Biomedical subjects
Publications and source records attributed to M Ali.
A new lanostane triterpenic ether, lanost-20(22)-en-3,19-ether, named adiantulanostene ether was isolated from Adiantum venustum. Its structure was elucidated on the basis of full spectral data analyses and chemical means.
Phytochemical studies on the aerial parts of Adiantum venustum resulted in the isolation of normethyl lupane-type, a normethyl oleanane-type and a lanostane-type triterpene. Structures of these triterpenes have been established as 30-normethyl lupane-20-one, 30-normethyl olean-3-one-30 beta-ol and lanost-20(22)-ene-30-ol on the basis of spectral data analyses and chemical methods.
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A new steroidal alkaloid, named antidysentericine, has been isolated from the seeds of Holarrhena antidysenterica and characterized as 3 beta-dimethylaminocon-5-enin-18-one (1).
We describe here eleven different mutations in SPINK5, encoding the serine protease inhibitor LEKTI, in 13 families with Netherton syndrome (NS, MIM256500). Most of these mutations predict premature termination codons. These results disclose a critical role of SPINK5 in epidermal barrier function and immunity, and suggest a new pathway for high serum IgE levels and atopic manifestations.
Garlic (Allium sativum) and onion (Allium cepa) are among the oldest of all cultivated plants. Additionally, both plants have been used as medicinal agents for thousands of years. Both garlic and onion have been shown to have applications as antimicrobial, antithrombotic, antitumor, hypolipidaemic, antiarthritic and hypoglycemic agents. In recent years, extensive research has focussed on the beneficial and medicinal properties of garlic and onions. In particular, the use of these agents in the treatment and prevention of cardiovascular disease and cancer is an area of considerable investigation and interest.
The use of fresh aqueous garlic extract is known to be effective in reducing thromboxane formation by platelets in both in vivo and in vitro animal models of thrombosis. In the present study, we studied the effect of Lichtwer garlic powder (containing 1.3% alliin equivalent to 0.6% allicin) on the serum cholesterol, triglyceride, glucose, protein, and systolic blood pressure in rats fed with a high cholesterol diet. Experimental rats were fed a 2% high cholesterol diet with and without garlic powder for 6 weeks. Control rats were fed a normal diet. The aqueous garlic powder extract was given orally to rats on a daily basis. It was observed that cholesterol-fed animals had a significant increase in serum cholesterol compared to the control group of rats fed on a normal diet. However, when the rats were fed with a high cholesterol diet mixed with garlic powder, there was a significant reduction in their serum cholesterol levels compared with the group which were on a diet containing high cholesterol without garlic powder. Serum triglyceride levels were also significantly lowered by garlic powder when compared to control and high cholesterol diet group rats. The blood pressure of the high cholesterol diet animals was significantly higher compared to the animals receiving the control diet. The blood pressure of the animals receiving garlic powder and high cholesterol diet was significantly lower as compared to the high cholesterol and control diet group. No significant changes were observed in the serum glucose and protein in all of the rats. These results show that garlic is beneficial in reducing blood cholesterol, triglycerides levels and systolic blood pressure in hypercholesterolemic rats. Our experimental results show that garlic may beneficially affect two risk factors for atherosclerosis--hyperlipidemia and hypertension.
We have shown previously that fresh garlic extract is effective in reducing thromboxane formation by platelets both in vivo and in vitro animal models of thrombosis. In the present study, the effect of different concentrations of a single dose of aqueous extracts of garlic and onion were evaluated on serum thromboxane-B(2)synthesis in rabbits. Different concentrations of garlic and onion were administered as single doses in the ear vein of rabbits. Rabbits were bled before and at different intervals after the infusion of garlic or onion extracts. Venous blood was collected and allowed to clot at 37 degrees C for 1 h. Thromboxane-B(2)level was measured in the serum by radioimmunoassay. It was observed that garlic inhibits the thrombin-induced platelet synthesis of TXB(2)in a dose-and time-dependent manner. Maximum inhibition of TXB(2)occurred between 0.5 h and 6 h at 25 and 100 mg kg(-1)garlic. At 24 h post-garlic infusion TXB(2)inhibition was reduced to 15% of the control and TXB(2)levels were comparable to that of the control values at 72 h pots-garlic infusion. Infusion of 100 mg kg(-1)onion extract did not elicit any inhibitory effect on TXB(2)synthesis in the serum of rabbit during the treatment period. The rapid recovery of platelet cyclooxygenase activity after infusion of a single dose of garlic suggests that garlic should be taken more frequently in order to achieve beneficial effects in the prevention of thrombosis.
Netherton syndrome (NS [MIM 256500]) is a rare and severe autosomal recessive disorder characterized by congenital ichthyosis, a specific hair-shaft defect (trichorrhexis invaginata), and atopic manifestations. Infants with this syndrome often fail to thrive; life-threatening complications result in high postnatal mortality. We report the assignment of the NS gene to chromosome 5q32, by linkage analysis and homozygosity mapping in 20 families affected with NS. Significant evidence for linkage (maximum multipoint LOD score 10.11) between markers D5S2017 and D5S413 was obtained, with no evidence for locus heterogeneity. Analysis of critical recombinants mapped the NS locus between markers D5S463 and D5S2013, within an <3.5-cM genetic interval. The NS locus is telomeric to the cytokine gene cluster in 5q31. The five known genes encoding casein kinase Ialpha, the alpha subunit of retinal rod cGMP phosphodiesterase, the regulator of mitotic-spindle assembly, adrenergic receptor beta2, and the diastrophic dysplasia sulfate-transporter gene, as well as the 38 expressed-sequence tags mapped within the critical region, are not obvious candidates. Our study is the first step toward the positional cloning of the NS gene. This finding promises a better understanding of the molecular mechanisms that control epidermal differentiation and immunity.
BACKGROUND: National legislation in Pakistan regulating blood banks has been introduced several times, but has never been passed. To support provincial-level efforts to develop legislation we conducted a study to evaluate blood-banking practices in Karachi, Pakistan, to identify areas that could be improved. METHODS: Thirty-seven blood banks were randomly selected from a list of 87 Karachi blood banks. The research team interviewed blood bank personnel, inspected available facilities and equipment, and observed blood collection using structured questionnaires and observation forms. RESULTS: Of the 37 selected facilities, 25 were operational and 24 agreed to participate. Twelve (50%) of the facilities reported regularly utilizing paid blood donors, while only six (25%) activity recruited volunteer donors. During observation only 8% of facilities asked donors about injecting drug use, and none asked donors any questions about high-risk sexual behaviour. While 95% of blood banks had appropriate equipment and reagents to screen for hepatitis B, only 55% could screen for HIV and 23% for hepatitis C. Twenty-nine percent of the facilities were storing blood products outside the WHO recommended temperature limits. IMPLICATIONS: Practices at most Karachi blood banks fell well below WHO standards. Findings from this study were instrumental in developing and passing legislation to regulate blood transfusion throughout Sindh Province, and suggest a method for improving blood transfusion practices in other developing countries.
Forty-three prenatal diagnoses of lethal urinary tract abnormalities were carried out during a five-year-period. The abnormalities were bilateral renal agenesis (56%), autosomal recessive polycystic kidney disease (16%), autosomal dominant polycystic kidney disease (14%), MECKEL-GRUBER syndrome and Prune-Belly syndrome (4%). The pregnancy was interrupted in thirty-five cases (81.4%).
OBJECTIVE: To see the etiology and prognostic factors related to mortality of patients with stroke. METHODS: Retrospective analysis of patients admitted with stroke in two hospitals of same locality over 8 years. RESULTS: Of the 12,454 cases admitted in medical units of hospital 796 (6.4%) had stroke. Majority of cases were between 4th and 6th decades of life. Fifty percent (304/606) were hypertensive, 19% (113/606) had cardiac disease and 18% (112/606) diabetes mellitus. Four percent (27/606) had previous history of stroke and 17% (102/606) were smokers. Of the 144 cases who had CT Scan 99 (69%) had infarct and 45 (31%) haemorrhage; overall mortality was 30% (288/971) and it was significantly high in cases over 60 years of age, cases with history of unconciousness at the onset and those with severe hypertension. Mortality rate in the community hospital was significantly higher (33%) as compared to private hospital (13%) (p 0.001). CONCLUSION: Cardiac disease is one of the precipitating factors of stroke with infarct being the major cause. Mortality increased with the advancement of age.
In rural Bangladesh, mothers were interviewed to identify factors that determine the use of oral rehydration therapy (ORT) for management of diarrhoea in children aged less than 5 years. The point prevalence of diarrhoea among 1,600 children was 11.6%, with 46% having acute watery diarrhoea. The overall ORT-use rate was 29%; only 17% of the cases used it adequately. Common reasons for not using ORS included misperception about diarrhoea and age of patients. Other reasons included incorrect assessments, severity, and difficulties with the administration of oral rehydration solutions. Promotion of ORT can be effected by improving the level of understanding of mothers with regard to assessment of severity, early initiation of treatment regardless of age, sex, type of diarrhoea, breast-feeding, and nutrition status.
OBJECTIVE: To see if Metformin Monotherapy affects glycemic control, serum lipid or lipoprotein levels in the treatment of type 2 diabetes who were poorly controlled with diet alone or despite maximal doses of (sulfonylurea) oral glucose lowering agents. DESIGN: A prospective, clinical intervention trial conducted between 1996-1997. SETTING: Two out patient diabetic clinics of Karachi. PATIENTS AND METHODS: A 12-week prospective clinical intervention trial. A total of 30 type 2 diabetic subjects were enrolled, of Whom 21 (12 men and 9 women) completed the study period. Their ages ranged between 35 and 70 years, (mean +/- SD 53.3 +/- 9.31) years, with a mean duration since diagnosis of diabetes was 4.5 +/- 2.3 years, body mass index (mean +/- SD) 26.8 +/- 3.53 kg/m2. They were previously treated with diet alone or had already been taking maximum doses of sulfonylurea monotherapy with suboptimal glycemic control, i.e., raised fasting blood glucose concentrations of 6-15 mmol/L or (108-270 mg/dL) on two occasions, with significant hyperglycemic symptoms. The patients were treated with metformin monotherapy with a follow up of 12 weeks. The initial dosage was 500 mg twice daily, and the dosage was increased to two or three tablets depending on the patient's metabolic changes. By comparing before and after 12 weeks therapy with metformin we assessed the importance of baseline parameters (glycemic control, serum lipid and lipoprotein concentrations, and measures of change in body weight and body mass index). RESULTS: Metformin therapy significantly decreased fasting blood glucose levels in all patients [(mean +/- SD) 227.2 +/- 37.5 to 168.6 +/- 20.5 mg/dl, p < 0.001)]. Serum total cholesterol decreased marginally [(mean +/- SD) 200.3 +/- 18.7 to 181.4 +/- 19.4 mg/dl, p < 0.01)]. Serum total triglycerides concentration also decreased [(mean +/- SD) 195.9 +/- 31.9 to 174.2 +/- 26.6 mg/dl, P < 0.01)]. Low-density lipoproteins declined [(mean +/- SD) 123.5 +/- 16.9 to 105.5 +/- 19.1 mg/dl, P < 0.01)], and very-low density lipoprotein cholesterol also decreased [(mean +/- SD) 39.2 +/- 6.4 to 34.8 +/- to 5.3 mg/dl, P < 0.01)]. Whereas, high-density lipoprotein cholesterol tended to increase [(mean +/- SD) 37.7 +/- 5.1 to 39.5 +/- 4.9 mg/dl, P < 0.01)], while no significant changes occurred in body weight and body mass index. CONCLUSION: Metformin treatment was effective, safe, and generally well tolerated.
OBJECTIVE: To assess the efficacy of acarbose monotherapy during 12-weeks treatment on the fasting glycemic level, lipid and lipoproteins profiles, in patients with type 2 diabetes mellitus. SETTING: Type 2 diabetics were selected from out patient department of Baqai Diabetes and Endocrine Centre, and one other diabetic clinic of Karachi, during 1996-97. DESIGN: A prospective intervention trial, and a 10 days screening period with a follow-up of 12 weeks. METHODS: Forty-four patients (36 men and 8 women, mean age 55.09 +/- 1.72 years) were included of whom 25 (56.81%) patients were previously treated with diet alone, 11(25%) with diet and glibenclamide, 5(11.36%) with diet and gliclazide, and 3(6.81%) with diet and chlorpropamide, more than at least 3 months known duration of diagnosed type 2 diabetes, body mass index (BMI) 23.69 +/- 0.49 kg/m2, were insufficiently controlled on diet alone, or diet plus sulfonylureas, were studied. The dosage of acarbose was started with 50 mg t.i.d with each meal, if necessary, was titrated upward on subsequent visits to 100 mg t.i.d with each meal, based on tolerability and efficacy. Fasting blood glucose, lipid and lipoprotein profiles were determined at the baseline and at the end of the study. RESULTS: Acarbose treatment was associated with significant reduction in fasting blood glucose from (mean +/- SE) 173.89 +/- 3.89 mg/dl at day 0 to 161.29 +/- 3.41 mg/dl at day 90 (P < 0.01). The serum total triglyceride level was (mean +/- SE) 188.85 +/- 5.91 mg/dl at entry, and was also significantly decreased to 158.57 +/- 4.48 mg/dl at day 90, this reduction was found statistically significant (P < 0.01). Whereas very-low density lipoprotein cholesterol reduced significantly from 33.08 +/- 1.09 mg/dl at day 0 to 31.02 +/- 0.95 mg/dl at day 90 (P < 0.01). Acarbose had no significant effect on serum total cholesterol, low-density lipoprotein cholesterol, and High-density lipoprotein cholesterol concentrations. Almost, all adverse experiences, as reported by patients on acarbose, were related to the digestive system and included diarrhea, flatulence, bloating and nausea. Most symptoms were of mild to moderate intensity and tended to improve with time. Overall, acarbose was well tolerated and the adverse experience profile was clinically acceptable. CONCLUSION: In type 2 diabetic patients, acarbose as monotherapy for 12 weeks resulted in beneficial effects on glycemic control, fasting blood glucose, mean serum total triglyceride and very-low density lipoprotein cholesterol decreased significantly. Perhaps attainment of normoglycemia on a long-term basis would result in more normal lipid and lipoprotein levels. Furthermore use of acarbose can be considered as a useful alternative in such type 2 patients, if they are difficult to control with diet alone or diet plus sulfonylureas (JPMA 50:152, 2000).
Phytochemical studies on the stem bark of Thevetia peruviana resulted in the isolation of six new ursane-type triterpenes, named peruvianursenyl acetate A, peruvianursenyl acetate B, isolupenyl acetate, peruvianursenyl acetate C, lupedienyl acetate and peruvianursenyl glucoside along with two known triterpenoids, namely alpha-amyrin acetate and lupeol acetate. The structures of the new phytoconstituents have been established as 23--nor methyl urs-12-en-4 alpha-ethylenic-18 alpha-H-3 beta-yl acetate, urs-5.21-dien-18 alpha-H-3 beta-yl acetate, lup-20 (29)-en-3 alpha-yl acetate, urs-12 en-18 alpha-H-3 beta-yl acetate, lup-5,20 (29)-dien-3 beta-yl acetate, and urs-12-en-18 alpha-H-3-O-beta-D-glucopyranoside, respectively.
We report herein for the first time the formation by freshly grown garlic roots and the structural characterization of 14,15-epoxide positional analogs of the hepoxilins formed via the 15-lipoxygenase-induced oxygenation of arachidonic acid. These compounds are formed through the combined actions of a 15(S)-lipoxygenase and a hydroperoxyeicosatetraenoic acid (HPETE) isomerase. The compounds were formed when either arachidonic acid or 15-HPETE were used as substrates. Both the "A"-type and the "B"-type products are formed although the B-type compounds are formed in greater relative quantities. Chiral phase high performance liquid chromatography analysis confirmed the formation of hepoxilins from 15(S)- but not 15(R)-HPETE, indicating high stereoselectivity of the isomerase. Additionally, the lipoxygenase was of the 15(S)-type as only 15(S)-hydroxyeicosatetraenoic acid was formed when arachidonic acid was used as substrate. The structures of the products were confirmed by gas chromatography-mass spectrometry of the methyl ester trimethylsilyl ether derivatives as well as after characteristic epoxide ring opening catalytically with hydrogen leading to dihydroxy products. That 15(S)-lipoxygenase activity is of functional importance in garlic was shown by the inhibition of root growth by BW 755C, a dual cyclooxygenase/lipoxygenase inhibitor and nordihydroguaiaretic acid, a lipoxygenase inhibitor. Additional biological studies were carried out with the purified intact 14(S), 15(S)-hepoxilins, which were investigated for hepoxilin-like actions in causing the release of intracellular calcium in human neutrophils. The 14,15-hepoxilins dose-dependently caused a rise in cytosolic calcium, but their actions were 5-10-fold less active than 11(S), 12(S)-hepoxilins derived from 12(S)-HPETE. These studies provide evidence that 15(S)-lipoxygenase is functionally important to normal root growth and that HPETE isomerization into the hepoxilin-like structure may be ubiquitous; the hepoxilin-evoked release of calcium in human neutrophils, which is receptor-mediated, is sensitive to the location within the molecule of the hydroxyepoxide functionality.
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