Expression,polymorphism analysis,reticulocyte binding and serological reactivity of two Plasmodium vivax MSP-1 protein recombinant fragments

Among the four parasite species causing malaria in humans, Plasmodium vivax prevails on both the Asian and the American continents. Several antigens from this parasite's erythrocytic stages have been characterised and some of them are considered to be good vaccine candidates. The P. vivax merozoite surface protein-1 (PvMSP-1) is a 200 kDa antigen, thought to mediate the initial contact between the merozoite and the erythrocyte. An effective blockage of this interaction could be important in anti-malarial vaccine design. This study analyses the genetic polymorphism, binding to both reticulocytes and erythrocytes, antigenicity and immunogenicity of two recombinant proteins belonging to the 33 kDa PvMSP-1 proteolytic fragment. Both regions showed very low genetic variation, bound reticulocytes with higher affinity than erythrocytes, were recognised by naturally P. vivax-infected patient sera and were immunogenic when used to immunise rabbits, making them good vaccine candidates against P. vivax, to be further preclinically tested in the Aotus monkey model.     

Caudal block with 4 mg x kg-1 (1.6 ml x kg-1) of bupivacaine 0.25% in children undergoing surgical correction of congenital pyloric stenosis

BACKGROUND: Since 1970, bupivacaine 0.25% in a dose of 4 mg x kg-1 (1.6 ml x kg-1) has been used at the Hospital Infantil de México for caudal block in children undergoing surgical correction of congenital pyloric stenosis (CPS). Although this dose is considered unsafe, in our experience, it has been associated with a high success rate and a low incidence of adverse events. This experience has not been previously documented. METHODS: A retrospective cohort of patients undergoing surgical correction of CPS was studied. Nineteen patients received general anaesthesia while 223 received caudal block. The latter were then grouped according to the sedation technique. The rate of successful caudal blocks and complications were considered the major outcomes of the study, whereas the postsurgical fasting period and hospital stay were considered secondary outcomes. RESULTS: The rate of success of caudal block was 96%. Anaesthetic complications related to bupivacaine were present in 1.3%. Mortality occurred in the postoperatory period in one septic patient who also was suffering from gastroschisis that required general anaesthesia. Postoperatory fasting period and hospital stay tended to be higher with general anaesthesia than caudal block. However, of the 19 patients receiving general anaesthesia, five suffered serious comorbidity and nine were failed caudal blocks. CONCLUSIONS: Caudal block with bupivacaine 0.25% (4 mg x kg-1) was associated with a low rate of anaesthetic complications. Further prospective studies to clarify the risks and benefits are required.     

Effect of two series of isoindolines over HDAC8 activity and expression

This work describes the effect of two series of isoindolines 1(a–g) and 2(a–g) on histone deacetylase 8 (HDAC8) activity by theoretical study (docking method) and experimental assays using a commercial kit, as well as the effect of isoindolines on HDAC8 expression on HeLa cells. The theoretical study show interactions of the isoindolines with two HDAC8 deep pockets; these binding sites were compared to those of HDAC8 inhibitor, Trichostatin A. It was demonstrated experimentally that tested compounds can act as HDAC8 inhibitors. The expression of HDAC8 by Western blot analysis, remain unchanged in HeLa cells treated with the isoindolines with the exception of compound 2b which seems to increase HDAC8 expression. In conclusion, isoindolines act as HDAC8 inhibitors because they do not decrease the protein expression.     

The genetic era of childhood cancer: Identification of high-risk patients and germline sequencing approaches

Childhood cancer is a leading cause of death by disease in children ages 5–14, for which there are no preventive strategies. Due to early-age of diagnosis and short period of exposure to environmental factors, increasing evidence suggests childhood cancer could have strong association with germline alterations in predisposition cancer genes but, their frequency and distribution are largely unknown. Several efforts have been made to develop tools to identify children with increased risk of cancer who may benefit from genetic testing but their validation and application on a large scale is necessary. Research on genetic bases of childhood cancer is ongoing, in which several approaches for the identification of genetic variants related to cancer predisposition have been used. In this paper, we discuss the updated efforts, strategies, molecular mechanisms and clinical implications for germline predisposition gene alterations and the characterization of risk variants in childhood cancer.