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.

Effects of atorvastatin on the pharmacokinetics of everolimus among kidney transplant recipients.

BACKGROUND: Hyperlipidemia occurs in up to 50% of kidney transplant (KT) recipients who take everolimus (EVL). As a result of this, statins are the most commonly prescribed lipid-lowering drugs among these patients. However, we are concerned whether there are any drug interactions between EVL and statins, because both of these drugs use the same pharmacokinetics pathway. Therefore, we assessed the effects of concomitant use of EVL and atorvastatin. METHODS: In this randomized, open-label, crossover study, 20 KT patients were assigned (1:1) to receive EVL with or without 20 mg atorvastatin for 1 month. One-month washout period was used before crossover. Plasma EVL concentrations were measured by homogeneous particle-enhanced turbidimetric immunoassay. Twelve-hour area under the time-concentration curve (AUC0-12) of EVL was calculated with the use of whole-blood EVL concentrations from 10 different time points (0, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, and 12 hours). RESULTS: The mean (SD) AUC0-12 for EVL and EVL plus atorvastatin was 155.9 (41.6) ng·h/mL and 151.3 (51.4) ng·h/mL, respectively (P > .05; paired t test). No difference of EVL Cmax or Tmax was found after atorvastatin coadministration. Even though the EVL AUC0-12 levels were not affected by atorvastatin coadministration in one-half of the subjects, for the rest of the patients, there were unpredictable changes in the EVL AUC0-12 levels. This may be due to the high intrapatient variability of EVL drug concentration (coefficient of variation ranges from 9.8% to 34.1%). CONCLUSIONS: Coadministration of atorvastatin with EVL in KT recipients did not affect the pharmacokinetics of EVL.

Therapeutic drug monitoring of mycophenolate mofetil for the treatment of severely active lupus nephritis.

BACKGROUND: Plasma mycophenolic acid (MPA) concentrations may predict therapeutic response in active lupus nephritis (LN). We determined the efficacy and safety of a concentration-controlled MPA regime in the treatment of severely active LN. METHODS: In this prospective study, 19 biopsy-proven class III/IV LN patients were treated with mycophenolate mofetil (MMF) for 48 weeks. The MMF dosage was based on maximal plasma MPA concentration at 1-hour post dose (MPA-C1). All patients had plasma MPA-C1 levels monitored weekly until achieving the targeted level of >13 mg/L. A low-dose steroid protocol was started at 0.5 mg/kg/day and rapidly tapered to 5 mg/day. Therapeutic response was evaluated at week 24 and week 48. MPA area-under-the curve (MPA-AUC0-12h) was measured at week 12 to verify the optimum dosage. RESULTS: No death or end-stage kidney disease occurred in this study. Seventeen patients (89%) responded to therapy at week 24 with four (21%) patients having complete response. There was no renal relapse at week 48 and four more patients had converted from partial response to complete response. Seventy eight percent of patients achieved the recommended MPA-AUC0-12h level. No association between plasma MPA concentrations and adverse reactions or infections was found. CONCLUSIONS: MPA-C1 may be a practical monitoring of MPA levels in patients with LN. It is convenient to monitor and may facilitate an optimum estimate of MPA exposure.

Analysis of climatic risk for cattle and buffalo production in northeast Thailand.

A study of thermal stress risk for cattle and buffalo was made in the Northeast Region of Thailand. Three-hourly air and dew-point temperatures from 15 selected meteorological stations for the period 1990 to 1999 were used to compute values of the temperature/humidity index (THI). Maps of isolines of THI values were generated by geographical software. A THI > or = 84 was assumed to represent conditions where production losses would be likely to occur. Across the study area, the mean total number of days with THI > or = 84 was 56. However, there was a strong north to south gradient across the region. The results suggest that the highest risk of loss to production in the cattle and buffalo industries is in the southern part of this region.