Increased BDNF Levels in Long-term Bipolar Disorder Patients

IntroductionBipolar disorder (BD) is a prevalent, chronic and progressive illness. There is a growing body of evidence indicating that brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of BD.ObjectiveThe aim of this study was to evaluate BDNF plasma levels in BD patients with long term illness in comparison with controls.Methods87 BD type I patients and 58 controls matched by age, gender and education level were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatric Interview and the patients by the Young Mania Rating Scale and the Hamilton Depression Rating Scale. The plasma levels of BDNF were measured by ELISA.ResultsOn average, patients had suffered from BD for 23.4 years. In comparison with controls, BD patients with mania presented a 1.90-fold increase in BDNF plasma levels (p = .001), while BD patients in remission presented a 1.64-fold increase in BDNF plasma levels (p = .03). BDNF plasma levels were not influenced by age, length of illness or current medications.ConclusionsThe present study suggests that long-term BD patients exhibit increased circulating levels of BDNF.     

Effect of the association of infra-red and red wavelength photobiomodulation therapy on the healing of post-extraction sockets of third lower molars: a split-mouth randomized clinical trial

Lasers in Medical Science - The aim of this study was to evaluate the effect of photobiomodulation therapy (PBMT) with the association of red and infra-red laser therapy in the healing of the...     

Evaluation of Schistosomiasis Mansoni Morbidity by Hepatic and Splenic Elastography

In patients with Mansoni schistosomiasis, it is fundamental to evaluate the disease morbidity, which is reflected by the severity of periportal fibrosis (PPF) and parameters of portal hypertension, as analyzed by ultrasonography (US). This study aimed to evaluate the morbidity of schistosomiasis by hepatic and splenic point shear-wave elastography (pSWE) and relate this to US parameters. The PPF pattern, the diameter of the portal and splenic veins and the size of the spleen were evaluated by US. Then, liver and spleen pSWEs were assessed in 74 patients using the same equipment. As the PPF pattern progressed, the splenic pSWE values significantly increased. Significant correlations between splenic pSWE, the longitudinal and transverse lengths of the spleen and the diameters of the portal and splenic veins were observed. These findings, however, were not observed through hepatic pSWE. In conclusion, the splenic pSWE has the potential for assessing morbidity in schistosomiasis mansoni.     

Oral administration of antioxidants improves skin wound healing in diabetic mice

Oxidative stress aggravates several long‐term complications in diabetes mellitus. We evaluated the effectiveness of the oral administration of antioxidants (vitamins E and C, 40 and 100 mg/kg b.w., respectively) on skin wound healing acceleration in alloxan‐induced diabetic mice. Mice were wounded 30 days after the induction of diabetes. Antioxidants were effective in preventing oxidative stress, as assessed by TBARS. The enzymes catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase were increased in diabetics on the 3rd day post‐wounding; catalase and glutathione peroxidase remained still augmented in diabetics after 14th day postwounding, and the treatment with vitamins restored their activities to control. After 3 days, diabetic mice showed lower infiltration of inflammatory cells (including CD11b⁺ and Ly6G⁺ cells) and reduced levels of KC, TNF‐α, IL‐1β, and IL‐12 p40 when compared with control mice. The treatment restored cytokine levels. After 14 days, diabetic mice showed late wound closure, persistent inflammation and delayed reepithelialization, accompanied by an increase in MIG⁺/CD206^? macrophages whereas CD206⁺/MIG^? macrophages were decreased. Cytokines IL‐12p40, TNF‐α, IL‐1β, and KC were increased and normal levels were restored after treatment with antioxidants. These results suggest that oxidative stress plays a major role in diabetic wound healing impairment and the oral administration of antioxidants improves healing by modulating inflammation and the antioxidant system with no effect on glycemia.     

Genotoxic and cytotoxic effects of iron sulfate in cultured human lymphocytes treated in different phases of cell cycle.

Iron (Fe) is a common chemical element that is essential for organisms as a co-factor in oxygen transport, but that in high amounts presents a significant risk of neurodegenerative disorders. The objective of this study was to evaluate the mutagenic potential of iron sulfate. The comet assay and chromosome aberration (CA) analysis were applied to determine the DNA-damaging and clastogenic effects of iron sulfate. Human lymphocytes were treated in the quiescent phase for the comet assay and proliferative phase during the G1, G1/S, S (pulses of 1 and 6 h), and G2 phases of the cell cycle for CA analysis, with 1.25, 2.5 and 5 microg/mL concentrations of FeSO(4).7H2O. All tested concentrations were cytotoxic and reduced significantly the mitotic index (MI) in all phases of the cell cycle. They also induced CA in G1, G1/S and S (pulses of 1 and 6 h) phases. Iron sulfate also induced polyploidy in cells treated during G1. In the comet assay, this metal did not induce significant DNA damage. Our results show that Fe causes alteration and inhibition of DNA synthesis only in proliferative cells, which explain the concomitant occurrence of mutagenicity and cytotoxicity, respectively, in the lymphocytes studied.     

Pisosterol induces monocytic differentiation in HL-60 cells.

The aim of this study was to determine whether the antiproliferative effects observed for pisosterol, a cytotoxic triterpene isolated from Pisolithus tinctorius, are related to cell differentiation induction using HL-60 cell line as a model. Also, the effects of pisosterol on normal human cells were examined in peripheral blood mononuclear cells (PBMC). The effects on cell viability and morphological changes were the first indications showing that pisosterol induces HL-60 differentiation. The demonstration of blue tetrazolium reduction in HL-60 cells exposed to pisosterol demonstrated differentiation in a dose- and time-dependent manner, reaching a maximum effect after 72 h incubation at 5 microg/mL. Assays for alpha-naphthyl acetate esterase activity indicated that pisosterol triggers differentiation towards a monocytic cell-like pathway. The antiproliferative effect of pisosterol was determined by inhibition of DNA synthesis based on BrdU incorporation into HL-60 proliferating cells. It appears that pisosterol-treated cells, despite displaying a differentiated phenotype, continued to proliferate at all doses tested after 72 h, with a slightly decrease at 5 microg/mL. Apoptosis was observed in pisosterol-treated cells in a dose-dependent way. Nevertheless, after the same period of incubation, no cytotoxicity was detected in PBMC in the presence of pisosterol even at 25 microg/mL, providing some evidence that pisosterol may be selective for tumor cells. The mechanisms underlying the effect of pisosterol in leukemia cells indicates the induction of a monocytic cell-like differentiation, suggesting that this compound could be used in the development of new pharmacological tools with potential therapeutic value in the management of leukemia with fewer side effects.     

A multi-exonic SPG4 duplication underlies sex-dependent penetrance of hereditary spastic paraplegia in a large Brazilian pedigree

SPG4 mutations are the most frequent cause of autosomal-dominant hereditary spastic paraplegia (HSP). SPG4 HSP is characterized by large inter- and intrafamilial variability in age at onset (AAO) and disease severity. The broad spectrum of SPG4 mutations has recently been further extended by the finding of large genomic deletions in SPG4-linked pedigrees negative for 'small' mutations. We had previously reported a very large pedigree, linked to the SPG4 locus with many affected members, which showed gender difference in clinical manifestation. Screening for copy number aberrations revealed the first case of a multi-exonic duplication (exon10_12dup) in the SPG4 gene. The mutation leads to a premature stop codon, suggesting that the protein product is not functional. The analysis of 30 individuals who carry the mutation showed that males have on average an earlier AAO and are more severely affected. The present family suggests that this HSP pathogenesis may be modulated by factors related to individual background and gender as observed for other autosomal dominant conditions, such as facio-scapulohumeral muscular dystrophy or amyloidosis. Understanding why some individuals, particularly women, are 'partially protected' from the effects of this and other pathogenic mutations is of utmost importance.