n-Type Fullerene-Carbon Dots: Synthesis and Electrochemical and Photophysical Properties.

The covalent incorporation of C60 and C70 derivatives of the well-known n-type organic semiconductor PCBM ([6,6]-phenyl-C61-butyric acid methyl ester) onto carbon dots (CD) is described. Morphological and structural characterization reveal combined features of both pristine starting materials (CD and PCBM). Electrochemical investigations evidenced the existence of additional reduction processes to that of CD or PCBM precursors, showing rich electron-acceptor capabilities, with multistep processes in an affordable and narrow electrochemical window (ca. 1.5 V). Electronic communication in the obtained nanoconjugated species were derived from steady-state absorption and emission spectroscopies, which showed bathochromically shifted absorptions and emissions well entering the red region. Finally, the lower fluorescence quantum yield of CD-PCBM nanoconjugates, compared with CD, and the fast decay of the observed emission of CD, support the existence of an electronic communication between both CD and PCBM units in the excited state.

Helical Bilayer Nanographenes: Impact of the Helicene Length on the Structural, Electrochemical, Photophysical, and Chiroptical Properties.

Helical bilayer nanographenes (HBNGs) are chiral π-extended aromatic compounds consisting of two π-π stacked hexabenzocoronenes (HBCs) joined by a helicene, thus resembling van der Waals layered 2D materials. Herein, we compare [9]HBNG, [10]HBNG, and [11]HBNG helical bilayers endowed with [9], [10], and [11]helicenes embedded in their structure, respectively. Interestingly, the helicene length defines the overlapping degree between the two HBCs (number of benzene rings involved in π-π interactions between the two layers), being 26, 14, and 10 benzene rings, respectively, according to the X-ray analysis. Unexpectedly, the electrochemical study shows that the lesser π-extended system [9]HBNG shows the strongest electron donor character, in part by interlayer exchange resonance, and more red-shifted values of emission. Furthermore, [9]HBNG also shows exceptional chiroptical properties with the biggest values of gabs and glum (3.6 × 10-2) when compared to [10]HBNG and [11]HBNG owing to the fine alignment in the configuration of [9]HBNG between its electric and magnetic dipole transition moments. Furthermore, spectroelectrochemical studies as well as the fluorescence spectroscopy support the aforementioned experimental findings, thus confirming the strong impact of the helicene length on the properties of this new family of bilayer nanographenes.

Beverages Rich in Resveratrol and Physical Activity Attenuate Metabolic Changes Induced by High-Fat Diet.

Consumption of saturated fat causes deleterious effects on health, which could be minimized through physical activity and foods with functional characteristics consumption. The aim of the study was to evaluate the beverage rich in resveratrol consumption and physical exercise in gut microbiota, body composition, lipid peroxidation, interleukin-6 (IL6) concentration and systolic blood pressure (SBP) of rats to the high-fat diet. Wistar rats were fed with control diet, high-fat diet (HFD), HFD and 15 mL solution of resveratrol, HFD and 15 mL of grape juice, HFD and 10 mL of red wine. All animals performed the physical training protocol five days a week. Grape juice and red wine composition were analyzed, SBP, body mass, consumption, adiposity and body composition, gut microbiota, lipid peroxidation and inflammation were evaluated. The grape juice (114.8 ± 22.5 mmHG) and red wine (129 ± 15.8 mmHg) groups showed lower SBP when compared to HFD (216.8 ± 20.6 mmHg) (p < 0.0001). The grape juice group (GJG) (39.1 ± 7) had a higher number of microbiota bands DNA when compared to the other groups (p = 0.002). The GJG (33.7 ± 6.7 pg/mL) presented lower concentration IL6 when compared to high-fat group (47.3 ± 16 pg/mL) (p = 0.003). GJG (4.7 ± 1.2 nmol/L) presented a lower concentration of TBARS when compared to control group (6.1 ± 1.4 nmol/L) and resveratrol group (6.6 ± 0.9 nmol/L), and the red wine group (7.4 ± 1.2 nmol/L) had a higher concentration of TBARS when compared to control group and GJG (p = 0.0001). The consumption of these beverages, especially grape juice, together with physical exercise, was able to promote beneficial changes even in the presence of a HFD.

An Ultra-Long-Lived Triplet Excited State in Water at Room Temperature: Insights on the Molecular Design of Tridecafullerenes.

Suitably engineered molecular systems exhibiting triplet excited states with very long lifetimes are important for high-end applications in nonlinear optics, photocatalysis, or biomedicine. We report the finding of an ultra-long-lived triplet state with a mean lifetime of 93 ms in an aqueous phase at room temperature, measured for a globular tridecafullerene with a highly compact glycodendrimeric structure. A series of three tridecafullerenes bearing different glycodendrons and spacers to the C60 units have been synthesized and characterized. UV/Vis spectra and DLS experiments confirm their aggregation in water. Steady-state and time-resolved fluorescence experiments suggest a different degree of inner solvation of the multifullerenes depending on their molecular design. Efficient quenching of the triplet states by O2 but not by waterborne azide anions has been observed. Molecular modelling reveals dissimilar access of the aqueous phase to the internal structure of the tridecafullerenes, differently shielded by the glycodendrimeric shell.

Anemia as very late-onset cytomegalovirus disease after kidney transplantation.

Very late-onset cytomegalovirus (CMV) disease after solid organ transplantation is not associated with classic risk factors; therefore, it does not follow a pattern of predictable appearance. A high index of suspicion is necessary to make an accurate diagnosis. Anemia has multiple etiologies among kidney transplanted recipients, and CMV could be one of them. We report the case of a kidney recipient with anemia refractory to treatment which proved to be secondary to extremely late CMV digestive disease.

Effectiveness of mycophenolate mofetil in C3 glomerulonephritis.

C3 glomerulonephritis is a clinicopathologic entity defined by the presence of isolated or dominant deposits of C3 on immunofluorescence. To explore the effect of immunosuppression on C3 glomerulonephritis, we studied a series of 60 patients in whom a complete registry of treatments was available over a median follow-up of 47 months. Twenty patients had not received immunosuppressive treatments. In the remaining 40 patients, 22 had been treated with corticosteroids plus mycophenolate mofetil while 18 were treated with other immunosuppressive regimens (corticosteroids alone or corticosteroids plus cyclophosphamide). The number of patients developing end-stage renal disease was significantly lower among treated compared with untreated patients (3 vs. 7 patients, respectively). No patient in the corticosteroids plus mycophenolate mofetil group doubled serum creatinine nor developed end-stage renal disease, as compared with 7 (significant) and 3 (not significant), respectively, in patients treated with other immunosuppressive regimens. Renal survival (100, 80, and 72% at 5 years) and the number of patients achieving clinical remission (86, 50, and 25%) were significantly higher in patients treated with corticosteroids plus mycophenolate mofetil as compared with patients treated with other immunosuppressive regimens and untreated patients, respectively. Thus, immunosuppressive treatments, particularly corticosteroids plus mycophenolate mofetil, can be beneficial in C3 glomerulonephritis.

Polymorphisms in CYP-mediated arachidonic acid routes affect the outcome of renal transplantation.

BACKGROUND: Arachidonic acid (AA) is metabolized by cytochrome P450 (CYP) enzymes to vasoactive metabolites (mainly epoxyeicosatrienoic acids) which are known to play a protective role against damaging processes that may occur after re-oxygenation of the graft. We aimed to investigate whether the presence of functional polymorphisms along these metabolic routes may play a role in the outcome of renal transplantation. DESIGN: One-hundred and forty Caucasian renal transplant recipients and 137 donors were included. We determined the presence of seven common functional polymorphisms in the five genes governing the CYP-mediated AA metabolic pathway (CYP2C8, CYP2C9, CYP2J2, CYP4A11 and CYP4F2). Associations with parameters and events related to graft function and survival were retrospectively investigated throughout the first year after grafting. RESULTS: The CYP2J2*7 allele of the donor was significantly associated with higher risk for delayed graft function [OR = 4·40 (1·45-13·37), P < 0·01] and lower death-censored graft survival [107·90 (84·19-131·62) vs. 176·89 (166·47-187·32) months for CYP2J2*1/*1 grafts; log-rank P = 0·015]. In addition, patients whose donors carried the CYP4A11 434S variant of the F434S polymorphism displayed impaired creatinine clearance, with statistically significant differences vs. 434FF subjects throughout the whole period of study (P < 0·05, P < 0·01, P < 0·001 and P < 0·05 for 1 week, 1 month, 5 months and 1 year after grafting, respectively). CONCLUSIONS: Taken together, these results indicate that variability in the CYP450 genes involved in the synthesis of eicosanoids from AA may have a significant impact on graft function and survival in renal transplantation.

Irisin and Cardiometabolic Disorders in Obesity: A Systematic Review.

Background: Overweight and obesity are global health issues, impacting a significant portion of young adults. Obesity is a complex condition influenced by genetics and environmental factors, leading to increased susceptibility to cardiovascular diseases (CVDs), hypertension, dyslipidemia, and insulin resistance. Irisin, a protein derived from the cleavage of fibronectin type III domain-containing protein 5, may have relationship with these cardiometabolic diseases. Objective: This systematic review aims to examine the relationship between serum irisin levels and obesity, particularly in individuals predisposed to cardiovascular risk factors. Methods: A thorough literature search was conducted in multiple databases, including "Science Direct," "Scopus," "PubMed," and "Lilacs," from July 2020. Inclusion criteria encompassed subjects with metabolic disorders (with or without obesity, BMI ≥30 kg/m2), clinical trials, and observational studies published between 2010 and June 2020. Exclusion criteria were animal studies, meta-analyses, systematic reviews, studies evaluating only healthy subjects, and those investigating disorders beyond cardiometabolic diseases. Results: Out of 151 identified articles, 30 met the inclusion criteria. These studies, published between 2013 and 2020, assessed adults (≥21 years) and included 26 observational studies and 4 clinical trials (n = 7585 subjects). All studies examined irisin's role in obesity and CVDs, often including associated diseases such as type 2 diabetes and hypertension. Despite varying sample sizes, the samples within the articles were homogeneous. Observational studies exhibited a low risk of bias in at least 60% of the evaluated domains. Clinical trials demonstrated a low risk of bias in at least 50% of the domains. Limitations. Although the systematic review provides valuable insights, it is limited by the available literature and the varying methodologies used across studies. Conclusion: The review suggests that irisin plays a significant role as both a preventive measure and a biomarker for comorbidities linked to obesity and cardiometabolic disorders. Future research should focus on standardized irisin measurement methods and diverse populations to further elucidate its mechanisms of action.

Curved Nanographenes: Multiple Emission, Thermally Activated Delayed Fluorescence, and Non-Radiative Decay.

The intriguing and rich photophysical properties of three curved nanographenes (CNG 6, 7, and 8) are investigated by time-resolved and temperature-dependent photoluminescence (PL) spectroscopy. CNG 7 and 8 exhibit dual fluorescence, as well as dual phosphorescence at low temperature in the main PL bands. In addition, hot bands are detected in fluorescence as well as phosphorescence, and, in the narrow temperature range of 100-140 K, thermally activated delayed fluorescence (TADF) with lifetimes on the millisecond time-scale is observed. These findings are rationalized by quantum-chemical simulations, which predict a single minimum of the S1 potential of CNG 6, but two S1 minima for CNG 7 and CNG 8, with considerable geometric reorganization between them, in agreement with the experimental findings. Additionally, a higher-lying S2 minimum close to S1 is optimized for the three CNG, from where emission is also possible due to thermal activation and, hence, non-Kasha behavior. The presence of higher-lying dark triplet states close to the S1 minima provides mechanistic evidence for the TADF phenomena observed. Non-radiative decay of the T1 state appears to be thermally activated with activation energies of roughly 100 meV and leads to disappearance of phosphorescence and TADF at T > 140 K.

Anti-glomerular Basement Membrane Glomerulonephritis: A Study in Real Life.

Introduction: Anti-glomerular basement membrane (anti-GBM) disease is a severe entity with few therapeutic options including plasma exchange and immunosuppressive agents. The aim of this study was to analyze the clinical and pathological features that predict the evolution of end-stage kidney disease (ESKD) and the kidney survival in a cohort of patients with anti-GBM disease with renal involvement in real life. Methods: A retrospective multicentre observational study including 72 patients from 18 nephrology departments with biopsy-proven anti-GBM disease from 1999 to 2019 was performed. Progression to ESKD in relation to clinical and histological variables was evaluated. Results: Creatinine at admission was 8.6 (± 4) mg/dL and 61 patients (84.7%) required dialysis. Sixty-five patients (90.3%) underwent plasma exchange. Twenty-two patients (30.6%) presented pulmonary hemorrhage. Kidney survival was worse in patients with creatinine levels > 4.7 mg/dL (3 vs. 44% p < 0.01) and in patients with > 50% crescents (6 vs. 49%; p = 0.03). Dialysis dependence at admission and creatinine levels > 4.7 mg/dL remained independent significant predictors of ESKD in the multivariable analysis [HR (hazard ratio) 3.13 (1.25-7.84); HR 3 (1.01-9.14); p < 0.01]. The discrimination value for a creatinine level > 4.7 mg/dL and 50.5% crescents had an area under the curve (AUC) of 0.9 (95% CI 0.82-0.97; p < 0.001) and 0.77 (95% CI 0.56-0.98; p = 0.008), respectively. Kidney survival at 1 and 2 years was 13.5 and 11%, respectively. Patient survival at 5 years was 81%. Conclusion: In real life, patients with severe anti-GBM disease (creatinine > 4.7 mg/dL and > 50% crescents) remained with devastating renal prognosis despite plasma exchange and immunosuppressive treatment. New therapies for the treatment of this rare renal disease are urgently needed.

A pilot study on the relation between dietary calcium and clinical parameters in renal transplant recipients.

OBJECTIVE: This aim of this study was to evaluate the association between dietary calcium and variables that include body mass index, abdominal obesity, metabolic profile, and blood pressure levels in renal transplant patients. DESIGN: A cross-sectional study was conducted. SETTING: Eligible patients were recruited from renal transplant outpatient clinics at Pedro Ernesto University Hospital, Rio de Janeiro, Brazil. PATIENTS: A total of 40 men and 34 women aged >18 years who had received kidney transplants in the past ≥12 months were included in this study. INTERVENTION: All patients underwent clinical, dietary, anthropometric, and biochemical evaluation. RESULTS: Participants were classified into the following 2 groups on the basis of their mean dietary calcium intake: group A (<600 mg/day) and group B (≥600 mg/day). Patients in group B presented significantly lower levels of waist circumference and waist-to-hip ratio as compared with those in group A (P = .04 and P = .005, respectively), after adjusting for confounding variables such as energy intake, gender, age, physical activity, time since transplantation, and prednisone dose. After controlling for potential confounders, including energy intake and physical activity, subjects in group B had a lower odds ratio for prevalent abdominal obesity as compared with those in group A (odds ratio, 0.17; 95% confidence interval, 0.03 to 0.94; P = .04). Body mass index was significantly lower in patients with higher calcium intake; however, this difference did not reach statistical significance after adjustments for confounding factors. Metabolic profile and blood pressure levels were similar in both groups. CONCLUSION: The findings of the present study suggest that a higher dietary calcium intake may be associated with lower abdominal adiposity in renal transplant patients.

[Glucose metabolism disorders in the risk factor control in Extremadura Study (COFRE Study)]. / Alteraciones del metabolismo glucídico en el estudio de control de factores de riesgo de Extremadura (estudio COFRE).

AIMS: To assess the prevalence and control of glucose metabolism disorders in a population of Extremadura (Spain) with at least one cardiovascular risk factor and to compare the characteristics of these patients with those who were normoglycemic in the risk factor control in Extremadura (COFRE study). PATIENTS AND METHODS: The prevalence and control of cardiovascular risk factors were recorded in a sample of 1,022 patients with at least one cardiovascular risk factor consecutively visiting a primary care office. Of these, 951 patients were included in the analysis. In all patients, fasting glycemia was recorded. Glycated hemoglobin was recorded in diabetic patients. RESULTS: A total of 320 patients (33.6%) were previously known to be diabetic (DM) and 84 (8.8%) had glycemia > or = 126 mg/dl without a previous diagnosis of diabetes (12 with glycemia above 200mg/dl). Impaired fasting glycemia (IFG) was found in 211 (22.2%) and normoglycemia (NG) in 336 (35.3%). Within the DM group, glycemia <126 mg/dl was found in only 31.4% but glycated hemoglobin lower than 7% was found in 46.8%. Triglyceride concentrations were higher in the IFG group than in the NG group (137 + or - 65 mg/dL vs 124 + or - 65 mg/dL, p=0,041). Pulse pressure was also higher, but no differences were found in diastolic blood pressure (DBP) or heart rate. Differences in systolic blood pressure (SBP) were at the limit of significance (DM 139.5 + or - 17 vs NG 136.5 + or - 16 mmHg; p=0.056). No significant differences were found in any of these parameters between the DM and IFG groups. CONCLUSIONS: The prevalence of glucose metabolism disorders was very high in the recruited sample. Patients with IFG showed higher pulse pressure and triglyceride concentrations than those with NG but there were no differences in comparison with DM patients. Diabetic control was poor when assessed by fasting glycemia but glycated hemoglobin showed better control.

Renal potassium handling in chronic kidney disease: Differences between patients with or wihtout hyperkalemia. / Manejo renal del potasio en la enfermedad renal crónica avanzada: diferencias entre pacientes con o sin hipercaliemia.

INTRODUCTION: Hyperkalemia (HK) is a common electrolyte disorder in chronic kidney disease (CKD), mainly in the advanced stages. A positive potassium balance due to reduced renal excretory capacity is likely the main pathogenic mechanism of HK. Research into the relative role of each pathogenic element in the development of HK in CKD may help to implement more suitable therapies. OBJECTIVE: To investigate renal potassium handling in advanced CKD patients, and to determine the differences between patients with or without HK. MATERIAL AND METHODS: Cross-sectional observational study in adult patients with stage 4-5 CKD pre-dialysis. Selection criteria included clinically stable patients and the ability to collect a 24hour urine sample correctly. Blood and urinary biochemical parameters were analysed including sodium and potassium (K). Fractional excretion of K (FEK) and K load relative to glomerular filtration (Ku/GFR) were calculated. HK was defined as a serum K concentration ≥5.5mmol/l. RESULTS: The study group consisted of 212 patients (mean age 65±14 years, 92 females) with a mean GFR of 15.0±4.2ml/min/1.73m2. 63 patients (30%) had HK. Patients with HK had lower mean bicarbonate levels with respect to patients with normal K levels (NK) (20.3±3.1 vs. 22.8±3.2 mEq/l, P<.0001), but no differences were noted in total urinary sodium and K excretion. While mean FEK values were lower in patients with HK (32.1±12.1% vs. 36.4±14.3%, P=.038), Ku/GFR values were significantly greater with respect to the NK subgroup (4.2±1.5 vs. 3.7±1.4 mmol/ml/min, P=0,049). FEK showed a strong linear correlation with Ku/GFR (R2=0.74), and partial linear regressions demonstrated that at a similar Ku/GFR level, the FEK of patients with HK was lower than that of NK patients. By multivariate linear and logistic regression analyses, both FEK and Ku/GFR were shown to be the main determinants of K serum levels and HK. CONCLUSIONS: Although the K load relative to glomerular filtration (Ku/GFR) is an important determinant of HK in advanced CKD, the most noteworthy characteristic associated with HK in these patients was the limitation of compensatory urinary K excretion, as indicated by lower FEK.

Detrimental effect of renin-angiotensin blockade on progression of chronic kidney disease at later stages: A matter of dosage adjustment? / Efecto negativo del bloqueo del sistema renina-angiotensina sobre la progresión de la enfermedad renal crónica avanzada: ¿una cuestión de ajuste de dosis?

INTRODUCTION: The renoprotective effect of renin-angiotensin (RAS) blockers (angiotensin converting enzyme inhibitors and angiotensin receptor blockers) has been questioned in patients with advanced chronic kidney disease (CKD). Moreover, combination therapy (dual RAS blockade) can further accelerate renal function decline in some populations at risk. However, it is unknown whether this adverse outcome is due to a dose-dependent effect or if it can be attributed more specifically to a drug interaction. Aim This study aims to investigate if the rate of renal function decline in advanced CKD patients is associated to the doses of RAS blockers, and if dual RAS blockade worsens renal function independently of major confounding factors. MATERIAL AND METHODS: Retrospective, observational study in an incident cohort of adult patients with CKD stage 4 or 5 not on dialysis, treated with RAS blockers for at least 3 months prior to the study inclusion. Inclusion criteria were: having at least three consecutive measurements of estimated glomerular filtration rate (eGFR) in a follow-up period >3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. Equipotent doses of RAS blockers were normalised for a body weight of 70kg or a body surface area of 1.73m2 (END-RASI). Associations of END-RASI or dual RAS blockade with the rate of renal function decline were analysed by uni- or multivariate linear regression models, accounting for major confounding variables. RESULTS: The study group consisted of 813 patients (mean age 64±14 years, 430 males) with a mean eGFR 14.9±4.2ml/min/1.73m2; 729 patients were on RAS blockade monotherapy and 84 on dual RAS blockade. Median END-RASI in the whole group was 0.91 (I.Q. ranges: 0.69-1.20). Patients on dual RAS blockade had significantly higher END-RASI than the rest of study patients (1.52±0.49 vs. 0.93±0.44; p<0.0001). In univariate linear regression, END-RASI were significantly correlated with eGFR decline (R=-0.149; p<0.0001). Patients on dual RAS blockade showed a significantly faster decline of renal function than the rest of the study patients (-6.19±5.57 vs. -3.04±5.37ml/min/1.73m2/year, p<0.0001). By multivariate linear regression, while dual RAS blockade remained independent and significantly associated with faster renal function decline (beta=-0.094; p=0.005), END-RASI (normalised either for body weight or surface area) did not reach statistical significance. CONCLUSION: END-RASI are significantly associated with the rate of renal function decline in advanced CKD patients. However, the detrimental effect of dual RAS blockade on CKD progression seems to be independent of END-RASI and other major confounding factors.

Successful correction of metabolic acidosis is difficult to achieve in chronic kidney disease. / Acidosis metabólica en la enfermedad renal crónica: dificultades para una corrección adecuada.

INTRODUCTION: Metabolic acidosis (MA) is a common complication of chronic kidney disease (CKD) and is associated with numerous adverse effects, which is why its correction is highly recommended. Oral sodium bicarbonate is the current treatment of choice. OBJECTIVES: To describe the prevalence of MA in advanced CKD patients and to determine the clinical and biochemical characteristics associated with its successful correction. MATERIAL AND METHODS: Retrospective, observational cohort study in adult patients with CKD stage 4-5. The inclusion criteria were: not being treated with alkali therapy at the time of inclusion, and to have at least three consecutive glomerular filtration rate (GFR) measurements and biochemical parameters during a minimum follow-up period of 3 months. Incident patients with serum bicarbonate<22 mEq/l were included in the follow-up study and treated with oral sodium bicarbonate. Correction was considered successful when more than half of the samples and the mean bicarbonate levels during individual follow-up were≥22 mEq/l. RESULTS: The study group consisted of 969 patients (age 65±14 years, 507 males) with a mean GFR of 14.8±4.5ml/min/1.73 m2. At baseline, 530 patients (55%) had serum bicarbonate<22mEq/l. They were treated with sodium bicarbonate and followed for 15 months. Satisfactory correction of MA was only achieved in 133 patients (25%). By multivariate logistic regression analysis, the main characteristics of patients with adequate control of MA were: age (OR=1.03; 95% CI 1.01 - 1.05), baseline GFR (OR=1.07; 1.02 - 1.12), and treatment with proton-pump inhibitors (OR=1.61; 95% CI 1.06 - 2.44). Patients who achieved successful correction of MA showed slower CKD progression (-1.67±3.71 vs -4.36±4.56ml/min/1.73 m2/year, P<.0001), and lower average serum potassium concentration (5.1±0.5 vs 5.3±0.5, P<.0001) than those who did not. However, there were no differences in the hospitalisation or mortality rate. CONCLUSION: MA is a common complication of advanced CKD but difficult to manage with current therapies. Due to the significant potential benefit of controlling MA, new, more effective therapies should be further researched.

[Analysis of the biochemical, anthropometric profile, and of antioxidant micronutrient ingestion in patients with resistant arterial hypertension]. / Análisis del perfil bioquímico y antropométrico, y de la ingesta de micronutrientes antioxidantes en pacientes con hipertensión arterial resistente.

INTRODUCTION: Introduction: resistant arterial hypertension (HAR) is associated with a high risk for cardiovascular events due to oxidative stress. Research has shown the beneficial effects of dietary antioxidants on cardiovascular health. Objective: to analyze and correlate the biochemical, anthropometric profile and intake of antioxidant micronutrients of patients with HAR. Material and methods: the patients underwent a biochemical assessment, and an anthropometric assessment to calculate body mass index (IMC), waist circumference (PCI), hip circumference (PCA), waist-to-hip ratio (ICC), and micronutrient intake assessment: vitamin A, vitamin C, vitamin E, selenium and zinc, estimated by a semi-quantitative food frequency questionnaire and 24-hour recall. The statistical analysis was performed using the SPSS Statistics 20 software. A p-value < 0.05 was considered significant. Results: sixty individuals with HAR were studied, with a mean age of 62.83 ± 10.73 years. Mean IMC was 31.01 ± 5.60 kg/m², PCI, 98.12 ± 15.04 cm, PCA, 110.55 ± 13.16 cm, and ICC, 0.879 ± 0.084. Regarding the biochemical profile, mean total colesterol was 187.65 ± 48.29 mg/dL, triglycerides, 136.38 ± 99.91 mg/dL; HDL-col, 49.00 ± 10.99 mg/dL; LDL-col, 112.01 ± 41.89 mg/dL; glucose, 105.37 ± 14.81 mg/dL, and glycated hemoglobin, 6.29 ± 1.76 %. The average daily intake of antioxidants was: vitamin A, 241.47 ± 191.87 µg/d; vitamin C, 147.02 ± 192.94 mg/d; vitamin E, 1.99 ± 1.82 mg/d; selenium, 36.80 ± 34.56 µg/d, and zinc, 99.91 ± 6.64 mg/d, where 91.38 %, 46.55 %, 93.10 %, 67.24 %, and 46.55 % of the sample were below the recommended intakes, respectively. Conclusion: inadequate antioxidant intake was observed in these patients with HAR, with a high prevalence of obesity, especially visceral adiposity and alterations in lipid profile, conditions that require a greater usage of these micronutrients. We suggest there is a need for dietary planning for these patients to improve their quality of life and their response to antihypertensive treatment.

INTRODUCCIÓN: Introducción: la hipertensión arterial resistente (HAR) se asocia a un alto riesgo de eventos cardiovasculares debido al estrés oxidativo. Los estudios han demostrado los efectos beneficiosos de los antioxidantes dietéticos sobre la salud cardiovascular. Objetivo: analizar y correlacionar el perfil bioquímico y antropométrico, y la ingesta de micronutrientes antioxidantes en pacientes con HAR. Material y métodos: los pacientes se sometieron a una evaluación bioquímica y antropométrica para calcular el índice de masa corporal (IMC), el perímetro de la cintura (PCI), el perímetro de la cadera (PCA), el índice cintura-cadera (ICC) y la ingesta de micronutrientes ­vitaminas A, C y E, selenio y zinc­ utilizando una encuesta de frecuencia de consumo alimentario y el recordatorio de 24 horas. El análisis estadístico se realizó utilizando el software SPSS Statistics 20, con un valor de p < 0,05 como significativo. Resultados: estudiamos a 60 individuos con HAR de 62,83 ± 10,73 años. El IMC medio fue de 31,01 ± 5,60 kg/m²; el PCI de 98,12 ± 15,04 cm, el PCA de 110,55 ± 13,16 cm y el ICC de 0,879 ± 0,084. Respecto al perfil bioquímico, el colesterol total medio fue de 187,65 ± 48,29 mg/dL, los triglicéridos de 136,38 ± 99,91 mg/dL, el HDL-col de 49,00 ± 10,99 mg/dL, el LDL-col de 112,01 ± 41,89 mg/dL, la glucemia de 105,37 ± 14,81 mg/dL y la hemoglobina glucosilada del 6,29 ± 1,76 %. La ingesta de antioxidantes fue: vitamina A: 241,47 ± 191,87 µg/d; vitamina C: 147,02 ± 192,94 mg/d; vitamina E: 1,99 ± 1,82 mg/d; selenio: 36,80 ± 34,56 µg/d, y zinc: 9,91 ± 6,64 mg/d, y el 91,38 %, 46,55 %, 93,10 %, 67,24 % y 46,55 % de la muestra se encontraron por debajo de lo recomendado, respectivamente. Conclusión: se observó una ingesta insuficiente de antioxidantes en los pacientes con HAR, que presentan una alta prevalencia de obesidad, especialmente de adiposidad visceral y alteraciones del perfil lipídico, afecciones que requieren un mayor uso de estos micronutrientes. Se sugiere la necesidad de una planificación dietética dirigida a estos pacientes para mejorar la calidad de vida y la respuesta al tratamiento antihipertensivo.

Mitochondrial Toxicogenomics for Antiretroviral Management: HIV Post-exposure Prophylaxis in Uninfected Patients.

Background: Mitochondrial genome has been used across multiple fields in research, diagnosis, and toxicogenomics. Several compounds damage mitochondrial DNA (mtDNA), including biological and therapeutic agents like the human immunodeficiency virus (HIV) but also its antiretroviral treatment, leading to adverse clinical manifestations. HIV-infected and treated patients may show impaired mitochondrial and metabolic profile, but specific contribution of viral or treatment toxicity remains elusive. The evaluation of HIV consequences without treatment interference has been performed in naïve (non-treated) patients, but assessment of treatment toxicity without viral interference is usually restricted to in vitro assays. Objective: The objective of the present study is to determine whether antiretroviral treatment without HIV interference can lead to mtDNA disturbances. We studied clinical, mitochondrial, and metabolic toxicity in non-infected healthy patients who received HIV post-exposure prophylaxis (PEP) to prevent further infection. We assessed two different PEP regimens according to their composition to ascertain if they were the cause of tolerability issues and derived toxicity. Methods: We analyzed reasons for PEP discontinuation and main secondary effects of treatment withdrawal, mtDNA content from peripheral blood mononuclear cells and metabolic profile, before and after 28 days of PEP, in 23 patients classified depending on PEP composition: one protease inhibitor (PI) plus Zidovudine/Lamivudine (PI plus AZT + 3TC; n = 9) or PI plus Tenofovir/Emtricitabine (PI plus TDF + FTC; n = 14). Results: Zidovudine-containing-regimens showed an increased risk for drug discontinuation (RR = 9.33; 95% CI = 1.34-65.23) due to adverse effects of medication related to gastrointestinal complications. In the absence of metabolic disturbances, 4-week PEP containing PI plus AZT + 3TC led to higher mitochondrial toxicity (-17.9 ± 25.8 decrease in mtDNA/nDNA levels) than PI plus TDF + FTC (which increased by 43.2 ± 24.3 units mtDNA/nDNA; p < 0.05 between groups). MtDNA changes showed a significant and negative correlation with baseline alanine transaminase levels (p < 0.05), suggesting that a proper hepatic function may protect from antiretroviral toxicity. Conclusions: In absence of HIV infection, preventive short antiretroviral treatment can cause secondary effects responsible for treatment discontinuation and subclinical mitochondrial damage, especially pyrimidine analogs such as AZT, which still rank as the alternative option and first choice in certain cohorts for PEP. Forthcoming efforts should be focused on launching new strategies with safer clinical and mitotoxic profile.

[Lipid control in diabetic patients in Extremadura (Spain)]. / Control de la dislipemia en pacientes diabéticos en Extremadura.

OBJECTIVE: Our study aimed to assess the prevalence and degree of control of dyslipemia, using the 2004 National Cholesterol Education Program criteria, as well as the use of cholesterol lowering drugs in a sample of diabetic patients followed up in primary care settings in Extremadura. PATIENTS AND METHODS: In this crosssectional, multicenter study the prevalence and control of cardiovascular risk factors was assessed in a sample of 1022 patients having at least one cardiovascular risk factors who were recruited by general practitioners. A total of 988 subjects were avalaible for statistic analysis of dyslipemia; 320 patients had diabetes mellitus (DM); 178 had at least one cardiovascular disease without diabetes and 506 patients without those diseases were used as control. RESULTS: Total cholesterol and low density lipoprotein (LDL) fraction were higher in the group control. High density lipoprotein (HDL)-cholesterol was lower in the group DM as compared to control. Triglycerides were higher in group DM. Women had higher HDL-cholesterol and lower triglycerides levels than men. Only 26.6% of diabetics subjetcs and 28.9% of group ECV were well controlled; 42.5% of the control group had LDL cholesterol < 130 mg/dl. 13.3% of diabetics patients suffering from coronary artery disease had LDL-cholesterol < 70 mg/dl. They were taking statins: DM, 56.6); ECV 61.6%; and control, 39.4%. From patients who did not take cholesterol lowering drugs 51.6% in group DM and 33.8% in group ECV would need to take them. CONCLUSIONS: The study shows a poor control of dyslipemia in diabetics subjects and high risk patients in spite of lower lipid levels when compared to lower risk population and a more frequent use of cholesterol lowering drugs. Nevertheless, statin use is still lower than currently recommended.

Association of hyperkalemia with clinical outcomes in advanced chronic kidney disease. / Asociación entre hiperkaliemia y evolución clínica en la enfermedad renal crónica avanzada.

INTRODUCTION: Patients with advanced chronic kidney disease (CKD) are at greatest risk of hyperkalemia (HK). The relationship between HK and negative outcomes (mortality or progression of renal insufficiency) in non-dialysis dependent CKD patients is controversial. AIMS: To determine the incidence, prevalence, and factors related with HK in a cohort of CKD patients, and its relationship with mortality, hospitalization rate, CKD progression, and dialysis initiation. MATERIAL AND METHODS: A retrospective, observational study in an incident cohort of adult patients with stage 4 or 5 CKD not on dialysis. Inclusion criteria were: having at least three consecutive estimated glomerular filtration rate (eGFR) measurements in a follow-up period >3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. HK was defined as serum K levels ≥5.5 meq/l. Associations of HK with outcomes were adjusted for major confounding variables in the multivariate analysis. RESULTS: The study group consisted of 1079 patients (574 males, mean age: 65±14 years) with mean baseline eGFR 14.8±4.5 ml/min/1,73 m2. Mean follow-up time was 15 months with a median of 7 serum sample determinations per patient. HK was observed at baseline in 26% of patients; in at least one serum sample during the individual follow-up period in 68%; or chronically (>50% of samples) in 33% of patients. By multivariate logistic regression, the best determinants of chronic HK were: male sex (OR = 1.529; 95% CI [1.154-2.025], p = .003), serum bicarbonate (OR = 0.863 [0.829-0.900], p <.0001), diuretic treatment (OR = 0.743 [0.556-0.992], p = .044), and angiotensin converting enzyme inhibitor and/or angiotensin receptor blockers (OR = 4.412 [2.915-6.678], p <.0001). Patients whose serum K levels were in the upper quartile showed a significantly faster CKD progression (-4.05±5.22 vs. -2.69±5.61 ml/min/1.73 m2/year, p <.0001), and more frequent dialysis initiation (63% vs. 57%, p = .115), though lower mortality (9% vs. 17%, p = .003) and hospitalization rates (2.68±5.94 vs. 3.16±6.77 days per year, p = .301) than the other study patients. However, in the multivariate analysis, average serum K levels were not independently associated with the clinical outcomes investigated. CONCLUSION: HK is a common biochemical finding in non-dialysis dependent CKD patients, mainly associated with prescribed medication. However, HK was not independently associated with major negative clinical outcomes.