RESUMO
PURPOSE: It has been demonstrated that variation in thyroid hormone levels even within normal range was associated with increased cardiovascular risk. However, available data are still insufficient on association between left ventricular hypertrophy (LVH) and thyroid hormone levels within euthyroid state. METHODS: In 69,298 Koreans with euthyroid function, we evaluated association between echocardiographically detected LVH and thyroid hormone levels within the normal range. Study participants were categorized into elderly (age ≥ 40) and younger (age < 40) groups, where subjects were divided into four groups according to quartile levels of thyroxine (FT4), triiodothyronine (FT3), and thyroid-stimulating hormone (TSH). Multivariable adjusted logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence interval (CI) for LVH (adjusted ORs [95% CI]) across quartile levels of thyroid hormones. RESULTS: In elderly group, adjusted ORs for LVH generally higher in the first quartile group than other quartile groups, despite no statistical significance in some cases (first quartile: reference, second quartile: 0.86 [0.67-1.11] in TSH, 0.75 [0.58-0.95] in FT4 and 0.63 [0.49-0.81] in FT3, third quartile: 0.70 [0.54-0.92] in TSH, 0.79 [0.61-1.02] in FT4 and 0.72 [0.55-0.93] in FT3, fourth quartile: 0.81 [0.65-1.04] in TSH, 0.85 [0.65-1.10] in FT4 and 0.58 [0.44-0.77] in FT3). This finding was similarly found in the younger group, despite discrepancy in some cases. CONCLUSION: In euthyroid state, low normal levels in FT4, FT3 and TSH were more strongly associated with LVH.
Assuntos
Biomarcadores/sangue , Hipertrofia Ventricular Esquerda/epidemiologia , Glândula Tireoide/fisiopatologia , Hormônios Tireóideos/sangue , Adulto , Feminino , Seguimentos , Humanos , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Testes de Função TireóideaRESUMO
PURPOSE: The influence of the dipeptidyl peptidase-IV inhibitor gemigliptin alone or in combination with the histone deacetylase inhibitor PXD101 on survival of thyroid carcinoma cells was investigated. METHODS: SW1736, TPC-1, 8505C and BCPAP human thyroid carcinoma cells were used. To assess cell survival, cell viability, the percentage of viable cells and dead cells, cytotoxic activity, ATP levels and FACS analysis were measured. To validate the impact of gemigliptin combined with PXD101, the interactions were estimated by obtaining combination index in cells treated with two agents. RESULTS: In cells treated with gemigliptin or PXD101, cell viability, the percentage of viable cells and ATP levels were reduced, and the percentage of dead cells and cytotoxic activity were elevated. In cells treated with both gemigliptin and PXD101, compared with PXD101 alone, cell death was augmented, and all of the combination index values were lower than 1.0, suggesting the synergism between gemigliptin and PXD101. The percentage of apoptotic cells, and the protein levels of Bcl2 and cleaved poly (ADP-ribose) polymerase were elevated, and the protein levels of xIAP and survivin were reduced. The protein levels of phospho-Akt and phospho-AMPK were elevated, and cell migration was reduced. CONCLUSIONS: Our results demonstrate that gemigliptin induces cytotoxicity in thyroid carcinoma cells. Moreover, gemigliptin has a synergistic activity with PXD101 in the induction of cell death through involvement of Bcl2 family proteins, xIAP and survivin as well as mediation of Akt and AMPK in thyroid carcinoma cells.
Assuntos
Biomarcadores Tumorais/metabolismo , Inibidores da Dipeptidil Peptidase IV/farmacologia , Sinergismo Farmacológico , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Piperidonas/farmacologia , Pirimidinas/farmacologia , Sulfonamidas/farmacologia , Neoplasias da Glândula Tireoide/patologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular , Humanos , Transdução de Sinais , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/metabolismo , Células Tumorais CultivadasRESUMO
AIMS: In this study, we compared the glucose-lowering effectiveness of insulin analogues and their combination according to baseline glycemic status in patients with type 2 diabetes (T2D) from the A1 chieve(®) study conducted in Korea. METHODS: This sub-analysis from the A1 chieve(®) study was a 24-week prospective, multicenter, non-interventional, open-labelled study. Of the 4058 patients, 3074 patients who had their HbA1c level measured at baseline were included in this sub-analysis. We classified patients into three groups according to baseline HbA1c levels: group I (HbA1c < 7.5%), group II (7.5% ≤ HbA1c < 9.0%) and group III (HbA1c ≥ 9.0%). RESULTS: Patients in group I showed no significant HbA1c reduction with any insulin regimens (detemir, aspart, detemir and aspart or biphasic aspart 30 (Novo Nordisk A/S, DK-2880 Bagsvaerd, Denmark) after 24 weeks of treatment. In group II, although HbA1c was decreased for all insulin regimens, there was no difference in mean HbA1c reduction among the four insulin regimens. In patients with a high baseline HbA1c level (group III), mean HbA1c reduction was the greatest in patients on a basal-bolus regimen (detemir and aspart, -3.50%) and lowest in patients on a bolus regimen (aspart, -1.81%; p < 0.001). CONCLUSION: For optimal glycaemic control, a basal-bolus regimen may be adequate for Korean patients with poorly controlled T2D (HbA1c ≥ 9.0%).
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/análogos & derivados , Adulto , Idoso , Feminino , Hemoglobinas Glicadas/análise , Humanos , Insulina/uso terapêutico , Insulina Aspart/uso terapêutico , Insulina Detemir/uso terapêutico , Insulina Glargina/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
SU5416, vascular endothelial cell growth factor receptor inhibitor, suppresses hypoxia-induced angiogenesis, growth, proliferation, and metastasis in cancer cells. CCAAT/enhancer-binding protein-homologous protein (CHOP) has pivotal roles in regulation of growth and survival. In the present study, we evaluated the effects of SU5416 on cell survival, p21, and PI3K/Akt signal pathway in FRO anaplastic thyroid carcinoma (ATC) cells. Moreover, we investigated the roles of CHOP in cell survival under condition of SU5416 treatment in FRO ATC cells. After SU5416 treatment, cell viability, PARP-1, and caspase-3 protein levels were not changed. p53 and p27 protein levels decreased while p21 protein levels increased. Phospho-Akt protein levels were not altered. In SU5416-treated situation, cell viability was not different before and after administration of either p21 siRNA or LY294002 whereas it was lessened after co-administration of p21 siRNA and LY294002. Compared to SU5416 treatment alone, cell viability was reduced with CHOP plasmid but it was unchanged with CHOP siRNA. PARP-1 and caspase-3 protein levels with CHOP plasmid were elevated whereas the protein levels with CHOP siRNA were similar. While CHOP plasmid transfection diminished p21 and phospho-Akt protein levels, CHOP siRNA transfection did not alter the protein levels. In conclusion, these results suggest that CHOP may sensitize FRO ATC cells to SU5416 thereby inhibiting cell survival by modulating p21 and PI3K/Akt signal pathway. Furthermore, these findings imply that CHOP may be a possible candidate as the chemosensitizing factor for induction of cytotoxicity in ATC cells exposed to SU5416.
Assuntos
Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Indóis/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirróis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/patologia , Fator de Transcrição CHOP/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Regulação para Baixo/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Técnicas de Silenciamento de Genes , Humanos , Carcinoma Anaplásico da Tireoide , Proteína Supressora de Tumor p53/metabolismoRESUMO
SU6656 is a small-molecule indolinone that selectively inhibits Src family kinase and induces death of cancer cells. The aim of the present study was to investigate the influence of SU6656 on cell survival and to assess the role of p21 and PI3K/Akt signaling in cell survival resulting from SU6656 treatment in anaplastic thyroid carcinoma (ATC) cells. When 8505C, CAL62, and FRO ATC cells were treated with SU6656, the viability of 8505C and CAL62 ATC cells decreased only after treatment with SU6656 at a dosage of 100 µM for 72 h, while the viability of FRO ATC cells decreased after treatment with SU6656 in a concentration- and time-dependent manner. Cell viability was not changed by pretreatment with the broad-spectrum caspase inhibitor z-VAD-fmk. Phospho-Src protein levels were reduced, and p21 protein levels were elevated. Phospho-ERK1/2 protein levels were multiplied without alteration of total ERK1/2, total Akt, and phospho-Akt protein levels. Regarding FRO ATC cells, the decrement of cell viability, the increment of cleaved PARP-1 protein levels, and the decrement of phospho-Src protein levels were shown in p21 siRNA- or LY294002-pretreated cells compared to SU6656-treated control cells. ERK1/2 siRNA transfection did not affect cell viability and protein levels of cleaved PARP-1, p21, and Akt. In conclusion, these results suggest that SU6656 induces caspase-independent death of FRO ATC cells by overcoming the resistance mechanism involving p21 and Akt. Suppression of p21 and Akt enhances the cytotoxic effect of SU6656 in FRO ATC cells.
Assuntos
Apoptose/efeitos dos fármacos , Caspases/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Indóis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sulfonamidas/farmacologia , Neoplasias da Glândula Tireoide/fisiopatologia , Caspases/genética , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismoRESUMO
Aim of the present study was to evaluate the effect of apigenin in combination with BRAFV600E inhibitor PLX4032 on cell survival, and to investigate the influence of Akt inhibition on the combined effect of apigenin and PLX4032 in ATC cells harboring BRAFV600E. In 8505C and FRO cells harboring BRAFV600E, after treatment of apigenin and PLX4032, the cell viability decreased, and the percentage of dead cells increased in a time- and concentration-dependent manner, respectively. In apigenin- and PLX4032- treated cells, compared with apigenin alone-treated cells, the cell viability was lessened, and the percentage of dead cells was multiplied. In the addition of PLX4032 to apigenin, compared with the treatment of apigenin alone, the protein levels of cleaved PARP-1 and cleaved caspase-3 were elevated, and phospho-ERK protein levels were reduced, and the protein levels of total ERK, c-Myc, BRAF, phospho-Akt, phospho-p70S6K and phospho-4EBP1 were not varied. Compared with the treatment of PLX4032 alone, phosphop70S6K protein levels were reduced, and the other protein levels were not altered. Phospho-ERK protein levels were reduced only in 8505C cells. Under the co-treatment of apigenin and PLX4032, administration of the PI3K inhibitor wortmannin further decreased the cell viability, and increased the percentage of dead cells. In conclusion, our results suggest that PLX4032 augments apigenin-induced cytotoxicity in ATC cells harboring BRAFV600E. Moreover, Akt suppression potentiates the combined effect of apigenin and PLX4032 in ATC cells harboring BRAFV600E.
Assuntos
Apigenina/farmacologia , Indóis/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Sulfonamidas/farmacologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Androstadienos/farmacologia , Apigenina/uso terapêutico , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/metabolismo , Carcinoma Anaplásico da Tireoide , Vemurafenib , WortmaninaRESUMO
In thyroid cells, the effects of all- TRANS retinoic acid (ATRA) on sodium/iodide symporter (NIS) and CCAAT/enhancer-binding protein-homologous protein (CHOP) under condition of endoplasmic reticulum (ER) stress have not been evaluated. In the present study, the relationships between NIS, CHOP, and p38 MAPK, and the effects of ATRA on NIS and CHOP expression as well as on p38 MAPK activation under condition of ER stress in thyroid cells were investigated. In FRTL5 thyroid cells, NIS mRNA and protein levels decreased following tunicamycin (TN) treatment, while CHOP mRNA and protein levels increased. In addition, while CHOP mRNA levels decreased after administration of tauro-UDCA and siCHOP, NIS mRNA levels were not altered. After pretreatment with SB203580, NIS mRNA levels decreased in non-TN-treated cells but increased in TN-treated cells. In contrast, CHOP mRNA levels decreased in both non-TN-treated and TN-treated cells. Exposure to ATRA decreased NIS mRNA levels in non-TN-treated cells but increased NIS mRNA levels in TN-treated cells. ATRA decreased CHOP mRNA levels in both non-TN-treated and TN-treated cells although the response was significant only in TN-treated cells. Phospho-p38 MAPK protein levels but not total p38 MAPK protein levels increased in TN-treated cells. ATRA attenuated this increase in phopho-p38 MAPK protein levels. In conclusion, our results demonstrate that ER stress may induce reciprocal changes in NIS and CHOP expression via p38 MAPK in FRTL5 thyroid cells, and that ATRA may attenuate ER stress-induced alterations in NIS and CHOP expression by modulating the phosphorylation of p38 MAPK in FRTL5 thyroid cells.
Assuntos
Retículo Endoplasmático/metabolismo , Simportadores/metabolismo , Glândula Tireoide/metabolismo , Fator de Transcrição CHOP/metabolismo , Animais , Linhagem Celular , Retículo Endoplasmático/genética , Ratos , Simportadores/genética , Fator de Transcrição CHOP/genética , Tretinoína , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Alpha-lipoic acid (ALA) has been shown to modulate cell death via PI3K/Akt signal pathway in various cells. In the present study, the effects of ALA on cell death and PI3K/Akt signal pathway linked to cell death-related proteins during endoplasmic reticulum (ER) stress in FRTL5 thyroid cells were evaluated. In FRTL5 thyroid cells, cell viability increased by ALA pretreatment in tunicamycin (TN)-treated cells. When TN was treated, CCAAT/enhancer-binding protein-homologous protein (CHOP) and Bax protein levels were elevated while Bcl-2 protein levels were reduced. ALA diminished CHOP and Bax protein levels, and augmented Bcl-2 protein levels in TN-treated cells. After exposure to TN, phospho-Akt protein levels were repressed whereas total Akt protein levels were not changed. ALA increased phospho-Akt protein levels but not total Akt protein levels in both non-TN-treated and TN-treated cells. After LY294002 administration in non-TN-treated cells, cell viability was reduced, and CHOP and Bax protein levels were elevated, and Bcl-2 protein levels were reduced. The CHOP, Bcl-2 and Bax protein levels were not different after LY294002 administration in TN-treated cells. LY294002 and wortmannin decreased cell viability, and increased CHOP and Bax protein levels, and decreased Bcl-2 protein levels in ALA-pretreated and TN-treated cells. In conclusion, these results suggest that ER stress may induce cell death by modulating PI3K/Akt signal pathway linked to cell death-related proteins in FRTL5 thyroid cells. Moreover, these findings imply that ALA may ameliorate ER stress-induced cell death by activating PI3K/Akt signal pathway and attenuating changes of cell death-related proteins in FRTL5 thyroid cells.
Assuntos
Retículo Endoplasmático/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Ácido Tióctico/farmacologia , Glândula Tireoide/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular , Retículo Endoplasmático/metabolismo , Retículo Endoplasmático/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Fator de Transcrição CHOP/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
AIM: To evaluate the efficacy and safety of a newly developed formulation of phentermine diffuse-controlled release (DCR) in patients with obesity. METHODS: This was a randomized, double-blind, placebo-controlled trial of 12 weeks of treatment with phentermine DCR 30 mg (n = 37) or placebo (n = 37), administered once daily in patients with obesity with controlled diabetes, hypertension or dyslipidaemia. The efficacy was evaluated by changes in body weight and waist circumference from baseline at 12 weeks and also changes in metabolic parameters, including lipid profiles and blood pressure. RESULTS: The participants in the phentermine DCR group showed significant reductions in body weight (-8.1 ± 3.9 vs. -1.7 ± 2.9 kg, p < 0.001) and waist circumference (7.2 ± 0.5 vs. 2.1 ± 0.6 cm, p < 0.001) compared with those in the placebo group. Weight reductions of 5% or greater from the baseline (95.8 vs. 20.8%, p < 0.001) and 10% or more (62.5 vs. 4.7%, p < 0.001) were achieved in the DCR phentermine group and placebo group, respectively. Total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels were significantly improved in the phentermine DCR group. However, there were no significant differences in systolic and diastolic blood pressure between the groups. Dry mouth and insomnia were the most common adverse events, but these were mild to moderate and transient. CONCLUSIONS: Short-term phentermine DCR treatment resulted in significant reduction in weight and improvement of metabolic parameters, including waist circumference and some lipid profiles, without clinically severe adverse events. Further study is needed to show long-term efficacy and safety of phentermine DCR in Korean patients with obesity.
Assuntos
Depressores do Apetite/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Angiopatias Diabéticas/prevenção & controle , Dislipidemias/tratamento farmacológico , Obesidade/tratamento farmacológico , Fentermina/uso terapêutico , Redução de Peso/efeitos dos fármacos , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Obesidade/complicações , Resultado do TratamentoRESUMO
BACKGROUND: In general, there is a response time between actual arterial hypoxemia and its detection by pulse oximeters. We compared the desaturation and resaturation response times between two types of pulse oximeters, transmission and reflectance pulse oximeters, to find out which oximeter has a more rapid response time. METHODS: Thirty-three ASA 1 or 2 patients were enrolled in this study. A transmission pulse oximeter was placed on the index finger and a reflectance pulse oximeter was placed on the forehead and monitored simultaneously. After the induction of general anesthesia without pre-oxygenation, we waited until the oxygen saturation value of any of two pulse oximeters declined to 90%, and then mask ventilation was started with 100% oxygen. Oxygen saturation was recorded at an interval of 2 s during this time. RESULTS: The desaturation response time of SpO(2) to 95% after apnea was 82.0 s (interquartile range: 67.0-98.5 s) vs. 94.0 s (interquartile range: 84.0-106.5 s) (P<0.001) and SpO(2) to 90% was 94.0 s (interquartile range: 75.5-109.5 s) vs. 100.0 s (interquartile range: 84.5-114.5 s) (P<0.001) in the reflectance and transmission oximeters, respectively. The resaturation response time from mask ventilation to 100% SpO(2) was 23.2+/-5.6 vs. 28.9+/-7.6 s (P<0.001) in the reflectance and transmission oximeters, respectively. CONCLUSION: In clinical situations in which rapid changes in oxygen saturation are expected, we recommend the forehead reflectance pulse oximeter because it responds more quickly in detecting oxygen desaturation and resaturation compared with the transmission pulse oximeter.
Assuntos
Oximetria/instrumentação , Oxigênio/sangue , Adulto , Androstanóis/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Apneia/sangue , Mama/cirurgia , Desenho de Equipamento , Feminino , Fentanila/administração & dosagem , Dedos/irrigação sanguínea , Testa/irrigação sanguínea , Humanos , Hipóxia/sangue , Pessoa de Meia-Idade , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Propofol/administração & dosagem , Respiração Artificial , Rocurônio , Tireoidectomia , Fatores de Tempo , Adulto JovemRESUMO
AIMS: Escherichia coli and Bacillus subtilis spores were treated with an atmospheric plasma mixture created by the ionization of helium and oxygen to investigate the inactivation efficiency of a low-temperature plasma below 70 degrees C. METHODS AND RESULTS: An electrical discharge plasma was produced at a radio frequency (RF) of 13.56 MHz, connected to a perforated circular electrode with a discharge spacing of 1-15 mm. The discharge gas was helium with 0-2% oxygen. For the plasma treatment, a dried E. coli cell or B. subtilis endospore suspension on a cover-glass was exposed to oxygen downstream of the plasma from holes in an RF-powered electrode. The sterilization effect of the RF plasma was highest with 0.2% oxygen, corresponding to the maximum production of oxygen radicals. CONCLUSIONS: Oxygen radicals generated by RF plasma are effective for the destruction of bacterial cells and endospores. SIGNIFICANCE AND IMPACT OF THE STUDY: Low-temperature atmospheric plasma can be used for the disinfection of diverse objects, especially for the inactivation of bacterial endospores.
Assuntos
Ionização do Ar , Microbiologia do Ar , Bacillus subtilis/crescimento & desenvolvimento , Escherichia coli/crescimento & desenvolvimento , Viabilidade Microbiana , Esterilização/métodos , Antibacterianos/farmacologia , Contagem de Colônia Microbiana , Eletricidade , Espécies Reativas de Oxigênio/farmacologiaRESUMO
To decipher the mechanistic roles of Mediator proteins in regulating developmental specific gene expression and compare them to those of TATA-binding protein (TBP)-associated factors (TAFs), we isolated and analyzed a multiprotein complex containing Drosophila Mediator (dMediator) homologs. dMediator interacts with several sequence-specific transcription factors and basal transcription machinery and is critical for activated transcription in response to diverse transcriptional activators. The requirement for dMediator did not depend on a specific core promoter organization. By contrast, TAFs are preferentially utilized by promoters having a specific core element organization. Therefore, Mediator proteins are suggested to act as a pivotal coactivator that integrates promoter-specific activation signals to the basal transcription machinery.
Assuntos
Drosophila/genética , Proteínas de Insetos/genética , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/genética , Sequência de Aminoácidos , Animais , Regulação da Expressão Gênica , Dados de Sequência Molecular , Homologia de Sequência de AminoácidosRESUMO
To determine the prevalence of Bartonella species and identify which species of Bartonella naturally infects the striped field mouse (Apodemus agrarius) in the Republic of Korea (ROK), spleens from 200 mice were assayed by nested polymerase chain reaction (nPCR) targeting the RNA polymerase subunit beta (rpoB) gene and the 16S-23S internal transcribed spacer (ITS) region for members of the genus Bartonella. Utilizing PCR techniques, the prevalence of Bartonella spp. ranged from 31.5% (63/200) to 62.0% (124/200) for the rpoB and ITS gene fragments, respectively. The most prevalent species, Bartonella grahamii, was assigned to 17 genotypes and closely related to the zoonotic pathogens, B. taylorii, B. tribocorum, B. phoceensis and B. henselae, which also were detected. Two Bartonella isolates (KRBG28 and KRBG32) were recovered from blood of A. agrarius captured in Gyeonggi Province, ROK. Comparison of the 16S rRNA, hemin-binding protein E (hbpE), glutamate dehydrogenase 1 (gdh1), invasion-associated protein B (ialB), cell division protein (ftsZ), citrate synthase (gltA), 60 kDa heat shock protein (groEL), rpoB gene fragments and the ITS region sequences from the isolates with GenBank was confirmed as B. grahamii. Phylogenetic analysis based on the alignment of concatenated sequences (4933 bp) of KRBG28 and KRBG32 clustered with B. grahamii, forming an independent clade between Asian and American/European B. grahamii genogroups.
Assuntos
Infecções por Bartonella/microbiologia , Bartonella/isolamento & purificação , Camundongos/microbiologia , Animais , Bartonella/classificação , Bartonella/genética , Primers do DNA/genética , Genótipo , Filogenia , Reação em Cadeia da Polimerase/métodos , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Baço/microbiologiaRESUMO
Daily repeated administration of cocaine (15 mg/kg, over a 7-day period) developed reverse tolerance to the ambulation-accelerating effect of cocaine. Intraperitoneal administration of ginseng total saponin (GTS, 100 and 200 mg/kg of body weight) prior to and during chronic administration of cocaine inhibited the development of reverse tolerance. Dopamine receptor supersensitivity was also developed in reverse tolerant mice that had received the same cocaine. The development of dopamine receptor supersensitivity was evidenced by the enhanced hypothermic response to apomorphine (1 mg/kg) and the enhanced ambulatory activity of apomorphine (4 mg/kg). GTS also prevented the development of dopamine receptor supersensitivity induced by the chronic administration of cocaine. These results provide that GTS may be useful for the prevention and therapy of the adverse action of cocaine. It is concluded that the development of reverse tolerance to the ambulation-accelerating effect of cocaine may be associated with the enhanced dopamine receptor sensitivity because both phenomena were blocked by GTS.
Assuntos
Cocaína/antagonistas & inibidores , Panax , Plantas Medicinais , Receptores Dopaminérgicos/efeitos dos fármacos , Saponinas/farmacologia , Animais , Cocaína/farmacologia , Relação Dose-Resposta a Droga , Tolerância a Medicamentos , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Atividade Motora/efeitos dos fármacosRESUMO
An antifungal bacterial strain, isolated from a greenhouse soil sample, inhibits growth of microflora nearby. It was selected for further studies of bacterial antifungal properties. This isolate was identified as a Pseudomonas sp. based on carbohydrate utilization, and other biochemical and physiological tests. Petri plate assay revealed that the Pseudomonas sp. exhibited antifungal activity against the plant pathogens, Pythium ultimum, Rhizoctonia solani, Phytophthora capsici, Botrytis cinerea and Fusarium oxysporum. Using direct inhibition bioassay on TLC plates after ethyl acetate extraction of the culture filtrate, we correlated antifungal activity with production of antifungal compounds. An antifungal antibiotic was isolated from the culture filtrate and was identified as N-butylbenzenesulphonamide. ED50, values of the N-butylbenzenesulphonamide against P. ultimum, P. capsici, R. solani, and B. cinerea were 73, 41, 33 and 102 ppm, respectively.
Assuntos
Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Pseudomonas/metabolismo , Sulfonamidas/isolamento & purificação , Sulfonamidas/farmacologia , Antifúngicos/química , Fusarium/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Estrutura Molecular , Plantas/microbiologia , Pseudomonas/química , Pseudomonas/classificação , Pythium/efeitos dos fármacos , Rhizoctonia/efeitos dos fármacos , Sulfonamidas/químicaRESUMO
It has been suggested that glucose metabolites and insulin are the most important factors inducing ATP-citrate lyase (ACL) by a high carbohydrate diet. We have used a primary culture of rat hepatocytes to confirm the role of glucose and insulin in terms of ACL gene expression. The results showed that glucose displayed a direct effect on ACL gene expression and the insulin helps the glucose effect. The nucleotide sequences from -512 to -485 of the ACL promoter are highly homologous (70%) to the sequences surrounding the carbohydrate response element (ChoRE) of the S14 gene. The gel retardation analysis using ChoRE of the S14 gene showed that the ACL promoter which contains the ChoRE-like sequence specifically inhibited the formation of the complex by the nuclear proteins isolated from rat liver. To localize the regions which are involved in the regulation of ACL gene expression, transient expression assay using ACL promoter-CAT (chloramphenicol acetyltransferase) constructs containing various lengths of a 5' flanking region of the ACL gene were carried out. The proximal promoter region -419 to -1 containing several potential Sp1 binding sites showed the strong enhancing effect, which increases the transcription of CAT genes in the various cell lines, such as the CHO (Chinese hamster ovary) cell, the HepG2 cell, and primary cultured rat hepatocytes. In response to glucose, among the ACL promoter-CAT constructs, only pNP33-CAT (-1342 to -1) showed a 2.64 fold increase in CAT activity by a high concentration of glucose. The activation of ACL gene expression by glucose seems to be regulated in a complicated manner involving interactions between the contexts of the several sequence elements and various transacting factors, which is not a simple mechanism directed only by a short sequence element.
Assuntos
ATP Citrato (pro-S)-Liase/genética , Regulação Enzimológica da Expressão Gênica , Animais , Sequência de Bases , Células CHO , Células Cultivadas , Cricetinae , Feminino , Glucose/farmacologia , Fígado/citologia , Fígado/enzimologia , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Ratos , Transcrição GênicaRESUMO
Subirrigation systems are increasingly used to water and fertilize greenhouse crops. They also appear to be well suited for the application of systemic pesticides. We conducted two studies to look at interactive effects ofimidacloprid application technique and irrigation method on plant uptake of imidacloprid and whitefly control. Drench applications of imidacloprid resulted in much higher concentrations in the leaves than applications to the bottom of pots after 14 d. However, imidacloprid efficacy in subirrigated plants was better if the imidacloprid was applied to the bottom of the pot than when an equal amount was applied as a drench. In drip-irrigated plants, imidacloprid efficacy was greater after a drench than after an application to the bottom of the pots. A second study showed that drench applications to drip-irrigated plants result in high imidacloprid concentrations in the bottom of the canopy, whereas bottom applications to subirrigated plants result in a more even distribution of imidacloprid throughout the plant. Surprisingly, the high leaf imidacloprid concentrations in the bottom layer of drip-irrigated plants did not result in improved whitefly control. Imidacloprid efficacy was better in subirrigated, bottom-treated plants than in drip-irrigated, drenched plants. Overall, results from these studies indicate that imidacloprid is very effective when applied to the bottom of subirrigated pots.
Assuntos
Agricultura/métodos , Hemípteros/fisiologia , Imidazóis , Controle de Insetos/métodos , Inseticidas , Animais , Imidazóis/metabolismo , Inseticidas/metabolismo , Neonicotinoides , Nitrocompostos , Folhas de Planta/metabolismo , ReproduçãoRESUMO
PURPOSE: Orthotopic liver transplantation (OLT) patients are known to show decreased intraoperative anesthetic requirements compared with patients undergoing other liver surgeries. The aim of this study was to determine the relationship between inhalational anesthetic requirements and the severity of liver disease among OLT patients. METHODS: Fifty patients undergoing first living donor OLT were divided into 2 groups: model for end-stage liver disease (MELD) score<20 (low-MELD group; n=25) versus, MELD score>or=20 (high-MELD group; n=25). Anesthesia was maintained with desflurane and inspired concentration was titrated to maintain the bispectral index between 40 and 50. Neither intraoperative opioid nor epidural or intrathecal analgesia was used. End-tidal desflurane concentration (ETdes) was measured every 5 minutes and averaged in 30-minute intervals. These values were divided into 3 phases: preanhepatic (P 0.5 hour, P 1 hour, and P 1.5 hours), anhepatic (A 0.5 hour, A 1 hour, A 1.5 hours, and A 2 hours), and postreperfusion (R 0.5 hour, R 1 hour, R 1.5 hours, R 2 hours, R 2.5 hours, and R 3 hours). Results were compared between the 2 groups. RESULTS: The demographic and intraoperative data were similar between the 2 groups. ETdes to maintain comparable anesthetic depth was significantly lower during the preanhepatic and anhepatic phases in the high-MELD than the low-MELD group, but there was no significant difference during the postreperfusion period. CONCLUSIONS: OLT patients with high MELD scores showed less inhalational anesthetic requirements during the preanhepatic and the anhepatic periods than those with low MELD scores.
Assuntos
Anestésicos Inalatórios/uso terapêutico , Hepatopatias/cirurgia , Falência Hepática Aguda/cirurgia , Transplante de Fígado/métodos , Adulto , Desflurano , Feminino , Hepatite C/complicações , Hepatite C/cirurgia , Humanos , Isoflurano/análogos & derivados , Isoflurano/uso terapêutico , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Hepatopatias/patologia , Falência Hepática Aguda/patologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
1. Ginseng total saponin (GTS), 200 mg/kg i.p. 3 hr prior to morphine, inhibited the development of reverse tolerance to the ambulatory-accelerating effect of morphine. 2. GTS, 200 mg/kg, also prevented the development of dopamine receptor supersensitivity induced by the chronic administration of morphine, 10 mg/kg a day for 7 days. 3. These results suggest that GTS may be useful for the prevention and therapy of the adverse action of morphine.
Assuntos
Morfina/farmacologia , Panax , Plantas Medicinais , Receptores Dopaminérgicos/efeitos dos fármacos , Saponinas/farmacologia , Animais , Apomorfina/farmacologia , Tolerância a Medicamentos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Atividade Motora/efeitos dos fármacosRESUMO
Nucleosome Remodeling Factor (NURF) is an ATP-dependent nucleosome remodeling complex that alters chromatin structure by catalyzing nucleosome sliding, thereby exposing DNA sequences previously associated with nucleosomes. We systematically studied how the unstructured N-terminal residues of core histones (the N-terminal histone tails) influence nucleosome sliding. We used bacterially expressed Drosophila histones to reconstitute hybrid nucleosomes lacking one or more histone N-terminal tails. Unexpectedly, we found that removal of the N-terminal tail of histone H2B promoted uncatalyzed nucleosome sliding during native gel electrophoresis. Uncatalyzed nucleosome mobility was enhanced by additional removal of other histone tails but was not affected by hyperacetylation of core histones by p300. In addition, we found that the N-terminal tail of the histone H4 is specifically required for ATP-dependent catalysis of nucleosome sliding by NURF. Alanine scanning mutagenesis demonstrated that H4 residues 16-KRHR-19 are critical for the induction of nucleosome mobility, revealing a histone tail motif that regulates NURF activity. An exchange of histone tails between H4 and H3 impaired NURF-induced sliding of the mutant nucleosome, indicating that the location of the KRHR motif in relation to global nucleosome structure is functionally important. Our results provide functions for the N-terminal histone tails in regulating the mobility of nucleosomes.