Search

Background: We used the Spanish national hospital discharge data from 2016 to 2022 to analyze procedures and hospital outcomes among patients aged ≥ 18 years admitted for ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) according to diabetes mellitus (DM) status (non-diabetic, type 1-DM or type 2-DM)., Methods: We built logistic regression models for STEMI/NSTEMI stratified by DM status to identify variables associated with in-hospital mortality (IHM). We analyzed the effect of DM on IHM., Results: Spanish hospitals reported 201,950 STEMIs (72.7% non-diabetic, 0.5% type 1-DM, and 26.8% type 2-DM; 26.3% female) and 167,285 NSTEMIs (61.6% non-diabetic, 0.6% type 1-DM, and 37.8% type 2-DM; 30.9% female). In STEMI, the frequency of percutaneous coronary intervention (PCI) increased among non-diabetic people (60.4% vs. 68.6%; p < 0.001) and people with type 2-DM (53.6% vs. 66.1%; p < 0.001). In NSTEMI, the frequency of PCI increased among non-diabetic people (43.7% vs. 45.7%; p < 0.001) and people with type 2-DM (39.1% vs. 42.8%; p < 0.001). In NSTEMI, the frequency of coronary artery by-pass grafting (CABG) increased among non-diabetic people (2.8% vs. 3.5%; p < 0.001) and people with type 2-DM (3.7% vs. 5.0%; p < 0.001). In the entire population, lower IHM was associated with undergoing PCI (odds ratio [OR] [95% confidence interval] = 0.34 [0.32-0.35] in STEMI; 0.24 [0.23-0.26] in NSTEMI) or CABG (0.33 [0.27-0.40] in STEMI; 0.45 [0.38-0.53] in NSTEMI). IHM decreased over time in STEMI (OR = 0.86 [0.80-0.93]). Type 2-DM was associated with higher IHM in STEMI (OR = 1.06 [1.01-1.11])., Conclusions: PCI and CABG were associated with lower IHM in people admitted for STEMI/NSTEMI. Type 2-DM was associated with IHM in STEMI., (© 2024. The Author(s).)

(1) Background: Radical prostatectomy has a high incidence of erectile dysfunction (ED). The aim was to determine if the expression of the nitric oxide synthase-3/soluble guanylate cyclase/phosphodiesterase 5 axis could be detected in buccal mucosa and if it could be differently expressed in patients with and without ED; (2) Methods: Erectile function from 38 subjects subjected to prostatectomy was evaluated using the International Index of Erectile Function-Erectile Function Domain before and one year after surgery. Nitric oxide synthase (NOS3), β1-subunit of soluble guanylate cyclase (sGC), phosphodiesterase-5 (PDE-5) expressions, and interleukin-6 and interleukin-10 content were measured in the buccal mucosa. PDE5A rs3806808 gene polymorphism was genotyped; (3) Results: One year after prostatectomy, 15 patients had recovered functional erection, and 23 showed ED. NOS3, β1-sGC, interleukin-6, and interleukin-10 expressions were not different between patients with and without ED after radical prostatectomy. Buccal mucosa levels of PDE-5 were higher in patients with ED compared to those who recovered erectile functionality. There were no differences found in the genotype of PDE5A polymorphism; (4) Conclusions: One year after prostatectomy, patients with ED had higher PDE5 levels in their buccal mucosa than patients who had recovered erectile function. Rs3806808 PDE5A gene polymorphism was not associated with increased PDE5 expression in buccal mucosa.

(1) Background: Artificial intelligence using machine learning techniques may help us to predict and prevent obesity. The aim was to design an interpretable prediction algorithm for overweight/obesity risk based on a combination of different machine learning techniques. (2) Methods: 38 variables related to sociodemographic, lifestyle, and health aspects from 1179 residents in Madrid were collected and used to train predictive models. Accuracy, precision, and recall metrics were tested and compared between nine classical machine learning techniques and the predictive model based on a combination of those classical machine learning techniques. Statistical validation was performed. The shapely additive explanation technique was used to identify the variables with the greatest impact on weight gain. (3) Results: Cascade classifier model combining gradient boosting, random forest, and logistic regression models showed the best predictive results for overweight/obesity compared to all machine learning techniques tested, reaching an accuracy of 79%, precision of 84%, and recall of 89% for predictions for weight gain. Age, sex, academic level, profession, smoking habits, wine consumption, and Mediterranean diet adherence had the highest impact on predicting obesity. (4) Conclusions: A combination of machine learning techniques showed a significant improvement in accuracy to predict risk of overweight/obesity than machine learning techniques separately.

Objectives : Both diabetes mellitus (DM) and gynaecological and colorectal cancers are highly prevalent diseases. Furthermore, the presence of DM constitutes a risk factor and poor prognostic indicator for these types of cancer. This study is based on the European Health Interview Surveys in Spain (EHISS) of 2014 and 2020. It aimed to determine the trends in adherence to screening tests for gynaecological cancers (breast and cervical) and colorectal cancer, compare adherence levels between populations with and without diabetes, and identify predictors of adherence in the population with diabetes. Methods : An epidemiological case-control study based on the EHISS data of 2014 and 2020 was conducted. The characteristics of participants who underwent screening tests were analysed based on the presence or absence of DM, and predictors of adherence to these preventive activities were identified. Results : A total of 1852 participants with reported DM and 1852 controls without DM, adjusted for age and sex, were included. A higher adherence to mammography was observed in women without diabetes compared to those with diabetes, although statistical significance was not reached (72.9% vs. 68.6%, p = 0.068). Similarly, higher Pap smear adherence was observed in the population without diabetes in the age group between 60 and 69 years compared to the population with diabetes (54.0% vs. 45.8%, p = 0.016). Pap smear adherence among women with diabetes was significantly higher in the EHISS of 2020 (52.0% in 2014 vs. 61.0% in 2020, p = 0.010), as was the case for faecal occult blood testing (13.8% in 2014 vs. 33.8% in 2020, p < 0.001), but it was not significant for mammography (70.4% in 2014 vs. 66.8% in 2020, p = 0.301). Overall, the predictors of adherence to screening tests were older age, history of cancer and higher education level. Conclusions : Adherence levels to cancer screening tests were lower in the population with diabetes compared to those without diabetes, although an improvement in Pap smear and faecal occult blood test adherence was observed in 2020 compared to 2014. Understanding predictors is important to improve adherence rates in the population with diabetes.

Background: The American Joint Committee on Cancer (AJCC), in its 8th edition, introduces modifications to the previous TNM classification, incorporating tumour depth of invasion (DOI). The aim of this research is to analyse the prognosis (in terms of disease-free survival and overall survival) of clinical early stage (I and II) squamous cell carcinomas of the oral tongue according to the DOI levels established by the AJCC in its latest TNM classification to assess changes to the T category and global staging system and to evaluate the association between DOI and other histological risk factors., Methods: A retrospective longitudinal observational study of a series of cases was designed. All patients were treated with upfront surgery at our institution between 2010 and 2019. The variables of interest were defined and classified into four groups: demographic, clinical, histological and evolutive control. Univariate and multivariate analyses were carried out and survival functions were calculated using the Kaplan-Meier method. Statistical significance was established for p values below 0.05., Results: Sixty-one patients were included. The average follow-up time was 47.42 months. Fifteen patients presented a loco-regional relapse (24.59%) and five developed distant disease (8.19%). Twelve patients died (19.67%). Statistically significant differences were observed, with respect to disease-free survival ( p = 0.043), but not with respect to overall survival ( p = 0.139). A total of 49.1% of the sample upstaged their T category and 29.5% underwent modifications of their global stage. The analysis of the relationship between DOI with other histological variables showed a significant association with the presence of pathological cervical nodes ( p = 0.012), perineural invasion ( p = 0.004) and tumour differentiation grade ( p = 0.034). Multivariate analysis showed association between depth of invasion and perineural invasion., Conclusions: Depth of invasion is a histological risk factor in early clinical stages of oral tongue squamous cell carcinoma. Depth of invasion impacts negatively on patient prognosis, is capable per se of modifying the T category and the global tumour staging, and is associated with the presence of cervical metastatic disease, perineural invasion and tumoural differentiation grade.

(1) Background: We aim to assess the time trend from 2014 to 2020 in the prevalence of physical activity (PA), identify gender differences and sociodemographic and health-related factors associated with PA among people with diabetes, and compare PA between people with and without diabetes. (2) Methods: We conducted a cross-sectional and a case-control study using as data source the European Health Interview Surveys for Spain (EHISS) conducted in years 2014 and 2020. The presence of diabetes and PA were self-reported. Covariates included socio-demographic characteristics, health-related variables, and lifestyles. To compare people with and without diabetes, we matched individuals by age and sex. (3) Results: The number of participants aged ≥18 years with self-reported diabetes were 1852 and 1889 in the EHISS2014 and EHISS2020, respectively. The proportion of people with diabetes that had a medium or high frequency of PA improved from 48.3% in 2014 to 52.6% in 2020 ( p = 0.009), with 68.5% in 2014 and 77.7% in 2020 being engaged in two or more days of PA ( p < 0.001). Males with diabetes reported more PA than females with diabetes in both surveys. After matching by age and gender, participants with diabetes showed significantly lower engagement in PA than those without diabetes. Among adults with diabetes, multivariable logistic regression showed confirmation that PA improved significantly from 2014 to 2020 and that male sex, higher educational level, and better self-rated health were variables associated to more PA. However, self-reported comorbidities, smoking, or BMI > 30 were associated to less PA. (4) Conclusions: The time trend of PA among Spanish adults with diabetes is favorable but insufficient. The prevalence of PA in this diabetes population is low and does not reach the levels of the general population. Gender differences were found with significantly more PA among males with diabetes. Our result could help to improve the design and implementation of public health strategies to improve PA among people with diabetes., Competing Interests: The authors declare no conflict of interest.

The incidence of hospitalizations of Parkinson´s disease (PD) in Spain suffered a steady rise from 1997 to 2012. However, data on the trends during the following decade (2010-2019) are lacking. Hospital admissions with a primary and secondary diagnosis of PD were selected using the Spanish National Hospital Discharge Database (SNHDD) for the period 2010-2019. The primary endpoint was the incidence of hospitalizations and in-hospital mortality, stratified in biannual periods. The incidence of PD hospitalizations increased progressively over time from 81.25 cases in 2010-2011 to 94.82 cases in 2018-2019 per 100,000 inhabitants. Male sex, age and comorbidity also increased progressively in PD inpatients. PD as a comorbid condition presented a higher increment (annual percentage of change, APC +1.71%, p < 0.05) than PD as the main reason of hospitalization (APC +1.26%, p < 0.05). In the multivariate regression model, factors associated with mortality were male sex (OR = 1.15, 95% CI 1.01-1.35), age (>80 years, OR = 12.76, 95% CI 3.96-29.64) and comorbidity (Charlson index ≥ 2, OR 1.77, 95% CI 1.69-1.85). Adjusted mortality by age, sex, comorbidity and diagnostic position remained stable. In conclusion, PD hospitalizations in Spain have increased, with a parallel increment in mean age, male sex and higher comorbidities. However, adjusted mortality remains unchanged. The burden of this disease may increase the complexity and costs of hospital care in the future.

The aim of this study is to evaluate the functional outcomes and quality of life (QoL) in oncologic patients with intraoral defects reconstructed with the buccinator myomucosal flap. A retrospective study was performed involving 39 patients with intraoral soft-tissue defects, reconstructed with a buccinator myomucosal flap during a six-year period. Patients completed the European Organization for Research and Treatment of Cancer questionnaires, the standard questionnaire (QLQ-C30) and the head-and-neck specific module (QLQ-H&N35). Thirty-nine patients with a mean age of 61.23 ± 15.80 years were included in the study. Thirty-three patients were diagnosed with an oncological condition (84.61%). Six patients (15.38%) developed orosinusal communication and underwent extensive debridement. The median global-health-status score was 79.27 and emotional performance was the lowest scoring, with a mean score of 76.93. As for the symptom items, the most outstanding were dental problems (33.33), oral opening (31.62) and dry mouth (37.61), followed by sticky saliva (24.79), problems with social eating (21.15) and pain (19.87). The most significant symptoms were radiotherapy-related adverse effects such as pain, fatigue, dental problems and dry mouth. Patients reconstructed with the buccinator myomucosal flap develop a good quality of life for all types of activities, and a correct function and aesthetics. Postoperative radiotherapy is associated with a poorer quality of life, and can lead to impairment of several symptoms such as swallowing, oral opening and dry mouth.

(1) Background: To assess the time trend in the prevalence of chronic neck pain (CNP), chronic low back pain (CLBP), and migraine or frequent headache (MFH) among people with diabetes in Spain from 2014 to 2020, this study identified sex differences and compared the prevalence of these pain sites between people with diabetes and age−sex-matched non-diabetic subjects. (2) Methods: The study design included a cross-sectional and a case−control study. The data were obtained from the European Health Interview Surveys for Spain conducted in 2014 and 2020. The presence of diabetes, CNP, CLBP, and MFH was self-reported. Study covariates included sociodemographic characteristics, comorbidities, lifestyles, and pain-related variables. (3) Results: Among people with diabetes, the prevalence of CNP, CLBP, and MFH did not improve from 2014 to 2020. Women with diabetes had a significantly higher prevalence of all the pain sites analyzed than men with diabetes. After matching by sex and age, the prevalence of CNP (26.0% vs. 21.1%; p < 0.001), CLBP (31.2% vs. 25.0%; p < 0.001), and MFH (7.7% vs. 6.5%; p = 0.028) was higher for people with diabetes than for those without diabetes. Self-reported mental disease was independently associated with reporting the three pain sites analyzed in people with diabetes. (4) Conclusions: The prevalence of CNP, CLBP, and MFH has remained stable over time. Remarkable sex differences were found, with a higher prevalence among women than men with diabetes. Diabetes was associated with reporting in all the pain sites analyzed. Self-reported mental disease was associated with reporting CNP, CLBP, and MFH.

Background: Mitochondria have been involved in host defense upon viral infections. Factor Xa (FXa), a coagulating factor, may also have influence on mitochondrial functionalities. The aim was to analyze if in human pulmonary microvascular endothelial cells (HPMEC), the SARS-CoV-2 (COVID-19) spike protein subunits, S1 and S2 (S1+S2), could alter mitochondrial metabolism and what is the role of FXA., Methods: HPMEC were incubated with and without recombinants S1+S2 (10 nmol/L each)., Results: In control conditions, S1+S2 failed to modify FXa expression. However, in LPS (1  μ g/mL)-incubated HPMEC, S1+S2 significantly increased FXa production. LPS tended to reduce mitochondrial membrane potential with respect to control, but in higher and significant degree, it was reduced when S1+S2 were present. LPS did not significantly modify cytochrome c oxidase activity as compared with control. Addition of S1+S2 spike subunits to LPS-incubated HPMEC significantly increased cytochrome c oxidase activity with respect to control. Lactate dehydrogenase activity was also increased by S1+S2 with respect to control and LPS alone. Protein expression level of uncoupled protein-2 (UCP-2) was markedly expressed when S1+S2 were added together to LPS. Rivaroxaban (50 nmol/L), a specific FXa inhibitor, significantly reduced all the above-mentioned alterations induced by S1+S2 including UCP-2 expression., Conclusions: In HPMEC undergoing to preinflammatory condition, COVID-19 S1+S2 spike subunits promoted alterations in mitochondria metabolism suggesting a shift from aerobic towards anaerobic metabolism that was accompanied of high FXa production. Rivaroxaban prevented all the mitochondrial metabolic changes mediated by the present COVID-19 S1 and S2 spike subunits suggesting the involvement of endogenous FXa., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2022 Khaoula Zekri-Nechar et al.)

Background and Objectives: Aspirin (ASA) is a commonly used antithrombotic drug that has been demonstrated to reduce venous thromboembolism. The aim was to analyze if geriatric COVID-19 patients undergoing a 100 mg/day Aspirin (ASA) treatment prior to hospitalization differ in hospital outcome compared to patients without previous ASA therapy. Materials and Methods: An observational retrospective study was carried out using an anonymized database including geriatric COVID-19 patients (March to April 2020) admitted to Madrid Hospitals Group. A group of COVID-19 patients were treated with low ASA (100 mg/day) prior to COVID-19 infection. Results: Geriatric ASA-treated patients were older (mean age over 70 years; n = 41), had higher frequency of hypertension and hyperlipidemia, and upon admission had higher D-dimer levels than non-ASA-treated patients (mean age over 73 years; n = 160). However, patients under ASA treatment did not show more frequent pulmonary thromboembolism (PE) than non-ASA-treated patients. ASA-treated geriatric COVID-19-infected patients in-hospital < 30 days all-cause mortality was more frequent than in non-ASA-treated COVID-19 patients. In ASA-treated COVID-19-infected geriatric patients, anticoagulant therapy with low molecular weight heparin (LMWH) significantly reduced need of ICU care, but tended to increase in-hospital < 30 days all-cause mortality. Conclusions: Prior treatment with a low dose of ASA in COVID-19-infected geriatric patients increased frequency of in-hospital < 30 days all-cause mortality, although it seemed to not increase PE frequency despite D-dimer levels upon admission being higher than in non-ASA users. In ASA-treated geriatric COVID-19-infected patients, addition of LMWH therapy reduced frequency of ICU care, but tended to increase in-hospital < 30 days all-cause mortality.

Purpose: Combination of Rivaroxaban plus Aspirin improved cardiovascular outcome in patients with stable cardiovascular disease. The aim was to determine if Rivaroxaban and acetylsalicylic acid alone or in combination may protect mitochondrial mitophagy in human coronary artery endothelial cells (HCAEC) exposed to D-glucose., Methods: HCAEC were incubated under different conditions: 5 mmol/L glucose D-glucose (control), 30 mmol/L D-Glucose with and without 50 nmol/L Rivaroxaban (Rivaroxaban), 0.33 mmol/L ASA (ASA) or Rivaroxaban (12.5 nmol/L)+ASA (0.33 mmol/L; (Riva+ASA)., Results: HCAEC incubated with D-glucose showed an increased Factor Xa expression. The mitochondrial content of Pink-1 and Parkin were significantly reduced in high glucose-incubated HCAEC compared to control. Rivaroxaban+ASA significantly increased the mitochondrial content of Pink-1 and Parkin, and the mitochondrial membrane potential compared to D-Glucose group. Both ASA alone and Riva+ASA reduced reactive oxygen species (ROS) and tissue factor production induced by high glucose exposure., Conclusion: Under high glucose condition combining Rivaroxaban+ASA increased the mitochondrial content of Pink-1 and Parkin, restored mitochondria membrane potential and reduced ROS and tissue factor expression in HCAEC. It suggests potential effects induced by dual use of Rivaroxaban and ASA on the coronary endothelium subjected to high glucose condition.

Background: This study's objectives were to compare the prevalence of mental disorders and consumption of psychiatric medications in asthmatic subjects with non-asthmatic controls and identify risk factors associated with psychiatric conditions., Methods: This was an epidemiological case-control study based on the 2020 European Health Survey in Spain self-reported data. Each asthmatic subject was paired with a non-asthmatic control. Study variables included demographics, use of healthcare services, comorbidities, and risky behaviours were compared., Results: There were 22,072 participants in the survey; 1151 cases and 1151 controls were selected. The prevalence of mental disorders (25.5% versus 13.4%; p < 0.001) and consumption of psychiatric medications (25.8% versus 15.6%; p < 0.001) were higher in cases than controls. In asthmatic subjects, female gender (OR 1.814; p = 0.001), age over 80 years (OR 2.558; p = 0.002), poor self-rated health (OR 2.047; p < 0.001), visits to a psychologist (OR 10.854; p < 0.001) and chronic pain (OR 1.938; p < 0.001) were independently associated with mental disorder diagnoses. Meanwhile, female sex (OR 1.710; p < 0.001), age over 80 years (OR 3.802; p < 0.001), poor self-rated health (OR 2.482; p < 0.001), visits to a psychologist (OR 2.694; p < 0.001) and chronic pain (OR 1.494; p = 0.012) were risk factors independently associated with psychiatric medication consumption., Conclusions: The prevalence of psychiatric conditions were higher in asthmatic subjects. Female gender, older age, worse self-rated health, visits to a psychologist and chronic pain were associated with psychiatric conditions in asthmatic subjects., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

(1) Background: This study aimed to analyze if the serum albumin levels of hospitalized SARS-CoV-2 (COVID-19) patients on admission could predict <30 days in-hospital all-cause mortality, and if glucose levels on admission affected this predictive ability. (2) Methods: A multicenter retrospective cohort of 1555 COVID-19-infected adult patients from public hospitals of the Madrid community were analyzed. (3) Results: Logistic regression analysis showed increased mortality for ages higher than 49 y. After adjusting for age, comorbidities and on-admission glucose levels, it was found that on-admission serum albumin ≥3.5 g/dL was significantly associated with reduced mortality (OR 0.48; 95%CI:0.36-0.62). There was an inverse concentration-dependent association between on-admission albumin levels and <30 days in-hospital all-cause mortality. However, when on-admission glucose levels were above 125 mg/dL, higher levels of serum albumin were needed to reach an association with survival. In vitro experiments showed that the spike protein S1 subunit of SARS-CoV-2 binds to native albumin. The binding ability of native albumin to the spike protein S1 subunit was decreased in the presence of an increasing concentration of glycated albumin. (4) Conclusions: On-admission serum albumin levels were inversely associated with <30 days in-hospital all-cause mortality. Native albumin binds the spike protein S1 subunit, suggesting that native albumin may act as a scavenger of the SARS-CoV-2 virus.

Microsurgical scalp reconstruction is indicated in patients with large scalp defects. The aim of this study was to compare the outcomes of scalp reconstruction in oncologic patients reconstructed with latissimus dorsi (LD), anterolateral thigh (ALT), and omental (OM) free flaps. Thirty oncologic patients underwent scalp reconstruction with LD (10), ALT (11), and OM (9) flaps. The length of the vascular pedicle, the operation time, the possibility of a two-team approach, the length of hospital stays, the complications, and the aesthetic results were evaluated. The OM flap was the flap with the shortest vascular pedicle length with a mean of 6.26 ± 0.16 cm, compared to the LD flap, which was 12.34 ± 0.55 cm and the ALT flap with 13.20 ± 0.26 cm ( p < 0.05). The average time of surgery was 6.6 ± 0.14 h in patients reconstructed with OM, compared to the LD flap, which was 8.91 ± 0.32 h and the ALT flap with 7.53 ± 0.22 h ( p < 0.05). A two-team approach was performed in all patients for OM flaps and ALT flaps, but only in two patients reconstructed with the LD flap ( p < 0.001). In patients reconstructed with the OM flap, a very satisfactory or satisfactory result was reported in seven patients (77.8%). Eight patients reported a very unsatisfactory or unsatisfactory result with LD flap (80%) and 10 patients with ALT flap (90.9%) ( p = 0.002). The mean hospital stay after surgery was not statistically significant ( p > 0.05). As for complications, two patients reconstructed with OM flap, five LT flaps, and two ALT flaps developed complications, not statistically significant ( p = 0.235). Omental flap, latissimus dorsi flap, and anterolateral thigh flap fulfill most of the characteristics for complex scalp reconstruction. The decision on which flap to use should be based on clinical aspects of the patients taking into account that the three flaps show similar rates of complications and length of hospital stay. Regarding the aesthetic outcome, OM flap or LD flap should be considered for reconstruction of extensive scalp defects.

(1) Background: To assess the prevalence of mental disorders (depression and anxiety), psychological distress, and psychiatric medications consumption among persons suffering from COPD; to compare this prevalence with non-COPD controls and to identify which variables are associated with worse mental health. (2) Methods: This is an epidemiological case-control study. The data were obtained from the Spanish National Health Survey 2017. Subjects were classified as COPD if they reported suffering from COPD and the diagnosis of this condition had been confirmed by a physician. For each case, we selected a non-COPD control matched by sex, age, and province of residence. Conditional logistic regression was used for multivariable analysis. (3) Results: The prevalence of mental disorders (33.9% vs. 17.1%; p < 0.001), psychological distress (35.4% vs. 18.2%; p < 0.001), and psychiatric medications consumption (34.1% vs. 21.9%; p < 0.001) was higher among COPD cases compared with non-COPD controls. After controlling for possible confounding variables, such as comorbid conditions and lifestyles, using multivariable regression, the probability of reporting mental disorders (OR 1.41; 95% CI 1.10-1.82).), psychological distress (OR 1.48; 95% CI 1.12-1.91), and psychiatric medications consumption (OR 1.38 95% CI 1.11-1.71) remained associated with COPD. Among COPD cases, being a woman, poor self-perceived health, more use of health services, and active smoking increased the probability of suffering from mental disorders, psychological distress, and psychiatric medication use. Stroke and chronic pain were the comorbidities more strongly associated with these mental health variables. (4) Conclusions: COPD patients have worse mental health and higher psychological distress and consume more psychiatric medications than non-COPD matched controls. Variables associated with poorer mental health included being a woman, poor self-perceived health, use of health services, and active smoking.

Background: To assess gender differences in the prevalence of self-reported mental disorders, psychological distress and psychotropic drug consumption, and to identify sociodemographic and health-related variables associated with these conditions in the male and female population (aged ≥ 18 years)., Methods: A cross-sectional study was carried on 22,141 subjects aged 18 and over, using data from the Spanish National Health Interview Survey 2017., Results: We found an overall prevalence of mental disorders, psychological distress and psychotropic drug consumption of 13.8%, 18.3% and 13.9%, respectively. After multivariable adjustment, women showed significantly increased probabilities of 1.74-fold for mental disorders, 1.26-fold for psychological distress and 1.26-fold for psychotropic drug consumption compared to men. Variables such as gender, age, nationality, marital status, educational level, self-rated health, the presence of different chronic disorders, alcohol consumption and smoking habit were independently associated with mental disorders, psychological distress and psychotropic drug consumption. Several variables showed a differential effect on mental health status and psychotropic drug consumption according to gender., Conclusions: Women suffer from mental disorders, experience psychological distress and consume psychotropic drugs significantly more than men in Spain. Possible explanations for these results may be related to differences in emotional processing, willingness to report diseases and even intrinsic biological traits. Screening for mental health status and psychotropic drug consumption should be considered, particularly in Spanish women, younger adults and individuals who are not married, are obese, have poor self-rated health, suffer from chronic diseases or have a smoking habit., Competing Interests: The authors declare no conflicts of interest.

Background: The purpose of this study was to assess and compare the prevalence of self-reported mental disorders, psychological distress, and psychotropic drug consumption among people with diabetes mellitus (DM) and matched non-DM controls., Methods: A case-controlled study using data from the Spanish National Health Interview Survey was conducted in 2017. We identified 2116 DM adults (aged ≥35 years). Non-DM controls were matched 1:1 by age, sex, and province of residence., Results: Prevalence of mental disorders (25.0% vs. 19.2%; p < 0.001), psychological distress (29% vs. 19.5%; p < 0.001), and consumption of psychiatric medications (29.7% vs. 23.5%; p < 0.001) among DM cases were higher than those among matched non-DM controls. The DM patient variables associated with experiencing a mental disorder, psychological distress, and consumption of psychiatric medications were: being a woman, worse self-rated health, and a visit to a psychologist within the last year. Older age (≥80 years) was associated with a lower probability of reporting mental disorders and psychological distress among DM cases. Not practicing physical exercise was significantly associated with experiencing psychological distress., Conclusions: Adults with DM included in our investigation have a significantly higher prevalence of mental disorders, psychological distress, and consumption of psychiatric medications than non-DM controls. It is necessary to implement screening strategies and psychological interventions to improve the mental health of DM patients in Spain, focusing especially on women and those aged 35 to 59 years.

Background: To analyze the incidence, use of therapeutic procedures, and in-hospital outcomes among patients suffering an ischemic stroke (IS) according to the presence of type 2 diabetes mellitus (T2DM) in Spain (2016-2018) and to assess the existence of sex differences., Methods: Matched-pair analysis using the Spanish National Hospital discharge., Results: IS was coded in 92,524 men and 79,731 women (29.53% with T2DM). The adjusted incidence of IS (IRR 2.02; 95% CI 1.99-2.04) was higher in T2DM than non-T2DM subjects, with higher IRRs in both sexes. Men with T2DM had a higher incidence of IS than T2DM women (IRR 1.54; 95% CI 1.51-1.57). After matching patients with T2DM, those with other comorbid conditions, however, significantly less frequently received endovascular thrombectomy and thrombolytic therapy. In-hospital mortality (IHM) was lower among T2DM men than matched non-T2DM men (8.23% vs. 8.71%; p < 0.001). Women with T2DM had a higher IHM rate than T2DM men (11.5% vs. 10.20%; p = 0.004). After adjusting for confounders, women with T2DM had a 12% higher mortality risk than T2DM men (OR 1.12; 95% CI 1.04-1.21)., Conclusions: T2DM is associated with higher incidence of IS in both sexes. Men with T2DM have a higher incidence rates of IS than T2DM women. Women with T2DM have a higher risk of dying in the hospital.

Background: Cutaneous squamous skin cell carcinoma (SCC) is the second most frequent type of non-melanoma skin cancer and is the second leading cause of death by skin cancer in Caucasian populations. However, at present it is difficult to predict patients with poor SCC prognosis., Objective: To identify proteins with expression levels that could predict SCC infiltration in SCC arising from actinic keratosis (SCC-AK)., Methods: A total of 20 biopsies from 20 different patients were studied; 10 were SCC-AK samples and 10 were taken from normal skin. Early infiltrated SCC-AK samples were selected based on histological examination, and to determine the expression of proteins, fresh skin samples were processed by two-dimensional electrophoresis., Results: The expression levels of three proteins, namely alpha hemoglobin and heat shock proteins 27 and 70 (Hsp27 and Hsp70, respectively) were significantly increased in SCC-AK samples with respect to normal control skin. However, only the expression level of Hsp70 protein positively correlated with the level of SCC-AK dermis infiltration. Immunohistological examination suggested that increased expression of Hsp70 proteins seemed to mainly occur in the cytoplasm of keratinocytes. The increased cytoplasmic Hsp70 expression in SCC-AK was confirmed by Western blot experiments., Conclusion: Cytoplasmic expression of Hsp70 could be a potential biomarker of early infiltration of SCC arising from AK., Competing Interests: The authors declare no conflict of interest.

Background: We aimed to (1) analyze time trends in the incidence and in-hospital outcomes of heart failure (HF) patients suffering Clostridioides difficile infection (CDI); (2) compare clinical characteristics of CDI patients between those with HF and matched non-HF patients; and (3) identify predictors of in-hospital mortality (IHM) among HF patients suffering CDI., Methods: Retrospective study using the Spanish National Hospital Discharge Database from 2001 to 2015. Patients of age ≥40 years with CDI were included. For each HF patient, we selected a year, age, sex, and readmission status-matched non-HF patient., Results: We found 44,695 patients hospitalized with CDI (15.46% with HF). HF patients had a higher incidence of CDI (202.05 vs. 145.09 per 100,000 hospitalizations) than patients without HF (adjusted IRR 1.35; 95%CI 1.31-1.40). IHM was significantly higher in patients with HF when CDI was coded as primary (18.39% vs. 7.63%; p < 0.001) and secondary diagnosis (21.12% vs. 14.76%; p < 0.001). Among HF patient's predictor of IHM were older age (OR 8.80; 95%CI 2.55-20.33 for ≥85 years old), those with more comorbidities (OR 1.68; 95%CI 1.12-2.53 for those with Charlson Comorbidity index ≥2), and in those with severe CDI (OR 6.19; 95%CI 3.80-10.02)., Conclusions: This research showed that incidence of CDI was higher in HF than non-HF patients. HF is a risk factor for IHM after suffering CDI.

(1) Background: We examined trends in incidence and outcomes in women with existing type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) compared with a control group without diabetes. (2) Methods: This was an observational, retrospective epidemiological study using the National Hospital Discharge Database. (3) Results: There were 2,481,479 deliveries in Spain between 2009 and 2015 (5561 mothers with T1DM, 4391 with T2DM, and 130,980 with GDM). Incidence and maternal age of existing diabetes and GDM increased over time. Women with T2DM were more likely to have obstetric comorbidity (70.12%) than those with GDM (60.28%), T1DM (59.45%), and no diabetes (41.82%). Previous cesarean delivery, preeclampsia, smoking, hypertension, and obesity were the most prevalent risk factors in all types of diabetes. Women with T1DM had the highest rate of cesarean delivery (Risk Ratio (RR) 2.34; 95% Confidence Interval (CI) 2.26-2.43) and prolonged maternal length of stay. Labor induction was higher in T2DM (RR 1.99; 95% CI 1.89-2.10). Women with T1DM had more severe maternal morbidity (RR 1.97; 95% CI 1.70-2.29) and neonatal morbidity (preterm birth, RR 3.32; 95% CI 3.14-3.51, and fetal overgrowth, RR 8.05; 95% CI 7.41-8.75). (4) Conclusions: existing and GDM incidence has increased over time. We found differences in the prevalence of comorbidities, obstetric risk factors, and the rate of adverse obstetric outcomes among women with different types of diabetes. Pregnant women with diabetes have the highest risk of adverse pregnancy outcomes., Competing Interests: The authors declare no conflict of interest.

Mitochondria dynamic is regulated by different proteins, maintaining a balance between fission and fusion. An imbalance towards mitochondrial fission has been associated with tumor cell proliferation. The aim of this study was to analyze whether pectin modifies the viability of human colon cancer cells and the expression of proteins involved in mitochondrial fusion and fission. The human colon carcinoma cell line HT29 cells was growth in 10% fetal bovine serum in the absence and presence of pectin. Pectin reduced HT29 cell viability in a concentration-dependent manner, reaching a plateau at 150~300 μmol/L pectin. The presence of 200 μmol/L pectin reduced the expression of dynamin-related protein-1 and increased expression of the mitochondrial fusion-associated proteins mitofusin-1 and 2. Expression of cyclin B1, a protein involved in G2/M transition, was found decreased in pectin-incubated HT29 cells. Moreover, expression of p53 protein, the amount of p53 in the nucleous and β-galactosidase activity, which are all biomarkers for cellular senescence, were significantly higher in pectin-incubated HT29 cells than in HT29 cells incubated without pectin. Expression of the protein B-cell lymphoma 2 (Bcl-2) homologous antagonist/killer was increased in response to incubation with pectin. However, incubation with pectin did not affect expression of Bcl-2-associated X protein or Bcl-2, or the caspase-3 activity. Overall, we concluded that pectin reduces the viability of human HT29 colon cancer cells, which is accompanied with a shift in the expression of proteins associated with mitochondrial dynamics towards mitochondrial fusion. Moreover, incubation with pectin favors cellular senescence over apoptosis in HT29 cells., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest.

The new technologies for data analysis, such as decision tree learning, may help to predict the risk of developing diseases. The aim of the present work was to develop a pilot decision tree learning to predict overweight/obesity based on the combination of six single nucleotide polymorphisms (SNP) located in feeding-associated genes. Genotype study was performed in 151 healthy individuals, who were anonymized and randomly selected from the TALAVERA study. The decision tree analysis was performed using the R package rpart. The learning process was stopped when 15 or less observation was found in a node. The participant group consisted of 78 men and 73 women, who 100 individuals showed body mass index (BMI) ≥ 25 kg/m 2 and 51 BMI < 25 kg/m 2 . Chi-square analysis revealed that individuals with BMI ≥ 25 kg/m 2 showed higher frequency of the allelic variation Ala67Ala in AgRP rs5030980 with respect to those with BMI <25 kg/m 2 . However, the variant Thr67Ala in AgRP rs5030980 was the most frequently found in individuals with BMI <25 kg/m 2 . There were no statistical differences in the other analyzed SNPs. Decision tree learning revealed that carriers of the allelic variants AgRP (rs5030980) Ala67Ala, ADRB2 (rs1042714) Gln27Glu or Glu27Glu, INSIG2 (rs7566605) 73 + 9802 with CC or GG genotypes and PPARG (rs1801282) with the allelic variants of Ala12Ala or Pro12Pro, will most likely develop overweight/obesity (BMI ≥ 25 kg/m 2 ). Moreover, the decision tree learning indicated that age and gender may change the developed three decision learning associated with overweight/obesity development. The present work should be considered as a pilot demonstrative study to reinforce the broad field of application of new data analysis technologies, such as decision tree learning, as useful tools for diseases prediction. This technology may achieve a potential applicability in the design of early strategies to prevent overweight/obesity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: To evaluate if rivaroxaban, an oral factor Xa (FXa) inhibitor, could modify the expression in vitro of inflammatory and oxidative stress biomarkers in abdominal aortic aneurysmal (AAA) sites showing intraluminal thrombus., Methods: AAA sites with intraluminal mural thrombus were obtained from six patients undergoing elective AAA repair. In addition, control abdominal aortic samples were obtained from six organ donors. AAA sites were incubated in the presence and absence of 50 nmol l -1 rivaroxaban., Results: AAA sites showing thrombus demonstrated higher content of FXa than control. Interleukin-6 levels released from AAA [Control: median: 23.45 (interquartile range: 16.17-37.15) vs. AAA: median: 153.07 (interquartile range: 100.80-210.69) pg ml -1  mg tissue -1 , P < 0.05] and the expression levels of nitric oxide synthase 2 were significantly higher in AAA than in control. The protein expression level of NADPH oxidase subunits gp67-and gp91-phox, but did not gp47-phox, were also significantly higher in the AAA sites than in control. Addition of rivaroxaban to AAA sites explants significantly reduced the release of interleukin-6 [median: 51.61 (interquartile range: 30.87-74.03) pg ml -1  mg tissue -1 , P < 0.05 with respect to AAA alone] and the content of nitric oxide synthase 2, gp67 and gp91-phox NADPH subunits. The content of matrix metallopeptidase 9 was significantly higher in the AAA sites as compared to control. Rivaroxaban also reduced matrix metallopeptidase 9 content in AAA sites to similar levels to control., Conclusions: FXa inhibition by rivaroxaban exerted anti-inflammatory and antioxidative stress properties in human AAA sites, suggesting a role of FXa in these mechanisms associated with the pathogenesis of AAA., (© 2017 The British Pharmacological Society.)

There is interest to analyse newer biomarkers to identify healthy individuals at risk to develop cardiovascular disease (CVD) incidents and death. To determine in healthy individuals new circulating protein biomarkers, whose systemic levels may be associated with the risk of future development of CVD incidents and death. The study was performed in 82 individuals from the Malmö Diet and Cancer study cohort, free from CVD of whom 41 developed CVD and 41 did not. Plasma proteins related to inflammation and thrombo-coagulating processes were analysed. α1-antitrypsin isotype 3 plasma levels were significantly higher while apolipoprotein J plasma levels were lower in participants that developed CVD incidents than those that did not develop acute cardiovascular episode. Of 82 participants, 17 died by CVD causes. There were proteins whose expression in plasma was significantly higher in participants suffering CVD death as compared with those that did not die by CVD. These proteins included: fibrinogen β-chain isotypes 1 and 3, fibrinogen-γ-chain isotype 2, vitamin D-binding protein isotypes 1, 2 and 3, α1-antitrypsin isotypes 3 and 6, haptoglobin isotypes 3,4,5 and 5, haemopexin isotypes 1 and 2, and Rho/Rac guanine nucleotide exchange factor 2. Moreover, apolipoprotein J plasma levels were found lower in participants that died by cardiovascular cause. Association between plasma levels of proteins and CVD death was independent of age, gender, conventional risk factors and plasma C-reactive protein levels. Several protein plasma levels and protein isotypes related to inflammation and thrombo-coagulating phenomena were independently associated with the risk of future CVD death., (© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

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 β-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., (© 2015 Society for Endocrinology.)

Aim: Further to its pivotal role in haemostasis, factor Xa (FXa) promotes effects on the vascular wall. The purpose of the study was to evaluate if FXa modifies the expression level of energy metabolism and oxidative stress-related proteins in femoral arteries obtained from type 2 diabetic patients with end-stage vasculopathy., Methods: Femoral arteries were obtained from 12 type 2 diabetic patients who underwent leg amputation. Segments from the femoral arteries were incubated in vitro alone and in the presence of 25 nmol l(-1) FXa and 25 nmol l(-1) FXa + 50 nmol l(-1) rivaroxaban., Results: In the femoral arteries, FXa increased triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase isotype 1 expression but decreased pyruvate dehydrogenase expression. These facts were accompanied by an increased content of acetyl-CoA. Aconitase activity was reduced in FXa-incubated femoral arteries as compared with control. Moreover, FXa increased the protein expression level of oxidative stress-related proteins which was accompanied by an increased malonyldialdehyde arterial content. The FXa inhibitor, rivaroxaban, failed to prevent the reduced expression of pyruvate dehydrogenase induced by FXa but reduced acetyl-CoA content and reverted the decreased aconitase activity observed with FXa alone. Rivaroxaban + FXa but not FXa alone increased the expression level of carnitine palmitoyltransferase I and II, two mitochondrial long chain fatty acid transporters. Rivaroxaban also prevented the increased expression of oxidative stress-related proteins induced by FXa alone., Conclusions: In femoral isolated arteries from type 2 diabetic patients with end-stage vasculopathy, FXa promoted disruption of the aerobic mitochondrial metabolism. Rivaroxaban prevented such effects and even seemed to favour long chain fatty acid transport into mitochondria., (© 2014 The British Pharmacological Society.)

Objective: To analyse if platelet responsiveness to aspirin (ASA) may be associated with a different ability of platelets to generate nitric oxide (NO)., Patients/methods: Platelets were obtained from 50 patients with stable coronary ischemia and were divided into ASA-sensitive (n = 26) and ASA-resistant (n = 24) using a platelet functionality test (PFA-100)., Results: ASA-sensitive platelets tended to release more NO (determined as nitrite + nitrate) than ASA-resistant platelets but it did not reach statistical significance. Protein expression of nitric oxide synthase 3 (NOS3) was higher in ASA-sensitive than in ASA-resistant platelets but there were no differences in the platelet expression of nitric oxide synthase 2 (NOS2) isoform. The highest NOS3 expression in ASA-sensitive platelets was independent of the presence of T-to-C mutation at nucleotide position -786 (T(-786) → C) in the NOS3-coding gene. However, platelet content of phosphorylated NOS3 at Serine (Ser)(1177), an active form of NOS3, was higher in ASA-sensitive than in ASA-resistant platelets. The level of platelet NOS3 Ser(1177) phosphorylation was positively associated with the closure time in the PFA-100 test. In vitro, collagen failed to stimulate the aggregation of ASA-sensitive platelets, determined by lumiaggregometry, and it was associated with a significant increase (p = 0.018) of NOS3 phosphorylation at Ser(1177). On the contrary, collagen stimulated the aggregation of ASA-resistant platelets but did not significantly modify the platelet content of phosphorylated NOS3 Ser(1177). During collagen stimulation the release of NO from ASA-sensitive platelets was significantly enhanced but it was not modified in ASA-resistant platelets., Conclusions: Functional platelet responsiveness to ASA was associated with the platelet content of phosphorylated NOS3 at Ser(1177).

Hypertension is a widely prevalent and important risk factor for cardiovascular diseases that increase with aging. The hallmark of hypertension in the elderly is increased vascular dysfunction. However, the molecular mechanisms by which increased blood pressure leads to vascular injury and impaired endothelial function are not well defined. In the present paper, we will analyze several mechanisms described in the scientific literature involved in hypertension in the elderly as endothelial dysfunction, increased oxygen delivery to tissues, inflammation, cellular apoptosis, and increased concentration of active metabolites. Also, we will focus on new molecular mechanisms involved in hypertension such as telomeres shortening, progenitor cells, circulating microparticles, and epigenetic factors that have appeared as possible causes of hypertension in the elderly. These molecular mechanisms may elucidate different origin for hypertension in the elderly and provide us with new targets for hypertension treatment.

The purpose of the study was to determine if an intensive pre- season training program modifies the inflammatory status in professional soccer players and if this inflammatory profile may be associated with the physical state. We compared plasma protein biomarkers, using proteomics, and the physiological state and cardiac function in 12 professional soccer players and 9 recreational soccer players. Reduced cardiac low frequency [LF] after the pre- season training program previous competition with respect to recreational soccer players was found. No differences were found in cardiac high frequency, cardiac high frequency/low frequency ratio, tension index and oxygen volume consumption. Alpha-1-antitrypsin isotype-3, fibrinogen-gamma isotypes-1, 2 and 3 and vitamin-D-binding protein isotype-1 were reduced in professionals players compared with those in recreational players. However, an increased content of alpha-1-antitrypsin isotype-6 and alpha-1-antichymotrypsin 1 and 4 were found in professional soccer players. Spearman's analysis showed a positive correlation between LF and fibrinogen-gamma chain isotype 3; but LF was negatively correlated with alpha-antichymotrypsin isotype 4. Professional soccer players submitted to an intensive training showed differences in the content of plasma proteins associated with inflammatory/oxidative stress and thrombosis with respect to recreational soccer players. Proteomics analysis in combination with the analysis of cardiac function assessment may be useful to know more in depth molecular processes associated with sport and intensive exercise. Key pointsProteomics allow us to find differences in the plasma protein content in sportsmen.Just after pre-season training program, professional soccer players showed lower content of circulating proteins associated with inflammation compared to recreational soccer players.Proteomic analysis in combination with the analysis of cardiac function may be useful to know more in depth molecular inflammatory and oxidative processes associated with the sport.

The aim of this study was to analyze the effect of 2 antiplatelet regimens on the inhibition of GP IIb/IIIa-dependent platelet activation and their association with the poststenting inflammatory response. Seventeen patients with acute myocardial infarction were divided into 2 groups: (A) clopidogrel plus tirofiban infusion administered together during inclusion (n = 10); (B) clopidogrel administered at inclusion and followed 2 hours after by tirofiban (n = 7). Blood samples were obtained at inclusion and at 24 and 48 hours after stenting. Before stenting, a greater reduction of GP IIb/IIIa-dependent platelet activation was found in both groups, although it was greater in group A than in group B. This statistical difference was not observed at 24 and 48 hours after the procedure. At 48 hours after stenting, interleukin-6, interleukin-10, soluble intracellular adhesion molecule-1, and soluble CD40 ligand plasma values were not different between experimental groups. By proteomics, different isoforms of the following proteins were identified: alpha 1-antitrypsin (ATT-1), fibrinogen gamma chain, apolipoprotein A-IV, apolipoprotein A-I, vitamin D binding protein, haptoglobin, and serotransferrin. At 48 hours after stenting, only the plasma expression of the ATT-1 isoform 5 was significantly increased in group A compared with group B. In conclusion, a greater inhibition of GP IIb/IIIa-dependent platelet activation before stenting was not correlated with a different inflammatory activity early after stenting.

F12511(S)-2',3',5'-trimethyl-4'-hydroxy-alpha-dodecylthio-alpha-phenylacetanilide (F12511) is a new Acyl-CoA cholesterol acyltransferase (ACAT) inhibitor that not only reduces the plasma cholesterol levels but also has anti-atherosclerotic actions in animals models. The study's aim was to analyze if F12511 may directly modify the ability of tumor necrosis factor--alpha (TNF-alpha)-incubated bovine aortic endothelial cells (BAEC) to express endothelial nitric oxide synthase (eNOS) protein and inflammatory-related proteins such as platelet endothelial cell adhesion molecule (PECAM) and CD40 ligand (CD40L). The addition of increasing concentrations of F12511 (10 to 10 mol/L) failed to modify the level of eNOS protein expressed in control BAEC. TNF-alpha (10 ng/mL) reduced the expression of eNOS protein. In TNF-alpha--incubated BAEC, F12511 protected eNOS expression in a concentration-dependent manner. TNF-alpha stimulated the expression of both CD40L and PECAM in cultured BAEC. F12511 (10 mol/L) failed to modify the expression of CD40L and PECAM in control and TNF-alpha-incubated BAEC. Reverse transcriptase polymerase chain reaction showed a marked expression of the ACAT-2 isoform and absent of expression of the ACAT-1 isoform in BAEC. The presence of ACAT-2 isoform in BAEC was further confirmed by Western blot. F12511 failed to modify the expression of the proinflammatory associated proteins PECAM and CD40L in the endothelium but protected eNOS expression in the endothelial cells exposed to inflammatory conditions.

The aim was to determine in circulating mononuclear cells from patients with erectile dysfunction (ED), the level of expression of endothelial nitric oxide synthase (eNOS), soluble guanylate cyclase (sGC) beta1-subunit and phosphodiesterase type-V (PDE-V). Peripheral mononuclear cells from nine patients with ED of vascular origin and nine patients with ED of neurological origin were obtained. Fourteen age-matched volunteers with normal erectile function were used as control. Reduction in eNOS protein was observed in the mononuclear cells from patients with ED of vascular origin but not in those from neurological origin. Although sGC beta1-subunit expression was increased in mononuclear cells from patients with ED, the sGC activity was reduced. However, only the patients with ED of vascular origin showed an increased expression of PDE-V. This work shows for the first time that, independently of the aetiology of ED, the expression of sGC beta1-subunit was increased in circulating mononuclear cells; however, the expression of both eNOS and PDE-V was only modified in the circulating mononuclear cells from patients with ED of vascular origin.