RESUMEN
Objective To evaluate the predictive and prognostic value of total tumor load (TTL) in sentinel lymph nodes (SLNs) in patients with infiltrating breast cancer after neoadjuvant systemic therapy (NST). Methods This retrospective multicenter study used data from a Spanish Sentinel Lymph Node database. Patients underwent intraoperative SLN biopsy after NST. TTL was determined from whole nodes using a one-step nucleic acid amplification (OSNA) assay and defined as the total sum of CK19 mRNA copies in all positive SLNs. Cox-regression models identified independent predictive variables, which were incorporated into a nomogram to predict axillary non-SLN metastasis, and identified prognostic variables for incorporation into a disease-free survival (DFS) prognostic score. Results A total of 314 patients were included; most had no lymph node involvement prior to NST (cN0; 75.0% of patients). Most received chemotherapy with or without biologic therapy (91.7%), and 81 patients had a pathologic complete response. TTL was predictive of non-SLN involvement (area under the concentration curve = 0.87), and at a cut-off of 15,000 copies/µL had a negative predictive value of 90.5%. Nomogram parameters included log (TTL + 1), maximum tumor diameter and study-defined NST response. TTL was prognostic of disease recurrence and DFS at a cut-off of 25,000 copies/µL. After a 5-year follow-up, DFS was higher in patients with ≤ 25,000 copies/µL than those with > 25,000 (89.9% vs. 70.0%; p = 0.0017). Conclusions TTL > 15,000 mRNA copies/µL was predictive of non-SLN involvement and TTL > 25,000 mRNA copies/µL was associated with a higher risk of disease recurrence in breast cancer patients who had received NST (AU)
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Humanos , Femenino , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Técnicas de Amplificación de Ácido Nucleico , Ganglio Linfático Centinela/patología , Metástasis Linfática , Terapia Neoadyuvante , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Biopsia del Ganglio Linfático CentinelaRESUMEN
OBJECTIVE: To evaluate the predictive and prognostic value of total tumor load (TTL) in sentinel lymph nodes (SLNs) in patients with infiltrating breast cancer after neoadjuvant systemic therapy (NST). METHODS: This retrospective multicenter study used data from a Spanish Sentinel Lymph Node database. Patients underwent intraoperative SLN biopsy after NST. TTL was determined from whole nodes using a one-step nucleic acid amplification (OSNA) assay and defined as the total sum of CK19 mRNA copies in all positive SLNs. Cox-regression models identified independent predictive variables, which were incorporated into a nomogram to predict axillary non-SLN metastasis, and identified prognostic variables for incorporation into a disease-free survival (DFS) prognostic score. RESULTS: A total of 314 patients were included; most had no lymph node involvement prior to NST (cN0; 75.0% of patients). Most received chemotherapy with or without biologic therapy (91.7%), and 81 patients had a pathologic complete response. TTL was predictive of non-SLN involvement (area under the concentration curve = 0.87), and at a cut-off of 15,000 copies/µL had a negative predictive value of 90.5%. Nomogram parameters included log (TTL + 1), maximum tumor diameter and study-defined NST response. TTL was prognostic of disease recurrence and DFS at a cut-off of 25,000 copies/µL. After a 5-year follow-up, DFS was higher in patients with ≤ 25,000 copies/µL than those with > 25,000 (89.9% vs. 70.0%; p = 0.0017). CONCLUSIONS: TTL > 15,000 mRNA copies/µL was predictive of non-SLN involvement and TTL > 25,000 mRNA copies/µL was associated with a higher risk of disease recurrence in breast cancer patients who had received NST.
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Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Técnicas de Amplificación de Ácido Nucleico , Ganglio Linfático Centinela/patología , Carga Tumoral , Femenino , Humanos , Metástasis Linfática , Terapia Neoadyuvante , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Biopsia del Ganglio Linfático CentinelaRESUMEN
PURPOSE: To assess the impact in pathological complete response (pCR) and outcome of two dose-dense neoadjuvant chemotherapy (DDNC) regimens among different histological subtypes determined by hormonal receptor (HR) and HER2 status in breast cancer patients. METHODS: A total of 127 breast cancer patients were treated with DDNC in two prospective studies. A: adriamycin 40 mg/m(2) on day (d) 1 plus paclitaxel 150 mg/m(2) and gemcitabine 2,000 mg/m(2) on d2 for six cycles (n = 54). B: epirubicin 90 mg/m(2), cyclophosphamide 600 mg/m(2) on d1 for three cycles, followed by paclitaxel 150 mg/m(2) and gemcitabine 2,500 mg/m(2) on d1 ± trastuzumab according to HER2 status (n = 73). Histological subtypes of breast cancer were 49 % HR+/HER2-, 17.5 % HR+/HER2+, 13.5 % HR-/HER2+ and 20 % HR-/HER2-. RESULTS: pCR (absence of invasive cells in breast and lymph node) was achieved in 35 patients (28 %). The pCR rate was significantly different between histological subtypes: HR+/HER2- (9 %), HR+/HER2+ (23 %), HR-/HER2+ (50 %), HR-/HER2- (56 %) (p < 0.001). The median follow-up was 81 months (r: 15-150 months). HR-/HER2- tumor subtype had a significantly worse DFS compared to HR+/HER2- (p = 0.02), RH+/HER2+ (p = 0.04) and HR-/HER2+ tumor subtypes (p = 0.02). HR-/HER2- tumor subtype had a significantly shorter OS compared to HR+/HER2- (p = 0.007), RH+/HER2+ (p = 0.05), and HR-/HER2+ (p = 0.03) tumor subtypes. However, no significant difference was observed in DFS and OS among HR-/HER2- tumors that achieved a pCR. CONCLUSIONS: HR-/HER2- and HR-/HER2+ subtypes had a high pCR rate to DDNC. HR-/HER2- tumors had a worse outcome compared to other tumor subtypes but no significant difference was observed among HR-/HER2- tumors that achieved a pCR (AU)
No disponible
Asunto(s)
Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Ganglios Linfáticos , Neoplasias , Neoplasias/complicacionesRESUMEN
PURPOSE: To assess the impact in pathological complete response (pCR) and outcome of two dose-dense neoadjuvant chemotherapy (DDNC) regimens among different histological subtypes determined by hormonal receptor (HR) and HER2 status in breast cancer patients. METHODS: A total of 127 breast cancer patients were treated with DDNC in two prospective studies. A: adriamycin 40 mg/m(2) on day (d) 1 plus paclitaxel 150 mg/m(2) and gemcitabine 2,000 mg/m(2) on d2 for six cycles (n = 54). B: epirubicin 90 mg/m(2), cyclophosphamide 600 mg/m(2) on d1 for three cycles, followed by paclitaxel 150 mg/m(2) and gemcitabine 2,500 mg/m(2) on d1 ± trastuzumab according to HER2 status (n = 73). Histological subtypes of breast cancer were 49 % HR+/HER2-, 17.5 % HR+/HER2+, 13.5 % HR-/HER2+ and 20 % HR-/HER2-. RESULTS: pCR (absence of invasive cells in breast and lymph node) was achieved in 35 patients (28 %). The pCR rate was significantly different between histological subtypes: HR+/HER2- (9 %), HR+/HER2+ (23 %), HR-/HER2+ (50 %), HR-/HER2- (56 %) (p < 0.001). The median follow-up was 81 months (r: 15-150 months). HR-/HER2- tumor subtype had a significantly worse DFS compared to HR+/HER2- (p = 0.02), RH+/HER2+ (p = 0.04) and HR-/HER2+ tumor subtypes (p = 0.02). HR-/HER2- tumor subtype had a significantly shorter OS compared to HR+/HER2- (p = 0.007), RH+/HER2+ (p = 0.05), and HR-/HER2+ (p = 0.03) tumor subtypes. However, no significant difference was observed in DFS and OS among HR-/HER2- tumors that achieved a pCR. CONCLUSIONS: HR-/HER2- and HR-/HER2+ subtypes had a high pCR rate to DDNC. HR-/HER2- tumors had a worse outcome compared to other tumor subtypes but no significant difference was observed among HR-/HER2- tumors that achieved a pCR.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/patología , Terapia Neoadyuvante , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/metabolismo , Carcinoma Lobular/mortalidad , Carcinoma Lobular/patología , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Doxorrubicina/administración & dosificación , Epirrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Pronóstico , Estudios Prospectivos , Inducción de Remisión , Tasa de Supervivencia , Trastuzumab , GemcitabinaRESUMEN
PURPOSE: To evaluate the pathologic complete response (pCR) rate of a combination of epirubicin (E) and cyclophosphamide (C) followed by paclitaxel (P) and gemcitabine (G) (+ trastuzumab[T]) in Her2+ patients) in a sequential and dose-dense schedule as neoadjuvant chemotherapy for stages II and III patients with breast cancer. Secondary endpoints: clinical response rate, disease free survival, safety and correlation between pCR and biologic markers. PATIENTS AND METHODS: Eligible patients were treated with E (90 mg/m²) and C (600 mg/m²) for 3 cycles (first sequence) followed by P (150 mg/m²) and G (2500 mg/m²) (second sequence) for 6 cycles. All drugs were administered on day 1, every 2 weeks, with prophylactic growth factor support. Weekly T (2 mg/kg [4 mg/kg first infusion]) was administered concomitantly with P and G in Her2+ patients. A core biopsy was performed before treatment for biologic markers assessment. Patients underwent surgery, radiotherapy, and adjuvant hormonal therapy according to institutional practice. RESULTS: Seventy-three patients were treated. A pCR was achieved in 27 (37%) patients (32.1%, Her2- and 50%, Her2+). pCR was significantly higher in tumors that were hormonal receptor negative, poorly differentiated and positive for Ki67 and p53. Breast-conserving surgery was performed in 47 patients (64.4%). Most frequent grade 3/4 hematologic and nonhematological toxicities included neutropenia (12%), nausea/vomiting (17%), and transient liver enzymes elevation (7%). One patient suffered an asymptomatic and reversible decrease in left ventricular ejection fraction. CONCLUSIONS: These results show a highly effective regimen in terms of pCR with a good toxicity profile in the neoadjuvant treatment of patients with breast cancer. The addition of trastuzumab increased pCR rate in Her2+ tumors.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ciclofosfamida/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Esquema de Medicación , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Epirrubicina/administración & dosificación , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Receptor ErbB-2/metabolismo , Análisis de Supervivencia , Trastuzumab , GemcitabinaRESUMEN
BACKGROUND: The goal of this study was to develop an animal model of intestinal injury induced by 5-fluorouracil (5-FU) in pigs. METHODS: Six domestic pigs were used as control (healthy group) and another 6 malnourished pigs orally received 5-FU (treated group). After 4 weeks of treatment, pigs were sacrificed and jejunum, ileum and colon were isolated for histological, immunological and biochemical analyses. RESULTS: 5-FU caused a decrease in the intestinal mass. Disaccharidase, and phosphate alkaline activities, and glutathione redox cycle were disrupted by 5-FU. Histopathological alterations in the crypts and villous were greater in the small intestine than in the colon. 5-FU decreased the number of peripheral and intestinal leukocytes, promoting an increase in T-cytotoxic cells and a decrease in T-helper and B cells. CONCLUSION: This pig model of intestinal dysfunction closely mimics the common side effects of cancer chemotherapy in humans, and provides a useful tool for evaluating novel antimucotoxic agents.
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Fluorouracilo/toxicidad , Intestinos/efectos de los fármacos , Modelos Animales , Porcinos , Animales , Peso Corporal/efectos de los fármacos , Forma de la Célula/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Fluorouracilo/administración & dosificación , Glutatión/metabolismo , Mucosa Intestinal/citología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Intestinos/citología , Microscopía Electrónica de Transmisión , Oxidación-ReducciónRESUMEN
On the morning of 11 March 2004, Madrid lived the worst terrorist attack in its modern history, resulting to 191 people killed and more than 1,800 injured. The attacks evidenced a series of significant deficiencies in forensic task planning, especially in using standardised post-mortem data forms and gathering ante-mortem medical and dental data, responsible for the delay in identifying corpses in the worst state, which had to wait for DNA analysis. Fortunately, the ultimate result can be considered satisfactory, given the rapid response of the forensic team in examination and identification of the large number of victims (80% of the victims were identified within 40 h), consequence of a good mortuary organization in the Pavilion 6 of the Madrid Trade Fair (IFEMA), the professional fervor whereupon the different involved professionals acted, some personal initiatives and the good general state of most of the corpses.
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Planificación en Desastres/organización & administración , Antropología Forense/organización & administración , Prácticas Mortuorias/organización & administración , Terrorismo , Conducta Cooperativa , Odontología Forense/organización & administración , Humanos , Relaciones Interprofesionales , EspañaRESUMEN
Epithelioid Hemangioendothelioma (EH) is a vascular neoplasm of soft tissue, recently described by Weiss and Enzinger. The biologic al behavior of the tumor has a intermediate malignant potential, in the sense that it has an indolent course, with the potential for recurrence, but rarely metastasizes. This tumor arises from medium- to large-sized vessels, primarily involves the soft tissues of the extremities, as well as the liver, lung, and bone, and rarely occurs in the head and neck region. Only fifteen well--documented cases of Epithelioid Hemangioendothelioma involving the head and neck region have been reported. Nine cases have been recently reported in the oral cavity. This is a report of one additional case in the tongue. Because of the intermediate malignant potential of Epithelioid Hemangioendothelioma, complete tumor resection is recommended for intraoral lesions.
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Hemangiosarcoma/patología , Neoplasias de la Lengua/patología , Anciano , Femenino , HumanosRESUMEN
In this study we report the effects of sunflower, virgin olive and fish oils on the progression of aortic lesions. A total of 24 male New Zealand rabbits (six per each group) were fed for 50 days on a diet containing 3% lard and 1.3% cholesterol, to induce atherosclerosis. An atherogenic control group (A) was killed after this period and three groups were fed for an additional period of 30 days with a diet composed of (1.75 g of supplemented oil and 98.25 of standard chow): sunflower oil (S), virgin olive oil (O) and fish oil (F). A control group (n=6) was fed with a standard chow diet for 80 days. LDL lipid composition and histological analysis of aortic atherosclerotic lesions were assayed. The atherogenic diet caused a significant increase of cholesterol levels in LDL and aorta tissue. Cholesterol ester content rose significantly in the aortic arch of groups S, O and F. Fatty streaks were found in all aortic sections, although only group S showed a significant progression of the lesion compared with group A. We conclude that the replacement of a high cholesterol-saturated fat diet by another cholesterol free-unsaturated fat diet does not regress atherosclerosis in rabbit. However, sunflower oil provokes a significant progression in lesion development, whereas diet enrichment with extra virgin olive oil and, to a lesser extent, fish oil, stops this progression.
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Enfermedades de la Aorta/fisiopatología , Arteriosclerosis/fisiopatología , Grasas Insaturadas en la Dieta/farmacología , Aceites de Pescado/farmacología , Aceites de Plantas/farmacología , Animales , Aorta/metabolismo , Aorta/patología , Enfermedades de la Aorta/patología , Arteriosclerosis/patología , Ésteres del Colesterol/metabolismo , LDL-Colesterol/sangre , LDL-Colesterol/metabolismo , Progresión de la Enfermedad , Ácidos Grasos/metabolismo , Lípidos/sangre , Masculino , Aceite de Oliva , Conejos , Aceite de GirasolRESUMEN
Anthocyanins are secondary plant metabolites responsible for the blue, purple, and red color of many plant tissues. The phenolic structure of anthocyanins conveys marked antioxidant activity in model systems via donation of electrons or hydrogen atoms from hydroxyl moieties to free radicals. Dietary intakes of anthocyanins may exceed 200 mg/day, however, little is known about their antioxidant potency in vivo. Consequently, the aim of this study was to establish whether anthocyanins could act as putative antioxidant micronutrients. Rats were maintained on vitamin E-deficient diets for 12 weeks in order to enhance susceptibility to oxidative damage and then repleted with rations containing a highly purified anthocyanin-rich extract at a concentration of 1 g/kg diet. The extract consisted of the 3-glucopyranoside forms of delphinidin, cyanidin, petunidin, peonidin, and malvidin. Consumption of the anthocyanin-repleted diet significantly improved (p <.01) plasma antioxidant capacity and decreased (p <.001) the vitamin E deficiency-enhanced hydroperoxides and 8-Oxo-deoxyguanosine concentrations in liver. These compounds are indices of lipid peroxidation and DNA damage, respectively. Dietary consumption of anthocyanin-rich foods may contribute to overall antioxidant status, particularly in areas of habitually low vitamin E intake.
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Antocianinas/uso terapéutico , Antioxidantes/farmacología , Daño del ADN/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Deficiencia de Vitamina E/tratamiento farmacológico , 8-Hidroxi-2'-Desoxicoguanosina , Abies/química , Animales , Desoxiguanosina/análogos & derivados , Desoxiguanosina/antagonistas & inhibidores , Desoxiguanosina/metabolismo , Depuradores de Radicales Libres/metabolismo , Depuradores de Radicales Libres/farmacología , Frutas/química , Peróxidos Lipídicos/antagonistas & inhibidores , Peróxidos Lipídicos/metabolismo , Hígado/metabolismo , Ratas , Ratas Endogámicas , Deficiencia de Vitamina E/dietoterapia , alfa-Tocoferol/administración & dosificaciónRESUMEN
Se presenta un estudio inmunohistoquímico de expresión de glicoproteína P en 44 tumores óseos malignos (32 osteosarcomas y 12 condrosarcomas) con el propósito de analizar la inmunorreactividad por estirpe histológico y su valor pronóstico potencial. El principio del procedimiento es la determinación de la molécula de glicoproteína P mediante un método inmunohistoquímico que emplea un cóctel de anticuerpos monoclonales específicos (JSB1 y MRK16) prediluidos y el procedimiento estándar de la fosfatasa-antifosfatasa alcalina, con incubación doble de anticuerpo secundario y ese complejo. Las muestras de tejido fueron obtenidas antes de la quimioterapia. La inmunoexpresión se clasificó en seis grados según una escala semicuantitativa de positividad celular.Hay que destacar la expresión intensa y constante de glicoproteína P en la membrana celular de los condrosarcomas (positividad del 100 por ciento y puntuación semicuantitativa de 3,83ñ 1,03). En los osteosarcomas la tinción fue menos constante (positividad del 59,37 por ciento y puntuación semicuantitativa de 2,79 ñ 1,81). Los pacientes con osteosarcomas localizados de alto grado (IIB) y que expresaban glicoproteína P tenían una menor supervivencia (log rank; p < 0,05) e intervalo libre de enfermedad (log rank; p < 0,001). Los hallazgos sustentan a la expresión de glicoproteína P como factor pronóstico en el osteosarcoma (AU)
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Femenino , Masculino , Humanos , Osteosarcoma/diagnóstico , Subfamilia B de Transportador de Casetes de Unión a ATP/análisis , Inmunohistoquímica/métodos , Condrosarcoma Mesenquimal/diagnóstico , Biomarcadores de Tumor/aislamiento & purificación , Osteosarcoma , Condrosarcoma Mesenquimal , Supervivencia sin Enfermedad , Metástasis de la Neoplasia , Estadificación de Neoplasias/métodosRESUMEN
The oxidation of low-density lipoproteins (LDL) plays an important role in the development of atherosclerosis. Curcumin is a yellow pigment obtained from rhizomes of Curcuma longa and is commonly used as a spice and food colouring. Curcumin and turmeric extracts have several pharmacological effects including antitumour, anti-inflammatory, antioxidant and antiinfectious activities although the precise mechanisms involved remain to be elicited. We evaluated the effect of an ethanol-aqueous extract obtained from rhizomes of C. longa on LDL oxidation susceptibility and plasma lipids in atherosclerotic rabbits. A total of 18 rabbits were fed for 7 weeks on a diet containing 95.7% standard chow, 3% lard and 1. 3% cholesterol, to induce atherosclerosis. The rabbits were divided into groups, two of which were also orally treated with turmeric extract at doses of 1.66 (group A) and 3.2 (group B) mg/kg body weight, respectively. A third group (group C) acted as a control. Plasma and LDL lipid composition, plasma alpha-tocopherol, plasma retinol, LDL TBARS, LDL lipid hydroperoxides and analysis of aortic atherosclerotic lesions were assayed. The low but not the high dosage decreased the susceptibility of LDL to lipid peroxidation. Both doses had lower levels of total plasma cholesterol than the control group. Moreover, the lower dosage had lower levels of cholesterol, phospholipids and triglycerides in LDL than the 3.2-mg dosage. In conclusion, the use of this extract could be useful in the management of cardiovascular disease in which atherosclerosis is important.
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Antioxidantes/administración & dosificación , Arteriosclerosis/tratamiento farmacológico , Arteriosclerosis/patología , Lipoproteínas LDL/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Administración Oral , Animales , Anticolesterolemiantes/administración & dosificación , Curcuma , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Hipercolesterolemia/prevención & control , Peroxidación de Lípido/efectos de los fármacos , Lipoproteínas LDL/metabolismo , Masculino , Conejos , Distribución Aleatoria , Valores de ReferenciaRESUMEN
The present study describes a clinical trial in which Spanish patients suffering from peripheral vascular disease (Fontaine stage II) were given specific lipid supplements. Designed as a longitudinal intervention study, patients were provided with olive oil for 3 months, followed by a 3 month wash-out period, then supplemented with a combination of fish oil and olive oil for the final 3 months. Changes in plasma and lipoprotein fatty acid composition and susceptibility of LDL to in vitro oxidation were examined. Furthermore, lipid-supplement-induced changes in LDL properties were measured as relative electrophoretic mobility and macrophage uptake. In addition, thirteen patients not provided with olive oil and fish oil were included as a control group and twenty healthy age-matched individuals were used as a reference group. A complete clinical study and a nutritional survey concerning food habits and lifestyle were performed every 3 months. Yao indices and claudicometry did not change significantly with dietary intervention although changes in plasma lipid composition suggested an improvement in the condition of the patients. The intake of the fish-oil supplement resulted in significantly increased plasma levels of eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) in comparison with baseline concentrations, olive-oil and control groups. Fish-oil consumption significantly decreased plasma triacylglycerol levels compared with the olive-oil period, control and reference groups. The susceptibility of LDL to Cu-mediated oxidation was lower in the patients consuming olive oil and the fish-oil supplement than in the control group, and the uptake of LDL by macrophages was significantly lower in the group supplemented with fish oil. In conclusion, consumption of olive oil together with a dietary supplement of fish oil may be useful in the nutritional management of patients suffering from peripheral vascular disease in terms of increasing plasma n-3 long-chain polyunsaturated fatty acids and decreasing susceptibility of LDL to oxidation.
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Aceites de Pescado/uso terapéutico , Claudicación Intermitente/dietoterapia , Lípidos/sangre , Enfermedades Vasculares Periféricas/dietoterapia , Aceites de Plantas/uso terapéutico , LDL-Colesterol/metabolismo , Humanos , Claudicación Intermitente/sangre , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Aceite de Oliva , Oxidación-Reducción , Enfermedades Vasculares Periféricas/sangre , EspañaRESUMEN
INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. The Intercellular Adhesion Molecule plays a fundamental part in the migration of T cells to the inflammed tissues. It is known that there is an increase in the expression of endothelial cells and other cells found in lesions of the central nervous system of MS patients. ICAM-I may be detected in its soluble form in serum and it is of interest to understand its behaviour in this liquid since it is easily accessible. MATERIAL AND METHODS: We studied the concentration of soluble ICAM-I in the serum of patients with MS: one group which had clinical attacks were studied whilst in remission; another had the chronic progressive clinical form and a third group had optic neuritis as the probable initial sign of the disorder. Within the different clinical forms, some patients received treatment with beta-interferon or azathioprine and others did not. RESULTS AND CONCLUSIONS: We found a significant increase in the levels of soluble ICAM-I in patients with inactive, untreated MS as compared with normal persons, with no difference found between the different clinical types.
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Enfermedades Autoinmunes/sangre , Molécula 1 de Adhesión Intercelular/sangre , Esclerosis Múltiple/sangre , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/terapia , Azatioprina/uso terapéutico , Humanos , Factores Inmunológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Interferón beta/uso terapéutico , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/terapia , Enfermedades del Sistema Nervioso/sangre , Neuritis Óptica/sangre , Neuritis Óptica/etiología , SolubilidadRESUMEN
Although decidual stromal cells (DSC) have classically been considered to play a nutritional role during pregnancy, several reports have demonstrated that they can also exert different immune activities. Furthermore, some authors have occasionally found antigens on DSC normally expressed by immune cells. In this study, we isolated and cultured 12 human DSC lines and studied them with immunocytochemistry and flow cytometry using monoclonal antibodies against antigens associated with hematopoietic cells. Decidual stromal cells exhibited a constant phenotype: they were CALLA (CD10)-positive and DR-positive, although the expression of CD45, the leukocyte common antigen, was found to be very weak or negative. We also detected myelomonocytic antigens CD11b (CR3), CD13, CD16 (Fc gamma RIII) and CD36, although DSC lacked CD14, CD15 and CD33. B cell antigens CD20, CD21 (CR3), CD23 (Fc epsilon RII) and CD24 were expressed. DRC-1, an antigen detected on follicular dendritic cells (FDC), was also observed on DSC. When these cells were cultured in the presence of progesterone, they expressed desmin and prolactin (PRL), findings that confirmed their identity as DSC. The phenotype described, together with the immune activities reportedly carried out by DSC, suggest that DSC may play a role in the maternal-fetal immune relationship.
Asunto(s)
Antígenos CD/análisis , Antígenos CD/biosíntesis , Decidua/inmunología , Decidua/metabolismo , Células Madre Hematopoyéticas/inmunología , Anticuerpos Monoclonales , Células Cultivadas , Decidua/citología , Femenino , Antígenos HLA/biosíntesis , Antígenos HLA-DR/análisis , Antígenos HLA-DR/biosíntesis , Antígenos de Histocompatibilidad Clase I/biosíntesis , Humanos , Neprilisina/análisis , Neprilisina/biosíntesis , Embarazo , Células del Estroma/inmunología , Células del Estroma/metabolismo , Células del Estroma/fisiologíaRESUMEN
PROBLEM: Although several studies have demonstrated that decidual stromal cells (DSC) can secrete cytokines in culture, none of these studies documented the purity of the cultures. Since other cells of the decidua, such as macrophages and epithelial cells, also produce cytokines, it is important to ensure purity of the culture so that cytokine production can be ascribed with confidence to DSC. METHOD: DSC from early human pregnancies were highly purified and maintained in culture. Basal secretion by these cells of IL-6, together with other cytokines considered critical for pregnancy (IL-1 beta, TNF alpha and IFN gamma), was measured with immunological techniques. RESULTS: We found that DSC in culture produce insignificant quantities of IL-1 beta, TNF alpha and IFN gamma, but appreciable amounts of IL-6. The production of this later cytokine was, however, inhibited by the effect of progesterone. CONCLUSIONS: Basal production of IL-6 by DSC may be involved in physiological functions at the maternal-fetal interface. Nevertheless, the secretion of this cytokine is regulated by progesterone, probably to prevent excessive production of this cytokine from triggering an inflammatory response that might compromise pregnancy.
Asunto(s)
Decidua/efectos de los fármacos , Decidua/metabolismo , Interleucina-6/metabolismo , Progesterona/farmacología , Antígenos CD/análisis , División Celular/inmunología , Células Cultivadas , Decidua/citología , Femenino , Humanos , Inmunofenotipificación , Embarazo , Células del Estroma/clasificación , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismoRESUMEN
The percentages of cells expressing immune markers were determined with immunohistochemistry and flow cytometry in early and term human decidua. Although we found no variation in the proportion of cells of bone marrow origin (CD45+), the percentages of T cells and CD16+ lymphocytes were significantly higher in term decidua. On the contrary, CD56+ lymphocytes, the most abundant leukocyte type in early decidua, decreased at term. These variations may reflex the immunological adaptations of decidua during pregnancy.
Asunto(s)
Decidua/citología , Leucocitos/inmunología , Antígenos CD/análisis , Antígenos de Diferenciación de Linfocitos T/análisis , Antígeno CD56 , Decidua/inmunología , Femenino , Citometría de Flujo , Humanos , Inmunohistoquímica , Antígenos Comunes de Leucocito/análisis , Embarazo , Primer Trimestre del Embarazo , Tercer Trimestre del Embarazo , Receptores de IgG/análisisRESUMEN
The expression of adhesion molecules by endothelial cells (EC) of early human decidua was studied with monoclonal antibodies and the immunoperoxidase technique. Although E-selectin, INCAM-110 and VCAM-1 were poorly detected on decidual EC, ICAM-1, P-selectin and DR antigens were highly expressed by these cells, some of which showed high endothelial venule-like morphology. Our results suggest that decidual EC are activated, and are probably involved in the active recruitment of leucocytes.