Mice deficient in CD38 develop an attenuated form of collagen type II-induced arthritis

CD38, a type II transmembrane glycoprotein expressed in many cells of the immune system, is involved in cell signaling, migration and differentiation. Studies in CD38 deficient mice (CD38 KO mice) indicate that this molecule controls inflammatory immune responses, although its involvement in these responses depends on the disease model analyzed. Here, we explored the role of CD38 in the control of autoimmune responses using chicken collagen type II (col II) immunized C57BL/6-CD38 KO mice as a model of collagen-induced arthritis (CIA). We demonstrate that CD38 KO mice develop an attenuated CIA that is accompanied by a limited joint induction of IL-1β and IL-6 expression, by the lack of induction of IFNγ expression in the joints and by a reduction in the percentages of invariant NKT (iNKT) cells in the spleen. Immunized CD38 KO mice produce high levels of circulating IgG1 and low of IgG2a anti-col II antibodies in association with reduced percentages of Th1 cells in the draining lymph nodes. Altogether, our results show that CD38 participates in the pathogenesis of CIA controlling the number of iNKT cells and promoting Th1 inflammatory responses

Non-irradiation-derived reactive oxygen species (ROS) and cancer: therapeutic implications

Owing to their chemical reactivity, radicals have cytocidal properties. Destruction of cells by irradiation-induced radical formation is one of the most frequent interventions in cancer therapy. An alternative to irradiation-induced radical formation is in principle drug-induced formation of radicals, and the formation of toxic metabolites by enzyme catalysed reactions. Although these developments are currently still in their infancy, they nevertheless deserve consideration. There are now numerous examples known of conventional anti-cancer drugs that may at least in part exert cytotoxicity by induction of radical formation. Some drugs, such as arsenic trioxide and 2-methoxy-estradiol, were shown to induce programmed cell death due to radical formation. Enzyme-catalysed radical formation has the advantage that cytotoxic products are produced continuously over an extended period of time in the vicinity of tumour cells. Up to now the enzymatic formation of toxic metabolites has nearly exclusively been investigated using bovine serum amine oxidase (BSAO), and spermine as substrate. The metabolites of this reaction, hydrogen peroxide and aldehydes are cytotoxic. The combination of BSAO and spermine is not only able to prevent tumour cell growth, but prevents also tumour growth, particularly well if the enzyme has been conjugated with a biocompatible gel. Since the tumour cells release substrates of BSAO, the administration of spermine is not required. Combination with cytotoxic drugs, and elevation of temperature improves the cytocidal effect of spermine metabolites. The fact that multidrug resistant cells are more sensitive to spermine metabolites than their wild type counterparts makes this new approach especially attractive, since the development of multidrug resistance is one of the major problems of conventional cancer therapy

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Upgrading of Wastewater Treatment Plants Through the Use of Unconventional Treatment Technologies: Removal of Lidocaine, Tramadol, Venlafaxine and Their Metabolites

The occurrence and removal efficiencies of the pharmaceuticals lidocaine (LDC), tramadol (TRA) and venlafaxine (VEN), and their major active metabolites monoethylglycinexylidide (MEGX), O-desmethyltramadol (ODT) and O-desmethylvenlafaxine (ODV) were studied at four wastewater treatment plants (WWTPs) equipped with activated sludge treatment technologies. In parallel to activated sludge treatment, the removal efficiency of the compounds in pilot- and full-scale projects installed at the WWTPs was investigated. Within these projects two different treatment methods were tested: adsorption onto powdered/granulated activated carbon (PAC/GAC) and ozonation. The metabolite MEGX was not detected in any sample. The concentrations of the target analytes in wastewater effluents resulting from activated sludge treatment ranged from 55 to 183 (LDC), 88 to 416 (TRA), 50 to 245 (ODT), 22 to 176 (VEN) and 77 to 520 ng L−1 (ODV). In the pilot project with subsequent treatment with PAC/GAC, the mean concentrations of the analytes were betweenThe first author would like to thank the Catholic Academic Exchange Service (KAAD) for financial support. The support of colleagues and staff of the Institute of Atmospheric and Environmental Sciences at the Goethe University Frankfurt am Main and of the Instituto Nacional del Carbon in Oviedo is gratefully acknowledged. Projects in Schwerte and Wuppertal are financial supported by the Ministry for Climate Protection, Environment, Agriculture, Nature Conservation and Consumer Protection of the German State of North Rhine-Westphalia. Thanks are due to Gregor Lorenz and Dieter Thöle from the Ruhrverband, Jochen Herr from the RWTH Aachen University, Peter Cornel and Gregor Knopp from Institut IWAR at the Technische Universität Damstadt, Helmut Volpert and Stefan Hoffmann from the Abwasserverband Langen-Egelsbach-Erzhausen and Catrin Bornemann from the Wupperverband, for sampling and for their assistance in questions about technical characteristics of the investigated WWTPs. COA thanks MICINN for financial support (grant CTM2008-01956). Thanks go to German Academic Exchange Service (DAAD) for covering traveling costs within the project PPP-Spain.We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)

Upgrading of Wastewater Treatment Plants Through the Use of Unconventional Treatment Technologies: Removal of Lidocaine, Tramadol, Venlafaxine and Their Metabolites

The occurrence and removal efficiencies of the pharmaceuticals lidocaine (LDC), tramadol (TRA) and venlafaxine (VEN), and their major active metabolites monoethylglycinexylidide (MEGX), O-desmethyltramadol (ODT) and O-desmethylvenlafaxine (ODV) were studied at four wastewater treatment plants (WWTPs) equipped with activated sludge treatment technologies. In parallel to activated sludge treatment, the removal efficiency of the compounds in pilot- and full-scale projects installed at the WWTPs was investigated. Within these projects two different treatment methods were tested: adsorption onto powdered/granulated activated carbon (PAC/GAC) and ozonation. The metabolite MEGX was not detected in any sample. The concentrations of the target analytes in wastewater effluents resulting from activated sludge treatment ranged from 55 to 183 (LDC), 88 to 416 (TRA), 50 to 245 (ODT), 22 to 176 (VEN) and 77 to 520 ng L−1 (ODV). In the pilot project with subsequent treatment with PAC/GAC, the mean concentrations of the analytes were betwee

Soporte nutricional en pacientes con abdomen abierto Nutricional support in patients with open abdomen

Objetivos: El soporte nutricional es fundamental en los pacientes con trauma severo para disminuir los efectos de la respuesta inflamatoria sistémica y el hipermetabolismo. Se diseñó un protocolo para evaluar la tolerancia y eficacia y del soporte nutricional, así como la evolución clínica en los pacientes post-operados con abdomen abierto. Pacientes y métodos: Se realizó un estudio descriptivo, prospectivo de pacientes intervenidos quirúrgicamente a quienes se les dejó el abdomen abierto con bolsa de Bogotá y recibieron soporte nutricional. Fueron excluidos del estudio aquellos pacientes que permanecieron menos de 4 días con el abdomen abierto. Un grupo recibió nutrición parenteral total (NPT) con mezclas tres en uno, otro grupo recibió nutrición enteral a través de yeyunostomía con aguja y catéter y un tercer grupo recibió soporte nutricional mixto. Ambiente: Servicio de Cirugía I del Hospital Universitario Ángel Larralde. IVSS Valencia (Venezuela). Período del estudio entre mayo del 2002 a mayo del 2005. Resultados: Ingresaron 24 pacientes al estudio, 46% recibió soporte nutricional mixto (enteral y parenteral), 33% exclusivamente NPT y 31% exclusivamente nutrición enteral. 75% evolucionaron favorablemente egresando al domicilio en buenas condiciones generales, 25% fallecieron debido a falla múltiple de órganos por sepsis severa. En relación al soporte nutricional, 66% de los pacientes no presentaron complicaciones, de los que recibieron nutrición parenteral 21% presentaron hiperglicemia y de los que recibieron nutrición enteral 13% presentaron diarrea. En cuanto a la eficacia de la nutrición enteral 69% de los pacientes alcanzaron el 80% de la meta calórica estimada entre el 4º y 5º día del inicio de la administración de la fórmula. Conclusión: El cuidado integral de los pacientes con abdomen abierto, sumado a un esquema de soporte nutricional que se ajuste las condiciones de cada paciente puede ayudar a disminuir la respuesta hipermetabólica así como la morbilidad y mortalidad.Objective: We have designed a protocol to evaluate the tolerance, effectiveness and the nutritional support in post-surgical patients with an open abdomen. Patients and methods: We have made a prospective descriptive study of patients submitted to surgery and left with an open abdomen with a Bogotá bag, and have received nutritional support. The patients who have stayed for less than 4 days with the open abdomen where excluded. A group received total parenteral nutrition (TPN) with mixtures all in one; another group received enteral nutrition (EN) through a needle catheter jejunostomy (NCJ) and a third group received mixed nutritional support. To evaluate the tolerance to EN, we have included those patients receiving this type of nutrition for at least 4 consecutive days without having diarrhea or pain. A jejunostomy catheter was placed in all patients by need o puncturing during the surgical act. Setting: The Surgical Department I of Ángel Larralde University Hospital, I.V.S.S. Valencia - Venezuela, during the period from May 2002 to May 2005. Results: 24 patients entered the study, 46% recived mixed nutritional support (Enteral and Parenteral), 33% exclusively TPN, and 31% exclusively EN. 75% have evolved favorably, discharged to their home in good general condition; 25% died from multiple organ failure due to severe sepsis. About nutritional support, 66% of the patients did not present complications; 21% of those receiving TPN presented hyperglycemia; and 13% of those receiving EN presented diarrhea. About EN effectiveness, 69% of the patients have reached 80% of the estimated caloric objective within days 4-5 from the beginning of formula administration. Conclusions: The integral care of the patients with an open abdomen, added to a nutritional support regimen tailored to each patient’s condition can help decreasing the hypermetabolic response, as well as moridity and mortality