119 research outputs found

    Por uma nova concepção de família : a possibilidade jurídica da adoção por casais homoafetivos

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    Orientador: Ana Carla Harmatiuk MatosMonografia (graduação) - Universidade Federal do Paraná, Setor de Ciências Jurídicas, Curso de Graduação em DireitoEste estudo pretende comprovar a possibilidade jurídica de adoção por casais homoafetivos, sob um viés especialmente constitucional. Isso porque, com a constitucionalização do Direito de Família, não é possível restringir direitos por mera interpretação literal da lei. As diferenças devem ser respeitadas, para atender às mudanças da sociedade e, principalmente, aos princípios da dignidade da pessoa humana e da igualdade. Se nossa legislação permite a adoção por indivíduo homossexual isoladamente, tal direito deve ser estendido aos casais que pretendam adotar em conjunto, a fim de satisfazer, principalmente, ao princípio do melhor interesse da criança. Ainda serão explorados por este trabalho: a definição desses e de outros princípios relacionados à adoção, a omissão legislativa sobre o tema e as novas doutrina e jurisprudência, as quais gradativamente vem admitindo a existência de uma entidade familiar homoafetiva e, ainda que timidamente, aprovando a adoção conjunta por pares homossexuais

    Recurrent Urinary Tract Infection: A Mystery in Search of Better Model Systems

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    Urinary tract infections (UTIs) are among the most common infectious diseases worldwide but are significantly understudied. Uropathogenic E. coli (UPEC) accounts for a significant proportion of UTI, but a large number of other species can infect the urinary tract, each of which will have unique host-pathogen interactions with the bladder environment. Given the substantial economic burden of UTI and its increasing antibiotic resistance, there is an urgent need to better understand UTI pathophysiology – especially its tendency to relapse and recur. Most models developed to date use murine infection; few human-relevant models exist. Of these, the majority of in vitro UTI models have utilized cells in static culture, but UTI needs to be studied in the context of the unique aspects of the bladder’s biophysical environment (e.g., tissue architecture, urine, fluid flow, and stretch). In this review, we summarize the complexities of recurrent UTI, critically assess current infection models and discuss potential improvements. More advanced human cell-based in vitro models have the potential to enable a better understanding of the etiology of UTI disease and to provide a complementary platform alongside animals for drug screening and the search for better treatments

    The human renal lymphatics under normal and pathological conditions

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    Ishikawa Y, Akasaka Y, Kiguchi H, Akishima-Fukasawa Y, Hasegawa T, Ito K, Kimura-Matsumoto M, Ishiguro S, Morita H, Sato S, Soh S & Ishii T (2006) Histopathology 49, 265–273 The human renal lymphatics under normal and pathological conditions AIMS: The renal lymphatics have not been fully documented in humans. The aim of this study was to clarify the morphology of the human renal lymphatic system under normal and pathological conditions by immunohistochemistry using anti-D2-40 antibody. METHODS AND RESULTS: Normal and pathological renal tissues obtained at autopsy as well as nephrectomy specimens with renal cell carcinoma (RCC) were used. Thin sections were immunostained with antibodies against D2-40 and CD31. In normal kidney, D2-40+ lymphatics were abundant in the interstitium around the interlobar and arcuate arteries/veins but sporadic in those around the glomeruli or between the tubules in the cortex. A few lymphatics contained erythrocytes in their lumina. Lymphatics were seldom present in the medulla. In RCC cases, lymphatics were evident at the tumour margin, whereas CD31+ capillaries were abundant throughout the tumour and lymphatics were increased in the fibrous interstitium around the tumour. Lymphatic invasion by RCC cells was also detectable. D2-40+ lymphatics were evident in other pathological conditions and end-stage kidney had a denser lymphatic distribution than normal kidney. CONCLUSIONS: Lymphatics are abundant around the arteries/veins and are also present in the renal cortex and medulla. D2-40 immunostaining is helpful for investigating the pathophysiological role of renal lymphatics

    Reassessment of Routine Midstream Culture in Diagnosis of Urinary Tract Infection

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    Midstream urine culture (MSU) remains the gold standard diagnostic test for confirming urinary tract infection (UTI). We previously showed that patients with chronic lower urinary tract symptoms (LUTS) below the diagnostic cut-off on MSU culture may still harbour bacterial infection, and that their antibiotic treatment was associated with symptom resolution. Here, we evaluated the results of the UK's MSU culture in symptomatic patients and controls. Next, we compared the bacterial enrichment capabilities of the MSU culture with a 50 µl uncentrifuged culture, a 30 ml centrifuged sediment culture, and 16S rRNA gene sequencing. This study was conducted on urine specimens from 33 LUTS patients attending their first clinical appointment (mean age = 49 years, standard deviation [SD] = 16.5), 30 LUTS patients on treatment (mean age = 47.8 years, SD = 16.8) whose symptoms had relapsed, and 29 asymptomatic controls (mean age = 40.7 years, SD = 15.7). We showed that the routine MSU culture, adopting the UK interpretation criteria tailored to acute UTI, failed to detect a variety of bacterial species, including recognised uropathogens. Moreover, the diagnostic MSU culture was unable to discriminate between patients and controls. In contrast, genomic analysis of urine enriched by centrifugation discriminated between the groups, generating a more accurate understanding of species richness. In conclusion, the UK's MSU protocol misses a significant proportion of bacteria, which include recognised uropathogens, and may be unsuitable for excluding UTI in patients with LUTS

    Class II MHC Self-Antigen Presentation in Human B and T Lymphocytes

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    Human CD4[superscript +] T cells process and present functional class II MHC-peptide complexes, but the endogenous peptide repertoire of these non-classical antigen presenting cells remains unknown. We eluted and sequenced HLA-DR-bound self-peptides presented by CD4[superscript +] T cells in order to compare the T cell-derived peptide repertoire to sequences derived from genetically identical B cells. We identified several novel epitopes derived from the T cell-specific proteome, including fragments of CD4 and IL-2. While these data confirm that T cells can present peptides derived from the T-cell specific proteome, the vast majority of peptides sequenced after elution from MHC were derived from the common proteome. From this pool, we identified several identical peptide epitopes in the T and B cell repertoire derived from common endogenous proteins as well as novel endogenous epitopes with promiscuous binding. These findings indicate that the endogenous HLA-DR-bound peptide repertoire, regardless of APC type and across MHC isotype, is largely derived from the same pool of self-protein.National Institutes of Health (U.S.) (grant P01AI039671)National Institutes of Health (U.S.) (P01AI045757

    Obstrução intestinal por fitobezoar: revisão integrativa

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    O fitobezoar é uma massa indigerível composta por vegetais e fibras de frutas, formando um corpo sólido capaz de causar obstrução intestinal. Embora apresente baixa prevalência, fitobezoar é uma etiologia importante em regiões geográficas com alto consumo de alimentos fibrosos. Avaliar a obstrução intestinal causada pelo fitobezoar e entender os fatores de risco. Trata-se de uma revisão integrativa na base de dados PUBMED utilizando os descritores “PHYTOBEZOAR AND OBSTRUCTION’’ para artigos publicados entre 2019 e 2024. Os fitobezoares são raramente as causas das obstruções intestinais (4% dos casos). A manifestação clínica pode variar de acordo com a localização exata do bezoar e de sua composição, o diagnóstico pode ser feito a partir de uma tomografia computadorizada com contraste. A formação de fístulas, ulcerações e aderências são complicações recorrentes, casos graves são comuns principalmente em pacientes com afecções pregressas no TGI. Pacientes com idades superiores a 65 anos passam por mais tratamentos cirúrgicos (60%) em relação a pacientes com idades inferiores (40%). Intervenções cirúrgicas prévias como o tratamento para úlcera péptica foi o maior fator de risco entre os pacientes, a idade não influenciou na prevalência. O fitobezoar é causa pouco prevalente de obstrução intestinal. No entanto, é de difícil diagnóstico e pode causar complicações graves para o paciente como perfuração e sangramento gástrico, formação de fístulas, ulcerações e aderências. A literatura é escassa com predomínio de relatos de caso, sendo necessário a realização de novos estudos mais robustos

    A mathematical model of microbial folate biosynthesis and utilisation: implications for antifolate development

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    The metabolic biochemistry of folate biosynthesis and utilisation has evolved into a complex network of reactions. Although this complexity represents challenges to the field of folate research it has also provided a renewed source for antimetabolite targets. A range of improved folate chemotherapy continues to be developed and applied particularly to cancer and chronic inflammatory diseases. However, new or better antifolates against infectious diseases remain much more elusive. In this paper we describe the assembly of a generic deterministic mathematical model of microbial folate metabolism. Our aim is to explore how a mathematical model could be used to explore the dynamics of this inherently complex set of biochemical reactions. Using the model it was found that: (1) a particular small set of folate intermediates are overrepresented, (2) inhibitory profiles can be quantified by the level of key folate products, (3) using the model to scan for the most effective combinatorial inhibitions of folate enzymes we identified specific targets which could complement current antifolates, and (4) the model substantiates the case for a substrate cycle in the folinic acid biosynthesis reaction. Our model is coded in the systems biology markup language and has been deposited in the BioModels Database (MODEL1511020000), this makes it accessible to the community as a whole

    Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

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    The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes
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