Trace elements in burned patients: Studies of zinc,copper and iron contents in serum

The significance of three trace elements in thermal injuries is stressed with reference to previous work. Zinc, copper and iron were simultaneously studied by means of atomic absorption spectrophotometry in a group of patients burned at a major disaster. Zinc and iron gave high values within the first 6 hours, descending to minimal values at the 48th hour post burn. The three remain low in close correlation to the burned surface area. Furthermore, copper and iron did not return to normal levels in the larger burns. Our study differs from others on the same subject in that the onset of decreased serum levels of trace elements occurs sooner in our series. We suggest that attempts be made to supplement the diet with trace elements to restore normal levels. This may well lead to an improvement in healing and an amelioration of the concomitant anaemia.     

Maternal serum alpha-fetoprotein (MSAFP) and fetal growth

Early mid-trimester screening of maternal serum alpha-fetoprotein (MSAFP) for the detection of neural tube defects is becoming a routine part of obstetrical care. In singleton pregnancies in the absence of fetal chromosomal abnormalities and anatomical anomalies high levels of AFP have been variably related to increased risk for low birthweight infant outcome. The overall relationship, if any, of maternal serum AFP to infant birthweight has, however, not been previously characterized. Between 15 and 20 weeks gestation, MSAFP values were determined for 110 women carrying single, anatomically and karyotypically normal fetuses. Statistical analysis utilizing polynomial and multilinear regression was used to determine the relationship of early mid-trimester MSAFP first to neonatal birthweight and then to gestational age and birthweight adjusted for gestational age. For every increase of one multiple of the median in MSAFP, neonatal birthweight fell 322 grams. This was accounted for almost entirely by decreased fetal growth; early mid-trimester MSAFP was linearly related to birthweight adjusted for gestational age ten times more strongly than to gestational age alone. The explanation for this relationship remains speculative, but the utility of routine AFP screening for the antenatal detection of intrauterine growth retardation certainly deserves further study.     

Candidate genes for hereditary colorectal cancer: Mutational screening and systematic review

Genome‐wide approaches applied for the identification of new hereditary colorectal cancer (CRC) genes, identified several potential causal genes, including RPS20, IL12RB1, LIMK2, POLE2, MRE11, POT1, FAN1, WIF1, HNRNPA0, SEMA4A, FOCAD, PTPN12, LRP6, POLQ, BLM, MCM9, and the epigenetic inactivation of PTPRJ. Here we attempted to validate the association between variants in these genes and nonpolyposis CRC by performing a mutational screening of the genes and PTPRJ promoter methylation analysis in 473 familial/early‐onset CRC cases, a systematic review of the published cases, and assessment of allele frequencies in control population. In the studied cohort, 24 (5%) carriers of (predicted) deleterious variants in the studied genes and no constitutional PTPRJ epimutations were identified. Assessment of allele frequencies in controls compared with familial/early‐onset patients with CRC showed association with increased nonpolyposis CRC risk of disruptive variants in RPS20, IL12RB1, POLE2, MRE11 and POT1, and of FAN1 c.149T>G (p.Met50Arg). Lack of association was demonstrated for LIMK2, PTPN12, LRP6, PTPRJ, POLQ, BLM, MCM9 and FOCAD variants. Additional studies are required to provide conclusive evidence for SEMA4A, WIF1, HNRNPA0 c.?110G>C, and FOCAD large deletions.     

Dieting in Spanish adolescent girls

This article examines the relation between dieting and non‐dieting adolescent girls and body mass index (BMI), eating attitudes and the influence of the aesthetic body shape model. Three hundred forty‐nine Spanish adolescent girls in their second year of secondary education were selected. The research design was a cross‐sectional ex post facto study and validated measures were used to assess the main variables. Fourteen per cent of the sample was on a diet. Of this group, 69% were overweight, 70% had disordered eating attitudes and 70% were influenced by the current aesthetic body shape model. In all situations, the scores for dieters were significantly higher than those for non‐dieters. Although there is not yet any clear consensus with regards to how adolescents interpret the term ‘diet’, the results indicate major differences between dieters and non‐dieters and that those who self‐report that they are on a diet present elements of the risk of developing eating and weight disorders. Copyright © 2007 John Wiley & Sons, Ltd and Eating Disorders Association.     

5-lipoxygenase inhibition reduces intrahepatic vascular resistance of cirrhotic rat livers: a possible role of cysteinyl-leukotrienes

BACKGROUND & AIMS: Cysteinyl-leukotrienes (Cys-LTs) increase intrahepatic vascular resistance in normal rat livers. CCl4 cirrhotic rat livers have increased Cys-LT production and 5-lipoxygenase messenger RNA (mRNA) expression. The aim of this study was to investigate the role of 5-lipoxygenase-derived eicosanoids regulating intrahepatic vascular tone in control and CCl4-induced cirrhotic rat livers. METHODS: In different groups of portally perfused control and cirrhotic rat livers, the following were analyzed: a portal perfusion pressure (PP) dose-response curve to LTD4; the effects on PP caused by either vehicle, the selective 5-lipoxygenase inhibitor AA-861, the selective Cys-LT1 receptor antagonist MK-571, or the dual Cys-LT1 and Cys-LT2 receptor antagonist BAY u9773; and immunohistochemistry for 5-lipoxygenase in liver sections of cirrhotic and control livers. RESULTS: Cirrhotic livers have a hyperesponse to LTD4. In control livers, AA-861 and MK-571 produced a moderate and similar reduction in PP. In cirrhotic livers, 5-lipoxygenase inhibition produced a marked and significantly greater reduction in PP than in controls. However, no effect on PP was observed after MK-571 or BAY u9773. 5-Lipoxygenase-positive cells were markedly increased in cirrhotic livers. CONCLUSIONS: Our results suggest that 5-lipoxygenase-derived eicosanoids may contribute to the increased intrahepatic vascular resistance of cirrhotic rat livers and therefore the pathogenesis of portal hypertension.     

Cyclooxygenase-derived products modulate the increased intrahepatic resistance of cirrhotic rat livers

In cirrhotic livers, increased resistance to portal flow, in part due to an exaggerated response to vasoconstrictors, is the primary factor in the pathophysiology of portal hypertension. Our aim was to evaluate the response of the intrahepatic circulation of cirrhotic rat livers to the alpha(1)-adrenergic vasoconstrictor methoxamine and the mechanisms involved in its regulation. A portal perfusion pressure dose-response curve to methoxamine was performed in control and cirrhotic rat livers preincubated with vehicle, the nitric oxide synthase blocker N(G)-nitro-L-arginine (L-NNA), indomethacin cyclooxygenase (COX) inhibitor, L-NNA + indomethacin, or the thromboxane (TX) A(2) receptor blocker SQ 29,548. TXA(2) production, COX-1 and COX-2 mRNA expression, and immunostaining for TXA(2) synthase were evaluated. Cirrhotic livers exhibited a hyperresponse to methoxamine associated with overexpression of COX-2 and TXA(2) synthase as well as with increased production of TXA(2). The hyperresponse to methoxamine of cirrhotic livers disappeared by COX inhibition with indomethacin but not after NO inhibition. SQ 29,548 also corrected the hyperresponse of cirrhotic livers to methoxamine. In conclusion, COX-derived prostanoids, mainly TXA(2), play a major role in regulating the response of cirrhotic livers to methoxamine.     

Suppression of chemokine receptor expression by RNA interference allows for inhibition of HIV-1 replication

OBJECTIVES: Duplexes of 21 base pair RNA, known as short-interfering RNA (siRNA), have been shown to inhibit gene expression by a sequence-specific RNA degradation mechanism termed RNA interference (RNAi). The objective of our study was to evaluate the effect of chemokine receptor gene suppression by RNAi on the entry and replication of HIV-1. METHODS: A flow cytometry and microscopy evaluation of HIV co-receptor expression of cells transfected with siRNA. An evaluation of the effect of siRNA on HIV entry and replication by intracellular p24 antigen detection, and virus production by infected cells, respectively. RESULTS: siRNA that target CXCR4 and CCR5 could effectively impede cell surface protein expression and their consequent function as HIV co-receptors. The inhibitory effect of RNAi directed to CXCR4 was detected 48 h after transfection of CXCR4+ U87-CD4+ cells. The expression of CXCR4 and CCR5 was blocked in 63 and 48% of positive cells by the corresponding siRNA. However, siRNA directed to CXCR4 or CCR5 did not have an effect on CD4 cells or green fluorescence protein expression. siRNA directed to CXCR4 did not suppress CCR5 expression or vice versa. The suppression of HIV-1 co-receptor expression effectively blocked the acute infection of CXCR4+ or CCR5+ U87-CD4+ cells by X4 (NL4-3) or R5 (BaL) HIV-1 strains. Inhibition of virus replication occurred regardless of the multiplicity of infection employed. CONCLUSION: Our results demonstrate that RNAi may be used to block HIV entry and replication through the blockade of cellular gene expression. Gene silencing by siRNA may become a valid alternative for HIV intervention.