La problemática de la alimentación: una experiencia de aprendizaje de Biología en el contexto de la educación popular, como herramienta de transformación social

La implementación del sistema Neoliberal en América Latina ha venido generando graves consecuencias a nivel educativo, familiar y comunitario y ha provocado una fuerte crisis alimentaria. Bajo éstas circunstancias, desde el año 1998, funcionan los Bachilleratos Populares en provincia de Buenos Aires y Capital Federal, surgiendo como proyectos educativos comprometidos con la realidad de nuestro pueblo y apuntando al desarrollo de un pensamiento crítico para la transformación social. Como docentes del Bachillerato Popular Roca Negra (Monte Chingolo, Lanús, provincia de Buenos Aires) desarrollamos la problemática de la alimentación en un marco de educación para la salud. Se trabajó con metodología taller (Algava, M, 2006), apostando a la construcción dialógica del conocimiento entre educadores y educandos, y analizando una situación concreta del barrio. El tratamiento integral de la problemática, tomando aspectos biológicos, sociales, culturales y económicos, generó resultados positivos en relación al empoderamiento en el espacio de construcción del Bachillerato y contribuyó a la valoración de la biología como herramienta de transformación social, asumiéndonos como sujetos activos, capaces de modificar la realidad.Departamento de Ciencias Exactas y Naturale

Commentary: Arginine vasopressin receptor 1a is a therapeutic target for castration-resistant prostate cancer

Prostate cancer patients managed with androgen-deprivation therapy usually recur after a few years and the disease gradually becomes castration-resistant prostate cancer (CRPC). The role of tumor cell plasticity, including processes such as transdifferentiation and epithelial-mesenchymal transition, is pivotal in the development of androgen receptor (AR)-indifferent tumor variants (1). Cell plasticity may allow CRPC progression and metastasis by favoring reactivation of AR signaling as a result of different mechanisms of transcriptome reprogramming. Interestingly, dissection of such mechanisms can lead to the identification of novel vulnerabilities of aggressive tumor cells that can be targeted therapeutically. The recent work by Zhao et al. (2) identified the vasopressin receptor 1a (AVPR1a) as a critical effector in CRPC expressing the AR coactivator VAV3 and the constitutively active AR variant AR-V7. They demonstrated that ectopic expression of AVPR1a is capable of conferring castration resistance and agonist treatment with the receptor ligand, the natural hormone arginine vasopressin, activates ERK and CREB, signaling molecules known to promote prostate cancer progression. Interestingly, depletion of AVPR1a or inhibition by the selective AVPR1a antagonist relcovaptan resulted in decreased CRPC cell proliferation and reduced bone metastatic growth in vivo. We completely agree with the authors in the sense that AVPR1a can be a potential target for CRPC therapy. We believe that clinical trials with relcovaptan are warranted, particularly in patients with bone-metastatic disease for which therapeutic options are limited. However, we want to point out that these results could be revealing other untapped antitumor properties of the vasopressin system-related drugs against prostate cancer cells. Our team has reported that the vasopressin analog desmopressin, a selective agonist for the vasopressin receptor 2 (AVPR2), significantly reduced tumor cell growth and migration in AR-negative CRPC (3). In vitro exposure to desmopressin also induced a dramatic decrease of the neuroendocrine markers chromogranin and neuron-specific enolase in aggressive CRPC cells (3). In prostate cancer, neuroendocrine transdifferentiation is known to be related with transition toward AR-indifference and metastatic phenotype. Besides, recent studies in orthotopic and heterotopic models of CRPC in athymic nude mice demonstrated an enhanced efficacy of docetaxel in combination with desmopressin (4, 5). Agonist activation of AVPR2 present in various human cancer cell lines has been associated with triggering of antiproliferative signaling pathways involving canonical adenylate cyclase/cAMP/PKA axis activation. cAMP blocks the proliferation of many cell types, both normal and transformed, through multiple downstream effectors. It is known that increased cAMP levels inhibit the Raf/MAPK/ERK signaling pathway in a PKA-dependent manner, but this is not the only mitogenic pathway impaired by cAMP (6). Although cytostatic effect after AVPR2 stimulation is robust, the underlying mechanism is intriguing since AVPR2-mediated cell signaling may eventually lead to phosphorylation of hundreds of PKA substrates granting a complex and seemingly contradictory framework of signaling pathways as evidenced in immortalized epithelial cells after stimulation with desmopressin (7). In this sense, high cAMP levels and PKA activation may eventually lead to phosphorylation and activation of CREB. However, many factors contribute to final cell response. It is known that cAMP can either stimulate or inhibit tumor cell apoptosis, and PKA is able to mediate cAMP-promoted proapoptotic responses depending on the cell type and the cell context (8). In addition, it has been reported a crosstalk of cAMP/PKA that can inhibit RhoA-mediated signaling, thus affecting the aggressive behavior of CRPC cells (9). Taken together, it seems that CREB activation is not prominent after AVPR2 selective agonist action on cancer cells, being favored certain antiproliferative signals. In breast cancer cells expressing AVPR1a and AVPR2, natural vasopressin can activate both receptors but its affinity is higher for AVPR1a and the number of functional AVPR2 tends to be relatively low. Thus, vasopressin elicits AVPR1a-dependent proliferative signals mediated by ERK activation that clearly predominate over AVPR2-dependent antiproliferative signals (10). On the contrary, when AVPR1a is blocked by selective antagonists such as relcovaptan or tumor cells are exposed to specific AVPR2 agonists such as desmopressin, significant antiproliferative effects are achievable in hormone-resistant breast cancer cell lines (10, 11). Desmopressin also contributed to reduce aggressiveness of mammary tumors during chemotherapy in an immunocompetent mouse model (12). We have conducted a Phase 2 dose-escalation clinical trial of desmopressin as a perioperative adjuvant in patients with breast cancer (NCT01606072). Desmopressin appeared safe when administered in two slow infusions before and after surgery, and a rapid postoperative drop in circulating tumor cells was detected after treatment (13). In addition, we documented a reduced intraoperative bleeding associated to the well-known hemostatic effects of the compound (13). From a wider perspective, the stimulating article by Zhao et al. (2) ratifies the relevance of the vasopressin system for searching novel therapeutic targets in hormone-resistant cancer and particularly in CRPC (Figure 1; see also Supplementary Table 1 for preclinical data summary). In this context, repurposing of already-used drugs with a non-oncology primary purpose stands as an interesting strategy to offer effective therapeutic options to cancer patients, allowing faster development and reducing safety concerns (14). The selective AVPR1a antagonist relcovaptan is a small-molecule inhibitor that has been safely and effectively used in clinical trials for Raynaud syndrome, dysmenorrhea and preterm labor. The specific AVPR2 agonist desmopressin is a synthetic peptide compound that has been employed for decades as an antidiuretic in the treatment of diabetic insipidus and enuresis, and as a hemostatic agent for the management of bleeding disorders, with a history of good tolerability and clinical effectiveness. Both compounds constitute promising therapeutic approaches for CRPC that deserve clinical testing either alone or in combination, as well as concurrently with standard chemotherapy regimens.Fil: Ripoll, Giselle Vanina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pifano, Marina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garona, Juan. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Preclinical efficacy of [V 4 Q 5 ]dDAVP, a second generation vasopressin analog, on metastatic spread and tumor-associated angiogenesis in colorectal cancer

Purpose Control of metastatic spread of colorectal cancer (CRC) remains as a major therapeutic challenge. [V 4 Q 5 ]dDAVP is a vasopressin peptide analog with previously reported anticancer activity against carcinoma tumors. By acting as a selective agonist of arginine vasopressin type 2 membrane receptor (AVPR2) present in endothelial and tumor cells, [V 4 Q 5 ]dDAVP is able to impair tumor aggressiveness and distant spread. Our aim was to evaluate the potential therapeutic benefits of [V 4 Q 5 ]dDAVP on highly aggressive CRC disease using experimental models with translational relevance. Materials and Methods Murine CT-26 and human Colo-205 AVPR2-expressing CRC cell lines were used to test the preclinical efficacy of [V 4 Q 5 ]dDAVP, both in vitro and in vivo. Results In syngeneic mice surgically implanted with CT-26 cells in the spleen, sustained intravenous treatment with [V 4 Q 5 ]dDAVP (0.3 jg/kg) dramatically impaired metastatic progression to liver without overt signs of toxicity, and also reduced experimental lung colonization. The compound inhibited in vivo angiogenesis driven by Colo-205 cells in athymic mice, as well as in vitro endothelial cell migration and capillary tube formation. [V 4 Q 5 ]dDAVP exerted AVPR2-dependent cytostatic activity in vitro (IC50 1.08 |jM) and addition to 5-fluorouracil resulted in synergistic antiproliferative effects both in CT-26 and Colo-205 cells. Conclusion The present preclinical study establishes for the first time the efficacy of [V 4 Q 5 ]dDAVP on CRC. These encouraging results suggest that the novel second generation vasopressin analog could be used for the management of aggressive CRC as an adjuvant agent during surgery or to complement standard chemotherapy, limiting tumor angiogenesis and metastasis and thus protecting the patient from CRC recurrence.Fil: Garona, Juan. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sobol, Natasha Tatiana. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pifano, Marina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Segatori, Valeria Inés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ripoll, Giselle Vanina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Expression of bladder cancer‑associated glycans in murine tumor cell lines

The characterization of murine cell lines is of great importance in order to identify preclinical models that could resemble human diseases. Aberrant glycosylation includes the loss, excessive or novel expression of glycans and the appearance of truncated structures. MB49 and MB49-I are currently the only two murine cell lines available for the development of preclinical bladder cancer models. The glycans Lewis X (LeX), Sialyl lewis X (SLeX) and Sialyl Tn (STn) have previously been associated with aggressiveness, dissemination and poor prognosis in human bladder cancer, additionally N-glycolyl GM3 (NGcGM3) is a neo-antigen expressed in many types of tumors; however, to the best of our knowledge, its expression has not previously been assessed in this type of cancer. Taking into account the relevance of glycans in tumor biology and considering that they can act as targets of therapies and biomarkers, the present study evaluated the expression of LeX, SLeX, STn and NGcGM3 in MB49 and MB49-I cells, in different growth conditions such as mono-layer cultures, three-dimensional multicellular spheroids and mouse heterotopic and orthotopic tumors. The expression of LeX was not detected in either cell line, whereas SLeX was expressed in monolayers, spheroids and orthotopic tumors of both cell lines. STn was only identified in MB49 monolayers and spheroids. There are no reports concerning the expression of NGcGM3 in human or murine bladder cancer. In our hands, MB49 and MB49-I expressed this ganglioside in all the growth conditions evaluated. The assessment of its expression in cancer cell lines and patient tumors is of great importance, considering the relevance of this ganglioside in tumor biology. The data obtained by the present study demonstrates that glycan expression may be substantially altered depending on the growth conditions, highlighting the importance of the characterization of murine cancer models. To the best of our knowledge, the present study is the first to examine the expression of cancer-associated glycans, in the two murine cell lines available for the development of preclinical studies in bladder cancer.Fil: Alberto, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Cuello, Héctor Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Gulino, Cynthia Antonella. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Pifano, Marina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Belgorosky, Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología; ArgentinaFil: Gabri, Mariano. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Eijan, Ana Maria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Segatori, Valeria Inés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Insight into the effect of the vasopressin analog desmopressin on lung colonization by mammary carcinoma cells in BALB/c mice

Background/Aim: Desmopressin (dDAVP) is a synthetic peptide analog of vasopressin with antidiuretic and hemostatic properties. Recent experimental evidence suggested that dDAVP can inhibit metastasis formation by agonist action on V2 vasopressin receptors present in both tumor and endothelial cells. We have examined the kinetics of dDAVP effect during metastatic colonization and its potential association with hemostasis. Materials and Methods: The experimental metastasis assay was performed by injecting F3II mammary carcinoma cells into the lateral tail vein of syngeneic female BALB/c mice. Results: Clinically relevant doses of dDAVP (0.3 to 2 μg/kg intravenously (i.v.)) produced a dose-dependent inhibition in the formation of lung nodules when administered during the first 24 hours after F3II tumor cell injection. The hemostatic agent tranexamic acid (10 mg/kg, i.v.) had not effect on metastasis formation in the same experimental conditions, while the anticoagulant enoxaparin (1 mg/kg, subcutaneously (s.c.)) did not modify the antimetastatic action of dDAVP. In vitro, dDAVP had a strong inhibitory effect on F3II cell colony formation. Conclusion: dDAVP interferes with early metastatic disease, and direct association of this effect with hemostatic mechanisms is unlikely.Fil: Garona, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Pifano, Marina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Scursoni, Alejandra Marcela. Municipalidad de Quilmes (buenos Aires). Hospital Zonal General de Agudos Doctor Isidoro Iriarte.; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Ripoll, Giselle Vanina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentin

Peptide Agonists of Vasopressin V2 Receptor Reduce Expression of Neuroendocrine Markers and Tumor Growth in Human Lung and Prostate Tumor Cells

Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies that express neuropeptides as synaptophysin, chromogranin A (CgA), and specific neuronal enolase (NSE), among others. Vasopressin (AVP) is a neuropeptide with an endocrine, paracrine, and autocrine effect in normal and pathological tissues. AVP receptors are present in human lung, breast, pancreatic, colorectal, and gastrointestinal tumors. While AVP V1 receptors are associated with stimulation of cellular proliferation, AVP V2 receptor (V2r) is related to antiproliferative effects. Desmopressin (dDAVP) is a synthetic analog of AVP that acts as a selective agonist for the V2r, which shows antitumor properties in breast and colorectal cancer models. Recently, we developed a derivative of dDAVP named [V4Q5]dDAVP, which presents higher antitumor effects in a breast cancer model compared to the parental compound. The goal of present work was to explore the antitumor properties of the V2r agonist dDAVP and its novel analog [V4Q5]dDAVP on aggressive human lung (NCI-H82) and prostate cancer (PC-3) cell lines with neuroendocrine (NE) characteristics. We study the presence of specific NE markers (CgA and NSE) and V2r expression in NCI-H82 and PC-3. Both cell lines express high levels of NE markers NSE and CgA but then incubation with dDAVP diminished expression levels of both markers. DDAVP and [V4Q5]dDAVP significantly reduced proliferation, doubling time, and migration in both tumor cell cultures. [V4Q5]dDAVP analog showed a higher cytostatic effect than dDAVP, on cellular proliferation in the NCI-H82 cell line. Silencing of V2r using small interfering RNA significantly attenuated the inhibitory effects of [V4Q5]dDAVP on NCI-H82 cell proliferation. We, preliminarily, explored the in vivo effect of dDAVP and [V4Q5]dDAVP on NCI-H82 small cell lung cancer xenografts. Treated tumors (0.3 μg kg−1, thrice a week) grew slower in comparison to vehicle-treated animals. In this work, we demonstrated that the specific agonists of V2r, dDAVP, and [V4Q5]dDAVP displays antitumor capacity on different human models of lung and prostate cancers with NE features, showing their potential therapeutic benefits in the treatment of these aggressive tumors.Fil: Pifano, Marina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garona, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Capobianco, Carla Sabrina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: González, Nazareno. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Ripoll, Giselle Vanina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentin

Persistencia de anticuerpos IgG contra SARS-CoV2 en personal de salud - provincia de Buenos Aires.

Aim: To evaluate the persistence of IgG antibodies to SARS-CoV2, in health workers of the public subsector of the Province of Buenos Aires, and correlate it with demographic variables (sex, age) and other health indicators (diagnosis of COVID-19, comorbidities and pregnancy). Methodology: Descriptive, observational, cross-sectional study. Health workers with a positive result in a first sample (N = 388) underwent a second test to evaluate the persistence of antibodies by ELISA. Results: Of the 386 people evaluated with a conclusive result, 296 had a first positive result between 30 and 90 days before the second test, of these, 90% had detectable antibodies. In those with a positive result more than 90 days ago (45), a significant decrease in persistence of 26.7% was observed. There were no significant associations between demographic and health variables and the second test result. Conclusion: Antibodies remain detectable for at least 90 days in 90% of the cases analyzed. It is main to continue this study over time to have a major period of time between tests. The information shown here throws interesting and promising data regarding the possible protection of new COVID-19 infections in personnel with high risk exposure. This evidence could contribute to decision-making, both at the local and regional level, for the adequate vaccination planning, as well as for the management in the event of a possible second wave scenario of COVID-19 pandemic in Latin America.Objetivo: evaluar la persistencia de los anticuerpos IgG contra SARS-CoV2, en trabajadores de salud del subsector público de la Provincia de Buenos Aires, y correlacionarla con variables demográficas (sexo, edad) y otros indicadores de salud (diagnóstico de COVID-19, comorbilidades y embarazo). Metodología: Estudio descriptivo, observacional, de corte transversal. Al personal de salud con un resultado positivo en una primera muestra (N=388) se les realizó una segunda prueba para evaluar la persistencia de anticuerpos mediante ELISA. Resultados: De las 386 personas evaluadas con resultado concluyente, 296 contaban con un primer resultado positivo entre los 30 y los 90 días anteriores a la segunda prueba, el 90% presentó anticuerpos detectables. En aquellas personas con un resultado positivo hacía más de 90 días (45) se observó una caída significativa en la persistencia del 26,7%. No hubo asociaciones significativas entre las variables demográficas y de salud y el resultado de la segunda prueba. Conclusión: Los anticuerpos se mantienen detectables por al menos 90 días en el 90% de los casos analizados. Resulta fundamental continuar este estudio en el tiempo para contar con un período de tiempo mayor entre pruebas. La información aquí mostrada arroja datos interesantes y prometedores en cuanto a la posible protección de nuevos contagios de COVID-19 en personal con alta exposición de riesgo. Estas evidencias podrían contribuir a la toma de decisiones, tanto a nivel local como regional, para la adecuada planificación de la vacunación, así como también, para el manejo de la pandemia ante una posible segunda ola de casos en América Latina

The novel desmopressin analogue [V4Q5]dDAVP inhibits angiogenesis, tumour growth and metastases in vasopressin type 2 receptor-expressing breast cancer models

Desmopressin (dDAVP) is a safe haemostatic agent with previously reported antitumour activity. It acts as a selective agonist for the V2 vasopressin membrane receptor (V2r) present on tumour cells and microvasculature. The purpose of this study was to evaluate the novel peptide derivative [V4Q5]dDAVP in V2r-expressing preclinical mouse models of breast cancer. We assessed antitumour effects of [V4Q5]dDAVP using human MCF-7 and MDA‑MB‑231 breast carcinoma cells, as well as the highly metastatic mouse F3II cell line. Effect on in vitro cancer cell growth was evaluated by cell proliferation and clonogenic assays. Cell cycle distribution was analysed by flow cytometry. In order to study the effect of intravenously administered [V4Q5]dDAVP on tumour growth and angiogenesis, breast cancer xenografts were generated in athymic mice. F3II cells were injected into syngeneic mice to evaluate the effect of [V4Q5]dDAVP on spontaneous and experimental metastatic spread. In vitro cytostatic effects of [V4Q5]dDAVP against breast cancer cells were greater than those of dDAVP, and associated with V2r-activated signal transduction and partial cell cycle arrest. In MDA‑MB‑231 xenografts, [V4Q5]dDAVP (0.3 µg/kg, thrice a week) reduced tumour growth and angiogenesis. Treatment of F3II mammary tumour-bearing immunocompetent mice resulted in complete inhibition of metastatic progression. [V4Q5]dDAVP also displayed greater antimetastatic efficacy than dDAVP on experimental lung colonisation by F3II cells. The novel analogue was well tolerated in preliminary acute toxicology studies, at doses ≥300-fold above that required for anti-angiogenic/antimetastatic effects. Our data establish the preclinical activity of [V4Q5]dDAVP in aggressive breast cancer, providing the rationale for further clinical trials.Fil: Garona, Juan. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pifano, Marina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Orlando, Ulises Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Pastrian, María Belén. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Iannucci, Nancy Beatriz. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ortega, Hugo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Ciencias Veterinarias del Litoral; Argentina. Universidad Nacional del Litoral; ArgentinaFil: Podesta, Ernesto Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ripoll, Giselle Vanina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

COVID-19 Y VULNERABILIDAD SOCIAL: ANALISIS DESCRIPTIVO DE UNA SERIE DE CASOS DEL AREA METROPOLITANA DE BUENOS AIRES*

Introduction: Morbidity and mortality due to COVID-19 constitutes a global public health problem, in Argentina and the Buenos Aires province. Populations with social vulnerability have a fragility which exposes them to grater risks.. Objective: To characterize the social vulnerability of a series of confirmed cases that reside in the Metropolitan Area of Buenos Aires. Methods: Descriptive cross-sectional study. Variables of gender, age, evolution and domicile were analyzed and categorized through the Socio-Territorial Vulnerability Index (STVI). Results: the age of the cases was between 20 and 59 years, 48% was female and the remaining male. 47% of the cases were from vulnerable areas. Hospitalizations were 28% of the cases, the majority from non-vulnerable areas. 3.8% of the cases reached intensive care. Vulnerable cases had a greater need for intensive care. The fatality rate was 2.4% and higher in men. After age 60, the fatality excess in vulnerable areas was statistically significant. Discussion: Among the cases, there were no important differences between residents of vulnerable and non-vulnerable areas. The differences were marked in severity (measured by ICU admission) and in the fatality rate of those over 60 years old, which was higher in vulnerable areas. Vulnerability was expressed in the evolution of the disease in those over 60 years of age.Introducción: La morbi-mortalidad por COVID-19 constituye un problema de salud pública en Argentina y la Provincia de Buenos Aires. Las poblaciones con vulnerabilidad social poseen una fragilidad que las expone a riesgos de manera potenciada. Objetivo: Caracterizar la vulnerabilidad social de una serie de casos confirmados con residencia en el Área Metropolitana Buenos Aires. Métodos: Estudio descriptivo de corte transversal. Fueron analizadas variables de sexo, edad, evolución y domicilio categorizadas por medio del Índice de Vulnerabilidad Socio Territorial. Resultados: la edad de los casos fue entre 20 y 59 años, el sexo fue un 48% mujeres y el restante varones. De zonas vulnerables hubo un 47% de casos. Las internaciones fueron el 28% de los casos, la mayoría de zonas no vulnerables. Llegaron a cuidados intensivos el 3,8% de los casos. Los casos con vulnerabilidad tuvieron mayor requerimiento de cuidados intensivos.  La letalidad fue de 2,4% y fue mayor en varones. A partir de los 60 años el exceso de letalidad en zonas vulnerables fue estadísticamente significativo. Discusión: Entre los casos no hubo diferencias importantes entre los residentes de zonas vulnerables y no vulnerables. Las diferencias estuvieron marcadas en la gravedad (medido por internación en UCI) y letalidad de los mayores de 60 años que fue mayor en zonas vulnerables. La vulnerabilidad se expresó en la evolución de la enfermedad de los mayores de 60 años.Introdução: A morbi mortalidade pela COVID-19 constitue um problema de saúde pública na Argentina e na provincia de Buenos Aires. A população com vulnerabilidade social possui uma fragilidade que expoe-as de maneira potenciada. Objetivos: Caraterizar a vulnerabilidade social de uma serie de casos confirmados com residencia na area metropolitana de Buenos Aires. Métodos: Estudo descritivo de corte transversal. Foram analisadas varaiveis de sexo, idade, evolução e domicilio categorizado por medio do índice de de Vulnerabilidade Socio territorial (IVST). Resultados: A idade dos casos foi entre 20 e 59 anos, o sexo femenino acumulou um 48% dos casos e o restante foram homens. Das zonas vulneraveis houve um 47% dos casos. As inernações foram o 28% dos casos, a maioria de casos não vulneráveis. Foram encaminhados para terapia intensiva o 3,8% dos casos. Os casos vulneraveis tiveram maior requerimento de cuidados intensivos. A letalidade foi de 2,4% e foi maior nos homens. A partir de 60 anos, o excesso da letalidade foi em casos com residência em zonas vulneráveis e isto foi estatisticamente significativo. Conclusões: Entre os casos não se acharam diferenças importantes com relaçáo à vulnerabilidade. As diferenças estiveram marcadas na gravidade dos casos onde os maiores de 60 anos requeriram maiores cuidados intensivos e foi mais elevada a letalidade. A vulnerabilidade expressou-se na evolução da doença

Nutraceutical emulsion containing valproic acid (NE-VPA): a drug delivery system for reversion of seizures in zebrafish larvae epilepsy model

Valproic acid (VPA) is an antiepileptic drug, which is currently used in neurodegenerative diseases. However, a high dose is required to obtain a therapeutic effect. Long-chain polyunsaturated fatty acids (PUFAs), such as omega 3 and omega 6, are efficient complements in treatments for neurological diseases. Previous studies have reported that a dietary supplement containing PUFAs together with the administration of antiepileptic drugs significantly reduces the frequency of seizures. Based on this, the main goal of this work was to obtain a complex based on VPA encapsulation in an oil/water (o/w) nutraceutical emulsion (NE) enriched with PUFAs for oral administration. Besides, encapsulation of VPA might reduce its dose and increase its therapeutic effect. In order to study its effect, we used a zebrafish larvae model of induced epileptiform behavior with the proconvulsant drug pentylenetetrazol (PTZ). Results have shown that when 100 μM VPA and fatty acids were combined in the NE (NE-VPA), the epileptiform behavior of PTZ-treated zebrafish larvae decreased significantly. Additionally, morphological changes, hepatotoxicity, lethality and heart rate were studied. Despite the fact that a high dose of VPA exerted a cardiotoxic effect, this was no longer detected after addition of this drug in the NE. This treatment exerted a significant antiepileptic effect and did not result in highly toxic or lethal effects. In order to develop an improved pharmaceutical treatment, and considering that all the components used are FDA approved for consumption, the NE-VPA selected might be easily incorporated into clinical trials.Instituto Multidisciplinario de Biología Celula