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Biomedical subjects

S M Ali

Publications and source records attributed to S M Ali.

At least 37 records · Page 2Linked to original sources
PubMed2001

Diabetic foot ulcer--a prospective study.

OBJECTIVE: To detect "Feet at Risk" early, its early diagnosis and treatment of foot ulceration to prevent amputation. SETTING AND METHOD: One hundred patients with diabetic foot problems were seen at Baqai Institute of Diabetology and Endocrinology from 06-01-97 to 14-04-99. Each Patient was examined for peripheral pulses, sensations and reflexes, for dryness of skin, deformity, callus and nail disorders and were photographed on first visit. RESULTS: There were 65% males and 35% females included in this study. Ninety nine patients were type II diabetics, 38% were either smokers or had other addictions (or were addicted to tobacco). Awareness about risk factors causing foot problems was lacking among all patients. Fifty percent patients were on oral hypoglycaemic agents, 48% were insulin treated, while 2% were on diet and exercise alone. Glycaemic control was poor in 70%, fair in 16% and was good in 14%, 31% were overweight and 5% patients were underweight. Duration of diabetes was greater than ten years in 58%, toes were affected in 44%, sole/metatarsal in 18%; rest included malleoli, heel etc. Eleven patients had ulcers on both feet. Neuropathic ulcer were 42%, neuro ischaemic 58%, Sixty nine percent patients were in the age group between 40-60 years. Cause unknown 29% blisters and boil 14%, trauma/cutting 17%, burns 8%, dry skin/callus 10%. Fundal changes were present in 37%; proteinuria in 37%, ischaemic heart disease in 20%, hypertension 18%, In 60% more than one antibiotic was used. Foot ulcers of fifty nine patients healed on conservative management, six patients had below knee amputation, fifteen had toe amputation; nine were still on treatment, eleven lost contact. CONCLUSION: Lack of awareness, poor glycaemic control and duration of diabetes were the main factors causing diabetic foot problems. This study also confirmed that microvascular complications should be screened in patients with diabetic foot ulcers. Foot care education would be the most important way of dealing with this major problem.

Adult↗
PubMed2000

Total synthesis of cryptophycin-24 (Arenastatin A) amenable to structural modifications in the C16 side chain.

Two efficient protocols for the synthesis of tert-butyl (5S,6R,2E, 7E)-5-[(tert-butyldimethylsilyl)oxy]-6-methyl-8-phenyl-2, 7-octadienoate, a major component of the cryptophycins, are reported. The first utilized the Noyori reduction and Frater alkylation of methyl 5-benzyloxy-3-oxopentanoate to set two stereogenic centers, which became the C16 hydroxyl and C1' methyl of the cryptophycins. The second approach started from 3-p-methoxybenzyloxypropanal and a crotyl borane reagent derived from (-)-alpha-pinene to set both stereocenters in a single step and provided the dephenyl analogue, tert-butyl (5S,6R,2E)-5-[(tert-butyldimethylsilyl)oxy]-6-methyl-2, 7-octadienoate, in five steps. This compound was readily converted to the 8-phenyl compound via Heck coupling. The silanyloxy esters were efficiently deprotected and coupled to the C2-C10 amino acid fragment to provide desepoxyarenastatin A and its dephenyl analogue. The terminal olefin of the latter was further elaborated via Heck coupling. Epoxidation provided cryptophycin-24 (arenastatin A).

Antineoplastic Agents↗
PubMed2000

Pharmacological basis for the use of peach leaves in constipation.

The aqueous crude extract (PPL.Cr) of peach leaves (Prunus persica) was studied for the possible presence of gut stimulatory constituent(s) to rationalize the folkloric use of the plant in constipation. PPL.Cr at the dose of 1-10 mg/ml caused a moderate degree of spasmogenic effect in isolated guinea-pig ileum. Pretreatment of the tissue with atropine (1 M) completely abolished the contractile effect of the plant extract similar to that of acetylcholine which is suggestive of a cholinergic mechanism. In isolated rabbit jejunum preparations, PPL.Cr produced a week spasmogenic effect followed by relaxation of the spontaneous contractions at higher doses. Bioassay-directed fractionation revealed that the spasmogenic activity was separated in the aqueous fraction, while the spasmolytic activity was concentrated in the ethyl acetate fraction. When tested against K(+)-induced contraction, both PPL.Cr and its ethyl acetate fraction (PPL.EtAc) caused a dose-dependent inhibition, suggesting calcium channel blockade (CCB). The presence of CCB in peach leaves was confirmed when pretreatment of the tissue with PPL.EtAc caused a dose-dependent rightward shift in the Ca(2+) dose-response curves, similar to that produced by verapamil. These data indicate that the plant contains spasmogenic (cholinomimetic) and spasmolytic (calcium antagonist) constituents, which are concentrated in the aqueous and ethyl acetate fractions, respectively. Furthermore, the laxative effect of the plant reported in the traditional system of medicine may be partially due to the cholinergic action, which was dominant over the spasmolytic component.

Acetylcholine↗
PubMed2000

Treatment of external genital warts in men with imiquimod 2% in cream. A placebo-controlled, double-blind study.

OBJECTIVE: The purpose of this double-blind, placebo-controlled study was to evaluate the safety, clinical efficacy and tolerability of imiquimod (2%) in cream to cure external genital warts in males. METHODS: Preselected male patients (n=60) ranging between 18 and 50 years of age (mean 24.2) harbouring 558 lesions (mean 9.3) with clinical, histopathological and polymerase chain reaction (PCR) confirmed diagnosis of human papilloma virus (HPV) infection were randomized to two parallel groups. Each patient was allocated a precoded 25g tube, and instructions on how to apply the trial medication to their lesions at home once daily for three consecutive days per week (max. 12 application in 4 weeks). To evaluate the safety, clinical efficacy and tolerance, patients were exa-mined on a weekly basis. Cure was defined as the total elimination of treated warts with PCR, and Southern blot hybridization confirmed negative HPV DNA. RESULTS: By the end of the treatment, 40% (24/60) patients and 49.8% (278/558) warts were cured. Breaking the code revealed that imiquimod cream had cured 70% (21/30) patients and 86.8% of warts, while placebo healed three subjects and 28 warts (P=0.0001). Eleven patients (18.3%), predominantly in the imiquimod cream group, experienced mild to moderate, non-objective, drug-related side effects with no dropouts. The study was followed up for 18 months from the first day of the treatment, and among the 26 cured patients, one in the imiquimod cream group and two in the placebo had a relapse after 14 months. CONCLUSION: The study demonstrated that 2% imiquimod in cream with mild non-objective side effects is safe, tolerable and significantly more effective than placebo in curing external genital warts in males.

Administration, Cutaneous↗
PubMed2000

Apoptosis in polycystic kidney disease: involvement of caspases.

Polycystic kidney disease (PKD) is characterized by the development of large renal cysts and progressive loss of renal function. Although the cause of the development of renal cysts is unknown, recent evidence suggests that excessive apoptosis occurs in PKD. With the use of terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, we have confirmed the presence of apoptotic bodies in cystic kidneys of congenital polycystic kidney (cpk) disease mice carrying a homozygous mutation at 3 wk of age. Apoptosis was localized primarily to the interstitium with little evidence of cell death in cyst epithelium or noncystic tubules. In addition, we observed that the expression of various caspases, bax and bcl-2, was upregulated in cystic kidneys. With the use of various substrates in enzyme activity assays, we have demonstrated a greater than sevenfold increase in caspase 4 activity and a sixfold increase in caspase 3 activity. These data suggest that there is a caspase-dependent apoptosis pathway associated with PKD and support the hypothesis that apoptotic cell death contributes to cyst formation in PKD.

Animals↗
PubMed2000

Management of intravaginal warts in women with 5-fluorouracil (1%) in vaginal hydrophilic gel: a placebo-controlled double-blind study.

The purpose of this placebo-controlled, double-blind study was to determine the safety, tolerability and clinical efficacy of 5-fluorouracil (1%) in a vaginal hydrophilic gel (hydroxyethylcellulose, 1%) to cure intravaginal papillomas in women. Pre-selected, 60 women ranging between 18 and 50 years of age (mean 24.6), having 312 vaginal condylomas (mean 5.2) joined the study. The diagnosis of human papillomavirus (HPV) was established with clinical, histopathological and polymerase chain reaction (PCR) techniques. Subjects were randomized into 2 parallel groups. Each patient was allocated a pre-coded tube 15 g (active or placebo) with graduated vaginal applicators (disposable), and instructions how to insert 4 g of the trial medication deep into the vagina once at bedtime on every other day (1, 3 and 5) per week, to visit the clinic on day 7 for clinical evaluations and to receive the same pre-coded replacement to continue the regimen for another week. A maximum 12 applications were to be used in 4 weeks. Cure was defined as absence of clinical signs of infection, re-confirmed by PCR and Southern blot hybridization negative HPV DNA. By the end of the treatment 48.4% patients and 51.9% lesions were cured. Breaking the code revealed that 5-fluorouracil (1%) gel had cured 83.3% patients and 87% intravaginal warts. Placebo resolved 13.3% patients and 14% condylomas; (active gel versus placebo; P < 0.001). Twelve patients (20%) mostly in the active gel experienced mild erythema, erosion and oedema, with no drop-outs. Among cured patients 3 had a relapse after 16 months. In conclusion, the clinical results of the study demonstrate that 5-fluorouracil (1%) in a vaginal hydrophilic gel is safe, tolerable and significantly more effective than placebo to cure intravaginal warts in women.

Administration, Intravaginal↗
PubMed2000

Vegetarian diet in the treatment of fibromyalgia.

Brain tryptophan is low in fibromyalgia. Intake of protein rich in large neutral amino acids is reported to lower brain tryptophan. This study was undertaken to assess whether any reduction of such proteins by exclusion of animal protein from the diet reduced pain and morbidity in fibromyalgia patients. It was an open, randomized controlled trial. 37 subjects with fibromyalgia were enrolled in the vegetarian diet and 41 in the amitriptyline groups. The outcome was assessed with the help of frequencies of fatigue, insomnia & non-restorative sleep, pain score on a 10-point VAS and tender point count. Fatigue, insomnia and non-restorative sleep were present in 41, 26 and 32 subjects before and in 3, 0 and 0 subjects respectively at six weeks of treatment in the amitriptyline group. The pain score and tender point count were 6.2 +/- 1.9 & 16.1 +/- 2.3 before and 2.3 +/- 1.3 & 6.4 +/- 3.0 after treatment. All these differences were significant (P < 0.001). In the vegetarian diet group, fatigue, insomnia and non-restorative sleep were present in 36, 24 and 27 subjects before and in 34, 29 and 29 subjects at six weeks of treatment. The pain score and tender point count were 5.7 +/- 1.8 and 15.7 +/- 2.4 before and 5.0 +/- 1.8 & 14.7 +/- 3.6 after treatment. All these differences were insignificant except that in the pain score. The decrease in the pain score, though significant, was much smaller than that in the amitriptyline group. So, it may be concluded that vegetarian diet is a poor option in the treatment of fibromyalgia.

Adult↗
PubMed1999

Potent inhibition of influenza sialidase by a benzoic acid containing a 2-pyrrolidinone substituent.

On the basis of the lead compound 4-(N-acetylamino)-3-guanidinobenzoic acid (BANA 113), which inhibits influenza A sialidase with a Ki of 2.5 microM, several novel aromatic inhibitors of influenza sialidases were designed. In this study the N-acetyl group of BANA 113 was replaced with a 2-pyrrolidinone ring, which was designed in part to offer opportunities for introduction of spatially directed side chains that could potentially interact with the 4-, 5-, and/or 6-subsites of sialidase. While the parent structure 1-(4-carboxy-2-guanidinophenyl)pyrrolidin-2-one (8) was only a modest inhibitor of sialidase, the introduction of a hydroxymethyl or bis(hydroxymethyl) substituent at the C5' position of the 2-pyrrolidinone ring resulted in inhibitors (9 and 12, respectively) with low micromolar activity. Crystal structures of these inhibitors in complex with sialidase demonstrated that the substituents at the 5'-position of the 2-pyrrolidinone ring interact in the 4- and/or 5-subsites of the enzyme. Replacement of the guanidine in 12 with a hydrophobic 3-pentylamino group resulted in a large enhancement in binding to produce an inhibitor (14) with an IC50 of about 50 nM against influenza A sialidase, although the inhibition of influenza B sialidase was 2000-fold less. This represents the first reported example of a simple, achiral benzoic acid with potent (low nanomolar) activity as an inhibitor of influenza sialidase.

Benzoates↗
PubMed1999

Design, synthesis, and structure-activity relationships of acetylene-based histamine H3 receptor antagonists.

New, potent, and selective histamine H3 receptor antagonists have been synthesized by employing the use of (1) an appropriately positioned nonpolar acetylene spacer group, (2) either a two-carbon straight chain linker or a conformationally restricting trans-cyclopropane ring between the C-4 position of an imidazole headgroup and the acetylene spacer, and (3) a Topliss operational scheme for side-chain substitution for optimizing the hydrophobic domain. Compounds 9-18 are examples synthesized with the two-carbon straight chain linker, whereas 26-31 are analogues prepared by incorporation of the trans-(+/-)-cyclopropane at the C-4 position of an imidazole headgroup. Synthesis of both the (1R,2R)- and (1S, 2S)-cyclopropyl enantiomers of the most potent racemic compound 31 (Ki = 0.33 +/- 0.13 nM) demonstrated a stereopreference in H3 receptor binding affinity for the (1R,2R) enantiomer 32 (Ki = 0.18 +/- 0.04 nM) versus the (1S,2S) enantiomer 33 (Ki = 5.3 +/- 0.5 nM). (1R,2R)-4-(2-(5,5-Dimethylhex-1-ynyl)cyclopropyl)imidazole (32) is one of the most potent histamine H3 receptor antagonists reported to date.

Acetylene↗
PubMed1999

Epithelin mRNA expression in polycystic kidney disease.

Epithelins are polypeptides that are preferentially expressed in epithelial cells and modulate growth. Epithelin expression is predominant in tissues of epithelial origin such as the kidney, spleen, lung, placenta, and colon. Because polycystic kidney disease involves abnormal proliferation of the proximal and/or distal tubule epithelial cells, we investigated epithelin mRNA expression in polycystic kidneys of mice homozygous for the mutation. Epithelin mRNA was highly expressed in the polycystic kidneys of homozygous mice when compared with the heterozygotes or wild type controls. A study on the time course of epithelin expression indicated that epithelin mRNA expression paralleled cyst formation and progression of the disease. A 2-fold increase in expression was observed at Day 15, a stage when cystic changes were first visible. This increase in expression was also observed at Day 21, a stage of maximum disease pathology, which ultimately results in the death of the animal. In situ hybridization localized epithelin mRNA predominantly to the epithelial cell layer surrounding the cysts. The high levels of epithelin in epithelial cells suggest a role in renal epithelial cell proliferation and cyst formation in polycystic kidney disease.

Age Factors↗
PubMed1999

Treatment of toenail onychomycosis with 2% butenafine and 5% Melaleuca alternifolia (tea tree) oil in cream.

The prevalence of onychomycosis, a superficial fungal infection that destroys the entire nail unit, is rising, with no satisfactory cure. The objective of this randomized, double-blind, placebo-controlled study was to examine the clinical efficacy and tolerability of 2% butenafine hydrochloride and 5% Melaleuca alternifolia oil incorporated in a cream to manage toenail onychomycosis in a cohort. Sixty outpatients (39 M, 21 F) aged 18-80 years (mean 29.6) with 6-36 months duration of disease were randomized to two groups (40 and 20), active and placebo. After 16 weeks, 80% of patients using medicated cream were cured, as opposed to none in the placebo group. Four patients in the active treatment group experienced subjective mild inflammation without discontinuing treatment. During follow-up, no relapse occurred in cured patients and no improvement was seen in medication-resistant and placebo participants.

Administration, Topical↗
PubMed1999

Determinants of mortality among children in the urban slums of Dhaka city, Bangladesh.

The growing slum population in the developing world is an increasing challenge for local health authorities. Little is known of the patterns of disease occurrence including treatment types offered in this population. The paper describes reported child mortality and its determinants, including the main diseases affecting children and treatments, in the slum population of Dhaka city, Bangladesh. 1500 households in three slum communities were included in a cross-sectional survey. Reported death rates in the households per 1000 children (0-107 months) within the last year from the interview were 20.5 for boys and 27.0 for girls. More girls than boys died in infancy (age < 12 months). The most frequent reported causes of deaths were tetanus in infancy and diarrhoea among children aged < or = 12 months. Vaccination coverage (DPT, polio, measles and BCG) was 73% for children < 3 years of age. The results showed that gender difference in mortality may have been influenced by the patterns of treatment received during sickness and the choice of treatment was determined by the financial ability of the households. Household income, children's vaccinations, TT immunization of mothers and personal cleanliness appeared to be significantly associated with child mortality. Despite the relatively high vaccination coverage for this population, child mortality remained alarmingly high, indicating that socioeconomic and environmental conditions must be improved to substantially reduce morbidity and mortality in this population.

Accidents↗
PubMed1999

Identification and pharmacological characterization of a series of new 1H-4-substituted-imidazoyl histamine H3 receptor ligands.

A new series of 1H-4-substituted imidazole compounds were synthesized and identified as potent and selective histamine (HA) H3 receptor ligands. These ligands establish that HA H3 antagonists exhibit stereoselective and conformational preferences in their binding to the HA H3 receptor. Structure-activity relationships were determined in vitro by HA H3 receptor-binding affinities using [3H]Nalpha-methylhistamine and rat cerebral cortical tissue homogenates. Several derivatives containing olefin, amide, and acetylene functional groups were identified as potent HA H3 receptor ligands. In the olefin series, GT-2227 (4-(6-cyclohexylhex-cis-3-enyl)imidazole) was identified as a potent HA H3 receptor ligand with a Ki of 4.2 +/- 0.6 nM, while the trans isomer (GT-2228) displayed a reduced potency (Ki = 15.2 +/- 2.4 nM). GT-2227 was also found to have excellent central nervous system penetration in an ex vivo binding paradigm (ED50 = 0.7 mg/kg i.p.). In the acetylene series, GT-2260 and GT-2286 both exhibited high affinity (Ki = 2.9 +/- 0.2 and 0.95 +/- 0.3 nM) and excellent central nervous system penetration profiles (ED50 = 0.43 and 0.48 mg/kg i.p., respectively). As a prototype for the series, GT-2227 showed high affinity for the human HA H3 receptor (3.2 nM) and minimal affinity for the human HA H1 (Ki = 13,407 +/- 540 nM) and H2 (Ki = 4,469 +/- 564 nM) receptor subtypes. GT-2227 also showed good selectivity for the HA H3 receptor over a broad spectrum of other neurotransmitter receptors (IC50 >/= 1 microM). Furthermore, GT-2227 improved acquisition in a cognitive paradigm without behavioral excitation or effect on spontaneous locomotor activity. In summary, the present studies demonstrate the development of novel HA H3-selective ligands, and lend support for the use of such agents in the treatment of disorders associated with cognitive or attentional deficits.

Animals↗
PubMed1999

Development of trans-2-[1H-imidazol-4-yl] cyclopropane derivatives as new high-affinity histamine H3 receptor ligands.

Previously, a novel series of 1H-4-substituted imidazole compounds were described as potent and selective histamine (HA) H3 receptor ligands (Yates et al., 1999). The present studies extend the structure-activity relationships for optimal HA H3 receptor affinity and central nervous system penetration by incorporation of a conformationally restricted cyclopropane nucleus. Moreover, the current studies extend our understanding of ligand-receptor interactions at the HA H3 receptor with the development of high affinity HA H3 receptor antagonists containing a stereochemical presentation. Structure-activity relationships were established from in vitro HA H3 receptor-binding affinities using [3H]Nalpha-methylhistamine and rat cortical tissue homogenates. Systematic optimization of multiple structural features critical for HA H3 receptor affinity provided some of the most potent HA H3 receptor agents described. For example, GT-2331 was determined to bind to a single population of HA H3 receptors with a Ki of 0.125 nM. In vivo, GT-2331 has a favorable central nervous system penetration profile with an ED50 of 0.08 mg/kg (i.p.) in rats and a long duration of action (T1/2 > 4 h). In addition, GT-2331 was extremely selective for the HA H3 receptor versus other HA receptors and a battery of neurotransmitter, neuropeptide, hormone, or enzyme systems. Several compounds were tested in vitro which suggested HA H3 receptor heterogeneity and are discussed in terms of structure-activity relationships for the HA H3 receptor.

Animals↗
PubMed1999

The incidentally discovered asymptomatic adrenal tuberculous mass mimicking malignancy.

Tuberculous adrenal mass without any tuberculous changes in other sites is a rare entity. In this study we describe such a case. A male patient of 47 years with 6 months history of anorexia and weakness was presented. Ultrasonography and computed tomography revealed a mass in the right adrenal gland. It was mistaken as a malignant neoplasm and the diagnosis was confirmed by surgical exploration.

Adrenal Gland Diseases↗
PubMed1998

Development of a sensitive and quantitative analytical method for 1H-4-substituted imidazole histamine H3-receptor antagonists utilizing high-performance liquid chromatography and dabsyl derivatization.

A sensitive and versatile analytical method utilizing high-performance liquid chromatography (HPLC) and precolumn derivatization of 1H-4-substituted imidazole compounds is described. A HPLC method using 4-dimethylaminoazobenzene-4'-sulfonyl chloride (dabsyl chloride) and ultraviolet (UV) detection was developed for the analysis of histamine (HA) H3-selective compounds in human plasma, rat plasma, or homogenized rat cortical tissue. The average intra- and inter-assay variability, over a range of 10 to 0.01 microg/ml, was determined to be acceptable. The lower limit of detection for the dabsylated ligands was estimated to be <1.0 ng/ml while the lower limit of quantitation (LLOQ) was determined to be 10 ng/ml of conjugate. This assay has demonstrated it's suitability for the sensitive quantitation of several structurally diverse 1H-4-substituted imidazole HA H3-receptor antagonists in biological matrices for pharmacokinetic and biodistribution studies.

Animals↗