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Biomedical subjects

S A Khalil

Publications and source records attributed to S A Khalil.

At least 19 recordsLinked to original sources

[Iodo-methyl norcholesterol scintigraphy in the localization of primary hyperaldosteronism].

UNLABELLED: The aim of the study was to investigate the accuracy of iodomethyl norcholesterol, a new adrenal isotopic scanning agent, in the strategy of aldosteronism localization. Among 1499 patients examined in the clinic in 1987, 49 presented with primary aldosteronism. Nine were explored by adrenal scintigraphy (SCI). Mean age was 50 +/- 10 ans, blood pressure was 188 +/- 26/110 +/- 17 mmHg. Initial serum kalemia was 3.2 +/- 0.4 mMol/l, urinary potassium 67 +/- 39 mMol/d; standing plasma active renin was 9.9 +/- 5.0 pg/ml (20 less than N less than 50), supine plasma aldosterone was 316 +/- 200 pg/ml (50 less than N less than 150) and aldosterone excretion rate was 49 +/- 27 microgr/day (N less than 17). Adrenal CT-scan correctly predicted unilateral adenoma in 7 patients (size from 5 to 15 mm). CT-scan was negative twice. Adrenal vein aldosterone sampling and phlebography confirmed adenoma in the 8th patient. 7 patients underwent surgery, with pathological confirmation of the diagnosis. The diagnosis of adrenal hyperplasia (AH) was made in the 9th patient. (table; see text) When compared to CT-scan, SCI is unuseful if a tumor (greater than or equal to 10 mm) is detected on CT-scan (2 SCI false-negative/5 CT-scan tumors). At the opposite, when CT-scan is negative, SCI localizes 2 tumors in 4 patients (2 adenomas). CONCLUSION: SCI should not be used as first step diagnosis procedure in the localization of primary aldosteronism.

19-Iodocholesterol

The role of porto-systemic shunts in the specific humoral immune response in patients with schistosomal hepatic fibrosis.

The present study was devoted to elucidate the role of collaterals (porto-systemic shunts) in the specific humoral immune response to schistosomal soluble egg antigen (SEA) in patients with schistosomal hepatic fibrosis (SHF). Twenty five patients with SHF with collaterals, ten patients with SHF without collaterals and twenty healthy control subjects constituted the material of this study. In vivo and in vitro tests for humoral immunity to SEA included serum immunoglobulins estimation, immediate intradermal test, indirect haemagglutination test and determination of B lymphocytes count in peripheral blood. Significant differences have been observed between cases without collaterals and those with collaterals; and in the latter group before and after decongestion. These results tend to consolidate the view of the role of collaterals in schistosomal antigenemia and subsequent humoral immune response.

Adult

Effect of magnesium trisilicate on nitrofurantoin absorption.

In vitro adsorption studies revealed that for an identical initial concentration of nitrofurantoin, magnesium trisilicate exhibited the greatest adsorptive capacity with bismuth oxycarbonate, talc, kaolin, and magnesium oxide exhibiting intermediate adsorptive powers, while aluminum hydroxide and calcium carbonate exhibited low or no adsorption properties. Trials to elute the drug with acidic or alkaline solution were unsuccessful. The in vivo absorption characteristics of nitrofurantoin and nitrofurantoin-magnesium trisilicate combination were evaluated in 6 healthy males. Administration of magnesium trisilicate with nitrofurantoin reduced the rate and extent of its excretion reflecting decrease in both rate and extent of absorption. The time during which the drug concentration in the urine was above the minimum effective concentration of 32 microgram/ml was also significantly reduced after administration of the antacid.

Adsorption

In vitro uptake of oral contraceptive steroids by magnesium trisilicate.

Some steroids used in oral contraceptives were adsorbed significantly by magnesium trisilicate. The adsorption affinity followed the sequence: ethindrone greater than mestranol greater than norethindrone greater than ethinyl estradiol. Adsorption data obtained at relatively low initial concentrations fitted a Langmuir plot; the values for monolayer adsorption ranged between 0.24 and 0.32 mg/g. At higher concentrations of the steroids, multilayer adsorption occurred. The results of desorption experiments made at 37 degrees in water and 0.05 N HCl suggested that desorption was incomplete and depended on the amount of steroid adsorbed. During the dissolution testing of a brand of contraceptive tablets containing norethindrone acetate, the presence of 0.5% (w/v) magnesium trisilicate in the medium resulted in almost complete reduction in the amount of the steroid remaining in solution after 1 hr.

Absorption

Effect of concomitant administration of magnesium trisilicate on GI absorption of dexamethasone in humans.

The oral absorption of dexamethasone in humans was compared to its absorption when coadministered with magnesium trisilicate. The bioavailability of dexamethasone was estimated by measuring the suppressive effect of the drug on the daily excretion of endogenous steroids. Administration of 1 mg of dexamethasone to six healthy male volunteers significantly decreased the urinary excretion of 11-hydroxycorticosteroids. However, the coadministration of magnesium trisilicate with dexamethasone decreased its absorption, as indicated by the increased urinary excretion of 11-hydroxycorticosteroids. The decrease in absorption was attributed to drug adsorption on the antacid surface. These results confirm previous in vitro findings.

11-Hydroxycorticosteroids

Instability of digoxin in acid medium using a nonisotopic method.

A selective nonisotopic assay was used to investigate the digoxin hydrolysis rates at 37 +/- 0.1 degrees over the pH 1.1--2.2 range. The colorimetric method adopted is based on the use of a xanthydrol reagent after extraction with chloroform. The spectrofluorometric method specified in the dissolution test for digoxin tablets was nonspecific because of digoxigenin interference. Digoxin hydrolysis followed specific acid hydrolysis, and K values of the apparent first-order reaction varied from 0.0357 to 0.0027 min-1 over the pH range used. The effect of the dissolution medium on digoxin stability during the dissolution tests of the tablets also was studied. Water (the BP medium) and 0.6% HCl (the USP medium) were compared using the fluorometric method and the xanthydrol method. In the USP medium (pH 1.3), no hydrolysis was revealed by the fluorometric estimation whereas the xanthydrol method showed about 74% hydrolysis. In water, the two methods revealed no hydrolysis. The extent of hydrolysis after 1 hr in the USP medium was studied using three brands of digoxin tablets of differing dissolution characteristics. The fast dissolving brand showed relatively more hydrolysis than the slow dissolving tablets.

Chemistry, Pharmaceutical

The in vitro adsorption of some antiepileptics on antacids.

The adsorption of the antiepileptics sulthiame, phenytoin, mephenytoin, mesuximide, phensuximide, ethosuximide, and primidone on various antacids or adsorbents was studied at 37 degrees C. The antacids or adsorbents used were magnesium trisilicate, aluminium hydroxide, bismuth oxidcarbonate, magnesium oxide, talc, kaolin and calcium carbonate. Magnesium trisilicate was found to be the strongest adsorbent for most of the antiepileptics tested. The other antacids or adsorbents were without an appreciable effect. Sulthiame exhibited the highest degree of interaction with magnesium trisilicate. Mesuximide, phensuximide and primidone showed intermediate adsorption properties. Mephenytoin and phenytoin had lower adsorption characters, while ethosuximide was the least adsorbed antiepileptic tested. The extent of elution was found to be inversely proportional to adsorption. Alkaline solution gave relatively higher eluting power than acid solution. The mechanism of adsorption of the various antiepileptics on antacids was discussed. The effect of magnesium trisilicate on the bioavailability of coadministered antiepileptics has still to be confirmed by in vivo testing.

Adsorption

Effect of chloroquine adsorption on acid reactivity of magnesium trisilicate.

Due to the adsorption of chloroquine by magnesium trisilicate, both the BP acid absorption test and the rate of hydrochloric acid uptake, as monitored by pH measurements, were significantly reduced. This reduction was dependent on the amount of chloroquine adsorbed, since multilayer adsorption produced relatively more suppressive effects than did monolayer adsorption. The presence of adsorbed chloroquine also decreased the amounts of magnesium released in an acid medium. The inhibition of the antacid property due to chloroquine adsorption may be attributed to the occupation of the reactive sites of the antacid surface by chloroquine and to a reduction of the surface of the antacid due to flocculation of the particles.

Adsorption

Effect of surfactants on absorption through membranes V: Concentration-dependent effect of a bile salt (sodium deoxycholate) on absorption of a poorly absorbable drug, phenolsulfonphthalein, in humans.

The effect of administration of 600-and 300-mg doses of sodium deoxycholate 1 hr before phenolsulfonphthalein solution is reported. The 600-mg dose caused a decrease in drug bioavailability as measured by the total amount excreted in 24 hr. The 300-mg dose cause and increase in the initial phenolsulfonphthalein absorption rate, suggesting a direct action of the bile salt on membrane permeability. The decrease in absorption upon administration of 600 mg was attributed to micellar entrapment of the drug molecule.

Adult

In vitro adsorption of some corticosteroids on antacids.

The adsorption of prednisone, prednisolone, fluprednisolone, betamethasone, triamcinolone, beta-methylprednisone acetate and hydrocortisone acetate on various antacids or adsorbents was studied at 37 degrees C. The antacids or adsorbents used were magnesium trisilicate, aluminum hydroxide, bismuth oxycarbonate, magnesium oxide, magnesium carbonate, calcium carbonate, talc, kaolin and charcoal. Magnesium trisilicate and charcoal had the highest adsorption capacity for the corticosteroids tested. Bismuth oxycarbonate and talc had intermediate adsorption properties while kaolin and aluminium hydroxide had lower effects. Other antacids were without any adsorption character. Results of the elution study confirmed the higher affinity of magnesium trisilicate over that of bismuth oxycarbonate and talc for the steroids tested. Further in vivo testings are still needed to assess the effect of antacids on the bioavailability of coadministered corticosteroids.

Adrenal Cortex Hormones

Effect of dioctyl sodium sulfosuccinate and poloxamer 188 on dissolution and intestinal absorption of sulfadiazine and sulfisoxazole in rats.

The influence of two medicinal surfactants, poloxamer 188 and dioctyl sodium sulfosuccinate, on the dissolution of sulfisoxazole and sulfadiazine was investigated. A dramatic increase in the dissolution rate was observed at all surfactant concentrations. Drug absorption from the rat small intestine was also studied, and a significant but less dramatic increase was noted. Dissolution rate and absorption could be correlated only qualitatively. The two surfactants had no effect on the amount of sulfisoxazole excreted by the rat in 24 hr.

Animals

Determination of hyoscyamine in BPC mixtures.

The hyoscyamine contents of four BPC mixtures (containing either belladonna or hyoscyamus tincture) were determined using the acid-dye technique. A sample size of 10 ml was required. The mean percentage recovery of hyoscyamine ranged from 99.73 to 101.03 from three mixtures; from the magnesium trisilicate and belladonna mixture, it was 94.8. The effects of pH and adsorption on the extraction of the alkaloid-dye complex from the mixtures examined are discussed.

Aluminum Hydroxide

Inhibitory effect of dioctyl sodium sulfosuccinate on pepsin activity.

The inhibitory effect of dioctyl sodium sulfosuccinate of hog pepsin activity was investigated over the pH 1.5-3.0 range. The inhibitory effect was studied using a natural substrate, hemoglobin, and a synthetic substrate, N-acetyl-L-phenylalanyl-L-diiodotyrosine. The mechanistic studies revealed that a substrate-inhibitor interaction was the major mechanism of inhibition with hemoglobin. However, some direct enzyme inhibition also was involved. With the synthetic substrate, the inhibition was due to a competition between the substrate and inhibitor molecules for the enzyme. The possible therapeutic significance of the inhibitory effect of the medicinal surfactant is discussed.

Octanols

Dissolution characteristics and oral absorption of digitoxin and digoxin coprecipitates.

A marked increase in the dissolution rates od digitoxin and digoxin was attained by dispersing the drugs in two inert solid carriers, poloxamer 188 and deoxycholic acid. The 1 and 10% (w/w) drug-carrier solid dispersions were prepared by the solvent method. The former dissolved significantly faster than the latter. The oral administration of 10% (w/w) digitoxin-carrier coprecipitates to mice significantly increased toxicity. This observed increase is attributed to an increase in the rate and, possibly, the extent of oral absorption of the drug. Although a 10% coprecipitate of digoxin in both carriers showed an increase in the dissolution rate, no increase in oral toxicity was observed. X-ray diffraction patterns indicated that both digitoxin and deoxycholic acid undergo crystalline modifications due to treatment by the solvent, but the exact nature of the drug-carrier solid dispersions was not revealed.

Animals