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Biomedical subjects

S M Ali

Publications and source records attributed to S M Ali.

At least 55 records · Page 3Linked to original sources
PubMed1998

Halohydrin analogues of cryptophycin 1: synthesis and biological activity.

The chloro-, bromo-, and iodo-derivatives 2-4 of the antimitotic drug cryptophycin 1 were synthesized by opening the epoxide ring. The biological activities of the compounds were tested in an in vitro microtubule assembly and a cell proliferation assay. The chloro-derivative 2 showed lower activity in the tubulin assay compared to 3 and 4, but they all showed similar inhibition in the proliferation assay.

Antineoplastic Agents↗
PubMed1998

High antagonist potency of GT-2227 and GT-2331, new histamine H3 receptor antagonists, in two functional models.

GT-2227 (4-(6-cyclohexylhex-cis-3-enyl)imidazole) and GT-2331 ((1R,2R)-4-(2-(5,5-dimethylhex-1-ynyl)cyclopropyl)imidazole) were developed as new potent histamine H3 receptor antagonists. The functional activity of these ligands on the histamine H3 receptor-mediated inhibition of neurogenic contraction of the guinea-pig jejunum and histamine H3 receptor-mediated inhibition of norepinephrine release from guinea-pig heart synaptosomes were investigated. GT-2227 and GT-2331 both antagonized the inhibitory effects of (R)-alpha-methylhistamine on the contraction induced by electrical field stimulation in the guinea-pig jejunum with pA2 values of 7.9+/-0.1 and 8.5+/-0.03, respectively. In addition, GT-2227 and GT-2331 antagonized the inhibition of norepinephrine release in cardiac synaptosomes by GT-2203 ((1R,2R)-trans-2-(1H-imidazol-4-yl)cyclopropylamine), a histamine H3 receptor agonist. The current results demonstrate the antagonist activity for both GT-2227 and GT-2331 in two functional assays for histamine H3 receptors.

Animals↗
PubMed1998

Early angiotensin converting enzyme inhibitor therapy after experimental myocardial infarction prevents left ventricular dilation by reducing infarct expansion: a possible mechanism of clinical benefits.

OBJECTIVE: To examine the effects of early angiotensin-converting enzyme (ACE) inhibitor therapy after myocardial infarction on infarct expansion in an experimental rat model. BACKGROUND: ACE inhibitor therapy within 24 h of acute myocardial infarction (AMI) reduces mortality by unknown mechanism(s). METHODS: Rats underwent permanent coronary artery occlusion. A treated group received enalapril (1.9+/-0.2 mg/kg) daily in drinking water beginning 2 h after coronary artery occlusion, a time too late to reduce infarct size. Rats were sacrificed 2 days or 2 weeks after myocardial infarction. Hearts were arrested and fixed at a constant pressure, then sectioned and photographed for morphometric analysis. RESULTS: Infarcts in the control group expanded between 2 days and 2 weeks after myocardial infarction (expansion index 0.7+/-0.1 versus 2.5+/-0.4, P< 0.05). However, infarct expansion remained unchanged in the enalapril group between 2 days and 2 weeks after myocardial infarction (expansion index 0.8+/-0.1 versus 1.3+/-0.1, NS). Two weeks after myocardial infarction, the enalapril group had fewer expanded infarcts than the control group (expansion index 1.3+/-0.1 versus 2.5+/-0.4, P< 0.05). While left ventricular volume increased in the control group between 2 days and 2 weeks after myocardial infarction (0.17+/-0.01 ml versus 0.36+/-0.03 ml, P< 0.05), it remained constant in the enalapril group (0.22+/-0.02 ml versus 0.25+/-0.03 ml, NS). Two weeks after myocardial infarction, the left ventricles were larger in the control group than in the enalapril group (0.36+/-0.03 ml versus 0.25+/-0.03 ml, P< 0.05). CONCLUSIONS: Treatment with enalapril initiated 2 h after AMI prevented left ventricular dilation by limiting infarct expansion. This may explain the mechanism by which ACE inhibitor therapy started within 24 h of an AMI improves survival 5-6 weeks after infarction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Angiotensin-converting enzyme inhibition alters clusterin mRNA expression in the kidney following renal mass reduction.

The effect of the angiotensin-converting enzyme inhibitor captopril on clusterin mRNA was examined in partially nephrectomized male rats. Urine protein excretion was measured 3, 7, and 28 days after removal of five sixths of the renal mass. Nephrectomy caused a progressive increase in clusterin mRNA levels in the remnant kidney. Maximal clusterin mRNA levels occurred 7 days after nephrectomy and declined 28 days after nephrectomy. Captopril, 250 mg/ml in drinking water, prevented the injury-induced increase in clusterin mRNA at 7 and 28 days. Captopril had no effect on clusterin in sham-operated rats. As expected, the urine protein excretion increased progressively after nephrectomy, and this was attenuated by administration of captopril in the drinking water. Therefore, clusterin is a marker of renal injury which, along with proteinuria, is modulated by angiotensin-converting enzyme inhibition.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Angiotensin-converting enzyme inhibition attenuates proteinuria and renal TGF-beta 1 mRNA expression in rats with chronic renal disease.

Evidence suggests that transforming growth factor beta 1 (TGF-beta 1), a multifunctional cytokine, induces renal extracellular matrix production and glomerular hypertrophy. The aim of the present study was to investigate the effect of captopril on the expression of TGF-beta 1 mRNA in a rat model of chronic renal failure: five-sixths nephrectomy. Chronic renal disease was induced by removal of the right kidney and ligation of three blood vessels supplying the left kidney. Sham-operated animals were used as controls. RNA was extracted from the viable remnant kidney of rats 1 day and 1 and 2 weeks following five-sixths nephrectomy and from the kidneys of rats who underwent sham surgery. TGF-beta 1 mRNA was induced within 24 h of partial nephrectomy, similar to that reported for early-onset genes. Subsequently, TGF-beta 1 mRNA expression continued to increase over the next 2-4 weeks. The upregulation of TGF-beta 1 correlated with the degree of proteinuria. Both the increase in TGF-beta 1 mRNA and proteinuria were abrogated by captopril treatment. In addition, no change in expression of ALK-5 or type II TGF-beta receptors following five-sixths nephrectomy was observed. These data suggest that captopril may protect against development of glomerulosclerosis and proteinuria by reducing TGF-beta 1 expression and hence matrix production.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

The age-related increase in renal clusterin mRNA is accelerated in obese Zucker rats.

Clusterin is a multifunctional glycoprotein associated with development and tissue injury. Because renal function decreases with advancing age in the obese Zucker rat, clusterin mRNA expression was examined in the kidney of young adult Zucker rats and compared with age-related changes in renal clusterin mRNA expression in Fischer 344 (F344) rats. Renal clusterin mRNA levels in the obese Zucker rat were 2.5-fold higher by 3 mo of age and fourfold higher at 5 mo of age compared with the lean strain. In comparison, renal clusterin mRNA in 12-mo-old F344 rats was twofold higher than in 3-mo-old animals and was tenfold higher at 24 mo of age. Clusterin mRNA was positively correlated with urinary protein excretion and negatively correlated with creatinine clearance in Zucker rats. Clusterin was increased in select nephrons of the obese Zucker rat kidney and in 24-mo-old F344 rat kidney as assessed by in situ hybridization. Increased expression of clusterin mRNA occurred mostly in the tubular epithelium of dilated, convoluted proximal tubules. These data indicate that renal clusterin mRNA levels increase as a function of age and that age-related increases in renal clusterin and the associated tubular abnormalities are accelerated in obese Zucker rats.

Aging↗
PubMed1998

Is the Barthel Scale appropriate in non-industrialized countries? A view of rural Pakistan.

PURPOSE: To determine if the Barthel Index, a conventional scale for assessing disability, is appropriate for stroke patients in rural Pakistan, rather than an observational study by visiting stroke patients in their homes. METHOD: Stroke patients attending hospital out patient clinics in Islamabad, together with others identified in local villages, were assessed to test the validity of the Barthel Activities of Daily Living Scale. RESULT: For each item on the disability scale, differences in local customs, lifestyle and architecture meant that the Barthel Scale was not appropriate in rural Pakistan. CONCLUSIONS: There is unlikely to be a disability scale which can be applicable universally. Care must be taken when standard scales are used for international comparisons of stroke disability.

Activities of Daily Living↗
PubMed1998

Hydatidosis: experience with hepatic and pulmonary hydatid disease.

From 1989-1992, 35 cases comprising of 20 hepatic and 15 pulmonary hydatid cysts were seen. Four patients with pulmonary hydatid disease had previous or concomitant hepatic hydatidosis compared to no concomitant pulmonary hydatid disease in the hepatic group. Hepatic hydatid disease had a greater tendency to be right sides, infected and calcified. Anaphylactic reactions occurred in 3 of 20 patients with hepatic hydatid disease against none in 15 patients with pulmonary disease. Management consisted of evacuation, drainage and obliteration of the residual cavity by capittonage in the lung and omentoplasty in the liver. Two patients, one hepatic and one with pulmonary hydatid disease developed infection of the residual cavity. Bronchocystic fistula occurred in 4 pulmonary and cystobiliary fistula in 2 hepatic hydatid disease patients. One patient with severe pleuropulmonary hydatidosis required a thoracoplasty. No recurrences have been noted in either group over a mean follow-up of 11 months (range 3 weeks- 3 years).

Adolescent↗
PubMed1998

Effect of interleukin-2 on experimental acute toxoplasmosis.

The traditional treatment of toxoplasmosis involves the use of pyrimethamine and sulphadiazine. This combination has a teratogenic effect and its use is limited especially in immunosuppressed cases. Spiramycin used safely during pregnancy is also not effective because it is toxoplasmistatic only. The potential efficiency of alternative immunotherapy was assessed. The present study was undertaken to evaluate the effect of exogenously supplied IL-2 on T. gondii infected mice. IL-2 was administered after infection (on days +2, +4, +6, +8), before and after infection (on days -3, -1, +2, +4, +6) and before infection (on days -8, -6, -4, -2). The date of infection was considered zero. Assessment of its effect was through: a) Parasitological study which included: parasite count, differentiation between living and dead tachyzoites and death rate of infection mice. b) Immunological study: detection of circulating antigen on the 3rd, 5th, 7th and 9th day p.i. The results showed that IL-2 was most effective when administered before and after infection in the form of significant reduction in parasitic count, least number of living tachyzoites, significant reduction in the death rate of infected mice and delayed appearance of circulating antigen with reduction in its level.

Animals↗
PubMed1998

An exercise training combined with dietary program for patients with hypertension.

A controlled clinical trial was conducted to determine whether combined exercise training and diet alone reduce blood pressure (BP), body weight and body mass index (BMI) in three weeks. Twenty eight patients with diastolic BP < or = 110 mmHg were assigned to a hypertensive group and another 28 subjects with diastolic BP < or = 90 mmHg were subjected to the same intervention as control group (normotensive group). Exercise training and diet reduced diastolic BP by 24.7 mmHg and systolic BP by 32.8 mmHg in hypertensive group. There was a mean decreased of 5.3 mmHg in the diastolic BP in the normotensive group (P < 0.001). The systolic BP decreased only minimally. The weight loss ranged from 1 kg to 3 kg in hypertensive and 1 kg to 2 kg in the normotensive group. The mean weight loss was 1.6 kg (0.7) in hypertensive and 1.5 kg (0.5) in the normotensive group. In both the groups the weight reduction was highly significant (P < 0.001) and moderately positive correlation was also noted with the fall of BPs. The mean fall of BMI was 0.61 kg/m2 (0.21) and 0.51 (0.2) kg/m2 in the hypertensive and normotensive groups respectively. The findings indicated that a combined exercise training and dietary program could lower BP in patients with mild to moderate hypertension, but its long-term consequences on morbidity and mortality remain to be determined.

Adult↗
PubMed1997

Butitaxel analogues: synthesis and structure-activity relationships.

N-Acyl analogues 8, 9, and 12-26 of butitaxel (3) were prepared in one or two steps from amines 5 and 6 through Schotten-Baumann acylation. Seventeen novel analogues, consisting of aliphatic carbamates, alicyclic amides, and heteroaromatic amides, were synthesized. They were evaluated for their in vitro ability to stimulate the formation of microtubules, their cytotoxicity toward B16 melanoma cells, and their solubility in water. The most potent analogue found in this study was N-debenzoyl-N-(2-thenoyl)butitaxel (20), possessing ca. 2-fold better tubulin assembly properties and cytotoxic activity against B16 melanoma cells than paclitaxel. Compound 20 was ca. 25 times more water soluble than paclitaxel.

Animals↗
PubMed1997

Phosphate excretion and phosphate transporter messenger RNA in uremic rats treated with phosphonoformic acid.

The prevention of phosphate retention in chronic renal disease may reduce both renal osteodystrophy and disease progression. We evaluated the expression of the sodium-dependent phosphate transporter, NaPi-2, and the response to phosphonoformic acid (PFA) in rats with 5/6 nephrectomy-induced renal failure. Partial nephrectomy resulted in a significant proteinuria and reduced renal function. In addition, there was an approximately 50% reduction in the expression of NaPi-2 mRNA. Treatment of rats for 48 hr with PFA (0.6% in glucose drinking fluid) had no effect on NaPi-2 mRNA; however, PFA resulted in a significant increase in fractional phosphate excretion in both normal (7 +/- 0.5% vs. 3 +/- 0.2%) and uremic (60 +/- 4% vs. 36 +/- 4%) rats. Plasma phosphate concentration was higher in uremic rats (2.5 +/- 0.1 mM) compared with normal rats (1.9 +/- 0.04 mM) but not in uremic rats treated with PFA (2.1 +/- 0.04 mM). These data suggest that PFA can increase renal phosphate excretion independent of changes in phosphate transporter expression and prevent phosphate retention.

Animals↗
PubMed1997

Serum IgE levels in patients with allergic problems and healthy subjects.

Total serum IgE levels were estimated in 219 patients with various allergic disorders (119 with bronchial asthma, 68 with allergic rhinitis and 32 with urticaria) and 240 healthy age matched subjects. Serum IgE levels were significantly (P < 0.001) higher in healthy males (mean 181 IU/ml) than females (mean 99 IU/ml). Higher levels were found in the age group 15 to 24 years and lowest in over 55 years. Males had higher IgE levels than females at any given age. Mean IgE levels were significantly (p < 0.001) higher in all three groups of patients than in healthy subjects. Among all age groups, the difference in mean IgE levels between allergic subjects and controls was significant. Positive skin test reactivity (to pollen and dust allergens) was found in 60% patients with asthma, 51% with allergic rhinitis, 46% with urticaria and in 4.5% healthy subjects. Patients with positive skin test had higher mean IgE levels as compared to those with negative skin test, but the difference was insignificant.

Adolescent↗
PubMed1997

Epidemiological study of endemic cretinism in a hyperendemic area.

A cross sectional survey was carried out to detect prevalence of cretinism in two rural areas of Bangladesh (one hyperendemic and the other non-endemic area). The size of the study population was four thousand five hundred and nine, the age ranged from 2 to 45 years. The prevalence of cretinism was 0.6% in the hyperendemic area, while there were no case of cretinism in the non-endemic zone. Of the 27 cretins, 18 (67%) were of the neurological type and 9 (33%) of mixed type. Males were more likely to be affected than females (p < 0.05). Cretinism was more prevalent in the 2-9 years age group. The hyperendemic area was deficient of iodine in food and the cretins were underweight. These observations call for a need for coordinated public health actions to control this serious problem.

Adolescent↗