Supplementary Material for: Culture-Proven Neonatal Sepsis in Japanese Neonatal Care Units in 2006–2008

<b><i>Background:</i></b> Recent Japanese epidemiology of neonatal sepsis and its predominant pathogens has not been reported. It is also unknown whether there are center differences in the incidence of neonatal sepsis, including early-onset sepsis (EOS) and late-onset sepsis (LOS) in Japan. <b><i>Objectives:</i></b> To investigate the morbidity and characteristics of neonatal sepsis in recent years and the differences in the incidence of sepsis among Japanese neonatal care units. <b><i>Methods:</i></b> We retrospectively collected the data of newborn infants with culture-proven sepsis that occurred in five Japanese centers of perinatal care from 2006 to 2008. The incidence of sepsis was calculated, including EOS and LOS, and compared among centers. <b><i>Results:</i></b> Morbidity from sepsis occurred in 51/6,894 (0.74%) infants. The incidence of EOS and LOS was 0.13 and 0.61%, respectively. The incidence of total sepsis and LOS in infants <1,000 g of birth weight was significantly higher than that in infants who weighed >1,000 g at birth, whereas there were no significant differences in the incidence of EOS between the different birth weights. Methicillin-resistant <i>Staphylococcus aureus</i> was the most common pathogen involved in morbidity and mortality of neonatal sepsis. Significant center differences were observed in the incidence of LOS, but not EOS. <b><i>Conclusions:</i></b> The majority of culture-proven neonatal sepsis is LOS, which differs among centers, especially in infants who weigh <1,000 g at birth in Japan. We consider that it is important to control nosocomial infection in newborn care units to further reduce the morbidity of neonatal sepsis in Japan

Serum C-reactive protein and thioredoxin levels in subjects with mildly reduced glomerular filtration rate

<p>Abstract</p> <p>Background</p> <p>Chronic kidney disease (CKD) is a newly recognized high-risk condition for cardiovascular disease (CVD), and previous studies reported the changes in inflammation and oxidative stress in advanced stages of CKD. We compared the levels of serum biomarkers for inflammation and oxidative stress between subjects with normal and mildly reduced glomerular filtration rate (GFR).</p> <p>Methods</p> <p>The subjects were 182 participants of a health check-up program including those with normal (≥ 90 mL/min/1.73 m², N = 79) and mildly reduced eGFR (60-89 mL/min/1.73 m², N = 103) which was calculated based on serum creatinine, age and sex. We excluded those with reduced eGFR < 60 mL/min/1.73 m². No one had proteinuria. We measured serum levels of C-reactive protein (CRP) and thioredoxin (TRX) as the markers of inflammation and oxidative stress, respectively.</p> <p>Results</p> <p>As compared with subjects with normal eGFR, those with mildly reduced eGFR had increased levels of both CRP and TRX. Also, eGFR was inversely correlated with these biomarkers. The associations of eGFR with these biomarkers remained significant after adjustment for age and sex. When adjustment was done for eight possible confounders, CRP showed significant association with systolic blood pressure, high density lipoprotein cholesterol (HDL-C) and non-HDL-C, whereas TRX was associated with sex significantly, and with eGFR and systolic blood pressure at borderline significance.</p> <p>Conclusions</p> <p>We showed the increased levels of CRP and TRX in subjects with mildly reduced eGFR. The eGFR-CRP link and the eGFR-TRX link appeared to be mediated, at least partly, by the alterations in blood pressure and plasma lipids in these subjects.</p

TRPC channel activation by extracellular thioredoxin

Mammalian homologues of Drosophila melanogaster transient receptor potential (TRP) are a large family of multimeric cation channels that act, or putatively act, as sensors of one or more chemical factor. Major research objectives are the identification of endogenous activators and the determination of cellular and tissue functions of these channels. Here we show the activation of TRPC5 (canonical TRP 5) homomultimeric and TRPC5-TRPC1 heteromultimeric channels by extracellular reduced thioredoxin, which acts by breaking a disulphide bridge in the predicted extracellular loop adjacent to the ion-selectivity filter of TRPC5. Thioredoxin is an endogenous redox protein with established intracellular functions, but it is also secreted and its extracellular targets are largely unknown. Particularly high extracellular concentrations of thioredoxin are apparent in rheumatoid arthritis, an inflammatory joint disease that disables millions of people worldwide. We show that TRPC5 and TRPC1 are expressed in secretory fibroblast-like synoviocytes from patients with rheumatoid arthritis, that endogenous TRPC5-TRPC1 channels of the cells are activated by reduced thioredoxin, and that blockade of the channels enhances secretory activity and prevents the suppression of secretion by thioredoxin. The data indicate the presence of a previously unrecognized ion-channel activation mechanism that couples extracellular thioredoxin to cell functio