Pancreatic and Hepatic Injury in COVID-19: A Worse Prognosis in NAFLD Patients?

The novel disease produced by SARS-CoV-2 mainly harms the respiratory tract, but it has shown the capacity to affect multiple organs. Epidemiologic evidence supports the relationship between Coronavirus Disease 2019 (COVID-19) and pancreatic and hepatic injury development, identified by alterations in these organ function markers. In this regard, it is important to ascertain how the current prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) might affect COVID-19 evolution and complications. Although it is not clear how SARS-CoV-2 affects both the pancreas and the liver, a multiplicity of potential pathophysiological mechanisms seem to be implicated; among them, a direct viral-induced injury to the organ involving liver and pancreas ACE2 expression. Additionally, immune system dysregulation, coagulopathies, and drugs used to treat the disease could be key for developing complications associated with the patient's clinical decline. This review aims to provide an overview of the available epidemiologic evidence regarding developing liver and pancreatic alterations in patients with COVID-19, as well as the possible role that NAFLD/NASH might play in the pathophysiological mechanisms underlying some of the complications associated with COVID-19. This review employed a comprehensive search on PubMed using relevant keywords and filters. From the initial 126 articles, those aligning with the research target were selected and evaluated for their methodologies, findings, and conclusions. It sheds light on the potential pathophysiological mechanisms underlying this relationship. As a result, it emphasises the importance of monitoring pancreatic and hepatic function in individuals affected by COVID-19.

Psycho-Neuro-Endocrine-Immunological Basis of the Placebo Effect: Potential Applications beyond Pain Therapy.

The placebo effect can be defined as the improvement of symptoms in a patient after the administration of an innocuous substance in a context that induces expectations regarding its effects. During recent years, it has been discovered that the placebo response not only has neurobiological functions on analgesia, but that it is also capable of generating effects on the immune and endocrine systems. The possible integration of changes in different systems of the organism could favor the well-being of the individuals and go hand in hand with conventional treatment for multiple diseases. In this sense, classic conditioning and setting expectations stand out as psychological mechanisms implicated in the placebo effect. Recent advances in neuroimaging studies suggest a relationship between the placebo response and the opioid, cannabinoid, and monoaminergic systems. Likewise, a possible immune response conditioned by the placebo effect has been reported. There is evidence of immune suppression conditioned through the insular cortex and the amygdala, with noradrenalin as the responsible neurotransmitter. Finally, a conditioned response in the secretion of different hormones has been determined in different studies; however, the molecular mechanisms involved are not entirely known. Beyond studies about its mechanism of action, the placebo effect has proved to be useful in the clinical setting with promising results in the management of neurological, psychiatric, and immunologic disorders. However, more research is needed to better characterize its potential use. This review integrates current knowledge about the psycho-neuro-endocrine-immune basis of the placebo effect and its possible clinical applications.

Specialized Proresolving Lipid Mediators: A Potential Therapeutic Target for Atherosclerosis.

Cardiovascular disease (CVD) is a global public health issue due to its high morbidity, mortality, and economic impact. The implementation of innovative therapeutic alternatives for CVD is urgently required. Specialized proresolving lipid mediators (SPMs) are bioactive compounds derived from ω-3 and ω-6 fatty acids, integrated into four families: Lipoxins, Resolvins, Protectins, and Maresins. SPMs have generated interest in recent years due to their ability to promote the resolution of inflammation associated with the pathogeneses of numerous illnesses, particularly CVD. Several preclinical studies in animal models have evidenced their ability to decrease the progression of atherosclerosis, intimal hyperplasia, and reperfusion injury via diverse mechanisms. Large-scale clinical trials are required to determine the effects of SPMs in humans. This review integrates the currently available knowledge of the therapeutic impact of SPMs in CVD from preclinical and clinical studies, along with the implicated molecular pathways. In vitro results have been promising, and as such, SPMs could soon represent a new therapeutic alternative for CVD.

Association of Newly Diagnosed Hypertension and Polypharmacy with Frailty in a Tertiary Hospital Patients from Maracaibo City, Venezuela.

BACKGROUND: As a syndrome of physiological vulnerability and multifactorial progressive decline tightly related to age, frailty has been associated with several illnesses, and in particular cardiovascular disease. OBJECTIVE: To assess the factors associated with the frailty syndrome in older adults evaluated in the outpatient clinic of a tertiary hospital from Maracaibo city, Venezuela. MATERIALS AND METHODS: An observational, analytical, cross-sectional study was performed on subjects of both genders, over 60 years old that went to the Internal Medicine outpatient clinic of the Hospital General del Sur "Dr. Pedro Iturbe" from Maracaibo city, Venezuela. Sampling was performed via a non-probabilistic, intentional method. For each subject with frailty or pre-frailty, a control subject was selected in a 1:1 ratio according to gender; several risk factors were interrogated. The state of frailty was determined through the FRAIL scale. RESULTS: Of the 201 assessed patients, 49.3% (n=99) were non-frail, 19.9% (n=40) were pre-frail and 30.8% (n=62) were frail. The population's overall age was 68.8±6.8 in non-frails, 69.1±7.7 in pre-frails, and 68.6±7.1 in frails. In the multivariate analysis, subjects with frailty and pre-frailty were most likely to be receiving polypharmacy (OR: 2.36, CI95%: 1.05-5.37; P=0.04) and have hypertension during the study (OR: 10.19, CI95%: 3.86-26.89; P<0.01). CONCLUSION: The newly diagnosed hypertension and presence of polypharmacy were the factors most associated with frailty and pre-frailty in older adults evaluated in a tertiary hospital from Maracaibo city, Venezuela.

Etelcalcetide and Paricalcitol in Chronic Kidney Disease: When the Target Is Inflammation.

Introduction: secondary hyperparathyroidism (SHP) is frequent in patients with chronic kidney disease (CKD), particularly in those in dialysis. To treat this complication, the current options available include phosphorus restriction, phosphate binders, the inhibition of parathyroid hormone (PTH) synthesis and secretion by the supplementation of vitamin D or VDR activators, or the use of calcimimetics. Beyond the control of PTH, the effects of the treatment of SHP on other biomarkers of risk may represent an additional benefit for this population. In this study, we explore the benefits of current SHP treatment options, mainly paricalcitol and/or etelcalcetide in the inflammatory state of hemodialysis (HD) patients. Results: the study finally included 142 maintenance HD patients (5 patients were excluded) followed for 6 months (dialysis vintage 26 ± 30 months, mean age 70 years old, 73% women, 81% Spanish white, 47% diabetic). In this case, 52 patients were on regular treatment with paricalcitol for SHP and 25 patients were eligible to initiate etelcalcetide. The baseline serum levels of Ca, P, PTH, Ferritin, albumin, C-reactive protein (CRP), and other variables were measured. We found serum PTH levels showed an improvement after the treatment with etelcalcetide again paricalcitol and no treatment (p < 0.04). Of note, serum levels of CRP were significantly lower in a small group of patients (n = 11) receiving paricalcitol + etelcalcetide compared to paricalcitol or etelcalcetide alone. The proportion of patients with CRP within target ranges (≤1.0 mg/dL) increased significantly after combined treatment (p < 0.001). Conclusions: etelcalcetide proved to safely reduce the PTH levels without significant adverse events and the possibility of a synergic anti-inflammatory effect with the simultaneous use of Paricalcitol in HD patients.

SGLT2i and GLP-1RA in Cardiometabolic and Renal Diseases: From Glycemic Control to Adipose Tissue Inflammation and Senescence.

Background. Over the last few years, the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) has increased substantially in medical practice due to their documented benefits in cardiorenal and metabolic health. In this sense, and in addition to being used for glycemic control in diabetic patients, these drugs also have other favorable effects such as weight loss and lowering blood pressure, and more recently, they have been shown to have cardio and renoprotective effects with anti-inflammatory properties. Concerning the latter, the individual or associated use of these antihyperglycemic agents has been linked with a decrease in proinflammatory cytokines and with an improvement in the inflammatory profile in chronic endocrine-metabolic diseases. Hence, these drugs have been positioned as first-line therapy in the management of diabetes and its multiple comorbidities, such as obesity, which has been associated with persistent inflammatory states that induce dysfunction of the adipose tissue. Moreover, other frequent comorbidities in long-standing diabetic patients are chronic complications such as diabetic kidney disease, whose progression can be slowed by SGLT2i and/or GLP-1RA. The neuroendocrine and immunometabolism mechanisms underlying adipose tissue inflammation in individuals with diabetes and cardiometabolic and renal diseases are complex and not fully understood. Summary. This review intends to expose the probable molecular mechanisms and compile evidence of the synergistic or additive anti-inflammatory effects of SGLT2i and GLP-1RA and their potential impact on the management of patients with obesity and cardiorenal compromise.

The Sick Adipose Tissue: New Insights Into Defective Signaling and Crosstalk With the Myocardium.

Adipose tissue (AT) biology is linked to cardiovascular health since obesity is associated with cardiovascular disease (CVD) and positively correlated with excessive visceral fat accumulation. AT signaling to myocardial cells through soluble factors known as adipokines, cardiokines, branched-chain amino acids and small molecules like microRNAs, undoubtedly influence myocardial cells and AT function via the endocrine-paracrine mechanisms of action. Unfortunately, abnormal total and visceral adiposity can alter this harmonious signaling network, resulting in tissue hypoxia and monocyte/macrophage adipose infiltration occurring alongside expanded intra-abdominal and epicardial fat depots seen in the human obese phenotype. These processes promote an abnormal adipocyte proteomic reprogramming, whereby these cells become a source of abnormal signals, affecting vascular and myocardial tissues, leading to meta-inflammation, atrial fibrillation, coronary artery disease, heart hypertrophy, heart failure and myocardial infarction. This review first discusses the pathophysiology and consequences of adipose tissue expansion, particularly their association with meta-inflammation and microbiota dysbiosis. We also explore the precise mechanisms involved in metabolic reprogramming in AT that represent plausible causative factors for CVD. Finally, we clarify how lifestyle changes could promote improvement in myocardiocyte function in the context of changes in AT proteomics and a better gut microbiome profile to develop effective, non-pharmacologic approaches to CVD.

The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror.

Type 2 Diabetes Mellitus (T2DM) is one of the most prevalent chronic metabolic disorders, and insulin has been placed at the epicentre of its pathophysiological basis. However, the involvement of impaired alpha (α) cell function has been recognized as playing an essential role in several diseases, since hyperglucagonemia has been evidenced in both Type 1 and T2DM. This phenomenon has been attributed to intra-islet defects, like modifications in pancreatic α cell mass or dysfunction in glucagon's secretion. Emerging evidence has shown that chronic hyperglycaemia provokes changes in the Langerhans' islets cytoarchitecture, including α cell hyperplasia, pancreatic beta (ß) cell dedifferentiation into glucagon-positive producing cells, and loss of paracrine and endocrine regulation due to ß cell mass loss. Other abnormalities like α cell insulin resistance, sensor machinery dysfunction, or paradoxical ATP-sensitive potassium channels (KATP) opening have also been linked to glucagon hypersecretion. Recent clinical trials in phases 1 or 2 have shown new molecules with glucagon-antagonist properties with considerable effectiveness and acceptable safety profiles. Glucagon-like peptide-1 (GLP-1) agonists and Dipeptidyl Peptidase-4 inhibitors (DPP-4 inhibitors) have been shown to decrease glucagon secretion in T2DM, and their possible therapeutic role in T1DM means they are attractive as an insulin-adjuvant therapy.

Lipid Accumulation Product Is More Related to Insulin Resistance than the Visceral Adiposity Index in the Maracaibo City Population, Venezuela.

BACKGROUND: Visceral adiposity is related to insulin resistance (IR), a metabolic state considered as a risk factor for other cardiometabolic diseases. In that matter, mathematical indexes such as the visceral adiposity index (VAI) and the lipid accumulation product (LAP) could indirectly assess IR based on visceral adiposity. OBJECTIVE: To evaluate the association and diagnostic accuracy of VAI and LAP to diagnose IR in the adult population of Maracaibo city. METHODS: This is a cross-sectional descriptive study with multistage sampling. Receiver operating characteristic (ROC) curves were built to determine VAI and LAP cutoff points to predict IR. A set of logistic regression models was constructed according to sociodemographic, psychobiologic, and metabolic variables. RESULTS: 1818 subjects were evaluated (51.4% women). The area under the curve (AUC) values for LAP and VAI were 0.689 (0.665-0.714) and 0.645 (0.619-0.670), respectively. Both indexes showed a higher IR risk in the upper tertile in bivariate analysis. However, in the logistic regression analysis for the IR risk, only the 2nd (OR: 1.91; 95% CI: 1.37-2.65; p < 0.01) and 3rd (OR: 5.40; 95% CI: 3.48-8.39; p < 0.01) LAP tertiles showed a significant increase. This behaviour was also observed after adjusting for hs-C-reactive protein (hs-CPR). CONCLUSION: Although both indexes show a low predictive capacity in individuals with IR in the Maracaibo city population, the LAP index was more strongly associated with IR.

Metabolic Syndrome: Is It Time to Add the Central Nervous System?

Metabolic syndrome (MS) is a set of cardio-metabolic risk factors that includes central obesity, hyperglycemia, hypertension, and dyslipidemias. The syndrome affects 25% of adults worldwide. The definition of MS has evolved over the last 80 years, with various classification systems and criteria, whose limitations and benefits are currently the subject of some controversy. Likewise, hypotheses regarding the etiology of MS add more confusion from clinical and epidemiological points of view. The leading suggestion for the pathophysiology of MS is insulin resistance (IR). IR can affect multiple tissues and organs, from the classic "triumvirate" (myocyte, adipocyte, and hepatocyte) to possible effects on organs considered more recently, such as the central nervous system (CNS). Mild cognitive impairment (MCI) and Alzheimer's disease (AD) may be clinical expressions of CNS involvement. However, the association between MCI and MS is not understood. The bidirectional relationship that seems to exist between these factors raises the questions of which phenomenon occurs first and whether MCI can be a precursor of MS. This review explores shared pathophysiological mechanisms between MCI and MS and establishes a hypothesis of a possible MCI role in the development of IR and the appearance of MS.

Advanced Glycation End Products: New Clinical and Molecular Perspectives.

Diabetes mellitus (DM) is considered one of the most massive epidemics of the twenty-first century due to its high mortality rates caused mainly due to its complications; therefore, the early identification of such complications becomes a race against time to establish a prompt diagnosis. The research of complications of DM over the years has allowed the development of numerous alternatives for diagnosis. Among these emerge the quantification of advanced glycation end products (AGEs) given their increased levels due to chronic hyperglycemia, while also being related to the induction of different stress-associated cellular responses and proinflammatory mechanisms involved in the progression of chronic complications of DM. Additionally, the investigation for more valuable and safe techniques has led to developing a newer, noninvasive, and effective tool, termed skin fluorescence (SAF). Hence, this study aimed to establish an update about the molecular mechanisms induced by AGEs during the evolution of chronic complications of DM and describe the newer measurement techniques available, highlighting SAF as a possible tool to measure the risk of developing DM chronic complications.

Age-specific waist circumference cutoff-points for abdominal obesity diagnosis: a personalized strategy for a large Venezuelan population.

BACKGROUND: Evidence shows that the ageing process is a determining factor in fat distribution, composition, and functionality. The goal of this research was to determine cut-off points for waist circumference according to age in the adult population from Maracaibo city, Venezuela. METHODOLOGY: The Metabolic Syndrome Prevalence Study is a descriptive, cross-sectional study with multi-stage randomized sampling. In this post-hoc analysis 1902 individuals ≥18 years and from both sexes were evaluated. Waist circumference ROC curves were built for each age group and sex, using metabolic phenotypes for classification. RESULTS: 52.2% (n = 992) were women, and the mean age was 38.7 ± 2. Cut-off points obtained for the <30 years age group were: 91 cm for women (Sensitivity: 96,8%, Specificity: 97,7%) and 94 cm for men (Sensitivity:100%, Specificity: 99,2%); for 30-49 years: women 94 cm (Sensitivity: 93.7%, Specificity: 97.1%) and men 95 cm (Sensitivity: 97.3%, Specificity: 100%); for ≥50 years: women 94 cm (Sensitivity: 91.8%, Specificity: 86.7%) and men 101 cm (Sensitivity: 100%, Specificity: 100%). CONCLUSION: The use of specific cut-off points according to age groups is proposed to determine abdominal obesity in Maracaibo city due to the underestimation seen in young people and the overestimation observed in older people when using a unique cut-off point.

Alzheimer's disease and type 2 diabetes mellitus: Pathophysiologic and pharmacotherapeutics links.

At present, Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are two highly prevalent disorders worldwide, especially among elderly individuals. T2DM appears to be associated with cognitive dysfunction, with a higher risk of developing neurocognitive disorders, including AD. These diseases have been observed to share various pathophysiological mechanisms, including alterations in insulin signaling, defects in glucose transporters (GLUTs), and mitochondrial dysfunctions in the brain. Therefore, the aim of this review is to summarize the current knowledge regarding the molecular mechanisms implicated in the association of these pathologies as well as recent therapeutic alternatives. In this context, the hyperphosphorylation of tau and the formation of neurofibrillary tangles have been associated with the dysfunction of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathways in the nervous tissues as well as the decrease in the expression of GLUT-1 and GLUT-3 in the different areas of the brain, increase in reactive oxygen species, and production of mitochondrial alterations that occur in T2DM. These findings have contributed to the implementation of overlapping pharmacological interventions based on the use of insulin and antidiabetic drugs, or, more recently, azeliragon, amylin, among others, which have shown possible beneficial effects in diabetic patients diagnosed with AD.

Clinical-epidemiological analysis of HDL2 and HDL3 subfractions in adults from Maracaibo city, Venezuela. / Análisis clínico-epidemiológico de las subfracciones HDL2 y HDL3 en adultos de la ciudad de Maracaibo, Venezuela.

OBJECTIVE: To carry out a clinical-epidemiological analysis of high-density lipoprotein cholesterol subfractions (HDL-C) in adults from Maracaibo, Venezuela. MATERIALS AND METHODS: A descriptive and cross-sectional study of the database from the Metbolic Syndrome Prevalence in Maracaibo Study was carried out. HDL3 and HDL2 serum concentration, as well as the HDL2/HDL3 ratio, were determined in 359 individuals of both sexes, over 18 years of age. Values obtained were evaluated according to sociodemographic, clinical and biochemical characteristics. RESULTS: Mean population age was 39.4 ± 15.2 years, and 51.5% were female. Differences in HDL-C subfraction levels were only observed in those subjects with low HDL-C levels. Women with hypertriglyceridemia showed significantly lower serum HDL3 and HDL2 concentrations than those with normal triglycerides (p=0.033), as well as a lower HDL3 level and HDL2 / HDL3 ratio in those with higher levels of ultra-sensitive C-reactive protein (us-CRP) (p<0.001). A significantly lower concentration of HDL2 was observed in men with some degree of hypertension (p=0.031), insulin resistance (p=0.050) and metabolic syndrome (p=0.003); while those with elevated us-CRP showed a lower concentration of HDL3 (p=0.011). CONCLUSION: HDL-C subfractions show varying clinical-epidemiological behavior in adults from Maracaibo. Lower serum levels are observed in men, differences only in those with low HDL-C; and no predominance of any subclass was observed according to sociodemographic, clinical and biochemical characteristics.

OBJETIVO: Realizar un análisis clínico-epidemiológico de las subfracciones de colesterol unido a lipoproteinas de alta densidad (HDL-C, por sus siglas en inglés) en adultos de la ciudad de Maracaibo, Venezuela. MATERIALES Y MÉTODOS: Se realizó un estudio descriptivo y transversal de la base de datos del Estudio de Prevalencia de Síndrome Metabólico de Maracaibo, que incluyó 359 individuos de ambos sexos, mayores de 18 años, a quienes se les determinó la concentración sérica de HDL3 y HDL2, así como el índice HDL2/HDL3; evaluando sus niveles según características sociodemográficas, clínicas y bioquímicas. RESULTADOS: La edad promedio de la población era 39,4 ± 15,2 años, y 51,5% era de sexo femenino. Solo se observaron diferencias en los niveles de HDL-C en aquellos sujetos con HDL-C bajas. Las mujeres con hipertriacilgliceridemia mostraron concentraciones séricas de HDL3 y HDL2 significativamente menores con respecto a aquellas con triacilglicéridos normales (p = 0,033); asimismo, se encontró una concentración menor de HDL3 y relación HDL2/HDL3 en aquellas con proteína C reactiva ultrasensible (PCR-us) elevada (p < 0,001). En hombres, se evidenció una concentración significativamente menor de HDL2 en aquellos con algún grado de hipertensión arterial (p = 0,031), insulinorresistencia (p = 0,050) y síndrome metabólico (p = 0,003); mientras que aquellos con PCR-us elevada mostraron una menor concentración de HDL3 (p = 0,011). CONCLUSIÓN: Las subfracciones de HDL-C muestran un comportamiento clínico epidemiológico variable en adultos de la población de Maracaibo, con promedios más bajos en los hombres, diferencias en los niveles únicamente en aquellos con HDL-C bajas, y sin predominio de alguna subclase según las características sociodemográficas, clínicas y bioquímicas.

Anti-Aging Effect of Metformin: A Molecular and Therapeutical Perspective.

Aging is a time-dependent inevitable process, in which cellular homeostasis is affected, which has an impact on tissue function. This represents a risk factor for the development of numerous non-transmissible diseases. In consequence, the scientific community continues to search for therapeutic measures capable of improving quality of life and delaying cellular aging. At the center of this research is metformin, a widely used drug in Type 2 Diabetes Mellitus treatment that has a reduced adverse effects profile. Furthermore, there is evidence that this drug has beneficial health effects that go beyond its anti-hyperglycemic properties. Among these effects, its geronto-protection capability stands out. There is growing evidence that points out to an increased life expectancy as well as the quality of life in model organisms treated with metformin. Therefore, there is an abundance of research centered on elucidating the mechanism through which metformin has its anti-aging effects. Among these, the AMPK, mTORC1, SIRT1, FOXO, NF.kB, and DICER1 pathways can be mentioned. Furthermore, studies have highlighted the possibility of a role for the gut microbiome in these processes. The next step is the design of clinical essays that have as a goal evaluating the efficacy and safety of metformin as an anti-aging drug in humans to create a paradigm in the medical horizon. The question being if metformin is, in fact, the new antiaging therapy in humans?

Análisis clínico-epidemiológico de las subfracciones HDL2 y HDL3 en adultos de la ciudad de Maracaibo, Venezuela / Clinical-epidemiological analysis of HDL2 and HDL3 subfractions in adults from Maracaibo city, Venezuela

RESUMEN Objetivo: Realizar un análisis clínico-epidemiológico de las subfracciones de colesterol unido a lipoproteinas de alta densidad (HDL-C, por sus siglas en inglés) en adultos de la ciudad de Maracaibo, Venezuela. Materiales y métodos: Se realizó un estudio descriptivo y transversal de la base de datos del Estudio de Prevalencia de Síndrome Metabólico de Maracaibo, que incluyó 359 individuos de ambos sexos, mayores de 18 años, a quienes se les determinó la concentración sérica de HDL3 y HDL2, así como el índice HDL2/HDL3; evaluando sus niveles según características sociodemográficas, clínicas y bioquímicas. Resultados: La edad promedio de la población era 39,4 ± 15,2 años, y 51,5% era de sexo femenino. Solo se observaron diferencias en los niveles de HDL-C en aquellos sujetos con HDL-C bajas. Las mujeres con hipertriacilgliceridemia mostraron concentraciones séricas de HDL3 y HDL2 significativamente menores con respecto a aquellas con triacilglicéridos normales (p=0,033); asimismo, se encontró una concentración menor de HDL3 y relación HDL2/HDL3 en aquellas con proteína C reactiva ultrasensible (PCR-us) elevada (p<0,001). En hombres, se evidenció una concentración significativamente menor de HDL2 en aquellos con algún grado de hipertensión arterial (p=0,031), insulinorresistencia (p=0,050) y síndrome metabólico (p=0,003); mientras que aquellos con PCR-us elevada mostraron una menor concentración de HDL3 (p=0,011). Conclusión: Las subfracciones de HDL-C muestran un comportamiento clínico epidemiológico variable en adultos de la población de Maracaibo, con promedios más bajos en los hombres, diferencias en los niveles únicamente en aquellos con HDL-C bajas, y sin predominio de alguna subclase según las características sociodemográficas, clínicas y bioquímicas.

ABSTRACT Objective: To carry out a clinical-epidemiological analysis of high-density lipoprotein cholesterol subfractions (HDL-C) in adults from Maracaibo, Venezuela. Materials and methods: A descriptive and cross-sectional study of the database from the Metbolic Syndrome Prevalence in Maracaibo Study was carried out. HDL3 and HDL2 serum concentration, as well as the HDL2/HDL3 ratio, were determined in 359 individuals of both sexes, over 18 years of age. Values obtained were evaluated according to sociodemographic, clinical and biochemical characteristics. Results: Mean population age was 39.4 ± 15.2 years, and 51.5% were female. Differences in HDL-C subfraction levels were only observed in those subjects with low HDL-C levels. Women with hypertriglyceridemia showed significantly lower serum HDL3 and HDL2 concentrations than those with normal triglycerides (p=0.033), as well as a lower HDL3 level and HDL2 / HDL3 ratio in those with higher levels of ultra-sensitive C-reactive protein (us-CRP) (p<0.001). A significantly lower concentration of HDL2 was observed in men with some degree of hypertension (p=0.031), insulin resistance (p=0.050) and metabolic syndrome (p=0.003); while those with elevated us-CRP showed a lower concentration of HDL3 (p=0.011). Conclusion: HDL-C subfractions show varying clinical-epidemiological behavior in adults from Maracaibo. Lower serum levels are observed in men, differences only in those with low HDL-C; and no predominance of any subclass was observed according to sociodemographic, clinical and biochemical characteristics.

Luminescent lanthanide complexes with a pyridine-bis(carboxamide)-bithiophene sensitizer showing wavelength-dependent singlet oxygen generation.

A new pyridine-bis(carboxamide)-based ligand with a bithiophene pendant, 2Tcbx, was synthesized. Its lanthanide ion (LnIII) complexes, [Ln(2Tcbx)2]3+, were isolated and their photophysical properties were explored. Upon excitation at 360 nm, these complexes display emission in the near-infrared (NIR) with efficiencies of 0.69% for LnIII = YbIII, 0.20% for LnIII = NdIII, and 0.01% for LnIII = ErIII, respectively. Concurrent 1O2 formation was seen for all complexes, with efficiencies of 19% for the YbIII complex, 25% for the NdIII complex, and 9% for the ErIII complex. When exciting at a longer wavelength, 435 nm, only LnIII emission was observed and larger efficiencies of LnIII-centered emission were obtained. The lack of 1O2 generation indicates that energy pathways involving different ligand conformations, which were investigated by transient absorption spectroscopy, are involved in the sensitization process, and enable the wavelength-dependent generation of 1O2.

Depression as an Immunometabolic Disorder: Exploring Shared Pharmacotherapeutics with Cardiovascular Disease.

Modern times have seen depression and cardiovascular disease (CVD) become notorious public health concerns, corresponding to alarming proportions of morbidity, mortality, decreased quality of life, and economic costs. Expanding comprehension of the pathogenesis of depression as an immunometabolic disorder has identified numerous pathophysiologic phenomena in common with CVD, including chronic inflammation, insulin resistance, and oxidative stress. These shared components could be exploited to offer improved alternatives in the joint management of these conditions. Abundant preclinical and clinical data on the impact of established treatments for CVD in the management of depression have allowed for potential candidates to be proposed for the joint management of depression and CVD as immunometabolic disorders. However, a large proportion of the clinical investigation currently available exhibits marked methodological flaws which preclude the formulation of concrete recommendations in many cases. This situation may be a reflection of pervasive problems present in clinical research in psychiatry, especially pertaining to study homogeneity. Therefore, further high-quality research is essential in the future in this regard.

Wavelength-Dependent Singlet Oxygen Generation in Luminescent Lanthanide Complexes with a Pyridine-Bis(Carboxamide)-Terthiophene Sensitizer.

Lanthanide ion (LnIII ) complexes, [Ln(3Tcbx)2 ]3+ (LnIII =YbIII , NdIII , ErIII ) are isolated with a new pyridine-bis(carboxamide)-based ligand with a 2,2':5',2''-terthiophene pendant (3TCbx), and their resulting photophysical properties are explored. Upon excitation of the complexes at 490 nm, only LnIII emission is observed with efficiencies of 0.29 % at 976 nm for LnIII =YbIII and 0.16 % at 1053 nm for LnIII =NdIII . ErIII emission is observed but weak. Upon excitation at 400 nm, concurrent 1 O2 formation is seen, with efficiencies of 11 % for the YbIII and NdIII complexes and 13 % for the ErIII complex. Owing to the concurrent generation of 1 O2 , as expected, the efficiency of metal-centered emission decreases to 0.02 % for YbIII and 0.05 % for NdIII . The ability to control 1 O2 generation through the excitation wavelength indicates that the incorporation of 2,2':5',2''-terthiophene results in access to multiple sensitization pathways. These energy pathways are unraveled through transient absorption spectroscopy.

Is "Leptin Resistance" Another Key Resistance to Manage Type 2 Diabetes?

Although novel pharmacological options for the treatment of type 2 diabetes mellitus (DM2) have been observed to modulate the functionality of several key organs in glucose homeostasis, successful regulation of insulin resistance (IR), body weight management, and pharmacological treatment of obesity remain notable problems in endocrinology. Leptin may be a pivotal player in this scenario, as an adipokine which centrally regulates appetite and energy balance. In obesity, excessive caloric intake promotes a low-grade inflammatory response, which leads to dysregulations in lipid storage and adipokine secretion. In turn, these entail alterations in leptin sensitivity, leptin transport across the blood-brain barrier and defects in post-receptor signaling. Furthermore, hypothalamic inflammation and endoplasmic reticulum stress may increase the expression of molecules which may disrupt leptin signaling. Abundant evidence has linked obesity and leptin resistance, which may precede or occur simultaneously to IR and DM2. Thus, leptin sensitivity may be a potential early therapeutic target that demands further preclinical and clinical research. Modulators of insulin sensitivity have been tested in animal models and small clinical trials with promising results, especially in combination with agents such as amylin and GLP-1 analogs, in particular, due to their central activity in the hypothalamus.