Generation of intersubtype human immunodeficiency virus type 1 recombinants in env gene in vitro: Influences in the biological behavior and in the establishment of productive infections

The occurrence of human immunodeficiency virus type 1 (HIV-1) recombinant genomes belonging to different subtypes is a common event in regions where more than two subtypes cocirculate. Although there are accumulating data toward an increase in the number of intersubtype recombinants, little has been addressed about the biological behavior of such mosaic genomes. This work reports the biological characterization of engineered in vitro HIV-1 intersubtype recombinants in the gp120 region. the recombinants possess the entire gp120 of B or F Brazilian Isolates in the Z6 (subtype D) backbone. Hers we show that this type of recombinant structure results in profound impairment to the establishment of productive infections in CD4-positive cells. the characterization of biological properties of those recombinant viruses demonstrated viral production occurring only during a transient peak early on infection and that they are not able to down-regulate the expression of CD4 receptor on the cell surface. We also report the phenotype reversion of one recombinant virus studied here, after 62 days in culture. Two amino acid substitutions in highly constant gp120 regions (C1 and C4) were identified in the revertant virus. the mutation occurring in the C4 region is localized near two amino acid residues critical for gp120/CD4 interaction. Based on these data, we suggest that failure in CD4 down-modulation by recombinant viruses can be due to a structural dysfunction of gp160 protein unable to block CD4 at the endoplasmic reticule. the possibilities that the establishment of latent infections can be directly related to the continuous expression of CD4 on the infected cell surface and that the occurrence of mutations in amino acid nearby residues critical for gp120/CD4 interaction can restore the fully productive infectious process are discussed. (C) 2000 Academic Press.Univ Fed Rio de Janeiro, Inst Biol, Dept Genet, Mol Virol Lab, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Disciplina Doencas Infecciosas & Parasitarias, Lab Retrovirol,UNIFESP,EPM, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Disciplina Doencas Infecciosas & Parasitarias, Lab Retrovirol,UNIFESP,EPM, São Paulo, BrazilWeb of Scienc

Uso das Pironofatoquinona como antiviral; composição farmacêutica contendo as Piranonaftoquinonas; medicamento contendo as Piranonaftoquinonas para tratamento de infecções causadas por virus da dengue

DepositadaDescreve o uso das Piranonaftoquinonas, assim como seus derivados, seus isômeros e seus sais como um agente antiviral, por inibir as enzimas ATPases viral. Além disso, também, faz parte desta invenção uma composição farmacêutica contendo as Piranonaftoquinonas descritas

Fibrossarcoma em sítio de osteossíntese de fêmur com pino e placa em um felino

A 6-year old spayed female Siamese cat was presented with a history of left limb acute lameness. Radiographic imaging revealed a complete comminuted diaphyseal femur fracture, which was corrected through intramedullary pin placement along with plate osteosynthesis. After two months the animal returned to the hospital presenting severe diffuse enlargement of the left hindlimb, characterized as a non-delimited, solid, and firm plaque-like mass surrounding the pin and bone, which extended from the femorotibiopatelar joint to the pelvis, and infiltrated the adjacent musculature. Incisional biopsy exam indicated a highly malignant sarcoma. The entire limb was surgically removed and sent to histopathological evaluation. Microscopically, the mass was composed of spindle shaped cells, displaying high pleomorphism and cellular atypia. Abundant collagen production was evidenced through Masson’s trichrome stain and strong cytoplasmic staining for vimentin. These results were consistent with fibrosarcoma. The cat went through one session of chemotherapy; however, tumor recurrence occurred 20 days later, and the animal was submitted to euthanasia. This is the first description of fibrosarcoma arising in the vicinity of an intramedullary pin and plate in a cat.Uma gata, castrada, 6 anos de idade, da raça Siamês, apresentou histórico clínico de claudicação aguda do membro pélvico esquerdo. O exame radiográfico revelou uma fratura completa cominutiva diafisária do fêmur, a qual foi corrigida através de osteossíntese pela implantação de um pino intramedular, além de placa metálica. Depois de dois meses, o felino retornou ao hospital apresentando aumento severo e difuso do membro pélvico, caracterizada por uma massa não delimitada, sólida, como uma placa, circundando o pino e o osso, a qual se estendia da articulação femorotibiopatelar até a pelve, e infiltrava a musculatura adjacente. A biópsia incisional indicou sarcoma de alta malignidade. O membro inteiro foi cirurgicamente removido e enviado para análise histopatológica. Microscopicamente, a massa era composta por células fusiformes, demonstrando alto pleomorfismo e atipia celular. Abundante produção de colágeno foi evidenciada através da técnica histoquímica de tricrômico de Masson e forte imunomarcação citoplasmática para vimentina. Esses resultados foram consistentes com fibrossarcoma. O felino foi submetido a uma sessão de quimioterapia, porém houve recorrência tumoral 20 dias após a sessão, e o paciente foi submetido a eutanásia. Essa é a primeira descrição de fibrossarcoma que surgiu em local próximo a implantação de pino intramedular e placa em um felino

Increased Serum Alkaline Phosphatase in a FeLV-Positive Cat

Background: Feline Leukemia Virus (FeLV) is an oncogenic virus that usually invades bone marrow causing non-regenerative anemia and thrombocytopenia. In FeLV positive cats, the myeloid leukemia is characterized by intense proliferation of blast cells in a bone marrow with myeloid precursor predominance and several malignancies degree. The leukocyte alkaline phosphatase is found secondary granules of mature neutrophils of humans, horses and cows but not in dogs and cats,which demonstrate the enzyme activity in myeloblast and promyeloblasts cells. In this case is describing a FeLV-positive case with leukemic disorder accompanied by extremely high levels of serum alkaline phosphatase.Case: A 8-year-old castrated male Domestic Short Hair cat with a 3-month history of convulsions, pica, vomits, lethargy, hypodipsia and anorexia was examined and showed mild dehydration, severe jaundice and hyperpnoea. Laboratory results evidenced severe normocytic hypochromic non-regenerative anemia, moderated leukocytosis with severe degenerativeneutrophil left shift, moderated lymphocytosis and severe thrombocytopenia. Serum biochemical profle showed mild hyperalbuminemia, moderated increment in alanine transaminase and severe increment in alkaline phosphatese. The cat waspositive for ELISA point of care FeLV antigen and negative for FIV antibodies. Urinalysis revealed moderated bilirubinuria and proteinuria. The bone marrow cytology showed high cellularity, increased of M:E ratio, rare megakaryocyte lineage, erythroid hypoplasia, myeloid hyperplasia with blast excess and dysgranulopoiesis.Discussion: FeLV is a virus that usually causes cytopenias and in this case this was well evidenced through a severe non regenerative anemia and thrombocytopenia. Generally, anemia is a non-neoplastic complication of FeLV mainly related to suppressive effects hematopoietic and stromal cells of the bone marrow. Nevertheless, in this case, the anemia also maybe attributable to the observed acute myeloid leukemia. Neutrophilia is an uncommon fnding in FeLV-infected cats, even more with the severe degenerative left shift as in the present case. This fnding could be associated to a myeloid hyperplasia. Some biochemical alterations, as hyperalbuminemia and increment in values of serum ALT could be explained by clinical observations like dehydration and some degree of hepatic enlargement, respectively. However, the excessive value forserum alkaline phosphatase activity is an unpublished fnding in cats. In humans high levels of ALP has been associated with neutrophilia and it is quite likely that a great amount of degenerative neutrophils may contribute for high leakage of ALP than in other circumstances of neutrophilia. This is the frst report of a FeLV-positive cat exhibiting extremely high serum values of the enzyme ALP, possibly attributable to acute myeloid leukemia.Keywords: neutrophilia, cytopenia, non-regenerative anemia, acute leukemia

O engatinhar: um estudo da idade de seu aparecimento e de sua relação com a aquisição da marcha

The present research aimed to investigate the age of appearance of crawling, its relationship with the walking acquisition. Thirty-five normal children between 5 and 13 months of age were selected from São Carlos' day-care, whose crawling and walking were not yet stated. The children were observed during 7 months and the ages of appearance of the motor behaviors were recorded in specific evaluation index cards. Statistical Survival Analysis of the data showed that most of the children began to crawl between 7 to 10 months of age (81%) and the largest probability of incidence occurred at the 7"' month (24%). Walking appeared between 10 and 15 months of age (83%); its largest probability of incidence occurred at the 13 month (21%). Just 5.7 % of all children did not present crawling as a transient mode of locomotion. Results obtained in the present study suggested an anticipation of the crawling acquisition when compared to findings of searched literature. Furthermore, the minimum latency period of 3 months between both motor behaviors seems to indicate that the crawling experience is a pre - requisite to gain the walking acquisition. Research was developed under permission of parents, according to the resolution 1/88 from CNS.O estudo investigou a idade de emergência do comportamento engatinhar e sua relação com a aquisição da marcha. Foram selecionadas 35 crianças normais, dos berçários da cidade de São Carlos, com idades entre 5 e 13 meses, que ainda não apresentavam o engatinhar e a marcha. Estas foram observadas por um período de 7 meses e os comportamentos motores, bem como a época de seus aparecimentos, foram registrados em fichas de avaliação. Através do teste Análise de Sobrevivência, evidenciou-se que a maioria das crianças iniciou o engatinhar entre o 7o e 10° meses de vida (71%), sendo que a maior probabilidade de incidência ocorreu no 7o mês (24%). A marcha iniciou-se entre o 10°e 15° meses de idade (83%), com maior probabilidade de incidência no 13" mês (21%). Apenas 5,7% da amostra não apresentou o engatinhar como forma transitória de locomoção. Os dados obtidos sugerem uma antecipação do início do engatinhar em relação aos achados da literatura. Além disso, diante da existência de um período de latência mínimo de 3 meses entre os comportamentos motores estudados, parece que a experiência do engatinhar constitui um pré-requisito para a aquisição da marcha. Pesquisa desenvolvida com anuência dos responsáveis pelos participantes do estudo, de acordo com a resolução 01/88 do CNS

AVALIAÇÃO MORFOLÓGICA E MORFOMÉTRICA DO ÚTERO DE CAMUNDONGOS FÊMEAS APÓS USO DE EXTRATO DE GRAVIOLA

The present study aimed to evaluate the effect of Annona muricata extract on the uterus of female mice by macro and microscopic analyzes. Twenty female mice were randomly assigned to four groups: control (saline solution), cyclophosphamide, and soursop leaf extract at two different concentrations (50 and 100 mg/kg). After seven days of the experiment, the females were euthanized and their wombs were collected and submitted for to macroscopic analysis, followed by histological processing for morphological and morphometric analyses of uterine layers and endometrial glands. The macroscopic characteristics of the uterus were maintained in all groups evaluated. Microscopically, no pathological changes were identified in the uterine cells. However, there was a significant increase in the myometrium layer after the treatment with cyclophosphamide (p<0.05). The internal endometrial glands diameter was significantly smaller in both groups treated with A. muricata extract compared to the control group (p<0.05), while the total glands diameter was significantly smaller only at the highest concentration of A. muricata extract compared to the control group (p<0.05). The administration of A. muricata leaf extract did not cause morphological changes to the uterus. Thus, the extract did not present uterine toxicity under the conditions evaluated.O presente estudo teve como objetivo avaliar o efeito do extrato de Annona muricata no útero de camundongos fêmeas por meio de análises macro e microscópicas. Vinte camundongos fêmeas foram aleatoriamente distribuídas em quatro grupos: controle (solução salina), ciclofosfamida e extrato de folhas de graviola em duas concentrações diferentes (50 e 100mg/kg). Após sete dias de experimento, as fêmeas foram eutanasiadas e seus úteros coletados e submetidos a análise macroscópica, seguida de processamento histológico para análises morfológicas e morfométricas das camadas do útero e das glândulas endometriais. As características macroscópicas do útero foram mantidas em todos os grupos avaliados. Microscopicamente, não foram identificadas alterações patológicas nas células uterinas. No entanto, houve um aumento significativo na camada do miométrio após o tratamento com ciclofosfamida (p<0,05). O diâmetro interno das glândulas endometriais foi significativamente menor em ambos os grupos tratados com extrato de A. muricata quando comparados ao grupo controle (p<0,05), enquanto o diâmetro total das glândulas foi significativamente menor somente na maior concentração de extrato de A. muricata quando comparado ao grupo controle (p<0,05). A administração do extrato de folhas de A. muricata não causou alterações morfológicas ao útero. Desta forma, o extrato não apresentou toxicidade uterina nas condições avaliadas

A ESCASSEZ QUE NUTRE A DOENÇA: DESDOBRAMENTOS DA INSEGURANÇA ALIMENTAR NA SAÚDE GLOBAL

The systematic and lasting lack of regular access to quality food in sufficient quantities to sustain a healthy existence is an extremely important problem. Food and nutrition, as fundamental pillars for the promotion and preservation of health, play a crucial role in ensuring the integral development and quality of life of individuals integrated into a society. This research explores the consequences of food insecurity on global health, highlighting the underlying factors, their manifestations and the cascading effects that can perpetuate the cycle of disease. This is an integrative literature review, through a search in the Virtual Health Library (VHL), using the Health Sciences Descriptors (DeCS): "Food Insecurity" and "Social Vulnerability", crossed with the Boolean operator "AND". Inclusion criteria: articles related to the theme, freely available, in full text, in Portuguese, published in the last five years (2018-2023). And as exclusion criteria: articles that did not address the theme, repeated in the aforementioned database, as well as abstracts, course completion works, dissertations and theses. The results show that food insecurity contributes to malnutrition, exacerbating nutritional deficiencies and increasing vulnerability to infectious diseases, especially in already susceptible populations. The analysis also highlights distinct geographical patterns, with conflict-affected areas showing higher levels of food insecurity and adverse health consequences. Therefore, an integrated approach is essential to tackle food insecurity and its impacts on global health. Promoting sustainable food systems, reducing structural inequalities and global collaboration emerge as crucial elements to overcome the interconnected challenges. This study highlights the urgency of comprehensive interventions to mitigate the adverse effects of food insecurity and promote health on a global scale.A ausência sistemática e duradoura de acesso regular a alimentos de qualidade em quantidades suficientes para sustentar uma existência saudável constitui uma problemática de extrema relevância. A alimentação e nutrição, enquanto pilares fundamentais para a promoção e preservação da saúde, desempenham um papel crucial no asseguramento do desenvolvimento integral e da qualidade de vida dos indivíduos integrados em uma sociedade. Esta pesquisa explora os desdobramentos da insegurança alimentar na saúde global, destacando os fatores subjacentes, suas manifestações e os efeitos em cascata que podem perpetuar o ciclo da doença. Trata-se de uma revisão integrativa de literatura, mediante a busca na Biblioteca Virtual em Saúde (BVS), pelos Descritores em Ciências da Saúde (DeCS): “Insegurança Alimentar” e “Vulnerabilidade Social”, em cruzamento com o operador booleano “AND”. Como critérios de inclusão: artigos relacionados à temática, disponíveis gratuitamente, em texto completo, em português, publicados nos últimos cinco anos (2018-2023). E como critérios de exclusão: artigos que não abordassem a temática, repetidos na base supracitada, além de resumos, trabalhos de conclusão de curso, dissertações e teses. Os resultados revelam que a insegurança alimentar contribui para a desnutrição, exacerbando deficiências nutricionais e aumentando a vulnerabilidade a doenças infecciosas, especialmente em populações já suscetíveis. A análise também destaca padrões geográficos distintos, com áreas afetadas por conflitos apresentando níveis mais elevados de insegurança alimentar e consequências adversas para a saúde. Portanto, a abordagem integrada é essencial para enfrentar a insegurança alimentar e seus impactos na saúde global. A promoção de sistemas alimentares sustentáveis, a redução de desigualdades estruturais e a colaboração global emergem como elementos cruciais para superar os desafios interconectados. Este estudo destaca a urgência de intervenções abrangentes para mitigar os efeitos adversos da insegurança alimentar e promover a saúde em escala global

A SARS-CoV-2 Negative Antigen Rapid Diagnostic in RT-qPCR Positive Samples Correlates With a Low Likelihood of Infectious Viruses in the Nasopharynx

Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) transmission occurs even among fully vaccinated individuals; thus, prompt identification of infected patients is central to control viral circulation. Antigen rapid diagnostic tests (Ag-RDTs) are highly specific, but sensitivity is variable. Discordant RT-qPCR vs. Ag-RDT results are reported, raising the question of whether negative Ag-RDT in positive RT-qPCR samples could imply the absence of infectious viruses. To study the relationship between negative Ag-RDT results with virological, molecular, and serological parameters, we selected a cross-sectional and a follow-up dataset and analyzed virus culture, subgenomic RNA quantification, and sequencing to determine infectious viruses and mutations. We demonstrated that RT-qPCR positive while SARS-CoV-2 Ag-RDT negative discordant results correlate with the absence of infectious virus in nasopharyngeal samples. A decrease in sgRNA detection together with an expected increase in detectable anti-S and anti-N IgGs was also verified in these samples. The data clearly demonstrate that a negative Ag-RDT sample is less likely to harbor infectious SARS-CoV-2 and, consequently, has a lower transmissible potential

Protocol for evaluating the in vitro effect of violet light-emitting diodes (LEDs) 410 nm ± 10 nm on yeast cultures

BACKGROUND: Candida spp and Malassezia spp cause superficial infections that may be resistant to conventional treatments. Violet light-emitting diodes (LEDs) therapy is a therapeutic alternative. PURPOSE: To describe the protocol for evaluating the antifungal effect of violet LEDs 410 nm ± 10 nm on Candida spp and Malassezia spp in vitro. PROTOCOL: LEDs 410 nm ± 10 nm are applied to a fungal suspension at fluences of 61.13 J/cm2, 91.70 J/cm2, and 183.39 J/cm2. The isolates are cultured for 48 to 72 hours. Colony forming units (CFUs) are quantified by visual counting and percent culture plate occupancy by digital analysis. Morphology is assessed by light microscopy and Gram staining, and yeast metabolism/function by transmission electron microscopy, assessment of reactive oxygen species, and DNA fragmentation. DATA ANALYSIS: the percentage of LEDs inhibition is calculated considering the growth of the negative control condition and the percentage of plate occupancy by yeasts by dividing the number of pixels classified as colonies by the total number of pixels on the plate. The morphological and functional aspects are described for the intervention and negative control. The ANOVA test is used to compare the mean percentages of growth inhibition and plate occupancy between the three fluences of LEDs 410 nm ± 10 nm and the negative control. ESTIMATED RESULTS: We intend to determine the antifungal effect of the different fluences of LEDs 410 nm ± 10 nm on Candida spp and Malassezia spp. The evaluation of other fungal species by this protocol should be investigated