Antigen host response differences between the animal-type strain and human-clinical Pythium insidiosum isolates used for serological diagnosis in Thailand.

The detection of Pythium insidiosum-specific-immunoglobulin-G antibody (Pi-Ab) with enzyme-linked immunosorbent assay (ELISA) test depends on the source of antigen. In this study, the Pi-Ab levels in 140 serum samples from patients with pythiosis were evaluated by ELISA using antigens from 10 P. insidiosum clinical isolates in comparison with antigen from the equine-standard-type strain. The ELISA values (EVs), calculated from antibody levels from serum of patients with pythiosis or other infections versus healthy controls, were significantly higher in the test with clinical-isolates antigen than the standard-equine-type strain (6.0 ± 2.6 vs 4.0 ± 1.7, respectively; P < .0001). ELISA with antigen from human source might be more proper diagnosis test.

Elevated expressions of myeloid-related proteins-8 and -14 are danger biomarkers for lupus nephritis.

Myeloid-related proteins, MRP-8 and -14, which have been identified as molecules that mediate the danger signaling in innate immune response, are also known as the DAMPs (damage associated molecular pattern molecules). The proteins were found in infiltrating macrophages and neutrophils at inflammatory sites. Their expression was correlated with severe forms of glomerulonephritis. Therefore, this study examined whether or not MRP-8 and -14 can be used as biomarkers for identifying severely active lupus nephritis (LN). Total blood leukocyte samples and renal biopsy tissues from a prospective cohort of LN patients were used to determine mRNA and protein expression levels of MRP-8 and -14. The mRNA levels of MRP-8 and -14 in total blood leukocytes were significantly higher in active LN patients than quiescent LN patients and healthy controls. Moreover, the mRNA levels of MRP-8 and -14 in the total blood leukocytes and kidney tissues were significantly correlated with therapeutic response and the mRNA expression levels in the kidney were associated with an early loss of the kidney function. MRP-8 and -14 can be used as non-invasive prognostic biomarkers in patients with LN.

A Simple Novel Technique to Estimate Tacrolimus Dosages During the Early Post Kidney Transplantation Period.

BACKGROUND: Tacrolimus pharmacokinetics prediction by CYP3A5 genotyping is not available in many Asian resource-limited settings. Therefore, an alternative technique is needed to estimate the dose of tacrolimus perioperatively. The 12-hour level after the first dose (C12-0) is an alternative technique for estimating the dose of tacrolimus. This simple and inexpensive calculation technique can be used by any transplantation center. METHODS: A prospective study on a cohort of 57 incident post-kidney transplant recipients was conducted. The whole-blood tacrolimus trough level (C12-0) was measured at 12 hours after the first dose (0.1 mg/kg) of orally administered tacrolimus during transplantation. Concomitant medications with CYP3A5 inhibitors/inducers were not allowed. Genotyping for CYP3A5 expression was carried out by reverse transcription polymerase chain reaction. The dosages and trough levels of tacrolimus at postoperative day 7 and postoperative months 1 to 3 were measured and analyzed for the dose requirements for therapeutic levels (mg/kg/d). RESULTS: The doses of tacrolimus were widely diverse, ranging from 0.049 to 0.260 mg/kg/d and 0.031 to 0.298 mg/kg/d at day 7 and months 1 to 3, respectively. There were 9, 28, and 20 patients (15.8%, 49.1%, and 35.1%) with CYP3A5 *1/*1, *1/*3, and *3/*3, respectively. The CYP3A5 genotypes were significantly correlated with the target tacrolimus dose at day 7 (r(2) = 0.307) and the stable dose at months 1 to 3 (r(2) = 0.337). The C12-0 level also was significantly correlated with the dose of tacrolimus at day 7 (r(2) = 0.546) and the stable dose at months 1 to 3 (r(2) = 0.406). CONCLUSIONS: There were strong correlations between the C12-0 level and the tacrolimus doses during the perioperative period at day 7 and the stable period at 1 to 3 months. Countries with limited resources for genotype testing can use the C12-0 level as an alternative to estimate the tacrolimus dose.

The outcomes of kidney transplantation in hepatitis B surface antigen (HBsAg)-negative recipients receiving graft from HBsAg-positive donors: a retrospective, propensity score-matched study.

The outcomes of kidney transplantation (KT) from hepatitis B surface antigen-positive [HBsAg(+)] donors to HBsAg(-) recipients remain inconclusive, possibly due to substantial differences in methodological and statistical models, number of patients, follow-up duration, hepatitis B virus (HBV) prophylactic regimens and hepatitis B surface antibody (anti-HBs) levels. The present retrospective, longitudinal study (clinicaltrial.gov NCT02044588) using propensity score matching technique was conducted to compare outcomes of KT between HBsAg(-) recipients with anti-HBs titer above 100 mIU/mL undergoing KT from HBsAg(+) donors (n = 43) and HBsAg(-) donors (n = 86). During the median follow-up duration of 58.2 months (range 16.7-158.3 months), there were no significant differences in graft and patient survivals. No HBV-infective markers, including HBsAg, hepatitis B core antibody, hepatitis B extracellular antigen and HBV DNA quantitative test were detected in HBsAg(+) donor group. Renal pathology outcomes revealed comparable incidences of kidney allograft rejection while there were no incidences of HBV-associated glomerulonephritis and viral antigen staining. Recipients undergoing KT from HBsAg(+) donors with no HBV prophylaxis (n = 20) provided comparable outcomes with those treated with lamivudine alone (n = 21) or lamivudine in combination with HBV immunoglobulin (n = 2). In conclusion, KT without HBV prophylaxis from HBsAg(+) donors without hepatitis B viremia to HBsAg(-) recipients with anti-HBs titer above 100 mIU/mL provides excellent graft and patient survivals without evidence of HBV transmission.

AP214, an analogue of alpha-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality.

Sepsis remains a serious problem in critically ill patients with the mortality increasing to over half when there is attendant acute kidney injury. alpha-Melanocyte-stimulating hormone is a potent anti-inflammatory cytokine that inhibits many forms of inflammation including that with acute kidney injury. We tested whether a new alpha-melanocyte-stimulating hormone analogue (AP214), which has increased binding affinity to melanocortin receptors, improves sepsis-induced kidney injury and mortality using a cecal ligation and puncture mouse model. In the lethal cecal ligation-puncture model of sepsis, severe hypotension and bradycardia resulted and AP214 attenuated acute kidney injury of the lethal model with a bell-shaped dose-response curve. An optimum AP214 dose reduced acute kidney injury even when it was administered 6 h after surgery and it significantly improved blood pressure and heart rate. AP214 reduced serum TNF-alpha and IL-10 levels with a bell-shaped dose-response curve. Additionally; NF-kappaB activation in the kidney and spleen, and splenocyte apoptosis were decreased by the treatment. AP214 significantly improved survival in both lethal and sublethal models. We have shown that AP214 improves hemodynamic failure, acute kidney injury, mortality and splenocyte apoptosis attenuating pro- and anti-inflammatory actions due to sepsis.

A novel simple hemoglobin dilution technique to measure hemodialysis vascular access flow.

Measurement of the vascular access flow rate (Q(a)) is a widely accepted method for surveillance and predicting access failure. Among current practical methods, the ultrasound dilution technique is standard, but this requires a costly device available in few hemodialysis (HD) centers. Here, we devised a simple hemoglobin dilution technique to accurately measure Q(a) without the need for any special machines. Before HD, values of Q(a) were determined in each of 30 patients by hemoglobin dilution and then, in the same session, by ultrasound dilution. There was a significant correlation between the two techniques using automated hemoglobin and hematocrit or centrifuge-measured hematocrit levels to calculate HD fluid-derived Q(a) values. Our study shows that the HD dilution technique, using no special device, is economical, highly accurate, and easy to perform, and can be used as an alternative to standard ultrasound dilution for vascular access surveillance.