Effect of Aframomum melegueta. Seed Extract on Castor Oil-Induced Diarrhea.

The effect of the aqueous (aq) seed extract of Aframomum melegueta. K. Schum. (Zingiberaceae) on castor oil-induced diarrhea, intestinal fluid secretion, and gastrointestinal transit was investigated in the study. Castor oil (10 ml/kg, p.o.) induced copious diarrhea in all rats 3 h after treatment. Furthermore, it produced a significant increase in the volume of intestinal fluid secretion in rats and also enhanced intestinal transit in mice. The aq seed extract of A. melegueta. (100-500 mg/kg, p.o.) offered significant protection against diarrhea induced by the oil. At a dose range of 250-500 mg/kg, the extract reduced significantly the volume of fluid secretion in castor oil-treated rats. At these doses, it also demonstrated a significant antitransit activity in a dose-related manner. Acetylsalicylic acid (100 mg/kg, p.o.) delayed diarrhea and reduced the number of animals with diarrheal droppings to 20%. At the same dose level, acetylsalicylic acid reduced significantly the volume of intestinal fluid secretion but lacked antitransit property in castor oil-treated animals. N.-Nitro-L-arginine methyl ester (L-NAME) (2.5-10 mg/kg, i.p.) dose-dependently reduced the number of animals with diarrhea. At 50 mg/kg i.p., it offered 100% protection against diarrhea induced by the oil. Furthermore, L-NAME (10 mg/kg, i.p.) significantly inhibited both the intestinal fluid secretion and gastrointestinal transit induced by castor oil. However, L-NAME (10 mg/kg, i.p.) did not significantly modify the antidiarrheal effect of A. melegueta.. L-Arginine, a substrate of nitric oxide synthase or isosorbide dinitrate, a nitric oxide donor, did not alter the effect of A. melegueta. on diarrhea. Ascorbic acid (100 mg/kg, p.o.) and α.-tocopherol (20 mg/kg, p.o.) reduced the number of animals with diarrhea to 80% and 70%, respectively. However, they both lacked significant activities on intestinal fluid secretion and gastrointestinal transit induced by castor oil. The combination of ascorbic acid (100 mg/kg, p.o.) or α.-tocopherol (20 mg/kg, p.o.) with A. melegueta. (500 mg/kg) offered higher protection against diarrhea than the extract alone. Considering these results together, it may be inferred that Aframomum melegueta. seed extract may be a useful antidiarrheal agent.

Effects of chronic oral nickel chloride administration on glycaemia and renal function in normal and diabetic rats.

Effects of nickel on glycaemia are conflicting. We have investigated the effects of oral administration of nickel chloride for 5 weeks on glycaemia and renal function in normal and streptozotocin-diabetic rats. The results show increase (P< 0.05) in plasma glucose and sodium and decrease (P< 0.05) in insulin concentrations only in normal experiment by comparison with normal control. Plasma potassium concentration was elevated (P< 0.05) only in diabetic experiment by comparison with diabetic control. Plasma urea levels were raised (P< 0.05) in both groups of experiments by comparison with respective controls and plasma creatinine level was elevated (P< 0.05) only in diabetic experiment. GFR was reduced (P< 0.05) only in normal experiment by comparison with control. Kidney weights in normal and diabetics were not effected by nickel chloride administration. Total food and water intakes in normal and diabetic experiments were lower by comparison with respective controls. These were accompanied by failure to increase body weights. In addition, total urine volume and sodium were reduced in normal and diabetic experiments. Urine potassium was lower only in normal experiment by comparison with normal control. We conclude that chronic nickel chloride administration induces hyperglycemia possibly through reduction in blood insulin levels and could be toxic to renal function.

Indomethacin and alpha-tocopheral enhanced survival in endotoxic rats.

Induced endotoxaemia was studied in healthy male albino rats injected intravenously with lipopolysaccharide from Escherichia coli at 10, 20 and 30 mg/kg dose levels. The endotoxic rats were closely observed for mortality within 48 hours and subsequently for seven days. Within five hours post administration over 50 pc mortality was observed at dose levels of 20 to 30 mg/kg. Pre-treatment of rats with Indomethacin (250 mg/kg) alone and alpha-tocopheral (100 mg/kg) produced significant protective effects with the mortality rate reduced to 50 pc at the highest endotoxin dose level. Interestingly a combination of both drugs significantly improved survival with an observed mortality of 20 pc. Prednisolone (500 mg/kg) either alone or in combination with indomethacin or alpha-tocopherol did not offer any advantage. Instead the mortality rate was significantly high. A combination of Indomethacin and alpha-tocopheral significantly improved survival in endotoxic rats.

Effects of calcium ions and atropine on endotoxin-induced contractility deficit in rat atrial muscle.

Isolated atrial muscle preparations obtained from rats injected (ip) with 3.7 x 10(9) per kg/body weight heat killed pure E. coli (endotoxin) were used to investigate the severity of induced mycocardial inotropic dysfunction and the effects of some autonotic agents and calcium. Both atrial strips were removed from endotoxin-shock rats at 48 and 72 hours post treatment. The control groups were given (ip) 0.2ml of isotonic saline and sacrificed at the same period as the treated groups. Maximum developed contractile force (amplitude) were significantly depressed in atrial strips of shock rats (p < 0.05). Maximum deficit in atrial contractility was characterised by altered responsiveness to low extra cellular Ca2+ (0.12mM) concentration. Increasing Ca2+ concentration by 1-3 mM in a normal Ca2+ medium significantly enhanced the contractile force by an increase of 88 +/- 5.9% (p < 0.005). Atropine (5 x 10(-7) - 1.5 x 10(-6)M) produced positive intropic effect with a maximum increase of 80 +/- 7.1% (p < 0.05) in the shock atrial strips. Noradrenaline (1 x 10(-7)-10(-6)) on the other hand, did not produce any significant inotropic effect. Concomitant administration of noradrenaline (1 x 10(-6)M) and atropine (1.5 x 10(-5)M) produced positive inotropic effect which is not greater in magnitude compared with atropine (5 x 10(-7)M). This study suggests that Ca2+ and atropine may provide beneficial effects in endotoxin-induced shock state. It also confirms the involvement of myocardium in the pathogenesis of this condition.

Interaction between frusemide and aspirin.

The effects of the combination of aspirin and frusemide were studied on salicylate excretion by aspirin and on the diuresis and excretion of K+ and Na+ by frusemide in normal human subjects. There was a paradoxical net reduction in the natriuresis induced by aspirin, from 29.4 +/- 3.57 m-equiv and frusemide from 31.9 +/- 1.27 to 23.7 +/- 1.56 m-equiv on combined administration. Frusemide caused a reduction of the kalliuretic effect induced by aspirin from 48.86 +/- 8.36 to 18.3 +/- 3.76 m-equiv. The amount of salicylate excreted over a 3-hr period gave increases of 9.6 and 12.0% when aspirin was administered before frusemide and vice versa, respectively, while there was a 30.4% reduction when administered concomitantly.

Electrophysiological correlates of the behavioral effects of tubocurarine in conscious cats.

The effects of tubocurarine on behavior, electrical activity, and auditory evoked potentials were studied in restrained conscious cats. Tubocurarine hydrochloride (doses of 0.05--1 micrograms intraventricularly) produced various central stimulatory effects characterized by EEG desynchronization, decrease in both low (7--9 Hz) and high (10--14 Hz) alpha waves, and decrease in the amplitude and area of the surface positive (P1) wave of auditory evoked potentials. Concomitant with the alterations in brain electrical activity tubocurarine hydrochloride produced generalized behavioral arousal phenomena and the cats became restless and exhibited miaowing and increased movement of the head and ears. Almost all parameters except behavior showed a distinct dose-response relationship. A correlation between the behavioral effects and the EEG analog was thus demonstrated.