Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 18 de 18
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Front Oncol ; 9: 993, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31632919

RESUMO

Glioblastoma (GBM) is the most prevalent malignant tumor in the central nervous system. Aerobic glycolysis, featured with elevated glucose consumption and lactate production, confers selective advantages on GBM by utilizing nutrients to support rapid cell proliferation and tumor growth. Pyruvate kinase 2 (PKM2), the last rate-limiting enzyme of glycolysis, is known to regulate aerobic glycolysis, and considered as a novel cancer therapeutic target. Herein, we aim to describe the cellular functions and mechanisms of a small molecular compound dimethylaminomicheliolide (DMAMCL), which has been used in clinical trials for recurrent GBM in Australia. Our results demonstrate that DMAMCL is effective on the inhibition of GBM cell proliferation and colony formation. MCL, the active metabolic form of DMAMCL, selectively binding to monomeric PKM2 and promoting its tetramerization, was also found to improve the pyruvate kinase activity of PKM2 in GBM cells. In addition, non-targeting metabolomics analysis reveals multiple metabolites involved in glycolysis, including lactate and glucose-6-phosphate, are decreased with DMAMCL treatment. The inhibitory effects of DMAMCL are observed to decrease in GBM cells upon PKM2 depletion, further confirming the importance of PKM2 in DMAMCL sensitivity. In conclusion, the activation of PKM2 by DMAMCL results in the rewiring aerobic glycolysis, which consequently suppresses the proliferation of GBM cells. Hence, DMAMCL represents a potential PKM2-targeted therapeutic agent against GBM.

2.
Int J Biol Sci ; 15(10): 2170-2181, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31592097

RESUMO

Hyperproteinemia is a severe metabolic disease characterized by abnormally elevated plasma protein concentrations (PPC). However, there is currently no reliable animal model for PPC, and the pathological mechanism of hyperproteinemia thus remains unclear. In this study, we evaluated the effects of hyperproteinemia on reproductive development in an invertebrate silkworm model with a controllable PPC and no primary disease effects. High PPC inhibited the synthesis of vitellogenin and 30K protein essential for female ovarian development in the fat body of metabolic tissues, and inhibited their transport through the hemolymph to the ovary. High PPC also induced programmed cell death in testis and ovary cells, slowed the development of germ cells, and significantly reduced the reproductive coefficient. Furthermore, the intensities and mechanisms of high-PPC-induced reproductive toxicity differed between sexes in this silkworm model.

3.
J Zhejiang Univ Sci B ; 20(9): 713-727, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379142

RESUMO

Production of reactive oxygen species (ROS) is a conserved immune response primarily mediated by NADPH oxidases (NOXs), also known in plants as respiratory burst oxidase homologs (RBOHs). Most microbe-associated molecular patterns (MAMPs) trigger a very fast and transient ROS burst in plants. However, recently, we found that lipopolysaccharides (LPS), a typical bacterial MAMP, triggered a biphasic ROS burst. In this study, we isolated mutants defective in LPS-triggered biphasic ROS burst (delt) in Arabidopsis, and cloned the DELT1 gene that was shown to encode RBOHD. In the delt1-2 allele, the antepenultimate residue, glutamic acid (E919), at the C-terminus of RBOHD was mutated to lysine (K). E919 is a highly conserved residue in NADPH oxidases, and a mutation of the corresponding residue E568 in human NOX2 has been reported to be one of the causes of chronic granulomatous disease. Consistently, we found that residue E919 was indispensable for RBOHD function in the MAMP-induced ROS burst and stomatal closure. It has been suggested that the mutation of this residue in other NADPH oxidases impairs the protein's stability and complex assembly. However, we found that the E919K mutation did not affect RBOHD protein abundance or the ability of protein association, suggesting that the residue E919 in RBOHD might have a regulatory mechanism different from that of other NOXs. Taken together, our results confirm that the antepenultimate residue E is critical for NADPH oxidases and provide a new insight into the regulatory mechanisms of RBOHD.

4.
J Cell Biochem ; 2018 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-30450651

RESUMO

Endocrine therapy is one of the main treatments for estrogen receptor-positive breast cancers. Tamoxifen is the most commonly used drug for endocrine therapy. However, primary or acquired tamoxifen resistance occurs in a large proportion of breast cancer patients, leading to therapeutic failure. We found that the combination of tamoxifen and ACT001, a nuclear factor-κB (NF-κB) signaling pathway inhibitor, effectively inhibited the proliferation of both tamoxifen-sensitive and tamoxifen-resistant cells. The tamoxifen-resistant cell line MCF7R/LCC9 showed active NF-κB signaling and high apoptosis-related gene transcription, especially for antiapoptotic genes, which could be diminished by treatment with ACT001. These results demonstrate that ACT001 can prevent and reverse tamoxifen resistance by inhibiting NF-κB activation.

5.
Front Physiol ; 9: 302, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29651251

RESUMO

Hyperproteinemia, which is characterized by an abnormally elevated plasma protein concentration (PPC), is a high-mortality, metabolic complication associated with severe liver and kidney disease. It is difficult to clinically distinguish the difference between the impacts of primary diseases and hyperproteinemia on tissues and organs, and there are no available animal models of hyperproteinemia. Here, we constructed an animal model of hyperproteinemia with a controllable PPC and no primary disease effects in the silkworm Bombyx mori that has attracted interest owing to its potential use in the pathological analysis of model animals. Silkworm have an open circulatory system in which each organ is directly immersed in hemolymph. The fat body (FB) of a silkworm, as a major organ for nutrient storage and energy metabolism, can effectively reflect hyperproteinemia-induced metabolic abnormalities in damaged visceral tissues. A pathogenesis study showed that hyperproteinemia attenuated cell autophagy and apoptosis by attenuating an endocrine hormone, thereby preventing FB remodeling during metamorphosis. Meanwhile, hyperproteinemia increased oxidative stress in the FB and resulted in a dysfunction of amino acid conversion. Supplementation with exogenous 20-hydroxyecdysone effectively mitigated the hyperproteinemia-mediated inhibition of FB remodeling.

6.
ACS Appl Mater Interfaces ; 8(40): 26794-26800, 2016 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-27654633

RESUMO

A simple hydrothermal method is developed for synthesizing crystalline MoS2@TiO2 nanohybrids with metal-organic framework (MOF) as precursor. At an optimal ratio of 14.6 wt % MoS2, the resultant material exhibits prominent catalytic activity for hydrogen evolution reaction (HER) with a high hydrogen production rate of 10 046 µmol h-1 g-1 under visible light illumination with fluorescein as photosensitizer. Furthermore, the synthesized catalyst also possesses an attractive electrocatalytic activity with an onset overpotential of -300 mV (vs RHE) and a Tafel slope of ∼81 mV dec-1. The enhanced catalyst performances are mainly attributed to the in situ formed active sites, featuring a uniform dispersion and strong connection of MoS2 and TiO2, which can facilitate electron transfer. In addition, the MoS2@TiO2 nanohybrids are highly stable and completely recyclable over HER.

7.
J Med Chem ; 58(17): 7007-20, 2015 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-26226279

RESUMO

Inspired by the biosynthesis of sesquiterpene lactones (SLs), herein we report the asymmetric total synthesis of the germacrane ring (24). The synthetic strategy features a selective aldol reaction between ß,γ-unsaturated chiral sulfonylamide 15a and aldehyde 13, as well as the intramolecular α-alkylation of sulfone 21 to construct a 10-membered carbocylic ring. The key intermediate 24 can be used to prepare the natural products costunolide and parthenolide (PTL), which are the key precursors for transformation into other SLs. Furthermore, the described synthetic sequences are amenable to the total synthesis of SL analogues, such as trifluoromethylated analogues 32 and 45. Analogues 32 and 45 maintained high activities against a series of cancer cell lines compared to their parent PTL and costunolide, respectively. In addition, 32 showed enhanced tolerance to acidic media compared with PTL. To our surprise, PTL and 32 showed comparable half-lives in rat plasma and in the presence of human liver microsomes.


Assuntos
Antineoplásicos/química , Sesquiterpenos/química , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Flúor , Meia-Vida , Halogenação , Humanos , Microssomos Hepáticos/metabolismo , Ratos , Sesquiterpenos/síntese química , Sesquiterpenos/farmacologia , Estereoisomerismo , Relação Estrutura-Atividade
8.
Asian Pac J Cancer Prev ; 16(7): 2659-64, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25854342

RESUMO

BACKGROUND: To examine the expression of cysteine-rich 61 (Cyr61/CCN1) protein in laryngeal squamous- cell carcinoma (LSCC) tissues, and its relationship with the tumor epithelial-mesenchymal transition (EMT), invasion, metastasis, and prognosis. MATERIALS AND METHODS: Immunohistochemistry was used to detect the expressions of Cyr61, Vimentin (Vim), and E-cadherin (E-cad) in 88 cases of LSCC tissues and 30 cases of tumor-adjacent normal tissues. Vim and E-cad were used as mesenchymal and epithelial markers, respectively, to determine the relationship between Cyr61 expression and the EMT of LSCC cells. In addition, clinical and histopathological data were combined to analyze the relationship between the positive-expression rates of Cyr61, Vim and E-cad and LSCC invasion, metastasis and prognosis. RESULTS: In LSCC tissues, Vim expression rate was significantly higher than that of the tumor-adjacent tissues, whereas E-cad expression rate was significantly lower than that of the tumor-adjacent tissues. The Vim expression rate was significantly higher in stages T3 and T4 than in stages T1 and T2 LSCC tissues, whereas E-cad expression rate was significantly lower in stages T3 and T4 than in stages T1 and T2 LSCC tissues. Compared to the group without lymph node metastasis, the Vim expression rate was significantly higher and the E-cad expression rate was significantly lower in the group with lymph node metastasis. The expression rate of Cyr61 was significantly higher in LSCC tissues than in the tumor-adjacent normal tissues. In addition, the Cyr61 expression rate was higher in stages T3 and T4 than in stages T1 and T2 LSCC, and higher in the group with lymph node metastasis than in the group without lymph node metastasis. The Vim expression rate was significantly higher in the Cyr61 positive group than in the Cyr61 negative group, whereas the E-cad expression rate was significantly higher in the Cyr61 negative group than in the Cyr61 positive group. Survival analysis indicated that survival rates of Cyr61 positive, Vim positive and E-cad negative groups were significantly lower than that of Cyr61 negative, Vim negative and E-cad positive groups, respectively. CONCLUSIONS: Cyr61 expression is closely associated with LSCC invasion and lymph node metastasis. Overexpression of Cyr61 may induce EMT and therefore leads to LSCC invasion and metastasis and poor prognosis. Cyr61 may become a new maker for clinical prediction of LSCC invasion and metastasis and a new target for LSCC treatment.


Assuntos
Carcinoma de Células Escamosas/patologia , Proteína Rica em Cisteína 61/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Caderinas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Imuno-Histoquímica , Laringe/patologia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxa de Sobrevida , Vimentina/metabolismo
9.
Growth Factors ; 33(2): 160-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25798996

RESUMO

Activity and half-life play key roles in the application of GHRH analogues. The GHRH monomers produced in a solid synthesizer were incubated, respectively, in NH4OH solution and lyophilized to obtain their dimers. The activities, specificities, and receptor affinities of the GHRH dimers were evaluated in rGH release/inhibition, rACTH/LH/PRL release, pituitary homogenate binding, and fluorescent staining. Compared to hGHRH(1-44)NH2 (S), PP-hGHRH(1-44)-GGC-CGG-hGHRH(44-1)-PP (2D), P-hGHRH(1-44)-GGC-CGG-hGHRH(44-1)-P (2E), (1)P-hGHRH(2-44)-GGC-CGG-hGHRH(44-2)-(1)P (2F), or hGHRH(1-44)-GGC-CGG-hGHRH(44-1) (2Y) had potency of 104 ± 16.7%, 94 ± 32.6%, 114 ± 16.6%, or 122 ± 14.5% and similar specificities. The inhibition effect of GHIH on rGH stimulated by GHRH dimer was in dose-/time-dependent manner. The staining of FITC-labeled dimer showed cytomembrane distribution and the binding ranking was 2F>2D>2Y>2E>S. 2F presents the strongest activity and the highest affinity to pituitary cells. The dimer with (1)Pro-GHRH stimulates stronger rGH release than that with (1)Tyr-GHRH and the N-terminal single cyclic amino acid is required for the stimulation.


Assuntos
Hormônio Liberador de Hormônio do Crescimento/análogos & derivados , Hormônio Liberador de Hormônio do Crescimento/química , Animais , Membrana Celular/metabolismo , Feminino , Corantes Fluorescentes/química , Hormônio do Crescimento/metabolismo , Hormônio Liberador de Hormônio do Crescimento/síntese química , Hormônios/metabolismo , Humanos , Ligantes , Fragmentos de Peptídeos/química , Hipófise/metabolismo , Ligação Proteica , Multimerização Proteica , Estrutura Terciária de Proteína , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/química
10.
J Psychiatr Res ; 53: 119-24, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24656425

RESUMO

The objective was to evaluate the efficacy and safety of add-on artemether in first-episode, untreated people with schizophrenia, who were Toxoplasma gondii seropositive, and explore the change in T. gondii antibodies during treatment. In this eight-week, double-blind, randomized, placebo-controlled trial, 100 T. gondii seropositive participants with schizophrenia were randomized to either the artemether or placebo group. Participants in the artemether group received 80 mg artemether once per day during the second week (days 8-14) and the fourth week (days 22-28). Participants in the placebo group received identical looking placebo capsules. Psychopathology, adverse side effects and cognitive function were measured using standardized instruments. The group × time interaction effects for the scores of the Positive and Negative Syndrome Scale (PANSS) subscales and performances on all cognitive components were not significant, only the main effect of group was significant. Compared to the placebo group, artemether group participants showed significantly greater reduction in the PANSS negative symptom scale (F(1,46) = 4.7, p = 0.03) and the Clinical Global Impressions Scale (F(1,96) = 6.2, p = 0.01) scores, but there were no significant differences in the PANSS positive symptom and general psychopathology scales (p > 0.05). There were also no significant differences between the two groups in performance on any of the Brief Assessment of Cognition in Schizophrenia (BACS) cognitive domains. The artemether-risperidone combination is safe and well tolerated, but artemether as an adjunct to risperidone does not appear to alleviate cognitive deficits of schizophrenia. Trial Registration Chinese Clinical Trial Register (ChiCTR) TRC-13003145.


Assuntos
Antifúngicos/uso terapêutico , Artemisininas/uso terapêutico , Transtornos Cognitivos/tratamento farmacológico , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia , Toxoplasma/patogenicidade , Adolescente , Adulto , Artemeter , Transtornos Cognitivos/etiologia , Feminino , Seguimentos , Humanos , Masculino , Transtornos Psicóticos/etiologia , Estudos Retrospectivos , Esquizofrenia/sangue , Esquizofrenia/complicações , Esquizofrenia/parasitologia , Estatísticas não Paramétricas , Adulto Jovem
11.
Ying Yong Sheng Tai Xue Bao ; 24(4): 1141-5, 2013 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-23898676

RESUMO

Rodent pests bring great damage to human beings, while rodenticide and sterilant can be used to control the pests. After ingesting sterilant, rodent pests lose their fertility, but in some cases, the sterile individuals may gain their fertility again, produce offspring, and enlarge population size. In this paper, the dynamic models of rodent pest population under lethal control and shortacting contraception control were formulated, and, with the prerequisite of the seasonal breeding of rodent pest population, the models were used to regularly analyze their behaviors and the effects of the contraception rate, lethal rate, control interval, and sterilant valid period on the dynamics of the pest population. The results showed that larger contraception rate and lethal rate and shorter control interval could have better control effect, making the controlled population become smaller and even died out. Short-acting sterilant limited the control effect. At the later period of breeding season, the rodent pest population controlled with short-acting sterilant would have a weak recovery.


Assuntos
Anticoncepção/veterinária , Muridae/crescimento & desenvolvimento , Reprodução/fisiologia , Controle de Roedores/métodos , Animais , Cruzamento , Modelos Teóricos , Muridae/fisiologia , Esterilização Reprodutiva/veterinária
12.
Artigo em Chinês | MEDLINE | ID: mdl-23433212

RESUMO

OBJECTIVE: To clarify the effect of aluminum exposure on the cognitive function in electrolytic workers and the prevalence of mild cognitive impairment (MCI) among them by prevalence survey, and to investigate its influential factors. METHODS: Sixty-six retired workers from the electrolysis workshop of an electrolytic aluminum plant were selected as an aluminum exposure group, while 70 retired workers from a flour mill in the same region were selected as a control group. MCI patients were screened out by Mini-Mental State Examination (MMSE); the blood aluminum level was measured by inductively coupled plasma-mass spectrometry; multivariate statistical analysis was used to investigate the influential factors for MMSE scores and the correlation between blood aluminum level and MCI prevalence. RESULTS: The aluminum exposure group showed a significantly higher blood aluminum level than the control group (25.18 ± 2.65 µg/L vs 9.97 ± 2.83 µg/L, P < 0.01). The total MMSE score of the aluminum exposure group (26.13 ± 2.57) was significantly lower than that of the control group (27.89 ± 1.91) (P < 0.05), particularly the scores on time and place orientation, short-term memory, calculation ability, and language skill (P < 0.05). The detection rate of MCI was significantly higher in the aluminum exposure group (18.2%) than in the control group (5.7%) (P < 0.01). The main influential factors for MMSE scores were gender, age, education level, and blood aluminum level. The logistic regression analysis indicated that the MCI prevalence was significantly correlated with blood aluminum level in the study population (OR = 1.168, P < 0.01). CONCLUSION: Long-term exposure to aluminum can cause cognitive disorders in electrolytic workers and may be one of the risk factors for MCI. Advanced age, male, low education level, and high blood aluminum level may be high-risk factors for cognitive impairment.


Assuntos
Alumínio/efeitos adversos , Cognição/efeitos dos fármacos , Exposição Ocupacional , Idoso , Estudos de Casos e Controles , Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/epidemiologia , Eletrólise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
13.
Gene ; 502(1): 46-52, 2012 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-22546222

RESUMO

Trypsin-like serine protease (TLS) plays an important role in many physiological processes including wound healing, phlogosis reaction, blood clotting, regeneration etc. In this paper, a 1216 bp full-length cDNA sequence of TLS including 39 bp 5' UTR and 355 bp 3'UTR coding for a theoretical 273 amino acids protein was cloned from Apostichopus japonicus by means of the RACE technique for the first time. Bioinformatic analysis revealed that the gene with a 20 residues N-terminal signal peptide and a conserved C-terminal domain belongs to the trypsin-like serine protease superfamily. His78, Asp130 and Ser223 are the principal residues of the catalytic center. In-situ hybridization (ISH) analysis revealed that the TLS gene was widely distributed in different tissues. The expression patterns during different regeneration stages of the TLS gene in the body wall, intestine and respiratory trees were investigated using real-time quantitative PCR. The results show that there was a remarkable and temporary up-regulation of TLS gene expression in the body wall within 1h and subsequent down-regulation of TLS similar to intestine and respiratory trees. With the recovery of tissues, the expression level of the TLS gene was gradually up-regulated and finally reached normal levels. TLS was regulated during different regeneration stages suggesting that TLS is important in the regeneration process of A. japonicus.


Assuntos
Serina Endopeptidases/genética , Stichopus/enzimologia , Stichopus/genética , Cicatrização/genética , Animais , Sequência de Bases , Clonagem Molecular , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Hibridização In Situ , Mucosa Intestinal/citologia , Mucosa Intestinal/enzimologia , Dados de Sequência Molecular , Especificidade de Órgãos , Filogenia , Reação em Cadeia da Polimerase em Tempo Real , Sistema Respiratório/citologia , Sistema Respiratório/enzimologia , Análise de Sequência de DNA , Serina Endopeptidases/metabolismo , Stichopus/fisiologia , Transcrição Genética
14.
Immunol Lett ; 143(2): 137-45, 2012 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-22285695

RESUMO

For the sea cucumber Apostichopus japonicus, a C-type lectin (AJCTL) was identified using rapid amplification of cDNA ends (RACE) PCR techniques. The full-length cDNA of AJCTL is composed of 710bp with a 618bp open reading frame (ORF) that encodes a polypeptide of 205 amino acids with a N-terminal signal peptide and a C-terminal C-type lectin domain (CTLD). The calculated molecular mass of the whole protein is 22.5kDa and its predicted isoelectric point is 5.59. AJCTL belongs to the group VII of regulatory proteins and it might function as a Ca(2+)-dependent monosaccharide binding lectin specifically and recognizing mannose-type ligands. In situ hybridization demonstrated that the expression of AJCTL was located in the body wall, longitudinal muscles, intestinum and respiratory tree. This became apparent especially in the cytoplasm of epidermal cells and granular haemocytes. Real-time PCR data suggested that AJCTL was mostly synthesized in the longitudinal muscles and intestinum and less pronounced in the respiratory tree and body wall of adults. After 12h stimulation by Vibrio harveyi, at increasing bacterial concentration gradient, the expression of AJCTL in sea cucumber increased as well. This indicated that CTL is related to an innate immune response.


Assuntos
Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Stichopus/genética , Stichopus/metabolismo , Sequência de Aminoácidos , Animais , Fenômenos Fisiológicos Bacterianos , Sequência de Bases , Clonagem Molecular , Expressão Gênica , Dados de Sequência Molecular , Especificidade de Órgãos/genética , Filogenia , Alinhamento de Sequência , Stichopus/classificação , Stichopus/microbiologia
15.
Sci Total Environ ; 408(19): 4052-5, 2010 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-20510440

RESUMO

Effects of delta-aminolevulinic acid dehydratase (ALAD) polymorphisms on the renal and neurobehavioral functions were investigated in Chinese workers from a storage battery plant exposed to inorganic lead. Blood and urine were collected from each worker to determine the ALAD genotypes, blood lead levels (PbB), urinary beta2-MG and urinary NAG activity. The World Health Organization Neurobehavioral Core Test Battery (WHO-NCTB) was used. Of the 135 lead workers tested for ALAD genotype, 126 were ALAD1-1, 9 were ALAD1-2 but none were ALAD2-2. The gene frequencies of ALADl-1 and ALADl-2 were 93.33% and 6.67%, respectively. The workers with ALAD1-2 genotype had significantly higher concentrations of PbB (62.52microg/dl vs. 41.02microg/dl), urinary NAG (22.01U/gCr vs. 13.49U/gCr), urinary beta2-MG (194.98microg/gCr vs. 112.88microg/gCr), and digit span backward (DSB) score (6.67 vs. 5.33) than those of ALAD1-1 genotype. Urinary NAG of ALAD1-2 genotype carriers was significantly higher than that of ALAD1-1 genotype under the same blood lead level (b(i) 0.75 vs. b(i) 0.29). Interaction between PbB and ALAD genotypes has a significant influence on NAG (P=0.02) and beta(2)-MG (P=0.01). It is postulated that the workers with the ALAD2 allele appear to be more susceptible to the effects of lead on renal injury, whereas neurobehavioral functions in ALAD1 homozygote tend to be more vulnerable.


Assuntos
Nefropatias/induzido quimicamente , Intoxicação do Sistema Nervoso por Chumbo em Adultos/genética , Chumbo/toxicidade , Exposição Ocupacional/estatística & dados numéricos , Polimorfismo de Nucleotídeo Único , Sintase do Porfobilinogênio/genética , Adulto , China/epidemiologia , Feminino , Frequência do Gene , Humanos , Rim , Nefropatias/epidemiologia , Nefropatias/genética , Chumbo/sangue , Chumbo/urina , Intoxicação do Sistema Nervoso por Chumbo em Adultos/epidemiologia , Masculino , Adulto Jovem
17.
Artigo em Chinês | MEDLINE | ID: mdl-18761791

RESUMO

OBJECTIVE: To study the role of lipid peroxidation injury and endoplasmic reticulum stress in Al-induced apoptosis. METHODS: Neurons from 0-3 day rats were cultured and treated with different concentrations of AlCl3.6H2O. Morphologic changes of neurons and endoplasmic reticulum were observed under fluorescent and transmission electron microscope; activities of superoxide dismutase (SOD), malondialdehyde (MDA) and ATP enzymes were detected. RESULTS: Typical morphologic changes in neurons apoptosis and endoplasmic reticulum were found under fluorescent and transmission electron microscope; SOD enzyme viability and ATP enzyme viability were significantly increased in the low-dosage group, but reduced in mid and high-dosage group (P < 0.01), whereas MDA levels decreased in the low-dosage group, but increased in mid and high-dosage group (P < 0.01). CONCLUSION: Aluminum may induce neurons apoptosis, and lipid peroxidation injury in endoplasmic reticulum plays an important role in the apoptosis progression.


Assuntos
Alumínio/toxicidade , Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/fisiologia , Peroxidação de Lipídeos/fisiologia , Neurônios/patologia , Animais , Células Cultivadas , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley
18.
Zhonghua Xin Xue Guan Bing Za Zhi ; 33(10): 885-8, 2005 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-16266472

RESUMO

OBJECTIVES: The purpose of this study was to evaluate the effects of the angiotensin-converting enzyme (ACE) inhibitor enalapril and diuretic indapamide on the peripheral blood pressure and the central blood pressure in Chinese patients with essential hypertension. METHODS: This study was a double blind, randomized study. Informed consent were given by all patients. After 2 weeks of placebo run-in period, 105 patients with mild or moderate essential hypertension were randomized to receive either enalapril (10 mg per day) or indapamide (2.5 mg per day) for 8 weeks. Radial pulse wave recordings were performed in all the patients before the active treatments were given and at the end of the study. Only those patients who have finished 8 weeks of active treatment in both groups were included into the final analysis. RESULTS: One hundred one patients (51 in enalapril group and 50 in indapamide group) completed the study. No significant difference (all P values > 0.05) was found in baseline data between the two groups. After 8 weeks of treatment, all the parameters of pulse wave (except heart rates in both groups and augmentation index in indapamide group) decreased significantly. Comparison of the 2 groups showed that there were no significant differences (all P values > 0.05) in all the parameters of pulse wave except that the central systolic blood pressure, augmentation and augmentation index were significantly lower in enalapril group than in indapamide group. In enalapril group, the reduced values of systolic blood pressure and pulse pressure in central aorta were significantly larger than those in brachial artery. However, the difference was not observed in indapamide group. CONCLUSIONS: Enalapril and indapamide are both similarly effective in reducing peripheral arterial blood pressure. Moreover, enalapril is more effective in reducing central systolic pressure and augmentation index than indapamide. The difference is probably due to the reduction of wave reflection caused by enalapril.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Enalapril/uso terapêutico , Hipertensão/fisiopatologia , Indapamida/uso terapêutico , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA