Análisis comparativo de anticuerpos monoclonales en la respuesta inflamatoria pulmonar, en un modelo experimental de ventilación mecánica / Comparative analysis of monoclonal antibodies in the pulmonary inflammatory response, in an experimental model of mechanic ventilation

Objetivo: Evaluar si el pretratamiento con anticuerpos monoclonales antiFNTα y anti-IL-6, administrados de manera independiente, atenúa el daño pulmonar en un modelo experimental de lesión pulmonar inducida por la ventilación mecánica. Materiales y Métodos: Se utilizaron 24 ratas Wistar que fueron separadas en cuatro grupos experimentales: 1) bajo Vt (n = 6): Vt 7 ml/kg, PEEP 5 cmH2O, 2) alto Vt (n = 6): Vt 25 ml/kg, ZEEP (PEEP = 0), 3) anti-IL-6 (n = 6): Vt 25 ml/kg, ZEEP y 30 mg/kg de tocilizumab intraperitoneal 24 h antes de la ventilación mecánica, 4) anti-FNTα (n = 6): Vt 25 ml/kg, ZEEP y 100 ug/kg de adalimumab intraperitoneal 24 h antes de la ventilación mecánica. Se evaluaron el daño histológico cuantificado según el puntaje reportado por Villar et al y la hemodinamia medida con la presión arterial media. Los datos fueron analizados con ANOVA y las pruebas de comparaciones múltiples de Dunn y de Tukey. Resultados: En el grupo tratado con anti-FNTα y en los animales tratados con anti-IL-6, se observó un menor daño histológico pulmonar que en el resto de los grupos. Por otro lado, no se encontraron diferencias en la mecánica pulmonar y en la presión arterial media entre grupos. Conclusiones: Bajo estas condiciones experimentales, los anticuerpos monoclonales anti-FNTα y anti-IL-6 mostraron efectos protectores a nivel pulmonar, lo que postula a estas drogas como estrategias promisorias para atenuar la lesión pulmonar inducida por la ventilación mecánica.(AU)

Objective: To evaluate whether pretreatment with monoclonal antibodies, anti- TNFα and anti-IL-6 administered independently attenuates lung damage in an experimental model of ventilator-induced lung injury. Materials and Methods: Twenty-four Wistar rats were used. Animals were divided into four experimental groups: 1) low Vt (n = 6): Vt 7 mL/kg, PEEP 5 cmH2O; 2) high Vt (n = 6): Vt 25 mL/kg, ZEEP (PEEP = 0); 3) anti-IL-6 (n = 6): Vt 25 mL/kg, ZEEP, and intraperitoneal tocilizumab 30 mg/kg, 24 hours prior to mechanical ventilation; 4) anti-TNFα (n = 6): Vt 25 mL/kg, ZEEP, and intraperitoneal adalimumab 100 µg/kg, 24 hours before the VM. Histological damage measured by Villar score, and hemodynamics measured with mean arterial pressure were evaluated. Data were analyzed using ANOVA, Dunn's multiple comparison test and Tukey's multiple comparison test. Results: In groups treated with anti-TNFα and anti-IL-6, less histological damage was observed in comparison with the rest of groups. On the other hand, no statistically significant differences were found in pulmonary mechanics and mean arterial pressure among groups. Conclusions: Under these experimental conditions, monoclonal antibodies anti-TNFα and anti-IL-6 showed protective effects on lungs, indicating that these drugs are promising strategies to attenuate ventilator-induced lung injury (AU)

Can breast cancer Hsp 27 (Heat Shock Protein 27000) expression influence axillary lymph node status?

The expression of heat shock protein 27 (Hsp 27) in breast cancers correlates with stage of disease, the lower the stage the higher the expression, and with the presence or absence of lymph node metastases; lymph node negative patients being more likely to express Hsp 27 (P<0.04).

Quantitative and functional study of breast cancer axillary lymph nodes and those draining other human malignant tumors.

Lymphocyte functional activity from lymph nodes draining human malignancies reflects the host immune response against tumour. Breast cancer is the neoplasia with the greatest amount of identified antigens but a weak inducer of a host efficient immune response. In our study we compared the mitogen stimulated-proliferative response of cells isolated from metastases-free lymph nodes draining breast cancer (Group 1), other malignant tumours (Group 2), and those obtained from patients without malignancies (Control group). A significant decrease of the proliferative response in cells isolated from lymph nodes draining breast cancer was observed comparing it to the other groups. Quantitative analysis of B and T cells showed a higher number of B cells than T cells in Groups 1 and 2. Moreover, Group 1 presented a two fold increase of T cells compared with Group 2. Our results suggest that the immunosuppression observed in lymph nodes draining breast cancer is higher than the inmunosuppression presented in other malignant tumours and that impaired function is not correlated with the increased number of T cells.

[Biology of heat shock proteins]. / Biologia de las proteinas del shock térmico.

Hsp (Heat shock proteins) are a family of constitutive proteins of all pro and eukariotic cells that play different physiological roles: they promote the folding (acquisition of tertiary structure) assembly, translocation and secretion of newly synthesized polypeptides and participate in the removal or repairing of denatured proteins acting as molecular chaperons. This family of proteins is composed by numerous members grouped according to their molecular weight. When cells are subjected to different stresses such as hyperthermic shock, radiation, toxins, viral infections, etc., Hsp are overexpressed. In this way, they exert a cytoprotective effect, making the cells resistant to apoptosis. In humans, Hsp are overexpressed in cancer cells from ovary, endometrium, breast, prostate, digestive tract, etc. In some cases, overexpression is correlated with an unfavorable outcome because these proteins could favour metastatic disease. Some authors associate them not only with proliferation but also with differentiation of the neoplastic tissue. Recent studies show their influence in resistance to chemotherapeutic drugs. In autoimmune diseases like rheumatoid arthritis, Hsp can suppress the inflammatory response. Nevertheless, their role in the immune system has not been well established.

[Dendritic cells and their role in pathology]. / Células dendríticas y su papel en patologia.

The aim of this review is to update the knowledge on dendritic cells (CD), as potent antigen-presenting cells (APC) expressing class II major histocompatibility (MHC) antigen. The different types of DC are derived from a common bone marrow precursor. They differentiate and migrate to lymphoid and non-lymphoid tissues under the influence of diverse stimuli. After binding antigen in their periphery they move to the lymph node activating T cells. Depending on the microenvironment, DC express several surface markers and secrete cytokines such as IL-12, Il-1 and TNF alpha. DC play a role in the pathogenesis of autoimmune and viral diseases being relevant in AIDS. These cells also infiltrate human tumors where they could be involved in the induction of anti-tumor immune response. The immunostimulatory properties of DC are currently applied in DC-based therapies of melanoma and lymphoma patients.

The safety and effectiveness of stepwise and low-dose administration of follicle stimulating hormone in WHO group II anovulatory infertile women: evidence from a large multicenter study in Spain.

PURPOSE: Our goal was to investigate the safety, effectiveness, and feasibility for the practicing physician of stepwise and low-dose administration of FSH in WHO group II anovulatory infertile women. METHODS: Infertile female patients (n = 234) suffering from WHO group II anovulation, and who failed to became pregnant with clomiphene citrate, were included in a multicenter, prospective, clinical study of treatment with a protocol of chronic low-dose and small incremental rises with urinary purified or highly purified FSH. Follicular development was monitored with ultrasonographic scans. RESULTS: The 234 patients received a total of 534 cycles of treatment, for a mean number of 2.3 treated cycles per patient. hCG was withheld in 65 (12.2%) cyles because of no response and in 28 (5.2%) cycles because of hyperresponse. Of the remaining 441 cycles, 419 (95%) were ovulatory, and in 198 (47.3%) of these cycles a single dominant follicle developed. There were 93 pregnancies (39.7% per patient), for a cycle fecundity rate of 17.4%. Cumulative conception rate after two treated cycles was 33.5%. There were 14 (15%) pairs of twins and 10 (10.8%) spontaneous miscarriages. The prevalence of complications was low with no cases of severe OHSS. Basal LH/FSH ratio was significantly higher in the pregnant group of patients than in nonpregnant women. CONCLUSIONS: Stepwise and chronic low-dose administration of FSH is a safe and effective method for treatment of WHO group II anovulatory infertility, mainly in those patients having high LH/FSH ratios.

[Identification of a tumor antigen associated to the estrogen receptor in axillary lymph nodes of breast cancer patients]. / Identificación de un antigeno tumoral asociado al receptor estrogénico en ganglios linfáticos axilares de pacientes con cáncer mamario.

Sixteen axillary lymph nodes were incubated with sera from patients with mammary carcinoma. Using immunofluorescence staining sera recognized antigenic determinants on follicular dendritic cells (FDC) within the follicle centers. These results were confirmed with isolated and cultured FDC that were incubated with the same sera. All the results were negative with normal sera. We also found a cell population positively reacting with a monoclonal antibody against an estrogen receptor associated protein (ERAP) in subcapsular and cortical sinusae and germinal centers. Phenotype identification of ERAP+ cells indicated that they presented characteristics of macrophages and FDC respectively. Lymph nodes from other malignancies were negative for ERAP. These findings suggest that the tumoral antigen could be either the protein associated with the estrogen receptor or the receptor itself. The ERAP could be transported by the macrophages from the tumor to the regional lymph nodes where it could be processed and maintained during a long time by FDC, since it is known that these are the most efficient antigen presenting cells.

[Intestinal obstruction caused by foreign body in a patient with colon neoplasm]. / Obstrucción intestinal por "cuerpo extraño" en paciente con neoplasia de colon.

A case of intestinal obstruction due to ingested "foreign body" (a patient's tooth) is described in an elderly man with cancer of the ascending colon, at that time, without clinical symptoms.

Demonstration and characterization of HLA-DR positive cells in the stroma of human endometrium.

The proportion of stromal cells expressing DR antigens of the HLA system or reacting with an anti-macrophage antibody was studied by immunohistochemical methods in human proliferative, secretory and post-menopausal endometria. DR+ cells showed a rounded morphology with short expansions and represented 13-25% of the stromal cells in the proliferative and 16-43% in the secretory endometrium. The cells reacting with the anti-macrophage antibody were similar to DR+ cells, but their number was between 1/2 and 1/10 of DR+ cells. In the post-menopausal endometria no DR+ cells or elements reacting with anti-macrophage antibody were observed. These results suggest that a significant proportion of endometrial stromal cells expressing type II histocompatibility antigens do not belong to the monocyte-phagocyte system and that their number is under hormonal regulation.

[Changes in nutritional and biochemical parameters in septic patients undergoing total parenteral nutrition. Their relationship with mortality]. / Evolución de parámetros nutricionales y bioquímicos en pacientes sépticos bajo NPT. Su relación con la mortalidad.

The response of 24 septic patients admitted into the ICU to total parenteral nutrition was studied, and the course of the parameters evaluated from non-surviving (14) and surviving patients was compared. Serum glucose, triglyceride, albumin, transferrin, prealbumin, RBP, zinc levels and CD4/CD8 ratio were measured at 48 hours, 4 days and 8 days after the onset of parenteral nutrition. Overall, a significant increase in prealbumin (p less than 0.01) and RBP (p less than 0.05) levels were the only findings to parenteral nutrition response. When the non-surviving and surviving groups were compared, the former showed a significant increase in serum triglyceride (p less than 0.001), while a significant increase in serum transferrin and CD4/CD8 ratio (p less than 0.01) was observed in the latter.

Ultraestructura del lecho capilar placentario en el retardo de crecimiento intrauterino / Ultraestructure of the capillary placental bed in the intrauterine growth retardation

El propósito del presente estudio ha sido analizar las alteraciones del lecho placentario, evaluando las características de las arterias espiraladas, en embarazadas con retardo de crecimiento idiopático y coincidentes con hipertensión arterial, comparando dichas alteraciones con las características normales de gestantes sanas. A tal efecto se realizó biopsia del lecho placentario mediante la obtención de un cono a bisturí de la decidua basal y miometrio, así como de la decidua corial. La población estudiada estuvo constituída por tres embarazadas normales, tres crecimientos fetales disminuídas de etiología idiopática y tres crecimientos intrauterinos retardados coincidentes con hipertensión arterial. El material fue estudiado con microscopía electrónica. Se describe la ultraestructura del lecho capilar de la placenta a término en el embarazo normal. En el crecimiento fetal disminuído idiopático la imagen ultraestructural fue semejante a la de las embarazadas normales. En contraste se observaron francas alteraciones en las arterias espiraladas del lecho capilar uterino.

Ultraestructura del lecho capilar placentario en el retardo de crecimiento intrauterino / Ultraestructure of the capillary placental bed in the intrauterine growth retardation

El propósito del presente estudio ha sido analizar las alteraciones del lecho placentario, evaluando las características de las arterias espiraladas, en embarazadas con retardo de crecimiento idiopático y coincidentes con hipertensión arterial, comparando dichas alteraciones con las características normales de gestantes sanas. A tal efecto se realizó biopsia del lecho placentario mediante la obtención de un cono a bisturí de la decidua basal y miometrio, así como de la decidua corial. La población estudiada estuvo constituída por tres embarazadas normales, tres crecimientos fetales disminuídas de etiología idiopática y tres crecimientos intrauterinos retardados coincidentes con hipertensión arterial. El material fue estudiado con microscopía electrónica. Se describe la ultraestructura del lecho capilar de la placenta a término en el embarazo normal. En el crecimiento fetal disminuído idiopático la imagen ultraestructural fue semejante a la de las embarazadas normales. En contraste se observaron francas alteraciones en las arterias espiraladas del lecho capilar uterino.(AU)

Acro-angiodermatitis del pie: a propósito de un caso clínico / Acroangiodermatitis of the foot: apropos of a clinical case

La acroangiodermatitis es una angiodermitis que se asemeja a la enfermedad de Favre y Chaix, con lesiones polimorfas de capilaritis, pápulas o nódulos y una insuficiencia venosa crónica del pie. Es la consecuencia de dos importantes factores patogénicos: a) el síndrome varicoso (Mali) y b) fístulas arteriofenosas (Bluefard). Se presenta un caso de acroangiodermatitis del pie por insuficiencia venosa crónica. Se hacen consideraciones sobre las características de esta afección, su patogenia y diagnóstico diferencial con el enfermedad de Kaposi

Acro-angiodermatitis del pie: a propósito de un caso clínico / Acroangiodermatitis of the foot: apropos of a clinical case

La acroangiodermatitis es una angiodermitis que se asemeja a la enfermedad de Favre y Chaix, con lesiones polimorfas de capilaritis, pápulas o nódulos y una insuficiencia venosa crónica del pie. Es la consecuencia de dos importantes factores patogénicos: a) el síndrome varicoso (Mali) y b) fístulas arteriofenosas (Bluefard). Se presenta un caso de acroangiodermatitis del pie por insuficiencia venosa crónica. Se hacen consideraciones sobre las características de esta afección, su patogenia y diagnóstico diferencial con el enfermedad de Kaposi (AU)

[Presence of antisinusoid antibodies in alcoholic hepatitis. Its probable pathogenic implications]. / Presencia de anticuerpos anti-sinusoide en las hepatitis alcohólicas. Su probable implicancia patogénica.

In nine patients with histological diagnosis of alcoholic hepatitis, in-situ deposition of autologous immunoglobulins (IgG, Iga, IgM) were investigated by inmmuno fluorescent techniques (IF). In three patients a linear fluorescent pattern was seen on the sinusoidal walls. The bound inmunoglobulins could be eluted by treatment with low pH buffers. In the same patients circulating antibodies against liver structures were investigated by indirect IF using normal murine or human liver as targets. In the same patients showing bound immunoglobulins in their liver, curculating antibodies against human sinusoids and not against murine liver could be found. On the basis of these findings the probable pathogenetic role of immune mechanism in alcoholic liver damage is discussed.

Presencia de anticuerpos anti-sinusoide en las hepatitis alcohólicas. Su probable implicancia patogénica. / [Presence of antisinusoid antibodies in alcoholic hepatitis. Its probable pathogenic implications]

In nine patients with histological diagnosis of alcoholic hepatitis, in-situ deposition of autologous immunoglobulins (IgG, Iga, IgM) were investigated by inmmuno fluorescent techniques (IF). In three patients a linear fluorescent pattern was seen on the sinusoidal walls. The bound inmunoglobulins could be eluted by treatment with low pH buffers. In the same patients circulating antibodies against liver structures were investigated by indirect IF using normal murine or human liver as targets. In the same patients showing bound immunoglobulins in their liver, curculating antibodies against human sinusoids and not against murine liver could be found. On the basis of these findings the probable pathogenetic role of immune mechanism in alcoholic liver damage is discussed.

Presencia de anticuerpos anti-sinusoide en las hepatitis alcohólicas. Su probable implicancia patogénica / [Presence of antisinusoid antibodies in alcoholic hepatitis. Its probable pathogenic implications]

In nine patients with histological diagnosis of alcoholic hepatitis, in-situ deposition of autologous immunoglobulins (IgG, Iga, IgM) were investigated by inmmuno fluorescent techniques (IF). In three patients a linear fluorescent pattern was seen on the sinusoidal walls. The bound inmunoglobulins could be eluted by treatment with low pH buffers. In the same patients circulating antibodies against liver structures were investigated by indirect IF using normal murine or human liver as targets. In the same patients showing bound immunoglobulins in their liver, curculating antibodies against human sinusoids and not against murine liver could be found. On the basis of these findings the probable pathogenetic role of immune mechanism in alcoholic liver damage is discussed.

The small intestine in diabetes mellitus. Correlation of clinical phenomena to histomorphometric findings in peroral biopsy material.

Biopsy material obtained from the first portion of the jejunum of 56 unselected diabetics and 21 normal controls was examined under the electron microscope (in 8 cases) or with a method of stereologic morphometry. Controls were found to have a villous volume (VVi) of 50.19 +/- 10.1%. All values below 40% were interpreted as an expression of deterioration of the mucous membrane. Altogether 12.5% of the diabetics showed total atrophy, and 20% had significant reduction of VVi. These changes did not correlate with intestinal disorders or other signs of diabetes. In total atrophy histochemical changes could be demonstrated. Microangiopathy was not observed in the intestinal mucosa.