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1.
Eur J Nutr ; 62(5): 2155-2164, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36997822

RESUMO

PURPOSE: Recent studies indicate that dysbiosis of gut microbiota and low-grade inflammation are important pathogenic determinants of type two diabetes mellitus (T2DM). The aim of this study is to investigate the effects of Lactobacillus GG on glycemic control, lipid profile, inflammatory parameters, and some gene expression levels in individuals with T2DM. METHODS: In a randomized, placebo-controlled trial, 34 women, aged 30-60 years with T2DM consumed daily probiotics or placebo for 8 weeks. The probiotic group consumed 10 × 109 Cfu/day Lactobacillus rhamnosus GG ATCC 53,103 (LGG), approved by the TR Ministry of Food, Agriculture, and Livestock. Anthropometric measurements, food diary, fasting blood, and fecal samples were taken at baseline and post-treatment. RESULTS: Fasting blood glucose was significantly decreased in probiotic (p = 0.049) and placebo (p = 0.028), but there was no difference between the groups. In the probiotic group, no significant difference was observed in HbA1c, fructosamine, lipid profile, and inflammatory variables compared to baseline. In this group, with LGG supplementation, mucin 2 and 3A (MUC2 and MUC3A) gene expressions increased more than ninefolds (p = 0.046 and p = 0.008, respectively) at post-treatment. Meanwhile, there was no significant change in any of the gene expressions in the placebo group. There was no significant difference in energy, protein, dietary fiber, and cholesterol intakes between placebo and probiotic groups during the study. However, daily fat intake (p = 0.003), body weight (p = 0.014), and body fat (p = 0.015) in the probiotic group were significantly decreased. CONCLUSION: In this study, the effects of a single probiotic strain were investigated for 8 weeks. At the end of the study, although there was no finding that clearly reflected on the glycemic parameters of T2DM, its beneficial effects on the expression of mucin genes, which are responsible for weight loss and protection of intestinal barrier functions, cannot be denied. Further studies are needed to reveal the importance of these findings. CLINICAL TRIAL REGISTRATION: ID: NCT05066152, October 4, 2021 retrospectively registered in ClinicalTrials.gov PRS web site.


Assuntos
Diabetes Mellitus Tipo 2 , Lacticaseibacillus rhamnosus , Probióticos , Humanos , Feminino , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/terapia , Glicemia/metabolismo , Mucinas , Lipídeos , Método Duplo-Cego
2.
Mol Biol Rep ; 49(2): 1151-1159, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35013863

RESUMO

BACKGROUND: Despite commonly use for treatment of type II diabetes, possible effects of glipizide on nuclear transport and DNA damage in cells are unknown. Since clinical response of glipizide may change with aging, the aim of the study was to investigate the effect of glipizide by comparing mature and senescent adipocytes. METHODS AND RESULTS: The effects of glipizide were investigated in 3T3-L1 adipocytes. Effective and lethal doses were determined by real-time monitoring iCELLigence system. Comet assay was performed to determine DNA damage and quantitative PCR was conducted to detect gene expression levels. RAN expressions were found to be up regulated in mature 180 µM glipizide treated adipocytes compared to control group (p < 0.05); whereas down regulated in senescent 180 µM glipizide treated adipocytes compared to their control adipocytes (p < 0.05). Olive Tail Moment values were significantly higher in mature 180 µM glipizide treated adipocytes (MTG) and senescent 180 µM glipizide treated adipocytes (STG) comparing their untreated controls (p < 0.001 and p < 0.001 respectively). Also class 5 comets that shows severe DNA damage were found to be higher in both MTG and STG groups than their controls (p < 0.001 and p < 0.001, respectively). OTM values were higher in STG than MTG (p < 0.001). CONCLUSIONS: This is the first study that reports glipizide caused DNA damage increasing with senescence in adipocytes. As a response to glipizide treatment Ran gene expression increased in mature; and decreased in senescent adipocytes. Further studies are needed to reveal the effect of glipizide on DNA and nuclear interactions in molecular level.


Assuntos
Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Glipizida/farmacologia , Células 3T3-L1/efeitos dos fármacos , Transporte Ativo do Núcleo Celular/fisiologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Diferenciação Celular , Dano ao DNA/genética , Glipizida/efeitos adversos , Glipizida/metabolismo , Camundongos
3.
Clin Lab ; 68(9)2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36125161

RESUMO

BACKGROUND: The aim of this study was to determine the Firmicutes/Bacteroidetes ratio in the gut microbiota and IL-1ß, IL-6, IL-8, TLR2, TLR4 and TLR5 gene expression levels in the blood of adult type 2 diabetes (T2D) patients and compare it with that of adult nondiabetic healthy controls (HC). METHODS: Between May 2016 and April 2017, 99 T2D patients and 99 HCs were enrolled in the study. Bacteroidetes and Firmicutes levels were assessed from stool sample DNA and IL-1ß, IL-6, IL-8, TLR2, TLR4, and TLR5 gene expression levels assesed from blood sample RNA via qPCR from both T2D patients and healthy controls. RESULTS: The Firmicutes/Bacteroidetes ratio detected in the stool of type 2 diabetes patients was found to be higher with a statistically significant difference (p < 0.0001). Gene expression levels of IL-1ß, IL-6, IL-8, TLR2, TLR4, and TLR5 were found to be upregulated. CONCLUSIONS: The highest upregulation was detected in IL-6 with 11 fold in T2D patients comparing with HCs. F/B ratio and gene expression levels were elevated in T2D patients. Firmicutes were positively correlated with studied gene expressions. A better understanding of the complex interaction between gut microbiota, environment, and diabetes will allow for more effective prevention and treatment strategies for T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Adulto , Bacteroidetes/genética , Bacteroidetes/metabolismo , Diabetes Mellitus Tipo 2/genética , Firmicutes/genética , Firmicutes/metabolismo , Microbioma Gastrointestinal/genética , Expressão Gênica , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-8/genética , RNA , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Receptor 5 Toll-Like/genética
4.
Bull Environ Contam Toxicol ; 104(6): 852-857, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32322934

RESUMO

Wastewater (WW) carry considerable amount of chemicals that could have mutagenic or cytotoxic effect from hospital discharges to aquatic environment. Our objective was to determinate the possible mutagenic and toxic effects of hospital originated WWs and effectiveness of the wastewater treatment plants (WTP) functions. In the study the mutagenic and cytotoxic potential of three hospitals and influent/effluent of a treatment plant WW collected in Istanbul and was examined using AMES, XTT, and lactate dehydrogenase (LDH) assays. Mutagenic effects were detected at both hospital discharges and advanced biological wastewater plant. We observed no cytotoxic effect in fibroblasts for LDH and XTT assays whereas high cytotoxicity for all samples was found in hepatocytes by XTT assay. According to the results even if advanced technology is used for treatment of WW, mutagenic and cytotoxic effects still remain, and the present technologies need to be further improved.


Assuntos
Mutagênicos/toxicidade , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/toxicidade , Purificação da Água/métodos , Células 3T3-L1 , Animais , Bioensaio , Sobrevivência Celular/efeitos dos fármacos , Hospitais , Camundongos , Testes de Mutagenicidade , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética
5.
Microb Pathog ; 108: 27-31, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28455139

RESUMO

Adenovirus 36 (Ad-36) has recently been suggested as a possible contributor to the current obesity epidemic. The aim of this study was to investigate the prevalence of Ad-36 antibodies in obese children, as well as investigate the role of serum leptin and lipid levels in Ad-36-obesity. Seventy-one obese children and 62 non-obese children were included as the patient group (PG), including the healthy control group (HCG), respectively. Simultaneously, Ad-36 antibodies and adipokine levels were assessed with serum neutralization assays (SNA) and ELISA. Ad-36 antibody was detected in 9 patients (12.7%) and 1 patient (1.6%) in both the PG and HCG, respectively, while a significant difference was detected between groups (p < 0.05). Although serum LDL, total cholesterol, triglycerides and leptin levels were detected significantly higher, adiponectin level was detected paradoxically lower in the PG. However, a significant difference was not detected for lipids and leptin levels; adiponectin levels were found to be significantly lower in Ad-36 antibody-positive PG (p < 0.05). In conclusion, we suggest there is an association between Ad-36 and obesity in children, including IL-6 levels increasing in obese children with Ad-36 seropositivity. Conversely, adiponectin levels in obese children with Ad-36 seropositivity were higher. As such, there is a need for studies to understand the mechanisms underlying this observation.


Assuntos
Adenovírus Humanos/imunologia , Adipocinas/sangue , Anticorpos Antivirais/sangue , Obesidade/sangue , Obesidade/epidemiologia , Obesidade/virologia , Infecções por Adenovirus Humanos/complicações , Infecções por Adenovirus Humanos/virologia , Adiponectina/sangue , Adolescente , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Colesterol/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-6/sangue , Leptina/sangue , Lipídeos/sangue , Masculino , Testes de Neutralização , Prevalência , Fatores de Risco , Triglicerídeos/sangue , Turquia
6.
Caries Res ; 49(3): 275-81, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25924601

RESUMO

Sweet taste is a powerful factor influencing food acceptance. The peripheral taste response to sugar is mediated by the TAS1R2/TAS1R3 taste receptors. The aim of the study was to determine the relationship between TAS1R2 (rs35874116 or rs9701796) and/or TAS1R3 (rs307355) single nucleotide polymorphisms with dental caries experience in schoolchildren. A total of 184 schoolchildren aged between 7 and 12 years (101 girls, 83 boys) were included in the study. Genomic DNA was extracted from saliva samples and the genotypes were identified by qPCR. The genotype frequencies were as follows: 6.6% for homozygous wild type, 41.8% for heterozygous and 51.6% for homozygous polymorphic genotype carriers of TAS1R2 gene rs35874116; 27.8% for heterozygous and 72.2% for homozygous polymorphic genotype carriers of TAS1R2 gene rs9701796, and 83.1% for homozygous wild type and 16.9% for heterozygous genotype carriers of TAS1R3 gene rs307355 polymorphism. A significant association was observed between total caries experience (dft + DMFT - decayed filled primary teeth + decayed, missing and filled permanent teeth) and TAS1R2 rs35874116 (p = 0.008) and TAS1R3 rs307355 (p = 0.04) gene polymorphisms but not for TAS1R2 gene rs9701796 polymorphism. TAS1R3 gene rs307355 polymorphism has been found to be an independent risk factor for dental caries experience by logistic regression analysis and to have increased the risk of caries. Moderate caries experience (4-7 caries) was found to be associated with TAS1R3 rs307355 heterozygous genotype, whereas high-risk caries experience (>8 caries) was found to be associated with TAS1R2 rs35874116 homozygous polymorphic genotype.


Assuntos
Índice CPO , Polimorfismo de Nucleotídeo Único/genética , Receptores Acoplados a Proteínas G/genética , Papilas Gustativas/fisiologia , Paladar/genética , Fatores Etários , Criança , Citosina , DNA/genética , Suscetibilidade à Cárie Dentária/genética , Feminino , Frequência do Gene/genética , Genótipo , Guanina , Heterozigoto , Homozigoto , Humanos , Masculino , Saliva/química , Timina , Dente Decíduo/patologia , Escovação Dentária
7.
Chron Respir Dis ; 12(1): 61-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25480424

RESUMO

Patients with chronic obstructive pulmonary disease (COPD) who have nocturnal oxygen desaturation (NOD) can be treated with nocturnal oxygen therapy (NOT) to avoid possible morbidity and mortality. Although there is no definite data recommending NOT alone, our aim is to evaluate the relationship between desaturation during the six-minute walk test (6MWT) and NOD in COPD. Fifty-five stable patients with COPD were enrolled in this study. The 6MWT and nocturnal oximetry were performed. Patients with comorbid diseases and respiratory failure were excluded. In total, 55 patients (49 males and 6 females, mean age: 65.8 ± 8.4 years) were analysed. Twenty-seven of the patients had moderate COPD and the remainder (n = 28) had severe COPD. Three patients (11%) with moderate COPD and 12 patients (42.9%) with severe COPD desaturated during 6MWT (p = 0.003). NOD was observed in five patients with severe COPD (17.9%). There were no patients with NOD in the moderate COPD group. Three (25%) of patients with severe COPD who desaturated during the 6MWT also had NOD. NOD was more common in patients with severe COPD and the patients with higher carbon dioxide levels (p = 0.02 and p = 0.001). Three patients (11%) with moderate COPD desaturated during the 6MWT; however they did not have NOD. Although the sample size in this study was too small to be conclusive, NOD was more common in desaturators during the 6MWT particularly in patients with severe COPD.


Assuntos
Hipóxia/diagnóstico , Oximetria , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Sono , Idoso , Teste de Esforço , Feminino , Humanos , Hipóxia/etiologia , Hipóxia/terapia , Masculino , Pessoa de Meia-Idade , Oxigenoterapia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Índice de Gravidade de Doença , Caminhada
8.
Pituitary ; 16(3): 333-40, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22926673

RESUMO

The aim of this study was to evaluate patients with Cushing's disease (CD) who had undergone transsphenoidal surgery in terms of depression, quality of life (QoL), and perception of body image in comparison to healthy controls. Forty patients with CD and 40 healthy controls matched for demographic characteristics were included in the study. The subjects were evaluated with the Beck depression inventory (BDI), the health survey-short form (SF-36) and the multidimensional body-self relations questionnaire (MBSRQ). Subgroups of the patients with CD were formed on the basis of remission status and BDI scores. In this study, QoL in the general health category and body image were lower in the patients with CD than in the healthy subjects. However, no differences in depression scores were found between the two groups. When the CD group was evaluated according to remission rate, the mean BDI score was significantly higher in the CD patients without remission than in both the CD patients with remission and the healthy subjects (p = 0.04). However, the physical functioning, bodily pain and general health scores of the CD patients without remission on the SF-36 questionnaire were lower than in the CD patients in remission and the healthy subjects (p = 0.002, p = 0.04, p = 0.002, respectively). Fitness evaluation, health evaluation and body areas satisfaction scores of the MBSRQ were significantly different in the three groups (p = 0.003, p = 0.009 and p = 0.001, respectively). In this study, patients with CD were found to have lower QoL, lower body image perception and higher levels of depression compared to healthy controls, particularly if the disease is persistant despite surgery.


Assuntos
Imagem Corporal/psicologia , Depressão/diagnóstico , Hipersecreção Hipofisária de ACTH/psicologia , Hipersecreção Hipofisária de ACTH/cirurgia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipófise/cirurgia , Qualidade de Vida/psicologia
9.
Per Med ; 19(5): 435-444, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35880438

RESUMO

Aim: To investigate the association of DPYD, MTHFR and TYMS polymorphisms on 5-fluorouracil (5-FU) related toxicities and patient survival. Materials & methods: A total of 103 colorectal cancer patients prescribed 5-FU were included in the study. Genotyping was conducted for several DPYD, MTHFR and TYMS polymorphisms using a microarray analyzer. Results: DPYD 496A>G polymorphism was found to be significantly associated with 5-FU related grade 0-2, but not severe toxicities (p = 0.02). Furthermore, patients with DPYD 85TC and CC genotypes had longer progression and overall survival times compared to TT genotypes in our study group (log rank = 6.60; p = 0.01 and log rank = 4.40; p = 0.04, respectively). Conclusion: According to our results, DPYD 496AG and GG genotypes might be protective against severe adverse events compared to the AA genotype. Another DPYD polymorphism, 85T>C, may be useful in colorectal cancer prognosis. Further studies for both polymorphisms should be conducted in larger populations to achieve accurate results.


5-fluorouracil (5-FU) is a widely used drug for chemotherapy in colorectal cancer. In this study, we investigated the relationship between the severity of 5-FU induced adverse events and several variations in DPYD, MTHFR and TYMS genes, which encode the enzymes involved in 5-FU metabolism in a total of 103 colorectal patients. We also examined the relationship between the polymorphisms and progression-free and overall survival times of the patients in our study group. Among the variations, DPDY 496A>G polymorphism was found to be associated with 5-FU induced adverse events. Also, the DPYD 85T>C polymorphism was detected to be associated with longer progression-free and overall survival times.


Assuntos
Neoplasias Colorretais , Di-Hidrouracila Desidrogenase (NADP) , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Di-Hidrouracila Desidrogenase (NADP)/genética , Fluoruracila/efeitos adversos , Genótipo , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético/genética , Timidilato Sintase/genética
10.
Rheumatol Int ; 31(9): 1147-51, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20349071

RESUMO

Tumour necrosis factor-alpha (TNF-α) antagonist drugs have been associated with increased risk of tuberculosis (TB). Tuberculin skin test (TST) is the most frequently used tool for identification of latent TB infection. We herein aimed to analyse the effect of TNF-α antagonists on the TST responses in a prospective study. The study group consisted of 182 patients (99 female, 83 male) who received TNF-α antagonists for various rheumatic disorders. All patients were evaluated with TST along with other parameters on the day of referral and on the 12th month visit. For those patients with a response of <5 mm induration at the initial evaluation, the TST was repeated to observe the booster effect. Out of 182 patients, 87 patients (48%) had a negative (0-4 mm) and 95 (52%) had a positive (≥ 5 mm) TST response at initial evaluation. The TST responses were converted from negative at initial visit to positive at 1-year repeat in 26 (30%) patients. A significant increase was observed in the diameters of TST that were repeated on the first year of TNF-α antagonist treatment (9.15 ± 0.55) compared to their initial diameters (6.60 ± 0.51) (P < 0.001). Increased TST responses in patients receiving TNF-α antagonists may be associated with the restoration of suppressed immune reactivity against TB antigens with the decreased disease activity. The meaning of TST conversion in the definition of latent TB infection and the need for chemoprophylaxis in these patients remains to be answered by further studies.


Assuntos
Antirreumáticos/efeitos adversos , Tuberculose Latente/diagnóstico , Tuberculose Latente/etiologia , Doenças Reumáticas/tratamento farmacológico , Teste Tuberculínico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Antirreumáticos/uso terapêutico , Feminino , Humanos , Masculino , Estudos Prospectivos
11.
Curr Drug Saf ; 16(3): 252-258, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33413066

RESUMO

BACKGROUND: Clopidogrel has been commonly prescribed as a selective P2Y12 receptor antagonist to reduce heart attack and stroke risk. Nearly 10% of absorbed clopidogrel is metabolized to active forms by cytochrome P450 (CYP) enzymes in the liver and 90% to inactive clopidogrel carboxylate by esterases. OBJECTIVE: Since different forms of clopidogrel have cytotoxic potential, our aim was to determine the effect of 7.5, 40, and 75µM clopidogrel over DNA damage in adipocytes and hepatocytes. METHODS: In the present study, DNA damage was investigated by Comet analysis using 3T3-L1 adipocytes and Alpha Mouse 12 (AML-12) hepatocytes. RESULTS: DNA fragmentation was found to be increased as a response to 7.5 µM, 40 µM, and 75 µM clopidogrel treatment compared to non-treated control groups in AML-12 hepatocytes (p<0.01, p<0.001, p<0.01 respectively) and 3T3-L1 adipocytes (p<0.001, p<0.001 and p<0.001respectively). DNA damage levels as a response to clopidogrel treatment were found to be higher in 3T3-L1 adipocytes than AML-12 hepatocytes. Also, DNA damage levels in adipocytes and hepatocytes were found to increase dose-dependently for 7.5 and 40 µM clopidogrel, whereas decreased as a response to 75 µM. CONCLUSION: According to our results, clopidogrel results in more DNA damage in adipocytes than in hepatocytes. The molecular mechanism of clopidogrel genotoxicity needs to be further investigated especially in adipose tissue.


Assuntos
Adipócitos , Leucemia Mieloide Aguda , Células 3T3-L1 , Animais , Clopidogrel/toxicidade , Dano ao DNA , Hepatócitos , Humanos , Camundongos
12.
Rheumatol Int ; 30(11): 1459-63, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19844718

RESUMO

The objective of this study is to estimate the incidence of active tuberculosis in patients with inflammatory diseases receiving tumor necrosis factor-alpha (TNF-alpha) antagonists and to figure out the characteristics of patients who develop tuberculosis. 702 patients with different inflammatory diseases receiving TNF-alpha antagonists were followed up from August 2005 to July 2008 at our department of chest disease. All patients had tuberculin skin test (TST) and postero-anterior chest radiograph (CXR) prior to anti TNF-alpha antagonist treatment. All patients with a TST result > or =5 mm or fibrotic lesions on CXR were administered chemoprophylaxis with isoniazid (INH) for 9 months. 6 (0.85%) patients developed active tuberculosis (4 pulmonary and 2 extrapulmonary) during the follow-up period. TST was found to be positive in 434 (61.8%) of the patients. Patients, who were already on immunosuppressive therapy and who were not, were compared for the difference in their TST results and no statistically significant difference was found. Chemoprophylaxis was administered overall to 583 (83.0%) patients among which 31 (5.3%) developed hepatotoxicity. Of the patients who developed active tuberculosis, all were decided to receive INH chemoprophylaxis, however, only three of them adhered proper treatment. Diagnostic accuracy of TST for detecting latent tuberculosis is high among patients with inflammatory diseases even in the setting of immunosuppression. The risk of development of active TB is increased in this group of patients despite chemoprophylaxis, but this risk remains within the acceptable limits even in a moderate-tuberculosis incidence country, if proper chemoprophylaxis regimen is adhered.


Assuntos
Imunossupressores/efeitos adversos , Tuberculose/etiologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Antituberculosos/efeitos adversos , Antituberculosos/uso terapêutico , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Imunossupressores/uso terapêutico , Isoniazida/efeitos adversos , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco/métodos , Fatores de Risco , Tuberculose/prevenção & controle
13.
Future Cardiol ; 16(6): 645-654, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32583677

RESUMO

Aim: Our aim was to examine the effect of CYP2C9 and VKORC1 polymorphisms on warfarin dose requirements in Turkish patients. Materials & methods: 24 warfarin prescribed patients were included and analyzed for eight VKORC1 and 6 CYP2C9 polymorphisms in the study. Results: Patients with CYP2C9 *1/*1 and VKORC1 -1639 GG and GA genotypes required higher warfarin doses in comparison to wild type VKORC1 genotype. Patients with CYP2C9 *1/*3 and VKORC1 -1639 GG genotypes simultaneously, required the lowest dose of warfarin (4.64 mg/day). Patients with CYP2C9 *1/*1 and VKORC1 9041 AA genotype were found to require higher warfarin doses. Conclusion: Our results provide additional evidence to support the hypothesis that CYP2C9 *2, *3, VKORC1 9041 G > A polymorphisms explain considerable proportion of inter-individual variability in warfarin dose requirement.


Assuntos
Anticoagulantes , Varfarina , Citocromo P-450 CYP2C9/genética , Genótipo , Humanos , Polimorfismo Genético , Vitamina K Epóxido Redutases/genética
14.
J Diabetes Complications ; 34(2): 107449, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31677982

RESUMO

AIM: The aim of this study was to determine and compare the levels of both Bacteroidetes and Firmicutes in the gut microbiota and TLR2/TLR4 gene expression in the blood of patients with type 1 diabetes mellitus (T1DM) and healthy individuals. These results may serve as a preliminary assessment to guide future research. METHOD: Between January and October 2014, stool and blood samples were collected from 53 adult T1DM patients and 53 age- and gender-matched healthy individuals. Bacteroidetes and Firmicutes levels were assessed from stool sample DNA and TLR2 and TLR4 expression levels were analyzed via qPCR using RNA from EDTA blood samples from both patients and healthy controls. RESULTS: The amounts of Bacteroidetes and Firmicutes were statistically significantly higher and lower, respectively, in the T1DM group than in the healthy control group (p < 0.001 and p < 0.001, respectively). In addition, the Firmicutes/Bacteroidetes ratios in patients with T1DM were significantly lower than in healthy controls. The TLR4 and TLR2 gene expression levels in T1DM patients were significantly upregulated and downregulated, respectively, compared to those in the control group. CONCLUSION: Our data are the first to show a relationship between T1DM and gut microbiota in our country. In addition, our results provide information about the connections between T1DM, gut microbiota, and TLR2 and TLR4 expression. We believe that Bacteroidetes and Firmicutes in the gut microbiota may play a role in the autoimmune process of T1DM and that these findings should be further investigated in the future.


Assuntos
Bacteroidetes/imunologia , Diabetes Mellitus Tipo 1 , Firmicutes/imunologia , Microbioma Gastrointestinal , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Adulto , Bacteroidetes/isolamento & purificação , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/microbiologia , Feminino , Firmicutes/isolamento & purificação , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/imunologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/microbiologia , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Receptor 2 Toll-Like/imunologia , Receptor 4 Toll-Like/imunologia , Turquia , Adulto Jovem
15.
Ann Thorac Med ; 14(3): 192-197, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31333769

RESUMO

OBJECTIVES: Obesity hypoventilation syndrome (OHS) and some neuromuscular diseases (NMD) present with hypercapnic respiratory failure. Arterial blood gas (ABG) analysis is important in the diagnosis, follow-up, and treatment response of these diseases. However, ABG sampling is difficult in these patients because of excessive subcutaneous fat tissue, muscle atrophy, or contracture. The aim of this study is to investigate the value of venous blood gas (VBG), which is an easier and less complicated method, among stable patients with OHS and NMD. METHODS: The study included stable OHS and NMD patients who had been previously diagnosed and followed up between March 2017 and May 2017 in the outpatient clinic. ABG was taken from all patients in room air, and peripheral VBG was taken within 5 min after ABG sampling. RESULTS: Thirty-six patients with OHS and 46 patients with NMD were included in the study. There was a moderate positive correlation between arterial and venous pH values for all patients (r s = 0.590, P < 0.001). There were a strong and very strong positive correlations between arterial and venous pCO2 and HCO3 values (r s = 0.725 and r s = 0.934, respectively) (P < 0.001). There was no correlation between arterial and venous pO2 and saturation values. There was an agreement in Bland-Altman method for the values of ABG and VBG (pH, pCO2, and HCO3). CONCLUSIONS: There was a correlation between ABG and VBG values (pH, pCO2, and HCO3). VBG parameters (pH, pCO2, and HCO3) can be used safely instead of ABG parameters which have many risks, during treatment and follow-up of patients with OHS and NMD.

16.
Clin Respir J ; 12(4): 1668-1675, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29028148

RESUMO

OBJECTIVES: To evaluate the characteristics of patients who developed tuberculosis while receiving tumor necrosis factor-alpha (TNF-α) antagonists and the related factors with tuberculosis. METHODS: Patient's demographics, tuberculin skin test (TST), isoniazid prophylaxis and type of TNF-α antagonist were recorded. TST conversion (≥5 mm increase) was evaluated for patients who had baseline and 1-year TST. RESULTS: Files of 1887 patients who were receiving TNF-α antagonists between August 2005 and June 2015 were evaluated. TST significantly increased at the end of 1 year (n = 748 baseline:7.36 ± 7.2 mm vs. 1 year:9.52 ± 7.5 mm, P < 0.001). One-third of patients (31.2%) who had negative TST at baseline had positive TST at 1 year. Tuberculosis developed in 22 patients (1.16%). The annual incidence of tuberculosis was 423/100 000 patient-year. TNF-α antagonist indications were ankylosing spondylitis (n = 8), inflammatory bovel diseases (n = 7) and rheumatoid arthritis (n = 4). Ten (45.5%) patients received infliximab, six (27.3%) patients received etanercept and six (27.3%) patients received adalimumab. Nineteen (86.4%) patients were under isoniazid prophylaxis. Twelve patients had extrapulmonary tuberculosis (54.5%; four lymph node, three pleura, two periton, one pericarditis, one intestinal, one joint). Atypical mycobacterium was detected in one patient. Adalimumab treatment (9.5× increase), male sex (15.6× increase) and previous tuberculosis disease history (11.5× increase) were risk factors for active tuberculosis. Conversion of TST was not found related with tuberculosis. CONCLUSIONS: Despite the high proportion of isoniazid prophylaxis, the incidence of tuberculosis in our patients receiving TNF-α antagonist was higher than the literature. Adalimumab treatment, male sex and previous tuberculosis disease history were found as risk factors for tuberculosis.


Assuntos
Adalimumab/efeitos adversos , Doenças do Tecido Conjuntivo/tratamento farmacológico , Isoniazida/uso terapêutico , Medição de Risco , Teste Tuberculínico/métodos , Tuberculose/epidemiologia , Adalimumab/uso terapêutico , Adulto , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Antituberculosos/uso terapêutico , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Tuberculose/etiologia , Tuberculose/prevenção & controle , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Turquia/epidemiologia , Adulto Jovem
17.
Dis Markers ; 23(3): 161-6, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17473385

RESUMO

Our aim was to determine whether lipoprotein lipase gene PvuII polymorphism can be considered as an independent risk factor for coronary artery disease (CAD) by conducting a meta-analysis of all available published trials, including our own study. In 7 seperate studies, 3289 subjects were screened for this substitution; meta-analysis included only some of these individuals. Among the 7 studies, 6 were performed on white subjects, whereas 1 was on patients with Saudi Arabic descent.Subgroup analysis indicated that individuals with PvuII substitution does not have an increased risk for CAD. The LPL-PvuII genotype and allele frequency distributions did not differ significantly between CAD patients and healthy controls. There was no difference in the distribution of LPL-PvuII genotypes between the healthy subjects and the patients with CAD. However, no significant differences in lipid variables (triglyceride and HDL-cholesterol) were determined for the PvuII polymorphisms in the patients with CAD. No significant differences were found in serum triglyceride and HDL-cholesterol levels for LPL-PvuII genotypes when the control and CAD groups were pooled. In conclusion, LPL-Pvu II polymorphism cannot be used as independent genetic risk factor for CAD.


Assuntos
Doença da Artéria Coronariana/genética , Desoxirribonucleases de Sítio Específico do Tipo II , Predisposição Genética para Doença , Lipídeos/sangue , Lipase Lipoproteica/genética , Polimorfismo Genético , Estudos de Casos e Controles , Doença da Artéria Coronariana/sangue , Humanos
19.
Acta Histochem ; 107(3): 199-205, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15993477

RESUMO

Estrogens and antiestrogens are known to have effects on prolactin (PRL)-producing cells in the anterior pituitary. This study was planned to investigate the effects of estrogen and tamoxifen at immunohistochemical and immunoelectron microscopic levels on PRL cells of female rat pituitary. Animals were divided into three groups of eight adult female rats each. The first group was the control group. 200-microg/day of estrogen was administered subcutaneously for 11 weeks to 16 rats. Tamoxifen was administered to eight of them for the last 15 days. In diethylstilbestrol (DES)-induced group, serum PRL levels and pituitary weights were found to be elevated when compared with the control group. In the DES plus tamoxifen group the readings were close to that of the control group. PRL-positive cells were enlarged and strongly immunostained in DES-induced group when assessed by light microscopy. Tamoxifen prevented this effect. At the ultrastructural level, in the tamoxifen treated group, PRL-producing cells contained both immunopositive and immunonegative secretory granules. Numerous PRL-producing cells exhibited progressive morphological changes in the nuclei compatible with the apoptotic process. The results of this study indicate that tamoxifen prevents not only the proliferative effect of estrogen but also inhibits the secretion mechanism of the cells.


Assuntos
Dietilestilbestrol/farmacologia , Antagonistas de Estrogênios/farmacologia , Estrogênios não Esteroides/farmacologia , Imuno-Histoquímica , Adeno-Hipófise/efeitos dos fármacos , Prolactina/metabolismo , Tamoxifeno/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/ultraestrutura , Feminino , Técnicas Imunoenzimáticas , Injeções Subcutâneas , Tamanho do Órgão/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Hipófise/patologia , Adeno-Hipófise/metabolismo , Adeno-Hipófise/patologia , Prolactina/sangue , Ratos , Ratos Wistar
20.
Anadolu Kardiyol Derg ; 5(2): 116-21, 2005 Jun.
Artigo em Turco | MEDLINE | ID: mdl-15939686

RESUMO

OBJECTIVE: To investigate the effects of phase II cardiac rehabilitation in 52 patients undergone coronary artery bypass surgery. METHODS: Gradual walking tests, cardio-pulmonary capacity tests and lipid profile were administered to patients selected for phase II cardiac rehabilitation before and after the programme. Training was started on 12-channel electrocardiogram controlled running bands 3 times a week for 20 min periods for 12 weeks fitting the programme. Low or intermediate level exercise programme was applied to patients. Cleveland Clinic Chronotropic Assessment exercise protocol was used during rehabilitation. RESULTS: As a result of phase II cardiac rehabilitation administered to 52 patients undergone coronary bypass operation, exercise capacity, oxygen consumption, anaerobic threshold, cardiac output mean values (p<0.001) and mean HDL cholesterol level (p<0.05) were found to increase, whereas body mass index, total cholesterol, LDL cholesterol and triglyceride mean levels reduced (p<0.001) significantly. CONCLUSION: In patients who have undergone coronary bypass surgery, phase II cardiac rehabilitation is a very useful programme in improvement of life quality and secondary prevention.


Assuntos
Ponte de Artéria Coronária , Tolerância ao Exercício , Infarto do Miocárdio/reabilitação , Infarto do Miocárdio/cirurgia , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/fisiopatologia , Consumo de Oxigênio , Triglicerídeos/sangue
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