RESUMO
Peripheral stimulation is known to influence the state of cortical excitability. The purpose of this study is to investigate whether peripheral magnetic stimulation has similar effects on cortical excitability to transcranial magnetic stimulation (TMS). A magnetic stimulator with a flat figure-of-eight coil was used for both TMS, and peripheral magnetic stimulation applied to the bilateral forearms. TMS was performed on the left primary motor cortex to evaluate influence of the peripheral magnetic stimulation, and motor evoked potential (MEP) was measured from the right first dorsal interosseous. Peripheral magnetic stimulation was performed at a stimulus frequency of 1 Hz or 10 Hz, to the stimulus sites on the right and left supination of the forearm. The effects of peripheral magnetic stimulation were evaluated by comparing the mean MEP amplitude elicited by TMS before and after peripheral magnetic stimulation. We found that cortical excitability varied according to the stimulation site and frequency of the peripheral magnetic stimulation. The inhibition of cortical excitability was observed following 1 Hz peripheral magnetic stimulation over the right forearm (p<;0.001). In contrast, increased cortical excitability was observed using 1 Hz peripheral magnetic stimulation over the left forearm and 10 Hz stimulation over either the right or left forearms. We suggest that peripheral magnetic stimulation has a similar effect to TMS, and can induce both facilitation and inhibition of cortical excitability.
Assuntos
Córtex Motor/fisiologia , Estimulação Magnética Transcraniana/métodos , Adulto , Eletromiografia , Potencial Evocado Motor/fisiologia , Feminino , Antebraço/fisiologia , Humanos , MasculinoRESUMO
The purpose of the present study was to use event-related potentials (ERP) to clarify the effect of magnetic stimulation on cognitive processing. A figure eight-shaped flat repetitive transcranial magnetic stimulation (rTMS) coil was used to stimulate either the region over the left or the right dorsolateral prefrontal cortex, which is considered to be the origin of the P300 component. Stimulus frequencies were 1.00, 0.75 and 0.50 Hz rTMS. The strength of the magnetic stimulation was set at 80% of the motor threshold for each participant. The auditory oddball task was used to elicit P300s before and shortly after rTMS, and comprised a sequence of sounds containing standard (1 kHz pure tone, 80% of trials) and deviant (2 kHz pure tone, 20% of trials) stimuli. We found that a 1.00 Hz rTMS pulse train over the left dorsolateral prefrontal cortex increased P300 latencies by 8.50 ms at Fz, 12.85 ms at Cz, and 11.25 ms at Pz. In contrast, neither 0.75 and 0.50 Hz rTMS pulse trains over the left dorsolateral prefrontal cortex nor 1.00, 0.75 and 0.50 Hz rTMS pulse trains over the right dorsolateral prefrontal cortex altered P300 latencies. These results indicate that rTMS frequency affects cognitive processing. Thus, we suggest that the effects of rTMS vary according to the activity of excitatory and inhibitory neurons in the cerebral cortex.
Assuntos
Cognição/fisiologia , Córtex Pré-Frontal/fisiologia , Estimulação Magnética Transcraniana/métodos , Adulto , Eletrodos , Potenciais Evocados P300/fisiologia , Feminino , Humanos , Magnetismo , Masculino , Adulto JovemRESUMO
BACKGROUND: The effects of L-carnitine on the hemodynamic state of chronic hemodialysis patients have been debated. In order to clarify the effect of administered L-carnitine on cardiac function and hypotensive episodes during the hemodialysis procedure, a randomized double-blind placebo-controlled study was performed for 3 months. METHODS AND RESULTS: TWENTY STABLE OUTPATIENTS UNDERGOING HEMODIALYSIS TREATMENT WERE DIVIDED INTO TWO GROUPS: controls (placebo) and treated patients (L-carnitine 900 mg p.o. daily). After 3 months, cardiac function was reevaluated by echocardiography, and hypotensive episodes during hemodialysis were assessed. Free and acyl carnitine levels increased significantly from 22.3 ± 7.1 to 140.3 ± 57.5 µmol/l and from 15.8 ± 2.8 to 94.8 ± 50.4 µmol/l, respectively, in the treated group. The ejection fraction significantly increased from 61.8 ± 16.0 to 64.4 ± 13.8% (p < 0.05) in the treated group. However, there was no difference in other echocardiographic parameters between the two groups. Hypotensive episodes significantly decreased from 4.0 ± 1.7 to 1.3 ± 0.9 times per month (p < 0.05), although patients' body weight did not change significantly. CONCLUSIONS: Beneficial effects of L-carnitine on the hemodynamic state of chronic hemodialysis patients were observed. L-Carnitine supplementation might be considered especially for chronic hemodialysis patients with unstable hemodynamic conditions.
RESUMO
In this paper, we report our studies of the effects of stimulating the bilateral supramarginal gyrus (SMG) with low-frequency transcranial magnetic stimulation (rTMS) or short-term rTMS on brain excitability in humans. We analyzed the effects of various durations of stimulation on P300 latencies of the event-related potential (ERP). Magnetic pulses were delivered using a figure-eight flat coil. The intensity of rTMS was set to 80 % of the subject's motor threshold. In each round of rTMS, 100 magnetic pulses were applied over the scalp at frequencies of 1.00, 0.75, and 0.50 Hz. ERPs were measured prior to magnetic stimulation as a control. The effects of magnetic stimulation were then determined by measuring its effects on P300 latencies elicited by an odd-ball task. These latencies were measured before and 0, 5, 10, and 15 min after the magnetic stimulation. 1.00 Hz low-frequency rTMS of the left SMG decreased P300 latencies for approximately 10 min. In contrast, 0.50 Hz rTMS of the left SMG resulted in delayed P300 latencies for approximately 15 min. We furthermore found that 0.75 Hz rTMS of the left SMG and 1.00, 0.75 and 0.5 Hz rTMS of the right SMG did not affect P300 latencies. These results suggest that the duration of the effects of rTMS depend on the frequency of stimulation.
Assuntos
Encéfalo/fisiologia , Estimulação Magnética Transcraniana , Eletroencefalografia , Potenciais Evocados , HumanosRESUMO
BACKGROUND: Short-chain fatty acids such as lactic acid produced by the intestinal bacterial flora have various physiological actions involved in health, and it is important to determine the concentrations of faecal short-chain fatty acids and evaluate their relationship with large intestinal diseases. In this study, we evaluated the highly selective and sensitive simultaneous measurement of both volatile and non-volatile short-chain fatty acid hydrazides using high-performance liquid chromatography (HPLC). MATERIALS AND METHODS: Faeces treated with ethanol were used as analytic samples. Short-chain fatty acids were measured as fatty acid hydrazides by HPLC. RESULTS: For 12 types of short-chain fatty acid, the results regarding linearity, recovery tests and reproducibility were favourable. Faeces treated with ethanol could be stored at room temperature. DISCUSSION: The stability of short-chain fatty acids in faeces at room temperature was statistically analysed. Faeces stored without treatment with ethanol showed increases/decreases in the concentrations of short-chain fatty acids, which may be due to assimilation by intestinal bacteria. However, specimen in 70% ethanol and stored in room temperature exhibited no substantial changes in concentrations of short-chain fatty acids up to seven days.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Testes de Química Clínica/métodos , Ácidos Graxos Voláteis/análise , Fezes/química , Manejo de Espécimes/métodos , Calibragem , Ácidos Graxos Voláteis/química , Humanos , Fatores de Tempo , VolatilizaçãoRESUMO
During thunderstorms on 20 September 2008, a simultaneous detection of gamma rays and electrons was made at a mountain observatory in Japan located 2770 m above sea level. Both emissions, lasting 90 sec, were associated with thunderclouds rather than lightning. The photon spectrum, extending to 10 MeV, can be interpreted as consisting of bremsstrahlung gamma rays arriving from a source which is 60-130 m in distance at 90% confidence level. The observed electrons are likely to be dominated by a primary population escaping from an acceleration region in the clouds.
RESUMO
In this study, we report the mass production of monodisperse emulsion droplets and particles using microfluidic large-scale integration on a chip. The production module comprises a glass microfluidic chip with planar microfabricated 16-256 droplet-formation units (DFUs) and a palm-sized stainless steel holder having several layers for supplying liquids into the inlets of the mounted chip. By using a module having 128 cross-junctions (i.e., 256 DFUs) arranged circularly on a 4 cm x 4 cm chip, we could produce droplets of photopolymerizable acrylate monomer at a throughput of 320.0 mL h(-1). The product was monodisperse, having a mean diameter of 96.4 microm, with a coefficient of variation (CV) of 1.3%. Subsequent UV polymerization off the module yielded monodisperse acrylic microspheres at a throughput of approximately 0.3 kg h(-1). Another module having 128 co-flow geometries could produce biphasic Janus droplets of black and white segments at 128.0 mL h(-1). The product had a mean diameter of 142.3 microm, with a CV of 3.3%. This co-flow module could also be applied in the mass production of homogeneous monomer droplets.
Assuntos
Emulsões/química , Emulsões/síntese química , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Microesferas , Desenho de Equipamento , Tamanho da PartículaRESUMO
The effect of mechanical stress generated within a three-dimensional bioreactor on the co-culture of hepatic parenchymal cells (PC) and hepatic nonparenchymal cells (NPC) was assessed to develop a bioartificial liver that can produce factors accelerating liver regeneration. A rotating radial flow bioreactor was used to provide mechanical stress to a co-culture of PC and NPC that were isolated from rats. They were co-cultured in the reactor under static or dynamic conditions. Albumin, interleukin-6 (IL-6), hepatocyte growth factor (HGF), and lactate dehydrogenase (LDH) were measured at intervals. Electron microscopy was also performed. LDH was not significantly different between the static and mechanical stress-loaded cultures, while albumin and interleukin-6 levels were higher in the latter at all sampling times. Only the co-cultures loaded with mechanical stress produced HGF in the early stage of culture (hours 3 and 6). Histologically, the cells retained their structure when cultured under dynamic conditions. These results suggested that an appropriate level of mechanical stress enabled co-cultures of PC and NPC to produce IL-6, HGF, and other factors that accelerate liver regeneration.
Assuntos
Fígado/citologia , Fígado/fisiologia , Regeneração/fisiologia , Técnicas de Cocultura , Fator de Crescimento de Hepatócito/análise , Humanos , Interleucina-6/análise , L-Lactato Desidrogenase/análise , Albumina Sérica/análise , Estresse MecânicoRESUMO
Rapid blood flow changes occur in the liver following a massive resection or in the grafted liver following transplantation, under which shear stress (SS) change induced by the flow change may determine the postoperative results. We observed changes in liver tissue structure and liver-specific function, and consequently assessed SS effect. The cultured liver tissue exposed to continuous application of moderate SS was shown to express and maintain a long-term liver-specific function. There was also evidence showing that destruction of the liver structure was inhibited. However, the cultured liver tissue not exposed to SS or exposed to high SS was shown to lose liver-specific function soon after expression. The liver structure was destroyed in the early stage of incubation. These results suggested that continuous application of appropriate SS has advantages over other types of stresses to protect liver tissue.
Assuntos
Hepatócitos/fisiologia , Fígado/fisiologia , Estresse Mecânico , Animais , Reatores Biológicos , Hepatócitos/citologia , Hepatócitos/ultraestrutura , L-Lactato Desidrogenase/análise , Masculino , Ratos , Ratos Endogâmicos F344 , Albumina Sérica/biossínteseRESUMO
A new surfactant-mediated separation method was developed for concentrating traces of gold ion in water. The methodology is based on the combination of selective complexation of gold(III) with polyoxyethylene(10)-p-isononylphenyl ether, PONPE-10, and strong binding of surfactant complex to hydrophobic polystyrene resins embedded in a PTFE fiber disk (Empore disk). A 400-fold concentration of gold(III) was achieved by 400 ml load of the sample containing 0.01% (w/v) PONPE-10 and 0.10 M nitric acid and by the subsequent elution with 1.0 ml of aqueous buffer solution of 0.01 M N-(dithiocarboxyl)sarcosine diammonium. Traces of gold (0.40 ng/l) in river water samples were successfully determined with inductively coupled plasma MS.
Assuntos
Éteres/química , Ouro/química , Polietilenoglicóis/química , Poliestirenos/química , Água/química , Espectrometria de MassasRESUMO
Liddle's syndrome is a rare form of autosomal-dominant salt-sensitive hypertension. Constitutive activation of the amiloride-sensitive distal renal epithelial sodium channel (ENaC) is essential for salt-sensitive hypertension. Recently, several DNA analysis studies have indicated that there is a mutation of C-terminus of either the beta or y subunit. We sequenced the C-termini of the beta and -gamma subunits of the ENaC in a Japanese family with hypertension and hypopotassemia without excess minerarocorticoids, clinically diagnosed as Liddle's syndrome. The mutation of the ENaC of this family was beta R564X. Since such case seem to be rare in the literature, detailed data are shown in this report.
Assuntos
Epitélio/química , Hipertensão/genética , Canais de Sódio/sangue , Canais de Sódio/genética , Aldosterona/sangue , Aldosterona/genética , Alcalose/sangue , Alcalose/genética , Sequência de Bases , Gasometria , Bloqueadores dos Canais de Cálcio/uso terapêutico , Análise Mutacional de DNA , Diagnóstico Diferencial , Diuréticos/uso terapêutico , Saúde da Família , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipopotassemia/diagnóstico , Hipopotassemia/tratamento farmacológico , Hipopotassemia/genética , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutagênese/genética , Mutação Puntual/genética , Potássio/sangue , Potássio/urina , Renina/genética , Renina/metabolismo , Espironolactona/uso terapêutico , Síndrome , Triantereno/uso terapêuticoRESUMO
Associations between polymorphisms of the cystatin C gene (CST3) at 5' flanking region and exon 1 in Caucasian patients with late onset AD and exon 1 in a US study of late onset AD have been reported. Clinically diagnosed Japanese patients with AD and Japanese normal control subjects were assessed for the presence of polymorphisms of CST3. The authors could not confirm the previously reported association between CST3 polymorphisms and AD in Japan. Age had no effect on the CST3 genotype.
Assuntos
Doença de Alzheimer/genética , Cistatinas/genética , Polimorfismo Genético/genética , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas E/genética , Cistatina C , Genótipo , Humanos , Japão , Desequilíbrio de Ligação/genéticaRESUMO
The effect of melatonin on the release of Arg-vasopressin (AVP) was analyzed in a suprachiasmatic nucleus-slice explant culture. The release of AVP into the culture medium exhibited a circadian rhythm, with higher level during the subjective day and lower level during the subjective night. Melatonin (500 nM) inhibited the release of AVP. Luzindole, a MT(2) (Mel 1b) melatonin receptor antagonist, attenuated the effect of melatonin on the AVP release. Results indicate that the inhibition of AVP release by melatonin in the suprachiasmatic nucleus-slice culture depends at least in part on the melatonin MT(2) receptor.
Assuntos
Antioxidantes/farmacologia , Arginina Vasopressina/metabolismo , Melatonina/farmacologia , Receptores de Superfície Celular/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Núcleo Supraquiasmático/metabolismo , Animais , Ritmo Circadiano/fisiologia , Relação Dose-Resposta a Droga , Atividade Motora/fisiologia , Técnicas de Cultura de Órgãos , Fotoperíodo , Ratos , Ratos Wistar , Receptores de Superfície Celular/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Receptores de Melatonina , Núcleo Supraquiasmático/efeitos dos fármacos , Triptaminas/farmacologiaRESUMO
Recent studies have shown that not only an enhanced renin-angiotensin system, but also relative volume retention might contribute to hypertension even in the early phase of a two-kidney, one-clip hypertensive model. To evaluate the role of renal depressor and natriuretic systems in the development of high blood pressure in the early phase of this model, we measured urinary excretion of kallikrein(uKAL), prostaglandin E2(uPGE2), and dopamine(uDA) in male Sprague-Dawley rats instrumented with a 0.2 mm diameter clip on the left renal artery(2K1C) and compared the results with those of sham-operated rats(sham). We also measured ouabain-like factor(OLF) in the plasma(pOLF) and urine(uOLF) in both groups. In 2K1C, systolic blood pressure(SBP) progressively increased and plasma renin activity was higher than the sham in the 3rd week. UDA and uPGE2 were not different between these groups, but uKAL attenuated in 2K1C in the 1st and 3rd week compared to the sham. There was a negative correlation between %delta SBP and %delta uKAL. On the other hand, uOLF increased in 2K1C in the 1st, 2nd and 3rd week compared to the sham. There was a positive correlation between SBP and uOLF. And pOLF was higher in 2K1C than in the sham. Furthermore there was a negative correlation between %delta uKAL and %delta uOLF. These results indicated that even in the early phase, suppression of the renal kallikrein-kinin system would contribute to high blood pressure in part, and OLF might play a compensatory role against the impaired natriuretic system in the kidney. However, OLF might contribute to blood pressure elevation through vasoconstriction in 2K1C.
Assuntos
Digoxina , Hipertensão/etiologia , Animais , Pressão Sanguínea , Cardenolídeos , Dinoprostona , Modelos Animais de Doenças , Dopamina/urina , Hipertensão/fisiopatologia , Sistema Calicreína-Cinina/fisiologia , Calicreínas/urina , Rim/fisiopatologia , Masculino , Natriurese , Ratos , Ratos Sprague-Dawley , Saponinas/sangue , Saponinas/urina , VasoconstriçãoRESUMO
PURPOSE: Macular corneal dystrophy (MCD) is an autosomal recessive inherited disorder that is accompanied by corneal opacity. Explants from MCD-affected corneas have been reported to synthesize low-sulfated KS, suggesting that sulfate groups attached to KS may play critical roles in maintaining corneal transparency. To clear the biosynthetic defect in the MCD cornea, sulfotransferase activities were determined that are presumably involved in the biosynthesis of KS: galactose-6-sulfotransferase (Gal6ST) activity and N-acetylglucosamine 6-O-sulfotransferase (GlcNAc6ST) activity. METHODS: Gal6ST and GlcNAc6ST activities, which were contained in the corneal extracts from corneas affected by MCD and keratoconus and from normal control corneas, were determined by measuring the transfer of (35)SO(4) from [(35)S]3'-phosphoadenosine 5'-phosphosulfate into the Gal residue of partially desulfated KS and the nonreducing terminal GlcNAc residue of GlcNAcbeta1-3Galbeta1-4GlcNAc (oligo A), respectively. RESULTS: The level of Gal6ST activity in corneal extracts from eyes with MCD, which was measured by using partially desulfated KS as an acceptor, was nearly equal to that in eyes with keratoconus and normal control eyes. In contrast, GlcNAc6ST activity in the extracts from MCD-affected corneas, which was measured by using oligo A as an acceptor, was much lower than in those in corneas with keratoconus and in normal control corneas. CONCLUSIONS: The decrease in GlcNAc6ST activity in the cornea with MCD may result in the occurrence of low- or nonsulfated KS and thereby cause corneal opacity.
Assuntos
Córnea/enzimologia , Distrofias Hereditárias da Córnea/enzimologia , Sulfotransferases/metabolismo , Adulto , Idoso , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Cromatografia em Papel , Distrofias Hereditárias da Córnea/cirurgia , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Sulfato de Queratano/biossíntese , Ceratocone/enzimologia , Ceratocone/cirurgia , Ceratoplastia Penetrante , Masculino , Pessoa de Meia-Idade , Carboidrato SulfotransferasesRESUMO
A noninvasive method for the diagnosis of cardiac calcinosis, a life-threatening complication in hemodialysis patients with end-stage renal disease (ESRD), has not, as yet, been firmly established. We tested whether whole body scanning with 99m-technetium methylene diphosphonate (MDP) might visualize cardiac calcinosis. In 19 consecutive chronic hemodialysis ESRD patients (13 males and 6 females, aged 40-81, mean 63 +/- 8 years) with cardiovascular disease [mitral annular calcinosis and/or calcified aortic valve (n = 4), hemodialysis cardiomyopathy (n = 1), coronary artery disease (n = 9) and peripheral artery atherosclerotic disease (n = 6)], MDP uptake in the heart was compared to that in 7 non-ESRD controls with hyperparathyroidism due to adenoma. Cardiac and lung field MDP uptake was confirmed in only 3 (16%) and 5 (26%) of the 19 ESRD subjects, respectively, but was absent in controls. Positive cardiac uptake was related to cardiac calcified complications (mobile intracardiac calcinosis, myocardial calcinosis and mitral annular calcification) and the duration of hemodialysis (p = 0.015). While it was statistically insignificant, subjects showing MDP uptake were elder and had higher serum Ca or Ca x P product and lower intact parathyroid hormone levels. These results suggest that cardiac calcinosis in ESRD patients can be detected noninvasively by myocardial scintigraphy with 99m-technetium MDP.
Assuntos
Calcinose/diagnóstico por imagem , Calcinose/etiologia , Cardiomiopatias/diagnóstico por imagem , Compostos Radiofarmacêuticos , Diálise Renal/efeitos adversos , Medronato de Tecnécio Tc 99m , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/farmacocinética , Medronato de Tecnécio Tc 99m/efeitos adversos , Medronato de Tecnécio Tc 99m/farmacocinética , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
BACKGROUND/AIMS: A new dosage formulation consisting of an anti-cancer drug bound to activated carbon particles was developed for a local injection against early gastric cancer so that the dosage formulation yields chemotherapeutic effects selectively to the lymph node metastases as well as to the primary lesion. METHODOLOGY: As a pilot study, the new dosage formulation, total of 50-200 mg of methotrexate only or total of 200 mg of methotrexate plus 8 mg of mitomycin C, was injected into the primary lesions and the adjacent gastric wall of 8 patients with early gastric cancer, guided by a gastrofiberscope before gastrectomy. The surgically resected specimens were examined histologically for the therapeutic effects on the primary lesion and its nodal metastasis. RESULTS: The therapeutic effects were seen in 2 of 4 lymph node metastases (50%) and 5 of 8 of the primary lesions (63%), as confirmed histologically with degeneration and/or necrosis. CONCLUSIONS: Preoperative local injection of the new dosage formulation will be useful to give chemotherapeutic effects on the potential metastases in the regional nodes as well as to the primary lesion.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carvão Vegetal , Metotrexato/administração & dosagem , Mitomicina/administração & dosagem , Terapia Neoadjuvante , Neoplasias Gástricas/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Feminino , Gastrectomia , Humanos , Injeções Intralesionais , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Mitomicina/efeitos adversos , Projetos Piloto , Estômago/patologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
The aim of this study was to determine the effect of Tang-Shen-Jiao-Nang (TSJN), a Chinese medicine used to treat diabetes mellitus, on insulin resistance and hypertension in fructose-fed rats (FFR). Six-week-old male Sprague-Dawley rats were fed either normal rat chow (control) or a fructose-rich chow (FFR) for 6 wk. For the last 2 or 4 wk of a 6-wk period of either diet, the rats were treated by gavage with gum arabic solution as a vehicle (control or FFR) or TSJN (800 mg/kg/d; FFR+TS), and then we performed the euglycemic hyperinsulinemic glucose clamp technique to estimate insulin sensitivity. Systolic blood pressure was measured weekly for 6 wk. At the end of the glucose clamp, the soleus muscle was dissected out for determination of muscle fiber composition by ATPase methods. Systolic blood pressure was elevated at 2 wk after the start of the fructose-rich chow feeding and persisted thereafter throughout the study. Systolic blood pressure during the glucose clamp in the FFR group was significantly higher than that in the control group. Although there was no effect on systolic blood pressure in rats treated with TSJN for the last 2 wk of their 6-wk diet, those treated with TSJN for the last 4 wk of their 6-wk diet had lower systolic blood pressure than did the rats in the FFR group. The average rate of glucose infusion during the glucose clamp, as a measure of insulin sensitivity (M value), was significantly lower in the FFR than in the controls (10.9 +/- 0.6 and 15.4 +/- 0.4, mg/kg/min, for FFR and controls, respectively; p< 0.01). Treatment with TSJN for 2 wk significantly improved the M value compared to that of the control level (15.1 +/- 0.5 mg/kg/min). The composite ratio of type I fibers in the soleus muscle was significantly decreased in the FFR compared to controls (75.0 +/- 1.7 and 81.7 +/- 1.5%, for FFR and controls, respectively; p< 0.01), and treatment with TSJN for 2 wk led to a recovery composite ratio of type I fiber to the same level as that of the control group (78.7 +/- 1.7% in FFR + TS). The M value was significantly correlated with the compositions of type I and type II fibers (for type I fibers, r= 0.45, p < 0.01, for type II fibers, r= -0.44, p< 0.05). These results suggest that the Chinese medicine TSJN may improve insulin resistance, lower the systolic blood pressure, and modulate muscle fiber composition in hypertensive and insulin-resistant fructose-fed rats.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Frutose , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Resistência à Insulina/fisiologia , Animais , Glicemia/análise , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Jejum/sangue , Técnica Clamp de Glucose , Frequência Cardíaca/efeitos dos fármacos , Masculino , Fibras Musculares Esqueléticas/classificação , Fibras Musculares Esqueléticas/ultraestrutura , Ratos , Ratos Sprague-DawleyRESUMO
The aim of this study was to compare the effects of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II receptor (AT) antagonist on insulin resistance, especially on muscle fiber composition in fructose-induced insulin-resistant and hypertensive rats. Six-week-old male Sprague-Dawley rats were fed either normal rat chow (control) or a fructose-rich diet (FFR). For the last two weeks of a six-week period of either diet, the rats were treated with gum arabic solution as a vehicle (control or FFR), angiotensin-converting enzyme inhibitor (FFR+ACE), temocapril (1 mg/kg/ day) or an angiotensin II receptor antagonist (FFR+AT), CS-866 (0.3 mg/kg/day), by gavage, and then the euglycemic hyperinsulinemic glucose clamp technique was performed to evaluate insulin sensitivity. At the end of the glucose clamp, the soleus muscle was dissected for determination of the muscle fiber composition by ATPase methods. Blood pressure at the glucose clamp in the FFR group was significantly higher than that of the control group, and both temocapril and CS-866 significantly lowered the blood pressure of the FFR group. The average rate of glucose infusion during the glucose clamp, as a measure of insulin sensitivity (M value), was significantly lower in the FFR rats compared to the controls (15.4 +/- 0.4, 10.9 +/- 0.6 mg/kg/min, for control and FFR, respectively, P < .01). Both temocapril and CS-866 partially improved the M values compared to FFR (13.2 +/- 0.7, 12.8 +/- 0.5 mg/kg/min, for FFR+ACE, FFR+AT, respectively, P < .01 compared with FFR, P < .05 compared with control). The composite ratio of type I fibers of the soleus muscle was decreased significantly in the FFR rats compared with the controls (82% +/- 2%, 75% +/- 2%, for control and FFR, respectively, P < .01), and both temocapril and CS-866 restored a composite ratio of type I fibers to the same level as that of the controls (81% +/- 1%, 80% +/- 1% for FFR+ACE and FFR+AT, respectively). The M value was significantly correlated with the composition of type I and type II fibers. These results suggest that the fiber composition of skeletal muscle is correlated to insulin resistance, and that both ACE inhibitors and AT antagonists may modulate the muscle fiber composition in a hypertensive and insulin-resistant animal model, fructose-fed rats, to the same extent.
Assuntos
Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Frutose/administração & dosagem , Resistência à Insulina , Animais , Anti-Hipertensivos/farmacologia , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Carboidratos da Dieta/administração & dosagem , Jejum , Glucose/farmacologia , Técnica Clamp de Glucose , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Imidazóis/farmacologia , Magnésio/administração & dosagem , Magnésio/sangue , Masculino , Fibras Musculares de Contração Rápida/química , Fibras Musculares de Contração Rápida/efeitos dos fármacos , Fibras Musculares Esqueléticas/química , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares de Contração Lenta/química , Fibras Musculares de Contração Lenta/efeitos dos fármacos , Músculo Esquelético/química , Músculo Esquelético/efeitos dos fármacos , Olmesartana Medoxomila , Ratos , Ratos Sprague-Dawley , Tetrazóis/farmacologia , Tiazepinas/farmacologiaRESUMO
BACKGROUND/AIM: Progressive cardiovascular calcification in dialysis patients with end-stage renal disease (ESRD) is a serious complication; however, the precise mechanism remains uncertain. We tested whether metabolic calcium abnormalities and hypoparathyroidism might have a correlation with cardiovascular complications in ESRD patients. METHODS: A series of 48 ESRD patients with cardiovascular diseases and/or congestive heart failure, aged 36-82 (61 +/- 12) years, 23 male and 25 female, were enrolled in this study. Serum total calcium (Ca, mmol/l), inorganic phosphate (mmol/l), and intact parathyroid hormone (iPTH, pg/ml) levels were determined in all cases. RESULTS: Organic heart disease was confirmed in 28 patients (58.3%), including 15 with coronary artery disease: 8 with aortic aneurysm, 8 with stenotic valvular heart disease, 9 with excessive mitral annular calcification, 3 with dialysis cardiomyopathy, and 7 with obstructive arterial disease. Serum iPTH measurement revealed hypoparathyroidism (iPTH <60) in 20 of 48 (41.7%) and hyperthyroidism (iPTH >/=200) in 13 of 48 (27.1%) subjects. The 20 patients with low iPTH had a higher prevalence of valvular heart disease, a higher total Ca level corrected for serum albumin (2.70 +/- 0.30 in low iPTH vs. 2.47 +/- 0.30 in normal iPTH, 2.35 +/- 0.20 in high iPTH, p = 0.003) and a higher tendency of vitamin D(3) analog use (65% in low iPTH vs. 33% in normal iPTH and 46% in high iPTH, p = 0.078). Moreover, corrected serum Ca exhibited a negative logarithmic correlation with serum iPTH: corrected Ca = -0.284x log (iPTH) + 3.021 (r = 0.637, p = 0.0001). Multiple logistic regression analysis revealed diabetes and hypoparathyroidism (iPTH <60) as risk factors for cardiovascular complications in ESRD. CONCLUSION: These results suggest that hypercalcemia and hypoparathyroidism in conjunction with vitamin D(3) use might play an important role in cardiovascular complications of chronic dialysis patients.