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We tested the gravitational 1/r^{2} law using a stationary torsion-balance detector and a rotating attractor containing test bodies with both 18-fold and 120-fold azimuthal symmetries that simultaneously tests the 1/r^{2} law at two different length scales. We took data at detector-attractor separations between 52 µm and 3.0 mm. Newtonian gravity gave an excellent fit to our data, limiting with 95% confidence any gravitational-strength Yukawa interactions to ranges <38.6 µm.
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BACKGROUND: Immune checkpoint blockade with Programmed cell death 1 (PD-1)/PD-L1 inhibitors has been effective in various malignancies and is considered as a standard treatment modality for patients with non-small-cell lung cancer (NSCLC). However, emerging evidence show that PD-1/PD-L1 blockade can lead to hyperprogressive disease (HPD), a flair-up of tumor growth linked to dismal prognosis. This study aimed to evaluate the incidence of HPD and identify the determinants associated with HPD in patients with NSCLC treated with PD-1/PD-L1 blockade. PATIENTS AND METHODS: We enrolled patients with recurrent and/or metastatic NSCLC treated with PD-1/PD-L1 inhibitors between April 2014 and November 2018. Clinicopathologic variables, dynamics of tumor growth, and treatment outcomes were analyzed in patients with NSCLC who received PD-1/PD-L1 blockade. HPD was defined according to tumor growth kinetics (TGK), tumor growth rate (TGR), and time to treatment failure (TTF). Immunophenotyping of peripheral blood CD8+ T lymphocytes was conducted to explore the potential predictive biomarkers of HPD. RESULTS: A total of 263 patients were analyzed. HPD was observed in 55 (20.9%), 54 (20.5%), and 98 (37.3%) patients according to the TGK, TGR, and TTF. HPD meeting both TGK and TGR criteria was associated with worse progression-free survival [hazard ratio (HR) 4.619; 95% confidence interval (CI) 2.868-7.440] and overall survival (HR, 5.079; 95% CI, 3.136-8.226) than progressive disease without HPD. There were no clinicopathologic variables specific for HPD. In the exploratory biomarker analysis with peripheral blood CD8+ T lymphocytes, a lower frequency of effector/memory subsets (CCR7-CD45RA- T cells among the total CD8+ T cells) and a higher frequency of severely exhausted populations (TIGIT+ T cells among PD-1+CD8+ T cells) were associated with HPD and inferior survival rate. CONCLUSION: HPD is common in NSCLC patients treated with PD-1/PD-L1 inhibitors. Biomarkers derived from rationally designed analysis may successfully predict HPD and worse outcomes, meriting further investigation of HPD.
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Antineoplásicos Inmunológicos/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Linfocitos T CD8-positivos/inmunología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/inmunología , Metástasis Linfática , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , Pronóstico , Tasa de Supervivencia , Carga TumoralRESUMEN
BACKGROUND: We conducted co-clinical trials in patient-derived xenograft (PDX) models to identify predictive biomarkers for the multikinase inhibitor dovitinib in lung squamous cell carcinoma (LSCC). METHODS: The PDX01-02 were established from LSCC patients enrolled in the phase II trial of dovitinib (NCT01861197) and PDX03-05 were established from LSCC patients receiving surgery. These five PDX tumors were subjected to in vivo test of dovitinib efficacy, whole exome sequencing and gene expression profiling. RESULTS: The PDX tumors recapitulate histopathological properties and maintain genomic characteristics of originating tumors. Concordant with clinical outcomes of the trial enrolled-LSCC patients, dovitinib produced substantial tumor regression in PDX-01 and PDX-05, whereas it resulted in tumor progression in PDX-02. PDX-03 and -04 also displayed poor antitumor efficacy to dovitinib. Mutational and genome-wide copy number profiles revealed no correlation between genomic alterations of FGFR1-3 and sensitivity to dovitinib. Of note, gene expression profiles revealed differentially expressed genes including FGF3 and FGF19 between PDX-01 and 05 and PDX-02-04. Pathway analysis identified two FGFR signaling-related gene sets, FGFR ligand binding/activation and SHC-mediated cascade pathway were substantially up-regulated in PDX-01 and 05, compared with PDX-02-04. The comparison of gene expression profiles between dovitinib-sensitive versus -resistant lung cancer cell lines in the Cancer Cell Line Encyclopedia database also found that transcriptional activation of 18 key signaling components in FGFR pathways can predict the sensitivity to dovitinib both in cell lines and PDX tumors. These results highlight FGFR pathway activation as a key molecular determinant for sensitivity to dovitinib. CONCLUSIONS: FGFR gene expression signatures are predictors for the response to dovitinib in LSCC.
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Bencimidazoles/uso terapéutico , Biomarcadores/sangre , Carcinoma de Células Escamosas/tratamiento farmacológico , Ensayos Clínicos como Asunto , Neoplasias Pulmonares/tratamiento farmacológico , Quinolonas/uso terapéutico , Receptores de Factores de Crecimiento de Fibroblastos/antagonistas & inhibidores , Carcinoma de Células Escamosas/genética , Humanos , Neoplasias Pulmonares/genética , Mutación , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal , Secuenciación del ExomaRESUMEN
This study was performed to examine whether capsaicin, the main pungent ingredient of red peppers, exerts protective effects against testicular injuries induced by transient scrotal hyperthermia. Capsaicin (0.33 mg kg-1 ) was administered subcutaneously to mice one hour before heat stress (HS) in a 43°C water bath for 20 min. After 7 days, mice exposed to HS showed low testicular weight, severe vacuolisation of seminiferous tubules followed by loss of spermatogenic cells, and appearance of multinucleated giant cells and remarkable TUNEL-positive apoptotic cells, as well as weak immunoreactivity of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in spermatogenic cells. Levels of lipid peroxidation and heat shock 70-kDa protein 1 (Hsp72) and BCL2-associated X protein (Bax) mRNA were greatly increased, but PHGPx, manganese superoxide dismutase (MnSOD), and B-cell lymphoma-extra large (Bcl-xL) mRNAs were significantly diminished in the testes by HS. However, capsaicin pre-treatment significantly suppressed the spermatogenic cell death, oxidative stress (levels of MDA, PHGPx immunoreactivity, and Hsp72, PHGPx, and MnSOD mRNA) and apoptosis (levels of TUNEL-positive cells, and Bcl-xL and Bax mRNA) in testes by HS. These suggest that capsaicin has a protective effect against spermatogenic cell death induced by scrotal hyperthermia through its antioxidative and anti-apoptotic activities.
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Apoptosis/efectos de los fármacos , Capsaicina/administración & dosificación , Calor , Escroto/fisiología , Espermatogénesis/fisiología , Animales , Antioxidantes , Glutatión Peroxidasa/análisis , Glutatión Peroxidasa/genética , Proteínas del Choque Térmico HSP72/genética , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Fosfolípido Hidroperóxido Glutatión Peroxidasa , ARN Mensajero/análisis , Espermatogénesis/efectos de los fármacos , Espermatozoides/citología , Espermatozoides/enzimología , Espermatozoides/fisiología , Superóxido Dismutasa/genética , Testículo/química , Testículo/citología , Testículo/fisiología , Proteína X Asociada a bcl-2/genéticaRESUMEN
Apoptosis during engraftment and inflammation induce poor islet xenograft survival. We aimed to determine whether overexpression of human heme oxygenase-1 (HO-1) or soluble tumor necrosis factor-α receptor type I with human IgG1 Fc (sTNF-αR-Fc) in porcine islets could improve islet xenograft survival. Adult porcine islets were transduced with adenovirus containing human HO-1, sTNF-αR-Fc, sTNF-αR-Fc/HO-1 or green fluorescent protein (control). Humanized mice were generated by injecting human cord blood-derived CD34(+) stem cells into NOD-scid-IL-2Rγ(null) mice. Both HO-1 and sTNF-αR-Fc reduced islet apoptosis under in vitro hypoxia or cytokine stimuli and suppressed RANTES induction without compromising insulin secretion. Introduction of either gene into islets prolonged islet xenograft survival in pig-to-humanized mice transplantation. The sTNF-αR-Fc/HO-1 group showed the best glucose tolerance. Target genes were successfully expressed in islet xenografts. Perigraft infiltration of macrophages and T cells was suppressed with decreased expression of RANTES, tumor necrosis factor-α and IL-6 in treatment groups; however, frequency of pig-specific interferon-γ-producing T cells was not decreased, and humoral response was not significant in any group. Early apoptosis of islet cells was suppressed in the treatment groups. In conclusion, overexpression of HO-1 or sTNF-αR-Fc in porcine islets improved islet xenograft survival by suppressing both apoptosis and inflammation. HO-1 or sTNF-αR-Fc transgenic pigs have potential for islet xenotransplantation.
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Diabetes Mellitus Experimental/prevención & control , Hemo-Oxigenasa 1/genética , Inmunoglobulina G/genética , Trasplante de Islotes Pancreáticos , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Animales , Apoptosis , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/cirugía , Modelos Animales de Enfermedad , Citometría de Flujo , Humanos , Islotes Pancreáticos/citología , Ratones , Ratones Endogámicos NOD , Ratones SCID , Reacción en Cadena en Tiempo Real de la Polimerasa , Porcinos , Trasplante HeterólogoRESUMEN
OBJECTIVES: The aim of this study was to evaluate the persistence with solifenacin therapy over a 12-month period in patients with overactive bladder (OAB). METHODS: This is a 52-week long, multicenter, prospective, observational study. The subjects were individuals ≥ 18 years old with OAB symptoms for ≥ 3 months, characterised by a total OAB Symptom Score (OABSS) of ≥ 3 and OABSS urgency item score of ≥ 2. Patients were prescribed 5 mg or 10 mg of solifenacin once daily for OAB symptoms. Drug persistence, reasons for discontinuation and factors related to the persistence were evaluated. RESULTS: A total of 1018 patients (329 men, 689 women) with a mean age of 59 years were included. The 52-week drug persistence rate was 22.1%. The drug persistence rates at 12, 24 and 36 weeks were 72.4%, 45.8% and 31.1% respectively. The three most common reasons for discontinuing therapy included symptom improvement in 30.4%, lack of efficacy in 13.4%, and a switch to another antimuscarinic agent in 10.8%. Older patients (odds ratio = 1.02, 95% CI: 1.01-1.04), and female patients (odds ratio = 1.94, 95% CI: 1.37-2.75) were more likely to continue the medication over the 12-month period than were younger, male patients. The number of nocturia episodes was negatively correlated with drug persistence (odds ratio = 0.83, 95% CI: 0.71-0.97). CONCLUSIONS: There was low persistence (22%) to solifenacin therapy for OAB symptoms over a 12-month period. Older patients, female patients and those with fewer episodes of nocturia were more persistent to therapy than were others.
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Succinato de Solifenacina/uso terapéutico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Urodinámica/efectos de los fármacos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Vejiga Urinaria Hiperactiva/fisiopatología , Agentes Urológicos/uso terapéuticoRESUMEN
OBJECTIVES: We hypothesised that paediatric chronic sinusitis patients might have various clinical characteristics, depending on age, compared symptoms, physical findings and clinical features in younger children and older adolescent patients who underwent endoscopic sinus surgery. DESIGN: A retrospective review of medical records. SETTING: A total of 195 paediatric patients who underwent Endoscopic sinus surgery were enrolled and medical records were reviewed. PARTICIPANTS: The subjects were divided into children (age < 12 years, n = 70, mean age = 9.6 years) and adolescents (age ≥ 12 years, n = 125, mean age = 14.7 years). MAIN OUTCOME MEASURES: Subjective symptoms, physical findings, CT images and clinical features were compared in children and adolescent groups. RESULTS: Cough and nasal obstruction were more common in adolescents, and sleep disturbance was more common in children. Nasal mucosal injection was more common in adolescents, whereas tonsils were larger in children. Septal deviation was a more common finding in adolescents, and total CT score and serum total IgE levels were higher in children. There was no statistical difference in rate of recurrence after endoscopic sinus surgery. CONCLUSION: The clinical features of paediatric chronic sinusitis differed between the younger and older groups. Symptomatic, anatomical and clinical differences between these two groups suggest that further study of paediatric chronic sinusitis should stratify patients by age to better understand the effects of treatment on each age group.
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Endoscopía/métodos , Sinusitis/cirugía , Adolescente , Factores de Edad , Niño , Enfermedad Crónica , Tos , Femenino , Humanos , Masculino , Obstrucción Nasal/cirugía , Estudios Retrospectivos , Sinusitis/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
We used a torsion pendulum and rotating attractor with 20-pole electron-spin distributions to probe dipole-dipole interactions mediated by exotic pseudo-Goldstone bosons with m(b)c(2)≤500 µeV and coupling strengths up to 14 orders of magnitude weaker than electromagnetism. This corresponds to symmetry-breaking scales F≤70 TeV, the highest reached in any laboratory experiment. We used an attractor with a 20-pole unpolarized mass distribution to improve laboratory bounds on CP-violating monopole-dipole forces with 1.5 µeV
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AIM: To explore the rate of add-on therapy with solifenacin in men with voiding and storage lower urinary tract symptoms (LUTS) after tamsulosin monotherapy and to explore predictive factors for starting solifenacin add-on therapy. METHODS: Men aged ≥ 45 years with IPSS ≥ 12 and symptoms of OAB (OAB-V8 ≥ 8, micturition ≥ 8/24 h, urgency ≥ 2/24 h) were enrolled to receive tamsulosin 0.2 mg once daily. After 4 weeks, men with residual symptoms of OAB and reported 'dissatisfied' or 'a little satisfied' were received solifenacin 5 mg in combination with tamsulosin monotherapy. Subjects completed an IPSS, a Quality of life (QoL) index, OAB V8, and an International Consultation of Incontinence Questionnaire (ICIQ)-Male LUTS, and patient perception of bladder condition (PPBC) at baseline and week 4. RESULTS: Of a total of 305 patients, 254 patients completed 4 weeks of tamsulosin treatment. For 176 patients, solifenacin was added (69.3%). Significant predictive factors of solifenacin add-on therapy included long LUTS duration, high IPSS, number of micturitions per 24 h, more urgency episodes, high urgency severity score in a voiding diary and high OAB V8 score. Based on multivariable analysis, potential predictive factors of solifenacin add-on therapy included long LUTS duration (OR = 1.008, 95% CI: 1.001-1.014), high serum PSA (OR = 1.543, 95% CI: 1.136-2.095) and small prostate size (OR = 0.970, 95% CI: 0.947-0.994) (p < 0.05). IPSS, daytime micturitions and urgency episodes, OAB V8 scores, ICIQ and PPBC were improved after tamsulosin monotherapy. CONCLUSIONS: Two thirds of men with voiding and storage LUTS needed to add anticholinergics after 4 weeks of tamsulosin monotherapy. Patients with longer lasting symptoms and storage symptoms with small prostate volume may require the anticholinergic add-on.
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Antagonistas de Receptores Adrenérgicos alfa 1/uso terapéutico , Antagonistas Muscarínicos/uso terapéutico , Succinato de Solifenacina/uso terapéutico , Sulfonamidas/uso terapéutico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Agentes Urológicos/uso terapéutico , Anciano , Anciano de 80 o más Años , Quimioterapia Combinada , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , TamsulosinaRESUMEN
AIMS: In spite of the reported efficacy and safety of antimuscarinics in men with OAB (overactive bladder) and BPO (benign prostatic obstruction), many patients do not persist with the treatment. We aimed to evaluate persistence and the reasons for the discontinuation of solifenacin add-on therapy in men with residual symptoms of OAB after tamsulosin monotherapy for BPO in a real clinical environment. METHODS: Men aged ≥ 45 years with IPSS ≥ 12 and symptoms of OAB (OAB-V8 ≥ 8, micturition ≥ 8/24 h, urgency ≥ 2/24 h) were prescribed tamsulosin 0.2 mg. After 4 weeks, men who had residual symptoms of OAB (OAB-V8 ≥ 8, micturition ≥ 8/24 h, urgency ≥ 1/24 h) and reported that they were 'dissatisfied' or 'a little satisfied' with the therapy were enrolled and prescribed solifenacin 5 mg in combination with tamsulosin. After 52 weeks, persistence and the reasons for the discontinuation of solifenacin were evaluated. Factors related to persistence were analysed. RESULTS: Of the 305 men who had been treated with tamsulosin, 176 were prescribed solifenacin. After 52 weeks, 44 (25%) remained on solifenacin therapy. Of the 132 who discontinued solifenacin, 85 were evaluated on the reason for discontinuation. The three most common reasons for discontinuation were adverse events (AEs) (35%), lack of efficacy (33%), and improvement in symptoms (16%). The aggravation of voiding symptoms was the most common AE leading to discontinuation. Retention was observed in 11 men. None of the demographical or clinical characteristics were significantly related to persistence. CONCLUSIONS: Only 25% men with OAB and BPO remained on antimuscarinic add-on therapy after 1 year, mostly because of AEs and lack of efficacy. Realistic data should be added to what is already known about antimuscarinic treatment in men by including patients who were excluded or who dropped out of well-designed clinical trials.
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Quimioterapia Combinada , Antagonistas Muscarínicos/uso terapéutico , Hiperplasia Prostática/tratamiento farmacológico , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Humanos , Masculino , Antagonistas Muscarínicos/efectos adversos , Quinuclidinas/administración & dosificación , Succinato de Solifenacina/farmacología , Succinato de Solifenacina/uso terapéutico , Sulfonamidas/farmacología , Sulfonamidas/uso terapéutico , Tamsulosina , Tetrahidroisoquinolinas/administración & dosificaciónRESUMEN
AIM: To assess the efficacy and safety of imidafenacin compared with propiverine for treatment of overactive bladder (OAB) in Korean patients. MATERIALS AND METHODS: Patients with OAB symptoms were randomised to double-blind treatment with 0.1 mg of imidafenacin twice daily (group A) or propiverine 20 mg once daily (group B) for 12-week regimen, and assessed for efficacy and safety. The primary efficacy outcome was per cent change of weekly urgency urinary incontinence (UUI) episodes at week 12. The secondary efficacy outcomes were changes in the micturitions per day, urine volume voided per micturition, urgency episodes per day, complete disappearance of incontinence episodes and severity of urgency from baseline to week 12. Quality of life and safety profiles were also compared. RESULTS: Of 162 patients randomised, 140 completed the study protocol. The per cent change of weekly UUI episodes at week 12 was -69.1% in group A and -70.4% in group B (both p < 0.0001). The lower limit of 95% one-sided confidence interval of the difference between the groups was above the non-inferiority margin (-19.42%). Other voiding parameters and quality of life significantly improved at week 12 in both the groups. The discontinuation rates caused by adverse events were low in both the groups. While dry mouth was the most common adverse event (group A: 28.4% vs. B: 30.4%, p = 0.783), the severity of dry mouth was significantly less in the group A than B (p = 0.042) There were no significant differences in other safety profiles. CONCLUSIONS: After the 12-week treatment of imidafenacin 0.1 mg twice daily, all OAB symptoms and quality of life improved. Imidafenacin was not inferior to propiverine for the reduction of UUI episodes, and was better tolerated than propiverine in the safety profile. Our results indicate that imidafenacin is a safe and effective drug in Korean patients with OAB.
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Bencilatos/administración & dosificación , Imidazoles/administración & dosificación , Antagonistas Muscarínicos/administración & dosificación , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Agentes Urológicos/administración & dosificación , Bencilatos/efectos adversos , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Imidazoles/efectos adversos , Masculino , Persona de Mediana Edad , Antagonistas Muscarínicos/efectos adversos , Estudios Prospectivos , Resultado del Tratamiento , Incontinencia Urinaria/tratamiento farmacológico , Micción/efectos de los fármacos , Agentes Urológicos/efectos adversosRESUMEN
With the recent availability of removable esophageal stents, endoscopic stenting has been utilized to treat refractory benign esophageal strictures (RBES). The objective of this study was to review the feasibility and effectiveness of removable esophageal stents to treat RBES. Patients who received removable esophageal stents for the treatment of RBES at the institution between 2004-2010 using its stent implantation logs and endoscopic database were retrospectively identified. Patient demographics, stricture etiology and location, stent and procedure characteristics, and clinical outcomes were obtained. Twenty-five patients with a mean age of 70 (72% male) underwent initial stent placement; 24 were successful. Overall clinical success was achieved in five of the 19 patients (26%) ultimately undergoing stent removal. RBES etiologies included anastomotic (13), radiation (5), peptic (3), chemotherapy (1), scleroderma (1), and unknown (2). Alimaxx-E (Merit-Endotek, South Jordan, UT, USA) stents were placed in 20 patients and Polyflex (Boston Scientific, Natick, MA, USA) stents were used in five patients. Immediate complications included failed deployment (1) and chest pain (7). Five patients died prior to stent removal. Stent migration was found in 53% (10/19) of patients who underwent stent removal: nine required additional therapy and one had symptom resolution. Out of the nine patients without stent migration, five required additional therapy and four had symptom resolution. Although placement of removable esophageal stents for RBES is technically feasible, it is frequently complicated by stent migration and chest pain. In addition, few patients achieved long-term stricture resolution after initial stenting. In this study, most patients ultimately required repeated stenting and/or dilations to maintain relief of dysphagia.
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Estenosis Esofágica/terapia , Stents , Adulto , Anciano , Anciano de 80 o más Años , Dolor en el Pecho/etiología , Trastornos de Deglución/etiología , Dilatación , Estenosis Esofágica/complicaciones , Esofagoscopía , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Falla de Prótesis , Retratamiento , Estudios Retrospectivos , Stents/efectos adversos , Insuficiencia del Tratamiento , Adulto JovenRESUMEN
It was discovered recently that infection by a protozoan parasite, Azumiobodo hoyamushi, is the most probable cause for soft tunic syndrome in an edible ascidian, Halocynthia roretzi (Drasche). In an attempt to develop measures to eradicate the causative parasite, various drugs were tested for efficacy in vitro and in vivo. Of the 20 antiprotozoal drugs having different action mechanisms, five were found potent (24-h EC50 < 10 mg L(-1) ) in their parasite-killing effects: formalin, H2 O2 , bithionol, ClO2 and bronopol. Moderately potent drugs (10 < 24-h EC50 < 100 mg L(-1) ) were quinine, fumagillin, amphotericin B, ketoconazole, povidone-iodine, chloramine-T and benzalkonium chloride. Seven compounds, metronidazole, albendazole, paromomycin, nalidixic acid, sulfamonomethoxine, KMnO4 , potassium monopersulphate and citric acid, exhibited EC50 > 100 mg L(-1) . When ascidians were artificially infected with A. hoyamushi, treated using 40 mg L(-1) formalin, bronopol, ClO2 , or H2 O2 for 1 h and then monitored for 24 h, very low mortality was observed. However, the number of surviving parasite cells in the ascidian tunic tissues was significantly reduced by treating with 40 mg L(-1) formalin or ClO2 for 1 h. The data suggest that we might be able to develop a disinfection measure using a treatment regimen involving commonly available drugs.
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Antiprotozoarios/farmacología , Kinetoplastida/efectos de los fármacos , Urocordados/parasitología , Animales , Acuicultura , Desinfectantes/farmacología , Kinetoplastida/fisiologíaRESUMEN
AIMS: Our objective was to compare the efficacy and safety of imidafenacin over fesoterodine in patients with overactive bladder (OAB). METHODS: This study is a randomised, double-blind, parallel-group, fesoterodine-controlled study in patients with continuous OAB symptoms for ≥ 3 months, daily mean voiding frequency (DMVF) ≥ 8, and daily mean urgency or urgency incontinence frequency ≥ 2. A twice-daily 0.1 mg imidafenacin with placebo, or once-daily 4 mg fesoterodine with placebo were administered for 12 weeks. The primary efficacy end-point was the difference in DMVF at 12 weeks. The secondary efficacy end-points were differences in daily mean: (i) voiding frequency at 4 and 8 weeks; (ii) urgency frequency; (iii) urgency incontinence frequency; (iv) incontinence frequency; (v) nocturia frequency; and (vi) quality of life score. The variables for safety analysis were adverse events, vital signs, residual urine volume and clinical laboratory tests. An efficacy analysis was conducted in per-protocol patients and the safety analysis was conducted in all randomised patients. RESULTS: The differences in DMVF at 12 weeks were -3.38 ± 3.63 and -2.45 ± 3.73 in the imidafenacin and fesoterodine groups, respectively, and the difference was not significant between the two groups. Imidafenacin was non-inferior to fesoterodine, and the lower limit of 95% two-sided confidence intervals was -0.53. The other six secondary end-points and variables for safety analysis showed no difference between the two groups. CONCLUSIONS: Imidafenacin was non-inferior to fesoterodine in terms of efficacy, and showed no significant difference in terms of safety.
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Compuestos de Bencidrilo/administración & dosificación , Imidazoles/administración & dosificación , Antagonistas Muscarínicos/administración & dosificación , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Análisis de Varianza , Compuestos de Bencidrilo/efectos adversos , Método Doble Ciego , Esquema de Medicación , Femenino , Estado de Salud , Humanos , Imidazoles/efectos adversos , Masculino , Persona de Mediana Edad , Antagonistas Muscarínicos/efectos adversos , Resultado del Tratamiento , Agentes UrológicosRESUMEN
INTRODUCTION: Selective cannulation fails in approximately 3â% of endoscopic retrograde cholangiography (ERC) procedures. An endoscopic ultrasound-guided rendezvous technique (EUSâ-âRV) may salvage failed cannulation. The aims of the current study were to determine the safety and efficacy of EUSâ-âRV. METHODS: A total of 40 patients underwent salvage EUSâ-âRV. EUSâ-âRV was attempted immediately after failed biliary cannulation. A dilated intra- or extra-hepatic biliary duct (IHBD or EHBD) was punctured from the stomach or the small intestine under EUS guidance followed by cholangiography and antegrade manipulation of the guide wire into the small intestine. Finally, the echoendoscope was exchanged for an appropriate endoscope and biliary cannulation was achieved over or adjacent to the guide wire. RESULT: EUS-RV appears safe and effective and may be considered as a primary salvage technique after failed cannulation. Antegrade manipulation of the guide wire into the small intestine was achieved in 29 of 40 patients (73â%; EHBD 25â/31 and IHBD 4/9). The reasons for failure were inability to advance the guide wire through an obstruction or a native ampulla. Re-attempt at ERC immediately after failed EUSâ-âRV was made in seven of the 11 patients, and was successful in four. The remaining seven patients underwent percutaneous drainage within 3 days. Complications occurred in five patients (13â%), including pancreatitis, abdominal pain, pneumoperitoneum, and sepsis/death, which was unlikely to be related to the procedure. CONCLUSION: EUSâ-âRV is safe and effective and should be considered as a primary salvage technique after failed cannulation. Immediate re-attempt at ERC after failed EUSâ-âRV is warranted, as EUS-guided cholangiogram can facilitate biliary cannulation in some cases. Finally, prompt alternative biliary drainage should be available.
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Enfermedades de los Conductos Biliares/cirugía , Colangiografía/métodos , Endoscopía del Sistema Digestivo/métodos , Terapia Recuperativa/métodos , Ultrasonografía Intervencional , Dolor Abdominal/etiología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de los Conductos Biliares/diagnóstico por imagen , Conductos Biliares/diagnóstico por imagen , Cateterismo/métodos , Colangiografía/efectos adversos , Drenaje/métodos , Endoscopía del Sistema Digestivo/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis/etiología , Neumoperitoneo/etiología , Estudios Retrospectivos , Terapia Recuperativa/efectos adversosRESUMEN
AIMS: To evaluate the efficacy and treatment satisfaction with low-dose (0.2 mg) tamsulosin in patients with symptomatic benign prostatic hyperplasia (BPH), and to investigate individual lower urinary tract symptoms according to treatment satisfaction. METHODS: A cross-sectional study was conducted in a total sample of 2574 patients from multiple centres. International Prostate Symptom Score (IPSS), prostate volume, uroflowmetry and combined medications were reviewed. Detailed questionnaires were used to assess treatment satisfaction and IPSS 8 weeks after treatment with low-dose tamsulosin. RESULTS: After 8 weeks of treatment with low-dose tamsulosin, IPSS improved significantly. Among the 2574 patients, 1,630 (63.42%) were satisfied and 940 patients (36.50%) were dissatisfied with low-dose tamsulosin. The reasons for dissatisfaction included efficacy problems (84.66%) and side effects (3.72%). Treatment satisfaction was affected by symptom duration, baseline IPSS, and prostate size (p = 0.0441, < 0.001, < 0.009, respectively). IPSS voiding (IPSS-V) and IPSS storage (IPSS-S) after treatment differed significantly depending on the degree of satisfaction (p < 0.001). IPSS-V after treatment did not improve in patients who were 'not satisfied' or 'totally not satisfied' (p = 0.170, 0.240, respectively). All the individual IPSS items except urgency (p = 0.1436) varied significantly with the degree of satisfaction (p < 0.001). CONCLUSIONS: Treating symptomatic BPH with low-dose tamsulosin improved IPSS, but more than one-third of patients were dissatisfied with the treatment. The main reason for dissatisfaction was efficacy problems, and the degree of satisfaction was related to symptom duration, baseline IPSS, and prostate size, and also to IPSS-V. In patients with severe LUTS, the tamsulosin dose should be increased earlier.
Asunto(s)
Antagonistas de Receptores Adrenérgicos alfa 1/administración & dosificación , Satisfacción del Paciente , Hiperplasia Prostática/tratamiento farmacológico , Sulfonamidas/administración & dosificación , Anciano , Anciano de 80 o más Años , Estudios Transversales , Humanos , Síntomas del Sistema Urinario Inferior/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Hiperplasia Prostática/psicología , Tamsulosina , Resultado del Tratamiento , Micción/efectos de los fármacosRESUMEN
AIM: To assess the effects of ginseng saponin on relaxation of the bladder and prostatic urethra and to determine its mechanism of action. MATERIALS AND METHODS: For the in vitro study, prostatic urethra muscle strips were harvested from 18 male New Zealand rabbits. The strips were mounted in organ baths and connected to force displacement transducers. After stabilization, maximal tissue contractions were obtained by the application of phenylepinephrine to the urethra strips, and a dose-response curve for ginseng saponin was constructed (10(-6)-10(-2)M). After pretreatment of urethra strips with N-nitro-L-arginine methyl ester (L-NAME), another dose-response curve for ginseng saponin was constructed. For the in vivo study, we used adult male Sprague-Dawley rats divided into three groups [control, partial bladder outlet obstruction (PBOO) and saponin-fed groups], and we monitored the vesical pressure (P(ves)) and urethral perfusion pressure (UPP). RESULTS: The ginseng saponin induced a significant dose-dependent relaxant effect on the prostatic urethra strips. A significant relaxant effect of ginseng saponin was observed from 10(-3)M, and ginseng saponin significantly relaxed urethra strips by 50.2 ± 20.26% at 10(-2)M. The relaxant effect was partially inhibited with L-NAME pretreatment. In the in vivo study, the change in UPP between baseline and relaxation was significantly higher in the saponin group than in the control or PBOO group (p < 0.001). The saponin group showed a significantly lower baseline P(ves) than the PBOO group. CONCLUSIONS: We observed a significant relaxation effect of ginseng saponin on the bladder and prostatic urethra in both in vitro and in vivo studies. The mechanism by which ginseng saponin induces relaxation appears to involve the nitric oxide/nitric oxide synthase pathway.
Asunto(s)
Relajación Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Panax , Extractos Vegetales/farmacología , Saponinas/farmacología , Uretra/efectos de los fármacos , Obstrucción del Cuello de la Vejiga Urinaria/tratamiento farmacológico , Vejiga Urinaria/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Técnicas In Vitro , Masculino , Músculo Liso/metabolismo , Músculo Liso/fisiopatología , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Panax/química , Fenilefrina/farmacología , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas , Presión , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/fisiopatología , Conejos , Ratas , Ratas Sprague-Dawley , Saponinas/aislamiento & purificación , Uretra/metabolismo , Uretra/fisiopatología , Vejiga Urinaria/metabolismo , Vejiga Urinaria/fisiopatología , Obstrucción del Cuello de la Vejiga Urinaria/etiología , Obstrucción del Cuello de la Vejiga Urinaria/metabolismo , Obstrucción del Cuello de la Vejiga Urinaria/fisiopatología , Urodinámica/efectos de los fármacosRESUMEN
PURPOSE: During mastication, mechanical pressure from the dentition is transmitted to the trabecular bone of the mandible. The occlusal forces, which could thus affect condylar growth, vary with tooth loss, age, and sex. The trabecular bone of the mandibular condyle is denser in dentate subjects than in edentate subjects. However, since the different tooth groups (incisor, premolar, and molar) have different functions, they could exert different effects on the mandibular condyle. The aim of this study was to elucidate the bone quantity of the Korean mandibular condyle according to the presence of teeth using micro-computed tomography (micro-CT), thereby clarifying the influences of tooth presence on the condylar microstructure. METHODS: Thirty-one sides were scanned and reconstructed into a 3D structure using a micro-CT system. The specimen was sectioned vertically, passing through the medial and lateral poles of the mandibular condyle (P0) to enable measurement of the trabecular bone ratio. Likewise, three additional images, parallel with P0, were acquired. Mean and standard deviation values were calculated, and the t test, one-way ANOVA and post hoc analysis were performed to examine the differences among each group, classified according to the presence of teeth and according to sex. RESULTS: The density of the trabecular bone of the mandibular condyle was significantly associated with the presence of the molars, but not the incisors or premolars. There were significant differences between sexes. CONCLUSIONS: The present study has provided data regarding the bone quantity of the trabeculae of the mandibular condyle according to the presence or absence of teeth.
Asunto(s)
Densidad Ósea , Cóndilo Mandibular/diagnóstico por imagen , Pérdida de Diente/diagnóstico por imagen , Diente/diagnóstico por imagen , Microtomografía por Rayos X/métodos , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Diente Premolar/diagnóstico por imagen , Cadáver , Dentición , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Incisivo/diagnóstico por imagen , Corea (Geográfico) , Masculino , Mandíbula/diagnóstico por imagen , Persona de Mediana Edad , Diente Molar/diagnóstico por imagen , Distribución por SexoRESUMEN
Yttria-doped bismuth oxide (YBO) powders were synthesized by ammonium carbonate coprecipitation for the preparation of electrolytes of an intermediate temperature solid oxide fuel cell (IT-SOFC). The starting salts were yttrium and bismuth nitrate. The crystal structures and the morphological characteristics of the particles were analyzed by XRD and SEM, respectively. The ionic conductivity of the sintered pellet was measured by an electrochemical impedance analyzer. The size of the calcined YBO powders were in the range of 20-100 nm as measured by SEM images. The YBO pellets had a face-centered cubic structure, and their crystallite size was about 54-88 nm. The ionic conductivity of the YBO pellets sintered at 800 degrees C was observed to be 2.7 x 10(-1) Scm-(-1) at 700 degrees C. The ball-milling of the YBO powder before it was pelletized was found to have been unrequired probably because of a good sinterability of the YBO powders that was prepared via the ammonium carbonate coprecipitation method. The results showed that the ammonium carbonate coprecipitation process could be used as the cost-efficient method of producing YBO electrolytes for IT-SOFC.