Osama S. Tayeb

Animal models for heat stroke studies.

Heat stroke is a medical emergency where quick diagnosis and management of victims are essential for positive prognosis. Several biochemical, physiological and hematological changes were observed in heat stroke. It seems that all of these changes are a consequence of induced tissue damage, or may have been a compensatory action by the body. Induction of hyperthermia and temperature measurement are important components in heat stroke studies to determine the stage of progression or regression of heat stroke. Several animal models have been established by investigators in heat related studies. Rats, dogs, monkeys, baboons, cows, rabbits, sheep and chicks have all been used in such studies that allow manipulation of exposure conditions and various designs of experiments. Amongst these species, rats, rabbits and sheep are the most suitable models because of their similarity to man in response to high temperature and in relation to their availability, cost and simplicity of handling. Such models may be used to study various pharmacological and biochemical parameters and functions concurrently. Further informations could also be obtained from isolated organ studies. The present review is to analyse and compare the available methodology for heat stroke studies.

Effect of dantrolene pretreatment on heat stroke in sheep.

Dantrolene is effective in the management of malignant hyperpyrexia. Due to the similarities of malignant hyperpyrexia and heat stroke, we have investigated the effect of dantrolene on heat stroke in sheep. Our study indicates that dantrolene pretreatment decreases the extent of heat stroke signs and some of the induced changes in enzymes and hormones. These results indicate that dantrolene may be a valuable drug in the prophylaxis against heat stroke attack in susceptible individuals.

Saudi-KAU Coupled Global Climate Model: Description and Performance

BackgroundA new coupled global climate model (CGCM) has been developed at the Center of Excellence for Climate Change Research (CECCR), King Abdulaziz University (KAU), known as Saudi-KAU CGCM.PurposeThe main aim of the model development is to generate seasonal to subseasonal forecasting and long-term climate simulations.MethodsThe Saudi-KAU CGCM currently includes two atmospheric dynamical cores, two land components, three ocean components, and multiple physical parameterization options. The component modules and parameterization schemes have been adopted from different sources, and some have undergone modifications at CECCR. The model is characterized by its versatility, ease of use, and the physical fidelity of its climate simulations, in both idealized and realistic configurations. A description of the model, its component packages, and parameterizations is provided.ResultsResults from selected configurations demonstrate the model’s ability to reasonably simulate the climate on different time scales. The coupled model simulates El Niño-Southern Oscillation (ENSO) variability, which is fundamental for seasonal forecasting. It also simulates Madden-Julian Oscillation (MJO)-like disturbances with features similar to observations, although slightly weaker.ConclusionsThe Saudi-KAU CGCM ability to simulate the ENSO and the MJO suggests that it is capable of making useful predictions on subseasonal to seasonal timescales.

Comparison of the fluorescence polarization immunoassay and the microbiological assay methods for the determination of gentamicin concentration in human serum.

The performance of the fluorescence polarization immunoassay (FPIA) was compared with that of a microbiological assay for the measurement of serum gentamicin concentrations. Within-run precision from duplicate assays of two concentrations (4 and 8 micrograms/ml) using FPIA and the microbiological assay yielded coefficients of variation (r) of 2.62%, 1.76% (n = 12) and 8.06%, 6.87% (n = 12), respectively. Day-to-day precision was estimated by repetitive analysis of 4 and 8 micrograms/ml control samples over a 3-week period. Coefficients of variation (r) were 2.57%, 3.09% (n = 8) and 10.71%, 14.20% (n = 8) for FPIA and the microbiological assay, respectively. Linear regression analysis performed on data from parallel determinations on 143 patient samples by the two methods showed correlations in the order of 0.74. The FPIA offers a rapid, efficient, and accurate system for therapeutic monitoring of gentamicin serum levels.

Effect of naloxone pretreatment on heat stroke in sheep

Endogenous opioid peptides have been shown to increase in heat stroke attacks and it has been suggested that they are involved in thermoregulation. The aim of the present investigation is to study the effect of naloxone pretreatment on the development of heat stroke in a sheep model. We observe that naloxone decreases the extent of heat stroke signs and some of the induced changes in enzymes and hormones. These observations indicate that naloxone may be a valuable drug in the prevention of heat stroke attacks in susceptible individuals.

Comparison of cytochrome P-450 content and conjugative enzymes in livers of camels (Camelus dromedarius), guinea-pigs (Cavia porcellus) and rats (Rattus norvegicus)

The activities of the conjugative enzymes, glutathione S-transferase and UDP-glucuronyl-transferase, have been measured in vitro in the livers of camels, guinea-pigs and rats. Some sex differences were observed in the levels of these conjugative enzymes. In rats and guinea-pigs, females had higher UDP-glucuronyltransferase activity than males. In camels, females had higher glutathione S-transferase activity than males. In these species, the cytochrome P-450 isozymes observed between the 50,000 and 60,000 mol. wt regions have been separated and characterized by SDS-polyacrylamide gel electrophoresis. Camels showed lower levels of all types of cytochrome P-450 isozymes, while guinea-pigs showed higher levels of most of these isozymes. In general, camels seemed to have the lowest drug-metabolizing enzyme activity when compared to rats and guinea-pigs.

A comparative study of liver mixed function oxidases in camels (Camelus dromedarius), guinea pigs (Cavia porcellus) and rats (Rattus norvegicus)

1. The activities of the drug-metabolizing enzymes, benzphetamine N-demethylase, 7-ethoxycoumarin O-deethylase and dicoumarol oxidation have been measured in vitro in the liver of camels, guinea pigs and rats. 2. In these species, levels of hepatic microsomal parameters namely microsomal protein, cytochrome P450, cytochrome b5 and NADPH-cytochrome c reductase have also been determined. 3. In general, camels seemed to have the lowest enzyme activity when compared to rats and guinea pigs. 4. Some sex differences were observed in the levels of enzymes studied. In rats and guinea pigs, males had higher benzphetamine N-demethylase than females. However, in camels and guinea pigs, females had higher 7-ethoxycoumarin O-deethylase when compared to males.

A heat released substance from rat ileal muscle

Change in body temperature is reported to induce changes in muscle contraction by unconfirmed mechanisms. Therefore, the changes in isolated rat ileal muscle contractions at different surrounding temperatures were studied. The contraction was decreased by increase of the surrounding temperature from 37 degrees C to 40 degrees C, while it was increased by decrease of the temperature to 30 degrees C. Further, bathing the muscle in a conditioned medium prepared by incubation of the ileal muscle at 40 degrees C caused a decrease in contraction at a surrounding temperature of 37 degrees C. This indicates that increase of the temperature around muscles induces a release of the substance that causes a decrease in the contractile response. The effects of this heat-released substance were not blocked by propranolol, phentolamine and naloxone, or edrophonium, which indicates that these effects are not produced through an interaction with cholinesterase enzyme, alpha or beta adrenergic receptors or opiate receptors.

CORRELATION BETWEEN PREDICTED AND MEASURED DIGOXIN SERUM CONCENTRATIONS

Measurement of digoxin serum concentration can be useful as a direct guide to the dose appropriate to individual patients. Therefore, we have attempted to predict digoxin serum concentration in 62 patients with a wide range of body weight, age and renal function, using creatinine clearance and individual digoxin dose. Creatinine clearance in each patient was determined by the Cockroft and Gault method (1). Digoxin clearance was determined by Scheiners method (2). Once digoxin clearance was determined, the predicted steady‐state serum concentration was calculated using general pharmacokinetic principles. Each patient was on digoxin therapy for at least 1 month. Digoxin serum concentration was measured by the newly developed fluorescence polarization immunoassay (FPIA). A linear regression analysis was performed on the data from the predicted and measured serum level which yielded a slope of 0·9463 intercept of 0·0950 and a correlation coefficient (r) of 0·9600. The method was found to be very useful to predict digoxin serum levels in overdosed and underdosed patients.

Application of transformation algorithm and nonparametric calculation in determining the reference intervals of some urine constituents and characteristics

We have applied a multi-stage computer algorithm for normalization of distributions and calculation of reference intervals of some urine characteristics and constituents. The study analyzed 24-h urines, collected from adult male Saudis from different socioeconomic classes, for volume, pH, osmolality, specific gravity, creatine, creatinine, urea and uric acid. Frequency distributions, for each analyte, were found to be nongaussian as judged by the coefficients of skewness and kurtosis, chi 2 and Kolmogorov-Smirnov tests, and from probability plots. Data were transformed to gaussian distributions by multistage log-power transformation. Stepwise, this procedure removed skewness and residual kurtosis. Using the gaussian transformed data the reference intervals were estimated parametrically as the mean +/- 2 SD. In addition, the non-parametric percentile technique was applied to estimate these values. The former intervals were found to have narrower 0.90 confidence limits than the latter. When established limits were compared with those reported for Western subjects urine volume and uric acid showed the most marked variation.