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Biomedical subjects

M Ahmadi

Publications and source records attributed to M Ahmadi.

At least 19 recordsLinked to original sources
PubMed2006

Surgical approach to vascular complications of intravenous drug abuse.

OBJECTIVE: To assess the complications related to intravenous drug abuse. DESIGN: Prospective study. METHODS: Intravenous drug abusers (IVDAs) with vascular complications were assessed. RESULTS: Sixty-two patients presented with swelling and tenderness in the groin, and 3 patients with similar lesions in the cubital fossa. Infected pseudoaneurysms and deep vein thrombosis (DVTs) were diagnosed in 41 and 31 patients respectively (27 patients had both lesions). In patients with infected pseudoaneurysms, 9 patients underwent excision with early revascularization and 32 patients underwent ligation without revascularization. For all patients with femoral vein thrombosis ligation and excision was performed. 4 patients with pure DVTs were managed conservatively. Disabling claudication occurred in 6 patients. Four of them underwent late revascularization with an acceptable outcome. CONCLUSIONS: Ligation without revascularization is the appropriate treatment of infected pseudoaneurysms in IVDAs. Late revascularization is of great importance in patients with disabling claudication after treatment of addiction. Pure septic DVTs can be managed conservatively.

Aneurysm, False↗
PubMed2005

Application of the central composite design and response surface methodology to the advanced treatment of olive oil processing wastewater using Fenton's peroxidation.

The central composite design (CCD) technique was used to study the effect of the Fenton's peroxidation on the removal of organic pollutants from olive oil mill wastewater (OMW). The ratio of hydrogen peroxide-to-Fe(II) (x1) was between 1.67 and 8.33. Fe(II) concentration was constant at 0.03 M while the H2O2 concentration was set at three levels: 0.05, 0.15 and 0.25 M. Based on the molarity ratio, the selected ratio were in the low range of Fe(II)-to-H2O2 ratio (<<1). While based on the wt/wt ratio, the tested Fe(II)-to-H2O2 ratios were in the range of < or =1:5. pH (x2) was between 3 and 5. The concentration of OMW (x3) was varied between 40 and 100%. The influence of these three independent variables on the four dependent variables, i.e. COD, total phenolics (TP), color and aromaticity removal was evaluated using a second-order polynomial multiple regression model. Analysis of variance (ANOVA) showed a high coefficient of determination (R2) value of 0.902-0.998, thus ensuring a satisfactory adjustment of the second-order regression model with the experimental data. H2O2-to-Fe(II) ratio had significant effect on all the four dependent variables. The positive sign for the regression coefficient of this regressor variable indicated that the level of the pollutant removal increased with the increased levels of factor x1 from 1.67 to 8.33 and this effect was the most pronounced for TP removal. pH had also significant effect on the pollutant removal and the effect was the most noticeable for TP reduction. The negative coefficient of this variable (pH) indicated that level of the pollutant removal decreased as the pH increased from 3 to 5. The negative coefficient of the interaction between variable x1 and x2 indicated that a simultaneous increase in H2O2-to-Fe(II) ratio with decrease in the pH of the reaction led to an increase in the COD, TP and color removal. Quadratic models were predicted for the response variable, i.e. pollutant removal, and the maximum model-predicted removals were 56, 100, 33 and 32% for COD, TP, color and aromaticity, respectively. Optimum conditions for this wastewater treatment was obtained based on the performance of the Fenton's peroxidation in the experiment where the H2O2-to-Fe(II) ratio was at its high level (8.33) and the pH and OMW concentration were 4 and 70%, respectively.

Food-Processing Industry↗
PubMed2003

Role of S-layer protein antigenic diversity in the immune responses of sheep experimentally challenged with Campylobacter fetus subsp. fetus.

Surface layer proteins (SLPs) are essential for induction of abortion by Campylobacter fetus subsp. fetus in experimentally challenged ewes. These proteins are encoded by multiple sap genes and vary in size and antigenicity. The role of SLP antigenic variation during experimental ovine infection was investigated. Following subcutaneous challenge, the SLPs were highly antigenic, and antibodies were detected in serum, milk, bile, and urine. Fecal anti-SLP antibodies were detected only in animals challenged orally. Ewes challenged with wild-type strain 23D with variable SLPs developed detectable circulating anti-SLP immunoglobulin G (IgG) antibodies by 2 weeks postchallenge. In contrast, ewes challenged with mutants of 23D that had fixed expression of a single SLP developed antibodies within 1 week postchallenge, suggesting that antigenic variation in SLPs may delay the host antibody response. Although not statistically significant, the data from challenge experiments in which vaccinated ewes were used suggested that SLP-expressing vaccines could protect animals from abortion and that this effect was independent of the SLP expressed, indicating involvement of conserved epitopes in the SLP. The conserved 184-amino-acid N-terminal region of the SLP, identified from previously published sequences, was epitope mapped with rabbit anti-SLP antisera by using overlapping synthetic 20-mer peptides. Two putative epitopes were identified at amino acids 81 to 110 and 141 to 160. Amino acids 81 to 100 also bound serum IgG antibodies from experimentally challenged sheep. Conserved antigenic regions of the SLP that induce protective immune responses may enable development of synthetic vaccine candidates for C. fetus subsp. fetus-associated ovine abortion.

Abortion, Veterinary↗
PubMed2000

Effect of P450 isozyme-selective inhibitors on in-vitro metabolism of retinoic acid by rat hepatic microsomes.

Cytochrome P450-mediated 4-hydroxylation of retinoic acid is an important pathway in the termination of its biological action and the activity of certain P450 isozymes has been studied in non-induced male rat hepatic microsomes using isozyme-selective inhibitors. The importance of the activity of the isozyme to retinoic acid metabolism was, 2A6 (diethyl dithiocarbamate as selective inhibitor) > 1A1/1A2 (7,8-benzoflavone) >> 1A1 (ellipticine) > 3A4 (naringenin, ketoconazole) as shown by the respective apparent IC50 values of 0.12, 0.34, 2.7, 9.25 and 13.5 microM with 2C8-10, 2D6 and 2E1 having little effect on metabolism. It is concluded that although the P450 3A family normally constitutes half the total rat hepatic P450 activity, other hepatic isozymes (1A1, 1A2 and 2A6) are also involved in retinoic acid metabolism. This suggests that the horizons for the design of potential anticancer agents acting through inhibition of retinoic acid metabolism may be widened to include structures which do not resemble the established hetereocyclic base P450 3A4 inhibitors.

Animals↗
PubMed2000

In-vitro metabolism of retinoic acid by different tissues from male rats.

Significant differences between the metabolism of retinoic acid by different tissues might be an important determinant of the effectiveness of a systemically administered inhibitor at a particular tissue site. Here the metabolism of retinoic acid has been studied in microsomal fractions from different tissues (liver, kidney, intestinal mucosa, lung, skin, brain) of the male rat to determine their relative metabolic activity. Kinetic analysis revealed major differences between the activity of different tissue microsomes. This is shown by the Vmax values for the metabolism of retinoic acid-liver (102+/-39.0 pmol (mg protein)(-1) min(-1)) was 100 times more active than the lung (1+/-0.03 pmol (mg protein)(-1) min(-1)), which was the least active. The range of Km values for microsomes from the different tissues was narrow (0.48-1.40 microM). Taking into account the mass of the tissue, the gross activity ranking for metabolism of retinoic acid was liver >> skin = kidney > brain > intestinal mucosa >> lung. It is concluded that metabolism of administered retinoic acid occurs mainly in the liver but that cellular retinoic acid levels in some other tissues (skin, kidney, brain) could be reduced (metabolized) to such an extent that higher levels might be observed after the use of inhibitors of retinoic acid metabolism.

Animals↗
PubMed1998

Some 1-[(benzofuran-2-yl)methyl]imidazoles as inhibitors of 17 alpha-hydroxylase: 17, 20-lyase (P450 17) and their specificity patterns.

Four 1-[(benzofuran-2-yl)methyl]imidazoles (1-4) have been evaluated as in-vitro inhibitors of human testicular and bovine adrenal microsomal 17 alpha-hydroxylase: 17,20-lyase (P450 17) as potential anti-prostatic agents. Their specificity towards other steroidogenic and liver enzymes has been compared with that of ketoconazole. All four compounds were inhibitors of the testicular enzyme (2, IC50 (concentration resulting in 50% inhibition) 0.185 microM; 4, IC50 0.18 microM) but less potent than ketoconazole (IC50 0.03 microM). Towards bovine adrenal enzyme 2 and 4 were 35- and 31-fold more potent than ketoconazole (IC50 = 39.8 microM). Compound 2 is a useful lead compound but although less potent than ketoconazole towards P450SCC and P450 11 beta, but not P450C21, at the enhanced dose required for equivalent effects in-vivo on P450 17 it is likely that cortisol and aldosterone production will be affected to a greater extent than with ketoconazole.

Animals↗
PubMed1998

Enantioselectivity of some 1-(benzofuran-2-yl)-1-(1-H-imidazol-1-yl) alkanes as inhibitors of P450Arom.

The low stereospecificity of the enantiomers of 1-[(benzofuran-2-yl)-4-chlorophenylmethyl]imidazole (6, R=H, R'=4'-Cl) and the corresponding 4-fluoro compound as inhibitors of aromatase (P450Arom) has been explored using 1-(5,7-dichlorobenzofuran-2-yl)-1-(1H-imidaz-1-yl)ethane (7, R1=R2=Cl, R=CH3), -propane (7, R1=R2=Cl, R=C2H5), and the corresponding 5,7-dibromo compounds resolved as their dibenzoyl-D (or -L) tartrates. Low enantioselectivity ratios of 4.8 (5,7-diCl) and 12.6 (5,7-diBr) were shown for the ethanes. The values for the corresponding propanes were 8.3 and 5.2, respectively, and for these compounds the stereoselectivity was reversed.

Alkanes↗
PubMed1996

Synthesis and biological evaluation of 3-(prop-2-enyl)- and 3-(prop-2-ynyl)pyrrolidine-2,5-dione derivatives as potential aromatase inhibitors.

3-(4'-Aminophenyl)pyrrolidine-2,5-dione (WSP3), a known reversible inhibitor of P450 aromatase, was modified using molecular graphics and our model of reversible inhibitor and substrate binding to resemble 10 beta-prop-2-ynylestr-4-ene-3,17-dione (PED), a mechanism-based inactivator of the enzyme. The analogues prepared were 3-substituted 3-(prop-2-enyl) or 3-(prop-2-ynyl) pyrrolidine-2,5-diones and their N-alkyl derivatives. The reported compounds demonstrated no irreversible (time-dependent) inhibition of the human placental P450 aromatase enzyme. However, some reversible activity was seen in several of the 3-(prop-2-ynyl) compounds.

Aminoglutethimide↗
PubMed1996

A dapsone-induced blood dyscrasia in the mouse: evidence for the role of an active metabolite.

In the female mouse, dapsone (50-500 mg kg-1, p.o.) caused a dose-related methaemoglobinaemia which peaked at 0.5-1 h with recovery to baseline values occurring by 4 h. Cimetidine (100 mg kg-1, p.o.), a known inhibitor of several hepatic P450 isozymes administered 1 h before dapsone, prevented the methaemoglobinaemia. In-vitro, dapsone required activation by mouse hepatic microsomes to cause methaemoglobin formation in mouse erythrocytes and cytotoxicity to human mononuclear leucocytes. In both instances, the toxic effects were markedly reduced by cimetidine. Daily dosing of mice with dapsone (50 mg kg-1, p.o.) for 3 weeks induced a blood dyscrasia, characterized by a fall of platelet and white blood cell counts, which was inhibited by cimetidine (100 mg kg-1, p.o. daily). It is concluded that an active metabolite of dapsone arising from a P450-dependent pathway is involved in the genesis not only of the methaemoglobinaemia but also the blood dyscrasia arising from repeated administration of the drug in this species.

Animals↗
PubMed1995

The demand for graduate education in health services administration: a case study.

This article documents research into the demand for graduate education in health services administration/management with a case study model. Research included background information on the profession, the history of graduate education in health services administration, health care administrator demographics and their perceptions of the demand for graduate-prepared professionals and their own educational needs, most appropriate degree to offer, and curriculum content. The findings support the trend toward a balance between specific and general health care business skills in graduate education. Other schools may benefit from the student profile, program delivery, appropriate degree information, and curriculum content findings as well as the research instrument design and methodology when assessing and planning graduate programs in health services administration/management.

Curriculum↗
PubMed1995

Metabolism of beclamide after a single oral dose in man: quantitative studies.

A simple reverse phase HPLC assay is described for the determination of the anticonvulsant compound, beclamide and its 3- and 4-hydroxyphenyl metabolites in urine. Following oral administration of 1 g beclamide to a panel of healthy volunteers, less than 0.4% of the dose was excreted unchanged in the 24-h urine and unconjugated 3- and 4-hydroxyphenyl metabolites were not detected. Based on examination of the urine after incubation with beta-glucuronidase and aryl sulphatase, it was found that these hydroxyl metabolites were excreted as both glucuronide and sulphate conjugates. For each metabolite the glucuronide was the major excretory product (approximately 10:1). The 24-h excretion of the combined conjugated metabolites was 7% (for the 3-hydroxy metabolite) and 24% (for the 4-hydroxy metabolite) of the dose. Approximately 22% of the administered dose of beclamide was excreted as hippuric acid. In view of the simplicity of assay, beclamide may be a useful tool substance with which to examine factors influencing the xenobiotic metabolic pathways of benzene ring hydroxylation and glucuronide and sulphate conjugation in man.

Administration, Oral↗
PubMed1993

1-pentyl-3-(4-aminophenyl)pyrrolidine-2,5-dione, a selective aromatase inhibitor: in vivo studies.

1-Pentyl, 1-hexyl and 1-heptyl-3-(4-aminophenyl)pyrrolidine-2,5-dione, potent inhibitors of aromatase, lower oestrogen levels in PMSG-stimulated female rats in a comparable manner to the inhibitor aminoglutethimide (AG) used clinically for the treatment of breast cancer. Pharmacokinetic studies in the rat show t 1/2 values for the 1-hexyl compound and AG of 1.8 and 5.5 h respectively. In 4 tests for CNS-depressant activity the overall order of activity was AG > 1-heptyl = 1- hexyl >> 1-pentyl. The 1-pentyl compound has less tendency than AG to depress white cell and platelet counts in mice and overall is the drug candidate for further studies.

Aminoglutethimide↗
PubMed1992

Some 1-, and 3-substituted 3-(4'-aminophenyl)pyrrolidine-2,5-diones as selective inhibitors of aromatase.

1-Alkyl-3-(4'aminophenyl)pyrrolidine-2,5-diones (7,R = C3H7-C7H15) are potent inhibitors of aromatase in vitro, the 1-hexyl (Ki = 62nM) being about 100-fold more potent than aminoglutethimide (AG), and more selective in their ratio of aromatase:CSCC inhibitory potency. The 1-pentyl, 1-hexyl and 1-heptyl derivatives are more stable to liver microsomal metabolism in vitro than AG possibly due to inhibition of the liver cytochrome P450s. 1,3-Dialkyl-3(4'-aminophenyl)pyrrolidine-2,5-diones (9) have been synthesised by a novel method. Although the higher homologues (di-pentyl and di-hexyl) are more potent in vitro as inhibitors of aromatase than AG, they are less active than their 1-alkyl counterparts with the same alkyl substituent.

Adrenal Glands↗