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1.
Am J Dermatopathol ; 39(6): e76-e78, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28525910

RESUMEN

We present a case of cutaneous apocrine carcinoma arising in the axilla of a 71-year-old man. The tumor had a significant component of histiocytoid and signet-ring cells as well as in situ carcinoma within the apocrine glands. The cells expressed GATA3, gross cystic disease fluid protein 15, androgen receptor, and E-cadherin. Estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 were negative. Clinical correlation was required to rule out a metastasis from the breast or the gastrointestinal tract. Although most cutaneous apocrine carcinomas do not behave aggressively, our patient developed bone metastases and eventually died of his disease. It is debated whether histiocytoid and signet-ring cell cutaneous carcinomas should be classified as apocrine neoplasm. The presence of in situ carcinoma associated with this kind of tumor has been reported only once in the literature. This characteristic and the immunohistochemical profile are in favor of apocrine differentiation.


Asunto(s)
Glándulas Apocrinas/patología , Carcinoma in Situ/patología , Carcinoma de Células en Anillo de Sello/secundario , Histiocitos/patología , Neoplasias Complejas y Mixtas/secundario , Neoplasias de las Glándulas Sudoríparas/patología , Anciano , Glándulas Apocrinas/química , Glándulas Apocrinas/cirugía , Biomarcadores de Tumor/análisis , Biopsia , Neoplasias Óseas/secundario , Carcinoma in Situ/química , Carcinoma in Situ/cirugía , Carcinoma de Células en Anillo de Sello/química , Carcinoma de Células en Anillo de Sello/cirugía , Diferenciación Celular , Resultado Fatal , Histiocitos/química , Humanos , Inmunohistoquímica , Masculino , Neoplasias Complejas y Mixtas/química , Neoplasias Complejas y Mixtas/cirugía , Neoplasias de las Glándulas Sudoríparas/química , Neoplasias de las Glándulas Sudoríparas/cirugía
2.
World J Surg Oncol ; 12: 332, 2014 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-25380618

RESUMEN

BACKGROUND: Appendiceal peritoneal carcinomatosis (PC) is rare and its long-term prognosis is poor. The aim of this study was to evaluate the results of an aggressive treatment approach used in our institution for the last eight years. METHODS: Data from all patients with PC arising from the appendix were prospectively collected and analyzed. Treatment consisted of complete surgical cytoreduction (CRS), followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin (460 mg/m2) at 43°C over 30 minutes. Ronnett's histologic classification was used for tumor grading. RESULTS: Between February 2003 and April 2011, 78 patients underwent laparotomy with curative intent. The mean follow-up period was 33.7 months. A total of 58 patients received HIPEC, but 11 patients could not have CRS and received no HIPEC. Nine patients with a negative second-look surgery also received no HIPEC. The five-year overall survival for the entire cohort was 66.2%; 100% for the negative second-look patients, 77% for the HIPEC patients and 9% for the unresectable patients (P<0.0001). A total of 15 patients (25.9%) had isolated peritoneal recurrence, no patient had visceral recurrence only, and five patients (8.6%) had both. In regards to the five-year disease-free survival for the HIPEC patients, histologic grade (disseminated peritoneal adenomucinosis 100%, peritoneal mucinous carcinomatosis with intermediate features 40%, peritoneal mucinous carcinomatosis 20%; p=0.0016) and completeness of cytoreduction (CCR-0 56%, CCR-1 24%; P=0.0172) were prognostic factors. There was one postoperative mortality. The major complication rate for patients treated with HIPEC was 40%, including intra-abdominal abcess (17%), hemorrhage (12%) and anastomotic leak (10%). One patient in the HIPEC group experienced temporary grade II neuropathy and grade III thrombocytopenia. CONCLUSIONS: This therapeutic approach seems both feasible and safe in selected patients. Recurrence is, however, frequent and represents a challenge.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Apéndice/mortalidad , Hipertermia Inducida , Recurrencia Local de Neoplasia/mortalidad , Compuestos Organoplatinos/uso terapéutico , Neoplasias Peritoneales/mortalidad , Seudomixoma Peritoneal/mortalidad , Adulto , Anciano , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/terapia , Quimioterapia Adyuvante , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Laparotomía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Oxaliplatino , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/terapia , Pronóstico , Estudios Prospectivos , Seudomixoma Peritoneal/patología , Seudomixoma Peritoneal/terapia , Tasa de Supervivencia
3.
BJU Int ; 111(4 Pt B): E202-6, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22937774

RESUMEN

OBJECTIVE: To assess retrospectively the safety and efficacy of an artificial urinary sphincter, the ZSI 375 device (Zephyr Surgical Implants, Geneva, Switzerland), in male patients with moderate-to-severe stress urinary incontinence after a prostate or bladder intervention. PATIENTS AND METHODS: The ZSI 375 device is a one-piece device consisting of an adjustable cuff, moulded to fit around the urethra, which is connected by a tube to a pump and a pressure-regulating tank. It has no abdominal reservoir. Patients underwent a perineal incision for cuff placement and an inguinal incision for pump and tank scrotal placement. Complications and pads used to manage incontinence were recorded. RESULTS: Between May 2009 and April 2011, 36 patients underwent ZSI 375 device placement. The median (range) follow-up was 15.4 (6-28) months. No patient experienced bladder overactivity, chronic urinary retention, or any other adverse effect after device activation. Complications leading to device removal arose in four patients (one case of erosion, three cases of infection). Social continence (0 or 1 pad/day) was achieved in 28/36 patients (78%) at 3 months and 26/36 patients (73%) at 6 months after device activation. In 12/14 patients for a sphincter closure pressure range of 60-70 cm H2O, in 3/3 patients for a range of 70-80 cm H2O and in 2/11 for a range of 90-100 cm, H2O social continence was achieved only after increasing the pressure of the cuff by trans-scrotal injection of saline. CONCLUSIONS: The ZSI 375 device is safe and effective but our follow-up may not have been long enough to identify all potential complications. Further research is needed to confirm these results and extend our investigation, for instance, to the peno-scrotal approach.


Asunto(s)
Implantación de Prótesis/métodos , Incontinencia Urinaria/cirugía , Esfínter Urinario Artificial , Anciano , Anciano de 80 o más Años , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Estudios Retrospectivos , Resultado del Tratamiento , Incontinencia Urinaria/fisiopatología
4.
World J Surg Oncol ; 9: 140, 2011 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-22035205

RESUMEN

BACKGROUND: Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm usually found in the pleura, soft tissues and visceral organs. We describe one case arising in the mesentery, which is an exceptional localization. CASE PRESENTATION: A 71-year-old man was referred to our establishment for a painless hypogastric mass. Further investigation revealed a vascular tumor, which was resected en bloc. Pathological findings confirmed solitary fibrous tumor of the mesentery. CONCLUSION: This is the second case of solitary fibrous tumor of the small intestine mesentery ever reported. It was managed by en bloc resection and close follow up considering the high risk of recurrence. Investigation should be made regarding the use of adjuvant systemic therapy to improve long-term survival for these patients.


Asunto(s)
Mesenterio/patología , Tumores Fibrosos Solitarios/patología , Neoplasias Vasculares/patología , Anciano , Humanos , Masculino , Mesenterio/cirugía , Pronóstico , Tumores Fibrosos Solitarios/cirugía , Neoplasias Vasculares/cirugía
5.
Can J Surg ; 52(2): 135-41, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19399209

RESUMEN

BACKGROUND: Peritoneal carcinomatosis (PC) originating in the appendix is a rare disease for which the long-term prognosis is poor. The aim of our study was to evaluate the results of an aggressive treatment approach used in our institution in the last decade. METHODS: We prospectively collected and analyzed data from all patients with PC. Treatment consisted of complete surgical cytoreduction of the tumour followed by intraperitoneal chemotherapy. Chemotherapy was either early postoperative intraperitoneal chemotherapy (EPIC) or hyperthermic intraperitoneal chemotherapy (HIPEC). We used Ronnett's classification for tumour grading (disseminated peritoneal adenomucinosis = grade 0, peritoneal mucinous carcinomatosis with intermediate features = grade 1 and peritoneal mucinous carcinomatosis = grade 2). RESULTS: From September 1997 to June 2005, 37 patients underwent laparotomy with curative intent; 13 received EPIC and 11 HIPEC. Thirteen patients could not have complete cytoreductive surgery and received no intraperitoneal chemotherapy. The estimated 5-year overall survival was 56% (95% confidence interval [CI] 34%-77%) for all patients, 58% (95% CI 30%-86%) for patients who underwent EPIC and 60% (95% CI 10%-100%) for patients who underwent HIPEC (p = 0.97). Histologic grade was an important prognostic indicator as all patients with grade 0 tumours survived whereas no patients with grade 2 tumours survived (p < 0.001). Patients with grade 1 tumours had an estimated 87% (95% CI 64%-100%) 5-year overall survival. There was no mortality attributed to surgery. The overall complication rate was 36%, including fistulas (16%), intra-abdominal abscesses (12%) and hemorrhage (9%). CONCLUSION: This therapeutic approach seems both feasible and safe in select patients. Patients with high-grade tumours are poor candidates for this treatment.


Asunto(s)
Adenocarcinoma Mucinoso/terapia , Antineoplásicos/administración & dosificación , Neoplasias del Apéndice/patología , Hipertermia Inducida , Neoplasias Peritoneales/terapia , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/secundario , Adulto , Anciano , Neoplasias del Apéndice/mortalidad , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Quimioterapia Adyuvante , Femenino , Fluorouracilo/administración & dosificación , Humanos , Infusiones Parenterales , Irinotecán , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/secundario , Complicaciones Posoperatorias , Estudios Prospectivos
6.
Ann Surg Oncol ; 15(10): 2701-8, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18654822

RESUMEN

BACKGROUND: Peritoneal carcinomatosis (PC) arising from the appendix is a rare disease for which the long-term prognosis is poor. The aim of this study was to evaluate the results of an aggressive approach used in our institution over the last 5 years. METHODS: Data from all patients with PC arising from the appendix were prospectively collected and analyzed. Treatment consisted in complete surgical cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin (460 mg/m(2)) in 2 L/m(2) of D5W at 43 degrees C during 30 min. Ronnett's histologic classification was used for tumor grading. RESULTS: From February 2003 to March 2007, 38 patients with PC arising from the appendix underwent laparotomy with curative intent. Mean follow-up was 23 months. Twenty-three patients received HIPEC but ten patients could not have complete cytoreductive surgery and received no HIPEC. Five patients with a negative second-look surgery also received no HIPEC. Three-year overall survival (OS) was 100% for the negative second-look patients, 86% for the HIPEC patients, and 29% for the unresectable patients (P = 0.0098). Three-year disease-free survival (DFS) was 49% for the HIPEC patients. Histologic grade was a prognostic factor with regard to DFS for the HIPEC patients (P = 0.011). There was one postoperative mortality. The overall major (grade III-V/V) complication rate for treated patients was 39%, including intra-abdominal abscess (22%), hemorrhage (18%), and anastomotic leak (9%). CONCLUSION: Although these results are preliminary, this therapeutic approach seems both feasible and safe in selected patients.


Asunto(s)
Adenocarcinoma Mucinoso/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Neoplasias del Apéndice/tratamiento farmacológico , Hipertermia Inducida , Compuestos Organoplatinos/uso terapéutico , Neoplasias Peritoneales/tratamiento farmacológico , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/secundario , Adulto , Anciano , Neoplasias del Apéndice/mortalidad , Neoplasias del Apéndice/patología , Terapia Combinada , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Infusiones Parenterales , Masculino , Persona de Mediana Edad , Oxaliplatino , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/secundario , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia
8.
Clin Nucl Med ; 40(7): e366-9, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26018706

RESUMEN

A 50-year-old woman presented to our institution with a 1-day history of right posterior thoracic pain and dyspnea. She had a previous history of conservative resection of a high-grade basal-like infiltrating ductal carcinoma of the right breast 2 years before, subsequently treated by chemotherapy and radiotherapy. A ventilation and perfusion (VQ) scintigraphy performed for suspected pulmonary embolism showed an abnormal deposition of (99m)Tc macroaggregated albumin ((99m)Tc-MAA) in the left lobe of the liver. This unusual finding prompted additional imaging that demonstrated a superior vena cava stenosis.


Asunto(s)
Constricción Patológica/diagnóstico por imagen , Hígado/diagnóstico por imagen , Imagen de Perfusión , Radiofármacos/farmacocinética , Agregado de Albúmina Marcado con Tecnecio Tc 99m/farmacocinética , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos X , Vena Cava Superior/diagnóstico por imagen , Femenino , Humanos , Persona de Mediana Edad , Imagen Multimodal , Vena Cava Superior/patología
9.
J Agric Food Chem ; 52(12): 3801-6, 2004 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-15186100

RESUMEN

The free amino acid profile and sugar (fructose, glucose, and sucrose) composition were determined in potato samples selected to give a large range of variation (a total of 66 samples). From these samples French fries were produced in a laboratory-scale simulation of an industrial process followed by a finish fry at 180 degrees C for 3.5 min using a restaurant fryer. The final product was blast frozen and analyzed for acrylamide. Acrylamide was detected in all samples, but its concentration varied significantly from 50 to 1800 ng/g. For isotope dilution (13C3) acrylamide analysis, samples were extracted with water, cleaned up on HLB Oasis polymeric and Accucat mixed mode anion and cation exchange SPE columns, and analyzed by LC-MS/MS. Statistical analysis of the data indicates that the effect of sugars and asparagine on the concentration of acrylamide in French fries is positive and significant (p < 0.001). It appears that one of the ways acrylamide formation in French fries can be effectively controlled is by the use of raw products with low sugar (and to a lesser degree, asparagine) content.


Asunto(s)
Acrilamida/análisis , Aminoácidos/análisis , Carbohidratos/análisis , Solanum tuberosum/química , Asparagina/análisis , Manipulación de Alimentos , Fructosa/análisis , Glucosa/análisis , Calor , Reacción de Maillard , Sacarosa/análisis
12.
J Agric Food Chem ; 60(18): 4688-96, 2012 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-22462494

RESUMEN

Potato consumption provides significant dietary contributions to several essential minerals, but the effects of cultivar and planting site are not well-understood. The mineral content of 16 cultivars, grown at 5 locations, was measured using inductively coupled plasma-optical emission spectroscopy and evaluated on a per serving basis for percent recommended daily intake (% RDI), emphasizing some minerals where global deficiencies are common (calcium, iron, selenium, and zinc). Discriminant analysis showed that both genotype and growing location were important. Differences in mineral content occurred between cultivars at each site, specific cultivars at different sites, and collectively between sites. 'Freedom', 'Yukon Gold', and particularly the very stable mineral source 'Russet Burbank' contributed most to the % RDI for minerals. One serving per day of these cultivars provides a significant contribution to the % RDI for the macrominerals magnesium, phosphorus, and potassium and the trace minerals copper, iron, selenium, and zinc.


Asunto(s)
Minerales/análisis , Tubérculos de la Planta/química , Solanum tuberosum/química , Oligoelementos/análisis , Adulto , Canadá , Humanos , Masculino , Persona de Mediana Edad , Valor Nutritivo , Tubérculos de la Planta/crecimiento & desarrollo , Solanum tuberosum/crecimiento & desarrollo , Especificidad de la Especie , Adulto Joven
13.
Int J Surg Oncol ; 2012: 180574, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22970358

RESUMEN

Introduction. Endocrine therapy (ET) is an integral part of breast cancer (BC) treatment with surgical resection remaining the cornerstone of curative treatment. The objective of this study is to compare the survival of elderly postmenopausal women with hormone receptor-positive early-stage BC treated with ET alone, without radiation or chemotherapy, versus ET plus surgery. Materials and Methods. This is a retrospective study based on a prospective database. The medical records of postmenopausal BC patients referred to the surgical oncology service of two hospitals during an 8-year period were reviewed. All patients were to receive ET for a minimum of four months before undergoing any surgery. Results. Fifty-one patients were included and divided in two groups, ET alone and ET plus surgery. At last follow-up in exclusive ET patients (n = 28), 39% had stable disease or complete response, 22% had progressive disease, of which 18% died of breast cancer, and 39% died of other causes. In surgical patients (n = 23), 78% were disease-free, 9% died of recurrent breast cancer, and 13% died of other causes. Conclusions. These results suggest that surgical resection is beneficial in this group and should be considered, even for patients previously deemed ineligible for surgery.

17.
J Am Coll Surg ; 206(4): 704-8, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18387477

RESUMEN

BACKGROUND: It is essential to have the highest level of confidence in axillary staging assessment. Many surgeons and pathologists believe that fewer lymph nodes are present in axillary dissection specimens of women treated by neoadjuvant chemotherapy. Consequently, the purpose of this study was to compare the lymph node counts of axillary dissection specimens from patients having received neoadjuvant chemotherapy with those of patients treated with primary operation. STUDY DESIGN: A retrospective analysis of a prospective database from our institution identified 283 women with invasive breast cancer who underwent level I and II axillary lymph node dissections. Women from the neoadjuvant chemotherapy group (n=107) were compared with those from the primary surgery group (n=176). The total number of lymph nodes harvested was considered as a continuous variable, but also dichotomized into two categories (< 10 and >or=10). Its correlation with the different variables was analyzed. RESULTS: The median number of lymph nodes retrieved in the neoadjuvant chemotherapy group was 10.0 (range 0 to 38) compared with 12.5 (range 0 to 30) in the control group (p=0.002). There were also significantly more patients with fewer than 10 lymph nodes recovered in the neoadjuvant group (45 versus 28%, p=0.007). Logistic regression showed that neoadjuvant chemotherapy was the only factor associated with retrieval of fewer than 10 lymph nodes. CONCLUSIONS: This study suggests that administration of neoadjuvant chemotherapy to breast cancer patients results in a reduced number of lymph nodes retrieved in the axillary dissection specimens.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama/patología , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Terapia Neoadyuvante , Axila , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Femenino , Humanos , Modelos Logísticos , Estadificación de Neoplasias , Estudios Retrospectivos
18.
J Am Coll Surg ; 206(6): 1116-21, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18501808

RESUMEN

BACKGROUND: Regression of breast tumors in response to neoadjuvant chemotherapy is variable. The goal of breast-conservation operation after neoadjuvant chemotherapy is generally to resect any residual tumor with negative margins. There are limited data about the success of achieving negative resection margins in these patients. The purpose of this study was to compare surgical margin involvement of breast-conservation resection specimens from patients treated initially with operation with those from patients receiving neoadjuvant chemotherapy. METHODS: Between January 2003 and June 2006, 478 breast-conservation operations were performed for invasive breast cancer at our institution. Seventy-six patients received neoadjuvant chemotherapy. Data collected included age, tumor size, nodal status, hormonal receptors and Her-2-neu status, lymphovascular invasion, histologic grade and type, use of guidewire, preoperative chemotherapy regimens, and microscopic evaluation of surgical margins. Univariate analyses and a regression model were used to identify factors associated with margin involvement. RESULTS: No statistical difference was observed for margin involvement between patients treated with neoadjuvant chemotherapy and those treated initially with operation (21% versus 18%; p = 0.52). Variables associated with positive margins in a logistic regression model were carcinoma type (43% of all lobular carcinomas had positive margins versus 16% in ductal carcinomas; p = 0.002) and hormonal receptor status (margin involvement was present in 20% of tumors that exhibited hormonal receptors versus 10% in negative receptors tumors; p = 0.014). CONCLUSIONS: Breast conservation after neoadjuvant systemic therapy yields no higher incidence of positive margins than primary surgical treatment. Special consideration should be accorded to lobular carcinoma, because our findings, consistent with previous studies, demonstrate an association with margin involvement.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Carcinoma Ductal/tratamiento farmacológico , Carcinoma Ductal/cirugía , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/cirugía , Mastectomía Segmentaria , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal/metabolismo , Carcinoma Ductal/patología , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patología , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Estudios Retrospectivos
19.
Am J Physiol Regul Integr Comp Physiol ; 289(2): R299-304, 2005 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-15774769

RESUMEN

Decreased levels of tetrahydrobiopterin (BH4), an absolute cofactor for nitric oxide synthase (NOS), lead to uncoupling of NOS into a superoxide v. nitric oxide producing enzyme, and it is this uncoupling that links it to the development of vascular disease. However, the effects of in vivo deficiency of BH4 on neointimal formation after vascular injury have not been previously investigated. Hph-1 mice, which display 90% deficiency in guanine triphosphate cyclohydrolase I, the rate limiting enzyme in BH4 synthesis, were used. Hph-1 and wild-type mice, treated with either vehicle or BH4 (n = 15 per group), were subjected to wire-induced femoral artery injury, and NOS expression and activity, inflammation, cell proliferation, superoxide production, and neointimal formation were assessed. The major form of NOS expressed over vessel wall after vascular injury was endothelial NOS. Hph-1 mice exhibited lower NOS activity (2.8 +/- 0.3 vs. 4.5 +/- 0.4 pmol/min/mg protein, P < 0.01), and higher aortic superoxide content (5.2 +/- 2.0 x 10(5) cpm vs. 1.6 +/- 0.7 x 10(5) cpm, P < 0.01) compared with wild-type controls, indicating uncoupling of NOS. Treatment of hph-1 mice with BH4 significantly increased NOS activity (from 2.8 +/- 0.3 to 4.1 +/- 0.4 pmol.min(-1).mg protein(-1), P < 0.05), and attenuated superoxide production (from 5.2 +/- 2.0 x 10(5) cpm to 0.8 +/- 0.7 x 10(5) cpm, P < 0.05). Hph-1 mice also had higher inflammatory reactions and more cell proliferation after vascular injury. Furthermore, hph-1 mice responded by a marked increase in neointimal formation at 4 wk after vascular injury, compared with wild-type controls (intima:media ratio: 4.5 +/- 0.5 vs. wild-type 0.7 +/- 0.1, P < 0.001). Treatment of hph-1 mice with BH4 prevented vascular injury-induced increase in neointimal formation (intima:media ratio: 1.4 +/- 0.1 vs. hph-1, P < 0.001). Treatment had no effect on wild-type controls. In summary, we describe, for the first time, that in vivo BH4 deficiency facilitates neointimal formation after vascular injury. Modulation of BH4 bioavailability is an important therapeutic target for restenosis.


Asunto(s)
Biopterinas/análogos & derivados , Arteria Femoral/lesiones , Arteria Femoral/patología , Túnica Íntima/patología , Animales , Aorta/enzimología , Aorta/metabolismo , Biopterinas/deficiencia , Biopterinas/farmacología , Proliferación Celular/efectos de los fármacos , Arteria Femoral/metabolismo , Hiperplasia , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Mutantes , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo II , Óxido Nítrico Sintasa de Tipo III , Superóxidos/metabolismo , Túnica Íntima/efectos de los fármacos , Vasculitis/etiología , Vasculitis/patología , Heridas y Lesiones/complicaciones , Heridas y Lesiones/metabolismo , Heridas y Lesiones/patología
20.
Med Sci Monit ; 9(1): BR37-42, 2003 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-12552235

RESUMEN

BACKGROUND: To define the pharmacokinetic and toxicity profile of raltitrexed administered by intraperitoneal route in a normothermic pig model. MATERIAL/METHODS: Twenty-one female pigs were divided in three groups. Under general anesthesia, pigs in groups 1 and 2 underwent laparotomy with resection of a small hepatic wedge, bowel anastomosis and portal and systemic vein catheterization. This was followed by an intraperitioneal delivery of raltitrexed: a dose of 1 mg was given to group 1 pigs, whereas group 2 received 2 mg. Serial sampling of portal blood, systemic blood and peritoneal fluid was then undertaken in both groups for pharmacokinetics studies. Pigs were followed daily for a period of 10 days after surgery with recordings of signs of toxicity. On day 10, an exploratory laparotomy was undertaken on each pig in order to assess peritoneal toxicity after which they were euthanized. Pigs in group 3 were used for bioavailability evaluation. RESULTS: Three deaths were recorded within 24 hours of surgery; a technical problem was identified in all cases and no deaths were the results of raltitrexed toxicity. A peritoneo-plasma gradient of 100:1 was obtained. Cmax in plasma were of 28 ng/ml and 54 ng/ml for group 1 and 2, respectively. Tmax were 180 min for both groups. AUCplasmatic was double in the 2 mg group compared to the 1 mg group. CONCLUSIONS: Raltitrexed administered by IP route in pigs is non-toxic. Pharmacologically, there are few interindividual variations and the small first-past effect did not significantly alter the high peritoneo-plasmatic gradient


Asunto(s)
Antimetabolitos Antineoplásicos/farmacocinética , Antimetabolitos Antineoplásicos/toxicidad , Quinazolinas/farmacocinética , Quinazolinas/toxicidad , Tiofenos/farmacocinética , Tiofenos/toxicidad , Animales , Temperatura Corporal , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacocinética , Inhibidores Enzimáticos/toxicidad , Femenino , Inyecciones Intraperitoneales , Modelos Estadísticos , Neoplasias/metabolismo , Porcinos , Factores de Tiempo
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