RESUMO
Yellow fever (YF) is a disease caused by the homonymous flavivirus that can be prevented by a vaccine containing attenuated viruses. Since some individuals cannot receive this vaccine, the development of alternatives is desirable. Here, we developed a recombinant baculovirus (rBV) surface display platform utilizing a chimeric E-NS1 protein as a vaccine candidate. A pBacPAK9 vector containing the baculoviral GP64 signal peptide, the YFV prM, E, NS1 and the ectodomain of VSV-G sequences was synthesized. This transfer plasmid and the bAcGOZA bacmid were cotransfected into Sf9 cells, and an rBV-E-NS1 was obtained, which was characterized by PCR, WB, IFI and FACS analysis. Mice immunized with rBV-E-NS1 elicited a specific humoral and cellular immune response and were protected after YFV infection. In summary, we have developed an rBV that expresses YFV major antigen proteins on its surface, which opens new alternatives that can be tested in a mouse model.
Assuntos
Anticorpos Antivirais , Baculoviridae , Proteínas não Estruturais Virais , Febre Amarela , Vírus da Febre Amarela , Animais , Baculoviridae/genética , Baculoviridae/imunologia , Camundongos , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Vírus da Febre Amarela/imunologia , Vírus da Febre Amarela/genética , Proteínas não Estruturais Virais/imunologia , Proteínas não Estruturais Virais/genética , Febre Amarela/prevenção & controle , Febre Amarela/imunologia , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/genética , Células Sf9 , Vacinas Virais/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/genética , Feminino , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/genética , Imunidade Celular , Camundongos Endogâmicos BALB C , Imunidade Humoral , Vetores Genéticos/genéticaRESUMO
No studies have evaluated the peripartum follicular dynamics resulting in foal heat under tropical environments. We aimed to assess retrospectively the peripartum follicular dynamics in Colombian Paso Fino mares that were inseminated at the foal heat, becoming pregnant or not. Records including follicular dynamics of pregnant mares prepartum and from foaling until foal heat ovulation were assessed in Colombian Paso Fino mares (CPF, n = 24) bred under permanent grazing in a tropical herd in Colombia. The number of ovarian follicles >10 mm before foaling and the largest follicle (F1) growth rate (mm/day) from foaling until the F1 reached the largest diameter (pre-ovulatory size) at the foal heat were assessed. Mares were inseminated at foal heat with 20 mL of semen (at least 500 million live spermatozoa) with >75% motility and 80% viability from a stallion of proven fertility. Ovulation was confirmed the day after follicles had reached the largest diameter. Quantitative data from follicular growth, the day at ovulation, from mares that became pregnant (PM) or not (NPM) at 16 days post-insemination were compared by one-way ANOVA, repeated measures ANOVA (follicle growth rate data) or Chi-square test (edema and cytology scores data). Epidemiological data, gestation length, and the number of follicles on third prepartum days did not significantly differ between PM and NPM (p > 0.05). Seventy-one percent of mares (17/24) got pregnant. Ovulatory follicles grew faster in the NPM group (n = 7), which ovulated between the seventh and ninth postpartum days, compared to PM (n = 17), which ovulated between the 11th and 13th postpartum days. Pre-ovulatory follicle diameter in PM (48.57 ± 0.8 mm) was significantly larger than in NPM (42.99 ± 1.0 mm) (p < 0.05). In addition, the PM edema score (2.93 ± 0.32 mm) on ovulation day was significantly lower (p < 0.05) than NPM (4.47 ± 0.05 mm). First postpartum ovulation occurred at 12.6 ± 0.3 and 8.5 ± 0.4 days (p < 0.05) in PM and NPM, respectively. Colombian Paso Fino mares bred under permanent grazing under tropical rainforest conditions with no foaling or postpartum complications showed a 71% gestation rate when inseminated at foal heat when ovulation occurs between the second and third postpartum week.
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Uterine involution, ovarian activity, and incidence of postpartum uterine disease (PUD) were assessed in forty-eight dairy cows from calving until the 10th postpartum week. Postpartum follow-up included evaluation of uterine involution and ovarian structures by B-mode, Doppler color, and Doppler spectral ultrasound of the right uterine artery in cows with no calving or postpartum uterine problems (healthy cows). Data from cows that developed PUD (PUD cows) were compared with healthy cows matched by herd and days in milk (DIM). Data were analyzed by descriptive statistics, simple regression, one-way ANOVA, or repeated ANOVA measures, and in data analysis of healthy cows, uterine horn diameter assessed by B-mode ultrasound ranged from 22.9 ± 2.4 to 19.4 ± 1.4 mm and 19.9 ± 2.2 to 20.5 ± 2.3 mm from the fourth to the seventh postpartum week in the left and right uterine horns, respectively (P > 0.05). During the study, 15 and 7 cows had corpus luteum in the left and right ovaries, respectively. The mean time for the first postpartum CL was 30.1 ± 3.2 DIM (min 8, max 67 DIM). In data analysis of PUD cows, uterine blood flow assessed by color Doppler ranged from 7.4 ± 4.0 to 43.75 ± 10.3% in cows that developed PUD compared to 16.7 ± 11.0% in healthy cows (P > 0.05). No statistically significant changes were found in resistance index, pulsatility index, time-averaged maximum velocity, time-averaged mean velocity, or diastole/systole ratio (D/S) in cows that developed PUD compared to healthy cows (P > 0.05). Finally, no correlation was found between Doppler spectral parameters and uterine involution (P > 0.05). Our data suggest that cows receiving transition diets and exhibiting normal calving undergo a rapid macroscopic uterine involution and ovarian follicular dynamics resumption. Complete ultrasound evaluation provides valuable data for assessing uterine involution in postpartum dairy cows.
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Background: It is still unelucidated how hormonal alterations affect developing organisms and their descendants. Particularly, the effects of androgen levels are of clinical relevance as they are usually high in women with Polycystic Ovary Syndrome (PCOS). Moreover, it is still unknown how androgens may affect males' health and their descendants. Objectives: We aimed to evaluate the multigenerational effect of prenatal androgen excess until a second generation at early developmental stages considering both maternal and paternal effects. Design And Methods: This is an animal model study. Female rats (F0) were exposed to androgens during pregnancy by injections of 1 mg of testosterone to obtain prenatally hyperandrogenized (PH) animals (F1), leading to a well-known animal model that resembles PCOS features. A control (C) group was obtained by vehicle injections. The PH-F1 animals were crossed with C males (m) or females (f) and C animals were also mated, thus obtaining 3 different mating groups: Cf × Cm, PHf × Cm, Cf × PHm and their offspring (F2). Results: F1-PHf presented altered glucose metabolism and lipid profile compared to F1-C females. In addition, F1-PHf showed an increased time to mating with control males compared to the C group. At gestational day 14, we found alterations in glucose and total cholesterol serum levels and in the placental size of the pregnant F1-PHf and Cf mated to F1-PHm. The F2 offspring resulting from F1-PH mothers or fathers showed alterations in their growth, size, and glucose metabolism up to early post-natal development in a sex-dependent manner, being the females born to F1-PHf the most affected ones. Conclusion: androgen exposure during intrauterine life leads to programing effects in females and males that affect offspring health in a sex-dependent manner, at least up-to a second generation. In addition, this study suggests paternally mediated effects on the F2 offspring development.
RESUMO
In this study, we examined infection with the highly neurovirulent GDVII, the less neurovirulent DA strains, and with a mutant DA, which lacks the L* protein (L*-1) involved in viral persistence and demyelinating disease, to analyze the direct effects of Theiler's murine encephalomyelitis virus (TMEV) replication using primary cultures of mouse brain hippocampal neurons. All viruses replicate in cultured neurons, with GDVII having the highest titers and L*-1 the lowest. Accordingly, all were positive for viral antigen staining 3 days postinfection (dpi), and DA and L*-1 were also positive after 12 dpi. NeuN + immunostaining showed an early and almost complete absence of positive cells in cultures infected with GDVII, an approximately 50% reduction in cultures infected with DA, and fewer changes in L*-1 strains at 3 dpi. Accordingly, staining with chloromethyltetramethylrosamine orange (Mitotracker OrangeTM) as a parameter for cell viability showed similar results. Moreover, at 1 dpi, the strain DA induced higher transcript levels of neuroprotective genes such as IFN-Iß, IRF7, and IRF8. At 3 dpi, strains GDVII and DA, but not the L*-1 mutant, showed lower PKR expression. In addition, confocal analysis showed that L*-1-infected neurons exhibited a decrease in spine density. Treatment with poly (I:C), which is structurally related to dsRNA and is known to trigger IFN type I synthesis, reduced spine density even more. These results confirmed the use of mouse hippocampal neuron cultures as a model to study neuronal responses after TMEV infection, particularly in the formation of spine density.
Assuntos
Theilovirus , Camundongos , Animais , Theilovirus/fisiologia , Neurônios , Coluna VertebralRESUMO
Accumulating evidence suggests that an altered maternal milieu and environmental insults during the intrauterine and perinatal periods of life affect the developing organism, leading to detrimental long-term outcomes and often to adult pathologies through programming effects. Hormones, together with growth factors, play critical roles in the regulation of maternal-fetal and maternal-neonate interfaces, and alterations in any of them may lead to programming effects on the developing organism. In this chapter, we will review the role of sex steroids, thyroid hormones, and insulin-like growth factors, as crucial factors involved in physiological processes during pregnancy and lactation, and their role in developmental programming effects during fetal and early neonatal life. Also, we will consider epidemiological evidence and data from animal models of altered maternal hormonal environments and focus on the role of different tissues in the establishment of maternal and fetus/infant interaction. Finally, we will identify unresolved questions and discuss potential future research directions.
Assuntos
Desenvolvimento Fetal , Hormônios Tireóideos , Gravidez , Animais , Feminino , Desenvolvimento Fetal/fisiologia , FetoRESUMO
Prenatal androgen exposure induces fetal programming leading to alterations in offspring health and phenotypes that resemble those seen in women with Polycystic Ovary Syndrome. It has been described that prenatal androgenization affects the reproductive axis and leads to metabolic and endocrine disorders. Adipose tissue plays a crucial role in all these functions and is susceptible to programming effects. Particularly, gonadal adipose tissue is involved in reproductive functions, so dysfunctions in this tissue could be related to fertility alterations. We aimed to investigate the extent to which prenatal hyperandrogenization is able to alter the functionality of gonadal adipose tissue in female adult rats, including lipid metabolism, adipokines expression, and de novo synthesis of steroids. Pregnant rats were treated with 1 mg of testosterone from day 16 to day 19 of pregnancy, and female offspring were followed until 90 days of age, when they were euthanized. The prenatally hyperandrogenized (PH) female offspring displayed two phenotypes: irregular ovulatory (PHiov) and anovulatory (PHanov). Regarding lipid metabolism, both PH groups displayed disruptions in the main lipid pathways with altered levels of triglyceride and increased lipid peroxidation levels. In addition, we found that Peroxisome Proliferator-Activated Receptors (PPARs) alpha protein expression was decreased in both PH phenotypes (p < 0.05), but no changes were found in PPARγ protein levels. Furthermore, regarding adipokines, no changes were found in Leptin and Adiponectin protein levels, but Chemerin protein levels were decreased in the PHiov group (p < 0.05). Regarding de novo synthesis of steroids, the PHanov group showed increased protein levels of Cyp17a1 and Cyp19, while the PHiov group only showed decreased protein levels of Cyp19 (p < 0.05). These results suggest that prenatal androgen exposure affects females' gonadal adipose tissue in adulthood, disturbing different lipid pathways, Chemerin expression, and de novo synthesis of steroids.
Assuntos
Síndrome do Ovário Policístico , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Ratos , Feminino , Animais , Androgênios , Aromatase , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/veterinária , Esteroides , Adipocinas , Triglicerídeos , Tecido Adiposo , Efeitos Tardios da Exposição Pré-Natal/veterináriaRESUMO
Introducción: en marzo del 2021 se registró el pico de incidencia de COVID-19 en Uruguay y un aumento de la infección en pediatría. Objetivo: describir las características clínicas, el tratamiento y la evolución de una serie de menores de 15 años con SIM-Ped S hospitalizados en dos centros de salud. Metodología: estudio descriptivo, retrospectivo, de los niños hospitalizados entre el 1/3 y el 31/6 de 2021 que cumplieron los criterios diagnósticos de SIM-Ped de la OMS. Se analizan variables clínicas, paraclínicas, tratamiento y evolución. Resultados: se incluyeron 12 niños, mediana de edad 7 años (22 meses-10 años). Se presentaron complicación posinfecciosas en 8 y en el curso de la infección en 4. Las manifestaciones fueron: fiebre (media 6 días, rango 3-10), digestivas 10 y mucocutáneas 7. Se presentaron como enfermedad Kawasaki símil 5 y como shock 2. La infección por SARS CoV-2 se confirmó por PCR en 6, serología 4 y test antigénico 2. Recibieron tratamiento en cuidados moderados 8 e intensivos 4: inmunoglobulina 9, corticoides 11, heparina 7 y ácido acetilsalicílico 7. Presentaron dilatación de arterias coronarias 2, alteraciones valvulares 2, disminución de la FEVI 2 y derrame pericárdico 2. Todos evolucionaron favorablemente. Conclusiones: en estos centros, los primeros casos de SIMS-Ped S coincidieron con el pico de incidencia de COVID-19 en el país. Predominaron las formas postinfecciosas en escolares con manifestaciones digestivas. Este estudio puede contribuir al reconocimiento de esta entidad y adecuar los algoritmos nacionales de manejo.
Introduction: in March 2021, there was a peak incidence of COVID-19 and an increase in pediatric infections in Uruguay. Objective: describe the clinical characteristics, treatment and evolution of a group of children under 15 years of age with SIM-Ped S hospitalized in two health centers. Methodology: descriptive, retrospective study of children hospitalized between 3/1 and 6/31 of 2021 who met the WHO diagnostic criteria for SIM-Ped. Clinical and paraclinical variables, as well as treatment and evolution were analyzed. Results: 12 children were included, median age 7 years (22 months-10 years). Eight of them showed post-infectious complications and 4 of them had complications during the course of the infection. The manifestations were: fever (mean 6 days, range 3-10), digestive symptoms 10 and mucocutaneous 7. Five of them presented a Kawasaki-like disease and 2 of them shock. SARS CoV-2 infection was confirmed by PCR in 6 cases, serology in 4 and antigenic test in 2. Eight of them received treatment in moderate care and 4 of them in intensive care: immunoglobulin 9, corticosteroids 11, heparin 7 and acetylsalicylic acid 7. Two of them presented dilated arteries coronary , valvular alterations 2, decreased LVEF 2 and pericardial effusion 2. All progressed favorably. Conclusions: in these centers, the first cases of SIMS-Ped S coincided with the peak incidence of COVID-19 in the country. Post-infectious forms predominated in schoolchildren who showed digestive manifestations. This study may contribute to the recognition of this entity and to the adaptation of national management algorithms.
Introdução: em março de 2021, foi registrado no Uruguai um pico de incidência da COVID-19 e um aumento dos casos da infecção pediátrica. Objetivo: descrever as características clínicas, tratamento e evolução de uma série de crianças menores de 15 anos com SIM-Ped S internadas em dois centros de saúde. Metodologia: estudo descritivo, retrospectivo, de crianças internadas entre 1/3 e 31/6 de 2021 que preencheram os critérios diagnósticos da OMS para o SIM-Ped. Foram analisadas variáveis clínicas e para-clinicas, tratamento e evolução. Resultados: foram incluídas 12 crianças, com idade média de 7 anos (22 meses-10 anos). Oito delas apresentaram complicações pós-infecciosas e 4 delas durante o curso da infecção. As manifestações foram: febre (média de 6 dias, intervalo 3-10), digestivas 10 e mucocutânea 7. Cinco delas apresentaram doença de Kawasaki-like e 2 delas sofreram Shock. A infecção por SARS CoV-2 foi confirmada por PCR em 6, sorologia em 4 e teste antigênico em 2. Oito delas receberam tratamento em cuidados moderados e 4 delas em cuidados intensivos: imunoglobulina 9, corticosteroides 11, heparina 7 e ácido acetilsalicílico 7. Duas delas apresentaram artérias coronárias dilatadas 2, alterações valvares 2, diminuição da FEVE 2 e derrame pericárdico 2. Todas evoluíram favoravelmente. Conclusões: nesses centros, os primeiros casos de SIMS-Ped S coincidiram com um pico de incidência de COVID-19 no país. As formas pós-infecciosas predominaram em escolares com manifestações digestivas. Este estudo pode contribuir para o reconhecimento desta entidade e adaptar algoritmos nacionais de gestão.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Síndrome de Resposta Inflamatória Sistêmica/complicações , COVID-19/complicações , Heparina/uso terapêutico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/tratamento farmacológico , Receptores de Glucocorticoides/uso terapêutico , Aspirina/uso terapêutico , Estudos Retrospectivos , Corticosteroides/uso terapêutico , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Doenças do Sistema Digestório/etiologia , Doenças do Sistema Digestório/tratamento farmacológico , Antipiréticos/uso terapêutico , Febre/etiologia , Febre/tratamento farmacológico , Avaliação de Sintomas , Antibacterianos/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/etiologia , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológicoRESUMO
Resumen: Introducción: En el siglo XX el parto pasó de ser atendido en casa al ámbito hospitalario. Se adoptaron de forma acrítica intervenciones inapropiadas e innecesarias que condujeron a una deshumanización del parto. Este es el modelo que existe actualmente en la mayoría de los hospitales españoles y que fue cuestionado por la OMS ya en 1996. Objetivo: Describir las diferencias que existen en los resultados obstétricos y neonatales en primíparas en dos modelos distintos de asistencia al parto (biomédico y humanizado). Método: Se llevó a cabo un estudio descriptivo, de corte transversal. Se obtuvo una muestra por conveniencia de 205 primíparas, 110 del modelo biomédico y 95 del humanizado. Se compararon los resultados obstétricos y neonatales en dos hospitales con modelos diferentes de asistencia al parto en España. Resultados: En el modelo humanizado de asistencia al parto se obtuvieron unos mejores resultados obstétricos (inicio espontáneo, parto eutócico, periné íntegro o desgarro de I grado y menos episiotomías) que en el biomédico. No hubo diferencias en los resultados neonatales. Conclusión: Los beneficios de instaurar un modelo humanizado de asistencia al parto deberían ser considerados por los responsables de políticas sanitarias y reflejados en la mujer y su criatura.
Resumo: Introdução: No século XX, o parto deixou de ser realizado em casa para ser realizado no ambiente hospitalar. Intervenções inadequadas e desnecessárias foram adotadas acriticamente, levando a uma desumanização do parto. Este é o modelo que existe atualmente na maioria dos hospitais espanhóis e que foi questionado pela Organização Mundial da Saúde já em 1996. Objetivo: O objetivo principal desse estudo é descrever as diferenças existentes nos resultados obstétricos e neonatais em primíparas em dois modelos distintos de assistência ao parto (biomédico e humanizado). Método: Foi realizado um estudo descritivo, transversal. Obteve-se uma amostra por conveniência de 205 primíparas, 110 do modelo biomédico e 95 do modelo humanizado. Os resultados obstétricos e neonatais foram comparados em dois hospitais com diferentes modelos de assistência ao parto na Espanha. Resultados: No modelo humanizado de assistência ao parto obtiveram-se melhores resultados obstétricos (início espontâneo, parto eutócico, períneo íntegro ou laceração grau I e menos episiotomias) do que no modelo biomédico. Não houve diferença nos resultados neonatais. Conclusão: Os benefícios da implementação de um modelo humanizado de assistência ao parto devem ser considerados pelos formuladores de políticas de saúde e refletidos na mulher e em seu bebê.
Abstract: Introduction: In the 20th century, childbirth went from being attended at home to the hospital setting. Inappropriate and unnecessary interventions were uncritically adopted, leading to a dehumanization of childbirth. This is the model that currently exists in most Spanish hospitals, which has been questioned by the World Health Organization as early as 1996. Objective: The aim is to describe the differences in obstetrical and neonatal results across two different models of maternity care (biomedical model and humanised birth). Method: A correlational descriptive and multicenter study was carried out. A convenience sample of 205 primiparous women, 110 biomedical model and 95 humanised model, were recruited. Obstetrical and neonatal results were compared in two hospitals with different models of maternity care in Spain. Results: The humanised model of maternity care produces better obstetrical outcomes (spontaneous beginning of labour, normal vaginal birth, intact perineum and I degree tear and less episiotomies) than the biomedical model. There were no differences in neonatal outcomes. Conclusion: The benefits of implementing a humanised model of delivery care should be considered by health policy makers and reflected in the woman and her baby.
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El virus de la viruela símica es un orthopoxvirus de características zoonóticas endémico en las regiones de África Central y África Occidental, donde causa brotes desde 1970. En las últimas décadas se registró un aumento exponencial de casos, probablemente asociado a la disminución en la inmunidad conferida por la vacuna antivariólica, discontinuada luego de la erradicación de la viruela. En los últimos años se registraron casos esporádicos fuera del continente africano, siempre relacionados epidemiológicamente a la permanencia en áreas endémicas o contacto con animales infectados. Desde el 13 de mayo de 2022 se encuentra en curso el mayor brote de viruela símica registrado fuera de las áreas endémicas de África, con casos en los cinco continentes. La extensión, el impacto y la duración del brote permanecen aún inciertos.
Monkeypox virus is an orthopoxvirus with zoonotic characteristics endemic in Central and West Africa regions, where it has caused outbreaks since 1970. An exponential increase in cases has been registered in the last decades, probably associated with a decrease in the immunity conferred by the smallpox vaccine, discontinued after smallpox eradication. In recent years, sporadic cases have been reported outside the African continent, always epidemiologically related to permanence in endemic areas or contact with infected animals. Since May 13, 2022, the largest monkeypox outbreak ever reported outside Africa endemic areas, with cases on the five continents, is unfolding. The extent, impact and duration of this outbreak still remain uncertain
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Humanos , Vacinas , Orthopoxvirus/imunologia , Infecções por Poxviridae/terapia , Doenças Endêmicas , Doenças Transmissíveis Emergentes/imunologia , Mpox/prevenção & controle , Mpox/terapia , Mpox/transmissão , Mpox/epidemiologiaRESUMO
Polycystic ovary syndrome (PCOS) is one of the major endocrine disorders affecting women of reproductive age. Its etiology remains unclear. It is suggested that environmental factors, and particularly the intrauterine environment, play key roles in PCOS development. Besides the role of androgens in PCOS pathogenesis, exposure to endocrine disruptors, as is Bisphenol A, could also contribute to its development. Although PCOS is considered one of the leading causes of ovarian infertility, many PCOS patients can get pregnant. Some of them by natural conception and others by assisted reproductive technique treatments. As hyperandrogenism (one of PCOS main features) affects ovarian and uterine functions, PCOS women, despite reaching pregnancy, could present high-risk pregnancies, including implantation failure, an increased risk of gestational diabetes, preeclampsia, and preterm birth. Moreover, hyperandrogenism may also be maintained in these women during pregnancy. Therefore, as an altered uterine milieu, including hormonal imbalance, could affect the developing organisms, monitoring these patients throughout pregnancy and their offspring development is highly relevant. The present review focuses on the impact of androgenism and PCOS on fertility issues and pregnancy-related outcomes and offspring development. The evidence suggests that the increased risk of pregnancy complications and adverse offspring outcomes of PCOS women would be due to the factors involved in the syndrome pathogenesis and the related co-morbidities. A better understanding of the involved mechanisms is still needed and could contribute to a better management of these women and their offspring. This article is categorized under: Reproductive System Diseases > Molecular and Cellular Physiology Reproductive System Diseases > Environmental Factors.
Assuntos
Hiperandrogenismo , Infertilidade , Síndrome do Ovário Policístico , Nascimento Prematuro , Feminino , Humanos , Hiperandrogenismo/complicações , Recém-Nascido , Infertilidade/complicações , Síndrome do Ovário Policístico/complicações , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/etiologiaRESUMO
It is known that prenatal hyperandrogenization induces alterations since early stages of life, contributing to the development of polycystic ovary syndrome affecting the reproductive axis and the metabolic status, thus promoting others associated disorders, such as dyslipidemia, insulin resistance, liver dysfunction, and even steatosis. In this study, we aimed to evaluate the effect of fetal programming by androgen excess on the hepatic lipid content and metabolic mediators at adult life. Pregnant rats were hyperandrogenized with daily subcutaneous injections of 1 mg of free testosterone from days 16 to 19 of pregnancy. The prenatally hyperandrogenized (PH) female offspring displayed two phenotypes: irregular ovulatory phenotype (PHiov) and anovulatory phenotype (PHanov), with different metabolic and endocrine features. We evaluated the liver lipid content and the main aspect of the balance between fatty acid (FA) synthesis and oxidation. We investigated the status of the peroxisomal proliferator-activated receptors (PPARs) alpha and gamma, which act as lipid mediators, and the adipokine chemerin, one marker of liver alterations. We found that prenatal hyperandrogenization altered the liver lipid profile with increased FAs levels in the PHanov phenotype and decreased cholesterol content in the PHiov phenotype. FA metabolism was also disturbed, including decreased mRNA and protein PPARgamma levels and impaired gene expression of the main enzymes involved in lipid metabolism. Moreover, we found low chemerin protein levels in both PH phenotypes. In conclusion, these data suggest that prenatal hyperandrogenization exerts a negative effect on the liver and alters lipid content and metabolic mediators' expression at adult age.
Assuntos
PPAR gama , Efeitos Tardios da Exposição Pré-Natal , Androgênios/metabolismo , Animais , Feminino , Desenvolvimento Fetal , Humanos , Metabolismo dos Lipídeos , Lipídeos , Fígado/metabolismo , PPAR gama/metabolismo , PPAR gama/farmacologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Introducción. Staphylococcus aureus es uno de los agentes infecciosos más prevalentes en niños y puede causar un variado espectro de presentaciones clínicas. La bacteriemia por S. aureus se asocia frecuentemente con complicaciones y metástasis infecciosas. Los datos epidemiológicos y clínicos sobre esta entidad, y sus complicaciones en pediatría son escasos. Objetivos. Describir la epidemiología, frecuencia, distribución y tipo de metástasis infecciosas en una serie de pacientes pediátricos con bacteriemia por S. aureus y evaluar posibles factores de riesgo para su aparición. Población y métodos. Estudio de corte transversal de pacientes pediátricos internados con bacteriemia por S. aureus en un hospital pediátrico de La Plata entre enero de 201 y junio de 2019. Resultados. Se analizaron 112 episodios de bacteriemia por S. aureus. La tasa de infección metastásica fue del 34,8 %; el pulmón fue la localización más frecuente. Los factores de riesgo principales para el desarrollo de metástasis infecciosas fueron la bacteriemia por S. aureus meticilino resistente (OR : 2,95; IC95 %: 1,19-7,83; p = 0,015) y la persistencia de hemocultivos de control positivos a las 48 horas (OR: 3,17; IC95 %: 1,22-8,46; p = 0,012). Conclusión. La tasa de metástasis infecciosas en pacientes con bacteriemia por S. aureus fue del 34,8 %. Los factores de riesgo asociados fueron la bacteriemia por S. aureus meticilino resistente y la persistencia de hemocultivos de control positivos a las 48 horas. Los órganos más afectados fueron el pulmón, el sistema osteoarticular, la piel y partes blandas.
Introduction. Staphylococcus aureus is one of the most prevalent infectious agents in children and may cause a wide variety of clinical presentations. S. aureus bacteremia is frequently associated with complications and metastatic infections. The epidemiological and clinical data about S. aureus bacteremia and its complications in pediatrics are scarce. Objectives. To describe the epidemiology, frequency, distribution, and type of metastatic infections in a series of pediatric patients with S. aureus bacteremia and assess possible risk factors for its development. Population and methods. Cross-sectional study of pediatric patients with S. aureus bacteremia admitted to a children's hospital of La Plata between January 2016 and June 2019. Results. A total of 112 S. aureus bacteremia events were analyzed. The rate of metastatic infection was 34.8 %; the lung was the most common infection site. The main risk factors for the development of metastatic infections were bacteremia due to methicillin-resistant S. aureus (odds ratio: 2.95; 95% confidence interval: 1.19-7.83; p = 0.015) and persistent positive control blood cultures at 48 hours (odds ratio: 3.17; 95 % confidence interval: 1.22-8.46; p = 0.012). Conclusion. The rate of metastatic infections among patients with S. aureus bacteremia was 34.8 %. Associated risk factors were bacteremia due to methicillin-resistant S. aureus and persistent positive control blood cultures at 48 hours. The most common organs affected included the lungs, the osteoarticular system, and the skin and soft tissue.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Bacteriemia/epidemiologia , Staphylococcus aureus Resistente à Meticilina , Pediatria , Argentina/epidemiologia , Staphylococcus aureus , Estudos Transversais , Estudos Retrospectivos , Hospitais PediátricosRESUMO
Introduction: Staphylococcus aureus is one of the most prevalent infectious agents in children and may cause a wide variety of clinical presentations. S. aureus bacteremia is frequently associated with complications and metastatic infections. The epidemiological and clinical data about S. aureus bacteremia and its complications in pediatrics are scarce. Objectives: To describe the epidemiology, frequency, distribution, and type of metastatic infections in a series of pediatric patients with S. aureus bacteremia and assess possible risk factors for its development. Population and methods: Cross-sectional study of pediatric patients with S. aureus bacteremia admitted to a children's hospital of La Plata between January 2016 and June 2019. Results: A total of 112 S. aureus bacteremia events were analyzed. The rate of metastatic infection was 34.8%; the lung was the most common infection site. The main risk factors for the development of metastatic infections were bacteremia due to methicillin-resistant S. aureus (odds ratio: 2.95; 95% confidence interval: 1.19- 7.83; p = 0.015) and persistent positive control blood cultures at 48 hours (odds ratio: 3.17; 95% confidence interval: 1.22-8.46; p = 0.012). Conclusion: The rate of metastatic infections among patients with S. aureus bacteremia was 34.8%. Associated risk factors were bacteremia due to methicillin-resistant S. aureus and persistent positive control blood cultures at 48 hours. The most common organs affected included the lungs, the osteoarticular system, and the skin and soft tissue.
Introducción. Staphylococcus aureus es uno de los agentes infecciosos más prevalentes en niños y puede causar un variado espectro de presentaciones clínicas. La bacteriemia por S. aureus se asocia frecuentemente con complicaciones y metástasis infecciosas. Los datos epidemiológicos y clínicos sobre esta entidad, y sus complicaciones en pediatría son escasos. Objetivos. Describir la epidemiología, frecuencia, distribución y tipo de metástasis infecciosas en una serie de pacientes pediátricos con bacteriemia por S. aureus y evaluar posibles factores de riesgo para su aparición. Población y métodos. Estudio de corte transversal de pacientes pediátricos internados con bacteriemia por S. aureus en un hospital pediátrico de La Plata entre enero de 2016 y junio de 2019. Resultados. Se analizaron 112 episodios de bacteriemia por S. aureus. La tasa de infección metastásica fue del 34,8 %; el pulmón fue la localización más frecuente. Los factores de riesgo principales para el desarrollo de metástasis infecciosas fueron la bacteriemia por S. aureus meticilino resistente (OR : 2,95; IC95 %: 1,19-7,83; p = 0,015) y la persistencia de hemocultivos de control positivos a las 48 horas (OR: 3,17; IC95 %: 1,22-8,46; p = 0,012). Conclusión. La tasa de metástasis infecciosas en pacientes con bacteriemia por S. aureus fue del 34,8 %. Los factores de riesgo asociados fueron la bacteriemia por S. aureus meticilino resistente y la persistencia de hemocultivos de control positivos a las 48 horas. Los órganos más afectados fueron el pulmón, el sistema osteoarticular, la piel y partes blandas.
Assuntos
Bacteriemia , Staphylococcus aureus Resistente à Meticilina , Pediatria , Argentina/epidemiologia , Bacteriemia/epidemiologia , Criança , Estudos Transversais , Hospitais Pediátricos , Humanos , Staphylococcus aureusRESUMO
OBJECTIVE: To analyse the knowledge and use of perineal protection methods during the expulsive stage by health professionals involved in childbirth and whether they correspond to the World Health Organization's recommendations. METHOD: This was a cross-sectional descriptive study aimed at health workers involved in births in Spain. RESULTS: Fifty-seven professionals participated in the study: midwives (47%), gynaecologists (25%), nurse residents (14%) and resident physicians (14%) in obstetrics and gynaecology. The degree of knowledge and use of perineal protection methods differed according to the position held and was very limited among gynaecologists and resident physicians. The only method recognized by all positions was "hands on" (p = 0.05). "Hands off " (p = 0.002), "delayed pushing" (p = 0.0001) and "maternal posture" (p = 0.03) were only known to midwives and nurse residents. "Flexion technique" (p = 0.035) and "delayed pushing" (p = 0.011) were used effectively by midwives and nurse residents. "Episiotomy" was erroneously identified as a method to protect the perineum by gynaecologists and resident physicians (p = 0.003). CONCLUSION: The degree of knowledge and use of perineal protection methods by health care professionals does not correspond to the recommendations of the World Health Organization.
Assuntos
Complicações do Trabalho de Parto , Períneo , Estudos Transversais , Parto Obstétrico , Episiotomia , Feminino , Humanos , GravidezRESUMO
BACKGROUND: Lipids are essential components of cells that participate in metabolic and endocrine regulation and reproductive functions. The main organs where lipid regulation takes place are the liver and adipose tissue. Besides, when each tissue- specific action cannot be exerted, it could lead to several endocrine-metabolic disorders closely related to PCOS, such as non-alcoholic fatty liver disease (NAFLD) and obesity. OBJECTIVE: This work aims to discuss the impact of lipid alterations on metabolic and reproductive health. Therefore, this review focus on the importance of carrying out an integrated study of the molecular pathways affected in PCOS for developing target therapies. RESULTS: Lipids play a major role in PCOS pathogenesis. In this regard, failures in lipid regulation, synthesis, and/or homeostasis contribute to metabolic and reproductive abnormalities, such as those seen in PCOS. Several lipid pathways and regulators are altered in this pathology, leading to dysfunctions that worsen reproductive functions. Therefore, there are several treatments to manage dyslipidemias. Non-pharmacological therapies are considered a first-line treatment being the pharmacological treatments a second-line option. CONCLUSION: The best treatment to improve the lipid profile is lifestyle intervention, a combination of hypocaloric diet and exercise. Regarding pharmacological therapies, a combination of fibrate and statins would be the most recommended drugs. Still, in PCOS women, treatment with metformin or TZDs not only modulates the lipid metabolism, but also improves ovulation. In addition, metformin with lifestyle interventions has positive effects on the metabolic and reproductive features of PCOS patients.
Assuntos
Resistência à Insulina , Metformina , Síndrome do Ovário Policístico , Dieta Redutora , Feminino , Humanos , Metabolismo dos Lipídeos , Obesidade/terapia , Síndrome do Ovário Policístico/terapia , Saúde ReprodutivaRESUMO
ABSTRACT Objective: To analyse the knowledge and use of perineal protection methods during the expulsive stage by health professionals involved in childbirth and whether they correspond to the World Health Organization's recommendations. Method: This was a cross-sectional descriptive study aimed at health workers involved in births in Spain. Results: Fifty-seven professionals participated in the study: midwives (47%), gynaecologists (25%), nurse residents (14%) and resident physicians (14%) in obstetrics and gynaecology. The degree of knowledge and use of perineal protection methods differed according to the position held and was very limited among gynaecologists and resident physicians. The only method recognized by all positions was "hands on" (p = 0.05). "Hands off " (p = 0.002), "delayed pushing" (p = 0.0001) and "maternal posture" (p = 0.03) were only known to midwives and nurse residents. "Flexion technique" (p = 0.035) and "delayed pushing" (p = 0.011) were used effectively by midwives and nurse residents. "Episiotomy" was erroneously identified as a method to protect the perineum by gynaecologists and resident physicians (p = 0.003). Conclusion: The degree of knowledge and use of perineal protection methods by health care professionals does not correspond to the recommendations of the World Health Organization.
RESUMO Objetivo: Analisar o grau de conhecimento e utilização dos métodos de proteção perineal durante o período expulsivo por parte dos profissionais sanitários implicados no parto e se ele se corresponde com as recomendações da Organização Mundial da Saúde. Método: Estudo descritivo de corte transversal dirigido a sanitários que assistem partos na Espanha. Resultados: Participaram no estúdio 57 profissionais: obstetras (47%), ginecologistas (25%), Enfermeiro Interno Residente (EIR) (14%) e Médico Interno Residente (MIR) (14%) em Obstetrícia e Ginecologia. Houve diferencias no grau de conhecimento e utilização segundo o cargo desempenhado, sendo muito limitado para ginecologistas e MIR. Os únicos métodos reconhecidos por todos os cargos foram "Hands On" (p = 0,05). "Hands off " (p = 0.002), "Controle de puxos" (p = 0.0001) y "Posturas no período expulsivo" (0.03) somente são conhecidos pelas obstetras e EIR. "Controle de deflexão da cabeça fetal" (0.035) e o "Controle de puxos" (p = 0.011) são efetivos para matronas e EIR. A "Episiotomia" se identificou erroneamente como protetor do períneo por ginecologistas e MIR (p = 0.003). Conclusão: O grau de conhecimento e uso dos métodos de proteção do períneo dos profissionais não se corresponde com as recomendações da Organização Mundial da Saúde.
RESUMEN Objetivo: Analizar grado de conocimiento y utilización de los métodos de protección perineal durante el periodo expulsivo de los profesionales sanitarios implicados en el parto y si se corresponde con las recomendaciones de la Organización Mundial de la Salud. Método: Estudio descriptivo de corte transversal dirigido a sanitarios que asisten partos en España. Resultados: Participaron en el estudio 57 profesionales: matronas (47%), ginecólogos (25%), Enfermero Interno Residente (EIR) (14%) y Médico Interno Residente (MIR) (14%) en Obstetricia y Ginecología. Hubo diferencias respecto al grado de conocimiento y utilización según el cargo desempeñado, siendo muy limitado para ginecólogos y MIR. Los únicos métodos reconocidos por todos los cargos fueron "Hands On" (p = 0,05). "Hands off " (p = 0.002), "Control de pujos" (p = 0.0001) y "Posturas en el periodo expulsivo" (0.03) sólo son conocidos por las matronas y EIR. "Control de deflexión de la cabeza fetal" (0.035) y el "Control de pujos" (p = 0.011) son efectivos para matronas y EIR. La "Episiotomía" se identificó erróneamente como protector del periné por ginecólogos y MIR (p = 0.003). Conclusión: El grado de conocimiento y uso de los métodos de protección del periné de los profesionales no se corresponde con las recomendaciones de la Organización Mundial de la Salud.
Assuntos
Períneo , Enfermagem Obstétrica , Parto , Episiotomia , TocologiaRESUMO
Prenatal androgen exposure affects reproductive functions and has been proposed as an underlying cause of polycystic ovary syndrome (PCOS). In this study, we aimed to investigate the impact of prenatal androgen exposure on ovarian lipid metabolism and to deepen our understanding of steroidogenesis regulation during adulthood. Pregnant rats were hyperandrogenized with testosterone and female offspring were studied when adult. This treatment leads to two different phenotypes: irregular ovulatory and anovulatory animals. Our results showed that prenatally hyperandrogenized (PH) animals displayed altered lipid and hormonal profile together with alterations in steroidogenesis and ovarian lipid metabolism. Moreover, PH animals showed alterations in the PPARg system, impaired mRNA levels of cholesterol receptors (Ldlr and Srb1) and decreased expression of the rate-limiting enzyme of de novo cholesterol production (Hmgcr). Anovulatory PH animals presented an increase of ovarian cholesteryl esters levels and lipid peroxidation index. Together with alterations in cholesterol metabolism, we found an impairment of the steroidogenic pathway in PH animals in a phenotype-specific manner. Regarding fatty acid metabolism, our results showed, in PH animals, an altered expression of Srebp1 and Atgl, which are involved in fatty acid metabolism and triglycerides hydrolysis, respectively. In conclusion, fatty acid and cholesterol metabolism, which are key players in steroidogenesis acting as a source of energy and substrate for steroid production, were affected in animals exposed to androgens during gestation. These results suggest that prenatal androgen exposure leads to long-term effects that affect ovary lipid metabolism and ovarian steroid formation from the very first steps.
Assuntos
Hormônios Esteroides Gonadais/biossíntese , Metabolismo dos Lipídeos/fisiologia , Ovário/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Testosterona/administração & dosagem , Animais , Colesterol/metabolismo , Feminino , Metabolismo dos Lipídeos/efeitos dos fármacos , Ovário/efeitos dos fármacos , Gravidez , RatosRESUMO
The New World arenavirus Junin (JUNV) is the etiological agent of Argentine hemorrhagic fever (AHF). Previous studies of human macrophage infection by the Old-World arenaviruses Mopeia and Lassa showed that while the non-pathogenic Mopeia virus replicates and activates human macrophages, the pathogenic Lassa virus replicates but fails to activate human macrophages. Less is known in regard to the impact of New World arenavirus infection on the human macrophage immune response. Macrophage activation is critical for controlling infections but could also be usurped favoring immune evasion. Therefore, it is crucial to understand how the JUNV infection modulates macrophage plasticity to clarify its role in AHF pathogenesis. With this aim in mind, we compared infection with the attenuated Candid 1 (C#1) or the pathogenic P strains of the JUNV virus in human macrophage cultures. The results showed that both JUNV strains similarly replicated and induced morphological changes as early as 1 day post-infection. However, both strains differentially induced the expression of CD71, the receptor for cell entry, the activation and maturation molecules CD80, CD86, and HLA-DR and selectively modulated cytokine production. Higher levels of TNF-α, IL-10, and IL-12 were detected with C#1 strain, while the P strain induced only higher levels of IL-6. We also found that C#1 strain infection skewed macrophage polarization to M1, whereas the P strain shifted the response to an M2 phenotype. Interestingly, the MERTK receptor, that negatively regulates the immune response, was down-regulated by C#1 strain and up-regulated by P strain infection. Similarly, the target genes of MERTK activation, the cytokine suppressors SOCS1 and SOCS3, were also increased after P strain infection, in addition to IRF-1, that regulates type I IFN levels, which were higher with C#1 compared with P strain infection. Together, this differential activation/polarization pattern of macrophages elicited by P strain suggests a more evasive immune response and may have important implications in the pathogenesis of AHF and underpinning the development of new potential therapeutic strategies.
Assuntos
Febre Hemorrágica Americana/imunologia , Vírus Junin/imunologia , Ativação de Macrófagos , Macrófagos/imunologia , Animais , Antígeno B7-1/imunologia , Antígeno B7-2/imunologia , Chlorocebus aethiops , Cricetinae , Citocinas/imunologia , Antígenos HLA-DR/imunologia , Febre Hemorrágica Americana/patologia , Humanos , Especificidade da Espécie , Células VeroRESUMO
Trypanosomatids are unicellular organisms that colonize a wide diversity of environments and hosts. For instance, Trypanosoma cruzi is a human pathogen responsible for Chagas diseases, while Leishmania tarentolae infects amphibians and became a biotechnological tool suitable for recombinant protein expression. T. cruzi antigens are needed for the development of improved epitope-based methods for diagnosis and treatment of Chagas disease. Molecular cloning for the production of recombinant proteins offers the possibility to obtain T. cruzi antigens at high yield and purity. L. tarentolae appears as the ideal expression host to obtain recombinant T. cruzi antigens with a structure and posttranslational modifications typical of trypanosomatids. In this chapter, we present a protocol for the analytical to mid-scale production of recombinant T. cruzi antigens, using L. tarentolae as expression host (LEXSY® inducible system).