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1.
Postepy Dermatol Alergol ; 37(2): 190-194, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32489353

RESUMO

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease caused by genetic, environmental, and still unknown factors which lead to deregulation of the immune system. Osteopontin (OPN) is a multifunctional glycoprotein, expressed in various cell types, and found to play key roles in immunity. OPN and variants of the OPN gene are involved in inflammatory conditions, however, their role in SLE are controversial. AIM: To investigate the frequency of single nucleotide polymorphism (SNP) rs1126616 (707 C/T) variants in the OPN gene and its associations with SLE manifestations in Polish patients. MATERIAL AND METHODS: The study population consisted of 83 SLE patients and 100 gender-, age- and ethnically matched healthy controls. DNA was extracted from whole blood samples using the standard procedure. Genotyping was performed by real-time polymerase chain reaction (RT-PCR). The association between clinical features of SLE and 707 C/T genotypes was determined. RESULTS: The mutant (CT, TT) genotypes were observed more frequently than the wild-type (CC) genotype in SLE patients compared to controls (p = 0.037). However, no association between 707 C/T variants and SLE clinical manifestations or laboratory parameters was found. CONCLUSIONS: The present data suggest that CT and TT genotypes of OPN 707 C/T SNP are associated with a higher SLE risk, but do not affect the clinical course of the disease in the Polish population.

2.
J Sep Sci ; 39(16): 3246-53, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27421088

RESUMO

A new method for the determination of the stereoisomers, in aqueous medium and serum, of the racemic aminoalkanol derivatives I and II of 1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.0(2,6) ]dec-8-ene-3,5,10-trione, which were found in earlier studies to be potential anticancer drugs, was developed and validated. The optimized conditions included 25 mM phosphate buffer adjusted to pH 2.5, containing γ-cyclodextrin at a concentration of 5% m/v, as background electrolyte, an applied voltage of +10 kV, and a temperature of 25°C. Separations were carried out using a fused-silica capillary. The developed method of determining the enantiomers of compounds I(S), I(R) and II(S), II(R) was characterized by the following parameters: a detection time within 10.8 min, a detection limit in the range of 141.2-141.7 ng/mL using the UV absorption detection at 200 nm. Good linearity (R(2) = 0.9989-0.9998) was achieved within the range of concentrations studied. A very good extraction yield of 95.4-99.7% was achieved, and recoveries were carried out from both aqueous solutions and matrix serum. The repeatability of the method for peak areas with an accuracy of the determined concentrations of the analytes in the range of 1.43-1.89%, and limits of quantitation in the range of 432.4-436.3 ng/mL were achieved.


Assuntos
Antineoplásicos/química , Eletroforese Capilar/métodos , Compostos Heterocíclicos com 3 Anéis/química , Antineoplásicos/sangue , Compostos Heterocíclicos com 3 Anéis/sangue , Humanos , Sensibilidade e Especificidade , Estereoisomerismo
3.
Mol Biol Rep ; 41(11): 7223-8, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25059118

RESUMO

Vitamin D appears to have an important role in the modulation of the central nervous system. Vitamin D exerts its biological effects through its interaction with the vitamin D receptor (VDR). Located on chromosome 12 (12q13.1), the VDR gene has many different polymorphisms. Some of them are known to affect the VDR function, such as FokI (rs2228570, T/C) single nucleotide polymorphism. We aimed to explore a potential relationship between FokI VDR polymorphism and impulsiveness in alcohol-dependent (AD) patients. The study population consisted of 148 patients diagnosed with alcohol dependence (DSM-IV criteria) and 212 healthy controls. DNA was extracted from whole blood samples using the standard procedure. Genotypes were analyzed using a real-time PCR method. We found that FokI VDR gene polymorphism was associated with impulsivity [Barratt Impulsiveness Scale (BIS)-11 total score; P = 0.014], and with attentional impulsivity (BIS-11 subscale; P = 0.002) in the male AD patients. Our results suggest that CC FokI genotype of the VDR gene is associated with a higher level of impulsivity in these patients. This finding supports the hypothesis that impulsiveness, which significantly contributes to development of alcohol dependence, has a genetic background.


Assuntos
Alcoolismo/fisiopatologia , Cromossomos Humanos Par 12/genética , Comportamento Impulsivo/fisiologia , Polimorfismo de Nucleotídeo Único/genética , Receptores de Calcitriol/genética , Adulto , Alcoolismo/genética , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polônia , Reação em Cadeia da Polimerase em Tempo Real , Estatísticas não Paramétricas
4.
J Sep Sci ; 37(23): 3564-70, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25280228

RESUMO

The purpose of this study, the direct separation of aminoalkanol derivatives I and II of 1,7-dimethyl-8,9-diphenyl-4-azatricyclo[5.2.1.0(2,6) ]dec-8-ene-3,5,10-trione, which was found in earlier studies as potential anticancer drugs, were performed. Capillary electrophoresis offers the possibility of fast, cheap, and reproducible separations for compounds I and II. In this paper, the simultaneous separation of I and II by capillary zone electrophoresis has been achieved within 8 min by use of 50 mM phosphate buffer of pH 2.5. Analysis of the two compounds in the serum plasma standards was conducted. Limits of detection of I and II by UV absorbance at 200 nm were achieved in the range of 156.3-156.6 ng/mL. The method was validated for linearity, accuracy, precision, limits of detection, and quantification. The calibration equation revealed a good linear relationship (r(2) = 0.998-0.999). Sufficient recovery was observed in the range of 96.3-99.5%. The method showed good reproducibility with intra- and interday precision of 0.97 and 1.76%, respectively. The quantification limits for the compounds were in the range of 477.0-479.8 ng/mL. The proposed method was applied to the analysis of real serum samples.


Assuntos
Antineoplásicos/isolamento & purificação , Eletroforese Capilar/métodos , Compostos Heterocíclicos com 3 Anéis/isolamento & purificação , Imidas/isolamento & purificação , Antineoplásicos/sangue , Compostos Heterocíclicos com 3 Anéis/sangue , Humanos , Imidas/sangue , Estrutura Molecular , Sensibilidade e Especificidade
5.
J Pediatr Gastroenterol Nutr ; 53(1): 93-9, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21694542

RESUMO

OBJECTIVE: Vitamin D status in infants depends on supplementation. We examined the vitamin D status in relation to supplementation dose and scheme in infants. PATIENTS AND METHODS: One hundred thirty-four infants age 6 months and 98 infants age 12 months (drop out 27%) were investigated. Vitamin D intake (diet, supplements), anthropometry, and 25-hydroxyvitamin D (25-OHD) serum concentration at the 6th and 12th months were assessed. RESULTS: Vitamin D intake of 1062 ± 694 IU at the 6th month was not different from that at the 12th month (937 ± 618 IU). Vitamin D intake expressed in international units per kilogram of body weight decreased from 141 ± 80 IU/kg at the 6th month to 93 ± 62 IU/kg at the 12th month (P < 0.0001), which was associated with a reduction in 25-OHD from 43 ± 20 ng/mL to 29 ± 12 ng/mL, respectively (P < 0.0001). In the subgroup of everyday supplemented infants (n = 43), vitamin D intake decreased from 143 ± 88 IU/kg at the 6th month to 118 ± 60 IU/kg at the 12th month (P < 0.05), which coincided with a reduction of 25-OHD from 40 ± 19 ng/mL to 32 ± 13 ng/mL (P < 0.01). In the subgroup with variable supplementation habits (n = 32), vitamin D intake decreased from 146 ± 79 IU/kg to 77 ± 56 IU/kg (P < 0.001), which was associated with a reduction of 25-OHD from 42 ± 21 ng/mL to 25 ± 8 ng/mL (P < 0.0001). 25-OHD concentration change between the 6th and the 12th months negatively correlated with the 25-OHD level assessed at the 6th month (r = -0.82; P < 0.0001). CONCLUSIONS: Vitamin D supplementation of infants should consider their rapid body weight increment. We postulate vitamin D daily dose close to 100 IU/kg body weight as favorable for infants up to age 12 months.


Assuntos
Suplementos Nutricionais , Estado Nutricional , Deficiência de Vitamina D/epidemiologia , Vitamina D/administração & dosagem , 25-Hidroxivitamina D 2/sangue , Calcifediol/sangue , Desenvolvimento Infantil , Estudos de Coortes , Dieta , Feminino , Humanos , Lactente , Masculino , Política Nutricional , Cooperação do Paciente , Pacientes Desistentes do Tratamento , Polônia/epidemiologia , Prevalência , Estudos Prospectivos , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/prevenção & controle , Aumento de Peso
6.
Psychiatry Res ; 190(1): 149-51, 2011 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-21621273

RESUMO

We investigated a relationship between selected polymorphisms: rs6313 in HTR2A, rs6295 in HTR1A and rs1386494 in TPH2, and suicidal behaviour in 150 alcohol-dependent patients. There was a significant association between more frequent C102C genotype in HTR2A and suicide attempts in alcoholic females. No differences in genotype distribution in HTR1A and TPH2 SNPs were found between patients with and without suicide attempts.


Assuntos
Alcoolismo/genética , Alcoolismo/psicologia , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Receptor 5-HT1A de Serotonina/genética , Receptor 5-HT2A de Serotonina/genética , Tentativa de Suicídio , Triptofano Hidroxilase/genética , Adulto , Fatores Etários , Idoso , Análise Mutacional de DNA , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
Acta Pol Pharm ; 68(1): 9-13, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21485696

RESUMO

In the human organism 58 cytochrome P450 (CYP) isoenzymes belonging to 18 families have been described. Isoenzyme CYP2D6 is an important human xenobiotic-metabolizing enzyme. CYP2D6 biotransforms a significant number of drugs, widely used in clinical practice, such as antidepressants, neuroleptics, antiarrhythmics, analgesics, antiemetics and anticancer agents. The occurrence of polymorphic variants of the enzyme results in different metabolic capacity ranging from poor to ultrarapid. Ultrarapid metabolizer phenotype explains lack of response and decreased levels of drugs which are metabolized by CYP2D6. Therefore, the identification of ultrarapid metabolizers as potential non-compliance cases requiring dose adjustment, has serious clinical importance. In this study we evaluate a long-PCR procedure for detecting CYP2D6 gene duplication.


Assuntos
Citocromo P-450 CYP2D6/genética , Duplicação Gênica , Farmacogenética , Reação em Cadeia da Polimerase/métodos , Citocromo P-450 CYP2D6/metabolismo , Genótipo , Humanos , Fenótipo , Reprodutibilidade dos Testes
8.
Appl Clin Genet ; 14: 417-425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675603

RESUMO

PURPOSE: Atopic dermatitis (AD) is a chronic, relapsing inflammatory disease, caused by environmental and genetic factors, which lead to immunological abnormalities. Osteopontin (OPN), also named secreted phosphoprotein 1 (SPP1), is a protein involved in the pathogenesis of numerous autoimmune and inflammatory conditions. However, its role in AD has not been fully elucidated. Therefore, we aim to gain an insight into the role of OPN in AD pathogenesis through investigating its gene single nucleotide polymorphisms (SNPs) and their possible associations with disease clinical features. PATIENTS AND METHODS: A total of 182 Caucasian participants (45 AD patients and 137 gender- and age-matched controls) were studied. Genomic DNA was isolated from peripheral blood samples. Genotyping for the rs1126616 C>T, rs1126772 A>G, rs9138 A>C, and rs3841116 T>G SNPs was performed by real time polymerase chain reaction (RT-PCR). RESULTS: The frequency of the minor TT genotype and the T allele of rs1126616 C>T was higher in AD patients compared to controls (P = 0.019, OD = 4.86, 95% CI = 1.46-16.20, and P = 0.047, OR = 1.77, 95% CI = 1.04-3.00, respectively) and was associated with the higher prevalence of asthma (P = 0.017, OR = 3.73, 95% CI = 0.71-19.67, and P = 0.004, OR = 3.96, 95% CI = 1.53-10.25, respectively). Likewise, the minor GG genotype and the G allele of rs1126772 A>G were more frequent in AD patients (P = 0.026, OR = 3.27, 95% CI = 1.29-8.33, and P = 0.013, OR = 1.94, 95% CI = 1.18-3.21, respectively) and were associated with the increased incidence of asthma (P = 0.016, OR = 5.06, 95% CI = 1.14-22.49, and P = 0.002, OR = 4.40, 95% CI = 1.71-11.35, respectively). Furthermore, haplotype frequency estimation determined the four-loci haplotype TGCT, as a significant risk factor for AD compared to controls (P = 0.031, OR = 9.48, 95% CI = 1.23-71.91). CONCLUSION: Our results suggest that the variation in the OPN gene might be associated with AD and increased incidence of asthma in Caucasians. Further studies should be conducted to look into the possible role of OPN as a biomarker for AD.

9.
J Pediatr Gastroenterol Nutr ; 51(1): 106-9, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20479682

RESUMO

BACKGROUND: : Depletion of beta-carotene (b-c) has not been extensively studied in children with chronic cholestatic liver disease. PATIENTS AND METHODS: : We assessed b-c serum concentration in 53 children with cholestatic liver disease: 19 patients operated on for biliary atresia, 12 with Alagille syndrome, and 22 with progressive familial intrahepatic cholestasis. To test b-c absorption, 6 children with chronic cholestasis received a load of 10 mg b-c/kg body weight. RESULTS: : We found decreased b-c concentrations in 45 patients. The absorption of b-c was not detectable in 5 of 6 children studied. CONCLUSIONS: : b-c depletion is a common problem of chronic cholestatic liver disease in childhood that can be attributed to disturbed intestinal absorption.


Assuntos
Colestase/complicações , Hepatopatias/complicações , Síndromes de Malabsorção/complicações , beta Caroteno/deficiência , Adolescente , Adulto , Síndrome de Alagille/sangue , Atresia Biliar/sangue , Atresia Biliar/cirurgia , Criança , Pré-Escolar , Colestase Intra-Hepática/sangue , Feminino , Humanos , Lactente , Absorção Intestinal , Síndromes de Malabsorção/sangue , Masculino , Adulto Jovem , beta Caroteno/sangue , beta Caroteno/farmacocinética
10.
Acta Pol Pharm ; 67(2): 129-36, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20369789

RESUMO

1H HR MAS (high resolution magic angle spinning) NMR is a promising tool in the in vitro characterisation of brain tumors. Brain tissue samples were collected from patients with intracranial tumors during surgery, frozen and lyophilized. The analysis of solid samples was performed by high-speed rotation (33 kHz) H MAS NMR. The most intense resonances arise from lipids (methylene mid-chain and methyl carbons of fatty acids). 1H MAS spectra obtained from the same histological type of brain tumors are similar; spectra of glioblastomas were different from those of meningiomas. 1H and 13C NMR solution spectra of lipid extracts confirmed the presence of aliphatic chains fatty acids and cholesterol as major constituents. Biochemical information on liberated fatty acid composition was obtained by gas-chromatography (GC). The glioma content of the linoleic acid (18:2n6) was found to be greater, whereas the level of docosahexaenoic acid (22:6n3) was significantly reduced.


Assuntos
Neoplasias Encefálicas/metabolismo , Cromatografia Gasosa/métodos , Lipídeos/análise , Espectroscopia de Ressonância Magnética/métodos , Adulto , Idoso , Química Encefálica , Neoplasias Encefálicas/química , Ácidos Graxos/análise , Liofilização , Humanos , Masculino , Pessoa de Meia-Idade
11.
Ginekol Pol ; 81(2): 149-53, 2010 Feb.
Artigo em Polonês | MEDLINE | ID: mdl-20232716

RESUMO

Adequate vitamin D intake and its status are important not only for bone health and Ca-P metabolism, but for optimal function of many organs and tissues throughout the body. Due to documented changes in dietary habits and physical activity level, both observed in growing children and adults, the prevalence of vitamin D insufficiency is continuously increasing. Basing on current literature review and opinions of National Consultants and experts in the field, polish recommendations for prophylactic vitamin D supplementation in infants, toddlers, children and adolescents as well as in adults, including pregnant and lactating women have been established.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Conhecimentos, Atitudes e Prática em Saúde , Prevenção Primária/organização & administração , Luz Solar , Deficiência de Vitamina D/prevenção & controle , Vitamina D/uso terapêutico , Adolescente , Adulto , Criança , Proteção da Criança/estatística & dados numéricos , Feminino , Humanos , Bem-Estar do Lactente/prevenção & controle , Recém-Nascido , Masculino , Programas Nacionais de Saúde/normas , Fenômenos Fisiológicos da Nutrição , Estado Nutricional , Polônia/epidemiologia , Gravidez , Complicações na Gravidez/prevenção & controle , Garantia da Qualidade dos Cuidados de Saúde/normas , Sociedades Médicas/normas , Adulto Jovem
12.
Pol Merkur Lekarski ; 28(164): 130-3, 2010 Feb.
Artigo em Polonês | MEDLINE | ID: mdl-20369742

RESUMO

Appropriate state procurement system for vitamin D is important not only for the proper functioning of the skeletal, maintaining calcium and phosphorus homeostasis, but also for a number of other organs and tissues in our body. In connection with the change in lifestyle including dietary habits change, the widespread use of UV filters and less outdoor activity, observed an increase in the percentage of vitamin D deficiency, both in population and developmental age and adults. Based on the results of recent scientific research team of experts provides recommendations for preventive Polish supply of vitamin D in infants, children, adolescents and adults, including pregnant women and nursing mothers.


Assuntos
Deficiência de Vitamina D/prevenção & controle , Vitamina D/administração & dosagem , Adolescente , Adulto , Aleitamento Materno , Criança , Suplementos Nutricionais , Comportamento Alimentar , Feminino , Alimentos Fortificados , Humanos , Lactente , Recém-Nascido , Masculino , Polônia , Gravidez , Adulto Jovem
13.
Expert Rev Mol Diagn ; 20(1): 49-56, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31795772

RESUMO

Introduction: Vitamin D-binding protein (DBP) performs a variety of functions as a transporter for various ligands and takes part in a number of systemic and local physiological and pathological processes. The knowledge about the pathomechanisms of this protein involvement justifies its use as a biomarker to confirm specific clinical diagnoses suggested by nonspecific signs and symptoms.Areas covered: DBP has properties of both systemic laboratory parameters measured in the blood plasma and specific parameters measured in variety of physiological fluids to assess local changes in specific body organs. Articles published in English between 1993 and 2019 were searched for in PubMed using terms DBP, vitamin D, and metabolites, inflammation. DBP is a transport protein and a regulator of immune and inflammatory processes.Expert opinion: DBP capacity for transporting numerous ligands and co-involvement of DBP in immune and inflammatory processes suggest that DBP may be used in laboratory diagnostics as a specific parameter to confirm pathomechanisms of several systemic diseases and local conditions. Changes in the concentration of DBP present in a variety of clinical material may provide valuable information for use in assessing the severity and treatment of pathological processes.


Assuntos
Reação de Fase Aguda/sangue , Cirrose Hepática/sangue , Insuficiência Renal/sangue , Proteína de Ligação a Vitamina D/sangue , Reação de Fase Aguda/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Humanos , Cirrose Hepática/metabolismo , Insuficiência Renal/metabolismo , Proteína de Ligação a Vitamina D/genética , Proteína de Ligação a Vitamina D/metabolismo
14.
Endokrynol Pol ; 60(2): 104-9, 2009.
Artigo em Polonês | MEDLINE | ID: mdl-19396753

RESUMO

Research on the regulation of mineral homeostasis have been continuing for the decades, with an effect of establishing the impression that the governing mechanisms are already fairly well known and understood. Revealing of the molecular mechanism of action of the Klotho protein, forced us to revise this knowledge. It is known already that Kloto is a unique regulatory efector playing key role in reversing the imbalanced extracellular Ca(++) concentrations, by affecting the intensity of the transepithelial transport and modulation of the parathormone excretion. In cooperation with the phosphaturic hormone - Fgf23 it regulates calcium concentration by suppression of 1,25(OH)(2)D synthesis, and reabsorption of phosphate in a distal convoluted part of nephron. Acting through these mechanisms Klotho takes part in the regulation of the mineral homeostasis of cerebrospinal fluid, blood and body fluids acting on the choroid plexus, parathyroid glands and distal convoluted nephrons. In that way Klotho becomes one of the main players in a complex and multilevel system of maintaining the mineral homeostasis of the organism.


Assuntos
Glucuronidase/metabolismo , Homeostase/fisiologia , Minerais/metabolismo , Animais , Cálcio/metabolismo , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Proteínas Klotho , Néfrons/metabolismo
15.
Med Sci Monit ; 14(12): PH65-70, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19043376

RESUMO

BACKGROUND: One of the most important risk factors for osteoporotic fractures in postmenopausal women is elevated bone turnover (EBT), occurring in 25-30% of this population. This study's aim was to find a correlation between bone resorption and bone formation markers to assess bone turnover rate and qualify an individual postmenopausal woman as a possible EBT subject. MATERIAL/METHODS: Three hundred twenty postmenopausal women (> or = one year after the last menstruation, < or = 70 years old) were enrolled at seven clinical sites in this cross-sectional observational study conducted within the EPOLOS. The group was a random sample of the population. The study was performed in a referral center involved in the diagnosis and treatment of osteoporosis. The exclusion criteria included pregnancy, cancer, fracture in the last year, and overweight (> 100 kg). Bone mineral density (BMD) measurements of the lumbar spine, total hip, trochanter, and femoral neck regions were performed. Bone resorption and formation rates were evaluated by serum levels of C-terminal telopeptide of type I collagen (CTX) and osteocalcin (OC), respectively. RESULTS: Using logistic regression to correlate the concentrations of CTX and OC it was possible not only to distinguish the EBT subgroup, but also to construct a simple nomogram for easy classification of individual patients as possible EBT subjects. EBT patients showed generally decreased BMD values and increased bone formation and resorption rates. CONCLUSIONS: Evaluation of both CTX and OC levels enables a more proper indication for EBT. The proposed nomogram may assist in evaluating outcome from the two markers of bone turnover.


Assuntos
Biomarcadores/sangue , Desenvolvimento Ósseo , Reabsorção Óssea , Pós-Menopausa , Absorciometria de Fóton , Idoso , Colágeno Tipo I/sangue , Colágeno Tipo I/química , Estudos Transversais , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Osteocalcina/sangue , Fragmentos de Peptídeos/sangue
16.
Acta Pol Pharm ; 65(3): 319-29, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18646551

RESUMO

In the human genome 684 alleles of CYP genes, and additionally 30 complete CYP pseudogenes, have been identified. So far 388 isoforms of 58 human CYP isoenzymes have been described at the phenotypic level. The molecular forms of many CYP isoenzymes responsible for drug biotransformation show a differentiated degree of specific catalytic activity - from increased, through normal and decreased to various extent, to trace or even absent. Depending on the homo- or heterozygous genotype, a broad palette of phenotypic forms may be present, differentiated in respect to biotransformation dynamics of specific drugs. The progress of molecular biology with particular consideration of genotyping and DNA microarray technologies has created a basis for the dynamic progress of pharmacogenetics, allowing fast and sensitive determination of the individual pharmacogenetic profile, encompassing a large set of CYP alleles extended by allelic variants of genes encoding other enzymes participating in drug metabolism. The possibility to evaluate the pharmacogenetic profile of patients together with the increasing knowledge about the mechanisms of inhibition, repression and also induction of enzymes participating in biotransformation of xenobiotics and endogenous compounds create increasing possibilities of elaborating optimal individualized pharmacotherapeutic strategies.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Preparações Farmacêuticas/metabolismo , Polimorfismo Genético , Alelos , Sistema Enzimático do Citocromo P-450/genética , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Farmacogenética , Fenótipo
17.
Artigo em Inglês | MEDLINE | ID: mdl-30294301

RESUMO

Confusion, apathy, recurrent vomiting, abdominal pain, polyuria, polydipsia, and dehydration are the most often noted clinical symptoms of vitamin D toxicity (VDT; also called vitamin D intoxication or hypervitaminosis D). VDT and its clinical manifestation, severe hypercalcemia, are related to excessive long-term intake of vitamin D, malfunctions of the vitamin D metabolic pathway, or the existence of coincident disease that produces the active vitamin D metabolite locally. Although VDT is rare, the health effects can be serious if it is not promptly identified. Many forms of exogenous (iatrogenic) and endogenous VDT exist. Exogenous VDT is usually caused by the inadvertent or improper intake of extremely high doses of pharmacological preparations of vitamin D and is associated with hypercalcemia. Serum 25-hydroxyvitamin D [25(OH)D] concentrations higher than 150 ng/ml (375 nmol/l) are the hallmark of VDT due to vitamin D overdosing. Endogenous VDT may develop from excessive production of an active vitamin D metabolite - 1,25(OH)2D in granulomatous disorders and in some lymphomas or from the reduced degradation of that metabolite in idiopathic infantile hypercalcemia. Endogenous VDT may also develop from an excessive production of 25(OH)D and 1,25(OH)2D in congenital disorders, such as Williams-Beuren syndrome. Laboratory testing during routine clinical examinations may reveal asymptomatic hypercalcemia caused by the intake of vitamin D even in doses recommended for the general population and considered safe. That phenomenon, called hypersensitivity to vitamin D, reflects dysregulated vitamin D metabolism. Researchers have proposed many processes to explain VDT. Those processes include elevated activity of 1α-hydroxylase or inhibited activity of 24-hydroxylase, both leading to increased concentration of 1,25(OH)D; increased number of vitamin D receptors; and saturation of the capacity of vitamin D binding protein. Increased public awareness of vitamin D-related health benefits might increase the risk of VDT due to self-administration of vitamin D in doses higher then recommended for age and body weight or even higher than the established upper limit intake values. Consequently, the incidence of hypercalcemia due to hypervitaminosis D might increase.

18.
J Steroid Biochem Mol Biol ; 175: 125-135, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28216084

RESUMO

Research carried out during the past two-decades extended the understanding of actions of vitamin D, from regulating calcium and phosphate absorption and bone metabolism to many pleiotropic actions in organs and tissues in the body. Most observational and ecological studies report association of higher serum 25-hydroxyvitamin D [25(OH)D] concentrations with improved outcomes for several chronic, communicable and non-communicable diseases. Consequently, numerous agencies and scientific organizations have developed recommendations for vitamin D supplementation and guidance on optimal serum 25(OH)D concentrations. The bone-centric guidelines recommend a target 25(OH)D concentration of 20ng/mL (50nmol/L), and age-dependent daily vitamin D doses of 400-800IU. The guidelines focused on pleiotropic effects of vitamin D recommend a target 25(OH)D concentration of 30ng/mL (75nmol/L), and age-, body weight-, disease-status, and ethnicity dependent vitamin D doses ranging between 400 and 2000IU/day. The wise and balanced choice of the recommendations to follow depends on one's individual health outcome concerns, age, body weight, latitude of residence, dietary and cultural habits, making the regional or nationwide guidelines more applicable in clinical practice. While natural sources of vitamin D can raise 25(OH)D concentrations, relative to dietary preferences and latitude of residence, in the context of general population, these sources are regarded ineffective to maintain the year-round 25(OH)D concentrations in the range of 30-50ng/mL (75-125nmol/L). Vitamin D self-administration related adverse effects, such as hypercalcemia and hypercalciuria are rare, and usually result from taking extremely high doses of vitamin D for a prolonged time.


Assuntos
Suplementos Nutricionais , Deficiência de Vitamina D/dietoterapia , Vitamina D/análogos & derivados , Vitamina D/administração & dosagem , Adolescente , Adulto , Fatores Etários , Peso Corporal , Comportamento Alimentar , Feminino , Humanos , Hipercalcemia/sangue , Hipercalcemia/induzido quimicamente , Hipercalcemia/patologia , Hipercalciúria/sangue , Hipercalciúria/induzido quimicamente , Hipercalciúria/patologia , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Vitamina D/efeitos adversos , Vitamina D/sangue , Deficiência de Vitamina D/sangue
19.
Artigo em Inglês | MEDLINE | ID: mdl-29904370

RESUMO

INTRODUCTION: Vitamin D deficiency is an important public health problem worldwide. Vitamin D deficiency confers a significant risk for both skeletal and non-skeletal disorders and a number of lifelong negative health outcomes. The objectives of this evidence-based guidelines document are to provide health care professionals in Poland, an updated recommendation for the prevention, diagnosis and treatment of vitamin D deficiency. METHODS: A systematic literature search examining the prevention and treatment strategies for vitamin D deficiency was conducted. Updated recommendations were developed using the Grading of Recommendations, Assessment, Development and Evaluation system describing the strength of the recommendation and the quality of supporting evidence. Twenty-seven contributors representing different areas of expertise and medical specialties, including pediatricians, geriatricians, endocrinologists, epidemiologists, nephrologists, gynecologists and obstetricians evaluated the available published evidence related to vitamin D, formulated the goals of this document and developed a common consolidated position. The consensus group, representing six national specialist consultants and eight Polish and international scientific organizations/societies, participated in the process of grading evidence and drawing up the general and specific recommendations. RESULTS: The updated recommendations define the diagnostic criteria for the evaluation of vitamin D status and describe the prevention and treatment strategies of vitamin D deficiency in the general population and in groups at increased risk of the deficiency. Age- and weight-specific recommendations for prevention, supplementation and treatment of vitamin D deficiency are presented, and detailed practice guidance is discussed regarding the management in primary and specialized health care. CONCLUSION: Vitamin D deficiency remains still highly prevalent in Poland, in all age groups. Currently, there is a great necessity to implement a regular supplementation with recommended doses and to develop an effective strategy to alleviate vitamin D deficiency in the population. These updated recommendations are addressed to health professionals and the authorities pursuing comprehensive health policies and should also be included in public health programs aimed at preventing a broad spectrum of chronic diseases.

20.
Acta Pol Pharm ; 64(2): 103-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17665858

RESUMO

A high performance liquid chromatography method for the determination of mianserin in human serum was developed and validated. Doxepin was used as an internal standard. Mianserin was extracted from human serum using a liquid-liquid extraction with hexane:isoamyl alcohol (99:1, v/v). The sample was then dissolved in 0.05 M phosphoric acid (pH=3.0), and after separation on a Hichrom RPB (250 x 4.6 mm, 5 mm) column, the analytes were measured by ultraviolet detection at 214 nm. The recovery ranged from 86.1 to 94.5% for mianserin. The method was specific and linear over the concentration range of 2.0-128.0 ng/mL. The limit of quantification (LOQ) was established at 2.0 ng/mL (CV=13.8%). The accuracy range was from 92.5 to 107.5%. The method was used to measure mianserin in human serum samples obtained from healthy volunteers who had received a single oral dose of 30 mg mianserin. Pharmacokinetic parameters obtained for the mianserin were in agreement with the existing data.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Mianserina/sangue , Administração Oral , Antagonistas Adrenérgicos alfa/administração & dosagem , Antagonistas Adrenérgicos alfa/sangue , Antagonistas Adrenérgicos alfa/farmacocinética , Calibragem , Humanos , Mianserina/administração & dosagem , Mianserina/farmacocinética , Reprodutibilidade dos Testes
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