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1.
Mod Rheumatol ; 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39096517

RESUMEN

OBJECTIVES: This study aimed to describe the treatment selection for systemic lupus erythematosus (SLE) using data from the Kyushu Collagen Disease Network for SLE (KCDN-SLE) registry, a multicenter prospective registry in Japan. METHODS: This study used data from patients registered between August 2022 and November 2023. Clinical characteristics, purpose of agent initiation, other candidate agents, and short-term efficacy and safety were evaluated. RESULTS: We analyzed 69 previously treated patients with SLE (mean age 43.7 years; 62 females, 7 males). Hydroxychloroquine, biological agents, and immunosuppressive agents were initiated during the maintenance phase in 12, 41, and 16 patients, respectively. In patients with active organ involvement, hydroxychloroquine and biological agents were widely used for initiation. In those who already achieved treatment goals, biological agents alone were predominantly selected. The SLE Disease Activity Index 2000 score and prednisolone dose declined significantly over a 6-month follow-up period. Among 48 patients with active disease, 22 achieved a lupus low disease activity state, but this had no evident association with the initiation of a biological agent. In total, 14 adverse events, predominantly infections, were observed. CONCLUSIONS: Biological agents were used preferentially, and the therapeutic agents were appropriately effective and mostly achieved the purpose of agent initiation.

2.
J Org Chem ; 80(9): 4392-7, 2015 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-25837012

RESUMEN

A metal-free method for fast and clean anilide formation from perfluoroaryl azide and thioacid is presented. The reaction proved highly efficient, displaying fast kinetics, high yield, and good chemoselectivity. The transformation was compatible with various solvents and tolerant to a wide variety of functional groups, and it showed high performance in polar protic/aprotic media, including aqueous buffer systems.


Asunto(s)
Anilidas/síntesis química , Azidas/química , Compuestos de Sulfhidrilo/química , Anilidas/química , Estructura Molecular
3.
Hinyokika Kiyo ; 59(9): 587-91, 2013 Sep.
Artículo en Japonés | MEDLINE | ID: mdl-24113758

RESUMEN

A 67-year-old man with castration-resistant prostate cancer associated with multiple bone metastases had been treated with zoledronic acid and docetaxel. Although there was no evidence of damage around the right lower jaw bone, the patient complained of pain in May 2011, which worsened during the next 2 weeks and was followed by difficulty with breathing. Computed tomographic (CT) findings of the cervical area showed swelling of the cervical tissue with air and tightening of the trachea, suggesting cellulitis caused by gas gangrene. He was intubated and treated with antibiotics. On the 12th hospital day, CT scan revealed a pharyngeal abscess and we performed a drainage operation. On the 20th hospital day, bone of the intraoral lower jaw was exposed, revealing that the infection was caused by osteonecrosis. Additional CT findings showed the abscess extending to the mediastinum and multiple liver metastases. Although antibiotic therapy was continued, the patient died of liver failure on the 61st day.


Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos/etiología , Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos/efectos adversos , Imidazoles/efectos adversos , Maxilares , Neoplasias de la Próstata/patología , Absceso Retrofaríngeo/etiología , Anciano , Antibacterianos/administración & dosificación , Antineoplásicos/efectos adversos , Conservadores de la Densidad Ósea/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Difosfonatos/uso terapéutico , Docetaxel , Drenaje , Resultado Fatal , Humanos , Imidazoles/uso terapéutico , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Absceso Retrofaríngeo/diagnóstico , Absceso Retrofaríngeo/cirugía , Absceso Retrofaríngeo/terapia , Taxoides/efectos adversos , Tomografía Computarizada por Rayos X , Ácido Zoledrónico
4.
Hinyokika Kiyo ; 58(10): 561-4, 2012 Oct.
Artículo en Japonés | MEDLINE | ID: mdl-23235280

RESUMEN

A 61-year-old man came to our hospital with a complaint of lower abdominal pain. Computed tomography (CT) and magnetic resonance imaging (MRI) around his abdominal area showed large multiple cysts in the pelvis suggesting a malignant tumor. He showed high levels of serum carbohydrate antigen 19- 9 (CA19-9) and carcinoembryonic antigen (CEA). The complete diagnostic studies, including upper gastrointestinal endoscopy and colonoscopy examinations, failed to demonstrate the presence of alimentary primary tumors. With the diagnosis of cystic tumor in the pelvis, the operation was performed. The cysts adhered firmly to the surrounding organs including bladder and peritonium, which could not be resected completely. A histopathological diagnosis was papillary adenocarcinoma positive for prostate specific antigen (PSA). Because the level of serum PSA was 9.39 ng/ml, prostate biopsy was performed and ductal adenocarcinoma of prostate was revealed. After the operation, the levels of serum CA19-9 and CEA decreased to a normal level. Androgen deprivation therapy (ADT) was started, and the level of PSA was normalized one month later. Ductal adenocarcinoma forming cysts is rare. We reviewed 15 cases reported in the Japanese literature.


Asunto(s)
Carcinoma Ductal/patología , Quistes/patología , Neoplasias de la Próstata/patología , Cistadenocarcinoma Papilar/patología , Humanos , Masculino , Persona de Mediana Edad , Espacio Retroperitoneal
5.
Hinyokika Kiyo ; 58(10): 557-60, 2012 Oct.
Artículo en Japonés | MEDLINE | ID: mdl-23235279

RESUMEN

A 65-year-old man was referred to our hospital because of an elevated value of prostate specific antigen (PSA) (10.9 ng/ml). An eight-core prostate biopsy was negative. One year later, serum PSA increased to 55. 8 ng/ml and pelvic magnetic resonance imaging (MRI) showed a left external iliac lymph node enlargement. A ten-core prostate biopsy was negative. Six months later, the serum PSA increased to 88.1 ng/ml, but an seventeen-core prostate biopsy was negative again. A positron emission tomographycomputed tomography scan showed nothing other than increased uptake localized to the left enlarged external iliac lymph node. Pelvic lymphadenectomy was performed and histological examination, including immunohistological staining with PSA, confirmed lymph node metastasis from prostate cancer. Androgen deprivation therapy was started and 2 month later, serum PSA declined to below 1.0 ng/ml.


Asunto(s)
Escisión del Ganglio Linfático , Neoplasias de la Próstata/patología , Anciano , Humanos , Inmunohistoquímica , Metástasis Linfática/patología , Masculino , Neoplasias Primarias Desconocidas/diagnóstico , Antígeno Prostático Específico/análisis , Antígeno Prostático Específico/sangre
6.
Hinyokika Kiyo ; 58(6): 291-3, 2012 Jun.
Artículo en Japonés | MEDLINE | ID: mdl-22874509

RESUMEN

A 43-year-old woman presented to our hospital with the chief complaints of gross hematuria and dysuria. Cystoscopy and magnetic resonance imaging showed a tumor on the dome of the bladder and large blood clots. Computed tomography demonstrated no findings of distant metastasis. Following transurethral resection of the tumor, the tumor was histologically diagnosed as myxofibrosarcoma with muscular invasion, and partial cystectomy was performed in September 2009. There has been no evidence of recurrence or metastasis for 24 months postoperatively. In addition, the Japanese literature on myxofibrosarcoma of the bladder was reviewed and discussed.


Asunto(s)
Fibrosarcoma/patología , Neoplasias de la Vejiga Urinaria/patología , Adulto , Femenino , Humanos
7.
Hinyokika Kiyo ; 58(9): 503-6, 2012 Sep.
Artículo en Japonés | MEDLINE | ID: mdl-23070391

RESUMEN

The patient was a 67-year-old man who was started on peritoneal dialysis for treatment of diabetic nephropathy in March 2010. He received an ABO-compatible living-donor kidney transplant from his wife in October 2010. The immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil, steroid and basiliximab. Before the operation, a bump on his forehead/temple region that was increasing in size for years was noted. The bump had a scaly surface and the top of the bump was sloughed on postoperative day 14. Histological examination suggested malignancy. On postoperative day 21, a skin biopsy was performed by dermatologists and squamous cell carcinoma was confirmed. On postoperative day 36, wide excision and transposition flap procedures were performed by the plastic surgeon. At 15 months after transplantation, the kidney graft was functioning well with a serum creatinine level of 0.84 mg/dl and there was no sign of recurrence of the squamous cell carcinoma.


Asunto(s)
Carcinoma de Células Escamosas/diagnóstico , Trasplante de Riñón , Neoplasias Cutáneas/diagnóstico , Anciano , Carcinoma de Células Escamosas/cirugía , Humanos , Terapia de Inmunosupresión/efectos adversos , Masculino , Neoplasias Cutáneas/cirugía , Trasplante de Piel , Factores de Tiempo
8.
Hinyokika Kiyo ; 57(3): 125-8, 2011 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-21586883

RESUMEN

Topiramate is an antiepileptic medicine that has been used adjunctively in the treatment of refractory seizures in Japan since 2007. Topiramate has been shown to inhibit specific carbonic anhydrase activity in the kidney and may induce a distal type of renal tubular acidosis. Case 1 : A 22-year-old male was referred to our hospital after complaining of left flank pain. He developed a seizure disorder and had been using topiramate for 4 months. Drip infusion pyelography showed a left ureteral stone. Case 2 : A 7-year-old boy presented with gross hematuria. He developed West syndrome and had been using topiramate for 6 months. A computed tomographic scan showed a right kidney stone.


Asunto(s)
Anticonvulsivantes/efectos adversos , Fructosa/análogos & derivados , Urolitiasis/inducido químicamente , Niño , Epilepsia/tratamiento farmacológico , Fructosa/efectos adversos , Humanos , Lactante , Cálculos Renales/inducido químicamente , Masculino , Espasmos Infantiles/tratamiento farmacológico , Topiramato , Adulto Joven
9.
Hinyokika Kiyo ; 56(7): 351-4, 2010 Jul.
Artículo en Japonés | MEDLINE | ID: mdl-20724806

RESUMEN

In recent times, the number of patients receiving antiplatelet drugs for the prevention of cardiovascular and cerebrovascular diseases has been increasing. We examined the possibility of early initiation of antiplatelet therapy after urological operations. Between April 2008 and February 2009, 62 patients who received antiplatelet drugs and underwent urological surgeries (open surgery, transurethral surgery and laparoscopic surgery) and prostate biopsies were examined. Of the 62 patients, 59 were randomized into 2 groups ; 32 patients receiving antiplatelet treatment initiation within 24 hours (early group) and 29 patients receiving this treatment more than 24 hours (late group) after the urological operation. The end point of this study was the re-cessation of antiplatelet therapy because of the development of postoperative complications (hematuria, blood loss, etc.) and cardiovascular and cerebrovascular events within 1 month. There was no significant difference in the urological events observed between these groups, including 2 of the 32 (6.3%) patients in the early group and 3 of the 27 (11.1%) in the late group. Cardiovascular and cerebrovascular diseases were not noted in any of the patients within 1 month. In conclusion, we think that it is possible to initiate antiplatelet therapy within 24 hours after urological operations and prostate biopsies in the absence of active blood loss. Early initiation may prevent the risk of cardiovascular and cerebrovascular disease in the future.


Asunto(s)
Inhibidores de Agregación Plaquetaria/administración & dosificación , Procedimientos Quirúrgicos Urológicos , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/prevención & control , Trastornos Cerebrovasculares/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Complicaciones Posoperatorias/prevención & control , Estudios Prospectivos
10.
Hinyokika Kiyo ; 56(7): 389-91, 2010 Jul.
Artículo en Japonés | MEDLINE | ID: mdl-20724814

RESUMEN

A 25-year-old woman had a urethrovaginal fistula caused by a foreign body in her vagina. The patient had sought an appointment with a gynecologist for removal of the foreign body in her vagina. However, one day before the scheduled appointment, she developed acute urinary retention and visited the emergency room of our hospital. A urinary catheter inserted into the urethra was found to come out through the vagina. The foreign body, a bottle cap made of polypropylene and measuring 48 x 28 mm in size, was removed. A cystourethroscopic examination confirmed the presence of the urethrovaginal fistula. Repeat cystourethroscopy performed after one month of conservative management showed a persistent urethrovaginal fistula, which had, in fact, increased in size as compared with that at the initial examination. Surgery was undertaken for repair of the fistula ; fistula closure was successfully accomplished by suture in three layers : urethral wall, subcutaneous tissue, and the vaginal wall. This is the second report of a urethrovaginal fistula caused by a foreign body in the vagina.


Asunto(s)
Cuerpos Extraños/complicaciones , Enfermedades Uretrales/etiología , Fístula Urinaria/etiología , Vagina , Fístula Vaginal/etiología , Adulto , Femenino , Humanos , Enfermedades Uretrales/cirugía , Fístula Urinaria/cirugía , Fístula Vaginal/cirugía
11.
Hinyokika Kiyo ; 55(9): 579-82, 2009 Sep.
Artículo en Japonés | MEDLINE | ID: mdl-19827623

RESUMEN

We report a case of signet-ring cell carcinoma of the urinary bladder. A 60-year-old man was hospitalized because of total macrohematuria. Cystoscopic examination revealed a non-papillary sessile tumor on the posterior wall of the urinary bladder. The pathological diagnosis was stage pT1 signet ring cell carcinoma. Upper gastrointestinal endoscopy and computed tomographic scanning revealed no involvement of other organs. Radical cystectomy and creation of an ileal neobladder were performed. The histopathological stage was pT3aN0M0. Adjuvant chemotherapy (TS-1) was performed and the patient is currently free from disease at eight months after the surgery. This disease is usually diagnosed at an advanced stage and has a poor prognosis. To our knowledge, this is the first case report on the creation of an ileal neobladder for the treatment of primary signet-ring cell carcinoma of the urinary bladder.


Asunto(s)
Carcinoma de Células en Anillo de Sello/cirugía , Neoplasias de la Vejiga Urinaria/cirugía , Derivación Urinaria/métodos , Carcinoma de Células en Anillo de Sello/diagnóstico , Carcinoma de Células en Anillo de Sello/patología , Quimioterapia Adyuvante , Cistectomía , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/patología
12.
Hinyokika Kiyo ; 55(7): 433-6, 2009 Jul.
Artículo en Japonés | MEDLINE | ID: mdl-19673434

RESUMEN

We report a case of acute scrotal hematoma associated with idiopathic thrombocytosis. A 75-year-old man visited our hospital for the treatment of a left scrotal mass that had been increasing in size; the mass had developed after the puncture of left testicular hydrocele. The patient was diagnosed with acute scrotal hematoma on the basis of ultrasonography findings. The patient underwent an emergency operation for the removal of the hematoma. On 2 days after the surgery we noticed an increase in the size of the hematoma. The patient had a 4-year clinical history of idiopathic thrombocytosis for which he had not received any treatment. Although the platelet count was slightly high at the time of the operation, complete hemostasis did not occur because of the existence of platelet dysfunction. The second hematoma was treated conservatively. To our knowledge, this is the first case report on the acute scrotal hematoma associated with idiopathic thrombocytosis.


Asunto(s)
Enfermedades de los Genitales Masculinos/etiología , Hematoma/etiología , Escroto , Trombocitosis/complicaciones , Anciano , Humanos , Masculino
13.
Hinyokika Kiyo ; 55(10): 615-8, 2009 Oct.
Artículo en Japonés | MEDLINE | ID: mdl-19926946

RESUMEN

A 30-year-old female was referred to our hospital complaining of left flank pain. She was diagnosed with a giant hydronephrosis in a horseshoe kidney. We performed a retroperitoneoscopic nephrectomy on the non-functioning moiety of the horseshoe kidney. After the placement of a ureteral catheter, she underwent a retroperitoneal nephrectomy. The feeding vessels consisted of four arteries and four veins. The thin isthmus of the horseshoe kidney was divided using scissors, without the need for electrocautery, and hemostasis was achieved using monopolar shears. Laparoscopic nephrectomy on a horseshoe kidney is a difficult surgery given the aberrant vessels and isthmus, so it tends to be avoided for reasons of safety. However, if appropriate preoperative imaging is carried out and the procedure is conducted in a careful manner, it can be made a safe and minimally invasive operation.


Asunto(s)
Hidronefrosis/cirugía , Riñón/anomalías , Laparoscopía , Nefrectomía/métodos , Adulto , Femenino , Humanos , Espacio Retroperitoneal
14.
Nihon Hinyokika Gakkai Zasshi ; 99(4): 601-5, 2008 May.
Artículo en Japonés | MEDLINE | ID: mdl-18536311

RESUMEN

A 68-year old female underwent laparoscopic vaginal hysterectomy for uterine wall perforation, following the removal of an intrauterine contraceptive device (IUD). The patient entered our hospital complaining of persistent genital bleeding, lower abdominal pain and urinary incontinence. She was diagnosed with a vesicovaginal fistula. The diameter of the fistula was over 3 cm and extended from the trigone to the internal urethral orifice, complicating the right distal ureteral obstruction. Therefore, curative surgery required a subtotal cystectomy and substitution cystoplasty due to severe urothelial changes, hydronephrosis and poor bladder compliance. An ileal neobladder (modified Studer's method) was successfully created and the postopertive course was uneventful. Although minor urinary incontinence persists, she can void through the urethra which has improved her quality of life.


Asunto(s)
Complicaciones Posoperatorias/cirugía , Fístula Vesicovaginal/cirugía , Anciano , Cistectomía , Femenino , Humanos , Histerectomía Vaginal , Calidad de Vida , Resultado del Tratamiento , Obstrucción Ureteral/cirugía , Derivación Urinaria/métodos
15.
Nihon Hinyokika Gakkai Zasshi ; 98(7): 826-31, 2007 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-18062213

RESUMEN

BACKGROUND: In Japan, patients suffering vesicosigmoidal fistula caused by diverculitis is increasing. Our aim is to report our seven cases and the literature review related with this disease. METHODS: A retrospective record review of seven patients in our hospital who were diagnosed and treated for vesicosigmoidal fistulas over a 12-year period from 1994 was performed. Data collection focused on symptoms, diagnostic studies, and methods of management. RESULTS: All of the patients were male whose ages ranged from 41 to 82 years, with a mean age of 60.7 years. All of the patients presented with some of the common presenting symptoms of pneumaturia, fecaluria, irritation, abdominal pain, recurrent urinary tract infection, macroscopic hematuria. In all cases, abnormal cystoscopic findings were observed. Onestage colectomy with partial cystectomy was underwent in all cases. CONCLUSION: Many of the patients suffering from vesicosigmoidal fistula caused by diverticulitis have urological symptoms. So the above mentioned examinations are required when the outpatients complained of pneumaturia, fecaluria, irritative voiding symptoms, reccurent urinary tract infection. After diagnosed, surgical treatment is the most standard therapy and when the appropriate operative method is selected, postoperative prognosis is favorable.


Asunto(s)
Diverticulitis del Colon/complicaciones , Fístula Intestinal/etiología , Enfermedades del Sigmoide/etiología , Fístula de la Vejiga Urinaria/etiología , Adulto , Anciano , Anciano de 80 o más Años , Colectomía , Cistectomía , Cistoscopía , Diverticulitis del Colon/diagnóstico , Diverticulitis del Colon/cirugía , Humanos , Fístula Intestinal/diagnóstico , Fístula Intestinal/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Enfermedades del Sigmoide/diagnóstico , Enfermedades del Sigmoide/cirugía , Fístula de la Vejiga Urinaria/diagnóstico , Fístula de la Vejiga Urinaria/cirugía
16.
Life Sci ; 76(19): 2185-92, 2005 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-15733933

RESUMEN

Oxygen radicals, such as superoxide radicals, embellishing DNA, protein, lipids, etc., and carrying out the obstacle of the function of a cell is known. It depends for the oxidant level in the living body on the balance of a generation system and an elimination system of oxygen radicals, and research which controls an oxidant level in the living body is briskly done by taking in the substance which eliminates an oxygen radical. We investigated scavenging effects of superoxide radicals by selenoureas and thioureas using a highly sensitive and quantitative chemiluminescence method. At 330 nM, five selenoureas and five thioureas scavenged fractions of superoxide radicals (O2-) ranging from 8.4% to 87.6%. Among five N,N-unsubstituted selenoureas and N,N-unsubstituted thioureas 1-selenocarbamoylpiperidine and 1-thiocarbamoylpyrrolidine were the most effective scavengers. A possibility that selenoureas could use it as a new superoxide anion-scavenging substance from the result of this research became clear.


Asunto(s)
Depuradores de Radicales Libres/química , Compuestos de Organoselenio/química , Oxidantes/química , Superóxidos/química , Tiourea/química , Urea/análogos & derivados , Urea/química , Relación Dosis-Respuesta a Droga , Luciferina de Luciérnaga/química , Depuradores de Radicales Libres/síntesis química , Indicadores y Reactivos , Compuestos de Organoselenio/síntesis química , Especies Reactivas de Oxígeno/química , Tiourea/síntesis química , Urea/síntesis química
17.
Eur J Pharm Sci ; 24(4): 291-5, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15734295

RESUMEN

We investigated the superoxide anion-scavenging effects of six selenocarbamates and four thiocarbamates, using a highly sensitive quantitative chemiluminescence method. At 333 nM, six selenocarbamates and four thiocarbamates scavenged in the range of 2.9-68.7% of O(2)*-. Se-methyl N-phenylselenocarbamate and Se-methyl N-(4-methylphenyl)selenocarbamate exhibited the strongest superoxide anion-scavenging activity among the Se-selenocarbamates. In contrast, the corresponding S-thiocarbamates had moderate inhibitory effect. The 50% inhibitory concentrations (IC(50)) of Se-methyl-N-phenylselenocarbamate and Se-methyl-N-(4-methylphenyl)selenocarbamate were determined to be 140 nM and 162 nM, respectively. Thus, these compounds acted in vitro as effective and potentially useful O(2)*- scavengers.


Asunto(s)
Carbamatos/farmacología , Depuradores de Radicales Libres/metabolismo , Compuestos de Selenio/farmacología , Superóxidos/metabolismo , Depuradores de Radicales Libres/farmacología , Tiocarbamatos/farmacología
18.
DNA Res ; 10(4): 147-53, 2003 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-14621293

RESUMEN

We obtained genetic information on sexual reproduction of the Closterium peracerosum-strigosum-littorale complex, a unicellular charophycean alga. Normalized cDNA libraries were constructed from cells in the sexual reproduction process, and a total of 1190 5'-end expressed sequence tags were established. Since 604 of these ESTs were classified into 174 non-redundant sequences, these 1190 ESTs include 760 unique sequences. Similarity search against a public non-redundant protein database indicated that 390 unique sequences had significant similarity to registered sequences. Among these 390 sequences, 3 were identical to and 4 were homologous to previously identified sex-pheromone genes. According to our study, 370 of 760 unique sequences are likely to be novel transcripts. These cDNA clones and EST sequence information may would be helpful for future functional analyses using DNA array technologies.


Asunto(s)
Eucariontes/genética , Etiquetas de Secuencia Expresada , Biblioteca de Genes , Secuencia de Aminoácidos , Medios de Cultivo , ADN Complementario/genética , Bases de Datos de Proteínas , Funciones de Verosimilitud , Datos de Secuencia Molecular , Filogenia , Análisis de Secuencia de ADN , Homología de Secuencia de Aminoácido , Atractivos Sexuales/genética
19.
Biochem Biophys Res Commun ; 352(2): 360-5, 2007 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-17126295

RESUMEN

The activation of extracellular receptor kinase (ERK) is one of the checkpoints to assess the activation of the classical Ras/mitogen-activated protein kinase (MAPK) cascade. Therefore, we tested more than 100 selenium-containing compounds for their ability to activate the MAPK signal pathway. Among them, we found that three selenazoles, 5-chloroacetyl-2-piperidino-1,3-selenazole (CS1), 5-chloroacetyl-2-morpholino-1,3-selenazole (CS2), and 5-chloroacetyl-2-dimethylamino-1,3-selenazole (CS3), induced the phosphorylation of ERK. These compounds also enhanced the phosphorylation of Akt, a signal transducing protein kinase for cell survival; and this phosphorylation was followed by suppression of cell death, thus suggesting that they had anti-apoptotic effects. Moreover, CSs 1-3 induced neurite outgrowth and facilitated the expression of neurofilament-M of PC12 cells, demonstrating that they induced neuronal differentiation of these cells. On the other hand, the CS-induced phosphorylation of MAPK was enhanced by buthionine sulfoximine (BSO), an activator of protein tyrosine phosphatases (PTPs), but inhibited by N-acetyl-l-cysteine (NAC), an inhibitor of receptor tyrosine kinase. These results imply that activation of some receptor tyrosine kinase(s) is involved in the mechanism of action of CSs 1-3. The activation of MAPK by CSs 1-3 was suppressed by U0126, a MEK inhibitor, but not by K252a, an inhibitor of TrkA; AG1478, an antagonist of epidermal growth factor receptor (EGFR); or by pertussis toxin. These results demonstrate that the CS-induced phosphorylation of Akt and MAP kinase (receptor tyrosine kinase(s)-MEK1/2-ERK1/2) cascades was responsible for suppression of apoptosis and facilitation of neuronal differentiation of PC12 cells, respectively. Our results suggest that CSs 1-3 are promising candidates as neuroprotective and/or neurotrophic agents for the treatment of various neurodegenerative neurological disorders.


Asunto(s)
Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Neuronas/citología , Neuronas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Compuestos de Selenio/administración & dosificación , Animales , Medio de Cultivo Libre de Suero , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Neuronas/efectos de los fármacos , Células PC12 , Ratas
20.
Biol Pharm Bull ; 29(7): 1404-7, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16819178

RESUMEN

We investigated the superoxide anion scavenging effects of 2-amino-1,3- selenazoles and bis-(2-amino-5-selenazoyl) ketones using a highly sensitive quantitative chemiluminescence method. At 166 microM, the 2-amino-1,3-selenazoles and bis-(2-amino-5-selenazoyl) ketones scavenged in the range of 10.0 to 80.0% of O(2)(-). Bis[2-dimethylamino-5-(1,3-selenazolyl)] ketone exhibited the strongest superoxide anion-scavenging activity among the six kinds of 2-amino-1,3-selenazoles and three kinds of bis-(2-amino-5-selenazoyl) ketones. The 50% inhibitory concentration (IC(50)) of bis[2-dimethylamino-5-(1,3-selenazolyl)] ketone was determined to be 37.1 microM. Thus, bis[2-dimethylamino-5-(1,3-selenazolyl)] ketone acted in vitro as effective and potentially useful O(2)(-) scavenger.


Asunto(s)
Depuradores de Radicales Libres/farmacología , Cetonas/farmacología , Compuestos de Organoselenio/farmacología , Superóxidos/metabolismo , Depuradores de Radicales Libres/química , Cinética , Espectroscopía de Resonancia Magnética , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Xantina Oxidasa/efectos de los fármacos , Xantina Oxidasa/metabolismo
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