RESUMEN
This study aims to evaluate the effects of adding alpha lipoic acid (ALA) to the in vitro ovarian tissue culture medium, either fresh or after vitrification/warming. For this purpose, 10 ovaries from five adult sheep were used. Each pair of ovaries gave rise to 16 fragments and were randomly distributed into two groups: fresh (n = 8) and vitrified (n = 8). Two fresh fragments were fixed immediately and considered the control, while another six were cultured in vitro for 14 days in the absence; presence of a constant (100 µM/0-14 day) or dynamic (50 µM/day 0-7 and 100 µM/day 8-14) concentration of ALA. As for the vitrified fragments, two were fixed and the other six were cultured in vitro under the same conditions described for the fresh group. All the fragments were subjected to morphological evaluation, follicular development and stromal density (classical histology), DNA fragmentation (TUNEL), senescence (Sudan Black), fibrosis (Masson's Trichome), and endoplasmic reticulum stress (immunofluorescence). Measurements of the antioxidant capacity against the free radicals 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and estradiol (E2) levels in the culture medium was performed. The results showed that in the absence of ALA, in vitro culture of vitrified ovarian fragments showed a significant reduction (P < 0.05) in follicular morphology and increased the presence of senescence and tissue fibrosis (P < 0.05). Dynamic ALA maintained E2 levels unchanged (P > 0.05) until the end of vitrified ovarian tissue culture and controlled the levels of ABTS and DPPH radicals in fresh or vitrified cultures. Therefore, it is concluded that ALA should be added to the vitrified ovarian tissue in vitro culture medium to reduce the damage that leads to loss of ovarian function. To ensure steroidogenesis during in vitro culture, ALA should be added dynamically (different concentrations throughout culture).
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Ácido Tióctico , Técnicas de Cultivo de Tejidos , Animales , Femenino , Ácido Tióctico/farmacología , Ovinos , Técnicas de Cultivo de Tejidos/veterinaria , Ovario/efectos de los fármacos , Folículo Ovárico/efectos de los fármacos , Antioxidantes/farmacología , Vitrificación , Criopreservación/veterinariaRESUMEN
Primaquine is the mainstream antimalarial drug to prevent Plasmodium vivax relapses. However, this drug can induce hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency. Nanostructure formulations of primaquine loaded with D-galactose were used as a strategy to target the drug to the liver and decrease the hemolytic risks. Nanoemulsion (NE-Pq) and nanochitosan (NQ-Pq) formulations of primaquine diphosphate containing D-galactose were prepared and characterized by their physicochemistry properties. Pharmacokinetic and biodistribution studies were conducted using Swiss Webster mice. A single dose of 10 mg/kg of each nanoformulation or free primaquine solution was administered by gavage to the animals, which were killed at 0.5, 1, 2, 4, 8, and 24 hours. Blood samples and tissues were collected, processed, and analyzed by high-performance liquid chromatography. The nanoformulation showed sizes around 200 nm (NE-Pq) and 400 nm (NQ-Pq) and physicochemical stability for over 30 days. Free primaquine solution achieved higher primaquine Cmax in the liver than NE-Pq or NQ-Pq at 0.5 hours. However, the half-life and mean residence time (MRT) of primaquine in the liver were three times higher with the NQ-Pq formulation than with free primaquine, and the volume distribution was four times higher. Conversely, primaquine's half-life, MRT, and volume distribution in the plasma were lower for NQ-Pq than for free primaquine. NE-Pq, on the other hand, accumulated more in the lungs but not in the liver. Galactose-coated primaquine nanochitosan formulation showed increased drug targeting to the liver compared to free primaquine and may represent a promising strategy for a more efficient and safer radical cure for vivax malaria.
Asunto(s)
Antimaláricos , Quitosano , Galactosa , Hígado , Primaquina , Primaquina/farmacocinética , Primaquina/química , Animales , Ratones , Hígado/metabolismo , Hígado/efectos de los fármacos , Galactosa/química , Quitosano/química , Antimaláricos/farmacocinética , Nanopartículas/química , Distribución Tisular , Nanoestructuras/química , MasculinoRESUMEN
Abstract Under salt stress conditions, plant growth is reduced due to osmotic, nutritional and oxidative imbalance. However, salicylic acid acts in the mitigation of this abiotic stress by promoting an increase in growth, photosynthesis, nitrogen metabolism, synthesis of osmoregulators and antioxidant enzymes. In this context, the objective was to evaluate the effect of salicylic acid doses on the growth and physiological changes of eggplant seedlings under salt stress. The experiment was conducted in a greenhouse, where the treatments were distributed in randomized blocks using a central composite matrix Box with five levels of electrical conductivity of irrigation water (CEw) (0.50; 1.08; 2.50; 3.92 and 4.50 dS m-1), associated with five doses of salicylic acid (SA) (0.00; 0.22; 0.75; 1.28 and 1.50 mM), with four repetitions and each plot composed of three plants. At 40 days after sowing, plant height, stem diameter, number of leaves, leaf area, electrolyte leakage, relative water content, and total dry mass were determined. ECw and SA application influenced the growth and physiological changes of eggplant seedlings. Increasing the ECw reduced growth in the absence of SA. Membrane damage with the use of SA remained stable up to 3.9 dS m-1 of ECw. The relative water content independent of the CEw increased with 1.0 mM of SA. The use of SA at the concentration of 1.0 mM mitigated the deleterious effect of salinity on seedling growth up to 2.50 dS m-1 of ECw.
Resumo Em condições de estresse salino, o crescimento das plantas é reduzido, em virtude, do desequilíbrio osmótico, nutricional e oxidativo. Contudo, o ácido salicílico atua na mitigação desse estresse abiótico por promover incremento no crescimento, fotossíntese, metabolismo do nitrogênio, síntese de osmorreguladores e enzimas antioxidantes. Nesse contexto, objetivou-se avaliar o efeito de doses de ácido salicílico sobre o crescimento e alterações fisiológicas de mudas de berinjela sob estresse salino. O experimento foi conduzido em casa de vegetação, onde os tratamentos foram distribuídos em blocos ao acaso utilizando uma matriz composta central Box com cinco níveis de condutividade elétrica da água de irrigação (CEa) (0,50; 1,08; 2,50; 3,92 e 4,50 dS m-1), associada a cinco doses de ácido salicílico (AS) (0,00; 0,22; 0,75; 1,28 e 1,50 mM), com quatro repetições e cada parcela composta por três plantas. Aos 40 dias após a semeadura, foram determinados a altura da planta, diâmetro do caule, número de folhas, área foliar, vazamento de eletrólito, teor relativo de água e massa seca total. A CEa e a aplicação de AS influenciaram no crescimento e nas alterações fisiológicas das mudas de berinjela. O aumento da CEa reduziu o crescimento na ausência de AS. O dano de membrana com o uso de AS manteve-se estável até 3,9 dS m-1 de CEa. O conteúdo relativo de água independentemente da CEa aumentou com 1 mM de SA. O uso de AS na concentração de 1 mM mitigou o efeito deletério da salinidade no crescimento das mudas até 2,50 dS m-1 de CEa.
Asunto(s)
Ácido Salicílico/farmacología , Solanum melongena/metabolismo , Fotosíntesis , Estrés Fisiológico , Hojas de la Planta/metabolismo , Plantones , Salinidad , Tolerancia a la Sal , Antioxidantes/metabolismoRESUMEN
Abstract Under salt stress conditions, plant growth is reduced due to osmotic, nutritional and oxidative imbalance. However, salicylic acid acts in the mitigation of this abiotic stress by promoting an increase in growth, photosynthesis, nitrogen metabolism, synthesis of osmoregulators and antioxidant enzymes. In this context, the objective was to evaluate the effect of salicylic acid doses on the growth and physiological changes of eggplant seedlings under salt stress. The experiment was conducted in a greenhouse, where the treatments were distributed in randomized blocks using a central composite matrix Box with five levels of electrical conductivity of irrigation water (CEw) (0.50; 1.08; 2.50; 3.92 and 4.50 dS m-1), associated with five doses of salicylic acid (SA) (0.00; 0.22; 0.75; 1.28 and 1.50 mM), with four repetitions and each plot composed of three plants. At 40 days after sowing, plant height, stem diameter, number of leaves, leaf area, electrolyte leakage, relative water content, and total dry mass were determined. ECw and SA application influenced the growth and physiological changes of eggplant seedlings. Increasing the ECw reduced growth in the absence of SA. Membrane damage with the use of SA remained stable up to 3.9 dS m-1 of ECw. The relative water content independent of the CEw increased with 1.0 mM of SA. The use of SA at the concentration of 1.0 mM mitigated the deleterious effect of salinity on seedling growth up to 2.50 dS m-1 of ECw.
Resumo Em condições de estresse salino, o crescimento das plantas é reduzido, em virtude, do desequilíbrio osmótico, nutricional e oxidativo. Contudo, o ácido salicílico atua na mitigação desse estresse abiótico por promover incremento no crescimento, fotossíntese, metabolismo do nitrogênio, síntese de osmorreguladores e enzimas antioxidantes. Nesse contexto, objetivou-se avaliar o efeito de doses de ácido salicílico sobre o crescimento e alterações fisiológicas de mudas de berinjela sob estresse salino. O experimento foi conduzido em casa de vegetação, onde os tratamentos foram distribuídos em blocos ao acaso utilizando uma matriz composta central Box com cinco níveis de condutividade elétrica da água de irrigação (CEa) (0,50; 1,08; 2,50; 3,92 e 4,50 dS m-1), associada a cinco doses de ácido salicílico (AS) (0,00; 0,22; 0,75; 1,28 e 1,50 mM), com quatro repetições e cada parcela composta por três plantas. Aos 40 dias após a semeadura, foram determinados a altura da planta, diâmetro do caule, número de folhas, área foliar, vazamento de eletrólito, teor relativo de água e massa seca total. A CEa e a aplicação de AS influenciaram no crescimento e nas alterações fisiológicas das mudas de berinjela. O aumento da CEa reduziu o crescimento na ausência de AS. O dano de membrana com o uso de AS manteve-se estável até 3,9 dS m-1 de CEa. O conteúdo relativo de água independentemente da CEa aumentou com 1 mM de SA. O uso de AS na concentração de 1 mM mitigou o efeito deletério da salinidade no crescimento das mudas até 2,50 dS m-1 de CEa.
RESUMEN
This study aims to define the best method (slow freezing or vitrification) and fragment size (1, 5, or 9 mm³) for prepubertal goat testis cryopreservation, as well as to evaluate testicular morphological integrity after cryopreservation and in vitro culture (IVC). Initially (experiment I), 1, 5, or 9 mm³ testis fragments were cryopreserved by slow freezing using a Mr. Frosty container with 20% Dimethylsulfoxide (DMSO) or vitrified using the Ovarian Tissue Cryosystem (OTC) device, (Equilibration solution - ES: 10% DMSO and 10% ethylene glycol - EG; Vitrification solution - VS: 20% DMSO and 20% EG) and then subjected to morphological analysis, type I and III collagen quantification and gene expression (Oct4, C-kit, Bax, and Bcl-2). Subsequently, (experiment II), fresh or cryopreserved by slow freezing testis fragments were cultured in vitro and submitted to morphological analysis by scanning electron microscopy. The data from the experiment I revealed fewer morphological alterations in 1 and 5 mm³ fragments after vitrification and slow freezing, respectively. The percentage of type I collagen fibers in 5 and 9 mm³ frozen was higher than in fresh or vitrified fragments. For type III collagen, fresh or frozen fragments of 1 and 5 mm3 showed a higher percentage than fragments of 9 mm3. Gene expression for Oct4 and C-kit after slow freezing or vitrification in the 5 mm3 fragments was lower than that observed in the fresh fragments. The Bax:Bcl-2 ratio in the 1 and 9 mm³ fragments was lower than in the 5 mm³ fragments for fresh fragments or after freezing. In experiment II, fragments cultured in vitro, previously frozen or not, showed more morphological alterations than fresh or frozen fragments. We concluded that slow freezing of 5 mm³ fragments was the best protocol for cryopreserving prepubertal goat testis and although the results of IVC are encouraging, it still needs improvement to restore testicular function after cryopreservation.
Asunto(s)
Dimetilsulfóxido , Cabras , Animales , Masculino , Proteína X Asociada a bcl-2 , Criopreservación/veterinaria , Proteínas Proto-Oncogénicas c-bcl-2 , Proteínas Proto-Oncogénicas c-kitRESUMEN
Under salt stress conditions, plant growth is reduced due to osmotic, nutritional and oxidative imbalance. However, salicylic acid acts in the mitigation of this abiotic stress by promoting an increase in growth, photosynthesis, nitrogen metabolism, synthesis of osmoregulators and antioxidant enzymes. In this context, the objective was to evaluate the effect of salicylic acid doses on the growth and physiological changes of eggplant seedlings under salt stress. The experiment was conducted in a greenhouse, where the treatments were distributed in randomized blocks using a central composite matrix Box with five levels of electrical conductivity of irrigation water (CEw) (0.50; 1.08; 2.50; 3.92 and 4.50 dS m-1), associated with five doses of salicylic acid (SA) (0.00; 0.22; 0.75; 1.28 and 1.50 mM), with four repetitions and each plot composed of three plants. At 40 days after sowing, plant height, stem diameter, number of leaves, leaf area, electrolyte leakage, relative water content, and total dry mass were determined. ECw and SA application influenced the growth and physiological changes of eggplant seedlings. Increasing the ECw reduced growth in the absence of SA. Membrane damage with the use of SA remained stable up to 3.9 dS m-1 of ECw. The relative water content independent of the CEw increased with 1.0 mM of SA. The use of SA at the concentration of 1.0 mM mitigated the deleterious effect of salinity on seedling growth up to 2.50 dS m-1 of ECw.
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Ácido Salicílico , Solanum melongena , Antioxidantes/metabolismo , Fotosíntesis , Hojas de la Planta/metabolismo , Ácido Salicílico/farmacología , Salinidad , Tolerancia a la Sal , Plantones , Solanum melongena/metabolismo , Estrés FisiológicoRESUMEN
Glucocorticoids and melatonin (MEL) show integrated and complex immunomodulatory effects, mostly described for endotherms, yet underexplored in amphibians. In this context, the RT-qPCR of molecules mediating inflammatory processes in amphibians is a valuable tool to explore the relationships among molecular biology, endocrine mediators, and immune response in these animals. In this study, toads (Rhinella diptycha) received an intraperitoneal saline injection or lipopolysaccharide (LPS; 2 mg/kg). Six hours post-injection, we analyzed plasma corticosterone (CORT) and MEL levels and pro- and anti-inflammatory molecules (IL-1ß, IL-6, IL-10, IFN-γ, and C1s). We found increased CORT and decreased MEL levels in response to LPS. Also, IL-1ß, IL-6, and IL-10 were upregulated in LPS-injected toads compared with saline-injected toads. Overall, our results demonstrate an LPS-induced inflammatory response with endocrine and immune modulation in R. diptycha toads, exhibiting expected patterns for an inflammatory stimulus within this time frame (6 h post-injection). Toads were responsive to LPS by secreting different cytokines, such as proinflammatory cytokines IL-1ß and IL-6, related to immune cell attraction to inflammatory sites and the anti-inflammatory cytokine IL-10, which limits the rate of leukocyte infiltration, inflammation, and downregulates the expression of proinflammatory cytokines. Increased circulating CORT levels are probably associated with the activation of the hypothalamus-pituitary-interrenal axis by the LPS and the endocrine actions of IL-6. Furthermore, decreased circulating MEL levels are likely due to inhibited MEL secretion by the pineal gland by inflammatory stimuli, indicating the activation/existence of the immune-pineal axis in amphibians.
Os glicocorticoides e a melatonina (MEL) apresentam efeitos imunomoduladores integrados e complexos, principalmente descritos para endotérmicos, porém pouco explorados em anfíbios. Nesse contexto, o RT-qPCR de moléculas mediadoras de processos inflamatórios em anfíbios é uma ferramenta valiosa para explorar as relações entre biologia molecular, mediadores endócrinos e resposta imune nesses animais. Neste estudo, sapos (Rhinella diptycha) receberam uma injeção intraperitoneal de solução salina ou lipopolissacarídeo (LPS; 2 mg/kg). Seis horas após a injeção, analisamos as concentrações plasmáticas de corticosterona (CORT) e MEL e moléculas pró e anti-inflamatórias (IL-1ß, IL-6, IL-10, IFN-γ e C1s). Encontramos aumento de CORT e diminuição da concentração de MEL em resposta ao LPS. Além disso, IL-1ß, IL-6 e IL-10 foram reguladas positivamente em sapos injetados com LPS em comparação com os sapos injetados com solução salina. No geral, nossos resultados demonstram uma resposta inflamatória induzida por LPS com modulação endócrina e imunológica em sapos R. diptycha, exibindo padrões esperados para um estímulo inflamatório dentro deste período (6 h pós-injeção). Os sapos foram responsivos ao LPS secretando diferentes citocinas, como as citocinas pró-inflamatórias IL-1ß e IL-6, relacionadas à atração de células imunes para os sítios inflamatórios e a citocina anti-inflamatória IL-10, que limita a taxa de infiltração leucocitária, inflamação, e diminui a expressão de citocinas pró-inflamatórias. As concentrações elevadas de CORT circulante estão provavelmente associados à ativação do eixo hipotálamo-hipófise-interrenal pelo LPS e às ações endócrinas da IL-6. Além disso, a diminuição da concentração circulante de MEL é provavelmente devida à inibição da secreção de MEL pela glândula pineal por estímulos inflamatórios, indicando a ativação/existência do eixo imune-pineal em anfíbios.
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Epidermal growth factor receptor (EGFR) signaling and components of the fibrinolytic system, including urokinase-type plasminogen activator (uPA) and thrombomodulin (TM), have been implicated in tumor progression. In the present study, we employed cBioPortal platform (http://www.cbioportal.org/), cancer cell lines, and an in vivo model of immunocompromised mice to evaluate a possible cooperation between EGFR signaling, uPA, and TM expression/function in the context of cervical cancer. cBioPortal analysis revealed that EGFR, uPA, and TM are positively correlated in tumor samples of cervical cancer patients, showing a negative prognostic impact. Aggressive human cervical cancer cells (CASKI) presented higher gene expression levels of EGFR, uPA, and TM compared to its less aggressive counterpart (C-33A cells). EGFR induces uPA expression in CASKI cells through both PI3K-Akt and MEK1/2-ERK1/2 downstream effectors, whereas TM expression induced by EGFR was dependent on PI3K/Akt signaling alone. uPA induced cell-morphology modifications and cell migration in an EGFR-dependent and -independent manner, respectively. Finally, treatment with cetuximab reduced in vivo CASKI xenografted-tumor growth in nude mice, and decreased intratumoral uPA expression, while TM expression was unaltered. In conclusion, we showed that EGFR signaling regulated expression of the fibrinolytic system component uPA in both in vitro and in vivo settings, while uPA also participated in cell-morphology modifications and migration in a human cervical cancer model.
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Fosfatidilinositol 3-Quinasas , Neoplasias del Cuello Uterino , Animales , Línea Celular Tumoral , Movimiento Celular , Receptores ErbB , Femenino , Humanos , Ratones , Ratones Desnudos , Pronóstico , Neoplasias del Cuello Uterino/tratamiento farmacológicoRESUMEN
Epidermal growth factor receptor (EGFR) signaling and components of the fibrinolytic system, including urokinase-type plasminogen activator (uPA) and thrombomodulin (TM), have been implicated in tumor progression. In the present study, we employed cBioPortal platform (http://www.cbioportal.org/), cancer cell lines, and an in vivo model of immunocompromised mice to evaluate a possible cooperation between EGFR signaling, uPA, and TM expression/function in the context of cervical cancer. cBioPortal analysis revealed that EGFR, uPA, and TM are positively correlated in tumor samples of cervical cancer patients, showing a negative prognostic impact. Aggressive human cervical cancer cells (CASKI) presented higher gene expression levels of EGFR, uPA, and TM compared to its less aggressive counterpart (C-33A cells). EGFR induces uPA expression in CASKI cells through both PI3K-Akt and MEK1/2-ERK1/2 downstream effectors, whereas TM expression induced by EGFR was dependent on PI3K/Akt signaling alone. uPA induced cell-morphology modifications and cell migration in an EGFR-dependent and -independent manner, respectively. Finally, treatment with cetuximab reduced in vivo CASKI xenografted-tumor growth in nude mice, and decreased intratumoral uPA expression, while TM expression was unaltered. In conclusion, we showed that EGFR signaling regulated expression of the fibrinolytic system component uPA in both in vitro and in vivo settings, while uPA also participated in cell-morphology modifications and migration in a human cervical cancer model.
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Humanos , Animales , Femenino , Ratas , Neoplasias del Cuello Uterino/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas , Pronóstico , Movimiento Celular , Línea Celular Tumoral , Receptores ErbB , Ratones DesnudosRESUMEN
Jambu, Acmella oleracea (L.), is a low-growing herb plant, with cylindrical, fleshy, decumbent and branched stem varying from 20 to 30 cm in height. It is an abundantly cultivated and consumed vegetable in the northern region of Brazil and usually consumed in preparations of typical foods of the Amazon region. So, this work aimed to compare the chemical composition and physical chemistry of powdered and jambu leaf mass. Acmella oleracea plants were selected, sanitized and their leaves were crushed (without adding water). The mass was dried in an oven with forced air circulation under different conditions of temperature (60, 70 and 80 °C) and relative humidity (13.09, 8.14 and 5.45%, respectively), in two layer thicknesses (0.5 and 1.0 cm). The physical, chemical, physicochemical parameters moisture content, water activity, ash, protein, lipids, pH, total titratable acidity and color were analyzed in powdered and fresh leaves. Contrast test was used to evaluate the interaction between the layer thicknesses at 5% level of significance. Considering the contrasts, the parameters total soluble solids, ash, protein and lipids do not differ from those in the fresh sample, demonstrating that these parameters are not modified or degraded with the drying conditions. The pH and color parameters differed from those of the fresh material, due to degradation, which can be linked to the rise in temperature sensitivity. The moisture content and water activity also differed and were reduced, contributing to conservation of the material. Contrast analysis made it possible to conclude that the physicochemical composition did not undergo modifications through the use of drying. In addition, a powdered material with reduced water activity was obtained.
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BACKGROUND: Regional heterogeneities and sociodemographic characteristics affect mortality and population survival in Brazil. However, for individuals with Down syndrome (DS) this information remains unknown. In this study, we analysed survival and mortality rates among DS individuals in the five Brazilian geographic regions. In addition, we investigated whether there is an association between mortality and sociodemographic factors across administrative regions. METHODS: Data between 1996 and 2016, comprising 10 028 records of deaths of individuals with DS, were collected from database records of the Department of Informatics of the Unified Health System. Data on race/ethnicity, sex, age and years of schooling were defined for the association analyses. Survival data were analysed according to the Kaplan-Meier method and Cox regression model. RESULTS: The number of deaths among people with DS has increased in recent years. Children are more susceptible to death, especially in the first years of life. Individuals living in the northern region, Indigenous women and people with no years of schooling have higher mortality. In the Southeast and South region, for White and Yellow, survival is related to a higher level of education. Ethnic factors and years of schooling influence risk for mortality across the administrative regions. CONCLUSIONS: These findings show that sociodemographic characteristics affect survival and are associated with the risk of mortality for people with DS. In addition, this suggests that differences in access to health services among Brazilian regions, especially in the first years of life, may affect the survival of individuals with DS.
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Síndrome de Down/mortalidad , Mortalidad/tendencias , Factores Socioeconómicos , Adolescente , Adulto , Brasil/epidemiología , Niño , Preescolar , Bases de Datos Factuales , Síndrome de Down/etnología , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Severe acute pancreatitis remains a life-threatening condition, responsible for many disorders of homeostasis and organ dysfunction. By means of a mnemonic 'PANCREAS', eight important steps in the management of severe acute pancreatitis are highlighted. These steps follow the principle of goal-directed therapy and should be borne in mind after diagnosis and during clinical treatment. The first step is perfusion: the goal is to reach a central venous pressure of 12-15mmHg, urinary output 0.5-1ml/kg/hour and inferior vena cava collapse index greater than 48%. Next is analgesia: multimodal, systemic and combined pharmacological agent and epidural block are possibilities. Third is nutrition: precocity, enteral feeding in gastric or post-pyloric position. Parenteral nutrition works best in difficult cases to achieve the individual total caloric value. Fourth is clinical: mild, moderate or severe pancreatitis according to the Atlanta criteria. Radiology is fifth: abdominal computed tomography on the fourth day for prognosis or to modify management. Endoscopy is sixth: endoscopic retrograde cholangiopancreatography (cholangitis, unpredicted clinical course and ascending jaundice); management of pancreatic fluid collection and 'walled-off necrosis'. Antibiotics come next: infectious complications are common causes of morbidity. The only rational indication for antibiotics is documented pancreatic infection. The last step is surgery: the dogma is represented by the 'three Ds' (delay, drain, debride). The preferred method is a minimally invasive step-up approach, which allows for gradually more invasive procedures when the previous treatment fails.
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Pancreatitis Aguda Necrotizante , Colangiopancreatografia Retrógrada Endoscópica , Nutrición Enteral , Humanos , Pancreatitis Aguda Necrotizante/diagnóstico por imagen , Pancreatitis Aguda Necrotizante/terapia , Guías de Práctica Clínica como Asunto , Pronóstico , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Nandrolone decanoate (ND) is an anabolic-androgenic steroid, and its indiscriminate use leads to subclinical alterations in the hypothalamic-pituitary-gonadal axis and androgen-dependent organs. OBJECTIVES: To evaluate the effects of ND, either alone or in combination with resistance exercise (RE), on the levels of sex hormones, converting enzymes, and steroid receptors and the morphology of the ventral prostate (VP) in adult and aged rats. METHODS: Forty Sprague-Dawley adult and aged rats were divided into four groups each, sedentary and trained with and without ND. The groups received treatments over 8 weeks. Adult animals were sacrificed immediately following treatment completion, while the aged groups were left untreated until 300 days of age. RESULTS: Adult and aged animals showed reductions in testosterone levels following the different treatments, and 17ß-estradiol levels were decreased in the ND-treated groups. The level of 5α-reductase type 2 (5αR2) and aromatase was increased significantly in the prostates of adult animals that performed RE. However, aromatase levels were decreased in the prostates of aged animals that performed RE and were treated with ND, while 5αR2 levels were reduced in aged animals that performed RE without ND treatment. When sex receptors levels were examined, the aged and trained animals presented low androgen receptor (AR) levels. Estrogen receptors (ERs) levels were increased in the prostates of adult animals that received ND. ERß levels were reduced after treatments in aged animals. The heights of the prostatic epithelium were reduced in all adult treated animals, coinciding with increases in PCNA and PAR4 levels. DISCUSSION: ND and RE alter the levels of hormone, converting enzymes, and sex steroid receptors and the morphology of the VP. These effects were observed in both adult and aged rats. CONCLUSION: ND, either with or without RE, during post-puberty stage is able to interfere with the morphophysiology of the prostate.
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Anabolizantes/efectos adversos , Nandrolona Decanoato/efectos adversos , Próstata/efectos de los fármacos , Entrenamiento de Fuerza , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/metabolismo , Animales , Aromatasa/metabolismo , Estradiol/sangre , Masculino , Antígeno Nuclear de Célula en Proliferación/metabolismo , Próstata/enzimología , Ratas Sprague-Dawley , Receptores de Trombina/metabolismo , Testosterona/sangreRESUMEN
The resistance of micro-organisms to antimicrobial agents has been a challenge to treat animal and human infections, and for environmental control. Lectins are natural proteins and some are potent antimicrobials through binding to carbohydrates on microbial surfaces. Oligomerization state of lectins can influence their biological activity and maximum binding capacity; the association among lectin polypeptide chains can alter the carbohydrate-lectin binding dissociation rate constants. Antimicrobial mechanisms of lectins include the pore formation ability, followed by changes in the cell permeability and latter, indicates interactions with the bacterial cell wall components. In addition, the antifungal activity of lectins is associated with the chitin-binding property, resulting in the disintegration of the cell wall or the arrest of de novo synthesis from the cell wall during fungal development or division. Quorum sensing is a cell-to-cell communication process that allows interspecies and interkingdom signalling which coordinate virulence genes; antiquorum-sensing therapies are described for animal and plant lectins. This review article, among other approaches, evaluates lectins as antimicrobials.
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Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Farmacorresistencia Microbiana , Hongos/efectos de los fármacos , Lectinas/farmacología , Animales , Infecciones Bacterianas/microbiología , Humanos , Micosis/microbiología , Percepción de Quorum/efectos de los fármacosRESUMEN
The relationships between morphology, performance, behavior and ecology provide evidence for multiple and complex phenotypic adaptations. The anuran body plan, for example, is evolutionarily conserved and shows clear specializations to jumping performance back at least to the early Jurassic. However, there are instances of more recent adaptation to habit diversity in the post-cranial skeleton, including relative limb length. The present study tested adaptive models of morphological evolution in anurans associated with the diversity of microhabitat use (semi-aquatic arboreal, fossorial, torrent, and terrestrial) in species of anuran amphibians from Brazil and Australia. We use phylogenetic comparative methods to determine which evolutionary models, including Brownian motion (BM) and Ornstein-Uhlenbeck (OU) are consistent with morphological variation observed across anuran species. Furthermore, this study investigated the relationship of maximum distance jumped as a function of components of morphological variables and microhabitat use. We found there are multiple optima of limb lengths associated to different microhabitats with a trend of increasing hindlimbs in torrent, arboreal, semi-aquatic whereas fossorial and terrestrial species evolve toward optima with shorter hindlimbs. Moreover, arboreal, semi-aquatic and torrent anurans have higher jumping performance and longer hindlimbs, when compared to terrestrial and fossorial species. We corroborate the hypothesis that evolutionary modifications of overall limb morphology have been important in the diversification of locomotor performance along the anuran phylogeny. Such evolutionary changes converged in different phylogenetic groups adapted to similar microhabitat use in two different zoogeographical regions.
Asunto(s)
Anuros/fisiología , Evolución Biológica , Ecosistema , Locomoción , Modelos Genéticos , Animales , Anuros/anatomía & histología , Miembro Posterior/anatomía & histología , Masculino , Selección GenéticaRESUMEN
Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) molecule is expressed on T-lymphocyte membrane and negatively influences the antigen-presenting process. Reduced expression of CTLA-4 due to gene polymorphisms is associated with increased risk of autoimmune disorders, whose physiopathology is similar to that of post-transfusion red blood cell (RBC) alloimmunization. Our goal was to evaluate if polymorphisms of CTLA-4 gene that affect protein expression are associated with RBC alloimmunization. This was a case-control study in which 134 sickle cell disease (SCD) patients and 253 non-SCD patients were included. All patients were genotyped for the polymorphisms 49A/G and -318C/T of CTLA-4 gene. The genotype frequency of -318C/T differed significantly between alloimmunized and nonalloimmunized SCD patients, irrespective of clinical confounders (p = .016). SCD patients heterozygous for -318T allele presented higher risk of alloantibody development (OR: 5.4, CI: 1.15-25.6). In conclusion, the polymorphism -318C/T of CTLA-4 gene is associated with RBC alloimmunization among SCD patients. This highlights the role played by CTLA-4 on post-transfusion alloantibody development.
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Anemia de Células Falciformes/genética , Enfermedades Autoinmunes/genética , Antígeno CTLA-4/genética , Eritrocitos/inmunología , Adulto , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/inmunología , Anemia de Células Falciformes/prevención & control , Células Presentadoras de Antígenos/inmunología , Células Presentadoras de Antígenos/patología , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Antígeno CTLA-4/inmunología , Eritrocitos/patología , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Inmunización/efectos adversos , Isoanticuerpos/inmunología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo , Linfocitos T/inmunología , Linfocitos T/patologíaRESUMEN
AIMS: This study aimed to evaluate new d-xylose-fermenting yeasts from Brazilian ecosystems for the production of second-generation ethanol. METHODS AND RESULTS: d-xylose-fermenting yeasts isolated from rotting wood and wood-boring insects were identified as the species Scheffersomyces parashehatae, Scheffersomyces illinoinensis, Spathaspora arborariae and Wickerhamomyces rabaulensis. Among the yeasts tested, those of Sc. parashehatae exhibited the highest ethanol production when cultivated on complex medium (Yp/set = 0·437 g g-1 ). Sheffersomyces illinoinensis and Sp. arborariae showed similar ethanol production in this assay (Yp/set up to 0·295 g g-1 ). In contrast, in sugarcane bagasse hemicellulosic hydrolysate, Sc. parashehatae and Sc. illinoinensis exhibited similar ethanol production (Yp/set up to 0·254 g g-1 ), whereas Sp. arborariae showed the lowest results (peak Yp/set = 0·160 g g-1 ). Wickerhamomyces rabaulensis exhibited a remarkable xylitol production (Yp/sxyl = 0·681 g g-1 ), but producing low levels of ethanol (Yp/set = 0·042 g g-1 ). CONCLUSIONS: The novel d-xylose-fermenting yeasts showed promising metabolic characteristics for use in fermentation processes for second-generation ethanol production, highlighting the importance of bioprospecting research of micro-organisms for biotechnological applications. SIGNIFICANCE AND IMPACT OF THE STUDY: This study widens the scope for future researches that may examine the native yeasts presented, as limited studies have investigated these species previously.
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Celulosa/metabolismo , Etanol/metabolismo , Polisacáridos/metabolismo , Saccharomycetales/metabolismo , Saccharum/metabolismo , Madera/microbiología , Brasil , Ecosistema , Fermentación , Saccharomycetales/clasificación , Saccharomycetales/genética , Saccharomycetales/aislamiento & purificación , Xilitol/biosíntesis , Xilosa/metabolismoRESUMEN
Objectives Anti-ribosomal P protein (anti-P) autoantibodies are highly specific for systemic lupus erythematosus (SLE). However, the evaluation of this autoantibody in childhood-onset SLE (cSLE) populations has been limited to a few small series, hampering the interpretation of the clinical and laboratorial associations. Therefore, the objective of this multicenter cohort study was to evaluate demographic, clinical/laboratorial features, and disease damage score in cSLE patients with and without the presence of anti-P antibody. Methods This was a retrospective multicenter study performed in 10 pediatric rheumatology services of São Paulo state, Brazil. Anti-P antibodies were measured by ELISA in 228 cSLE patients. Results Anti-P antibodies were observed in 61/228 (27%) cSLE patients. Frequencies of cumulative lymphadenopathy (29% vs. 15%, p = 0.014), acute confusional state (13% vs. 5%, p = 0.041), mood disorder (18% vs. 8%, p = 0.041), autoimmune hemolytic anemia (34% vs. 15%, p = 0.001), as well as presence of anti-Sm (67% vs. 40%, p = 0.001), anti-RNP (39% vs. 21%, p = 0.012) and anti-Ro/SSA antibodies (43% vs. 25%, p = 0.016) were significantly higher in cSLE patients with anti-P antibodies compared to those without these autoantibodies. A multiple regression model revealed that anti-P antibodies were associated with autoimmune hemolytic anemia (odds ratio (OR) = 2.758, 95% confidence interval (CI): 1.304-5.833, p = 0.008) and anti-Sm antibody (OR = 2.719, 95% CI: 1.365-5.418, p = 0.004). The SLICC/ACR damage index was comparable in patients with and without anti-P antibodies ( p = 0.780). Conclusions The novel association of anti-P antibodies and autoimmune hemolytic anemia was evidenced in cSLE patients and further studies are necessary to determine if anti-P titers may vary with this hematological manifestation.
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Anemia Hemolítica Autoinmune/epidemiología , Autoanticuerpos/metabolismo , Lupus Eritematoso Sistémico/complicaciones , Trastornos del Humor/epidemiología , Proteínas Ribosómicas/inmunología , Adolescente , Edad de Inicio , Anemia Hemolítica Autoinmune/inmunología , Niño , Preescolar , Femenino , Humanos , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/psicología , Masculino , Análisis de Regresión , Estudios Retrospectivos , Adulto JovenRESUMEN
9-cis-epoxycarotenoid dioxygenase (NCED) encodes a key enzyme in abscisic acid (ABA) biosynthesis. Little is known regarding the regulation of stress response by NCEDs at physiological levels. In the present study, we generated transgenic tobacco overexpressing an NCED3 ortholog from citrus (CsNCED3) and investigated its relevance in the regulation of drought stress tolerance. Wild-type (WT) and transgenic plants were grown under greenhouse conditions and subjected to drought stress for 10 days. Leaf predawn water potential (Ψwleaf), stomatal conductance (gs), net photosynthetic rate (A), transpiration rate (E), instantaneous (A/E) and intrinsic (A/gs) water use efficiency (WUE), and in situ hydrogen peroxide (H2O2) and abscisic acid (ABA) production were determined in leaves of irrigated and drought-stressed plants. The Ψwleaf decreased throughout the drought stress period in both WT and transgenic plants, but was restored after re-watering. No significant differences were observed in gs between WT and transgenic plants under normal conditions. However, the transgenic plants showed a decreased (P ≤ 0.01) gs on the 4th day of drought stress, which remained lower (P ≤ 0.001) than the WT until the end of the drought stress. The A and E levels in the transgenic plants were similar to those in WT; therefore, they exhibited increased A/gs under drought conditions. No significant differences in A, E, and gs values were observed between the WT and transgenic plants after re-watering. The transgenic plants had lower H2O2 and higher ABA than the WT under drought conditions. Our results support the involvement of CsNCED3 in drought avoidance.
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Dioxigenasas/biosíntesis , Nicotiana/fisiología , Proteínas de Plantas/biosíntesis , Ácido Abscísico/biosíntesis , Adaptación Fisiológica , Citrus/enzimología , Citrus/genética , Dioxigenasas/genética , Dioxigenasas/metabolismo , Sequías , Hojas de la Planta/enzimología , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Estrés Fisiológico , Nicotiana/enzimología , Nicotiana/genética , Nicotiana/metabolismoRESUMEN
AIM: This was to assess the antimicrobial effectiveness of pastes used as intracanal medicaments against Enterococcus faecalis in necrotic immature teeth. METHOD: An agar-disc diffusion method over a period of 30 days was used. The following medications were analysed: triple antibiotic paste (TAP) I; double antibiotic paste (DAP) I; DAP I with calcium hydroxide; calcium hydroxide paste with saline solution 0.9 %; calcium hydroxide paste with chlorhexidine 2 % gel; DAP II; DAP II with zinc oxide; DAP II with calcium hydroxide; and saline solution 0.9 % as control. The diameters of the halos of inhibition (in mm) of tested medicaments were determined and analysed with one-way analysis of variance and Tukey's post hoc tests. RESULTS: TAP I (G1) was significantly more effective against E. faecalis, and showed the largest halo of inhibition during all the experiments. DAP groups (G2 and G6) also showed inhibiting bacterial growth with said inhibition remaining stable throughout the 30-day period. In contrast, G4 and G5 groups, in which Ca(OH)2 was added to saline and chlorhexidine, had no antibacterial effect. CONCLUSIONS: TAP and DAP showed better antibacterial efficacy and remained active for 30 days. Combination of Ca(OH)2 with antibiotics should be avoided, due to the possibility of antibiotic hydrolysis.