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OBJECTIVE: the key factors identification in radiation dose formation in population of radiologically contaminatedareas of Zhytomyr oblast in the current period of accident through complex radiation and hygienic monitoring in reference settlements in 2021. MATERIALS AND METHODS: For complex radiationhygienic monitoring in Zhytomyr oblast, 10 settlements were chosen - Narodychi, Selets, Bazar, Rudnya Bazarska, Khrystynivka - zone 2, Motiyki, Zalissya, Davydky, Radcha, Nova Radcha - zone 3 of Narodychi district, in which the highest radiation doses were recorded after the accident at the Chornobyl Nuclear Power Plant. The research was carried out in June 2021. In order to determine the doses of internal radiation, 645 measurements were performed on whole body counters (WBC) (478 adults and 167 children). The 44 samples of milk, 45 samples of potatoes and vegetables, and 38 samples of wild products were collected in local farms and measured for the 137Cs and 90Sr content. Residents of the studied settlements (n = 220, 175 adults, and 45 children) were interviewed about the levels of consumption of staple foodstuffs. External radiation doses were evaluated in all the studied settlements. Mathematical, dosimetry, and radiochemical methods were applied. RESULTS AND CONCLUSIONS: Annual effective radiation doses of Zhytomyr oblast population in 2021 were formedmainly due to internal radiation ones that not exceeded 1.8 mSv * year-1 in adults and 0.5 mSv * year-1 in children against the radiologically contaminated territories (RCT) criterion of 1 mSv * year-1. Intake of 137Cs with milk and wild mushrooms, which traditionally occupy a significant part of diet in Zhytomyr oblast area and have consistently high levels of radioactive cesium contamination, remains a key factor of internal radiation dose forming in residents of the surveyed settlements of Zhytomyr oblast.
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Accidente Nuclear de Chernóbil , Monitoreo de Radiación , Niño , Adulto , Humanos , Carga Corporal (Radioterapia) , Radioisótopos de Cesio/análisis , Radioisótopos de Estroncio , Ucrania/epidemiología , Dosis de Radiación , Monitoreo de Radiación/métodosRESUMEN
OBJECTIVE: The key factors identification in radiation dose formation in population of radiologically contaminatedareas of Rivne oblast in the current period of accident through comprehensive radiation and hygienic monitoring inreference settlements in 2020 and estimation of their impact on dose formation were the study objectives. MATERIALS AND METHODS: Comprehensive radiation and hygienic monitoring of settlements in Rivne oblast(province) was provided in Stare Selo, Vezhytsia, Perekhodychi, and Drozdyn villages of Rokytne district, where thehighest radiation doses were registered after the ChNPP accident. Studies were conducted in September 2020.Measurements (n=696, 318 adults, and 378 children) were performed using the whole body counters (WBC) to deter-mine the internal radiation doses. The 48 samples of milk, 45 samples of potatoes and vegetables, and 35 samplesof wild products were collected in local farms and measured for the 137Cs and 90Sr content. Residents of the studiedsettlements (n=229, 140 adults, and 89 children) were interviewed about the levels of consumption of staple food-stuffs. External radiation doses were evaluated in all the studied settlements. Mathematical, dosimetric, and radio-chemical methods were applied. RESULTS AND CONCLUSIONS: Annual effective radiation doses of the Rivne oblast population in 2020 were formedmainly due to internal radiation ones that not exceeded 1.24 mSv · year-1 in adults and 0.65 mSv · year-1 in childrenagainst the RCT criterion of 1 mSv · year-1. Further 1.2-1.9-fold decrease in the annual internal radiation doses vs.the results of WBC-monitoring in autumn of 2017 was registered in the surveyed settlements. The latter confirmeda time pattern of radiation levels gradual reduction at the current stage of Chornobyl accident since 2011. Intakeof 137Cs with milk and wild mushrooms, which traditionally occupy a significant part of diet in the Rivne Polissya areaand have consistently high levels of radioactive cesium contamination, remains a key factor of internal radiationdose forming in residents of the surveyed settlements of Rivne oblast.
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Radioisótopos de Cesio , Accidente Nuclear de Chernóbil , Relación Dosis-Respuesta en la Radiación , Exposición a Riesgos Ambientales/estadística & datos numéricos , Exposición a la Radiación/estadística & datos numéricos , Monitoreo de Radiación/estadística & datos numéricos , Recuento Corporal Total , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Radioisótopos de Cesio/análisis , Niño , Preescolar , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Exposición a la Radiación/efectos adversos , Liberación de Radiactividad Peligrosa/estadística & datos numéricos , Medición de Riesgo/estadística & datos numéricos , Población Rural/estadística & datos numéricos , Ucrania , Adulto JovenRESUMEN
PURPOSE: This study aimed at investigating the efficacy of percutaneous transhepatic biliary stenting (PTBS) combined with 125I seeds intracavitary irradiation in the treatment of extrahepatic cholangiocarcinoma (EHC) and to preliminarily explore the prognostic values of inflammation-based scores in these patients. METHODS: A total of 113 clinically/pathologically diagnosed cases of EHC who received PTBS combined with 125I seeds implantation were retrospectively analyzed. The postoperative changes of clinical symptoms and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total serum bilirubin (TBIL), direct bilirubin (DBIL), and albumin (ALB) were observed. Preoperative clinical data were extracted to calculate inflammation-based scores, including systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelets-to-lymphocyte ratio (PLR). Kaplan-Meier survival curves and Cox regression analyses were used to evaluate the prognostic significance of inflammation-based scores. RESULTS: After operation, clinical symptoms such as jaundice and fever significantly improved in all patients. At 1 month and 3 months postoperatively, serum levels of ALT, AST, ALP, TBIL, and DBIL significantly reduced, and ALB significantly increased, compared with preoperative values. The median survival time of the patients was 12 months and the 1-year survival rate was 56.8%. Univariate analysis revealed that factors related to overall survival were CA19-9, TBIL, ALB, SII, and NLR. Multivariate analysis further identified SII and NLR as independent prognostic models. CONCLUSION: The combination of PTBS and 125I seeds intracavitary irradiation is an effective palliative treatment for advanced EHC. Elevated SII and NLR can be used to predict poor survival.
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Neoplasias de los Conductos Biliares/mortalidad , Procedimientos Quirúrgicos del Sistema Biliar/mortalidad , Colangiocarcinoma/mortalidad , Mediadores de Inflamación/metabolismo , Inflamación/diagnóstico , Radioisótopos de Yodo/uso terapéutico , Stents , Anciano , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/terapia , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patología , Colangiocarcinoma/terapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Masculino , Siembra Neoplásica , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
INTRODUCTION: The lack of evidence that proves the benefit of traditional and complementary medicines (T & CM) in treating chronic medical conditions does not deter its usage among patients worldwide. Prevalence of usage among post-stroke patients in Malaysia especially is unknown. This study aims to determine the prevalence, practice and perception of T & CM use among stroke survivors attending an outpatient rehabilitation program in a teaching hospital. METHODS: A cross-sectional study was conducted among 104 post stroke patients attending an outpatient rehabilitation program. A structured self-administered questionnaire was used to collect data on sociodemographic and clinical profile of patients, as well as types of therapy used and perception on T & CM usage. Descriptive analysis was done, and bivariate analysis was used to determine associations between categorical data. RESULTS: Mean age of patients was 62 years (SD 12.2), 54% were Chinese and 75% of the patients had ischaemic stroke. Mean age of T & CM users was younger compared to non- T & CM users (61 years vs. 66 years, p=0.04). Two-thirds (66%) of patients admitted to concurrent T & CM usage while attending conventional post stroke rehabilitation. Acupuncture (40.4%), massage (40.4%) and traditional Chinese medicine (11.5%) were the most common T & CM used. Positive perception was recorded in terms of ability of T & CM usage to relieve post stroke symptoms (68%), and it was safe to use because it was made from 'natural sources'. Negative perception recorded: T & CM caused significant adverse effects (57.6%) and was not safe to be used in combination with other conventional medicines (62.5%). CONCLUSIONS: Concurrent T & CM usage among post-stroke patients attending structured outpatient rehabilitation program is widely practised especially acupuncture, massage and traditional Chinese medicines. Overall the perception towards its use is favourable.
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UNLABELLED: This study showed that risedronate 150-mg once a month provides similar efficacy and safety at 2 years compared with risedronate 5-mg daily for the treatment of postmenopausal osteoporosis. This adds to the range of risedronate dosing options and provides an alternative for patients who prefer once-a-month dosing. INTRODUCTION: Risedronate is effective in the treatment of postmenopausal osteoporosis in oral daily, weekly, or on two consecutive days per month doses. This 2-year randomized, double-blind, multicenter study assesses the efficacy and safety of a single risedronate 150-mg once-a-month oral dose compared with the 5-mg daily regimen. METHODS: Women with postmenopausal osteoporosis were randomly assigned to receive risedronate 5-mg daily (n = 642) or 150-mg once a month (n = 650) for 2 years. Bone mineral density (BMD), bone turnover markers, new vertebral fractures, and adverse events were evaluated. The primary efficacy endpoint was the mean percent change from baseline in lumbar spine BMD after 1 year. RESULTS: Four hundred ninety-eight subjects in the daily group (77.6 %) and 513 subjects in the once-a-month group (78.9 %) completed the study. After 24 months, the mean percent change in lumbar spine BMD was 3.9 % (95 % confidence interval [CI], 3.43 to 4.42 %) and 4.2 % (95 % CI, 3.68 to 4.65 %) in the daily and once-a-month groups, respectively. The once-a-month regimen was determined to be non-inferior to the daily regimen. The mean percent changes in BMD at the hip were similar in both dose groups, as were changes in biochemical markers of bone turnover. The incidence of adverse events, adverse events leading to withdrawal, and upper gastrointestinal tract adverse events were similar in the two treatment groups. CONCLUSIONS: After 2 years, treatment with risedronate 150-mg once a month provided similar efficacy and tolerability to daily dosing and provides an alternative for patients who prefer once-a-month oral dosing.
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Conservadores de la Densidad Ósea/administración & dosificación , Ácido Etidrónico/análogos & derivados , Osteoporosis Posmenopáusica/tratamiento farmacológico , Administración Oral , Anciano , Biomarcadores/sangre , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/efectos adversos , Conservadores de la Densidad Ósea/uso terapéutico , Método Doble Ciego , Esquema de Medicación , Ácido Etidrónico/administración & dosificación , Ácido Etidrónico/efectos adversos , Ácido Etidrónico/uso terapéutico , Femenino , Fémur/fisiopatología , Humanos , Vértebras Lumbares/fisiopatología , Persona de Mediana Edad , Osteoporosis Posmenopáusica/fisiopatología , Ácido Risedrónico , Resultado del TratamientoRESUMEN
CONTEXT: The FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial showed denosumab significantly reduced the risk of fractures in postmenopausal women with osteoporosis. OBJECTIVE: We evaluated the effect of denosumab on the incidence of new vertebral and hip fractures in subgroups of women at higher risk for these fractures. DESIGN: FREEDOM was a 3-yr, randomized, double-blind, placebo-controlled, phase 3 trial. PARTICIPANTS AND SETTING: Postmenopausal women (N = 7808) with osteoporosis were enrolled at 213 study sites worldwide. INTERVENTIONS: Subjects received s.c. denosumab (60 mg) or placebo every 6 months and daily supplements of calcium (≥1000 mg) and vitamin D (≥400 IU). MAIN OUTCOME MEASURES: This post hoc analysis evaluated fracture incidence in women with known risk factors for fractures including multiple and/or moderate or severe prevalent vertebral fractures, aged 75 yr or older, and/or femoral neck bone mineral density T-score of -2.5 or less. RESULTS: Compared with placebo, denosumab significantly reduced the risk of new vertebral fractures in women with multiple and/or severe prevalent vertebral fractures (16.6% placebo vs. 7.5% denosumab; P < 0.001). Similarly, denosumab significantly reduced the risk of hip fractures in subjects aged 75 yr or older (2.3% placebo vs. 0.9% denosumab; P < 0.01) or with a baseline femoral neck bone mineral density T-score of -2.5 or less (2.8% placebo vs. 1.4% denosumab; P = 0.02). These risk reductions in higher-risk individuals were consistent with those seen in patients at lower risk of fracture. CONCLUSIONS: Denosumab reduced the incidence of new vertebral and hip fractures in postmenopausal women with osteoporosis at higher risk for fracture. These results highlight the consistent antifracture efficacy of denosumab in patients with varying degrees of fracture risk.
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Anticuerpos Monoclonales/uso terapéutico , Fracturas de Cadera/epidemiología , Fracturas de Cadera/prevención & control , Ligando RANK/uso terapéutico , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/prevención & control , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados , Denosumab , Método Doble Ciego , Femenino , Fracturas de Cadera/etiología , Humanos , Incidencia , Osteoporosis Posmenopáusica/complicaciones , Posmenopausia , Riesgo , Fracturas de la Columna Vertebral/etiología , Resultado del TratamientoRESUMEN
The thermoelectric performance of EuCd(2)Sb(2) and YbCd(2)Sb(2) was improved by mixed cation occupation. The composition, structure, and thermoelectric properties of Yb(x)Eu(1-x)Cd(2)Sb(2) (x=0, 0.5, 0.75, and 1) have been investigated. Polycrystalline samples are prepared by direct reaction of the elements. Thermoelectric properties were investigated after densification of the materials by spark plasma sintering. Yb(x)Eu(1-x)Cd(2)Sb(2) crystallizes in the P3m1 space group. The lattice parameters increase with the europium content. These materials show low electrical resistivity, high Seebeck coefficient, and low thermal conductivity together with high carrier concentration and high carrier mobility. ZT values of 0.88 and 0.97 are obtained for Yb(0.5)Eu(0.5)Cd(2)Sb(2) and Yb(0.75)Eu(0.25)Cd(2)Sb(2) at 650 K, respectively.
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Ceiba pentandra (L.) Gaertn (kapok) is a natural sorbent that exhibits excellent hydrophobic-oleophilic characteristics. The effect of packing density, the oil types and solvent treatment on the sorption characteristics of kapok was studied in a batch system. Oil sorption capacity, retention capacity, entrapment stability and kapok reusability were evaluated. Based on SEM and FTIR analyses, kapok fiber was shown to be a lignocellulosic material with hydrophobic waxy coating over the hollow structures. Higher packing density at 0.08 g/ml showed lower sorption capacity, but higher percentage of dynamic oil retention, with only 1% of oil drained out from the test cell. Kapok remained stable after fifteen cycles of reuse with only 30% of sorption capacity reduction. The oil entrapment stability at 0.08 g/ml packing was high with more than 90% of diesel and used engine oil retained after horizontal shaking. After 8h of chloroform and alkali treatment, 2.1% and 26.3% reduction in sorption capacity were observed, respectively, as compared to the raw kapok. The rigid hollow structure was reduced to flattened-like structure after alkali treatment, though no major structural difference was observed after chloroform treatment. Malaysian kapok has shown great potential as an effective natural oil sorbent, owing to high sorption and retention capacity, structural stability and high reusability.
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Biodegradación Ambiental , Ceiba/metabolismo , Aceites/farmacocinética , Adsorción , Conservación de los Recursos Naturales , Interacciones Hidrofóbicas e Hidrofílicas , Malasia , Aceites/aislamiento & purificación , SolventesRESUMEN
UNLABELLED: Changes in bone mineral density and bone strength following treatment with zoledronic acid (ZOL) were measured by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA). ZOL treatment increased spine and hip BMD vs placebo, assessed by QCT and DXA. Changes in trabecular bone resulted in increased bone strength. INTRODUCTION: To investigate bone mineral density (BMD) changes in trabecular and cortical bone, estimated by quantitative computed analysis (QCT) or dual-energy X-ray absorptiometry (DXA), and whether zoledronic acid 5 mg (ZOL) affects bone strength. METHODS: In 233 women from a randomized, controlled trial of once-yearly ZOL, lumbar spine, total hip, femoral neck, and trochanter were assessed by DXA and QCT (baseline, Month 36). Mean percentage changes from baseline and between-treatment differences (ZOL vs placebo, t-test) were evaluated. RESULTS: Mean between-treatment differences for lumbar spine BMD were significant by DXA (7.0%, p < 0.01) and QCT (5.7%, p < 0.0001). Between-treatment differences were significant for trabecular spine (p = 0.0017) [non-parametric test], trabecular trochanter (10.7%, p < 0.0001), total hip (10.8%, p < 0.0001), and compressive strength indices at femoral neck (8.6%, p = 0.0001), and trochanter (14.1%, p < 0.0001). CONCLUSIONS: Once-yearly ZOL increased hip and spine BMD vs placebo, assessed by QCT vs DXA. Changes in trabecular bone resulted in increased indices of compressive strength.
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Conservadores de la Densidad Ósea/administración & dosificación , Difosfonatos/administración & dosificación , Imidazoles/administración & dosificación , Osteoporosis Posmenopáusica/tratamiento farmacológico , Absorciometría de Fotón/métodos , Anciano , Anciano de 80 o más Años , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/uso terapéutico , Fuerza Compresiva/efectos de los fármacos , Difosfonatos/uso terapéutico , Esquema de Medicación , Femenino , Cuello Femoral/efectos de los fármacos , Cuello Femoral/fisiopatología , Estudios de Seguimiento , Articulación de la Cadera/efectos de los fármacos , Articulación de la Cadera/fisiopatología , Humanos , Imidazoles/uso terapéutico , Vértebras Lumbares/efectos de los fármacos , Vértebras Lumbares/fisiopatología , Osteoporosis Posmenopáusica/fisiopatología , Tomografía Computarizada por Rayos X/métodos , Ácido ZoledrónicoRESUMEN
UNLABELLED: Postmenopausal women with osteoporosis received 75 mg risedronate on two consecutive days each month or 5 mg daily for 12 months. Changes in bone mineral density and bone turnover markers were similar between treatments. Risedronate 75 mg twice monthly was effective and safe suggesting a new, convenient dosing schedule. INTRODUCTION: Patients perceive less frequent dosing as being more convenient. This 2-year trial evaluates the efficacy and safety of a new monthly oral regimen of risedronate; 1 year results are presented here. METHODS: Postmenopausal women with osteoporosis (n = 1229) were randomly assigned to double-blind treatment with 75 mg risedronate on two consecutive days each month (2CDM), or 5 mg daily. The primary endpoint was the percent change from baseline in lumbar spine (LS) bone mineral density (BMD) at month 12. Secondary efficacy was evaluated by mean percent changes from baseline in BMD in LS, total hip, trochanter, and femoral neck, and bone turnover markers (BTMs). RESULTS: Risedronate 75 mg 2CDM was non-inferior to 5 mg daily (treatment difference 0.21; 95% CI -0.19 to 0.62). Mean percent change in LS-BMD was 3.4% +/- 0.16 and 3.6% +/- 0.15 respectively. Mean percent changes in BMD and BTMs were significant and similar for both treatment groups. New vertebral fractures occurred in 1% of subjects with either treatment. Both treatments were generally well tolerated and safe. CONCLUSIONS: Risedronate 75 mg 2CDM was non-inferior in efficacy and did not show a difference in safety vs. 5 mg daily after 12 months, leading to a similar benefit.
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Conservadores de la Densidad Ósea/administración & dosificación , Ácido Etidrónico/análogos & derivados , Osteoporosis Posmenopáusica/tratamiento farmacológico , Absorciometría de Fotón , Administración Oral , Anciano , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/efectos adversos , Método Doble Ciego , Esquema de Medicación , Ácido Etidrónico/administración & dosificación , Ácido Etidrónico/efectos adversos , Femenino , Cuello Femoral , Humanos , Vértebras Lumbares , Persona de Mediana Edad , Huesos Pélvicos , Ácido Risedrónico , Resultado del TratamientoAsunto(s)
Antineoplásicos/líquido cefalorraquídeo , Arsenicales/líquido cefalorraquídeo , Leucemia Promielocítica Aguda/tratamiento farmacológico , Manitol/metabolismo , Neoplasias Meníngeas/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Óxidos/líquido cefalorraquídeo , Adulto , Antineoplásicos/uso terapéutico , Apoptosis , Trióxido de Arsénico , Arsenicales/uso terapéutico , Femenino , Humanos , Inyecciones Intravenosas , Leucemia Promielocítica Aguda/líquido cefalorraquídeo , Leucemia Promielocítica Aguda/patología , Imagen por Resonancia Magnética , Neoplasias Meníngeas/líquido cefalorraquídeo , Neoplasias Meníngeas/patología , Recurrencia Local de Neoplasia/patología , Óxidos/uso terapéutico , Inducción de RemisiónRESUMEN
OBJECTIVE: To search for a method to enhance tissue expansion. METHOD: A new type of expander with an agent delivery system was used to expand soft tissue in 15 patients. During expansion Papaverine was delivered through the delivery system into the tissue around the expanders. RESULTS: It took 26 days to expand to the anticipated volume in the new expansion method group (NEM) and 51 days in the general expansion method group (GEM) (P < 0.01). Before operation the NEM group was over-expanded by 92.4% while the GEM group was over-expanded by 27.12%. At full expansion the blood flow of the expanded area of the two groups was 1.27 (NEM) and 0.64 (GEM). The immediate skin retraction of the two groups was 20.17% (NEM) and 38.26% (GEM). CONCLUSION: The new expansion method can accelerate expansion speed and improve the quality of expanded skin and flap.
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Sistemas de Liberación de Medicamentos , Teofilina/administración & dosificación , Dispositivos de Expansión Tisular , Expansión de Tejido/métodos , HumanosRESUMEN
With respect to the connection between triglyceride (TG) and non-insulin-dependent diabetes mellitus (NIDDM), previous reports have shown that TG accumulation in the liver and muscle is one of the causes of insulin resistance, and TG accumulation in pancreatic islets induces impairment of pancreatic beta-cell function. This experiment examined the relationship between an amelioration of hypertriglyceridemia (HTG), a decrease in TG accumulation in tissues, and an improvement of NIDDM by food restriction. In this experiment using Otsuka Long-Evans Tokushima fatty (OLETF) rats developing NIDDM and Long-Evans Tokushima Otsuka (LETO) rats as controls, sequential changes in body weight and TG content in tissue were measured and biochemical blood tests, an insulin euglycemic clamp test, and histopathologic examination of the pancreas and liver were performed. OLETF rats were allocated to a food-satiated group (satiated) or 30% food-restricted group (restricted). As a result, several findings were more evident in the restricted group than in the satiated group: (1) reductions in body weight and intraabdominal fat weight, decreases in plasma TG, insulin, and glucose levels, a decrease in the TG secretion rate, and an increase in plasma lipoprotein lipase (LPL) activity, (2) decreases in the TG content in the liver, pancreas, and muscle, (3) improvement of the glucose infusion rate (GIR), and (4) a marked reduction of TG accumulation in the liver and pancreatic islets on histopathologic examination. These results indicate that the improved HTG caused a reduction in TG accumulation in the liver and muscle, thereby improving insulin resistance. Moreover, the decrease in TG accumulation in pancreatic islets suggests an improvement of pancreatic beta-cell function.
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Diabetes Mellitus Tipo 2/dietoterapia , Triglicéridos/sangre , Animales , Glucemia/metabolismo , Peso Corporal , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/genética , Modelos Animales de Enfermedad , Técnica de Clampeo de la Glucosa , Histocitoquímica , Hipertrigliceridemia/sangre , Hipertrigliceridemia/dietoterapia , Hipertrigliceridemia/genética , Insulina/sangre , Lipoproteína Lipasa/sangre , Hígado/metabolismo , Hígado/patología , Masculino , Músculo Esquelético/metabolismo , Tamaño de los Órganos , Páncreas/metabolismo , Páncreas/patología , Ratas , Ratas Endogámicas OLETF , Ratas Long-EvansRESUMEN
We conducted protein loading to examine the progression and pathogenesis of diabetic nephropathy. For this experiment, male OLETF, LETO, F344 and BN rats were used. This experiment was performed on rats between 5 and 30 weeks of age. Examination parameters included body weight, food intake, oral glucose tolerance test (OGTT), urinary protein level (UP), urinary albumin level (UA), glomerular filtration rate (GFR), kidney weights, light microscopy (LM) and electron microscopy (EM). In the protein-loaded OLETF group, the UP level was markedly increased 20 weeks or more after birth. In OLETF control group, GFR were higher than those in other strains. Glomerular hypertrophy and kidney weights were markedly increased in protein-loaded groups in OLETF rats. Thirty weeks after birth, EM showed that the number of polyethyleneimine (PEI) of the glomerular basement membrane (GBM) in protein-loaded OLETF group was significantly decreased compared to that in control group. These changes in OLETF rats were more marked in the protein-loaded group than those in the control group. LM showed that the number of exudative lesions with fibrin-cap in the protein-loaded OLETF group was significantly increased than those in control group. In OLETF rats, protein loading caused deterioration of nephropathy at 30 weeks of age. Therefore, it was demonstrated that not only blood sugar control but also protein intake factors play important roles in the deterioration of nephropathy in OLETF rats.
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Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/etiología , Ingestión de Alimentos , Proteínas/metabolismo , Albuminuria/orina , Animales , Glucemia/análisis , Peso Corporal , Proteínas en la Dieta/administración & dosificación , Modelos Animales de Enfermedad , Tasa de Filtración Glomerular/fisiología , Prueba de Tolerancia a la Glucosa , Insulina/sangre , Corteza Renal/ultraestructura , Glomérulos Renales/patología , Masculino , Microscopía Electrónica , Polietileneimina/química , Proteinuria/orina , Ratas , Ratas Endogámicas BN , Ratas Endogámicas F344 , Ratas Endogámicas OLETF , Flujo Plasmático Renal/fisiología , Organismos Libres de Patógenos Específicos , Estadísticas no ParamétricasRESUMEN
The liver plays a central role in lipoprotein metabolism. In particular, very-low density lipoprotein (VLDL) is assembled in the hepatocytes and secreted into the blood circulation. The VLDL is then catabolized to low-density lipoprotein by lipoprotein lipase and hepatic triglyceride lipase. Obese subjects, especially those with visceral fat accumulation, are frequently associated with hyperlipidemia, non-insulin-dependent diabetes mellitus (NIDDM), and hypertension. The mechanism of hyperlipidemia in visceral fat obesity has not yet been elucidated. Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model of NIDDM, characterized by obesity with visceral fat accumulation, hyperlipidemia, and late-onset insulin resistance. To elucidate the mechanism of hyperlipidemia observed in OLETF rats, we focused on the production of VLDL by the liver and investigated hepatic messenger RNA (mRNA) levels of microsomal triglyceride transfer protein (MTP), acyl-coenzyme A synthetase (ACS), and apolipoprotein B (apo B), which play important roles in VLDL synthesis and secretion. In 6-week-old OLETF rats, in which insulin resistance had not been manifested, visceral fat weight was already higher and portal free fatty acid (FFA) and VLDL-triglyceride levels were elevated compared with the control rats. Hepatic ACS activity and mRNA levels, and MTP mRNA levels were also increased in OLETF rats, whereas apo B mRNA levels were similar; these results suggest that the enhanced expression of both ACS and MTP genes associated with visceral fat accumulation before developing insulin resistance may be involved in the pathogenesis of hyperlipidemia in obese animal models with NIDDM.
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Proteínas Portadoras/metabolismo , Coenzima A Ligasas/metabolismo , Hipertrigliceridemia/metabolismo , Obesidad/metabolismo , Proteínas Represoras , Proteínas de Saccharomyces cerevisiae , Tejido Adiposo/anatomía & histología , Factores de Edad , Animales , Apolipoproteínas A/metabolismo , Peso Corporal , Lipoproteínas VLDL/análisis , Masculino , ARN Mensajero/análisis , Ratas , Ratas Mutantes , Triglicéridos/análisisRESUMEN
Hypertriglyceridemia is known to be a feature of obesity-related NIDDM, but the patho-etiological significance of this association is obscure. The effects of triglycerides (TGs) on beta-cell function and morphological changes in pancreas were examined using in vivo and in vitro approaches in male OLETF rats at ages 6, 12, and 30 weeks, with their diabetes-resistant counterpart, LETO rats, as normal controls. The results showed that, in the fasting state, plasma TGs in OLETF rats were increased 2.5-fold at age 6 weeks, 3.3-fold at age 12 weeks, and 6.2-fold at age 30 weeks, compared with age-matched LETO rats. The TG content in islets from 12-week-old OLETF rats was significantly increased when compared with those from their age-matched counterparts, but this was not the case with the 6-week-old OLETF rats. Therefore, the islets from 6-week-old rats were cultured with either free fatty acids (FFAs; 1.0 mmol/l sodium oleate) or TG (5.0 mmol/l Intralipide) for 72 h. Several abnormalities in OLETF rats were evident, in contrast to the results from control LETO rats: 1) glucose-induced insulin secretion was more inhibited by either FFAs or TGs in the presence of 27.7 mmol/l glucose, a result associated, at least in part, with reduced glucokinase activity in the islets; 2) a marked elevation in TG content was found in the islets; and 3) the deposition of fat droplets in the enlarged islets, even in the beta-cells, was found by Oil Red O-insulin double staining at age 30 weeks. In conclusion, hypertriglyceridemia resulted in significant TG stores in the islets, which subsequently inhibited glucose-induced insulin secretion, at least in part, via reduced glucokinase activity in the islets. Fat droplets in islets, therefore, may play an important role in hastening the development of NIDDM in this rat model.
Asunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Hipertrigliceridemia/fisiopatología , Insulina/metabolismo , Islotes Pancreáticos/fisiopatología , Lípidos/análisis , Páncreas/fisiopatología , Animales , Células Cultivadas , Mapeo Cromosómico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patología , Ácidos Grasos no Esterificados/metabolismo , Ácidos Grasos no Esterificados/farmacología , Glucoquinasa/metabolismo , Hipertrigliceridemia/genética , Hipertrigliceridemia/patología , Insulina/análisis , Secreción de Insulina , Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/patología , Masculino , Páncreas/patología , Ratas , Ratas Mutantes , Triglicéridos/metabolismo , Triglicéridos/farmacología , Cromosoma XRESUMEN
1. Carteolol, a non-selective beta-blocker with intrinsic sympathomimetic activity, admixed in a pellet diet was administered to Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of spontaneous non-insulin-dependent diabetes mellitus with mild obesity. A high dose of carteolol (0.02%) suppressed bodyweight gain without affecting food and water consumption until the appearance of glycosuria. Carteolol tended to reduce the cumulative incidence of glycosuria at 26 weeks after the beginning of administration (55, 17 and 25% in control rats, and in rats fed a low (0.002%) and high dose of carteolol, respectively). 2. At the 26th week of administration, the high dose of carteolol decreased visceral fat weight, such as that of retroperitoneal and epididymal adipose tissue, whereas the liver and the kidney were not affected. 3. Although plasma glucose and triglyceride levels in non-fasted rats were elevated with age, carteolol tended to delay the increases in those parameters. Carteolol suppressed the increase in plasma glucose levels, which indicate the diabetic pattern, in a 25th week oral glucose tolerance test. 4. These findings indicate that carteolol induces improvements in bodyweight and carbohydrate and lipid metabolism in an obese condition. Consequently, carteolol may be useful for the treatment of hypertension with obesity in order to prevent cardiovascular events.
Asunto(s)
Antagonistas Adrenérgicos beta/farmacología , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/sangre , Lípidos/sangre , Tejido Adiposo/efectos de los fármacos , Animales , Carteolol/farmacología , Colesterol/sangre , Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Glucosuria/prevención & control , Insulina/sangre , Masculino , Ratas , Triglicéridos/sangreRESUMEN
The male Otsuka Long-Evans Tokushima Fatty (OLETF) rat shows insulin resistance in skeletal muscle and visceral obesity. To obtain information on the mechanism of the insulin resistance in the diabetic rats, we examined the content of insulin-regulated glucose transporter (GLUT4) in skeletal muscles. The results indicate that the total content of the transporter is significantly decreased (P < 0.05) in muscles of the diabetic rats. Plasma membrane content of the GLUT4 protein in muscles of the diabetic rats was increased in the basal state as compared to control rats. Hyperinsulinemic clamps increased GLUT4 levels in the plasma membrane of control rats but failed to do so in the diabetic rats. The distribution of GLUT4 in OLETF rat is reminiscent of the characteristics of human non-insulin-dependent diabetes mellitus.
Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Proteínas de Transporte de Monosacáridos/metabolismo , Proteínas Musculares , Músculo Esquelético/metabolismo , Animales , Glucemia/metabolismo , Membrana Celular/metabolismo , Diabetes Mellitus Tipo 2/sangre , Modelos Animales de Enfermedad , Técnica de Clampeo de la Glucosa , Transportador de Glucosa de Tipo 1 , Transportador de Glucosa de Tipo 4 , Humanos , Técnicas In Vitro , Insulina/sangre , Resistencia a la Insulina , Masculino , Ratas , Ratas EndogámicasRESUMEN
A sample of 871.3 patients/year was conformed by 205 postmenopausal women, aged 64.8 +/- 18.2 years (mean +/- SD), followed up during 51 +/- 12 months. All have osteoporosis, diagnosis assessed through radiological findings of at least one atraumatic fracture or vertebral crush ("severe osteoporosis" according to the new WHO classification). Each woman received 100 mg/day oral pamidronate (enteric coated soft gelatin capsules), half an hour before breakfast. Additional calcium and vitamin D were supplemented as follows: Total daily calcium = 1 g provided by diet and/or calcium carbonate. Vitamin D equivalent to 400-1200 IU/day. All patients were recommended to improve their physical activity, at least by walking exercise. Clinical examination radiological, bone mineral density (BMD) and biochemical studies were periodically performed. But, fracture indicence was the end-point of the study. Same was related to the 1,673 fall episodes recorded in the sample. In addition, height loss, lumbar BMD, proximal femur BMD, are also reported. Data has been cross-sectional collected in March 1995. All patients improved the symptomatology, specifically pain. This, and the good tolerability of the treatments proved to be considerably favorable for their compliance. Within the observation period, only 12 patients decreased their height (5.85%; mean = 0.85 cm; range = 0.5-2.0 cm). Lumbar spine BMD increased in 90% of 48 women. Mean gain after 2 years was 5.3 +/- 1.0% (p < 0.001). Proximal femur increased in 78% of other 32 women. Mean gain 6.3 +/- 0.7% (p < 0.001) after 2 years. A total of 78 new fractures were recorded, 47 vertebral crush, 29 forearm fractures and 2 hip fractures. Its incidence related to the fall episodes was of 2.8; 1.7 and 0.12% respectively. When compared with a historical estimated data, from an untreated population (Cummings SR et al, 1994), both, the total number of new fractures and the new hip fractures were significantly lower (p < 0.01) in our treated population than the reference data. Pamidronate, in oral doses of 100 mg/day, adequately supplemented with calcium and vitamin D, proved to be effective and a well tolerated therapy. The low rate of height's loss, BMD significant increases in subgroups of patients and the low rate of new fractures, strongly support the use of the compound to treat severe osteoporotic women. To our knowledge, this is the first time, that the new fracture incidence is related to the fall frequency reported in a bisphosphonate treated sample.