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Biomedical subjects

I Khan

Publications and source records attributed to I Khan.

At least 55 records · Page 3Linked to original sources
PubMed2001

Selective suppression of renal Na+/H+ exchanger isoform-3 by prolonged stimulation of rats with adrenocorticotropic hormone.

Prolonged stimulation with adrenocorticotropic hormone (ACTH) causes hypertension and increases Na+ intake and urine output in humans and animals. However, its biochemical basis remains to be established. Since renal Na+/H+ exchanger isoforms (NHE) and the sodium pump play an important role in this condition, their levels were examined in rats stimulated with ACTH. Male Wistar rats received daily sc injection of ACTH (30 microg/100 g of body wt) for 4 d. Half of the ACTH-stressed rats were kept for four additional days without injection of ACTH (poststimulation). In a third group, the animals were treated with dexamethasone (50 microg/100 g of body wt) daily for 4 d. A fourth group consisted of unstressed control animals. Levels of NHE proteins were measured by Western blot analysis. Sodium pump activity was assessed by the level of ouabain-sensitive K-stimulated p-nitrophenylphosphatase activity (PNP) in the renal cortex. ACTH caused a selective decrease in NHE-3, but not of NHE-1 or alpha-actin levels. Interestingly, this ACTH-induced change was not duplicated in the animals treated with dexamethasone. Immunofluorescence data demonstrated that NHE-3 is located in the renal proximal tubules. PNP activity, on the contrary, was increased in both the ACTH-stimulated and dexamethasone-treated animals. More important, these changes in NHE-3 and PNP activity returned to the control level poststimulation. In conclusion, while PNP upregulation may be mediated by adrenocortical glucocorticoid, a role for glucocorticoids in the suppression of NHE-3 is less clear. These changes might impair renal tubular Na+ reabsorption and hence increase Na+ and water excretion in ACTH stimulation, thus acting as a counterbalance to normalize blood pressure in ACTH-stimulated animals.

4-Nitrophenylphosphatase↗
PubMed2001

Problem-based learning variant: transition phase for a large institution.

OBJECTIVE: To compare students' test scores and perceptions of problem-based learning (PBL) and lecture-based learning (LBL) by applying a PBL-variant. METHOD: For the transition from LBL to PBL, PBL was varied for one discipline only and for a large group of students. Two hundred forty nine second year medical students were taught a topic of Biochemistry by the LBL method and then 141 of these were taught another topic by the PBL-variant. At the conclusion of each topic an MCQ test was given. One week later a 9 item questionnaire was given to the 50 students now attending classes to assess their perceptions of the 2 teaching formats. The test scores of the two methods were compared. Students' ratings were differentiated by the Wilcoxon Signed-Rank test. RESULTS: There was no significant difference in the test scores by PBL or LBL, but PBL received significantly higher student ratings (p < 0.05) than LBL in self-study time, library time, number of books and computer consulted, enthusiasm for the topic, group discussion, depth of knowledge and interest taken in the teaching format. But there was no significant difference in students' ratings of the teacher's importance in either PBL or LBL. CONCLUSION: PBL variant and LBL produced similar MCQ test scores but the former is more conducive to enthusiastic self-study. Thus in the transition phase, PBL may be applied to one discipline and a large group of students without undermining its merits.

Biochemistry↗
PubMed2000

Sol-gel trapping of functional intermediates of hemoglobin: geminate and bimolecular recombination studies.

The encapsulation of proteins in porous sol-gels is a promising technique for generating, trapping, and probing functionally significant nonequilibrium protein species. An essential step needed in the pursuit of that goal is establishing the degree to which the sol-gel limits conformational change upon adding or removing substrates. In the present study, geminate recombination and solvent phase bimolecular recombination of CO to human adult hemoglobin (HbA) are used as sensitive probes of the degree of conformational constraint within the sol-gel. Two forms of CO saturated encapsulated HbA are generated. In one case, designated [COHbA], the equilibrium form of COHbA is directly encapsulated. In the second case, designated as [deoxyHbA] + CO, the equilibrium form of deoxyHbA is encapsulated and only after the sample has aged is CO introduced to the HbA through the porous sol-gel matrix. Three different preparative protocols are used to generate the sol-gels for each of the two forms of encapsulated COHbA. The kinetic traces obtained from these encapsulated samples allow for an easy evaluation of the extent to which the sol-gel is locking in the initial tertiary/quaternary structure. The results show that the sol-gel encapsulated samples can be used with pulsed laser sources and that one of the tested encapsulation protocols is far superior with respect to conformational locking. This protocol is used to trap and probe nonequilibrium forms such as the liganded T state of HbA, a species whose properties are needed to fully explore allostery in HbA.

Buffers↗
PubMed2000

Pindolol occupancy of 5-HT(1A) receptors measured in vivo using small animal positron emission tomography with carbon-11 labeled WAY 100635.

Positron emission tomography (PET), following an intravenous injection of [carbonyl-(11)C]WAY 100635, was used to image central 5-HT(1A) receptors in rat following pretreatment with graded doses of (-)-pindolol (0.001-3 mg/kg, i.v.). The use of PET had advantages over ex vivo radioligand binding methods in that it produced parametric image volumes and reduced errors due to inter-rat variability. Time-radioactivity curves from regions of interest (ROI) acquired from individual rats enabled the estimation of specific binding of the radioligand using a compartmental model with reference tissue input. Binding potential (BP) of [(11)C]WAY 100635 was estimated for frontal cortex and hippocampus (postsynaptic), and midbrain raphe nuclei (presynaptic). In the latter ROI, pindolol dose-dependently decreased BP. The saturation curve could be fitted to a single-site model up to the lowest dose of pindolol used, giving an ED(50) (dose to cause 50% occupancy) value of 0.26 +/- 0. 05 mg/kg, and inclusion of control (nonpindolol-treated) rats did not affect the fit. In contrast, in cortex and hippocampus ROI, low doses of pindolol caused an increase in BP compared with controls. Pindolol doses greater than approximately 0.1 mg/kg, resulted in a dose-dependent decrease in BP, and ED(50) values in cortex and hippocampus were estimated as 0.44 +/- 0.13 and 0.48 +/- 0.12 mg/kg, respectively. The increase in [(11)C]WAY 100635 binding at low pindolol doses is feasibly related to a decrease in basal receptor occupancy following reduced release of endogenous 5-HT. Considering the apparently greater potency of pindolol at the midbrain raphe ROI, this effect could be mediated via agonist activity at the autoreceptor.

Animals↗
PubMed2000

Evidence-based medicine and health economics: a case study of end stage renal disease.

This paper explores the potential for use of an economic evaluation framework alongside systematic reviews. Clinical issues in dialysis therapy for end stage renal disease are used as case studies. The effectiveness data required were obtained from a systematic review of randomized controlled trials. Resource use and cost data were obtained from three sources; the identified randomized controlled trials, a separate review of observational studies and primary data collection. The results of the case studies show that, although simple economic evaluations were possible, issues arose, such as how transferable results are between settings and how appropriate it is to focus on the average patient. The interface between economic evaluation and systematic reviews needs to be further developed in order to ensure that the best available evidence can be used to inform future policy and research.

Chi-Square Distribution↗
PubMed2000

SERCA pump isoform expression in endothelium of veins and arteries: every endothelium is not the same.

Endothelium from rat aorta expresses sarco/endoplasmic reticulum Ca2+(SERCA) pump gene SERCA3 where as the smooth muscle expresses SERCA2. This has led to the postulate that vascular endothelium expresses SERCA3. To test this postulate, we examined the SERCA2 and SERCA3 mRNA expression in endothelium and smooth muscle dissected from coronary artery, coronary vein, aorta and vena cava of pig. Smooth muscle from all arteries and veins expressed only the SERCA2 mRNA. Endothelium from coronary artery, coronary vein and aorta expressed both SERCA2 and SERCA3 mRNA but the endothelium from vena cava did not express SERCA3 mRNA although it expressed SERCA2. These observations support the postulate that vascular endothelium expresses SERCA3 but the affirmation is equivocal because vena cava endothelium does not express SERCA3.

Animals↗
PubMed2000

Blood pressure elevations in riluzole-treated patients with amyotrophic lateral sclerosis.

OBJECTIVE: To determine whether riluzole is associated with blood pressure elevations in patients with amyotrophic lateral sclerosis (ALS). BACKGROUND: Though previously reported, hypertension is not considered a frequent adverse effect of riluzole. METHODS: We reviewed data from 35 consecutive ALS patients on riluzole, and 88 randomly selected controls without and 20 patients with ALS who were not on riluzole. RESULTS: A significantly greater number of ALS patients on riluzole had blood pressure elevations (28 of 35 patients) compared to controls (26 of 88, p<0.001; 8 of 20, p = 0. 007). Median systolic and diastolic blood pressures were both significantly higher in riluzole-treated (140/86 mm Hg) than in control patients without ALS (120/70 mm Hg, p<0.001). Systolic, but not diastolic, blood pressures were significantly higher in riluzole-treated patients than in controls with ALS (126 mm Hg, p = 0.002). CONCLUSIONS: Riluzole treatment may be associated with mild blood pressure elevations. Future prospective trials of riluzole should closely assess hypertension.

Adult↗
PubMed2000

Vitamin A deficiency in mice enhances the colonic level of purine enzyme activity.

BACKGROUND: Vitamin A is an important nutritional factor that regulates normal growth and functions of epithelial cells of the gastrointestinal tract. OBJECTIVE: The objective of this study was to examine the role of vitamin A on the histological and biochemical changes in the colon of mice. METHODS: To address this issue, vitamin A deficiency (VAD) was developed in mice by placing them on a VAD diet from weaning up to 120-170 days. Infiltration of inflammatory cells in the colon was determined histologically. Activities of adenosine deaminase, adenylate deaminase, purine nucleoside phosphorylase and myeloperoxidase were determined. RESULTS: VAD in mice induced a significant increase in the number of mast cells per 100 crypts. There was also an abundance of other connective tissue cells such as plasma cells, lymphocytes and neutrophils around the crypts in the lamina propria. The colonic activity of adenosine deaminase and adenylate deaminase was increased due to VAD, whereas purine nucleoside phosphorylase activity remained unchanged. Immunohistochemical analysis showed an increased expression of adenosine deaminase in VAD mice colon. The increase in myeloperoxidase activity was not statistically significant. CONCLUSIONS: VAD causes upregulation of purine enzyme, which together with an increased number of inflammatory cells might exacerbate colonic injuries in VAD condition.

AMP Deaminase↗
PubMed2000

A complication in anticoagulation using low-molecular weight heparin in a patient with a mechanical valve prosthesis. A case report.

All mechanical heart valves are thrombogenic, and are associated with thromboembolic complications becomes ineffective. when anticoagulation Controversy exists with regard to the appropriate and safe anticoagulation regimen of gravid women with mechanical heart valve prostheses. While oral anticoagulants such as warfarin may be associated with fetal complications, the role of low-molecular weight heparin (LMWH) and heparinoids (and their respective appropriate dosage) have still to be determined. In developing countries such as Saudi Arabia, the prevalence of rheumatic fever is high, as is the percentage of female patients with mechanical heart valves and who are of child-bearing age. Thus, the issue of adequate anticoagulation on one hand, and avoidance of warfarin-induced embryopathy on the other hand, is crucial. To date, few reports are available of LMWH as sole anticoagulant in patients with mechanical heart valves. We report a case of massive valve thrombosis with subsequent pulmonary edema after warfarin anticoagulation was changed to LMWH during pregnancy, and administered at too low a dose.

Adult↗
PubMed1999

Temperature dependent quaternary state relaxation in sol-gel encapsulated hemoglobin.

Samples of human adult hemoglobin (HbA) encapsulated in a wet porous sol-gel are prepared under aerobic and anaerobic conditions. Resonance Raman spectroscopy is used to compare equilibrium deoxyHbA to the nonequilibrium deoxy species generated by deoxygenating an encapsulated oxyHbA sample. The spectra of the deoxygenated samples as a function of delay subsequent to deoxygenation reveal a marked slow down by the gel of the two phases of relaxation: the tertiary relaxation associated with the transition from the liganded R to deoxy R conformations and the quaternary relaxation associated with the deoxy R to deoxy T transition. The temperature dependence (4-80 degrees C) of the relaxation indicates that the internal viscosity of the gel is greatly enhanced at the lower temperatures. At 80 degrees C the tertiary and quaternary relaxations occur over minutes to hours, respectively, whereas at 4 degrees C both relaxations are essentially frozen. These results demonstrate the impressive potential of using sol-gel encapsulation as a means of studying substrate binding induced conformational changes in proteins.

Gels↗
PubMed1999

An automated radiosynthesis of 2-[11C]thymidine using anhydrous [11C]urea derived from [11C]phosgene.

2-[11C]Thymidine has been produced from [11C]methane via [11C]phosgene and [11C]urea. Anhydrous [11C]urea was prepared from [11C]phosgene by reaction with liquid ammonia. This novel approach avoids the problems associated with the synthesis of anhydrous [11C]urea from [11C]cyanide. A fully automated system based on a modular approach and under PLC control has been developed. The system provides 2-[11C]thymidine reliably and reproducibly for clinical PET studies. The radiosynthesis takes 45-50 min from [11C]methane and the average yield was 1.5-3.3 GBq (40-90 mCi). The specific radioactivity was typically in the range 29.6-51.8 GBq mumol-1 (0.8-1.4 Ci mumol-1) at EOS corresponding to 6-12 micrograms of stable thymidine. The radiochemical yield of 2-[11C]thymidine was ca. 14% from [11C]methane.

Carbon Radioisotopes↗
PubMed1999

Studies on purine enzymes in experimental colitis.

Although the role of adenosine deaminase (ADA), adenylate deaminase (AMP-DA), purine nucleoside phosphorylase (PNP) is well documented in gastric and intestinal carcinoma, their role in inflammatory bowel diseases remains unknown. In the present study, we investigated the profile of these enzymes in blood and intestinal tissues during colitis. Colitis induced in Wistar rats by acetic acid was monitored by a marker enzyme myeloperoxidase (MPO). The tissue levels of MPO increased on 1, 2, 5 and 6 days post-administration (PA) of acetic acid and declined to the control levels by day 7 PA. In parallel the blood levels of ADA and AMP-DA decreased on days 1, 2 and 5 without any significant change on days 6 and 7 PA. Similar observations were recorded for these enzymes in the cytosolic extracts of colonic tissue specimens. In contrast, PNP remained unaltered in both blood and tissue samples. These findings suggest an inverse-relationship between inflammation and purine deaminases in both blood and tissues.

AMP Deaminase↗
PubMed1999

Altered expression of the Na+/H+ exchanger isoform-3 in experimental colitis: effect of garlic.

The sodium-hydrogen exchanger isoform, NHE-3 is essential for the absorption of sodium and water from intestine. Whether this protein plays any role in inflammatory bowel disease is less understood. To address this issue, NHE-3 mRNA and protein levels were estimated in the terminal ileum and colon of the rats having colitis induced with trinitrobenzenesulphonic acid (TNBS). The effect of garlic (Allium sativum) was also evaluated on the expression of NHE-3. The animals were treated with garlic extract intraperitoneally starting 2 h before the TNBS administration until day 4 post-TNBS administration and were sacrificed on day 5. In control animals, the levels of NHE-3 in colon was higher than the ileum. As a result of colitis, the levels of NHE-3 protein and mRNA increased both in the colon and terminal ileum. Garlic treatment of the colitic animals resulted in a selective suppression of NHE-3 in the terminal ileum. Colitis caused an induction of the myeloperoxidase activity, the marker of inflammation in the colon but not in the ileum. These findings suggest that induction of NHE-3 is not primarily due to inflammation. Selective suppression of this protein in ileum by garlic may cause loss of sodium chloride and water during colitis.

Animals↗
PubMed1999

Molecular basis of altered contractility in experimental colitis: expression of L-type calcium channel.

Colitis in experimental animals or idiopathic inflammatory bowel disease, such as ulcerative colitis or Crohn's disease in humans, is associated with reduced muscle contraction. This is predicted to be due to disturbance of Ca2+ homeostasis in the inflamed muscle cell. However, the underlying molecular mechanism remains to be elucidated. Since the catalytic alpha-1 subunit of the L-type Ca2+ channel regulates Ca2+ influx, levels of the alpha-1 mRNA and protein were examined. Colitis induced by intrarectal administration of trinitrobenzenesulfonic acid was monitored by measuring the myeloperoxidase activity and histology. The levels of mRNA and protein were estimated using RT-PCR and immunoblotting. Myeloperoxidase activity increased in the inflamed colon, and the lamina propria and muscle layers showed infiltration of inflammatory cells and loss of crypts. Two alternatively spliced alpha-1 mRNA isoforms were detected in the colonic muscle. The ratio of unspliced to spliced mRNA isoforms remained unaltered in inflamed muscle. In contrast, the level of corresponding protein isozymes decreased in the colitic animals. Thus colitis-induced reduction in the alpha-1 protein may account for the reduced colonic contractility seen in colitis.

Animals↗
PubMed1999

Seizure disorders in people with intellectual disability: an analysis of differences in social functioning, adaptive functioning and maladaptive behaviours.

The present study is an investigation into the effects of seizure disorders/epilepsy on psychopathology, social functioning, adaptive functioning and maladaptive behaviours using a sample of 353 people diagnosed with a seizure disorder, and either severe or profound intellectual disability. People with a diagnosis of seizure disorder were found to have significantly less social and adaptive skills when compared to developmentally disabled controls with no seizure disorder diagnosis. Additionally, patterns of maladaptive behaviours were identified for individuals with seizure disorders and found to be similar to those found in people without seizure activity. The implications of the present findings are discussed.

Activities of Daily Living↗
PubMed1999

Expression of the Na(+)-H+ exchanger isoform-1 and cyclooxygenases in human placentas: their implications in preeclampsia.

The sodium hydrogen exchanger isoform, NHE-1 plays an important role in electrolyte and water homeostasis. These functions are compromised in pregnancies complicated with preeclampsia. At present it is not known whether NHE-1 expression is altered during preeclampsia. In the present study the placental level of NHE-1 protein was measured using immunoblotting. Since prostaglandins regulate the secretory and absorptive functions, the levels of prostaglandin E-2 as well as the expression of cyclooxygenase-1 and -2 were also estimated. The amount of NHE-1 protein and cyclooxygenase-2 was reduced in preeclamptic placentas, whereas the level of cyclooxygenase-1 remained unaltered. In contrast, prostaglandin E-2 concentration was higher in preeclampsia. Suppression of NHE-1 might render the placenta with impaired uptake of water and electrolytes and therefore may be involved in the pathogenesis of preeclampsia. While prostaglandin E-2 may play a role in preeclampsia, these findings discount the induction of cyclooxygenase-genes for this increase.

Adult↗
PubMed1999

Prostaglandin F(2alpha) induces a rapid decline in progesterone production and steroidogenic acute regulatory protein expression in isolated rat corpus luteum without altering messenger ribonucleic acid expression.

With interest in steroidogenic acute regulatory protein (StAR) involvement in the luteolytic process, we studied changes in serum progesterone levels and the concomitant expression of StAR mRNA and protein (37-, 32-, and 30-kDa forms) in postovulatory Day 7 corpora lutea (CL) isolated from rats 1 h after injection with prostaglandin F(2alpha) (PGF(2alpha), n = 6) or saline (n = 6). Serum progesterone levels were determined by RIA, StAR and beta-actin mRNA expression by Northern analysis, and StAR and beta-actin protein expression by Western analysis. Adrenal, brain, and spleen from control animals were used as positive and negative controls for StAR expression. Scanning optical densitometry measurements were standardized by dividing the signal strength from each StAR autoradiogram lane by that from the corresponding beta-actin autoradiogram lane. ANOVA was used for significance testing, with alpha set at 0.05. The 37-, 32-, and 30-kDa forms of StAR protein were expressed in all adrenal samples, whereas only the 37- and 30-kDa forms were found in CL. Serum progesterone levels and expression of the 30-kDa and 37-kDa forms of the StAR protein in CL were all found to be significantly lower in the PGF(2alpha)-treated than the saline-treated group. StAR mRNA expression was not significantly different in the saline- and PGF(2alpha)-treated rats. The rapid decline in StAR protein expression that accompanies PGF(2alpha) induced luteolysis, therefore, does not result from significant decline in mRNA expression.

Actins↗