RESUMO
SUMMARY: Osteoarthritis (OA) is an inflammatory disease that damages the joints and affects millions of people worldwide. The potential inhibitory effects of the antidiabetic drug metformin combined with captopril, the angiotensin-converting enzyme inhibitor, on diabetes-induced damage to the knee joint articular cartilage associated with the inhibition of glycemia, dyslipidemia, and inflammation has not been investigated before. Therefore, we induced diabetes in rats using high carbohydrate and fat diets and a single injection of streptozotocin (50 mg/kg). The protective group of rats was pre-treated with combined daily doses of metformin (Met; 200 mg/kg body weight) and captopril (Cap; 150 mg/kg body weight) for 14 days before diabetic induction and continued on metformin and resveratrol until the end of the experiment at week 12. Harvested tissues obtained from knee joints were prepared for basic histology staining with haematoxylin and eosin (H&E) and examined under light microscopy. Representative H&E images showed that OA was developed in the diabetic rats as demonstrated by a profound damage to the knee joints such as irregular eroded and a sharp decrease in the thickness of the articular cartilage surface and abnormal remodeling of the subchondral bone that were substantially ameliorated by Met+Cap. Met+Cap also significantly (p< 0.05) reduced blood levels of glucose, glycated hemoglobin (HbA1c), dyslipidemia, and the inflammatory biomarkers, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-α) induced by diabetes. In addition, a significant (p≤ 0.0014) correlation between the articular cartilage thickness and the blood levels of glucose, HbA1c, triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein- cholesterol (HDL-C), and hs-CRP were observed. Thus, we demonstrate that Met+Cap effectively protect the knee joint against injuries induced secondary to diabetes in rats, possibly due to the inhibition of glycemia, dyslipidemia, and biomarkers of inflammation.
RESUMEN: La osteoartritis (OA) es una enfermedad inflamatoria que daña las articulaciones y afecta a millones de per- sonas en todo el mundo. No se han investigado los posibles efectos inhibidores del fármaco antidiabético metformina combinado con captopril, el inhibidor de la enzima convertidora de angiotensina, sobre el daño inducido por la diabetes en el cartílago articular de la articulación de la rodilla asociado con la inhibición de la glucemia, dislipidemia e inflamación. En este estudio fue inducida la diabetes en ratas con dietas altas en carbohidratos y grasas y una sola inyección de estreptozotocina (50 mg / kg). El grupo protector de ratas se pretrató con dosis diarias combinadas de metformina (Met; 200 mg / kg de peso corporal) y captopril (Cap; 150 mg / kg de peso corporal) durante 14 días antes de la inducción diabética. El tratamiento se continuó con metformina y resveratrol hasta el final del experimento en la semana 12. Los tejidos obtenidos de las articulaciones de la rodilla se prepararon para la tinción de histología básica con hematoxilina y eosina (H&E) y se examinaron con microscopía óptica. Imágenes representativas de H&E mostraron que la OA se desarrolló en las ratas diabéticas, como lo evidencia un daño profundo en las articulaciones de la rodilla, como la erosión irregular y una fuerte disminución en el grosor de la superficie del cartílago articular y remodelación anor- mal del hueso subcondral que fueron mejorados sustancialmente por Met + Cap. Met + Cap. También redujo significativamente (p <0.05) los niveles sanguíneos de glucosa, hemoglobina glicosilada (HbA1c), dislipidemia y los biomarcadores inflamatorios, proteína C reactiva de alta sensibilidad (hs-CRP), interleucina-6 (IL-6), y factor de necrosis tumoral alfa (TNF-α) inducido por diabetes. Además, una correlación significativa (p≤ 0,0014) entre el grosor del cartílago articular y los niveles sanguíneos de glucosa, HbA1c, triglicéridos (TG), lipoproteínas-colesterol de baja densidad (LDL- C), lipoproteínas de alta densidad-colesterol (HDL-C) ) y hs-CRP. Así, demostramos que Met + Cap protege eficazmente la articulación de la rodilla contra lesiones inducidas por diabetes en ratas, posiblemente debido a la inhibición de la glicemia, dislipidemia y biomarcadores de inflamación.
Assuntos
Animais , Ratos , Captopril/administração & dosagem , Osteoartrite do Joelho/tratamento farmacológico , Complicações do Diabetes , Traumatismos do Joelho/tratamento farmacológico , Metformina/administração & dosagem , Captopril/uso terapêutico , Osteoartrite do Joelho/etiologia , Modelos Animais de Doenças , Quimioterapia Combinada , Traumatismos do Joelho/etiologia , Articulação do Joelho/efeitos dos fármacos , Metformina/uso terapêuticoRESUMO
Menopause complications such as cardiovascular and bone diseases represent a major public health concern. We sought to determine whether a high-fat diet (HFD) can augment ovariectomy-induced bone resorption in a rat model of menopause possibly via the upregulation of the inflammatory biomarkers and dyslipidemia. Rats were either ovariectomized and fed a standard laboratory chow (model group) or were ovariectomized and fed with a HFD for 15 weeks before being sacrificed. Ovariectomy significantly (p<0.05) increased body weight, dyslipidemia, insulin resistance, pro-inflammatory cytokines tumor necrosis factor-a (TNF-α) and interleukin-6 (IL-6), and biomarker of bone resorption, nuclear factor-kB (NF-kB), which were augmented by feeding animals with a HFD. This was confirmed through immunohistochemical study, where ovariectomy induced expression of p65/NF-kB protein in tibia bone sections of the model group, which were augmented by HFD. HFD augments ovariectomy-induced bone resorption through increased inflammatory biomarkers and NF-kB in rats.
Las complicaciones de la menopausia, como las enfermedades cardiovasculares y óseas, representan un importante problema de salud pública. Intentamos determinar si una dieta alta en grasas (HFD) puede aumentar la resorción ósea inducida por ovariectomía en un modelo de menopausia en ratas, a través de la regulación positiva de los biomarcadores inflamatorios y la dislipidemia. Las ratas fueron ovariectomizadas y alimentadas con una comida estándar de laboratorio (grupo modelo) o fueron ovariectomizadas y alimentadas con un HFD durante 15 semanas antes de ser sacrificadas. La ovariectomía aumentó significativamente (p <0,05) el peso corporal, dislipidemia, resistencia a la insulina, citocinas proinflamatorias, factor de necrosis tumoral a (TNF-α) e interleucina-6 (IL-6), y el biomarcador de resorción ósea, factor nuclear-kB (NF-kB), que se aumentaron alimentando animales con un HFD. Esto se confirmó a través del estudio inmunohistoquímico, donde la ovariectomía indujo la expresión de la proteína p65 / NF-kB en secciones de hueso de tibia del grupo modelo, que fueron aumentadas por HFD. HFD aumenta la resorción ósea inducida por ovariectomía a través del aumento de biomarcadores inflamatorios y NF-kB en ratas.
Assuntos
Animais , Feminino , Ratos , Reabsorção Óssea/patologia , Dieta Hiperlipídica/efeitos adversos , Triglicerídeos/análise , Reabsorção Óssea/etiologia , Resistência à Insulina , Menopausa , Ovariectomia/efeitos adversos , Ratos Wistar , Modelos Animais de Doenças , Dislipidemias/complicaçõesRESUMO
Paracetamol (also called acetaminophen, or APAP) overdose causes acute damage to the liver and kidneys in both humans and experimental animal models via the induction of the oxidative stress pathway. We sought to determine whether the combined antioxidants and anti-inflammatory compounds, resveratrol (RES) and quercetin (QUR) can protect against kidney injury induced by a toxic dose of APAP in a rat model of APAP-induced acute kidney injury. Rats were either received a single dose of APAP (2 g/kg) before being sacrificed after 24 hours or were pre-treated for 7 days with combined doses of RES (30 mg/kg) and QUR (50 mg/kg) before being given a single dose of APAP and then sacrificed 24 hours post APAP ingestion. Harvested kidney tissues were prepared for light microscopy staining, and tissue samples were assayed for (i) biomarkers of oxidative stress and antioxidant, malondialdehyde (MDA) and superoxide dismutase (SOD); and (ii) biomarkers of inflammation, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Hematoxylin and eosin (H&E) stained images showed that APAP overdose induced acute kidney injury as demonstrated by widening of glomeruli space (Bowman space), tubular dilatation, numerous cellular debris in the renal tubules with tubular epithelial degeneration, and vacuolization, which were effectively protected by RES+QUR except a partial protection of the glomeruli space was observed. In addition, APAP significantly (p<0.05) modulated tissue levels of MDA, SOD, TNF-α, and IL-6, which were protected by RES+QUR. Furthermore, a significant (p<0.0001) positive correlation was observed between glomeruli space and TNF-α, (r=0.8899), IL-6 (r=0.8986), and MDA (r=0.8552), whereas glomeruli space scoring versus SOD showed negative correlation (r= - 0.7870). We conclude that resveratrol plus quercetin substantially protects against APAP-induced acute kidney injury in rats, possibly via the augmentation of antioxidants and inhibition of oxidative stress and inflammation.
La sobredosis de paracetamol (también llamado acetaminofen o APAP) causa un daño agudo en el hígado y los riñones, tanto en humanos como en modelos animales experimentales, a través de la inducción de la vía del estrés oxidativo. Intentamos determinar si los antioxidantes y los compuestos antiinflamatorios combinados, el resveratrol (RES) y la quercetina (QUR) pueden proteger contra la lesión renal inducida por una dosis tóxica de APAP en un modelo de rata de lesión renal aguda inducida por APAP. Las ratas recibieron una dosis única de APAP (2 g / kg) antes de ser sacrificadas después de 24 horas o se trataron previamente durante 7 días con dosis combinadas de RES (30 mg / kg) y QUR (50 mg / kg), antes de ser tratadas, se administró una dosis única de APAP y luego fueron sacrificadas 24 horas después de la ingestión. Los tejidos renales recolectados se tiñeron con H-E y fueron observados a través de microscopía óptica. Las muestras de tejido se analizaron para (i) biomarcadores de estrés oxidativo y antioxidante, malondialdehído (MDA) y superóxido dismutasa (SOD); y (ii) biomarcadores de inflamación, factor de necrosis tumoral alfa (TNF-α) e interleucina-6 (IL-6). Las imágenes teñidas con H & E mostraron que la sobredosis de APAP indujo daño renal agudo como lo demuestra la ampliación del espacio glomerular, la dilatación tubular, numerosos desechos celulares en los túbulos renales con degeneración epitelial tubular y la vacuolización, que se protegieron eficazmente con RES + QUR Se observó una protección parcial del espacio glomerular. Además, APAP modificó significativamente (p <0.05) los niveles tisulares de MDA, SOD, TNF-α e IL-6, que estaban protegidos por RES + QUR. Además, se observó una correlación positiva significativa (p <0,0001) entre el espacio glomerular y el TNF-α, (r = 0,8899), IL-6 (r = 0,8986) y MDA (r = 0,8552), mientras que la puntuación del espacio glomerular versus SOD mostró correlación negativa (r = - 0,7870). Concluimos que el resveratrol más quercetina protege sustancialmente contra la lesión renal aguda inducida por APAP en ratas, posiblemente a través del aumento de antioxidantes y la inhibición del estrés oxidativo y la inflamación.
Assuntos
Animais , Ratos , Quercetina/uso terapêutico , Injúria Renal Aguda/tratamento farmacológico , Resveratrol/uso terapêutico , Acetaminofen/toxicidade , Quercetina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Modelos Animais de Doenças , Quimioterapia Combinada , Injúria Renal Aguda/induzido quimicamente , Resveratrol/farmacologia , Acetaminofen/antagonistas & inibidores , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêuticoRESUMO
The current study aimed to provide the topography and renal biopsy of the standing mare kidneys by laparoscopy w ithout CO2 insufflation and to compare between the use of biopsy needle and forceps. Five clinically healthy adult nonpregnant mares weighing 250300 Kg and aging 79 years were used in the current work. The gasless laparoscopic renal biopsy appeared simple, safe, reliable, minimal invasive, timesaving and economical technique. The parallel biopsy portals provided easy and accessible biopsy procedure than dorsal or ventral portals. The biopsies taken from the lateral surface were less hemorrhagic than those taken from the caudal pole. This study recommended the laparoscopic forceps because the biopsy forceps provided satisfactory and representative specimens with minimal hemorrhage than Tru-cut needle.
El presente estudio tuvo como objetivo proporcionar la topografía y la biopsia renal de los riñones en la yegua de pie, por laparoscopía sin insuflación de CO2, y comparar entre el uso de la biopsia con aguja y pinzas. Fueron utilizadas en este studio cinco yeguas adultas no gestantes clínicamente sanas con un peso de 250300 Kg y edad de 79 años. La biopsia renal laparoscópica sin gas es un método seguro, confiable y mínimamente invasivo, económico y permite además ahorrar tiempo. Los portales de biopsia paralelas permiten un procedimiento de biopsia de fácil acceso. Las biopsias tomadas de la superficie lateral fueron menos hemorrágicas que aquellas obtenidas desde el polo caudal. Este estudio recomienda las pinzas laparoscópicas debido a que, a diferencia de la aguja Tru-cut, demostraron ser satisfactorias con una hemorragia mínima.
Assuntos
Animais , Feminino , Laparoscopia/veterinária , Rim/anatomia & histologia , Postura , Biópsia por Agulha , Laparoscopia/métodos , CavalosRESUMO
OBJECTIVE: Evaluate the association of Helicobacter pylori infection with anti-parietal cell antibodies (APCA) and anti-intrinsic factor antibodies (AIFA) and their impact on vitamin B12 serum level. PATIENTS AND METHODS: One hundred patients (M/F: 43/57; age 46.5 ± 17.5 years) who underwent upper gastrointestinal endoscopy at King Abdullah University Hospital, Irbid, Jordan were enrolled in the study. The patients were grouped as H. pylori-infected (n = 81) or H. pylori negative (n = 19) by histopathological examination. Fasting serum vitamin B12 levels, antiparietal cell antibodies and anti-intrinsic factor antibodies for patients and controls were determined. RESULTS: Anti-parietal cell antibodies and anti-intrinsic factor antibodies were positive in 9.9% and 18.5% of H. pylori-positive patients respectively. None of the H. pylori negative subjects had anti-parietal cell antibodies or anti-intrinsic factor antibodies. Serum vitamin B12 level was lower in the H. pylori-infected patients (275 ± 70.4 pg/mL) than in controls (322.9 ± 60.7 pg/mL; p 0.05). H. pylori was positive in 94% of the low-vitamin B12 group compared with 64.6% of the normal-vitamin B12 group (p 0.5). CONCLUSION: Patients with H. pylori infection are more likely to have anti-parietal cell antibodies and anti-intrinsic factor antibodies. There was an association between H. pylori infection and lower vitamin B12 levels. H. pylori infection might be a significant factor in the pathogenesis of autoimmune gastritis.
Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Autoanticorpos/sangue , Gastrite Atrófica/imunologia , Helicobacter pylori , Infecções por Helicobacter/imunologia , Fator Intrínseco/imunologia , Células Parietais Gástricas/imunologia , /sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Técnica Indireta de Fluorescência para Anticorpo , Gastrite Atrófica/sangue , Gastrite Atrófica/parasitologia , Infecções por Helicobacter/sangue , Infecções por Helicobacter/patologiaRESUMO
OBJECTIVE: Evaluate the association of Helicobacter pylori infection with anti-parietal cell antibodies (APCA) and anti-intrinsic factor antibodies (AIFA) and their impact on vitamin B12 serum level. PATIENTS AND METHODS: One hundred patients (M/F: 43/57; age 46.5±17.5 years) who underwent upper gastrointestinal endoscopy at King Abdullah University Hospital, Irbid, Jordan were enrolled in the study. The patients were grouped as H. pylori-infected (n=81) or H. pylori negative (n=19) by histopathological examination. Fasting serum vitamin B12 levels, anti-parietal cell antibodies and anti-intrinsic factor antibodies for patients and controls were determined. RESULTS: Anti-parietal cell antibodies and anti-intrinsic factor antibodies were positive in 9.9% and 18.5% of H. pylori-positive patients respectively. None of the H. pylori negative subjects had anti-parietal cell antibodies or anti-intrinsic factor antibodies. Serum vitamin B12 level was lower in the H. pylori-infected patients (275±70.4pg/mL) than in controls (322.9±60.7pg/mL; p<0.05). H. pylori was positive in 94% of the low-vitamin B12 group compared with 64.6% of the normal-vitamin B12 group (p<0.5). CONCLUSION: Patients with H. pylori infection are more likely to have anti-parietal cell antibodies and anti-intrinsic factor antibodies. There was an association between H. pylori infection and lower vitamin B12 levels. H. pylori infection might be a significant factor in the pathogenesis of autoimmune gastritis.
Assuntos
Autoanticorpos/sangue , Gastrite Atrófica/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori , Fator Intrínseco/imunologia , Células Parietais Gástricas/imunologia , Vitamina B 12/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Gastrite Atrófica/sangue , Gastrite Atrófica/parasitologia , Infecções por Helicobacter/sangue , Infecções por Helicobacter/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Four doses of nicotinic acid, added in the drinking water of broilers, were offered in order to study its effect on performance and heat production in heat stress conditions (6 h of 35° C). Doses were 15, 100, 330 and 1000 mg/L. There was no effect of dose on weight gain, feed intake, feed efficiency, water intake and rectal temperature. Slight changes due to the doses of nicotinic acid and heat stress in the blood parameters of the birds were noted. Heat production (kcal/h/metabolic weight) decreased in 100 and 1000 mg/L dose as compared to 15 mg/L dose. There was no benefit using nicotinic acid in those doses in heat stress alleviation.
Foram oferecidas 4 doses de ácido nicotínico (AN) na água de beber de frangos de corte, a fim de estudar seu efeito no desempenho e na produção de calor em condições de estresse por calor (6 h de 35º C). As doses foram 15, 100, 330 e 1000 mg/L. Não houve efeito do AN nas doses usadas para ganho de peso, consumo de alimento, eficiência alimentar, consumo de água e temperatura retal. Foram observadas algumas alterações devido ao AN e estresse por calor nos parâmetros sangüíneos das aves. A produção de calor (kcal/h/peso metabólico) diminuiu com o uso de 100 e 1000 mg/L comparados com 15 mg/L. Nas dosagens usadas não foi observado efeito benéfico do AN no controle do estresse por calor.
RESUMO
Four doses of nicotinic acid, added in the drinking water of broilers, were offered in order to study its effect on performance and heat production in heat stress conditions (6 h of 35° C). Doses were 15, 100, 330 and 1000 mg/L. There was no effect of dose on weight gain, feed intake, feed efficiency, water intake and rectal temperature. Slight changes due to the doses of nicotinic acid and heat stress in the blood parameters of the birds were noted. Heat production (kcal/h/metabolic weight) decreased in 100 and 1000 mg/L dose as compared to 15 mg/L dose. There was no benefit using nicotinic acid in those doses in heat stress alleviation.
Foram oferecidas 4 doses de ácido nicotínico (AN) na água de beber de frangos de corte, a fim de estudar seu efeito no desempenho e na produção de calor em condições de estresse por calor (6 h de 35º C). As doses foram 15, 100, 330 e 1000 mg/L. Não houve efeito do AN nas doses usadas para ganho de peso, consumo de alimento, eficiência alimentar, consumo de água e temperatura retal. Foram observadas algumas alterações devido ao AN e estresse por calor nos parâmetros sangüíneos das aves. A produção de calor (kcal/h/peso metabólico) diminuiu com o uso de 100 e 1000 mg/L comparados com 15 mg/L. Nas dosagens usadas não foi observado efeito benéfico do AN no controle do estresse por calor.
RESUMO
We studied the pharmacokinetics of vincristine in children with acute lymphocytic leukemia by means of a specific high-performance liquid chromatographic assay with ultraviolet and electrochemical detection and a limited sampling strategy. Our objectives were to characterize the disposition of vincristine in pediatric patients, to determine clinical, demographic, or biochemical variables related to variability in vincristine pharmacokinetic parameters, and to assess the relationship between pharmacokinetic parameters and vincristine neurotoxicity. Plasma samples were collected at 5 and 30 minutes, and 1, 3, and 24 hours after a rapid intravenous injection during 3 minutes. Vincristine-induced neurotoxicity was retrospectively evaluated by chart review. Pharmacokinetic studies were completed for 64 doses in 54 children between 2 months and 18 years of age (median, 4.3 years), including 2-month-old monozygous twin girls. Vincristine clearance, estimated by Bayesian methods, was highly variable, with a mean (SD) clearance of 19.9 (14.9) ml/min per kilogram or 482 (342) ml/min per square meter. Mean clearance for all subjects was faster than in published studies of adults, which may be related in part to the greater specificity of the assay used in our study, as well as to age-related differences in drug disposition. Vincristine-associated neurotoxicity was frequent but mild and was not predicted by vincristine systemic exposure; however, neurotoxicity may have been underestimated. Clearance in one patient who received concomitant treatment with pentobarbital exceeded the 75th percentile for all patients, and four of five patients receiving concomitant histamine2 antagonists had clearances below the 25th percentile for all subjects, suggesting that drugs that induce or inhibit hepatic cytochrome P-450 enzymes may affect vincristine disposition. Further studies are needed to identify the factors responsible for interpatient variability in vincristine disposition and to develop improved dosing guidelines.