RESUMO
C-reactive protein to albumin (CRP/Alb) ratio, a novel inflammation-based prognostic score, was first developed as a prognostic score for septic patients. Recent reports show that CRP/Alb ratio is also a prognostic score for cancer patients, including esophageal cancer. However, the role of CRP/Alb ratio for those with neoadjuvant chemotherapy (NAC) and the changes of CRP/Alb ratio around NAC have never been discussed. The aim of this study is to evaluate the significance of CRP/Alb ratio around NAC for patients with cStage II/III esophageal squamous cell cancer (ESCC). A total of 149 patients who were diagnosed as cStage II/III ESCC were enrolled between February 2007 and December 2014. We retrospectively investigated the relation between pre-NAC and post-NAC CRP/Alb ratio and short and long outcomes. The optimal cutoff level for pre-NAC and post-NAC CRP/Alb ratio was 0.030 and 0.048, respectively. There was no relation between CRP/Alb ratio level and postoperative outcomes. Post-NAC CRP/Alb ratio < 0.048 had a significantly higher overall survival rate than CRP/Alb ratio ≥0.048 (P< 0.001). Univariate analysis showed that cT, cN, pre-NAC CRP/Alb ratio < 0.030 and post-NAC CRP/Alb ratio < 0.048 was prognostic factors (P= 0.003, P= 0.022, P= 0.033, and P< 0.001, respectively). Multivariate analysis showed that cT and post-NAC CRP/Alb ratio < 0.048 was independent prognostic factors (P= 0.030 and P< 0.001, respectively). Post-NAC CRP/Alb ratio is an independent prognostic factor in patients with cStage II/III ESCC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteína C-Reativa/metabolismo , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/terapia , Albumina Sérica/metabolismo , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Proteína C-Reativa/efeitos dos fármacos , Carcinoma de Células Escamosas/secundário , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Neoplasias Esofágicas/patologia , Esofagectomia , Feminino , Fluoruracila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Albumina Sérica/efeitos dos fármacos , Taxa de SobrevidaRESUMO
BACKGROUND: Stimulation of transient receptor potential ankyrin 1 (TRPA1), which abundantly expressed in enterochromaffin cells (ECC), has been reported to exert apparently contradictory results in in vitro contractility and in vivo gastrointestinal (GI) transit evaluations. The pharmaceutical-grade Japanese traditional medicine daikenchuto (TU-100) has been reported to be beneficial for postoperative ileus (POI) and accelerate GI transit in animals and humans. TU-100 was recently shown to increase intestinal blood flow via stimulation of TRPA1 in the epithelial cells of the small intestine (SI). METHODS: The effects of various TRPA1 agonists on motility were examined in a manipulation-induced murine POI model, in vitro culture of SI segments and an ECC model cell line, RIN-14B. KEY RESULTS: Orally administered TRPA1 agonists, aryl isothiocyanate (AITC) and cinnamaldehyde (CA), TU-100 ingredients, [6]-shogaol (6S) and γ-sanshool (GS), improved SI transit in a POI model. The effects of AITC, 6S and GS but not CA were abrogated in TRPA1-deficient mice. SI segments show periodic peristaltic motor activity whose periodicity disappeared in TRPA1-deficient mice. TU-100 augmented the motility. AITC, CA and 6S increased 5-HT release from isolated SI segments and the effects of all these compounds except for CA were lost in TRPA1-deficient mice. 6S and GS induced a release of 5-HT from RIN-14B cells in a dose- and TRPA1-dependent manner. CONCLUSIONS & INFERENCES: Intraluminal TRPA1 stimulation is a potential therapeutic strategy for GI motility disorders. Further investigation is required to determine whether 5-HT and/or ECC are involved in the effect of TRPA1 on motility.
Assuntos
Modelos Animais de Doenças , Trânsito Gastrointestinal/efeitos dos fármacos , Trânsito Gastrointestinal/fisiologia , Íleus/tratamento farmacológico , Canal de Cátion TRPA1/agonistas , Canal de Cátion TRPA1/fisiologia , Acroleína/análogos & derivados , Acroleína/farmacologia , Acroleína/uso terapêutico , Amidas/farmacologia , Amidas/uso terapêutico , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Íleus/fisiopatologia , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Naftoquinonas/farmacologia , Naftoquinonas/uso terapêutico , Técnicas de Cultura de ÓrgãosRESUMO
Bovine colostrum is a rich source of tissue repair and growth factors, and inhibits gastrointestinal injury induced by the side effects of nonsteroidal antiinflammatory drugs (NSAID), such as indomethacin. Nonsteroidal antiinflammatory drugs are drugs with analgesic and antipyretic effects, but in higher doses they have inflammatory effects. The pathogenesis of small intestinal damage caused by NSAID is unclear. The present study was performed to investigate the antiinflammatory effects of skimmed, sterilized, and concentrated bovine late colostrum on intestinal injury induced by side effects of NSAID, and then to identify the active ingredient in the colostrum for intestinal tissue. In Japan, the sale of bovine colostrum within 5 d after parturition is prohibited by law. Therefore, we focused on bovine late colostrum obtained from healthy lactating cows 6 to 7 d after parturition. Proliferation of small intestine epithelial cells was stimulated in mice fed the colostrum for 1 wk. With regard to indomethacin-induced enteropathy, both prefeeding and postfeeding with colostrum facilitated growth of the intestinal villi, indicating preventive and healing effects. Furthermore, to identify the active ingredient in the colostrum responsible for this effect, the casein and whey fractions were prepared from the colostrum and fed to normal mice. Only the colostrum casein fraction stimulated intestinal villus elongation, whereas the whey fraction and mature milk casein showed no such effect. Taken together, these observations indicate that the skimmed, sterilized, and concentrated bovine late colostrum, especially the casein fraction, could be used to treat the injurious effects of NSAID in the intestine and could be effective for treatment of other ulcerative conditions in the bowel, suggesting that the colostrum has therapeutic potential for intestinal inflammation.
Assuntos
Colostro/metabolismo , Intestinos/lesões , Animais , Caseínas/metabolismo , Bovinos , Feminino , Indometacina/efeitos adversos , Mucosa Intestinal/metabolismo , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/lesões , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Intestinos/efeitos dos fármacos , Intestinos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Proteínas do Leite/metabolismo , Proteínas do Soro do LeiteRESUMO
Rotavirus is the most important etiologic agent of severe gastroenteritis. Previously, we reported that skimmed and concentrated bovine late colostrum (SCBLC) obtained from normal unimmunized cows at 6 to 7d after parturition effectively prevented against human rotavirus (HRV)-induced severe gastroenteritis in vivo, when administered as a single dose 60 min before viral inoculation. In the present study, we examined the efficacy of multiple administrations of SCBLC at smaller dosages after viral inoculation in vivo. We demonstrate that multiple administrations within 24h after virus inoculation resulted in earlier recovery from diarrheal symptoms, in an administration frequency-dependent manner. Furthermore, we investigated whether isolated IgG anti-HRV activity in SCBLC was equivalent to that of IgG isolated from bovine mature milk as measured by in vitro activity assays. We found that IgG-containing fractions from SCBLC and mature milk exhibited approximately the same level of anti-HRV activity. We concluded that the SCBLC contains a high level of IgG against HRV-induced severe gastroenteritis, which will be possible to use in protective effects in immunocompromised hosts, such as children and the elderly. Multiple doses of SCBLC during the early stages of infection or lower dosage of SCBLC given as a single dose both resulted in relief of diarrheal symptoms.
Assuntos
Colostro/imunologia , Diarreia/prevenção & controle , Infecções por Rotavirus/terapia , Animais , Animais Lactentes/imunologia , Bovinos , Diarreia/imunologia , Diarreia/virologia , Modelos Animais de Doenças , Gastroenterite/imunologia , Gastroenterite/prevenção & controle , Gastroenterite/virologia , Humanos , Imunoglobulina G/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ensaio de Radioimunoprecipitação , Rotavirus/imunologia , Infecções por Rotavirus/imunologiaRESUMO
OBJECTIVE: In this study, we develop methods to measure galvanotaxis of fibroblasts and determined the optimum conditions of electrical stimulation. METHOD: An inverted 35mm dish containing cell suspensions (3×105 primary human skin fibroblasts, DMEM, and 10% FBS) was placed on the centre of a 100mm dish. The 35mm dish was removed 24 hours later, and culture medium was added to the 100mm dish. Fibroblasts were randomised (double-blind) into three groups, where electrical stimulation was given at varying intensities: 0UA (control), 50UA, and 100UA. Electrical stimulation (frequency=0.3Hz) was conducted, for a duration of 4 hours, with platinum electrodes in a CO2 incubator. We took pictures immediately before and 20 hours after stimulation. We calculated the migration ratio to the negative pole by dividing the area of attached fibroblasts after stimulation with that before stimulation. RESULTS: The migration ratio to the negative pole was significantly higher in the 100UA group than in the control group (p<0.05). The ratios were 0.902±0.292 in the control group, 1.128±0.253 in the 50UA group, and 1.24±0.300 in the 100UA group. CONCLUSION: This study observed the change in cell proliferation during the initial 24-hour period after plating and was thus able to quantitatively evaluate the migration. The results suggest that a low-intensity direct current promotes migration to the negative pole of human dermal fibroblasts, which is charged with positive electricity. Several clinical reports using the methods in this study showed the microcurrent efficacy for pressure ulcer healing. Electrical stimulation based on our in vitro experiment might be important for the development of physical therapy for pressure ulcers.
Assuntos
Movimento Celular/fisiologia , Terapia por Estimulação Elétrica , Fibroblastos/fisiologia , Úlcera por Pressão/terapia , Pele/citologia , Adulto , Células Cultivadas , Método Duplo-Cego , Humanos , Masculino , Distribuição AleatóriaRESUMO
AIM: To characterize the complementary production of two types of siderophores in Azotobacter vinelandii. METHODS AND RESULTS: In an iron-insufficient environment, nitrogen-fixing A. vinelandii produces peptidic (azotobactin) and catechol siderophores for iron uptake to be used as a nitrogenase cofactor. Molybdenum, another nitrogenase cofactor, was also found to affect the production level of siderophores. Wild-type cells excreted azotobactin into molybdenum-supplemented and iron-insufficient medium, although catechol siderophores predominate in molybdenum-free environments. Two gene clusters were identified to be involved in the production of azotobactin and catechol siderophores through gene annotation and disruption. Azotobactin-deficient mutant cells produced catechol siderophores under the molybdenum-supplemented and iron-insufficient conditions, whereas catechol siderophore-deficient mutant cells extracellularly secreted excess azotobactin under iron-deficient condition independent of the concentration of molybdenum. This evidence suggests that a complementary siderophore production system exists in A. vinelandii. CONCLUSIONS: Molybdenum was found to regulate the production level of two types of siderophores. Azotobacter vinelandii cells are equipped with a complementary production system for nitrogen fixation in response to a limited quantity of metals. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study identifying A. vinelandii gene clusters for the biosynthesis of two types of siderophores and clarifying the relationship between them.
Assuntos
Azotobacter vinelandii/genética , Molibdênio/metabolismo , Família Multigênica , Sideróforos/biossíntese , Azotobacter vinelandii/metabolismo , Catecóis/metabolismo , Meios de Cultura , Marcação de Genes , Genes Bacterianos , Ferro/metabolismo , Mutação , Peptídeos/metabolismo , Sideróforos/genéticaRESUMO
The first results on the feasibility of using (236)U to reconstruct the level and spatial distribution of close-in fallout deposition from the Hiroshima A-bomb are reported, coupled with the use of global fallout (137)Cs and (239+240)Pu. The results for global fallout (236)U in soil samples (0-30cm) from Ishikawa prefecture showed that the deposition density of (236)U from the global fallout can be accurately evaluated using AMS. All deposited (236)U, (137)Cs and (239+240)Pu appeared to have been recovered using 30-cm cores. It was also noted from the depth profiles for (236)U/(239+240)Pu and (236)U/(137)Cs ratios that the downward behavior of (236)U in the soil was apparently similar to that of (239+240)Pu, while the (137)Cs was liable to be retained in upper layers compared with (236)U and (239+240)Pu. The accumulated levels were 1.78×10(13)atomsm(-2) for (236)U, 4340Bqm(-2) for (137)Cs and 141Bqm(-2) for (239+240)Pu. The ratios of (236)U/(137)Cs and (236)U/(239+240)Pu were (4.10±0.12)×10(9) and (1.26±0.04)×10(11)atomsBq(-1), respectively. Results of (236)U, (137)Cs and (239+240)Pu measurements for the seven soil cores (0-30cm) from Hiroshima were discussed on the basis of ratios of (236)U/(137)Cs and (236)U/(239+240)Pu by comparing with those from the background area in Ishikawa, indicating that the global fallout dominates the current level of (236)U accumulation in soil in the Black-rain area around Hiroshima after the Hiroshima bomb, and the contribution of the close-in fallout (236)U produced by the Hiroshima A-bomb seems difficult to observe.
Assuntos
Armas Nucleares , Monitoramento de Radiação/métodos , Cinza Radioativa/análise , Poluentes Radioativos do Solo/análise , Urânio/análise , Radioisótopos de Césio/análise , Estudos de Viabilidade , Japão , Plutônio/análise , II Guerra MundialRESUMO
BACKGROUND: Falecalcitriol is a novel vitamin D analog, which has a greater potential to suppress parathyroid hormone (PTH) and a longer half-life. There are few studies to compare clinical effects of oral falecalcitriol treatment with those of intravenous calcitriol treatment. METHODS: Twenty-one patients with moderate to severe SHPT were included in a random 2 x 2 crossover trial with the two vitamin D analogs (12 weeks for each treatment). The primary endpoint measure was a decrease in serum intact PTH (iPTH) level, and the secondary outcome measures included changes in serum calcium (Ca), phosphate (P), and metabolic bone marker levels. RESULTS: Both treatments decreased iPTH and whole PTH (wPTH) levels by similar degrees (iPTH, -200.1 +/- 107.0 with falecalcitriol vs. -200.8 +/- 114.9 pg/ml with calcitriol, p = 0.9895; wPTH, -137.1 +/- 73.1 with falecalcitriol vs. -120.4 +/- 81.1 pg/ml with calcitriol, p = 0.5603). Serum Ca, P, and Ca x P product levels at the end of each treatment were comparable and the frequencies of hypercalcemia and hyperphosphatemia were also similar during each treatment period. Although intravenous calcitriol treatment significantly changed intact osteocalcin and cross-linked N-telopeptide of type I collagen after 12 weeks, oral falecalcitriol treatment did not change any bone metabolic marker level. CONCLUSION: The present study showed that oral falecalcitriol treatment is effective for PTH suppression, and Ca and P metabolism in hemodialysis patients with moderate to severe SHPT, as well as intravenous calcitriol administration.
Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Calcitriol/análogos & derivados , Calcitriol/administração & dosagem , Hiperparatireoidismo Secundário/tratamento farmacológico , Administração Oral , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Cálcio/sangue , Colágeno Tipo I/sangue , Colágeno Tipo I/efeitos dos fármacos , Estudos Cross-Over , Feminino , Humanos , Hiperparatireoidismo Secundário/etiologia , Injeções Intravenosas , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Osteocalcina/sangue , Osteocalcina/efeitos dos fármacos , Hormônio Paratireóideo/sangue , Peptídeos/sangue , Peptídeos/efeitos dos fármacos , Fósforo/sangue , Diálise Renal/efeitos adversos , Resultado do TratamentoRESUMO
The global fallout (236)U level in soil was deduced from measurements of (236)U, (239+240)Pu and (137)Cs in surface soils which are solely influenced by global fallout. A total of 12 soil cores from the depths of 0-10, 0-20 and 0-30 cm were collected at a flat forest area in Japan. Concentrations of (239+240)Pu and (238)U were determined by alpha-particle spectrometry, while the (236)U/(238)U ratio was measured with accelerator mass spectrometry (AMS). Consistent (236)U/(239)Pu ratios between 0.212 and 0.253 were found. Using this ratio, the total global fallout of (236)U on the earth is estimated to be as much as ca. 900 kg. This knowledge will contribute to the promotion of research on U isotopes, including (236)U, for the fields of geo-resources, waste management and geochemistry.
Assuntos
Poluentes Radioativos do Solo/análise , Urânio/análise , Japão , Espectrometria de MassasRESUMO
Genetic disruption of Nrf2 greatly enhances susceptibility to prooxidant- and carcinogen-induced experimental models of various human disorders; but the mechanisms by which this transcription factor confers protection are unclear. Using Nrf2-proficient (Nrf2(+/+)) and Nrf2-deficient (Nrf2(-/-)) primary epithelial cultures as a model, we now show that Nrf2 deficiency leads to oxidative stress and DNA lesions, accompanied by impairment of cell-cycle progression, mainly G(2)/M-phase arrest. Both N-acetylcysteine and glutathione (GSH) supplementation ablated the DNA lesions and DNA damage-response pathways in Nrf2(-/-) cells; however only GSH could rescue the impaired colocalization of mitosis-promoting factors and the growth arrest. Akt activation was deregulated in Nrf2(-/-) cells, but GSH supplementation restored it. Inhibition of Akt signaling greatly diminished the GSH-induced Nrf2(-/-) cell proliferation and wild-type cell proliferation. GSH depletion impaired Akt signaling and mitosis-promoting factor colocalization in Nrf2(+/+) cells. Collectively, our findings uncover novel functions for Nrf2 in regulating oxidative stress-induced cell-cycle arrest, especially G(2)/M-checkpoint arrest, and proliferation, and GSH-regulated redox signaling and Akt are required for this process.
Assuntos
Glutationa/metabolismo , Mitose/genética , Fator 2 Relacionado a NF-E2/genética , Acetilcisteína/farmacologia , Animais , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Células Cultivadas , Dano ao DNA/genética , Proteínas de Ligação a DNA/metabolismo , Glutationa/farmacologia , Camundongos , Camundongos Mutantes , Mitose/efeitos dos fármacos , Oxirredução , Estresse Oxidativo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Proteínas Supressoras de Tumor/metabolismoRESUMO
This study evaluated the efficacy and safety of barnidipine for the treatment of mild-to-moderate essential hypertension in Chinese patients. A total of 131 patients were randomized to receive either barnidipine (10 -15 mg) or felodipine (5 - 10 mg) once daily for 4 weeks. Both drugs reduced blood pressure significantly, with > or = 87% of patients obtaining a marked or moderate effect. The mean +/- SD reductions in systolic and diastolic blood pressure were 19.2 +/- 13.6 and 14.4 +/- 7.0 mmHg, respectively, for barnidipine treatment, and 20.3 +/- 11.3 and 14.7 +/- 7.7 mmHg, respectively, for felodipine treatment. There were no significant differences between the two drugs in terms of anti-hypertensive effect, heart rate, laboratory test results or incidence of adverse events. More patients taking felodipine experienced palpitations, but this difference was not statistically significant. Barnidipine is as efficacious and safe as felodipine in the treatment of essential hypertension in Chinese patients.
Assuntos
Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Felodipino/uso terapêutico , Hipertensão/tratamento farmacológico , Nifedipino/análogos & derivados , Adulto , Idoso , Povo Asiático , Pressão Sanguínea/efeitos dos fármacos , China/etnologia , Feminino , Humanos , Hipertensão/etnologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nifedipino/uso terapêuticoRESUMO
This study compared barnidipine, a calcium-channel blocker, and benazepril, an angiotensin-converting enzyme inhibitor, in 85 Chinese patients with renal parenchymal hypertension (diastolic blood pressure range 95 - 110 mmHg). Patients were randomly assigned to receive either 10 mg barnidipine or 10 mg benazepril orally daily for 4 weeks. In patients with diastolic blood pressure > 90 mmHg after 2 weeks of treatment, the dose of barnidipine or benazepril was increased by 5 or 10 mg, respectively. Both the barnidipine-treated group (n = 43) and the benazepril-treated group (n = 42) showed significant mean reductions from baseline in sitting systolic and diastolic blood pressures. The decrease in diastolic blood pressure with benazepril was significantly greater than with barnidipine treatment. Sitting heart rate was not changed by either drug. There was no significant difference in adverse events between the two groups. Barnidipine is similar to benazepril for the treatment of renal parenchymal hypertension.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Benzazepinas/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão Renal/tratamento farmacológico , Nifedipino/análogos & derivados , Adolescente , Adulto , Idoso , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Benzazepinas/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/efeitos adversos , China , Feminino , Humanos , Hipertensão Renal/fisiopatologia , Masculino , Pessoa de Meia-Idade , Nifedipino/efeitos adversos , Nifedipino/uso terapêuticoRESUMO
The chronic inhibition of nitric oxide (NO) synthesis with Nomega-nitro-L-arginine methyl ester (L-NAME) induces a preeclampsia-like syndrome including hypertension and intrauterine growth retardation (IUGR) in pregnant rats. We tested the traditional herbal medicine Toki-shakuyaku-san (TS) for beneficial effects in this model. L-NAME was infused subcutaneously into pregnant rats from day 14 of gestation. TS (1 g/kg, 2 g/kg) was administered by gavage from day 14 to 20. Systolic blood pressure was measured on day 19. On day 20, rats were sacrificed and serum NO levels, placental weight, fetal body weight, fetal cerebrum weight and the thickness of the cerebral cortex were analyzed. TS (1 g/kg, 2 g/kg) inhibited L-NAME-induced hypertension. The decrease in fetal body weight, cerebrum weight and thickness of the cerebral cortex was abrogated by TS (2 g/kg). The effect of TS on blood pressure was found only in the rats that were both pregnant and infused with L-NAME. L-arginine, at the amount equivalent to that contained in TS, showed no effect. Further, the change in serum NO levels induced by TS was only marginal. TS thus improved the hypertension and IUGR in preeclampsia rats induced by L-NAME in a NO-independent manner. These data suggested that TS may be beneficial for the treatment and prevention of preeclampsia.
Assuntos
Anti-Hipertensivos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Fitoterapia , Plantas Medicinais , Pré-Eclâmpsia/tratamento farmacológico , Administração Oral , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Retardo do Crescimento Fetal/tratamento farmacológico , Feto/efeitos dos fármacos , Masculino , NG-Nitroarginina Metil Éster , Óxido Nítrico/sangue , Pré-Eclâmpsia/induzido quimicamente , Gravidez , Ratos , Ratos Sprague-DawleyRESUMO
Recent work on isolated sinoatrial node cells from rabbit has suggested that sarcoplasmic reticulum Ca2+ release plays a dominant role in the pacemaker potential, and ryanodine at a high concentration (30 micromol/L blocks sarcoplasmic reticulum Ca2+ release) abolishes pacemaking and at a lower concentration abolishes the chronotropic effect of beta-adrenergic stimulation. The aim of the present study was to test this hypothesis in the intact sinoatrial node of the rabbit. Spontaneous activity and the pattern of activation were recorded using a grid of 120 pairs of extracellular electrodes. Ryanodine 30 micromol/L did not abolish spontaneous activity or shift the position of the leading pacemaker site, although it slowed the spontaneous rate by 18.9+/-2.5% (n=6). After ryanodine treatment, beta-adrenergic stimulation still resulted in a substantial chronotropic effect (0.3 micromol/L isoproterenol increased spontaneous rate by 52.6+/-10.5%, n=5). In isolated sinoatrial node cells from rabbit, 30 micromol/L ryanodine slowed spontaneous rate by 21.5+/-2.6% (n=13). It is concluded that sarcoplasmic reticulum Ca2+ release does not play a dominating role in pacemaking in the sinoatrial node. The full text of this article is available at http://www.circresaha.org.
Assuntos
Relógios Biológicos/fisiologia , Cálcio/metabolismo , Retículo Sarcoplasmático/metabolismo , Nó Sinoatrial/metabolismo , Potenciais de Ação/fisiologia , Agonistas Adrenérgicos beta/farmacologia , Animais , Relógios Biológicos/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/fisiologia , Separação Celular , Técnicas Eletrofisiológicas Cardíacas , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Técnicas In Vitro , Isoproterenol/farmacologia , Microeletrodos , Coelhos , Rianodina/farmacologia , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Nó Sinoatrial/citologiaRESUMO
Onion (Allium cepa L.; 1C=15,000 Mb) is an agriculturally important plant. The genome of onion has been extensively studied at the conventional cytogenetic level, but molecular analyses have lagged behind due to its large genome size. To overcome this bottleneck, a partial bacterial artificial chromosome (BAC) library of onion was constructed. The average insert size of the BAC library was about 100 kb. A total of 48,000 clones, corresponding to 0.32 genome equivalent, were obtained. Fluorescent in situ hybridization (FISH) screening resulted in identification of BAC clones localized on centromeric, telomeric, or several limited interstitial chromosomal regions, although most of the clones hybridized with entire chromosomes. The partial BAC library proved to be a useful resource for molecular cytogenetic studies of onion, and should be useful for further mapping and sequencing studies of important genes of this plant. BAC FISH screening is a powerful method for identification of molecular cytogenetic markers in large-genome plants.
Assuntos
Cromossomos Artificiais Bacterianos/genética , DNA de Plantas/genética , Cebolas/genética , Centrômero/genética , Cromossomos/genética , Sondas de DNA , Biblioteca Gênica , Genoma de Planta , Hibridização in Situ Fluorescente , CariotipagemRESUMO
OBJECTIVES: To evaluate the relation between brain displacement, clinical signs and symptoms, and local cerebral blood flow (lCBF) in patients with chronic subdural haematoma (CSDH). METHODS: Forty five patients (age range 58-87 years, mean 71.9 (SD 8.4)) with unilateral CSDH were studied. Patients were categorised into three groups: I, headache (n=16); II, paresis (n=14); and III, mental change (n=15). T1 weighted MR images were obtained in all patients preoperatively. Quantitative values of maximum haematoma thickness, midline shift, and brain rotation angle were measured on axial and coronal MR images. In 21 patients, lCBF was measured by Xe enhanced CT. Values for lCBF were obtained in selected regions of interest in the frontal cortex, thalamus, and hemisphere on both the haematoma and contralateral sides. RESULTS: The lCBF reduction in the ipsilateral frontal cortex showed the best linear correlation with haematoma thickness (r=0.57), whereas the reduction in the ipsilateral thalamus had the most significant correlation with pineal shift (r=0.65) and third ventricle incline (r=0.67). In patients with paresis, lCBF decreased significantly on the ipsilateral side of both the frontal cortex and thalamus (p<0.05), whereas patients with mental change showed a significant reduction of lCBF on both sides of the thalamus (p<0.01) and in the ipsilateral frontal cortex (p<0.01). CONCLUSIONS: The lCBF reduction and clinical symptoms correlated well with local brain displacement in patients with CSDH. The lCBF in the central cerebral area including the thalamus was reduced in patients with clinical signs. The mental changes found were thought to derive from mild impairment of consciousness due to upper brain stem displacement.
Assuntos
Circulação Cerebrovascular , Hematoma Subdural Crônico/diagnóstico , Hematoma Subdural Crônico/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Tronco Encefálico/irrigação sanguínea , Tronco Encefálico/fisiopatologia , Estudos de Casos e Controles , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/fisiopatologia , Estado de Consciência , Lobo Frontal/irrigação sanguínea , Lobo Frontal/fisiopatologia , Cefaleia/etiologia , Hematoma Subdural Crônico/classificação , Hematoma Subdural Crônico/complicações , Hematoma Subdural Crônico/cirurgia , Humanos , Modelos Lineares , Imageamento por Ressonância Magnética/normas , Transtornos Mentais/etiologia , Pessoa de Meia-Idade , Condução Nervosa , Paresia/etiologia , Tempo de Reação , Índice de Gravidade de Doença , Tálamo/irrigação sanguínea , Tálamo/fisiopatologia , Tomografia Computadorizada por Raios X/normasRESUMO
GATA-1 is a transcription factor essential for erythroid/megakaryocytic cell differentiation. To investigate the contribution of individual domains of GATA-1 to its activity, transgenic mice expressing either an N-terminus, or an N- or C-terminal zinc finger deletion of GATA-1 (Delta NT, Delta NF or Delta CF, respectively) were generated and crossed to GATA-1 germline mutant (GATA-1.05) mice. Since the GATA-1 gene is located on the X-chromosome, male GATA-1 mutants die by embryonic day 12.5. Both Delta NF and Delta CF transgenes failed to rescue the GATA-1.05/Y pups. However, transgenic mice expressing Delta NT, but not the Delta NF protein, were able to rescue definitive hematopoiesis. In embryos, while neither the Delta CF protein nor a mutant missing both N-terminal domains (Delta NTNF) was able to support primitive erythropoiesis, the two independent Delta NT and Delta NF mutants could support primitive erythropoiesis. Thus, lineage-specific transgenic rescue of the GATA-1 mutant mouse revealed novel properties that are conferred by specific domains of GATA-1 during primitive and definitive erythropoiesis, and demonstrate that the NT and NF moieties lend complementary, but distinguishable properties to the function of GATA-1.
Assuntos
Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/fisiologia , Eritropoese/genética , Regulação da Expressão Gênica no Desenvolvimento , Sistema Hematopoético/embriologia , Fatores de Transcrição/química , Fatores de Transcrição/fisiologia , Animais , Linhagem Celular , Proteínas de Ligação a DNA/genética , Embrião de Mamíferos/anatomia & histologia , Embrião de Mamíferos/irrigação sanguínea , Embrião de Mamíferos/citologia , Eritrócitos/fisiologia , Fatores de Ligação de DNA Eritroide Específicos , Fator de Transcrição GATA1 , Heme/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Estrutura Terciária de Proteína , RNA Mensageiro/biossíntese , Deleção de Sequência , Transativadores/química , Transativadores/genética , Transativadores/fisiologia , Fatores de Transcrição/genética , Dedos de ZincoRESUMO
Inchin-ko-to (ICKT) prevents Fas-mediated liver injury. This study evaluates the effect of ICKT on conventional markers of liver function (LF) and liver fibrosis in 18 postoperative biliary atresia (BA) patients aged 3 to 23 years with elevated glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), gamma-glutamyl transpeptidase (gammaGTP) but normal serum total bilirubin (T-Bil) levels. ICKT (0.15 g/kg per day) was administered orally for 1 year. Serum GOT, GPT, gammaGTP, total bile acids (TBA), and T-Bil as markers of LF and hyaluronic acid (HA), prolyl hydroxylase (PH), procollagen III peptide (PIIIP), and type IV collagen as markers of liver fibrosis were measured before and after treatment in each patient and compared statistically. All patients tolerated ICKT well, and there were no side effects. The percentage of subjects who improved after ICKT was 45% for serum GOT, 72% for GPT, 72% for gammaGTP, 72% for TBA, 67% for HA, 40% for PH, 50% for PIIIP, and 23% for type IV collagen. Changes in the mean values of all serum markers were statistically significant (P < 0.01). It is concluded that long-term administration of ICKT in postoperative BA patients improves liver status as assessed by markers of LF and fibrosis.
Assuntos
Atresia Biliar/cirurgia , Medicamentos de Ervas Chinesas/uso terapêutico , Cirrose Hepática/prevenção & controle , Inibidores de Fosfodiesterase/uso terapêutico , Fitoterapia , Portoenterostomia Hepática , Complicações Pós-Operatórias/prevenção & controle , Adolescente , Adulto , Atresia Biliar/mortalidade , Criança , Pré-Escolar , Humanos , Japão/epidemiologia , Testes de Função Hepática , Cuidados Pós-Operatórios , Taxa de SobrevidaRESUMO
A high-performance liquid chromatographic method with electrochemical detection was developed for the determination of twelve tea catechins including four major catechins: epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG); four of their epimers at the C-2 position, C, GC, CG and GCG; and four methylated catechin derivatives, epigallocatechin-3-O-(3-O-methyl)gallate, gallocatechin-3-O-(3-O-methyl)gallate, epigallocatechin-3-O-(4-O-methyl)gallate and epicatechin-3-O-(3-O-methyl)gallate. These catechins were separated on an ODS C18 reversed-phase column by isocratic elution with 0.1 M NaH2PO4 buffer (pH 2.5)-acetonitrile (87:13) containing 0.1 mM EDTA.2Na. The detection limits (S/N = 3) of these catechins were approximately 10-40 pmol ml-1 at an applied voltage of 600 mV. Extracting these catechins from tea leaf powder with H2O-acetonitrile (1:1) at 30 degrees C for 40 min inhibited the epimerization at C-2 significantly from these epicatechins compared to extraction with hot water at 90 degrees C. This analytical method is sensitive to and appropriate for the simultaneous determination of various biologically active catechins in green tea.
Assuntos
Catequina/análise , Chá/química , Catequina/química , Cromatografia Líquida de Alta Pressão , Eletroquímica/métodosRESUMO
A 314-bp tandemly repeated DNA sequence, named pAc074, was characterized in Allium cepa by fluorescence in situ hybridization (FISH) analyses using random amplified fragment as probe. The nucleotide sequences of the clone pAc074 is partially homologous to the satellite DNA sequences, ACSAT1, ACSAT2, and ACSAT3, of A. cepa with 81%, 81% and 78% similarity, respectively. Our sequential C-banding and FISH with pAc074 probe also clearly showed a close relation between Cheterochromatin at telomeric region and pAc074 sequences on all the chromosomes except on chromosome 6. On the long arm of chromosome 7, pAc074 sequences appeared as interstitial band which did not correspond to C-heterochromatin bands. Instead, the C-heterochromatin bands corresponded with the 5S rDNA signals. This is the first evidence of simultaneous banding of the 5S rDNA and C-band in A. cepa.