Gallbladder disease and pancreatic cancer risk: a multicentric case-control European study.

BACKGROUND AND AIMS: The overall evidence on the association between gallbladder conditions (GBC: gallstones and cholecystectomy) and pancreatic cancer (PC) is inconsistent. To our knowledge, no previous investigations considered the role of tumour characteristics on this association. Thus, we aimed to assess the association between self-reported GBC and PC risk, by focussing on timing to PC diagnosis and tumour features (stage, location, and resection). METHODS: Data derived from a European case-control study conducted between 2009 and 2014 including 1431 PC cases and 1090 controls. We used unconditional logistic regression models to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) adjusted for recognized confounders. RESULTS: Overall, 298 (20.8%) cases and 127 (11.6%) controls reported to have had GBC, corresponding to an OR of 1.70 (95% CI 1.33-2.16). The ORs were 4.84 (95% CI 2.96-7.89) for GBC diagnosed <3 years before PC and 1.06 (95% CI 0.79-1.41) for ≥3 years. The risk was slightly higher for stage I/II (OR = 1.71, 95% CI 1.15-2.55) vs. stage III/IV tumours (OR = 1.23, 95% CI 0.87-1.76); for tumours sited in the head of the pancreas (OR = 1.59, 95% CI 1.13-2.24) vs. tumours located at the body/tail (OR = 1.02, 95% CI 0.62-1.68); and for tumours surgically resected (OR = 1.69, 95% CI 1.14-2.51) vs. non-resected tumours (OR = 1.25, 95% CI 0.88-1.78). The corresponding ORs for GBC diagnosed ≥3 years prior PC were close to unity. CONCLUSION: Our study supports the association between GBC and PC. Given the time-risk pattern observed, however, this relationship may be non-causal and, partly or largely, due to diagnostic attention and/or reverse causation.

Risk of pancreatic cancer associated with family history of cancer and other medical conditions by accounting for smoking among relatives.

Background: Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods: Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. Results: FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. Conclusions: The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies.

Really does temperature reduction and norepinephrine have similar effects on the energy metabolism in rat brown adipose tissue?

CONTEXT: Heat generation by brown adipose tissue (BAT) in response to temperature reduction seems to be entirely related to sympathetic nervous stimulation. OBJECTIVE: To analyse if temperature reduction and norepinephrine may differently affect the expression of proteins related to energy metabolism in BAT. MATERIALS AND METHODS: Isolated rats BAT was incubated with/without norepinephrine (10-6 mol/L, 24 h at 32 °C and 37 °C). RESULTS: In BAT, 32 °C increased the protein expression levels of carnitine palmitoyltransferase-I and -II, mitochondrial uncoupling protein-1 (UCP-1) and the expression and activity of lactate dehydrogenase. Mitochondrial F1-ATP synthase α-chain expression was decreased at 32 °C compared to 37 °C. Norepinephrine and at 32 °C exposure, UCP-1 expression was increased but cytochrome-c oxidase and F1-ATP synthase α-chain expression was reduced with respect to 37 °C. DISCUSSION: Sympathetic stimulation seems not to be the only factor associated with heat generation. CONCLUSIONS: Temperature reduction by itself exerts some different effects on the expression of proteins related to the energy metabolism than norepinephrine.

A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in late adulthood; therefore, many patients suffer or have suffered from other diseases. Identifying disease patterns associated with PDAC risk may enable a better characterization of high-risk patients. METHODS: Multimorbidity patterns (MPs) were assessed from 17 self-reported conditions using hierarchical clustering, principal component, and factor analyses in 1705 PDAC cases and 1084 controls from a European population. Their association with PDAC was evaluated using adjusted logistic regression models. Time since diagnosis of morbidities to PDAC diagnosis/recruitment was stratified into recent (<3 years) and long term (≥3 years). The MPs and PDAC genetic networks were explored with DisGeNET bioinformatics-tool which focuses on gene-diseases associations available in curated databases. RESULTS: Three MPs were observed: gastric (heartburn, acid regurgitation, Helicobacter pylori infection, and ulcer), metabolic syndrome (obesity, type-2 diabetes, hypercholesterolemia, and hypertension), and atopic (nasal allergies, skin allergies, and asthma). Strong associations with PDAC were observed for ≥2 recently diagnosed gastric conditions [odds ratio (OR), 6.13; 95% confidence interval CI 3.01-12.5)] and for ≥3 recently diagnosed metabolic syndrome conditions (OR, 1.61; 95% CI 1.11-2.35). Atopic conditions were negatively associated with PDAC (high adherence score OR for tertile III, 0.45; 95% CI, 0.36-0.55). Combining type-2 diabetes with gastric MP resulted in higher PDAC risk for recent (OR, 7.89; 95% CI 3.9-16.1) and long-term diagnosed conditions (OR, 1.86; 95% CI 1.29-2.67). A common genetic basis between MPs and PDAC was observed in the bioinformatics analysis. CONCLUSIONS: Specific multimorbidities aggregate and associate with PDAC in a time-dependent manner. A better characterization of a high-risk population for PDAC may help in the early diagnosis of this cancer. The common genetic basis between MP and PDAC points to a mechanistic link between these conditions.

Chronic and remitting trajectories of depressive symptoms in the elderly. Characterisation and risk factors.

BACKGROUND: In elderly general population sub-syndromal clinically significant levels of depressive symptoms are highly prevalent and associated with high co-morbidity and increased mortality risk. However changes in depressive symptoms over time and etiologic factors have been difficult to characterise notably due to methodological shortcomings. Our objective was to differentiate trajectories of depressive symptoms over 10 years in community-dwelling elderly men and women using statistical modelling methods which take into account intra-subject correlation and individual differences as well as to examine current and life-time risk factors associated with different trajectories. METHODS: Participants aged 65 and over were administered standardised questionnaires and underwent clinical examinations at baseline and after 2, 4, 7 and 10 years. Trajectories over time of the Center for Epidemiologic Studies Depression scores were modelled in 517 men and 736 women separately with latent class mixed models which include both a linear mixed model to describe latent classes of trajectories and a multinomial logistic model to characterise the latent trajectories according to baseline covariates (socio-demographic, lifestyle, clinical, genetic characteristics and stressful life events). RESULTS: In both genders two different profiles of symptom changes were observed over the 10-year follow-up. For 9.1% of men and 25% of women a high depressive symptom trajectory was found with a trend toward worsening in men. The majority of the remaining men and women showed decreasing symptomatology over time, falling from clinically significant to very low levels of depressive symptoms. In large multivariate class membership models, mobility limitations [odds ratio (OR) = 4.5, 95% confidence interval (CI) 1.6-12.9 and OR = 4.9, 95% CI 2.3-10.7, in men and women respectively], ischemic pathologies (OR = 2.9, 95% CI 1.0-8.3 and OR = 3.1, 95% CI 1.0-9.9), and recent stressful events (OR = 4.5, 95% CI 1.1-18.5, OR = 3.2, 95% CI 1.6-6.2) were associated with a poor symptom course in both gender as well as diabetes in men (OR = 3.5, 95% CI 1.1-10.9) and childhood traumatic experiences in women (OR = 3.1, 95% CI 1.6-5.8). CONCLUSIONS: This prospective study was able to differentiate patterns of chronic and remitting depressive symptoms in elderly people with distinct symptom courses and risk factors for men and women. These findings may inform prevention programmes designed to reduce the chronic course of depressive symptomatology.

Endothelial damage in major depression patients is modulated by SSRI treatment, as demonstrated by circulating biomarkers and an in vitro cell model.

There is a link between depression, cardiovascular events and inflammation. We have explored this connection through endothelial dysfunction, using in vivo and in vitro approaches. We evaluated circulating biomarkers of endothelial dysfunction in patients with major depression at their diagnosis (MD-0) and during antidepressant treatment with the selective serotonin reuptake inhibitor escitalopram, for 8 and 24 weeks (MD-8 and MD-24). Results were always compared with matched healthy controls (CON). We measured in vivo circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) in blood samples, and assessed plasma levels of soluble von Willebrand factor (VWF) and vascular cell adhesion molecule-1 (VCAM-1). CEC counts, soluble VWF and VCAM-1 were statistically elevated in MD-0 (P<0.01 versus CON) and gradually decreased during treatment. Conversely, EPC levels were lower in MD-0, tending to increase throughout treatment. In vitro studies were performed in human endothelial cells cultured in the presence of sera from each study group. Elevated expression of the inflammation marker intercellular adhesion molecule-1 and oxidative stress, with lower presence of endothelial nitric oxide synthase and higher reactive oxygen species production, were found in cells exposed to MD-0 sera (P<0.05 versus CON). These results were normalized in cells exposed to MD-24 sera. Thrombogenicity of extracellular matrices generated by these cells, measured as expression of VWF, tissue factor and platelet reactivity, showed non-significant differences. We provide a model of cultured endothelial cells reproducing endothelial dysfunction in naive patients with major depression, demonstrating endothelial damage and inflammation at diagnosis, and recovering with selective serotonin reuptake inhibitor treatment for 24 weeks.

Patterns of selective serotonin reuptake inhibitor use and risk of falls and fractures in community-dwelling elderly people: the Three-City cohort.

In this population-based elderly cohort, participants using selective serotonin reuptake inhibitor (SSRI) antidepressants have an increased risk of falls and fractures notably when the treatment was continued over 4 years. Among the various SSRI types, citalopram only was at significant risk for falls and fluoxetine for fractures. INTRODUCTION: Increased risk of falls and fractures has been reported in elderly users of SSRIs. However, biases were insufficiently addressed notably temporality between exposure and outcome and confounding by residual depression. Our objective was to examine the associations between SSRIs and fall or fracture incidence focusing on their chronic use and different types of SSRIs. METHODS: The population-based cohort included participants aged 65 years and above, who had not fallen before inclusion (n = 6599) or were free of recent fracture (n = 6823) and were followed up twice over 4 years. New fall and fracture events were self-reported and defined as at least two falls and one fracture, respectively, during the previous 2 years. SSRI users were compared with those taking no antidepressants. Hazard ratios (HRs) were estimated using Cox models with delayed entry and adjusted for many confounders including residual depressive symptoms. RESULTS: Incidence of falls was 19.3 % over 4 years and that of fractures 9.5 %. After multi-adjustment, SSRI intake was significantly associated with a higher risk of falls (HR, 95 % CI = 1.58, 1.23-2.03) and fractures (HR, 95 % CI = 1.61, 1.16-2.24). The risks were significantly increased by 80 % in those continuing the treatment over 4 years. Citalopram intake only was at significant risk for falls and fluoxetine for fractures. CONCLUSIONS: In this large community-dwelling elderly sample, SSRI users were at higher risk of falls and fractures. This association was not due to reverse causality or residual depressive symptoms. Different SSRI drugs may have specific adverse effects on falls and fractures.

Metabolic differences between white and brown fat from fasting rabbits at physiological temperature.

It has been suggested that activated brown adipose tissue (BAT) shows increased glucose metabolic activity. However, less is known about metabolic activity of BAT under conditions of fasting and normal temperature. The aim of this study was to compare the possible differences in energetic metabolism between BAT and white adipose tissue (WAT) obtained from rabbits under the conditions of physiological temperature and 24 h after fasting conditions. The study was carried out on New Zealand rabbits (n=10) maintained for a period of 8 weeks at 23±2 °C. Food was removed 24 h before BAT and WAT were obtained. Protein expression levels of the glycolytic-related protein, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate dehydrogenase were higher in WAT than that in BAT. The expression level of carnitine palmitoyltransferase 1 (CPT1) and CPT2, two fatty acid mitochondrial transporters, and the fatty acid ß-oxidation-related enzyme, acyl CoA dehydrogenase, was higher in BAT than in WAT. Cytosolic malate dehydrogenase expression and malate dehydrogenase activity were higher in WAT than in BAT. However, lactate dehydrogenase expression and lactate content were significantly higher in BAT than in WAT. In summary, this study for the first time, to our knowledge, has described how under fasting and normal temperature conditions rabbit BAT seems to use anaerobic metabolism to provide energetic fuel, as opposed to WAT, where the malate-aspartate shuttle and, therefore, the gluconeogenic pathway seem to be potentiated.

C-reactive protein gene variants: independent association with late-life depression and circulating protein levels.

C-reactive protein (CRP) is a heritable biomarker of systemic inflammation that is commonly elevated in depressed patients. Variants in the CRP gene that influence protein levels could thus be associated with depression but this has seldom been examined, especially in the elderly. Depression was assessed in 990 people aged at least 65 years as part of the ESPRIT study. A clinical level of depression (DEP) was defined as having a score of ⩾16 on The Center for Epidemiologic Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Five single-nucleotide polymorphisms spanning the CRP gene were genotyped, and circulating levels of high-sensitivity CRP were determined. Multivariable analyses adjusted for socio-demographic characteristics, smoking, ischemic pathologies, cognitive impairment and inflammation-related chronic pathologies. The minor alleles of rs1130864 and rs1417938 were associated with a decreased risk of depression in women at Bonferroni-corrected significance levels (P=0.002). CRP gene variants were associated with serum levels in a gender-specific manner, but only rs1205 was found to be nominally associated with both an increased risk of DEP and lower circulating CRP levels in women. Variants of the CRP gene thus influence circulating CRP levels and appear as independent susceptibility factors for late-life depression.

Artificially-induced organelles are optimal targets for optical trapping experiments in living cells.

Optical trapping supplies information on the structural, kinetic or rheological properties of inner constituents of the cell. However, the application of significant forces to intracellular objects is notoriously difficult due to a combination of factors, such as the small difference between the refractive indices of the target structures and the cytoplasm. Here we discuss the possibility of artificially inducing the formation of spherical organelles in the endoplasmic reticulum, which would contain densely packed engineered proteins, to be used as optimized targets for optical trapping experiments. The high index of refraction and large size of our organelles provide a firm grip for optical trapping and thereby allow us to exert large forces easily within safe irradiation limits. This has clear advantages over alternative probes, such as subcellular organelles or internalized synthetic beads.

Cervical necrotizing fasciitis: report of 6 cases and review of literature.

OBJECTIVE: Necrotizing fasciitis in the cervical region is a rare entity, characterized by a fulminant infection that causes extensive necrosis of the subcutaneous tissue and fascial planes, with high mortality and morbidity rates. The origin is generally odontogenic or pharyngeal, involving a mixed flora of microorganisms. Descending infection and mediastinal involvement are usually associated and are the main complications. The aim of the present study was to review the cases treated in our department and analyze diagnosis and treatment, supplementing the understanding of the disease. METHODS: A retrospective study was performed on the clinical records of patients admitted to our center between January 2005 and June 2010 with diagnosis of necrotizing cervical fasciitis. RESULTS: Six clinical records were reviewed. The origin of the infection was mainly oropharyngeal and odontogenic, with a mixed flora of Prevotella, Peptostreptococcus and coagulase-negative Staphylococcus. All patients presented mediastinal involvement: superior mediastinitis in 4 patients and superior and postero-inferior mediastinitis in 2 cases. All patients underwent early drainage by bilateral cervicotomy with mediastinal drainage by a cervical approach in those with superior mediastinal affection, and associated thoracotomy, in a single surgical step, for postero-inferior mediastinitis. Temporary tracheotomy was performed in all cases. All received broad spectrum antibiotics, with a medium hospital stay of 37 days. There were no deaths reported. CONCLUSION: Concerning cervical necrotizing fasciitis, early diagnosis and surgical treatment associated to antibiotics and intensive medical care are essential to obtain a favorable outcome.

The Spanish Pancreatic Club recommendations for the diagnosis and treatment of chronic pancreatitis: part 1 (diagnosis).

Chronic pancreatitis (CP) is a relatively uncommon, complex and heterogeneous disease. The absence of a gold standard applicable to the initial phases of CP makes its early diagnosis difficult. Some of its complications, particularly chronic pain, can be difficult to manage. There is much variability in the diagnosis and treatment of CP and its complications amongst centers and professionals. The Spanish Pancreatic Club has developed a consensus on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. A list of questions was drafted, and two experts reviewed each question. Then, a draft was produced and shared with the entire panel of experts and discussed in a face-to-face meeting. This first part of the consensus addresses the diagnosis of CP and its complications.

The Spanish Pancreatic Club's recommendations for the diagnosis and treatment of chronic pancreatitis: part 2 (treatment).

Chronic pancreatitis (CP) is a complex disease with a wide range of clinical manifestations. This range comprises from asymptomatic patients to patients with disabling symptoms or complications. The management of CP is frequently different between geographic areas and even medical centers. This is due to the paucity of high quality studies and clinical practice guidelines regarding its diagnosis and treatment. The aim of the Spanish Pancreatic Club was to give current evidence-based recommendations for the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts on this disease. These experts were selected according to clinical and research experience in CP. A list of questions was made and two experts reviewed each question. A draft was later produced and discussed with the entire panel of experts in a face-to-face meeting. The level of evidence was based on the ratings given by the Oxford Centre for Evidence-Based Medicine. In the second part of the consensus, recommendations were given regarding the management of pain, pseudocysts, duodenal and biliary stenosis, pancreatic fistula and ascites, left portal hypertension, diabetes mellitus, exocrine pancreatic insufficiency, and nutritional support in CP.

Genetic characterization of a reciprocal translocation present in a widely grown barley variety.

Artificially induced translocation stocks have been used to physically map the barley genome; however, natural translocations are extremely uncommon in cultivated genotypes. Albacete is a barley variety widely grown in recent decades in Spain and carrying a reciprocal translocation which obviously does not affect its agronomical fitness. This translocation has been characterized by a combination of cytological and molecular genetic approaches. Firstly, recombination frequencies between markers on chromosomes 1H and 3H were estimated to determine the boundaries of the reciprocal interchange. Secondly, 1H-3H wheat barley telosome addition lines were used to assign selected markers to chromosome arms. Thirdly, fluorescence in situ hybridization (FISH) with rDNA probes (5S and 18S-5.8S-26S) and microsatellite probes [(ACT)(5), (AAG)(5) and (CAG)(5)] was used to determine the locations of the translocation breakpoints more precisely. Fourthly, fine-mapping of the regions around the translocation breakpoints was used to increase the marker density for comparative genomics. The results obtained in this study indicate that the translocation is quite large with breakpoints located on the long arms of chromosomes 1H and 3H, between the pericentromeric (AAG)(5) bands and above the (ACT)(5) interstitial distal bands, resulting in the reciprocal translocation 1HS.1HL-3HL and 3HS.3HL-1HL. The gene content around the translocation breakpoints could be inferred from syntenic relationships observed among different species from the grass family Poaceae (rice, Sorghum and Brachypodium) and was estimated at approximately 1,100 and 710 gene models for 1H and 3H, respectively. Duplicated segments between chromosomes Os01 and Os05 in rice derived from ancestral duplications within the grass family overlap with the translocation breakpoints on chromosomes 1H and 3H in the barley variety Albacete.

Dronedarone.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with substantial morbidity and mortality. Dronedarone is an amiodarone-like benzofuran which lacks the iodine moiety and presents a methane sulfonyl group that decreases its lipophilicity, thus shortening the half-life and decreasing tissue accumulation. Like amiodarone, dronedarone blocks multiple cardiac ion channels and ß-adrenoceptors, presenting electrophysiological characteristics of all four Vaughan Williams classes of antiarrhythmic drugs. In clinical trials, dronedarone has been found effective for both rhythm and rate control. Dronedarone was more effective than placebo in maintaining sinus rhythm in patients with paroxysmal and/or persistent AF and was also effective for ventricular rate control during AF recurrences, providing incremental rate control on top of standard drugs in permanent AF. Furthermore, in the ATHENA trial, dronedarone reduced the incidence of hospitalization due to cardiovascular events or death in patients with nonpermanent AF. Even when dronedarone was less effective than amiodarone in decreasing AF recurrence, it had a better safety profile, being devoid of thyroid, pulmonary and neurological toxicity. This review analyzes the electrophysiological and pharmacological properties, as well as the efficacy and safety of dronedarone in patients with atrial fibrillation.

Factors associated with initial participation in a population-based screening for colorectal cancer in Catalonia, Spain: a mixed-methods study.

OBJECTIVE: To identify barriers and facilitators associated with participation in the first round of a population-based program for colorectal cancer (CRC) in Catalonia, Spain and to identify strategies for motivating and supporting behavioral change. MATERIAL AND METHODS: A two-part, mixed-methods design was used. In first place, a prospective study of individuals aged 50-69 years (n=1961) was conducted in 2006-2007. Secondly, focus groups were undertaken with participants and non-participants of the CRC screening, in 2008. RESULTS: Intention to participate was an important determinant of participation (82.9% vs 65.9%, OR=2.56, 95%CI:1.95-3.36) in addition to knowledge about CRC and its early detection. Respondents who reported that CRC may be asymptomatic in early stages enrolled in the screening program more frequently than those who thought CRC is always symptomatic (49.4% vs 44.8%, OR:1.82; 95%CI:1.3-2.6). Barriers for participation mentioned in focus groups were competing perceived for other health problems and other demands as well as misunderstanding about personal relevance of the screening. CONCLUSION: Individuals' perceptions of CRC are amenable to change through education-based interventions. Increasing public knowledge related to the burden of CRC and its preventive potential may be an effective way for improving participation in a population-based screening program.

Linkage map construction involving a reciprocal translocation.

This paper is concerned with a novel statistical-genetic approach for the construction of linkage maps in populations obtained from reciprocal translocation heterozygotes of barley (Hordeum vulgare L.). Using standard linkage analysis, translocations usually lead to 'pseudo-linkage': the mixing up of markers from the chromosomes involved in the translocation into a single linkage group. Close to the translocation breakpoints recombination is severely suppressed and, as a consequence, ordering markers in those regions is not feasible. The novel strategy presented in this paper is based on (1) disentangling the "pseudo-linkage" using principal coordinate analysis, (2) separating individuals into translocated types and normal types and (3) separating markers into those close to and those more distant from the translocation breakpoints. The methods make use of a consensus map of the species involved. The final product consists of integrated linkage maps of the distal parts of the chromosomes involved in the translocation.

Increased cyclic guanosine monophosphate production and endothelial nitric oxide synthase level in mononuclear cells from sildenafil citrate-treated patients with erectile dysfunction.

Mononuclear cells express enzymes involved in the NO/cyclic guanosine monophosphate (cGMP) generating system, as well as PDE5. The objective of the study was to determine the effect of sildenafil citrate administration on the level of proteins involved in the NO/cGMP generating system in mononuclear cells from patients with ED. Twenty-one patients with ED (International Index of Erectile Function-Erectile Function Domain (IIEF-EFD) 17.9+/-0.8) were enrolled and 100 mg sildenafil citrate on-demand was administered during 12 weeks. All patients showed cardiovascular risk factors. After sildenafil citrate administration, IIEF-EFD score was improved (26+/-1.2 P<0.05). In the mononuclear cells, the protein level of endothelial NO synthase (eNOS) was higher after sildenafil citrate treatment. It was accompanied by reduction in the circulating plasma levels of both high-sensitive C-reactive protein and soluble intercellular adhesive molecule-1. The protein level of soluble guanylate cyclase and PDE5 did not change in the mononuclear cells after sildenafil citrate treatment. However, in the mononuclear cells exogenous NO induced a higher cGMP production after 12-weeks sildenafil citrate administration. In conclusion, in mononuclear cells from patients with ED sildenafil citrate administration increased the level of eNOS protein and increased cGMP production in response to NO. Moreover, sildenafil citrate administration reduced the plasma circulating levels of two biomarkers associated with inflammation.

[Testosterone, endothelial function, cardiovascular health and androgen deficiency in the old man]. / Testosterona, función endotelial, salud cardiovascular y androgenodeficiencia del varón añoso.

Testosterone determination in an old men population has demonstrated its about the as general health marker, not only sexual, prompting a greater in to arrest for this analytic determination and the potential relations of testosterone with other markers of cardiovascular health, obesity, hypertension, erectile dysfunction, sarcopenia, metabolic syndrome, ageing, and other conditions. We specifically review the relationship between cardiovascular health, erectile dysfunction, and androgen deficiency, processes easily recognizable, prevented and treated. Current information gives such a prominence to testosterone as a health reference that its determination seems to be inexcusable in the ageing male consult.