RESUMEN

BACKGROUND: Prostate cancer (PCa) is the first in terms of occurrence in Europe and second in Poland. The PCa risk factors include: genetic load, obesity, diet rich in fat, hypertriglyceridemia, and exposure to androgens. The prostate-specific antigen (PSA) level may be elevated in prostate cancer or other prostate disorders. Fat tissue secretes adipocytokines, which increase the risk of cancer development and metastasis. OBJECTIVES: The aims of the study were to investigate the relationship between circulating levels of PSA, adipocytokines: omentin, leptin, hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) in serum obtained from patients with benign prostate hyperplasia (BPH) and prostate cancer (PCa). METHODS: Forty patients diagnosed with BPH and forty diagnosed with PCa were assessed for the purpose of the study. The concentrations of omentin, leptin, HGF, and VEGF were determined using enzyme-linked immunosorbent assays (EIA). RESULTS: PSA level was significantly higher in the PCa group than in BPH (18.2 versus 9 ng/mL, p < 0.01), while volume of prostate gland was significantly higher in the BPH group than in PCa (39.1 versus 31.1 cm3, p = 0.02). HGF, VEGF, omentin, and leptin concentrations were significantly higher in PCa group than in BPH (359.5 versus 294.9 pg/mL, p = 0.04; 179.3 versus 127.3 pg/mL, p < 0.01; 478.8 versus 408.3 ng/mL, p = 0.01; 15.7 versus 11.2 ng/mL, p = 0.02, resp.). The multiple logistic regression analysis demonstrated that only omentin and PSA levels were independent predictors of PCa in studied subjects. CONCLUSIONS: PSA level as well as the level of omentin may be valuable markers of PCa with clinical significance, when compared to PSA.

Asunto(s)

Biomarcadores de Tumor/sangre , Citocinas/sangre , Lectinas/sangre , Leptina/sangre , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Anciano , Proteínas Ligadas a GPI/sangre , Factor de Crecimiento de Hepatocito/sangre , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Hiperplasia Prostática/sangre , Hiperplasia Prostática/patología , Neoplasias de la Próstata/patología , Curva ROC , Factor A de Crecimiento Endotelial Vascular/sangre

RESUMEN

UNLABELLED: Multiple sclerosis (MS) prevalence is higher in geographic regions with less sunlight exposure. Melatonin participates in the effects of sunlight in healthy individuals and could play a role in MS pathophysiology. Melatonin crosses the blood-brain barrier and exerts antioxidative, immunomodulatory, and anti-inflammatory effects. Chronic fatigue syndrome concerns 80 - 90% MS patients. The pathophysiology of chronic fatigue syndrome is unknown, however activation of immune, inflammatory, oxidative and nitrosative stress mechanisms and plasma lipid peroxide elevation was reported. Homocysteine increases plasma lipid hydroperoxides levels. The aim was to determine the effect of melatonin supplementation on chronic fatigue syndrome in MS patients and evaluate plasma lipid hydroxyperoxides (LHP) and homocysteine concentrations as a potential biochemical fatigue biomarkers. Into a case-control prospective study 102 MS patients divided according receiving immunomodifying MS treatment into groups: RRMS-pretreated, RRMS-INF-beta, SP/PPMS-mitoxantrone, RRMS-relapse were enrolled. Patients were supplemented with melatonin over 90 days. Plasma LHP, homocysteine concentration, brain MRI and fatigue score were examined. Results show that LHP concentrations were significantly higher in all studied MS groups vs. CONTROLS: In all MS patient groups melatonin application resulted in significant decrease in plasma LHP concentrations. Plasma homocysteine concentration was similar in healthy people, RRMS-pretreated, RRMS-INF-beta and SP/PP-MS-mitoxantrone groups. However, in the RRMS-relapse group plasma levels of homocysteine were significantly higher compared to the RRMS-pretreated group. There were no significant differences in plasma homocysteine concentration in the studied groups before and after melatonin application. The fatigue score was significantly lower in RRMS pretreated group compared to RRMS-INF-beta and SP/PP MS-mitoxantrone treated patients. Plasma lipid hydroxyperoxides could be potential biochemical chronic fatigue syndrome biomarker in MS patients and homocysteine could be a potential marker of acute phase of MS. Melatonin exerts beneficial effects in MS patients based on its' proved antioxidative properties.

Asunto(s)

Antioxidantes/farmacología , Suplementos Dietéticos , Síndrome de Fatiga Crónica/sangre , Homocisteína/sangre , Peróxidos Lipídicos/sangre , Melatonina/farmacología , Esclerosis Múltiple/sangre , Adulto , Antioxidantes/uso terapéutico , Encéfalo/diagnóstico por imagen , Síndrome de Fatiga Crónica/tratamiento farmacológico , Femenino , Humanos , Factores Inmunológicos/farmacología , Factores Inmunológicos/uso terapéutico , Interferón beta/farmacología , Interferón beta/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Melatonina/uso terapéutico , Persona de Mediana Edad , Mitoxantrona/farmacología , Mitoxantrona/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Adulto Joven

RESUMEN

Visfatin/eNampt is a novel adipokine, secreted by visceral and subcutaneous fat, which could be involved in the development of obesity-associated cancer. Only few studies revealed reactive oxygen species (ROS)-dependent action of visfatin in endothelial cells, myotubes and melanoma cells. The potential pro-apoptotic properties of visfatin/eNampt in human colorectal HCT-116 cells remain unknown. The aim of the study was to examine the effects of visfatin/eNampt on cell viability along with the determination of apoptosis/necrosis extent and ROS level in HCT-116 cells. Additionally antioxidant enzymes' activities (i.e catalase (CAT), gluthatione peroxidase (GSH-Px)), and lipid peroxidation intensity in HCT-116 cells line was evaluated. Viability of HCT-116 cells was decreased after visfatin/eNampt treatment for 24 hours. The number of apoptotic cells in tested cells treated with increasing visfatin/eNampt concentrations (10, 100, 250 ng/ml) was elevated compared to untreated cells (6.4%, 9.7%, 16% vs. 3.2%; respectively). After 24 hours in the visfatin/eNampt treated group (10 - 100 ng/ml) CAT and GSH-Px activities significantly increased and this observation was accompanied by the decrease of ROS level when compared to the control group. Interestingly ROS level (using DCF detection technique) and lipid peroxidation ratio were increased in cells stimulated by visfatin/eNampt in concentration of 250 ng/ml along with the decreased activity of selected antioxidant enzymes when compared to remaining study groups, including control. We concluded that visfatin/eNampt induces decrease of cell viability and apoptosis boost in human colorectal cancer HCT-116 cells line. Visfatin/eNampt affected the level of ROS as well as antioxidant capacity, however the association of ROS level and apoptosis rate was not linear. The role for visfatin/eNampt in cancer redox status in vitro may provide a greater insight into the association between fat derived visfatin/eNampt and its endocrine action in colorectal carcinoma cells.

Asunto(s)

Supervivencia Celular/efectos de los fármacos , Citocinas/farmacología , Nicotinamida Fosforribosiltransferasa/farmacología , Estrés Oxidativo/efectos de los fármacos , Apoptosis/efectos de los fármacos , Catalasa/metabolismo , Glutatión Peroxidasa/metabolismo , Células HCT116 , Humanos , Peroxidación de Lípido/efectos de los fármacos , Malondialdehído/metabolismo , Necrosis , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

The aim of this study was to determine the effectory mechanisms: vasopressin, renin-angiotensin system and proopiomelanocortin-derived peptides (POMC), partaking in the effects of serotonin through central serotonin 1A receptor (5-HT1A) receptors in haemorrhagic shock in rats. The study was conducted on male Wistar rats. All experimental procedures were carried out under full anaesthesia. The principal experiment included a 2 hour observation period in haemorrhagic shock. Drugs used - a selective 5-HT1A agonist 8-OH-DPAT (5 µg/5 µl); V1a receptor antagonist [ß-mercapto-ß, ß-cyclo-pentamethylenepropionyl(1),O-me-Tyr(2),Arg(8)]AVP (10 µg/kg); angiotensin type I receptor antagonist (AT1) ZD7155 (0.5 mg/kg, i.v.); angiotensin-converting-enzyme inhibitor captopril (30 mg/kg, i.v.); melanocortin type 4 (MC4) receptor antagonist HS014 (5 µg, i.c.v.). There was no influence of ZD715, captopril or blocking of the V1a receptors on changes in the heart rate (HR), mean arterial pressure (MAP), peripheral blood flow or resistance caused by the central stimulation of 5-HT1A receptors (P≥0.05). However, selective blocking of central MC4 receptors caused a slight, but significant decrease in HR and MAP (P<0.05). POMC derivatives acting via the central MC4 receptor participate in the resuscitative effects of 8-OH-DPAT. The angiotensin and vasopressin systems do not participate in these actions.

Asunto(s)

8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Proopiomelanocortina/fisiología , Receptor de Melanocortina Tipo 4/fisiología , Agonistas del Receptor de Serotonina 5-HT1/farmacología , Choque Hemorrágico/fisiopatología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Presión Arterial/efectos de los fármacos , Captopril/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Naftiridinas/farmacología , Péptidos Cíclicos/farmacología , Ratas , Ratas Wistar , Receptor de Melanocortina Tipo 4/antagonistas & inhibidores , Receptores de Vasopresinas/fisiología

RESUMEN

The aim of the study was to assess the expression and subcellular localization of visfatin in HCT-116 colorectal carcinoma cells after cytokinesis failure using Cytochalasin B (CytB) and the mechanism of apoptosis of cells after CytB. We observed translocation of visfatin's antigen in cytB treated colorectal carcinoma HCT-116 cells from cytosol to nucleus. Statistical and morphometric analysis revealed significantly higher area-related numerical density visfatin-bound nano-golds in the nuclei of cytB-treated HCT-116 cells compared to cytosol. Reverse relation to visfatin subcellular localization was observed in un-treated HCT-116 cells. The total amount of visfatin protein and visfatin mRNA level in HCT-116 cells was also decreased after CytB treatment. Additionally, CytB significantly decreased cell survival, increased levels of G2/M fractions, induced bi-nuclei formation as well as increased reactive oxygen species (ROS) level in HCT-116 cells. CytB treatment showed cytotoxic effect that stem from oxidative stress and is connected with the changes in the cytoplasmic/nuclear amount of visfatin in HCT-116 cells.

Asunto(s)

Neoplasias Colorrectales/metabolismo , Citocalasina B/farmacología , Nicotinamida Fosforribosiltransferasa/metabolismo , Apoptosis , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cromatografía de Fase Inversa , Oro/química , Humanos , Nanoestructuras/química , Transporte de Proteínas/efectos de los fármacos

RESUMEN

The discovery of MT1, MT2, and MT3 melatonin receptors on adipose tissue cells gives grounds for considering the possibility of melatonin as a factor which influences energy storage through modulation of metabolism and adipocyte proliferation. To date only a few contradictory studies have been published on the influence of melatonin on preadipocytes. The aim of the present study is to evaluate the influence of melatonin at physiological and supraphysiological concentrations on the proliferation of 3T3-L1 murine preadipocytes after 3 and 24 hours of the experiment and to determine the participation of membrane melatonin MT2 receptors, and for the first time--MT3, in its melatonin action during a 24-hour experiment. The 3T3-L1 murine preadipocyte cell line were cultured with or without melatonin at 10⁻³ and 10⁻9 mol/L, with or without melatonin antagonists luzindole (10⁻4 mol/L) and prazosin (10⁻5 mol/L). Cell proliferation was determined by means of labeled [³H]-thymidine incorporation in the DNA of the cell. Melatonin at both physiological and supraphysiological concentrations has a stimulating effect on the number of 3T3-L1 preadipocytes. The application of luzindole inhibits the above effect of melatonin both at 10⁻³ mol/L and 10⁻9 mol/L concentrations (P<0.05). The presence of prazosin does not have a statistically significant influence on the effects of melatonin action. Summarizing, it has been proven that melatonin exerts a proproliferative effect on 3T3-L1 preadipocytes at physiological and supraphysiological concentrations, partially by MT2, and not by MT3 receptors.

Asunto(s)

Adipocitos/efectos de los fármacos , ADN/metabolismo , Melatonina/farmacología , Receptor de Melatonina MT2/metabolismo , Timidina/metabolismo , Células 3T3-L1 , Adipocitos/citología , Adipocitos/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Ratones , Prazosina/farmacología , Receptor de Melatonina MT2/antagonistas & inhibidores , Receptores de Melatonina/antagonistas & inhibidores , Receptores de Melatonina/metabolismo , Triptaminas/farmacología

RESUMEN

Visfatin has recently been established as a novel adipokine that is predominantly expressed in visceral fat. Recombinant visfatin has immunomodulating properties, which can activate human leukocytes in vitro to induce cytokine production (IL-1ß, TNF-α, and IL-6). Only few studies have investigated the effect of visfatin on prostate, breast, ovarian cancer as well as astrocytoma cell biology. There have been no studies on the cytokine secretion in human melanoma cells in response to visfatin stimulation along with intracellular protein kinases inhibitors. ELISA assay was performed in supernatants of Me45 cells stimulated with visfatin in the presence or the absence of specific pharmacological inhibitors of the indicated protein kinases (p38, MEK 1, PI3k and JAK kinase) and nuclear factor kappa B (NK-κB) inhibitor. Intracellular reactive oxygen species level was measured in 2', 7'-dichlorodihydrofluorescein diacetate (H2DCF-DA)-loaded cells using a fluorescent measurement system. For determination of NF-κB activation, activated NF-κB p65 subunit was determined using an EZ-TFA-detect chemiluminescent transcription factor assay. We report that visfatin led to the significant increase in IL-6 and IL-8 level in culture supernatants of human malignant melanoma Me45 cells. Additionally visfatin resulted in the increase of the intracellular reactive oxygen species level. PI3k and NF-κB pathways were activated upon visfatin stimulation. The results may reflect the fact that PI3k pathway stimulation by visfatin may further lead to NF-κB activation and pro-inflammatory response.

Asunto(s)

Antineoplásicos/farmacología , Citocinas/metabolismo , Melanoma/tratamiento farmacológico , Nicotinamida Fosforribosiltransferasa/farmacología , Estrés Oxidativo/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Antineoplásicos/efectos adversos , Línea Celular , Línea Celular Tumoral , Cromonas/efectos adversos , Cromonas/farmacología , Cumarinas/efectos adversos , Cumarinas/farmacología , Citocinas/efectos adversos , Citocinas/genética , Citocinas/farmacología , Inhibidores Enzimáticos/efectos adversos , Inhibidores Enzimáticos/farmacología , Humanos , Melanoma/inmunología , Melanoma/metabolismo , Morfolinas/efectos adversos , Morfolinas/farmacología , FN-kappa B/agonistas , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Proteínas de Neoplasias/agonistas , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/metabolismo , Nicotinamida Fosforribosiltransferasa/efectos adversos , Nicotinamida Fosforribosiltransferasa/genética , Fosfatidilinositol 3-Quinasa/química , Fosfatidilinositol 3-Quinasa/metabolismo , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/farmacología , Transducción de Señal/efectos de los fármacos , Factor de Transcripción ReIA/metabolismo

RESUMEN

The bleeding and haemorrhage is strictly related with accidents and many medical procedures. In some conditions it leads to hypovolaemia and further to hypovolaemic shock. Under conditions of haemorrhagic shock, heart rate and blood pressure critically collapse. Reversing the sympathoinhibitory phase of hypovolaemia could be crucial for clinical management of injured patients after haemorrhage. Systemic administration of 5-HT1A agonists seams to produce resuscitating effects. The aim of this study was to investigate the participation of central serotonin and, in particular, 5-HT1A receptors in cardiovascular regulation in haemorrhagic shock in rats. Intracerebroventricular (i.c.v.) administration of serotonin (5-HT) increased the heart rate (HR), mean arterial pressure (MAP) and implicated that all haemorrhaged animals survived for the whole observation time (2 hours). Similar, although significantly more minor, effects were achieved after selective 5-HT1A activation. Moreover, the i.c.v. administration of selective 5-HT1A antagonist before i.c.v. 5-HT injection partially inhibited 5-HT induced changes. The results of the present work indicate that 5-HT plays an important role in the reversal of the haemorrhagic shock in rats. These effects are at least partially dependent on activation of 5-HT1A receptors.

Asunto(s)

Receptor de Serotonina 5-HT1A/fisiología , Serotonina/farmacología , Choque Hemorrágico/fisiopatología , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Piperazinas/farmacología , Ratas , Ratas Wistar , Antagonistas de la Serotonina/farmacología , Agonistas de Receptores de Serotonina/farmacología

RESUMEN

Adipocytokine profile seems to play a distinct role in the pathogenesis of chronic hepatitis C (CHC). Chemerin and vaspin are recently described adipocytokines with various suggested functions and potential to modulate inflammatory response and insulin resistance (IR). We assessed chemerin, vaspin and leptin serum concentration and studied their association with IR laboratory and morphological features in patients with hepatitis C. The study included 40 patients with hepatitis C and 20 healthy volunteers, similar in age and body mass index (43.6 +/- 11.6 vs 40.9 +/- 11.8 years and 25.0 +/- 4.1 vs 23.9 +/- 3.3 kg/m(2), respectively). Patients had to have a normal lipid profile, and diabetes was an exclusion criteria. Serum chemerin and leptin levels and IR were significantly higher in patients with hepatitis C when compared to the controls (P = 0.02, P = 0.02 and P = 0.02, respectively), whereas vaspin level was significantly decreased (P = 0.01). Serum chemerin was negatively associated with necro-inflammatory grade (r = (-0.49), P = 0.01). The lowest levels of serum chemerin were found in patients with moderate/severe inflammation (P = 0.03). Serum leptin tended to be up-regulated in patients with minimal inflammatory activity. Serum vaspin was higher, although not significantly, when fibrosis was more advanced. IR was positively associated with fibrosis stage (r = 0.33, P = 0.03). Serum chemerin and leptin were related to each other (r = 0.45, P = 0.02).Our findings support a complex interaction between the analysed adipokines and pathogenesis of inflammatory process in CHC. The role of chemerin and vaspin in pathogenesis of inflammatory response should be further investigated.

Asunto(s)

Adipoquinas/sangre , Quimiocinas/sangre , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/patología , Resistencia a la Insulina , Serpinas/sangre , Adulto , Femenino , Humanos , Inflamación/patología , Péptidos y Proteínas de Señalización Intercelular , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad

RESUMEN

Visfatin is a new adipokine involved in several processes. The data concerning visfatin in chronic hepatitis C (CHC) is small. To assess visfatin serum concentration and to study its association with biochemical and morphological features in CHC. Seventy nonobese patients with CHC (Group 1) confirmed by the presence of serum hepatitis C virus (HCV)-RNA and 20 healthy volunteers (Group 2), similar in age and BMI with normal fasting glucose and lipid profile were included. Visfatin was significantly increased in Group 1 compared with Group 2 (55.6 +/- 23.1 vs 23.7 +/- 3.8 ng/mL; P < 0.001). Visfatin was negatively associated with necro-inflammatory activity grade (r = -0.36; P = 0.007). The lowest levels were found in patients with the most advanced inflammation: grades 3-4 - 46.8 +/- 17.1, grade 2 - 52.6 +/- 18.4 and grade 1 - 75.2 +/- 27.6 ng/mL; P = 0.017. A significant difference was also shown comparing patients with minimal inflammatory activity to the rest of the cohort (P = 0.009). Visfatin receiver operating characteristic curve analysis for different necro-inflammatory activity - grade 1 vs grades 3-4 with area under the curve 0.81 indicated a good discriminant power for differentiation of moderate/severe inflammation, with the cut-off set at 57.6 ng/mL (sensitivity 75%, specificity 90%, positive predictive value 0.90, negative predictive value 0.75). Serum visfatin concentration increases significantly in CHC patients. These findings suggest that visfatin is important in the pathogenesis of the inflammatory process in CHC. Visfatin may play a dual role as a pro-inflammatory or/and protective factor. The measurement of visfatin serum concentration may serve as an additional tool in distinguishing more advanced grades of the necro-inflammatory activity.

Asunto(s)

Citocinas/sangre , Hepatitis C Crónica/patología , Nicotinamida Fosforribosiltransferasa/sangre , Suero/química , Adulto , Biomarcadores , Femenino , Hepatitis C Crónica/diagnóstico , Humanos , Hígado/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad

RESUMEN

Among the proteins secreted by adipocytes, acylation stimulating protein (ASP), which plays a crucial role in energetic balance regulation, merits particular attention. ASP is a protein of the C3 complement system, responsible for glucose and lipids metabolism in an insulin-independent mechanism. ASP's role during pregnancy and its interactions with pregnancy hormones remains unknown. The lipogenic character of ASP may impose a question as to what extent this hormone participates in pregnant women lipogenesis, and what is the basal and postprandial ASP secretion during the second trimester of pregnancy. The results of the examinations of 26 pregnant women during the second trimester of their first pregnancy were analyzed. Due to the limited data available in the literature, a control group was examined. The group consisted of 8 healthy non-pregnant patients within similar age ranges. Blood samples were collected in order to determine ASP, total cholesterol, HDL, LDL and triglyceride levels. Basal ASP levels present in obese pregnant women (group OBP; 30.20 +/- 2.13 ng/mL) were significantly higher than those in the healthy control group (group LnP; 20.49 +/- 1.97 ng/mL), P<0.05. Mann-Whitney U test- analysis of these group differences indicated that OBP patients had significantly higher ASP levels than controls at 30 (P<0.01), 60 (P<0.01), and 120 (P<0.01) min after a meal. After a meal, the incremental ASP area under the curve in group OBW patients was significantly higher from that observed in control group LnP (718,9 +/- 263,9 ng/mL x 2h vs. 35,1 +/- 14,6 ng/mL x 2h, P<0.05). Basal concentration of triglycerides, total cholesterol and LDL cholesterol were significantly higher in all pregnant women compared to the group of non-obese non-pregnant women. It was found that lipid parameters were highly dependent upon body mass gain during pregnancy. Group OBP demonstrated significantly higher basal concentrations of all parameters of lipid metabolism in comparison with the remaining groups of pregnant patients. In conclusion, we found abnormalities of ASP and lipid profiles in lean, overweight, and obese pregnant women strictly connected with obesity. Acylation stimulating protein correlated with lipid parameters, suggesting increased risk of dyslipidemia in obese pregnant women.

Asunto(s)

Complemento C3a/análisis , Obesidad/sangre , Complicaciones del Embarazo/sangre , Aumento de Peso , Adulto , Índice de Masa Corporal , Estudios de Casos y Controles , Complemento C3a/metabolismo , Femenino , Humanos , Obesidad/metabolismo , Embarazo , Complicaciones del Embarazo/metabolismo , Segundo Trimestre del Embarazo , Aumento de Peso/fisiología , Adulto Joven

RESUMEN

Tumor angiogenesis is believed to be a prognostic indicator associated with tumor growth and metastasis. Microvessel density (MVD) assessment with common endothelial markers such as CD34 has been found to influence prognosis among endometrial carcinoma patients. The CD105/endoglin antibody has been reported to preferentially bind to proliferated endothelial cells in tissues participating in angiogenesis. The aim of this study was to evaluate the quantification of angiogenesis by assessing MVD in endometrial lesions when comparing the performance of anti-CD34 and anti-CD105 in women with benign and malignant endometrial changes. The study included 58 women (37 postmenopausal) with normal, hyperplastic and malignant endometrium in which preoperative transvaginal sonography was performed. Histological results of the removed endometrium were correlated with MVD assessed in "hot areas" where high densities of microvessels were detected within tumoral tissue. Endometrial cancer was confirmed in 37 women (3 premenopausal). Benign hyperplasia (14 cases), secretory or proliferative endometrium (5 cases) or endometrial atrophy (2 cases) was found in the remaining women. Malignant changes were mostly noted as FIGO stage I and II (28 cases) and had a low (1 or 2) histological grade (29 cases). Median MVD's assessed with CD105 and CD34 were 10.4 and 32.3, respectively. Median MVD assessed with CD34 was almost twice higher in women with endometrial cancer than in women with benign endometrium (CD34 MVD = 41.8 vs. 27.6, p=0.004). In cases of CD105 MVD significant differences between women with benign and malignant endometrial changes were also found (CD105 MVD = 11.8, vs. 6.4; p=0.00007). The menopausal status, but not the clinical stage or histological grading was significantly correlated with both CD34 MVD (p=0.02) and CD105 MVD (p=0.0003). A significant correlation was also found between CD34 and CD105 measured MVD (p=0.000001). In conclusion, transition from endometrial hyperplasia to endometrial cancer appears to be accompanied by microvessel density changes. MVD assessed with both CD34 and CD105 antibodies could be used as a potential prognostic factor in women with endometrial cancer. Our study showed that endoglin, by staining the proliferating microvessels could be more specific and sensitive marker for tumor neoangiogenesis than the more commonly used marker, CD34.

Asunto(s)

Biomarcadores de Tumor/análisis , Neoplasias Endometriales/irrigación sanguínea , Microvasos , Neovascularización Patológica/diagnóstico por imagen , Antígenos CD/análisis , Antígenos CD/biosíntesis , Antígenos CD34/análisis , Antígenos CD34/biosíntesis , Endoglina , Neoplasias Endometriales/diagnóstico por imagen , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Femenino , Humanos , Microvasos/diagnóstico por imagen , Microvasos/metabolismo , Persona de Mediana Edad , Estadificación de Neoplasias , Neovascularización Patológica/metabolismo , Pronóstico , Receptores de Superficie Celular/análisis , Receptores de Superficie Celular/biosíntesis , Estudios Retrospectivos , Ultrasonografía

RESUMEN

The aim of the study were to answer the question 1.) Whether circulating pro-inflammatory markers of endothelial dysfunction and due to chronic low-grade inflammation of obesity, are altered in untreated lean, young relatively healthy polycystic ovary syndrome (PCOS) patients in comparison with healthy controls; 2.) Whether postprandial plasma concentration pattern of ghrelin and PYY can be predictable as risk factors for atherosclerosis and depend of obesity. Forty young women with PCOS were divided in two groups: 19 lean and 21 obese. The control group included 20 lean, healthy volunteers. Plasma total and active ghrelin, total PYY and PYY(3-36), serum adiponectin and insulin were measured using RIA technique, serum sCD40L, visfatin, sP-, sE-selectins, resistin by EIA. Composition of test meal was: 527 kcal total and consisted of 24.1% fat, 54.4% carbohydrate and 21.5% protein. Total and active ghrelin and total PYY were significantly lower in obese PCOS women, whereas active ghrelin was also significantly lower in lean PCOS women compared to controls. Postprandial plasma total ghrelin levels decrease were blunted in lean and obese compared to controls (12.8 % and 18.2% vs 28.2 %). Postprandial plasma active ghrelin decreased in lean and obese PCOS groups (49.9 % and 44.1 %) and controls (63.8 %). PCOS subjects exhibited smaller rises in postprandial levels of total PYY. Postprandial plasma PYY(3-36) levels increased in obese PCOS women (30.9 %) and controls (41%), whereas lean PCOS women exhibited blunted increase (11.5%). sCD40L levels increased, whereas adiponectin decreased in PCOS groups independently, whereas rise in visfatin, sE- and sP-selectin and the fall in adiponectin was associated with obesity. sP- and sE -selectins correlated positively with obesity. In summary, our study provides the first evidence that lean untreated young PCOS women contribute to the so called "pancreatic islet adaptation to insulin resistance" because of ghrelin and PYY profiles. We confirmed existing of low-grade chronic inflammation in early stage of visceral obesity in lean PCOS patients. The lost endogenous "islet adaptation to insulin resistance" may lead to endothelial dysfunction and promote acceleration of atherosclerosis.

Asunto(s)

Ghrelina/sangre , Péptido YY/sangre , Síndrome del Ovario Poliquístico/metabolismo , Periodo Posprandial , Adiponectina/sangre , Aterosclerosis/etiología , Biomarcadores/sangre , Índice de Masa Corporal , Enfermedad Crónica , Endotelio Vascular/fisiopatología , Femenino , Humanos , Inflamación/metabolismo , Insulina/sangre , Obesidad/metabolismo , Obesidad/fisiopatología , Factores de Riesgo , Adulto Joven

Asunto(s)

Presión Sanguínea/fisiología , Sistema Nervioso Central/fisiología , Histamina/metabolismo , Serotonina/metabolismo , Animales , Antagonistas de los Receptores Histamínicos/metabolismo , Masculino , Ratas , Ratas Wistar , Receptores Histamínicos/metabolismo

Asunto(s)

Amitriptilina/metabolismo , Antidepresivos Tricíclicos/metabolismo , Histamina , Choque Hemorrágico/tratamiento farmacológico , Animales , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Histamina/metabolismo , Histamina/farmacología , Histamina/uso terapéutico , Masculino , Ratas , Ratas Wistar

Asunto(s)

Sistema Cardiovascular/metabolismo , Histamina/metabolismo , Derivación Portocava Quirúrgica , Choque Hemorrágico , Animales , Circulación Sanguínea/fisiología , Presión Sanguínea , Frecuencia Cardíaca , Masculino , Ratas , Ratas Endogámicas Lew

RESUMEN

Metabolic syndrome (MS), defined as central obesity, hyperinsulinemia, insulin resistance, hypertension, dyslipidemia and glucose intolerance, has been associated with inflammatory biomarkers and cardiovascular diseases. This study was carried out on three groups of women; lean controls, moderately obese with MS (OB-MS) and morbidly obese with MS (MOB-MS). The main objectives were: 1. to analyze the plasma levels of total and acylated ghrelin, peptide YY(3-36) (PYY(3-36)), cholecystokinin (CCK), gastrin and insulin levels under basal conditions and in response to a standard mixed meal, and 2. to elucidate the relationship between the plasma levels of these gut peptides and metabolic syndrome parameters. Plasma levels of the gut hormones were measured by radioimmunoassays at time 0 just before the meal and at 30, 60 and 120 min after a meal ingestion. Traditional lipid profile and high-sensitivity C reactive protein (hs-CRP), the strongest biomarker of inflammation were also determined in OB-MS and MOB-MS. When compared to OB-MS, MOB-MS exhibited much higher anthropometric parameters such as waist circumference, higher fat mass and higher plasma levels of low density lipoprotein-cholesterol (LDL-C) and hs-CRP. Both these obese groups revealed significantly higher values of body mass index (BMI), fat mass, total cholesterol (TC), LDL-C, fasting glucose, fasting insulin, insulin resistance (IR) calculated from homeostatic model assessment (HOMA) and hs-CRP compared to the values recorded in lean subjects. Fasting PYY(3-36) level was lower, while fasting acylated ghrelin was higher in MOB-MS than in OB-MS. Plasma total and acylated ghrelin levels were significantly lower in OB-MS compared to lean women. In MOB-MS women the fasting PYY(3-36) levels were lower compared to lean controls and OB-MS, whilst postprandially in both OB-MS and MOB-MS, it was much lower than in lean women. The fasting plasma levels of total and acylated ghrelin and their postprandial decrease were significantly smaller in both obese groups compared to lean subjects. Plasma hs-CRP levels correlated positively with BMI, waist circumference, fat mass, fasting glucose, HOMA IR and fasting active ghrelin, whilst it negatively correlated with plasma fasting and total ghrelin. Moreover, plasma fasting acylated ghrelin correlated positively with fat mass. Fasting total ghrelin correlated positively with BMI, HDL-C and negatively with HOMA IR. We conclude that MS features of obesity are closely related to fasting and postprandial alterations of concentrations of PYY(3-36), CCK and ghrelin, suggesting that determination of gut hormones controlling food intake might be considered as a valuable tool to assess the progression of MS to comorbidities of obesity.

Asunto(s)

Hormonas Gastrointestinales/sangre , Síndrome Metabólico/metabolismo , Obesidad/metabolismo , Hormonas Peptídicas/sangre , Periodo Posprandial , Acilación , Adulto , Glucemia/metabolismo , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Colecistoquinina/sangre , LDL-Colesterol/sangre , Ayuno/sangre , Femenino , Gastrinas/sangre , Gastrinas/metabolismo , Ghrelina/sangre , Humanos , Insulina/sangre , Resistencia a la Insulina , Obesidad Mórbida/metabolismo , Péptido YY/sangre , Polonia

RESUMEN

Maternal obesity has been reported as a risk factor for various maternal and fetal complications. The aim of the present study was to examine the patterns of basal and postprandial plasma concentrations of certain gut hormones affecting food intake such as acylated ghrelin, peptide YY(3-36) (PYY(3-36)), cholecystokinin (CCK), insulin and glucose in pregnant women with varying body mass gain during physiological pregnancy. The study included 34 women with singleton pregnancies in the 2(nd) trimester of gestation. The examined pregnant women were divided into 4 groups; I. control pregnancy (CP) with weight gain below 0.5 kg/week; II. overweight low weight gain <1 kg/week (OLWG), III. overweight high weight gain >1 kg/week (OHWG); morbidly obese pregnant with weight gain >1.5 kg/week (MOP). The basal acylated-ghrelin levels in MOP subjects were significantly higher than those in CP and no usual suppression of acylated ghrelin after the meal observed in CP as well as in OLWG and OHWG was found in MOP women. Basal PYY(3-36) plasma levels were similar in CP, OLWG and OHWG but in MOP was significantly reduced and no significant increase in hormone level, typically observed in CP, was detected after a meal in overweight or obese women studied. The fasting CCK and C-reactive protein (CRP) levels in MOP subjects were significantly higher than those in CP and other overweight women. In conclusion, we found that pregnant women with overweight and obesity exhibit significant changes in fasting and postprandial gut hormones affecting food intake such as acylated ghrelin, PYY(3-36) and CCK as well as in CRP and these changes might contribute, at least in part, the development of obesity in pregnancy.

Asunto(s)

Hormonas Gastrointestinales/sangre , Obesidad/metabolismo , Hormonas Peptídicas/sangre , Periodo Posprandial , Complicaciones del Embarazo/metabolismo , Acilación , Adulto , Apetito , Glucemia/metabolismo , Índice de Masa Corporal , Proteína C-Reactiva/metabolismo , Colecistoquinina/sangre , Ayuno , Femenino , Gastrinas/sangre , Ghrelina/sangre , Homeostasis , Humanos , Insulina/sangre , Obesidad/fisiopatología , Obesidad Mórbida/metabolismo , Obesidad Mórbida/fisiopatología , Péptido YY/sangre , Polonia , Embarazo , Complicaciones del Embarazo/fisiopatología , Aumento de Peso

RESUMEN

There is now growing evidence that the reactive oxygen species have an influence on proliferation and antioxidative status of various cell types. The aim of the study was to investigate the effects of different concentrations of leptin, ghrelin, angiotensin II and orexins on proliferation, culture medium malondialdehyde (MDA) levels and antioxidative enzymes activities: superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in 3T3 L1 preadipocytes cell culture. Cell proliferation was measured using [(3)H]tymidine incorporation. In 3T3-L1 cells leptin caused a significant reduction in proliferation (by 36%) compared to control. Ghrelin increased preadipocyte proliferation, and the effect was stronger in higher dose (by 39%), while proproliferatory effect of angiotensin II was stronger in lower doses (by 47%). All used doses of orexin A significantly increased 3T3 L1 cell proliferation (from 21% to 160%), while orexin B caused a marked reduction (from 35% to 70%) of this proliferation. The effects of both orexins were dose-dependent. Leptin and ghrelin increased activity of SOD, CAT, GSH-Px and decreased level of MDA. Angiotensin II treatment stimulated only SOD and CAT activities. Influence of orexins was different on various enzymes. Orexin A increased MDA levels, while orexin B caused a marked decrease in MDA levels. Our results strongly suggest the effects of appetite affecting hormones such as leptin and ghrelin on proliferation and antioxidative enzyme activities of preadipocyte cell lines. Orexin A was found to be the most efficient proliferative-signalling hormone, while orexin B revealed the most significant inhibitory effect on preadipocytes proliferation.

Asunto(s)

Adipocitos/efectos de los fármacos , Angiotensina II/farmacología , Ghrelina/farmacología , Péptidos y Proteínas de Señalización Intracelular/farmacología , Leptina/farmacología , Neuropéptidos/farmacología , Estrés Oxidativo , Células 3T3-L1 , Adipocitos/enzimología , Adipocitos/fisiología , Angiotensina II/fisiología , Animales , Catalasa/metabolismo , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Ghrelina/fisiología , Glutatión Peroxidasa/metabolismo , Péptidos y Proteínas de Señalización Intracelular/fisiología , Leptina/fisiología , Malondialdehído/metabolismo , Ratones , Neuropéptidos/fisiología , Orexinas , Superóxido Dismutasa/metabolismo

RESUMEN

The relation between snoring and obstructive sleep apnea as well as hypothyroidism is the object of interest of many authors. The respiratory disturbances during sleep are often observed in patients suffering from hypothyroidism. The relation of snoring to overweight in those patients has not been taken into account. The aim of the study was to evaluate the relations between hypothyroidism and quantitative and qualitative respiratory disturbances during sleep. Additional aim was to establish the relations of sleep apnea syndrome, snoring, hypothyroidism and overweight. The subjects included 15 patients (11 females and 4 males) aged from 28 to 73 (mean 50.3) suffering from hypothyroidism. All of them underwent thyroid testing before and after the hormonal treatment. TSH and fT4 concentrations were determined. At the same time the sleep assessment (PolyMESAM) was performed twice. Data were obtained from sleep studies and questionnaires (Epworth sleepiness scale). After the thyroid hormones stabilization significant decrease of snoring severity was observed. On the contrary, the respiratory disturbance index (RDI), desaturation index (DI), the lowest saturation (LSAT) did not change significantly, however, the Epworth scale score showed significant improvement. The correlations showed the strong relation between loud snoring and TSH (r=0.73, p<0.01) and fT4 (r=-0.66, p<0.003) concentrations before the treatment. The analysis showed no correlation between body mass (BMI) and snoring. The hormonal stabilization in patients suffering from hypothyroidism causes improvement in snoring severity. Based on our investigation the relationship between hypothyroidism and severity of snoring and excessive daytime somnolence was confirmed. It indicates a possible connection between hypothyroidism and upper airway resistance syndrome.

Asunto(s)

Hipotiroidismo/complicaciones , Sobrepeso/complicaciones , Apnea Obstructiva del Sueño/etiología , Ronquido/etiología , Adulto , Anciano , Índice de Masa Corporal , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/epidemiología , Masculino , Persona de Mediana Edad , Sobrepeso/epidemiología , Apnea Obstructiva del Sueño/epidemiología , Ronquido/epidemiología , Tirotropina/sangre , Tiroxina/sangre , Tiroxina/uso terapéutico