Anticorpos antieritrocitários envolvidos na Doença Hemolítica Perinatal: uma revisão da literatura

A doença hemolítica perinatal (DHPN) é caracterizada pela destruição das hemácias fetais por anticorpos da classe IgG presentes na circulação materna. Esses anticorpos, dirigidos contra antígenos eritrocitários presentes nas hemácias do feto, atravessam a barreira placentária e promovem a hemólise prematura dos eritrócitos, levando à anemia fetal. O presente estudo teve como objetivo fazer um levantamento bibliográfico acerca dos principais anticorpos antieritrocitários irregulares envolvidos na DHPN. Foi realizada uma revisão integrativa. Para tal, se procedeu levantamento de artigos científicos nas bases de dados Scientific Eletronic Library Online, (Scielo), Pubmed e Scopus. Dentre os anticorpos irregulares, o anti-D ainda é considerada a principal causa de DHPN. Como o referido antígeno desenvolve-se nos eritrócitos fetais a partir da sexta semana e a circulação fetal já está bem estabelecida com 4 semanas de gestação, a sensibilização por anti-D pode, teoricamente, se instalar desde o segundo mês de gestação. Além do anti-D, outras especificidades de anticorpos dirigidos contra antígenos do Sistema RH incluem: anit-c e em menor prevalência anti-C-, anti-E e anti-e. Já o anti-K do Sistema Kell é a segunda causa de DHPN, após o anti-D. Outros anticorpos incluem aqueles do sistema Duffy, Kidd, MNS e Diego. A ocorrência da hemorragia feto materna com consequente sensibilização da gestante bem como a transfusão de sangue não compatível constitui a base da etiopatogenia da DHPN. Dessa forma, o conhecimento acerca de potentes classes de anticorpos, além do anti-D, envolvidos na doença supracitada, é relevante para melhoria do prognóstico principalmente pela inexistência de imunoprofilaxia

III Diretriz Brasileira de Insuficiência Cardíaca Crônica

Universidade de São Paulo Faculdade de Medicina Hospital das ClínicasUniversidade Federal do Rio Grande do Sul Hospital de Clínicas de Porto AlegreUniversidade de Pernambuco Faculdade de Ciências Médicas de PernambucoUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUniversidade Federal de Minas Gerais Faculdade de MedicinaFaculdade de Medicina de São José do Rio PretoFundação Universitária de Cardiologia do Rio Grande do Sul Instituto de CardiologiaRede Labs D'OrUniversidade Federal FluminenseUniversidade do Estado do Rio de Janeiro Faculdade de Ciencias MédicasInstituto Dante Pazzanese de CardiologiaSanta Casa de MisericórdiaUniversidade de Pernambuco Pronto Socorro Cardiológico de PernambucoHospital Pró CardíacoHospital de MessejanaPontifícia Universidade Católica do ParanáUniversidade Federal de Goiás Faculdade de MedicinaUniversidade de São Paulo Faculdade de Medicina de Ribeirão PretoReal e Benemerita Sociedade de Beneficência PortuguesaFaculdade de Ciências Médicas de Minas GeraisUNIFESP, EPMSciEL

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Anti-Infective Potential of Marine Invertebrates and Seaweeds from the Brazilian Coast

This manuscript describes the evaluation of anti-infective potential in vitro of organic extracts from nine sponges, one ascidian, two octocorals, one bryozoan, and 27 seaweed species collected along the Brazilian coast. Antimicrobial activity was tested against Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212), Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC 25922) and Candida albicans (ATCC 10231) by the disk diffusion method. Antiprotozoal activity was evaluated against Leishmania braziliensis (MHOM/BR/96/LSC96-H3) promastigotes and Trypanosoma cruzi (MHOM/BR/00/Y) epimastigotes by MTT assay. Activity against intracellular amastigotes of T. cruzi and L. brasiliensis in murine macrophages was also evaluated. Antiviral activity was tested against Herpes Simplex Virus type 1 (HSV-1, KOS strain) by the plaque number reduction assay (IC50). Cytotoxicity on VERO cells was evaluated by the MTT assay (CC50). The results were expressed as SI = CC50/IC50. The most promising antimicrobial results were obtained against S. aureus and C. albicans with Dragmacidon reticulatum. Among the seaweeds, only Osmundaria obtusiloba showed moderate activity against P. aeruginosa. Concerning antiprotozoal activity, Bugula neritina, Carijoa riseii, Dragmaxia anomala and Haliclona (Halichoclona) sp. showed the most interesting results, mainly against extracellular promastigote forms of L. braziliensis (66, 35.9, 97.2, and 43.6% inhibition, respectively). Moreover, six species of seaweeds Anadyomene saldanhae, Caulerpa cupressoides, Canistrocarpus cervicornis, Dictyota sp., Ochtodes secundiramea, and Padina sp. showed promising results against L. braziliensis (87.9, 51.7, 85.9, 93.3, 99.7, and 80.9% inhibition, respectively), and only Dictyota sp. was effective against T. cruzi (60.4% inhibition). Finally, the antiherpes activity was also evaluated, with Haliclona (Halichoclona) sp. and Petromica citrina showing the best results (SI = 11.9 and SI > 5, respectively). All the active extracts deserve special attention in further studies to chemically characterize the bioactive compounds, and to perform more refined biological assays

Efeitos da adição de inoculantes microbianos sobre o perfil fermentativo da silagem de alfafa adicionada de polpa cítrica Effects of microbial inoculants on chemical composition and fermentation characteristics of alfalfa silage added with citrus pulp

A cultura de alfafa (19% de MS), cortada com 10% dos perfilhos floridos, foi armazenada em 32 silos experimentais confeccionados a partir de baldes plásticos portando válvulas. A alfafa picada foi homogeneizada e submetida a quatro tratamentos com ou sem a adição de 12% de polpa cítrica peletizada: controle, Sil-All® (S. faecium, P. acidilactici, L. plantarum, amilase, hemicelulase e celulase), Silobac® (L. plantarum, S. faecium e Lactobacillus sp.) e Pioneer 1174® (S. faecium e L. plantarum). Os silos foram abertos após 133 dias para análise da composição bromatológica, perfil fermentativo e estabilidade aeróbia. Apenas na silagem não adicionada de polpa, todos os inoculantes aumentaram os teores de etanol, o Pioneer aumentou o pH e o Silobac reduziu a concentração de ácido acético. Independentemente da presença de polpa, todos os inoculantes diminuíram as perdas de MS; o Silobac e o Pioneer diminuíram a DIVMS e o Pioneer aumentou o N-NH3. Os inoculantes não afetaram as concentrações dos ácidos lático, propiônico ou butírico, bem como a estabilidade aeróbia, independentemente da presença da polpa. De forma geral, a adição de polpa cítrica melhorou a composição bromatológica e o perfil fermentativo, mas piorou as perdas e a estabilidade aeróbia.<br>Alfalfa crop (19.0% DM) was harvested at 35 days and ensiled in 32 plastic experimental silos, consisting of four treatments with or without 12% of citrus pulp: control, Sil-All® (S. faecium, P. acidilactici, L. plantarum, amylase, hemicellulase, and cellulase), Silobac® (L. plantarum, S. faecium, and Lactobacillus sp.) and Pioneer 1174® (S. faecium and L. plantarum). Silos were opened 133 days after ensiling and sampled to proceed chemical analyses. Only in citrus pulp-free silage, all inoculants increased ethanol concentration; Pioneer increased pH, and Silobac decreased acetic acid concentration, compared to control. Independently of citrus pulp, all inoculants decreased DM losses; Silobacâ and Pioneer decreased IVDDM, and Pioneer increased NH3-N. Inoculants did not influence lactic, propionic and butyric acids concentrations and neither aerobic stability. Citrus pulp improved chemical composition and fermentation characteristics, but worsened DM losses and aerobic stability