Pro-collagen I COOH-terminal trimer induces directional migration and metalloproteinases in breast cancer cells.

Breast and prostatic carcinomas, melanoma, and endothelial cell lines are chemoattracted by medium conditioned by mature osteoblasts. The chemoattractant for endothelial cells was identified with C3, carboxyl-terminal trimer of pro-collagen type I. We report that C3 induces directional migration and proliferation, the expression of tissue inhibitor of metalloproteinases-2, pro-metalloproteinase-2 and -9, and their activation in MDA MB231 cells, without changing the expression of tissue inhibitor of metalloproteinases-1 and of metalloproteinase-14. Antiserum against metalloproteinase-2 or -9 or -14, tissue inhibitor of metalloproteinases-1, or GM6001 inhibits the C3-induced migration. Urokinase and its receptor are detected and unchanged upon exposure to C3. The antibody against urokinase or addition of plasminogen activator inhibitor inhibits migration. Blocking antibodies to integrins alpha(2), alpha(6), beta(1), and beta(3) inhibit chemotaxis and do not change urokinase and urokinase receptor expression. Blockage of alpha(2), beta(1), and beta(3) integrins affect differently the induction by C3 of pro-metalloproteinase-2 and -9 and of tissue inhibitor of metalloproteinases-2. Chemotaxis to C3 is also inhibited by genistein, by pertussis toxin, which also inhibits C3-induced pro-metalloproteinase -2 and -9, but not urokinase expression. Wortmannin partially inhibits C3-induced cell migration. Other, but not all, breast carcinoma lines tested responded to C3 with migration and pro-metalloproteinase-2 induction. Presently C3 is the only agent known to induce migration specifically of both endothelial and breast carcinoma cells. The mitogenic and motogenic role of C3 in vitro might prefigure a role in in vivo carcinogenesis and in the establishment of metastasis

Trimer Carboxyl Propeptide of Collagen I Produced by Mature Osteoblasts Is Chemotactic for Endothelial Cells

During the second phase of osteogenesis in vitro, rat osteoblasts secrete inducer(s) of chemotaxis and chemoinvasion of endothelial and tumor cells. We report here the characterization and purification from mature osteoblast conditioned medium of the agent chemotactic for endothelial cells. The chemoactive conditioned medium specifically induces directional migration of endothelial cells, not affecting the expression and activation of gelatinases, cell proliferation, and scattering. Directional migration induced in endothelial cells by conditioned medium from osteoblasts is inhibited by pertussis toxin, by blocking antibodies to integrins alpha(1), beta(1), and beta(3), and by antibodies to metalloproteinase 2 and 9. The biologically active purified protein has two sequences, coincident with the amino-terminal amino acids, respectively, of the alpha(1) and of the alpha(2) carboxyl propeptides of type I collagen, as physiologically produced by procollagen C proteinase. Antibodies to type I collagen and to the carboxyl terminus of alpha(1) or alpha(2) chains inhibit chemotaxis. The chemoattractant is the propeptide trimer carboxyl-terminal to type I collagen, and its activity is lost upon reduction. These data illustrate a previously unknown function for the carboxyl-terminal trimer, possibly relevant in promoting endothelial cell migration and vascularization of tissues producing collagen type I

Hospitalizações curtas: impacto da aplicação de uma área de observação no serviço de emergência pediátrica da Asociación Española

Ana Laura Casuriaga Lamboglia: Asistente de Clínica Pediátrica “C”, Facultad de Medicina, Universidad de la República, Uruguay. Pediatra, Asociación Española, Uruguay.-- Mariana Más Gómez: Pediatra, Asociación Española, Uruguay. Prof. Adj. Departamento de Emergencia Pediátrica, Facultad de Medicina, Universidad de la República, Uruguay.-- Paola Cassanello Pagani: Pediatra, Asociación Española, Uruguay.-- Jeannette Galazka Cukier: Pediatra, Asociación Española, Uruguay.-- Teresa Picón Manduca: Pediatra, Asociación Española, Uruguay.-- Gustavo Giachetto Larraz: Pediatra, Asociación Española, Uruguay. Profesor de Clínica Pediátrica “C”, Facultad de Medicina, Universidad de la República, Uruguay.-- Contacto: [email protected] racionalización de las admisiones hospitalarias constituye un aspecto clave de la gestión clínica. En 2014 en un estudio realizado en el Servicio de Pediatría de la Asociación Española, el 34% de los niños presentaron hospitalizaciones breves. Se propuso la creación de un área de observación que comenzó a funcionar en 2015. El objetivo de este estudio es valorar el impacto generado por la implementación de un área de observación en el Servicio de emergencia sobre las hospitalizaciones breves. Se realizó un estudio cuasi-experimental en el que se incluyeron todos los menores de 15 años que presentaron hospitalizaciones breves en dos períodos: pre y post implementación del área de observación. Se compararon la frecuencia y las características de las hospitalizaciones breves en ambos periodos. Se consideró significativo p<0.05. Las hospitalizaciones breves representaron el 34% en el período uno versus 12% en el período dos (p<0.05). La mediana mensual fue 54 (29 a 66) y 16 (9 a 30), respectivamente (p<0.05). Se observó una reducción significativa de las hospitalizaciones breves en niños mayores de 1 año (90% vs 67,5%) y en el horario de 0-6 horas (38% vs 26%). Se observó una reducción significativa en las hospitalizaciones por traumatismo encefalocraneano y otros traumas (16% vs 5%) y por convulsiones (8% vs. 4%). No se registraron fallecimientos. La implementación del área de observación en el servicio de emergencia impactó positivamente al reducir significativamente la frecuencia de hospitalizaciones breves en la institución. Resulta necesario continuar avanzando en la mejora de los procesos de gestión clínica. Futuros estudios son necesarios para evaluar el impacto en la calidad asistencial.Hospital admissions streamlining is a key aspect of clinical management. In a study carried out during 2014 in the Pediatrics Service of the Asociación Española, 34% of children had short stay hospital admissions. A proposal was made to create an observation area, which started working in 2015. The objective of this study was to assess the impact of implementing an observation area in the Emergency service on short stay admissions. A quasi-experimental study was conducted, including all children below 15 years of age with short stay admissions during two periods: before and after implementation of an observation area. Frequency and characteristics of the short stay admissions were compared for both periods. Significance was considered at p<0.05. Short stay admissions were 34% in period 1 versus 12% in period 2(p<0.05). Monthly median was 54 (29 to 66) and 16 (9 to 30) respectively (p<0.05). A signifi cant reduction in short stay admissions was observed in children older than 1 year (90% vs 67, 5%) and in the 0-6 hours shift (38% vs 26%). A significant reduction was observed in hospitalizations due to cranioencephalic trauma and other trauma (16% vs 5%) and due to seizures (16% vs 5%). No deaths were recorded. Implementation of the observation area in the emergency service had a positive impact in the signifi cant reduction of the frequency of short stay admissions in the institution. It is necessary to continue on advancing in the improvement of clinical management processes. Further studies are needed to assess impact on the quality of care.A racionalização das admissões hospitalares é um aspecto fundamental do gerenciamento clínico. Em 2014, em um estudo realizado no Serviço Pediátrico da Asociación Española, 34% das crianças apresentaram hospitalizações breves. Foi proposta a criação de uma área de observação que começou a operar em 2015. O objetivo deste estudo é avaliar o impacto gerado pela implementação de uma área de observação no Serviço de Emergência em hospitalizações curtas. Foi realizado um estudo quase experimental em que foram incluídas todas as crianças menores de 15 anos que tiveram hospitalizações curtas em dois períodos: pré e pós-implementação da área de observação. A frequência e as características das hospitalizações curtas foram comparadas em ambos os períodos. Foi considerado signifi cativo p <0,05. As hospitalizações curtas representaram 34% no período 1 contra 12% no período 2 (p <0,05). A mediana mensal foi de 54 (29 a 66) e 16 (9 a 30), respectivamente (p <0,05). Houve uma redução significativa nas internações curtas em crianças com mais de 1 ano (90% vs. 67,5%) e nas 0-6 horas (38% vs. 26%). Observou-se uma redução signifi cativa nas internações por traumatismo crânio encefálico e outros traumas (16% vs 5%) e convulsões (8% vs. 4%). Não foram registradas mortes. A implementação da área de observação no serviço de emergência teve um impacto positivo, reduzin do signifi cativamente a freqüência de hospitalizações breves na instituição. É necessário continuar avançando na melhoria dos processos de gerenciamento clínico. Estudos futuros são necessários para avaliar o impacto na qualidade dos cuidados

Metals detected by ICP/MS in wound tissue of war injuries without fragments in Gaza

<p>Abstract</p> <p>Background</p> <p>The amount and identity of metals incorporated into "weapons without fragments" remain undisclosed to health personnel. This poses a long-term risk of assumption and contributes to additional hazards for victims because of increased difficulties with clinical management. We assessed if there was evidence that metals are embedded in "wounds without fragments" of victims of the Israeli military operations in Gaza in 2006 and 2009.</p> <p>Methods</p> <p>Biopsies of "wounds without fragments" from clinically classified injuries, amputation (A), charred (C), burns (B), multiple piercing wounds by White Phosphorus (WP) (M), were analyzed by ICP/MS for content in 32 metals.</p> <p>Results</p> <p>Toxic and carcinogenic metals were detected in folds over control tissues in wound tissues from all injuries: in A and C wounds (Al, Ti, Cu, Sr, Ba, Co, Hg, V, Cs and Sn), in M wounds (Al, Ti, Cu, Sr, Ba, Co and Hg) and in B wounds (Co, Hg, Cs, and Sn); Pb and U in wounds of all classes; B, As, Mn, Rb, Cd, Cr, Zn in wounds of all classes, but M; Ni was in wounds of class A. Kind and amounts of metals correlate with clinical classification of injuries, exposing a specific metal signature, similar for 2006 and 2009 samples.</p> <p>Conclusions</p> <p>The presence of toxic and carcinogenic metals in wound tissue is indicative of the presence in weapon inducing the injury. Metal contamination of wounds carries unknown long term risks for survivors, and can imply effects on populations from environmental contamination. We discuss remediation strategies, and believe that these data suggest the need for epidemiological and environmental surveys.</p

Specific Association of Teratogen and Toxicant Metals in Hair of Newborns with Congenital Birth Defects or Developmentally Premature Birth in a Cohort of Couples with Documented Parental Exposure to Military Attacks: Observational Study at Al Shifa Hospital, Gaza, Palestine

This study was undertaken in Gaza, Palestine, in a cohort of babies born in 2011. Hair samples of newborns were analyzed for metal load by DRC-ICP-MS. We report specific level of contamination by teratogen/toxicants metals of newborn babies, environmentally unexposed, according to their phenotypes at birth: normal full term babies, birth defects or developmentally premature. The occurrence of birth defects was previously shown to be correlated in this cohort to documented exposure of parents to weapons containing metal contaminants, during attacks in 2009. We detect, in significantly higher amounts than in normal babies, different specific teratogen or toxicant elements, known weapons’ components, characteristic for each of birth defect or premature babies. This is the first attempt to our knowledge to directly link a phenotype at birth with the in utero presence of specific teratogen and/or toxicant metals in a cohort with known episodes of acute exposure of parents to environmental contamination by these same metals, in this case delivered by weaponry The babies were conceived 20–25 months after the major known parental exposure; the specific link of newborn phenotypes to war-remnant metal contaminants, suggests that mothers’ contamination persists in time, and that the exposure may have a long term effect

Long Term Risks to Neonatal Health from Exposure to War—9 Years Long Survey of Reproductive Health and Contamination by Weapon-Delivered Heavy Metals in Gaza, Palestine

Introduction: High levels of environmental contaminants with long term effects and teratogenic and carcinogenic potential, such as heavy metals, were introduced by weaponry in war areas in the last decades. Poorer reproductive health and increases in non-communicable diseases were reported after wars and are the suspected long term effects of contamination by stable war remnants. Although potentially affecting millions of people, this is still an understudied issue of public health. Background: Gaza, Palestine since 2006 has been an object of repeated severe military attacks that left heavy metals remnants in the environment, in wound tissues and that were assumed by the population. Retrospective studies showed a progressive increase in birth defects since the 2006 attacks. In 2011 we started surveillance at birth alongside analysis of the heavy metals load carried by pregnant women and their babies. Methods: We used protocols for birth registration which also document the extent of exposures to attacks, war remnants and to other environmental risks that allow comparison of 3 data sets&mdash;2011, 2016 and 2018&ndash;2019 (4000&ndash;6000 women in each set). By ICP/MS analysis we determined the content of 23 metals in mothers&rsquo; hair. Appropriate statistical analysis was performed. Results: Comparison of data in birth registers showed a major increase in the prevalence in birth defects and preterm babies between 2011 and 2016, respectively from 1.1 to 1.8% and from 1.1 to 7.9%, values remaining stable in 2019. Negative outcomes at birth in 2016 up to 2019 were associated with exposure of the mothers to the attacks in 2014 and/or to hot spots of heavy metals contamination. Metal loads since the attacks in 2014 were consistently high until 2018&ndash;2019 for barium, arsenic, cobalt, cadmium, chrome, vanadium and uranium, pointing to these metals as potential inducers for the increased prevalence of negative health outcomes at birth since 2016. Conclusions: Bodily accumulation of metals following exposure whilst residing in attacked buildings predispose women to negative birth outcomes. We do not know if the metals act in synergy. Trial for mitigation of the documented negative effects of high metal load on reproductive health, and ensuing perinatal deaths, could now be done in Gaza, based on this documentary record. High load of heavy metals may explain recent increases in non-communicable diseases and cancers at all ages in Gaza. Modern war&rsquo;s legacy of diseases and deaths extends in time to populations and demands monitoring

Inhibition of dimethyl sulfoxide induced erythropoietic differentiation of murine erythroleukemia cells in culture

The dimethyl sulfoxide induced erythropoietic differentiation of murine erythroleukemia cells, as determined by scoring benzidine positive cells, is inhibited by mitomycin C at concentrations that have no effect on cell proliferation. The inhibition occurs only when cells are treated with mitomycin C during induction and has a limit value of about 50%, independent of mitomycin C concentration. This limit value does not depend on cell heterogeneity since genetically homogeneous subclones, derived from DS19 clone, show levels of mitomycin C inhibition between 16 and 50%. Treatment with mitomycin C at different times after dimethyl sulfoxide addition shows that cell sensitivity to inhibition is not homogeneous during the induction period; it is maximal between 18 and 24 h from the start of induction and is observed with a concentration of mitomycin C as low as 25 fM. The inhibition of the benzidine positive phenotypic expression appears irreversible since this effect is observed on cells even several generations after those which were actually treated

Four polygamous families with congenital birth defects from Fallujah Iraq

Abstract: Since 2003, congenital malformations have increased to account for 15% of all births in Fallujah, Iraq. Congenital heart defects have the highest incidence, followed by neural tube defects. Similar birth defects were reported in other populations exposed to war contaminants. While the causes of increased prevalence of birth defects are under investigation, we opted to release this communication to contribute to exploration of these issues. By using a questionnaire, containing residential history and activities that may have led to exposure to war contaminants, retrospective reproductive history of four polygamous Fallujah families were documented. Our findings point to sporadic, untargeted events, with different phenotypes in each family and increased recurrence. The prevalence of familial birth defects after 2003 highlights the relevance of epigenetic mechanisms and offers insights to focus research, with the aim of reducing further damage to people&apos;s health