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1.
Clin Exp Hypertens ; 42(6): 545-552, 2020 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-32037898

RESUMEN

BACKGROUND: Renin is the starting point of the renin angiotensin (RA) system cycle. Aliskiren (AL), which is a direct renin inhibitor, suppressed the entire RA cycle. In the present study, the efficacy of add-on of AL treatment in patients with essential hypertension (HT) was investigated. METHODS: This study was a multi-center, open-label, prospective, observational study. Study subjects were patients with essential HT and poor blood pressure (BP) control, who had received calcium channel blocker monotherapy or angiotensin II receptor blocker monotherapy or had not received any BP lowering drugs. Following add-on of AL for 12 months, BP and additional laboratory findings were analyzed. RESULTS: A total of 150 subjects were enrolled. There were 50 dropout subjects including discontinuation. Dropouts were the highest in the ARB combination therapy group at 9 subjects due to adverse events, and 3 of them were due to hyperkalemia. A significantly higher number of patients with chronic kidney disease (CKD) dropped out compared to patients without CKD (φ = 0.166, p < .05). BP before add-on of AL was 155/88 mmHg. After add-on of AL, BP was significantly improved and this lowering was sustained for 3 months (136/78 mmHg, p < .001), 6 months (136/77 mmHg, p < .001) and 12 months (134/78 mmHg, p < .001). In contrast, add-on of AL increased the potassium level and decreased the estimated glomerular filtration rate. CONCLUSION: While add-on AL treatment achieved a favorable and sustained decrease of BP in this study, caution is necessary with regard to elevation of potassium levels and renal impairment.


Asunto(s)
Amidas , Fumaratos , Hiperpotasemia , Insuficiencia Renal , Renina/antagonistas & inhibidores , Anciano , Amidas/administración & dosificación , Amidas/efectos adversos , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Antihipertensivos/clasificación , Presión Sanguínea/efectos de los fármacos , Quimioterapia Combinada , Femenino , Fumaratos/administración & dosificación , Fumaratos/efectos adversos , Tasa de Filtración Glomerular , Humanos , Hiperpotasemia/inducido químicamente , Hiperpotasemia/prevención & control , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud , Insuficiencia Renal/inducido químicamente , Insuficiencia Renal/diagnóstico , Insuficiencia Renal/prevención & control , Sistema Renina-Angiotensina/efectos de los fármacos
2.
J Urol ; 195(6): 1927-35, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26767520

RESUMEN

PURPOSE: We examined the functional role of endogenous IGF-1 (insulin-like growth factor-1) in the recovery phase of stress urinary incontinence induced by simulated childbirth trauma using an IGF-1 receptor inhibitor. MATERIALS AND METHODS: Simulated birth trauma was induced by vaginal distension in female Sprague Dawley® rats. The IGF-1 receptor antagonist JB-1 (10 and 100 µg/kg per day) or vehicle was continuously delivered from 1 day before vaginal distension for 7 days using subcutaneous osmotic pumps. Seven, 14 and 21 days after vaginal distension the effect of JB-1 treatment was examined by functional analyses, including leak point and urethral baseline pressure, and urethral responses during passive increments in intravesical pressure, as well as molecular analyses in urethral tissues, including phosphorylation of Akt, apoptotic changes and peripheral nerve density using Western blot and immunohistochemistry. RESULTS: On functional analyses vehicle treated rats with vaginal distension had significantly decreased leak point and urethral baseline pressure, and urethral responses at 7 days, which recovered to the normal level 14 and 21 days after vaginal distension. In the JB-1 treated vaginal distension group leak point and urethral baseline pressure, and urethral responses were still significantly reduced 21 days after vaginal distension. On molecular analyses JB-1 treatment increased apoptotic cells, induced a significant decrease in phosphorylated Akt and prolonged the decrease of peripheral nerve density in urethral tissues. CONCLUSIONS: Suppression of endogenous IGF-1 activity delayed recovery from stress urinary incontinence induced by simulated childbirth trauma in rats. Thus, IGF-1 is likely to be an important endogenous mediator for functional recovery from childbirth related stress urinary incontinence. This suggests that IGF-1 could be an effective target for treating stress urinary incontinence in women.


Asunto(s)
Complicaciones del Trabajo de Parto/tratamiento farmacológico , Oligopéptidos/uso terapéutico , Parto , Receptor IGF Tipo 1/antagonistas & inhibidores , Incontinencia Urinaria de Esfuerzo/tratamiento farmacológico , Animales , Femenino , Complicaciones del Trabajo de Parto/etiología , Complicaciones del Trabajo de Parto/fisiopatología , Embarazo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Recuperación de la Función , Incontinencia Urinaria de Esfuerzo/etiología , Incontinencia Urinaria de Esfuerzo/fisiopatología , Vagina/fisiopatología
3.
BMC Microbiol ; 16(1): 224, 2016 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-27678340

RESUMEN

BACKGROUND: Despite the high prevalence of genotype 1b hepatitis C virus (HCV) among patients, a cell culture system that permits entire viral life cycle of genotype 1b isolates is limited. To develop a cell-cultured hepatitis C virus (HCVcc) of genotype 1b, the proper combination of HCV genomic variants and host cells is essential. HCV genomes isolated from patients with distinctive symptoms may provide the variants required to establish an HCVcc of genotype 1b. RESULTS: We first established subgenomic replicons in Huh7 cells using HCV cDNAs isolated from two patients: one with fulminant hepatitis after liver transplantation (TPF1) and another with acute hepatitis and moderate symptoms (sAH). Replicons established from TPF1 and sAH showed mutations in NS4B and in NS3 and NS5A, respectively. Using these replication machineries, we constructed HCV genomic RNAs for each isolate. Virus infectivity was evaluated by a focus-forming assay, which is dependent on the intracellular expression of core antigen, and production of virus particles was assessed by density-gradient centrifugation. Infectious virus was only observed in the culture medium of cells transfected with TFP1 HCV RNA. A chimeric genome with the structural segment (5'-untranslated region [UTR] through NS2) from sAH and the replication machinery (NS3 through 3'-UTR) from TPF1 exhibited greater infectivity than did TFP1, despite formation of deficient virus particles in sAH, suggesting that this genomic segment potentiates virus particle formation. To identify the responsible variants, infectious virus formation was assessed in a chimeric genome carrying parts of the sAH structural segment of the TPF1 genome. A variant in NS2 (M170T) was identified that enhanced infectious virus formation. HCVcc carrying an NS2 gene encoding the M170T substitution and adaptive mutations in NS4B (referred to as TPF1-M170T) infected naïve cured Huh7 cells in a CD81-dependent manner. CONCLUSIONS: We established a novel HCVcc of genotype 1b in Huh7 cells by introducing an amino acid variant in NS2 and adaptive mutations in NS4B from HCV genomic RNA isolated from a patient with fulminant HCV after liver transplantation.

4.
Microbiol Immunol ; 60(1): 26-34, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26634303

RESUMEN

The development of effective hepatitis C virus (HCV) vaccines is essential for the prevention of further HCV dissemination, especially in developing countries. Therefore the aim of this study is to establish a feasible and immunocompetent surrogate animal model of HCV infection that will help in evaluation of the protective efficacy of newly developing HCV vaccine candidates. To circumvent the narrow host range of HCV, an HCV genotype 1b-based chimeric clone carrying E1, E2 and p6 regions from GB virus B (GBV-B), which is closely related to HCV, was generated. The chimera between HCV and GBV-B, named HCV/G, replicated more efficiently as compared with the HCV clone in primary marmoset hepatocytes. Furthermore, it was found that the chimera persistently replicated in a tamarin for more than 2 years after intrahepatic inoculation of the chimeric RNA. Although relatively low (<200 copies/mL), the viral RNA loads in plasma were detectable intermittently during the observation period. Of note, the chimeric RNA was found in the pellet fraction obtained by ultracentrifugation of the plasma at 73 weeks, indicating production of the chimeric virus. Our results will help establish a novel non-human primate model for HCV infection on the basis of the HCV/G chimera in the major framework of the HCV genome.


Asunto(s)
Virus GB-B/fisiología , Hepatitis Viral Animal/virología , Enfermedades de los Monos/virología , Platirrinos/virología , Replicación Viral/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Quimera/genética , Quimera/virología , Modelos Animales de Enfermedad , Infecciones por Flaviviridae/virología , Virus GB-B/genética , Virus GB-B/inmunología , Humanos , Datos de Secuencia Molecular , ARN Viral/genética , Vacunas contra Hepatitis Viral/inmunología , Proteínas no Estructurales Virales
5.
Urol Int ; 92(4): 477-81, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24643089

RESUMEN

AIMS: To demonstrate changes in the number of suburothelial myofibroblasts in the rat bladder due to chronic urinary retention (CUR). METHODS: Bladder specimens were obtained from 12-week-old Wistar female rats that were divided into two groups: a CUR group and a sham-operated group. In the CUR rats, the urethra was intubated with a polyethylene catheter, and a double 4-0 silk ligature was placed around the proximal urethra, after which the catheter was removed. After 8 weeks, the cystometric findings and immunohistochemical staining of the suburothelial myofibroblasts were compared between the groups. RESULTS: The bladder weight of the control rats was 0.20 ± 0.01 g and that of CUR rats 1.6 ± 0.4 g. The bladder capacity of the control rats was 0.5 ± 0.3 ml and that of the CUR rats 12.9 ± 3.1 ml. The number of suburothelial myofibroblasts of the control rats was 417 ± 123 and that of the CUR rats 44 ± 42. The number of suburothelial myofibroblasts in the CUR rats was significantly less than that observed in the sham-operated rats (p < 0.01). CONCLUSIONS: In this study, we demonstrated that mechanical stress over a long period on the bladder wall can decrease the number of suburothelial myofibroblasts. The reduced expression of suburothelial myofibroblasts may be related to prolongation of the micturition interval by CUR.


Asunto(s)
Miofibroblastos/patología , Obstrucción del Cuello de la Vejiga Urinaria/terapia , Vejiga Urinaria/patología , Retención Urinaria , Animales , Catéteres , Femenino , Fibroblastos/metabolismo , Inmunohistoquímica , Tamaño de los Órganos , Polietileno , Ratas , Ratas Wistar , Estrés Mecánico , Micción
6.
Pediatr Int ; 56(6): 902-908, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24758352

RESUMEN

BACKGROUND: Despite the fact that functional lower urinary tract symptoms are common among people with Down syndrome (DS), their voiding function has not been studied precisely. Our goal was to assess the lower urinary tract functions in DS. METHODS: Fifty-five DS children aged 5-15 years old and 35 age-matched control children were evaluated by ultrasonography and uroflowmetry. RESULTS: Eleven (20%) DS children had no uresiesthesia, 21 (38%) were urinated under guidance, nine (16%) urinated fewer than three times a day, two (4%) urinated more than 10 times a day, three (5%) used diapers, and 26 (47%) had urinary incontinence. Seven (13%), 15 (27%), and 10 (18%) DS children had weak, prolonged and intermittent urination, respectively, and seven (13%) had urination with straining. In contrast, none of the control subjects had urinary problems. In the uroflowmetrical analysis, 10 (18%), 20 (37%), 11 (20%) and five (9%) DS children showed "bell-shaped," "plateau," "staccato" and "interrupted" patterns, respectively; the remaining nine (16%) could not be analyzed. In contrast, 21 (60%), one (3%), four (11%), three (9%) and two (6%) control subjects showed bell-shaped, tower-shaped, plateau, staccato and interrupted patterns, respectively; the remaining four (11%) could not be analyzed. Residual urine was demonstrated in four (7%) DS children and one (3%) control child. CONCLUSIONS: Lower urinary tract symptoms and abnormal uroflowmetry findings, which can lead to further progressive renal and urinary disorders, are common in DS children. Therefore, lower urinary tract functions should be assessed at the life-long regular medical check-ups for subjects with DS.


Asunto(s)
Síndrome de Down/complicaciones , Síndrome de Down/fisiopatología , Síntomas del Sistema Urinario Inferior/etiología , Sistema Urinario/fisiopatología , Trastornos Urinarios/etiología , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Humanos , Masculino , Reología , Urodinámica
7.
Int J Urol ; 20(5): 522-9, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23050675

RESUMEN

OBJECTIVES: Myostatin, a member of the transforming growth factor-ß superfamily, is a negative regulator of myogenesis in skeletal muscle. We examined the effect of myostatin and myostatin inhibition by an antagonistic agent, follistatin, on growth of human urethral rhabdosphincter satellite cells (muscle stem cells) to develop a new strategy for treatment of stress urinary incontinence. METHODS: Rhabdosphincter satellite cells were cultured and selected by magnetic affinity cell sorting using an anti-neural cell adhesion molecule antibody. The cells were transfected with simian virus-40 antigen to extend their lifespan. A cell proliferation assay, a cell cycle analysis and an investigation of signal transduction were carried out. The autocrine action of endogenous myostatin by western blotting, real-time reverse transcription polymerase chain reaction and immunoneutralization using an anti-myostatin antibody was also evaluated. RESULTS: Selectively cultured cells expressed markers of striated muscles and successfully differentiated into myotubes. Myostatin inhibited proliferation of these cells through Smad2 phosphorylation and cell cycle arrest. Inhibitory effects of myostatin were reversed by addition of follistatin. However, rhabdosphincter satellite cells did not appear to use autocrine secretion of myostatin to regulate their proliferation. CONCLUSIONS: Inhibition of myostatin function might be a useful pathway in the development of novel strategies for stimulating rhabdosphincter cells regeneration to treat stress urinary incontinence.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Miostatina/farmacología , Uretra/efectos de los fármacos , Incontinencia Urinaria de Esfuerzo/tratamiento farmacológico , Comunicación Autocrina , Puntos de Control del Ciclo Celular/efectos de los fármacos , Células Cultivadas , Evaluación Preclínica de Medicamentos , Humanos , Miostatina/uso terapéutico , Transducción de Señal/efectos de los fármacos
8.
Appl Radiat Isot ; 202: 111061, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37793241

RESUMEN

Activity of 225Ac was measured by the digital anti-coincidence spectroscopy technique using a 4πα-γ detector configuration, composed of a sandwich type 4π plastic scintillator and Ge detectors. Ultrathin plastic scintillators were used for selective detection of α-particles emitted from 225Ac and its progenies, and the α-counting efficiencies of a 4π plastic scintillation detector for individual nuclides in the decay chain were determined as well. A list-mode multichannel analyzer was employed to record coincidence/anti-coincidence events for off-line analyses. The time difference distribution spectra revealed α-particle emission following 213Po decay without ß-particle interference from 213Bi.

9.
Auris Nasus Larynx ; 50(6): 952-959, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37164815

RESUMEN

OBJECTIVE: Head and neck cancer (HNC) is a tumor occurring in various primary sites with limited chemotherapy options for its treatment. Recently, comprehensive genomic profiling (CGP) testing has become clinically widespread. In this study, we examined the utility of CGP in diagnosing and treating HNC. METHODS: This study included 29 patients with HNC who underwent CGP testing at the Gifu University Hospital between December 2019 and April 2022. We analyzed the types of gene mutations and tumor mutational burden (TMB) based on the CGP results. Squamous cell carcinoma accounted for 55.2%, and other cancers accounted for 44.8%. And we investigated the correlation of prognosis with gene mutations and TMB. RESULTS: Gene mutations were detected in TP53(48.3%), CDKN2A (27.6%), CDKN2B (17.2%), NOTCH1 (17.2%), PIK3CA (17.2%), ARID1A (13.8%), and NF1 (13.8%). TP53, CDKN2A and CDKN2B mutations significantly decreased survival rate in HNC. Five cases (17.2%) were TMB-high and 82.8% were TMB-low. In SCC cases treated with immune checkpoint inhibitors, TMB-high had better Overall survival than TMB-low. And all patients with TMB-high were oropharyngeal cancer. CONCLUSION: Although there were no cases in which effective treatment was actually performed based on the results of CGP, many gene mutations have been detected and several gene mutations correlated with prognosis. Furthermore, TMB can be used as a biomarker to predict the therapeutic effects of immune checkpoint inhibitors in cases of SCC.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/tratamiento farmacológico , Mutación , Pronóstico , Biomarcadores de Tumor/genética
10.
Biochim Biophys Acta ; 1810(12): 1150-9, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22001438

RESUMEN

BACKGROUND: Scavenger receptors are generally expressed in macrophages and vascular endothelial cells and some scavenger receptors are thought to contribute to the development of atherosclerosis. METHODS: We cloned the cDNA of a zebrafish CL-P1 (collectin placenta 1) and performed a knockdown study using its antisense morpholino oligonucleotides (MO). RESULTS: Zebrafish CL-P1 (zCL-P1) is 51% identical to human CL-P1 in its amino acid sequence. Microbes and OxLDL bound to zCL-P1 cDNA transfected cells. zCL-P1 mRNA expression gradually increased after 6hours post-fertilization (hpf), reached its highest level at 24hpf, and then decreased, which is similar to the gene expression pattern of Tie-2. The knockdown of zCL-P1 led to an increase in the number of zebrafish embryos with severe morphological abnormalities such as short body lengths and defects in the dorsal aorta at 48hpf. Simultaneous injection of both MO and synthetic zCL-P1 or zVEGF mRNA rescued the abnormal phenotype. CONCLUSIONS: In vivo knockdown study shows that zCL-P1 is implicated in vasculogenesis and those of our in vitro study support its role as a scavenger receptor. GENERAL SIGNIFICANCE: These results suggest that zCL-P1 might be essential for vasculogenesis during the early embryonic phase in bone fish.


Asunto(s)
Receptores Depuradores/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Células CHO , Clonación Molecular , Cricetinae , Cricetulus , ADN Complementario , Técnicas de Silenciamiento del Gen , Inmunohistoquímica , Hibridación in Situ , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Receptores Depuradores/fisiología , Pez Cebra
11.
Urol Int ; 89(2): 241-5, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22777104

RESUMEN

PURPOSE: To demonstrate the change in the expression of angiotensin II type 1 receptor (AT1) in the rat bladder with partial bladder outlet obstruction (P-BOO). MATERIALS AND METHODS: Bladder specimens were obtained from 12-week-old Wistar female rats that were divided into two groups, a P-BOO group and a control group. The rats of the P-BOO group were divided into six groups: a sham-operated control group, 1 day postoperatively, 2 days postoperatively, 4 days postoperatively, 7 days postoperatively and 14 days postoperatively. The cystometric findings and immunohistochemical staining of the detrusor muscle with the AT1 antibody were compared in each group. RESULTS: AT1 localized on the cell membrane of the detrusor smooth muscle and in cytoplasm of suburothelial myofibroblasts in the control rats. The expression of AT1 disappeared in the detrusor muscle and suburothelial myofibroblasts in P-BOO, but AT1 was highly expressed in urothelial cells 1 day after surgery. The expression of AT1 in urothelial cells gradually decreased with time after surgery. AT1 completely disappeared in urothelial cells 14 days after surgery. CONCLUSIONS: The present study demonstrated that the site of AT1 expression changes in response to the mechanical stress caused by P-BOO, and finally there was no expression of AT1 in rat bladder tissue following P-BOO. These data suggest the change in AT1 expression may play a role in bladder function.


Asunto(s)
Regulación de la Expresión Génica , Receptor de Angiotensina Tipo 1/biosíntesis , Obstrucción del Cuello de la Vejiga Urinaria/fisiopatología , Vejiga Urinaria/metabolismo , Animales , Femenino , Inmunohistoquímica/métodos , Músculo Liso/patología , Ratas , Ratas Wistar , Estrés Mecánico , Factores de Tiempo , Vejiga Urinaria/patología , Obstrucción del Cuello de la Vejiga Urinaria/metabolismo , Urotelio/patología
12.
Materials (Basel) ; 15(3)2022 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-35160956

RESUMEN

Self-pierce riveting of three thin sheets of 980 MPa steel and 5052 aluminum alloy was performed to investigate the effect of sheet configuration on the deforming behaviors of the sheets and the rivet and joint strength. When the lower sheet was aluminum alloy, the joining range was relatively wide, i.e., the interlock hooking the rivet leg tended to be large. In the sheet configuration in which the upper and lower sheets were A5052 and the middle sheet was 980 MPa steel, the rivet leg spread out moderately and the joint without defects was obtained. In the lower 980 MPa steel sheet, fracture tended to occur due to the low ductility of the lower sheet, and the joining range was narrow with the small interlock although the three sheets were joined by an appropriate die shape. In joint strength of joined three sheets, fracture occurred in the lower-strength aluminum alloy sheet if interlocks of about 300 µm and 150 µm could be formed in the lower aluminum alloy sheet and 980 MPa steel sheet, respectively.

13.
Materials (Basel) ; 15(4)2022 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-35207859

RESUMEN

A low pressure sealed-air hot tube gas forming process of ultra-high strength steel tubes was developed not only to change the cross-section of the hollow products by bulging but also to increase the strength of components. Gas-formed components are typically formed by a controlled-gas pressure with extremely high internal pressure, which leads to affected production costs and safety. Moreover, compressing the gas with high pressure requires high energy during its preparation. Therefore, to simplify the internal pressure controlling system and improve the safety factor in gas forming processes, the sealed-air tubes are formed with a quite low initial pressure. The pressure of the sealed air increased with increasing temperature of the air inside the resistance-heated tube, and the bulging deformation was controlled only by axial feeding. The effects of the initial pressure and heating temperature on the bulging deformation and quenchability of the tubes, and the effect of the starting time of axial feeding on the bulging behavior were examined. Consequently, ultra-high strength steel bulged parts were produced even in low initial internal pressure and with the rapid heating of the tubes.

14.
J Virol ; 84(11): 5824-35, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20237083

RESUMEN

In this study, we used an RNA polymerase I (Pol I) transcription system for development of a reverse genetics protocol to produce hepatitis C virus (HCV), which is an uncapped positive-strand RNA virus. Transfection with a plasmid harboring HCV JFH-1 full-length cDNA flanked by a Pol I promoter and Pol I terminator yielded an unspliced RNA with no additional sequences at either end, resulting in efficient RNA replication within the cytoplasm and subsequent production of infectious virions. Using this technology, we developed a simple replicon trans-packaging system, in which transient transfection of two plasmids enables examination of viral genome replication and virion assembly as two separate steps. In addition, we established a stable cell line that constitutively produces HCV with a low mutation frequency of the viral genome. The effects of inhibitors of N-linked glycosylation on HCV production were evaluated using this cell line, and the results suggest that certain step(s), such as virion assembly, intracellular trafficking, and secretion, are potentially up- and downregulated according to modifications of HCV envelope protein glycans. This Pol I-based HCV expression system will be beneficial for a high-throughput antiviral screening and vaccine discovery programs.


Asunto(s)
Biotecnología/métodos , Hepacivirus/genética , ARN Polimerasa I/metabolismo , Transcripción Genética , Replicación Viral/genética , Línea Celular , Genoma Viral , Hepatitis C/virología , Humanos , Transfección , Proteínas Virales
15.
Oncology ; 80(1-2): 84-91, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21677451

RESUMEN

OBJECTIVES: The prophylactic effect of FOLFOX regimen, a standard regimen for unresectable colorectal cancer (CRC), was investigated in the adjuvant setting of CRC cases with distant metastases. METHODS: The study population included 116 CRC patients with synchronous metastases and 91 patients with metachronous metastases who had undergone curative operation in our hospital between 2000 and 2009. Clinicopathological parameters of CRC, postoperative chemotherapeutic regimen, recurrence rate, and relapse-free survival (RFS) were analyzed retrospectively. RESULTS: After resection of CRC and synchronous metastases, 53 (84%) out of 63 patients without chemotherapy, and 38 (83%) out of 46 that received 5-fluorouracil (5-FU) alone or with leucovorin (LV) developed recurrent tumors. By contrast, only 1 (17%) among 6 patients who underwent FOLFOX treatment showed recurrence. The FOLFOX group exhibited significantly improved RFS as compared to the 5-FU (+ LV) or surgery-alone group (p = 0.03, p = 0.007, respectively). On the other hand, in patients with metachronous metastases, tumor-relapse rate and RFS were not significantly influenced by post-metastasectomy therapies. CONCLUSIONS: In this retrospective analysis, the adjuvant administration of FOLFOX appeared to reduce the risk of relapse in a small group of CRC patients with synchronous metastases. Prospective randomized trials will be required to confirm the benefits of this management strategy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Recurrencia Local de Neoplasia , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante , Neoplasias Colorrectales/cirugía , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Estimación de Kaplan-Meier , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Modelos Logísticos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Estudios Retrospectivos , Tasa de Supervivencia
16.
Circ J ; 75(4): 791-9, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21427500

RESUMEN

BACKGROUND: It is not yet clear whether glycemic control affects the clinical outcome of percutaneous coronary intervention (PCI) in diabetic patients. METHODS AND RESULTS: This study compared the effects of glycemic control on the clinical outcome in 2 groups of patients with diabetes mellitus (DM) who underwent PCI: a poor-glycemic-control group, who showed greater than 6.9% HbA(1c) at the time of PCI (Pre-HbA(1c)) (`≥6.9 group', n=334 patients) and a good-glycemic-control group, who showed less than <6.9% at Pre-HbA(1c) (`<6.9 group', n=212 patients). The patients in the ≥6.9 group were further divided into 2 groups for further comparisons: a `DM control group' and a `Poor control group'. At follow-up (300 days), the incidence of major adverse cardiac event (MACE) was significantly (P<0.05) lower in the <6.9 group (18.4% vs. 26.2%). However, there was no difference in MACE between the DM control group and the Poor control group. In a multivariate analysis, there was no relationship between the incidence of MACE and Pre-HbA(1c), Pre-HbA(1c)≥6.9% or the HbA(1c) difference (Pre-HbA(1c)-HbA(1c) at follow-up). CONCLUSIONS: Clinical outcomes in the <6.9 group were superior to those in the ≥6.9 group as pre-PCI glycemic control affected the baseline characteristics. The results suggested that glycemic control started at PCI was not associated with an improvement in the clinical outcome at follow-up.


Asunto(s)
Angioplastia Coronaria con Balón , Glucemia , Angiopatías Diabéticas/terapia , Índice Glucémico , Anciano , Angiopatías Diabéticas/sangre , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad
17.
J AOAC Int ; 94(6): 1770-7, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22320083

RESUMEN

An analog of aildenafil, which is a potent and highly selective inhibitor of phosphodiesterase 5, was found in a dietary supplement marketed for enhancement of sexual function. The compound was isolated by silica gel column chromatography, and its structure was identified by means of 13C-NMR spectrometry, 1H-NMR spectrometry, high-resolution MS, and X-ray structure determination. The compound was identified to be sulfoaildenafil (other names: thioaildenafil, dimethyl sildenafil thione, and thiomethisosildenafil). Sulfoaildenafil is very similar to the compound thiohomosildenafil. As it is difficult to distinguish between them by LC-photodiode array detector analysis, ultra-performance LC (UPLC)/MS, ion trap LC/MS/MS (LC/IT-MS/MS), and GC/MS were performed. The mass spectra of thiohomosildenafil by UPLC/MS and LC/IT-MS/MS showed mass fragments of m/z 58, 72, and 355, and the mass spectrum by GC/MS showed mass fragments of m/z 56, 72, and 420. Some of these fragments had low intensities, but they were useful for distinguishing between the two compounds. The relationship between aildenafil (other names: dimethylsildenafil and methisosildenafil) and homosildenafil is similar to that between sulfoaildenafil and thiohomosildenafil. Therefore, these compounds were also examined.


Asunto(s)
Suplementos Dietéticos/análisis , Piperazinas/análisis , Sulfonas/análisis , Cromatografía Liquida/métodos , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 5/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Espectroscopía de Resonancia Magnética/métodos , Estructura Molecular , Inhibidores de Fosfodiesterasa 5/análisis , Espectrometría de Masas en Tándem/métodos
18.
Gan To Kagaku Ryoho ; 38(10): 1627-32, 2011 Oct.
Artículo en Japonés | MEDLINE | ID: mdl-21996957

RESUMEN

We investigated the effectiveness of prophylactic FOLFOX after curative resection of synchronous metastases in patients with colorectal cancer (CRC). Clinicopathological information including postoperative chemotherapy, such as a therapeutic regimen, relapse-free survival (RFS), site of recurrence, etc., was retrospectively analyzed in 116 CRC patients with synchronous distant metastases, and 63 patients with metachronous metastases who had received surgery in our hospital between 2000 and 2009. Fifty-three patients (84%) out of 63 without adjuvant chemotherapy, and 38 (83%) out of 46 patients that received oral or intravenous 5-fluorouracil (5-FU) (alone or with leucovorin (LV)or isovorin) developed recurrent tumor(s) afterwards. The median RFSs were 119 and 281 days, respectively. By contrast, a single patient among 6 who underwent FOLFOX (up to 12 therapeutic courses) showed recurrence 476 days after surgery. The RFS of the FOLFOX was significantly higher than that of the 5-FU (+LV) or surgery alone (p=0. 03, p=0. 007, respectively). In conclusion, the FOLFOX regimen is more beneficial for CRC patients with synchronous metastasis as adjuvant chemotherapy than 5-FU (+LV) or other followup strategies.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Femenino , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/tratamiento farmacológico , Compuestos Organoplatinos/uso terapéutico , Recurrencia , Estudios Retrospectivos
19.
Abdom Radiol (NY) ; 46(7): 2993-3001, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33555389

RESUMEN

PURPOSE: The descending branch of the left colic artery (dLCA) is under-recognized and has not been clearly defined. The dLCA is often confused with the sigmoid artery (SA) originating from the left colic artery (LCA). We clarified the anatomical characteristics of the dLCA and searched for surrogate measures to identify it. METHODS: Arterial phase, venous phase, and three-dimensional images of abdominal arteries were created in 411 patients using contrast-enhanced computed tomography (CT). We analyzed the branching patterns of the inferior mesenteric artery (IMA) based on CT. The dLCA was defined as the artery originating from the LCA that flows into the marginal artery along the descending colon. We tested three candidate diagnostic measures for the dLCA using positional relationships and the segment length of vessels. RESULTS: Arteries from the LCA were present in 360 patients, among which 459 dLCAs and 165 SAs were identified in 333 and 146, respectively. By the first measure of identifying the artery with its root lateral to the inferior mesenteric vein (IMV) as the dLCA, the sensitivity, specificity, and accuracy rate were 94%, 87%, and 92%, respectively. The second measure of identifying the artery with its root higher than the root of the IMA as the dLCA and the third of identifying the artery with its root located > 27.6 mm from the root of LCA as the dLCA yielded lower accuracy rates (69% and 89%, respectively). CONCLUSION: Our study demonstrated that dLCAs are prevalent (93%) and may be easily found lateral to the IMV in clinical practice.


Asunto(s)
Arteria Mesentérica Inferior , Venas Mesentéricas , Arterias , Humanos , Imagenología Tridimensional , Arteria Mesentérica Inferior/diagnóstico por imagen , Tomografía Computarizada por Rayos X
20.
Materials (Basel) ; 13(21)2020 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-33114102

RESUMEN

One thin 5000 series aluminium alloy sheet and two thin 980 MPa grade cold rolled ultra-high strength steel sheets were joined by self-pierce riveting and mechanical clinching processes. The joinabilities for a combination of the aluminium and steel sheets in both processes were investigated for different die shapes in the experiment and finite element simulation. In self-pierce riveting, the three sheets were successfully joined for both combinations of the upper and lower aluminium alloy sheets by optimizing the shapes of a die and rivet. In mechanical clinching, the three sheets were successfully joined by an optimum die for the configuration of the upper aluminium alloy sheet. On the other hand, the three sheets for the configuration of the lower aluminium alloy sheet were not joined even by optimizing the die shape in the both finite element simulation and experiment, because the material flow of the steel sheets was insufficient to form the two interlocks. The tension-shear loads for the clinched and riveted sheets with the adhesive were almost the same, because the load for the adhesive was the highest. In the cross-tension test, however, the load by the adhesive was comparatively small.

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