Prevention of ethanol-induced gastric lesions in rats by natural honey, and its possible mechanism of action.

The effects and the mechanism of natural honey on absolute ethanol-induced gastric lesions were studied in rats. Drugs and/or honey were administered subcutaneously or orally to 48-h fasted animals at different time intervals before oral administration of ethanol (0.5 ml/100 g). Mucosal damage and pH were measured 1 h later. Honey afforded protection against gastric damage and reversed the changes in pH induced by ethanol. The effects of honey were dose- and time-dependent. Thus, pretreatment with honey (1.25 g/kg) 30 min before ethanol provided more than 80% protection. On the other hand, administration of honey simultaneously with or 5 min after ethanol failed to offer protection. The cyclooxygenase inhibitor indomethacin (IND) did not alter the protective effects when given before or after honey. The protective effects of honey could be reversed by treatment with the sulfhydryl (SH) blocker N-ethylmaleimide (NEM). Combined IND and NEM treatment caused greater reduction of the protective effects, but the values were not significantly different from those obtained with NEM alone. Thus, the gastroprotective effects of honey appeared to be mediated through SH-sensitive processes. Furthermore, the protective effects were supported by both macroscopic and microscopic findings. It is suggested that honey may be used clinically in preventing/reducing ethanol-induced gastric lesions in humans.     

Vascular endothelium.

Endothelium lines all blood vessels and the cardiac cavities and has a central role in cardiovascular homeostasis. It releases several potent substances which mediate the control of vascular tone and cardiac contraction. Endothelial dysfunction is implicated in many disease states. Elucidation of the underlying mechanisms is likely to lead to novel therapeutic strategies.     

Menstrual-Linked Asthma

This study was conducted to determine the occurrence of menstrual-linked asthma (MLA) in India in 100 consecutive female asthmatics in the reproductive age group. The patients were required to respond to a questionnaire concerning the relationship between their asthma and the menstrual cycle. Twenty-three patients had subjective perception of deterioration in symptoms of asthma in relation to the menstrual cycle. Ten patients from both groups were also required to maintain a daily peak expiratory flow rate (PEFR) diary for 2 consecutive menstrual cycles. The mean total duration of illness in patients with MLA was significantly longer than in patients without cyclic exacerbation. Cough and breathlessness were also significantly more severe as was the disease. This was evidenced by the more frequent emergency room visits and hospitalizations in these patients. Menstrual-linked worsening of asthma was most common in the premenstrual week (17 patients). In 8 of these 17 patients, this phenomenon continued to occur during the menstrual week also. Interestingly, 1 patient complained of deterioration of asthma 2 days after menstruation was over. Such an observation is yet to be recorded. Fourteen patients reported an increase in symptoms with almost every cycle while 3 had worsening related to specific season only. Sixteen patients often required extra medication during the premenstrual and/or menstrual weeks. A significant association was also observed between severity of premenstrual syndrome and MLA. The mean PEFR values over 2 cycles revealed a significant fall in the morning as well as evening values in the premenstrual and menstrual weeks as compared to the midcycle week in patients with MLA. This fall was maximal in the premenstrual week. Such a fall was not observed in asthmatics without menstrual exacerbation of symptoms. MLA was detected in about a fourth of the female asthmatics in India and it appears to represent a more severe form of the disease. This study also documented that MLA was associated with an increase in airway resistance and was not simply due to an increased perception of symptoms during the premenstrual or menstrual weeks.     

Effects of probucol on renal function in rats with bilateral ureteral obstruction

To ascertain the potential role of reactive oxygen metabolites in the pathophysiology of obstructive uropathy, we examined the effect of probucol, an antioxidant agent, on renal function in normal rats and rats with unilateral release of bilateral ureteral obstruction (BUO) of 24 hours duration. Rats were fed either a standard diet or a standard diet containing one percent probucol for two weeks prior to study. Probucol lowered serum cholesterol in both normal and BUO rats. Probucol did not significantly affect renal function in normal rats. BUO rats given probucol had greater inulin and PAH clearances at three to five hours and three days following release of BUO than rats with BUO not given probucol. Kidneys from obstructed rats had higher levels of malondialdehyde, an index of lipid peroxidation, a greater number of leukocytes in the cortex, decreased levels of reduced glutathione and increased levels of oxidized glutathione. Renal cortex from obstructed rats treated with probucol had significantly higher levels of reduced glutathione than kidneys of obstructed rats not given probucol. A decrease in cholesterol, using another lipid-lowering agent, lovastatin, did not modify renal function in rats with BUO. The data can be interpreted to indicate a role for reactive oxygen species in the pathophysiology of obstructive nephropathy. The improved renal function seen in probucol-treated rats with BUO may be due to an effect of this agent in affecting accumulation of reactive oxygen metabolites and/or decreasing the number of leukocytes infiltrating the renal cortex.     

Effects of risk-associated human dietary macrocomponents on processes related to carcinogenesis in human-flora-associated (HFA) rats

Dietary fat, beef protein and fibre have been shown to modulatecancer risk in humans and the present study examined the biologicaleffects in human-flora-associated (HFA) rats of altering intakelevels within the normal human range. Two control groups, oneHFA and the other germfree (GF), consumed a human diet low infat, fibre and beef for 4 weeks; three other groups consumedhuman diets similar except for independent 3-fold increasesin fat, beef protein or fibre. After 2 weeks on the diets, magneticallyrecoverable microcapsules were given orally to the rats andsubsequently recovered from the faeces to assess endogenouscross-linking agents. After 4 weeks, measurements were madeof gut microfloral enzyme activities, hepatic activation ofdietary mutagens and hepatic DNA adducts by ³²P-postlabelling.Activation in vitro of the dietary mutagens 2-amino-3-methyl-3H-imidazo[4,5-f]quinolline (IQ) and 2-amino-l-methyl-6- phenytimidazo[4,5-b]pyridine(PhIP) by hepatic S9, formation of endogenous hepatic DNA adductsin vivo and the ß-glucuronidase activity of caecalcontents were all increased in the sequence high fat > highfibre > high beef = control. Of the two DNA adducts foundin all HFA rats, only one was present in GF controls, indicatingthat the human gut microflora (subject to human dietary modulation)either releases a DNA-adducting product able to act outsidethe gastrointestinal tract, or stimulates the generation ofsuch a product by mammalian processes. Caecal nitrate reductaseactivity was highest in rats fed the high beef diet, whilstentrapment of cross-linking agents was highest in those fedthe high fibre diet. These results show that risk-related componentsof human diets interact with human gut microflora to modulatethe production of endogenous DNA-adducting and cross-linkingsubstances.     

THE EFFECT OF SOME α2-ADRENOCEPTOR AGONISTS AND ANTAGONISTS ON GASTROINTESTINAL TRANSIT IN MICE: INFLUENCE OF MORPHINE, CASTOR OIL AND GLUCOSE

1. The effects of graded doses of the α₂-adrenoceptor agonists clonidine, tizanidine and BHT-920, and the α₂-adrenoceptor antagonists yohimbine and idazoxan, on gastrointestinal transit were investigated in mice using the charcoal meal test. 2. The agonists produced significant and dose-dependent decreases in gastrointestinal transit, and the antagonists produced the opposite effect. In affecting the gastrointestinal transit, clonidine (1 mg/kg) was as effective as tizanidine (12 mg/kg) and BHT-920 (40 mg/kg), while yohimbine (2 mg/kg) was as effective as idazoxan (1 mg/kg). 3. Morphine (2, 4 and 8 mg/kg) significantly inhibited gastrointestinal transit. This effect was significantly reversed by the co-administration of yohimbine (2 mg/kg) and idazoxan (1 mg/kg). 4. The acute administration of glucose (5.04 g/kg, i.p.) potentiated the inhibition of gastrointestinal transit produced by clonidine (1 mg/kg) and BHT-920 (40 mg/kg). Glucose treatment, however, had no significant effect on the increase in gastrointestinal transit induced by yohimbine (2 mg/kg) or idazoxan (1 mg/kg). 5. Castor oil (0.25 mL/mouse, orally) induced diarrhoea in saline-treated animals within about 45 min. Clonidine (1 mg/kg), tizanidine (12 mg/kg) and BHT-920 (40 mg/kg) delayed the occurrence of diarrhoea to 2.1, 1.2 and 1.4 h, respectively.     

Hypothalamic-hypophyseal-testicular abnormalities and erectile dysfunction

Forty-five men presenting with erectile dysfunction were evaluated through history and nocturnal penile tumescence, Doppler, and EMG studies. Fifteen were classified as having organic and 30 as having psychogenic impotence. Three men had mild hypergonadotropism with low testosterone levels. One had hyperprolactinemia. No case of hypogonadotropic hypogonadism was detected. Six patients who had psychogenic impotence had low levels of testosterone.