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1.
Indoor Air ; 32(3): e13019, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35347782

RESUMO

As COVID-19 continues to spread, infection risk on public transport is concerning. Air exchange rates (ACH) and advection-diffusion of CO2 and particles were determined in a route bus to evaluate the infection risk. ACH increased with bus speed whether windows were open or closed, and ACH were greater when more windows were open. With two open windows, ACH was greater when a front and rear window were open than when two rear windows were open. With both front and rear ventilation fans set to exhaust, ACH was more than double that when both were set to supply. With air conditioning (AC) off, CO2 and particles spread proportionally at the same rate from a source, whereas with the AC on, the spread rate of particles was about half that of CO2 , because particles might be trapped by a prefilter on the AC unit. Infection risk can be reduced by equipping AC unit with an appropriate filter. Calculations with a modified Wells-Riley equation showed that average infection risk was reduced by 92% in the moving bus with windows open comparing to with windows closed. When the bus was moving with windows closed, exhaust fan operation reduced the average risk by 35%.


Assuntos
Poluição do Ar em Ambientes Fechados , COVID-19 , Aerossóis , Poluição do Ar em Ambientes Fechados/análise , Dióxido de Carbono , Humanos , Ventilação
2.
Appl Opt ; 57(2): 225-229, 2018 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-29328168

RESUMO

The preparation of nanoscale fine bubbles in water is an innovative technology, but no precise method for simultaneously measuring the size and concentration of such bubbles had previously been developed. We have developed a method for simultaneously determining the size and concentration of fine bubbles in water by a light-scattering technique. Dynamic light scattering gives the diffusion constant and particle size of fine bubbles, whereas static light scattering provides their concentration or molar mass. Static light scattering also provides the radius of gyration of the bubbles, thereby providing a means for validating measurements of the sizes of the fine bubbles.

3.
J Pharm Sci ; 112(12): 3248-3255, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37813302

RESUMO

Flow imaging microscopy (FIM) is widely used to characterize biopharmaceutical subvisible particles (SVPs). The segmentation threshold, which defines the boundary between the particle and the background based on pixel intensity, should be properly set for accurate SVP quantification. However, segmentation thresholds are often subjectively and empirically set, potentially leading to variations in measurements across instruments and operators. In the present study, we developed an objective method to optimize the FIM segmentation threshold using poly(methyl methacrylate) (PMMA) beads with a refractive index similar to that of biomolecules. Among several candidate particles that were evaluated, 2.5-µm PMMA beads were the most reliable in size and number, suggesting that the PMMA bead size analyzed by FIM could objectively be used to determine the segmentation threshold for SVP measurements. The PMMA bead concentrations measured by FIM were highly consistent with the indicative concentrations, whereas the PMMA bead size analyzed by FIM decreased with increasing segmentation threshold. The optimal segmentation threshold where the analyzed size was closest to the indicative size differed between an instrument with a black-and-white camera and that with a color camera. Inter-instrument differences in SVP concentrations in acid-stressed recombinant adeno-associated virus (AAV) and protein aggregates were successfully minimized by setting an optimized segmentation threshold specific to the instrument. These results reveal that PMMA beads can aid in determining a more appropriate segmentation threshold to evaluate biopharmaceutical SVPs using FIM.


Assuntos
Produtos Biológicos , Microscopia/métodos , Polimetil Metacrilato , Refratometria , Tamanho da Partícula
4.
Chem Pharm Bull (Tokyo) ; 59(8): 972-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21804241

RESUMO

In recent years, the number of patients suffering from diseases, such as cancer, apoplexy, osteoporosis, hypertension, and type 2 diabetes mellitus is increasing worldwide. Type 2 diabetes, a lifestyle-related disease, is recognized as a serious disease. Various types of pharmaceutics for diabetes have been used. Since the relationship between diabetes and biometals such as vanadium, copper, and zinc ions has been recognized for many years, we have been developing the anti-diabetic metal complexes as new candidates. We found that several zinc(II) (Zn) complexes exhibit glucose-lowering activity for treating type 2 diabetes. High doses of salicylates have been known to reverse hyperglycemia and hyperinsulinemia in type 2 diabetic patients. These findings strongly suggest that the combined use of Zn and salicylates achieves the synergism in treating type 2 diabetes. Because aspirin, acetyl salicylic acid, has a chelating ability, we used it as a ligand to Zn. Several Zn-salicylate complexes were prepared and their biological activities were examined in this study. The complexes with an electron-withdrawing group in the ligand exhibited higher in vitro insulinomimetic activity than those of Zn complexes with an electron-donating group in the ligand. When bis(aspirinato)Zn (Zn(asp)2) complex was orally administered on KK-A(y) mice with hereditary type 2 diabetes, the diabetic state was improved. In addition, this complex exhibited normalizing effects on serum adiponectin level and high blood pressure in metabolic syndrome. In conclusion, Zn(asp)2 complex is newly proposed as a potent anti-diabetic and anti-metabolic syndrome agent.


Assuntos
Aspirina/análogos & derivados , Aspirina/uso terapêutico , Complexos de Coordenação/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , Adiponectina/sangue , Administração Oral , Animais , Aspirina/administração & dosagem , Aspirina/química , Aspirina/farmacocinética , Pressão Sanguínea/efeitos dos fármacos , Complexos de Coordenação/administração & dosagem , Complexos de Coordenação/química , Complexos de Coordenação/farmacocinética , Teste de Tolerância a Glucose , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Hipoglicemiantes/farmacocinética , Resistência à Insulina , Leptina/metabolismo , Masculino , Camundongos , Relação Estrutura-Atividade
5.
Anal Sci ; 35(9): 1045-1051, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31178550

RESUMO

The most important parameter for light-scattering measurements in the Rayleigh scattering region is the Rayleigh ratio, which is necessary to obtain the absolute scattered light intensity from the relative scattered light intensity. The absolute scattered light intensity is directly related to the molar masses of polymers, colloids, biomolecules, and the like. A new Rayleigh ratio was determined by measuring static light scattering from certified reference materials with highly accurate certified values of the molecular weight determined by several other techniques, such as MALDI-TOF mass spectrometry or size-exclusion chromatography. The new Rayleigh ratio can be used for evaluating the uncertainty of the molecular weight of polymers and macromolecules, as measured by light scattering.

6.
Rejuvenation Res ; 11(5): 945-56, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18922047

RESUMO

BACKGROUND: Aging-associated nitro-oxidative stress causes tissue injury and activates proinflammatory pathways that play an important role in the pathogenesis of aging-associated cardiovascular dysfunction. It has been recently reported, that the copper(II)-aspirinate complex (CuAsp) exerts not only the well-known anti-inflammatory and platelet antiaggregating effects of aspirin, but, due to its superoxide dismutase mimetic activity, it acts as a potent antioxidant as well. In this study we investigated the effects of CuAsp on aging-associated myocardial and endothelial dysfunction. METHODS AND RESULTS: Aging and young rats were treated for 3 weeks with vehicle, or with CuAsp (200 mg/kg per day per os). Left ventricular pressure-volume relations were measured by using a microtip pressure-volume conductance catheter, and indexes of contractility (e.g., slope of end-systolic pressure-volume relationships [ESPVR] [E(es)], and dP/dt(max) - end-diastolic volume [EDV]) were calculated. In organ bath experiments for isometric tension with isolated aortic rings, endothelium-dependent and -independent vasorelaxation were investigated by using acetylcholine and sodium nitroprusside. When compared to the young controls, aging rats showed impaired left ventricular contractility (E(es), 0.51 +/- 0.04 vs. 2.16 +/- 0.28 mmHg/microL; dP/dt(max) - EDV, 10.71 +/- 2.02 vs. 37.23 +/- 4.18 mmHg/sec per microL; p < 0.05) and a marked endothelial dysfunction (maximal relaxation to acetylcholine: 66.66 +/- 1.30 vs. 87.09 +/- 1.35%; p < 0.05). Treatment with CuAsp resulted in reduced nitro-oxidative stress, improved cardiac function (E(es), 1.21 +/- 0.17 vs. 0.51 +/- 0.04 mmHg/microL; dP/dt(max) - EDV, 23.40 +/- 3.34 vs. 10.71 +/- 2.02 mmHg/sec per microL; p < 0.05) and higher vasorelaxation to acetylcholine in aging animals (94.83 +/- 0.73 vs. 66.66 +/- 1.30%; p < 0.05). The treatment did not influence the cardiovascular functions of young rats. CONCLUSIONS: Our results demonstrate that oxidative stress and inflammatory pathways contribute to the pathogenesis of cardiovascular dysfunction in the aging organism, which can be reversed by CuAsp.


Assuntos
Envelhecimento/efeitos dos fármacos , Envelhecimento/fisiologia , Aspirina/análogos & derivados , Sistema Cardiovascular/efeitos dos fármacos , Sistema Cardiovascular/fisiopatologia , Administração Oral , Envelhecimento/genética , Envelhecimento/patologia , Animais , Antioxidantes/administração & dosagem , Aspirina/administração & dosagem , Sequência de Bases , Sistema Cardiovascular/patologia , Ciclo-Oxigenase 2/genética , Primers do DNA/genética , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Técnicas In Vitro , Óxido Nítrico Sintase Tipo II/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos Lew
7.
Arch Dermatol Res ; 300 Suppl 1: S51-6, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17968570

RESUMO

Reactive oxygen species (ROS) play important roles in the process of ultraviolet-induced skin damage or photoaging. Although many enzymatic and chemical methods have been developed for evaluating ROS, evaluation methods for ROS generation in living systems are quite limited. Here we propose a unique system to visualize UVB-induced ROS and investigate the biological impact of ROS. In brief, a human skin equivalent model (HSEM) was exposed to UVB. Emitted luminescence from the HSEM was visualized and semi-quantified by using a chemiluminescent probe (CLA) and an ultra low-light imaging apparatus. The effects of anti-oxidative compounds such as ascorbate, beta-carotene, superoxide dismutase (SOD), and yeast ferment filtrate (YFF) on the HSEM were evaluated by semi-quantification of emitted chemiluminescence (CL) intensities, MTT assay and 8-hydroxy-2'-deoxyguanosine (8-OHdG) staining. Visualization of time- and space-dependent dynamics of ROS generation in the HSEM was successfully achieved by utilizing a sensitive two-dimensional ultra-low light luminograph. Treatments with beta-carotene and SOD effectively suppressed CL intensity, indicating the generation of 1O2 and O2 .- in the HSEM under UVB exposure. Tested anti-oxidative compounds also attenuated UVB-induced CL and ameliorated the induced skin damages in terms of 8-OHdG formation and cell death. As a conclusion, this model is useful for not only visualizing the production of UVB-induced ROS in real-time but also evaluating the efficacy of topically applied anti-oxidative compounds to suppress ROS generation and attenuate sequential chemical and biological responses.


Assuntos
Espécies Reativas de Oxigênio , Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , 8-Hidroxi-2'-Desoxiguanosina , Antioxidantes/farmacologia , Desoxiguanosina/análogos & derivados , Desoxiguanosina/biossíntese , Humanos , Medições Luminescentes , Pele/metabolismo
8.
J Biomater Appl ; 22(5): 449-64, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17494957

RESUMO

Newly synthesized vanadyl-poly(gamma-glutamic acid) complex (VO-gamma-PGA) with a VO(O4) coordination mode was found to have potent antidiabetic activity in streptozotocin (STZ)-induced type 1 diabetic mice (STZ-mice), compared with that of a solution containing only vanadyl sulfate, VOSO4. This was the first example of orally active vanadyl complex of gamma-PGA for treating STZ-mice. To better define its efficacy, we examined here the effects of VO-gamma-PGA treatment in STZ-mice by oral administration at the dose of 10 mg V/kg body mass for a longer period time than our previous study. The improvement in diabetic states in STZ-mice compared with saline-treated nondiabetic normal Std ddY mice. It was found that the elevated blood glucose levels in STZ-mice significantly decreased after 3 days and sustained the normalized blood glucose level around 180-200 mg/dL (10-11.1 mM) for the last 14 days, which is close to the blood glucose levels 100-200 mg/dL (5.6-11.1 mM) in nondiabetic normal Std ddY mice. The improvement in diabetes was strongly corelated by the improvement in oral glucose tolerance ability, glycosylated hemoglobin (HbA1c) levels and blood pressure, and serum parameters. The present results confirmed that VO-gamma-PGA complex is a promising, orally active insulin-mimetic agent to treat type 1 diabetic mice.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Ácido Poliglutâmico/uso terapêutico , Vanadatos/uso terapêutico , Administração Oral , Animais , Pressão Sanguínea , Diabetes Mellitus Tipo 1/sangue , Teste de Tolerância a Glucose , Hipoglicemiantes/administração & dosagem , Masculino , Camundongos , Estreptozocina
9.
Chem Biodivers ; 5(8): 1615-1621, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18729096

RESUMO

In the 21st century, there has been a dramatic worldwide increase in the prevalence of metabolic syndromes, including diabetes mellitus (DM). Several synthetic pharmaceutical agents have been developed and used for the treatment of type-2 DM; however, these compounds have several problems such as side effects, hypoglycemia, and weight gain. Therefore, new drugs are required for DM therapy. We have proposed that some vanadyl complexes function as potent insulin-mimetic and antidiabetic agents in type-1 and type-2 DM animal models. In this article, we review the possible action mechanism of insulin-mimetic and antidiabetic vanadyl complexes, focusing on a recently proposed complex, bis(allixinato)oxovanadium(IV), with respect to the insulin-signaling pathway in cultured adipocytes.


Assuntos
Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Hipoglicemiantes/farmacologia , Insulina/química , Compostos Organometálicos/farmacologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Hipoglicemiantes/química , Hipoglicemiantes/metabolismo , Compostos Organometálicos/química , Compostos Organometálicos/metabolismo , Transdução de Sinais/efeitos dos fármacos
10.
Yakugaku Zasshi ; 128(3): 317-22, 2008 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-18311049

RESUMO

The number of patients suffered from diabetes mellitus has increased over the decades probably because of both lifestyle- and diet-changes. There are two types of diabetes mellitus. Type 1 diabetes mellitus is due to the autoimmune-mediated destruction of pancreatic B cells, which results in absolute insulin deficiency, thus the patients require insulin injections. Type 2 diabetes mellitus is due to the insulin resistance and abnormal insulin secretion, thus the patients require exercise, diet control and/or oral hypoglycemic medicines. Each treatment, however, has some problems involving physical and mental burden, and formation of self-antibodies for insulin injections, and the severe side effects and discontinuation of insulin synthesis in the pancreas for hypoglycemic medicines. To overcome these important problems and find the replacements for the insulin injections and synthetic medicines, we attempted to develop new antidiabetic metallocomplexes with novel structures and mechanisms. In 1990, we first presented orally active vanadyl (+4 oxidation state of oxo-vanadium) complexes including vanadyl-cysteine methyl ester complex, which normalized hyperglycemia in the streptozocin (STZ)-induced type 1 diabetic rats. Based on these findings, we have developed a wide variety of vanadyl complexes with different coordination environments around vanadyl ion. Following the study, we also challenged to develop orally active zinc complexes since 2002. This review focuses on our recent development of vanadyl and zinc complexes for anti-diabetic and anti-metabolic syndromes, together with the propose for the possible action mechanism of these complexes in adipocytes.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Desenho de Fármacos , Hipoglicemiantes , Vanadatos , Compostos de Zinco , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Transportador de Glucose Tipo 4/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , Vanadatos/farmacologia , Vanadatos/uso terapêutico , Compostos de Zinco/farmacologia , Compostos de Zinco/uso terapêutico
11.
J Clin Invest ; 110(3): 331-40, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12163452

RESUMO

Nitric oxide (NO) derived from endothelial NO synthase (eNOS) is regarded as a protective factor against atherosclerosis. Therefore, augmentation of eNOS expression or NO production by pharmacological intervention is postulated to inhibit atherosclerosis. We crossed eNOS-overexpressing (eNOS-Tg) mice with atherogenic apoE-deficient (apoE-KO) mice to determine whether eNOS overexpression in the endothelium could inhibit the development of atherosclerosis. After 8 weeks on a high-cholesterol diet, the atherosclerotic lesion areas in the aortic sinus were unexpectedly increased by more than twofold in apoE-KO/eNOS-Tg mice compared with apoE-KO mice. Also, aortic tree lesion areas were approximately 50% larger in apoE-KO/eNOS-Tg mice after 12 weeks on a high-cholesterol diet. Expression of eNOS and NO production in aortas from apoE-KO/eNOS-Tg mice were significantly higher than those in apoE-KO mice. However, eNOS dysfunction, demonstrated by lower NO production relative to eNOS expression and enhanced superoxide production in the endothelium, was observed in apoE-KO/eNOS-Tg mice. Supplementation with tetrahydrobiopterin, an NOS cofactor, reduced the atherosclerotic lesion size in apoE-KO/eNOS-Tg mice to the level comparable to apoE-KO mice, possibly through the improvement of eNOS dysfunction. These data demonstrate that chronic overexpression of eNOS does not inhibit, but accelerates, atherosclerosis under hypercholesterolemia and that eNOS dysfunction appears to play important roles in the progression of atherosclerosis in apoE-KO/eNOS-Tg mice.


Assuntos
Arteriosclerose/patologia , Biopterinas/análogos & derivados , Expressão Gênica , Óxido Nítrico Sintase/genética , Animais , Aorta/enzimologia , Apolipoproteínas E/genética , Biopterinas/metabolismo , Biopterinas/farmacologia , Bovinos , Modelos Animais de Doenças , Feminino , Hemodinâmica , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II , Óxido Nítrico Sintase Tipo III
12.
Free Radic Res ; 41(1): 110-9, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17164184

RESUMO

Polyphenols are widely distributed in various fruits, vegetables and seasonings. It is well known that they have several physiological effects due to their antioxidative activities. Their activities depend on structural characteristics that favour the formation of their corresponding stable radicals. During the examination at which pH values, the polyphenol radicals are stabilized, we confirmed that polyphenol radicals were stabilized in NaHCO3/Na2CO3 buffer (pH 10) rather than in physiological pH region. Then, we measured electron spin resonance (ESR) spectra at pH 10 to examine the characteristics of free radical species derived from caffeic acid (CA) with an unsaturated side chain, dihydrocaffeic acid (DCA) with a saturated side chain, chlorogenic acid (ChA) and rosmarinic acid (RA). In analyzing the radical structures, ESR simulation, determinations of macroscopic and microscopic acid dissociation constants and molecular orbital (MO) calculation were performed. In CA, the monophenolate forms were assumed to participate in the formation of free radical species, while in DCA, the diphenol form and the monophenolate forms were presumed to contribute to the formation of free radical species. On the basis of the results, we propose the possible structures of the free radical species formed from polyphenols under alkaline conditions.


Assuntos
Ácidos Cafeicos/metabolismo , Flavonoides/metabolismo , Radicais Livres/química , Radicais Livres/metabolismo , Fenóis/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Concentração de Íons de Hidrogênio , Polifenóis
13.
Life Sci ; 80(8): 759-66, 2007 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-17137606

RESUMO

In order to find orally active Zn(II) complexes that can treat diabetes mellitus (DM) at low doses, four new Zn(II)-dithiocarbamate complexes with Zn(II)-sulfur coordination bonds were prepared and their in vitro insulinomimetic activity and in vivo anti-diabetic ability were evaluated. Among the Zn(II)-dithiocarbamate complexes, the bis(pyrrolidine-N-dithiocarbamate)zinc(II) (Zn(pdc)(2)) complex was found to be the most effective in terms of inhibiting free fatty acid-release and enhancing glucose-uptake in adipocytes. After oral administration of the Zn(pdc)(2) complex to KK-A(y) mice with obesity and type 2 DM, we observed that the high blood glucose levels in the mice were lowered from approximately 500 mg/dL to 350 mg/dL within 6 days, and the effect was maintained during the administration period. Also, indicators of insulin resistance such as serum insulin, leptin, and triglyceride levels were also reduced compared with those in untreated mice. Moreover, the Zn(pdc)(2) complex improved not only the hypertension in the mice, but also the adiponectin level in the serum. On the basis of the results, the Zn(pdc)(2) complex is proposed to improve hyperglycemia and insulin resistance in type 2 DM animals on daily oral administrations.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Compostos Organometálicos/administração & dosagem , Tiocarbamatos/administração & dosagem , Sulfato de Zinco/administração & dosagem , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adiponectina/sangue , Administração Oral , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , Modelos Animais de Doenças , Glucose/metabolismo , Teste de Tolerância a Glucose , Insulina/sangue , Leptina/sangue , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/genética , Síndrome Metabólica/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Triglicerídeos/sangue
14.
J Inorg Biochem ; 101(4): 692-9, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17316811

RESUMO

Zinc (Zn) is an essential trace element with multiple regulatory functions, involving insulin synthesis, secretion, signaling and glucose transport. Since 2000, we have proposed that Zn complexes with different coordination environments exhibit high insulinomimetic and antidiabetic activities in type 2 diabetic animals. However, the molecular mechanism for the activities is still unsolved. The purpose of this study was to reveal the molecular mechanism of several types of Zn complexes in 3T3-L1 adipocytes, with respect to insulin signaling pathway. Obtained results shows that bis(1-oxy-2-pyridine-thiolato)Zn(II), Zn(opt)2, with S(2)O(2) coordination environment induced most strongly Akt/protein kinase B (Akt/PKB) phosphorylation, in which the optimal phosphorylation was achieved at a concentration of 25 microM, and this Zn(opt)2-induced Akt/PKB phosphorylation was inhibited by wortmannin at 100 nM. Further, the phosphorylation was maximal at 5-10 min stimulation, in agreement with the Zn uptake which was also maximal at 5-10 min stimulation. The Akt/PKB phosphorylation was in concentration- and time-dependent manners. Zn(opt)2 was also capable to translocate GLUT4 protein to the plasma membrane. We conclude that Zn(opt)2 was revealed to exhibit both insulinomimetic and antidiabetic activities by activating insulin signaling cascade through Akt/PKB phosphorylation, which in turn caused the GLUT4 translocation from the cytosol to the plasma membrane.


Assuntos
Adipócitos/efeitos dos fármacos , Insulina/farmacologia , Compostos Organometálicos/farmacologia , Zinco/química , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/metabolismo , Androstadienos/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Relação Dose-Resposta a Droga , Transportador de Glucose Tipo 4/metabolismo , Immunoblotting , Camundongos , Microscopia de Fluorescência , Modelos Biológicos , Compostos Organometálicos/química , Compostos Organometálicos/farmacocinética , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Wortmanina
15.
J Inorg Biochem ; 101(6): 967-75, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17467804

RESUMO

Aluminum (Al) has been proposed as one of the critical environmental factors responsible for several neurodegenerative diseases such as Alzheimer's disease. However, the suggested mechanism involving the contribution of reactive oxygen species still remains controversial. We have first attempted to identify Al compounds either in its ionic or complexed forms that cause oxidative stress in biological systems. For this purpose, we examined the effect of inorganic Fe(2+)- and organic radical initiator (2,2'-azobis (2-amidinopopane) hydrochloride; AAPH)-induced lipid peroxidation by using aluminum (Al(3+)) nitrate and tris(maltolato)aluminum(III) complex (ALM) with respect to molecular oxygen (O(2)) consumption and membrane fluidity change in liposomes as biological membrane models. The following important results were obtained: (1) ALM enhanced the lipid peroxidation induced by Fe(2+) and AAPH in phosphatidylcholine liposomes; this corresponded well with the promotion of O(2) uptake in the same liposomes, (2) Al(3+) increased both lipid peroxidation and O(2) consumption in phosphatidylserine liposomes in the presence of Fe(2+), and (3) both Al(3+) and ALM affected the membrane fluidity on the inner side. It has been concluded that ALM induces higher lipid peroxidation in liposomes than Al(3+); this finding will be useful to gain an insight into the role of Al in cellular damage in relation to oxidative stress.


Assuntos
Compostos de Alumínio/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Lipossomos , Estresse Oxidativo/efeitos dos fármacos , Animais , Bovinos , Espectroscopia de Ressonância de Spin Eletrônica , Fluidez de Membrana , Mitocôndrias/efeitos dos fármacos , Consumo de Oxigênio , Marcadores de Spin
16.
Macromol Biosci ; 7(4): 456-66, 2007 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-17429807

RESUMO

The complexation between cupric ions (Cu(II)) and poly(gamma-glutamic acid) (gamma-PGA) in aqueous solutions (pH 3-11) has been studied by UV-visible absorption and electron spin resonance (ESR) techniques. Formation of the Cu(II)-gamma-PGA complex is confirmed by the observation of the blue shift of the absorption band in the visible region, anisotropic line shapes in the ESR spectrum at room temperature, and a computer simulation of the visible absorption spectrum of the complex. The structure of the Cu(II)-gamma-PGA complex, depending on the pH, has been determined. The in vitro insulin-mimetic activity of the Cu(II)-gamma-PGA complex is examined by determining both inhibition of free fatty acid release and glucose uptake in isolated rat adipocytes treated with epinephrine, in which the concentration of the Cu(II)-gamma-PGA complex for 50% inhibition of free fatty acid release is very similar to that of CuSO4. However, it is significantly lower than that of a previously reported insulin-mimetic bis(3-hydroxypicolinato)copper(II), [Cu(3hpic)2], complex.


Assuntos
Adipócitos/metabolismo , Materiais Biomiméticos/farmacologia , Cobre/farmacologia , Ácidos Graxos/metabolismo , Hipoglicemiantes/farmacologia , Insulina , Ácido Poliglutâmico/análogos & derivados , Adipócitos/citologia , Animais , Materiais Biomiméticos/química , Células Cultivadas , Cobre/química , Sulfato de Cobre/farmacologia , Relação Dose-Resposta a Droga , Concentração de Íons de Hidrogênio , Hipoglicemiantes/química , Masculino , Ácido Poliglutâmico/química , Ácido Poliglutâmico/farmacologia , Ratos , Espectrofotometria Ultravioleta
17.
J Pharm Pharmacol ; 59(3): 437-44, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17331348

RESUMO

Recently, we reported that [meso-tetrakis(4-sulfonatophenyl)porphyrinato]oxovanadium(IV)(4-), VO(tpps), shows in-vitro insulin-mimetic and in-vivo anti-diabetic activity in streptozotocin (STZ)-induced type 1 diabetic mice. This result prompted us to examine its ability in type 2 diabetic model KKA(y) mice with insulin resistance. We studied the in-vivo anti-diabetic activity of VO(tpps), compared with that of vanadium(IV) oxide sulfate, VS, as control. Both compounds were orally administered at doses of 5-10 mg (0.1-0.2 mmol) V/kg body weight to the KKA(y) mice for 28 days. VO(tpps) normalized the hyperglycaemia within 15 days, while VS lowered the blood glucose concentration only by a small degree. In addition, metabolic syndromes characterized by insulin and leptin resistance were significantly improved in VO(tpps)-treated KKA(y) mice compared with those treated with VS. The improvement in diabetes was validated by oral glucose tolerance test and decrease in HbA(1c) concentration. Based on these observations, VO(tpps) is proposed to be an orally active oxovanadium(IV)-porphyrin complex for treating not only type 2 diabetes but also metabolic syndromes in animals.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Metaloporfirinas/uso terapêutico , Animais , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/análise , Hipoglicemiantes/administração & dosagem , Leptina/metabolismo , Masculino , Metaloporfirinas/administração & dosagem , Camundongos
18.
J Trace Elem Med Biol ; 21(1): 43-51, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17317525

RESUMO

Antioxidative activity and polyphenol and trace metal content in bran from ancient rice varieties (red and black rice) and a present-day variety of rice (Koshihikari) were measured. The antioxidative properties of rice bran in terms of scavenging and quenching activity for reactive oxygen species (ROS), including superoxide anion radicals (*O(2)(-)), hydroxyl radicals (*OH), singlet oxygen ((1)O(2)) and lipid peroxide (LOO*), correlated well with polyphenol and trace metal content. In particular, the possibly that Mn content greatly contributes to the antioxidative properties of rice bran was revealed.


Assuntos
Antioxidantes/metabolismo , Metais/química , Oryza/química , Oryza/metabolismo , Flavonoides/química , Oryza/classificação , Fenóis/química , Extratos Vegetais/química , Polifenóis , Espécies Reativas de Oxigênio/química
19.
Biofactors ; 29(4): 213-23, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18057552

RESUMO

The diabetic state is known to induce oxidative stress in its mechanism, which in turn is responsible for the complications of diabetes mellitus (DM). Recently, we found that Zn(II) complexes have in vitro insulinomimetic and in vivo blood glucose-lowering activities. During our study on the development of new Zn(II) complexes with antioxidative ligands involving L-cysteine, L-cysteine-methylester, and N-acetyl-L-cysteine (nac), we found a new (N-acetyl-L-cysteinato)Zn(II) (Zn(nac)) complex by evaluating of both its in vitro insulinomimetic and in vivo potencies. The insulinomimetic activity of Zn(nac) with respect to the inhibition of free fatty acid release in isolated rat adipocytes treated with epinephrine was higher than that of a well-known insulinomimetic VOSO4, being equivalent to that of ZnSO4. The blood glucose level of hyperglycemic KK-Ay mice with type 2 DM was reduced by daily intraperitoneal injections of Zn(nac) for 28 days. Their serum insulin, HbA1c, TCHO, and UN levels were remarkably decreased, indicating that Zn(nac) improved the insulin resistance of the mice. The improvement of DM by Zn(nac) was also confirmed by the oral glucose tolerance test. In conclusion, Zn(nac) complex is proposed to attenuate both hyperglycemia and hyperinsulinemia in KK-Ay mice by decreasing serum insulin, HbA1c, UN, and TCHO levels.


Assuntos
Acetilcisteína/química , Acetilcisteína/farmacologia , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Insulina , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Antioxidantes/farmacologia , Nitrogênio da Ureia Sanguínea , Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Teste de Tolerância a Glucose , Hemoglobinas/efeitos dos fármacos , Hiperglicemia/tratamento farmacológico , Hiperinsulinismo/tratamento farmacológico , Hipoglicemiantes/química , Insulina/sangue , Resistência à Insulina , Masculino , Camundongos , Camundongos Knockout , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Zinco
20.
J Air Waste Manag Assoc ; 57(2): 211-20, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17355082

RESUMO

Because of recent concerns about the health effects of ultrafine particles and the indication that particle toxicity is related to surface area, we have been examining techniques for measuring parameters related to the surface area of fine particles, especially in the 0.003- to 0.5-microm size range. In an earlier study, we suggested that the charge attached to particles, as measured by a prototype of the Electrical Aerosol Detector (EAD, TSI Inc., Model 3070), was related to the 1.16 power of the mobility diameter. An inspection of the pattern of particle deposition in the lung as a function of particle size suggested that the EAD measurement might be a useful indicator of the surface area of particles deposited in the lung. In this study, we calculate the particle surface area (micrometer squared) deposited in the lung per cubic centimeter of air inhaled as a function of particle size using atmospheric particle size distributions measured in Minneapolis, MN, and East St. Louis, IL. The correlations of powers of the mobility diameter, Dx, were highest for X = 1.1-1.6 for the deposited surface area and for X = 1.25 with the EAD signal. This overlap suggested a correspondence between the EAD signal and the deposited surface area. The correlation coefficients of the EAD signal and particle surface area deposited in the alveolar and tracheobronchial regions of the lung for three breathing patterns are in the range of Pearson's r = 0.91-0.95 (coefficient of determination, R2 = 0.82-0.90). These statistical relationships suggest that the EAD could serve as a useful indicator of particle surface area deposited in the lung in exposure and epidemiologic studies of the human health effects of atmospheric particles and as a measure of the potential surface area dose for the characterization of occupational environments.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental/instrumentação , Pulmão/metabolismo , Aerossóis , Difusão , Humanos , Illinois , Minnesota , Modelos Estatísticos , Tamanho da Partícula , Alvéolos Pulmonares/fisiologia , Propriedades de Superfície
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