Complement-dependent cytotoxicity crossmatch in solid organ transplantation: The gold standard or golden history?

Complement-dependent cytotoxicity crossmatch (CDC-XM) has been considered for many years the standard of practice for determining compatibility in solid organ transplantation (SOT). However, as this method is laborious, time intensive and lacks sensitivity and specificity, it has been replaced in many laboratories worldwide by flow cytometry crossmatch (FCXM) and/or virtual crossmatch (vXM). With this study we intend to show the relevance of performing CDC-XM in the era of virtual crossmatching. We retrospectively analyzed 1,007 consecutive T and B cell deceased donor (DD) CDC-XMs performed in parallel using non-treated and dithiothreitol (DTT) treated sera between May 2022 and January 2023 in waitlisted patients with no donor specific antibodies (DSA) against HLA-A, B and/or DR antigens. Thirty five of 1,007 (3.5%) T cell crossmatches and 132 of 1,007 (13.1%) B cell crossmatches were positive with non-treated sera. Correlation with the vXM demonstrated no DSA in any of the positive T cell crossmatches. DSA were also absent in 126/132 positive B cell crossmatches, indicating a high rate of false positive CDC-XM. Indeed, only 4/35 T cell and 13/132 B cell CDC-XM remained positive after treatment with DTT, confirming that false positive reactivity with non-treated sera is high. Class I HLA DSA against C locus antigens were present in 17/1,007 T cell crossmatches and none were detected by CDC-XM (sensitivity = 0%). Similarly, only 6/77 B cell crossmatches with DSA targeting HLA-C, DQ and/or DP antigens were CDC-XM positive (sensitivity = 7.8%). Furthermore, only 4/6 positive B cell CDC-XM were confirmed to have complement binding potential using the C1q assay, suggesting additional false positive reactivity in 2/6 of the positive CDC-XM. Our study demonstrates that CDC-XM exhibits poor sensitivity, high false positive reactivity (especially without DTT treatment) and does not meaningfully contribute to pre-transplant compatibility testing in the context of vXM based allocation. Furthermore, the use of CDC-XM can unnecessarily delay or even prevent safe and appropriate transplant allocation.

HLA class II eplet mismatch load improves prediction of dnDSA development after living donor kidney transplantation.

HLA donor-specific antibodies developed de novo after transplant remain a major cause of chronic allograft dysfunction. Our study main purpose was to determine whether HLA MM, assessed traditionally and by HLA total and AbVer eplet mismatch load (EptMM and EpvMM) assessed with HLAMatchMaker, had impact on dnDSA development after living donor kidney transplantation (LDKT). We retrospectively analysed a cohort of 96 LDKT between 2008 and 2017 performed in Hospital Santo António. Seven patients developed dnDSA-II and EpvMM and EptMM were greater in dnDSA-II group compared to the no dnDSA-II (18.0 ± 8.7 versus 9.9 ± 7.9, p = .041 and 41.3 ± 18.9 versus 23.1 ± 16.7, p = .018), which is not observed for AgMM (2.29 versus 1.56; p = .09). In a multivariate analysis, we found that preformed DSA (HR = 7.983; p = .023), living unrelated donors (HR = 8.052; p = .024) and retransplantation (HR = 14.393; p = .009) were predictors for dnDSA-II (AUC = 0.801; 0.622-0.981). HLA-II EpvMM (HR = 1.105; p = .028; AUC = 0.856) showed to be a superior predictor of dnDSA-II, when compared to AgMM (HR = 1.740; p = .113; AUC = 0.783), when adjusted for these clinical variables. Graft survival was significantly lower within dnDSA-II patient group (36% versus 88%, p < .001). HLA molecular mismatch analysis is extremely important to minimize risk for HLA-II dnDSA development improving outcome and increasing chance of retransplant lowering allosensitization.

Degree of HLA class II eplet mismatch load improves prediction of antibody-mediated rejection in living donor kidney transplantation.

BACKGROUND: HLA mismatching is a well known risk factor for worst outcomes in kidney transplantation. METHODS: In the present study, HLA antigen and eplet mismatches were determined in 151 living donor-recipient pairs transplanted between 2007 and 2014 and rejection episodes and graft survival were evaluated. RESULTS: We found that high HLA-II eplet mismatch load (EpMM ≥ 13, versus low EpMM ≤ 5), was an independent predictor of AMR (adjusted HR = 14.839; P = 0.011), while HLA-II AgMM was not. We also showed that HLA-II EpMM load was a significant better predictor of AMR than AgMM (c-statistic = 0.064; P = 0.023). After discriminating HLA-II into HLA-DR and HLA-DQ loci we demonstrated that high versus low eplet mismatch load for HLA-DR (T3 ≥ 6 versus T = 0-1, p = 0.013) and HLA-DQ (T3 ≥ 7 versus T = 0-1, p = 0.009) are independent predictors for AMR. HLA-II EpMM increased discrimination performance of the classical HLA-II AgMM risk model (IDI, 0.061, 95%CI: 0.005-0.195) for AMR. Compared with AgMM, HLA-II eplet model adequately reclassified 13 of 17 patients (76.5%) with AMR and 92 of 134 patients (68.7%) without AMR (cfNRI, 0.785, 95%CI: 0.300-1.426). CONCLUSIONS: Our study evidences that eplet-based matching is a refinement of the classical HLA antigen mismatch analysis in LDKT and is a potential biomarker for personalized assessment of alloimmune risk.

Acute appendicitis may no longer be a predominant disease of the young population.

BACKGROUND: Some authors consider acute appendicitis as the main cause of acute surgical abdomen. Incident in all ages, contemporary literature suggests that is more frequent in children and young adults, male predominantly. This study aims to test the hypothesis that the disease in question is no longer prevalent in young adults (excluding children) in the surveyed region. METHODS: 1150 cases of emergency surgery were performed and prospectively analyzed. 300 cases of appendicitis in adults were selected and variables studied. Patients under 13 years old were excluded. RESULTS: 190 patients older than 60 years had a diagnosis of acute appendicitis confirmed by biopsy. There is a predominance of males. The elderly population takes less time to seek medical assistance and has fewer complications, despite being more often admitted to the ICU due to other comorbidities. CONCLUSIONS: A trend regarding acute appendicitis epidemiology may exist. In the specific studied region acute appendicitis is no longer a disease prevalent in young adults. Surgeons and emergency physicians must be aware that acute appendicitis may no longer be predominantly common in young adults in their own specific region. Multicenter studies are needed to determine whether these data are reproduced in a geographical area of greater extent.

Predictors of chest drainage complications in trauma patients.

OBJECTIVE: to identify predictors of chest drainage complications in trauma patients attended at a University Hospital. METHODS: we conducted a retrospective study of 68 patients submitted to thoracic drainage after trauma, in a one-year period. We analyzed gender, age, trauma mechanism, trauma indices, thoracic and associated lesions, environment in which the procedure was performed, drainage time, experience of the performer, complications and evolution. RESULTS: the mean age of the patients was 35 years and the male gender was the most prevalent (89%). Blunt trauma was the most frequent, with 67% of cases, and of these, 50% were due to traffic accidents. The mean TRISS (Trauma and Injury Severity Score) was 98, with a mortality rate of 1.4%. The most frequent thoracic and associated lesions were, respectively, rib fractures (51%) and abdominal trauma (32%). The mean drainage time was 6.93 days, being higher in patients under mechanical ventilation (p=0.0163). The complication rate was 26.5%, mainly poor drain positioning (11.77%). Hospital drainage was performed in 89% of cases by doctors in the first year of specialization. Thoracic drainage performed in prehospital care presented nine times more chances of complications (p=0.0015). CONCLUSION: the predictors of post-trauma complications for chest drainage were a procedure performed in an adverse site and mechanical ventilation. The high rate of complications demonstrates the importance of protocols of care with the thoracic drainage.

Predictors of chest drainage complications in trauma patients / Fatores preditores de complicações da drenagem de tórax em pacientes vítimas de trauma

ABSTRACT Objective: to identify predictors of chest drainage complications in trauma patients attended at a University Hospital. Methods: we conducted a retrospective study of 68 patients submitted to thoracic drainage after trauma, in a one-year period. We analyzed gender, age, trauma mechanism, trauma indices, thoracic and associated lesions, environment in which the procedure was performed, drainage time, experience of the performer, complications and evolution. Results: the mean age of the patients was 35 years and the male gender was the most prevalent (89%). Blunt trauma was the most frequent, with 67% of cases, and of these, 50% were due to traffic accidents. The mean TRISS (Trauma and Injury Severity Score) was 98, with a mortality rate of 1.4%. The most frequent thoracic and associated lesions were, respectively, rib fractures (51%) and abdominal trauma (32%). The mean drainage time was 6.93 days, being higher in patients under mechanical ventilation (p=0.0163). The complication rate was 26.5%, mainly poor drain positioning (11.77%). Hospital drainage was performed in 89% of cases by doctors in the first year of specialization. Thoracic drainage performed in prehospital care presented nine times more chances of complications (p=0.0015). Conclusion: the predictors of post-trauma complications for chest drainage were a procedure performed in an adverse site and mechanical ventilation. The high rate of complications demonstrates the importance of protocols of care with the thoracic drainage.

RESUMO Objetivo: identificar fatores preditores de complicações da drenagem torácica em pacientes vítimas de trauma, atendidos em um Hospital Universitário. Métodos: estudo retrospectivo de 68 pacientes submetidos à drenagem torácica pós-trauma, no período de um ano. Foram analisadas as seguintes variáveis: sexo, idade, mecanismo de trauma, índices de trauma, lesões torácicas e associadas, ambiente em que foi realizado o procedimento, tempo de permanência do dreno, grau de experiência do executor do procedimento, complicações e evolução. Resultados: a média de idade dos pacientes foi de 35 anos e o sexo masculino foi o mais prevalente (89%). O trauma contuso foi o mais frequente, com 67% dos casos, e destes, 50% por acidentes de trânsito. A média do TRISS (Trauma and Injury Severity Score) foi 98, com taxa de mortalidade de 1,4%. As lesões torácicas e associadas mais frequentes foram, respectivamente, fraturas de costelas (51%) e trauma abdominal (32%). A média de permanência do dreno foi de 6,93 dias, sendo maior nos pacientes sob ventilação mecânica (p=0,0163). A taxa de complicações foi de 26,5%, com destaque para o mau posicionamento do dreno (11,77%). A drenagem hospitalar foi realizada, em 89% dos casos, por médicos do primeiro ano de especialização. A drenagem torácica realizada no atendimento pré-hospitalar apresentou nove vezes mais chances de complicações (p=0,0015). Conclusão: os fatores preditores de complicações para drenagem torácica pós-trauma foram: procedimento realizado em local adverso e ventilação mecânica. A alta taxa de complicações demonstra a importância dos protocolos de cuidados com a drenagem torácica.

Chronic nicotine treatment decreases LPS signaling through NF-κB and TLR-4 modulation in the hippocampus.

The hippocampus is a brain region that is rich in nicotinic acetylcholine receptors (nAChRs), especially the α7 subtype. The hippocampus is severely affected in disorders that have a neuroinflammatory component, such as Alzheimer's disease, Parkinson's disease, and schizophrenia. Previous studies demonstrated both in vivo and in vitro that nicotine inhibits immunological responses, including those that are triggered by the inflammatory agent lipopolysaccharide (LPS), the endotoxin of Gram-negative bacteria. The present study investigated whether chronically administered nicotine interferes with the nuclear binding of nuclear factor-κB (NF-κB) and the expression of LPS-induced inflammatory response genes. The results indicated that chronic nicotine administration (0.1mg/kg, s.c., 14days) inhibited the LPS-induced nuclear binding of NF-κB and mRNA expression levels of Tnf, Il1b, Nos2, and Tlr4. The presence of both the selective α7 nAChR antagonist methyllycaconitine (MLA; 5.0mg/kg i.p., 14days) and the nonselective nAChR antagonist mecamylamine (Meca; 1.0mg/kg, s.c., 14days) reversed the inhibitory effects of nicotine. These results suggest that the chronic activation of α7- and αxßy-containing nAChRs reduces acute inflammatory responses in the brain.

Winter course in physiology: a successful example of continuing education for secondary school teachers in Brazil.

In international surveys, Brazilian students have been consistently ranking low in science. Continuing education for secondary school teachers is certainly a way to change this situation. To update teachers and provide teaching and learning experiences for graduate students, our department organized a "Winter Course in Physiology" where schoolteachers had the opportunity to attend lectures that were offered by graduate students and participate in discussions on teaching and learning strategies and their applicability, considering different schools and student age groups. This work evaluated the ways in which the Winter Course in Physiology improves continuing education for secondary school teachers. Graduate students prepared, presented, and discussed with the audience the concepts, content, and topics of the program, which were previously presented to the organizing committee and a supervising professor. Potential participants were recruited based on their curriculum vitae and a letter of intent. During the course, they completed a questionnaire that graded different aspects of course organization and lectures. The results indicated that the Winter Course was positively evaluated. Most topics received a grade of ≥4.0, considering a range of 1.0 (low) to 5.0 (high). In a followup, both the participants and instructors reported positive impacts on their overall knowledge in physiology. Schoolteachers reported improvements in the performance and participation of their students. In conclusion, the results suggested that the Winter Course is a good way to promote continuing education for schoolteachers and promote university outreach. It also provided an important experience for graduate students to develop teaching skills.

Using mass spectrometry-based peptidomics to understand the brain and disorders such as Parkinson's disease and schizophrenia.

The numerous efforts invested in the identification of biomarkers for neurodegenerative and neuropsychiatric disorders, such as Parkinson's disease and schizophrenia, are justified because these disorders affect several million people worldwide. Although genetic implications and the role of the environment have been shown in the progression of those disorders, together with anatomical and neurochemical characteristics, an integrated view of the biochemical pathways involved in the pathophysiology of these disorders is still being unraveled. The use of proteomic methodologies, molecular mechanisms and potential biomarker candidates for the prognosis, diagnosis and treatment of brain disorders has been discussed. Similar methodologies can be applied for the large-scale identification of peptides to characterize the brain peptidome with the aim of closing the knowledge gaps that remain. Brain cells contain a large number of peptides that play pivotal roles in cell communication. Peptidome studies have recently identified more than 800 peptides in mouse brain extracts, with half of them derived from secretory pathways. For example, several of these peptides were identified as bioactive neuropeptides that activate G-coupled receptors. In addition, intracellular peptides derived from nuclear, cytosolic and mitochondrial proteins have been identified, including the hemopressins, which act with high selectivity for the cannabinoid receptor type 1. Considering the importance of peptides in cell signaling, the present review intends to discuss the recent findings of the peptidome field, focusing on Parkinson's disease and schizophrenia. New approaches to evaluate intracellular peptide signaling at the protein-protein interaction level and the future perspectives of peptides as intracellular modulators of signal transduction are explored.

Acute intestinal obstruction due to gallstone ileus.

OBJECTIVE: To perform a systematic review of the history, available image exams and clinical approach to the diagnosis and treatment of gallstone ileus. METHOD: Retrospective study in a university hospital including all cases of SBO treated over a period of 23 years. According to the surgical treatment the patients were divided into two groups: (1) enterolithotomy with cholecystectomy performed later (two-stage surgery); and (2) enterolithotomy, cholecystectomy and fistula closure (one-stage surgery). RESULTS: Twelve patients were included in the study, including 11 females (91,6%), with a mean age of 72.2 years. All patients presented associated diseases, mainly arterial hypertension (75%). All except one patient had multiple SBO symptoms. Gallstone ileus diagnosis was achieved in six patients (50%) before laparotomy. There were 8 patients in group 1 and 4 in group 2, and the morbidity was, respectively, 33.3% and 8.3%. Overall mortality was 16.6% (one patient in each group). CONCLUSIONS: Gallstone ileus should be suspected in the elderly with SBO symptoms. Early diagnosis can reduce post-operative complications. Treatment is urgent laparotomy, and surgical treatment must be individualized for each case. The majority of patients in this study were treated with enterolithotomy, with cholecystectomy being performed later in two symptomatic patients.

Microglial cells are involved in the susceptibility of NADPH oxidase knockout mice to 6-hydroxy-dopamine-induced neurodegeneration.

We explored the impact of Nox-2 in modulating inflammatory-mediated microglial responses in the 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD) model. Nox1 and Nox2 gene expression were found to increase in striatum, whereas a marked increase of Nox2 expression was observed in substantia nigra (SN) of wild-type (wt) mice after PD induction. Gp91(phox-/-) 6-OHDA-lesioned mice exhibited a significant reduction in the apomorphine-induced rotational behavior, when compared to wt mice. Immunolabeling assays indicated that striatal 6-OHDA injections reduced the number of dopaminergic (DA) neurons in the SN of wt mice. In gp91(phox-/-) 6-OHDA-lesioned mice the DA degeneration was negligible, suggesting an involvement of Nox in 6-OHDA-mediated SN degeneration. Gp91(phox-/-) 6-OHDA-lesioned mice treated with minocycline, a tetracycline derivative that exerts multiple anti-inflammatory effects, including microglial inhibition, exhibited increased apomorphine-induced rotational behavior and degeneration of DA neurons after 6-OHDA injections. The same treatment also increased TNF-α release and potentiated NF-κB activation in the SN of gp91(phox-/-)-lesioned mice. Our results demonstrate for the first time that inhibition of microglial cells increases the susceptibility of gp91(phox-/-) 6-OHDA lesioned mice to develop PD. Blockade of microglia leads to NF-κB activation and TNF-α release into the SN of gp91(phox-/-) 6-OHDA lesioned mice, a likely mechanism whereby gp91(phox-/-) 6-OHDA lesioned mice may be more susceptible to develop PD after microglial cell inhibition. Nox2 adds an essential level of regulation to signaling pathways underlying the inflammatory response after PD induction.

The human oligodendrocyte proteome.

Myelination of the CNS is performed by oligodendrocytes (OLs), which have been implicated in brain disorders, such as multiple sclerosis and schizophrenia. We have used the human oligodendroglial cell line MO3.13 to establish an OL reference proteome database. Proteins were prefractionationated by SDS-PAGE and after in-gel digestion subjected to nanoflow LC-MS analysis. Approximately 11 600 unique peptides were identified and, after stringent filtering, resulted in 2290 proteins representing nine distinct biological processes and various molecular classes and functions. OL-specific proteins, such as myelin basic protein (MBP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), as well as other proteins involved in multiple sclerosis and schizophrenia were also identified and are discussed. Proteins of this dataset have also been classified according to their chromosomal origin for providing useful data to the Chromosome-centric Human Proteome Project (C-HPP). Given the importance of OLs in the etiology of demyelinating and oligodendrogial disorders, the MO3.13 proteome database is a valuable data resource. The MS proteomics data have been deposited to the ProteomeXchange with identifier PXD000263 (http://proteomecentral.proteomexchange.org/dataset/PXD000263).

Abdome agudo por obstrução por ileobiliar / Acute intestinal obstruction due to gallstone ileus

OBJETIVO: descrever a experiência na abordagem dos doentes com abdome agudo por obstrução por IB, desde o diagnóstico até o tratamento definitivo. MÉTODOS: estudo retrospectivo incluindo todos os casos de IB tratados em um período de 23 anos. De acordo com a abordagem cirúrgica realizada, os pacientes foram divididos em dois grupos (1) enterolitotomia com colecistectomia no segundo momento; e (2) enterolitotomia, colecistectomia e abordagem da fístula. RESULTADOS: Doze pacientes foram incluídos, sendo 11 mulheres (91,6%), com média de idade de 72,2 anos. Todos os pacientes apresentavam doenças associadas, principalmente hipertensão arterial sistêmica (75%). Dois pacientes não apresentavam sintomas significativos de obstrução intestinal. O diagnóstico de IB foi realizado em seis pacientes (50%) antes da laparotomia. O grupo 1 foi constituído de oito pacientes e o grupo 2 de quatro, e a morbidade foi, respectivamente, 33,3% e 8,3%. A mortalidade foi 16,6% (um paciente de cada grupo). CONCLUSÃO: O manejo do IB deve ser individualizado. O tratamento da obstrução mediante remoção do cálculo biliar por enterotomia proximal é a escolha inicial para o tratamento do IB. A colecistectomia e a correção da fístula bilioentérica podem ser realizadas juntamente com a remoção do cálculo, no entanto, em pacientes com comorbidades significativas, esses procedimentos devem ser realizados posteriormente.

OBJECTIVE: To perform a systematic review of the history, available image exams and clinical approach to the diagnosis and treatment of gallstone ileus. METHOD: Retrospective study in a university hospital including all cases of SBO treated over a period of 23 years. According to the surgical treatment the patients were divided into two groups: (1) enterolithotomy with cholecystectomy performed later (two-stage surgery); and (2) enterolithotomy, cholecystectomy and fistula closure (one-stage surgery). RESULTS: Twelve patients were included in the study, including 11 females (91,6%), with a mean age of 72.2 years. All patients presented associated diseases, mainly arterial hypertension (75%). All except one patient had multiple SBO symptoms. Gallstone ileus diagnosis was achieved in six patients (50%) before laparotomy. There were 8 patients in group 1 and 4 in group 2, and the morbidity was, respectively, 33.3% and 8.3%. Overall mortality was 16.6% (one patient in each group). CONCLUSIONS: Gallstone ileus should be suspected in the elderly with SBO symptoms. Early diagnosis can reduce post-operative complications. Treatment is urgent laparotomy, and surgical treatment must be individualized for each case. The majority of patients in this study were treated with enterolithotomy, with cholecystectomy being performed later in two symptomatic patients.

NADPH oxidase and the degeneration of dopaminergic neurons in parkinsonian mice.

Several lines of investigation have implicated oxidative stress in Parkinson's disease (PD) pathogenesis, but the mechanisms involved are still unclear. In this study, we characterized the involvement of NADPH oxidase (Nox), a multisubunit enzyme that catalyzes the reduction of oxygen, in the 6-hydroxydopamine- (6-OHDA-) induced PD mice model and compared for the first time the effects of this neurotoxin in mice lacking gp91(phox-/-), the catalytic subunit of Nox2, and pharmacological inhibition of Nox with apocynin. Six-OHDA induced increased protein expression of p47(phox), a Nox subunit, in striatum. gp91(phox-/-) mice appear to be completely protected from dopaminergic cell loss, whereas the apocynin treatment conferred only a limited neuroprotection. Wt mice treated with apocynin and gp91(phox-/-) mice both exhibited ameliorated apomorphine-induced rotational behavior. The microglial activation observed within the striatum and the substantia nigra pars compacta (SNpc) of 6-OHDA-injected Wt mice was prevented by apocynin treatment and was not detected in gp91(phox-/-) mice. Apocynin was not able to attenuate astrocyte activation in SN. The results support a role for Nox2 in the 6-OHDA-induced degeneration of dopaminergic neurons and glial cell activation in the nigrostriatal pathway and reveal that no comparable 6-OHDA effects were observed between apocynin-treated and gp91(phox-/-) mice groups.

Different approaches, one target: understanding cellular mechanisms of Parkinson's and Alzheimer's diseases / Abordagens diferentes, um único objetivo: compreender os mecanismos celulares das doenças de Parkinson e de Alzheimer

Neurodegenerative disorders are undoubtedly an increasing problem in the health sciences, given the increase of life expectancy and occasional vicious life style. Despite the fact that the mechanisms of such diseases are far from being completely understood, a large number of studies that derive from both the basic science and clinical approaches have contributed substantial data in that direction. In this review, it is discussed several frontiers of basic research on Parkinson´s and Alzheimer´s diseases, in which research groups from three departments of the Institute of Biomedical Sciences of the University of São Paulo have been involved in a multidisciplinary effort. The main focus of the review involves the animal models that have been developed to study cellular and molecular aspects of those neurodegenerative diseases, including oxidative stress, insulin signaling and proteomic analyses, among others. We anticipate that this review will help the group determine future directions of joint research in the field and, more importantly, set the level of cooperation we plan to develop in collaboration with colleagues of the Nucleus for Applied Neuroscience Research that are mostly involved with clinical research in the same field.

Os transtornos neurodegenerativos são, sem dúvida, um problema crescente nas ciências da saúde, dado o aumento da expectativa de vida e de estilos de vida pouco saudáveis. Embora os mecanismos de tais doenças ainda estejam longe de ser esclarecidos, vários estudos que derivam tanto da ciência básica quanto de abordagens clínicas contribuíram nessa direção. Na presente revisão, são discutidas linhas de frente da pesquisa básica sobre as doenças de Parkinson e Alzheimer, em que grupos de pesquisas de três departamentos do Instituto de Ciências Biomédicas da Universidade de São Paulo estão envolvidos em um esforço multidisciplinar. O foco principal desta revisão envolve os modelos animais desenvolvidos para se estudar os aspectos celulares e moleculares daquelas doenças neurodegenerativas, incluindo o estresse oxidativo, a sinalização da insulina e as análises proteômicas, dentre outros. Antecipamos que esta revisão irá auxiliar o grupo a determinar as futuras direções da pesquisa conjunta nessa área e, o mais importante, estabelecer o nível de cooperação que planejamos desenvolver juntamente com colegas do Núcleo de Apoio à Pesquisa em Neurociência Aplicada que estão envolvidos com pesquisa clínica na mesma área.

Different approaches, one target: understanding cellular mechanisms of Parkinson's and Alzheimer's diseases.

Neurodegenerative disorders are undoubtedly an increasing problem in the health sciences, given the increase of life expectancy and occasional vicious life style. Despite the fact that the mechanisms of such diseases are far from being completely understood, a large number of studies that derive from both the basic science and clinical approaches have contributed substantial data in that direction. In this review, it is discussed several frontiers of basic research on Parkinson's and Alzheimer's diseases, in which research groups from three departments of the Institute of Biomedical Sciences of the University of São Paulo have been involved in a multidisciplinary effort. The main focus of the review involves the animal models that have been developed to study cellular and molecular aspects of those neurodegenerative diseases, including oxidative stress, insulin signaling and proteomic analyses, among others. We anticipate that this review will help the group determine future directions of joint research in the field and, more importantly, set the level of cooperation we plan to develop in collaboration with colleagues of the Nucleus for Applied Neuroscience Research that are mostly involved with clinical research in the same field.

Estudo epidemiológico de queimaduras atendidas nas Unidades de Atendimento Integrado de Uberlândia-MG entre 2000 a 2005 / Epidemiological study of burns attended at the Integrated Assistance Units of Uberlandia-MG between 2000 and 2005

Objetivo: Verificar os aspectos epidemiológicos de queimaduras atendidas nas Unidades de Atendimento Integrado (UAIs) de Uberlândia-MG. Método: O trabalho foi realizado com dados referentes aos casos de queimaduras registrados nas UAIs, no período de 2000 a 2005. Foram analisadas as seguintes variáveis: número de pessoas queimadas, faixa etária, local do corpo acometido e profundidade da lesão. Resultados: Houve 12.707 queimaduras, com pico em 2002, seguido de redução nos dois anos seguintes e um novo aumento em 2005. A UAI Roosevelt foi a que apresentou maior quantidade de casos. Houve prevalência dos acidentes na faixa etária entre 20-39 anos, seguido pela faixa de 0-19 anos. Na faixa pediátrica, houve predomínio entre 1-4 anos. Foi observado um porcentual significativo de casos em que o grau da lesão não foi classificado, totalizando 46%. As lesões de segundo grau foram responsáveis por 33% dos casos classificados. A região ocular correspondeu a 13% das queimaduras. Conclusão: Os centros de atendimento primário e secundário refletem de forma mais fidedigna a prevalência do número de queimados. Observou-se diminuição no número de queimados após a lei que proibiu a venda do álcool líquido e posterior aumento quando a lei foi revogada. Houve a prevalência de queimaduras na faixa etária de 20 aos 39 anos, associadas a casos de acidentes de trabalho. As lesões de segundo grau responderam pela maioria dos casos classificados. A queimadura ocular obteve expressividade quando comparada ao restante do corpo. Os dados desse trabalho foram utilizados para originar o projeto de extensão "Uberlândia não quer se queimar".

Objective: To verify the epidemiologic aspects of burns attended at the Integrated Assistance Units (IAUs) of Uberlandia-MG. Methods: This research was realized with data referring to the cases of burns attended at the IAUs between 2000 to 2005. The number of burns, age, part of the body injured and profundity of burn were analised. Results: There were 12.707 burn incidents, with a peak in 2002, followed by a reduction in the subsequent two years and a new increase in 2005. The Roosevelt neighborhood IAU presented the biggest quantity of cases. There was a prevalence of accidents in the age between 20 and 39 years, followed by the age between 0 and 19 years. In the pediatric range, there was predominance between the age of 1 and 4 years. There is an important percentage of cases where the grade of burns were not classified, around 46%. Second grade burns were responsible for 33% of the classified cases. The ocular region corresponded to 13% of the burns. Conclusion: The centers for primary and secondary care reflect in a more trustworthy way the prevalence of the number of burn victims. A decrease in the number of burn victims was observed after the law that prohibited the sale of the liquid alcohol was passed and then a subsequent increase when the law was revoked. There was the prevalence of burns in the age group from 20 to the 39 years, associated with job accidents. The lesions of second grade answered for most of the classified cases. Ocular burns obtained expressiveness when compared to the remaining of the body. The data of this work was used to originate the extension project "Uberlandia doesn't want to burn itself".