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OBJECTIVE: Exposure to airborne pollutants during pregnancy appears to be associated with uterine growth restriction and adverse neonatal outcome. Proprotein convertase subtilisin/kexin type (PCSK9), the key modulator of low-density lipoprotein (LDL) metabolism, increases following particulate matter (PM10) exposure. Because maternal cholesterol is required for fetal growth, PCSK9 levels could be used to evaluate the potential impact of airborne pollutants on fetal growth. DESIGN: A cohort of 134 healthy women during early pregnancy (11-12 weeks of gestational age) was studied. RESULTS: A significant association between circulating PCSK9 levels and three tested air pollutants (PM10, PM2.5, nitric oxide (NO2)) was found. Of importance, gestational age at birth was reduced by approximately 1 week for each 100 ng/mL rise in circulating PCSK9 levels, an effect that became more significant at the highest quartile of PM2.5 (with a 1.8 week advance in delivery date for every 100 ng/mL rise in circulating PCSK9; p for interaction = 0.026). This finding was supported by an elevation of the odds ratio for urgent cesarean delivery for each 100 ng/mL rise in PCSK9 (2.99, 95% CI, 1.22-6.57), similar trends being obtained for PM10 and NO2. CONCLUSIONS: The association between exposure to air pollutants during pregnancy and elevation in PCSK9 advances our understanding of the unforeseen influences of environmental exposure in terms of pregnancy associated disorders.
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Contaminantes Atmosféricos , Proproteína Convertasa 9 , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Femenino , Desarrollo Fetal , Edad Gestacional , Humanos , Italia , Exposición Materna/efectos adversos , EmbarazoRESUMEN
BACKGROUND: Primary hyperparathyroidism (PHPT) is a common cause of secondary osteoporosis in postmenopausal women. Th17 lymphocytes and the released cytokine IL-17A play an important role in bone metabolism. Th17 cells have been shown to be activated by PTH, and peripheral blood T cells from patients affected with PHPT express higher levels of IL-17A mRNA than controls. AIM: To investigate circulating levels of IL-17A and the ratio RANKL/OPG, as markers of osteoclastogenesis, in 50 postmenopausal PHPT women compared with postmenopausal osteoporotic non-PHPT women (n = 20). RESULTS: Circulating levels of IL-17A were similarly detectable in most PHPT and non-PHPT osteoporotic women (12.9 (8.4-23.1) vs. 11.3 (8.3-14.3) pg/ml, median (range interquartile), P = 0.759), at variance with premenopausal women where IL-17A was undetectable. In PHPT women, any significant correlations could be detected between circulating IL-17A levels and PTH levels. Nonetheless, significant negative correlations between circulating IL-17A and ionized calcium levels (r = -0.294, P = 0.047) and urine calcium excretions (r = -0.300, P = 0.045) were found. Moreover, PHPT women were characterized by positive correlations between IL-17A levels and femur neck (r = 0.364, P = 0.021) and total hip (r = 0.353, P = 0.015) T-scores. Circulating IL-17A levels did not show any significant correlation with sRANKL, OPG, and sRANKL/OPG ratio in PHPT women. CONCLUSIONS: In postmenopausal PHPT women, circulating IL-17A levels were similar to those detected in postmenopausal non-PHPT women, showing a disruption of the relationship observed in postmenopausal osteoporosis among circulating PTH, sRANKL, OPG, IL-17A, and bone demineralization in postmenopausal PHPT women. The data support an osteogenic effect of IL-17A in postmenopausal PHPT women.
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Hiperparatiroidismo Primario/sangre , Interleucina-17/sangre , Posmenopausia/sangre , Anciano , Calcio/sangre , Calcio/orina , Femenino , Humanos , Hiperparatiroidismo Primario/orina , Interleucina-17/orina , Persona de Mediana Edad , Osteoprotegerina/sangre , Osteoprotegerina/orina , Posmenopausia/orina , Receptor Activador del Factor Nuclear kappa-B/sangre , Receptor Activador del Factor Nuclear kappa-B/orinaRESUMEN
Many studies, focused on identifying new biomarkers for coronary artery disease (CAD) risk computation and monitoring, suggested a potential diagnostic role for fatty acids (FA). In the present study, we explored the potential diagnostic role of FA by using a data mining approach based on fourth generation artificial neural networks (ANN). Forty-one male subjects were enrolled. According to coronary angiography, 31 displayed CAD and 10 did not (non-CAD, control group). FA analysis was performed on plasma samples using a gas chromatography-mass spectrometry system and analyses were performed by an ANN method. The variables most closely related to CAD were low levels of alpha-linolenic acid, eicosapentaenoic acid, eicosatetraenoic and docosahexaenoic acids. High levels of 1,1-dimethoxyhexadecane, total dimethyl acetals and docosatetraenoic acid were related to non-CAD condition. This subset of variables, which were most closely correlated to the target diagnosis, achieved a consistent predictive rate. The average accuracy obtained was 76.5%, with 93% of sensitivity and 60% of specificity. The area under the ROC curve was equal to 0.79. In conclusion, our study highlighted the association between different plasma FA species, CAD and non-CAD conditions. The specific subset of variables could be of interest as a new diagnostic tool for CAD management.
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Biomarcadores/sangre , Enfermedad de la Arteria Coronaria/sangre , Ácidos Grasos/sangre , Redes Neurales de la Computación , Anciano , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Magnesium (Mg) and calcium (Ca) are the principal essential elements involved in endothelial cell homeostasis. Extracellular changes in the levels of either alter endothelial contraction and dilatation. Consequently Mg and Ca imbalance is associated with a high risk of endothelial dysfunction, the main process observed during acute aortic dissection (AAD); in this clinical condition, which mainly affects elderly men, smooth muscle cell alterations lead to intimal tears, creating a false new lumen in the media of the aorta. AAD patients have a high risk of mortality as a result of late diagnosis because often it is not distinguished from other cardiovascular diseases. We investigated Mg and Ca total circulating levels and the associated pro-inflammatory mediators in elderly AAD patients, to gain further information on the pathophysiology of this disorder, with a view to suggesting newer and earlier potential biomarkers of AAD. RESULTS: Total circulating Mg and Ca levels were both lower in AAD patients than controls (p < 0.0001). Using Ca as cut-off, 90% of AAD patients with low Ca (<8.4 mg/dL) came into the type A classification of AAD. Stratifying AAD according to this cut-off, Mg was lower in patients with lower total Ca. Compared to controls, both type A and B AAD patients had higher levels of all the pro-coagulant and pro-inflammatory mediators analyzed, including sP-sel, D-dimer, TNF-α, IL-6, and CRP (p < 0.05). Dividing types A and B using the Stanford classification, no significant differences were found (p > 0.05) The levels of both ICAM-1 and EN-1 were lower in AAD than in a control group (p < 0.0001 and p < 0.05 respectively). CONCLUSIONS: These findings suggest that low Mg and Ca in AAD elderly patients may contribute to altering normal endothelial physiology and also concur in changing the normal concentrations of different mediators involved in vasodilatation and constriction, associated with AAD onset and severity.
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BACKGROUND: Acute aortic dissection (AAD) is an event which may be rapidly fatal without early diagnosis and treatment. Aging is one of the main risk factors that could leading to AAD. To date, no specific biomarkers are available to increase the speed of diagnosis. CD40 ligand (CD40L), myeloperoxidase (MPO), matrix metalloproteinase (MMP)-1, -2, -9 and metallopeptidase tissue inhibitor 1 (TIMP-1) are biologically related molecules which integrate inflammation, tissue injury and remodeling, all events associated to AAD. Our is a pilot study to evaluate whether circulating levels of these molecules may be used as potential biomarkers in timely diagnosis of AAD. RESULTS: Within 24 h of symptom onset, circulating CD40L, MPO, MMP-1,-2,-9 and TIMP-1 were quantified by enzyme-linked immunosorbent assays in 22 patients (40-86 years of age) with AAD of ascending aorta (type A according to Stanford classification) and 11 patients with AAD of descending aorta (type B). 30 healthy individuals age matched were used as control group compared to controls, both type A and B AAD patients had higher CD40L (p < 0.001) and MPO (p < 0.01) levels. MMP-1 was higher in the overall AAD group (p < 0.01). After Stanford classification, type A group had increased level compared to both control and type B (p < 0.01 and p < 0.05, respectively). TIMP-1 was higher in both A and B groups compared to controls (p < 0.001). No differences were observed in MMP-2 and MMP-9 levels. CONCLUSIONS: The simultaneous evaluation of CD40L, MPO and MMP-1 and TIMP-1, which may contribute to structural changes in aortic tissue in AAD patients, seems to be a novel promising diagnostic panel.
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BACKGROUND AND AIMS: In coronary artery disease (CAD) epicardial adipose tissue (EAT) shows an elevated inflammatory infiltrate. Toll-like receptors (TLRs) are important mediators of adipose tissue inflammation and they are able to recognize endogenous products released by damaged cells. Because adipocyte death may be driven by hypertrophy, our aim was to investigate in CAD and non-CAD patients the association between EAT adipocyte size, macrophage infiltration/polarization and TLR-2 and TLR-4 expression. METHODS AND RESULTS: EAT biopsies were collected from CAD and non-CAD patients. The adipocyte size was determined by morphometric analysis. Microarray technology was used for gene expression analysis; macrophage phenotype and TLRs expression were analyzed by immunofluorescence and immunohistochemical techniques. Inflammatory mediator levels were determined by immunoassays. EAT adipocytes were larger in CAD than non-CAD patients and do not express perilipin A, a marker of lipid droplet integrity. In CAD, EAT is more infiltrated by CD68-positive cells which are polarized toward an M1 state (CD11c positive) and presents an increased pro-inflammatory profile. Both TLR-2 and TLR-4 expression is higher in EAT from CAD and observed on all the CD68-positive cells. CONCLUSIONS: Our findings suggested that EAT hypertrophy in CAD promotes adipocyte degeneration and drives local inflammation through increased infiltration of macrophages which are mainly polarized towards an M1 state and express both TLR-2 and TLR-4.
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Tejido Adiposo/patología , Enfermedad de la Arteria Coronaria/genética , Macrófagos/patología , Pericardio/patología , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/metabolismo , Adipocitos/metabolismo , Adolescente , Adulto , Anciano , Biopsia , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/patología , Humanos , Hipertrofia , Masculino , Persona de Mediana Edad , Perilipina-1/genética , Perilipina-1/metabolismo , Receptor Toll-Like 2/genética , Receptor Toll-Like 4/genética , Regulación hacia Arriba , Adulto JovenRESUMEN
BACKGROUND AND AIMS: Alterations in epicardial adipose tissue (EAT) biology (i.e. increased fat thickness and inflammation) have been described in coronary artery disease (CAD) patients. In addition to its classic role in the regulation of calcium-phosphate homeostasis, vitamin D may exert immune-regulatory and anti-inflammatory effects. Whether EAT inflammation may be linked to vitamin D deficiency is still unknown. In the present study we evaluated plasma 25-hydroxycholecalciferol (25OHD) level in CAD patients and its relationship with EAT ability to locally metabolize vitamin D, EAT expression of inflammation-related molecules and EAT thickness. METHODS AND RESULTS: Plasma 25OHD level was quantified by an immunoluminometric assay. EAT expression of inflammation-related molecules (MCP-1, PTX3, TNFα, IL-6, adiponectin), vitamin D receptor (VDR), CYP27B1 (25OHD-activating enzyme) and CYP24A1 (1,25-dihydroxycholecalciferol-metabolizing enzyme) was performed by microarray. EAT thickness was quantified by echocardiography. Median plasma 25OHD level was 10.85 ng/mL and 83% of CAD patients displayed 25OHD level below 20 ng/mL. At decreasing plasma 25OHD concentration, we observed a down-regulation in CYP27B1 and CYP24A1 level and an increased expression of VDR and pro-inflammatory cytokines (MCP-1, PTX3, TNFα, IL-6) at EAT level. No correlation was observed between plasma 25OHD level and EAT thickness. CONCLUSION: Our data suggest an increased activation of inflammatory pathways at EAT level possibly related to systemic and local vitamin D deficiency in CAD patients. Whether maintaining an optimal vitamin D status may be helpful to reduce EAT inflammation and to prevent CAD and its progression needs further investigation.
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Tejido Adiposo/fisiopatología , Enfermedad de la Arteria Coronaria/fisiopatología , Inflamación/fisiopatología , Pericardio/fisiopatología , Deficiencia de Vitamina D/fisiopatología , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/genética , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/metabolismo , Adiponectina/genética , Adiponectina/metabolismo , Anciano , Anciano de 80 o más Años , Glucemia/metabolismo , Índice de Masa Corporal , Peso Corporal , Proteína C-Reactiva/genética , Proteína C-Reactiva/metabolismo , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/complicaciones , Regulación hacia Abajo , Humanos , Inflamación/complicaciones , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Persona de Mediana Edad , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Componente Amiloide P Sérico/genética , Componente Amiloide P Sérico/metabolismo , Triglicéridos/sangre , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Vitamina D3 24-Hidroxilasa/genética , Vitamina D3 24-Hidroxilasa/metabolismoRESUMEN
Parathormone (PTH) has been suggested to affect the cardiovascular system. Teriparatide (TPT), the hormonally active 1-34 fragment of PTH, provides an anabolic treatment for osteoporosis. The aim of the present study was to evaluate the cardiometabolic effects of 18-month treatment with 20 µg/ die teriparatide subcutaneosly. Fourteen women with postmenopausal severe osteoporosis treated with once-daily sc 20 µg TPT (67.6 ± 2.5 years; BMI 27.7 ± 1.0 kg/m²) and 24 age- and BMI-matched severe osteoporotic women treated with iv yearly 5 mg zoledronate (ZLN) were evaluated at baseline and at 12-18 months of treatment for anthropometric measures, calcium, glucose and lipid metabolic parameters, and assessment of cardiac geometry by conventional echocardiography. TPT was effective in increasing mean lumbar spine bone mineral density with no clinically relevant changes in calcium metabolism parameters. TPT patients experienced an increase of BMI (27.7 ± 1.0 at baseline vs 29.0 ± 1.0 kg/m² at last evaluation, P=0.005) and mean whole body fat percentage (37.0 ± 2.1 vs 40.3 ± 1.9%, P=0.05), associated with increased serum leptin levels (17.3 ± 2.1 vs 22.9 ± 3.0 ng/ml; P=0.049). Glucose and lipid parameters were not affected by TPT as well as by ZLN treatment. Furthermore, TPT was associated with a decrease in systolic blood pressure; a decrease in the fractional shortening (41.2 ± 2.3 vs 36.9 ± 1.2; P=0.05) and an increase in the relative wall thickness (0.39 ± 0.01 vs 0.48 ± 0.01 mm; P=0.002), suggestive for concentric cardiac remodeling, was detected by echocardiographic monitoring. These changes could not be detected in bone active drug-free age- and metabolic-matched controls. In conclusion, long-term TPT therapy might affect cardiometabolic and cardiac geometry parameters in severe osteoporotic women, though changes are not clinically relevant.
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Osteoporosis Posmenopáusica/tratamiento farmacológico , Teriparatido/uso terapéutico , Anciano , Presión Sanguínea/efectos de los fármacos , Composición Corporal/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/uso terapéutico , Calcio/metabolismo , Difosfonatos/uso terapéutico , Femenino , Corazón/efectos de los fármacos , Humanos , Imidazoles/uso terapéutico , Teriparatido/efectos adversos , Ácido ZoledrónicoRESUMEN
Endothelial dysfunction and the disruption of the nitric oxide-cyclic guanosine monophosphate (cGMP) pathway have been considered the early mechanisms for the development of erectile dysfunction (ED). Myeloperoxidase (MPO), a heme-containing enzyme mainly released by activated neutrophils and monocytes, may contribute to endothelial dysfunction by promoting oxidation of different substrates and thus may play a role in ED. MPO level and its correlation with different plasma biomarkers of endothelial dysfunction were studied in patient with ED of arteriogenic (A-ED) and non-arteriogenic (NA-ED) to assess potential differences between the two ED subgroups. Diagnosis of ED was based on the International Index of Erectile Function Score. Its etiology was classified with penile echo-color Doppler at baseline and after intracavernous injection of prostaglandin E1. MPO, soluble (s) cGMP, sICAM-1, sVCAM-1 and sP-Selectin were measured by enzyme-linked immunosorbent assay. MPO concentration in A-ED was significantly higher compared to control subjects and NA-ED patients. Plasmatic cGMP level resulted lower both in A-ED and in NA-ED patients, whereas no difference has been observed between the two ED groups. sICAM-1 concentration resulted higher in A-ED compared both to controls and NA-ED. sVCAM-1 level was the same in controls, A-ED and NA-ED patients. sP-Selectin concentration resulted higher both in A-ED and in NA-ED patients than in controls, whereas no difference has been observed between the two ED groups. Correlation analysis indicated a positive correlation between plasmatic MPO, sICAM-1 and sP-Selectin levels. MPO may represent an important link between oxidation, inflammation and cardiovascular diseases and may also represent a potential marker to distinguish between the two subgroups of ED patients. Moreover, in ED subjects circulating cGMP may reflect the local signaling dysfunction. The use cGMP as a potential marker for monitoring the disease needs further investigation.
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Endotelio Vascular/fisiopatología , Disfunción Eréctil/enzimología , Peroxidasa/sangre , Biomarcadores/sangre , GMP Cíclico/sangre , Endotelio Vascular/enzimología , Humanos , Molécula 1 de Adhesión Intercelular/sangre , Masculino , Persona de Mediana EdadRESUMEN
The plasma concentration of asymmetrical dimethylarginine (ADMA), an inhibitor of nitric oxide synthase, has been linked to endothelial dysfunction. We investigated the relation between ADMA, symmetric dimethylarginine (SDMA) and L-arginine concentrations and erectile dysfunction. We compared plasma levels of ADMA, SDMA and L-arginine in 61 men in good health with erectile dysfunction of arteriogenic and non-arteriogenic origin. Diagnosis of erectile dysfunction was based on the International Index of Erectile Function Score and its aetiology was classified with penile echo-colour-Doppler in basal condition and after intracavernous injection of prostaglandin E1. The ADMA and SDMA concentrations were significantly higher in men with arteriogenic erectile dysfunction compared with those with erectile dysfunction of non-arteriogenic origin (p < 0.05) and the concentrations in both subgroups were significantly higher than in controls (p < 0.001). There was a negative correlation between ADMA and International Index of Erectile Function Score only in arteriogenic erectile dysfunction subgroup. L-arginine did not differ significantly neither between the two erectile dysfunction subgroups (p > 0.05) nor between each of the two erectile dysfunction subgroups and controls (p > 0.05). The L-arginine/ADMA and the L-arginine/SDMA ratios in arteriogenic erectile dysfunction subgroups were significantly lower than both in controls (p < 0.05) and in non-arteriogenic erectile dysfunction patients (p < 0.05); the two ratios in non-arteriogenic erectile dysfunction patients did not differ from those in the controls (p > 0.05). We conclude that ADMA and SDMA concentrations are significantly higher and L-arginine/ADMA ratio lower in patients who have arteriogenic erectile dysfunction compared with both patients with non-arteriogenic erectile dysfunction and controls. The negative correlation between ADMA and severity of erectile dysfunction is present only in patients with arteriogenic erectile dysfunction. This study supports the importance to always distinguish arteriogenic from non-arteriogenic erectile dysfunction patients to study the complicate erectogenic mechanisms that lead to erectile dysfunction and also to provide potential therapeutic agents for patients with arteriogenic erectile dysfunction.
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Arginina/análogos & derivados , Disfunción Eréctil/sangre , Impotencia Vasculogénica/sangre , Adulto , Arginina/sangre , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Interleukin-18 (IL-18) is a member of the interleukin-1 family of cytokines produced constitutively by different cell types and by adipose tissue. Due to the link between obesity, inflammation and cardiovascular diseases, we aimed to measure IL-18 circulating level in patients undergoing open-heart surgery both for elective coronary artery bypass grafting (CABG) or for valve replacement (VR), and we also evaluated whether epicardial adipose tissue (EAT) depot may be a potential source of IL-18. Circulating IL-18 protein was quantified by enzyme-linked immunosorbent assay. IL-18, IL-18 receptor 1 (IL-18 R1) and IL-18 receptor accessory protein (IL-18-RAP) gene expression in EAT depot were evaluated by one colour microarray platform. EAT thickness was measured by echocardiography. In this study we found that all cardiovascular patients (CABG and VR) have increased circulating IL-18 level compared to healthy control subjects (p < 0.0001), but no statistical significant difference was observed between CABG and VR groups (p = 0.35). A great increase in the gene expression of IL-18 (p < 0.05), IL-18 R1 (p < 0.01) and IL-18 RAP (p < 0.001) was observed in EAT samples obtained from CABG vs VR patients. In conclusion, CABG and VR patients had similar increased level of circulating IL-18 protein, but in EAT depots isolated from CABG gene expression of IL-18, IL-18 R1 and IL-18-RAP resulted higher than in VR patients. Future investigation on local IL-18 protein production, its autocrine-paracrine effect and its correlation with plasmatic IL-18 level could give more information on the relationship between IL-18 and coronary artery disease.
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Tejido Adiposo/metabolismo , Puente de Arteria Coronaria , Implantación de Prótesis de Válvulas Cardíacas , Interleucina-18/sangre , Pericardio/metabolismo , Adulto , Anciano , Femenino , Humanos , Interleucina-6/sangre , Interleucina-8/sangre , Masculino , Persona de Mediana Edad , Circunferencia de la CinturaRESUMEN
We evaluated the effect of different inflammatory conditions on iron status and, as a consequence, the possible use of iron markers as indicators of infection in the diagnosis of postoperative prosthetic orthopaedic joint infections. The study population was consisted of 26 patients undergoing revision of total hip or total knee joint arthroplasty and subdivided into three groups according to the cause of prosthesis implant failure: 10 as having had previous infection (Group A), 10 patients were categorized as having infection (Group B); and the remaining 6 (Group C) as not having infection. These patients were assayed for mean corpuscular haemoglobin concentration (MCHC) and serum values of iron (Fe), ferritin (Fer), transferrin (Tf), soluble transferrin receptor (sTfR), and transferrin saturation (sat Tf). Septic patients display statistically significant lower serum iron concentration, higher sTfR and ferritin levels, lower, but not statistically significant, MCHC compared to non septic ones. Little differences were observed for Tf, sat Tf, tibc, TfR index, among the three groups of patients. Our study suggests that iron status parameters, in particular serum iron, ferritin, sTfR and TfR index, could be useful tools for the early detection and the diagnosis of orthopaedic prosthetic joint infections.
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Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Hierro/sangre , Artropatías/diagnóstico , Complicaciones Posoperatorias/diagnóstico , Infecciones Relacionadas con Prótesis/diagnóstico , Adulto , Anciano , Biomarcadores , Femenino , Ferritinas/sangre , Humanos , Artropatías/sangre , Masculino , Persona de Mediana Edad , Proyectos Piloto , Complicaciones Posoperatorias/sangre , Infecciones Relacionadas con Prótesis/sangre , Receptores de Transferrina/análisis , Transferrina/análisisRESUMEN
BACKGROUND: The 5'-AMP-activated protein kinase (AMPK) plays a fundamental role in regulating energy homeostasis as well as feeding and metabolism, through central and peripheral actions. AMPK is activated by conditions causing ATP depletion and by different metabolic molecules, such as adiponectin and AMPK agonist, such as 5-aminoimidazole- 4-carboxamide-1-ß-D-ribofuranoside (AICAR). AMPK activation has also been shown to affect the migration of different cell types and to participate in the central control of reproductive function, although information concerning AMPK and the development of the hypothalamic reproductive compartment is lacking. AIM: To explore whether AMPK activation by globular adiponectin (gAdipo) and AICAR may affect the migratory ability of GnRH neurons. MATERIALS AND METHODS: We used GN11 immature GnRH neurons (in vitro model system), RT-PCR and Western blot analysis, and Boyden's chamber assay. RESULTS: gAdipo did not affect FBS-stimulated migration of GN11 cells and activated AMPK through the mandatory phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and Akt, which also interact one to each other. AICAR treatment inhibited FBS-stimulated GN11 cell migration, through a long-lasting activation of AMPK. A downstream activation of ERK1/2 by AICAR was also observed and inhibition of ERK1/2 amplified AICAR-induced inhibition of migration. CONCLUSIONS: The direct, but not the indirect, activation of AMPK appears to negatively affect FBSinduced GN11 cell migration, suggesting that the final balance between pro-migratory and anti-migratory actions may also depend upon the specific sequence of intracellular signals activated by one agent.
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Proteínas Quinasas Activadas por AMP/fisiología , Aminoimidazol Carboxamida/farmacología , Movimiento Celular/efectos de los fármacos , Neuronas/fisiología , Adiponectina/farmacología , Animales , Línea Celular , Activación Enzimática , Hormona Liberadora de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Ratones , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Fosforilación , Receptores de Adiponectina/biosíntesisRESUMEN
There is a universally recognized need to identify new, reliable markers of inflammation that can aid in the rapid diagnosis of orthopaedic joint prosthesis infections (OJP-Is). Since prompt diagnosis is key to timely intervention in the course of infection, different molecules have been studied. In this study, we examined three groups of patients: those with prosthesis infection, those without infection, and a third group with previous infection in whom the infection had been cleared. Four presumed markers of infection were tested: procalcitonin (PCT); C-reactive protein (CRP); interleukin-6 (IL-6); and soluble intercellular adhesion molecule-1 (sICAM-1). The results showed that PCT cannot be considered as a good marker of periprosthetic infection as no statistically significant difference in serum PCT levels emerged between patients with infection and controls or patients without infection. In contrast, both sICAM-1 and CRP may be considered as good markers of infection, as measurement of their levels allowed us to distinguish between patients with and without infection, and between patients with infection and those with previous infection, since marker levels quickly returned to baseline values after clearance of the infection. IL-6 was found to be a good marker for inflammation, as it distinguished between patients with infection and the other groups. In the patients with previous infection, the IL-6 values remained high versus the controls but lower and with a statistically significant difference versus the patients with infection. Further studies are needed to determine the cut-off value of IL-6 between patients with infection and those with previous infection.
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Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Proteína C-Reactiva/metabolismo , Calcitonina/sangre , Prótesis de Cadera/efectos adversos , Mediadores de Inflamación/sangre , Molécula 1 de Adhesión Intercelular/sangre , Interleucina-6/sangre , Prótesis de la Rodilla/efectos adversos , Infecciones Relacionadas con Prótesis/inmunología , Precursores de Proteínas/sangre , Antibacterianos/uso terapéutico , Artroplastia de Reemplazo de Cadera/instrumentación , Artroplastia de Reemplazo de Rodilla/instrumentación , Biomarcadores/sangre , Péptido Relacionado con Gen de Calcitonina , Femenino , Humanos , Italia , Masculino , Valor Predictivo de las Pruebas , Infecciones Relacionadas con Prótesis/sangre , Infecciones Relacionadas con Prótesis/diagnóstico , Infecciones Relacionadas con Prótesis/microbiología , Infecciones Relacionadas con Prótesis/terapia , Reoperación , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Sex hormones and adipokines seem to differently interact in both genders at different ages. AIM: To comparatively evaluate the serum level of adipokines and sex hormones in healthy non-pharmacologically treated premenopausal women, post-menopausal women, and elderly women, and in age-matched men. SUBJECTS: From the historical cohort of the Brisighella Heart Study we selected 199 adult healthy subjects (males: 89; females: 110), aged 62.5±12.4 yr. Men and women included in the age-class subgroups were matched for body mass index (BMI), waist circumference, blood pressure, heart rate, fasting plasma glucose, plasma lipids. RESULTS: Leptin did not differ among various age classes in men, while pre-menopausal women displayed significantly lower serum leptin than post-menopausal women (-6.7 ± 2.2 pg/ml, p=0.036). Post-menopausal women had significantly greater serum leptin when compared with age-matched men (+13.1 ± 2.0 pg/ml, p<0.001); the same was observed for elderly women when compared with elderly men (+11.2 ± 2.3 pg/ml, p<0.001). At any age, women had significantly lower serum testosterone/estrone ratio than age-matched men (p<0.01). Serum DHEAS was inversely proportional to age in both genders. The main predictors of adiponectin level are age in men (p=0.027) and BMI in women (p=0.003). The main predictors of leptin level are BMI and the testosterone/estrone ratio in both sexes (p<0.05). The testosterone/estrone ratio is also the main predictor of ghrelin levels in women (p=0.006). CONCLUSION: Sex hormones and adipokines show specific interactions in the two genders and in different age-classes in a representative sample of adult healthy subjects.