Titanocene–gold complexes containing N-heterocyclic carbene ligands inhibit growth of prostate, renal, and colon cancers in vitro

We report on the synthesis, characterization, and stability studies of new titanocene complexes containing a methyl group and a carboxylate ligand (mba = −OC(O)-p-C6H4-S−) bound to gold(I)−N-heterocyclic carbene fragments through the thiolate group: [(η5 -C5H5)2TiMe(μ-mba)Au(NHC)]. The cytotoxicities of the heterometallic compounds along with those of novel monometallic gold−N-heterocyclic carbene precursors [(NHC)Au(mbaH)] have been evaluated against renal, prostate, colon, and breast cancer cell lines. The highest activity and selectivity and a synergistic effect of the resulting heterometallic species was found for the prostate and colon cancer cell lines. The colocalization of both titanium and gold metals (1:1 ratio) in PC3 prostate cancer cells was demonstrated for the selected compound 5a, indicating the robustness of the heterometallic compound in vitro. We describe here preliminary mechanistic data involving studies on the interaction of selected mono- and bimetallic compounds with plasmid (pBR322) used as a model nucleic acid and the inhibition of thioredoxin reductase in PC3 prostate cancer cells. The heterometallic compounds, which are highly apoptotic, exhibit strong antimigratory effects on the prostate cancer cell line PC3

Heterometallic titanium–gold complexes inhibit renal cancer cells in vitro and in vivo

Following recent work on heterometallic titanocene–gold complexes as potential chemotherapeutics for renal cancer, we report here on the synthesis, characterization and stability studies of new titanocene complexes containing a methyl group and a carboxylate ligand (mba ¼ S–C6H4–COO) bound to gold(I)-phosphane fragments through a thiolate group [(h-C5H5)2TiMe(m-mba)Au(PR3)]. The compounds are more stable in physiological media than those previously reported and are highly cytotoxic against human cancer renal cell lines. We describe here preliminary mechanistic data involving studies on the interaction of selected compounds with plasmid (pBR322) DNA used as a model nucleic acid, and with selected protein kinases from a panel of 35 protein kinases having oncological interest. Preliminary mechanistic studies in Caki-1 renal cells indicate that the cytotoxic and anti-migration effects of the most active compound 5 [(h-C5H5)2TiMe(m-mba)Au(PPh3)] involve inhibition of thioredoxin reductase and loss of expression of protein kinases that drive cell migration (AKT, p90-RSK, and MAPKAPK3). The co-localization of both titanium and gold metals (1 : 1 ratio) in Caki-1 renal cells was demonstrated for 5 indicating the robustness of the heterometallic compound in vitro. Two compounds were selected for further in vivo studies on mice based on their selectivity in vitro against renal cancer cell lines when compared to non-tumorigenic human kidney cell lines (HEK-293T and RPTC) and the favourable preliminary toxicity profile in C57BL/6 mice. Evaluation of Caki-1 xenografts in NOD.CB17-Prkdc SCID/J mice showed an impressive tumor reduction (67%) after treatment for 28 days (3 mg per kg per every other day) with heterometallic compound 5 as compared with the previously described [(h-C5H5)2Ti {OC(O)-4-C6H4-P(Ph2)AuCl}2] 3 which was non-inhibitory. These findings indicate that structural modifications on the ligand scaffold affect the in vivo efficacy of this class of compounds

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Harnessing biomolecules for bioinspired dental biomaterials

Dental clinicians have relied for centuries on traditional dental materials (polymers, ceramics, metals, and composites) to restore oral health and function to patients. Clinical outcomes for many crucial dental therapies remain poor despite many decades of intense research on these materials. Recent attention has been paid to biomolecules as a chassis for engineered preventive, restorative, and regenerative approaches in dentistry. Indeed, biomolecules represent a uniquely versatile and precise tool to enable the design and development of bioinspired multifunctional dental materials to spur advancements in dentistry. In this review, we survey the range of biomolecules that have been used across dental biomaterials. Our particular focus is on the key biological activity imparted by each biomolecule toward prevention of dental and oral diseases as well as restoration of oral health. Additional emphasis is placed on the structure–function relationships between biomolecules and their biological activity, the unique challenges of each clinical condition, limitations of conventional therapies, and the advantages of each class of biomolecule for said challenge. Biomaterials for bone regeneration are not reviewed as numerous existing reviews on the topic have been recently published. We conclude our narrative review with an outlook on the future of biomolecules in dental biomaterials and potential avenues of innovation for biomaterial-based patient oral care

Guía Clínica Española del Acceso Vascular para Hemodiálisis

El acceso vascular para hemodiálisis es esencial para el enfermo renal tanto por su morbimortalidad asociada como por su repercusión en la calidad de vida. El proceso que va desde la creación y mantenimiento del acceso vascular hasta el tratamiento de sus complicaciones constituye un reto para la toma de decisiones debido a la complejidad de la patología existente y a la diversidad de especialidades involucradas. Con el fin de conseguir un abordaje consensuado, el Grupo Español Multidisciplinar del Acceso Vascular (GEMAV), que incluye expertos de las cinco sociedades científicas implicadas (nefrología [S.E.N.], cirugía vascular [SEACV], radiología vascular e intervencionista [SERAM-SERVEI], enfermedades infecciosas [SEIMC] y enfermería nefrológica [SEDEN]), con el soporte metodológico del Centro Cochrane Iberoamericano, ha realizado una actualización de la Guía del Acceso Vascular para Hemodiálisis publicada en 2005. Esta guía mantiene una estructura similar, revisando la evidencia sin renunciar a la vertiente docente, pero se aportan como novedades, por un lado, la metodología en su elaboración, siguiendo las directrices del sistema GRADE con el objetivo de traducir esta revisión sistemática de la evidencia en recomendaciones que faciliten la toma de decisiones en la práctica clínica habitual y, por otro, el establecimiento de indicadores de calidad que permitan monitorizar la calidad asistencial.Vascular access for haemodialysis is key in renal patients both due to its associated morbidity and mortality and due to its impact on quality of life. The process, from the creation and maintenance of vascular access to the treatment of its complications, represents a challenge when it comes to decision-making, due to the complexity of the existing disease and the diversity of the specialities involved. With a view to finding a common approach, the Spanish Multidisciplinary Group on Vascular Access (GEMAV), which includes experts from the five scientific societies involved (nephrology [S.E.N.], vascular surgery [SEACV], vascular and interventional radiology [SERAM-SERVEI], infectious diseases [SEIMC] and nephrology nursing [SEDEN]), along with the methodological support of the Cochrane Center, has updated the Guidelines on Vascular Access for Haemodialysis, published in 2005. These guidelines maintain a similar structure, in that they review the evidence without compromising the educational aspects. However, on one hand, they provide an update to methodology development following the guidelines of the GRADE system in order to translate this systematic review of evidence into recommendations that facilitate decision-making in routine clinical practice, and, on the other hand, the guidelines establish quality indicators which make it possible to monitor the quality of healthcare