Recombinant feline interferon omega therapy in cats naturally infected with Feline Immunodeficiency Virus : clinical, viral and immunological relevance

Tese de Doutoramento em Ciências Veterinárias Especialidade de ClínicaType-I Interferons are well-known cytokines which among their main functions are key components of the host immune response against viral infections. Due to its immune modulation properties, they are commonly used in the therapeutic approach of various diseases such as retroviral infections. Recombinant feline interferon omega (rFeIFN-ω) is the first interferon licensed for use in veterinary medicine. Although it is commonly administered in retroviral infections, namely in Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) infected cats, few studies reported its clinical benefits and mechanisms of action. This thesis aims to clarify the main properties of the licensed rFeIFN-ω protocol (3 cycles of 5 daily subcutaneous administrations of 1MU/kg beginning on days 0, 14 and 60) in naturally retroviral infected cats living in an animal shelter, evaluating its effect not only on clinical improvement but also on concurrent viral excretion, viremia/proviral load and various immune biomarkers such as acute phase proteins and cytokine profile. Recognizing the non specific and subtle clinical presentation of the majority of FIV-infected cats, this work also presents and evaluates an alternative oral rFeIFN-ω protocol (0.1MU/cat during 90 days) to be used in client-owned FIV-infected cats. Results showed that the licensed rFeIFN-ω protocol induces a significant clinical improvement, with a concurrent reduction of opportunistic viral infections and an increase on acute phase proteins (APP) profile. The alternative protocol also revealed an important clinical improvement but without significant changes on opportunistic viral infections (which were of low level in the tested group) or on APP profile. In both protocols, no changes were remarked on viremia neither on T-helper 1/T-helper 2 cytokine profiles meaning that this compound may lack an anti-viral activity for retroviruses in vivo and do not act on the acquired immune response of FIV-positive cats. However, there was a significant reduction of the interleukin-6 plasma levels (pro-inflammatory cytokine) in cats treated with the licensed protocol and a decrease on its mRNA expression in cats treated orally. This shows that rFeIFN-ω can have anti-inflammatory properties, which are more evident in the higher doses of the licensed protocol. More than contributing for a better knowledge of rFeIFN-ω, this thesis explores its immune modulation properties and validates a new oral protocol which can be included on future FIV-guidelines.Resumo - A terapêutica com interferão ómega felino em gatos naturalmente infectados com o vírus da imunodeficiência felina: relevância clinica, virológica e imunitária - Os interferões do tipo I são citoquinas chave do sistema imunitário. Devido às suas propriedades imunomoduladoras, são um recurso terapêutico frequente em diferentes doenças como as infecções retrovirais. O interferão ómega felino (rFeIFN-ω) é o primeiro interferão licenciado para medicina veterinária. Apesar do seu uso no tratamento de infeções retrovirais como o vírus da imunodeficiência felina (FIV) e o vírus da leucemia felina (FeLV), são poucos os estudos que fundamentam o seu benefício clinico. Esta tese visa clarificar as propriedades terapêuticas e imunomoduladoras do protocolo licenciado de rFeIFN-ω (3 ciclos de 5 administrações subcutâneas de 1MU/kg uma vez ao dia a iniciar aos dias 0, 14 e 60) em gatos naturalmente infectados por retrovírus e residentes em gatil. Em detalhe, este trabalho avalia o efeito deste fármaco na melhoria clinica, na excreção de vírus concomitantes, na virémia/provirus e na variação de diferentes marcadores imunitários como proteínas de fase aguda e perfil de citoquinas. Esta tese contempla ainda o desenvolvimento de um protocolo terapêutico alternativo baseado na administração oral de rFeIFN-ω (0.1MU/gato durante 90 dias consecutivos) para uso em gatos FIV-positivos domésticos, os quais apresentam geralmente um quadro clinico subtil e pouco específico. Os resultados revelaram que o protocolo licenciado induz uma melhoria clinica significativa com redução concomitante das infecções oportunistas e um aumento do perfil de proteínas de fase aguda (APP). O protocolo alternativo revelou-se eficaz na melhoria clinica dos animais tratados, apesar de não induzir alterações significativas do perfil de APPs nem das infecções concomitantes (residuais no grupo de estudo). Ambos os protocolos não induziram alterações na virémia nem no perfil de citoquinas participantes nas respostas T-helper 1 ou T-helper 2 o que sugere que este composto não apresenta propriedades anti-virais nem actua na imunidade adquirida de gatos FIV positivos. Verificou-se contudo um decréscimo dos niveis plasmáticos de Interleucina-6 (citoquina pro-inflamatória) em gatos tratados com o protocolo subcutâneo e uma redução da sua expressão (mRNA) em gatos tratados por vira oral. Tal demonstra que o rFeIFN-ω apresenta propriedades anti-inflamatórias, as quais são mais evidentes aquando do tratamento com o protocolo licenciado. Mais que uma contribuição para um melhor conhecimento do rFeIFN-ω, esta tese explora as suas propriedades imunomoduladoras e valida um novo protocolo oral, o qual poderá ser incluído em futuras guidelines para o tratamento de gatos FIV-positivos.Trabalho financiado também pelo Centro de Investigação Interdisciplinar em Sanidade Animal (CIISA) da Faculdade de Medicina Veterinária, Universidade de Lisboa e Virbac (Centro de Custos phD_Virbac)

Ultrasonographic detected adrenomegaly in Clinically Ill Cats: a retrospective study

This retrospective study aimed to assess the prevalence of ultrasonographic detected adrenomegaly in clinically ill cats, evaluating the final established diagnosis, describe adrenal ultrasound findings and if the adrenomegaly was suspected or incidental. Abdominal ultrasonography reports of cats presenting to a veterinary teaching hospital between October 2018 and February 2021 were retrospectively reviewed. Cats showing adrenomegaly (one or both glands having a dorsoventral axis >4.8 mm) were selected and medical records respectively evaluated. Nine-hundred and eighty-three ultrasonographical reports were selected, of which, 68 (7%) disclosed adrenomegaly. European/Domestic Short-Hair (62/68; 91%) male (44/68; 65%) castrated (35/44; 80%) cats were overrepresented. Adrenomegaly was an incidental finding in 62/68 (91%) cats while in 6/68 (9%) it was identified in the context of investigating a potential adrenal disease. Concerning established diagnosis, chronic kidney disease was overrepresented (25/68; 37%), followed by endocrinopathies (20/68; 29%). Adrenomegaly was bilateral in 53% (36/68) of cases. In unilateral cases (32/68; 47%), it was more prevalent on the left side (23/32; 72%), with a normal-sized contralateral adrenal gland. Left adrenal demonstrated a larger size and a tendency to oval shape. This study assesses the prevalence of adrenomegaly in clinically ill cats, reinforcing it can be an incidental ultrasound finding.info:eu-repo/semantics/publishedVersio

Ultrasonographic Detected Adrenomegaly in Clinically Ill Cats: A Retrospective Study

This retrospective study aimed to assess the prevalence of ultrasonographic detected adrenomegaly in clinically ill cats, evaluating the final established diagnosis, describe adrenal ultrasound findings and if the adrenomegaly was suspected or incidental. Abdominal ultrasonography reports of cats presenting to a veterinary teaching hospital between October 2018 and February 2021 were retrospectively reviewed. Cats showing adrenomegaly (one or both glands having a dorsoventral axis >4.8 mm) were selected and medical records respectively evaluated. Nine-hundred and eighty-three ultrasonographical reports were selected, of which, 68 (7%) disclosed adrenomegaly. European/Domestic Short-Hair (62/68; 91%) male (44/68; 65%) castrated (35/44; 80%) cats were overrepresented. Adrenomegaly was an incidental finding in 62/68 (91%) cats while in 6/68 (9%) it was identified in the context of investigating a potential adrenal disease. Concerning established diagnosis, chronic kidney disease was overrepresented (25/68; 37%), followed by endocrinopathies (20/68; 29%). Adrenomegaly was bilateral in 53% (36/68) of cases. In unilateral cases (32/68; 47%), it was more prevalent on the left side (23/32; 72%), with a normal-sized contralateral adrenal gland. Left adrenal demonstrated a larger size and a tendency to oval shape. This study assesses the prevalence of adrenomegaly in clinically ill cats, reinforcing it can be an incidental ultrasound finding

Effect of whey storage on physicochemical properties, microstructure and texture profile of ricotta cheese

The aim of this study is to evaluate the effect of whey storage period (0, 24, 48 and 72 h) on the physicochemical parameters, color, texture and microstructure of fresh ricotta during storage. Sweet whey and acid whey were evaluated based on titratable acidity, pH, fat, cryoscopy, and density, while ricotta was based on yield, fat, protein, ash, acidity, pH, moisture, total solids, color, texture, and microstructure. This was done with analysis of variance in a completely randomized design using Tukey test at 5% probability. Whey pH values increased with storage time. Ricotta made with stored whey had average yield of 5.33%, with decreased fat content and pH, and increased acidity. There were subtle differences in color and texture of ricotta during storage; its hardness and gumminess decreased, resulting in microstructure compression. It is concluded that the production of ricotta with whey stored for up to 72 h makes the product appropriate for consumption.Key words: Byproduct, fat, fresh cheese, ricotta, whey cheese, organoleptic properties

Plasma and urinary metanephrine and normetanephrine concentrations using liquid chromatography with tandem mass spectrometry in healthy cats and in a cat with pheochromocytoma

BACKGROUND: Pheochromocytoma (PCC) is rare in cats and plasma (PL) and urinary (U) metanephrines (metanephrine [MN]; normetanephrine [NMN]) measurement is rarely described in cats. OBJECTIVES: We evaluated the utility of PL and U MNs measurement in 10 healthy cats and a cat with a confirmed diagnosis of pheochromocytoma (PheoCat), using liquid chromatography with tandem mass spectrometry (LC-MS-MS). METHODS: Urine and EDTA PL samples collected from each of the 10 cats and the PheoCat were promptly stored at -80°C and remained frozen until analysis. To evaluate U MNs stability, an additional urine sample collected from the healthy cats was refrigerated for 24 hours before freezing. Urinary creatinine concentration (Creat) was assessed using the same spot urine samples to calculate U MNs-to-creatinine ratios. RESULTS: The PL-MN and PL-NMN median concentrations of the healthy cats were 2.73 and 7.02 nmol/L, respectively. The median U-MN/Creat and U-NMN/Creat ratios were 70 and 139 μg/g, respectively. The PheoCat had a PL-MN of 3.68 nmol/L, PL-NMN of 66.27 nmol/L, U-MN/Creat of 179 μg/g, and U-NMN/Creat of 1262 μg/g. The PheoCat had markedly increased concentrations of both PL and U MNs when compared to the healthy cats. No significant difference was found between U MNs measured in urine samples that underwent 24 hours of refrigeration in comparison to those that were frozen immediately. CONCLUSIONS: We report preliminary reference intervals for PL and U MNs in cats using LC-MS-MS and the potential clinical applicability of these biomarkers for the diagnosis of PCC in cats

Fluxos de nitrogênio em feijoeiro irrigado influenciados pela cobertura morta e a fertilização mineral

The objective of this work was to measure the fluxes of N2O‑N and NH3‑N throughout the growing season of irrigated common‑bean (Phaseolus vulgaris), as affected by mulching and mineral fertilization. Fluxes of N2O‑N and NH3‑N were evaluated in areas with or without Congo signal grass mulching (Urochloa ruziziensis) or mineral fertilization. Fluxes of N were also measured in a native Cerrado area, which served as reference. Total N2O‑N and NH3‑N emissions were positively related to the increasing concentrations of moisture, ammonium, and nitrate in the crop system, within 0.5 m soil depth. Carbon content in the substrate and microbial biomass within 0.1 m soil depth were favoured by Congo signal grass and related to higher emissions of N2O‑N, regardless of N fertilization. Emission factors (N losses from the applied mineral nitrogen) for N2O‑N (0.01–0.02%) and NH3‑N (0.3–0.6%) were lower than the default value recognized by the Intergovernmental Panel on Climate Change. Mulch of Congo signal grass benefits N2O‑N emission regardless of N fertilization.O objetivo deste trabalho foi medir os fluxos de N2O‑N e NH3‑N, ao longo de uma safra de feijoeiro irrigado (Phaseolus vulgaris), influenciados pelo uso ou não de cobertura morta e fertilização mineral. Os fluxos de N2O‑N e NH3‑N foram avaliados em áreas com ou sem cobertura de braquiária (Urochloa ruziziensis) ou fertilização mineral. Os fluxos de N também foram medidos em uma área nativa de Cerrado, a qual serviu como referência. As emissões de N2O‑N and NH3‑N foram positivamente relacionadas ao aumento da umidade e das concentrações de amônio e nitrato na área cultivada, na camada até 0,5 m de profundidade do solo. O conteúdo de C no substrato e a atividade microbiana na camada até 0,1 m de profundidade do solo foram favorecidos pela presença da palhada de braquiária e estiveram relacionadas com maiores emissões de N2O‑N, independentemente da fertilização nitrogenada. Os fatores de emissão (perdas de N a partir do nitrogênio mineral adicionado) para N2O‑N (0,01–0,02%) e NH3‑N (0,3–0,6%) foram menores do que o valor estabelecido pelo Painel Intergovernamental de Mudanças Climáticas. A cobertura com braquiária aumenta a emissão de N2O‑N, independentemente da fertilização com nitrogênio

An extensive reef system at the Amazon River mouth

Large rivers create major gaps in reef distribution along tropical shelves. The Amazon River represents 20% of the global riverine discharge to the ocean, generating up to a 1.3 x 10(6)-km(2) plume, and extensive muddy bottoms in the equatorial margin of South America. As a result, a wide area of the tropical North Atlantic is heavily affected in terms of salinity, pH, light penetration, and sedimentation. Such unfavorable conditions were thought to imprint a major gap in Western Atlantic reefs. We present an extensive carbonate system off the Amazon mouth, underneath the river plume. Significant carbonate sedimentation occurred during lowstand sea level, and still occurs in the outer shelf, resulting in complex hard-bottom topography. A permanent near-bottom wedge of ocean water, together with the seasonal nature of the plume's eastward retroflection, conditions the existence of this extensive (similar to 9500 km(2)) hard-bottom mosaic. The Amazon reefs transition from accretive to erosional structures and encompass extensive rhodolith beds. Carbonate structures function as a connectivity corridor for wide depth-ranging reef-associated species, being heavily colonized by large sponges and other structure-forming filter feeders that dwell under low light and high levels of particulates. The oxycline between the plume and subplume is associated with chemoautotrophic and anaerobic microbial metabolisms. The system described here provides several insights about the responses of tropical reefs to suboptimal and marginal reef-building conditions, which are accelerating worldwide due to global changes.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERS)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)BrasoilMCTIBrazilian NavyU.S. NSFGordon and Betty Moore Foundation (GBMF)Univ Fed Rio de Janeiro UFRJ, Inst Biol, BR-21941599 Rio De Janeiro, RJ, BrazilUniv Fed Rio de Janeiro, COPPE, Inst Alberto Luiz Coimbra Posgrad & Pesquisa Engn, Lab Sistemas Avancados Gestao Prod, BR-21941972 Rio de Janeiro, RJ, BrazilInst Pesquisas Jardim Bot Rio de Janeiro, BR-22460030 Rio De Janeiro, RJ, BrazilUniv Sao Paulo, Inst Oceanog, BR-05508120 Sao Paulo, SP, BrazilUniv Fed Espirito Santo, Dept Oceanog, BR-29199970 Vitoria, ES, BrazilUniv Estadual Norte Fluminense, Lab Ciencias Ambientais, Ctr Biociencias & Biotecnol, BR-28013602 Campos Dos Goytacazes, RJ, BrazilUniv Fed Fluminense, Inst Geociencias, BR-24210346 Niteroi, RJ, BrazilUniv Fed Fluminense, Inst Biol, BR-24210130 Niteroi, RJ, BrazilUniv Fed Rio de Janeiro, Museo Nacl, BR-20940040 Rio De Janeiro, RJ, BrazilFed Univ Para, Inst Estudos Costeiros, BR-68600000 Braganca, PA, BrazilUniv Fed Sao Paulo, Dept Ciencias Mar, BR-11070100 Santos, SP, BrazilUniv Fed Pernambuco, Dept Oceanog, BR-50670901 Recife, PE, BrazilUniv Georgia, Dept Marine Sci, Athens, GA 30602 USAUniv Fed Paraiba, BR-58297000 Rio Tinto, PB, BrazilUniv Estadual Santa Cruz, Dept Ciencias Biol, BR-45650000 Ilheus, BA, BrazilUniv Fed Sao Paulo, Dept Ciencias Mar, BR-11070100 Santos, SP, BrazilU.S. NSF: OCE-0934095GBMF: 2293GBMF: 2928Web of Scienc

Os aspectos atuais epidemiológicos e clínicos da Monkeypox: uma revisão de literatura

Neste artigo propomos um estudo que visa entender a fisiopatologia da Varíola dos Macacos, bem como seu quadro clínico e sua epidemiologia atual. Revisão de literatura de caráter exploratório, com uma avaliação de pesquisas e casos da prática clínica, em que se fez uma análise da epidemiologia da Varíola dos Macacos e seu quadro clínico. Foram selecionados 31 estudos para compor essa revisão de literatura. Entre as bases de dados selecionadas estão: PubMed, BVS, Google Scholar e SciELO. A análise das pesquisas mostrou uma ascensão da Monkeypox por todo o mundo após o ano de 2022.  A sintomatologia tem sido muito diversa, tendo como principais sinais e sintomas lesões cutâneas, febre e linfadenopatias. A maioria dos casos não precisou de hospitalização. Contudo, em pacientes imunossuprimidos, crianças e gestantes a infecção se mostrou mais perigosa. A Monkeypox deixou de ser endêmica da África Ocidental no ano de 2022 e vem tomando proporções globais desde então. É de suma importância pesquisas epidemiológicas de rotina para que a doença seja controlada de perto e para que os profissionais da saúde tenham consciência de seu quadro clínico para a adequada notificação da doença

Auditory stimulation with Mozart sonata k-448 and heavy metal music improves short-term memory in rats

Objectives. We aimed to assess the effect of both classical and heavy metal music on short-term and long-term memory. Methods. Male rats were separated into three groups: Mozart (n=14), rats were exposed to Mozart´s K-448 piano sonata; Heavy Metal (n=15), rats were exposed to Psychosocial (band: Slipknot), and Control (n=12), rats were exposed to ambient sounds in an acoustically isolated room. The animals were exposed to the music for 8 hours per day, between 10:00 pm to 06:00 am, with an intensity of 50-75 dB, for 61 consecutive days. Twenty-four hours after the final day of adjustment to the enclosure the animals were individually exposed for 5 minutes in the enclosure to explore two identical objects. Ninety minutes after the object recognition training session, the animals were submitted to the short-term memory test and twenty-eight days after the object recognition training session, the animals were submitted to a long-term memory test. Results. There was no modification amongst the three groups during the object recognition training. Regarding the short-term memory test both Mozart (U=33.00, p=0.016, FDR-corrected) and Heavy Metal (U=44.00, p=0.033, FDR-corrected) groups revealed a higher percentage value of significance compared to the control group. In contrast, there was no significant change in relation to the long-term memory test. Conclusion. Mozart Sonata K-448 and heavy metal music achieved beneficial effects on the short-term memory in rats