Hyperuricaemia and gout

Gout is a painful, inflammatory disease that affects more men than women. The incidence of gout has increased substantially over the past few decades, as evidenced by information from the Rochester project. Some of the risk factors for the development of gout include: increased ethanol intake, high dietary purine consumption, obesity and the use of certain drugs, such as diuretics. Another important risk factor for the development of gout is hyperuricaemia. Hyperuricaemia results from an imbalance between the rate of production and excretion of uric acid in the body. An excess of uric acid thus builds up in the body, supersaturating body fluids and leading to the formation of monosodium urate crystals. These crystals accumulate in tissue and around joints, leading to an acute gout attack. Gout can be divided into four phases, namely asymptomatic hyperuricaemia, acute gout attacks or recurrent gout, intercritical gout and chronic tophaceous gout. Various treatment options are available for gout, and the treatment for each gout patient is determined by the stage of the disease. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, corticotropin and colchicine are used for the treatment of acute gout attacks. Allopurinol and probenecid are used for long-term hypouricaemic therapy, while NSAIDs and colchicine are prescribed for the prophylaxis of future gout attacks. All of these treatments have side effects, ranging from mild to life-threatening in nature. There is a need for novel gout therapies that have fewer side effects but are still as effective.Keywords: hyperuricaemia; gout; gout treatmen

ApuA, a multifunctional x-glucan-degrading enzyme of Streptococcus suis, mediates adhesion to porcine epithelium and mucus

We have identified apuA in Streptococcus suis, which encodes a bifunctional amylopullulanase with conserved -amylase and pullulanase substrate-binding domains and catalytic motifs. ApuA exhibited properties typical of a Gram-positive surface protein, with a putative signal sequence and LPKTGE cell-wall-anchoring motif. A recombinant protein containing the predicted N-terminal -amylase domain of ApuA was shown to have -(1,4) glycosidic activity. Additionally, an apuA mutant of S. suis lacked the pullulanase -(1,6) glycosidic activity detected in a cell-surface protein extract of wild-type S. suis. ApuA was required for normal growth in complex medium containing pullulan as the major carbon source, suggesting that this enzyme plays a role in nutrient acquisition in vivo via the degradation of glycogen and food-derived starch in the nasopharyngeal and oral cavities. ApuA was shown to promote adhesion to porcine epithelium and mucus in vitro, highlighting a link between carbohydrate utilization and the ability of S. suis to colonize and infect the host

Genetic and phenotypic parameters of pelt traits in a Karakul control flock

Genetic parameters of 16 pelt trais and birth mass were calculated in a Karakul control flock (n =2058; rams= 305) with a half-sib analysis. Moderately high heritabilities were estimated for pelt traits. No antagonistic genetic correlation was found between pattern and hair quality. The genetic correlations between pattern and pelt traits were lower than those estimated for hair quality and the other pelt traits. The expected correlated response from selection for hair quality may be a decrease in the occurrence of brittle hair, hair thickness, metallic, skin thickness, occurence of feathers, hair stiffness and an increase in hair length, lustre and curl breadth. Selection for pattern may result in a decrease in bandedness, a slight increase in lustre and in the occurrence of feathers, and a moderate decrease in curl type and hair length. Genetic estimates obtained in this study are compared with previous estimates obtained in Karakul sheep. Genetiese parameters van 16 pelseienskappe en van geboortemassa is in 'n Karakoelkontrole-kudde( n =2058; ramme = 305) met behulp van die halfsib-metodeb eraam. Matige hoe oorerflikhede is vir pelseienskappe beraam. Geen antagonistiese genetiese korrelasie is tussen patroon en haarkwaliteit gevind nie. Die genetiese korrelasies tussen patroon en ander pelseienskappe was heelwat laer as die tussen haarkwaliteit en die ander pelseienskappe. Die verwagte gekorreleerde responsie van seleksie vir haarkwaliteit mag 'n afname in die voorkoms van breekhare, haardikte, metaalagtigheid, veldikte, voorkoms van vere, haarstyfte, en 'n toename in haarlengte, glans en krulgrootte wees. Seleksie vir patroon mag 'n afname in die voorkoms van bande, 'n effense toename in glans en in die voorkoms van vere en 'n matige afname in krultipe en haarlengte veroorsaak. Genetiese parameters verkry in hierdie studie word met ander studiesb y Karakoelskape vergelyk.Keywords: Karakul, pelt traits, genetic and phenotypic parameters

Effect of organically and conventionally produced diets on jejunal gene expression in chickens

Using a nutrigenomics approach we studied the response of second-generation chickens at a transcriptional level to organically grown feed ingredients compared with conventionally grown feed ingredients. Both diets consisted of the same amounts of ingredients, the only difference was the production method. Gene expression was analysed in jejuni using whole genome chicken cDNA arrays. After analysis, forty-nine genes were found to be differentially regulated between chickens fed on the different diets, independent of their genetic background. Of these forty-nine genes, seven genes were involved in cholesterol biosynthesis. Genes involved in cholesterol biosynthesis were higher expressed in jejuni from organically fed birds. Other genes found to be regulated were involved in immunological processes, such as B-G protein (part of chicken major histocompatibility complex), chemokine ah221, and the immunoglobulin heavy chain. Using quantitative PCR the effect of genetic background on the differential expression of genes was studied. Differences in gene expression existed between animals fed different diets as well as between different chicken lines. This indicated that diet and genetic background influence the transcriptional response of the jejunum. This is the first time that significant differences in gene expression were shown between animals on diets with organically or conventionally produced ingredient

Uricult trio as a screening test for bacteriurla in pregnancy

Objective. To establish the effectiveness in an indigent urban population of Uricult Trio as a screening test for asymptomatic bacteriuria in pregnancy and in diagnosing urinary tract infections (UTI) in symptomatic pregnant women. likelihood ratios were established for positive and negative Uricult Trio test results.Subjects. Two populations of patients from the Pretoria region were involved: (J) asymptomatic pregnant women attending the antenatal clinic for the first time or presenting in labour; and (iI) pregnant women with symptoms suggestive of UTI.Method. A midstream urine specimen was collected from the two populations of patients, plated onto the Uricult Trio and sent to the laboratory for culture.Results. The prevalence of asymptomatic bacteriuria in this population was 23%, and for women with symptoms suggestive of UTI, 29%. The likelihood ratios for a positive test were 1.8 and 1.5 for asymptomatic and symptomatic patients respectively. The likelihood ratios for a negative test were 0.35 and 0.44 for asymptomatic and symptomatic patients respectively. Escherichia coli was the causative agent . in 36% of cases.Conclusion. Uricult Trio is not effective as a screening test for asymptomatic bacteriuria in pregnancy or for diagnosing UTIs in women with symptoms suggestive of infection

ArgR is an essential local transcriptional regulator of the arcABC-operon in Streptococcus suis and crucial for biological fitness in acidic environment

Streptococcus suis is one of the most important pathogens in pigs and can also cause severe infections in humans. Despite its clinical relevance very little is known about the factors contributing to its virulence. Recently, we identified a new putative virulence factor in Streptococcus suis, the arginine deiminase system (ADS), an arginine catabolic enzyme system encoded by the arcABC-operon, which enables Streptococcus suis to survive in acidic environment. In this study, we focused on ArgR, an ADS associated regulator belonging to the ArgR/AhrC arginine repressor family. Using an argR knock-out strain we could show that ArgR is essential for arcABC-operon expression and necessary for the biological fitness of Streptococcus suis. By cDNA expression microarray analyses and quantitative real time RT-PCR we found that the arcABC-operon is the only gene cluster regulated by ArgR, which is in contrast to many other bacteria. Reporter gene analysis with gfp under the control of the arcABC promoter demonstrated that ArgR is able to activate the arcABC promoter. Electrophoretic mobility shift assays with fragments of the arcABC promoter and recombinant ArgR, and chromatin immunoprecipitation with antibodies directed against ArgR revealed that ArgR interacts with the arcABC promoter in vitro and in vivo by binding to a region from -147 to 72 bp upstream of the transcriptional start point. Overall our results show that in Streptococcus suis ArgR is an essential, system specific transcriptional regulator of the ADS directly interacting with the arcABC promoter in vivo

Phase Transitions in High Purity Zr Under Dynamic Compression

We present results from ramp compression experiments on high-purity Zr that show the $\alpha \rightarrow \omega$, $\omega \rightarrow \beta$, as well as reverse $\beta \rightarrow \omega$ phase transitions. Simulations with a multi-phase equation of state and phenomenological kinetic model match the experimental wave profiles well. While the dynamic $\alpha \rightarrow \omega$ transition occurs $\sim 9$ GPa above the equilibrium phase boundary, the $\omega \rightarrow \beta$ transition occurs within 0.9~GPa of equilibrium. We estimate that the dynamic compression path intersects the equilibrium $\omega - \beta$ line at $P= 29.2$ GPa, and $T = 490$ K. The thermodynamic path in the interior of the sample lies $\sim 100$ K above the isentrope at the point of the $\omega \rightarrow \beta$ transition. Approximately half of this dissipative temperature rise is due to plastic work, and half is due to the non-equilibrium $\alpha \rightarrow \omega$ transition. The inferred rate of the $\alpha \rightarrow \omega$ transition is several orders of magnitude higher than that measured in dynamic diamond anvil cell (DDAC) experiments in an overlapping pressure range. We discuss a model for the influence of shear stress on the nucleation rate. The small fractional volume change $\Delta V/V \approx 0.1$ at the $\alpha \rightarrow \omega$ transition amplifies the effect of shear stress, and we estimate that for this case shear stress is equivalent to a pressure increase in the range of several GPa. Correcting our transition rate to a hydrostatic rate brings it approximately into line with the DDAC results, suggesting that shear stress plays a significant role in the transformation rate

Low nonpaternity rate in an old Afrikaner family

Extrapair paternity is a crucial parameter for evolutionary explanations of reproductive behavior. Early studies and human testis size suggest that human males secure/suffer frequent extrapair paternity. If these high rates are indeed true, it brings into question studies that use genealogies to infer human life history and the history of diseases since the recorded genealogies do not reflect paths of genetic inheritance. We measure the rate of nonpaternity in an old Afrikaner family in South Africa by comparing Y-chromosome short tandem repeats to the genealogy of males. In this population, the nonpaternity rate was 0.73%. This low rate is observed in other studies that matched genealogies to genetic markers and more recent studies that also find estimates below 1%. It may be that imposed religious morals have led to reduced extrapair activities in some historic populations. We also found that the mutation rate is high for this family, but is unrelated to age at conception.http://www.ehbonline.orghb2016Genetic

Role of glucose and CcpA in capsule expression and virulence of Streptococcus suis

Streptococcus suis is one of the most important pathogens in pigs and is also an emerging zoonotic agent. After crossing the epithelial barrier, S. suis causes bacteraemia, resulting in meningitis, endocarditis and bronchopneumonia. Since the host environment seems to be an important regulatory component for virulence, we related expression of virulence determinants of S. suis to glucose availability during growth and to the sugar metabolism regulator catabolite control protein A (CcpA). We found that expression of the virulence-associated genes arcB, representing arcABC operon expression, cps2A, representing capsular locus expression, as well as sly, ofs, sao and epf, differed significantly between exponential and early stationary growth of a highly virulent serotype 2 strain. Deletion of ccpA altered the expression of the surface-associated virulence factors arcB, sao and eno, as well as the two currently proven virulence factors in pigs, ofs and cps2A, in early exponential growth. Global expression analysis using a cDNA expression array revealed 259 differentially expressed genes in early exponential growth, of which 141 were more highly expressed in the CcpA mutant strain 10¿ccpA and 118 were expressed to a lower extent. Interestingly, among the latter genes, 18 could be related to capsule and cell wall synthesis. Correspondingly, electron microscopy characterization of strain 10¿ccpA revealed a markedly reduced thickness of the capsule. This phenotype correlated with enhanced binding to porcine plasma proteins and a reduced resistance to killing by porcine neutrophils. Taken together, our data demonstrate that CcpA has a significant effect on the capsule synthesis and virulence properties of S. suis