Many undesired side effects or therapeutic failures of drugs are the result of differences or changes in drug metabolism, primarily depending on the levels and activities of cytochrome P450 (P450) enzymes. To assess whether P450 expression profiles can reflect hepatic drug metabolism, we compared P450 mRNA levels in the liver or peripheral leukocytes with the corresponding hepatic P450 activities. A preliminary P450 genotyping for the most frequent polymorphisms in white populations (CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP2D6*3, CYP2D6*4, CYP2D6*6, and CYP3A5*3) was carried out before P450 phenotyping, excluding the donors with nonfunctional alleles of CYP2C9, CYP2C19, and CYP2D6 and those with a functional CYP3A5*1 allele from a correlation analysis. The hepatic mRNA levels of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 displayed a strong association with P450 activities in the liver, whereas the expression of CYP1A2, CYP2C9, CYP2C19, and CYP3A4 in leukocytes was proven to reflect the hepatic activities of these P450 species. The leukocytes were found to be inappropriate cells for the assessment of hepatic CYP2B6 and CYP2D6 activities. Combining the results of P450 genotyping and phenotyping analyses, patients' drug-metabolizing capacities can be estimated by the P450 expression in the liver and in leukocytes with some limitations. Patients' genetic and nongenetic variations in P450 status can guide the appropriate selection of drugs and the optimal dose, minimizing the risk of harmful side effects and ensuring a successful outcome of drug therapy.

Our results confirm that MIS reflects both energy-protein wasting and inflammation in kidney transplant recipients. This simple instrument appears to be a useful tool to assess the presence of protein-energy wasting in this patient population.

Aims Inter‐individual variability in dose requirements of calcineurin inhibitors (CNI) has been linked to genetic polymorphisms of CYP3A enzymes. CYP3A5*3, CYP3A4*1B and CYP3A4*22 alleles of liver grafts may explain about one third of the inter‐individual differences in pharmacokinetics of ciclosporin and tacrolimus in recipients. However, non‐genetic factors, influencing CYP3A expression, can contribute to the variability of CYP3A function due to phenoconversion. The present study evaluated the association between CYP3A4 expression combined with CYP3A5 genotype of donor livers and recipients' CNI therapy after transplantation. Methods The contribution of donors' CYP3A5 genotype and CYP3A4 expression to the blood concentrations and dose requirements of CNIs was evaluated in 131 liver transplant recipients. Results The recipients with grafts from normal CYP3A4 expresser donors carrying CYP3A5*3/*3 required CNI maintenance doses more or less similar to the bodyweight‐controlled starting doses (9.1 mg kg−1 of ciclosporin and 0.1 mg kg−1 of tacrolimus). The patients transplanted with grafts from low CYP3A4 expressers required substantial reduction (by about 50%, 4.2 mg kg−1 of ciclosporin, 0.047 mg kg−1 of tacrolimus, P < 0.001), while the recipients with grafts from high expressers or with grafts carrying at least one copy of the functional CYP3A5*1 allele required an increase (by about 50% [12.8–13.8 mg kg−1] for ciclosporin and 100% [0.21 mg kg−1] for tacrolimus, P < 0.001) of the initial CNI dose for achieving target blood concentrations. Conclusions Donor livers' CYP3A‐status, taking both CYP3A5 allelic variations and CYP3A4 expression into account, can better identify the risk of CNI over‐ or underexposure, and may contribute to the avoidance of misdosing‐induced graft injury in the early post‐operative period.

The MIS is independently associated with PTA in the kidney-transplanted population with eGFR lower than or equal to 60 mL/min/1.73 m(2).

Qualitative PCR is an accurate method for the detection of CMV in the mucosa of the GI tract. Further investigations are needed for determination of the exact pathological role of detected CMV.

ABSTRACT:Dehydroepiandrosterone (DHEA), the major precursor of androgens and estrogens, has several beneficial effects on the immune system, on memory function, and in modulating the effects of diabetes, obesity, and chemical carcinogenesis.

Elevated procalcitonin (PCT) levels are observed early after orthotopic liver transplantation (OLTx). The aim of this study was to evaluate the changes in systemic and regional PCT serum levels from the time of organ harvesting until the early postoperative phase of OLTx ( n=28) and to investigate the prognostic suitability of postoperative changes in PCT level for the outcome of OLTx ( n=61). Only in seven of 28 donors were higher PCT levels found (0.84+/-0.43 ng/ml). During organ preservation, hepatectomy, and in the anhepatic phase, the PCT levels were in the normal range; in 11 of 28 cases hepatic vein PCT levels were higher during graft flush with own blood than the systemic or portal vein samples at the same time (1.27+/-0.43 ng/ml vs 0.16+/-0.26 ng/ml and 0.23+/-0.15 ng/ml, respectively, P<0.02). The elevation of PCT levels began immediately after graft reperfusion (1.04+/-0.77 ng/ml vs 0.27+/-0.22 ng/ml, P<0.001), and the levels at postoperative day 2 were significantly higher in the case of postoperative complications (30.6+/-19.6 ng/ml vs 4.8+/-3.6 ng/ml, P<0.001).

Summary: This study examined the hypothesis that the level of postischemic reperfusion affects the severity of the resulting neuronal necrosis. In rats, tissue Po 2 % was monitored as an index of flow (reoxygenation) at four cortical sites by chronically implanted platinum elec trodes. Twenty minutes of total global cerebral ischemia was followed by 30 min of reoxygenation. The level of reoxygenation was controlled to maintain the P0 2 nearly constant at one or more of the cortical electrodes. Tissue from within 400 fLm of each of 19 electrode sites among seven rats was evaluated histologically. There was a posAn important controversy in brain ischemia re search is whether the time course of reperfusion after ischemia can influence the extent or degree of neuronal injury. It seems desirable to terminate the ischemic energy deficit and acidosis as quickly as possible. Some brain regions that develop multiple capillary occlusions during ischemia may not regain circulation ("no reflow") when the main feeding vessel is reopened unless hypertension with global hyperemia is induced. But such hyperemia may ag gravate postischemic edema. It has not been con clusively established, however, if the resulting edema contributes significantly to subsequent tis sue injury.Recent research has revealed at least three pro cesses that contribute to neuronal necrosis: opening