Abstract The SARS-CoV-2 coronavirus pandemic calls for coordinated efforts by the scientific community for the development of vaccines. The most advanced strategies have focused on modifications of technologies that were already under development for other viruses, such as SARS, MERS, and even Influenza. Classic and new technologies, such as inactivated and attenuated viruses (non-replicative and replicative), DNA and mRNA vaccines, and nanoparticles containing SARS-CoV-2 antigens, are some of the strategies currently investigated. Although there is a very high expectation for the effectiveness of the most advanced vaccine candidates, there are still no established correlates of protection. Previous experience in vaccine development for other pathogens shows that differences in vaccine formulation can result in diverse immune responses and consequently, different protective properties. Therefore the importance of continuing investigations on a broad range of strategies. Expertise in vaccine development in Brazil was refocused to the new coronavirus. Impressive collaboration between institutions will support further developments until we have available a safe, effective, and economically viable vaccine. Established competence and collaborations will allow preparedness for future challenges and can also be used to address local issues as neglected infectious diseases.

Several isatin derivatives have shown important biological activities, which have attracted interest from researchers. For this reason, the present study aimed to evaluate the anti-inflammatory and antinociceptive effects of the isatin derivative (Z)-2-(5-chloro-2-oxoindolin-3-ylidene)-N-phenyl-hydrazinecarbothioamide (COPHCT) in mice. Three doses of this compound were tested: 1.0, 2.5, and 5.0 mg/kg. The anti-inflammatory activity was assessed using the carrageenan-induced paw edema model and the zymosan-induced air pouch model. The evaluation of the antinociceptive effect was performed through the formalin test and the acetic acid-induced abdominal writhing test. The paw edema assay demonstrated that all doses of the compound showed a significant reduction of the edema in the second hour evaluated, but a better response was observed in the fourth hour. The zymosan-induced air pouch model indicated that the compound, in all doses, significantly reduced leukocyte migration and total protein concentration levels. In the formalin test, the doses 1.0, 2.5, and 5.0 mg/kg of COPHCT showed activity only in the second phase, with reduction in paw pain time of 73.61, 79.46, and 73.85%, respectively. The number of abdominal writhings decreased with the increasing dose, but only 5.0 mg/kg COPHCT exhibited a significant response, with a reduction of 24.88%. These results demonstrated the ability of this compound to interfere in the anti-inflammatory activity of edema, vascular permeability, and cell migration. In addition, its possible antinociceptive effect may be related to the dose used.

RESUMO: O objetivo desta pesquisa foi avaliar a influência das células do colostro no desenvolvimento imune em bezerras leiteiras durante os primeiros 28 dias de vida. Os animais foram distribuídas em 2 grupos: COL+ (n=9) recebeu colostro fresco de suas próprias mães; e COL- (n=10) recebeu pool de colostro congelado sem células viáveis oriundo de vacas doadoras. Estas bezerras foram avaliadas antes da ingestão do colostro (D0); às 48 horas (D2) e semanalmente entre o D7 e D28. O desenvolvimento da imunidade foi avaliada pela fenotipagem das subpopulações celulares do sangue e produção de citocinas pelas células mononucleares sanguíneas após 72 horas de estimulação com concanavalina A (ConA), Staphylococcus aureus (S. aureus) e Escherichia coli (E. coli) inativadas. O histórico clínico das bezerras foi marcado por elevada frequência de diarreias em ambos os grupos. Entretanto, COL- apresentou maior intensidade de diarreia (escore de fezes ~ 3 de 4) e maior temperatura retal no D7 do que as bezerras COL+. Além disso, broncopneumonia (n=1) e inflamações umbilicais foram diagnosticadas apenas nas bezerras COL-. O grupo COL- apresentou menor concentração de ferro sérico e maior número de linfócitos no D7 do que o grupo COL+. COL- também apresentou maior frequência de anemias que o grupo COL+ no D21 e D28. Em geral, a fração das subpopulações celulares foram semelhantes entre os dois grupos ao longo do tempo estudado, exceto na semana 1, onde as bezerras COL- apresentaram maior proporção de CD45RO+ (P=0.07). Observou-se um constante aumento de CD45RO+ com declínio concomitante de CD45RO- ao longo do estudo, indicando o desenvolvimento da resposta imune. A proporção de células CD14MHCII+ aumentou de acordo com a idade (P≤0.05). As medianas das citocinas produzidas a partir do PBMC não estimuladas apresentaram valores abaixo do nível de detecção em ambos os grupos. O PBMC do COL+ estimulado com ConA secretou elevada concentração de IL17 na semana 2 (COL+=2060.0pg/mL e COL-=0.0pg/ml, P=0.00). PBMC do COL+ estimuladas com S. aureus inativado (P=0.05) e E. coli inativada (P=0.05) secretaram níveis mais elevados de IL17 que as bezerras COL- na semana 4. Outros picos de IL17 foram observados no COL+ na semana 2, porém não foi possível detectar diferenças estatísticas entre os grupos. Conclui-se que as bezerras alimentadas com colostro fresco e congelado apresentaram perfil similar entre as proporções das subpopulações celulares. O aumento de células expressando os marcadores de memória CD45RO+ e CD14MHCII+ demonstram, ao longo do experimento, o amadurecimento do sistema imune específico das bezerras após estimulação natural por patógenos após o nascimento. A maior secreção de IL17 pelas células das bezerras COL+ indica que as células maternas podem modular resposta imune Th17 direcionada aos antígenos bacterianos. Este mecanismo poderia ser responsável pela rápida e eficiente quimiotaxia de neutrófilos e eliminação dos microrganismos bacterianos. Os diferentes perfis de citocinas podem ser responsáveis pelos diferentes históricos clínicos relatados para as bezerras COL+ e COL-.

ABSTRACT: The objective of this study was to evaluate the influence of viable cells from colostrum on immune development in dairy heifer calves during the first 28 days of life. The animals were distributed between 2 groups: COL+ (n=9) receiving fresh whole colostrum from their own damns; and COL- (n=10) receiving pooled frozen colostrum, containing no viable cells, from a pool of donor cows. These calves were assessed before colostrum intake (D0), 48 hours of age (D2), and weekly from D7 to D28. The development of immunity was evaluated by assessment of the phenotype of blood leukocyte subsets, and induced cytokine production after 72 hours of stimulation in culture with concanavalin A (ConA), killed Staphylococcus aureus (S.aureus) and killed Escherichia coli (E. coli) by peripheral blood mononuclear cell (PBMC). The clinical history of these calves was marked by a high frequency of diarrhea in both groups. However, COL- had greater diarrhea intensity scores (fecal score~3 of 4), and rectal temperature on D7 than COL+ calves. Moreover, bronchopneumonia (n=1) and navel inflammation were observed only in COL- calves. COL- had a lower concentration of serum iron, and a higher absolute number of lymphocytes on D7 than COL+. COL- also had a higher percentage of anemic calves than the COL+ calves on D21 and D28. In general, the percent of cells within each subset of leukocytes was similar between the groups over the experiment, except on week 1 when COL- calves had a higher percentage of lymphocytes expressing CD45RO+ (P=0.07). A steady increase in CD45RO+ and concomitant decline in CD45RO- leukocytes was observed over the course of the study, indicating the development of immune memory. The proportion of CD14MHCII+ leukocytes increased with age (P≤0.05). The median background cytokine production by PBMC that were not stimulated was below the level of detection of the assays used for both groups. The PBMC from COL+ calves stimulated with ConA secreted a larger quantity of IL-17 week 2 (COL+=2060.0pg/mL and COL-=0.0pg/mL, P=0.00). PBMC from COL+ calves stimulated with killed S. aureus whole cell antigen (P=0.05) and killed E. coli whole cell antigen (P=0.05) also secreted higher levels of IL17 than COL- calves at week 4. Clear production of IL17 was observed in PBML from COL+ calves at week 2, but the difference was not statistical different between groups. In conclusion, calves fed fresh and frozen colostrum showed no difference in cells subset profile overall. The increased percentage of leukocytes expressing the memory CD45RO+ or CD14MHCII+ over the course of the experiment indicated a maturation of the adaptive immune response after natural exposure to pathogens in the environment of the calf. The enhanced IL17 secretion by COL+ calves indicated that viable maternal cells modulated T-cell Th17 production that was primed by bacterial antigens. This mechanism could be responsible for quick and efficient activation of neutrophils for bacterial clearance. The differences in cytokine production observed between groups may help to explain the different clinical pictures observed for calves COL+ and COL- calves.

Introdução: Fibromialgia é uma condição que envolve dor crônica generalizada. Além disso, mulheres de meia idade com fibromialgia apresentam alterações no padrão de marcha, expondo-se prematuramente a um padrão de marcha semelhante ao encontrado na população idosa. Objetivo: Determinar os parâmetros espaciais (linear e angular) da marcha de mulheres com fibromialgia e compará-los com idosas sem essa condição. Métodos: 25 mulheres (10 no grupo com fibromialgia e 15 no grupo de idosas) se qualificaram como voluntárias para participar do estudo. A análise cinemática foi realizada por meio de um sistema optoeletrônico, e as variáveis lineares e angulares foram determinadas. Resultados: Ambos os grupos apresentaram similaridades na velocidade da marcha, tamanho da passada, cadência e amplitude de movimento do quadril, joelho e tornozelo (p > 0,05), exceto para a rotação da pelve, na qual o grupo com fibromialgia apresentou maior rotação de quadril (p < 0,05) quando comparado ao grupo de idosas. Além disso, houve correlação negativa no grupo com fibromialgia entre rotação do quadril e dor no glúteo (r = -0,69; p < 0,05), e entre obliquidade da pelve e dor na região do trocanter maior (r = -0,69; p < 0,05). Conclusão: Mulheres de meia idade com fibromialgia apresentaram um padrão de marcha similar ao de idosas, o qual é caracterizado por amplitude de movimento, tamanho da passada e velocidade da marcha reduzidos.

Background: Fibromyalgia is a condition which involves chronic pain. Middle-aged individuals with fibromyalgia seem to exhibit changes in gait pattern, which may prematurely expose them to a gait pattern which resembles that found in the elderly population. Objective: To determine the 3 D spatial (linear and angular) gait parameters of middle-aged women with fibromyalgia and compare to elderly women without this condition. Methods: 25 women (10 in the fibromyalgia group and 15 in the elderly group) volunteered to participate in the study. Kinematics was performed using an optoelectronic system, and linear and angular kinematic variables were determined. Results: There was no difference in walking speed, stride length, cadence, hip, knee and ankle joints range of motion between groups, except the pelvic rotation, in which the fibromyalgia group showed greater rotation (P < 0.05) compared to the elderly group. Also, there was a negative correlation with pelvic rotation and gluteus pain (r = - 0.69; P < 0.05), and between pelvic obliquity and greater trochanter pain (r = - 0.69; P < 0.05) in the fibromyalgia group. Conclusion: Middle-aged women with fibromyalgia showed gait pattern resemblances to elderly, women, which is characterized by reduced lower limb ROM, stride length and walking speed.

O objetivo deste trabalho foi avaliar o efeito de quatro níveis de adubação orgânica (0, 3, 6, e 9 kg m-2) na produção de óleo essencial de Lippia sidoides Cham. (Verbenacea) e de suas pragas. Observou-se maior número de ácaro vermelho Tetranychus sp. (Acari: Tetranychiidae) na face inferior das folhas dos terços medianos e basais das plantas de L. sidoides com oito semanas de idade cultivadas com 6 kg m-2 de adubo orgânico. Por outro lado, a menor quantidade deste ácaro foi notada na testemunha (0 kg m-2). L. sidoides cultivada com 6 kg m-2 de adubo orgânico produziu maior quantidade de óleo essencial. Observou-se maior número de cochonilhas Phenacoccus sp. (Hemiptera: Pseudococcidae) nas folhas apicais, sem distinção de face foliar, das plantas de L. sidoides com nove e 10 semanas de idade cultivadas com 3 kg m-2 de adubo orgânico. Não se detectou efeito significativo de adubo orgânico sobre Aphis gossypii Glover (Hemiptera: Aphididae). Contudo, observou-se maior número desse pulgão bem como de seu predador Scymnus sp. (Coleoptera: Coccinelidae) nas faces abaxiais das folhas basais das plantas de L. sidoides com oito semanas de idade. A dose de adubo orgânico recomendada para produção de óleo essencial de L. sidoides é de 6 kg m-2. Contudo, essa dosagem favorece o ataque de Tetranychus sp. e, quando necessário, deve-se dirigir a pulverização sempre para a face inferior da folha, local preferencial de ataque dos artrópodes.

The objective of this paper was to study the effect of four levels of organic fertilization (0, 3, 6 and 9 kg m-2) to produce the essential oil of Lippia sidoides Cham. (Verbenacea) and its pests. A higher number of red mite Tetranychus sp. (Acari: Tetranychiidae) was observed on the abaxial face of the median and basal leaves of L. sidoides plants with eight weeks of age cultivated with 6 kg m-2 of organic fertilization. On the other hand, the smallest number of this mite was noted in control (0 kg m-2). L. sidoides cultivated with 6 kg m-2 of organic fertilization produced a greater quantity of essential oil. The highest number of mealy bug Phenacoccus sp. (Hemiptera: Pseudococcidae) was observed on the apical leaves (both leaf surfaces) of L. sidoides plants with nine and ten weeks of age cultivated with 3 kg m-2 of organic fertilization. No significant effect of the organic fertilization on Aphis gossypii Glover (Hemiptera: Aphididae) was detected. However, a greater number of this aphid and of its predator Scymnus sp. (Coleoptera: Coccinelidae) was observed on the abaxial face of the bottom leaves of L. sidoides plants with eight weeks of age. The dose of organic fertilization recommended for the production of essential oil of L. Sidoides is 6 kg m-2, however, one must pay attention to the fact this dosage favors the attack by Tetranychus sp.. And, when needed, pulverization must always be directed to the lower surface of the leaf.

Calcium (Ca2+) is a versatile second messenger that regulates a wide range of cellular functions. Although it is not established how a single second messenger coordinates diverse effects within a cell, there is increasing evidence that the spatial patterns of Ca2+ signals may determine their specificity. Ca2+ signaling patterns can vary in different regions of the cell and Ca2+ signals in nuclear and cytoplasmic compartments have been reported to occur independently. No general paradigm has been established yet to explain whether, how, or when Ca2+ signals are initiated within the nucleus or their function. Here we highlight that receptor tyrosine kinases rapidly translocate to the nucleus. Ca2+ signals that are induced by growth factors result from phosphatidylinositol 4,5-bisphosphate hydrolysis and inositol 1,4,5-trisphosphate formation within the nucleus rather than within the cytoplasm. This novel signaling mechanism may be responsible for growth factor effects on cell proliferation.

Estimaram-se, no estado de Minas Gerais, a prevalência e a distribuição espacial da anemia infecciosa eqüina (AIE) em propriedades com eqüídeos de serviço. As amostras de sangue, de 6540 eqüídeos de 1940 rebanhos foram coletadas no período de setembro de 2003 a março de 2004, nos 853 municípios do estado. Utilizaram-se dois testes de laboratório em seqüência: ELISA, usando-se antígeno recombinante gp90, e imunodifusão em gel de ágar (IDGA). As prevalências foram de 5,3% [IC=4,3 a 6,3%] para rebanhos e de 3,1% [IC=2,2 a 3,9%] para animais. O estado de Minas Gerais foi considerado área endêmica para AIE. As mais altas prevalências para rebanhos e para animais foram encontradas na região Norte/Noroeste, seguida pela região Vale do Mucuri/Jequitinhonha.

The prevalence and spatial distribution of equine infectious anemia (EIA) were estimated in livestock herds where equids were used as draft power and for transportation in the State of Minas Gerais, Brazil. Serum samples were collected from September/2003 to March/2004 in 853 municipalities of the state. The sample comprised 6,540 equids from 1,940 herds. Two laboratorial tests were performed in sequence: ELISA using a recombinant gp90 protein, following by the AGID. The prevalence in the herds was estimated in 5.3% [CI = 4.3 to 6.3%], and 3.1% [CI = 2.2 to 3.9%] of the animals tested were positive. Minas Gerais was considered an endemic region for EIA. The highest prevalence for herds and animals was found in North/Northwest region (strata) followed by Vale do Mucuri/Jequitinhonha region.

OBJETIVO: A reestenose intra-stent é a maior limitação das intervenções coronárias percutâneas. O carbeto de silício amorfo (SiC-a), substância antitrombótica e antiinflamatória capaz de reduzir a deposição de fibrina, plaquetas e leucócitos sobre o stent, apresenta potencial de prevenir a hiperplasia neo-intimal e a reestenose. MÉTODOS: Estudo prospectivo, randomizado e tipo rótulo aberto comparando pacientes com doença coronariana tratados com e sem stents revestidos com o SiC-a, utilizando a angiografia quantitativa e o ultra-som intracoronário. Foram incluídos 100 pacientes (50 em cada grupo) a fim de mensurar o volume de hiperplasia neo-intimal intra-stent/extremidades. Como os stents comparados apresentavam extensões diferentes, o volume de hiperplasia foi analisado em valores absolutos (por paciente) e relativos (por milímetro de extensão do stent). Avaliaram-se ainda os eventos cardíacos maiores e os resultados da angiografia quantitativa. RESULTADOS: Os grupos apresentaram características de base semelhantes. Todos os pacientes foram tratados com sucesso. No 6° mês de evolução foram reestudados 94% dos casos dos dois grupos, obtendo-se ultra-som em 92%. O volume de hiperplasia neo-intimal absoluto foi significativamente maior nos tratados com os stents revestidos (51.2 DP 18.8 mm³ vs 41.9 DP 16.4 mm³; p=0.014), porém o relativo foi semelhante (2.9 DP 1.0 mm³/mm stent vs 2.5 DP 0.9 mm³/mm stent; p=0.108). A obstrução volumétrica da luz também foi similar (36.4 DP 11.1% vs 37.9 DP 10.9%; p=0.505). O diâmetro mínimo da luz (1.9 DP 0.7 mm vs 1.8 DO 0.6 mm; p=0.552), a reestenose (19.1% vs 17%; p>0.999) e a revascularização do vaso-alvo (16% vs 14%; p>0.999) não diferiram. CONCLUSÃO: Os stents revestidos apresentaram resultados clínicos, angiográficos e ultra-sonográficos similares aos controles.

OBJECTIVE: In-stent restenosis remains a major limitation following coronary stent implantation. Amorphous silicon-carbide (a-SiC) coating has been shown to improve stent biocompatibility, therefore, reducing local inflammation and thrombus generation. Due to the latter, a-SiC coating might have an impact on the prevention of neointimal hyperplasia (NIH) and restenosis. METHODS: This prospective, randomized, open-label trial compared a-SiC-coated (group A) versus uncoated (group B) stent implantation in de novo lesions. We included 100 patients (50 patients in each group) and the primary end-point was in-stent volume of NIH measured by intravascular ultrasound. RESULTS: All patients underwent successful stent deployment. Although absolute NIH volume was greater in A (51.2 mm³ SD 18.8 mm³ versus 41.9 mm³ SD 16.4 mm³; P = 0.014), relative (divided per mm of stent length) NIH volume was similar (2.9 mm³/mm stent SD 1.0 mm³/mm stent versus 2.5 mm³/mm stent SD 0.9 mm³/mm stent; P = 0.108). Late loss, restenosis, and major adverse cardiac events (MACE) were similar. CONCLUSION: A-SiC-coated stents did not reduce either NIH or MACE at long-term follow-up.

A distribuição de anticorpos neutralizantes para o herpesvirus bovino 1 (HVB 1) foi estudada em quatro faixas etárias de bovinos, em 21 rebanhos de leite e de corte. Os resultados da sorologia foram analisados e relacionados com as respostas de questionários aplicados aos responsáveis pelos rebanhos. As taxas de freqüência de anticorpos neutralizantes para o HVB 1 foram comparadas segundo a aptidão e a faixa etária. Fatores como tipo de manejo e idade dos animais influenciaram na distribuição de anticorpos para o HVB 1.

The distribution of neutralizing antibodies to bovine herpesvirus 1 (BHV 1) was studied in 21 beef and dairy cattle herds, in four different age groups. The results were analyzed and related with answers given to a questionnaire proposed to the farmers. The frequency rates of neutralizing antibodies for the BHV 1 were compared according to the dairy or beef herds and age of the animals. The animal husbandry and age influenced the distribution of neutralizing antibodies to this virus.

Os venenos de Bolhrops são compostos por várias frações protéicas. Dentre elas, as miotoxinas induzem lesões musculares importantes. A purificação deste componente envolve várias etapas e, embora forneça frações puras, é muito trabalhosa. Neste trabalho foi descrito um método rápido para o isolamento da fração miotóxica do veneno de Bothrops neuwiedi (jararaca pintada), utilizando-se uma etapa única de purificação por Cromatografia Liquida de Alta Eficiência (CLAE). O procedimento completo demorou apenas 30 min. Foram isoladas duas frações com atividade miotóxica, cuja pureza foi verificada por eletroforese em gel de poliacrilamida-SDS. A injeção intramuscular no músculo tibial anterior de ratos induziu alterações morfológicas precoces, indicando que a membrana plasmática foi a primeira estrutura celular afetada pela fração miotóxica. A lesão muscular obtida foi tipicamente mionecrótica e foi observado infiltrado inflamatório.

Bothrops venoms are composed by several protein fractions. Among these fractions there are myotoxins which induce an important muscle lesion. The purification of this component involves some steps, although providing a pure material, is time consuming. In the present study, we describe a quick method for myotoxin fraction isolation from the venom of Bolhrops nsuwiedi using one-step high performance liquid chromatography (HPLC). The complete procedure took 30 min. The pur6+y of the two myotoxic fractions isolated was assessed by SDS-PAGE. Upon i.m. injection into rat tibialis anterior, both toxins induced early morphological changes, indicating that the plasma membrane was the first cellular structure affected. Afterwards, the lesion was typically myonecrotic and inflammatory infiltrate was present.

Abstract - An Aerated Submerged Biological Filter was used to promote biological nitrification of a synthetic saline wastewater. Black PVC corrugated plates were used to make the structured packing of the 6 liter reactor. Nitrate, nitrite, and ammonia concentrations, pH and DO were periodically measured, according to APHA (1985). In spite of the deleterious effect of salinity, it was possible to obtain nitrogen removal efficiencies as high as 95% for a 25 g/L salt concentration after a three-day reaction in the batch reactor. Continuous operation using a NaCl concentration of 25 g/L was tested using three different hydraulic retention times: 7, 15, and 25 hours. An increase in ammonia removal was observed when the retention time was increased from 7 to 15 hours. However, no further notable increase was obtained for a 25 hour retention time, showing that nitrogen removal tends towards a maximum limit of about 80%.