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Khattab, M. M., A. M. Moustafa, O. A. Al-Shabanah, and A. S. el-Khatib, "INVOLVEMENT OF NITRIC OXIDE IN CARBON TETRACHLORIDE-INDUCED ACUTE HEPATOTOXICITY IN MICE", Res. Commun. Pharmacol. Toxicol, vol. 7, issue 1-2, pp. 53-64, 2002.
Khayyal, M. T., M. A. El-Ghazaly, and A. S. el-Khatib, "Mechanisms involved in the antiinflammatory effect of propolis extract.", Drugs under experimental and clinical research, vol. 19, issue 5, pp. 197-203, 1993. Abstract

Propolis is a natural product produced by the honey bee. The extract contains amino acids, flavanoids, terpenes and cinnamic acid derivatives. In various in vitro models propolis extract was shown to inhibit platelet aggregation and to inhibit eicosanoid synthesis, suggesting that it might have potent antiinflammatory properties. A 13% aqueous extract was tested orally in three dose levels (1, 5 and 10 ml/kg) on the carrageenan rat paw oedema model and on adjuvant-induced arthritis in rats. In both models, the extract showed potent dose-related antiinflammatory activity, which compared well with that of diclofenac (as a reference standard). The extract was then tested on an isolated sensitized guinea pig lung preparation to study its effect on the release of prostaglandins, leukotrienes and histamine. It is concluded that propolis extract has potent antiinflammatory properties in vivo. Its activity can be well correlated with its effects on the release of various mediators of inflammation.

Khayyal, M. T., M. A. El-Ghazaly, A. S. el-Khatib, A. M. Hatem, P. J. F. de Vries, S. el-Shafei, and M. M. Khattab, "A clinical pharmacological study of the potential beneficial effects of a propolis food product as an adjuvant in asthmatic patients.", Fundamental & clinical pharmacology, vol. 17, issue 1, pp. 93-102, 2003 Feb. Abstract

The aqueous extract of propolis has been formulated as a nutritional food product and administered, as an adjuvant to therapy, to patients with mild to moderate asthma daily for 2 months in the framework of a comparative clinical study in parallel with a placebo preparation. The diagnosis of asthma was made according to the criteria of patient classification of the National Institutes of Health and Global Initiative for Asthma Management. At inclusion, the pulmonary forced expiratory volume in the first second (FEV1) as a percentage of the forced vital capacity (FVC) was more than 80% in mild persistent cases, and between 60 and 80% in moderate persistent cases, showing an increase in the degree of reversibility of > 15% in FEV1. All patients were on oral theophylline as controller therapy, none was receiving oral or inhaled corticosteroids, none had other comorbidities necessitating medical treatment, and all were from a middle-class community and had suffered from asthma for the last 2-5 years. Twenty-four patients received the placebo, with one drop-out during the study, while 22 received the propolis extract, with no drop-outs. The age range of the patients was 19-52 years; 36 were male and 10 female. The number of nocturnal attacks was recorded on a weekly basis, while pulmonary function tests were performed on all patients at the beginning of the trial, 1 month later and at the termination of the trial. Immunological parameters, including various cytokines and eicosanoids known to play a role in asthma, were measured in all patients at the beginning of the trial and 2 months later. Analysis of the results at the end of the clinical study revealed that patients receiving propolis showed a marked reduction in the incidence and severity of nocturnal attacks and improvement of ventilatory functions. The number of nocturnal attacks dropped from an average of 2.5 attacks per week to only 1. The improvement in pulmonary functions was manifested as a nearly 19% increase in FVC, a 29.5% increase in FEV1, a 30% increase in peak expiratory flow rate (PEFR), and a 41% increase in the forced expiratory flow rate between 25 and 75% of the vital capacity (FEF25-75). The clinical improvement was associated with decreases by 52, 65, 44 and 30%, respectively, of initial values for the pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, ICAM-1, interleukin (IL)-6 and IL-8, and a 3-fold increase in the 'protective' cytokine IL-10. The levels of prostaglandins E2 and F2alpha and leukotriene D4 were decreased significantly to 36, 39, and 28%, respectively, of initial values. Patients on the placebo preparation showed no significant improvement in ventilatory functions or in the levels of mediators. The findings suggest that the aqueous propolis extract tested is potentially effective as an adjuvant to therapy in asthmatic patients. The benefits may be related to the presence in the extract of caffeic acid derivatives and other active constituents.

Khayyal, M. T., M. El-Ghazaly, A. S. el-Khatib, and A. Hatem, "Tolerability of mofebutazone in asthmatic patients.", International journal of clinical pharmacology research, vol. 15, issue 4, pp. 145-51, 1995. Abstract

Twenty-seven human volunteer asthmatic patients were each given one tablet of mofebutazone (300 mg) twice daily for 15 days. Pulmonary ventilatory function test (forced expiratory volume test) as well as bronchoalveolar lavage (BAL) were performed one day before initiation of treatment and one day after completion of the course; in the BAL, prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha) and leukotrienes (LTs) were also estimated. It was found that there was no increase in the incidence or severity of the asthmatic attacks during the course of mofebutazone treatment. The drug tended to improve the tested pulmonary ventilatory functions or at least to leave them unchanged. All the mofebutazone-treated individuals showed a dramatic reduction in the concentrations of PGE2, PGF2alpha and LTs in their BAL, but there was no consistent correlation between the extent of reduction and the degree of benefit or worsening sustained by any individual patient. It is evident from the present study that mofebutazone has shown good tolerability which was associated with an improvement in the pulmonary ventilatory functions, a fact that would seem to advocate the use of this non-steroidal antiinflammatory drug (NSAID) in asthmatic patients whenever a need for such therapy becomes necessary.

Khayyal, M. T., A. S. el-Khatib, M. El-Ghazaly, and A. Hatem, "Inhibition of leukotriene release by mofebutazone: a possible clinical advantage.", International journal of clinical pharmacology research, vol. 13, issue 5, pp. 255-61, 1993. Abstract

The isolated perfused lung preparation from actively sensitized guinea-pigs was used; after it was challenged with antigen, mediators such as histamine, prostaglandins and leukotrienes were released into the lung effluent. It was found that treatment of the perfused lungs before and during challenge with mofebutazone (10 micrograms/ml) inhibited the immunological release of prostaglandins as well as leukotrienes. Phenylbutazone, on the other hand, at the same dose level inhibited the release of prostaglandins, whereas the release of leukotrienes was much less affected by the drug. Histamine release was not altered by either drug. When clinically mofebutazone tablets (300 mg) were given as an analgesic twice daily for 15 days to a number of asthmatic volunteers including 3 aspirin-sensitive individuals, there was no increase in the incidence or intensity of the asthmatic attacks, even in the aspirin-sensitive patients. Pulmonary ventilatory functions which showed a certain obstructive pattern were not worsened by the treatment and even tended to be somewhat improved.

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