metabolism and plasma arginine-8-vasopressin level in conscious rats.

Although synthetic atrial natriuretic polypeptide (ANP) is known to influence the water and electrolyte metabolism and arginine-8-vasopressin (AVP) secretion, the physiological role of endogenous ANP in the rat brain is still unclear. Accordingly, an investigation was made of the effects of intracerebroventricular (icv) administration of human h-ANP antiserum, which can neutralize endogenous ANP, on the water intake, urine output, urinary excretion of potassium and sodium, and plasma AVP level in normally hydrated rats. Apart from the water intake, all the parameters were also determined in 48-h water-deprived rats after h-ANP antiserum treatment. The icv administration of the h-ANP antiserum significantly increased the spontaneous water intake, urine output and urinary potassium excretion in rats given water ad libitum. These effects developed by 24 h after icv treatment. The h-ANP antiserum had no effect on the urine volume in 48-h water-deprived rats, suggesting a primary effect of endogenous ANP in the brain on the spontaneous water intake in rats given water ad libitum. These results suggest that ANP may have a physiologically important role in the central regulation of the water and electrolyte metabolism. The h-ANP antiserum did not alter the basal and dehydration-induced AVP release. This raises the possibility that the endogenous ANP in the brain may not participate in the control of AVP secretion.

Hyponatremia and increased secretion of vasopressin induced by vincristine administration in rat.

Administration of vincristine resulted in a hyponatremic state and concurrent elevation of the plasma immunoreactive arginine8-vasopressin (IR-AVP) level in rats. Development of the vincristine-induced hyponatremia and hypoosmolality was accompanied by a loss in weight, a decreased water intake and a large reduction in the daily urine sodium excretion. The cause of the sodium loss is thought to be the diarrhea observed during vincristine treatment. Hematocrit and serum urea nitrogen levels were increased. It is concluded that the condition differs from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH): the increase in plasma IR-AVP concentration may be associated with dehydration due to vincristine toxicity.

Effects of L-carnitine in acute myocardial ischaemia.

Data in the literature suggest that exogenous L-carnitine improves the metabolic function of ischaemic heart cells: it enhances the transport of long-chain fatty acids into the mitochondria, stimulates the slowed beta-oxidation, and moderates the accumulation of amphiphilic acyl esters. A study has therefore been made of the cardiac effects of L-carnitine in dog experiments (n = 8). The left anterior descending coronary artery (LAD) was isolated in anaesthetized, thoracotomized animals in situ. After a control occlusion and equilibration period, the LAD was again ligated at the time of L-carnitine infusion (100 mg/kg iv. during 10 min). The agent diminished the maximal conduction delay and the degree of epicardial ST-segment elevation in the ischaemic myocardial region, and the free fatty acid concentration of the arterial blood, but it did not influence the frequency of ventricular extrasystoles. The anti-ischaemic effect of L-carnitine was manifest only during the infusion, and its discontinuation was immediately followed by an enhanced ST-segment elevation. In the dose applied, the substance did not affect the heart rate, systemic mean arterial pressure, left ventricular end-diastolic pressure (LVEDP), or left ventricular contractility (LV dP/dtmax). In the canine myocardial infarction model employed it was observed that the duration of the anti-ischaemic effect of L-carnitine (100 mg/kg iv.) is very short, and it has no significant antiarrhythmic action.

Gastrointestinal mucosal gamma-glutamyl transpeptidase activity changes in different ulcer models of rat.

The experiments presented gave evidence that changes in gamma-glutamyl transpeptidase activity-under experimental circumstances-seem to be in close connection with gastro-intestinal ulceration. In the pre-ulcerative period in both gastric and duodenal ulcer models, the mucosal gamma-glutamyl transpeptidase activity is higher than normal, while in the definitive ulcerative stage the gastric gamma-glutamyl transpeptidase activity is significantly decreased but in the duodenum it remained on normal level. This phenomenon may reflect to a difference in the pathomechanism of the gastric and duodenal ulceration.

Effect of the vasopressin antagonist d/CH2/5Tyr/Et/VAVP on the antidiuretic action of exogenous and endogenous vasopressin.

The effect of [1-(beta-mercapto-beta, beta- cyclopentamethylene -propionic acid),2-0- ethyltyrosine ,4-valine]-arginine vasopressin on the water metabolism was studied in rats. The compound decreases the antidiuretic action of exogenous vasopressin in Brattleboro rats; in rats without diabetes insipidus it causes temporary polyuria and eliminates the response of antidiuresis to an osmotic stimulus. The results indicate that this compound can block the antidiuretic action of both exogenous and endogenous vasopressin.

Prevention of hyponatraemia and cerebral oedema by the vasopressin antagonist d/CH2/5Tyr/Et/VAVP in rats treated with pitressin tannate.

A rat model of the Schwartz-Bartter syndrome was created by the administration of a high dose of a long-acting vasopressin preparation (pitressin tannate ) together with a forced water intake. The treatment led to water retention, hypernatriuria , marked hyponatraemia (in 4-5 days) and severe cerebral oedema. These changes could be prevented by the simultaneous administration of [1-(beta-mercapto-beta, beta- cyclopentamethylene -propionic acid),2-0- ethyltyrosine ,4-valine]arginine vasopressin. The observations indicate that this vasopressin antagonist analogue might be of use in the future as an effective drug against the Schwartz-Bartter syndrome.

Effect of the vasopressin antagonist d(CH2)5 Tyr(Et)VAVP on diuresis in rat.

The effect of [1-(beta-mercapto-beta,beta- cyclopentamethylene -propionic acid)2-0- ethyltyrosine ,4-valine] arginine vasopressin on the water metabolism was studied in rat. The compound was found to be able to block the antidiuretic action of both exogenous and endogenous vasopressin. A rat model of the Schwartz-Bartter syndrome was created by the administration of a high dose of a posterior pituitary preparation (Pitressin tannate ) together with a forced water intake. The antagonist prevented water retention and averted the enhanced natriuresis and hyponatraemia, and cerebral oedema did not develop. The observations suggest that this vasopressin antagonist might be of use in the future as an effective drug against the Schwartz-Bartter syndrome.

Laboratory method for measuring small amounts of tissue glycogen.

A procedure is reported which is well applicable for the quantitative determination of glycogen, especially in cases of a small glycogen content in a small amount of tissue. The method consists of extraction of glycogen by boiling potassium hydroxide, precipitation with ethanol, hydrolysis with sulphuric acid, and determination of the glycogen in form of glucose obtained with orthotoluidine.