Evaluation of oxidative stress and brain-derived neurotrophic factor levels related to crack-use detoxification.

Crack is a central nervous system stimulant extracted from the Erythroxylum coca plant. It is considered the most potent and addictive form of cocaine, and its euphoric effects are attained within a few seconds after consumption. Alteration of biological markers of oxidative stress and brain-derived neurotrophic factor (BDNF) could be related to the severity of crack withdrawal symptoms in patients undergoing rehabilitation. Thus, the objective of this study was to evaluate if the crack consumption and the drug detoxification process during 14 days in hospitalization regime was able to modify the oxidative status and BDNF levels, in male crack-abstinent patients. The crack detoxification process increased the glutathione (GSH), total thiol content (GST), nitric oxide (NO), and superoxide dismutase (SOD) levels, and reduced the mean BDNF levels. Moreover, a positive correlation was found between the number of hospital admission days and SOD values and between the GST levels and crack-use time after 14 days of detoxification. Furthermore, a negative correlation between the frequency of crack use and NO levels on the first day of hospitalization was also found. In conclusion, the results of this study indicated that crack consumption causes increased oxidative stress in drug users and that the detoxification process during 14 days was sufficient to improve oxidative parameters and antioxidant defenses of the patients, which could positively contribute to rehabilitation process. In addition, we also observed a great variability in the BDNF levels of the patients during the detoxification process, resulting in a reduction in the mean values of this neurotrophin.

Inhibitory effect of Campomanesia xanthocarpa in platelet aggregation: Comparison and synergism with acetylsalicylic acid.

BACKGROUND AND AIMS: Cardiovascular diseases of thrombotic origin are related to high mortality and standard therapeutic agent used in this case is acetylsalicylic acid (ASA), but serious adverse events may occur. However, recent data has suggested the plant Campomanesia xanthocarpa has antiplatelet activity and could be a viable alternative. In this study we investigated the effects of the encapsulated powder of this plant in human platelet aggregation. METHODS: 23 healthy subjects were randomly divided into three groups: (1) ASA (100mg), (2) C. xanthocarpa (1000mg) or (3) synergism (500mg of C. xanthocarpa plush 50mg of ASA); daily for five days. Antiplatelet activity was determined by turbidimetric method using ADP or arachidonic acid (AA) agonists before, 5 and 8days after treatments. RESULTS: Treatment with C. xanthocarpa and synergism caused a reduction of 8±13.5% and 12.5±5% in platelet aggregation induced by ADP after 5days of treatment, respectively, returning to basal levels after 8days. For AA agonist, 5days of treatment with C. xanthocarpa, ASA or synergism caused a reduction of 46±15%, 36±12% and 69.3±6% in platelet aggregation, respectively, and first two groups returned to baseline values 8days after treatment ended. Synergism group prolonged antiplatelet effect maintaining aggregation reduction after 8days the end of treatment. CONCLUSION: C. xanthocarpa showed antiplatelet action when stimulated by agonist AA, and contributed to the antiplatelet effect when associated with ASA for both agonists, allowing dose reduction to 50mg.

Evaluation of Salt Intake, Urinary Sodium Excretion and Their Relationship to Overhydration in Chronic Kidney Disease Patients.

The purpose of this study was to estimate sodium intake in a group of patients with chronic kidney disease (CKD) and to correlate the results with the urinary excretion values of sodium and signs of fluid overload. We included patients with CKD in different stages. Urinary sodium was measured in 24 h urine samples. Body composition monitor (BCM) was used to estimate the hydration status. Sixty patients (38 ± 15 ml/min of GFR) presented 4.14 ± 1.71 g/24 h of urinary sodium excretion. Overhydration was detected in 50% of the patients by the BCM. There was a positive correlation between the measured sodium excretion values and BCM, ICW, ECW and TBW. In conclusion, markers of overhydration evaluated by BCM were positively correlated with urinary sodium excretion.

Marcadores clínicos e bioquímicos de gravidade do diabetes mellitus gestacional / Clinical and biochemical markers of gravity of gestational diabetes mellitus

O diabetes mellitus gestacional (DMG) é uma patologia da segunda metade da gestação caracterizada por uma insulinorresistência que está intimamente relacionada ao resultado perinatal adverso e se não diagnosticada e tratada pode trazer sérios problemas tanto para a mãe quanto para o feto. O objetivo deste trabalho foi realizar uma revisão da literatura sobre marcadores clínicos e bioquímicos de gravidade do DMG. Trata-se de uma revisão de literatura nas bases de dados PubMed, SciELO e Cochrane. Foram selecionados 50 artigos, mas apenas 25 tiveram relevância para serem discutidos nesta revisão. Após análise pôde-se concluir que com os novos critérios-diagnósticos e um aumento na incidência dessa patologia é de grande valia identificar marcadores clínicos e bioquímicos que estão relacionados aos resultados perinatais adversos e à necessidade de tratamento complementar à dieta

The gestational diabetes mellitus (GDM) is a second half of pregnancy disease characterized by insulin resistance that is closely related to perinatal outcome and if undiagnosed and untreated can cause serious problems for both mother and fetus. The objective of this study was to review the literature on clinical and biochemical markers of GDM severity. This is a literature review in PubMed, SciELO and Cochrane. Fifty articles were selected, but only 25 were relevant to be discussed in this review. After their analysis it was concluded that with the new diagnostic criteria and an increased incidence of this pathology is of great value to identify clinical and laboratory markers that are related to adverse perinatal outcomes and the need to supplement the diet treatment

Immune regulatory properties of multipotent mesenchymal stromal cells: Where do we stand?

Multipotent mesenchymal stromal cells (MSC) can be isolated and efficiently expanded from almost every single body tissue and have the ability of self-renewal and differentiation into various mesodermal cell lineages. Moreover, these cells are considered immunologically privileged, related to a lack of surface expression of costimulatory molecules required for complete T cell activation. Recently, it has been observed that MSC are capable of suppressing the immune response by inhibiting the maturation of dendritic cells and suppressing the function of T lymphocytes, B lymphocytes and natural killer cells in autoimmune and inflammatory diseases as a new strategy for immunosuppression. The understanding of immune regulation mechanisms by MSC is necessary for their use as immunotherapy in clinical applications for several diseases.

Glycemic and lipidic profile in diabetic patients undergoing dialysis / Controle glicêmico e lipídico no paciente diabético em diálise

OBJECTIVE: The aim of this study is to assess the clinical care pattern and to compare the lipid and glycemic profile in a group of diabetic patients undergoing both hemodialysis (HD) and peritoneal dialysis (PD) and to correlate these data using biomarkers of cardiovascular risk. SUBJECTS AND METHODS: The first phase consisted in performing a survey on demographic data, questions about the medical team and glycemic control. In the second phase, patients were assessed through laboratorial data on their glycemic and lipid profile at a single center for HD and PD. RESULTS: 91 patients was the total population; 70 patients (77 percent) answered the survey; 66 patients (94 percent) considered the nephrologist the physician responsible for caring for their glycemic control. Second phase: 59 patients were assessed, 29 undergoing HD and 30 undergoing PD. Fifty-seven percent of the patients had HbA1c above 7 percent; the level of glycemic markers in patients undergoing peritoneal dialysis was significantly higher than in patients undergoing hemodialysis: HbA1c (9.37 ± 0.5) vs. (7.37 ± 0.49) p < 0.01; fasting glycemia (170 ± 15) vs. (126 ± 15) mg/dL p < 0.05. We found a positive correlation between HbA1c and hyperfibrinogenemia (r = 0.4437, p < 0.0005). CONCLUSIONS: The data reveal that glycemic control in diabetic patients undergoing renal replacement therapy (RRT) is neglected. Peritoneal dialysis is related to the worst level of glycemic markers, possibly due to the glucose content in the dialysis solution, and higher levels from HbA1c have a positive correlation with hyperfibrinogenesis in this population.

OBJETIVO: Avaliar as características dos cuidados clínicos dos pacientes em diálise, comparar o controle glicêmico e lipídico entre os pacientes diabéticos em hemodiálise (HD) e em diálise peritoneal (DP) e correlacionar os dados laboratoriais com biomarcadores de risco cardiovascular. SUJEITOS E MÉTODOS: A primeira etapa consistiu de um questionário abordando variáveis demográficas, questões sobre a equipe multidisciplinar, incluindo a equipe médica e sobre o controle glicêmico. Na segunda, os pacientes foram avaliados com exames laboratoriais para controle glicêmico e perfil lipídico numa unidade de HD e DP. RESULTADOS: Dos 91 pacientes avaliados, setenta (77 por cento) responderam ao questionário. Destes, 66 (94 por cento) consideraram o nefrologista o médico responsável pelo cuidado do seu controle glicêmico. Na segunda etapa, foram avaliados 59 pacientes: 29 em HD e 30 em DP. Cinquenta e sete por cento dos pacientes diabéticos em diálise apresentaram HbA1c acima de 7 por cento, sendo que aqueles em diálise peritoneal apresentam níveis de marcadores glicêmicos significativamente piores do que os pacientes diabéticos em HD, HbA1c: (9,37 ± 0,5) vs. (7,37 ± 0,49) p < 0.01; glicemia de jejum: (170 ± 15) vs. (126 ± 15) mg/dL, p < 0.05. Encontramos uma correlação positiva entre HbA1c e hiperfibrinogenemia (r = 0.4437, p < 0.0005). CONCLUSÕES: Nossos dados permitem inferir que o controle glicêmico da população diabética em terapia renal de substituição (TRS) é negligenciado. A diálise peritoneal está relacionada com piora nos níveis de marcadores glicêmicos, possivelmente em decorrência do conteúdo de glicose das soluções de diálise, e os níveis elevados de HbA1c estão associados com hiperfibrinogenemia nesta população.

Glycemic and lipidic profile in diabetic patients undergoing dialysis.

OBJECTIVE: The aim of this study is to assess the clinical care pattern and to compare the lipid and glycemic profile in a group of diabetic patients undergoing both hemodialysis (HD) and peritoneal dialysis (PD) and to correlate these data using biomarkers of cardiovascular risk. SUBJECTS AND METHODS: The first phase consisted in performing a survey on demographic data, questions about the medical team and glycemic control. In the second phase, patients were assessed through laboratorial data on their glycemic and lipid profile at a single center for HD and PD. RESULTS: 91 patients was the total population; 70 patients (77%) answered the survey; 66 patients (94%) considered the nephrologist the physician responsible for caring for their glycemic control. Second phase: 59 patients were assessed, 29 undergoing HD and 30 undergoing PD. Fifty-seven percent of the patients had HbA1c above 7%; the level of glycemic markers in patients undergoing peritoneal dialysis was significantly higher than in patients undergoing hemodialysis: HbA1c (9.37 ± 0.5) vs. (7.37 ± 0.49) p < 0.01; fasting glycemia (170 ± 15) vs. (126 ± 15) mg/dL p < 0.05. We found a positive correlation between HbA1c and hyperfibrinogenemia (r = 0.4437, p < 0.0005). CONCLUSIONS: The data reveal that glycemic control in diabetic patients undergoing renal replacement therapy (RRT) is neglected. Peritoneal dialysis is related to the worst level of glycemic markers, possibly due to the glucose content in the dialysis solution, and higher levels from HbA1c have a positive correlation with hyperfibrinogenesis in this population.

Formação in vitro de túbulos capilares a partir de células de sangue de cordão umbilical humano com perspectivas para aplicação terapêutica / In vitro formation of capillary tubules from human umbilical cord blood cells with perspectives for therapeutic application

OBJETIVO: As células progenitoras endoteliais (CPE), caracterizadas pelo marcador CD133+, contribuem para a neovascularização, e o aumento no número dessas células pode ser uma ferramenta terapêutica promissora. O sangue de cordão umbilical humano contém um número significante de CPE, sugerindo a possibilidade do uso destas células para a revascularização de tecidos isquêmicos. O objetivo desse trabalho foi analisar a funcionalidade das células CD133+ diferenciadas in vitro. MÉTODOS: As células diferenciadas foram caracterizadas por citometria de fluxo; a expressão do mRNA de VEGF foi avaliada por RT-PCR e a funcionalidade, por meio de ensaios de formação de túbulos capilares. RESULTADOS: As células diferenciadas perderam os marcadores de CPE, mantiveram em níveis baixos os marcadores das linhagens hematopoética e monocíticas e aumentaram a expressão dos marcadores de células endoteliais adultas. As células diferenciadas apresentaram transcritos no mRNA de VEGF e mostraram-se capazes de formar túbulos capilares in vitro. CONCLUSÃO: As células CD133+ diferenciadas in vitro em células endoteliais demonstraram serem funcionalmente ativas, abrindo perspectiva para seu uso futuro em aplicações terapêuticas.

OBJECTIVE: Endothelial progenitor cells (EPC) caracterized by the CD133+ marker, contribute to the neovascularization. Increasing EPC number in vitro could be a promising therapeutic tool. Human umbilical cord blood maintains a significant number of EPC, suggesting the possibility to use these cells to induce the revascularization of ischemic tissues. The aim of this study was to analize the in vitro function of differentiated CD133+ cells. METHODS: Cells were characterized by flow cytometry, VEGF mRNA expression was evaluated by the RT-PCR analysis and the functionally by essays of capillary tubes formation. RESULTS: Differentiated cells lost EPC markers, maintained low levels of markers for hematopoietic and monocytic cell lines and increased the expression of adult endothelial cell markers. Differentiated cells expressed VEGF mRNA and were capable to induce in vitro capillary tubules formation. CONCLUSION: CD133+ cells differentiated into endothelial cells in vitro are functionally active initiating the possibility of their use in future therapeutic applications.

In vitro formation of capillary tubules from human umbilical cord blood cells with perspectives for therapeutic application.

OBJECTIVE: Endothelial progenitor cells (EPC) characterized by the CD133+ marker, contribute to the neovascularization. Increasing EPC number in vitro could be a promising therapeutic tool. Human umbilical cord blood maintains a significant number of EPC, suggesting the possibility to use these cells to induce the revascularization of ischemic tissues. The aim of this study was to analyze the in vitro function of differentiated CD133+ cells. METHODS: Cells were characterized by flow cytometry, VEGF mRNA expression was evaluated by the RT-PCR analysis and the functionally by essays of capillary tubes formation. RESULTS: Differentiated cells lost EPC markers, maintained low levels of markers for hematopoietic and monocytic cell lines and increased the expression of adult endothelial cell markers. Differentiated cells expressed VEGF mRNA and were capable to induce in vitro capillary tubules formation. CONCLUSION: CD133+ cells differentiated into endothelial cells in vitro are functionally active initiating the possibility of their use in future therapeutic applications.

Co-localization of nestin and insulin and expression of islet cell markers in long-term human pancreatic nestin-positive cell cultures.

Strategies to differentiate progenitor cells into beta cells in vitro have been considered as an alternative to increase beta cell availability prior to transplantation. It has recently been suggested that nestin-positive cells could be multipotential stem cells capable of expressing endocrine markers upon specific stimulation; however, this issue still remains controversial. Here, we characterized short- and long-term islet cell cultures derived from three different human islet preparations, with respect to expression of nestin and islet cell markers, using confocal microscopy and semi-quantitative RT-PCR. The number of nestin-positive cells was found to be strikingly high in long-term cultures. In addition, a large proportion (49.7%) of these nestin-positive cells, present in long-term culture, are shown to be proliferative, as judged by BrdU incorporation. The proportion of insulin-positive cells was found to be high in short-term (up to 28 days) cultures and declined thereafter, when cells were maintained in the presence of 10% serum, concomitantly with the decrease in insulin and PDX-1 expression. Interestingly, insulin and nestin co-expression was observed as a rare event in a small proportion of cells present in freshly isolated human islets as well as in purified islet cells cultured in vitro for long periods of time. In addition, upon long-term subculturing of nestin-positive cells in 10% serum, we observed reappearance of insulin expression at the mRNA level; when these cultures were shifted to 1% serum for a month, expression of insulin, glucagon and somatostatin was also detected, indicating that manipulating the culture conditions can be used to modulate the nestin-positive cell's fate. Attempts to induce cell differentiation by plating nestin-positive cells onto Matrigel revealed that these cells tend to aggregate to form islet-like clusters, but this is not sufficient to increase insulin expression upon short-term culture. Our data corroborate previous findings indicating that, at least in vitro, nestin-positive cells may undergo the early stages of differentiation to an islet cell phenotype and that long-term cultures of nestin-positive human islet cells may be considered as a potential source of precursor cells to generate fully differentiated/ functional beta cells.

Clonagem e caracterização de genes regulados por glicose em ilhotas pancreáticas humanas / Cloning and characterization of glucose regulated genes in human pancreatic islets

O Diabetes mellitus (DM) do tipo 1 é uma doença causada pela destruição, por mecanismo auto-imune, da células (BETA) das ilhotas pancreáticas, produtoras de insulina. O tratamento convencional da doença é realizado por meio de injeções diárias de insulina exógena. O transplante de ilhotas pancreáticas inclui-se, atualmente, como uma das alternativas terapêuticas à insulinoterapia. Entretanto, para atingir a insulino-independência, é necessário transplantar um grande número de ilhotas por paciente. O conhecimento do mecanismo de proliferação das células (BETA) pode possibilitar a realização do transplante a partir da expansão celular ex vivo...