Extravasation of Chemotherapy

Extravasation of chemotherapy is a feared complication of anticancer therapy. The accidental leakage of cytostatic agents into the perivascular tissues may have devastating short-term and long-term consequences for patients. In recent years, the increased focus on chemotherapy extravasation has led to the development of international guidelines that have proven useful tools in daily clinical practice. Moreover, the tissue destruction in one of the most dreaded types of extravasation (ie, anthracycline extravasation) now can effectively be prevented with a specific antidote, dexrazoxane.     

Acute infections in children are accompanied by oxidative modification of LDL and decrease of HDL cholesterol, and are followed by thickening of carotid intima-media.

BACKGROUND: Atherosclerosis begins early in life. Infections might contribute to the pathogenesis of atherosclerosis. In this study, we investigated whether acute infections in children could alter the carotid wall morphology and the lipid profile. METHODS: Mean carotid intima-media thickness (IMT) was measured by high-resolution ultrasound in 28 hospitalised children (mean age: 5+/-2 years), who fulfilled the diagnostic criteria of acute infections (body temperature, >38 degrees C; C-reactive protein, >15mg/ml, and clinical), and in 20 age- and gender-matched controls. Antibodies against oxidised low-density lipoprotein (anti-oxLDL antibodies), as well as total and high-density lipoprotein cholesterol (HDL-C) were analysed in all children. The infection group was investigated both during the acute illness and 3 months after clinical recovery (post-infection). RESULTS: During the acute illness, the infection group had elevated anti-oxLDL antibodies and decreased HDL-C, as compared to those obtained at 3 months and in controls (p<0.05). These changes in the infection group were followed, at 3 months, by thickening of carotid intima-media. Those who received antibiotics during their acute illness had less carotid thickening than those who were not treated with antibiotics (p<0.05). CONCLUSION: Acute infections in children seem to be accompanied by enhanced oxidative modification of LDL and by decrease in HDL-C. These lipid changes may be followed by thickening of carotid artery intima-media. These findings suggest that, in childhood, acute infections could be associated with increased risk of atherosclerosis, and warrant further studies on this topic.     

Haplotypic association of DDAH1 with susceptibility to pre-eclampsia

Association between pre-eclampsia (PEE1) and the dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2 genes, which play a role in the regulation of nitric oxide synthesis and release, was studied. In a case-control study design single nucleotide polymorphisms (SNPs) were determined at eight sites in the DDAH1 gene and at one site (Pro231Pro) in the DDAH2 gene from 132 women with pre-eclampsia and 112 healthy controls. Three SNPs in the DDAH1 gene were associated with pre-eclampsia, showing complete linkage disequilibrium with each other, but none of the associations in the allele or genotype data reached statistical significance in either of the genes after the correction for multiple testing. Haplotype frequencies were estimated using a population based on a maximum likelihood method (EM algorithm). Four common DDAH1 haplotypes were present and a significant association of haplotypes H2 and H3 with pre-eclampsia (P=0.03) was found. The risk of pre-eclampsia was greatest in individuals (odds ratio: 3.93; 95% confidence interval: 1.54-9.99) who had two copies of the high-risk haplotypes (H2 or H3). The observed haplotypic association provides the first evidence of the importance of DDAH1 polymorphisms in pre-eclampsia susceptibility.     

Training effects of cross-country skiing and running on maximal aerobic cycle performance and on blood lipids

Summary Two experiments were carried out to compare the cardiorespiratory and metabolic effects of cross-country skiing and running training during two successive winters. Forty-year-old men were randomly assigned into skiing (n = 15 in study 1,n = 16 in study 2), running (n = 16 in study 1 andn = 16 in study 2) and control (n = 17 in study 1 andn = 16 in study 2) groups. Three subjects dropped out of the programme. The training lasted 9–10 weeks with 40-min exercise sessions three times each week. The training intensity was controlled at 75%–85% of the maximal oxygen consumption (VO_2max) using portable heart rate metres and the mean heart rate was 156–157 beats·min^–1 in the training groups. In the pooled data of the two studies the mean increase in theVO_2max (in ml·min^–1·kg^–1) on a cycle ergometer was 17% for the skiing group, 13% for the running group and 2% for the control group. The increase inVO_2max was highly significant in the combined exercise group compared to the control group but did not differ significantly between the skiing and running groups. The fasting serum concentrations of lipoproteins and insulin did not change significantly in any of the groups. These results suggested that training by cross-country skiing and running of the same duration and intensity at each session for 9–10 weeks improved equally the cardiorespiratory fitness of untrained middle-aged men.     

Acquired Resistance of Escherichia coli to Complement Lysis by Binding of Glycophosphoinositol-Anchored Protectin (CD59)

Protectin (CD59) is a glycophosphoinsitol (GPI)-anchored defender of human cells against lysis by the membrane attack complex of complement. In this study, we examined whether protectin released from human cell membranes can incorporate into the surface of gram-negative bacteria. Analysis by using radiolabeled protectin, immunofluorescence, flow cytometry, and whole-cell enzyme-linked immunosorbent assay demonstrated that protectin bound to nonencapsulated Escherichia coli EH237 (Re) and EH234 (Ra) in a calcium-dependent manner. The incorporation required the GPI-phospholipid moiety since no binding of a phospholipid-free soluble form of protectin was observed. Mg²⁺ did not enhance the binding, and a polysialic acid capsule prevented it (strain IH3080 [O18:K1:H8]). Bound protectin inhibited the C5b-9 neoantigen expression on complement-treated bacteria. Protection against complement lysis was observed in both a colony counting assay and a bioluminescence assay, where viable EH234 bacteria expressing the luciferase gene emitted green light in the presence of the luciferine substrate. In general, two- to four-times-higher serum concentrations were needed to obtain 50% lysis of protectin-coated versus noncoated bacteria. The results indicate that protectin can incorporate in a functionally active form into the cell membranes of the two nonencapsulated deep rough E. coli strains studied.     

Carbonic anhydrase gene expression in CA II-deficient (Car2−/−) and CA IX-deficient (Car9−/−) mice

Using real-time PCR and immunohistochemistry, we have examined the expression of carbonic anhydrase isozymes (CA) I, II, III, IV, IX, XII, XIII and XIV in the brain, kidney, stomach and colon of the wild-type, CA II-deficient ( Car2^−/− ), and CA IX deficient ( Car9^−/− ) mice. The expression of Car4, Car12, Car13 and Car14 mRNAs did not show any significant deviations between the three groups of mice, whereas both groups of CA deficient mice showed decreased expression levels of Car1 in the colon and Car3 in the kidney. The Car2 mRNA level was greatly reduced but not completely abolished in all four tissues from the Car2^−/− mice in which no CA II protein was expressed. Sequencing the Car2 cDNA isolated from C57BL6 Car2^−/− mice revealed two nucleotide differences from the wild-type C57BL6 mice. One is a silent polymorphism found in Car2 mRNA from wild-type DBA mice, which is the strain that provided the original mutagenized chromosome. The second change is a mutation that causes prematurely terminated translation at codon 155 (Gln155X). Car9 mRNA and CA IX protein expression levels were up-regulated about 2.5- and 3.6-fold, respectively, in the stomach of the Car2^−/− mice. These results suggest that the loss of function of cytosolic CA II in the stomach of Car2^−/− mice leads to up-regulation of an extracellular CA, namely CA IX, which is expressed on the cell surface of the gastric epithelium.     

Estrogen receptor genotype modulates myocardial perfusion in young men

Most of the effects of estrogens are mediated by estrogen receptors. Vascular endothelial cells and smooth muscle cells express estrogen receptor (ESR1) in both genders. A long genotype group of a common thymine-adenine (TA) dinucleotide repeat polymorphism in the regulatory region of this gene has previously been related to coronary artery disease. The present study examined whether coronary blood flow is affected by this genotype. A total of 49 healthy men were genotyped by PCR and divided into three groups according to median number of the ESR1 promoter TA repeat (=19), i.e., in the short allele genotype group both alleles were of fewer than 19 repeats whereas in the long allele group both alleles were 19 repeats or more. The intermediate group comprised men who had one short and one long allele. Myocardial blood flow was measured by positron emission tomography using [¹⁵O]water, performed at rest and during adenosine stimulation. Men with long alleles had lower adenosine-stimulated coronary flow than those with short alleles and those with one short and one long allelle. Our results suggest that adenosine-stimulated myocardial perfusion is lower in subjects with ESR1 long alleles than the other TA repeat genotypes.     

Heterogeneous expression of CD59 on human Purkinje cells

The expression of CD59 and other complement regulators was studied in human cerebellum from 14 individuals with no cerebellar pathology, from one patient with multiple sclerosis (MS) and from two patients with paraneoplastic cerebellar degeneration (PCD). CD59 was present on the Purkinje cells at various levels in eight of the 14 cases with no cerebellar pathology. CD59 was also present on the Purkinje cells of the patient with MS, but not on the scarce remaining Purkinje cells of the two patients with PCD. Other complement regulators (CD35, CD46 and CD55) were not expressed on the Purkinje cells, whereas CD59, CD46 and CD55 were present on the molecular, granulosa and endothelial cells. The results suggest that Purkinje cells not expressing CD59 could be especially prone to complement-mediated damage.