Effectiveness of a new rutin Cu(II) complex in the prevention of lipid peroxidation and hepatotoxicity in hypercholesterolemic rats.

A new rutin copper(II) complex (R-Cu2) was prepared and characterized by spectroscopic methods and elemental analysis. The effects of rutin and R-Cu2 were evaluated on the prevention of hypercholesterolemia in animals feed with high-cholesterol diet (HCD) for 8 weeks. The animals (n = 5) were neither fed with HCD nor treated (control group), or were treated with vehicle, 10 mg/kg simvastatin, rutin (16 and 160 µmol/kg), and R-Cu2 (16 and 160 µmol/kg) administered orally. Total cholesterol (TC) levels were significantly increased (p < .01) in all HCD groups. In rutin and R-Cu2 groups, it was observed a discrete, but not significant, TC and LDL-induced increase inhibition compared with vehicle-treated group. R-Cu2 treatment significantly decreased (p < .05) plasma triglycerides compared with the vehicle-treated group. All groups receiving treatments maintained the malondialdehyde at normal levels. Serum NO levels were reduced in animals treated with rutin and R-Cu2 compared with the vehicle-treated group. In addition, the results also showed that the groups treated with rutin and R-Cu2 reduced significantly (p < .01), the number of neutrophils and prevented histological changes in all evaluated liver zones. R-Cu2 group maintained the ALT, AST, and ALP enzymes at normal levels. Thus, the effects of R-Cu2 in modulating inflammation and protecting liver damage were confirmed. PRACTICAL APPLICATIONS: Rutin, a plant-derived flavonoid, is one of phenolic compounds well known as a nutraceutical due to its antioxidant and anti-inflammatory properties. Findings of this study demonstrate the effects of both rutin and R-Cu2 in modulating inflammation and protecting liver damage in hypercholesterolemic rats. However, some effects analyzed became more evident in R-Cu2. Thereby, it was shown that the synthesis of a new flavonoid compound (R-Cu2) could be applied as a nutraceutical benefit option to prevent hypercholesterolemia condition.

Clinical randomized trial study of hearing aids effectiveness in association with Ginkgo biloba extract (EGb 761) on tinnitus improvement / Estudo clínico randomizado da eficácia da prótese auditiva associada ao extrato de Ginkgo biloba (EGb 761) na melhoria do zumbido

Abstract Introduction: Tinnitus is defined as the perception of sound without its actual presence in the environment. It has been the subject of a great number of studies, especially considering its consequences on patient's quality of life. Objective: This study aimed to investigate the effect of hearing aids and/or Ginkgo biloba extract EGb 761 on tinnitus in patients with hearing loss. Methods: This is a trial randomized-controlled treatment, parallel, double-blind, with three-arm. Thirty-three adults subjects were divided into three groups: group 1 — subjects undergoing drug therapy with Ginkgo biloba extract EGb 761; group 2 — individuals fitted with digital hearing aids; group 3 — individuals submitted to drug therapy with Ginkgo biloba extract EGb 761 and using hearing aids. The tinnitus handicap inventory and visual analogue scale were used to evaluate self-perception of tinnitus loudness and severity before treatment and 90 days after treatment. Results: This study demonstrated a significant correlation between tinnitus handicap inventory and visual analogue scale, before and after treatment. We observed a significant improvement in self-perception of tinnitus loudness and severity after 90 days of treatment with Ginkgo biloba extract EGb 761 and/or hearing aids. No correlation was found between tinnitus onset time and self-perception of tinnitus loudness and severity. Hearing aids were more effective in patients with a shorter tinnitus onset time and Ginkgo biloba extract was effective regardless of tinnitus duration. Conclusions: It was possible to prove the effectiveness of the hearing aids and/or Ginkgo biloba extract EGb 761 treatment, which shows success in the control of tinnitus contributing to the improvement of this symptom.

Resumo Introdução: O zumbido é definido como a percepção de um som sem a sua presença real no ambiente e tem sido objeto de um grande número de estudos, especialmente devido às suas consequências na qualidade de vida do paciente. Objetivo: Investigar o efeito de próteses auditivas e/ou extrato de Ginkgo biloba EGb 761 sobre o zumbido em pacientes com perda auditiva. Método: Ensaio clínico randomizado controlado, paralelo, duplo-cego, com três braços. Trinta e três indivíduos adultos foram divididos em três grupos: Grupo 1 - indivíduos submetidos à terapia medicamentosa com extrato de Ginkgo biloba EGb 761; Grupo 2 - indivíduos equipados com próteses auditivas digitais; Grupo 3 - indivíduos submetidos à terapia medicamentosa com extrato de Ginkgo biloba EGb 761 e próteses auditivas. O Tinnitus handicap inventory e a escala visual analógica foram usados para avaliar a autopercepção de intensidade e da gravidade do zumbido antes do tratamento e 90 dias após o tratamento. Resultados: Este estudo demonstrou uma correlação significante entre o Tinnitus handicap inventory e a escala visual analógica, antes e após o tratamento. Observou-se melhoria significativa na autopercepção de loudness e da intensidade do zumbido após 90 dias de tratamento com extrato de Ginkgo biloba EGb 761 e/ou prótese auditiva. Não foi encontrada correlação entre o tempo de início do zumbido e a autopercepção da intensidade e gravidade do zumbido. As próteses auditivas foram mais eficazes em pacientes com menor tempo de início de zumbido e o extrato de Ginkgo biloba foi eficaz, independentemente da duração do zumbido. Conclusões: Foi possível comprovar a eficácia do tratamento com a prótese auditiva e/ou extrato de Ginkgo biloba EGb 761, o que demonstra sucesso no controle do zumbido e contribui para a melhoria desse sintoma.

Clinical randomized trial study of hearing aids effectiveness in association with Ginkgo biloba extract (EGb 761) on tinnitus improvement.

INTRODUCTION: Tinnitus is defined as the perception of sound without its actual presence in the environment. It has been the subject of a great number of studies, especially considering its consequences on patient's quality of life. OBJECTIVE: This study aimed to investigate the effect of hearing aids and/or Ginkgo biloba extract EGb 761 on tinnitus in patients with hearing loss. METHODS: This is a trial randomized-controlled treatment, parallel, double-blind, with three-arm. Thirty-three adults subjects were divided into three groups: group 1 - subjects undergoing drug therapy with Ginkgo biloba extract EGb 761; group 2 - individuals fitted with digital hearing aids; group 3 - individuals submitted to drug therapy with Ginkgo biloba extract EGb 761 and using hearing aids. The tinnitus handicap inventory and visual analogue scale were used to evaluate self-perception of tinnitus loudness and severity before treatment and 90 days after treatment. RESULTS: This study demonstrated a significant correlation between tinnitus handicap inventory and visual analogue scale, before and after treatment. We observed a significant improvement in self-perception of tinnitus loudness and severity after 90 days of treatment with Ginkgo biloba extract EGb 761 and/or hearing aids. No correlation was found between tinnitus onset time and self-perception of tinnitus loudness and severity. Hearing aids were more effective in patients with a shorter tinnitus onset time and Ginkgo biloba extract was effective regardless of tinnitus duration. CONCLUSIONS: It was possible to prove the effectiveness of the hearing aids and/or Ginkgo biloba extract EGb 761 treatment, which shows success in the control of tinnitus contributing to the improvement of this symptom.

Evaluation of the anti-inflammatory action of curcumin analog (DM1): Effect on iNOS and COX-2 gene expression and autophagy pathways.

This work describes the anti-inflammatory effect of the curcumin-analog compound, sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate (DM1), and shows that DM1 modulates iNOS and COX-2 gene expression in cultured RAW 264.7 cells and induces autophagy on human melanoma cell line A375.

Tissue-specific expression of IL-15RA alternative splicing transcripts and its regulation by DNA methylation.

The human IL-15RA gene encoding the alpha chain of the IL-15 receptor is expressed in a variety of immune and non-immune cell types from different tissues, and generates multiple splicing events of functional importance. We aimed to evaluate expression of IL-15RA transcripts generated by alternative usage of transcription start site (Var1 and Var2) and by deletion of exon 3 (Del3), exon 2 (Del2), or both (Del2,3) in different human tissues. Since a CpG island was found near to the IL-15RA gene transcription start site, we also investigated the role of DNA methylation on the expression of IL-15RA full-length and alternative transcripts fragments in peripheral blood mononuclear cells (PBMC). IL-15RA transcription of functional (full-length and del 3) and non-functional (del 2 and del 2,3) variants was detected in many tissues, however, the number of different IL-15RA transcripts variants detected in each tissue did not correlate with the level of gene expression. IL-15RA transcript variants Var1 and Var2 presented similar expression levels in different human tissues. However, we found a distinct expression profile of functional and non-functional IL-15RA transcripts fragments. A preferential expression of transcripts that bind IL-15 compared to IL-15 non-binding transcripts was seen in the tissues investigated. When PBMC cultures were treated with 5-azacitidine (AZA), a DNA methyltransferase inhibitor, we detected a significant increase in IL-15RA copy number. Only alternative exon skipping events of Var1 (Del 2, Del 3 and Del 2, 3) were altered by AZA treatment, which is consistent with the CpG island localization in the regulatory region 5' upstream of the transcription start site of Var1 and not of Var2. Therefore, this work shows a broad expression pattern of functional IL-15RA splicing forms and suggests a regulatory role of DNA methylation in IL-15RA transcript Var1 expression in mononuclear cells.

Expression in bacteria of the gene encoding the gp43 antigen of paracoccidioides brasiliensis: immunological reactivity of the recombinant fusion proteins.

gp43 is the major diagnostic antigen of Paracoccidioides brasiliensis, the agent of paracoccidioidomycosis (PCM) in humans. In the present study, cDNA of the gp43 gene (PbGP43) was obtained by reverse transcriptase PCR, inserted into a pGEX vector in frame with the glutathione S-transferase (GST) gene, and expressed in Escherichia coli as inclusion bodies. Immunoblotting showed that all sera from patients with chronic pulmonary and acute lymphatic forms of PCM reacted with the recombinant fusion protein of the mature gp43 (381 amino acids). Reactivity with fusion proteins containing subfragments of the N-terminal, internal, or C-terminal regions occurred eventually, and the C-terminal region was the most antigenic. Lack of reactivity with the subfragments may be due to the conformational nature of the gp43 epitopes. Sera from patients with aspergillosis, candidiasis, and histoplasmosis did not react with the gp43-GST fusion protein. Our results suggest that recombinant gp43 corresponding to the processed antigen can be a useful tool in the diagnosis of PCM.