188 research outputs found

    A randomized, double blind, cross-over, placebo-controlled clinical trial to assess the effects of Candesartan on the insulin sensitivity on non diabetic, non hypertense subjects with dysglyce mia and abdominal obesity. "ARAMIA"

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    BACKGROUND: The raising prevalence of type-2 diabetes mellitus and obesity has been recognized as a major problem for public health, affecting both developed and developing countries. Impaired fasting plasma glucose has been previously associated with endothelial dysfunction, higher levels of inflammatory markers and increased risk of developing insulin resistance and cardiovascular events. Besides life-style changes, the blockade of the renin-angiotensin system has been proposed as a useful alternative intervention to improve insulin resistance and decrease the number of new type-2 diabetes cases. The aim of this clinical trial is to study the effect of the treatment with Candesartan, an angiotensin II receptor antagonist, on the insulin resistance, the plasma levels of adipoquines, oxidative stress and prothrombotic markers, in a group of non diabetic, non hypertensive, dysglycemic and obese subjects. METHODS AND DESIGN: A randomized, double blind, cross-over, placebo-controlled, clinical trial was designed to assess the effects of Candesartan (up to 32 mg/day during 6 months) on the Homeostasis Model Assessment (HOMA) index, lipid profile, protrombotic state, oxidative stress and plasma levels of inflammatory markers. The participants will be recruited in the "Fundación Cardiovascular de Colombia". Subjects who fullfil selection criteria will receive permanent educational, nutritional and exercise support during their participation in the study. After a 15 days-run-in period with placebo and life-style recommendations, the patients who have a treatment compliance equal or greater than 80% will be randomlly assigned to one of the treatment groups. Group A will receive Candesartan during 6 months and placebo during 6 months. Group B will receive placebo during the first 6 months, and then, Candesartan during the last 6 months. Control visits will be programed monthly and all parameters of interest will be evaluated every 6 months. HYPOTHESIS: Treatment with Candesartan, could improve the HOMA index, the response to the oral glucose tolerance test and reduce the plasma levels of adipoquines, oxidative stress and prothrombotic markers, in non diabetic, non hypertense subjects with dysglycemia and abdominal obesity, recruited from a population at high risk of developing insulin resistance. These effects are independent of the changes in arterial blood pressure. Trial registration: NCT0031920

    Melatonin as an Anti-Aging Therapy for Age-Related Cardiovascular and Neurodegenerative Diseases

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    The concept of “aging” is defined as the set of gradual and progressive changes in an organism that leads to an increased risk of weakness, disease, and death. This process may occur at the cellular and organ level, as well as in the entire organism of any living being. During aging, there is a decrease in biological functions and in the ability to adapt to metabolic stress. General effects of aging include mitochondrial, cellular, and organic dysfunction, immune impairment or inflammaging, oxidative stress, cognitive and cardiovascular alterations, among others. Therefore, one of the main harmful consequences of aging is the development and progression of multiple diseases related to these processes, especially at the cardiovascular and central nervous system levels. Both cardiovascular and neurodegenerative pathologies are highly disabling and, in many cases, lethal. In this context, melatonin, an endogenous compound naturally synthesized not only by the pineal gland but also by many cell types, may have a key role in the modulation of multiple mechanisms associated with aging. Additionally, this indoleamine is also a therapeutic agent, which may be administered exogenously with a high degree of safety. For this reason, melatonin could become an attractive and low-cost alternative for slowing the processes of aging and its associated diseases, including cardiovascular and neurodegenerative disorders.Fil: Martín Giménez, Virna Margarita. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina. Universidad Catolica de Cuyo - Sede San Juan. Facultad de Ciencias de la Alimentación, Bioquímicas y Farmacéuticas. Instituto de Investigación en Ciencias Químicas; ArgentinaFil: de Las Heras, Natalia. Universidad Complutense de Madrid. Facultad de Medicina. Departamento de Fisiología; EspañaFil: Lahera Juliá, Vicente. Universidad Complutense de Madrid. Facultad de Medicina. Departamento de Fisiología; EspañaFil: Tresguerrés, Jesús A. F.. Universidad Complutense de Madrid. Facultad de Medicina. Departamento de Fisiología; EspañaFil: Reiter, Russel. University of Texas at San Antonio; Estados UnidosFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Cátedra de Farmacología; Argentin

    Abnormal Distribution and Function of Circulating Monocytes and Enhanced Bacterial Translocation in Major Depressive Disorder

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    Introduction: Major depressive disorder (MDD) patients experience a systemic inflammatory stage. Monocytes play an important role in innate inflammatory responses and may be modulated by bacterial translocation. Our aim was to investigate the subset distribution and function of circulating monocytes, levels of proinflammatory cytokines, gut barrier damage, and bacterial translocation in MDD patients. Methods: Twenty-two MDD patients without concomitant diseases and 14 sex- and age-matched healthy controls were studied. The levels of circulating CD14++CD16- (classical), CD14++CD16++ (intermediate) and CD14- CD16++ (nonclassical) monocytes and the intracytoplasmic tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 expression in the presence or absence of lipopolysaccharide (LPS) stimulation were analyzed by polychromatic flow cytometry. The serum TNF-α, IL-1β, IL-6, and IL-10 levels were measured by Luminex. LPS-binding protein (LBP), intestinal fatty acidbinding protein (I-FABP), and zonulin were measured by enzyme-linked immunosorbent assay (ELISA). Results: MDD patients had a significant increase in the frequency of intermediate monocytes and a significant decrease in the frequency of classical monocytes compared to those in the healthy controls. MDD patients had a significantly increased percentage of classical monocytes that expressed IL-1β, intermediate monocytes that expressed IL-1β and IL6 and nonclassical monocytes that expressed IL-1β, and decreased levels of nonclassical monocytes that expressed IL6 compared to those in the healthy controls. MDD patients had significantly increased levels of circulating TNF-α, IL-1β, LBP, and I-FABP compared to those in the healthy controls. MDD patients with high LBP levels had a significant reduction in the number of circulating monocytes compared to that in the normal-LBP MDD patients, which can be mainly ascribed to a decrease in the number of intermediate and nonclassical monocytes. Conclusions: We have demonstrated that compared to the healthy controls, MDD patients show a marked alteration in circulating monocytes, with an expansion of the intermediate subset with increased frequency of IL-1β and IL-6 producing cells. These patients also exhibited a systemic proinflammatory state, which was characterized by the enhanced serum TNF-α and IL-1β levels compared to those in the healthy controls. Furthermore, MDD patients showed increased LBP and I-FABP levels compared to those in healthy controls, indicating increased bacterial translocation and gut barrier damage

    Group and sex differences in social cognition in bipolar disorder, schizophrenia/schizoaffective disorder and healthy people

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    Background: Impairment of social cognition is documented in bipolar disorder (BD) and schizophrenia/schizoaffective disorder (SCH). In healthy individuals, women perform better than men in some of its sub-domains. However, in BD and SCH the results are mixed. Our aim was to compare emotion recognition, affective Theory of Mind (ToM) and first- and second-order cognitive ToM in BD, SCH and healthy subjects, and to investigate sex-related differences. Methods: 120 patients (BD = 60, SCH = 60) and 40 healthy subjects were recruited. Emotion recognition was assessed by the Pictures of Facial Affect (POFA) test, affective ToM by the Reading the Mind in the Eyes Test (RMET) and cognitive ToM by several false-belief stories. Group and sex differences were analyzed using parametric (POFA, RMET) and non-parametric (false-belief stories) tests. The impact of age, intelligence quotient (IQ) and clinical variables on patient performance was examined using a series of linear/logistic regressions. Results: Both groups of patients performed worse than healthy subjects on POFA, RMET and second-order false-belief (p < 0.001), but no differences were found between them. Instead, their deficits were related to older age and/or lower IQ (p < 0.01). Subthreshold depression was associated with a 6-fold increased risk of first-order false-belief failure (p < 0.001). Sex differences were only found in healthy subjects, with women outperforming men on POFA and RMET (p ≤ 0.012), but not on first/second-order false-belief. Limitations: The cross-sectional design does not allow for causal inferences. Conclusion: BD and SCH patients had deficits in emotion recognition, affective ToM, and second-order cognitive ToM, but their performance was comparable to each other, highlighting that the differences between them may be subtler than previously thought. First-order cognitive ToM remained intact, but subthreshold depression altered their normal functioning. Our results suggest that the advantage of healthy women in the emotional and affective aspects of social cognition would not be maintained in BD and SCH

    Women with psychotic episodes during pregnancy show increased markers of placental damage with Tenney-Parker changes

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    y. Psychosis is a hazardous and functionally disruptive psychiatric condition which may affect women in pregnancy, entailing negative consequences for maternofetal well-being. The precise pathophysiological basis and consequences of a psychotic episode in pregnancy remain to be further elucidated. The placenta is a pivotal tissue with many functions in the gestational period, critically influencing the fate and development of pregnancy. Although detrimental alterations have been observed in women undergoing severe psychiatric disorders in pregnancy, there are little studies evaluating the consequences of suffering from a psychotic episode in the placental tissue In this work, we have evaluated the histopathological consequences of a first episode of psychosis in pregnancy (FE-PW; N=22) and compare them with healthy pregnant women (HC-PW; N=20) by using histological, immunohistochemical and gene expression techniques. Our results define that the placental tissue of FE-PW display an increase in the number of placental villi, bridges, syncytial knots and syncytial knots/villi. Besides, we have also observed an enhanced gene and protein expression in FE-PW of the hypoxic marker HIF-1α, together with the apoptotic markers BAX and Bcl-2. To our knowledge, this is the first study demonstrating significant histopathological changes in the placenta of women suffering a new-onset psychotic episode in pregnancy. Further studies should be aimed at deepening the knowledge about the pernicious effects of psychosis in the maternofetal tissues, as well as the potential implications of these alterations

    Mindfulness based cognitive therapy improves frontal control in bipolar disorder: a pilot EEG study

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    <p>Abstract</p> <p>Background</p> <p>Cognitive processing in Bipolar Disorder is characterized by a number of attentional abnormalities. Mindfulness Based Cognitive Therapy combines mindfulness meditation, a form of attentional training, along with aspects of cognitive therapy, and may improve attentional dysfunction in bipolar disorder patients.</p> <p>Methods</p> <p>12 euthymic BD patients and 9 control participants underwent record of electroencephalography (EEG, band frequency analysis) during resting states (eyes open, eyes closed) and during the completion of a continuous performance task (A-X version, EEG event-related potential (ERP) wave component analysis). The individuals with BD completed an 8-week MBCT intervention and record of EEG was repeated.</p> <p>Results</p> <p>(1) Brain activity, individuals with BD showed significantly decreased theta band power, increased beta band power, and decreased theta/beta ratios during the resting state, eyes closed, for frontal and cingulate cortices. Post MBCT intervention improvement over the right frontal cortex was seen in the individuals with BD, as beta band power decreased. (2) Brain activation, individuals with BD showed a significant P300-like wave form over the frontal cortex during the cue. Post MBCT intervention the P300-like waveform was significantly attenuated over the frontal cortex.</p> <p>Conclusions</p> <p>Individuals with BD show decreased attentional readiness and activation of non-relevant information processing during attentional processes. These data are the first that show, MBCT in BD improved attentional readiness, and attenuated activation of non-relevant information processing during attentional processes.</p

    What to consider when pseudohypoparathyroidism is ruled out: IPPSD and differential diagnosis

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    Background: Pseudohypoparathyroidism (PHP) is a rare disease whose phenotypic features are rather difficult to identify in some cases. Thus, although these patients may present with the Albright''s hereditary osteodystrophy (AHO) phenotype, which is characterized by small stature, obesity with a rounded face, subcutaneous ossifications, mental retardation and brachydactyly, its manifestations are somewhat variable. Indeed, some of them present with a complete phenotype, whereas others show only subtle manifestations. In addition, the features of the AHO phenotype are not specific to it and a similar phenotype is also commonly observed in other syndromes. Brachydactyly type E (BDE) is the most specific and objective feature of the AHO phenotype, and several genes have been associated with syndromic BDE in the past few years. Moreover, these syndromes have a skeletal and endocrinological phenotype that overlaps with AHO/PHP. In light of the above, we have developed an algorithm to aid in genetic testing of patients with clinical features of AHO but with no causative molecular defect at the GNAS locus. Starting with the feature of brachydactyly, this algorithm allows the differential diagnosis to be broadened and, with the addition of other clinical features, can guide genetic testing. Methods: We reviewed our series of patients (n = 23) with a clinical diagnosis of AHO and with brachydactyly type E or similar pattern, who were negative for GNAS anomalies, and classify them according to the diagnosis algorithm to finally propose and analyse the most probable gene(s) in each case. Results: A review of the clinical data for our series of patients, and subsequent analysis of the candidate gene(s), allowed detection of the underlying molecular defect in 12 out of 23 patients: five patients harboured a mutation in PRKAR1A, one in PDE4D, four in TRPS1 and two in PTHLH. Conclusions: This study confirmed that the screening of other genes implicated in syndromes with BDE and AHO or a similar phenotype is very helpful for establishing a correct genetic diagnosis for those patients who have been misdiagnosed with "AHO-like phenotype" with an unknown genetic cause, and also for better describing the characteristic and differential features of these less common syndromes
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