Global slowing of network oscillations in mouse neocortex by diazepam

SCHEFFZUK, C. , KUKUSHKA, V. , VYSSOTSKI, A. L. , DRAGUHN, A. , TORT, A. B. L. , BRANKACK, J. . Global slowing of network oscillations in mouse neocortex by diazepam. Neuropharmacology , v. 65, p. 123-133, 2013.

Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

Amphotericin B (AmB), an antifungal agent that presents a broad spectrum of activity, remains the gold standard in the antifungal therapy. However, sometimes the high level of toxicity forbids its clinical use. The aim of this work was to evaluate and compare the efficacy and toxicity in vitro of Fungizon™ (AmB-D) and two new different AmB formulations. Methods: three products were studied: Fungizon™, and two Fungizon™ /Lipofundin™ admixtures, which were diluted through two methods: in the first one, Fungizon™ was previously diluted with water for injection and then, in Lipofundin™ (AmB-DAL); the second method consisted of a primary dilution of AmB-D as a powder in the referred emulsion (AmB-DL). For the in vitro assay, two cell models were used: Red Blood Cells (RBC) from human donors and Candida tropicallis (Ct). The in vitro evaluation (K+ leakage, hemoglobin leakage and cell survival rate-CSR) was performed at four AmB concentrations (from 50 to 0.05mg.L-1). Results: The results showed that the action of AmB was not only concentration dependent, but also cellular type and vehicle kind dependent. At AmB concentrations of 50 mg.L-1, although the hemoglobin leakage for AmB-D was almost complete (99.51), for AmB-DAL and AmB-DL this value tended to zero. The p = 0.000 showed that AmB-D was significantly more hemolytic. Conclusion: The Fungizon™- Lipofundin™ admixtures seem to be the more valuable AmB carrier systems due to their best therapeutic index presented

Ensaio clínico duplo-cego controlado e randômico, comparando a eficácia da Clofazimina com a Cloroquina, no tratamento das lesões cutâneas do Lúpus Eritematoso Sistêmico

PURPOSE: To evaluate the capacity of clofazimine (CFZ) to control cutaneous activity of systemic lupus erythematosus (SLE), compared with chloroquine diphosphate (CDP). METHODS: A prospective, randomized, controlled, double blind clinical trial was carried out in thirty-three patients with SLE and cutaneous lesions (malar rash and/or discoid lupus and/or subacute cutaneous lupus), after approval by the respective Ethics Committee. Sixteen patients received clofazimine - 100mg/day (CFZ group) and 17 received chloroquine diphosphate - 250mg/day (CDP group), during six months. Both groups applied broad-spectrum sunscreens twice a day. The dose of prednisone was kept stable during the study. Cutaneous lesions were evaluated by 2 blinded observers and photographed at baseline and at months 1, 2, 4 and 6. RESULTS: Thirty-three patients began and 27 completed the 6 months of treatment. The groups were homogeneous and comparable in terms of demographic and clinical characteristics. Five CFZ-patients and one CDP-patients dropped out due to severe flare of disease requiring other treatment. At the end of the study, 12 CFZ-patients (75%) and 14 CDP-patients (82,4%) presented complete or near-complete remission of skin lesions; intention-to-treat analysis showed no significant difference in the response rates between groups. Side effects in both groups were frequent, but patients didn t have to discontinue the drugs. CONCLUSIONS: Clofazimine and chloroquine were effective in controlling cutaneous lesions in SLE patients

Desenvolvimento de emulsões o/a contendo extrato glicólico de açai e avaliação da atividade fotoprotetora

Sunscreen use is the most common photoprotection alternative used by the population, and so these products should offer improved protection with broad - spectrum, UVA and UVB protection . Vegetal substances have recently been considered as resources for sunscreen formulations due to their UV spectrum absorption and antioxidant properties. The Euterpe oleracea Mart., popularly known as açai, in its che mical composition contain polyphenols compounds, such as anthocyanins and flavonoids , to which antioxidant properties have been attributed . The aim of this work was to develop O/W sunscreens emulsions con taining açai glycolic extract ( AGE) and to evaluate both their physical stability , safety and photoprotective efficacy. The safety of the extract was evaluated by in vitro phototoxicity and cytotoxicity tests. Emulsions containing AGE and sunscreens were formulated using different types and concentrations o f polymeric surfactant (Acrylates/C 10 - 30 Alkyl Acrylate Crosspolymer and Sodium Polyacrylate). The influence of two rheology modifiers (Polyacrylamide (and) C13 - 14/Isoparaffin (and) Laureth - 7 and Carbomer) on the stability was also investigated. Physical stability was evaluated by preliminary and accelerated studies. The macroscopic analyses, pH value and electrical conductivity determinations and rheological behavior were evaluated at different time intervals . The in vivo Sun Protect Factor ( SPF ) was determined according to the International Sun Protection Factor Test Method – 2006 and UVA Protection Factor (FPUVA), wavelength critical and reason SPF/FPUVA were performed according to the method Colipa 2011. The extract did not present cytotoxic ity and phototoxic ity . The stable emulsion containing 5% glycolic extract of açai and 1.0% of sodium poliyacrylate showed pseudoplastic and thixotropic behavior . The sunscreen emulsion containing açai glycolic extract showed a SPF 25.3 and PF - UVA = 14.97. Whe n açai glycolic extract was added in the emulsion sunscreen, no significant increase in the in vivo SPF and FPUVA values were observed. This emulsion showed 1.69 of the SPF/PF - UVA ratio and a critical wavelength value of 378 nm, so may therefore be conside red a sunscreen with UVA and UVB protection.

Determinantes genéticos e ambientais das doenças hipertensivas da gravidez

The development of complex diseases such as preeclampsia are determined by both environmental and genetic factors, but there is also interaction among these factors. Preeclampsia is a pregnancy-specific disorder characterized by de-novo hypertension and proteinuria after 20th week of gestation. There is a broad spectrum of clinical presentations related to hypertensive disorders of pregnancy (HDP) that can range from mild preeclampsia to eclampsia (seizures) or HELLP syndrome (Hemolysis, Elevation of Liver enzymes, Low Platelets). Those clinical outcomes might be linked to different pathological mechanisms. Our work aims to identify factors (i.e. genes and environmental) associated with the HDP’s clinical spectrum. Using a case-control approach, we selected a total of 1498 pregnant women for epidemiological and genetic studies, encompassing 755 normotensive (control); 518 preeclampsia; 84 eclampsia; and 141 HELLP. Women were genotyped for 18 SNPs across 5 candidate genes (FLT1, ACVR2A, ERAP1, ERAP2 and LNPEP). For the environmental factors, we found maternal age, parity status and pre-gestational body mass index as important risk factors associated with disease. Genes were associated in a phenotype-specific manner: ACVR2A with early preeclampsia (rs1424954, p=0.002); FLT1 with HELLP syndrome (rs9513095, p=0.003); and ERAP1 with eclampsia (rs30187, p=0.03). Our results suggest that different genetic mechanisms along with specific environmental factors might determine the clinical spectrum of HDP. In addition, phenotype refinement seems to be an essential step in the search for complex disease genes

Avaliação funcional e estrutural de um novo peptídeo antimicrobiano do escorpião Tityus stigmurus

In Brazil, there is a high incidence of venomous animals. Among them, scorpions are highlighted by their medical importance, and for being their venom a source of several molecules with biological and pharmacological activity not yet fully understood, including several bioactive peptides. Antimicrobial peptides (AMPs) are components of the immune system in prokaryotes and eukaryotes, used in the first line of defense against microorganisms. In the present study, we characterized the first PAM previously identified through transcriptome of the venom gland of the scorpion Tityus stigmurus, named Stigmurin. The characteristics of Stigmurin were investigated by computational modeling and construction of dendrogram. In vitro tests investigated the antibacterial, antifungal, haemolytic and cytotoxic effects of crude venom and Stigmurin. In addition, the structural characteristics of Stigmurin were investigated by circular dochroism in water, 2, 2 , 2- trifluoethanol (TFE) and sodium dodecyl sulfate (SDS) and the models were refined by molecular dynamics simulations. The results showed that the selected sequence encodes a mature protein of 17 amino acid residues and the dendrogram reveals a case of convergent evolution. The crude venom showed no antimicrobial activity, however, Stigmurin exhibited a broad spectrum of antibacterial activity, with minimal inhibitory concentrations (MIC) ranging from 31.25 and 250 µg/mL for different strains, while the hemolytic activity at these concentrations was low. In cytotoxicity studies, the crude venom was unable to reduce cell viability in VERO E6 cells; in contrast, its activity in SiHa cells was significantly higher, corresponding to IC50 of 3.6 µg/mL. For Stigmurin the concentration sable to decrease cell viability of Vero E6 and SiHa cells in 50% were 275.67 µg/mL and 212.54 µg/mL, respectively. The dichroism spectra revealed the conformational flexibility, with predominating extended and β–sheet structures, as well as a remark able renaturation ability. The results suggest that Stigmurin could be considered as a potential antiinfective drug

Global slowing of network oscillations in mouse neocortex by diazepam

SCHEFFZUK, C. , KUKUSHKA, V. , VYSSOTSKI, A. L. , DRAGUHN, A. , TORT, A. B. L. , BRANKACK, J. . Global slowing of network oscillations in mouse neocortex by diazepam. Neuropharmacology , v. 65, p. 123-133, 2013.

Similarity between the in vitro activity and toxicity of two different fungizone™ / lipofundin™ admixtures

Amphotericin B (AmB), an antifungal agent that presents a broad spectrum of activity, remains the gold standard in the antifungal therapy. However, sometimes the high level of toxicity forbids its clinical use. The aim of this work was to evaluate and compare the efficacy and toxicity in vitro of Fungizon™ (AmB-D) and two new different AmB formulations. Methods: three products were studied: Fungizon™, and two Fungizon™ /Lipofundin™ admixtures, which were diluted through two methods: in the first one, Fungizon™ was previously diluted with water for injection and then, in Lipofundin™ (AmB-DAL); the second method consisted of a primary dilution of AmB-D as a powder in the referred emulsion (AmB-DL). For the in vitro assay, two cell models were used: Red Blood Cells (RBC) from human donors and Candida tropicallis (Ct). The in vitro evaluation (K+ leakage, hemoglobin leakage and cell survival rate-CSR) was performed at four AmB concentrations (from 50 to 0.05mg.L-1). Results: The results showed that the action of AmB was not only concentration dependent, but also cellular type and vehicle kind dependent. At AmB concentrations of 50 mg.L-1, although the hemoglobin leakage for AmB-D was almost complete (99.51), for AmB-DAL and AmB-DL this value tended to zero. The p = 0.000 showed that AmB-D was significantly more hemolytic. Conclusion: The Fungizon™- Lipofundin™ admixtures seem to be the more valuable AmB carrier systems due to their best therapeutic index presented