Central nervous system site of action for the hypotensive effect of clonidine in the cat

The purpose of our study was to determine whether clonidine exerts its centrally mediated hypotensive action at three sites that influence arterial pressure located in the medulla, specifically associated with the intermediate area of the ventrolateral medulla. The "intermediate area" lies approximately 1.5 mm caudal to the border of the trapezoid body (caudal border) and 4 mm lateral to the midline. One of the sites that influence arterial pressure lies in the nucleus reticularis rostroventrolateralis. The second site lies in close proximity to the rostral part of the nucleus reticularis lateralis (rLRN) and also near the A1 area. The third site lies in the most rostral area and medial to the nucleus reticularis rostroventrolateralis, that is in the nucleus paragigantocellularis lateralis. Unilateral microinjections of 0.22 and 0.43 nmol of clonidine into the rLRN produced dose-dependent decreases in arterial pressure. The 0.43 nmol dose of clonidine had no effect when unilaterally or bilaterally microinjected into either the nucleus reticularis rostroventrolateralis or into the nucleus paragigantocellularis lateralis. Microinjection of the alpha-2 adrenoceptor antagonist, idazoxan (16.6 nmol), unilaterally into rLRN had no effect per se, but prevented the hypotensive effect of a subsequent microinjection of clonidine. Similarly, bilateral microinjection of idazoxan into rLRN counteracted the hypotensive effect of i.v. administered clonidine. These data indicate that clonidine acts at alpha-2 adrenoceptors in the rLRN to produce hypotension.     

Effect of two different types of malnutrition on the rate of elimination of ethanol in rats

Rats were fed "3% casein" or a "calorie deficient" diet, in the form of commercial pellet diet (SDS) at 50% of the amount consumed by the control group, which was fed SDS pellets ad libitum. Both of the deficient groups showed failure of weight gain in comparison with the control group. Blood levels of ethanol were measured for 3 hr after intraperitoneal injection of 1 or 1.5 g/kg at 15, 29 and 36 days after commencement of the diet. In addition the calorie deficient group was studied immediately after feeding as well as in the fasting state. Blood levels of ethanol were measured and the apparent volume of distribution and rate of removal of ethanol from the blood were calculated. A rate of ethanol metabolism/g of liver was derived. The rate of removal of ethanol was markedly decreased in the 3% casein group to less than half of control values. Three hours after injection of ethanol circulating levels were less than 50 mg/100 ml in the control and calorie deficient groups but over 200 mg/100 ml in the group fed protein deficient diets. There were no major changes in volume of distribution and the only explanation for the finding is that there is a failure of ethanol metabolism in the rats fed the low protein diet. The implication is that protein deficient human populations who often consume considerable quantities of ethanol may have a high level of tissue exposure to ethanol though the rate of metabolite formation may be low.     

Demethylpeceyline, A New Dimeric Indoline Alkaloid from Petchia ceylanica

A new dimeric indoline alkaloid has been isolated from the leaves of PETCHIA CEYLANICA. Its structure has been assigned as 1 on the basis of spectral studies. Its stereochemistry has been established by NOE difference measurements.     

Absence of psychosocial bias in the under-reporting of unintentional childhood injuries.

Bias resulting from under-reporting has been largely ignored by studies that have examined the relationships between psychosocial factors and unintentional childhood injuries. This study was part of a larger investigation that examined associations between psychosocial factors and unintentional childhood injuries in a sample of 781 children. Visits to an accident and emergency department and their general practitioners were used to determine whether the children or their mothers were under-reporters. "Under-reporters" were compared with "reporters" on a variety of family, behavioural, and development factors. The analyses showed that under-reporters did not differ significantly from the remainder of the sample in terms of psychosocial factors central to the main study.     

Hepatosplenic schistosomiasis. Pathophysiology and treatment.

HSS represents a special model of intrahepatic portal hypertension characterized by a presinusoidal portal block and a well-preserved liver parenchyma. Symmers' fibrosis appears in a small but significant proportion of patients with a high worm load. Its pathogenesis is not well established, although experimental and clinical studies point to egg granulomata as the main pathogenetic factor. The eggs carried continuously through the portal circulation produce inflammation and gross amputation of the intrahepatic veins, portal and periportal granulomas, and, eventually, a coarse perilobular fibrosis ("pipe-stem"). Portal hypertension, esophageal varices, and hepatosplenomegaly are the main consequences of these morphologic changes. Gastrointestinal bleeding is the most frequent cause of death. Unlike in cirrhosis, advanced liver failure is not seen except when HSS is associated with liver lesions from other causes such as virus and alcoholism. Helminthiasis treatment is based on chemotherapy with praziquantel or oxamniquine. Bleeding esophageal varices are managed by sclerotherapy or surgical procedures. Splenectomy with gastroesophageal devascularization seems to be the best choice.     

The effect of nitroglycerin on response to tracheal intubation. Assessment by radionuclide angiography

The effect of intravenous (IV) nitroglycerin (NTG) on perioperative myocardial ischemia as detected by single pass radionuclide angiocardiography was studied in 20 patients scheduled for elective coronary artery bypass grafting (CABG). Ten patients, selected at random, received IV NTG 1 microgram.kg-1.min-1 (NTG group) and 10 others, IV saline (control group). Anesthetic induction consisted of midazolam 0.2 mg.kg-1, vecuronium 0.1 mg.kg-1, and 50% N2O in O2. ECG leads I, II, and V5 were monitored for ST segment changes. Single pass radionuclide angiocardiography (RNA) was performed at 5 times: prior to induction, prior to tracheal intubation, and at 1, 3.5, and 6 min following intubation. The presence of new regional wall motion abnormalities (RWMA) was determined from each RNA study as compared with the preinduction measurement. Apart from one patient in the control group who developed a new "v" wave after intubation, there was no evidence of ischemia by pulmonary capillary wedge pressure. No ECG evidence of ischemia was detected in any patient. Despite this, new regional wall motion abnormalities were observed in 3 patients in the control group and 1 patient in the NTG group. Blood pressure and heart rate responses of patients with new RWMA were not significantly different from other patients. The low incidence of ischemia in this population precludes a definitive statement regarding the efficacy of IV NTG, but the lower incidence of RWMA in the NTG group suggests a protective effect.     

Extended structural variation of a pentanucleotide repeat in the GSTP1 gene: characterisation in a normal population and in thyroid and gastric tumours

The promoter region of the human GSTP1 gene contains a polymorphic short tandem repeat (STR) locus consisting of pentanucleotide repeat units (ATAAA). In this work we report the existence of a total of 26 alleles in a Caucasian population. While differences in size (ranging from one to five base pairs) were responsible for the major variation, in five size-defined classes, two alternative sequences were found. Automatic fragment sizing and sequencing analysis revealed that this polymorphism is of a highly complex nature in contrast with previous reports. A genetic population study was carried out on a random sample from Portugal showing no deviation from Hardy-Weinberg equilibrium. Somatic instability studies were also performed on gastric and thyroid tumours using this STR: no instability was detected in thyroid tumour tissues when compared with their normal counterpart but in gastric tumour tissues microsatellite instability (MSI) was detected in 9.6% of the cases and loss of heterozygosity (LOH) also in 9.6% of the cases studied. The results obtained with GSTP1 in gastric cancer were compared with previously reported data on MSI using BAT-26 and several dinucleotide repeat markers.     

Cardiovascular and respiratory changes during acute pulmonary edema produced by nephrotoxic serum in the rat

The intravenous injection of rabbit anti-rat kidney serum in rats produces, with a latency of 30 to 60 seconds, the triad sinus bradycardia (or S-A blockade), systemic hypotension and apnea. Recordings of the intracardiac pressures showed a rise in the right and a simultaneous fall in the left ventricular pressure, 30 to 60 seconds after the serum injection. These initial effects were followed by pulmonary edema and death. Bilateral vagotomy prevented the bradycardia and apnea, but not the intracardiac changes, edema and death. Atropine also prevented the bradycardia, but not the apnea, edema and death. Experiments using alpha and beta adrenergic blocking agents seem to indicate that the edema is not caused by the release of catecholamines. It is suggested that the edema could be explained by a rise in the pulmonary capillary pressure, due to the antigen-antibody reaction. The triad bradycardia, systemic hypotension and apnea seems to be the first sign of the pulmonary edema, is reflex in nature, and is assumed to be due to stimulation of J receptors in the lungs, by a mechanical effect (edema). Phenylbutazone and acetylsalicylic acid give a partial protection against the pulmonary edema. Ultramorphological observations of lungs with edema were described.     

Effect of losartan on sodium appetite of hypothyroid rats subjected to water and sodium depletion and water, sodium and food deprivation

The involvement of angiotensin AT1 receptors in sodium appetite was studied in hypothyroid rats treated with the angiotensin II antagonist losartan. Losartan was administered chronically by the oral route or acutely by the subcutaneous route after water and sodium depletion or water, sodium and food deprivation. Three days after addition of losartan to the food at the dose of 1.0 mg x g(-1), the rats significantly reduced (P < 0.02) their spontaneous intake of 1.8% NaCl. Increasing the dose of losartan to 2.0 and 4.0 mg x g(-1) did not reduce NaCl intake; in contrast, the intensity of the sodium appetite gradually returned to previous levels. The simultaneous administration of captopril, an angiotensin converting enzyme inhibitor, and losartan significantly increased (P < 0.05) NaCl intake and after captopril removal NaCl intake returned to the levels observed with losartan treatment alone. The administration of losartan 4 days after the beginning of captopril treatment significantly reduced (P < 0.0001) NaCl intake. Following acute administration of losartan, water- and sodium-depleted rats significantly reduced their NaCl and water intake (P < 0.001). The administration of losartan also induced a significant reduction in NaCl and water intake in water, NaCl and food-deprived rats (P < 0.0001 and P < 0.001, respectively). The present results show that chronic treatment with oral losartan inhibited spontaneous sodium appetite in hypothyroid rats. Continuation of treatment rendered rats resistant to the blockade of AT1 receptors. Water and sodium depletion and water, NaCl and food deprivation induced sodium appetite, which in the short term depends on cerebral angiotensinergic activity mediated by the activation of AT1 receptors.