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Biomedical subjects

S Ahmed

Publications and source records attributed to S Ahmed.

At least 235 records · Page 13Linked to original sources
PubMed1999

A novel molecular modelling study of inhibitors of the 17alpha-hydroxylase component of the enzyme system 17alpha-hydroxylase/17,20-lyase (P-450(17alpha)).

The enzyme 17alpha-hydroxylase/17,20-lyase (P-450(17alpha) has recently become the focus of research into the fight against hormone dependent prostate cancer. However, the specific nature of this enzyme, in particular, the dual role of its active site, remains unknown. In our drive to elucidate further information regarding P-450(17alpha), and in light of our experience of other cytochrome P-450 enzymes, we chose to consider each part of this complex enzyme separately (i.e. the 17alpha-hydroxylase (17alpha-OHase) and the 17,20-lyase components). We therefore initiated a series of molecular modelling studies involving the construction of a 'substrate heme complex' for each of the two components. Here, we consider the construction and use of the complex for the 17alpha-OHase component of this enzyme. Using this approach, we have successfully considered: the binding of steroidal and non-steroidal reversible inhibitors: the structural features necessary for potent inhibition: and, rationalised the mode of action of a number of compounds whose inhibitory activity has not been previously explained, for example aminoglutethimide (an inhibitor of another related cytochrome P-450 enzyme, aromatase AR). The study concludes that the ability of the inhibitors of 17alpha-OHase to undergo polar polar interaction with the active site and for the compounds to closely mimic the substrate plane is a major factor in determining potency. Factors such as log P (log of the partition coefficient value for the distribution of a compound between octanol and water) would then appear to determine the extent of overall inhibitory activity. Overall, the study suggests that the novel substrate-heme complex approach has provided a good approximation of the 17alpha-OHase active site and has proved to be a useful tool in drug design and discovery.

Enzyme Inhibitors↗
PubMed1999

Preparation and characterization of poly (D,L-lactide-co-glycolide) microspheres for controlled release of poly(L-lysine) complexed plasmid DNA.

PURPOSE: To produce and characterize controlled release formulations of plasmid DNA (pDNA) loaded in poly (D,L-lactide-co-glycolide) (PLGA) microspheres both in free form and as a complex with poly (L-lysine). METHODS: Poly (L-lysine) (PLL) was used to form pDNA/PLL complexes with complexation ratio of 1:0.125 and 1:0.333 w/w to enhance the stability of pDNA during microsphere preparation and protect pDNA from nuclease attack. pDNA structure, particle size, zeta potential, drug loading, in vitro release properties, and protection from DNase I were studied. RESULTS: The microspheres were found to be spherical with average particle size of 3.1-3.5 microm. Drug loading of 0.6% was targeted. Incorporation efficiencies of 35.1% and 29.4-30.6% were obtained for pDNA and pDNA/PLL loaded microspheres respectively. Overall, pDNA release kinetics following the initial burst did not correlate with blank microsphere polymer degradation profile suggesting that pDNA release is convective diffusion controlled. The percentage of supercoiled pDNA in the pDNA and pDNA/PLL loaded microspheres was 16.6 % and 76.7-85.6% respectively. Unencapsulated pDNA and pDNA/PLL degraded completely within 30 minutes upon the addition of DNase I. Encapsulation of DNA/PLL in PLGA microspheres protected pDNA from enzymatic degradation. CONCLUSIONS: The results show that using a novel process, pDNA can be stabilized and encapsulated in PLGA microspheres to protect pDNA from enzymatic degradation.

Biocompatible Materials↗
PubMed1999

Outcome of transphenoidal surgery for acromegaly and its relationship to surgical experience.

BACKGROUND: A number of surgical series have been reported on the treatment of acromegaly and their results vary widely. The acceptable definition of remission has changed in recent years and it is known, though in a small series, that growth hormone levels of > 5 mU/l are still associated with an increased mortality from the condition. We have analysed data at this centre and examined the outcome of transphenoidal surgery for acromegaly, compared our results with recently published series from other centres and also assessed factors which might effect outcome including whether there is any demonstrable effect of the experience of the surgeon on outcome. PATIENTS AND METHODS: We have analysed data from all of our 139 patients in whom follow up data are available who have undergone initial transphenoidal surgery for acromegaly by one surgeon at this centre, between 1974 and 1995. Follow up was for a median of 5 years (range 1 month to 17 years). RESULTS: 67% of patients achieved the criterion for remission (mean GH < 5 mU/l). Success was related to tumour size and preoperative growth hormone values. Thus 91% of patients with microadenomas were in remission postoperatively compared to 46% of patients with macroadenomas. Analysis of the results according to the year of operation showed an improvement in success rates with time. More than 15 years ago, the success rate according to the growth hormone criteria set was 48% and the failure rate 52%. In contrast in the last 5 years analysed, the overall success rate was 74% with a failure rate of 26% (P < 0.04). The success rate for microadenomas was 50% initially, then remained 100%. The case mix was analysed and no change was found. We have also demonstrated an improvement in pituitary function (including normalization of preoperative elevated prolactin) with time so that pre 1981 16% of patients' pituitary function improved perioperatively but 10 years later this figure had risen to 34% (P < 0.03). There was no change over time in the development of pituitary hypofunction, complication rate or recurrence rate. CONCLUSION: Surgical treatment is a safe and effective treatment for acromegaly and remains the first choice of treatment for most acromegalic patients. The results of this centre compare favourably with series from other centres. We have demonstrated improved results, both in terms of post operative growth hormone values and pituitary function tests with time and increasing neurosurgical experience. We conclude that outcome for the surgical treatment for acromegaly is best achieved with one surgeon specialising in pituitary surgery. Improved operative outcome thus achieved has major cost implications and avoids the necessity for consideration of postoperative radiotherapy and the use of expensive growth hormone suppressing drugs in the postoperative period.

Acromegaly↗
PubMed1999

INS VNTR allelic variation and dynamic insulin secretion in healthy adult non-diabetic Caucasian subjects.

AIMS: To elucidate the relationship between the human insulin gene INS VNTR regulatory polymorphism and insulin secretion. The polymorphism arises from tandem repetition of 14-15 bp oligonucleotides. In Caucasians, repeat number varies from 26 to over 200, with two main and discrete allele size classes: class I (26-63 repeats) and class III (141-209 repeats). Class I allele homozygosity is associated with elevated risk of developing Type 1 diabetes, while the class III allele has been associated with increased risk of Type 2 diabetes, polycystic ovary syndrome (PCOS) and with larger size at birth, which may influence development of adult disease. METHODS: Thirty-one healthy adult subjects with normal glucose tolerance, underwent an intravenous glucose tolerance test with one minute sampling. Seventeen subjects were homozygous for class I alleles (14 excluding individuals carrying alleles associated with parent-of-origin effects and heterogeneity in allele transmission) and 14 homozygous for class III alleles. The groups were well matched. RESULTS: No significant differences in amount or rate of insulin secretion, or beta cell function were detected between the two groups. There was a difference in pattern of pulsatile insulin secretion with more 9-minute oscillations in class I homozygotes (P<0.026). The after-load glucose concentration was also higher in subjects with class I alleles (P<0.03). CONCLUSIONS: These results warrant further analysis of possible association between allelic variation of the INS VNTR and the pulsatility of insulin secretion.

Adult↗
PubMed1999

Experimental study on hemolysis in centrifugal blood pumps: improvement of flow visualization method.

To evaluate rotary blood pumps, flow visualization is commonly applied to determine the flow patterns in a centrifugal blood pump, which have a relationship to its hemolytic performance. However, it is very troublesome to visualize the flow near the vanes due to the high rotational speed of the impeller. The rotational speed of the impeller in a centrifugal blood pump is usually several hundred revolutions per minute. In this study, we combined a high-speed video camera based imaging method and an optical system in which the image of the rotating impeller was kept stationary. In the optical system, a prism rotating at half the speed of the impeller reflected the image of the impeller. The resultant reflected image was observed by a high-speed video camera through a half mirror. With this optical setup, the image through the half mirror became stationary, and the path of a specific tracer particle could be traced for a longer duration. A longer duration of measurements and better quality of the obtained images were realized through this improvement. Movement of a specific tracer from the inlet portion to the outlet portion of the impeller could be examined using the developed method.

Acrylic Resins↗
PubMed1999

Successful replantation of penile amputation (post-circumcision) complicated by prolonged ischaemia.

Circumcision is one of the most commonly performed surgical procedures. Whereas, in modern Saudi Arabia, the majority of circumcisions are performed in a hospital set-up, traditional ritual circumcisions are still performed in the community. We report a case of a 4-year-old boy with amputation of the penis after ritual circumcision. Replantation was successful despite an ischaemia time of 18 h.

Amputation, Traumatic↗
PubMed1999

Stability of poly(L-lysine)-complexed plasmid DNA during mechanical stress and DNase I treatment.

The aim of this study was to investigate the formation and stability of complexes between plasmid DNA (pDNA) and poly(L-lysine) (PLL). Formation of pDNA/PLL complexes with various ratios was determined by a fluorescence spectrophotometric method using fluorescamine. The effects of sonication, vortexing, and exposure to DNase I on the stability of free pDNA and pDNA/PLL complexes are discussed. A linear correlation between PLL added and PLL bound was obtained with overall reaction efficiency of 84.2-92.6%. Sonication degraded both free and PLL-complexed pDNA within 15 sec of vortexing. However, vortexing did not alter the stability of free and complexed pDNA. Dramatic increase in the protection of pDNA in pDNA/PLL complexes was observed in the DNase I digestion experiment; 68.1-89.0% of total pDNA in the pDNA/PLL complexes was protected from DNase I digestion compared to only 19.2% of total pDNA that remained undegraded after DNase I treatment of free pDNA. An increase in the PLL/pDNA ratio led to an increase in the protection of supercoiled pDNA; 15.5-38.2% of supercoiled pDNA pin PLL/pDNA complexes was protected after DNase I treatment. The results show that complexation of pDNA with PLL can stabilize the supercoiled structure of pDNA for the development of biodegradable microspheres as a delivery system for pDNA. Stability of pDNA/PLL complex can be monitored by PicoGreen dye and fluorescence densitometric assay methods.

DNA↗
PubMed1999

Infant feeding practices in rural Bangladesh: policy implications.

Although breastfeeding is almost universal in Bangladesh, proper breastfeeding is on the decline due to several factors. To assess the knowledge and practices of mothers regarding breastfeeding, data were collected from 2105 mothers during May-August 1996 in two rural areas of Bangladesh. The findings show that mothers' knowledge regarding proper breastfeeding is poor. Among all the women interviewed, only 12 per cent stated that the first food for newborns should be colostrum, and 27 per cent knew that exclusive breastfeeding should be given for at least 5 months. In practice, of the 1878 women who had live births, 10 per cent gave colostrum only, while the rest gave pre-lacteal feeds to their infants. Only 15 per cent of the infants were exclusively breastfed at 5 months of age. A significant relationship was found to exist between knowledge and practice of giving colostrum. Also, women between 20 and 24 years of age were more likely to give colostrum as well as to breastfeed exclusively for the first 5 months. Women who had their deliveries attended by medically trained personnel and those who already knew about the appropriate duration of exclusive breastfeeding were also more likely to practice exclusive breastfeeding for the first 5 months. The study suggests that steps should be taken to strengthen further the ongoing breastfeeding programme for improving breastfeeding knowledge and practice in rural Bangladesh.

Adult↗
PubMed1999

Endothelial cell growth factor enhances musculocutaneous flap survival through the process of neovascularization.

The effect of an angiogenic growth factor-endothelial cell growth factor (ECGF)-was tested in the rat transverse rectus abdominis musculocutaneous (TRAM) flap model based on a single inferior vascular pedicle. The animals were divided into three groups (N = 8 per group) after flap elevation. In group A (control), each animal received both local and local intra-arterial injections of 1 ml saline. In group B (local), each received a 2-mg ECGF local injection and 1-ml saline local intra-arterial injection. In group C (local intra-arterial), each received a 1-ml saline local injection and a 2-mg ECGF local intra-arterial injection. All animals were evaluated on postoperative day 7. There was a significant increase in the percentage of the skin paddle survival area of the TRAM flap in both ECGF-treated groups when compared with the control group (group B vs. group A, p < 0.001; group C vs. group A, p < 0.001). This correlated with a significant increase in vascularity in both ECGF-treated groups compared with the control group (group B vs. group A, p = 0.007; group C vs. group A, p = 0.021). The results between groups B and C were not significant. ECGF, when administered via either local or local intra-arterial route, enhances musculocutaneous flap survival through the process of neovascularization.

Analysis of Variance↗
PubMed1999

Glyceryl trinitrate, a nitric oxide donor, suppresses renal oxidant damage caused by potassium bromate.

Nitric oxide (NO) is a short-lived, readily diffusible intracellular messenger molecule associated with multiple organ-specific regulatory functions. Endogenous stimulation or exogenous administration of NO have been shown to inhibit production of reactive oxygen species (ROS) and expression of oxidant-mediated molecular or tissue injury. Potassium bromate (KBrO3) is one such potent renal oxidant that acts through generation of ROS-mediated lipid peroxidation, and causes increased ornithine decarboxylase activity, enhanced rate of DNA synthesis and depletion of the antioxidant armoury of the tissue. In this study, we elucidate the effect of exogenous NO administration, using the NO donor glyceryl trinitrate (GTN), on KBrO3-induced nephrotoxicity, oxidative stress and cell proliferation. KBrO3 administration at a dose of 125 mg/kg body weight results in significant (P < 0.001) depletion in renal glutathione (GSH) content, and glutathione reductase (GR) activity with a concomitant increase in microsomal lipid peroxidation, and blood urea nitrogen (BUN) and creatinine levels. Parallel to these changes, we found significant enhancement in ornithine decarboxylase (ODC) activity and rate of renal DNA synthesis. Subsequent administration of GTN resulted in dose-dependent amelioration of GSH content and GR activity with concomitant inhibition of lipid peroxidation, and BUN and creatinine levels. In addition, GTN administration to KBrO3-intoxicated rats resulted in significant dose-dependent down regulation of enhanced ODC activity and rate of [3H]-thymidine incorporation in renal DNA, providing support for the protective role of NO in attenuation of KBrO3-induced oxidative stress and cell proliferation. Enhancement of oxidative tissue injury and cell proliferation on administration of the NO inhibitor, L-NAME, further demonstrates the protective efficacy of endogenous NO. These data suggest that NO inhibits KBrO3-induced tissue injury, oxidative stress and proliferative response in the rat kidney.

Animals↗
PubMed1999

Ellagic acid ameliorates nickel induced biochemical alterations: diminution of oxidative stress.

Nickel, a major environmental pollutant is known for its clastogenic, toxic and carcinogenic potentials. The present investigation shows that ellagic acid proves to be exceptional in the amelioration of the nickel-induced biochemical alterations in serum, liver and kidney. Administration of nickel (250 micromol Ni/kg body wt) to female Wistar rats, resulted in increase in the reduced glutathione (GSH) content [kidney (*P<0.05) and liver (**P<0.001)] and Glutathione-S-transferase (GST) and glutathione reductase (GR) activities [kidney and liver, (**P<0.001)]. Ellagic acid treatment to the intoxicated rats leads to the formation of soluble ellagic acid-metal complex which facilitates excretion of nickel from the cell or tissue, thus ameliorating nickel-induced toxicity, as evident from the down regulation of GSH content, GST and GR activities with concomitant restoration of glutathione peroxidase (GPx) activity in liver and kidney. Our data shows that ellagic acid maintains cell membrane integrity through sequestration of metal ions from the extracellular fluid, as evident from the alleviated levels of serum glutamate oxaloacetate transaminase, (SGOT), serum glutamate pyruvate transaminase (SGPT) and lactate dehydrogenase (LDH) when compared to nickel treated group. Similarly, the enhanced blood urea nitrogen (BUN) and serum creatinine levels that are indicative of renal injury showed a reduction of about 45 and 40%, respectively. The data also show that treatment of ellagic acid after 30 min of nickel administration exhibits maximum inhibition in a dose-dependent manner. In summary, our data suggests that ellagic acid act as an effective chelating agent in suppressing nickel-induced renal and hepatic biochemical alterations.

Animals↗
PubMed1999

Management of reproductive tract infections in rural Bangladesh.

This study was undertaken to identify existing reproductive tract infection (RTI) treatment practices of the government family planning (FP) paramedics in rural Bangladesh. It also assessed the knowledge and perceptions of the clients about RTIs as well as the service-seeking behaviour of the clients and their husbands. Data on paramedic treatment practices were collected by observing paramedic-client interactions at the family welfare centres (FWCs) and satellite clinics (SCs). One hundred clients seeking RTI treatment were observed. The same clients were interviewed at departure from the health-care facility to assess their knowledge and perceptions about RTIs as well as service-seeking behaviour of the clients and their husbands. Twenty-four village practitioners were also interviewed to assess their knowledge on the subject. Results of the study showed that in the treatment of RTI, paramedics of government FP services commonly: (i) did not do a physical examination, (ii) used a substandard dosage of drugs, and (iii) made no attempt to notify or treat male partners. Thirty-one of the 97 clients reported that their husbands had some kind of genital problem. It was revealed from the study that as an alternative to the government FP services, the clients and their husbands often seek RTI treatment from the village practitioners though the village practitioners' knowledge concerning RTI is poor. Based on the findings of this study, it is recommended that the knowledge and skills of the paramedics and village practitioners for RTI treatment be strengthened. Prevention of RTI through awareness campaigns is essential for the control of RTIs, and especially of STDs.

Bangladesh↗