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The COVID-19 pandemic changed the routines of people, consequently changing the daily lives of their pets. Behavioral and emotional changes caused by the stress resulting from restrictions of social isolation and their consequences in the human-animal relationship have been discussed. However, there are still no studies that identify the factors that affect behavior and which are the most susceptible groups. The purpose of this study is to identify behavioral and emotional changes on dogs during the COVID-19 pandemic and their effects on the quality of life of animals and their owners. The methodology used was online questionnaires, which were posted on social networks aimed to dog owners in Rio de Janeiro state, Brazil. The results showed that age, sex, dog size, type of home, and restrictions imposed differently affected the type of behavioral change. However, the most frequent type of change was the worsening of previous conditions. Neutered behaviors directly interfered in the lives of owners and their pets, as owners managed the situation and sought information without guidance from a veterinarian, with the possibly consequence of worsening the situation in the future. Veterinarians should actively investigate behavioral changes that have occurred through anamnesis to avoid abandonment and instability in the human-animal relationship.
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Objetivo: El objetivo de nuestro estudio fue adaptar y validar el Score de Condición de Raynaud (SCR) en pacientes con Esclerosis Sistémica (SSc) que concurren a un hospital público de Argentina. Materiales y Métodos: Para la adaptación, reumatólogos tradujeron al español la versión original en inglés. Para evaluar la validez de constructo se utilizó: Cuestionario de Capacidad Funcional HAQ (HAQ), Índice Duruöz (ID), validados al español para Argentina, Escala Visual Análoga (EVA) de Raynaud por un experto y Score de Rodnan modificado (mRSS). Para evaluar reproducibilidad, se evaluó de forma aleatoria un subgrupo de pacientes sin mediar cambios en el tratamiento ni en la condición clínica 10 días después de la evaluación basal. Resultados: Se incluyeron 35 pacientes con diagnóstico de SSc. La correlación entre SCR y EVA del médico fue de 0.89; SCR y HAQ 0.58; SCR y mRSS 0.61; SCR e ID 0.57 indicando una muy buena correlación principalmente con el EVA del médico y siendo todos estadísticamente significativos. La reproducibilidad fue de 0.998. Conclusiones: Los resultados muestran que el SCR es una herramienta confiable y válida para esta población argentina con SSc.
Objetive: The aim of our study was to adapt and validate the Raynaud's Condition Score (RCS) in patients with Systemic Sclerosis (SSc) who attend a public hospital in Argentina. Materials and Methods: For adaptation, rheumatologists translated to Spanish the original version in English. To assess the construct validity we used: Health Assesment Questionnaire (HAQ), Duruöz´s Hand Index (DHI), spanish validation for Argentina, Raynaud Visual Analogue Scale (VAS) by an expert and Modified Rodnan skin score (mRSS). To assess reproducibility, a subgroup of patients was randomly evaluated with no changes in treatment or clinical condition ten days after the baseline evaluation. Results: A total of 35 patients with SSc were included. The correlation between RCS and Raynaud VAS by an expert was 0.89; RCS and HAQ 0.58; RCS and mRSS 0.61; RCS and DHI 0.57 indicating a very good correlation mainly between the studied Score and the Raynaud VAS and being all statistically significant. The reproducibility was 0.998. Conclusion: The results show that the RCS is a reliable and valid tool for this argentinian population with SSc.
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Enfermedad de Raynaud , Esclerodermia Sistémica , Estudio de EvaluaciónRESUMEN
While the role of cytokine genes has been well documented in the context of Leishmania (Viannia) braziliensis infection, no studies have addressed the influence of human leukocyte antigen-G (HLA-G) in susceptibility/resistance to American Tegumentary Leishmaniasis (ATL). Here, we evaluated the influences of HLA-G, IL-10, TNF-A and IFN-G in the susceptibility and clinical manifestations of ATL. DNA of 114 ATL patients and 346 healthy individuals were sequenced for well-documented polymorphisms in HLA-G 3' untranslated region (UTR), in IL-10 and TNF-A promoters and in IFN-G intron 1. Soluble HLA-G (sHLA-G) and cytokine levels were evaluated by ELISA and flow cytometry, respectively. Analyses were performed using GraphPad and R-package software. Individuals bearing HLA-G +3142G/G showed an association with increased risk for ATL, whereas those carrying the HLA-G +3142C/G and one copy of UTR6 haplotype, showed an association with decreased risk for ATL. sHLA-G was overexpressed in "susceptible" patients compared to the "resistant'' one, and also in patients bearing +3142G/G genotype. From these results, HLA-G +3142G/G may be considered as genotype of susceptibility and UTR6 as marker of protection to ATL. Our findings showed a participation of HLA-G in the pathogenesis of the ATL.
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Región de Flanqueo 3'/genética , Genotipo , Antígenos HLA-G/genética , Leishmaniasis/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Niño , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
Heren, we analyzed Treg cells as potential biomarkers of disease activity in systemic lupus erythematosus (SLE) patients. Peripheral blood mononuclear cells from 30 SLE patients (15 active: SLEDAI > 6/15 SLE remission: SLEDAI< 6) and 15 healthy volunteers were purified. Treg immunophenotyping was performed using CD4, CD25, CD45, CD127, and FOXP3 markers. CD4+FOXP3+ Treg activation state was investigated based on CD45RA and FOXP3 expression. To increase the accuracy of our findings, a multivariate linear regression was performed. We showed a significant increase in the frequency of CD4+FOXP3+ Treg cells in SLE patients. However, unlike all other Treg cells phenotypes analyzed, only eTreg (CD4+FOXP3highCD45RA-) (p=0.01) subtype was inversely correlated with disease activity while Foxp3+nontreg (CD4+FOXP3lowCD45RA-) (p=0.003) exerted a direct influence in the outcome of the disease. Foxp3+nontreg cells were the most consistent SLE active indicator, confirmed by multiple linear regression analyses. In summary, our results demonstrate Foxp3+nontreg cells as new biomarkers in the search of an effective therapeutic strategy in SLE.
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Biomarcadores , Lupus Eritematoso Sistémico/inmunología , Linfocitos T Reguladores , Adulto , Brasil , Antígenos CD4 , Femenino , Citometría de Flujo , Factores de Transcripción Forkhead , Humanos , Subunidad alfa del Receptor de Interleucina-2 , Antígenos Comunes de Leucocito , Leucocitos Mononucleares , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Thiazolidine-2,4-dione ring system is used as a pharmacophore to build various heterocyclic compounds aimed to interact with biological targets. In the present study, benzylidene-2,4-thiazolidinedione derivatives (compounds 2-5) were synthesized and screened against cancer cell lines and the genotoxicity and cytotoxicity of the most active compound (5) was investigated on normal and lung cancer cell line. METHODS: For in vitro cytotoxic screening, the MTT assay was used for HL60 and K562 (leukemia), MCF-7 (breast adenocarcinoma), HT29 (colon adenocarcinoma), HEp-2 (cervix carcinoma) and NCI-H292 (lung carcinoma) tumor cell lines and Alamar-blue assay was used for non-tumor cells (PBMC, human peripheral blood mononuclear cells) were used. Cell morphology was visualized after Giemsa-May-Grunwald staining. DNA content, phosphatidylserine externalization and mitochondrial depolarization were measured by flow cytometry. Genotoxicity was assessed by Comet assay. RESULTS: 5-(2-Bromo-5-methoxybenzylidene)-thiazolidine-2,4-dione (5) presented the most potent cytotoxicity, especially against NCI-H292 lung cancer cell line, with IC50 value of 1.26µg/mL after 72h incubation. None of the compounds were cytotoxic to PBMC. After 48h incubation, externalization of phosphatidylserine, mitochondrial depolarization, internucleosomal DNA fragmentation and morphological alterations consistent with apoptosis were observed in NCI-H292 cells treated with compound (5). In addition, compound (5) also induced genotoxicity in NCI-H292 cells (2.8-fold increase in damage index compared to the negative control), but not in PBMC. CONCLUSION: Compound 5 presented selective cytotoxic and genotoxic activity against pulmonary carcinoma (NCI-H292 cells).
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Antineoplásicos/farmacología , Citotoxinas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Mutágenos/farmacología , Tiazolidinedionas/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Ensayo Cometa/métodos , Fragmentación del ADN/efectos de los fármacos , Células HL-60 , Humanos , Células K562 , Leucocitos Mononucleares/efectos de los fármacos , Células MCF-7RESUMEN
The arsenal of drugs available to treat infections caused by eukaryotic and prokaryotic microbes has been declining exponentially due to antimicrobial resistance phenomenon, leading to an urgent need to develop new therapeutic strategies. Host-directed immunotherapy has been reported as an attractive option to treat microbial infections. It consists in the improvement of host defenses by increasing the expression of inflammatory mediators and/or controlling of inflammation-induced tissue injury. Although the in vitro antimicrobial and immunomodulatory activities of lectins have been extensively demonstrated, few studies have evaluated their in vivo effects on experimental models of infections. This review aims to highlight the experimental use of immunomodulatory plant lectins to improve the host immune response against microbial infections. Lectins have been used in vivo both prophylactically and therapeutically resulting in the increased survival of mice under microbial challenge. Other studies successfully demonstrated that lectins could be used in combination with parasite antigens in order to induce a more efficient immunization. Therefore, these plant lectins represent new candidates for management of microbial infections. Furthermore, immunotherapeutic studies have improved our knowledge about the mechanisms involved in host-pathogen interactions, and may also help in the discovery of new drug targets.
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Cryptococcus gattii is one of the main causative agents of cryptococcosis in immunocompetent individuals. Treatment of the infection is based on the use of antimycotics, however, the toxicity of these drugs and the increase of drug-resistant strains have driven the search for more effective and less toxic therapies for cryptococcosis. pCramoll are isolectins purified from seeds of Cratylia mollis, a native forage plant from Brazil, which has become a versatile tool for biomedical application. We evaluated the effect of pCramoll alone and in combination with fluconazole for the treatment of mice infected with C. gatti. pCramoll alone or in combination with fluconazole increased the survival, reduced the morbidity and improved mice behavior i.e., neuropsychiatric state, motor behavior, autonomic function, muscle tone and strength and reflex/sensory function. These results were associated with (i) decreased pulmonary and cerebral fungal burden and (ii) increased inflammatory infiltrate and modulatory of IFNγ, IL-6, IL-10, and IL-17A cytokines in mice treated with pCramoll. Indeed, bone marrow-derived macrophages pulsed with pCramoll had increased ability to engulf C. gattii, with an enhanced production of reactive oxygen species and decrease of intracellular fungal proliferation. These findings point toward the use of pCramoll in combination with fluconazole as a viable, alternative therapy for cryptococcosis management.
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Criptococosis/tratamiento farmacológico , Cryptococcus gattii/efectos de los fármacos , Cryptococcus gattii/patogenicidad , Combinación de Medicamentos , Fabaceae/química , Fluconazol/uso terapéutico , Lectinas/uso terapéutico , Extractos Vegetales/uso terapéutico , Acetilglucosaminidasa/metabolismo , Animales , Encéfalo/microbiología , Encéfalo/patología , Brasil , Proliferación Celular , Criptococosis/fisiopatología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Fluconazol/farmacología , Inmunomodulación , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Lectinas/farmacología , Pulmón/microbiología , Pulmón/patología , Macrófagos/microbiología , Ratones , Ratones Endogámicos C57BL , Peroxidasa/metabolismo , Fagocitosis , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno , Semillas/química , Tasa de SupervivenciaRESUMEN
In this study, the endochitinase chiA74 gene lacking its secretion signal peptide sequence (chiA74∆sp) was fused in frame with the sequence coding for the C-terminal crystallization domain and transcription terminator of cry1Ac. The chimeric gene was expressed under the strong pcytA-p/STAB-SD promoter system in an acrystalliferous Cry-B strain of Bacillus thuringiensis and B. thuringiensis subsp. kurstaki HD73. We showed that the chimeric ChiA74∆sp produced amorphous inclusions in both Cry-B and HD73. In addition to the amorphous inclusions putatively composed of the chimera, bipyramidal Cry1Ac crystals, smaller than the wild-type crystal, were observed in recombinant HD73, and chitinase activity was remarkably higher (75-fold) in this strain when compared with parental HD73. Moreover, we observed that lyophilized samples of a mixture containing Cry1Ac, amorphous inclusions, and spores maintained chitinase activity. Amorphous inclusions could not be separated from Cry1Ac crystals by sucrose gradient centrifugation. Interestingly, the chitinase activity of purified Cry1Ac/amorphous inclusions was 51-fold higher compared to purified Cry1Ac inclusions of parental HD73, indicating that the increased enzymatic activity was due primarily to the presence of the atypical amorphous component. The possibility that the chimera is occluded with the Cry1Ac crystal, thereby contributing to the increased endochitinolytic activity, cannot be excluded. Finally, bioassays against larvae of Spodoptera frugiperda with spore/crystals of HD73 or spore-crystal ChiA74∆sp chimeric inclusions of recombinant HD73 strain showed LC50s of 396.86 and 290.25 ng/cm2, respectively. Our study suggests a possible practical application of the chimera in formulations of B. thuringiensis-based lepidopteran larvicides.
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Bacillus thuringiensis/genética , Proteínas Bacterianas/genética , Agentes de Control Biológico , Quitinasas/genética , Endotoxinas/genética , Proteínas Hemolisinas/genética , Cuerpos de Inclusión/química , Animales , Bacillus thuringiensis/ultraestructura , Toxinas de Bacillus thuringiensis , Proteínas Bacterianas/biosíntesis , Quitinasas/biosíntesis , Quitinasas/metabolismo , Endotoxinas/biosíntesis , Proteínas Hemolisinas/biosíntesis , Cuerpos de Inclusión/ultraestructura , Larva , Regiones Promotoras Genéticas , Señales de Clasificación de Proteína , Proteínas Recombinantes de Fusión/análisis , Proteínas Recombinantes de Fusión/biosíntesis , Eliminación de Secuencia , Spodoptera/crecimiento & desarrolloRESUMEN
Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a serious health concern due to the lack of effective vaccines or satisfactory treatment. In the search for new compounds against this neglected disease, we have previously demonstrated that the compound 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile) (MBHA3), derived from the Morita-Baylis-Hillman reaction, effectively caused a loss of viability in both the epimastigote and trypomastigote forms. However, the mechanisms of parasite death elicited by MBHA3 remain unknown. The aim of this study was to better understand the morphophysiological changes and the mechanism of cell death induced by MBHA3 treatment on T. cruzi. To perform this analysis, we used confocal microscopy and flow cytometry to monitor the fluorescent probes such as annexin-V/propidium iodide (AV/PI), calcein-AM/ethidium homodimer (CA/EH), acridine orange (AO) and rhodamine 123 (Rho 123). Lower concentrations of MBHA3 led to alterations in the mitochondrial membrane potential and AO labeling, but did not decrease the viability of the epimastiogote forms, as determined by the CA/EH and AV/PI assays. Conversely, treatment with higher concentrations of MBHA3 led to extensive plasma membrane damage, loss of mitochondrion membrane potential, DNA fragmentation and acidification of the cytoplasm. Our findings suggest that at higher concentrations, MBHA3 induces T. cruzi epimastigote death by necrosis in a mitochondrion-dependent manner.
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Acrilonitrilo/análogos & derivados , Alcoholes Bencílicos/farmacología , Muerte Celular/efectos de los fármacos , Enfermedad de Chagas/tratamiento farmacológico , Trypanosoma cruzi/efectos de los fármacos , Acrilonitrilo/farmacología , Acrilonitrilo/uso terapéutico , Alcoholes Bencílicos/uso terapéutico , Membrana Celular/efectos de los fármacos , Enfermedad de Chagas/parasitología , Citoplasma/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Microscopía Confocal , NitrilosRESUMEN
BACKGROUND: Fructose administration rapidly induces oxidative stress that triggers compensatory hepatic metabolic changes. We evaluated the effect of an antioxidant, R/S-α-lipoic acid on fructose-induced oxidative stress and carbohydrate metabolism changes. METHODS: Wistar rats were fed a standard commercial diet, the same diet plus 10% fructose in drinking water, or injected with R/S-α-lipoic acid (35mg/kg, i.p.) (control+L and fructose+L). Three weeks thereafter, blood samples were drawn to measure glucose, triglycerides, insulin, and the homeostasis model assessment-insulin resistance (HOMA-IR) and Matsuda indices. In the liver, we measured gene expression, protein content and activity of several enzymes, and metabolite concentration. RESULTS: Comparable body weight changes and calorie intake were recorded in all groups after the treatments. Fructose fed rats had hyperinsulinemia, hypertriglyceridemia, higher HOMA-IR and lower Matsuda indices compared to control animals. Fructose fed rats showed increased fructokinase gene expression, protein content and activity, glucokinase and glucose-6-phosphatase gene expression and activity, glycogen storage, glucose-6-phosphate dehydrogenase mRNA and enzyme activity, NAD(P)H oxidase subunits (gp91(phox) and p22(phox)) gene expression and protein concentration and phosphofructokinase-2 protein content than control rats. All these changes were prevented by R/S-α-lipoic acid co-administration. CONCLUSIONS: Fructose induces hepatic metabolic changes that presumably begin with increased fructose phosphorylation by fructokinase, followed by adaptive changes that attempt to switch the substrate flow from mitochondrial metabolism to energy storage. These changes can be effectively prevented by R/S-α-lipoic acid co-administration. GENERAL SIGNIFICANCE: Control of oxidative stress could be a useful strategy to prevent the transition from impaired glucose tolerance to type 2 diabetes.
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Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Fructosa/farmacología , Hígado/metabolismo , Estrés Oxidativo , Ácido Tióctico/farmacología , Animales , Glucoquinasa/análisis , Glucoquinasa/genética , Masculino , NADPH Oxidasas/análisis , NADPH Oxidasas/genética , Ratas , Ratas WistarRESUMEN
Studies suggest the influence of immune response on the successful treatment of American tegumentary leishmaniasis (ATL), and indicate the existence of protective immunity in self-healed patients. Thus, the aim of this work was to quantify interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin (IL-) 10, IL-17, IL-22 and nitric oxide (NO) in culture supernatants of PBMC from patients with active disease (AD), after treatment (AT), and from self-healed (SH) and healthy subjects (CT), in response to Leishmania (Viannia) braziliensis insoluble antigen (AgIns). All groups of patients produced IFN-γ, indicating a predominant proinflammatory profile. AD and AT patients presented TNF-α levels, with a slight increase after therapy, whereas it was weakly quantified in SH. Interestingly, NO secretion was significant in these individuals, whereas IL-17 appeared in low levels and seems to be regulated by NO. Although IL-22 was detected in AD, its role is still questionable. The presence of IL-10 in all groups of patients suggests that the cytokine plays distinct roles in the disease. These results indicate that specific cellular immunity takes part against Leishmania, but with some similarities between the different clinical states herein described; these mediators seem to be necessary for the cure to occur.
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Citocinas/biosíntesis , Leishmania braziliensis/inmunología , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/metabolismo , Óxido Nítrico/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Protozoos/inmunología , Citocinas/inmunología , Femenino , Humanos , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: To evaluate whether co-administration of R/S-α-lipoic acid can prevent the development of oxidative stress and metabolic changes induced by a fructose-rich diet (F). METHODS: We assessed glycemia in the fasting state and during an oral glucose tolerance test, triglyceridemia and insulinemia in rats fed with standard diet (control) and fructose without or with R/S-α-lipoic acid. Insulin resistance and hepatic insulin sensitivity were also calculated. In liver, we measured reduced glutathione, protein carbonyl groups, antioxidant capacity by ABTS assay, antioxidant enzymes (catalase and superoxide dismutase 1 and 2), uncoupling protein 2, PPARδ and PPARγ protein expressions, SREBP-1c, fatty acid synthase and glycerol-3-phosphate acyltransferase-1 gene expression, and glucokinase activity. RESULTS: R/S-α-lipoic acid co-administration to F-fed rats a) prevented hyperinsulinemia, hypertriglyceridemia and insulin resistance, b) improved hepatic insulin sensitivity and glucose tolerance, c) decreased liver oxidative stress and increased antioxidant capacity and antioxidant enzymes expression, d) decreased uncoupling protein 2 and PPARδ protein expression and increased PPARγ levels, e) restored the basal gene expression of PPARδ, SREBP-1c and the lipogenic genes fatty acid synthase and glycerol-3-phosphate acyltransferase, and f) decreased the fructose-mediated enhancement of glucokinase activity. CONCLUSIONS: Our results suggest that fructose-induced oxidative stress is an early phenomenon associated with compensatory hepatic metabolic mechanisms, and that treatment with an antioxidant prevented the development of such changes. GENERAL SIGNIFICANCE: This knowledge would help to better understand the mechanisms involved in liver adaptation to fructose-induced oxidative stress and to develop effective strategies to prevent and treat, at early stages, obesity and type 2 diabetes mellitus.
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Antioxidantes/farmacología , Dieta/efectos adversos , Fructosa/efectos adversos , Hígado/metabolismo , Edulcorantes/efectos adversos , Ácido Tióctico/farmacología , Animales , Antioxidantes/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Fructosa/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Resistencia a la Insulina , Canales Iónicos/genética , Canales Iónicos/metabolismo , Hígado/patología , Masculino , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/genética , Obesidad/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genética , Oxidorreductasas/biosíntesis , Oxidorreductasas/genética , PPAR delta/genética , PPAR delta/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Ratas , Ratas Wistar , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Edulcorantes/farmacología , Proteína Desacopladora 2RESUMEN
AIM: To evaluate the role of uncoupling protein 2 (UCP2) and peroxisome proliferator-activated receptors (PPARs) in the response of liver to glycoxidative stress triggered by administration of a fructose-rich diet (FRD). MAIN METHODS: We assessed blood glucose in the fasting state and after a glucose load (glucose-oxidase method), serum triglyceride (enzymatic measurement), insulin (radioimmunoassay), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (colorimetric kits) in control and FRD animals. In liver, we measured UCP2, PPARα, PPARδ and PPARγ gene (real-time PCR) and protein (Western blot) expression, fatty acid synthase (FAS) and glycerol-3-phosphate acyltransferase (GPAT) gene expression, as well as triglyceride content. KEY FINDINGS: Blood glucose, serum insulin and triglyceride levels, homeostasis model assessment of insulin resistance (HOMA-IR) indexes and impaired glucose tolerance were higher in FRD rats. Whereas UCP2 and PPARδ gene and protein expression increased in these animals; PPARγ levels were lower and those of PPARα remained unchanged. FRD also increased the mRNA expression of PPARδ target genes FAS and GPAT. SIGNIFICANCE: Our results suggest that a) the increased UCP2 gene and protein expression measured in FRD rats could be part of a compensatory mechanism to reduce reactive oxygen species production induced by the fructose overload, and b) PPARs expression participates actively in the regulation of UCP2 expression, and under the metabolic condition tested, PPARδ played a key role. This knowledge would help to better understand the mechanisms involved in liver adaptation to fructose-induced glycoxidative stress, and to develop appropriate prevention strategies in obesity and type 2 diabetes.
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Dieta , Fructosa/metabolismo , Canales Iónicos/metabolismo , Hígado/metabolismo , Proteínas Mitocondriales/metabolismo , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Animales , Glucemia/metabolismo , Regulación de la Expresión Génica , Insulina/sangre , Resistencia a la Insulina , Canales Iónicos/genética , Masculino , Proteínas Mitocondriales/genética , Receptores Activados del Proliferador del Peroxisoma/genética , Ratas , Ratas Wistar , Triglicéridos/sangre , Proteína Desacopladora 2RESUMEN
AIMS: The effect of a three-week fructose-rich diet (FRD) upon gene expression, protein and activity levels of liver antioxidant system and carbohydrate metabolism was studied. MAIN METHODS: Serum glucose (fasting and after a glucose load), triglyceride and insulin levels of normal male Wistar rats were measured. In liver, we measured gene/protein expression and enzyme activity of catalase (CAT), copper-zinc-superoxide dismutase (CuZnSOD) and glutathione peroxidase (GSHPx); reduced glutathione (GSH); protein carbonyl content; thiobarbituric acid reactive substances (TBARS) content and microsomal membrane susceptibility to lipid peroxidation; glucokinase (GK), glucose-6-phosphatase (G-6-Pase) and glucose-6-phosphate dehydrogenase (G-6-PDH) activity; and glycogen, pyruvate, lactate and triglyceride content. KEY FINDINGS: Similar body weights and caloric intake were recorded in both groups. FRD rats had higher serum glucose, insulin and triglyceride levels, molar insulin:glucose ratio, HOMA-IR values and impaired glucose tolerance, whereas CAT, CuZnSOD and GSHPx relative gene expression levels were significantly lower. CAT and CuZnSOD protein expression, CAT activity and GSH content were also lower, while protein carbonyl content was higher. No differences were recorded in CuZnSOD, MnSOD and GSHPx activity, TBARS content and membrane susceptibility to lipid peroxidation. Glycogen, lactate and triglyceride content and GK, G-6-Pase and G-6-PDH activity were significantly higher in FRD rats. SIGNIFICANCE: In the presence of oxidative stress, the liver exhibits changes in the carbohydrate and lipid metabolic pathways that would decrease reactive oxygen species production and their deleterious effect, thus inducing little impact on specific antioxidant mechanisms. This knowledge could facilitate the design and implementation of strategies to prevent oxidative stress-induced liver damage.
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Antioxidantes/metabolismo , Dieta , Carbohidratos de la Dieta/farmacología , Fructosa/farmacología , Hígado/efectos de los fármacos , Hígado/metabolismo , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Conducta de Ingestión de Líquido/efectos de los fármacos , Prueba de Tolerancia a la Glucosa , Glutatión/metabolismo , Insulina/sangre , Peroxidación de Lípido/efectos de los fármacos , Hígado/enzimología , Masculino , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas Wistar , Triglicéridos/sangreRESUMEN
OBJECTIVES: To determine the prevalence of metal contact allergy among the children seen at a health center children with metal allergies in terms of risk factors. METHODS: This was an uncontrolled cross-sectional study undertaken at a health center in Belo Horizonte, Brazil. Children aged from 0 to 12 years were recruited when they presented at the health center for routine pediatric consultations and were given contact tests for chrome, cobalt and nickel. Statistical analyses were conducted on test readings taken at 96 hours. Results classed as weak (+), strong (++) or extreme (+++) were defined as "reaction," while those classed as doubtful, negative or irritant were defined as "no reaction." RESULTS: A total of 144 children completed the study protocol. Of these, 4.9% exhibited a reaction to chrome, 9.7% to cobalt and 20.1% to nickel. Patients with pierced ears were more likely to react to nickel than those without pierced ears (p = 0.031 and odds ratio = 2.8). CONCLUSIONS: In view of the current tendency for the prevalence of nickel allergy to increase, parents should be warned about its association with ear piercing. Further studies are needed to determine the ideal age for ear piercing and the ideal materials for earrings.
Asunto(s)
Perforación del Cuerpo/efectos adversos , Dermatitis Alérgica por Contacto/etiología , Níquel/efectos adversos , Brasil/epidemiología , Niño , Preescolar , Dermatitis Alérgica por Contacto/epidemiología , Métodos Epidemiológicos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Pruebas del Parche , Factores de RiesgoRESUMEN
OBJETIVOS: Determinar a prevalência da alergia de contato aos metais em crianças que frequentam um centro de saúde e caracterizar o subgrupo com alergia em relação aos fatores de risco. MÉTODOS: Estudo transversal não controlado, conduzido em um centro de saúde de Belo Horizonte (MG). Foram incluídas crianças com idades entre 0 e 12 anos que se apresentaram para consulta pediátrica de rotina, sendo aplicados testes de contato para o cromo, o cobalto e o níquel. As análises estatísticas foram realizadas com base na leitura do teste em 96 horas. Leituras classificadas como fraca (+), forte (++) ou extrema (+++) foram consideradas como reação, enquanto as classificadas como duvidosa, negativa ou irritativa foram consideradas como não reação. RESULTADOS: Completaram o estudo 144 crianças. Destas, 4,9 por cento apresentaram reação ao cromo, 9,7 por cento ao cobalto e 20,1 por cento ao níquel. Os pacientes com orelha perfurada tiveram mais chance de reação ao níquel do que aqueles sem essa característica (p = 0,031 e odds ratio = 2,8). CONCLUSÕES: Em face da tendência atual ao aumento da alergia ao níquel, familiares devem ser alertados sobre a sua associação com a perfuração das orelhas. Estudos posteriores são necessários para avaliar a idade ideal para a perfuração das orelhas e o material ideal para brincos.
OBJECTIVES: To determine the prevalence of metal contact allergy among the children seen at a health center and to characterize children with metal allergies in terms of risk factors. METHODS: This was an uncontrolled cross-sectional study undertaken at a health center in Belo Horizonte, Brazil. Children aged from 0 to 12 years were recruited when they presented at the health center for routine pediatric consultations and were given contact tests for chrome, cobalt and nickel. Statistical analyses were conducted on test readings taken at 96 hours. Results classed as weak (+), strong (++) or extreme (+++) were defined as "reaction," while those classed as doubtful, negative or irritant were defined as "no reaction." RESULTS: A total of 144 children completed the study protocol. Of these, 4.9 percent exhibited a reaction to chrome, 9.7 percent to cobalt and 20.1 percent to nickel. Patients with pierced ears were more likely to react to nickel than those without pierced ears (p = 0.031 and odds ratio = 2.8). CONCLUSIONS: In view of the current tendency for the prevalence of nickel allergy to increase, parents should be warned about its association with ear piercing. Further studies are needed to determine the ideal age for ear piercing and the ideal materials for earrings.
Asunto(s)
Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Perforación del Cuerpo/efectos adversos , Dermatitis Alérgica por Contacto/etiología , Níquel/efectos adversos , Brasil/epidemiología , Dermatitis Alérgica por Contacto/epidemiología , Métodos Epidemiológicos , Pruebas del Parche , Factores de RiesgoRESUMEN
We evaluated the relative role of different regulatory mechanisms, particularly 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFK2/FBPase-2), in liver glucokinase (GK) activity in intact animals with fructose-induced insulin resistance and impaired glucose and lipid metabolism. We measured blood glucose, triglyceride and insulin concentration, glucose tolerance, liver triglyceride content, GK activity, and GK and PFK2 protein and gene expression in fructose-rich diet (FRD) and control rats. After 3 weeks, FRD rats had significantly higher blood glucose, insulin and triglyceride levels, and liver triglyceride content, insulin resistance, and impaired glucose tolerance. FRD rats also had significantly higher GK activity in the cytosolic fraction (18.3 +/- 0.35 vs. 11.27 +/- 0.34 mU/mg protein). Differences in GK protein concentration (116% and 100%) were not significant, suggesting a potentially impaired GK translocation in FRD rats. Although GK transcription level was similar, PFK2 gene expression and protein concentration were 4- and 5-fold higher in the cytosolic fraction of FRD animals. PFK2 immunological blockage significantly decreased GK activity in control and FRD rats; in the latter, this blockage decreased GK activity to control levels. Results suggest that increased liver GK activity might participate in the adaptative response to fructose overload to maintain glucose/triglyceride homeostasis in intact animals. Under these conditions, PFK2 increase would be the main enhancer of GK activity.