Effect of ipriflavone on Wistar rats and their litters

PURPOSE: Evaluate the effects of ipriflavone during fetogenesis, since no studies have been conducted to assess its effect during this period. METHODS: 60 pregnant rats were divided randomly into four groups (n=15). G-control (1 mL of distilled water) and three groups treated intragastrically with ipriflavone from the 16th to the 20th post coitus (PC) day: G-300 (300 mg/kg), G-1,500 (1,500 mg/kg) and G-3,000 (3,000 mg/kg). The animals were weighed, anaesthetized intraperitoneally with xylazine and ketamine at doses of 180 mg/kg and 10 mg/kg, respectively, and sacrificed by total exsanguination on the 21st day. A complete blood count was performed and serum cholesterol, triglycerides, AST, ALT, urea, creatinine, and glucose were determined in pregnant rats. After laparotomy, the liver, kidneys, adrenals, spleen and ovaries were removed and weighed; fetuses and placentas were also weighed to obtain the average weight of the litters. Four fetuses (two males and two females) were chosen at random for the determination of the length and weight of brain, liver, kidneys and lungs. Statistical analysis: ANOVA followed by Dunnett's test. For raw data without normal distribution and homoscedasticity, we used the Kruskal-Wallis test followed by the Mann-Whitney test. Proportions were analyzed by the χ2 test (p<0.05). RESULTS: Triglyceride levels (mg/dL) were: Control-G (138.8±21.8), G-300 (211.2±63.9) G-1,500 (251.5±65.2) G-3,000 (217.7±49.6); p<0.05. The body weight of fetuses (g) was: G-Control (male 3.3±0.3; female 3.1±0.3), G-300 (male 3.4±0.2; female 3.1±0.4), G-1,500 (male 3.5±0.3; female 3.2±0.3), G-3,000 (male 3.4±0.5; female 3.1±0.4). CONCLUSION: Ipriflavone did not cause maternal toxicity, but increased triglyceride levels and reduced hematocrit at higher doses. The body and organ weights of the fetuses did not change with dam treatment. There were no external malformations or fetal deaths.OBJETIVO: Avaliar os efeitos da ipriflavona durante a fetogênese, já que não foram encontrados estudos visando avaliar seu efeito durante este período. MÉTODOS: Foram utilizadas 60 ratas prenhes, distribuídas aleatoriamente em quatro grupos (n=15). G-controle (1 mL de água destilada) e três grupos tratados com ipriflavona, via intragástrica, do 16º ao 20º dia pós-coito (PC): G-300 (300 mg/kg), G-1500 (1.500 mg/kg) e G-3000 (3.000 mg/kg). Os animais foram pesados e sacrificados no 21º dia por exsanguinação total sob anestesia (xilazina (10 mg/kg) e quetamina (90 mg/kg) via intraperitoneal. Foi realizado hemograma completo e dosagens séricas de colesterol, triglicérides, AST, ALT, ureia, creatinina e glicose das ratas prenhes. Após laparotomia foram removidos e pesados fígado, rim, suprarrenais, baço e ovários; os fetos e placentas foram pesados obtendo-se o peso médio das ninhadas. Quatro fetos (dois machos e duas fêmeas) por mãe foram aleatoriamente designados para obter-se o comprimento e peso de cérebro, fígado, rins e pulmões. Para a análise estatística utilizou-se o teste ANOVA seguido do teste de Dunnet; para dados não homocedásticos e sem distribuição normal, foi usado o teste de Kruskal-Wallis, seguido de Mann-Whitney; as proporções foram analisadas pelo teste do χ2 (p<0,05) RESULTADOS: Níveis de triglicérides (mg/dL): G-Controle (138,8±21,8); G-300 (211,2±63,9); G-1500 (251,5±65,2); G-3000 (217,7±49,6); p<0.05. Peso corporal dos fetos (g): G-Controle (machos 3,3±0,3; fêmeas 3,1±0,3); G-300 (machos 3,4±0,2; fêmeas 3,1±0,4); G-1500 (machos 3,5±0,3; fêmeas 3,2±0,3); G-3000 (machos 3,4±0,5; fêmeas 3,1±0,4). CONCLUSÃO: A ipriflavona não causou toxicidade materna, mas elevou níveis de triglicérides e reduziu o hematócrito em doses elevadas, o tamanho, peso corporal e de órgãos fetais não foram alterados. Não foram observadas malformações externas nem mortes fetais

Therapeutic ultrasound effect on pregnant rats

PURPOSE: to evaluate the effect of exposure of female rats to therapeutic ultrasound in the pre-implantation phase. METHODS: pregnant Wistar female rats have been exposed to 3 MHz, 0.6 W/cm2 ultrasound, pulsatile ultrasound (PUS) or continuous ultrasound (CUS), and controls, unplugged ultrasound (UUS), for five minutes. The rats were sacrificed at the 20th day post-insemination. Biochemical and hematological analyses have been done. Animals have been submitted to necropsy in order to identify lesions of internal organs, and to remove and weight the liver, kidneys and ovaries. Alive, malformed, dead and reabsorbed fetuses have been counted. RESULTS: the rats have not presented changes in their body and organs weight, and neither in their reproductive capacity, but there has been an increase in triglycerides in the PUS and CUS groups, when compared to the UUS group. The fetuses' relative weights of the heart (0.7 ± 0.9), liver (9.8 ± 0.8), kidneys (6.2 ± 0.8) and lungs (3.8 ± 0.4) increased in the CUS, when compared to the heart (0.7 ± 0.9), liver (9.8 ± 0.8), kidneys (6.2 ± 0.8) e lungs (3.8 ± 0.4) of the UUS. CONCLUSIONS: in the experimental model, the therapeutic ultrasound used has not caused meaningful maternal toxicity. Pulsatile waves have not changed fetal morphology, but continuous waves have caused increase in the relative weight of the fetuses' heart, liver, lungs and kidneys.OBJETIVO: avaliar o efeito da exposição de ratas ao ultra-som terapêutico na fase de pré-implantação. MÉTODOS: ratas Wistar prenhes foram expostas, na fase de pré-implantação, ao ultra-som de 3 MHz, 0,6 W/cm2, com ondas pulsadas (USP) ou ondas contínuas (USC), e os controles (USS) ao ultra-som desligado, por cinco minutos. As ratas foram sacrificadas no 20º dia pós-inseminação. Foram feitas análises bioquímicas e hematológicas. Os animais foram submetidos à necrópsia para identificação de lesões de órgãos internos, remoção e pesagem de fígado, rins e ovários. Foram contados os fetos vivos, malformados, mortos e reabsorvidos. Os fetos, seus cérebros, pulmões, fígados, rins e placentas foram pesados. Os dados obtidos foram analisados por ANOVA – uma via – seguida de teste de Dunnett, qui quadrado ou Kruskal-Wallis (α = 0,05). RESULTADOS: as ratas não apresentaram alteração de peso corporal, de órgãos e nem na capacidade reprodutiva, mas houve o aumento dos triglicérides em ambos os grupos, quando comparados ao USS. Os pesos relativos do coração (0,7 ± 0,9), fígado (9,8 ± 0,8), rins (6,2 ± 0,8) e pulmão (3,8 ± 0,4) dos fetos aumentaram no USC, quando comparados ao coração (0,6 ± 0,1), fígado (8,8 ± 0,5), rins (5,52 ± 0,5) e pulmão (3,4 ± 0,4) do USS. CONCLUSÕES: no modelo experimental usado, o ultra-som terapêutico não causou toxicidade materna significativa. Ondas pulsadas não alteraram a morfologia fetal, mas as ondas contínuas acarretaram aumento nos pesos relativos do coração, fígado, pulmão e rins dos fetos

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Desenvolvimento fetal em ratas wistar tratadas com ipriflavona durante a fetogênese

The ipriflavone is a synthetic derivative of the isoflavone daidzein, marketed with the aim of preventing and / or treating osteoporosis. It was verified in vitro that ipriflavone (IP) induced apoptosis in gastric epithelial cells and inhibited proliferation and DNA synthesis of bone tumor cells. The daidzein, the precursor of ipriflavone, had anti-implantation effect in rats and reduced production of progesterone in human trophoblast cells. Genistein is structurally similar to ipriflavone, has harmful effects on the blastocysts of mice, cultured in vitro and in vivo. The fetogenesis is a period of embryonic development in which there is intense mitosis and cell proliferation, which characterize the growth and differentiation of various organ systems, finishing the formation of reproductive system and central nervous systems of final development of the limbs and face. All these processes can be altered by the effects of iproflavone, but there are no studies to assess them, the purpose of this study was to evaluate fetal development in rats treated with aqueous solution of Ipriflavone during the fetogênese. 60 rats were used at 10 days post-coitus (pc), maintained under controlled temperature, humidity and ventilation, which were randomly distributed in one control group - C (1 ml of distilled water) and three treated groups T1, T2 and T3 that received, respectively, 300, 1500 and 3000mg/kg of ipriflavone, intragastric, from 16 to 20 pc. The animals were euthanized at 21º days pc. Variables analyzed: maternal organ weights (liver, kidney, supra kidney, spleen and ovary), length and fetal body weight, weight of placenta, brain, liver, kidney and lung. Statistics gathering data analysis: ANOVA followed by Dunnett test (α = 0.05). The experimental procedure was approved by the Ethics Committee on Animal Experimentation of Federal University of Juiz de Fora (Protocol No. 024/2008). Treatment with aqueous suspension of ipriflavone caused no significant difference in any of the variables studied. We can conclude that in the experimental model used, the ipriflavone did not cause maternal toxicity and significant changes in fetal development.A ipriflavona (IP) é uma isoflavona sintética derivada da daidzeína, comercializada com a finalidade de prevenir e/ou tratar a osteoporose. Foi verificado in vitro que a IP induziu a apoptose em células epiteliais gástricas e inibiu a proliferação e síntese de DNA de células tumorais óssea. A daidzeína, precursora da IP, teve efeito antiimplantação em ratas e redução da produção de progesterona em células trofoblásticas humanas. A genisteína, estruturalmente semelhante a ipriflavona, exerce efeitos lesivos no blastocisto de camundongos, cultivados in vitro e in vivo. A fetogênese é um período do desenvolvimento embrionário no qual ocorre intensa mitose e proliferação celular, que caracterizam o crescimento e a diferenciação de vários sistemas orgânicos, de finalização da formação dos sistemas reprodutivo e nervoso central, do desenvolvimento final dos membros e face. Todos esses processos podem ser alterados pelos efeitos da IP, mas não foram encontrados estudos para sua avaliação, sendo o objetivo do presente trabalho avaliar o desenvolvimento fetal em ratas tratadas com solução aquosa de IP durante o período de fetogênese. Foram utilizadas 60 ratas no 10 dia pós-coito (pc), mantidas em condições controladas de temperatura, umidade e ventilação, as quais foram distribuídas, aleatoriamente, em um grupo controle - C (1ml de água destilada) e três tratados T1, T2 e T3 que receberam, respectivamente, 300; 1500 e 3000mg/kg de IP, via intragástrica, nos dias 16 a 20 pc. Os animais foram eutanaziados no 210 dia pc. Variáveis analisadas: peso de órgãos maternos (fígado, rim, supra renal, baço e ovário), comprimento e peso corporal fetal, peso de placentas, cérebro, fígado, rins e pulmão fetais. Análise estatística dos dados: ANOVA seguida de teste de Dunnet (α =0.05). O procedimento experimental foi aprovado no Comitê de Ética em Experimentação Animal da Universidade Federal de Juiz de Fora (protocolo nº 024/2008). O tratamento com suspensão aquosa de IP não causou diferença significativa em nenhuma das variáveis estudadas. Podemos concluir que no modelo experimental utilizado, a ipriflavona não causou toxicidade materna e alterações significativas no desenvolvimento fetal

Aspectos ecológicos da helmintofauna de Hoplias malabaricus (Bloch, 1794) (Characiformes, Erythrinidae) da Represa Dr. João Penido (Juiz de Fora-MG, Brasil)

O objetivo do presente trabalho foi o estudo das infrapopulações e infracomunidades de parasitos de Hoplias malabaricus (Bloch, 1794) da represa Dr. João Penido, município de Juiz de Fora, MG. Entre novembro de 2004 e março de 2005 foram coletados 89 exemplares de H. malabaricus, dos quais 92,1% estavam parasitados por pelo menos uma espécie de parasito. Realizou-se o cálculo do fator de condição relativo (Kn) para cada peixe. Foram coletadas três espécies de nematóides: Contracaecum sp. e Eustrongylides ignotus, em estágio larvar e Procamallanus (Spirocamallanus) hilarii em estágio adulto. Contracaecum sp. foi a espécie dominante com maiores valores de abundância, prevalência, freqüência de dominância e dominância relativa média. Os parasitos de H. malabaricus apresentaram padrão típico de distribuição agregado. A comunidade de nematóides observada pode ser caracterizada como pouco diversa e com baixa uniformidade na distribuição. A prevalência e a abundância totais correlacionaram-se positivamente ao comprimento total, mesmo resultado obtido quando considerado a prevalência e a abundância de E. ignotus e Contracaecum sp.. Não foi observada influência do parasitismo no fator de condição relativo dos peixes. No presente trabalho a mudança da dieta durante a ontogênese de H. malabaricus e o ambiente do reservatório parecem ser os principais fatores que contribuíram para a estrutura comunitária de parasitos

Desenvolvimento Embrionário em Ratas (Rattus norvegicus Berkenhout, 1769) Tratadas com Óleo Essencial de Rosmarinus Officinalis Linn.

O óleo essencial de Rosmarinus officinalis é utilizado em perfumes e cosméticos, na indústria alimentícia e em medicamentos, apresentando também atividade antimicrobiana. Há informações de que o óleo essencial poderia estar envolvido com alterações de membrana celular e que outros extratos de R. officinalis poderiam interferir com síntese/secreção de hormônios esteroidianos, concentração de glicose e proliferação de células endoteliais, processos que poderiam alterar o desenvolvimento embrio-fetal, o que levou a se planejar o presente trabalho com o objetivo de verificar o desenvolvimento fetal em ratas tratadas com R. officinalis. Ratas Wistar do Biotério do Centro de Biologia da Reprodução foram inseminadas por machos férteis comprovada e distribuídas aleatoriamente em grupos controle e tratados 1, 2 e 3 (T1, T2 e T3) que receberam, respectivamente: 242 mg/ kg; 484 mg/ kg e 968 mg/ kg de óleo essencial de R. officinalis. Os animais foram tratados do 80 ao 150  dia pós-coito e submetidos a eutanásia por excesso de anestesia no 210 dia. Variáveis observadas: indícios clínicos, hematológicos e bioquímicos de toxicidade materna e parâmetros reprodutivos, peso corporal e de órgãos maternos e fetais. Não foram observadas diferenças significativas nas variáveis maternas analisadas, havendo apenas aumento da concentração de uréia que não foi esclarecido. O peso corporal e o de cérebro dos fetos foram menores em T3 com relação ao grupo controle. Conclui-se que o óleo essencial de Rosmarinus officinalis, no desenho experimental usado, causou diminuição do peso corporal e do cérebro fetais, possivelmente devido a alterações metabólicas maternas

INTRA UTERINE GROWTH RETARDATION IN RATS TREATED WITH ESSENTIAL OIL OF ROSMARINUS OFFICINALIS LINN

The essential oil of Rosmarinus officinalis L. (EORO) is used in cosmetics, in the food industry and in medicines, presenting antimicrobial and antifungal activity. Aim of the study: to observe maternal toxicity and embryo development after treatment of dams with EORO. Inseminated rats were distributed in four groups (n =15): Control (C) (saline 0.5ml) and treated with 242 (T1), 48 4 (T2) and 968 mg/Kg (T3) of EORO, from the fifth to the seventh dpc and sacrificed on the 15th dpc. Variables analyzed: maternal behavior, body weight gain, food consumption, kidneys, liver and ovaries weight, hemogram, number of corpora lutea, implants, live, dead, malformed fetuses and placenta and fetuses weight. Statistics: Dunnett and Chi-square tests (?=0.05). The EORO higher dose reduced (