Synthesis and uterotrophic activity of 2-substituted estradiol and ring A fused pyranone and furanone derivatives

Several new modified estradiol analogs have been synthesized and examined as potential estrogens. Nuclear modification involved the introduction of various substituents at the 2-position of estradiol and fusion of a heterocylic ring to position 2, 3 of ring A of the steroidal nucleus. Uterine weight assays in rats have shown that all tested compounds produced a moderate increase in uterine weight

Helicobacter pylori, hypergastrinaemia and duodenal ulcer: a causal relationship

The relation between Helicobacter pylori infection and fasting gastrin was evaluated in 60 subjects [20 H. pylori positive duodenal ulcer patients, 20 H. pylori positive normal upper gastrointestinal tract [GIT] endoscopy and 20 H. pylori negative subjects]. H. pylori infection was determined by histopathology of endoscopy taken antral biopsy. Fasting serum gastrin was assayed with specific radioimmunoassay systems. Results clearly indicated that fasting gastrin was higher in H. pylori positive patients compared with H. pylori negative subjects. Fasting gastrin concentration in serum samples of H. pylori positive patients with duodenal ulcer was insignificantly higher than those with normal upper GIT endoscopy, suggesting that similar mechanisms are involved in increasing serum concentration of this variable in both population groups. Eradication of H. pylori infection from patients with active duodenal ulcers is a accompanied by fall in basal gastrin level to values near to those with H. pylori negative patients. According to these results, it is evident that basal hypergastrinaemia, which is an important hormonal factor in the pathogenesis of duodenal ulcer disease, can be or partially due to antral mucosal invasion by H. pylori infection

Effects of cimetidine or ranitidine on local anaesthetic toxicity induced on the central nervous system in rats

Seventy-two rats were used in this study to demonstrate the effect of histaminergic receptor blockers [H2 blockers]; namely, cimetidine or ranitidine, when administered 20 minutes prior to lidocaine on lidocaine induced central nervous system toxicity. The animals were classified into three main groups, each was further subdivided into four subgroups to study the effects of variable dosage regimens as follows: Intraperitoneal 30, 45, 60 or 75 mg/kg lidocaine alone or together with intraperitoneal cimetidine 15, 50, 100, or 200 mg/kg, respectively, or ranitidine 7.5, 25, 50 or 100 mg/kg, respectively. The results indicated that the lidocaine toxic dose was 60 mg/kg when given alone or with ranitidine while it was 45 mg/kg when lidocaine was combined with cimetidine. Again cimetidine also enhanced the convulsive effect of lidocaine and delayed its recovery period. In conclusion, ranitidine may be a safer component of premedication than cimetidine when adverse drug interactions, specially with local anesthetics, are considered

Effect of nifedipine, verapamil and diltiazem on some cardiovascular parameters, electrolytes, and acid-base balance in halothane anaesthetized dogs

Since nifedipine, verapamil and diltiazem have distinct cardiovascular effect, thus, it is important to study their interactions with anesthetic agents. The aim of this work is to study the hemodynamic effects of these drugs during halothane anesthesia. Also, the possible electrolyte and acid base changes produced by them are studied. Equipotent hypotensive doses of the three calcium channel blockers are administered by continuous infusion to three groups of animals to produce a uniform [25-30%] reduction in blood pressure. It is found that calcium channel blocking agents during halothane anesthesia produced a stable decrease in blood pressure in different mechanisms. Verapamil and diltiazem decreases blood pressure by decreasing cardiac output, while nifedipine produces its hypotensive effect by decreasing the systemic vascular resistance. The changes in serum sodium, potassium, calcium and magnesium levels and in PaO2, PaCO2 and pH are all insignificant

Effect of added analgesic clonidine or vasoconstrictor epinephrine to bupivacaine spinal anesthesia [experimental study on dogs]

In an attempt to study the effect of either clonidine or epinephrine on the duration of bupivacaine spinal anesthesia, 18 dogs were studied, they were divided into three equal groups, each of six dogs. In group 1, 1 ml bupivacaine [5 mg/ml] alone was injected intrathecally, whereas in group 2, clonidine [150 mug] was added to bupivacaine and in group 3 epinephrine in a dose of 200 mug was added to bupivacaine. It was found that clonidine as an adjunct to bupivacaine spinal anesthesia may provide advantage over epinephrine including prolongation of the duration of both motor and sensory blockade with more effect on the duration of sensory blockade

effect of lormetazepam and midazolam on some monoamines and amino acid levels in the brains of guinea pigs

The effect of lormetazepam and midazolam on norepinephrine, dopamine, gamma-amino-butyric acid [GABA], L-glutamic acid and their enzymes were investigated in both acute and chronic experiments. A significant decrease in the levels of norepinephrine and dopamine was observed in midazolam group in acute and chronic studies, while an insignificant change was observed with lormetazepam. Both drugs caused a significant increase in GABA and glutamic acid decarboxylase in L-glutamic acid and gamma-aminobutyric alpha ketoglutaric transaminase activity [GABA-T]

Propionic acid derivatives and the functions of the liver and the kidney in albino rats

A comparative study on the effects of two propionic acid derivatives on liver and kidney functions and their withdrawal was performed on sixty adult male albino rats that were divided into two equal pirprofen and ketoprofen groups. Each group, 30 rats, was equally subdivided into a control, a drug treated [receiving either pirprofen [30 rrig/kg] or ketoprofen [12 mg/ kg] for three weeks] and a withdrawal subgroups [after one month of either drug cessation] .With the use of pirprofen, a highly significant increase in aspartate aminotransferase [ASAT], alanine amino-tansferase [ALAT], alkaline phosphatase, creatinine and blood urea and a highly significant decrease in total proteins and prothrombin activity were observed. After one month drug withdrawal, no significant changes in ASAT, ALAT, total proteins, and blood urea were observed but a significant decrease in prothrombin activity and an increase in alkaline phosphatase was still reported. Upon ketoprofen administration, a highly significant decrease in total proteins and prothrombin activity and a highly significant increase in all the rest of hepatic and renal parameters was recorded. While upon one month drug withdrawal, these significant changes were still observed except for blood urea that was insignificantly changed in comparison to the control. From all the above findings one could conclude that, though pirprofen appears safer than ketoprofen, yet both should not be used habhazardly. Also, upon their therapeutic administration, routine liver and kidney functions should be accessed to guarantee for safety usage

Changes in renal function induced by long term treatment with bisoprolol, compared to other beta-adrenocepter blockers

The effect of long term treatment with bisoprolol, a new cardioselective beta-adrenoceptor blocker on some kidney function tests in the rat was studied and compared to atenolol and propranolol. Results showed that the oral administration of bisoprolol [10 mg/kg] caused a highly significant increase in plasma creatinine by 83% and 88% when measured after 3 and 5 weeks of daily treatment, respectively [P <0.001]. Significant increase [P <0.001] in plasma urea reaching 46% and 53% difference from control values was found when measured after 3 and 5 weeks of daily treatment, respectively. On the other hand, no significant change in plasma creatinine and urea levels were observed after oral daily treatment of rats with atenolol [50 mg/kg] for 1, 3 and 5 weeks. Treatment of rats with propranolol [30 mg/kg] elevated plasma creatinine level insignificantly by 6%, 24% and 25% when measured after 1, 3 and 5 weeks, respectively [P >0.05]. This was accompanied by minimal changes in plasma urea. All three beta-blockers tested, had no significant effect on total plasma proteins. Results showed that beta-adrenoceptor blockers produce changes in the kidney function regardless of their cardioselectivity. The possible mechanisms of action by which bisoprolol induced such changes were discussed