An electrochemically fabricated cobalt iron oxyhydroxide bifunctional electrode for an anion exchange membrane water electrolyzer.

For an anion exchange membrane water electrolyzer (AEMWE), exploring bifunctional electrodes with low cost and high efficiency is a crucial task for future renewable energy systems. Herein, we report a simple method to fabricate cobalt iron oxyhydroxide (CozFe1-zOxHy) bifunctional electrodes for AEMWEs. The bifunctional electrodes were prepared via one-pot electrodeposition on Ti paper (TP). By adjusting the electrodeposition conditions, the morphology and composition of CozFe1-zOxHy/TP could be controlled. The Co65Fe35OxHy/TP electrode demonstrated the highest activity for overall water electrolysis owing to the maximized synergy effect between Co and Fe. The bifunctional activities of Co65Fe35OxHy/TP were well retained at -50 and 50 mA cm-2 for 12 h. Co65Fe35OxHy/TP, which shows the highest bifunctional activity, was employed in an AEMWE single cell as the anode and cathode. The AEMWE single cell employing Co65Fe35OxHy/TP showed a current density of 0.605 A cm-2 at a cell voltage of 2.0 Vcell. The calculated energy efficiency of the single cell is 55.7% at 2.0 A cm-2, which is comparable with those of the state-of-the-art AEMWE single cells with bifunctional electrodes. Furthermore, the cell voltage of the single cell with Co65Fe35OxHy/TP showed negligible degradation for 50 h at 0.6 A cm-2.

Förster Resonance Energy Transfer-Based Single-Cell Imaging Reveals Piezo1-Induced Ca2+ Flux Mediates Membrane Ruffling and Cell Survival.

A mechanosensitive ion channel, Piezo1 induces non-selective cation flux in response to various mechanical stresses. However, the biological interpretation and underlying mechanisms of cells resulting from Piezo1 activation remain elusive. This study elucidates Piezo1-mediated Ca2+ influx driven by channel activation and cellular behavior using novel Förster Resonance Energy Transfer (FRET)-based biosensors and single-cell imaging analysis. Results reveal that extracellular Ca2+ influx via Piezo1 requires intact caveolin, cholesterol, and cytoskeletal support. Increased cytoplasmic Ca2+ levels enhance PKA, ERK, Rac1, and ROCK activity, which have the potential to promote cancer cell survival and migration. Furthermore, we demonstrate that Piezo1-mediated Ca2+ influx upregulates membrane ruffling, a characteristic feature of cancer cell metastasis, using spatiotemporal image correlation spectroscopy. Thus, our findings provide new insights into the function of Piezo1, suggesting that Piezo1 plays a significant role in the behavior of cancer cells.

Distinct calcium regulation of TRPM7 mechanosensitive channels at plasma membrane microdomains visualized by FRET-based single cell imaging.

Transient receptor potential subfamily M member 7 (TRPM7), a mechanosensitive Ca2+ channel, plays a crucial role in intracellular Ca2+ homeostasis. However, it is currently unclear how cell mechanical cues control TRPM7 activity and its associated Ca2+ influx at plasma membrane microdomains. Using two different types of Ca2+ biosensors (Lyn-D3cpv and Kras-D3cpv) based on fluorescence resonance energy transfer, we investigate how Ca2+ influx generated by the TRPM7-specific agonist naltriben is mediated at the detergent-resistant membrane (DRM) and non-DRM regions. This study reveals that TRPM7-induced Ca2+ influx mainly occurs at the DRM, and chemically induced mechanical perturbations in the cell mechanosensitive apparatus substantially reduce Ca2+ influx through TRPM7, preferably located at the DRM. Such perturbations include the disintegration of lipid rafts, microtubules, or actomyosin filaments; the alteration of actomyosin contractility; and the inhibition of focal adhesion and Src kinases. These results suggest that the mechanical membrane environment contributes to the TRPM7 function and activity. Thus, this study provides a fundamental understanding of how the mechanical aspects of the cell membrane regulate the function of mechanosensitive channels.

Anti-cancer potential of persimmon (Diospyros kaki) leaves via the PDGFR-Rac-JNK pathway.

Persimmon leaves are known to have some beneficial effects, including ROS elimination, lipid circulation, and neuronal protection. However, their anti-cancer properties and the underlying mechanisms remain unclear. Herein, we show that treatment with the ethanol extract of persimmon, Diospyros kaki, leaves (EEDK) induces cancer cell death and inhibits cell proliferation. Using fluorescence resonance energy transfer (FRET) technology with genetically-encoded biosensors, we first found that EEDK stimulates a PDGFR-Rac signaling cascade in live cells. Moreover, we found that downstream of the PDGFR-Rac pathway, JNKs are activated by EEDK. In contrast, JNK-downstream inhibitors, such as CoCl2, T-5224, and pepstatin A, attenuated EEDK-induced cell death. Thus, we illustrate that the PDGFR-Rac-JNK signaling axis is triggered by EEDK, leading to cancer cell death, suggesting the extract of persimmon leaves may be a promising anti-cancer agent.

Suppressing breast cancer by exercise: consideration to animal models and exercise protocols.

PURPOSE: Exercise is thought to have a significant effect on chemotherapy, and previous studies have reported that exercise can increase patient survival. Thus, in this review, we aimed to summarize various animal models to analyze the effects of exercise on breast cancer. METHODS: We summarized types of breast cancer animal models from various reports and analyzed the effects of exercise on anti-cancer factors in breast cancer animal models. RESULTS: This review aimed to systematically investigate if exercise could aid in suppressing breast cancer. Our study includes (a) increase in survival rate through exercise; (b) the intensity of exercise should be consistent and increased; (c) a mechanism for inhibiting carcinogenesis through exercise; (d) effects of exercise on anti-cancer function. CONCLUSION: This review suggested the necessity of a variety of animal models for preclinical studies prior to breast cancer clinical trials. It also provides evidence to support the view that exercise plays an important role in the prevention or treatment of breast cancer by influencing anticancer factors.

Microcellular Environmental Regulation of Silver Nanoparticles in Cancer Therapy: A Critical Review.

Silver nanoparticles (AgNPs) play significant roles in various cancer cells such as functional heterogeneity, microenvironmental differences, and reversible changes in cell properties (e.g., chemotherapy). There is a lack of targets for processes involved in tumor cellular heterogeneity, such as metabolic clampdown, cytotoxicity, and genotoxicity, which hinders microenvironmental biology. Proteogenomics and chemical metabolomics are important tools that can be used to study proteins/genes and metabolites in cells, respectively. Chemical metabolomics have many advantages over genomics, transcriptomics, and proteomics in anticancer therapy. However, recent studies with AgNPs have revealed considerable genomic and proteomic changes, particularly in genes involved in tumor suppression, apoptosis, and oxidative stress. Metabolites interact biochemically with energy storage, neurotransmitters, and antioxidant defense systems. Mechanobiological studies of AgNPs in cancer metabolomics suggest that AgNPs may be promising tools that can be exploited to develop more robust and effective adaptive anticancer therapies. Herein, we present a proof-of-concept review for AgNPs-based proteogenomics and chemical metabolomics from various tumor cells with the help of several technologies, suggesting their promising use as drug carriers for cancer therapy.

Nanoporous Nickel Phosphide Cathode for a High-Performance Proton Exchange Membrane Water Electrolyzer.

Hydrogen production via a proton exchange membrane water electrolyzer (PEMWE) is an essential technology to complement discontinuity of renewable energies. Development of a high-efficiency and cost-effective gas diffusion electrode (GDE), which is a key component of this technology, remains a challenge. Here, we report a high-performance Ni phosphide GDE prepared by simple electrochemical methods. Selective leaching of excess Ni in electrodeposited NixP1-x enabled fabrication of a nanoporous NiP GDE with a large electrochemical surface area (ECSA). In half-cell tests, the nanoporous NiP GDE demonstrated a hydrogen-evolving current density of -10 mA/cm2 at an overpotential of 103 mV with good stability. In the single-cell tests, the PEMWE employing a nanoporous NiP cathode exhibited a current density of 1.47 A/cm2 at a cell voltage of 2.0 V, which was the competitive performance among state-of-the-art non-noble cathodes reported to date.

Effect of Electronic Cigarettes on Smoking Reduction and Cessation in Korean Male Smokers: A Randomized Controlled Study.

INTRODUCTION: New approaches to electronic cigarettes (e-cigarettes) as a form of nicotine replacement therapy (NRT) may reduce the rates of tobacco-related disease and mortality. Therefore, we investigated the effect of e-cigarettes on smoking cessation compared with nicotine gum. METHODS: A total of 150 subjects were randomly assigned to 2 groups and each was allocated a 12-week supply of either e-cigarettes or nicotine gum. The continuous abstinence rate, 7-day point prevalence of abstinence, smoking reduction rate and amount, and tolerability were evaluated. RESULTS: There were no statistically significant differences in the effectiveness-related parameters of smoking cessation, such as 9- to 12-week, 9- to 24-week, and 12- and 24-week point prevalence of abstinence, between the 2 groups. However, although the reduction in cigarette smoking was similar, the proportion of subjects who showed smoking reduction at 24 weeks was higher in the e-cigarette group than the nicotine gum group. In addition, adverse events were significantly less frequent in the e-cigarette group than in the nicotine gum group. CONCLUSIONS: In our study, the effect of e-cigarettes on smoking cessation was similar compared with that of nicotine gum, a well-documented NRT. In addition, e-cigarettes were well tolerated by the study population. Therefore, the use of e-cigarettes as an NRT may be considered for smoking-cessation purposes. A large-scale prospective randomized controlled trial is necessary to clarify our results.

Dang-Gui-Liu-Huang Tang a traditional herbal formula, ameliorates imiquimod-induced psoriasis-like skin inflammation in mice by inhibiting IL-22 production.

BACKGROUND: The traditional herbal formula, Dang-Gui-Liu-Huang Tang (DGLHT) has been previously shown to inhibit T lymphocyte proliferation and suppress dendritic cell function. Hypothesis/Purpose: To assess the therapeutic value of DGLHT for the treatment of psoriasis, a Th1 and/or Th17 cell-mediated inflammatory skin disease, and to investigate the underlying molecular mechanisms. METHODS: An in vivo mouse model of imiquimod (IMQ)-induced psoriasis-like inflammation was used to investigate the effect of DGLHT. The anti-inflammatory effects of an ethanolic extract of DGLHT (DGLHT-E) and the mechanism responsible were examined in an in vitro model using IL-1α, IL-17A, IL-22, oncostatin M, plus TNF-α (M5) stimulated HaCaT cells. The anti-proliferative effect of DGLHT-E was examined by analyzing the expression levels of K16, K17 and Ki67 in IL-22 stimulated HaCaT cells. RESULTS: Topical application of 1% DGLHT-E significantly reduced psoriasis-like symptoms including scaling and epidermal hyperplasia in IMQ-treated mice. Immunohistochemical studies showed that DGLHT-E exerted potent anti-inflammatory effects by inhibiting IL-22 production in local skin lesions. DGLHT-E also attenuated the productions of CXCL10 and CCL20 in M5-stimulated HaCaT cells by suppressing the ERK1/2, JNK and STAT3 signaling pathways. Furthermore, berberine hydrochloride, a primary constituent of DGLHT-E inhibited the expressions of the proliferation markers K16 and K17 in IL-22 stimulated HaCaT cells. CONCLUSION: These results suggested that DGLHT-E offers a possible treatment for psoriasis, and that berberine hydrochloride might be a useful component of ointment-based treatments for psoriatic lesions.

Discrepancy between Self-Reported and Urine-Cotinine Verified Smoking Status among Korean Male Adults: Analysis of Health Check-Up Data from a Single Private Hospital.

BACKGROUND: Enquiry into smoking status and recommendations for smoking cessation is an essential preventive service. However, there are few studies comparing self-reported (SR) and cotinine-verified (CV) smoking statuses, using medical check-up data. The rates of discrepancy and under-reporting are unknown. METHODS: We performed a cross-sectional study using health examination data from Healthcare System Gangnam Center, Seoul National University Hospital in 2013. We analyzed SR and CV smoking statuses and discrepancies between the two in relation to sociodemographic variables. We also attempted to ascertain the factors associated with a discrepant smoking status among current smokers. RESULTS: In the sample of 3,477 men, CV smoking rate was 11.1% higher than the SR rate. About 1 in 3 participants either omitted the smoking questionnaire or gave a false reply. The ratio of CV to SR smoking rates was 1.49 (95% confidence interval [CI], 1.38-1.61). After adjusting for confounding factors, older adults (≥60 years) showed an increased adjusted odds ratio (aOR) for discrepancy between SR and CV when compared to those in their twenties and thirties (aOR, 5.43; 95% CI, 2.69-10.96). Educational levels of high school graduation or lower (aOR, 2.33; 95% CI, 1.36-4.01), repeated health check-ups (aOR, 1.45; 95% CI, 1.03-2.06), and low cotinine levels of <500 ng/mL (aOR, 2.03; 95% CI, 1.33-3.09), were also associated with discordance between SR and CV smoking status. CONCLUSION: Omissions and false responses impede the accurate assessment of smoking status in health check-up participants. In order to improve accuracy, it is suggested that researcher pay attention to participants with greater discrepancy between SR and CV smoking status, and formulate interventions to improve response rates.

Protective Effect of Areca catechu Leaf Ethanol Extract Against Ethanol-Induced Gastric Ulcers in ICR Mice.

Gastric ulcer is a common digestive disorder that results in considerable suffering. Hence, this digestive pathology has been the focus of a number of recent studies. Although numerous drugs have been developed to treat gastric ulcers, therapeutic approaches for many of the complications associated with these drugs remain to be identified. For this reason, many natural compounds have been explored as alternatives for these drugs. In this study, we have investigated the effectiveness of Areca catechu leaf ethanol extract (ACE) for treating ethanol-induced gastric ulcers in mice. We performed histological as well as immunohistochemical examinations to explore the therapeutic properties of ACE. We also examined the levels of inflammatory signaling molecules to confirm the anti-inflammatory effects of ACE. The histochemical data demonstrate that ACE can protect the mucosal epithelium as well as the vascular supply in the gastric tract. Furthermore, ACE significantly reduced the expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 receptor (IL-6R), inducible NO synthase (iNOS), cyclooxygenase 2 (COX2), and nuclear factor-kappa B (NF-κB). Taken together, these data suggest that ACE administration may have the potential as an alternative treatment for gastric ulcer because of its cytoprotective and anti-inflammatory effects and ability to promote the rejuvenation and revascularization of the damaged gastric epithelium.

Dietary Fat Intake and the Risk of Metabolic Syndrome in Korean Adults.

BACKGROUND: The effect of dietary fat intake on the risk of cardiovascular disease remains unclear. We investigated the association between dietary fat and specific types of fat intake and the risk of metabolic syndrome. METHODS: The study population included 1,662 healthy adults who were 50.2 years of age and had no known hypertension, diabetes, hyperlipidemia, or metabolic syndrome at the initial visit. Dietary intake was obtained from a 1-day food record. During 20.7 months of follow-up, we documented 147 cases of metabolic syndrome confirmed by self-report, anthropometric data, and blood test results. The intakes of total fat, vegetable fat, animal fat, saturated fatty acid (SFA), polyunsaturated fatty acid (PUFA), monounsaturated fatty acid (MUFA), and cholesterol level divided by quintile. Multivariate analyses included age, sex, body mass index, smoking status, alcohol intake, physical activity, total calorie, and protein intake. RESULTS: Vegetable fat intake was inversely associated with metabolic syndrome risk (odds ratio for the highest vs. the lowest quintile, 0.33; 95% confidence interval, 0.14 to 0.76). Total fat, animal fat, SFA, PUFA, MUFA, and cholesterol intakes showed no association with metabolic syndrome. Vegetable fat intake was inversely associated with the risk of hypertriglyceridemia among the components of metabolic syndrome. CONCLUSION: These data support an inverse association between vegetable fat and the risk of metabolic syndrome.

Factors Associated with Diffusely Increased Splenic F-18 FDG Uptake in Patients with Cholangiocarcinoma.

OBJECTIVES: Although diffuse splenic (18)F-fluorodeoxyglucose (F-18 FDG) uptake exceeding hepatic activity, is considered abnormal, its clinical significance is rarely discussed in the literature. The aim of this study was to determine the contributing factors causing diffusely increased splenic FDG uptake in patients with cholangiocarcinoma. METHODS: From January 2010 to March 2013, 140 patients (84 men, 56 women) were enrolled in this study. All patients had been diagnosed with cholangiocarcinoma and underwent F-18 FDG positron emission tomography/computed tomography (PET/CT) for the pretreatment staging work up. Clinical records were reviewed retrospectively. Various hematological parameters, C-reactive protein (CRP) level, CEA, CA19-9, pancreatic enzymes and liver function tests were conducted within 2 days after the F-18 FDG PET/CT study. RESULTS: Diffuse splenic uptake was observed in 23 patients (16.4%). Of those, 19 patients (82.6%) underwent endoscopic retrograde cholangiopancreastography (ERCP) 7 days before F-18 FDG PET/CT. The CRP level (p < 0.001) and white blood cell count (p = 0.023) were significantly higher in the group of patients with diffuse splenic FDG uptake. The hemoglobin (p < 0.001) and the hematocrit (p < 0.001) were significantly lower in patients with diffuse splenic FDG uptake. Pancreatic enzymes, liver function test results, and tumor markers were not significantly different between the patients who did or did not have diffusely increased splenic FDG uptake. The significant factors for diffuse splenic F-18 FDG uptake exceeding hepatic F-18 FDG uptake on multivariate analysis included: performing ERCP before F-18 FDG PET-CT (odds ratio [OR], 77.510; 95% CI, 7.624-132.105), and the presence of leukocytosis (OR, 12.436; 95% CI, 2.438-63.445) or anemia (OR, 1.211; 95% CI, 1.051-1.871). CONCLUSION: In conclusion, our study demonstrated that concurrent inflammation could be associated with diffusely increased splenic FDG uptake. We suggest that performing ERCP before F-18 FDG PET/CT could cause acute inflammation which may induce splenic FDG activity.

The optimal follow-up period in patients with above 5-year disease-free survival after curative liver resection for hepatocellular carcinoma.

PURPOSE: Although many patients with hepatocellular carcinoma experience recurrence within 2 years after hepatectomy, some patients with T1 and T2 hepatocellular carcinoma show recurrence-free survival for more than 5 years after surgery. This study was designed to analyze the optimal follow-up period on patients with T1 and T2 hepatocellular carcinoma (HCC) showing recurrence-free survival 5 years after surgery. METHODS: One hundred seventy patients underwent hepatectomy from January 1995 to December 1999. Numbers of patients with T1 and T2 HCC were 76 and 73, respectively. The recurrence patterns of patients experiencing recurrence more than 5 years after liver resection were analyzed in aspect of clinicopathological features and follow-up period. RESULTS: Thirteen patients experienced recurrence more than 5 years after surgery. Only age was found as a significant factor for recurrence. Eight patients were checked regularly with 6-month intervals and the others were checked with 12-month or more intervals. The size of the recurrent tumors in the 6-month interval group had a median of 1.1 cm (range, 1 to 4.2 cm) and the size of the recurrent tumors in the 12-month or more interval group had a median of 3 cm (range, 1.6 to 4 cm). The tumor size was significantly smaller in the 6-month interval group. CONCLUSION: Though the patients with early stage HCC showed high overall survival, some patients experienced a late recurrence of more than 5 years after surgery. Patients less than 60 years old with early stage HCC should be checked regularly with 6-month intervals even over 5 years after liver resection.

Significance of the development of the inner ear third window effect after endolymphatic sac surgery in Ménière disease patients.

OBJECTIVES/HYPOTHESIS: The goal of this study was to identify the clinical significance of the low-frequency air-bone gap (LFABG) that often develops after endolymphatic sac surgery. STUDY DESIGN: Prospective study. METHODS: Sixteen patients who had been diagnosed with definite Ménière disease and underwent endolymphatic sac surgery were studied. The surgical outcome was evaluated based on the 1995 guidelines of the American Academy of Otolaryngology-Head and Neck Surgery. The number of patients who developed LFABGs (a mean air-bone gap >10 dB HL at 250, 500, and 1,000 Hz) after surgery was determined, and the significance of the LFABGs was evaluated by analyzing their relation with the surgical outcome. RESULTS: The vertigo spells of nine patients were completely controlled (class A). The number of vertigo spells was reduced by 60% to 99% in 6 patients (class B) and by 20% to 59% in 1 patient (class C). Postoperative LFABGs were observed in 13 patients. The mean LFABG of the patients in class A was significantly larger than that of the patients in classes B and C (25.0 ± 7.6 dB nHL in class A vs. 10.0. ± 7.5 dB nHL in class B and C; P = .005). CONCLUSIONS: Based on the data of the current study, we conjectured that the correlation of large LFABGs with excellent vertigo control in this study may be due to a third window phenomenon related to bony decompression of the endolymphatic sac and duct, and may serve as a favorable prognostic marker.

Current strategy for the treatment of symptomatic spontaneous isolated dissection of superior mesenteric artery.

OBJECTIVE: Spontaneous isolated dissection of the superior mesenteric artery (SIDSMA) is extremely rare. Various treatment options are currently available, including conservative management, anticoagulation, endovascular stenting, and surgical repair. Herein, we present our experience in the treatment of symptomatic SIDSMA. METHODS: A retrospective study was conducted on 14 consecutive patients with symptomatic SIDSMA between January 2000 and January 2010. All patients had acute onset abdominal pain. The decision to intervene was based on patient symptoms and signs, as well as the morphologic characteristics of superior mesenteric artery (SMA) dissection on computed tomography (CT) angiography. Endovascular stenting (ES) was indicated in patients with severe compression of the true lumen or dissecting aneurysm likely to rupture. Self-expandable stents were placed via a right common femoral approach. None of the patients underwent anticoagulation, and patients who underwent ES were maintained on antiplatelet therapy for 3 months postoperatively. RESULTS: The median age of the study subjects was 59 years (range, 50-75 years). The median follow-up time was 27.5 months (range, 2-64 months). Treatment included conservative management without the use of anticoagulation in seven patients, ES in six, and necrotic bowel resection in one. Four patients with severe compression of the true lumen or large dissecting aneurysm underwent ES as a primary treatment. ES was additionally performed in two patients in whom initial conservative treatment failed (increasing dissecting aneurysm at 7-day follow-up CT scan in one and a reappearance of abdominal pain after resuming diet in the other). The median fasting time was significantly shorter in patients with primary ES (2.5 days) than in those managed conservatively (8.0 days). No complications associated with the SIDSMA or ES were developed. The patency of stents was demonstrated on follow-up CT scans up to 60 months (range, 1-60 months). CONCLUSIONS: Conservative management without anticoagulation can be applied successfully to the patients with symptomatic SIDSMA. Primary endovascular stenting is indicated if patients have suspected bowel ischemia, compression of the true lumen of the SMA >80%, or SMA aneurysm of >2.0 cm in diameter on initial CT scan. Endovascular stenting can also be provided to the patients in whom initial conservative treatment failed, as a rescue therapy.

CYP3A5 *1 allele: impacts on early acute rejection and graft function in tacrolimus-based renal transplant recipients.

BACKGROUND: Tacrolimus is a major immunosuppressant, which has a narrow therapeutic range and wide interindividual variation. The effects of genetic polymorphisms of cytochrome P450 3A (CYP3A) 5 and Adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) genes on the achievement of target tacrolimus trough levels and clinical outcomes in renal transplants were evaluated. METHODS: A total of 62 patients participated in this prospective study. After an initial fixed oral dose (0.08 mg/kg two times per day), tacrolimus doses were adjusted to a target range based on daily measurement of blood trough concentration. Every patient underwent 10-day scheduled biopsy. Both the patients and investigators were blinded for the genetic polymorphisms. RESULTS: Those subjects expressing CYP3A5 (n=29) evidenced significantly lower tacrolimus trough levels between days 1 and 5 after transplantation, when compared with nonexpressers (n=33). Significantly higher overall incidences of early T-cell-mediated rejection (TCR) of at least Banff grade 1 in severity (P=0.017), including clinical rejection within 10 days and subclinical rejection in biopsies at postoperative day 10 were detected in CYP3A5 expressers. The severity of TCR according to Banff '07 classification was associated with CYP3A5 genotypes (P=0.012). Moreover, multivariate analysis identified CYP3A5 expression as an independent risk factor for TCR (odds ratio: 2.79; P=0.043). Significantly lower estimated glomerular filtration rates until 1 month and numerically lower estimated glomerular filtration rates by 12 months were noted in the CYP3A5 expressers. The genetic polymorphisms of the ABCB1 genes exerted no significant effects. CONCLUSION: We confirmed the significant effects of CYP3A5 polymorphism on the achievement of target tacrolimus trough levels and the development of acute rejection in early period after transplantation and consequent renal allograft function.