Comparative effect of tiaprofenic acid and piroxicam alone and as adjuvants to praziquantel in schistosoma mansoni infected mice

Non-steroidal anti-inflammatory drugs [NSAIDs] [tiaprofenic acid and piroxicam] have been used alone and as adjuvants to praziquantel in treating hepatic granuloma in Schistosoma mansoni infected mice. Granuloma diameter, histamine metabolism, cyclic AMP and PGE2 levels have been measured at the end of treatment. Tiaprofenic acid effectively reduced the size of hepatic granuloma, significantly increased histamine forming capacity, CAMP level and significantly decreased plasma PGE2 level. Piroxicam had no significant effect on granuloma size, significantly decreased histamine forming capacity, CAMP and PGE2 levels. The combined therapy of either of the drugs with praziquantel did not result in an additive effect

Effect of ramipril [HOE 498] on the central monoaminergic system in normotensive and doca-salt hypertensive rats

Acute and chronic effects of ramipril in normotensive and DOCA-salt hypertensive rats, respectively, were investigated on the brain monoaminergic system and the renin-angiotensin system [RAS]. Acute ramipril treatment in normotensive rats produced a significant drop in plasma angiotensin converting enzyme [ACE] and brain monoamine oxidase [MAO] activities accompanied by a significant rise in brain 5-hydroxytryptamine [5-HT] level. Changes in brain catecholamines [CA]; namely, norepinephrine [NE] and dopamine [DA], were insignificant, possibly pointing to a longer duration of action needed by ramipril to exert its direct control inhibition on the sympathetic tone. On the other hand, chronic ramipril treatment in DOCA-salt hypertensive rats produced a significant drop in plasma ACE and brain MAO associated with a significant rise in brain NE, DA and 5-HT levels, the blood pressure and heart rate values were also controlled to reach nearly normal values. These data suggested that chronic administration of ramipril might have partly diminished secondary sympathetic activity and slowed down brain CA and 5-HT turnover. Moreover, the data emphasize the modulating role of the RAS on central sympathetic activity during both the normotensive and the hypertensive and the hypertensive states

Effect of propranolol on brain monoamines, monoamine oxidase, and angiotensin converting enzyme in docasalt hypertensive rats: Potentiation by converting enzyme inhibition

The effect of chronic treatment with propranolol [2 mg/kg, s.c. for two weeks] on brain monoamines; namely, norepinephrine [NE], dopamine [DA] and serotonin [5-HT], brain monoamine oxidase [MAO] and plasma angiotensin converting enzyme [ACE] activities, as well as blood pressure and heart rate changes were investigated in DOCA-salt hypertensive rats. Furthermore, the acute effects of propranolol on the same parameters in normotensive rats, and their possible interaction when combined with AGE inhibition were also demonstrated. Chronic treatment with propranolol resulted in decrease of the systolic blood pressure in DOCA-salt hypertensive rats, with evident bradycardia. Brain monoamine levels increase significantly, this was accompanied by significant inhibition of MAO and aCE activities. These changes might reflect a decrease in monoamine turnover in the brains of propranolol treated DOCA salt hypertensive rats, which may or may not be related to central B-adrenoreceptors. On the other hand, acute administration of propranolol to normotensive rats revealed less prominent effects. On combination with the ACE inhibitor, ramipril, and evident synergistic effect was observed. These data substantiate the possibility of an interaction between the enzymes involved in the renin-angiotensin system [RAS] and the sympathetic nervous system, which on combination could lead to potentiation

Effect of oxamniquine and praziquantel on liver monoamine oxidase [MAO] in schistosoma mansoni infected mice

The hepatic MAO activity was determined in Schistosoma mansoni infected mice after the eighth week of infection. A marked drop in enzyme activity was noticed. Treatment of these infected mice using one of the recently introduced antischistosomal agents, either oxamniquine or praziquantel, resulted in improvement of MAO activity to the normal level. This may suggest that regression of the pathological changes, accompanying schistosomal hepatic fibrosis in mice, may result from early effective treatment

Pirenzepine and ranitidine as single agents and in combination in protection of the gastric mucosa against phenylbutazone injury

The protective effect of pirenzepine and/or ranitidine on phenylbutazone induced gastric ulcerations has been studied in the rat. Phenylbutazone produced severe gastric lesions in the glandular part of the stomach, which was accompanied with a significant increase in acid and pepsin. Pretreatment of the phenylbutazone treated rats with pirenzepine [100 mg/kg, X2 orally] significantly protected the rats and this was accompanied by significant lowering in acid and pepsin and a significant rise in the mucin content. While, pretreatment of the phenylbutazone treated rats with ranitidine [150 mg, X2 orally], also protected the animals against ulceration, but was accompanied with only a drop in acidity. Pretreatment of these animals with the drug combination [using only half of the dose of that used singly] afforded a higher protection ratio, a higher drop in acidity and pepsin and a marked rise in the mucin content. The data presented confirm the role of reduced acidity and peptic activity [aggressive factors] in the protection against phenylbutazone induced gastric lesions. It also emphasizes the necessity of giving preventive medications in the form of anti-ulcer agents when given anti inflammatory agents, bearing in mind the defensive factors involved. The study might also explain the synergistic anti-ulcer effect of the combined treatment with muscurinic M-blockers and histamine H2 blockers

Effect of long term ranitidine treatment on gastric mucosal histamine content, histamine forming capacity and diamine oxidase activity in normal and restrained rats

The role of histamine in stress ulcer development was studied in female rats by measuring the level of gastric mucosal histamine, gastric histidine decarboxylase activity and intestinal diamine oxidase activity. Long-term administration of ranitidine, a new histamine H2-receptor antagonist, significantly protected the animals against the production of gastric lesions, in spite of the fact that the gastric mucosal histamine level and the gastric histidine decarboxylase activity were found to be best explained by its antisecretory action of H2-receptor antagonism, since no correlation was found between ulcer protection and gastric mucosal histamine content, histidine decarboxylase and diamine oxidase activities

Pharmacokinetics of chloramphenicol in plasma and lymph in patients with schistosomal hepatic fibrosis

This work was undertaken on 10 schistosomal patients to compare the pharmacokinetics of chloramphenicol in plasma and lymph of schistosomal patients in the immediate postoperative period following splenectomy. Cannulation of the thoracic duct was performed, while the patients were under general anesthesia. Intramuscular injection of chloramphenicol every 12 hours. Serial blood and lymph samples were obtained from each patient for up to 12 hours after the first dose of drug administration, for assay of chloramphenicol. Chloramephnicol pharmacokinetics followed a two-compartment open system. The distribution phase was present, but was not very prominent. Peak concentrations of chloramphenicol were spread over a wide range from 6.7 mug/ml to 24 mug/ml. The time required to reach peak concentration averaged about 2 hours. Delayed appearance of chloramphenicol in lymph was noted, and the lag period ranged between 5 and 30 minutes. A shift in the time of peak concentration of this antibiotic in lymph was also obtained. Time to reach peak concentration was about 3 hours. The maximum concentration in thoracic duct lymph was about 60% of the peak in plasma. The mean level of chloramephnicol in lymph and plasma after 12 hours from the injection was too low [2.5 mug/ml] to satisfy the requirements for effective therapy for sensitive anaerobes [MIC 10-20 mug/ml] or aerobes [MIC about 5 mug/ml]. The average concentrations after 8 hours of the first dose were above 4 mug/ml in plasma and lymph and is expected to increase on repeated injections. It is therefore suggested that a dosing schedule every 8 hours may prove satisfactory for immediate postoperative treatment of schistosomal patients

Effect of nifedipine on phenylbutazone and restraint induced gastric ulceration in the rat

The effect of nifedipine on phenylbutazone [PBZ] - and restraint induced gastric ulcerations had been studied in the rat. Both PBZ [200 mr/kg] and restraint caused severe lesions in the glandular part of the stomach. Associated with stress ulcer production, the gastric histamine content was significantly increased, while PBZ treatment did not alter mucosal histamine. Pretreatment of restrained rats with nifedipine [3 mg/kg] significantly protected the animals against stress induced gastric damage and this was accompained by a non-significant change in the histamine content of the gastric mucosa. However, administration of the same dose of nifedipine did not protect the rats from developing PBZ ulceration, but significantly increased histamine content in these rats. The data indicate that gastric histamine does not seem to play a role in the antiulcer effect of nifedipine against stress mucosal lesions

Effect of the calcium antagonist verapamil on gastric secretion and mucosal histamine in man

The effect of i.v. injection of verapamil [5 mg] on the gastric secretion as well as mucosal histamine content was investigated in 10 healthy volunteer subjects. Gastric secretion and mucosal biopsies [from body and pylorus] were collected before and after verapamil administration. Verapamil significantly increased the volume of gastric juice, acid output and pepsin activity; however, the mucin content was not altered. During gastroduodenoscopy, after verapamil injection excess gastric juice and redness of the gastric mucosa were a consistent finding in all cases. The drug caused nonsignificant changes in the gastric mucosal histamine content whether in the body or the pylorus regions. The study suggested that gastric secretory stimulation of verapamil might not be mediated by mucosal histamine, but it could be attributed to the vasodilator effect of the drug

Effect of verapamil on histamine and pentagastrin-stimulated gastric acid secretion in man

The effect of verapamil on the histamine and the pentagastrin-stimulated gastric acid secretion had been studied in normal volunteers. Histamine, pentagastrin, or verapamil increased the volume of gastric secretion and acidity when given separately. However, when histamine was followed by verapamil, the volume and acidity dropped, while pentagastrin followed by verapamil administration did not alter the volume nor the acidity. On the other hand, when histamine was proceeded by verapamil, a nonsignificant drop in volume and a significant drop in acidity could be traced, but pentagastrin proceeded by verapamil administration caused a nonsignificant rise in the studied parameters. The data suggested that calcium partly acts as a second messenger, together with cAMP, in the histamine-induced gastric acid secretion. While, the role of calcium in the gastrinergic pathway remains to be further elucidated

Interaction of epinephrine, propranolol, histamine, cimetidine and mepyramine maleate on vesicle smooth muscle of guinea pigs and rabbits

The effect of histamine on the isolated vesical smooth muscle preparation of guinea pigs and rabbits was studied. Isolated muscle strips were mounted in an organ bath that was filled with Tyrode's solution [37°C] and bubbled with carbogen. Histamine [2 micro g/ml in guinea pigs and 3-4 micro g/ml in rabbits] had a contractile effect that was not blocked by neither atropine [0.7 micro g/ml] nor by phentolamine [4 micro g/ml]. The histamine-induced contractions were specifically antagonized by mepyramine maleate [5 micro g/ml] but not by cimetidine [10 micro g/ml]. The effect of mepyramine maleate was studied on the epinephrine-induced inhibition [5 micro g/ml] on the same preparation in both species, in the presence or absence of propranolol [5 micro g/ml]. Mepyramine maleate alone significantly potentiated the epinephrine-induced inhibition in both species. When propranolol was added prior to epinephrine, the reverse occurred and contraction was noted. When both mepyramine maleate and propranolol were added prior to epinephrine, it failed to elicit a response. From this study histamine was found to affect the vesical smooth muscles through mediation of H[1]-receptors in both species. Thus, a possible beneficial effect of antihistamines is suggested in patients suffering from allergic disorders of the lower urinary tract

Pharmacodynamics of the adrenaline induced rise in portal pressure in dogs

"Ten mongrel dogs were used to study the effect of mepyramine maleate [H[1]-blocker] and/or phentolamine hydrochloride on the adrenaline-induced changes in portal pressure and systemic arterial pressure. Through the cannulated portal vein, adrenaline injection [2 micro g/Kg] induced a significant rise in portal pressure and systemic arterial pressure. When mepyramine maleate [1 mg/Kg] was injected prior to adrenaline, the increased portal pressure diminished whereas the increased systemic arterial pressure was potentiated. When phentolamine hydrochloride [1 mg/Kg] was injected prior to adrenaline, the rise in portal pressure was lower than the rise obtained in the previous two experiments, whereas the systemic arterial pressure dropped to near normal values. When the animals were pretreated by mepyramine and phentolamine, adrenaline failed to produce a rise in both portal pressure and systemic arterial pressure. These findings demonstrate that the rise in portal pressure in dogs following adrenaline injection via the portal vein is mainly through activation of alpha-receptors in the portal radicles and suggest, in addition, that its effect is possibly through indirect histamine release from the portal tree

Effect of some drugs on the peritoneal membrane in resistant ascites of schistosomal origin

The influence of some drugs on the ascitic fiuid-plasma barrier was studied in 10 schistosomal patients suffering from resistant ascites. Fibrinolysin, dexamethazone, heparin, and Vitamin B complex, were able to improve transmission through such a barrier with the possible corection of some factors that lead to resistancy of ascites as hypoalbuminaemia, hypo-natraemia, and hypovolaemia. Intraascitic injection of such drugs with mersalyl caused diuresis. The present study gives a further evidence that the barrier is biologically active

"Effects of testosterone and stilbestrol on the liver and lymphoreticular system schistosoma infected mice"

The effects of stilbestrol d testosterone on schistosoma infected mice were studied. Stilbestrol increased the death rate of infected mice, aggravated the schistosomal hyperplasia. Testosterone, on the other hand, significantly diminished the death rate, protected the liver from many of the deleterious effects produced by schistosomasis and minimized the stimulating effect on the lymphoreticular system. The role played by stilbestrol on lymphoreticular hyperplasia and its possible relation to lymphoma in schistosoma infected patients is discussed. The possible therapeutic value of the male hormone, testosterone, in males infected with schistosomiasis is suggested and the possible danger of contraceptive pills [containing oestrogen] in females infected with schistosomiash is raised