Predicting single and mixture toxicity of petrogenic polycyclic aromatic hydrocarbons to the copepod Oithona davisae

In the present study, the acute toxicity of 10 polycyclic aromatic hydrocarbons (PAHs) associated with the Prestige fuel oil spill (Spain, 2002) were evaluated, either as single substances or in mixtures, in adults of the copepod Oithona davisae. All but dimethylphenanthrene had negative effects on O. davisae survival at concentrations below their water solubility, with 48-h median lethal concentrations for naphthalene and pyrene of 56.1 and 0.8 micromol/L, respectively, making these the least and most toxic compounds. Polycyclic aromatic hydrocarbons had narcotic effects on copepods, as evidenced by the lack of motility at lower concentrations than those causing death. Naphthalene showed the greatest narcotic effects, and phenanthrene showed minor effects. Acute toxicity of the tested PAHs was inversely related (r2 = 0.9) with their octanol-water partition coefficient, thereby confirming the validity of the baseline quantitative structure-activity regression models for predicting the toxicity of PAH compounds in copepod species. When supplied in mixtures, the toxic effect of PAHs was additive. These results indicate that the many PAHs in an oil spill can be considered unambiguous baseline toxicants (class 1) acting additively as nonpolar narcotics in copepods; hence, their individual and combined toxicity can be predicted using their octanol-water partition coefficient.     

Fractures above and below a modular nail for knee arthrodesis. A case report

Several techniques have been advocated for knee arthrodesis, and there has been an increasing interest in modular intramedullary nails in the recent last years. We report a case of femoral and tibial fractures at each end of a modular nail in a solidly fused knee 8 months after an arthrodesis.     

Fetal growth regulation and intrauterine growth retardation

Gestational age and neonatal anthropometric parameters are currently used to evaluate fetal growth and are predictive factors of perinatal and postnatal morbidity and mortality. We performed a retrospective analysis of neonatal anthropometric parameters (weight, vertex-heel length and head circumference) in 1,470 live preterm neonates born between 1997 and 2002 and a prospective analysis of the same parameters in 1,786 live newborns of both sexes born in 2001 and 2002, products of single 37-42 week uncomplicated pregnancies in healthy Spanish Caucasian mothers. A progressive increase in these parameters with gestational age and sexual dimorphism were observed from the 30th week of gestational age onwards, with statistically-significant differences (p<0.05) at 38-42 weeks of gestational age. An increase in weight and length values in relation to previous Spanish studies was also documented in preterm newborns. It is estimated that 10-15% of children born small for gestational age (SGA) do not experience catch-up growth by the age of 3 years and may have short stature in adulthood. Preliminary data of a cross-sectional study on spontaneous growth in boys and girls born SGA without postnatal catch-up growth show that their +2 SD values of height are similar to -2 SD values of our normal control population of children born with adequate weight and length for gestational age (AGE). However, weight +2 SD values are similar to mean values of control children born AGE. In summary, our data show sexual dimorphism in neonatal anthropometric growth parameters and that these parameters change with time and may be updated. In addition children born SGA without postnatal catch-up are shorter and have higher weight than age-, height- and sex-matched controls born AGE.     

Primary amenorrhea in a woman with a cryptic complex chromosome rearrangement involving the critical regions Xp11.2 and Xq24

OBJECTIVE: To characterize a complex chromosome rearrangement (CCR) previously detected by G-banding in peripheral blood lymphocytes, as 46,X,-2,-11,-22,-X,+mar 1+mar2+mar3+mar4 in a patient with primary amenorrhea. DESIGN: Case report. SETTING: University faculty of Medicine and hospital. PATIENT(S): A 36-year-old woman with primary amenorrhea. INTERVENTION(S): Fluorescence in situ hybridization (FISH). MAIN OUTCOME MEASURE(S): Use of commercially available M-FISH probe (24 colors simultaneously) and whole chromosome painting probes for chromosomes 2, 11, 22, and X to characterize the CCR. RESULT(S): The use of conventional and multiple FISH allowed the redefinition of the CCR, showing a cryptic insertion of chromosome 11 in marker 3 previously suspected by M-FISH. The combination of G-banding and FISH data revealed that four chromosomes and seven breakpoints, including 2q21, 2q31, 11q22.1, 11q22.3, 22q13.3, Xp11.21, and Xq24, were implicated in this CCR. CONCLUSION(S): This report confirms the importance of a combination of G-banding and FISH (M-FISH and conventional FISH) techniques to characterize the de novo CCR. These techniques also were useful in defining two possible critical chromosome regions, Xp11.21 and Xq24, in which genes of potential interest for a primary amenorrhea could be located.     

Xanthine oxidoreductase and preservation injury in human liver transplantation

BACKGROUND: Preservation injury is a major cause of primary graft dysfunction in liver transplantation (LT). Oxidative damage is considered to be the first event leading to graft damage. Xanthine oxidoreductase (XOR) and neutrophil activation, two sources of reactive oxygen species, could play a role in the development of graft dysfunction. METHODS: We determined activities of XOR forms, polymorphonuclear elastase (PMN-E), aminotransferases, and hyaluronic acid in plasma of 20 patients undergoing LT. Samples were taken from the radial artery (RA) before the anhepatic phase; from the portal vein (PV) before reperfusion; from graft caval effluent (CE) at reperfusion; and from RA, PV, and the hepatic vein (HV) 10 and 90 min postreperfusion. RESULTS: The graft, but not recipient bowel, released XOR into blood (XOR in CE, median, 61.2 mU/g protein [range, 1.9-160.4 vs. undetectable in PV before reperfusion). Circulating XOR was transformed from dehydrogenase to reversible oxidase (XOrev) (XOrev-to-XOR ratio, 48.1% in CE and 65.1% in HV 90 min postreperfusion). Neutrophil activation was detected in the recipients before reperfusion, and in liver at early post-reperfusion (median PMN-E was 0.85 microg/g protein [range, 0.01-1.58] in RA before the anhepatic phase; 2.22 microg/g protein [range, 0.20-5.88] in PV prereperfu-sion; and 3.60 microg/g protein [range, 0.48-6.78] in HV 10 min postreperfusion). XOR, but none of the other markers, was higher in the CE of patients with moderate primary graft dysfunction than in those with slight primary graft dysfunction. CONCLUSIONS: XOR release and neutrophil activation are produced during LT, and they are potentially injurious mechanisms associated with this therapy.     

Changes of matrix metalloproteinase-9 and its tissue inhibitor (TIMP-1) after autologous hematopoietic stem cell transplantation in multiple sclerosis

Elevated levels of matrix metalloproteinase-9 (MMP-9) associates with predictors of multiple sclerosis (MS) activity. We analysed serum levels and mRNA expression of MMP-9 and its inhibitor TIMP-1 in peripheral mononuclear cells of 14 MS patients after autologous hematopoietic stem cell transplantation (AHSCT). All but 2 patients stabilized after AHSCT. A significant decrease of MMP-9 levels was seen up to 36 months after AHSCT. TIMP-1 levels did not change. MMP-9 mRNA levels correlated with the CD4+ T cell count (p<0.0001). The significant and persistent change in MMP-9 activity after AHSCT may be caused in part by the effect of AHSCT in the CD4+ T cell count.     

A1 adenosine receptors accumulate in neurodegenerative structures in Alzheimer disease and mediate both amyloid precursor protein processing and tau phosphorylation and translocation

Immunostaining of adenosine receptors in the hippocampus and cerebral cortex from necropsies of Alzheimer disease (AD) patients shows that there is a change in the pattern of expression and a redistribution of receptors in these brain areas when compared with samples from controls. Adenosine A1 receptor (A1R) immunoreactivity was found in degenerating neurons with neurofibrillary tangles and in dystrophic neurites of senile plaques. A high degree of colocalization for A1R and betaA4 amyloid in senile plaques and for A1R and tau in neurons with tau deposition, but without tangles, was seen. Additionally, adenosine A2A receptors, located mainly in striatal neurons in controls, appeared in glial cells in the hippocampus and cerebral cortex of patients. On comparing similar samples from controls and patients, no significant change was evident for metabotropic glutamate receptors. In the human neuroblastoma SH-SY5Y cell line, agonists for A1R led to a dose-dependent increase in the production of soluble forms of amyloid precursor protein in a process mediated by PKC. A1R agonist induced p21 Ras activation and ERK1/2 phosphorylation. Furthermore, activation of A1R led to and ERK-dependent increase of tau phosphorylation and translocation towards the cytoskeleton. These results indicate that adenosine receptors are potential targets for AD.     

BRAF mutations characterize colon but not gastric cancer with mismatch repair deficiency

Genes from the RAF family are Ras-regulated kinases involved in growth cellular responses. Recently, a V599E hotspot mutation within the BRAF gene was reported in a high percentage of colorectal tumors and significantly associated to defective mismatch repair (MMR). Additionally, BRAF mutations were described only in K-Ras-negative colon carcinomas, suggesting that BRAF/K-Ras activating mutations might be alternative genetic events in colon cancer. We have addressed to what extent the tumorigenic-positive selection exerted by BRAF mutations seen in colorectal MMR-deficient tumors was also involved in the tumorigenesis of gastric cancer. Accordingly, BRAF mutations were detected in 34% (25/74) of colorectal MMR-deficient tumors and in 5% (7/142) of MMR-proficient colorectal cases (P=0.0001). All mutations found in the MSI cases corresponded to the previously reported hotspot V599E. Two D593K and a K600E additional mutations were also detected in three MSS cases. However, only one mutation of BRAF was found within 124 MSS gastric tumors and none in 37 MSI gastric tumors, clearly suggesting that BRAF mutations are not involved in gastric tumorigenesis. Nonetheless, a high incidence of mutations of K-Ras was found within the MSI gastric group of tumors (P=0.0005), suggesting that the activation of K-Ras-dependent pathways contributes to the tumorigenesis of gastric cancers with MMR deficiency. Accordingly, our results show evidences that BRAF mutations characterize colon but not gastric tumors with MMR deficiency and are not involved in the tumorigenesis of gastric cancer of the mutator phenotype pathway.     

Pre/post assessment of an HIV infection prevention intervention targeted at teenagers in Southern Tarragona,Spain

BACKGROUND: Human immuno-deficiency virus (HIV) infection is one of the leading public health problems in our country. Preventive education has shown itself to be a useful tool for curtailing this disease. The objective of this study is that of assessing the effectiveness of a preventive intervention at the Secondary Schools in the Baix Ebre and Montsià areas of the Tortosa Healthcare District aimed at reducing the risk of HIV transmission and furthering the knowledge of this disease. METHOD: A pre/post intervention study was conducted with no control group. A total of 19 schools, corresponding to the fourth year of Compulsory Secondary Education and first year of "Bachillerato" studies were invited to participate. The activity consisted of a workshop 60-90 minutes in length, in conjunction with educational material. A questionnaire was used as the gauging tool. RESULTS: Twelve schools agreed to participate, a total of 896 answers having been gotten for the pre-test and 805 answers for the post-test. A statistically significant increase was found for 52% (10/19) of the items regarding the correct answers on the post-test. A statistically significant improvements was found in four of the five items (80%) related to attitudes, and in five of the eight (62.5%) items related to overall knowledge of this infection following the intervention. A statistically significant improvement regarding prevention-related knowledge was found solely in one of the six items (16.6%). CONCLUSIONS: Preventive activities in the form of participational workshops are a good way of furthering the knowledge and improving the attitudes regarding HIV/AIDS of the participating teenagers. As no curative treatment exists for this disease, prevention from the educational realm is of importance for curtailing increased HIV transmission.