Potential effect of Olea europea leaves, Sonchus oleraceus leaves and Mangifera indica peel extracts on aromatase activity in human placental microsomes and CYP19A1 expression in MCF-7 cell line: Comparative study.

Aromatase inhibitors (AIs) provide novel approaches to the adjuvant therapy for postmenopausal women with estrogen-receptor-positive (ER+) breast cancers. In this study, different plant extracts from Olea europaea leaves (OLE), Sonchus oleraceus L. (SOE) and Mangifera indica peels (MPE) were prepared to identify phytoconstituents and measure antioxidant capacities. The effects of these three extracts on aromatase activity in human placental microsomes were evaluated. Additionally, the effects of these extracts on tissue-specific promoter expression of CYP19A1 gene in cell culture model (MCF-7) were assessed using qRT-PCR. Results showed a concentration-dependent decrease in aromatase activity after treatment with OLE and MPE, whereas, SOE showed a biphasic effect. The differential effects of OLE, SOE and MPE on aromatase expression showed that OLE seems to be the most potent suppressor followed by SOE and then MPE. These findings indicate that OLE has effective inhibitory action on aromatase at both the enzymatic and expression levels, in addition to its cytotoxic effect against MCF-7 cells. Also, MPE may be has the potential to be used as a tissue-specific aromatase inhibitor (selective aromatase inhibitor) and it may be promising to develop a new therapeutic agent against ER+ breast cancer.

Postmarketing pharmacokinetic and pharmacodynamic equivalence of generic and brand atenolol in Egypt.

Concerns have been raised regarding the postmarketing quality of generic drugs. This study assessed the pharmacokinetic and pharmacodynamic equivalence of generic and brand atenolol tablets in 24 healthy male volunteers in a single-dose, open, randomized, two-period crossover study under fasting conditions. Blood samples were collected for 24 h post dosing and assayed for atenolol using HPLC. Blood pressure and heart rate were measured at baseline and throughout blood sampling. The mean plasma concentration-time curves for both products were similar. Pharmacokinetic and statistical analysis indicated bioequivalence based on the mean ratios of log-transformed Cmax and AUC values. Both products had similar time courses of pharmacodynamic activity with a significant fall in blood pressure and heart rate (maximum after ~5 h) followed by a gradual increase towards baseline. Both products were well tolerated. Both atenolol products were bioequivalent in the postmarketing setting and can be used interchangeably in clinical practice.

Buccal versus lingual mucosal graft urethroplasty for complex hypospadias repair.

OBJECTIVES: To compare surgical outcomes and donor site complications of buccal and lingual mucosa used as ventral onlay graft for complex hypospadias cases. PATIENTS & METHODS: Forty four cases with complex hypospadias after failed previous surgery were prospectively included. All had severely scarred penile skin with reasonable residual urethral plate. Cases were categorized into two groups: Group I (23) where buccal mucosal graft [BMG] was used and group II (21) where lingual mucosal graft [LMG] was used. Donor site complications as well as functional and esthetic outcomes were recorded for each group. RESULTS: Mean follow up was 20.8 months (range 12-24). Average graft harvesting time was 24 min for BMG and 19 min for LMG. Donor site pain was reported with both techniques but recovery was earlier with LMG. Slurred speech and difficult tongue protrusion were reported with lingual but not buccal grafts; however mouth tightness, peri-oral numbness and persistent oral discomfort were reported only with buccal grafts. Successful urethroplasty was obtained in 78.2% of BMG compared to 76.1% of LMG. CONCLUSION: Surgical outcomes of LMG urethroplasty were comparable to those of BMG in complex hypospadias cases. Compared to buccal mucosa, LMG is easy to harvest, with minimal donor site complications.

Assessment of the pharmaceutical quality of omeprazole capsule brands marketed in Egypt.

The pharmaceutical quality of 7 local omeprazole capsule brands in Egypt was assessed relative to the proprietary product (Losec). Drug content, content uniformity, drug release (using USP test for enteric coated articles and a modified release test) were determined. Products were subjected to a 3-month stability study. Of the 7 brands, 6 had satisfactory drug content and content uniformity. All brands passed the USP drug release test. The modified release test proved to be more discriminative. After 3 months storage, drug content of 3 brands remained > 90% and 2 of these brands maintained drug release above 75%. Changes in pellet appearance during storage were indicative of omeprazole chemical degradation.

Drug compliance among hypertensive patients in Tabuk, Saudi Arabia.

OBJECTIVE: To estimate the compliance rate and associated factors among a population of hypertensive subjects registered in hospitals and primary health care centres. DESIGN: A prospective study carried out on a sample of hypertensive subjects. METHOD: Compliance with treatment by the study sample was measured using the pill-counting method. The reasons for noncompliance are listed and the status of blood pressure control among compliant and noncompliant subjects is reported. RESULTS: The compliance rate was 53.0%. It was associated positively with male sex, and negatively with older age, symptoms of illness and drug side effects. The degree of blood pressure control was worse among noncompliant subjects. Reasons for noncompliance included the asymptomatic nature of hypertension, a shortage of drugs, side effects, forgetfulness and lack of health education. CONCLUSIONS: The compliance rate was low in this study and was accompanied by inadequate blood pressure control among noncompliant subjects. Disoriented behavior regarding hypertension and its medications was observed.

An unusual complication of a fractured femur in a child: case report.

Comminuted femoral fractures are uncommon in children. Described is a case of a 5-year-old child with a comminuted femoral fracture with displacement of the fragments in the anterior abdominal wall.

The relationship between the thrombotic and infectious complications of central venous catheters.

OBJECTIVES: To assess the frequency of thrombotic and infectious complications of long-term use of vascular catheters in cancer patients and to determine whether the two types of complication are related. DESIGN: Case series. SETTING: A 500-bed tertiary cancer center. PATIENTS: Seventy-two cancer patients. INTERVENTIONS: During a 16-month period, postmortem examinations of catheterized veins and contralateral uncatheterized veins were done on all patients with indwelling central venous catheters who met study criteria. MAIN OUTCOME MEASURES: Catheter-related septicemia determined by clinical and microbiological data as well as postmortem pathology; venous pathological changes such as mural hemorrhage, thrombosis, calcification, ulceration, and inflammation. RESULTS: Premortem clinical and microbiological data were obtained retrospectively on all patients. Pathological changes were noted in 35 catheterized veins (49%) compared with five contralateral control veins (9.2%) (P < .001). Mural thrombi were noted in 27 catheterized veins (38%) compared with only one contralateral control vein (1.4%) (P < .001). Other pathological changes consisted of four central venous catheter-related mural thrombi (5.6%) in the right atrium and four instances (5.6%) of nonbacterial thrombotic endocarditis, three involving the tricuspid and one the mitral valves. Seven patients had catheter-related septicemia. Of the 31 patients with mural thrombosis of the catheterized vein or right atrium, seven developed catheter-related septicemia, whereas none of the 41 patients with normal catheterized veins and atria developed catheter-related septicemia (P < .01). CONCLUSIONS: Thrombotic complications are common in catheterized veins and are often associated with catheter sepsis.

Value of finger arterial blood pressure in diagnosis of vascular changes in some connective tissue diseases.

This study was performed in 60 patients with the following connective tissue diseases: rheumatoid arthritis (RA--20 patients), systemic lupus erythematosus (SLE--20), and progressive systemic sclerosis (scleroderma = PSS--20). Twenty normal persons served as controls. All patients and controls were subjected to complete history taking, complete physical examination, and laboratory investigations including: rheumatoid factor, anti-DNA, LE cell test, antinuclear factor (ANF), and ECG. Finger arterial blood pressure (FABP) readings using an 8 MHz Doppler flow detector with a 24-mm-diameter cuff at a temperature of 24 degrees C were made in all cases and controls. The mean age of incidence in patients with RA was 37.8 years; in those with SLE, 21.5 years; in those with PSS 34.6 years; and in the control group, 33.7 years. Women were predominant both in the diseases and the control groups. The FABP was measured in all groups and the range of difference between the brachial and finger arterial blood pressure in each group was estimated. In the control group the mean difference was 27.7 mm Hg; in the RA group, 45.8 mm Hg; in the SLE group, 58.1 mm Hg; and in the PSS group, 70.9 mm Hg. There were no significant peripheral vascular changes in the small arteries in the RA group, whereas in the SLE and PSS groups there was a significant difference, which suggests different underlying microvascular changes. The FABP appears to be a diagnostic tool in the diagnosis of PSS and it helps in differentiation between various types of collagen disease in equivocal cases.

[Iodo-methyl norcholesterol scintigraphy in the localization of primary hyperaldosteronism]. / Apport de la scintigraphie au iodo-méthyl norcholestérol dans la localisation de l'hyperaldostéronisme primaire.

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.

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.

Influence of high fat diet on GI absorption of griseofulvin tablets in man.

A controlled crossover study was carried out on five volunteers to substantiate reported effects of fat intake on the bioavailability of griseofulvin. The urinary excretion of 6-demethylgriseofulvin was monitored for 24 h following the administration of 125-mg griseofulvin tablets in the fasting state and after a fatty diet. Statistical analysis of excretion data indicated a significant increase in both rate and extent of absorption of griseofulvin as a result of fat intake. Excretion rate profiles obtained permitted insight into mechanisms possibly involved in the observed drug-diet interaction.

Bioavailability of different brands of griseofulvin tablets and its correlation to dissolution data.

A bioavailability study was carried out in man on five brands of griseofulvin tablets. Urinary excretion of free and total 6-demethylgriseofulvin was monitored for 24 h after single 125 mg doses. The bioavailability information, deduced from metabolite excretion data, pointed to inter-brand differences in rate but not extent of griseofulvin absorption. Correlations were sought between in vivo data and previousely determined dissolution parameters using a two phase system. Based on the correlation coefficients obtained, dissolution data proved predictive of absorption rates of griseofulvin tablets. Meaningful correlation between dissolution rate and extent of griseofulvin absorption was not observed.

In vitro antidiabetics-antacid interactions.

The adsorption of the oral antidiabetics metformin hydrochloride, glibenclamide, acetohexamide, tolbutamide, carbutamide, tolazamide and glymidine on various antacids or adsorbents was studied at 37 degrees C. The antacids or adsorbents used were magnesium trisilicate, aluminium hydroxide, calcium carbonate, magnesium oxide, bismuth oxycarbonate, talc, kaolin as well as charcoal. None of the substances tested, with the exception of charcoal, exhibited superior adsorptive properties for all the drugs. Magnesium trisilicate and calcium carbonate were the best adsorbents for metformin hydrochloride. Acetohexamide and glibenclamide were adsorbed to an appreciable extent on most antacids. Tolbutamide showed an adsorption tendency towards talc. Most antacids slightly adsorbed carbutamide, while magnesium trisilicate showed a higher adsorption capacity for tolazamide and glymidine. The dissolution rate of acetohexamide in magnesium oxide suspension (5:400) increased about 40-fold after 10 min, whle in magnesium trisilicate suspension (5:400) it increased about 7-fold. On the other hand, magnesium trisilicate did not influence the dissolution rate of metformin hydrochloride. The probable variation in the bioavailability of orally administered antidiabetics when coadministered with antacids was discussed. However, further in vivo studies are needed before a final assessment for such drug-antacid interaction can be confirmed.

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.

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.