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1.
Oncogene ; 36(22): 3149-3158, 2017 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-27991926

RESUMEN

Chronic inflammation (CI) is a risk factor for pancreatic cancer (PC) including the most common type, ductal adenocarcinoma (PDAC), but its role and the mechanisms involved are unclear. To investigate the role of CI in PC, we generated genetic mouse models with pancreatic specific CI in the presence or absence of TP53. Mice were engineered to express either cyclooxygenase-2 (COX-2) or IκB kinase-2 (IKK2), and TP53+/+ or TP53f/f specifically in adult pancreatic acinar cells by using a full-length pancreatic elastase promoter-driven Cre. Animals were followed for >80 weeks and pancreatic lesions were evaluated histologically and immunohistochemically. The presence of K-ras mutations was assessed by direct sequencing, locked nuclei acid (LNA)-based PCR, and immunohistochemistry. We observed that sustained COX-2/IKK2 expression caused histological abnormalities of pancreas, including increased immune cell infiltration, proliferation rate and DNA damage. A minority of animals with CI developed pre-neoplastic lesions, but cancer was not observed in any TP53+/+ animals within 84 weeks. In contrast, all animals with CI-lacking TP53 developed various subtypes of PC, including acinar cell carcinoma, ductal adenocarcinoma, sarcomatoid carcinoma and neuroendocrine tumors, and all died within 65 weeks. No evidence of K-ras mutations was observed. Variations in the activity of the Hippo, pERK and c-Myc pathways were found in the diverse cancer subtypes. In summary, chronic inflammation is extremely inefficient at inducing PC in the presence of TP53. However, in the absence of TP53, CI leads to the development of several rare K-ras-independent forms of PC, with infrequent PDAC. This may help explain the rarity of PDAC in persons with chronic inflammatory conditions.


Asunto(s)
Carcinoma Ductal Pancreático/patología , Inflamación/patología , Neoplasias Pancreáticas/patología , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Enfermedad Crónica , Modelos Animales de Enfermedad , Genes ras , Inflamación/genética , Inflamación/metabolismo , Ratones , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteína p53 Supresora de Tumor/genética
2.
Hum Reprod ; 31(10): 2313-20, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27591238

RESUMEN

STUDY QUESTION: What factors inform a woman's decision-making about oocyte freezing to preserve fertility for social and medical reasons? SUMMARY ANSWER: Women lacked knowledge about the costs and viability of oocyte freezing as a fertility preservation option for social and medical reasons, and identified health consequences, costs, and viability as being particularly influential in their decision-making. WHAT IS KNOWN ALREADY: Having only recently become a viable fertility preservation option, relatively little is known about childless women's beliefs or knowledge about oocyte freezing for social or medical reasons. STUDY DESIGN, SIZE, DURATION: A cross sectional study of 500 childless women was conducted in August, 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 500 childless, presumed fertile, women from 18 to 38 years of age completed an online, self-report questionnaire assessing beliefs and knowledge about oocyte freezing to preserve fertility for social or medical reasons. MAIN RESULTS AND THE ROLE OF CHANCE: Financial costs (85.6%), health risks to themselves (86.4%) or their offspring (87.8%), and success rates (82%) were the primary factors that women felt would influence their decision to freeze their oocytes. Partner's feelings (88.6%), prognosis for a full recovery (85.4%), and concerns about the health effects of the hormones or oocyte retrieval procedure (85.4%) were identified as being particularly important when considering oocyte freezing for medical reasons. Consistent with their perceptions of having little or no knowledge about oocyte freezing, there was an overall correct response rate of 33% to the 12 knowledge questions. LIMITATIONS, REASONS FOR CAUTION: The online format and use of a survey company to recruit participants may have increased the risk of self-selection bias and limit the generalizability of these findings. The findings may also be limited by the fact that the participants were not facing cancer treatments, and the younger participants were not nearing the end of their reproductive lifespan, and therefore would not have had reason to learn about, or consider, fertility preservation for medical or social reasons. WIDER IMPLICATIONS OF THE FINDINGS: Given the worldwide trend towards delaying childbearing and the increasing availability of oocyte freezing as an option to preserve women's fertility, it is likely these results could be extended to wider North American, European, and Australasian populations of English speaking childless women. STUDY FUNDING/COMPETING INTERESTS: No specific funding. No competing interests.


Asunto(s)
Toma de Decisiones , Preservación de la Fertilidad/psicología , Conocimientos, Actitudes y Práctica en Salud , Recuperación del Oocito , Oocitos , Adolescente , Adulto , Estudios Transversales , Femenino , Congelación , Humanos , Técnicas Reproductivas Asistidas/psicología , Adulto Joven
3.
Hum Exp Toxicol ; 35(8): 799-807, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26429926

RESUMEN

BACKGROUND: This article is devoted to the inquiry of three diseases of the liver: alcoholic liver disease (ALD), primary biliary cirrhosis (PBC), and autoimmune hepatitis (AIH). The aim of the study was to assess the changes in populations of circulating lymphocytes expressing antiapoptotic bcl-2 molecule and proapoptotic Fas (cluster of differentiation 95(CD95)) receptor in patients with ALD, AIH, and PBC. MATERIALS AND METHODS: The study population consisted of 110 patients with ALD (n = 50), PBC (n = 30), and AIH (n = 30) and age-matched healthy volunteers (n = 25). Peripheral blood lymphocytes were isolated, stained with monoclonal antibodies against CD4, CD8, and CD19 antigen; intracellular bcl-2; and surface Fas receptor (CD95) antigens, and estimated using the flow cytometric method. RESULTS: Bcl-2 expression was the highest in CD4+ and CD19+ T lymphocytes in ALD; however, only the differences in median/mean fluorescence intensity values of CD4+bcl-2+ lymphocytes between ALD and PBC group and CD19+bcl-2+ between ALD and PBC groups were statistically significant, indicating the different role of B cells in pathology of ALD and PBC. In contrast to that, statistically significant higher percentage of CD4+, CD8+, and CD19+ bearing Fas receptor in all groups of patients with liver diseases in comparison with the control subjects were estimated. The highest expression of Fas in CD4+ lymphocytes in ALD and in CD8+ cells of PBC and AIH groups were detected. CONCLUSION: Low expression of bcl-2 molecule and high expression of Fas in peripheral blood lymphocytes indicate significant dysregulation of apoptotic mechanisms not only in the liver but also in peripheral blood lymphocytes in all examined groups, especially in ALD group.


Asunto(s)
Apoptosis , Hepatitis Autoinmune/sangre , Cirrosis Hepática Biliar/sangre , Hepatopatías Alcohólicas/sangre , Proteínas Proto-Oncogénicas c-bcl-2/genética , Linfocitos T/metabolismo , Receptor fas/genética , Antígenos CD19/inmunología , Apoptosis/genética , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Estudios de Casos y Controles , Femenino , Citometría de Flujo , Hepatitis Autoinmune/genética , Hepatitis Autoinmune/patología , Humanos , Cirrosis Hepática Biliar/genética , Cirrosis Hepática Biliar/patología , Hepatopatías Alcohólicas/genética , Hepatopatías Alcohólicas/patología , Masculino , Persona de Mediana Edad , Linfocitos T/inmunología
4.
Hum Reprod ; 30(2): 353-63, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25480922

RESUMEN

STUDY QUESTION: How effective is online education in increasing knowledge of fertility and assisted reproductive technologies (ART), and changing beliefs about the timing of parenthood? SUMMARY ANSWER: Exposure to an online educational intervention resulted in immediate changes in participants' beliefs about the ideal timing of parenthood, and a significant increase in their knowledge of fertility and ART treatments and options; most of these changes were not sustained over time, particularly for men. WHAT IS KNOWN ALREADY: Research has identified significant gaps in men's and women's knowledge of fertility and ART, contributing to the trend to delay childbearing. Effective educational programs need to be developed, to support informed fertility and child-timing decisions. STUDY DESIGN, SIZE, DURATION: Pre-post intervention study of 199 currently childless men and women, and a 6-month follow-up of 110 of these participants. PARTICIPANTS/MATERIALS, SETTING, METHODS: One hundred and ninety-nine childless participants between the ages of 18 and 35 were asked to complete 4 beliefs and 22 knowledge questions prior to, and immediately after, reading 10 online posts related to: fertility testing and preservation, fertility history and lifespan, the effects of health and fitness on fertility, and assisted reproduction. Six months later, 110 of the original sample repeated the 26-item survey. MAIN RESULTS AND THE ROLE OF CHANCE: Participants' fertility and ART knowledge scores increased significantly immediately after the intervention, as did their confidence in their fertility and ART knowledge. Participants' beliefs about the ideal and latest age a woman or man should consider producing a child decreased. However, 6 months later, participants' beliefs and knowledge levels largely returned to their pre-intervention levels, particularly for the men in the study. LIMITATIONS, REASONS FOR CAUTION: The sample size and the recruitment methods may limit the generalizability of these findings. WIDER IMPLICATIONS OF THE FINDINGS: Previous studies have demonstrated the short-term efficacy of online educational approaches to increase fertility knowledge and support informed family planning decisions. Web-based approaches have the benefit of being easily and conveniently accessed by individuals worldwide. However, the findings of the current study call into question the long-term efficacy of online fertility education, and suggest that variables such as gender and relevance need to be considered in assessing the efficacy of online fertility education strategies.


Asunto(s)
Envejecimiento , Fertilidad , Conocimientos, Actitudes y Práctica en Salud , Educación del Paciente como Asunto , Salud Reproductiva/educación , Adolescente , Adulto , Canadá , Femenino , Estudios de Seguimiento , Estado de Salud , Humanos , Internet , Masculino , Responsabilidad Parental/psicología , Aptitud Física , Conducta Reproductiva/psicología , Técnicas Reproductivas Asistidas/efectos adversos , Universidades , Adulto Joven
5.
Oncogene ; 33(4): 532-5, 2014 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-23334325

RESUMEN

Oncogenic Ras mutations are widely considered to be locked in a permanent 'On' state and 'constitutively active'. Yet, many healthy people have cells possessing mutant Ras without apparent harm, and in animal models mutant Ras causes transformation only after upregulation of Ras activity. Here, we demonstrate that oncogenic K-Ras is not constitutively active but can be readily activated by upstream stimulants to lead to prolonged strong Ras activity. These data indicate that in addition to targeting K-Ras downstream effectors, interventions to reduce K-Ras activation may have important cancer-preventive value, especially in patients with oncogenic Ras mutations. As other small G proteins are regulated in a similar manner, this concept is likely to apply broadly to the entire Ras family of molecules.


Asunto(s)
Transformación Celular Neoplásica/metabolismo , Neoplasias/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/genética , Animales , Western Blotting , Línea Celular Tumoral , Transformación Celular Neoplásica/genética , Electroforesis en Gel de Poliacrilamida , Genes ras/genética , Humanos , Ratones , Ratones Mutantes , Mutación , Neoplasias/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo
6.
Hum Reprod ; 27(8): 2405-12, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22684907

RESUMEN

STUDY QUESTION: What are the childbearing intentions of currently childless men and women? What is their attitude towards, and willingness to use, assisted human reproduction (AHR) treatments and family-building options should they be faced with fertility challenges in the future? SUMMARY ANSWER: Men and women expect to become parents significantly later in life than they believe is ideal. If faced with future fertility challenges, respondents were open to using IVF, but were not positively predisposed to third-party family-building options. WHAT IS KNOWN ALREADY: Delayed childbearing is an increasing worldwide phenomenon that has considerable health and fertility-related implications. Research to date has focused primarily on women, and indicates a lack of knowledge about the fertility life span and the limitations of AHR in fully compensating for age-related fertility declines. STUDY DESIGN, SIZE, DURATION: Cross-sectional study of 2000 childless women and 599 childless men, conducted between April 2010 and May 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 2599 childless, presumed fertile individuals between the ages of 20 and 50 years. An online questionnaire assessed fertility beliefs and intentions and willingness to use AHR. MAIN RESULTS AND THE ROLE OF CHANCE: The findings indicate that men and women expect to become parents significantly later in life than they believe is ideal. If faced with fertility challenges in the future, both men and women were open to using IVF. Men were significantly more willing to consider using donated eggs and embryos, gestational surrogacy and fertility preservation. Women were significantly more willing to consider using home fertility testing, IVF, ICSI and donor sperm. Overall, the childless respondents were not positively predisposed to third party-family-building options. LIMITATIONS: The geographic specificity of the sample, the online format and recruitment methods may limit the generalizability of these findings. WIDER IMPLICATIONS OF THE FINDINGS: Given the worldwide trend towards delayed childbearing, and the widespread availability of AHR, it is likely that these findings could extend to the wider North American, European and Australasia populations of English- and French-speaking childless men and women. However, it should be noted that international differences exist, especially concerning regulations governing the funding of AHR and payment for gametes and surrogacy. It is significant that women and men in this study indicated a lack of willingness to consider the use of third third-party treatments--the very options they may need to use in building their families, if the increasing trend towards delayed childbearing continues. STUDY FUNDING/COMPETING INTERESTS: This research was funded by a grant from the Canadian Institutes of Health Research and Assisted Human Reproduction Canada #PAH-103594, 2009/10. No competing interests.


Asunto(s)
Infertilidad/terapia , Intención , Conducta Reproductiva , Técnicas Reproductivas Asistidas/estadística & datos numéricos , Adulto , Actitud Frente a la Salud , Canadá , Estudios Transversales , Femenino , Fertilización In Vitro/métodos , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales
7.
Hum Exp Toxicol ; 31(5): 438-46, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22076495

RESUMEN

Little is known about effects of alcohol consumption on dendritic cell (DC) function and resultant immune response. However, quantitative and qualitative disturbances of DCs are speculated to be involved in alcohol-related as well as in other liver pathology. The present study aimed to evaluate changes in circulating DC subsets in alcoholic liver disease (N = 43), autoimmune hepatitis (N = 26) and primary biliary cirrhosis (N = 20). DCs isolated from the peripheral blood of recruited participants were stained with monoclonal antibodies against blood dendritic cell antigens (BDCAs) and estimated using the flow cytometry. Myeloid DCs were defined as BDCA-1(+)/CD19(-) cells, and lymphoid DCs as BDCA-2(+)/CD123(+) cells. Total numbers of circulating DCs in subjects with some liver diseases were markedly lower than in the healthy participants (p = 0.03). There was a significantly lower percentage of circulating BDCA-2(+)/CD123(+) (p = 0.02), and a tendency for the percentage of circulating BDCA-1(+)/CD19(-) cells to decrease in patients with liver diseases compared to the controls (p = 0.09). These results may suggest that decreased numbers of DCs may be responsible for reduced adaptive immune responses and increased susceptibility to infections and cancer development observed in patients exposed to alcohol. Moreover, numerical abnormalities of DCs may contribute to the breakdown of self-tolerance, a feature of autoimmune diseases.


Asunto(s)
Trastornos Inducidos por Alcohol/inmunología , Enfermedades Autoinmunes/inmunología , Células Dendríticas/inmunología , Hepatopatías/inmunología , Adulto , Trastornos Inducidos por Alcohol/epidemiología , Enfermedades Autoinmunes/epidemiología , Estudios de Casos y Controles , Células Dendríticas/citología , Femenino , Citometría de Flujo , Humanos , Hepatopatías/epidemiología , Masculino , Persona de Mediana Edad
8.
J Physiol Pharmacol ; 58(3): 441-53, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17928641

RESUMEN

The transmission of extracellular proliferation and differentiation signals into their intracellular targets is mediated by a signaling cascade culminating in mitogen-activated protein kinase (MAPK) also known as ERK. In pancreatic acinar cells both cholecystokinin (CCK) and epidermal growth factor (EGF) are known to stimulate ERK. Regulatory interactions among individual receptor-coupled signaling cascades are critically important for establishing cellular responses in the face of multiple stimuli. The aim of our study was to evaluate the effect of concomitant stimulation of G protein-coupled receptors (GPCR) and EGF receptors on ERK activity in isolated pancreatic acinar cells. ERK activity was determined by means of Western-blotting, with the use of the antibody which recognizes active, tyrosine-phosphorylated kinase (pY-ERK). pY-ERK level was strongly elevated by 10 nM CCK-8, 100 microM carbachol (CAR), or 100 nM EGF. The addition of EGF to 60 min-lasting incubations of acini with CCK-8 or CAR caused abrupt decrease of pY-ERK level to 56 and 59% of control, respectively. Similar phenomenon was observed when short stimulation with CCK-8 or CAR was superimposed on the effect of EGF. After the addition of EGF to acini incubated previously with phorbol ester TPA, strong decrease in pY-ERK level was also observed. In conclusion, in pancreatic acinar cells, concomitant stimulation with CCK or CAR and EGF has strong inhibitory effect on ERK cascade. This inhibitory cross-talk may be mediated, at least partially, by protein kinase C (PKC). These mutual inhibitory interactions demonstrate novel mechanism for integration of multiple signals generated by activation of G-protein-coupled and growth factor receptors in pancreatic acinar cells.


Asunto(s)
Colecistoquinina/farmacología , Factor de Crecimiento Epidérmico/farmacología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Páncreas Exocrino/efectos de los fármacos , Animales , Western Blotting , Carbacol/farmacología , Receptores ErbB/metabolismo , Masculino , Agonistas Muscarínicos/farmacología , Páncreas Exocrino/citología , Páncreas Exocrino/metabolismo , Fosforilación/efectos de los fármacos , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/efectos de los fármacos , Proteínas Tirosina Quinasas/metabolismo , Ratas , Ratas Wistar , Receptores Acoplados a Proteínas G/metabolismo , Sincalida/farmacología , Acetato de Tetradecanoilforbol/farmacología , Factores de Tiempo
9.
Arch Immunol Ther Exp (Warsz) ; 49(2): 139-46, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11348018

RESUMEN

To assess the level of oxidative stress, measured as prooxidant-antioxidant imbalance in the blood of patients with alcohol-related injury of the liver and pancreas, we determined superoxide ion (O2*-) production by neutrophils isolated from the peripheral blood of 3 groups of patients. Patients with compensated alcoholic liver cirrhosis (n=16), with alcoholic chronic pancreatitis (n=20), and with concomitant cirrhosis and pancreatitis (n=10) were included in this study. All patients had consumed at least 70 g of pure alcohol per day over 5 years. They had not abstained before admission to hospital. The control group consisted of 16 healthy non-alcohol-abusive subjects. As antioxidative enzymes (AOE) present in sera play a very important role in the regulation of plasma reactive oxygen species (ROS) levels and in the protection of plasma compounds against ROS action, we also examined the serum activity of catalase (CAT), superoxide dismutase (SOD), total activity, and the glutathione peroxidase (GPx) serum concentration. Neutrophils of patients with concomitant alcoholic liver cirrhosis and pancreatitis exhibited, similarly to the neutrophils of patients with chronic alcoholic pancreatitis, an enhanced ability to produce superoxide anions in vitro. In contrast, neutrophils of patients with alcoholic liver cirrhosis exhibited a defect in resting and PMA-induced superoxide anion production. The AOE activity in the sera of patients was also significantly changed. Total SOD activity was enhanced in all groups of patients with alcoholic liver cirrhosis, chronic pancreatitis and with concomitant injury of both organs. CAT activity was only increased in the sera of patients with liver cirrhosis or pancreatitis, but not in the patients with concomitant cirrhosis and pancreatitis. GPx concentration was only diminished in the patients with chronic pancreatitis. It seems likely that oxidative stress, defined as the imbalance between prooxidant and antioxidant activity, is highest in the blood of patients with chronic pancreatitis and, especially, in patients with concomitant liver cirrhosis and pancreatitis.


Asunto(s)
Cirrosis Hepática Alcohólica/complicaciones , Cirrosis Hepática Alcohólica/metabolismo , Estrés Oxidativo , Pancreatitis Alcohólica/complicaciones , Pancreatitis Alcohólica/metabolismo , Adulto , Anciano , Catalasa/sangre , Femenino , Glutatión Peroxidasa/sangre , Humanos , Técnicas In Vitro , Cirrosis Hepática Alcohólica/etiología , Masculino , Persona de Mediana Edad , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Pancreatitis Alcohólica/etiología , Superóxido Dismutasa/sangre , Superóxidos/sangre , Acetato de Tetradecanoilforbol/farmacología
10.
Pancreas ; 22(3): 261-6, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11291927

RESUMEN

To determine the possible role of oxidative stress in alcoholic pancreatitis, the authors measured the ability of blood neutrophils of 22 patients with acute and 20 patients with chronic alcoholic pancreatitis to produce superoxide anion (O2-) and hydrogen peroxide (H2O2), spontaneously and after in vitro stimulation with phorbol ester and compared it with that of neutrophils isolated from the blood of 16 healthy controls. In addition, they measured serum activities of superoxide dismutase, catalase, and the serum concentration of glutathione peroxidase (GPx). Phorbol ester-induced O2- and H2O2 production in neutrophils of patients with acute and chronic pancreatitis was greater than in controls, but these differences, except of superoxide anion production by neutrophils of patients with chronic pancreatitis, were not statistically significant because of large individual differences. Spontaneous resting production of O2- and H2O2 by neutrophils of patients with chronic pancreatitis was significantly greater than in the controls. Superoxide dismutase and catalase activity was greater in sera of both groups of patients with acute and chronic alcoholic pancreatitis than in controls, but GPx concentration was significantly less in the sera of patients with chronic pancreatitis. Impaired GPx production and increased production of O2- and H2O2 by neutrophils may result in increased lipid peroxidation and could play a role in the pathogenesis of chronic alcoholic pancreatitis.


Asunto(s)
Estrés Oxidativo , Pancreatitis Alcohólica/sangre , Enfermedad Aguda , Adulto , Aniones , Catalasa/sangre , Enfermedad Crónica , Femenino , Glutatión Peroxidasa/sangre , Humanos , Peróxido de Hidrógeno/sangre , Peroxidación de Lípido , Masculino , Persona de Mediana Edad , Neutrófilos/metabolismo , Ésteres del Forbol/farmacología , Superóxido Dismutasa/sangre , Superóxidos/sangre , Acetato de Tetradecanoilforbol/farmacología
11.
Alcohol ; 23(1): 29-34, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11282449

RESUMEN

Chronic alcoholism complicated by alcoholic liver disease is characterized by activation of the inflammatory response system. To evaluate the role of cytokines in the progress of alcoholic cirrhosis, we assessed serum level of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-8 and the antiinflammatory cytokines IL-2, IL-10, and transforming growth factor (TGF)-beta in patients with compensated and decompensated alcoholic liver cirrhosis. Compensated alcoholic cirrhosis was characterized by increased IL-6 (6.3+/-2.9 vs. HP 2.2+/-1.4 pg/ml in controls) and decreased IL-10 (HP 4.1+/-3.5 vs. 6.4+/-5.4 pg/ml in controls). TNF-alpha, IL-8, and TGF-beta1 levels were comparable to those found in controls. In sera of patients with decompensated alcoholic liver cirrhosis, besides increased IL-6 (11.2+/-7.7 pg/ml), increased concentrations of TNF-alpha (25.1+/-4.5 vs. 9.1+/-7.0 pg/ml in controls) and IL-8 (171.7+/-294.0 vs. 2.7+/-2.9 pg/ml in controls) were also detected. TGF-beta1 and IL-10 levels were similar to those found in controls. These results strongly indicate that a significant derangement of the balance between proinflammatory and antiinflammatory signals is characteristic of compensated and especially of decompensated alcoholic cirrhosis.


Asunto(s)
Citocinas/sangre , Cirrosis Hepática Alcohólica/sangre , Adulto , Biomarcadores/sangre , Femenino , Humanos , Interleucinas/sangre , Masculino , Persona de Mediana Edad , Estadísticas no Paramétricas , Factor de Crecimiento Transformador beta/sangre , Factor de Necrosis Tumoral alfa/metabolismo
12.
Pol Merkur Lekarski ; 11(64): 340-3, 2001 Oct.
Artículo en Polaco | MEDLINE | ID: mdl-11770315

RESUMEN

Interferon alpha (INF) is routine treatment in patients with chronic hepatitis C. Many controlled investigations were evaluated to establish the optimal schedule of treatment with sustained virological and biochemical response. Recently, multicentre meta-analyses suggest that combination therapy (INF + Ribavirin) was more effective than treatment with interferon alone. The aim of this study was to compare the efficacy of four schedules of antiviral treatment in 445 patients with chronic hepatitis C. Combination therapy (INF + Ribavirin) given for 6 mo. and monotherapy (INF) for 18 mo. were more effective than interferon alone given for 6 mo. Treatment with INF alone for 6 mo. was demonstrated to be insufficient.


Asunto(s)
Antivirales/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Ribavirina/administración & dosificación , Antivirales/efectos adversos , Esquema de Medicación , Quimioterapia Combinada , Femenino , Humanos , Interferón-alfa/efectos adversos , Masculino , Polonia/epidemiología , Ribavirina/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
13.
Arch Immunol Ther Exp (Warsz) ; 48(4): 301-7, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11059648

RESUMEN

Although altered cytokine homeostasis has been implicated in the pathogenesis of both alcoholic liver and pancreas diseases, the serum cytokine pattern characteristic of concomitant alcoholic liver cirrhosis and pancreatitis has not been examined. In this paper we examine the serum levels of proinflammatory cytokines, such as IL-6, IL-8, TNF-alpha, and also antiinflammatory ones, such as IL-10 and TGF-beta, in 22 patients with alcoholic liver cirrhosis and 28 patients with chronic pancreatitis and compare them with those detected in the sera of 14 patients with concomitant alcoholic cirrhosis and pancreatitis. All patients were heavy alcohol drinkers, consuming more than 70 g of pure alcohol per day for at least 5 years. The control group consisted of 33 age- and sex-matched healthy subjects receiving an annual health examination. They were not addicted to alcohol and confirmed to be free of major cardiopulmonary, gastrointestinal and hepatobiliary-pancreatic diseases. The results indicated that the cytokine pattern in the sera of patients with concomitant liver cirrhosis and pancreatitis was characterized by increased levels of two proinflammatory cytokines: TNF-alpha, the concentration of which seemed to be influenced by both liver and pancreas injury, and IL-6, which seemed to be rather connected with pancreas injury. Increased levels of IL-8, which were detected in the sera of patients with cirrhosis, pancreatitis and concomitant cirrhosis and pancreatitis, were rather connected with exacerbation of the disease processes which occurred only in some of the patients. No significant changes in the levels of IL-10 or TGF-beta were detected in the sera of patients with chronic pancreatitis and concomitant cirrhosis and pancreatitis, while in patients with cirrhosis significantly decreased levels of IL-10 were found. A significant imbalance between proinflammatory/antiinflammatory signals was especially characteristic of alcoholic cirrhosis and concomitant cirrhosis with pancreatitis.


Asunto(s)
Citocinas/sangre , Cirrosis Hepática Alcohólica/sangre , Pancreatitis/sangre , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Femenino , Humanos , Interleucina-10/sangre , Interleucina-6/sangre , Interleucina-8/sangre , Cirrosis Hepática Alcohólica/complicaciones , Masculino , Persona de Mediana Edad , Pancreatitis/complicaciones , Factor de Necrosis Tumoral alfa/análisis
14.
Postepy Hig Med Dosw ; 52(1): 49-65, 1998.
Artículo en Polaco | MEDLINE | ID: mdl-9608231

RESUMEN

Chronic alcoholism is a disease, which is known to affect individual's resistance to infections. Alcohol has a variety of short- and long-term effects on cell mediated and humoral immune response. Alcohol also affects the production, site of action and metabolism of cytokines, which are regulatory peptides of the immune and inflammatory response of lymphocytes, monocytes/macrophages and a variety of other cell types. In this review, current knowledge regarding the effect of alcohol on the immune system and the release and action of cytokines in humans and in animal models, in vivo and in vitro, is presenting. Furthermore, the role of cytokines in development of alcoholic liver disease is also discussed.


Asunto(s)
Formación de Anticuerpos/efectos de los fármacos , Enfermedades Autoinmunes/inducido químicamente , Citocinas/efectos de los fármacos , Etanol/farmacología , Inmunidad Celular/efectos de los fármacos , Hepatopatías Alcohólicas/inmunología , Animales , Humanos , Interferones/inmunología , Interleucinas/inmunología , Lipopolisacáridos/metabolismo , Hígado/efectos de los fármacos , Hígado/inmunología , Factor de Crecimiento Transformador beta/inmunología , Factor de Necrosis Tumoral alfa/inmunología
16.
Arch Immunol Ther Exp (Warsz) ; 45(2-3): 183-7, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9597085

RESUMEN

Blood leukocytes of 16 patients with alcoholic liver cirrhosis and 18 healthy controls were induced for interferon (IFN) production by phytohemagglutinin (PHA) and concanavalin A (ConA) in the presence or absence of isoprinosine and levamisole at concentrations of 10 micrograms/ml and 1 ng/ml. This interferon was neutralized in 87-95% by anti-HuIFN-gamma monoclonal antibodies. In the presence of the drugs the IFN-gamma production was enhanced, however, IFN-gamma titers yielded from leukocytes of cirrhotic patients were still below the titers observed in stimulated and unstimulated blood leukocytes of healthy controls. For example, IFN titers induced by PHA in the presence of levamisole (1 ng/ml) in cirrhotic patients were 2.5 times lower (20.2 +/- 11.1 U/ml) in comparison to healthy subjects (50.6 +/- 27.3 U/ml).


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Inosina Pranobex/farmacología , Interferón gamma/biosíntesis , Leucocitos/efectos de los fármacos , Levamisol/farmacología , Cirrosis Hepática Alcohólica/sangre , Adulto , Anciano , Concanavalina A/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Interferón gamma/genética , Leucocitos/metabolismo , Cirrosis Hepática Alcohólica/patología , Activación de Linfocitos/efectos de los fármacos , Persona de Mediana Edad , Fitohemaglutininas/farmacología
17.
Pol Tyg Lek ; 51(23-26): 324-5, 1996 Jun.
Artículo en Polaco | MEDLINE | ID: mdl-9273520

RESUMEN

In 1993, 80 patients (43 female and 37 male) with tick-borne encephalitis were hospitalized in Clinic of Neuroinfections and Parasitic Diseases of Medical School in Bialystok. 6 (7.5%) patients were jaundiced, 16 (20%) had hepatomegaly. We noticed increased enzymatic activity of aspartate aminotransferase (x = 74.5 U/l) in 9 (11.25%) cases, alanine aminotransferase (x = 89.5 U/l) in 11 (13.75%) cases, increased level of bilirubin in blood (from 1.4 to 3.5 mg/dl) in 7 (8.75%) cases. Protein level in blood was average x = 5.95 g/dl, percentage of albumin was average x = 48.61%, globulin--x = 14.62%. Prothrombin index and ammonia blood level were in normal range. Observed pathological changes were transient and referred mainly to patients with severe clinical course of disease.


Asunto(s)
Encefalitis Transmitida por Garrapatas/complicaciones , Hepatopatías/etiología , Adolescente , Adulto , Anciano , Alanina Transaminasa/metabolismo , Aspartato Aminotransferasas/metabolismo , Bilirrubina/sangre , Femenino , Humanos , Hepatopatías/diagnóstico , Hepatopatías/enzimología , Masculino , Persona de Mediana Edad
18.
Arch Immunol Ther Exp (Warsz) ; 44(2-3): 97-101, 1996.
Artículo en Inglés | MEDLINE | ID: mdl-8915512

RESUMEN

Sixteen male and female patients with alcoholic cirrhosis and 13 healthy controls were included in the study. The level of interferon (IFN) and tumor necrosis factor (TNF) activity was examined in the sera and also in cultures in peripheral blood leukocytes (PBL) after in vitro stimulation with the cytokine inducers. In sera of patients with alcoholic cirrhosis higher IFN and TNF levels were detected than in controls. However, after induction with Newcastle disease virus (NDV), phytohemagglutinin M (PHA) and lipopolysaccharide from E. coli (LPS), PBL from cirrhotic patients produced lower IFN levels in comparison to controls. In contrast to depressed ability to produce IFNs, TNF production was higher in PBL of cirrhotic patients induced by PHA and a low dose of LPS (1 microgram/ml). NDV induced comparable levels of TNF in both groups. It appears likely that cells of cirrhotic patients were suppressed by an unknown factor or were hyporeactive for IFN production, but synthesis and release of TNF was enhanced, suggesting that cells producing TNF were preactivated in vivo. Mechanism of such preactivation is discussed.


Asunto(s)
Interferón gamma/biosíntesis , Leucocitos Mononucleares/metabolismo , Cirrosis Hepática Alcohólica/sangre , Factor de Necrosis Tumoral alfa/biosíntesis , Adulto , Femenino , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Lipopolisacáridos/farmacología , Masculino , Persona de Mediana Edad
20.
Przegl Epidemiol ; 49(3): 257-60, 1995.
Artículo en Polaco | MEDLINE | ID: mdl-7491420

RESUMEN

The purpose of this work was to evaluate detection of antibodies IgM and IgG against B. burgdorferi. We examined presence of IgM in 96 serum samples from patients suspected of Lyme disease. We looked for IgG in serum samples of 48 forest workers who submitted frequent tick bites in last two years. Among 96 patients whose sera were examined we had positive results in both tests in 5 cases and in 25 cases positive results were achieved only in test II. In 48 serum samples which we examined for presence of IgG in 2 cases positive results were in both tests, in 1 case positive in test II and negative in test I in 3 cases positive result in test I and negative in test II. According to these results we drew following initial conclusions: 1) obtained results testify better sensitivity and specificity of test II which consists of recombinant antigens of Borrelia burgdorferi, 2) no essential difference was shown in detection IgG among two used tests.


Asunto(s)
Ensayo de Inmunoadsorción Enzimática/métodos , Enfermedad de Lyme/diagnóstico , Femenino , Humanos , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Masculino , Sensibilidad y Especificidad
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