Variation in the Sodium-Dependent Vitamin C Transporter 2 Gene Is Associated with Risk of Acute Coronary Syndrome among Women

Background

Vitamin C is associated with a lower risk of coronary heart disease possibly due to its anti-oxidative effects, beneficial effects on endothelial function and importance in collagen synthesis. The sodium-dependent vitamin C transporter 2 is responsible for the transport of vitamin C into various cells and malfunction of this protein leads to reduced vitamin C in tissue, including the arterial wall. We tested the hypothesis that candidate variations rs6139591 and rs1776964 in the gene coding for sodium-dependent vitamin C transporter 2 are associated with development of acute coronary syndrome.

Design

In the Danish Diet, Cancer and Health cohort study, we performed a case-cohort study among 57,053 subjects aged 50–64 years.

Results

During a mean follow-up period of 6.4 years, we identified 936 cases and randomly selected a sub-cohort (n = 1,580) with full information on genotypes and covariates. Using Cox proportional hazard models, we found that women with the rs6139591 TT genotype and a lower than median dietary vitamin C intake had a higher risk of acute coronary syndrome compared with those with the CC genotype (adjusted HR 5.39, 95% confidence interval, 2.01–14.50). We also observed a not as strong but positive although inconsistent association for women at a higher than median intake of vitamin C rich food. For the rs1776964 polymorphism, we found a higher risk (adjusted HR 3.45, 95% CI, 1.16–10.28) among TT-homozygous women with higher than median vitamin C intake compared with the CC genotype and low vitamin C intake. Among men, weaker and non-significant associations were observed for both polymorphisms.

Conclusion

Genetic variation in the sodium-dependent vitamin C transporter 2 is associated with risk of incident acute coronary syndrome in women. The genotype effects may not be fully compensated by a higher intake of vitamin C rich food.     

Molecular phylogenetic evidence that the phylum Haplosporidia has an alveolate ancestry

The phylogenetic position of the phylum Haplosporidia among other protists was investigated with the complete 16S-like rRNA gene sequences from two species in the phylum: Haplosporidium nelsoni, a parasite of oysters, and Minchinia teredinis, a parasite of shipworms. Because the lack of obvious morphological homologies with other protists hampered decisions regarding taxonomic composition for sequence alignment and phylogenetic analysis, the complete sequences for these two haplosporidians were directed as search queries to the blast/ncbi.nlm.nih.gov electronic mail server. The results of this heuristic similarity search provided a basis for constructing a preliminary higher-taxonomic-level analysis comparing the haplosporidians with species from the slime molds, fungi, algae, amoebae, ciliates, dinoflagellates, and apicomplexans. Maximum parsimony yielded equivocal results, whereas transversionally weighted parsimony suggested an affinity with the alveolates (i.e., the ciliates, dinoflagellates, and apicomplexans). Multiple alignment of the two haplosporidian sequences against 17 taxa in a secondary analysis focusing on the alveolates and subsequent parsimony analysis placed the phylum Haplosporidia as a monophyletic group within the Alveolata and as a taxon of equal rank with the other three alveolate phyla. The precise placement within the Alveolata was sensitive to weighting.      

How hierarchical is language use?

It is generally assumed that hierarchical phrase structure plays a central role in human language. However, considerations of simplicity and evolutionary continuity suggest that hierarchical structure should not be invoked too hastily. Indeed, recent neurophysiological, behavioural and computational studies show that sequential sentence structure has considerable explanatory power and that hierarchical processing is often not involved. In this paper, we review evidence from the recent literature supporting the hypothesis that sequential structure may be fundamental to the comprehension, production and acquisition of human language. Moreover, we provide a preliminary sketch outlining a non-hierarchical model of language use and discuss its implications and testable predictions. If linguistic phenomena can be explained by sequential rather than hierarchical structure, this will have considerable impact in a wide range of fields, such as linguistics, ethology, cognitive neuroscience, psychology and computer science.     

Treatment of cryptorchidism with human chorionic gonadotropin or gonadotropin releasing hormone. A double-blind controlled study of 243 boys

We have conducted a modified double-blind study on the effect of human chorionic gonadotropin (hCG), gonadotropin releasing hormone (GnRH) and placebo on bilateral and unilateral maldescended testes. One hundred and fifty-five boys with bilateral and 88 boys with unilateral cryptorchidism fulfilled the inclusion criteria and completed the treatment protocol. The boys were between 1 and 13 years of age. hCG was administered as intramuscular injections twice weekly for 3 weeks. GnRH and placebo were given intranasally. hCG was superior to GnRH and placebo in the treatment of bilateral maldescended testes (p = 0.0009). Both testes descended in 25% of the boys following treatment with hCG, and improvement in the position of the testes was obtained in a further 25% of the cases. hCG administration resulted in complete testicular descent in 14% of boys with unilateral cryptorchidism compared with 3 and 0% after placebo and GnRH, respectively (p = 0.07). The testis had moved to a more distal position in 46% of the boys treated with hCG. There was no significant difference between the treatment groups with regard to age or initial position of the testes. We conclude that a success rate of 25% justifies the use of hCG in the treatment of maldescended testes, whereas the study did not support a general use of GnRH administered intranasally.     

Induction and prevention of chilling injury to radicle tips of imbibing cottonseed

Cottonseed exposed to a temperature of 5° during hydration are killed, or the subsequent germination performance of surviving seed is seriously inhibited. Exposure to chilling for periods as short as 30 minutes reduces germination speed and induces root abnormalities, while chilling for 12 hours may kill all seed. Sensitivity to chilling persists during the initial 2 to 4 hours of hydration. Seeds imbibed 4 hours at 31°, then dried, retain immunity to chilling. An irreversible event that is blocked or disrupted by chilling apparently occurs during early seed hydration.     

The effect of histamine stimulation and H2 -receptor inhibition on the pituitary prolactin and ACTH release and on cortisol secretion in human males

The effects of histamine (HA) on prolactin (PRL), ACTH, and cortisol secretion in human males were investigated. Specific H2 -receptor blockade caused an immediate and significant PRL release, while specific H2 -receptor stimulation (HA and mepyramine) was without effect on PRL secretion. HA significantly stimulated both ACTH and cortisol secretion, and this stimulation was probably mediated through H2 -receptors, H2 -receptor blockade caused a late, but significant ACTH release. This release was not accompanied by a release of cortisol, and might therefore be due to a spontaneous oscillation in ACTH secretion. The results support the theory that HA acts as a modulator of human ACTH secretion. A similar effect on PRL secretion as postulated by others could not be confirmed in this study.     

Effect of Nitrite and Nitrate on Toxin Production by Clostridium botulinum and on Nitrosamine Formation in Perishable Canned Comminuted Cured Meat

Comminuted ham was formulated with different levels of sodium nitrite and nitrate, inoculated with Clostridium botulinum, and pasteurized to an internal temperature of 68.5 C. When added to the meat, nitrite concentrations decreased, and cooking had little effect on them. Nitrite concentrations decreased more rapidly during storage at 27 than at 7 C; however they remained rather constant at formulated levels throughout the experiment at both incubation temperatures. The level of nitrite added to the meat greatly influenced growth and toxin production of C. botulinum. The concentration of nitrite necessary to effect complete inhibition was dependent on the inoculum level. With 90 C. botulinum spores/g of meat, botulinum toxin developed in samples formulated with 150 but not with 200 mug of nitrite per g of meat. At a spore level of 5,000/g, toxin was detected in samples with 400 but not with 500 mug of nitrite per g of the product incubated at 27 C. At lower concentrations of nitrite, growth was retarded at both spore levels. No toxin developed in samples incubated at 7 C. Nitrate showed a statistically significant inhibitory effect at a given nitrite level; however, the effect was insufficient to be of practical value. Analyses for 14 volatile nitrosamines from samples made with varying levels of nitrite and nitrate were negative at a detection level of 0.01 mug of nitrite or nitrate per g of meat.     

Amino-acids and peptides. Part 48. Synthesis of bradykinyl-chloromethane

An analogue of the local tissue hormone bradykinin, in which the terminal carboxy group is replaced by a chloromethyl ketone function, has been synthesised. A protected octapeptide, synthesised by the picolyl ester "handle" procedure, was coupled to N delta, N omega-dibenzyloxycarbonyl-L-arginyl-choromethane; the product was deprotected by hydrogen fluoride, giving bradykinyl-chloromethane. The preservation of the reactive chloromethyl ketone group and the entire structure of the product was confirmed by fast atom bombardment mass spectrometry. On the rat uterus and guinea-pig ileum bradykinyl-chloromethane was a weak agonist showing no antagonism of responses to bradykinin.