Risk of subsequent health disorders among living kidney donors.

Few studies have investigated the risk of physiological sequelae in living kidney donors (KDs). We conducted a population-based cohort study using the National Health Insurance Research Database of Taiwan, which covers more than 99% of citizens.We comprehensively investigated the risk of medical disorders after kidney donation in living KDs using a maximum follow-up of 13 years. From January 1997 to December 2010, 1081 living KDs and 1082 age- and sex-matched non-KDs were eligible. Primary outcomes comprised end-stage renal disease, chronic kidney disease, stroke, cancer, acute myocardial infarction, acute renal failure (ARF), and diabetes.The adjusted hazard ratios (HRs) for developing ARF, diabetes, hyperlipidemia, hypertension, cancer, end-stage renal disease, acute myocardial infarction, and stroke were similar between the KD and non-KD cohorts (P > .05). Although differences in the adjusted HRs of ARF were nonsignificant, the cumulative incidence rate of ARF 13 years after donation was 7.48 per 1000 person-years in the KD cohort compared with 3.46 in the matched non-KD cohort. The incidence rate ratio for ARF between donors and nondonors significantly increased to 2.16 (95% confidence interval, 1.61-2.71).Living KDs experienced no significant health disorders following kidney donation but should be alert to the higher incidence rate of ARF.

Risk of acute myocardial infarction in upper tract urothelial carcinoma patients receiving radical nephroureterectomy: a population-based cohort study.

BACKGROUND: The outcomes of upper tract urothelial carcinoma (UTUC) receiving radical nephroureterectomy were usually limited to small sample size, case-control studies, and often focused on cancer progression. Risk of acute myocardial infarction (AMI) in these patients was never investigated. RESULTS: The overall incidences of AMI were 3.39, 1.44, and 1.70 per 10,000 person-years in the radical nephroureterectomy, nonnephroureterectomy, and non-UTUC cohorts, respectively. Multivariable Cox proportional hazard regression analysis revealed a significantly higher AMI risk in the radical nephroureterectomy cohort [adjusted HR (aHR) = 1.83, 95% confidence interval (CI) = 1.08-3.11], compared with non-UTUC cohorts. The risk of mortality were the highest in patients with UTUC who had undergone radical nephroureterectomy [adjusted HR (aHR) = 5.37, 95% confidence interval (CI) = 4.80-6.02]. MATERIALS AND METHODS: From the Taiwan National Health Insurance claims data, 1,359 patients with UTUC who had undergone radical nephroureterectomy and 3,154 patients with UTUC who had undergone nephron sparing surgery and were newly diagnosed between 2000 and 2010 were identified. For each patient, 4 individuals without UTUC were randomly selected and frequency matched by age, sex, and diagnosis year. CONCLUSIONS: Patients with UTUC who have undergone radical nephroureterectomy are at a higher risk of developing AMI, compared with those receiving nephron sparing surgery.

Comparative risk of chronic kidney diseases in patients with urolithiasis and urological interventions: a longitudinal population-based study.

Large cohort studies on whether any association existed between urological interventions for urolithiasis and the development of CKD are lacking. From claims data of the National Health Insurance (NHI) program of Taiwan, we identified 54,433 patients newly diagnosed with urolithiasis during 1998-2010. For each case, four individuals without urolithiasis were randomly selected and frequency matched by age, sex, and diagnosis year. Both groups were followed up until the end of 2010. Incident CKD events were identified by the International Classification of Diseases, Ninth Revision (ICD-9) code in the NHI registration database. The overall incidence of periodontal diseases was 1.85-fold greater in the urolithiasis group than in the comparison group (33.9 vs 18.3 per 10,000 person-years; 95 % confidence interval [CI] 1.81-1.90). Compared with the adjusted hazard ratios (aHRs) of nonurolithiasis patients, those of patients with urolithiasis increased with the number of medical visits (from 0.91 [95 % CI 0.83-1.00] to 10.6 [95 % CI 9.48-11.8]) and urological interventions (from 1.22 [95 % CI 1.10-1.35] to 86.4 [95 % CI 67.6-110.6]). The aHR was similar in different urological intervention methods, extracorporeal shock wave lithotripsy, ureteroscopy, percutaneous nephrostolithotomy, and open stone surgery. The urological intervention for urolithiasis is associated with an increased risk of CKD. We should be aware of the risk for CKD, especially in patients who have received multiple urological interventions and those elderly.

Proteome Profiling of Urinary Exosomes Identifies Alpha 1-Antitrypsin and H2B1K as Diagnostic and Prognostic Biomarkers for Urothelial Carcinoma.

MALDI-TOF spectrometry has not been used for urinary exosome analysis. We used it for determining UC biomarkers. From 2012 to 2015, we enrolled 129 consecutive patients with UC and 62 participants without UC. Exosomes from their urine were isolated, and analyzed through MALDI-TOF spectrometry. Immunohistochemical (IHC) analysis of another 122 UC and 26 non-UC tissues was conducted to verify the discovered biomarkers. Two peaks at m/z 5593 (fragmented peptide of alpha-1-antitrypsin; sensitivity, 50.4%; specificity, 96.9%) and m/z 5947 (fragmented peptide of histone H2B1K sensitivity, 62.0%; specificity, 92.3%) were identified as UC diagnosis exosome biomarkers. UC patients with detectable histone H2B1K showed 2.29- and 3.11-fold increased risks of recurrence and progression, respectively, compared with those with nondetectable histone H2B1K. Verification results of IHC staining revealed significantly higher expression of alpha 1-antitrypsin (p = 0.038) and H2B1K (p = 0.005) in UC tissues than in normal tissues. The expression of alpha 1-antitrypsin and H2B1K in UC tissues was significantly correlated with UC grades (p < 0.05). Urinary exosome proteins alpha 1-antitrypsin and histone H2B1K, which are identified through MALDI-TOF analysis, could facilitate rapid diagnosis and prognosis of UC.

Radiosensitization of non-small cell lung cancer by kaempferol.

The aim of the present study was to determine whether kaempferol has a radiosensitization potential for lung cancer in vitro and in vivo. The in vitro radio-sensitization activity of kaempferol was elucidated in A-549 lung cancer cells by using an MTT (3-(4 5-dimethylthiazol-2-yl)-25-diphenyl-tetrazolium bromide) assay, cell cycle analysis and clonogenic assay. The in vivo activity was evaluated in the BALB/c nude mouse xenograft model of A-549 cells by hematoxylin and eosin staining and immunohistochemistry, and the tumor volume was recorded. Protein levels of the apoptotic pathway were detected by western blot analysis. Treatment with kaempferol inhibited the growth of A-549 cells through activation of apoptotic pathway. However, the same doses did not affect HFL1 normal lung cell growth. Kaempferol induced G2/M cell cycle arrest and the enhancement of radiation-induced death and clonogenic survival inhibition. The in vivo data showed that kaempferol increased tumor cell apoptosis and killing of radiation. In conclusion, the findings demonstrated that kaempferol increased tumor cell killing by radiation in vitro and in vivo through inhibition of the AKT/PI3K and ERK pathways and activation of the mitochondria apoptosis pathway. The results of the present study provided solid evidence that kaempferol is a safe and potential radiosensitizer.

Tissue polypeptide specific antigen (TPS) as a tumor marker in renal cell carcinoma.

Tissue polypeptide specific antigen (TPS) is a new tumor marker that indicates tumor proliferative rate rather than tumor burden. The purpose of this study was to assess the clinical value of TPS in patients with renal cell carcinoma (RCC). Serum levels of TPS were measured in 30 patients with locoregional and in 20 patients with advanced disease before and after therapy. The results showed that: (1) the detection sensitivity of TPS for RCC is 60.0%; (2) the detection sensitivity of TPS in advanced RCC (100.0%) was significantly higher than in locoregional RCC (33.3%); (3) the 10 locoregional RCC patients without recurrence had normal serum TPS levels during a follow-up period of 1 year; and (4) the 8 advanced RCC patients with good response during therapy had normal serum TPS levels, while 12 patients with poor disease had significantly elevated serum TPS levels during a follow-up period of 1 year. Our results suggest that TPS may have a potential clinical role as a valuable tumor marker for RCC, especially in advanced diseases and follow-up therapy response.

Glial cell line-derived neurotrophic factor gene delivery via a polyethylene imine grafted chitosan carrier.

Parkinson's disease is known to result from the loss of dopaminergic neurons. Direct intracerebral injections of high doses of recombinant glial cell line-derived neurotrophic factor (GDNF) have been shown to protect adult nigral dopaminergic neurons. Because GDNF does not cross the blood-brain barrier, intracerebral gene transfer is an ideal option. Chitosan (CHI) is a naturally derived material that has been used for gene transfer. However, the low water solubility often leads to decreased transfection efficiency. Grafting of highly water-soluble polyethylene imines (PEI) and polyethylene glycol onto polymers can increase their solubility. The purpose of this study was to design a non-viral gene carrier with improved water solubility as well as enhanced transfection efficiency for treating Parkinsonism. Two molecular weights (Mw =600 and 1,800 g/mol) of PEI were grafted onto CHI (PEI600-g-CHI and PEI1800-g-CHI, respectively) by opening the epoxide ring of ethylene glycol diglycidyl ether (EX-810). This modification resulted in a non-viral gene carrier with less cytotoxicity. The transfection efficiency of PEI600-g-CHI/deoxyribonucleic acid (DNA) polyplexes was significantly higher than either PEI1800-g-CHI/DNA or CHI/DNA polyplexes. The maximal GDNF expression of PEI600-g-CHI/DNA was at the polymer:DNA weight ratio of 10:1, which was 1.7-fold higher than the maximal GDNF expression of PEI1800-g-CHI/DNA. The low toxicity and high transfection efficiency of PEI600-g-CHI make it ideal for application to GDNF gene therapy, which has potential for the treatment of Parkinson's disease.

Leu27IGF2 plays an opposite role to IGF1 to induce H9c2 cardiomyoblast cell apoptosis via Galphaq signaling.

This study examines the role of IGF2/mannose 6-phosphate receptor (IGF2R) signaling in the signaling transduction regulation and cell apoptosis in H9c2 cardiomyoblast cells. However, it is difficult to recognize the distinct activation of IGF2 signaling without interfacing with IGFI receptor (IGF1R) after exposure to IGF2. Leu27IGF2, an analog of IGF2 that interacts selectively with the IGF2R, was used to specifically activate IGF2R signaling in this study. DNA fragmentation and TUNEL assay revealed that in contrast to IGF1 treatment preventing angiotensin II and AG1024-induced cell apoptosis, Leu27IGF2 appears to synergistically increase apoptosis in those cells. We further found cell apoptosis induction and an increase in the active form of caspase 3 in the treatment of cells with Leu27IGF2, but not IGF1. To detect the interaction between IGF2R and Galphaq using the immunoprecipitation assay, we found that IGF2R could directly interact with Galphaq and after treatment with Leu27IGF2 the binding ability of Galphaq to IGF2R had increased. This sequentially resulted in the phosphorylation of phospholipase C-beta, a key downstream modulator of Galphaq, on serine 537. Moreover, disruption of the Galphaq protein by small interferon RNA reduced the cell apoptosis induced by Leu27IGF2. Our findings demonstrate that IGF2R activation appears to induce cell apoptosis via Galphaq-deriving signaling cascades and its effect is completely different from IGF1R survival signaling.

Detecting metastatic pelvic lymph nodes by 18F-2-deoxyglucose positron emission tomography in patients with prostate-specific antigen relapse after treatment for localized prostate cancer.

AIM: To evaluate whether positron emission tomography (PET) with (18)F-2-deoxyglucose (FDG) can detect pelvic lymph node metastases in prostate cancer patients who had elevated serum prostate-specific antigen (PSA) levels after treatment. METHODS: Twenty-four patients with a rising serum PSA level after treatment for localized prostate cancer were examined with FDG-PET before pelvic lymph node dissection. All patients had negative findings on whole body bone scan and equivocal pelvic computed tomography (CT) results. The results of FDG-PET were then compared to the histology of the pelvic lymph nodes obtained at surgery. RESULTS: Lymph node metastases were detected by histopathological examination in 16/24 (66.7%) patients. At the sites with histopathologically proven metastases, increased FDG uptake was found in 12/16 (75.0%) patients. In addition, there were 4 patients with false-negative results, but no patient with a false-positive result on FDG-PET images. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of FDG-PET in detecting metastatic pelvic lymph nodes were 75.0, 100.0, 83.3, 100.0, and 67.7%, respectively. CONCLUSIONS: These results suggest that FDG-PET may be a valuable diagnostic tool in the staging of pelvic lymph nodes in patients with PSA relapse after treatment of localized prostate cancer when the whole body bone scan is negative and pelvic CT findings are equivocal.