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Objective Serum levels of creatinine in neonates are quite variable and suffer interference from the immature kidney and maternal creatinine concentration. The aim of this study was to measure novel biomarkers of glomerular and tubular function in healthy preterm neonates at 72 h and 3 weeks of life. Methods Urine samples were collected in 40 preterm neonates with 28–34 incomplete weeks of gestational age. None of the participants had comorbidities, malformations and infections. The samples were collected at 72 h of life and at 3 weeks after birth. Measurements of Calbindin, Collagen IV, FABP1, αGST, IP-10, KIM-1, Osteoactivin, Renin, TFF-3, TIMP-1, α-1-Microglobulin, Albumin, Clusterin, Cystatin C, EGF, Lipocalin-2/NGAL and Osteopontin were performed using panels 1 and 2 of multiplex kits of kidney injury. Data were analyzed using the software GraphPad Prism version 6.0. Results The preterm neonates included 55% of males with gestational age of 30 ± 1 weeks. The most frequent maternal condition associated with preterm birth was preeclampsia (80%). Molecules related to glomerular function showed a significant increase in the concentrations obtained at 3 weeks of life compared to 72 h of life. Markers related to tubular injury (KIM-1 and NGAL) also showed an increase. On the other hand, cystatin C did not change. Conclusion The elevation of molecules related to glomerular function indicates an increase of glomerular filtration rate from 72 h up until 3 weeks of life, which was not clearly detected with the measurement of cystatin C.

Chagas disease (CD) is a tropical zoonosis caused by the protozoan Trypanosoma cruzi. Severe autonomic dysfunction like reduced cardiac catecholamine-containing or acetylcholinesterase-positive innervation have been reported in CD. Renin-angiotensin system (RAS) seems to participate in the regulation of adrenal catecholamine secretion by adrenal medullary chromaffin cells, which might be dependent of nitric oxide (NO) pathways. To investigate the levels of RAS components in the adrenal gland during the acute infection with Y strain T. cruzi and in response to acute administration of an inhibitor of the enzyme NO synthase, L-NAME. Male Holtzman rats were inoculated intraperitoneally with Y strain T. cruzi and received L-NAME or tap water from one day before the infection until 13 or 17 days post-inoculation (dpi). The concentration of RAS molecules in the adrenal tissue was evaluated by ELISA immunoassay. Angiotensin converting enzyme 1 (ACE1) levels were significantly lower at 17 dpi when compared to 13 dpi. No significant differences were found compared with baseline, and no changes were detected in adrenal tissue levels of angiotensin converting enzyme 2 (ACE2), angiotensin II, or angiotensin-(1-7). Moreover, the treatment with L-NAME did not influence the levels of RAS components in adrenal tissue during the course of T. cruzi infection. We provided the first evidence that levels of RAS molecules change in the adrenal gland during acute phase of T. cruzi infection. Future studies are necessary to fully address the role of NO in RAS-associated adrenal gland function in CD.

Made available in DSpace on 2018-11-27T07:08:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-02-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundacao de Amparo Pesquisa do Estado de Sao Paulo Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Budesonide (BUD) is a glucocorticoid widely used for the treatment of ulcerative colitis. In this work, we propose the study of the system BUD-HP-beta-CD inclusion complex incorporated into PL 407 and PL407-PL403 thermoreversible hydrogels, considering physico-chemical and pharmaceutical aspects. Complexation between BUD and HP-beta-CD was confirmed by phase solubility studies (1:1 stoichiometry, Kc = 8662.8 M-1), DSC, FTIR and microscopy analyzes. BUD solubility in simulated upper and lower colon fluids was improved in a dependence of HP-beta-CD and PL 407 or PL407-PL403 association. Micellar hydrodynamic diameter studies showed the interaction between HP-beta-CD and PL blocks, as well as the reorganization of the micellar system in the presence of BUD and its inclusion complex. Micellization temperature (T-m) was not shifted, but sol-gel phase transition studies showed that in the presence of BUD, HP-beta-CD or BUD:HP-beta-CD complex, the association PL407-PL403 favored the gel formation close to the physiological temperature. Physico-chemical and in vitro release assays studies revealed no competitive displacement of BUD from the HP-beta-CD cavity evoked by PL407 or PL407-PL403 addition. These findings point out the BUD-HP-beta-CD in PL-based hydrogels as strategies for future investigations on development of new pharmaceutical formulations for the treatment of ulcerative colitis. (C) 2015 Elsevier B.V. All rights reserved. Univ Fed Abc, Ctr Ciencias Nat & Humanas, BR-09210580 Santo Andre, SP, Brazil State Univ Julio de Mesquita Filho, Dept Enviroment Engn, Sorocaba, SP, Brazil Univ Estadual Campinas, Inst Biol, Dept Biochem, Campinas, SP, Brazil Fac Dent Sao Leopoldo Mand, Campinas, SP, Brazil State Univ Julio de Mesquita Filho, Dept Enviroment Engn, Sorocaba, SP, Brazil Fundacao de Amparo Pesquisa do Estado de Sao Paulo: FAPESP 2014/26200-9 Fundacao de Amparo Pesquisa do Estado de Sao Paulo: 2014/14457-5 CNPq: CNPq 487619/2012-9 CNPq: 309612/2013-6

Ana Claudia Mendonça dos Santos,1 Alessandra Cristina Santos Akkari,1 Iasmin Rosanne Silva Ferreira,2 Cintia Rodrigues Maruyama,3 Monica Pascoli,3 Viviane Aparecida Guilherme,4 Eneida de Paula,4 Leonardo Fernandes Fraceto,5 Renata de Lima,3 Patrícia da Silva Melo,2 Daniele Ribeiro de Araujo1 1Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, 2Faculdades Integradas Metropolitanas de Campinas, Campinas, 3Departamento de Biotecnologia, Universidade de Sorocaba, Sorocaba, 4Departamento de Bioquímica, Universidade Estadual de Campinas, Campinas, 5Departamento de Engenharia Ambiental, Universidade Estadual ‘Júlio de Mesquita Filho’, Sorocaba, São Paulo, Brazil Abstract: In this work, poloxamer (PL)-based binary hydrogels, composed of PL 407 and PL 188, were studied with regard to the physicochemical aspects of sol-gel transition and pharmaceutical formulation issues such as dissolution-release profiles. In particular, we evaluated the cytotoxicity, genotoxicity, and in vivo pharmacological performance of PL 407 and PL 407–PL 188 hydrogels containing tramadol (TR) to analyze its potential treatment of acute pain. Drug–micelle interaction studies showed the formation of PL 407–PL 188 binary systems and the drug partitioning into the micelles. Characterization of the sol-gel transition phase showed an increase on enthalpy variation values that were induced by the presence of TR hydrochloride within the PL 407 or PL 407–PL 188 systems. Hydrogel dissolution occurred rapidly, with approximately 30%–45% of the gel dissolved, reaching ~80%–90% up to 24 hours. For in vitro release assays, formulations followed the diffusion Higuchi model and lower Krel values were observed for PL 407 (20%, Krel =112.9±10.6 µg·h-1/2) and its binary systems PL 407–PL 188 (25%–5% and 25%–10%, Krel =80.8±6.1 and 103.4±8.3 µg·h-1/2, respectively) in relation to TR solution (Krel =417.9±47.5 µg·h-1/2, P72 hours) pointed to PL-based hydrogels as a potential treatment, by subcutaneous injection, for acute pain. Keywords: micelle, cytotoxicity, genotoxicity, analgesia

Arthritics diseases, such as rheumatoid arthritis and osteoarthritis are chronic inflammatory and one of the most prevalent health conditions that cause disability (pain and functional limitation of joints). Despite the research advances, the treatment of those pathological conditions remains ineffective, since the pharmacological therapy is palliative, reducing only the symptoms and, in some cases, the chronic progression of the disease. In this context, the development of new formulations for controlled release would be interesting for reducing the number of injections and would also increase the patient compliance. In this article, we present a review of the cyclodextrin (CD)-based delivery systems focusing from conventional guest-host inclusion complexes and CD-polysulphates, until supramolecular architectures such as drug-CD-polymers conjugates, pseudorotaxanes, hydrogels as well as double-carrier systems and other systems. In particular, this article focuses the main CD-based delivery systems described in the literature emphasizing their possible administration by intra-articular route on the treatment of arthritic diseases, concentrating on their development and also performance as in vivo experimental therapeutic systems.

Poloxamers (PL) are copolymers A-B-A type consisting of ethylene oxide (EO) and propylene oxide (PO) units in a triblock EOx–POy–EOx arrangement. These copolymers are interesting due to their ability for temperature-dependent gel formation, as a result of their self-assembling in micelles. Several studies have demonstrated the application of the thermoreversible copolymers as drug-delivery systems in order to prolong the drug release, to sustain the effectiveness, and also to reduce local and/or systemic toxicity, connecting the expertise of different research fields such as Biochemistry, Nanotechnology, Biopharmaceutics, Pharmacology, and Toxicology. Then, the purpose of this chapter involves a discussion about PL copolymers in the light of those research fields.