DA DISCRICIONARIEDADE À TEORIA DA DECISÃO: A CRÍTICA HERMENÊUTICA DO DIREITO E OS LIMITES DO POSITIVISMO JURÍDICO

O tema é discricionariedade nas teorias do positivismo antes e depois de Dworkin desde a crítica hermenêutica do direito e sua teoria da decisão. O problema é: há a possibilidade de uma teoria da decisão no positivismo, seja ele qual for, mantendo-se intactos os seus princípios metodológicos da descrição e da separação entre direito e moral? O objetivo é apresentar a crítica hermenêutica do direito e sua oposição à discricionariedade dos positivismos. A conclusão é a de que a crítica hermenêutica não é apenas negativa com relação aos positivismos, ela é também positiva e construtiva de uma teoria da decisão

Clinical phenotypic variability in an Italian family bearing the IVS6+ 5_8delGTGA mutation in PGRN gene

Background Frontotemporal dementia (FTD) is a complex presenile disorder characterized by behavioural changes and executive functions, expression of fronto-temporal degeneration. Hereditary FTD accounts for 20-30% of cases and, in the past decade, mutations in the microtubule associated protein tau (MAPT)gene were identified as a main genetic causes of familial FTD. In 2006, mutations in the gene encoding progranulin (PGRN) were reported, to account for a wide part of the familial FTD cases. Clinically, an high phenotypic variability within and among the kindreds is reported in the familial FTD associated with PGRN mutations and occasionally the memory deficits are the first symptoms, resembling Alzheimer's disease (AD). We report an Italian family with dementia associated with a PGRN mutation characterized by a deletion of 4 base pairs inside the intron 6 of the gene, leading to haploin sufficiency In our kindred, all three affected patients carried the mutation, but presented very different clinical phenotypes, evoking FTD, AD and rapidly-progressive dementia mimicking prion disease. Methods Informations on the members of the first, second and third generations were obtained conducting interviews with relatives, while for the three patients studied, the clinical evidence of dementia symptoms and their characterization was documented directly with sequential neurological examinations, cognitive assessments and neuroimaging. Blood sample collection and DNA extraction from peripheral blood lymphocytes for genetic analysis were performed after written informed consent of the patients. Results In our pedigree, the PGRN mutated patients are affected by dementia with three different clinical pictures: FTD, AD and rapidly progressive dementia mimicking prion disease. Neuropsychological examinations supported these diagnoses, documenting generalized deficits of cortical functions in AD patient and deficits in executive functions and in language in FTD patient. Regarding neuroimaging, in the same two cases MRI results do not correspond to the clinical diagnosis. Conclusions These findings confirms the marked heterogeneity of the clinico-radiological features in patients with PGNR mutations and underline the need of considering mutations of this gene as causes of familial dementing diseases with atypical or uncommon features or discrepancies between the clinical and the neuroimaging findings

Letter to the Editor: Acute Effects of Intravenous Administration of Pamidronate in Patients with Osteoporosis

We read the interesting article “Acute Effects of Intravenous Administration of Pamidronate in Patients with Osteoporosis” in the Journal of Korean Medical Science by Lim et al. (1). We would like to comment and compare these data to a study recently published by our research group (2). The two studies had different initial aims, but still they share the same results in determining the modulatory effect of inflammation of aminobisphosphonates, such as pamidronate. The pamidronate belongs to the family of aminobisphosphonates (N-BPs), currently the major class of drugs used for the treatment of osteoporosis and other diseases characterized by increased bone resorption. The immune modulation exerted by pamidronate has not yet fully been understood (3). In vitro experiments have shown an anti-inflammatory effect of this N-BP; (4, 5) as well as a pro-inflammatory one (6, 7). Moreover contrasting results were obtained when pamidronate was used for the treatment of different inflammatory or immunologic diseases, such as rheumatoid arthritis (8,9) or systemic sclerosis. The aminobiphosphonates act on farnesylpyrophosphate synthase (FPPS) and inhibit the mevalonate pathway, the latter being responsible for production of cholesterol and isoprenoid lipids. In particular we can hypothesize that the inflammatory phenotype is due to lack of enzymes downstream the FPPS, and in particular the lack of geranylgeranyl-pyrophosphate (GGPP) could be associated to the activation of caspase-1 and the high IL-1β release. Lim et al. (1) emphasized that in vivo infusion of pamidronate at a therapeutic dose of 30 mg increased production of two inflammatory cytokines, IL-6 and TNF-α in serum. The increase is an acute effect after intravenous injection (1). Recently, our group demonstrated that pamidronate is able to increase the sensitivity to bacterial compounds both in the murine macrophagic cell line (Raw 264.7) and in Balb/c mice, by an incremental release of IL1β. These findings are in agreement with published data concerning inflammatory modulation in alendronate treated-mice (2). Moreover the effect of pamidronate does not depend on its concentration, whereas it may be involved in the increase of susceptibility to pro-inflammatory compounds such as muramildipeptide or lipopolysaccaride (2). In summary, we agree with the study by Lim et al. (1) and we emphasize the pivotal role of pamidronate in the modulation of inflammatory response

Sleep deprivation impairs emotional memory retrieval in mice: Influence of sex

The deleterious effects of paradoxical sleep deprivation on memory processes are well documented. However, non-selective sleep deprivation occurs more commonly in modern society and thus represents a better translational model. We have recently reported that acute total sleep deprivation (TSD) for 6 h immediately before testing impaired performance of male mice in the plus-maze discriminative avoidance task (PM-DAT) and in the passive avoidance task (PAT). in order to extend these findings to females, we examined the effect of (pre-test) TSD on the retrieval of different memory tasks in both male and female mice. Animals were tested using 3 distinct memory models: 1) conditioning fear context (CFC), 2) PAT and 3) PM-DAT. in all experiments, animals were totally sleep-deprived by the gentle interference method for 6 h immediately before being tested. in the CFC task and the PAT, TSD induced memory impairment regardless of sex. in PM-DAT, the memory impairing effects of TSD were greater in females. Collectively, our results confirm the impairing effect of TSD on emotional memory retrieval and demonstrate that it can be higher in female mice depending on the memory task evaluated. (C) 2012 Elsevier Inc. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Associacao Fundo de Pesquisa Pesquisa (AFIP)Universidade Federal de São Paulo, Dept Farmacol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Farmacol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, BR-04023062 São Paulo, BrazilFAPESP: 1998/14303-3Web of Scienc

Food restriction increases long- term memory persistence in adult or aged mice

Food restriction (FR) seems to be the unique experimental manipulation that leads to a remarkable increase in lifespan in rodents. Evidences have suggested that FR can enhance memory in distinct animal models mainly during aging. However, only few studies systemically evaluated the effects FR on memory formation in both adult (3-month-old) and aged (18-24-month-old) mice. Thus, the aim of the present study was to investigate the effects of acute (12 h) or repeated (12 h/day for 2 days) FR protocols on learning and memory of adult and aged mice evaluated in the plus-maze discriminative avoidance task (PM-DAT), an animal model that concurrently (but independently) evaluates learning and memory, anxiety and locomotion. We also investigated the possible role of FR-induced stress by the corticosterone concentration in adult mice. Male mice were kept at home cage with food ad libitum (CTRL-control condition) or subjected to FR during the dark phase of the cycle for 12 h/day or 12 h/2 days. the FR protocols were applied before training, immediately after it or before testing. Our results demonstrated that only FR for 2 days enhanced memory persistence when applied before training in adults and before testing in aged mice. Conversely, FR for 2 days impaired consolidation and exerted no effects on retrieval irrespective of age. These effects do not seem to be related to corticosterone concentration. Collectively, these results indicate that FR for 2 days can promote promnestic effects not only in aged mice but also in adults. (C) 2013 Elsevier Inc. All rights reserved.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Farmacol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Farmacol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, BR-04024002 São Paulo, BrazilWeb of Scienc

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients