Protocolo estadual para atendimento de casos suspeitos ou confirmados de síndrome inflamatória multssistêmica em adultos (SIM-A) associada à covid-19 / State protocol for the care of suspected or confirmed cases of multisystemic inflammatory syndrome in adults (SIM-A) associated with covid-19

Desde abril de 2020, em vários países da Europa, América do Norte e inclusive no Brasil, foram identificados casos de crianças e adolescentes com uma nova apresentação clínica associada à Covid-19 e caracterizada por um quadro inflamatório tardio e exacerbado, denominada em português como Síndrome Inflamatória Multissistêmica Pediátrica (SIM-P). Evidências posteriores mostram que, em casos raros, indivíduos adultos (acima dos 20 anos) também podem desenvolver uma síndrome semelhante, associada à infecção atual ou anterior pelo SARS-CoV-2.1-3. Relatos desses pacientes destacam o reconhecimento de uma síndrome hiperinflamatória multissistêmica em adultos, com heterogeneidade de sinais e sintomas clínicos.4 A maioria dos pacientes apresenta febre e hipotensão e uma pequena parcela pode apresentar sintomas similares à síndrome de Kawasaki, síndrome de ativação macrofágica e síndrome do choque tóxico.5 No Brasil, a síndrome foi nomeada de Síndrome Inflamatória Multissistêmica em Adultos (SIM-A). Alguns casos suspeitos dessa condição já foram identificados no país e notificados voluntariamente pelos profissionais de saúde da assistência.

Relatório de recomendação para adoção de um protocolo estadual para atendimento de casos suspeitos ou confirmados de síndrome inflamatória multissistêmica em adultos (SIM-A) associada à covid-19 / Recommendation report for the adoption of a state protocol for the care of suspected or confirmed cases of multisystemic inflammatory syndrome in adults (SIM-A) associated with covid-19

Este relatório refere-se à análise crítica da Nota Técnica do Ministério da Saúde nº 38/2022-DEIDT/SVS/MS1 apresentada pela DIVE/SES/SC para a elaboração de um Protocolo Estadual de Atendimento para Casos Suspeitos ou Confirmados de Síndrome Inflamatória Multissistêmica em Adultos (SIM-A) associada à Covid-19. Na Nota Técnica emitida pelo Ministério da Saúde consta uma breve contextualização, objetivos da notificação, quadro clínico de SIM-A, definições de casos, exames complementares, exames específicos para COVID-19, manejo clínico, notificação e registro. Este relatório visa avaliar e emitir um parecer técnico embasado em evidências científicas sobre a disponibilização do medicamento Imunoglobulina Humana intravenosa (IGHIV) para o tratamento de SIM-A, fluxo de acesso ao medicamento e avaliação do impacto orçamentário, para posterior elaboração de um Protocolo Estadual para esta síndrome, destinado aos profissionais da saúde, pacientes e gestores do estado de Santa Catarina.

Protocolo estadual para tratamento farmacológico da hipertensão arterial pulmonar no âmbito do SUS em Santa Catarina complementar ao protocolo clínico e diretrizes terapêuticas do ministério da saúde / State protocol for the pharmacological treatment of pulmonary arterial hypertension within the scope of the SUS in Santa Catarina, complementary to the clinical protocol and therapeutic guidelines of the Ministry of Health

A Hipertensão Pulmonar (HP) é uma síndrome clínica e hemodinâmica ampla. O conceito recente, apresentado no 6º Simpósio Mundial em 2018 , define a HP como uma pressão média da artéria pulmonar >20 mm/Hg e Teste de Reatividade Vascular Pulmonar (RVP) ≥3 woods em repouso, aferidos obrigatoriamente pelo cateterismo cardíaco direito.

Protocolo estadual para atendimento de casos suspeitos ou confirmados de síndrome de trombose com trombocitopenia (STT) associada à vacinação com vacinas de vetor de adenovírus não replicante contra a covid-19 / State protocol for the care of suspected or confirmed cases of thrombosis syndrome with thrombocytopenia (STT) associated with vaccination with non-replicating adenovirus vector vaccines against covid-19

Os efeitos generalizados exercidos pela pandemia da doença do Coronavírus 2019 (COVID-19) obrigaram governos e instituições de saúde mundiais a deslocar recursos para a contenção da crise sanitária e a desenvolver métodos para reduzi-los. As vacinas foram elencadas como principal método para conter a pandemia, com mais de um bilhão de doses administradas em todo o mundo. Entre as vacinas produzidas até o momento para combate ao vírus causador, SARS-CoV-2, estão as vacinas de vetores de adenovírus da Oxford-AstraZeneca (AZD1222) e a da Johnson & Johnson (Ad26.COV2.S). Após a implementação da vacinação em massa da população mundial, relatou-se um distúrbio pró-trombótico extremamente raro associado a ambas vacinas com trombocitopenia concomitante e desenvolvimento de anticorpos antiplaquetários fator 4 (anti-PF4). Esta desordem foi denominada inicialmente como Síndrome da Trombose com Trombocitopenia (STT) e posteriormente como Trombose Trombocitopênica Imune induzida por Vacina (TTIV). Os primeiros casos de trombose relacionados à vacinação para o SARS-CoV-2 começaram a ser reportados no final de fevereiro de 2021. Os relatos levaram à abertura de uma investigação pelas Agências do Reino Unido de Regulação de Produtos de Saúde e Medicina (MHRA) e Europeia de Medicina (EMA), as quais anunciaram em 11 de março de 2021 que não havia uma associação identificada. Entretanto, três grupos de cientistas da Noruega, Alemanha e Reino Unido reportaram, na semana seguinte, um caso de trombose localizada no seio venoso cerebral com trombocitopenia e anticorpos antiplaquetários fator 4 em um indivíduo que havia recebido a vacina da Oxford-AstraZeneca. Após maiores investigações, em 7 de abril de 2021, MHRA e EMA anunciaram a nova Síndrome de Trombose com Trombocitopenia e anticorpos antiplaquetários fator 4. Em 11 de novembro de 2021, houve a elaboração de uma definição de caso para STT, realizada pelo Brighton Collaboration, a qual engloba 5 critérios: (1) evidência de trombocitopenia sem exposição recente à heparina; (2) presença de trombose ou tromboembolismo confirmado por exame de imagem, procedimento cirúrgico, exame patológico ou dor de cabeça persistente com elevação de D-dímero (sugerindo trombose de seio venoso cerebral); (3) sintomas clínicos de trombose (Quadro 1); (4) exames de imagem e achados laboratoriais que confirmem o diagnóstico de trombose ou tromboembolismo; (5) achados laboratoriais que confirmem o diagnóstico de anticorpos de ativação plaquetária mediados por trombose, como enzima-imunoensaio (EIA) positivo para anti-PF4 e teste funcional positivo de ativação plaquetária com adição de PF4.

Relatório de recomendação final para adoção de um protocolo estadual no estado de Santa Catarina complementar ao protocolo clínico e diretrizes terapêuticas do ministério da saúde para tratamento farmacológico da hipertensão pulmonar no âmbito do SUS / Final recommendation report for the adoption of a state protocol in the state of Santa Catarina complementary to the clinical protocol and therapeutic guidelines of the Ministry of Health for pharmacological treatment of pulmonary hypertension within the scope of the SUS

Este relatório refere-se à análise crítica do documento "Diagnóstico e Tratamento de Hipertensão Pulmonar'', elaborado pela ACAPTI e enviado como proposta para elaboração de Protocolo Estadual de Hipertensão Pulmonar, contemplando o tratamento farmacológico de HP grupo 1 (HAP) e grupo 4 (HPTEC). No documento encaminhado pelo demandante consta uma breve introdução e contextualização da patologia, diagnóstico clínico e exames complementares, critérios de inclusão e exclusão, especialidades médicas, estratificação de risco e seguimento, tratamento medicamentoso, algoritmo de tratamento medicamentoso, acessos aos medicamentos e centros de referência. Os itens relacionados ao diagnóstico foram mantidos neste relatório, conforme o documento enviado pelo demandante. Este relatório visa avaliar e emitir um parecer técnico embasado em evidências científicas sobre a disponibilização do medicamento Selexipague, a disponibilização da terapia combinada (Ambrisentana, Bosentana, Sildenafila, Ilopros a e Selexipague) para o tratamento da HP grupo 1 (HAP), a disponibilização do medicamento Riociguate para tratamento de HP grupo 4 (HPTEC), algoritmo de tratamento medicamentoso e fluxo de acesso aos medicamentos, para posterior elaboração de um Protocolo Estadual para a patologia solicitada. O Protocolo Estadual será elaborado complementarmente ao protocolo do Ministério da Saúde, assim, caso os medicamentos englobados nele sejam incorporados para a patologia em questão pela CONITEC, o fornecimento dos mesmos passa a ser por meio do CEAF.

Relatório de recomendação para adoção de um protocolo estadual para atendimento de casos suspeitos ou confirmados de síndrome de trombose com trombocitopenia (STT) associada à vacinação com as vacinas de vetor de adenovírus não replicante contra a covid-19 em Santa Catarina / Recommendation report for the adoption of a state protocol for the care of suspected or confirmed cases of thrombosis syndrome with thrombocytopenia (STT) associated with vaccination with non-replicating adenovirus vector vaccines against covid-19 in Santa Catarina

Este relatório refere-se à análise crítica dos documentos apresentados pelo CRIE/DIVE/SES/SC para a elaboração de um Protocolo Estadual de atendimento para casos de Síndrome de Trombose com Trombocitopenia (STT) associada à vacinação com vacinas de vetor de adenovírus não replicante contra a COVID-19, baseados na Nota Técnica CGPNI/DEIDT/SVS/MS nº 933/2021. Na Nota Técnica emitida pelo Ministério da Saúde consta uma breve contextualização, a investigação da STT, protocolo de investigação laboratorial, manejo clínico de casos e definição de casos para investigação de STT. O documento enviado pelo CRIE/DIVE/SES/SC intitulado "Fluxograma de Atendimento TTS" apresentou os dados da nota supracitada resumidos com a adição de um fluxograma de atendimento hospitalar. Este relatório visa avaliar e emitir um parecer técnico embasado em evidências científicas sobre a disponibilização dos medicamentos Imunoglobulina Humana intravenosa (IGHIV) e Rivaroxabana para o tratamento de STT, fluxo de aces o aos medicamentos e avaliação do impacto orçamentário, para posterior elaboração de um Protocolo Estadual para esta síndrome, destinado aos profissionais da saúde, pacientes e gestores do estado de Santa Catarina.

Clerodane Diterpenes from the Marine Sponge Raspailia bouryesnaultae Collected in South Brazil.

The marine sponge Raspailia bouryesnaultae, collected in South Brazil, was selected for detailed investigation considering the results of a screening that pointed to an in vitro antiproliferative effect against non-small cells of human lung cancer (A549) and anti-herpes activity against Herpes Simplex virus type 1 (KOS and 29R strains) of ethanolic extracts. The fractionation and chemical investigation of the sponge's hexanic fraction led to the isolation and structural elucidation of six clerodane diterpenes. The main component was identified as the already-reported raspailol (1), isolated from a sponge of the same genus collected in New Zealand. The structure of a new diterpene (2) with a rearranged skeleton was established by high-resolution mass spectrometry (HRMS) and 1D and 2D Nuclear magnetic resonance spectroscopy (NMR) experiments, and named here as raspadiene. Furthermore, four diterpenes were elucidated as isomers of clerodane diterpenes previously obtained from plants, namely kerlinic acid (3), kerlinic acid methyl ester (4), annonene (5), and 6-hydroxyannonene (6). They differ in their stereochemistry, since these diterpenes are characterized by a trans ring fusion at the decalin moiety and the relative configuration of the two methyl groups at C-8 and C-9 in a cis relationship (type trans/cis). The Raspailia diterpenes have a cis ring fusion at the decalin moiety, and the two methyl groups at C-8 and C-9 are in a trans relationship (type cis/trans). The isolated compounds were evaluated for their potential antiproliferative effects on human cancer cell line A549, and it was observed that the diterpenes bearing a hydroxyl group at C-6 exhibited moderate cytotoxic activity, with 50% inhibitory concentration (IC50) values lower than 25 µM. The evaluation of the potential anti-herpes activity against Herpes Simplex Virus type 1 (HSV-1, KOS and 29R strains) showed that the more promising results were observed for the new compound 2, since it inhibited HSV-1 (KOS and 29R strains) replication by 83% and 74%, respectively.

Molecular networking prospection and characterization of terpenoids and C15-acetogenins in Brazilian seaweed extracts.

Molecular networking (MN) can efficiently dereplicate extracts and pure compounds. Red algae of the genus Laurencia are rich in halogenated secondary metabolites, mainly sesquiterpenes and C15-acetogenins. Brown algae of the genus Dictyopteris produce mainly C11-hydrocarbons, sesquiterpenes and sulfur-containing compounds, while Dictyota and Canistrocarpus are reported to contain mainly diterpenes. This study performs an exploratory MN analysis of 14 extracts from algae collected in Brazil (including the oceanic islands) and characterizes the secondary metabolites from the analyzed species. The extracts and some isolated metabolites were analyzed by LC-MS using the FastDDA algorithm, and the MS/MS spectra were submitted to GNPS and displayed in Cytoscape 3.5.1. The GNPS platform generated 68 individual nodes and nine family networks. The MN exploratory analysis indicated chemical differences among species, and also in sampling sites for the same species. For some extracts, it was possible to identify mass values that could correspond to terpenoids and C15-acetogenins that have already been isolated from those or related species. An interesting chemodiversity was highlighted between Laurencia catarinensis from two nearby islands, and this was revealed and was also suggested by the family networks. Many nodes in the MN could not be characterized, and these metabolites can be used as targets for isolation in future works.

C15 acetogenins from the Laurencia complex: 50 years of research – an overview

Abstract Acetogenins are secondary metabolites derived from the polyketide pathway and their potential role as chemotaxonomical markers for red algae belonging to the Laurencia complex has been long pointed out. C15 acetogenins from algae are quite different from plant acetogenins: they are usually halogenated, and have an enyne or a bromoallene terminal group. Since they were first reported, laurencin and other algal acetogenins have inspired great curiosity among natural product chemists and also those working with synthesis. This paper reviews the literature about C15 acetogenins, focusing on their distribution, chemical and biological aspects, including their reported biological activities.

Cytotoxic activity of semi-synthetic derivatives of elatol and isoobtusol.

In the present study, the in vitro cytotoxic effects of six semi-synthetic derivatives of elatol (1) and isoobtusol (2) were investigated. Chemical modifications were performed on the hydroxyl groups aiming to get derivatives of different polarity, namely the hemisuccinate, carbamate and sulfamate. The structural elucidation of the new derivatives was based on detailed NMR and MS spectroscopic analyses. The in vitro cytotoxicity of compounds 1 to 8 was evaluated against A459 and RD tumor cell lines with CC50 values ranging from 4.93 to 41.53 µM. These results suggest that the structural modifications performed on both compounds could be considered a good strategy to obtain more active derivatives.

Evaluation of impacts of climate change and local stressors on the biotechnological potential of marine macroalgae: a brief theoretical discussion of likely scenarios

Climate change can be associated with variations in the frequency and intensity of extreme temperatures and precipitation events on the local and regional scales. Along coastal areas, flooding associated with increased occupation has seriously impacted products and services generated by marine life, in particular the biotechnological potential that macroalgae hold. Therefore, this paper analyzes the available information on the taxonomy, ecology and physiology of macroalgae and discusses the impacts of climate change and local stress on the biotechnological potential of Brazilian macroalgae. Based on data compiled from a series of floristic and ecological works, we note the disappearance in some Brazilian regions of major groups of biotechnological interest. In some cases, the introduction of exotic species has been documented, as well as expansion of the distribution range of economically important species. We also verify an increase in the similarities between the Brazilian phycogeographic provinces, although they still remain different. It is possible that these changes have resulted from the warming of South Atlantic water, as observed for its surface in southeastern Brazilian, mainly during the winter. However, unplanned urbanization of coastal areas can also produce similar biodiversity losses, which requires efforts to generate long-term temporal data on the composition, community structure and physiology of macroalgae.

Anti-tumour effects of elatol, a marine derivative compound obtained from red algae Laurencia microcladia.

OBJECTIVES: This paper aims to evaluate the anti-tumour properties of elatol, a compound (sesquiterpene) isolated from algae Laurencia microcladia. METHODS: In-vitro and in-vivo anti-tumour properties of elatol were investigated using: MTT assays to assess the cytotoxic effects; flow cytometry analysis to examine the cell cycle and apoptosis; Western blot analysis for determination of the expression of cell cycle and apoptosis proteins; and study of in-vivo tumour growth in mice (C57Bl6 mice bearing B16F10 cells). KEY FINDINGS: Elatol exhibited a cytotoxic effect, at least in part, by inducing cell cycle arrest in the G(1) and the sub-G(1) phases, leading cells to apoptosis. Western blot analysis demonstrated that elatol reduced the expression of cyclin-D1, cyclin-E, cyclin-dependent kinase (cdk)2 and cdk4. A decrease in bcl-xl and an increase in bak, caspase-9 and p53 expression was also observed. In the in-vivo experiment, treatment with elatol was able to reduce tumour growth in C57Bl6 mice. CONCLUSIONS: Elatol promotes a delay in the cell cycle, probably in the G(1)/S transition, activating the apoptotic process and this could be responsible, at least in part, for the in-vivo effects observed. Taken together, the in-vitro and in-vivo experiments suggested that elatol has anti-tumour properties. Further studies should be conducted to clarify the mechanism of action.

Antifouling activities against colonizer marine bacteria of extracts from marine invertebrates collected in the Colombian Caribbean Sea and on the Brazilian coast (Santa Catarina).

The growth inhibition of 12 native marine bacteria isolated from Aplysina sponge surfaces, the shell of a bivalve, and Phytagel immersed for 48 h in sea water were used as indicator of the antifouling activity of the extracts of 39 marine organisms (octocorals, sponges, algae, and zoanthid) collected in the Colombian Caribbean Sea and on the Brazilian coast (Santa Catarina). Gram-negative bacteria represented 75% of the isolates; identified strains belonged to Oceanobacillus iheyensis, Ochrobactrum pseudogrignonense, Vibrio campbellii, Vibrio harveyi, and Bacillus megaterium species and seven strains were classified at genus level by the 16S rRNA sequencing method. The extracts of the octocorals Pseudopterogorgia elisabethae, four Eunicea octocorals, and the sponges Topsentia ophiraphidites, Agelas citrina, Neopetrosia carbonaria, Monanchora arbuscula, Cliona tenuis, Iotrochota imminuta, and Ptilocaulis walpersii were the most active, thus suggesting those species as antifoulant producers. This is the first study of natural antifoulants from marine organisms collected on the Colombian and Brazilian coasts.

Cytotoxic halogenated metabolites from the Brazilian red alga Laurencia catarinensis.

Seven new (1-7) and seven previously reported (8-14) halogenated metabolites were isolated from the organic extract of the Brazilian red alga Laurencia catarinensis. The structure elucidation and the assignment of the relative configurations of the new natural products were based on detailed NMR and MS spectroscopic analyses, whereas the structure of metabolite 6 was confirmed by single-crystal X-ray diffraction analysis. The absolute configuration of metabolite 1 was determined using the modified Mosher's method. The in vitro cytotoxicity of compounds 1-14 was evaluated against HT29, MCF7, and A431 cell lines.

Avaliação de extratos de macroalgas bênticas do litoral catarinense utilizando o teste de letalidade para Artemia salina / Evaluation of macroalgae from Santa Catarina’s coast with the brine shrimp assay

Foram coletadas amostras de algas marinhas de 19 espécies (sendo 4 pertencentes ao filo Chlorophyta, 5 ao filo Phaeophyta e 10 ao filo Rhodophyta) em dois locais do litoral catarinense. Os extratos etanólicos foram submetidos ao teste de letalidade para larvas de Artemia salina com objetivo de realizar uma triagem das espécies. Dos 26 extratos testados, 25 apresentaram toxicidade significativa em pelo menos uma das 3 concentrações testadas. O grupo de algas vermelhas (Rhodophyta) foi o que obteve maior porcentagem de extratos com resultados estatisticamente significativos pelo método do qui-quadrado e também menores valores de CL50, com destaque para Acanthophora spicifera, Hypnea musciformis e Pterocladiella capillacea. Observaram-se diferenças entre as espécies de um mesmo gênero (Codium decorticatum e Codium isthmocladium) e também a influência de fatores ambientais (Hypnea musciformis) na toxicidade dos extratos.

Samples of 19 macroalgae species (4 Chlorophyta, 5 Phaeophyta and 10 Rhodophyta) have been collected from two points of Santa Catarina's coast. The ethanolic extracts were avaluated with the brine shrimp assay in order to perform a screening for potential toxicity. A total of 25 extracts presented significant results in one or more of the tested concentrations. The phylum Rhodophyta presented more statistically significant results with the chi-square test, as well as lower values of LC50. The extracts of Acanthophora spicifera (from Canasvieiras and Ilha do Francês), Hypnea musciformis and Pterocladiella capillacea (both from Ilha do Francês) presented LC50 below 50 mg/mL. Differences between the species of same genus (Codium decorticatum and Codium isthmocladium) and the influence of environmental factors (Hypnea musciformis) were observed.

In vivo assessment of the regulation of transforming growth factor alpha, epidermal growth factor (EGF), and EGF receptor in the human endometrium by medroxyprogesterone acetate.

PURPOSE: The present study evaluated the in vivo effect of medroxyprogesterone acetate (MPA) on the localization of immunoreactive transforming growth factor alpha (TGFalpha), epidermal growth factor (EGF), and their common receptor (EGF-R) in the human endometrium. METHODS: The study design was a randomized clinical trial enrolling 36 healthy women with regular menstrual cycles. The participants were randomly assigned into three groups: groups 1 (n = 11) and 2 (n = 17) received placebo and were submitted to endometrial biopsy during the proliferative and secretory phases of menstrual cycle, respectively; group 3 (n = 8) received MPA (10 mg/day) for 10 days followed by endometrial biopsy, which was performed during the secretory phase. Immunohistochemistry was used to localize TGFalpha, EGF, and EGF-R in the endometrial tissue. RESULTS: TGFalpha was present markedly in the luminal and glandular epithelia but also in the periglandular stroma, with a distribution pattern similar in the three experimental groups. EGF immunostaing was equally distributed in epithelial and stromal layers of the endometrium and remained unchanged in endometrial samples from women treated with MPA compared to placebo. EGF-R was expressed only in the epithelium. The intensity of EGF-R immunostaining was higher in secretory than in proliferative endometrium and was further increased by administration of MPA (p < 0.05, chi-square test). CONCLUSION: The present results suggest that the progestogen-induced in vivo differentiation of secretory endometrium does not require dramatic changes in the expression of EGF or TGFalpha, whereas EGF-R may be up regulated.

Gene expression of type 2 17 beta hydroxysteroid dehydrogenase in scalp hairs of hirsute women.

Androgens are the main hormonal regulators of human hair growth and they are related to clinical conditions such as hirsutism. The aim of this study was to analyze the gene expression of androgen receptor (AR) and type 2 17 beta hydroxysteroid dehydrogenase (17 beta-HSD) in keratinocytes of plucked scalp hairs from hirsute patients and normal subjects. We studied 58 women with hirsutism (31 with polycystic ovary syndrome (PCOS), 27 with idiopathic hirsutism (IH)); 15 control women; and 10 control men. Hirsutism was assessed by a modified Ferriman-Gallwey method. Hormonal status was assessed between days 2 and 10 of the menstrual cycle or on any day when the patients were amenorrheic. AR and type 2 17 beta-HSD mRNA levels were estimated by reverse transcription-polymerase chain reaction (RT-PCR). AR expression was similar in all groups. Type 2 17 beta-HSD gene expression in untreated hirsute patients was lower (2.1+/-0.10) than in normal women (3.1+/-0.17), and similar to men (1.8+/-0.22). Comparing hirsute patients, type 2 17 beta-HSD expression was higher in treated PCOS (3.0+/-0.34 versus 2.2+/-0.13) and IH patients (2.5+/-0.19 versus 2.0+/-0.15); hirsutism score was lower (P=0.003, PCOS; P=0.003, IH); and SHBG levels were higher (P=0.001, PCOS; P=0.024, IH) in treated patients. The free androgen index was lower in treated women (P=0.024 for the IH group). In conclusion, the lower expression of type 2 17 beta-HSD mRNA in scalp hairs of untreated hirsute patients suggests androgen metabolism disturbances with predominance of more potent androgens, as occurs in men. The enzyme's higher gene expression in treated hirsute patients could be an indirect evidence of restored enzyme activity and intracellular androgen metabolism.