RESUMO
Fig A) Radiografía de cráneo en proyección lateral: se observan múltiples lesiones radiolúcidas distribuidas en todo el cráneo. B) Acercamiento donde se evidencian múltiples lesiones en sacabocado, compatibles con mieloma múltiple(AU)
Assuntos
Humanos , Masculino , Feminino , Neoplasias Cranianas/diagnóstico por imagem , Mieloma Múltiplo/diagnóstico por imagemRESUMO
Natural killer (NK) cells play a crucial role in cervical cancer (CC). As estrogens and prolactin (PRL) have been reported to be involved in CC, the present study attempted to elucidate the effects of both hormones on NK cells in CC. For this purpose, NKL cells, as well as CC-derived cell lines (HeLa, SiHa and C33A) and non-tumorigenic keratinocytes (HaCaT cells) were stimulated with 17ß-estradiol (E2; 10 nM), PRL (200 ng/ml), or both (E2 and PRL) for 48 h. The expression of hormone receptors (estrogen receptor α and ß, G protein-coupled estrogen receptor 1 and PRL receptor) and NK cell activating receptors [natural killer group 2D (NKG2D), natural cytotoxicity triggering receptor 3, natural cytotoxicity triggering receptor 2 and natural cytotoxicity triggering receptor 1] were measured using western blot analysis and flow cytometry, respectively. In the HeLa, SiHa, C33A and HaCaT cells stimulated with the hormones, the expression of NKG2D ligands [MHC class I polypeptide-related sequence A/B (MICA/B)] on the membrane and the soluble form of MICA was evaluated using flow cytometry and ELISA. Cytotoxicity assay was performed using GFP-transfected K562 cells as target cells. E2 reduced NKL cell-mediated cytotoxicity, while PRL exerted the opposite effect. NKL cells expressed different hormone receptor forms, of which PRL only induced a decrease in NKG2D expression compared to the untreated control NKL cells. PRL increased MICA/B expression in HeLa cells and E2 and PRL reversed this effect. However, in SiHa cells, the concurrent incubation with the two hormones decreased MICA/B expression. E2 and PRL, either alone or in combination, decreased soluble MICA secretion in all CC cell lines, while E2 solely increased soluble MICA secretion in SiHa cells. On the whole, the present study provides evidence that E2 and PRL mediate the mechanisms through which NK and CC cells mediate a cytotoxic response and these have an antagonistic effect on NK cell-mediated cytotoxicity.
RESUMO
Resumen La esclerosis lateral amiotrófica (ELA) es una enfermedad neurológica degenerativa que afecta la vía piramidal, a lo largo de su primera y segunda motoneurona. En Estados Unidos de América, la ELA es mejor conocida como enfermedad de Lou Gehrig, en alusión al jugador de béisbol de los Yankees que murió en 1941 debido a esta patología. Etimológicamente, esclerosis significa endurecimiento y hace referencia al estado de la médula espinal en las fases avanzadas de la enfermedad. Lateral significa "al lado" y pone de manifiesto la ubicación del daño en la médula espinal. Por último, el término amiotrófica significa "sin nutrición muscular" y se refiere a la pérdida de señales que los nervios envían normalmente a los músculos. La etiología de este trastorno es desconocida, se considera esporádico en 90 a 95% de los casos y con tendencia familiar en 5%. La supervivencia al momento del diagnóstico ronda el 20% a los 3-5 años.
Abstract Amyotrophic lateral sclerosis (ALS) is a degenerative neurological disease that affects the pyramidal pathway, along its first and second motor neurons. In the United States of America, ALS is better known as Lou Gehrig's disease, alluding to the Yankees baseball player who died in 1941 from this condition. Etymologically, Sclerosis means hardening and refers to the state of the spinal cord in the advanced stages of the disease. Lateral means "to the side" and reveals the location of the spinal cord damage. Finally, the term amyotrophic means "without muscle nutrition" and refers to the loss of signals that the nerves normally send to the muscles. The etiology of this disorder is unknown, it is considered sporadic in 90-95% of cases and with a familial tendency in 5%. Survival at diagnosis is around 20% at 3-5 years.
RESUMO
Psoriasis is a chronic inflammatory disease that presents skin rashes which can arise through plaques. The aim of this work was to compare the effectiveness of short-term physical agents treatment on macroscopic morphology (area and erythema) in patients with plaque psoriasis. This prospective randomized experimental study included fourteen subjects, medically diagnosed with psoriasis, with more than one plaque in the skin and voluntarily without topical treatment. All subjects completed the study that consisted of 12 treatment sessions divided in control (C), artificial balneotherapy (AB), phototherapy (PT) or balneophototherapy (BPT) groups. After session 12, there was a significant reduction of the plaque area by all treatments when compared to C group and BPT was the most effective one. However, only AB and PT presented a reduction of erythema. Regarding severity, 9 patients changed to a lower category on the PASI test, and 5 of them maintained a mild psoriasis, but lowered their score. Finally, 13 of 14 subjects improved their quality of life. The physical agents used reduced the severity of psoriasis and improved quality of life of patients after 12 sessions of treatment during a onemonth period. The BPT was the more effective in controlling psoriasis by diminishing its area and PT by attenuating the erythema.
La Psoriasis es una enfermedad inflamatoria crónica que presenta irritación cutánea que puede derivar a placas. El objetivo de este trabajo fue comparar la efectividad del tratamiento a corto plazo con agentes físicos en la morfología macroscópica (área y eritema) en pacientes con placas de psoriasis. Estudio experimental, prospectivo, randomizado. Catorce sujetos participaron con diagnóstico médico de psoriasis, con más de una placa en la piel y sin tener tratamiento tópico de forma voluntaria. Todos los sujetos completaron el estudio, el cual consistió de 12 sesiones de tratamiento dividido en grupo control (C), BA, FT y BFA. Posterior a la sesión 12, se observó una reducción significativa en toda el área de las placas que recibieron tratamiento al compararlas al grupo C y el grupo BFA fue el más efectivo. Sin embargo, solo los grupos BA y FT presentaron una reducción del eritema. Respecto a la severidad, 9 pacientes cambiaron de la baja categoría en el test de PASI y 5 de ellos se mantuvieron en el nivel medio, pero disminuyeron su puntaje. Finalmente, 13 de 14 sujetos mejoraron su calidad de vida. Los agentes físicos usados redujeron la severidad de la psoriasis y mejoraron la calidad de vida de los pacientes después de 12 sesiones de tratamiento durante el período de un mes. La BFA fue la más efectiva en controlar la psoriasis por la disminución en el área y la FT por la atenuación del eritema.
Assuntos
Humanos , Masculino , Feminino , Adulto , Fototerapia/métodos , Psoríase/terapia , Balneologia/métodos , Psoríase/patologia , Psoríase/psicologia , Qualidade de Vida , Fatores de Tempo , Índice de Gravidade de Doença , Estudos Prospectivos , Inquéritos e Questionários , Resultado do TratamentoRESUMO
OBJECTIVES: Acute kidney injury is a serious complication with unacceptably high mortality that lacks of specific curative treatment. Therapies focusing on the hydraulic behavior have shown promising results in preventing structural and functional renal impairment, but the underlying mechanisms remain understudied. Our goal is to assess the effects of renal decapsulation on regional hemodynamics, oxygenation, and perfusion in an ischemic acute kidney injury experimental model. METHODS: In piglets, intra renal pressure, renal tissue oxygen pressure, and dysoxia markers were measured in an ischemia-reperfusion group with intact kidney, an ischemia-reperfusion group where the kidney capsule was removed, and in a sham group. RESULTS: Decapsulated kidneys displayed an effective reduction of intra renal pressure, an increment of renal tissue oxygen pressure, and a better performance in the regional delivery, consumption, and extraction of oxygen after reperfusion, resulting in a marked attenuation of acute kidney injury progression due to reduced structural damage and improved renal function. CONCLUSIONS: Our results strongly suggest that renal decapsulation prevents the onset of an intrinsic renal compartment syndrome after ischemic acute kidney injury.
Assuntos
Injúria Renal Aguda/complicações , Síndromes Compartimentais/prevenção & controle , Hepatectomia , Rim/irrigação sanguínea , Injúria Renal Aguda/etiologia , Animais , Síndromes Compartimentais/etiologia , Hemodinâmica/fisiologia , Hepatectomia/métodos , Traumatismo por Reperfusão/complicações , SuínosRESUMO
Chronic peritoneal dialysis (PD) therapy is equally efficient as hemodialysis while providing greater patient comfort and mobility. Therefore, PD is the treatment of choice for several types of renal patients. During PD, a high-glucose hyperosmotic (HGH) solution is administered into the peritoneal cavity to generate an osmotic gradient that promotes water and solutes transport from peritoneal blood to the dialysis solution. Unfortunately, PD has been associated with a loss of peritoneal viability and function through the generation of a severe inflammatory state that induces human peritoneal mesothelial cell (HPMC) death. Despite this deleterious effect, the precise molecular mechanism of HPMC death as induced by HGH solutions is far from being understood. Therefore, the aim of this study was to explore the pathways involved in HGH solution-induced HPMC death. HGH-induced HPMC death included influxes of intracellular Ca2+ and Na+. Furthermore, HGH-induced HPMC death was inhibited by antioxidant and reducing agents. In line with this, HPMC death was induced solely by increased oxidative stress. In addition to this, the cPKC/NOX2 and PI3K/Akt intracellular signaling pathways also participated in HGH-induced HPMC death. The participation of PI3K/Akt intracellular is in agreement with previously shown in rat PMC apoptosis. These findings contribute toward fully elucidating the underlying molecular mechanism mediating peritoneal mesothelial cell death induced by high-glucose solutions during peritoneal dialysis.
RESUMO
Propolis is a polyphenol-rich resinous substance extensively used to improve health and prevent diseases. The effects of polyphenols from different sources of propolis on atherosclerotic lesions and inflammatory and angiogenic factors were investigated in LDL receptor gene (LDLr-/-) knockout mice. The animals received a cholesterol-enriched diet to induce the initial atherosclerotic lesions (IALs) or advanced atherosclerotic lesions (AALs). The IAL or AAL animals were divided into three groups, each receiving polyphenols from either the green, red or brown propolis (250 mg/kg per day) by gavage. After 4 weeks of polyphenol treatment, the animals were sacrificed and their blood was collected for lipid profile analysis. The atheromatous lesions at the aortic root were also analyzed for gene expression of inflammatory and angiogenic factors by quantitative real-time polymerase chain reaction and immunohistochemistry. All three polyphenol extracts improved the lipid profile and decreased the atherosclerotic lesion area in IAL animals. However, only polyphenols from the red propolis induced favorable changes in the lipid profiles and reduced the lesion areas in AAL mice. In IAL groups, VCAM, MCP-1, FGF, PDGF, VEGF, PECAM and MMP-9 gene expression was down-regulated, while the metalloproteinase inhibitor TIMP-1 gene was up-regulated by all polyphenol extracts. In contrast, for advanced lesions, only the polyphenols from red propolis induced the down-regulation of CD36 and the up-regulation of HO-1 and TIMP-1 when compared to polyphenols from the other two types of propolis. In conclusion, polyphenols from propolis, particularly red propolis, are able to reduce atherosclerotic lesions through mechanisms including the modulation of inflammatory and angiogenic factors.
Assuntos
Inibidores da Angiogênese/farmacologia , Aterosclerose/tratamento farmacológico , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Própole/química , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Colesterol/sangue , Regulação para Baixo , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Inflamação/prevenção & controle , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator de Crescimento Derivado de Plaquetas/genética , Fator de Crescimento Derivado de Plaquetas/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores de LDL/genética , Receptores de LDL/metabolismo , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Regulação para Cima , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo , Fatores de Crescimento do Endotélio Vascular/genética , Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Interindividual differences in activity and expression of the metabolizing enzymes cytochrome P450 (CYP) 3A4 and 3A5 and the multidrug efflux pump P-glycoprotein (P-gp, encoded by ABCB1 gene) contribute considerably to lipid-lowering efficacy of statin treatment in subjects with hypercholesterolemia. Variability in the activity of CYP3A4, CYP3A5 and P-gp could be considered to result from genetic polymorphisms encoding their genes. However, the available data indicate that the frequencies of ABCB1, CYP3A4 and CYP3A5 gene polymorphisms differ significantly across populations. Thus, the aim of the present study was to determine the allelic frequency of three common variants of these genes in Chilean individuals with primary hypercholesterolemia (HC) and controls. A total of 135 unrelated patients (44 +/- 7 years old) with diagnosis of hypercholesterolemia (Total cholesterol 240 mg/dL) and 120 normolipidemic healthy controls (40 +/- 10 years old; total cholesterol 200 mg/dL) were included in this study. The 3435C>T (MDR1), -290A>G (CYP3A4) and 6986A>G (CYP3A5) gene polymorphisms were analyzed by PCR-RFLP. The genotype distribution for 3435C>T variant of ABCB1 in HC patients (CC: 49 percent, CT: 37 percent, TT: 14 percent) and controls (CC: 41 percent, CT: 48 percent, TT: 11 percent) was comparable (P=0.186). Similarly, the genotype distribution for -290A>G polymorphism of CYP3A4 in HC subjects (AA: 73 percent, AG: 27 percent, GG: 0 percent) and controls (AA: 71 percent, AG: 29 percent, GG: 0 percent) was equivalent (P = 0.863). Finally, the genotype distribution for 6986A>G variant of CYP3A5 in HC individuals (AA: 4 percent, AG: 41 percent, GG: 55 percent) and controls (AA: 4 percent, AG: 47 percent, GG: 49 percent) was similar (P=0.594). The allelic frequencies of 3435C>T (ABCB1), -290A>G (CYP3A4) and 6986A>G (CYP3A5) polymorphisms are similar between Chilean HC patients and controls, and comparable to frequencies found in Asian populations.
Polimorfismos de los genes CYP3A4, CYP3A5 y ABCB1 se han asociado a variaciones en la respuesta a fármacos hipolipemiantes, como las estatinas; principales medicamentos utilizados para disminuir los niveles plasmáticos de colesterol (CT). Sin embargo, la frecuencia de estas variantes genéticas puede variar entre las poblaciones. Así, el objetivo de este trabajo fue evaluar la frecuencia de tres polimorfismos de los genes CYP3A4, CYP3A5 y ABCB1, relacionados previamente a la respuesta a estatinas, en individuos chilenos hipercolesterolémicos (HC) y controles. Se analizaron 135 sujetos con diagnóstico de hipercolesterolemia primaria (CT 240 mg/dL) y 120 controles (CT 200 mg/dL) pertenecientes a la Región de La Araucanía (Chile). La genotipificación de las variantes genéticas se efectuó mediante la técnica de reacción en cadena de la polimerasa seguido de restricción enzimática (PCR-RFLP). La distribución de genotipos para la variante 3435C>T del gen ABCB1 en los individuos HC (CC: 49 por ciento, CT: 37 por ciento, TT: 14 por ciento) y controles (CC: 41 por ciento, CT: 48 por ciento, TT: 11 por ciento) fue semejante (P = 0,186). De forma similar, la distribución de genotipos para el polimorfismo -290A>G del gen CYP3A4 en los pacientes HC (AA: 73 por ciento, AG: 27 por ciento, GG: 0 por ciento) y controles (AA: 71 por ciento, AG: 29 por ciento, GG: 0 por ciento) fue equivalente (P = 0,863). Del mismo modo, la distribución de genotipos para la variante 6986A>G del gen CYP3A5 en el grupo HC (AA: 4 por ciento, AG: 41 por ciento, GG: 55 por ciento) y grupo control (AA: 4 por ciento, AG: 47 por ciento, GG: 49 por ciento) fue similar (P = 0,594). En resumen, nuestro estudio demuestra que las frecuencias de los polimorfismos 3435C>T (ABCB1), -290A>G (CYP3A4) y 6986A>G (CYP3A5) no difieren entre individuos HC y controles, y son comparables a las frecuencias encontradas en poblaciones asiáticas. Su efecto sobre el tratamiento con estatinas en la población chilena debe ser...
Assuntos
Humanos , Masculino , Feminino , Adulto , Anticolesterolemiantes/farmacocinética , Anticolesterolemiantes/uso terapêutico , Hipercolesterolemia/genética , Hipercolesterolemia/tratamento farmacológico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Estudos de Casos e Controles , Chile , /genética , Frequência do Gene , Genes MDR , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Polimorfismo Genético , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
En el presente estudio se evaluó el efecto del propóleos sobre el metabolismo de la glucosa en ratones C57/BL-6 con diabetes mellitus tipo 2 inducida por dieta alta en grasa. Se midieron los cambios en las concentraciones séricas de lípidos, glucosa e insulina, y el efecto sobre la captación de 2-deoxi-[2,6-3H]-D-glucosa, síntesis de [14C]-glicógeno y descarboxilación de [U-14C]-D-glucosa inducida por insulina en músculo aislado. Los resultados muestran que en ratones diabéticos, el tratamiento con propóleos (150 mg/kg/día) reduce los niveles de insulina e índice HOMA (P<0.05). También disminuyó la obesidad abdominal de estos animales (P<0.05). Por otro lado, no modificó las concentraciones plasmáticas de glucosa, colesterol total y triglicéridos. Se observó también que la captación de 2-deoxi-[2,6-3H]-D-glucosa, síntesis de [14C]-glicógeno y descarboxilación de [U-14C]-D-glucosa inducida por insulina en músculo sóleo de ratones tratados con propóleos fue significativamente superior al grupo control (P<0.05). En resumen, nuestros datos confirman que el propóleos es capaz de modular el metabolismo de glucosa en ratones C57/BL-6 con diabetes mellitus tipo 2 inducida por dieta alta en grasa. Los datos obtenidos constituyen un importante antecedente que avala el posible uso del propóleos como fuente de polifenoles con actividad antidiabetogénica.
In the current study, we investigated the effect of propolis on diabetic mice undergoing propolis treatment (150 mg/kg/day) for a 6 week period. We also evaluated serum lipids, glucose, insulin levels and the effect on glucose uptake of 2-deoxy-D-[2,6-3H] glucose, [14C]-glycogen synthesis and [U-14C]-D-glucose decarboxylation induced by insulin in muscle tissue. Our results show that treatment with propolis (150 mg/kg/day) reduced insulin and HOMA index (P<0.05). Propolis also lowered abdominal obesity (P<0.05). No effects over serum glucose, total cholesterol and triglycerides levels were observed. We also observed that uptake of 2-deoxy-D-[2,6-3H] glucose, [14C]-glycogen synthesis and [U-14C]-D-glucose decarboxylation induced by insulin in soleus muscle of mice treated with propolis were significantly greater than control group (P<0.05). In summary, our data establishes that propolis modulates glucose metabolism. This result constitutes important data indicating that propolis can be used as a polyphenols source with antidiabetogenic activity.
Assuntos
Ratos , /induzido quimicamente , /metabolismo , Própole/administração & dosagem , Própole/metabolismo , Glucose/antagonistas & inibidores , Ratos/metabolismoRESUMO
Fundamento y Objetivo: Debido a las alteraciones observadas en la condición física de pacientes con insuficiencia renal crónica se ha demostrado la utilidad de someter a estos pacientes a un entrenamiento físico. El cociente respiratorio es utilizado normalmente como un medio no invasivo para estimar el umbral anaeróbico en sujetos sometidos a entrenamiento físico. Este estudio tuvo como objetivo evaluar la utilidad del cociente respiratorio como método indirecto para estimar el umbral anaeróbico y como indicador de detención en una ergometría en pacientes con insuficiencia renal crónica. Pacientes y método: Se realizó una cicloergometría con análisis de gases espirados en un grupo de pacientes con insuficiencia renal crónica (n=17) y en un grupo de sujetos sanos (n=18). Los cocientes respiratorios en reposo y con 30, 60 y 100 W fueron comparados entre ambos grupos. Resultados: No se observaron diferencias entre individuos sanos y pacientes en el cociente respiratorio en reposo; sin embargo, durante la prueba con diferentes intensidades de trabajo se observaron diferencias estadísticamente significativas entre ambos grupos. Conclusiones: En el caso de los nefrópatas, las diferencias observadas en el cociente respiratorio pueden atribuirse a exceso de producción de CO2. Per esta razón, la utilización del cociente respiratorio como un medio no invasivo para estimar el umbral anaeróbico parece ser no recomendable en pacientes con insuficiencia renal crónica.
Background and Objective: Due to changes observed in the physical condition of patients with chronic renal failure it has been demonstrated the usefulness of the physical training on these patients. The respiratory quotient is normally used as a non-invasive method for estimating the anaerobic threshold in subjects undergoing physical training. This study aimed to evaluate the usefulness of the respiratory quotient as an indirect method to estimate the anaerobic threshold and as an indicator to stop the ergometry in patients with chronic renal failure. Patients and Methods: We conducted a cycle-erge metry with expired gas analysis in patients with chronic renal failure (n = 17) and in a group of healthy subjects (n= 18). The respiratory quotients at rest and with 30, 60 and 100 W were compared between groups. Results: No differences in the respiratory quotient were observed between healthy subjects and patients at rest, however, statistically significant differences were found between groups with different intensities of work. Conclusions: Because the observed differences in respiratory quotients could be attributed to an excess on production of CO2 in chronic renal failure patients, the use of respiratory quotient as a non-invasive method for estimating the anaerobic threshold seems to be not recommended in these patients.