Bruna Maria Ascoli

Group B Streptococcus detection: comparison of PCR assay and culture as a screening method for pregnant women

Streptococcus agalactiae or group B Streptococcus (GBS) is one of the most important causal agents of serious neonatal infections. Numerous assays have been evaluated for GBS screening in order to validate a fast and efficient method. The aim of this study was to compare the culture technique (established as the gold standard) with the molecular method of polymerase chain reaction (PCR) with specific primers (atr gene). Two hundred and sixty-three samples were analyzed. Vaginal samples were collected, according to the Centers for Disease Control and Prevention (CDC) recommendations, from women over 35 weeks of pregnancy at Hospital de Clínicas de Porto Alegre (HCPA). Two different extraction methods were tested in all samples collected. PCR technique yielded 71 (26.99%) positive results. Sensitivity and specificity for PCR were 100% and 86.88%, respectively. PCR demonstrated a shorter turnaround time than the culture. The molecular methodology proved to be a useful screening for GBS, allowing effective treatment to be initiated in shorter time to prevent newborn infection.

Germination and growth inhibitory effects of Hypericum myrianthum and H. polyanthemum extracts on Lactuca sativa L.

Germination and growth inhibitory effects of ethanolic crude extracts of Hypericum myrianthum and H. polyanthemum aerial parts on lettuce (Lactuca sativa) were investigated. The germination was retarded in all the tested concentrations. After seven days the final germination percentage of the most concentrated extracts was significantly reduced by both extracts in comparison with the control. The radicles length was significantly affected showing necrosis. Both species present phenolic compounds as the main components and they could be responsible for the inhibition of the germination and growth of Lactuca sativa.

Serum magnesium and proton-pump inhibitors use: a cross-sectional study

OBJECTIVE The aim of this study was to evaluate the association of serum magnesium levels with proton pump inhibitors (PPIs) use and other factors. METHODS This was a cross-sectional study of 151 patients admitted with acute diseases in the Internal Medicine Division of the Hospital de Clinicas de Porto Alegre, after the exclusion of conditions that are commonly associated with hypomagnesemia: diarrhea; vomiting; chronic alcohol use; severely uncompensated diabetes mellitus; and chronic use of laxatives, diuretics or other drugs causing magnesium deficiency. RESULTS All patients had normal serum magnesium levels. Serum albumin and creatinine levels were positively associated with serum magnesium levels, after adjusting for confounders. There was no difference between mean serum magnesium levels of PPI users and non-users, nor between men and women; there was also no correlation among age, serum phosphorus, and potassium levels with serum magnesium levels. Limitations of this study include the absence of an instrument for measuring adherence to PPI use and the sample size. CONCLUSION The association of PPI use and hypomagnesemia is uncommon. Congenital defects in the metabolism of magnesium may be responsible for hypomagnesemia in some patients using this drug class.

Progesterone and its metabolites as therapeutic targets in psychiatric disorders

Introduction: Neurosteroids are molecules that regulate physiological functions of the CNS. There is increasing evidence suggesting that impaired neurosteroid biosynthesis has been associated with distinct psychiatric disorders. This review summarizes data from studies that have investigated the relationship between progesterone (PROG) and psychiatric disorders as well as the mechanisms potentially involved in PROG-induced neuroprotection. Areas covered: The review covers the role of PROG and its metabolites in psychiatric disorders, focusing on results from preclinical and some clinical studies that support the relationship between alterations on PROG levels and pathophysiology of psychiatric illness. We also discussed the main mechanisms underlying the neuroprotective effects of PROG metabolites. Expert opinion: Our review points out the possible relationship between PROG and its metabolites and the pathophysiology of psychiatric disorders. Furthermore, both preclinical and clinical studies show that certain treatments (antidepressants or antipsychotics) may normalize the levels of PROG, suggesting that the amelioration of psychiatric symptoms may occur due to upregulation of PROG metabolites. Therefore, these results give support to new possibilities of treatment for patients with psychiatric symptoms from anxiety- and depressive-like behaviors to aggressive behaviors.

Evaluation of cytokines, oxidative stress markers and brain-derived neurotrophic factor in patients with fibromyalgia - A controlled cross-sectional study.

OBJECTIVES Previous studies measuring serum levels of biomarkers of inflammation/oxidative stress and neurotrophins levels in fibromyalgia (FM) have rendered inconsistent results. In the present study, our aim was to explore the levels of interleukins, oxidative stress markers and brain-derived neurotrophic factor (BDNF) in patients with FM in relation to depression and severity of disease. METHODS In a prospective controlled cross-sectional study, serum concentrations of IL-6, IL-8, IL-10, TNF-α, thiobarbituric acid reactive substances (TBARS), protein carbonyl and BDNF were measured in 69 FM patients and 61 healthy controls (all women). In the FM group, the Fibromyalgia Impact Questionnaire (FIQ), the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HDRS) were applied. Mann Whitneys and Spearman correlation tests were used for statistical analysis. RESULTS The FM patients demonstrated a significant impact of the disease on quality of life (FIQ 70.2±17.8) and most of them had depression at some level (82.6% and 87.0% as assessed by BDI and HDRS, respectively). Most biomarkers (IL-6, IL-8, TNF-α, TBARS and protein carbonyl) and BDNF did not differ significantly between patients and controls, but the IL-10 levels were higher in FM patients (adjusted p=0.041). Among FM patients, there was no correlation of HDRS, FIQ, and BDI scores with any biomarker tested here. CONCLUSION We observed no significant differences in biomarkers between FM patients and controls, except for higher levels of IL-10 (an anti-inflammatory cytokine) in patients. The levels of biomarkers were not correlated with parameters of disease and depression severity.

The role of macrophage polarization on bipolar disorder: Identifying new therapeutic targets

Objective: Bipolar disorder is a chronic, severe and disabling disease; however, its pathophysiology remains poorly understood. Recent evidence has suggested that inflammation and immune dysregulation play a significant role in the pathophysiology of bipolar disorder. This review is aimed to highlight the importance of systemic inflammation in modulating the inflammatory response of microglia and hence its potential involvement with bipolar disorder. We also discuss novel therapeutic strategies that emerge from this new research. Method: This article presents a theoretical synthesis of the effects of systemic inflammation on the immune response of the central nervous system in bipolar disorder. The complex relationship between stress, pro-inflammatory cytokines and microglial dysfunction is summarized, emphasizing the role of the kynurenine pathway in this process and, consequently, their effects on neuronal plasticity. Results: Bipolar patients demonstrate increased serum levels of pro-inflammatory cytokines (interleukin-1β, interleukin-6 and tumor necrosis factor-α) and lower hypothalamic–pituitary–adrenal axis sensitivity. This imbalance in the immune system promotes a change in blood–brain barrier permeability, leading to an inflammatory signal spread in the central nervous system from the periphery, through macrophages activation (M1 polarization). Chronic microglial activation can result in neuronal apoptosis, neurogenesis inhibition, hippocampal volume reduction, lower neurotransmitters synthesis and cytotoxicity, by increasing glutamate production and kynurenine metabolism. Conclusions: This review provides an overview of the mechanisms involved in the immune system imbalance and its potential involvement in the pathophysiology of bipolar disorder. Consequently, new strategies that normalize the immune-inflammatory pathways may provide a valuable therapeutic target for the treatment of these disorders.

Mesenchymal stem cells for the treatment of neurodegenerative and psychiatric disorders

Mesenchymal stem cells (MSCs) are multipotent progenitor cells that have the capacity to differentiate into all lineages of mesodermal origin, e.g., cartilage, bone, and adipocytes. MSCs have been identified at different stages of development, including adulthood, and in different tissues, such as bone marrow, adipose tissue and umbilical cord. Recent studies have shown that MSCs have the ability to migrate to injured sites. In this regard, an important characteristic of MSCs is their immunomodulatory and anti-inflammatory effects. For instance, there is evidence that MSCs can regulate the immune system by inhibiting proliferation of T and B cells. Clinical interest in the use of MSCs has increased considerably over the past few years, especially because of the ideal characteristics of these cells for regenerative medicine. Therapies with MSCs have shown promising results neurodegenerative diseases, in addition to regulating inflammation, they can promote other beneficial effects, such as neuronal growth, decrease free radicals, and reduce apoptosis. Notwithstanding, despite the vast amount of research into MSCs in neurodegenerative diseases, the mechanism of action of MSCs are still not completely clarified, hindering the development of effective treatments. Conversely, studies in models of psychiatric disorders are scarce, despite the promising results of MSCs therapies in this field as well.

Depression and Mania Induce Pro-inflammatory Activation of Macrophages Following Application of Serum from Individuals with Bipolar Disorder

Objective Evidence has suggested that immune imbalance is involved with bipolar disorder (BD); however, its precise mechanism is poorly understood. This study investigated whether biochemical changes in the serum from BD patients could modulate the phenotype of cultured macrophages. Methods Eighteen subjects with BD and five healthy individuals were included in this study. The human monocyte cell line U-937 was activated with phorbol 12-myristate 13-acetate (PMA) and polarization was induced with RPMI-1640 media supplemented with 10% serum from each patient for 24 hours. Gene expression of selected M1 and M2 markers was assessed by quantitative PCR. Results Macrophages exposed to serum of manic and depressive BD patients displayed an increase of interleukin-1β (6.40±3.47 and 9.04±5.84 vs. 0.23±0.11; p<0.05) and tumor necrosis factor-α (2.23±0.91 and 2.03±0.45 vs. 0.62±0.24; p=0.002 and p=0.004, respectively) compared to euthymic group (there was no difference between euthymic and controls). In parallel, U-937 macrophages treated with serum of patients in acute episode displayed a down-regulation of CXCL9 (0.29±0.20 vs. 1.86±1.61; p=0.006) and CXCL10 expression (0.36±0.15 and 0.86±0.24 vs. 1.83±0.88; p<0.000 and p=0.04) compared to the euthymia group. Conclusion Our results are consistent with previous studies showing that changes in peripheral blood markers could modulate M1/M2 polarization in BD. The evidence of macrophages as source of inflammatory cytokines might be helpful to unravel how the mononuclear phagocyte system is involved in the etiology of BD.

Social instigation and repeated aggressive confrontations in male Swiss mice: analysis of plasma corticosterone, CRF and BDNF levels in limbic brain areas

Introduction: Agonistic behaviors help to ensure survival, provide advantage in competition, and communicate social status. The resident-intruder paradigm, an animal model based on male intraspecific confrontations, can be an ethologically relevant tool to investigate the neurobiology of aggressive behavior. Objectives: To examine behavioral and neurobiological mechanisms of aggressive behavior in male Swiss mice exposed to repeated confrontations in the resident intruder paradigm. Methods: Behavioral analysis was performed in association with measurements of plasma corticosterone of mice repeatedly exposed to a potential rival nearby, but inaccessible (social instigation), or to 10 sessions of social instigation followed by direct aggressive encounters. Moreover, corticotropin-releasing factor (CRF) and brain-derived neurotrophic factor (BNDF) were measured in the brain of these animals. Control mice were exposed to neither social instigation nor aggressive confrontations. Results: Mice exposed to aggressive confrontations exhibited a similar pattern of species-typical aggressive and non-aggressive behaviors on the first and the last session. Moreover, in contrast to social instigation only, repeated aggressive confrontations promoted an increase in plasma corticosterone. After 10 aggressive confrontation sessions, mice presented a non-significant trend toward reducing hippocampal levels of CRF, which inversely correlated with plasma corticosterone levels. Conversely, repeated sessions of social instigation or aggressive confrontation did not alter BDNF concentrations at the prefrontal cortex and hippocampus. Conclusion: Exposure to repeated episodes of aggressive encounters did not promote habituation over time. Additionally, CRF seems to be involved in physiological responses to social stressors.

Cell therapy in the treatment of bipolar mania in an animal model: a proof of concept study

INTRODUCTION The rationale of mesenchymal stem cells (MSCs) as a novel therapeutic approach in certain neurodegenerative diseases is based on their ability to promote neurogenesis. Hippocampal atrophy has been related to bipolar disorder (BD) in preclinical, imaging and postmortem studies. Therefore, the development of new strategies to stimulate the neurogenesis process in BD is crucial. OBJECTIVES To investigate the behavioral and neurochemical changes induced by transplantation of MSCs in a model of mania-like behavior induced by lisdexamfetamine dimesylate (LDX). METHODS Wistar rats (n=65) received one oral daily dose of LDX (10 mg/kg) or saline for 14 days. On the 8th day of treatment, the animals additionally received intrahippocampal saline or MSC (1 µL containing 25,000 cells) or lithium (47.5 mg/kg) as an internal experimental control. Two hours after the last administration, behavioral and neurochemical analyses were performed. RESULTS LDX-treated rats had increased locomotor activity compared to saline-saline rats (p=0.004), and lithium reversed LDX-related hyperactive behavior (p<0.001). In contrast, the administration of MSCs did not change hyperlocomotion, indicating no effects of this treatment on LDX-treated rats (p=0.979). We did not find differences between groups in BDNF levels (p>0.05) in the hippocampus of rats. CONCLUSION Even though these results suggest that a single intrahippocampal injection of MSCs was not helpful to treat hyperactivity induced by LDX and neither influenced BDNF secretion, we cannot rule out the possible therapeutic effects of MSCs. Further research is required to determine direct effects of LDX on brain structures as well as in other pathophysiological targets related to BD.