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1.
Arch Med Sci ; 20(1): 167-188, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38414480

RESUMO

Introduction: The objective of this study was to estimate the safety profile of pulmonary hypertension-specific therapies using placebo-controlled and active comparator trials. Material and methods: The search corpus comprised Medline, Scopus, Embase and Clinical Trials databases. A systematic review and meta-analysis was performed to assess the relative risk of severe events and discontinuations as well as of adverse drug reactions (ADRs) classified into 26 categories and 21 subcategories defined by the Medical Dictionary for Regulatory Activities (MedRA). Results: Pulmonary hypertension-specific therapies had the greatest effect on such events as flushing and headache as well as jaw pain, limb pain and myalgia or gastrointestinal disorders. The relative risk for ADRs in patients receiving monotherapy (vs. placebo/supportive therapies) and combined regimens (vs. monotherapy) was significantly increased. The risk of cessation for the combined regimen was slightly higher (Qinter-group, p = 0.0778). Such ADRs as blood and lymphatic system disorders with the anemia subgroup, gastrointestinal disorders with diarrhea and nausea subgroups, respiratory and thoracic diseases or nervous system disorders with headache tended to occur more often in combination regimens as compared to monotherapy. Conclusions: About half of the main categories and subcategories of adverse reactions according to MedRA were associated with a relatively high frequency and hazard ratio. Their risk can be increased when combination regimens are used, especially.

2.
J Pers Med ; 12(10)2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36294722

RESUMO

Aim and Methods: Data from the CARDIOPLUS study (a prospective, multicenter, non-interventional study, which was conducted among patients and physicians from ambulatory patient care in Poland) were used to assess whether primary care behavioral counseling interventions to improve diet, increase physical activity, stop smoking and reduce alcohol consumption improve outcomes associated with cardiovascular (CVD) risk factors, metabolic parameters, compliance and satisfaction with treatment in adults. The study was carried out throughout Poland in the period from July to December 2019. Results: The study included 8667 patients­49% women and 51% men aged (63 ± 11 years)­and 862 physician-researchers. At the 3-month follow-up, there was a significant reduction in body weight (p = 0.008); reduction of peripheral arterial pressure, both systolic (p < 0.001) and diastolic (p < 0.001); reduction in total cholesterol levels (p < 0.001), triglycerides (p < 0.001), and LDL cholesterol (p < 0.001). The percentage of respondents who fully complied with the doctor's recommendations increased significantly. The respondents assessed their own satisfaction with the implemented treatment as higher (by about 20%). Conclusions: As a result of pro-health education in the field of lifestyle modifications, a significant reduction of risk factors for cardiovascular diseases, as well as improved compliance and satisfaction with pharmacological treatment, was observed. Thus, appropriate personalized advice on lifestyle habits should be given to each examinee in a positive, systematic way following the periodic health check-ups in order to reduce the person's risk and improve the effectiveness of the treatment.

3.
Ginekol Pol ; 92(7): 481-486, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33844248

RESUMO

OBJECTIVES: The aim of the study was to determine how the type of delivery affects the stress response cycle and the level of cortisol, progesterone and corticoliberin. MATERIAL AND METHODS: The study was conducted among 26 pregnant women admitted to the Gynecology and Obstetrics Ward due to an approaching delivery date or the onset of labor. The participants were aged between 20 and 41 years, with a mean age of approximately 30 years. After delivery, blood was drawn in parallel from the maternal antecubital vein, the umbilical cord vein and the umbilical cord artery. The levels of stress hormones were assessed by ELISA. The results were subjected to statistical analyses, and correlation coefficients were calculated for individual variable pairs. The analysis also examined the participation of pregnant woman in antenatal education. RESULTS: A high correlation was observed between cortisol and progesterone levels in venous and arterial cord blood and physiological delivery. The mean cortisol level was 247.37 ng/mL in venous cord blood and 233.59 ng/mL in arterial blood and the respective mean progesterone levels were 331.81 ng/mL and 342.36 ng/mL. The highest cortisol concentration was determined in the primiparas umbilical cord blood (236.182 ng/mL in the vein, 230.541 ng/mL in the artery). Correlation between cortisol level in venous and arterial cord blood and prenatal education was also noted (venous cord blood: r = -0.5477; F = 10.2833; p = 0.0038; cord arterial blood: r = -0, 4436; F = 5.8789; p = 0.0232). CONCLUSIONS: The results obtained emphasize the importance of the hypothalamic-pituitary-adrenal (HPA) axis as one of the potential mechanisms actively involved in childbirth. The determined levels of cortisol and progesterone in the maternal and umbilical cord blood varied significantly depending on the type of delivery, with higher concentrations being observed in the case of natural delivery. In addition, the highest levels of cortisol were determined in primiparas; however, lowered umbilical cord blood cortisol levels were observed in pregnant women who had participated in antenatal education, regardless of the number of deliveries.


Assuntos
Trabalho de Parto , Adulto , Feminino , Sangue Fetal , Humanos , Hidrocortisona , Parto , Gravidez , Veias Umbilicais , Adulto Jovem
4.
Eur J Pharmacol ; 897: 173952, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33617827

RESUMO

The variability inherent in animal models and the methods used to define drug response can lead to highly divergent results when evaluating new drug candidates. Several guidelines exist for high-quality and comprehensive reporting of experiments with animals. The present survey makes a quantitative demonstration of whether compliance with good preclinical practice guidelines can affect the results and reduce risk of over- or underestimation of treatment benefit. This meta-analysis was performed on more than 400 animal studies concerning pulmonary hypertension, where a wide range of potential therapeutic agents have been recently positively assessed in preclinical experiments. The experiments were reviewed according to the selected methodological and statistical items being recommended to report in papers. A quantitative evaluation was performed of their impact on effect size, which defined the efficacy of particular drug candidates. In addition, the paper also examines whether the quality score calculated for the papers included in the analysis changed over the previous 25 years. In conclusion, some information in experimental studies is often missed or incomplete, which complicates the correct evaluation and comprehension of obtained results. This in turn could subsequently increase the potential hazards involved in translating positive experimental outcomes to possible clinical benefits in patients.


Assuntos
Anti-Hipertensivos/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Projetos de Pesquisa/estatística & dados numéricos , Pesquisa Translacional Biomédica/estatística & dados numéricos , Animais , Interpretação Estatística de Dados , Modelos Animais de Doenças , Humanos , Hipertensão Pulmonar/fisiopatologia , Registros Públicos de Dados de Cuidados de Saúde , Especificidade da Espécie
5.
Int J Rheum Dis ; 22(12): 2119-2124, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31637859

RESUMO

AIM: It is commonly assumed that a genetically determined polymorphism of xenobiotic biotransformation plays a particular role in the development of such disease entities in which chemical compounds and environmental pollutants are relevant etiologic factors. Systemic sclerosis (SSc, scleroderma) belongs to diseases of connective tissue, characterized by chronic inflammation developing on an autoimmune background. The current state of knowledge on the etiopathogenesis of autoimmune diseases indicates the existence of many factors affecting the development of the disease, including factors of the external environment. Considering all the above, a study on a role of genetic polymorphisms of glutathione S-transferase has been undertaken in which predisposition to SSc in a Polish population was assessed. METHODS: The study was carried out in 161 subjects: 61 patients with SSc and 100 healthy volunteers. A determination of the polymorphism of GSTM1 and GSTT1 was performed with a multiplex PCR (polymerase chain reaction). The GSTP1 polymorphism was determined by using the PCR restriction fragment length polymorphism. RESULTS: The risk of developing SSc was 3-fold higher for persons with the null GSTM1 and GSTT1 genotypes (odds ratio [OR] = 3.3; P = .0051). The risk for SSc was also demonstrated to be over 2.5-fold greater in the GSTP1 Ile/Val genotype individuals (OR = 2.62; P = .0037). Carriers of the GSTP1 Val variant allele had a greater than 2-fold increase in SSc risk (OR = 2.41; P = .0006). CONCLUSION: The genetic polymorphism of glutathione S-transferase may affect the risk of SSc in a Polish population.


Assuntos
Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Polimorfismo Genético , Escleroderma Sistêmico/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polônia/epidemiologia , Medição de Risco , Fatores de Risco , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/enzimologia , Escleroderma Sistêmico/epidemiologia , Adulto Jovem
6.
Vascul Pharmacol ; 110: 55-63, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30145225

RESUMO

A systematic review and meta-analysis was performed to test candidate therapeutic approaches in pulmonary hypertension (PH). The efficacy of 522 interventions with >200 unregistered drugs was tested on 7254 animals. We propose a modified formula to assess meta-data that concerns the contribution of PH animal model to the denoted efficacy of tested agents. The measure of efficacy expressed as a response ratio for right ventricle systolic pressure was 0.48 (95% CI, 0.46-0.50; P < 0.00001), mean pulmonary artery pressure was 0.54 (0.52-0.56; P < 0.00001), right ventricle hypertrophy was 0.49 (0.48-0.51; P < 0.00001) and pulmonary artery wall thickness was 0.58 (0.56-0.61; P < 0.00001). Only 41 out of 522 interventions were ineffective. The most potent agents to improve both haemodynamic and hypertrophic parameters were ATP-sensitive potassium channel openers with iptakalim, Rho/ROCK inhibitors with fasudil, RAAS regulators with adenosine and ACE2 activators, and anti-inflammatories with n-3 polyunsaturated fatty acids and NF-кB inhibitors.


Assuntos
Anti-Hipertensivos/farmacologia , Pressão Arterial/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Artéria Pulmonar/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/fisiopatologia , Hipertrofia Ventricular Direita/metabolismo , Hipertrofia Ventricular Direita/fisiopatologia , Hipertrofia Ventricular Direita/prevenção & controle , Terapia de Alvo Molecular , Artéria Pulmonar/metabolismo , Artéria Pulmonar/fisiopatologia , Transdução de Sinais/efeitos dos fármacos , Remodelação Vascular/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
7.
Arch Dermatol Res ; 310(6): 515-522, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29948283

RESUMO

Bullous pemphigoid (BP) constitutes the most prevalent disease in the group of bullous dermatoses with the autoimmune background. Some authors suggest that certain cytokines (IL-2, IFN-γ) may be transported by P-glycoprotein (P-gp), the product of the ABCB1 gene. ABCB1 polymorphism might affect not only the effectiveness of treatment with drugs that are P-gp substrates but also contribute to the development of diseases, including BP. In the present work, we resolved to conduct a haplotype analysis of ABCB1 in patients with BP and to answer the question of whether any of the haplotypes are able to affect the incidence of this entity. The study involved 71 patients with BP and 100 healthy volunteers. Determination of polymorphisms 1236C > T and 3435C > T in ABCB1 was carried out with the PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) method. The 2677G > T/A ABCB1 polymorphism was analyzed with the allele-specific PCR method. It was observed that the 1236T-2677G-3435T haplotype occurred with a statistically significantly lower frequency in patients with BP than in controls (1.4 vs. 10.0%). Carriers of this haplotype were also shown to have had a low relative risk for BP (OR = 0.13, p = 0.003). Haplotype analysis of ABCB1 conducted in patients with BP demonstrated that the 1236T-2677G-3435T haplotype may protect against development of this entity.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Predisposição Genética para Doença , Penfigoide Bolhoso/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/imunologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Haplótipos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Penfigoide Bolhoso/epidemiologia , Penfigoide Bolhoso/imunologia , Polimorfismo de Fragmento de Restrição , Adulto Jovem
8.
Wiad Lek ; 70(2 pt 2): 386-394, 2017.
Artigo em Polonês | MEDLINE | ID: mdl-29059663

RESUMO

Pulmonary hypertension (PH) is a pathophysiological disorder that may involve multiple clinical conditions characterizing with by an abnormal increase in mean pulmonary arterial pressure. It is a rare, debilitating disease with a poor prognosis. Despite significant progress in diagnosis and management, including disease-targeted therapies as well as development of specialized centres, PH remains a chronic disease without a cure. If untreated, it leads to right heart failure and premature death, and a multifactorial pathomechanism impacts negatively on further prognosis. Insufficient social awareness or non-specific initial symptoms accompany to delayed diagnosis and specialist treatment. In the following pages, we will review the currently classification, etiology as well as and diagnostic algorithms in PH. We discuss approved treatments, especially specific dug therapy for pulmonary arterial hypertension, and recently approved strategies for its refund. We also summarize the general measures for patients and their caregivers, as well as the role of support groups, and specialized centers in Poland.


Assuntos
Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/terapia , Diagnóstico Tardio , Insuficiência Cardíaca , Humanos , Polônia , Prognóstico
9.
Postepy Hig Med Dosw (Online) ; 71(0): 577-588, 2017 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28791952

RESUMO

Pulmonary hypertension (PH) is a rare disorder associated with abnormally elevated pulmonary pressures that, if untreated, leads to right heart failure and premature death. Special population include patents with pulmonary arterial hypertension (PAH). A greater understanding of the epidemiology, pathogenesis, and pathophysiology of PAH has led to significant advances over the past few years. Modern drug therapy provides a significant improvement in patient symptomatic status and a slower rate of clinical deterioration. Despite this, PAH remains a chronic disease without a cure. There is a need for the development of novel therapies and therapeutic strategies, as treatment options are neither universally available nor always effective, possibly due to the large number of mediator and signaling pathways with downstream effectors which are implicated in the pathobiology of PH, and which are not fully reversed during PAH therapy. In the following pages, we review novel strategies for treatment of PAH. For this purpose we summarized the role of specific drug therapies that involve: endothelin receptor antagonists (ERA), phosphodiesterase type 5 inhibitors (PDE-5i) and prostacyclin and prostanoids (PGI2). We focused on novel molecular mechanisms in PAH of recently approved: Guanylate cyclase stimulator and non-prostanoid IP receptor agonist. We discussed novel approach to combined therapy, as well as a new generation of investigational drugs and promising PAH-associated signaling pathways, such as, PDGF, RhoA/ROCK RAAS, HT-5 and others.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Quimioterapia Combinada , Antagonistas dos Receptores de Endotelina/uso terapêutico , Guanilato Ciclase/efeitos dos fármacos , Humanos , Inibidores da Fosfodiesterase 5/uso terapêutico , Prostaglandinas/uso terapêutico
10.
Pharmacol Rep ; 69(3): 532-535, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28363184

RESUMO

BACKGROUND: Recent studies reveal that nerve growth factor (NGF) plays a critical role in the pathobiology of pulmonary hypertension (PH). The aim of the present study is to clarify the relationship between NGF signaling and treatment with PDGF or ROCK inhibitors in an animal model of PH. METHODS: Lung tissues were obtained from animals with monocrotaline (MCT)-challenged PH which had been administered long term imatinib, fasudil or statin. Reversal of disease was indicated by decreases in right ventricle pressure (RVP) and hypertrophy. NGF expression was examined at the mRNA and protein levels using quantitative real-time PCR reaction and ELISA. RESULTS: MCT significantly increased NGF mRNA and protein content in lung tissue. ROCK inhibitor (fasudil) and PDGF inhibitor (imatinib) caused significant decreases in NGF mRNA and protein content when administered alone, with no further effects noted when used in combination. CONCLUSION: The beneficial reversal of MCT-mediated effects in PH caused by PDGF or ROCK inhibition may be also partially mediated by decreased NGF signaling.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Fator de Crescimento Neural/metabolismo , Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Quinases Associadas a rho/antagonistas & inibidores , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipertensão Pulmonar/fisiopatologia , Mesilato de Imatinib/farmacologia , Masculino , Monocrotalina/farmacologia , Fator de Crescimento Neural/genética , Inibidores de Proteínas Quinases/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos
11.
J Pharm Sci ; 106(5): 1275-1284, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28088455

RESUMO

When performing in vitro dissolution testing, especially in the area of biowaivers, it is necessary to follow regulatory guidelines to minimize the risk of an unsafe or ineffective product being approved. The present study examines model-independent and model-dependent methods of comparing dissolution profiles based on various compared and contrasted international guidelines. Dissolution profiles for immediate release solid oral dosage forms were generated. The test material comprised tablets containing several substances, with at least 85% of the labeled amount dissolved within 15 min, 20-30 min, or 45 min. Dissolution profile similarity can vary with regard to the following criteria: time point selection (including the last time point), coefficient of variation, and statistical method selection. Variation between regulatory guidance and statistical methods can raise methodological questions and result potentially in a different outcome when reporting dissolution profile testing. The harmonization of existing guidelines would address existing problems concerning the interpretation of regulatory recommendations and research findings.


Assuntos
Formas de Dosagem , Liberação Controlada de Fármacos , Controle de Medicamentos e Entorpecentes/estatística & dados numéricos , Preparações Farmacêuticas/química , Liberação Controlada de Fármacos/fisiologia , Controle de Medicamentos e Entorpecentes/métodos , Preparações Farmacêuticas/metabolismo , Solubilidade
12.
Pharm Dev Technol ; 22(1): 103-110, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27291386

RESUMO

OBJECTIVE: In vitro dissolution testing provides useful information at clinical and preclinical stages of the drug development process. METHODS: The study includes pharmaceutical papers on dissolution research published in Polish journals between 2010 and 2015. They were analyzed with regard to information provided by authors about chosen methods, performed validation, statistical reporting or assumptions used to properly compare release profiles considering the present guideline documents addressed to dissolution methodology and its validation. RESULTS: Of all the papers included in the study, 23.86% presented at least one set of validation parameters, 63.64% gave the results of the weight uniformity test, 55.68% content determination, 97.73% dissolution testing conditions, and 50% discussed a comparison of release profiles. The assumptions for methods used to compare dissolution profiles were discussed in 6.82% of papers. By means of example analyses, we demonstrate that the outcome can be influenced by the violation of several assumptions or selection of an improper method to compare dissolution profiles. DISCUSSION AND CONCLUSION: A clearer description of the procedures would undoubtedly increase the quality of papers in this area.


Assuntos
Preparações Farmacêuticas/química , Análise de Variância , Técnicas de Química Analítica/métodos , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Publicações Periódicas como Assunto , Solubilidade , Estudos de Validação como Assunto
13.
Acta Pol Pharm ; 74(2): 587-596, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29624263

RESUMO

Due to increasing importance of the advisory role for physicians and patients played by the pharmacist over the last decade, it seems appropriate to evaluate if and why pharmacists are interested in postgraduate medical education. The purpose of the study was to develop and validate an instrument to assess such motives, with special interest to Polish community pharmacists. A self-administered questionnaire was completed by a sample of participants of community pharmacist specialization programs and it was analyzed in relation to participants of other postgraduate courses. They were asked to rank their motives on a Likert-like scale and the underlying dimensions for study motives were identified using exploratory and confirmatory techniques. The reasons for taking specialization for community pharmacists were similar as compared to participants of other postgraduate studies. However, the autotelic factor was not so strong and the crucial reason was that such postgraduate training was required to be promoted in work. Basing on Polish results, we propose the division of motives into three groups - autotelic, instrumental and coincidental. The validated self-administered questionnaire based on this division displayed acceptable construct validity and internal consistency, and therefore can be proposed as an example tool to assess the particular motives and expectations of potential postgraduate students and employees in the pharmaceutical job market. The promotion of postgraduate education among pharmacists can improve the quality of pharmaceutical service.


Assuntos
Atitude do Pessoal de Saúde , Serviços Comunitários de Farmácia , Educação de Pós-Graduação em Farmácia , Motivação , Farmacêuticos/psicologia , Adulto , Escolaridade , Feminino , Humanos , Masculino , Projetos Piloto , Polônia , Inquéritos e Questionários
14.
Acta Pol Pharm ; 74(3): 1001-1010, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-29513971

RESUMO

The objective was to examine the motivation for studying pharmacy. A self-administered questionnaire, developed and validated by the authors, was completed by a sample of 414 Polish pharmaceutical students (Year I - Year 5). The students ranked their motives on a Likert-like scale and their underlying dimensions were identified using exploratory and confirmatory techniques. Several socio-demographic variables and future pharmaceutical career plans were-also identified. The reliability and validity of the proposed questionnaire were confinued. Factor analysis revealed three factors determining the choices of the respondents: coincidental, instrumental and autotelic. Two of the top three reasons for studying pharmacy were autotelic. A relatively small percentage of respondents chose a pharmaceutical education due to coincidence. The motivation for choosing a pharmaceutical career remained relatively stable among students of all the study years. The practice point of our survey can be that, basing on Polish case, we,propose the validated self-administered questionnaire that displays acceptable construct validity and internal consistency, and can serve as an example tool to assess the particular motives and expectations of potential students and employees in the pharmaceutical area.


Assuntos
Escolha da Profissão , Educação em Farmácia , Motivação , Estudantes de Farmácia/psicologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Polônia , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto Jovem
15.
Arch Med Sci ; 12(4): 898-905, 2016 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-27478473

RESUMO

INTRODUCTION: It remains controversial whether statins have a beneficial effect on pulmonary arterial hypertension (PAH). This study is intended to evaluate whether statin, co-administered with Rho-kinase inhibitor, could enhance its efficacy. Although Rho-kinase inhibitors, including fasudil, have been reported to improve pulmonary hypertension in experimental and clinical studies, the combination of these agents has not been tested in the treatment of pulmonary hypertension (PH). MATERIAL AND METHODS: The effects of such a regimen on hemodynamics, right ventricle hypertrophy, and Rho-associated protein kinase (ROCK) activity in experimental monocrotaline (MCT)-induced pulmonary hypertension were examined. Fourteen days after monocrotaline injection (60 mg/kg), male rats were treated orally for another 14 days with fasudil (15 mg/kg per day), or with a combination of fasudil + rosuvastatin (10 mg/kg per day). RESULTS: The drug combination reversed the MCT-induced increase in right ventricle pressure (RVP) and reduced right ventricular hypertrophy (RV/LV + S ratio) more than Rho kinase inhibitor alone. The simultaneous administration of fasudil and rosuvastatin caused a further decrease of RhoA kinase activity in isolated lung tissues as compared to fasudil alone. CONCLUSIONS: The results indicate that rosuvastatin intensifies the beneficial effects of Rho-kinase inhibitor on the Rho/Rho-kinase pathway and such a combination may represent an option for the treatment of pulmonary arterial hypertension.

16.
Prz Gastroenterol ; 11(4): 276-281, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28053683

RESUMO

INTRODUCTION: Irritable bowel syndrome (IBS) and celiac disease (CD) share some gastrointestinal symptoms. Celiac disease should be considered in a differential diagnosis of IBS. AIM: To estimate the prevalence of predispositions to CD in patients with IBS and its subtypes. MATERIAL AND METHODS: The study included 48 patients (40 women, 8 men; average age: 41.1 ±14.6 years) with IBS, and a control group: 20 healthy volunteers. All participants completed a questionnaire on their current gastrointestinal symptoms and had a blood sample taken to determine the HLA-DQ2/DQ8 antigens and serum concentration of anti-tTG IgA and anti-DGP IgA and IgG. RESULTS: The presence of HLA-DQ2 or DQ8 was found in 50% of patients (n = 24) with IBS. In the control group the presence of HLA-DQ2 was found in 4 (20%) patients and nobody had HLA-DQ8. Increased levels of anti-tTG IgA were found in 5 (10.42%) patients with IBS, anti-DGP in 4 (8.33%), and anti-DGP IgG in 3 (6.25%). In the control group positive test result for anti-tTG was found in 2 (10%) patients; nobody had elevated anti-DGP IgA or IgG. A concomitant positive result of genetic testing and any elevated serum antibodies specific to CD was found in 12.5% of IBS patients (n = 6) and in none of the control group. CONCLUSIONS: Patients with IBS, regardless of the subtype, significantly more often than healthy controls have the predisposing genetic factors (HLA-DQ2/DQ8) underlying the development of CD.

17.
Ginekol Pol ; 86(6): 448-52, 2015 Jun.
Artigo em Polonês | MEDLINE | ID: mdl-26255453

RESUMO

OBJECTIVES: The aim of the study was to investigate the effectiveness of erythromycin in preventing intrauterine infection caused by group B streptococcus (GBS). MATERIAL AND METHODS: The study included 20 pregnant women with GBS-positive screening or whose laboratory screening was not available, who delivered between April 17, 2013 and July 22, 2013. The women were given 600 mg of erythromycin intravenously After delivery blood was drawn in parallel from maternal antecubital vein and umbilical cord artery Serum erythromycin concentrations were evaluated using enzyme-linked immunosorbent assay (ELISA) kit. Statistical analysis for measurable and non-measurable characteristics were performed, correlation coefficients for each pair of variables were calculated in order to investigate the sought dependence. RESULTS: Mean placental transfer of erythromycin was 2.04%. There was a high correlation between umbilical artery serum and maternal serum erythromycin concentration. Selected variables of mothers in the control group had no effect on serum erythromycin concentration in the umbilical artery CONCLUSIONS: Transplacental transfer of erythromycin is limited (2.04%). Intravenous application of erythromycin at a dose of 600 mg does not allow to achieve the value of MIC50 and MIC90 for erythromycin against strains S. agalactiae in umbilical artery serum, what suggests a compromised efficacy in the treatment of intrauterine fetal infections. At the same time, the placenta seems to be an effective barrier reducing fetal exposure when this macrolide is used to treat maternal infections.


Assuntos
Antibacterianos/sangue , Antibacterianos/farmacocinética , Eritromicina/sangue , Eritromicina/farmacocinética , Complicações Infecciosas na Gravidez/tratamento farmacológico , Infecções Estreptocócicas/tratamento farmacológico , Antibacterianos/administração & dosagem , Antibioticoprofilaxia , Ensaio de Imunoadsorção Enzimática , Eritromicina/administração & dosagem , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/prevenção & controle , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Troca Materno-Fetal/efeitos dos fármacos , Placenta/efeitos dos fármacos , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Infecções Estreptocócicas/microbiologia
18.
Int J Mol Sci ; 16(7): 14608-22, 2015 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-26132566

RESUMO

BACKGROUND: Administration of diagnostic activities of 131I, performed in order to detect thyroid remnants after surgery and/or thyroid cancer recurrence/metastases, may lead to reduction of iodine uptake. This phenomenon is called "thyroid stunning". We estimated radiation absorbed dose-dependent changes in genetic material, in particular in sodium iodide symporter (NIS) gene promoter, and NIS protein level in human thyrocytes (HT). MATERIALS AND METHODS: We used unmodified HT isolated from patients subjected to thyroidectomy exposed to 131I in culture. The different 131I activities applied were calculated to result in absorbed doses of 5, 10, and 20 Gy. RESULTS: According to flow cytometry analysis and comet assay, 131I did not influence the HT viability in culture. Temporary increase of 8-oxo-dG concentration in HT directly after 24 h (p < 0.05) and increase in the number of AP-sites 72 h after termination of exposition to 20 Gy dose (p < 0.0001) were observed. The signs of dose-dependent DNA damage were not associated with essential changes in the NIS expression on mRNA and protein levels. CONCLUSIONS: Our observation constitutes a first attempt to evaluate the effect of the absorbed dose of 131I on HT. The results have not confirmed the theory that the "thyroid stunning" reduces the NIS protein synthesis.


Assuntos
Radioisótopos do Iodo/efeitos adversos , Doses de Radiação , Compostos Radiofarmacêuticos/efeitos adversos , Glândula Tireoide/efeitos da radiação , Absorção de Radiação , Apoptose , Células Cultivadas , Dano ao DNA , Humanos , Simportadores/genética , Simportadores/metabolismo , Glândula Tireoide/citologia , Glândula Tireoide/metabolismo
19.
Postepy Hig Med Dosw (Online) ; 69: 294-301, 2015 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-25748620

RESUMO

The objective of this work was to demonstrate the usage of biodegradable polymers, made of calcium alginate and dibutyrylchitin, in the design of cellular scaffolds having broad application in reconstructive therapy (dentistry, orthopedics). To visualize cells seeded on calcium alginate and dibutyrylchitin polymers DAPI staining of fibroblasts nuclei was used. The cytotoxicity of the materials and microscopic evaluation of the viability of seeded cells was tested with a PKH 67 fluorescent dye. To assess the cellular toxicity the proliferation of fibroblasts adjacent to the tested polymers was examined. The vitability of cells seeded on polymers was also evaluated by measuring the fluorescence intensity of calcein which binds only to live cells. The conducted experiments (DAPI and PKH 67 staining) show that the tested materials have a positive influence on cell adhesion crucial for wound healing - fibroblasts. The self-made dibutyrylchitin dressing do not cause the reduction of viability of cells seeded on them. The in vitro study illustrated the interactions between the tested materials, constructed of calcium alginate or dibutyrylchitin and mouse fibroblasts and proved their usefulness in the design of cellular scaffolds. Examined polymers turned out to be of great interest and promise for cellular scaffolds design.


Assuntos
Alginatos/química , Materiais Biocompatíveis/uso terapêutico , Quitina/análogos & derivados , Fibroblastos/fisiologia , Alicerces Teciduais/química , Animais , Materiais Biocompatíveis/química , Adesão Celular/fisiologia , Divisão Celular , Sobrevivência Celular , Células Cultivadas , Estruturas Celulares , Quitina/química , Fibroblastos/citologia , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Camundongos , Ferimentos e Lesões/terapia
20.
Ginekol Pol ; 86(1): 33-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25775873

RESUMO

OBJECTIVES: The aim of this study was to investigate the effectiveness of erythromycin in preventing fetal and intrauterine group B streptococcal (GBS) infections. The study evaluated the penetration of erythromycin through the placenta, by comparing umbilical vein and maternal serum erythromycin concentrations. MATERIAL AND METHODS: The study subjects were 42 pregnant women, with GBS-positive screening or whose laboratory screening was not available, who delivered between 17th April 2013 and 22nd July 2013. The women were given 600 mg of erythromycin intravenously. After delivery blood was drawn from the mother's antecubital vein and umbilical cord vein. Serum erythromycin concentrations were evaluated using enzyme-linked immunosorbent assay (ELISA) kit. The percentage and correlation between umbilical vein and maternal serum erythromycin concentration were calculated. Based on regression function parameters selected factors: maternal age, maternal body weight, gestational age at delivery related to the umbilical vein serum erythromycin concentration, were investigated. Results: A total of 42 umbilical vein-maternal serum pairs were included in the analysis. The mean umbilical vein-maternal serum erythromycin concentration percentage was 2.64 ± 1.55%. There was a moderate correlation between umbilical vein serum and maternal serum erythromycin concentration. Pregnancy complications and selected variables of mothers in control group had no effect on the serum erythromycin concentration in the umbilical vein. CONCLUSIONS: Intravenous application of erythromycin at a dose of 600 mg, allowed to achieve therapeutic concentration in maternal serum. However, when it comes to placental transfer of erythromycin, the lack of therapeutic concentration in umbilical vein serum was observed. The limited transplacental transfer of erythromycin, which was approximately 2.6%, suggests compromised efficacy in the treatment of intrauterine fetal infections. On the other hand, the placenta seems to produce an effective barrier reducing the fetal exposure when erythromycin is used exclusively to treat maternal infections.


Assuntos
Anti-Infecciosos/administração & dosagem , Eritromicina/administração & dosagem , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Troca Materno-Fetal , Placenta/efeitos dos fármacos , Complicações Infecciosas na Gravidez/tratamento farmacológico , Infecções Estreptocócicas/tratamento farmacológico , Antibioticoprofilaxia , Estudos de Casos e Controles , Feminino , Humanos , Recém-Nascido , Doenças do Recém-Nascido/prevenção & controle , Injeções Intravenosas , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Infecções Estreptocócicas/microbiologia
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