Evidences of endocytosis via caveolae following blood–brain barrier breakdown by Phoneutria nigriventer spider venom

Spider venoms contain neurotoxic peptides aimed at paralyzing prey or for defense against predators; that is why they represent valuable tools for studies in neuroscience field. The present study aimed at identifying the process of internalization that occurs during the increased trafficking of vesicles caused by Phoneutria nigriventer spider venom (PNV)-induced blood–brain barrier (BBB) breakdown. Herein, we found that caveolin-1α is up-regulated in the cerebellar capillaries and Purkinje neurons of PNV-administered P14 (neonate) and 8- to 10-week-old (adult) rats. The white matter and granular layers were regions where caveolin-1α showed major upregulation. The variable age played a role in this effect. Caveolin-1 is the central protein that controls caveolae formation. Caveolar-specialized cholesterol- and sphingolipid-rich membrane sub-domains are involved in endocytosis, transcytosis, mechano-sensing, synapse formation and stabilization, signal transduction, intercellular communication, apoptosis, and various signaling events, including those related to calcium handling. PNV is extremely rich in neurotoxic peptides that affect glutamate handling and interferes with ion channels physiology. We suggest that the PNV-induced BBB opening is associated with a high expression of caveolae frame-forming caveolin-1α, and therefore in the process of internalization and enhanced transcytosis. Caveolin-1α up-regulation in Purkinje neurons could be related to a way of neurons to preserve, restore, and enhance function following PNV-induced excitotoxicity. The findings disclose interesting perspectives for further molecular studies of the interaction between PNV and caveolar specialized membrane domains. It proves PNV to be excellent tool for studies of transcytosis, the most common form of BBB-enhanced permeability.     

Calorie restriction promotes remyelination in a Cuprizone-Induced demyelination mouse model of multiple sclerosis

Metabolic Brain Disease - Over the past few decades several attempts have been made to introduce a potential and promising therapy for Multiple sclerosis (MS). Calorie restriction (CR) is a dietary...     

Myeloperoxidase gene polymorphism predicts fibrosis severity in women with hepatitis C

Oxidative stress plays an important role on liver fibrosis progression in the course of hepatitis C virus (HCV) infection. Myeloperoxidase (MPO) is an enzyme released by neutrophils and macrophages, responsible for generating hypochlorous acid and reactive oxygen species (ROS) that may lead to liver injury in HCV infection. On the other hand, antioxidant enzymes such as manganese superoxide dismutase (SOD) controls ROS-mediated damage. The aim of the present study was to investigate the influence of MPO G-463A and SOD2 Ala16Val polymorphisms in the severity of liver fibrosis in individuals with chronic HCV infection. The present study included 270 patients with chronic HCV recruited from the Gastrohepatology Service of the Oswaldo Cruz University Hospital/Liver Institute of Pernambuco (Recife, Northeastern Brazil). All patients underwent liver biopsy, which was classified according METAVIR score. The SNPs were determined by real-time PCR. After multivariate analysis adjustment, the GG genotype of MPO and the presence of metabolic syndrome were independently associated with fibrosis severity in women (P = 0.025 OR 2.25 CI 1.10–4.59 and P = 0.032 OR 2.32 CI 1.07–5.01, respectively). The presence of the GG genotype seems to be a risk factor for fibrosis severity in women with HCV.     

Methotrexate concentrations in synovial membrane and trabecular and cortical bone in rheumatoid arthritis patients

Objective. To determine methotrexate (MTX) concentrations in the synovial membrane (SM) and cortical and trabecular bone of rheumatoid arthritis (RA) patients. Methods. Ten RA patients (9 women, 1 man; mean ± SD age 49.2 ± 10.6, mean disease duration 13.2 ± 9.9 years) undergoing surgical procedures for rheumatoid articular lesions participated in this study. Mean ± SD MTX treatment duration was 26.4 ± 21.3 months. The day preceding surgery, 10 mg of MTX was administered intramuscularly. During surgery, a mean ± SD of 19.7 ± 2.6 hours after MTX administration, SM, bone fragments, and blood were collected simultaneously. MTX was assayed by fluorescence polarization immunoassay in plasma and tissues. Results. The mean ± SD plasma concentration was 0.0252 ± 0.01 nmoles/ml at the time of tissue sampling. The mean MTX concentration in SM was 0.285 ± 0.159 nmoles/gm. The mean MTX concentrations in trabecular and cortical bone were 0.292 ± 0.164 and 0.286 ± 0.126 nmoles/gm, respectively. Conclusion. After intramuscular administration, high MTX concentrations are found in SM and cortical and trabecular bone of RA patients.     

Preparation of GO/SiO2/PEA as a new solid base catalyst for the green synthesis of some spirooxindole derivatives

Efficient and green one pot multi component synthesis of some spirooxindole derivatives in the presence of graphene oxide functionalized with 2-(1-piperazinyl) ethylamine (GO/SiO₂/PEA) as a solid base catalyst was studied. GO/SiO₂/PEA has been obtained through a two step reaction and characterized by Fourier transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDX), thermo gravimetric analysis (TGA), Raman spectroscopy and X-ray diffraction (XRD). Green reaction conditions, short reaction times, reusable catalyst and a high to excellent yield of products are some of the advantageous of the presented method.

Efficient and green one pot multi component synthesis of some spirooxindole derivatives in the presence of graphene oxide functionalized with 2-(1-piperazinyl) ethylamine (GO/SiO₂/PEA) as a solid base catalyst was studied.