Association of the lipoprotein receptor-related protein 2 gene with gout and non-additive interaction with alcohol consumption

Introduction

The T allele of a single nucleotide polymorphism (SNP: rs2544390) in lipoprotein receptor-related protein 2 (LRP2) is associated with higher serum urate and risk of gout in Japanese individuals. SNP rs2544390 also interacts with alcohol consumption in determining hyperuricemia in this population. We investigated the association of rs2544390 with gout, and interaction with all types of alcohol consumption in European and New Zealand (NZ) Māori and Pacific subjects, and a Māori study cohort from the East Coast region of NZ’s North Island.

Methods

Rs2544390 was genotyped by Taqman®. From NZ a total of 1205 controls and 1431 gout cases clinically ascertained were used. Publicly available genotype and serum urate data were utilized from the Atherosclerosis Risk in Communities (ARIC) study and the Framingham Heart Study (FHS). Alcohol consumption data were obtained by consumption frequency questions in all study cohorts. Multivariate adjusted logistic regression was done using STATA.

Results

The T allele of rs2544390 was associated with increased risk of gout in the combined Māori and Pacific Island cohort (OR = 1.20, P = 0.009), and associated with gout in the European subjects, but with a protective effect (OR = 0.79, P_Unadjusted = 0.02). Alcohol consumption was positively associated with risk of gout in Māori and Pacific subjects (0.2% increased risk/g/week, P = 0.004). There was a non-additive interaction between any alcohol intake and the risk of gout in the combined Māori and Pacific cohorts (P_Interaction = 0.001), where any alcohol intake was associated with a 4.18-fold increased risk in the CC genotype group (P = 6.6x10^-5), compared with a 1.14-fold increased risk in the CT/TT genotype group (P = 0.40). These effects were not observed in European subjects.

Conclusions

Association of the T-allele with gout risk in the Māori and Pacific subjects was consistent with this allele increasing serum urate in Japanese individuals. The non-additive interaction in the Māori and Pacific subjects showed that alcohol consumption over-rides any protective effect conferred by the CC genotype. Further exploration of the mechanism underlying this interaction should generate new understanding of the biological role of alcohol in gout, in addition to strengthening the evidence base for reduction of alcohol consumption in the management of gout.     

Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part I: Chemical diversity, impacts on plant biology and human health

Plant natural products derived from phenylalanine and the phenylpropanoid pathway are impressive in their chemical diversity and are the result of plant evolution, which has selected for the acquisition of large repertoires of pigments, structural and defensive compounds, all derived from a phenylpropanoid backbone via the plant-specific phenylpropanoid pathway. These compounds are important in plant growth, development and responses to environmental stresses and thus can have large impacts on agricultural productivity. While plant-based medicines containing phenylpropanoid-derived active components have long been used by humans, the benefits of specific flavonoids and other phenylpropanoid-derived compounds to human health and their potential for long-term health benefits have been only recognized more recently. In this part of the review, we discuss the diversity and biosynthetic origins of phenylpropanoids and particularly of the flavonoid and stilbenoid natural products. We then review data pertaining to the modes of action and biological properties of these compounds, referring on their effects on human health and physiology and their roles as plant defense and antimicrobial compounds. This review continues in Part II discussing the use of biotechnological tools targeting the rational reconstruction of multienzyme pathways in order to modify the production of such compounds in plants and model microbial systems for the benefit of agriculture and forestry.     

Biological effects of power frequency magnetic fields: Neurochemical and toxicological changes in developing chick embryos

BACKGROUND: There are several reports that indicate a linkage between exposure to power frequency (50 - 60 Hz) magnetic fields with abnormalities in the early embryonic development of the chicken. The present study was designed to understand whether power frequency electromagnetic fields could act as an environmental insult and invoke any neurochemical or toxicological changes in developing chick embryo model. METHODS: Fertilized chicken eggs were subjected to continuous exposure to magnetic fields (50 Hz) of varying intensities (5, 50 or 100 microT) for a period of up to 15 days. The embryos were taken out of the eggs on day 5, day 10 and day 15. Neurochemical (norepinephrine and 5-hydroxytryptamine) and amino acid (tyrosine, glutamine and tryptophan) contents were measured, along with an assay of the enzyme glutamine synthetase in the brain. Preliminary toxicological investigations were carried out based on aminotransferases (AST and ALT) and lactate dehydrogenase activities in the whole embryo as well as in the liver. RESULTS: The study revealed that there was a significant increase (p < 0.01 and p < 0.001) in the level of norepinephrine accompanied by a significant decrease (p < 0.01 and p < 0.001) in the tyrosine content in the brain on day 15 following exposure to 5, 50 and 100 microT magnetic fields. There was a significant increase (p < 0.001) in glutamine synthetase activity resulting in the significantly enhanced (p < 0.001) level of glutamine in the brain on day 15 (for 100 microT only). The possible mechanisms for these alterations are discussed. Further, magnetic fields had no effect on the levels of tryptophan and 5-hydroxytryptamine in the brain. Similarly, there was no effect on the activity of either aminotransferases or lactate dehydrogenase in the whole embryo or liver due to magnetic field exposure. CONCLUSIONS: Based on these studies we conclude that magnetic field-induced changes in norepinephrine levels might help explain alterations in the circadian rhythm, observed during magnetic field stress. Also, the enhanced level of glutamine can act as a contributing factor for developmental abnormalities.     

EFFECTS OF HUMAN ACTIVITIES ON STRUCTURE AND COMPOSITION OF WOODY SPECIES OF THE NOKREK BIOSPHERE RESERVE OF MEGHALAYA,NORTHEAST INDIA

Aims Our study was conducted in the Nokrek Biosphere Reserve (NBR) in the Garo hills districts of Meghalaya, Northeast India. Our aim was to assess the effects of human activities on plant diversity,population structure and regeneration.Methods We selected a representative 1.2 hm2 stand in both the core and buffer zones of NBR. Structure and composition were determined by randomly sampling square quadrats, population structure was assessed by determining age structure, and regeneration was assessed by measuring densities of seedling, sapling and adult trees.Important findings More woody species were recorded from the core zone than the buffer zone (87 vs. 81 species), and there were a large number of tropical, temperate, and Sino-Himalayan, Burma-Malaysian and Malayan elements, primitive families and primitive genera. The trees were distributed in three distinct strata,canopy, subcanopy and sapling. Subcanopy and sapling layers had the highest species richness (81％ -88％ ). Lauraceae and Euphorbiaceae were the dominant families in terms of the number of species, and a large number of families were represented by single species. Most woody species (57 ％ - 79 ％ ) were contagiously distributed and had low frequency ( ＜ 20％ ). Although stand density was high in the buffer zone, its basal area was low compared to the stand in the core zone. Low similarity and high β-diversity indicate marked differences in species composition of the stands. Shannon diversity index was high in both the stands, while Simpson dominance index was low. The diameter-class distribution for dominant species revealed that the most had a large number of young individuals in their populations. Preponderance of tree seedlings, followed by a steep decline in population density of saplings and adult trees, indicated that the seedling to sapling stage was the most critical in the life cycle of the tree populations. Most species (42 ％ - 48 ％ ) had no regeneration,25 ％ - 35 ％ had good/fair regeneration, and the rest had poor regeneration or reoccurred as immigrants.     

Quality and reactive oxygen species of extended canine semen after vitamin C supplementation

The objective of this study was to evaluate the quality of extended dog semen processed with diluents containing various concentrations of vitamin C. Ejaculates from five dogs were collected, pooled and evaluated for concentration, sperm motility, rapid steady forward movement (RSF-movement), viability, acrosomal integrity and by the hypo-osmotic swelling test. Also, superoxide (O(2)(-)*) production, hydroxyl radicals (OH*) and total reactive oxygen species (tROS) were determined. The pool was divided in five aliquots, which were diluted to a final concentration of 66 x 10(6) spermatozoa/ml with a Tris-glucose-egg yolk extender containing one of the following concentrations of vitamin C (0, 0.1, 0.5, 1 or 2.5 mM). The semen aliquots were chilled and preserved at 4 degrees C. Portions of chilled semen were removed at 24 and 72 h, and semen quality was evaluated after rewarming. This process was repeated 10 times in pooled semen of the same origin and data were analysed by one-way analysis of variance. At both times, none of the semen quality parameters were positively influenced (p>0.05) by vitamin C supplementation. At 24 h, none of the reactive oxygen species (O(2)(-)*, OH*, tROS) were significantly altered. At 72 h, significant reductions of O(2)(-)* production were observed by the concentrations of 0.1, 0.5 and 2.5 mM compared with the 0 mM concentration (p=0.049). Also, at 72 h, the 2.5 mM concentration showed significantly lower OH* values in comparison with the control group (p=0.048). In conclusion, addition of vitamin C to semen extenders does not benefit the quality of canine extended spermatozoa.     

Sudden expansion of a single brown bear maternal lineage across northern continental Eurasia after the last ice age: a general demographic model for mammals?

The brown bear has proved a useful model for studying Late Quaternary mammalian phylogeography. However, information is lacking from northern continental Eurasia, which constitutes a large part of the species' current distribution. We analysed mitochondrial DNA sequences (totalling 1943 bp) from 205 bears from northeast Europe and Russia in order to characterize the maternal phylogeography of bears in this region. We also estimated the formation times of the sampled brown bear lineages and those of its extinct relative, the cave bear.
Four closely related haplogroups belonging to a single mitochondrial subclade were identified in northern continental Eurasia. Several haplotypes were found throughout the whole study area, while one haplogroup was restricted to Kamchatka. The haplotype network, estimated divergence times and various statistical tests indicated that bears in northern continental Eurasia recently underwent a sudden expansion, preceded by a severe bottleneck. This brown bear population was therefore most likely founded by a small number of bears that were restricted to a single refuge area during the last glacial maximum. This pattern has been described previously for other mammal species and as such may represent one general model for the phylogeography of Eurasian mammals. Bayesian divergence time estimates are presented for different brown and cave bear clades. Moreover, our results demonstrate the extent of substitution rate variation occurring throughout the phylogenetic tree, highlighting the need for appropriate calibration when estimating divergence times.     

Control of positive end-expiratory pressure (PEEP) for small animal ventilators

Background  

The positive end-expiratory pressure (PEEP) for the mechanical ventilation of small animals is frequently obtained with water seals or by using ventilators developed for human use. An alternative mechanism is the use of an on-off expiratory valve closing at the moment when the alveolar pressure is equal to the target PEEP. In this paper, a novel PEEP controller (PEEP-new) and the PEEP system of a commercial small-animal ventilator, both based on switching an on-off valve, are evaluated.     

Antisense inhibition of the sucrose transporter in potato: effects on amount and activity

The sucrose proton-cotransporter gene from potato (StSUT1) is mainly expressed in the phloem of mature, exporting leaves. To study the in vivo role of the protein, potato plants were transformed with antisense constructs of the sucrose transporter cDNA under control of the CaMV35S and the rolC promoters, respectively. Both types of transgenic plant develop symptoms characteristic of an inhibition of phloem loading. To determine the level of inhibition, immunological and transport studies were performed. Purified antibodies directed against a peptide from the central loop of SUT1 recognized a transporter with an apparent molecular mass of 47 kDa in leaf plasma membrane vesicles. Antisense repression under control of the non-specific CaMV35S promoter led to a strong reduction in SUT1 protein, whereas no such reduction could be detected when the companion cell-specific rolC promoter was used. Similarily. sucrose uptake in plasma membrane vesicles was reduced by 50–75% in CaMV35S but not in rolC plants. These data suggest that, unlike the rolC promoter, the sucrose transporter is expressed not only in the companion cells but also in other leaf cells. However, inhibition of the transporter by rolC-controlled antisense repression is sufficient to impair phloem loading.     

Pulmonary function and fuel use: A population survey

Background

In the backdrop of conflicting reports (some studies reported adverse outcomes of biomass fuel use whereas few studies reported absence of any association between adverse health effect and fuel use, may be due to presence of large number of confounding variables) on the respiratory health effects of biomass fuel use, this cross sectional survey was undertaken to understand the role of fuel use on pulmonary function.

Method

This study was conducted in a village of western India involving 369 randomly selected adult subjects (165 male and 204 female). All the subjects were interviewed and were subjected to pulmonary function test. Analysis of covariance was performed to compare the levels of different pulmonary function test parameters in relation to different fuel use taking care of the role of possible confounding factors.

Results

This study showed that biomass fuel use (especially wood) is an important factor for deterioration of pulmonary function (particularly in female). FEV₁ (p < .05), FEV₁ % (p < .01), PEFR (p < .05) and FEF_25–75 (p < .01) values were significantly lower in biomass fuel using females than nonusers. Comparison of only biomass fuel use vs. only LPG (Liquefied Petroleum Gas) use and only wood vs. only LPG use has showed that LPG is a safer fuel so far as deterioration of pulmonary function is concerned. This study observes some deterioration of pulmonary function in the male subjects also, who came from biomass fuel using families.

Conclusion

This study concluded that traditional biomass fuels like wood have adverse effects on pulmonary function.