CYP2C19 polymorphism affects single-dose pharmacokinetics of oral pantoprazole in healthy volunteers.

Objectives: Pantoprazole is metabolized by cytochrome P450 2 C19, which shows genetic polymorphism. The effect of CYP2C19 polymorphism on single-dose pharmacokinetics of oral pantoprazole in healthy volunteers was evaluated.

Methods: Pantoprazole pharmacokinetics was determined in 32 healthy volunteers after a 40-mg single oral dose of the drug.

Effect of the ADRB1 1165C>G and 145A>G polymorphisms on hemodynamic response during dobutamine stress echocardiography.

Purpose: The aim of this study was to determine an association between the ADRB1 1165C>G and 145A>G polymorphisms and hemodynamic response [heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure] to dobutamine during dobutamine stress echocardiography (DSE).

Methods: The study involved 144 patients with clinical indications for DSE. The PCR-restriction fragment length polymorphism method was used to identify the ADRB1 1165C>G and 145A>G polymorphisms.

The SLC19A1 80G>A polymorphism is not associated with male infertility.

Previous studies have revealed that genetic factors may be involved in regulating folate turnover, e.g. methylenetetrahydrofolate reductase polymorphism in the development of male infertility.

Association of the MDR1 (ABCB1) gene 3435C>T polymorphism with male infertility.

Infertility is a common problem affecting one in six couples, and in 30% of infertile couples, the male factor is a major cause due to defective sperm quality. P-glycoprotein (P-gp), a product of the MDR1 (ABCB1) gene, may be a link between genetic and environmental factors contributing to the development of male infertility because pesticides (P-gp substrates) are well established factors of male infertility. The aim of the present study was to examine the effect of the MDR1 gene 3435C>T polymorphism on male infertility.

Association of calpain-10 gene polymorphism and posttransplant diabetes mellitus in kidney transplant patients medicated with tacrolimus.

New-onset, posttransplant diabetes mellitus (PTDM) has a high incidence after kidney transplantation in patients medicated with tacrolimus, and may adversely affect the patient and graft survival. The pathophysiology of PTDM closely mimics that of type II diabetes mellitus (T2DM). One of possible genetic factors predisposing to PTDM might be polymorphism in calpain-10 gene (CAPN10), previously associated with increased risk of T2DM in general population.

The effect of 677C>T and 1298A>C MTHFR polymorphisms on sulfasalazine treatment outcome in rheumatoid arthritis.

Despite the availability of several new agents for the treatment of rheumatoid arthritis (RA), sulfasalazine remains the mainstay because of both cost and experience with its use. Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and several polymorphisms have been described in the MTHFR gene. Of these, the 677C>T and 1298A>C polymorphisms have been associated with altered enzyme activity.

677C > T and 1298A > C MTHFR polymorphisms affect arechin treatment outcome in rheumatoid arthritis.

Despite the availability of several new agents for the treatment of rheumatoid arthritis (RA), arechin (hydroxychloroquine) remains the mainstay because of both cost-effectiveness and experience with its use. However, there is considerable variation in response to this drug, with toxicity limiting treatment in some patients. Methylenetetrahydrofolate reductase (MTHFR) is involved in the folate metabolism and has been shown to be polymorphic what affects the enzyme activity.

Effect of ABCB1 (MDR1) 3435C >T and 2677G >A,T polymorphisms and P-glycoprotein inhibitors on salivary digoxin secretion in congestive heart failure patients.

The aim of the present study was to evaluate the effects of ABCB1 ( MDR1 ) gene polymorphism on P-glycoprotein model substrate, i.e. digoxin, salivary secretion.

Impact of ABCB1 (MDR1) gene polymorphism and P-glycoprotein inhibitors on digoxin serum concentration in congestive heart failure patients.

Digoxin, a drug of narrow therapeutic index, is a substrate for common transmembrane transporter, P-glycoprotein, encoded by ABCB1 ( MDR1 ) gene. It has been suggested that ABCB1 polymorphism, as well as co-administration of P-glycoprotein inhibitors, may influence digoxin bioavailability. The aim of the present study was to evaluate the effects of ABCB1 gene polymorphism and P-gp inhibitor co-administration on steady-state digoxin serum concentration in congestive heart failure patients.

Reduced folate carrier-1 80G>A polymorphism affects methotrexate treatment outcome in rheumatoid arthritis.

The folate antagonist methotrexate (MTX) is a drug currently used in the treatment of rheumatoid arthritis (RA). MTX enters the cells through the reduced folate carrier (RFC-1) and is activated to polyglutamates. Previous studies have shown that RFC-1 expression may influence the efficacy of therapy with MTX.

The effect of 3435C>T MDR1 gene polymorphism on rheumatoid arthritis treatment with disease-modifying antirheumatic drugs.

Objective: Rheumatoid arthritis (RA) is a multifactorial disease, with immunological, genetical as well as environmental factors being implicated in its pathogenesis. Treatment of RA is based mainly on drugs modulating the course of the disease, e.g.

[The influence of IL-6 polymorphism on efficacy of treatment of rheumatoid arthritis patients with methotrexate and prednisone].

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which cytokines play an important role. The therapy of RA is associated with application of the drugs modulating the immune response via inhibiting the cytokine production. The common drugs used in RA therapy are methotrexate and prednisone.

Frequency of common MDR1 gene variants in a Polish population.

P-glycoprotein (P-gp) is a transmembrane transporter playing an important role in drug efflux. There is growing evidence that P-gp activity may be related to haplotypes of MDR1 gene. In the current study, the frequencies of common functional polymorphisms in MDR1 gene (2677G > A,T and 3435C > T) were evaluated using PCR-RFLP and allele-specific amplification, in a group of 204 healthy individuals of Caucasian origin from Poland.

Acetylation genotype and phenotype in patients with systemic lupus erythematosus.

Unlabelled: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting various tissues and organs. In the studies on SLE etiopathogenesis, a potential role of genetically determined impairment of xenobiotic metabolism has been emphasized. N-acetyltransferase 2 enzyme (NAT2) exhibits gene polymorphism and the acetylation rate with NAT2 involvement varies from person to person.

Polymorphism in the P-glycoprotein drug transporter MDR1 gene in colon cancer patients.

Objective: The P-glycoprotein, a product of MDR1 (multiple drug resistance 1) gene, is a membrane efflux pump localized in epithelial cells in the small and large intestine, a part of the gastrointestinal barrier that protects cells against xenobiotics from our diet, bacterial toxins, drugs and other biologically active compounds, possibly carcinogens. In the present study, an association of MDR1 gene polymorphism and the occurrence of colon cancer were evaluated.

Methods: The study population consisted of 184 unrelated sporadic colon cancer patients and 188 healthy unrelated controls.

MDR1 gene polymorphism in allogeenic kidney transplant patients with tremor.

P-glycoprotein (P-gp), an ATP-dependent efflux pump, is a membrane protein encoded by MDR1 gene, which demonstrates functional polymorphism. It is present in endothelial cells of the blood-brain barrier. P-gp pays a role in transmembrane transport of various xenobiotics, thus limiting their accumulation in the central nervous system.

Lack of association between arylamine N-acetyltransferase 2 (NAT2) polymorphism and systemic sclerosis.

Objectives: It has been shown that exposure to some environmental toxins may induce scleroderma-like illness in predisposed individuals, but the etiopathogenesis of the idiopathic form of systemic sclerosis (SSc) remains obscure. The genetic background of this illness has been confirmed in multiple studies. We investigated whether patients with SSc differ from healthy subjects with regard to the enzymatic activity of polymorphic N-acetyltransferase 2 (NAT2).

[Evaluation of methotrexate levels in biological fluids released from bone cement filling].

The authors present an analysis of methotrexate concentration in blood, urine and drainage liquid (both deep and superficial), as well as the results of biochemical analysis of blood and urine in a population of 42 patients treated surgically because of pathologic fractures of long bones. In 8 of the 42 patients chemotherapy was applied 14 days before the surgical procedure. Lithic lesions in the long bones were filled with cement with 2 g of methotrexate and further stabilisation was achieved by applying metal implants.

Genotype of N-acetyltransferase 2 (NAT2) polymorphism in children with immunoglobulin E-mediated food allergy.

We investigated whether patients with immunoglobulin E-mediated food allergy differed from healthy individuals with regard to genotype of the polymorphic enzyme N -acetyltransferase 2 (NAT2). The genetic polymorphism of acetylation can alter the toxic and therapeutic response to certain xenobiotics and may be also a factor that influences the susceptibility toward certain partly chemically induced diseases. We compared 136 children with immunoglobulin E-mediated food allergy with 123 healthy children.

[Effect of therapeutic drug monitoring of amitriptyline and genotyping on efficacy and safety of depression therapy].

Modern pharmacotherapy is based on precise adjustment of a dosage schedule to individual requirements of patient. Therapeutic drug monitoring is a method that allows for a more effective treatment approach, especially in the case of a narrow therapeutic index of a drug. Tricyclic antidepressant drugs are characterised by narrow therapeutic index as well as relationship between serum drug concentration and side effects.

CYP2D6 and GSTM1 genotypes in a Polish population.

Objective: The aim of the present study was to investigate the distribution of the CYP2D6 and GSTM1 genotypes in a Polish population.

Methods: One hundred and forty-five unrelated healthy individuals from the western region of Poland were studied. The CYP2D6 genotype was analysed by means of polymerase chain reaction (PCR) amplification for the CYP2D6*3 and CYP2D6*4 alleles.

N-acetylation and hydroxylation polymorphisms in type II diabetics with microvascular disturbances.

The N-acetylation and hydroxylation (CYP2D6) genetic polymorphisms were assessed in 43 healthy subjects and in 84 type II (non-insulin-dependent) diabetics. The proportions of slow and fast acetylators as well as poor and extensive metabolisers in a group of diabetics suffering from microvascular disturbances (nephropathy, retinopathy and neuropathy) were compared with the control group and with diabetics without such complications. Sulphadimidine was used as a probe for polymorphic acetylation and debrisoquine for CYP2D6.

Comparative pharmacokinetics of theophylline in rabbits and in humans with hyperlipidemia.

Unlabelled: The study was carried out on male rabbits divided into two groups: a control and an experimental one, fed on a high-fat diet. Humans were also ascribed into two groups: control and those affected with primary, mixed form of hyperlipidemia. The animals and humans were given theophylline intravenously as a single dose.

[Comparative pharmacokinetics of theophylline in hyperlipidemia in animals and humans].

The incidence of hereditary hyperlipidemia amounts to about 8% and rises when secondary causes of lipid metabolism disturbances are taken into consideration. In contemporary literature there is paucity of data on the influence of hyperlipidemia on pharmacokinetics of drugs. That is especially important in the case of drugs characterized by a narrow therapeutic index, such as theophylline, which can be administered to patients affected by an altered lipid status.

Ginkgo biloba extract inhibits the development of experimental atherosclerosis in rabbits.

Forty male mongrel rabbits were divided into 4 equal groups: (1) controls, (2) animals receiving a high-fat diet (HFD) containing cholesterol and coconut oil, (3) HFD + standardized. Ginkgo biloba extract (GB), and (4) HFD + rutin (as a well known substance it was used for comparison of pure single flavonol diglycoside activity with total extract). The experiment lasted 12 weeks.