RESUMEN
Patients with breast cancer-related lymphedema (BCRL) need a life-long self-care program that they can adhere to enable them to manage their lymphedema. The objective of this study was to assess the effectiveness of a holistic BCRL self-care program that patients could easily adhere to and comply with. A prospective, longitudinal, comparative study between affected arms and unaffected arms in unilateral breast cancer patients was implemented over a six-month period. Both the lymphedematous and unaffected arms of 23 patients with unilateral BCRL were followed and measured. The daily 10-minute holistic BCRL self-care program consisted of modified Japanese rajio taiso (Japanese radio calisthenics), a gentle arm exercise combined with deep breathing, skin moisturizing care using a traditional lymphatic drainage technique, and basic self-care education. Arm and edema volume, relative volume change, resistance of the skin to compression (fibrosis), lymphedema-related symptoms, skin condition, and self-care were assessed. At the end of six-months the volume of all limb segments and resistance of the tissues to compression at all measurement points of the affected arm were significantly reduced. On the unaffected side, only the volume of the forearm and the whole arm was significantly reduced and fibrosis significantly reduced only in the forearm. There was no significant difference in edema volume and relative volume change. Lymphedema-related symptoms significantly improved. Perceived adherence, effectiveness, burden, score and average time for self-care significantly increased. Our results demonstrate that this 10-minute self-care program may improve BCRL and its self-care.
Asunto(s)
Linfedema del Cáncer de Mama/terapia , Neoplasias de la Mama/cirugía , Ejercicios Respiratorios/métodos , Terapia por Ejercicio/métodos , Escisión del Ganglio Linfático , Drenaje Linfático Manual/métodos , Mastectomía , Autocuidado/métodos , Cuidados de la Piel/métodos , Actividades Cotidianas , Adulto , Anciano , Aromaterapia , Axila , Quimioterapia Adyuvante , Citrus paradisi , Femenino , Humanos , Japón , Estudios Longitudinales , Mastectomía Segmentaria , Persona de Mediana Edad , Aceites Volátiles/uso terapéutico , Cooperación del Paciente , Educación del Paciente como Asunto , Estudios Prospectivos , Radioterapia Adyuvante , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Restriction of diffusion has been reported in the early phase of secondary neuronal degeneration, such as wallerian degeneration. The purpose of this study was to investigate postoperative transient reduced diffusion in the ipsilateral striatum and thalamus as a remote effect of surgery. MATERIALS AND METHODS: Six hundred two postoperative MR imaging examinations in 125 patients after cerebral surgery were retrospectively reviewed, focusing on the presence of reduced diffusion in the striatum and/or thalamus. The distribution of reduced diffusion in the striatum was classified into 3 groups: anterior, central, and posterior. Reduced diffusion in the thalamus was also classified on the basis of the anatomic locations of the thalamic nuclei. Further follow-up MRI was available in all patients with postoperative reduced diffusion, and acute infarctions were excluded. The patient medical records were reviewed to evaluate neurologic status. RESULTS: Restriction of diffusion was observed in the striatum and/or thalamus ipsilateral to the surgical site in 17 patients (13.6%). The distribution of signal abnormality correlated with the location of the operation, in concordance with the architecture of the striatocortical and thalamocortical connections. Reduced diffusion was observed from days 7 to 46 after the operation, especially during days 8-21. The signal abnormalities completely resolved on follow-up examinations. The median follow-up period was 202 days (interquartile range, 76-487 days). CONCLUSIONS: Postoperative transient reduced diffusion in the ipsilateral striatum and/or thalamus likely represents an early phase of secondary neuronal degeneration based on its characteristic distribution and time course. Clinically, this reduced diffusion should not be mistaken for postoperative ischemic injury.
Asunto(s)
Cuerpo Estriado/patología , Imagen por Resonancia Magnética/estadística & datos numéricos , Procedimientos Neuroquirúrgicos/estadística & datos numéricos , Tálamo/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Japón/epidemiología , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Medición de Riesgo , Adulto JovenRESUMEN
ETHNOPHARMACOLOGICAL SIGNIFICANCE: Bupleuri radix is a commonly prescribed Oriental herbal medicine containing extracts of different Bupleuri species. We wished to determine whether two of these species, Bupleurum scorzoneraefolium and Bupleurum falcatum, or their active ingredients, saikosaponins a, c, and d, could prevent the development of immune-complex nephritis in nephrotoxic serum treated mice. MATERIALS AND METHODS: Immune-complex nephritis was created in C57BL/6 mice by administration of nephrotoxic serum containing anti-basement membrane antibodies. Mice were next given one of five treatments: Bupleurum scorzoneraefolium, Bupleurum falcatum, saikosaponin a, saikosaponin c, or saikosaponin d. Proteinuria, blood urea nitrogen, creatinine, and renal histological changes were then examined. RESULTS: Saikosaponin c almost completely prevented the development of nephritis, although immune-complex deposition was not affected. Bupleurum falcatum and saikosaponin d had a significant, although lesser effect, and Bupleurum falcatum and saikosaponin a showed no effect. CONCLUSIONS: The mechanism of action of saikosaponin c and the reasons for the difference between the two bupleuri species should be investigated further in order to find the best way to utilize the therapeutic effect of Bupleuri radix on nephritis.
Asunto(s)
Bupleurum/química , Riñón/efectos de los fármacos , Nefritis/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Animales , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Técnica del Anticuerpo Fluorescente Directa , Riñón/patología , Ratones , Ratones Endogámicos C57BL , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/análisis , Ácido Oleanólico/farmacología , Proteinuria/orina , Conejos , Saponinas/análisis , Saponinas/farmacología , Factores de TiempoRESUMEN
BACKGROUND: Seasonal allergic rhinitis (SAR) induced by Japanese cedar pollens is a major problem in Japan. Omalizumab, a humanized monoclonal anti-IgE antibody, improves symptoms associated with SAR, but a comparative study with an anti-allergy drug has not yet been conducted. OBJECTIVE: To compare the efficacy and safety of omalizumab with suplatast tosilate, a selective T-helper type 2 (Th2) cytokine inhibitor, in patients with Japanese cedar pollen-induced SAR. METHODS: A randomized, double-blind, double-dummy study was conducted in 308 Japanese patients with a history of moderate-to-severe SAR who showed a CAP-RAST value (> or =2+) specifically to Japanese cedar pollens. Patients were treated for 12 weeks with omalizumab plus placebo of suplatast tosilate or suplatast tosilate plus placebo of omalizumab. RESULTS: The mean daily nasal symptom medication scores (sum of the daily nasal symptom severity score and daily nasal rescue medication score) were significantly lower in the omalizumab group than in the suplatast tosilate group during three evaluation periods (P<0.001). The omalizumab group also had significantly lower mean daily nasal severity scores, each of the mean daily nasal and ocular symptom severity scores (sneezing, runny nose, stuffy nose, itchy nose, itchy eyes, watery eyes, and red eyes). Omalizumab reduced rescue medication requirements, and the proportion of days with any rescue medication use in the omalizumab group was significantly lower. Serum-free IgE levels markedly decreased in the omalizumab group and it was associated with clinical efficacy. The adverse reaction profiles were similar between the two groups. The overall incidence of injection site reactions was higher in the omalizumab group than in the suplatast tosilate group, but all these events were of mild degree. No anti-omalizumab antibodies were detected. CONCLUSION: Omalizumab showed significantly greater improvements than suplatast tosilate in the treatment of SAR induced by Japanese cedar pollens.
Asunto(s)
Antialérgicos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Arilsulfonatos/uso terapéutico , Polen/inmunología , Rinitis Alérgica Estacional/tratamiento farmacológico , Compuestos de Sulfonio/uso terapéutico , Adulto , Anticuerpos Antiidiotipos , Anticuerpos Monoclonales Humanizados , Pueblo Asiatico , Método Doble Ciego , Femenino , Humanos , Inmunoglobulina E/sangre , Japón , Masculino , Persona de Mediana Edad , Omalizumab , Rinitis Alérgica Estacional/inmunología , Resultado del TratamientoRESUMEN
A technique for preparing nuclear reaction targets of various thicknesses was developed by using common filtration technique of hydroxide precipitates with a porous Al(2)O(3) membrane filter. Uniformity was found to be within a few % in each thickness. Durability for beam irradiation was also confirmed. The preparation procedure is convenient and the method is appropriate for several target materials, including not only precious materials but also radioactive materials with low contamination.
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Óxido de Aluminio/química , Óxido de Aluminio/efectos de la radiación , Precipitación Fraccionada , Iones Pesados , Física Nuclear/métodos , Ultrafiltración/métodos , Ensayo de MaterialesRESUMEN
BACKGROUND: An antimicrobial susceptibility test for Helicobacter pylori before second-line treatment is often performed, although whether the test is truly necessary remains unknown. PATIENTS AND METHODS: Eighty-two patients with H. pylori infection for whom first-line treatment with a 1-week proton pump inhibitor/amoxicillin-clarithromycin (AC) regimen had failed were randomly assigned to two groups: those having or not having the susceptibility test before re-treatment. The cure rates for these two groups were compared. RESULTS: Five of the 82 patients were excluded from the analysis. For 38 patients in the susceptibility-test group, we used what we considered the best regimen based on susceptibility testing: 10 patients [no resistance to clarithromycin (CAM)] received the lansoprazole-amoxicillin-clarithromycin regimen, 22 patients [19 CAM resistant, metronidazole (MNZ) susceptible; three failure of culture] were given the lansoprazole-amoxicillin-metronidazole (LAM) regimen, and six patients (both MNZ and CAM resistant) received dual therapy with omeprazole (OPZ) and amoxicillin (AMOX) in which the OPZ dose was determined by the CYP2C19 gene polymorphism. For 39 patients in the group with no susceptibility testing, LAM regimens were prescribed. The intention-to-treat (ITT)-based cure rates in the groups with and without susceptibility testing were 81.6% (95% confidence interval; 66-92%) and 92.4% (79-98%), respectively, and there was no significant difference between these two groups. CONCLUSION: Susceptibility testing is not necessarily required before second-line therapy if the first-line treatment has been performed using proton pump inhibitor/AC regimens.
Asunto(s)
Antibacterianos , Quimioterapia Combinada/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Adulto , Anciano , Pruebas Respiratorias , Farmacorresistencia Bacteriana , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
To enhance the effect of radio-immunotherapy for solid cancers, whole-body mild hyperthermia was added, and its effects on the pharmacokinetics of radiolabelled antibody, outcome of radio-immunotherapy, and radiosensitivity of the tumour were investigated. Nude mice bearing human colon cancer xenografts were heated to 40 degrees C for 3 or 6 h. After heating, mice received intravenous (i.v.) injections of [131I]-labelled anti-carcinoembryonic antigen (CEA) monoclonal antibody. Although 6-h heating did not alter the biodistribution of the radiolabelled antibody, and alone did not show any therapeutic effect on tumour growth, when combined with radio-immunotherapy, the therapeutic effect on tumour growth was significantly enhanced. Three-hour heating also significantly enhanced the effect of radio-immunotherapy. Colony formation assay showed that the radiosensitivity of the tumour was significantly enhanced after heating, which was achieved by a reduction of the hypoxic fraction of the tumour. In conclusion, the addition of whole-body mild hyperthermia significantly enhanced the therapeutic effect of radio-immunotherapy by increasing the radiosensitivity of the tumour.
Asunto(s)
Antígeno Carcinoembrionario/uso terapéutico , Neoplasias del Colon/terapia , Hipertermia Inducida/métodos , Radioinmunoterapia/métodos , Animales , Neoplasias del Colon/irrigación sanguínea , Terapia Combinada/métodos , Humanos , Radioisótopos de Yodo/uso terapéutico , Ratones , Ratones Desnudos , Resultado del Tratamiento , Ensayos Antitumor por Modelo de Xenoinjerto/métodosRESUMEN
The diethyl ether extract of Anemarrhenae Rhizoma (rhizomes of Anemarrhena asphodeloides Bunge) showed testosterone 5alpha-reductase inhibitory activity. Two major constituents, cis-hinokiresinol (1) and 2,6,4'-trihydroxy-4-methoxybenzophenone (2) were identified as the active principles. The inhibitory activity of 1 was superior to that of ethinylestradiol, but that of 2 was weak.
Asunto(s)
Inhibidores de 5-alfa-Reductasa , Inhibidores Enzimáticos/análisis , Plantas Medicinales , Animales , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
We sought to assess the effects of oral supplementation of L-arginine, the precursor of nitric oxide (NO), on hemodynamics and exercise capacity in patients with pulmonary hypertension. Acute hemodynamic responses to oral L-arginine (0.5 g/10 kg body weight) or placebo were examined in 19 patients with primary or precapillary secondary pulmonary hypertension. Cardiopulmonary exercise tests were performed to measure peak oxygen consumption (peak V O(2)) and the ventilatory response to carbon dioxide production (V E-V CO(2) slope) before and 1 wk after treatment with L-arginine (1.5 g/10 kg body weight/d) or placebo. Oral supplementation of L-arginine significantly increased plasma L-citrulline, which indicated enhancement of NO production. Supplemental L-arginine produced a 9% decrease in mean pulmonary arterial pressure (53 +/- 4 to 48 +/- 4 mm Hg, p < 0.05) and a 16% decrease in pulmonary vascular resistance (14.8 +/- 1.5 to 12.4 +/- 1.4 Wood units, p < 0.05). L-arginine modestly decreased mean systemic arterial pressure (92 +/- 4 to 87 +/- 3 mm Hg, p < 0.05). A 1-wk supplementation of L-arginine resulted in a slight increase in peak V O(2) (831 +/- 88 to 896 +/- 92 ml/min, p < 0.05) and a significant decrease in the V E- V CO(2) slope (43 +/- 4 to 37 +/- 3, p < 0.05) without significant systemic hypotension. Hemodynamics and exercise capacity remained unchanged during placebo administration. These results suggest that oral supplementation of L-arginine may have beneficial effects on hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension.
Asunto(s)
Arginina/administración & dosificación , Tolerancia al Ejercicio/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Hipertensión Pulmonar/tratamiento farmacológico , Administración Oral , Análisis de Varianza , Método Doble Ciego , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Hipertensión Pulmonar/fisiopatología , Masculino , Persona de Mediana Edad , Probabilidad , Valores de Referencia , Resultado del TratamientoRESUMEN
Anti-human rotavirus (HRV) activity of hot water extracts from Stevia rebaudiana (SE) was examined. SE inhibited the replication of all four serotypes of HRV in vitro. This inhibitory effect of SE was not reduced on the prior exposure of SE to HCl for 30 min at pH 2. Binding assay with radiolabeled purified viruses indicated that the inhibitory mechanism of SE is the blockade of virus binding. The SE inhibited the binding of anti-VP7 monoclonal antibody to HRV-infected MA104 cells. The inhibitory components of SE were found to be heterogeneous anionic polysaccharides with different ion charges. The component analyses suggested that the purified fraction named as Stevian with the highest inhibitory activity consists of the anionic polysaccharide with molecular weight of 9800, and contains Ser and Ala as amino acids. Analyses of sugar residues suggest uronic acid(s) as sugar components. It did not contain amino and neutral sugars and sulfate residues. These findings suggest that SE may bind to 37 kD VP7 and interfere with the binding of VP7 to the cellular receptors by steric hindrance, which results in the blockade of the virus attachment to cells.
Asunto(s)
Antígenos Virales , Antivirales/farmacología , Proteínas de la Cápside , Plantas Medicinales , Rotavirus/efectos de los fármacos , Animales , Anticuerpos Antivirales/farmacología , Cápside/metabolismo , Línea Celular , Cromatografía por Intercambio Iónico , Chrysanthemum cinerariifolium , Relación Dosis-Respuesta a Droga , Concentración de Iones de Hidrógeno , Peso Molecular , Extractos Vegetales/química , Extractos Vegetales/farmacología , Polisacáridos/aislamiento & purificación , Unión Proteica , Receptores Virales/efectos de los fármacos , Rotavirus/genética , Replicación Viral/efectos de los fármacosRESUMEN
To investigate the role of phosphatidylglycerol (PG) in photosynthesis, we constructed a mutant defective in the CDP-diacylglycerol synthase gene from a cyanobacterium, Synechocystis sp. PCC6803. The mutant, designated as SNC1, required PG supplementation for growth. Growth was repressed in PG-free medium concomitantly with the decrease in cellular content of PG. These results indicate that PG is essential, and that SNC1 is defective in PG synthesis. Decrease in PG content was accompanied by a reduction in the cellular content of chlorophyll, but with little effect on the contents of phycobilisome pigments, which showed that levels of chlorophyll-protein complexes decreased without alteration of those of phycobilisomes. Regardless of the decrease in the PG content, CO(2)-dependent photosynthesis by SNC1 was similar to that by the wild type on a chlorophyll basis, but consequently became lower on a cell basis. Simultaneously, the ratio of oxygen evolution of photosystem II (PSII) measured with p-benzoquinone to that of CO(2)-dependent photosynthesis, which ranged between 1.3 and 1.7 in the wild type. However, it was decreased in SNC1 from 1.3 to 0.4 during the early growth phase where chlorophyll content and CO(2)-dependent photosynthesis were little affected, and then finally to 0.1, suggesting that PSII first lost its ability to reduce p-benzoquinone and then decreased in its level and actual activity. These results indicate that PG contributes to the accumulation of chlorophyll-protein complexes in thylakoid membranes, and also to normal functioning of PSII.
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Cianobacterias/fisiología , Fosfatidilgliceroles/fisiología , Fotosíntesis , Tilacoides/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Cianobacterias/enzimología , Cianobacterias/genética , Cartilla de ADN , Diacilglicerol Colinafosfotransferasa/genética , Datos de Secuencia Molecular , Fenotipo , Proteínas del Complejo del Centro de Reacción Fotosintética/metabolismo , Ficobilisomas , Pigmentos Biológicos/metabolismoRESUMEN
Apoptosis of sinusoidal endothelial cells (SECs) is one of the initial events in the development of ischemia-reperfusion injury of the liver. Glycine has been shown to diminish ischemia-reperfusion injury in the liver and improve graft survival in the rat liver transplantation model. Here, we investigated the effect of glycine on apoptosis of primary cultured rat SECs induced by vascular endothelial growth factor (VEGF) deprivation. Isolated rat SECs were cultured in EBM-2 medium supplemented with 10% fetal bovine serum (FBS) and growth factors including 20 ng/mL VEGF for 3 days. SECs at 3 days of culture showed spindle-like shapes; however, cells started shrinking and detaching from dishes by VEGF deprivation. Apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated d-uridine triphosphate (dUTP)-biotin nick end labeling (TUNEL) staining in these conditions. Control SECs contained only a few percent of TUNEL-positive cells; however, they started increasing 4 hours after VEGF deprivation, and the percentage of TUNEL-positive cells reached about 50% at 8 hours and almost 100% at 16 hours after VEGF deprivation. Interestingly, this increase in TUNEL-positive cells after VEGF deprivation was prevented significantly when glycine (1-10 mmol/L) was added to the medium, the levels being around 60% of VEGF deprivation without glycine. Furthermore, strychnine (1 micromol/L), a glycine receptor antagonist, inhibited this effect of glycine, suggesting the possible involvement of the glycine receptor/chloride channel in the mechanism. Moreover, Bcl-2 protein levels in SECs were decreased 8 hours after VEGF deprivation, which was prevented almost completely by glycine. It is concluded that glycine prevents apoptosis of primary cultured SECs under VEGF deprivation.
Asunto(s)
Apoptosis/efectos de los fármacos , Factores de Crecimiento Endotelial/deficiencia , Glicina/farmacología , Hígado/fisiología , Linfocinas/deficiencia , Animales , Células Cultivadas , Endotelio/citología , Endotelio/fisiología , Glicina/antagonistas & inhibidores , Hígado/citología , Masculino , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Wistar , Estricnina/farmacología , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
The antimicrobial susceptibility testing for Mycobacterium tuberculosis by the bioluminescence assay of adenosine triphosphate(ATP) derived from living mycobacteria was improved introducing filamentous cell treatment(FCT) reported for beta-lactam susceptibility test of Pseudomonas aeruginosa by Hattori. Before ATP extraction, bacterial cells were treated with the FCT reagent for 30 minutes at room temperature. Adenosine phosphate deaminase in the FCT reagent simultaneously digested the extracted ATP and released ATP in a liquid culture of M. tuberculosis H37Rv and the RLU level was decreased markedly. Using this improved ATP method, we determined the ATP contents of M. tuberculosis inoculated into Middle-brook 7H9 broth medium with or without drugs. In ethambutol(EB) susceptibility, the ATP method reported previously, showed false-resistance when judged within 7 days. To eliminate false-resistance in EB susceptibility we applied the modified ATP method with FCT treatment to strains determined EB susceptible by reference methods. Using this modified ATP method, we could judge EB susceptibility of 5 ATCC reference strains within 3 days, and these of 15 clinical isolates of M. tuberculosis within 5 days. And all the results obtained were coincident between the ATP method and the reference methods. The reproducibility of this modified ATP method was evaluated with six ATCC reference strains at the concentrations of 0.1 microgram/ml of isoniazid(INH), 2.0 micrograms/ml of rifampicin(RFP), 2.5 micrograms/ml of EB, 2.0 micrograms/ml of streptomycin(SM), and 5.0 micrograms/ml of kanamycin(KM). The test was repeated six times. Reduction of ATP contents were observed in susceptible strains but not in resistant ones within 3 days of cultivation and susceptibilities to drugs could be determined within 3 days at every time when combined FCT to the ATP method. And highly reproducible results were obtained. It is strongly suggested that this modified method is simple, rapid, highly reproducible and nonradiometric, and could be used for the assessment of drug susceptibility for M. tuberculosis.
Asunto(s)
Adenosina Trifosfato/análisis , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/química , Mediciones LuminiscentesRESUMEN
The potential of 111Indium (111In)-labelled internalising anti-integrin alpha 3 antibody GA17 in the radioimmunotherapy of human glioblastoma xenografts in nude mice was investigated. A radioisotope retention assay showed a rapid release of radioiodine from the glioblastoma cells after the binding of 125I-GA17, whilst 111In-GA17 was retained in the cells for a longer time period. The glioblastoma xenografts showed a high and prolonged uptake of 111In-GA17, and tumour uptake of 125I-GA17 was lower and decreased with time. In the mice which received two injections of 18.5 MBq of 111In-GA17, the growth of the subcutaneous tumour was significantly suppressed compared with the untreated group and mice injected with an 111In-labelled control antibody. These results indicate that GA17 was internalized into the glioblastoma cells and that 111In was retained within the cancer cells. The injection of a high-dose of 111In-GA17 can suppress the growth of tumour xenografts in nude mice.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Glioblastoma/radioterapia , Radioisótopos de Indio/uso terapéutico , Radioinmunoterapia/métodos , Animales , Anticuerpos Monoclonales/farmacocinética , División Celular , Glioblastoma/metabolismo , Glioblastoma/patología , Humanos , Radioisótopos de Indio/farmacocinética , Radioisótopos de Yodo/farmacocinética , Radioisótopos de Yodo/uso terapéutico , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Trasplante HeterólogoRESUMEN
The anti-tumor and anti-metastatic effects of O-(chloroacetyl-carbamoyl) fumagillol (TNP-470), an angiogenesis inhibitor, and cisplatin (CDDP), an anti-neoplastic agent, were investigated using our established liver-metastasizing pancreatic carcinoma line, HPC-3H4. HPC-3H4 was injected into the spleens of nude mice. Mice were randomly divided into 5 groups; a control group given saline solution, a group receiving 45 mg/kg TNP-470, a group receiving 90 mg/kg TNP-470, a group receiving 90 mg/kg TNP-470 in combination with 0.25 mg/kg CDDP, and a group receiving 0.25 mg/kg CDDP. In the control group, liver metastasis developed in 14 of 15 mice (93.3%). Liver metastasis developed in 9 of 11 mice (81.8%) receiving 0.25 mg/kg CDDP. It developed in 11 of 15 mice (73.3%) receiving 45 mg/kg TNP-470, in 17 of 18 mice (94.4%) receiving 90 mg/kg TNP-470, and in 4 of 10 mice (40%) receiving 90 mg/kg TNP-470 in combination with 0.25 mg/kg CDDP. TNP-470 in combination with CDDP displayed a significant inhibitory effect on liver metastasis compared to the control. Although TNP-470 alone and CDDP alone had no effect on the tumor growth in vivo, 90 mg/kg TNP-470 in combination with 0.25 mg/kg CDDP had a significant effect. In vitro examinations demonstrated that the growth of HPC-3H4 cells was only mildly inhibited by TNP-470, but the production of vascular endothelial growth factor (VEGF) by HPC-3H4 was clearly inhibited by TNP-470. The inhibitory effect on the production of VEGF was not strong with CDDP treatment. These results indicate that the angiogenesis inhibitor TNP-470 in combination with low-dose CDDP has inhibitory activity against liver metastasis of human pancreatic carcinoma.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Hepáticas/prevención & control , Neoplasias Hepáticas/secundario , Neovascularización Patológica/prevención & control , Neoplasias Pancreáticas/patología , Sesquiterpenos/administración & dosificación , Animales , División Celular , Cisplatino/administración & dosificación , Ciclohexanos , Factores de Crecimiento Endotelial/antagonistas & inhibidores , Femenino , Humanos , Linfocinas/antagonistas & inhibidores , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , O-(Cloroacetilcarbamoil) Fumagilol , Sesquiterpenos/toxicidad , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
It has been reported that the number of living bacteria is correlated to their ATP contents. Based on this, ATP measurement was applied to the susceptibility test for Mycobacterium tuberculosis to antimicrobial agents. ATP was extracted from the bacterial suspension prepared from M. tuberculosis H37Rv grown on 1% Ogawa medium and measured by bioluminescent assay. The highest relative light units (RLU) was obtained when ATP was extracted with the reagent supplied by Kikkoman Inc. (Chiba, Japan) at 100 degrees C for 3 minutes. The amounts of ATP recovered was constant at 100 degrees C for 8 minutes. The ATP contents correlated well with the number of bacteria expressed as CFU. The ATP contents of M. tuberculosis H37Rv inoculated into the Middlebrook 7H9 broth medium containing antituberculous agents were measured at days of 0, 3, 5 and 7. The control culture showed the time-dependent increase in the RLU values, while cultures supplemented with antimicrobial agents reduced their ATP contents concomitant with the concentrations of drugs. The growth of tubercle bacilli was expressed as RLU ratio, the ratio of RLU in the drug-containing cultures to those in drug-free ones. RLU ratio of 0.5 or less was determined as sensitive and the ratio of more than 0.5 as resistant to drugs. The inoculum size of bacteria did not affect the days giving RLU ratio below 0.5 or 0.3. Within 7 days, susceptibilities to drugs could be determined. In conclusion, this test is simple, rapid, sensitive and highly reproducible and useful for the assessment of susceptibility.
Asunto(s)
Adenosina Trifosfato/análisis , Antituberculosos/farmacología , Mediciones Luminiscentes , Pruebas de Sensibilidad Microbiana/métodos , Mycobacterium tuberculosis/efectos de los fármacos , Etambutol/farmacología , Estudios de Evaluación como Asunto , Isoniazida/farmacología , Kanamicina/farmacología , Mycobacterium tuberculosis/metabolismo , Rifampin/farmacología , Estreptomicina/farmacologíaRESUMEN
Leptin, ob gene product, inhibits feeding behavior and stimulates energy expenditure in rodents. Corticotropin-releasing hormone (CRH) and neuropeptide Y (NPY), which act in the hypothalamus to influence energy homeostasis, may mediate the anorexic effect of leptin. The present studies were undertaken to examine the possible involvement of hypothalamic CRH in the anorexigenic action of leptin in male Wistar rats. Recombinant leptin (2 microg/rat), microinjected into the third ventricle, inhibited food intake at 2 h by 33.3% (P < 0.01) in rats that were deprived of food for 18 h. The intracerebroventricular injection of 2 microg leptin also increased hypothalamic CRH content (P < 0.05) at 2 h after its administration. Simultaneous intracerebroventricular administration of 5 microg/rat alpha-helical CRH 9-41 (alpha-hCRH), a CRH antagonist, with 2 microg/rat leptin attenuated the anorexic effect of leptin by 2 h. In contrast, single intracerebroventricular injection of alpha-hCRH did not affect food consumption in food-deprived rats. These results implicate hypothalamic CRH as an important mediator of the anorexic effect of leptin in food-deprived rats.
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Anorexia/fisiopatología , Ventrículos Cerebrales/fisiología , Hormona Liberadora de Corticotropina/metabolismo , Ingestión de Energía/efectos de los fármacos , Hipotálamo/fisiología , Proteínas/farmacología , Animales , Anorexia/inducido químicamente , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Ventrículos Cerebrales/efectos de los fármacos , Corticosterona/sangre , Hormona Liberadora de Corticotropina/química , Hormona Liberadora de Corticotropina/farmacología , Privación de Alimentos , Hipotálamo/efectos de los fármacos , Inyecciones Intraventriculares , Leptina , Masculino , Neuropéptido Y/administración & dosificación , Neuropéptido Y/farmacología , Proteínas/administración & dosificación , Ratas , Ratas Wistar , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacologíaRESUMEN
Novel scalarane sesterterpenes (1-4) were isolated from a sponge, Hyrtios erecta (order Dictyoceratida). They were characterized by means of spectral analyses, X-ray crystallography, and chemical reactions. Compound 1 showed potent in vitro and in vivo antitumor activities. In addition, the structure-activity relationship was also discussed using computer-assisted structure matching of 1 and aragusterols.
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Antineoplásicos/aislamiento & purificación , Poríferos/química , Terpenos/aislamiento & purificación , Animales , Antineoplásicos/farmacología , Cristalografía por Rayos X , Ensayos de Selección de Medicamentos Antitumorales , Leucemia P388/tratamiento farmacológico , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Ratones , Conformación Molecular , Extractos Vegetales/química , Sesterterpenos , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , Relación Estructura-Actividad , Terpenos/farmacología , Células Tumorales CultivadasRESUMEN
OBJECTIVE: Withdrawal of testosterone prevents the development of hyperglycaemia in male Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats, a model of non-insulin-dependent diabetes mellitus (NIDDM), but the exact mechanism has not been established. The present studies were undertaken to examine a possible role of testosterone in the development of obesity in young OLETF rats who have not shown marked hyperphagia. METHODS: Body weight, food intake and circulating concentrations of metabolic factors including immunoreactive leptin (IRL) were measured at five weeks of age in young male OLETF rats and their lean controls, Long-Evans-Tokushima-Otsuka (LETO) rats. At six weeks of age, both LETO and OLETF rats were bilaterally orchiectomized (Orchx) and half of each group implanted with a silastic tube containing testosterone. After a three week observation period, all animals were killed and circulating concentrations of metabolic factors and the ob gene expression in retroperitoneal white adipose tissues were measured. RESULTS: Body weight and 24h food intake were already increased in OLETF rats at five weeks of age. Serum testosterone concentrations were significantly lower in OLETF rats than in LETO rats. Expression of the ob gene was significantly decreased in the retroperitoneal white adipose tissue of OLETF rats, and their serum IRL concentrations were lower. Food intake and body weight gain for three weeks after the operation were significantly lower in the Orchx group of OLETF rats than in the sham-operated group. Hyperglycaemia, accompanied by hyperinsulinaemia, was attenuated by orchiectomy in OLETF rats. Circulating IRL concentrations were significantly higher in OLETF rats than in LETO rats and decreased by orchiectomy. Testosterone supplement reversed all of the changes caused by orchiectomy in OLETF rats. In contrast, the changes, which were observed after orchiectomy in OLETF rats, were not obvious in LETO rats. CONCLUSION: The present data indicate that testosterone plays a role in the development of obesity and NIDDM in young OLETF rats, but that changes of leptin production in white adipose tissue may not be important in the development of obesity in young OLETF rats.
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Diabetes Mellitus Tipo 2/complicaciones , Ingestión de Alimentos/fisiología , Obesidad/etiología , Biosíntesis de Proteínas , Testosterona/fisiología , Animales , Secuencia de Bases , Glucemia/análisis , Glucemia/metabolismo , Estudios de Cohortes , Corticosterona/sangre , Corticosterona/metabolismo , Cartilla de ADN/química , Diabetes Mellitus Tipo 2/cirugía , Modelos Animales de Enfermedad , Implantes de Medicamentos , Ingestión de Alimentos/efectos de los fármacos , Estradiol/sangre , Estradiol/metabolismo , Hormona Folículo Estimulante/sangre , Hormona Folículo Estimulante/metabolismo , Hiperglucemia/prevención & control , Insulina/sangre , Leptina , Hormona Luteinizante/sangre , Hormona Luteinizante/metabolismo , Masculino , Obesidad/sangre , Obesidad/fisiopatología , Orquiectomía , Reacción en Cadena de la Polimerasa , Proteínas/análisis , Proteínas/genética , ARN Mensajero/análisis , ARN Mensajero/efectos de los fármacos , ARN Mensajero/genética , Ratas , Testosterona/administración & dosificación , Testosterona/sangre , Aumento de Peso/efectos de los fármacos , Aumento de Peso/fisiologíaRESUMEN
The effect of the administration route and dose of streptavidin or biotin on the biodistribution of radioactivity in multistep targeting was studied in nude mice bearing intraperitoneal (IP) colon cancer xenograft. The multistep targeting included a two-step method using biotinylated antibody and radiolabeled streptavidin and a three-step method with radiolabeled biotin based on the two-step method. A monoclonal antibody, MLS128, which recognizes Tn antigen on mucin, was biotinylated and injected intravenously (i.v.) or i.p. in nude mice bearing human colon cancer LS180 IP xenografts for pretargeting. In the two-step method, i.p.-injected streptavidin showed a higher tumor uptake and tumor-to-nontumor ratios than i.v.-injected streptavidin regardless of administration route of pretargeting. The tumor uptake of radiolabeled streptavidin was increased with a high dose of biotinylated antibody pretargeting, but decreased with an increasing dose of streptavidin. In the three-step targeting, i.p. injection also gave a higher tumor uptake of radiolabeled biotin than i.v. injection. In conclusion, i.p. administration of radiolabeled streptavidin or biotin resulted in more efficient IP tumor targeting with the multistep methods.