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Biomedical subjects

Z H Israili

Publications and source records attributed to Z H Israili.

At least 19 recordsLinked to original sources
PubMed2006

Ethnopharmacological survey of plants used in the traditional treatment of hypertension and diabetes in south-eastern Morocco (Errachidia province).

This survey was undertaken in the Errachidia province in south-eastern Morocco in order to inventory the main medicinal plants used in folk medicine to treat arterial hypertension and diabetes mellitus. Four hundred individuals who knew about and/or had used the medicinal plants for the indicated diseases, including some herbal healers, were interviewed throughout different regions of the province. The inventory of medicinal plants is summarized in a synoptic table, which contains the scientific, vernacular and common name of the plant, its ecological distribution, the part of the plant and the preparation used and the therapeutic indication. Extensive investigations have brought to light 64 medicinal plants belonging to 33 families; of these, 45 are used for diabetes, 36 for hypertension, and 18 for both diseases. Of these plants, 34% grow in the wild, 44% are cultivated, and 22% are not indigenous to the area and are brought from other parts of Morocco or from outside the country. The survey shows that 78% of the patients regularly use these medicinal plants. In this region, the most frequently used plants to treat diabetes include Ajuga iva, Allium cepa, Artemisia herba-alba, Carum carvi, Lepidium sativum, Nigella sativa, Olea europaea, Peganum harmala, Phoenix dactylifera, Rosmarinus officinalis, and Zygophyllum gaetulum, and those to treat hypertension include Ajuga iva, Allium cepa, Allium sativum, Artemisia herba-alba Asso, Carum carvi, Nigella sativa, Olea europea, Rosmarinus officinalis, Origanum majorana, Peganum harmala, and Phoenix dactylifera. The local people recognize the toxic plants and are very careful in using such plants, which are Citrullus colocynthis, Datura stramonium, Nerium oleander, Nigella sativa, Peganum harmala and Zygophyllum gaetulum. Our survey shows that traditional medicine in the south-eastern Moroccan population has not only survived but has thrived in the transcultural environment and intermixture of many ethnic traditions and beliefs.

Anti-Infective Agents↗
PubMed2001

Human alpha-1-glycoprotein and its interactions with drugs.

For about half a century, the binding of drugs to plasma albumin, the "silent receptor," has been recognized as one of the major determinants of drug action, distribution, and disposition. In the last decade, the binding of drugs, especially but not exclusively basic entities, to another plasma protein, alpha 1-acid glycoprotein (AAG), has increasingly become important in this regard. The present review points out that hundreds of drugs with diverse structures bind to this glycoprotein. Although plasma concentration of AAG is much lower than that of albumin, AAG can become the major drug binding macromolecule in plasma with significant clinical implications. Also, briefly reviewed are the physiological, pathological, and genetic factors that influence binding, the role of AAG in drug-drug interactions, especially the displacement of drugs and endogenous substances from AAG binding sites, and pharmacokinetic and clinical consequences of such interactions. It can be predicted that in the future, rapid automatic methods to measure binding to albumin and/or AAG will routinely be used in drug development and in clinical practice to predict and/or guide therapy.

Drug Interactions↗
PubMed2000

Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension.

Angiotensin II receptor blockers (ARBs) represent a new class of effective and well tolerated orally active antihypertensive agents. Recent clinical trials have shown the added benefits of ARBs in hypertensive patients (reduction in left ventricular hypertrophy, improvement in diastolic function, decrease in ventricular arrhythmias, reduction in microalbuminuria, and improvement in renal function), and cardioprotective effect in patients with heart failure. Several large long-term studies are in progress to assess the beneficial effects of ARBs on cardiac hypertrophy, renal function, and cardiovascular and cerebrovascular morbidity and mortality in hypertensive patients with or without diabetes mellitus, and the value of these drugs in patients with heart disease and diabetic nephropathy. The ARBs specifically block the interaction of angiotensin II at the AT1 receptor, thereby relaxing smooth muscle, increasing salt and water excretion, reducing plasma volume, and decreasing cellular hypertrophy. These agents exert their blood pressure-lowering effect mainly by reducing peripheral vascular resistance usually without a rise in heart rate. Most of the commercially available ARBs control blood pressure for 24 h after once daily dosing. Sustained efficacy of blood pressure control, without any evidence of tachyphylaxis, has been demonstrated after long-term administration (3 years) of some of the ARBs. The efficacy of ARBs is similar to that of thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors or calcium channel blockers in patients with similar degree of hypertension. Higher daily doses, dietary salt restriction, and concomitant diuretic or ACE inhibitor administration amplify the antihypertensive effect of ARBs. The ARBs have a low incidence of adverse effects (headache, upper respiratory infection, back pain, muscle cramps, fatigue and dizziness), even in the elderly patients. After the approval of losartan, five other ARBs (candesartan cilexetil, eprosartan, irbesartan, telmisartan, and valsartan) and three combinations with hydrochlorothiazide (irbesartan, losartan and valsartan) have been approved as antihypertensive agents, and some 28 compounds are in various stages of development. The ARBs are non-peptide compounds with varied structures; some (candesartan, losartan, irbesartan, and valsartan) have a common tetrazolo-biphenyl structure. Except for irbesartan, all active ARBs have a carboxylic acid group. Candesartan cilexetil is a prodrug, while losartan has a metabolite (EXP3174) which is more active than the parent drug. No other metabolites of ARBs contribute significantly to the antihypertensive effect. The variation in the molecular structure of the ARBs results in differences in the binding affinity to the receptor and pharmacokinetic profiles. The differences observed in lipid solubility, absorption/distribution, plasma protein binding, bioavailability, biotransformation, plasma half-life, and systemic elimination influence the time of onset, duration of action, and efficacy of the ARBs. On the basis of the daily mg dose, the antihypertensive potency of the ARBs follows the sequence: candesartan cilexetil > telmisartan approximately = losartan > irbesartan approximately = valsartan > eprosartan. After oral administration, the ARBs are rapidly absorbed (time for peak plasma levels = 0.5-4 h) but they have a wide range of bioavailability (from a low of 13% for eprosartan to a high of 60-80% for irbesartan); food does not influence the bioavailability, except for valsartan (a reduction of 40-50%) and eprosartan (increase). A limited dose-peak plasma levels/areas under the plasma level-time curve proportionality is observed for some of the ARBs. Most of these drugs have high plasma protein binding (95-100%); irbesartan has the lowest binding among the group (90%). The steady-state volumes of distribution vary from a low of 9 L (candesartan) to a high of 500 L (telmisartan). (ABSTRACT TRUNCATE

Administration, Oral↗
PubMed1995

ACE inhibitors. Differential use in elderly patients with hypertension.

High blood pressure (BP) in the elderly must not be ignored as a normal consequence of aging. The criteria for the diagnosis of hypertension and the necessity to treat it are the same in elderly and younger patients. The aim of treatment of elderly hypertensive patients is to decrease BP safely and to reduce risk factors associated with cerebrovascular, cardiovascular and renal morbidity and mortality. The treatment of elderly hypertensive patients should be adjusted according to the needs of the individual, based upon age, race, severity of hypertension, co-existing medical problems, other cardiovascular risk factors, target-organ damage, risk-benefit considerations and costs. In addition to the elevated BP, other cardiovascular risk factors include smoking, glucose intolerance, hyperinsulinaemia, dyslipidaemia, hypercreatininaemia, peripheral vascular disease, left ventricular hypertrophy, and microalbuminuria (or albuminuria). Thus, the choice of initial antihypertensive therapy in elderly hypertensive patients should be based not only on the expected response, but also on the effects of therapy on lipid, potassium, glucose and uric acid levels, and left ventricular anatomy and function. Co-existing medical conditions (such as asthma, diabetes mellitus, heart failure, renal failure, gout, coronary artery disease, hyperlipidaemia and peripheral vascular disease) are major determinants for the selection of antihypertensive medications. With previous therapies (diuretics, beta-blockers, etc.), good BP control in the elderly was associated with clear and statistically significant reductions in stroke-related morbidity and mortality, but the overall effects on cardiovascular and renal complications of hypertension was either more variable or less obvious. Angiotensin converting enzyme (ACE) inhibitors are not only efficacious antihypertensive agents in the elderly, but also appear promising in counteracting some of the cardiovascular and renal consequences of hypertension. They are well tolerated and have a relatively low incidence of adverse effects. ACE inhibitors possess ancillary characteristics that are potentially beneficial for many elderly patients, including reduction of left ventricular mass, lack of metabolic and lipid disturbances, no adverse CNS effects, no risk of induction of heart failure, and a low risk of orthostatic hypotension. Since ACE inhibitors may improve perfusion to the heart, kidney and brain, they are well worth considering for the treatment of elderly patients with hypertensive target organ damage, especially in patients with heart failure, and diabetic patients with early nephropathy.

Aged↗
PubMed1992

Cough and angioneurotic edema associated with angiotensin-converting enzyme inhibitor therapy. A review of the literature and pathophysiology.

OBJECTIVE: To review available information on cough and angioneurotic edema associated with angiotensin-converting enzyme (ACE) inhibitors. DATA SOURCES: All relevant articles from 1966 through 1991 were identified mainly through MEDLINE search and article bibliographies. STUDY SELECTION: More than 400 articles were identified; 200 reporting incidence or possible mechanisms for the side effects or both were selected. DATA EXTRACTION AND SYNTHESIS: All pertinent information, including incidence and mechanisms of ACE inhibitor-induced cough and angioedema, was reviewed and collated. CONCLUSIONS: Cough occurs in 5% to 20% of patients treated with ACE inhibitors, recurring with reintroduction of the same or another ACE inhibitor. It is more common in women. The mechanism may involve accumulation of prostaglandins, kinins (such as bradykinin), or substance P (neurotransmitter present in respiratory tract C-fibers); both bradykinin and substance P are degraded by ACE. A 4-day trial of withdrawal of the ACE inhibitor or temporary substitution of another class of antihypertensive agent inexpensively and easily ascertains if the ACE inhibitor caused the cough. Change to another ACE inhibitor or additive therapy with nonsteroidal anti-inflammatory drugs is not recommended. Prompt recognition of ACE inhibitor-related cough can prevent unnecessary diagnostic testing and treatment. Angioedema occurs in 0.1% to 0.2% of patients receiving ACE inhibitors. The onset usually occurs within hours or, at most, 1 week after starting therapy. The mechanism may involve autoantibodies, bradykinin, or complement-system components. Treatment involves first protecting the airway, followed by epinephrine, antihistamines, and corticosteroids if needed. Therapy is then resumed with an alternate class of antihypertensive agent.

Angioedema↗
PubMed1987

Pharmacokinetics of antituberculosis drugs in patients.

The pharmacokinetics of rifampin, isoniazid, and ethambutol were determined in 26 ambulatory male patients (aged 49.5 +/- 9.9 yr) with tuberculosis. Rifampin and isoniazid were given individually or together, with or without ethambutol; studies were done after a single dose and after chronic administration. Under the study conditions, with large variability in the extent of disease and physical status and history of alcohol and tobacco abuse and narrow age range, the pharmacokinetics of these three antituberculosis drugs were not modified significantly by patient age. Furthermore, appreciable drug-drug interactions did not occur when the three drugs were administered concurrently. Self-induction of rifampin clearance by chronic dosing with the drug may lead to subtherapeutic levels of rifampin. Administration of isoniazid and ethambutol in two divided doses resulted in peak plasma concentrations below the accepted therapeutic levels of the two drugs. Our findings indicate that at least in the middle-aged patients with tuberculosis, the current single daily dose, multiple-drug regimen is therapeutically sound pharmacokinetically, and clinicians do not have to make adjustments in dosages of these drugs for age and the extent of disease.

Adult↗
PubMed1986

Adenosine release from isolated rat adipocytes: influence of fat cell concentration and cell size.

The release of adenosine by isolated rat adipocytes into the incubation medium was studied in relation to fat cell size and concentration. Incubations were carried out for 60 min at 37 degrees C in Krebs-Ringer bicarbonate-albumin medium containing 6 mM glucose. 2'-Deoxycoformycin was added to inhibit endogenous adenosine deaminase activity (maximal suppression was achieved at 0.8 microM concentration of the inhibitor). The data show that (a) the amount of adenosine released into the medium was similar for the first and second 30-min incubation periods; (b) increasing adipocyte concentration markedly inhibited adenosine release; and (c) large fat cells (volume greater than 300 pl) released significantly more adenosine (per fat cell) into the medium than smaller fat cells (volume less than 180 pl) when incubated at concentrations of less than or equal to 350,000 cells/ml. Above this cell concentration, differences between adenosine release and cell size were not noted. Adenosine release by isolated rat adipocytes appears to be a precisely regulated process which is exquisitly sensitive to the number of fat cells in the incubation medium and, to a certain extent, to the adipocyte size.

Adenosine↗
PubMed1981

Marrow cell kinetics in patients treated with methotrexate and citrovorum factor.

Methotrexate (MTX) was administered by continual intravenous infusion for 24 hours in doses ranging from 200-800 mg/m2 to 16 patients who had metastatic cancers and normal bone marrows and 11 patients with acute leukemia. Citrovorum factor (CF) was administered every 6 hours for 12-15 doses beginning 36 hours after the start of the MTX infusion. Plasma and urine were collected to measure MTX concentration. Daily bone marrow aspirates were obtained for measuring intracellular MTX concentration, labelling index (LI), mitotic index (MI), grain count distribution, cellular DNA distribution by flow cytometry (FCM), and marrow morphology. The plasma MTX concentration proved to be a function of dose and creatinine clearance. There was a positive correlation between the creatinine clearance and MTX clearance. The intracellular MTX concentration correlated highly with the plasma concentration. The LI, grain count, and proportion of cells in S phase increased on days 2 and 3. The magnitude of the changes on days 2 and 3 was dose related. The MI fell on day 2 and recovered by day 4. Transient megaloblastic changes occurred. The cell cycle perturbations in leukemic marrow were less pronounced than those in normal marrows. These observations are consistent with a transient, dose related, S phase delay.

Acute Disease↗
PubMed1981

A nonmetabolized analogue of phenytoin.

Nine novel analogues of 5,5-diphenylhydantoin bearing a CF3 group(s) in the meta or para position of one or both rings were synthesized. Preliminary evaluation of all the analogues (performed by the ADD Program, NIH) indicated no significant anticonvulsant activity against electrical or chemical shock in mice at doses of less than or equal to 100 mg/kg. The analogue 5,5-bis[4-(trifluoromethyl)phenyl]hydantoin (1) was synthesized labeled with 14C in the 4 position of the hydantoin ring. Certain physicochemical properties (pKa, partition ratio, protein binding, etc.) and the LD50 of 1 in mice (40 mg/kg, ip; 100 mg/kg, po) were determined. The disposition of [14C]1 was determined in rodents. The compound was excreted unchanged in rat feces (94% in 18 days), urinary excretion less than 0.5%. The half-life of elimination of [14C]1 from plasma was 67-72 h (ip and iv) in rats and 115 h (ip) in mice. Studies of tissue distribution and biliary excretion of [14C]1 indicate low tissue/plasma ratios (due to high plasma binding, 97%) and low biliary excretion. The lack of metabolism of [14C]1 may possibly be explained by (1) the strong electron-withdrawing effects of CF3 substituents, (2) the preemption of the primary metabolic sites, (3) the accompanying steric hindrance, and (4) the apparent inability of the CF3 group to undergo the NIH shift.

Animals↗
PubMed1978

New spectrophotofluorometric assay for probenecid.

A new spectrophotofluorometric assay for probenecid is presented based on conversion of the drug to a fluorescent anthranilic acid derivative. The assay is especially applicable with "clean" biological fluids such as cerebrospinal fluid and offers severalfold greater sensitivity than the commonly used UV method.

Animals↗