Posterior reversible encephalopathy syndrome and graft-versus-host disease after liver transplantation: a case report and review of the literature.

Case (description): A 52-year-old male patient presented with seizures on the 16th day post liver transplantation suggesting tacrolimus-associated posterior reversible encephalopathy syndrome (PRES). On the 18th day, the patient was diagnosed with graft-versus-host disease (GVHD). Calcineurin inhibitor (CNI) was stopped and the patient received 1 g methylprednisolone and 25 g immunoglobulin. However, on the 21st day, the patient's clinical condition progressively worsened and he died of multi-organ failure. GVHD could have occurred with PRES because the CNI dose was reduced. The best treatment for patients with PRES and GVHD is using immunosuppressants other than CNI. Antibody preparations and steroids could be a standard treatment.

Population pharmacokinetic analysis of tacrolimus early after Chinese pediatric liver transplantation.

OBJECTIVE: The purpose of this study was to describe the population pharmacokinetics (PK) of tacrolimus (TAC) in 52 Chinese pediatric patients early after liver transplantation. METHODS: Details of drug dose, sampling times and concentrations were collected retrospectively from routine therapeutic drug monitoring data from the first day after surgery. A total of 488 concentration data were obtained and analyzed by a nonlinear mixed-effect modeling (NONMEM) method. A number of demographic and clinical variables were tested for their influence on TAC PK parameters. RESULTS: The PK of TAC were best described by a one-compartment model with first-order absorption and elimination. Apparent clearance (CL/F) and apparent volumes of distribution (V/F) in final population model were 5.72 L/h and 131 L, respectively. The absorption rate constant (Ka) was fixed in 4.48 h-1. The inter-individual variabilities in CL/F and V/F were 13.5% and 78.1%. In the final analysis performed in all 52 patients, the post-operation day (POD) and alanine aminotransferase (ALT) influenced TAC CL/F and V/F, and total protein (TP) was the only covariate retained on V/F. CONCLUSION: A population PK model of TAC was developed in Chinese pediatric patients early after liver transplantation. It identified significant relationships between the PK of TAC and the characteristics of the patients. POD, ALT, and TP were identified as the main factors influencing the PK of TAC. The developed model could be useful to optimize individual pediatric TAC dosing regimen in routine clinical practice.

Population pharmacokinetics of intravenous levofloxacin 500 mg/day dosage in infected patients.

The purpose of this study was to explore the population pharmacokinetic features of levofloxacin in Chinese infected patients. A total of 27 Chinese adult infected patients were treated with intravenous levofloxacin (500 mg/day). In total, 49 plasma samples of levofloxacin were collected immediately after intravenous dripping and before administration on the 3rd, 4th or 5th day. A nonlinear mixed effect model was used to model the population pharmacokinetic (PK) behavior of levofloxacin. The final population pharmacokinetic models were validated using the bootstrap method. Some covariates, including demographic characteristics and hematological and biological indicators, were analyzed. A structural model was developed based on a one-compartment model with intravenous infusion and first-order elimination. The typical population values for pharmacokinetic parameters of apparent clearance (CL) and apparent distribution volume (V) were 5.84 L/h and 43.3L, respectively. The inter-individual variabilities of CL and V were 7.75% and 6.4%, respectively, while the intra-individual variability of observed concentrations was 0.06 microg/mL. The covariates of age and AST influenced the CL and V values determined by the final model. The present study developed population pharmacokinetic models for levofloxacin in infected Chinese patients. The results detailed here could provide a reference for individualized levofloxacin therapy in the clinical setting.

[Response of Topsoil Fungal Community Structure to Soil Improvement Measures in Degraded Forest of Red Soil Region].

Soil fungal community structure and diversity are highly sensitive to variations in the external environment, as well as soil improvement measures. In order to clarify the effects of soil improvement measures on topsoil fertility or quality, a field experiment was conducted in eroded forest of a red soil region. Organic fertilizer, biochar, and lime+microbial fertilizer were added to the topsoil, respectively. After four years, the chemistry properties and nutrients in the topsoil were measured, and the diversity and composition of fungi were analyzed. The results showed that the additions of organic fertilizer, biochar, and lime+microbial fertilizer reduced fungal richness in topsoil, compared to that with no fertilizer addition (CK). Among them, lime+microbial fertilizer had the most negative effect on fungal richness. The three soil improvement measures also affected the diversity of topsoil fungi, but the impacts were not significant. The dominant fungal phyla in the topsoil were Ascomycota (31.29%-46.55%) and Basidiomycota (30.07%-70.71%), and the dominant fungal genera were Amphinema and Archaeorhizomyces. The effects of soil improvement measures on fungal community structure in the topsoil were different; organic fertilizer increased the relative abundance of Ascomycetes and Archaeopteroides, and biochar enhanced the relative abundance of Basidiomycetes and Archaeopteroides, whereas lime+microbial fertilizer improved the relative abundance of Basidiomycetes and Archaeopteroides. Fungal diversity and community structure in the topsoil was affected by edaphic factors, and fungal richness was regulated by pH value, whereas fungal community structure was influenced by pH, total nitrogen, and organic carbon. This study provides scientific guidance for soil improvement and ecological restoration below the canopy in eroded forests of red soil regions.

Optimization of tigecycline dosage regimen for different infections in the patients with hepatic or renal impairment.

OBJECTIVE: The objective of this study was to investigate the cumulative fraction of response (CFR) of various tigecycline dosing regimens in patients with hepatic or renal impairment. METHODS: Monte Carlo simulations were performed using pharmacokinetic parameters and microbiological data to evaluate various tigecycline regimens in patients with hepatic or renal impairment. RESULTS: For HAP and cIAI, the regimen of 25 mg q12h achieved CFR values of >90% in Child-Pugh C patients against Gram-positive bacteria and partial Gram-negative bacteria (Escherichia coli and Klebsiella oxytoca). However, dose increases of tigecycline was mostly required for Enterobacter cloacae, Klebsiella pneumoniae and Acinetobacter baumanni. The conventional tigecycline regimen (50 mg q12h) was effective for HAP and cIAI caused by Gram-positive bacteria and Escherichia coli in patients with renal impairment. For HAP caused by Klebsiella pneumoniae and Enterobacter cloacae, patients with severe renal failure can use the standard dose regimen 50 mg q12h, and other patients need to increase the dose of tigecycline. However, when treating cSSSI caused by Acinetobacter baumannii, Enterobacter cloacae and Klebsiella pneumoniae, all tigecycline maintenance doses have a CFR <90%. CONCLUSIONS: It is necessary to optimize tigecycline dosage regimens in patients with hepatic or renal impairment in order to maximise clinical response and minimise the probability of exposure-related toxicity.

[Accumulation Characteristics and Release Regularity of Nutrients in Sediments of a Surface-flow Constructed Wetland After Long-term Operation].

Sediments serve as an important carrier during the migration and transformation of pollutants in surface-flow constructed wetlands. Exploring the accumulation characteristics and release patterns of nutrients is of great significance for assessing the purification functions of constructed wetlands after long-term operation. The contents of total organic carbon (TOC), total nitrogen (TN), and total phosphorus (TP) in sediments at various locations of the 5-year-old Yanlong Lake surface-flow constructed wetland were analyzed and static release experiments with cylindrical core samples were carried out. The results showed that after five years, sediments at this site have become moderately polluted and the nutrient accumulation level is mainly being affected by the influent flow, water depth, and plant effects. Additionally, ① nutrients in sediments were found to increase along the flow direction; ② they also increase as the depth of overlying water increases and are relatively affected by the carbon; ③ healthier growth of the wetland plants could lead to more nutrients being accumulated in sediments. The release trend of nutrients fell after a rise and basically reached equilibrium after 20 days, and the release rate was mainly affected by the accumulation level of nutrients, which is similar to the trend in light nutrient containing reservoirs. Plant residues contained in the sediments were associated with the stronger release of nutrients. These results can provide a scientific basis for solutions aimed at maintaining the purification capacity of long-running surface-flow constructed wetlands.

Population Pharmacokinetics of Rifampicin in Chinese Patients With Pulmonary Tuberculosis.

Rifampicin (RIF) induces cytochrome P450, which in turn catalyzes drug metabolism; however, pharmacokinetic studies on this phenomenon in the Chinese population, especially in the context of disease, are limited. Therefore, we sought to establish population-based pharmacokinetic models of RIF in a Chinese population with pulmonary tuberculosis (TB). Clinical data were retrospectively collected from 54 patients with pulmonary TB and analyzed alongside RIF blood levels from 95 samples collected prior to RIF administration and between 2 and 12 hours after treatment. HPLC was used to measure serum RIF concentrations. A nonlinear mixed model used to characterize RIF pharmacokinetics and the data generated from the present study were validated using a bootstrap method. Covariates, including demographics, as well as hematological and biological indicators were analyzed. We observed a 1-compartment model with first-order absorption. Typical population values of apparent clearance (CL/F) and apparent volume of distribution (VD /F) were 4.02 L/h and 57.8 L, respectively. No covariate significantly changed the parameters of CL/F and VD . The present study may serve as a foundation for individualized therapy and offer a basis for pharmacokinetic-pharmacodynamic (PK-PD) analysis.

The Effects of TiO2 Nanodot Films with RGD Immobilization on Light-Induced Cell Sheet Technology.

Cell sheet technology is a new strategy in tissue engineering which could be possible to implant into the body without a scaffold. In order to get an integrated cell sheet, a light-induced method via UV365 is used for cell sheet detachment from culture dishes. In this study, we investigated the possibility of cell detachment and growth efficiency on TiO2 nanodot films with RGD immobilization on light-induced cell sheet technology. Mouse calvaria-derived, preosteoblastic (MC3T3-E1) cells were cultured on TiO2 nanodot films with (TR) or without (TN) RGD immobilization. After cells were cultured with or without 5.5 mW/cm(2) UV365 illumination, cell morphology, cell viability, osteogenesis related RNA and protein expression, and cell detachment ability were compared, respectively. Light-induced cell detachment was possible when cells were cultured on TR samples. Also, cells cultured on TR samples showed better cell viability, alongside higher protein and RNA expression than on TN samples. This study provides a new biomaterial for light-induced cell/cell sheet harvesting.

[Relationship between hMSH2 and FHIT gene expression in non-small cell lung cancer].

BACKGROUND & OBJECTIVE: Abnormality of FHIT gene has been proved to be frequent in certain malignant tumors closely related to environmental oncogenic factors, such as lung cancer. Foreign scholars have begun to explore the relationship between FHIT gene and other tumor suppressor genes, which are implicated in the pathogenesis of lung cancer. This study was designed to investigate the relationship between hMSH(2) and FHIT protein expression and to explore the correlation of hMSH(2) and FHIT protein expression with clinicopathologic features of lung cancer. METHODS: Immunohistochemical analysis of hMSH(2) and FHIT protein expression in 40 lung cancer cases and 15 adjacent non-cancer lung tissues was performed; the positive rates of FHIT and hMSH(2) proteins were measured by image analysis system. RESULTS: (1)The positive rates of FHIT and hMSH(2) proteins were 58.2% and 45.8% respectively in lung cancer tissues compared with 89.1% and 65.3% in non-cancer lung tissues. The expression levels of FHIT and hMSH(2) proteins were significantly lower in lung cancer tissues than that in non-cancer lung tissues (P< 0.01). (2)Reduced expression levels of both proteins were significantly related to tumor histology. The positive rate of the FHIT protein was 52.2% in squamous cell carcinoma compared with 63.4% in adenocarcinomas(P< 0.01), whereas the positive rate of the hMSH(2) protein was 35.6% in adenocarcinomas compared with 53.2% in squamous cell carcinoma(P< 0.01). (3)A correlation between FHIT reduced expression and lymph node metastasis was observed(P< 0.01). The positive rate of the FHIT protein was 54.1% in lung cancer tissues with metastasis compared with 60.5% in lung cancer tissues without metastasis. No association was found between hMSH(2) reduced expression and nodal metastasis(P >0.05). (4)Loss of FHIT protein correlated significantly with lasting and heavy smoking(P< 0.01). The positive rate of the FHIT protein was 53.1% in smoking group compared with 66.1% in non-smoking group. The reduction of hMSH(2) expression was not associated with smoking(P >0.05). (5)An inverse correlation was found between hMSH(2) reduced expression and FHIT protein loss (P< 0.01, RR=-0.54). CONCLUSION: FHIT gene may be a negative regulatory gene of hMSH(2) gene, and play an important role in the inactivation mechanism of hMSH(2) gene.

[Expression of HIF-1 alpha and its relationship to apoptosis and proliferation in lung cancer].

BACKGROUND & OBJECTIVES: Hipoxia-inducible factor-1 is a transcriptive factor that regulates genes involved in metabolism, angiogenesis, proliferation, and apoptosis. This study was designed to investigate the expression of hypoxia inducible facter-1 alpha(HIF-1 alpha) and its relationship to bcl-2, Bax, PCNA in lung cancer. METHOD: Immunohistochemical streptavidin/peroxidase(SP) was used to examine the expression of HIF-1a, bcl-2, Bax, and PCNA in 60 cases of lung cancer. RESULTS: In 60 cases of lung cancer, positive rate for HIF-1a was 28.3% (17/60), specially the positive rate of small cell lung cancer(66.7%) was significantly higher than non-small cell lung cancer (21.6%). HIF-1a expression increased as clinical stage and metastasis increased(P < 0.01). The positive rate of bcl-2, Bax, and PCNA were 31.7% (19/60), 40.0% (24/60), 76.7% (46/60), respectively. Inverse relationship was found between the expression of HIF-1 alpha and bcl-2; while the correlation of HIF-1 alpha and Bax was positive(P < 0.01). The relationship between HIF-1 alpha and Bax was positive(P < 0.01). The relationship between HIF-1 alpha and PCNA was not observed(P > 0.05). CONCLUSION: HIF-1 alpha is correlated with apopotosis, but has no relationship with proliferation.