The influence of age, sex and education on the phenomenology of depressive symptoms in a population-based sample aged 75+ years with major depression: the Pietà Study.

OBJECTIVES: Late-life depression (LLD) is the most common mental disorder among the elderly, but its clinical features remain unclear, especially among older adults. We sought to investigate if age, sex and education could influence the severity or frequency of LLD symptoms. METHODS: We evaluated 639 community-dwelling individuals aged 75+ years in Caeté (MG), Brazil. We used the Mini International Neuropsychiatric Interview to diagnose major depression according to DSM-IV criteria and the GDS-15 to measure depression severity. RESULTS: Excluding 174 individuals diagnosed with dementia, 54 (11.6%) of the remaining 457 individuals were diagnosed with LLD; 77.8% of which were female. On average, these participants were aged 81.0 ± 4.8 years and had 2.7 ± 3.3 years of schooling. Symptom severity was not influenced by sociodemographic variables. Death/suicidal ideation was more frequent among men, while psychomotor disturbance was more present in women (p = 0.04 and p = 0.042). More educated individuals (≥ 4 years) also reported a higher frequency of psychomotor disturbance (p = 0.039). CONCLUSIONS: Severity of depressive episode was not influenced by sociodemographic variables. Sex and educational level had a significant impact on symptom profiles.

iNOS Activity Modulates Inflammation, Angiogenesis, and Tissue Fibrosis in Polyether-Polyurethane Synthetic Implants.

There is considerable interest in implantation techniques and scaffolds for tissue engineering and, for safety and biocompatibility reasons, inflammation, angiogenesis, and fibrosis need to be determined. The contribution of inducible nitric oxide synthase (iNOS) in the regulation of the foreign body reaction induced by subcutaneous implantation of a synthetic matrix was never investigated. Here, we examined the role of iNOS in angiogenesis, inflammation, and collagen deposition induced by polyether-polyurethane synthetic implants, using mice with targeted disruption of the iNOS gene (iNOS(-/-)) and wild-type (WT) mice. The hemoglobin content and number of vessels were decreased in the implants of iNOS(-/-) mice compared to WT mice 14 days after implantation. VEGF levels were also reduced in the implants of iNOS(-/-) mice. In contrast, the iNOS(-/-) implants exhibited an increased neutrophil and macrophage infiltration. However, no alterations were observed in levels of CXCL1 and CCL2, chemokines related to neutrophil and macrophage migration, respectively. Furthermore, the implants of iNOS(-/-) mice showed boosted collagen deposition. These data suggest that iNOS activity controls inflammation, angiogenesis, and fibrogenesis in polyether-polyurethane synthetic implants and that lack of iNOS expression increases foreign body reaction to implants in mice.

Cholinesterase inhibitors modulate autonomic function in patients with Alzheimer´s disease and mixed dementia.

Cholinesterase inhibitors (ChEIs), the mainstay treatment for dementia, have systemic actions that can affect cardiovascular and autonomic nervous system (ANS). Thirty-nine patients with Alzheimer´s disease or mixed dementia underwent a comprehensive clinical evaluation, prior to and during ChEIs therapy, including orthostatic challenge, electrocardiogram (EKG) and heart rate variability (HRV) spectral analysis through Holter recordings. ChEIs therapy determined a decrease in supine diastolic blood pressure (BP) and in both diastolic and systolic BP in orthostatic position (79.8 ± 9.0 vs. 76.4 ± 9.3 mmHg, p=0.012; 79.9 ± 11.6 vs. 75.3 ± 9.9, p=0.005 and 144.6 ± 25.8 vs. 137.6 ± 21.1, p=0.020, respectively). Spectral analysis revealed no difference on static HRV components, but, during orthostatic challenge, an increase in LF/HF ratio (2.2±2.4 vs. 4.6±5.9, p=0.011) and a reduction in HF component emerged (1604.3 ± 5610.1 vs. 266.1 ± 525.5, p=0.010). ChEIs showed no influence on EKG parameters or on the occurrence of orthostatic hypotension. Treatment with ChEIs was associated with functional improvement of the ANS behavior and to a decrease in supine DBP and in both orthostatic SBP and DBP.

Renin-angiotensin system in the pathogenesis of liver fibrosis.

Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of homeostatic mechanisms that maintain the liver ecosystem. In spite of many studies regarding the development of fibrosis, the understanding of the pathogenesis remains obscure. The hepatic tissue remodeling process is highly complex, resulting from the balance between collagen degradation and synthesis. Among the many mediators that take part in this process, the components of the Renin angiotensin system (RAS) have progressively assumed an important role. Angiotensin (Ang) II acts as a profibrotic mediator and Ang-(1-7), the newly recognized RAS component, appears to exert a counter-regulatory role in liver tissue. We briefly review the liver fibrosis process and current aspects of the RAS. This review also aims to discuss some experimental evidence regarding the participation of RAS mediators in the pathogenesis of liver fibrosis, focusing on the putative role of the ACE2-Ang-(1-7)-Mas receptor axis.

The renin-angiotensin system in a rat model of hepatic fibrosis: evidence for a protective role of Angiotensin-(1-7).

BACKGROUND/AIMS: The circulating renin-angiotensin system (RAS) [plasma renin activity (PRA), Angiotensin (Ang) I, Ang II and Ang-(1-7)] was evaluated in a model of hepatic fibrosis in rats. To investigate the pathophysiological involvement of Ang-(1-7), animals were treated with the Ang-(1-7) Mas receptor antagonist, A-779. METHODS: RAS components, liver function and histology were examined in male Wistar rats (220-300 g). Animals were submitted to sham-surgery or ligature of the bile duct and evaluated 1, 2, 4 and 6 weeks later. Blood samples were obtained to determine biochemical parameters and RAS components. A second group was treated with A-779 or vehicle to measure liver hydroxyproline and total transforming growth factor beta-1 (TGFbeta1). RESULTS: PRA and Ang I were significantly elevated in rats at 4 and 6 weeks compared to sham-operated animals. Ang II and Ang-(1-7) progressively increased over the 6 weeks. Changes in RAS profile correlated with histological signs of fibrosis and deterioration in liver function. Pharmacological blockade of the Ang-(1-7) receptor aggravated liver fibrosis with a significant elevation in hydroxyproline and total TGFbeta(1). CONCLUSIONS: Hepatic fibrosis was associated with RAS activation in our model. Our data also suggested that Ang-(1-7) played a protective role in hepatic fibrosis.