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Biomedical subjects

Z Mohamed

Publications and source records attributed to Z Mohamed.

16 recordsLinked to original sources
PubMed2006

The influence of CYP3A gene polymorphisms on cyclosporine dose requirement in renal allograft recipients.

Cyclosporine is a substrate of cytochrome P-450 3A (CYP3A) subfamily of enzymes and characterized by a narrow therapeutic range with wide interindividual variation in pharmacokinetics. A few single-nucleotide polymorphisms detected in CYP3A genes have been shown to correlate significantly with the CYP3A protein expression and activity. We therefore postulated that these polymorphisms could be responsible for some of the interindividual variation in cyclosporine pharmacokinetics. The objective of our study is to determine correlation if any between single-nucleotide polymorphisms of CYP3A5 and CYP3AP1 on cyclosporine dose requirement and concentration-to-dose ratio in renal allograft recipients. Cyclosporine-dependent renal allograft recipients were genotyped for CYP3A5 A6986G and CYP3AP1 G-44A. The cyclosporine dosages prescribed and the corresponding cyclosporine trough levels for each patient were recorded so that cyclosporine dose per weight (mg/kg/day) and concentration-to-dose ratio (C(0)/D, whereby C(0) is trough level and D is daily dose per weight) could be calculated. A total of 67 patients were recruited for our study. The dose requirement for 1, 3, and 6 months post-transplantation ranged 2.3-11.4, 1.0-9.0, and 1.4-7.2 mg/kg/day, respectively. Patients with *1*1*1*1 (n=5) CYP3A5- and CYP3AP1-linked genotypes needed higher dose of cyclosporine compared to patients with *1*3*1*3 (n = 27) and *3*3*3*3 (n = 33) linked genotypes in months 3 and 6 post-transplantation (P < 0.016). The identification of patients with *1*1*1*1 by CYP3A5 and CYP3AP1 genotyping may have a clinically significant and positive impact on patient outcome with reduced rejection rate by providing pretransplant pharmacogenetic information for optimization of cyclosporine A dosing.

Adult↗
PubMed2005

Alopecia areata treatment with a phototoxic dose of UVA and topical 8-methoxypsoralen.

Twenty-five patients with alopecia totalis (AT) or alopecia universalis and 124 patients with alopecia areata (AA) were treated with photochemotherapy, combining topical 8-methoxypsoralen (8-MOP) with UV irradiation of the scalp at a phototoxic dose. The mean energy required was 15 J/cm2 for AA and 42 J/cm2 for AT. Ninety-four patients had multiple bald patches and 12 with AT had complete or > 50% hair regrowth. Positive treatment results did not seem to depend on the age of onset or the duration of the disease. Few side-effects of topical psoralens plus UVA (PUVA) treatment were noted, except a for few days of slight erythema caused by the high dose of UV.

Administration, Topical↗
PubMed2004

Genetic polymorphism of cytochrome P450 2C19 in healthy Malaysian subjects.

AIMS: Impaired S-mephenytoin 4'-hydroxylation is a well-described genetic polymorphism affecting drug metabolism in humans. Although ethnic differences in its distribution of polymorphism has been described, it is not known whether there is an ethnic heterogeneity of the structure and expression of the CYP2C19 enzyme in the Malaysian population. METHODS: Study subjects were 142 healthy, unrelated Malaysians aged 18-29 years. Baseline omeprazole and 2-h postingestion omeprazole and 5'-hydroxyomeprazole concentrations were measured for CYP2C19 phenotype determination. Identification of CYP2C19 genotypes was performed with the use of polymerase chain reaction. RESULTS: Phenotyping of CYP2C19 revealed that the prevalence of poor metabolizers (PMs) in the Malaysian population was 14.1%, whereas prevalence of PMs in genotyping was 12.6%. The PM genotypic prevalence rate was 5.6% in Malays, 19.1% in Chinese and 10.0% in Indian subjects. There were significant differences in PM genotypic prevalence rates among the three primary ethnic groups (P < or = 0.05). CONCLUSIONS: Phenotyping and genotyping revealed significant differences in the prevalence rates among the three ethnic groups in Malaysia, with Chinese recording highest prevalence.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2003

Evidence of an interaction between nifedipine and nafcillin in humans.

AIMS: Nafcillin (Wyeth Laboratories, Philadelphia, PA, USA) has been reported to induce the metabolism of cyclosporin and warfarin, which are known substrates of cytochrome P-450 (CYP). However, there has not been any report to date on its possible interaction with nifedipine, an index substrate of the enzyme, CYP3A4. METHODS: Nine healthy normotensive subjects participated in this randomized placebo-controlled two-way crossover study examining the effects of 5 days' pretreatment of nafcillin 500 mg or placebo four times daily on the pharmacokinetics of an oral dose of nifedipine 10 mg. Plasma nifedipine concentrations were measured by gas chromatography-mass spectro. RESULTS: The area under the plasma nifedipine concentration-time curve (AUC0-alpha) in nafcillin-pretreated subjects (80.9 +/- 32.9 micro g l-1 h-1) was significantly decreased compared with subjects who received only nifedipine (216.4 +/- 93.2 micro g l-1 h-1) (P < 0.001). Total plasma clearance of nifedipine (CL/F) was significantly increased with nafcillin pretreatment (138.5 +/- 42.0 l h-1 vs 56.5 +/- 32.0 l h-1) (P < 0.002). CONCLUSIONS: The results show that nafcillin pretreatment markedly increased the clearance of nifedipine and suggest that nafcillin is a potent inducer of CYP enzyme.

Adult↗
PubMed1996

Linkage of a medium sized Scottish autosomal dominant retinitis pigmentosa family to chromosome 7q.

Retinitis pigmentosa is a group of hereditary retinopathies which is both clinically and genetically heterogeneous. Autosomal dominant (ADRP), autosomal recessive (ARRP), and X linked recessive (XLRP), as well as digenic forms of inheritance have been reported. ADRP has been linked to 3q, 6p, 7p, 7q, 8cen, 17p, 17q, and 19q. Three unrelated ADRP families have been reported to show linkage to 7q. We tested a Scottish ADRP family with microsatellite markers mapping within the 7q31-q35 region, and found three markers (D7S487, D7S514, D7S530) showing statistically significant evidence of linkage. A maximum two point lod score of 3.311 at 0% recombination was obtained for D7S514.

Adolescent↗
PubMed1993

Probing the functions of endogenous lectins: effects of a monoclonal antibody against the neural crest-stage lectin of Xenopus laevis on trunk development.

Trunk neural crest of Xenopus laevis has been confronted prior to migration with whole or fragments of a monoclonal antibody raised against the carbohydrate-binding site of the endogenous neural crest-stage galactoside binding lectin (Milos et al.: Anat. Embryol., 182:319-327 '90). External fin formation was inhibited in confronted regions but extensive internal matrix develops suggesting interiorization of fin tissue. In the regions of missing fin, the myotomes overgrew the neural tube and dorsal root ganglion neuronal numbers became more variable. Melanophore numbers in regions of missing fin did not change but a significantly greater proportion of the pigment cells localized on the muscle surface that had overgrown the neural tube suggesting that the pigment cell population redistributed itself to occupy a greater myotomal area.

Animals↗
PubMed1992

Caffeine as a probe for human cytochromes P450: validation using cDNA-expression, immunoinhibition and microsomal kinetic and inhibitor techniques.

The molecular basis for the use of caffeine (CA; 1,3,7-trimethylxanthine) as a probe for specific human cytochromes P450 has been investigated. The CA 1-, 3- and 7-demethylations (to form theobromine, paraxanthine and theophylline, respectively) all followed biphasic kinetics in human liver microsomes. Mean apparent Km values for the high- and low-affinity components of the demethylations ranged from 0.13-0.31 nM and 19.2-30.0 mM, respectively. cDNA-expressed CYP1A2 catalysed all three CA demethylations, and the apparent Km for CA 3-demethylation (the major metabolic pathway in humans) by the expressed enzyme was similar to the Km for the high-affinity liver microsomal CA 3-demethylase. IC50 values for inhibition of the CA demethylations by alpha-naphthoflavone were similar for both expressed CYP1A2 and the high-affinity microsomal demethylases. Moreover, CA was a competitive inhibitor of expressed CYP1A2 catalysed phenacetin O-deethylation, with the apparent Ki (0.080 mM) closely matching the apparent Km (0.082 mM) for CA 3-demethylation by the expressed enzyme. Expressed CYP1A1 was additionally shown to catalyse the 3-demethylation of CA, although activity was lower than that observed for CYP1A2. While these data indicate that CYP1A2 is responsible for the high-affinity component of human liver CA 3-demethylation, two limitations associated with the use of CA as an in vitro probe for CYP1A2 activity have been identified: (i) CA 3-demethylation reflects hepatic CYP1A2 activity only at appropriately low substrate concentrations; and (ii) CA is a non-specific CYP1A substrate and CYP1A1 may therefore contribute to CA 3-demethylase activity in tissues in which it is expressed. An anti-CYP3A antibody essentially abolished the 8-hydroxylation of CA to form trimethyluric acid, suggesting formation of this metabolite may potentially serve as a marker of CYP3A isozyme(s) activity.

Benzoflavones↗
PubMed1992

[Adrenal myelolipoma: a new case. Review].

We report a case of symptomatic myelolipoma with a good evolution at three and a half years' follow up. The clinical features and the diagnosis of this tumor type are discussed. In this case, as in most cases, CT proved to be the most useful in making the diagnosis. Like most of the cases, the patient was middle aged, obese and hypertensive. The etiology, pathogenesis, clinical features and diagnosis of this disease entity are reviewed. The treatment modalities utilized according to the specific features of each case are discussed.

Adrenal Gland Neoplasms↗
PubMed1991

[Current status of transcatheter arterial embolization in urology].

We report our experience of 155 transcatheter arterial embolization (TAE) procedures performed over a period spanning 12 months. The changes relative to the therapeutic approach in renal tumors are discussed. Palliative TAE has increased in comparison to presurgical TAE and the range of possibilities in benign renal pathological conditions has been extended (trauma, hemorrhage, hypertension, etc.). The morbidity ascribable to this technique continues to be low. New embolization materials (ethanol, fine particles, etc.) that are more effective and produce less side effects have become available. To date, TAE continues to be a highly effective therapeutic modality with specific indications and scant morbidity.

Catheterization↗
PubMed1990

Localization of endogenous galactoside-binding lectin during morphogenesis of Xenopus laevis.

A monoclonal antibody has been produced against Xenopus laevis galactoside-binding neural-crest-stage lectin. This antibody inhibits lectin-mediated hemagglutination. Using this antibody in conjunction with immunohistochemical techniques, lectin deposition has been studied in embryos and tadpoles at different stages of morphogenesis, from initial neural crest migration, up to the formation of a swimming tadpole. Lectin levels change during development in different regions of the embryo and tadpole, decreasing in migratory cells, and increasing in sites where cells become more adhesive to one another. The results suggest that galactoside-binding lectins may be an important class of cellular adhesion molecules during these stages of development.

Animals↗
PubMed1987

Role of antigen-presenting cells in the cytotoxic T-cell response to minor histocompatibility antigens (MIHA). I. In vitro function of cells pulsed with MIHA in vivo.

Although antigen-presenting cells (APC) appear to be able to process minor histocompatibility antigens (MIHA) expressed on allogeneic cells and present them in association with intrinsic H-2 of the APC in vivo, this does not occur in vitro. This could be due to fundamentally different mechanisms of antigen handling by APC in vitro, or it could represent compromised APC function. In order to distinguish these possibilities, we designed a system in which BALB/c spleen cells are transferred into an MIHA-disparate irradiated host and allowed to reside for 2-3 days; the spleen cells of the repopulated host are removed and used as stimulator cells for the CTL response of primed BALB/c responder cells to DBA/2 MIHA. These cells are referred to as in vivo-pulsed APC (IVP-APC). Donor BALB/c cells are able to pick up DBA/2 MIHA after a passage in DBA/2 hosts and efficiently present MIHA to primed CTL precursors to generate DBA/2-specific CTL. The donor cell type able to pick up and present MIHA is present in spleen but not thymus or bone marrow, is Thy-1.2 negative, Ia+, and nylon wool-adherent. Its stimulatory capacity is as efficient on a per cell basis as that of DBA/2 spleen cells. The generation of IVP-APC requires repopulation of the irradiated host, which must express MIHA foreign to the BALB/c donor cells. When we attempted to generate IVP-APC in H-2 incompatible hosts, we found that, although the IVP-APC could present H-2 antigens, they were unable to present MIHA in association with intrinsic APC H-2 antigens. Use of intra-H-2 recombinant strains as host mice indicated that compatibility of donor and host at the KI region of H-2 was essential for the generation of IVP-APC able to present apparently unprocessed MIHA to primed BALB/c responder cells. Thus, we were unable to reproduce the antigen-processing function of APC encountering antigen in situ using an adoptive transfer method of pulsing APC with MIHA in vivo. In addition, we suggest that our results may impose constraints on the formulation of models to account for the association of MIHA with H-2 antigens.

Animals↗
PubMedDate not supplied

[New permanent expandable prosthesis for the treatment of urethral stenosis].

The paper presents our initial experience in the treatment of urethral stenosis through implantation of a "Wallstent" self expanding resident prosthesis. A total of eleven prosthesis were placed in 10 patients with excellent results, from a clinical, urodynamic, radiological and endoscopic point of view, in 9 of them after 5 months. We believe that this kind of prosthesis can be a valid alternative to other established therapeutic options in the management of urethral stenosis. Long-term monitoring, however, will be necessary in order to corroborate the excellent results obtained in this short/medium-term observation.

Adult↗