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1.
Rheumatology (Oxford) ; 56(5): 844-852, 2017 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-28160477

RESUMEN

Objectives: The arachidonate 5-lipoxygenase activating protein (ALOX5AP) regulates synthesis of leukotrienes (LTs), which are important mediators of inflammation and connective tissue remodelling. The aim of this study was to evaluate if single nucleotide polymorphisms (SNPs) of ALOX5AP confer risk of SSc and/or SSc-related organ involvement. Methods: Seven SNPs of ALOX5AP (rs17222814, rs17216473, rs10507391, rs4769874, rs9551963, rs9315050 and rs7222842) were genotyped in a cohort of 977 patients with SSc and 558 healthy controls from centres collaborating within the European Scleroderma Trials and Research group. In 22 SSc patients, concentrations of cysteinyl LTs and LT B4 (LTB4) were measured in the supernatants of ionophore-stimulated peripheral blood mononuclear cells (PBMCs) by means of commercially available enzyme immunoassay kits. Results: Significant association was found between rs10507391 polymorphism (T/A) of ALOX5AP and the risk of SSc [odds ratio (OR) 1.27 (95% CI 1.07, 1.50), P < 0.05 vs controls], the presence of SSc-related interstitial lung disease on high-resolution CT of the lungs [OR 1.45 (95% CI 1.17, 1.79), P < 0.05 vs patients without SSc-related interstitial lung disease] as well as with restrictive ventilatory defect [forced vital capacity <70% of predicted; OR 1.51 (95% CI 1.16, 1.97), P < 0.05 vs SSc patients without pulmonary restriction]. PBMCs from SSc carriers of rs10507391 allele A synthesized greater amounts of cysteinyl LTs as compared with SSc patients with rs10507391 TT genotype ( P < 0.05). Synthesis of LTB4 did not differ significantly between the two groups. Conclusion: The results of our study indicate that the genetic variants of ALOX5AP might play a role in the development of SSc-related pulmonary fibrosis.


Asunto(s)
Proteínas Activadoras de la 5-Lipooxigenasa/genética , Polimorfismo de Nucleótido Simple/genética , Fibrosis Pulmonar/genética , Esclerodermia Sistémica/genética , Estudios de Casos y Controles , Células Cultivadas , Femenino , Frecuencia de los Genes , Heterocigoto , Homocigoto , Humanos , Leucocitos Mononucleares/fisiología , Masculino , Trastornos Respiratorios/genética
2.
Prz Menopauzalny ; 16(1): 12-18, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28546802

RESUMEN

Oestrogens act on target cells through α and ß receptors (ERα and ERß). Expression of oestrogen receptors is associated with the age and menopausal condition of women. The aim of the study was an immunohistochemical evaluation of ERα and ERß receptors in epithelium of the vaginal mucous membrane of women subjected to different forms of hormonal therapy (HTM). Oestrogen receptors ERα and ERß were identified using immunohistochemical methods and evaluated in smears of vaginal mucous membranes collected from 60 patients subjected to HTM (including 20 patients after oral therapy, 20 patients after transdermal therapy, and 20 patients after vaginal therapy). The results showed a significant change in immunoreactivity of both studied receptors after three months of hormone therapy. The biggest differences in the changes of intensity of ERα and ERß reactions were observed in patients subjected to vaginal therapy. Immunostaining for α receptor showed differences between three types of hormone therapy. The highest increase in the overall intensity occurred after three months of topical therapy. Immunostaining for Erß also varied for different types of hormone therapy. The results indicate that hormone therapy administered vaginally is the most effective in the treatment of urogenital ailments during menopause. In addition, topical therapy eliminates adverse effects of systemic oestrogen.

3.
Mediators Inflamm ; 2015: 340934, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25653477

RESUMEN

Purpose. To evaluate the relationship between the expression of orbital tissue mRNA for FOXP3, CTLA-4/CD28/CD80/CD86, and CD40/CD40 and the severity of Graves' orbitopathy (GO). Material and Methods. Orbital tissue was obtained from 26 patients with GO, with mild (n = 6) or severe GO (n = 20), and 7 healthy controls. The expression of mRNA of FOXP3, CTLA-4/CD28/CD80/CD86, CD40/CD40L was measured by RT-PCR. TCR and CD3 were evaluated by immunohistochemistry. Results. Higher mRNA for FoxP3 (relative expression: 1.4) and CD40 (1.27) and lower expression of CTLA-4 (0.61) were found in the GO tissues versus controls. In severe GO as compared to mild GO higher mRNA expression for FoxP3 (1.35) and CD40 (1.4) and lower expression for CTLA-4 (0.78), CD28 (0.62), and CD40L (0.56) were found. A positive correlation was found between FOXP3 mRNA and CD3 infiltration (R = 0.796, P = 0.0000001). Conclusions. The enhanced FOXP3 mRNA expression in GO samples may suggest the dysfunction of FOXP3 cells in the severe GO. The diminished mRNA expression of CTLA-4 in severe GO may indicate inadequate T regulatory function. The enhanced mRNA expression of CD40 in severe GO and negative correlation to CRP mRNA may suggest their role in the active and inactive GO.


Asunto(s)
Antígenos B7/genética , Antígenos CD28/genética , Antígenos CD40/genética , Ligando de CD40/genética , Antígeno CTLA-4/genética , Factores de Transcripción Forkhead/genética , Oftalmopatía de Graves/genética , Oftalmopatía de Graves/metabolismo , Adulto , Complejo CD3/metabolismo , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
4.
Tumour Biol ; 35(5): 4619-28, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24500664

RESUMEN

As the current staging system is imprecise for estimating prognosis of early stage non-small cell lung cancer (NSCLC), it is important to identify other methods for selecting high-risk patients after failed surgical treatment. The aim of the study was to evaluate the expression of 23 genes as putative prognostic markers in early stage NSCLC. The study was performed on 109 pairs of tumor and matched unaffected lung tissue surgical specimens taken from stage I and II NSCLC patients. We evaluated the mRNA level of 23 genes using the real-time PCR method. The difference in the expression between the tumor and normal tissue for each gene was analyzed using a general linear model. The influence of gene expression on survival was analyzed by using the proportional hazards model. Eighteen out of the 23 genes showed statistically significant differences in expression between the tumor and non-tumor tissue. For 12 genes (ITGB1, ITGB3, CXCL1, CXCL8, CXCL9, CXCL10, CXCL11, CXCR3, CXCR4, TNF, CHKA, AGFG1, and CTC1), the expression was lower, and for six genes (ITGA5, IL8, IL6, CXCL2, CXCL3, and CXCL12), it was higher in the tumor tissue as compared to the matched normal tissue. Expression changes were more pronounced in squamous cell carcinomas than in adenocarcinomas or large cell carcinomas. Of all the analyzed genes, only CXCL5 was found to statistically significantly (p = 0.04) influence both overall and disease-free survival. Among the 23 genes previously suggested to be relevant for early staged NSCLC patients' postoperative outcome, only CXCL5 showed a statistically significant prognostic effect.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Quimiocina CXCL5/genética , Neoplasias Pulmonares/genética , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Reacción en Cadena en Tiempo Real de la Polimerasa
5.
Mediators Inflamm ; 2014: 412158, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25309050

RESUMEN

PURPOSE: To assess FGF-ß, TGF-ß, and COX2 expression and immunocompetent cells in the orbital tissue of patients with severe and mild Graves' orbitopathy. PATIENTS AND METHODS: Orbital tissue was taken from 27 patients with GO: (1) severe GO (n = 18), the mean clinical activity score (CAS) being 8.5 (SD 2.5); and (2) mild GO (n = 9), the mean CAS being 2.2 (SD 0.8), and from 10 individuals undergoing blepharoplasty. The expression of CD4+, CD8+, CD20+, and CD68 and FGF-ß, TGF-ß, and COX2 in the orbital tissue was evaluated by immunohistochemical methods. RESULTS: We demonstrated predominant CD4+ T cells in severe GO. CD68 expression was observed in the fibrous connective area of mild GO and was robust in severe GO, while the prominent TGF-ß expression was seen in all GO. Increased FGF-ß expression was observed in the fibroblasts and adipocytes of severe GO. No expression of COX2 was found in patients with GO. CONCLUSIONS: Macrophages and CD4 T lymphocytes are both engaged in the active/severe and long stage of inflammation in the orbital tissue. FGF-ß and TGF-ß expression may contribute to tissue remodeling, fibrosis, and perpetuation of inflammation in the orbital tissue of GO especially in severe GO.


Asunto(s)
Tejido Adiposo/metabolismo , Tejido Conectivo/metabolismo , Fibrosis/metabolismo , Oftalmopatía de Graves/metabolismo , Inflamación/metabolismo , Órbita/metabolismo , Adulto , Biomarcadores/metabolismo , Femenino , Humanos , Inmunohistoquímica , Técnicas In Vitro , Masculino , Persona de Mediana Edad
6.
J Neurooncol ; 115(1): 119-25, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23877362

RESUMEN

Meningiomas are common primary brain tumors. However, they are often complicated by significant peritumoral brain edema, which leads to surgery difficulties and prolonged hospitalization. The aim of this study was to evaluate the presence of mast cells and expression of hypoxia inducible factor-1 (HIF-1) in correlation with the grade of meningioma and presence of peritumoral brain edema. Immunohistochemistry was performed with specific antibodies against tryptase (mast cells) and HIF-1 in low grade meningiomas (estimated as G1) and high grade meningiomas (estimated as G2 or G3). Peritumoral brain edema observed in MRI was graded using Steinhoff classification. Tryptase expression was observed in 40.4 % low grade meningiomas and in 90 % high grade cases; HIF-1 in 55.7 % low grade and in 84 % high grade meningiomas. There was a statistically significant correlation between HIF-1 and tryptase expression in both groups (p = 0.003). Presence of peritumoral brain edema statistically correlated with tryptase (p = 0.001) and HIF-1 expression (p = 0.004). Mast cells as well as hypoxia are involved in meningioma progression, and may be associated with the formation of peritumoral brain edema leading to surgery complication and recovery. Therefore, they may be useful markers in predicting the clinical course of meningioma cases.


Asunto(s)
Biomarcadores/metabolismo , Edema Encefálico/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Mastocitos/patología , Neoplasias Meníngeas/metabolismo , Meningioma/metabolismo , Edema Encefálico/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Mastocitos/metabolismo , Neoplasias Meníngeas/patología , Meningioma/patología , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Triptasas/metabolismo
7.
Int J Neurosci ; 123(9): 657-62, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23550771

RESUMEN

PURPOSE: Primary brain tumors are common type of neoplasms. The most common are astrocytic tumors, so do meningiomas of various grades. The etiology is still unknown; however, there are lots of data presenting new theories about genetic alterations responsible for low- or high-grade astrocytic tumors development as well as meningiomas, despite this the results are divergent. The aim of the study was to evaluate hypoxia-inducible factor-1 (HIF-1) expression in meningiomas and astrocytic tumors of various grades. MATERIAL AND METHODS: One hundred six cases of astrocytic tumors were divided into diffused astrocytoma (24 cases), anaplastic astrocytoma (40 cases) and glioblastoma groups (42 cases). Among glioblastoma group, 30 cases were secondary glioblastoma. One hundred fifty-four meningioma cases were divided as low-grade meningioma (G1: 104 cases) and high-grade meningioma groups (G2: 43 cases and G3: 7 cases). Twelve low-grade meningiomas transformed into high-grade tumors, 17 low-grade meningiomas recur within 12 years. HIF-1 expression was estimated using immunohistochemistry under the light microscope. Statistical analysis was performed in all examined groups. RESULTS: HIF-1 expression was observed in 37.5% cases of diffused astrocytomas, in anaplastic astrocytomas 27.5% tumors were HIF-1 positive, in the glioblastoma goup HIF-1 expression was observed in 83.3% cases. All secondary glioblastomas were positive for HIF-1. Low-grade meningiomas were positive for HIF-1 in 55.7%, in high-grade meningiomas, HIF-1 expression was observed in 84%. All meningiomas, which progressed from low- to high-grade meningiomas, were HIF-1 positive. CONCLUSION: HIF-1 expression is associated with the development and progression of both astrocytic tumors and meningiomas.


Asunto(s)
Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Meníngeas/metabolismo , Meningioma/metabolismo , Neoplasias Encefálicas/clasificación , Neoplasias Encefálicas/patología , Femenino , Glioma/clasificación , Glioma/patología , Humanos , Masculino , Neoplasias Meníngeas/patología , Meningioma/patología , Persona de Mediana Edad
8.
Exp Lung Res ; 38(6): 281-5, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22646306

RESUMEN

Although a direct association between mast cells and cancer tumors is generally accepted, the exact nature of this relationship appears contradictory. The aim of this study was to clarify the effect of mast cells on tumor angiogenesis and outcome in Non-small cell lung cancer (NSCLC) patients. The tissue specimens evaluated were from patients with NSCLC who had undergone resection with curative intent at the Medical University of Bialystok Hospital. Of the 90 patients studied, 67 were men. Average age at surgery was 59.68 years. Study population included 29 cases of adenocarcinoma, 44 cases of squamous cell carcinoma, and 17 cases of large cell carcinoma. The authors counted mast cells and microvessels in tumor sections. Mast cells were observed in small groups around vessels and in the cancer parenchyma. At a magnification of 200×, the number of mast cells was 28.90 ± 16.6. Intramural microvessels in endothelial cells were found in small groups, mostly at the margin. At a magnification of 200×, the number of microvessels was 221.69 ± 120.36. Spearman correlation was observed in patients with adenocarcinoma, and also in patients with stage II disease. This study did not show correlation between mast cells count and survival rate, and correlation between microvessel count and survival rate. In this study, mast cells infiltration of the tumor islets was not associated with patients' survival. The authors did not find correlation between mast cells count and angiogenesis, except only in patients with adenocarcinoma, and in patients with stage II disease.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/irrigación sanguínea , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/irrigación sanguínea , Neoplasias Pulmonares/patología , Mastocitos/patología , Recuento de Células , Células Endoteliales/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Microvasos/patología , Persona de Mediana Edad , Neovascularización Patológica/patología , Pronóstico
9.
Acta Obstet Gynecol Scand ; 91(8): 936-43, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22568870

RESUMEN

OBJECTIVE: To analyse the expression of 15 genes encoding receptors and enzymes associated with the molecular mechanism of the tocolytic drugs atosiban (oxytocin receptor antagonist), nifedipine (calcium channel blocker) and celecoxib (selective cyclo-oxygenase-2 inhibitor) in preterm labor patients with premature rupture of fetal membranes in relation to symptoms of intrauterine infection and preterm labor risk factors. DESIGN: Experimental molecular study. SETTING: Tertiary obstetric care center. SAMPLE: Myometrial samples were obtained during cesarean sections from 35 patients who delivered preterm with unverified symptoms of intrauterine infection, 35 patients who delivered preterm without symptoms of intrauterine infection and 90 women who delivered at term. METHODS: The Micro Fluidic Profiling Card analytic system was used to evaluate mRNA expression of the genes of interest. MAIN OUTCOME MEASURES: The relative quantification values for mRNA expression. RESULTS: The median oxytocin receptor and cyclo-oxygenase-2 mRNA expression in preterm patients with clinical symptoms of intrauterine infection was significantly higher than in preterm patients without symptoms. The median mRNA expression of ß(1) , ß(3) and ß(4) subunits of the L-type calcium channel and prostaglandin E(2) receptor was significantly higher in preterm patients compared with term patients. CONCLUSIONS: The mRNA expression of hormones, enzymes and their receptors associated with tocolytic actions can differ in various clinical conditions. The expression of these genes is regulated at different levels and can be modified by inflammatory factors, which affect their functions.


Asunto(s)
Canales de Calcio Tipo L/metabolismo , Dinoprostona/metabolismo , Rotura Prematura de Membranas Fetales/metabolismo , Perfilación de la Expresión Génica , Trabajo de Parto Prematuro/tratamiento farmacológico , Trabajo de Parto Prematuro/metabolismo , Tocolíticos/farmacología , Adulto , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio Tipo L/genética , Celecoxib , Inhibidores de la Ciclooxigenasa 2/farmacología , Dinoprostona/genética , Endometritis/microbiología , Femenino , Regulación del Desarrollo de la Expresión Génica , Humanos , Nifedipino/farmacología , Oxitócicos/farmacología , Embarazo , Segundo Trimestre del Embarazo , Tercer Trimestre del Embarazo , Nacimiento Prematuro/tratamiento farmacológico , Nacimiento Prematuro/metabolismo , Pirazoles/farmacología , ARN Mensajero/metabolismo , Sulfonamidas/farmacología , Nacimiento a Término/metabolismo , Tocolíticos/uso terapéutico , Vasotocina/análogos & derivados , Vasotocina/farmacología
10.
Med Sci Monit ; 17(8): BR216-220, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21804458

RESUMEN

BACKGROUND: Astrocytic tumors are the primary brain tumors, which often progress to glioblastoma, a highly malignant neoplasm of the central nervous system. There is much new data regarding to the formation and progression of these tumors; however, glioblastoma remains one of the most fatal neoplasms in humans. The aim of the study was to evaluate the role of c-erbB-2 protein expression in various groups of astrocytic tumors. MATERIAL/METHODS: 65 cases of astrocytic tumors were divided into 3 groups: diffuse astrocytoma (group I; n=17 cases), anaplastic astrocytoma (group II; n=23 cases) and glioblastoma (group III; n=25 cases). C-erbB-2 protein expression was estimated semiquantitatively on immunohistochemically stained tissue sections using antibodies against c-erbB-2 protein. Statistical analysis was performed in all examined groups. RESULTS: The c-erbB-2 protein expression was observed in 15 out of 17 cases (88.3%) in group I, 22 out of 25 cases (88%) cases in group II, and in 19 out of 23 cases (82.6%) in group III. There were no statistically significant differences between the examined groups. The strongest c-erbB-2 immunoexpression was observed in low grade astrocytomas (diffuse astrocytomas G2); in the glioblastoma group the c-erbB-2 protein expression was weak and 17.4% of cases were negative. CONCLUSIONS: C-erbB-2 protooncogene alteration is an early phenomenon in glial tumor development and progression.


Asunto(s)
Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Receptor ErbB-2/metabolismo , Astrocitoma/patología , Neoplasias Encefálicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Receptor ErbB-2/genética
11.
Int J Cancer ; 127(3): 612-21, 2010 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-19960433

RESUMEN

This study was conducted to evaluate the significance of circulating free DNA (CFDNA), p53 antibody (p53-Ab) and mutations of KRAS gene in the development of endometrial cancer (EC). A total of 109 patients with EC (87 patients with Type I and 22 patients with Type II) took part in this study. KRAS mutations and CFDNA were detected by means of the PCR-RFLP and enriched by the PCR-RFPL method. ELISA was used to analyze plasma p53-Ab. Tissue expression of P53 protein was evaluated immunohistochemically (IHC). The frequency of KRAS mutations was especially high in Grade 2 of Type I EC. CFDNA was frequently detected in patients with early stage of Type II EC at a low level of grade. It is noteworthy that the p53-Ab positive rate increased in the higher grade of Type I tumors. A significant difference in the number of cases with the p53-Ab was found in the advanced stage of Type I tumors. The frequency of KRAS and p53-Ab correlates with tumor stage only in the Type I EC. Plasma CFDNA and p53-Ab offer a chance to develop a procedure for EC Type II diagnosis. The association between tumor cells related to CFDNA and p53-Ab with Type II tumor suggests that it might potentially serve as a marker in predicting the prognosis and offers a possibility to individualize treatment regimen.


Asunto(s)
ADN/sangre , Neoplasias Endometriales/genética , Genes ras , Mutación Puntual , Proteína p53 Supresora de Tumor/inmunología , Anciano , Anticuerpos/sangre , Secuencia de Bases , Cartilla de ADN , Neoplasias Endometriales/sangre , Neoplasias Endometriales/inmunología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción
12.
Ginekol Pol ; 81(6): 422-5, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20695190

RESUMEN

BACKGROUND: Angiogenesis is of crucial importance for endometrial tumor growth and Vascular Endothelial Growth Factor (VEGF) is the key mediator of angiogenesis. OBJECTIVE: The purpose of our study was to assess the prognostic value of VEGF and its receptors in relation to endometrioid endometrial carcinomas. MATERIAL AND METHODS: In this study we conducted an immunohistochemical evaluation of VEGF and VEGFRs expression in 84 tissue samples obtained from endometrioid endometrial cancer patients undergoing curative surgical treatment. RESULTS: Out of 84 cancers, strong positive expression of VEGF was seen in 35 (42%) tumors. The overall strong positive rates were 33% for VEGFR-1 and for 15% for VEGFR-2. There was a significant correlation between clinical stage and VEGF and VEGFR-1 overexpression (p=0.027 and p=0.004, respectively). Additionally there was a significant correlation between histological grade and VEGF and VEGFR-1 overexpression (p<0.001 and p<0.01, respectively). The 5-year DFS of patients with VEGF and VEGFR-1 overexpression was significantly lower than that of those with a weakly positive or negative tumor (p<0.001). CONCLUSION: Immunohistochemical evaluation of VEGF and VEGFR-1 overexpression may be a useful marker for predicting 5-year DFS in endometrioid endometrial cancer.


Asunto(s)
Carcinoma Endometrioide/metabolismo , Neoplasias Endometriales/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Anciano , Carcinoma Endometrioide/patología , Supervivencia sin Enfermedad , Neoplasias Endometriales/patología , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Polonia , Pronóstico , Análisis de Supervivencia
13.
Pharmacol Rep ; 61(3): 496-503, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19605949

RESUMEN

Diabetes causes changes in the myocardium, which are often called diabetic cardiomyopathy. This condition has been extensively investigated in animal models with high glucose levels. Nevertheless, it has not been investigated whether moderate hyperglycemia, in the absence of other features of metabolic syndrome, may also cause similar changes in the heart. The aim of the study was to assess changes in the myocardium in an animal model of mild type 1 diabetes. Moderate hyperglycemia was induced in 8- to 10-week-old male C57BL6J mice by 5 intraperitoneal injections of streptozotocin (40 mg/kg). After 16 weeks, they were sacrificed, and left ventricle (LV) dimensions and extent of cardiac fibrosis were assessed by morphometry. The abundance of CCN proteins in LVsamples was assessed using western blotting, while activity of metalloproteinase 2 was established in zymography. Real time PCR was used to investigate the expression of transforming growth factor beta1 (TGFbeta1) and atrial natriuretic peptide. Mice with moderate hyperglycemia presented comparable cardiac dimensions with fibrosis and hypertrophy parameters as the non-diabetic controls. However, the abundance of profibrotic CCN2 protein was significantly increased in hyperglycemic animals (1.67 +/- 0.28 vs. 1 +/- 0.47, p < 0.05). Interestingly, this change was independent from the TGFbeta1 expression, as its RNA abundance was similar in both groups. Moderate hyperglycemia also caused an increase in the activity of the metalloproteinase 2 (1.21 +/- 0.17 vs. 1 +/- 0.07, p < 0.05). Despite diabetes, no profound changes in cardiac morphology were found. In our animal model, moderate hyperglycemia caused activation of a profibrotic gene expression program, which was counterbalanced by the increase of metalloproteinase activity.


Asunto(s)
Biomarcadores/metabolismo , Cardiomiopatías/diagnóstico , Cardiomiopatías/patología , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Diabetes Mellitus Experimental/patología , Hiperglucemia/patología , Miocardio/patología , Remodelación Ventricular , Animales , Factor Natriurético Atrial/metabolismo , Proteínas CCN de Señalización Intercelular/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Modelos Animales de Enfermedad , Hiperglucemia/inducido químicamente , Hiperglucemia/complicaciones , Hiperglucemia/metabolismo , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Miocardio/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo
14.
Pharmacol Rep ; 61(3): 504-13, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19605950

RESUMEN

Interleukin 6 (IL-6) is a pleiotropic cytokine that is highly expressed in response to ischemia and reperfusion. It has dichotomous roles in the heart, functioning both as an inflammatory mediator as well as a protective agent. The aim of this study was to evaluate the effect of IL-6 deficiency on the expression of apoptotic regulatory proteins under both baseline conditions and following induction of ischemia and reperfusion in the mouse heart. C57BL/6J IL-6-/-(TMKopf) (IL6KO) and C57BL/6J mice (WT) were subjected to 30 minutes of local reversible myocardial ischemia in vivo or a sham operation. The expression of Bcl-2, Bax and STAT3 in the heart was assessed by western blotting. Under both baseline conditions and following the sham operation, IL-6 deficiency was associated with reduced expression of Bcl-2 and Bax. The TUNEL-FITC, Evans blue and tetrazolium chloride staining of the hearts following ischemia and reperfusion revealed similar injury in operated IL6KO and WT animals. There was increased STAT3 phosphorylation in operated mice regardless of the genotype. Bcl-2 and Bax expression was also comparable between the mouse strains following ischemia and reperfusion. In summary, these results indicated that IL-6 deficiency affected the basal expression of apoptotic regulators, but this did not profoundly alter the extent of reperfusion injury or apoptosis in the mouse heart following ischemia and reperfusion.


Asunto(s)
Proteínas Reguladoras de la Apoptosis/metabolismo , Apoptosis/genética , Ventrículos Cardíacos/metabolismo , Interleucina-6/fisiología , Proteínas Proto-Oncogénicas/metabolismo , Daño por Reperfusión/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Animales , Modelos Animales de Enfermedad , Ventrículos Cardíacos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Proto-Oncogénicas c-bcl-2 , Daño por Reperfusión/patología , Factor de Transcripción STAT3/metabolismo
15.
J Clin Virol ; 42(2): 156-9, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18353714

RESUMEN

BACKGROUND: Understanding the distribution of HCV genotypes has implications for prognosis and therapy of hepatitis C. OBJECTIVES: To describe the distribution of HCV genotypes in Poland in relation to route of transmission and year of infection. STUDY DESIGN: Patients with chronic liver disease were evaluated at the Department of Infectious Diseases, Bialystok (Poland). HCV genotype was determined by means of 5'UTR sequencing and comparison with known sequences of particular genotypes. RESULTS: The genotypes mostly frequently detected were genotype 1 (57.5%); genotype 3 (31.3%); and genotype 4 (8.4%). Genotype 1 constituted the majority of HCV infections caused by blood transfusion (68.8%) and only 34.8% of HCV infections in the intravenous drug use (IVDU) group (p<0.05). In contrast genotype 3 constituted the majority of HCV infections in the IVDU group (56.5%). We observed a significant increase in the proportion of genotype 3 infections detected after 2000--from 19.1% to 38.9%. CONCLUSIONS: The relative proportion of genotype 1b in Poland has decreased and that of genotype 3a has increased, especially among IVDU.


Asunto(s)
Hepacivirus/clasificación , Hepacivirus/genética , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/transmisión , Regiones no Traducidas 5'/genética , Adulto , Femenino , Genotipo , Hepacivirus/aislamiento & purificación , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Polonia/epidemiología , Reacción en Cadena de la Polimerasa , ARN Viral/sangre , Factores de Riesgo , Análisis de Secuencia de ADN , Abuso de Sustancias por Vía Intravenosa/complicaciones , Factores de Tiempo , Reacción a la Transfusión
16.
Thromb Res ; 123(1): 166-70, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18452978

RESUMEN

INTRODUCTION: The aim of the present study was to establish whether the presence of chronic viral hepatitis (PVH) could be implicated in the elevation of oxidative stress (SOX) and haemostasis system in haemodialysis (HD) patients. MATERIALS AND METHODS: In HD patients with and without PVH and in controls we compared the markers of: coagulation pathway- tissue factor (TF) and its inhibitor (TFPI), prothrombin fragment F (1+2) (F (1+2)); fibrinolysis: tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA) and its soluble receptor (suPAR), plasminogen activator inhibitor 1 (PAI-1), plasmin/antiplasmin complexes (PAP); and a marker of SOX-Cu/Zn superoxide dismutase (Cu/Zn SOD) levels. RESULTS: Patients, particularly those with PVH, showed a significant increase in the markers of the coagulation, fibrinolysis and oxidative status as compared to controls. All parameters of coagulation/fibrinolysis system were directly associated with the PVH and Cu/Zn SOD levels, and there was a relationship between the PVH and Cu/Zn SOD levels. Multivariable analysis showed that PVH and increased SOX were identified as independent variables significantly associated with the disturbances of coagulation/fibrinolysis system in these patients. CONCLUSIONS: We concluded that PVH is a novel determinant of the increased oxidative stress as well as the disturbances of coagulation/fibrinolysis system in haemodialysis patients.


Asunto(s)
Coagulación Sanguínea , Fibrinólisis , Hepatitis C Crónica/sangre , Estrés Oxidativo , Diálisis Renal , Adulto , Anciano , Femenino , Hepatitis C Crónica/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Superóxido Dismutasa/sangre
17.
Clin Chim Acta ; 389(1-2): 61-6, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18155162

RESUMEN

BACKGROUND: Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases associated with tumor progression. It was proved that expression of MMP-9 in human esophageal cancer tissues correlated with stages of the disease. The aim of the present study was to determine potential clinical use of serum MMP-9 as a tumor marker of esophageal cancer. METHODS: The study included 89 patients with esophageal cancer and 30 healthy subjects (control group). We assayed serum levels of MMP-9 and classical tumor markers (SCC-Ag and CEA). We defined the prognostic value and diagnostic criteria for the measurands. RESULTS: Serum levels of MMP-9, CEA and SCC-Ag in esophageal cancer (EC) patients were statistically higher than in the control group. MMP-9 serum concentrations were associated with clinical stages of EC and tumor size. The diagnostic sensitivity of MMP-9 (70%) was higher than tumor markers and increased in combination with SCC-Ag (92%). The area under the ROC curve for MMP-9 (0.733) was lower than for SCC-Ag (0.811) and higher than for CEA (0.673). In Cox's univariate analysis serum MMP-9, SCC-Ag and CEA were not significant for prognosis of EC. CONCLUSION: The results suggest the usefulness of MMP-9 as a tumor marker in diagnosis, but not in prognosis of esophageal cancer.


Asunto(s)
Antígenos de Neoplasias/sangre , Biomarcadores de Tumor/sangre , Antígeno Carcinoembrionario/sangre , Neoplasias Esofágicas/sangre , Metaloproteinasa 9 de la Matriz/sangre , Serpinas/sangre , Anciano , Estudios de Casos y Controles , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Curva ROC , Sensibilidad y Especificidad
18.
Przegl Epidemiol ; 62 Suppl 1: 62-8, 2008.
Artículo en Polaco | MEDLINE | ID: mdl-22320038

RESUMEN

UNLABELLED: Bacteria virulent proteins, among other vacA, have a significant role in the occurrence of gastric mucositis. AIM: The aim of the study was the evaluation of occurrence rate of alleles s1 and s2 of Helicobacter pylori vacA genome in children and adults, inhabitants of the Podlasie province. It was also to determine the correlation between infection with a determined s1 or s2 vacA genotype of the bacterium and the degree of severity and activity of antral mucositis. METHODS: 68-H. pylori infected persons (38 children and 30 adults) were examined, vacA genotypes of 70 H. pylori strain were evaluated. RESULTS: The degree of inflammatory changes in antral mucosa was differentiated and depended on vacA alleles of H. pylori strain. Allele s1 more frequently coexisted with moderate and severe antral mucositis in adults than in children (56.3% vs 50,0%, respectively). Allele s1 occurrence correlated with high activity inflammation in 47.5% of cases, medium activity--18.6%, and low activity--5.1%. CONCLUSIONS: Allele s1 was more frequently stated both in children and adults (86.8% and 81.3%, respectively) as compared to allele s2. Allele s1 also more frequently coexisted with low-activity inflammation or with no-activity inflammation of antral mucositis in children than in adults (36.8% vs 18.8%, respectively).


Asunto(s)
Proteínas Bacterianas/genética , Mucosa Gástrica/patología , Genoma Bacteriano/genética , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/genética , Polimorfismo Genético , Adolescente , Adulto , Alelos , Niño , Preescolar , Femenino , Mucosa Gástrica/microbiología , Frecuencia de los Genes , Infecciones por Helicobacter/patología , Humanos , Masculino , Persona de Mediana Edad , Polonia , Adulto Joven
19.
Przegl Epidemiol ; 62 Suppl 1: 69-74, 2008.
Artículo en Polaco | MEDLINE | ID: mdl-22329018

RESUMEN

UNLABELLED: Intensity of gastric mucosa and/or duodenal inflammation and their clinical consequences in response to Helicobacter pylori infection depend on a given strain virulence. A receptor protein IceA, induced by contact with epithelium gene A, is one of important proteins in the process of infection. Examinations of iceA genotype have show that the rate of occurrence of H. pylori strains containing iceA1 or iceA2 is differentiated in various regions of the world. OBJECTIVE: The aim of the study was the evaluation of H. pylori iceA alleles occurrence in infected children and adults, inhabitants of the Bialystok Province regarding the place of living (country, town). METHODS: H. pylori genotyping was carried out on the basis of the analyses bacterial gene iceA, and allelo-specific PCR were used to determine the former gene and two variants of the gene--iceA1 and iceA2. RESULTS: Out of 50 analyzed genotypes of H. pylori , the presence of iceA gene was observed in 47 strains of bacteria. iceA allele was presented in 25 isolates of examined bacteria DNA (53.2%) while iceA2--in 29 (61.7%). No iceA alleles were isolated from 3 DNA isolates (6%) whereas in 7 examined isolates (14.0%), the coexistence of both iceA alleles (iceA1 and iceA2) was observed. After excluding isolates of H. pylori DNA with coexisting iceA1 and iceA2 (7 persons), it was stated that iceA1 allele occurred in 19 examined isolates (45.0%) and iceA2--in 23 (55.0%). CONCLUSIONS: The occurrence of H. pylori strains of iceA2 genotype was more frequent in adults (59.1%). The occurrence of H. pylori strains of iceA2 genotype was more frequent in persons living in the country and town (52.4% and 54.5%, respectively).


Asunto(s)
Proteínas Bacterianas/aislamiento & purificación , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/aislamiento & purificación , Adulto , Niño , Enfermedad Crónica , Femenino , Frecuencia de los Genes , Genotipo , Infecciones por Helicobacter/genética , Helicobacter pylori/genética , Humanos , Masculino , Polonia/epidemiología , Reacción en Cadena de la Polimerasa , Prevalencia , Factores de Riesgo , Población Rural/estadística & datos numéricos , Población Urbana/estadística & datos numéricos
20.
Pol Przegl Chir ; 91(2): 30-37, 2018 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-31032810

RESUMEN

The aim of this work was to describe, interpret and highlight the impact of neuroanatomy in the region of the larynx on intraoperative neuromonitoring (IONM) during thyroidectomy. A rich network of anastomoses of the recurrent laryngeal nerve (RLN) and superior laryngeal nerve (SLN) may have impact on the results of thyroidectomy and partial laryngectomy. Intraoperative neuromonitoring is a useful tool in the armamentarium of a head and neck surgeon but it will never replace profound knowledge of surgical anatomy and good surgical technique.


Asunto(s)
Nervios Laríngeos/anatomía & histología , Laringectomía , Traumatismos del Nervio Laríngeo Recurrente/prevención & control , Nervio Laríngeo Recurrente/fisiología , Humanos , Monitoreo Intraoperatorio/métodos , Glándula Tiroides/cirugía
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