Glucosamine and Silibinin Alter Cartilage Homeostasis through Glycosylation and Cellular Stresses in Human Chondrocyte Cells.

Osteoarthritis is more prevalent than any other form of arthritis and is characterized by the progressive mechanical deterioration of joints. Glucosamine, an amino monosaccharide, has been used for over fifty years as a dietary supplement to alleviate osteoarthritis-related discomfort. Silibinin, extracted from milk thistle, modifies the degree of glycosylation of target proteins, making it an essential component in the treatment of various diseases. In this study, we aimed to investigate the functional roles of glucosamine and silibinin in cartilage homeostasis using the TC28a2 cell line. Western blots showed that glucosamine suppressed the N-glycosylation of the gp130, EGFR, and N-cadherin proteins. Furthermore, both glucosamine and silibinin differentially decreased and increased target proteins such as gp130, Snail, and KLF4 in TC28a2 cells. We observed that both compounds dose-dependently induced the proliferation of TC28a2 cells. Our MitoSOX and DCFH-DA dye data showed that 1 µM glucosamine suppressed mitochondrial reactive oxygen species (ROS) generation and induced cytosol ROS generation, whereas silibinin induced both mitochondrial and cytosol ROS generation in TC28a2 cells. Our JC-1 data showed that glucosamine increased red aggregates, resulting in an increase in the red/green fluorescence intensity ratio, while all the tested silibinin concentrations increased the green monomers, resulting in decreases in the red/green ratio. We observed increasing subG1 and S populations and decreasing G1 and G2/M populations with increasing amounts of glucosamine, while increasing amounts of silibinin led to increases in subG1, S, and G2/M populations and decreases in G1 populations in TC28a2 cells. MTT data showed that both glucosamine and silibinin induced cytotoxicity in TC28a2 cells in a dose-dependent manner. Regarding endoplasmic reticulum stress, both compounds induced the expression of CHOP and increased the level of p-eIF2α/eIF2α. With respect to O-GlcNAcylation status, glucosamine and silibinin both reduced the levels of O-GlcNAc transferase and hypoxia-inducible factor 1 alpha. Furthermore, we examined proteins and mRNAs related to these processes. In summary, our findings demonstrated that these compounds differentially modulated cellular proliferation, mitochondrial and cytosol ROS generation, the mitochondrial membrane potential, the cell cycle profile, and autophagy. Therefore, we conclude that glucosamine and silibinin not only mediate glycosylation modifications but also regulate cellular processes in human chondrocytes.

A functional chicken-liver hydrolysate-based supplement ameliorates alcohol liver disease via regulation of antioxidation, anti-inflammation, and antiapoptosis.

Tons of broiler livers are produced yearly in Taiwan but always considered waste. Our team has successfully patented and characterized a chicken-liver hydrolysate (CLH) with several biofunctions. Chronic alcohol consumption causes hepatosteatosis or even hepatitis, cirrhosis, and cancers. This study was to investigate the hepatoprotection of CLH-based supplement (GBHP01™) against chronic alcohol consumption. Results showed that GBHP01™ could reduce (p < .05) enlarged liver size, lipid accumulation/steatosis scores, and higher serum AST, ALT, γ-GT, triglyceride, and cholesterol levels induced by an alcoholic liquid diet. GBHP01™ reduced liver inflammation and apoptosis in alcoholic liquid-diet-fed mice via decreasing TBARS, interleukin-6, interleukin-1ß, and tumor necrosis factor-α levels, increasing reduced GSH/TEAC levels and activities of SOD, CAT and GPx, as well as downregulating CYP2E1, BAX/BCL2, Cleaved CASPASE-9/Total CASPASE-9 and Active CASPASE-3/Pro-CASPASE-3 (p < .05). Furthermore, GBHP01™ elevated hepatic alcohol metabolism (ADH and ALDH activities) (p < .05). In conclusion, this study prove the hepatoprotection of GBHP01™ against alcohol consumption.

Perioperative complications of using freezing nitrogen ethanol composite to treat bone tumors: Clinical experience from a single center.

BACKGROUND: The cryoablation efficacy of semisolid freezing nitrogen ethanol composite (FNEC) has been demonstrated. We aimed to investigate the feasibility of adjuvant FNEC-assisted cryoablation in different bone cavity types by assessing the perioperative complication rates. METHODS: The medical charts of patients who received intraoperative adjuvant cryoablation using semisolid FNEC for bone tumors from December 2013 to January 2018 were reviewed. The bone cavities were categorized into three types according to liquid spill potential (type 1, able to hold liquid without limb manipulation; type 2, required extensive limb manipulation to retain liquid; type 3, unable to retain liquid). The overall complication rate and the complication rates stratified by bone cavity type were determined. RESULTS: Among the 76 patients, 30.3%, 57.9%, and 11.8% had type 1, 2, and 3 bone cavities, respectively. The mean follow-up time for perioperative complications was 43.5 ± 24.1 days. Five patients experienced complications, including two cases of skin damage, two cases of skin infection, and one case of fracture, yielding an overall perioperative complication rate of 6.4%. All cases of skin damage and skin infection were superficial and manageable by oral antibiotics. The patient with a pathologic fracture recovered well after being treated with open reduction and plate fixation. No neuropraxia was noted within the first few days postsurgery in any patient. The complication rates in type 1, 2, and 3 bone cavities were 13%, 4.6%, and 0%, respectively. CONCLUSION: All bone cavity types had a low incidence of perioperative complications after treatment with adjuvant FNEC-assisted cryoablation. Semisolid FNEC-assisted cryoablation is a feasible alternative to overcome the liquid spill potential in bone cavities resulting from tumor resection and intralesional curettage.

Hepatic-Modulatory Effects of Chicken Liver Hydrolysate-Based Supplement on Autophagy Regulation against Liver Fibrogenesis.

Chicken-liver hydrolysates (CLHs) have been characterized as performing several biofunctions by our team. This study aimed to investigate if a CLH-based supplement (GBHP01TM) can ameliorate liver fibrogenesis induced by thioacetamide (TAA) treatment. Our results showed that the TAA treatment caused lower body weight gains and enlarged livers, as well as higher serum ALT, AST, and ALP levels (p < 0.05). This liver inflammatory and fibrotic evidence was ameliorated (p < 0.05) by supplementing with GBHP01TM; this partially resulted from its antioxidant abilities, including decreased TBARS values but increased TEAC levels, reduced GSH contents and catalase/GPx activities in the livers of TAA-treated rats (p < 0.05). Additionally, fewer nodules were observed in the appearance of the livers of TAA-treated rats after supplementing with GBHP01TM. Similarly, supplementing GBHP01TM decreased fibrotic scars and the fibrotic score in the livers of TAA-treated rats (p < 0.05). Moreover, the increased hepatic IL-6, IL-1ß, and TNF-α levels after TAA treatment were also alleviated by supplementing with GBHP01TM (p < 0.05). Meanwhile, GBHP01TM could decrease the ratio of LC3B II/LC3B I, but upregulated P62 and Rab7 in the livers of TAA-treated rats (p < 0.05). Taking these results together, the CLH-based supplement (GBHP01TM) can be characterized as a natural agent against liver fibrogenesis.

Comparing radial lengthening osteotomy with ulnar shortening osteotomy to treat ulnar impaction syndrome after distal radius fracture malunion.

INTRODUCTION: Distal radius mal-unions often cause radius shortening and ulnar impaction syndrome. The modern treatments of ulnar impaction syndrome following distal radius mal-union are ulnar shortening osteotomy (USO) and distal radius lengthening osteotomy (DRLO). However, there are few studies to compare long-term outcomes of these two treatments. This study compares isolated USO to DRLO for the treatment of ulnar impaction syndrome following distal radius mal-union. MATERIALS AND METHODS: We retrospectively reviewed 68 patients with extra-articular distal radius mal-unions treated by isolated USO in 36 patients and DRLO in 32 patients. Pain visual analog scale (VAS), wrist motion, grip strength, radiographic parameters including sigmoid inclination, DASH score, and perioperative complications were analyzed. Mean follow-up was 62.6 months. RESULTS: The postoperative VAS scores for pain on exertion were less in the DRLO group than the USO group (1.2 vs. 2.8, p = 0.02). The DASH scores were 16.7 and 29.8 in the DRLO and USO groups, respectively (p = 0.02). The reduction of pain and improvement of function showed significantly better in the DRLO group. The mean operative time was shorter in the USO group. Most of the sigmoid inclinations were changed in DRLO. There were two re-operations following USO for painful nonunion and two patients had subsequent DRUJ osteoarthritis at the last follow-up. CONCLUSION: Although both treatments improved range of motion, grip strength, and VAS for pain, DRLO was found in better reduction of pain and improvement of function. USO is a simpler procedure with a shorter operative time but it has an increased potential to cause subsequent osteoarthritis of the DRUJ as its incongruity of DRUJ after USO especially in reverted inclination. DRLO can be a preferred method for treating USWP in relevant distal radial mal-union.

The Decisive Case-Control Study Elaborates the Null Association between ADAMTS5 rs226794 and Osteoarthritis in Asians: A Case-Control Study and Meta-Analysis.

BACKGROUND: Osteoarthritis is an important health issue for the elderly. Many studies indicate that genetics is an important risk factor for osteoarthritis, and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) is one gene that is most frequently implicated. Many recent studies have examined the relationship between a polymorphism in the ADAMTS5 gene (rs226794) and the risk for developing osteoarthritis without definitive results. OBJECTIVE: In this case-control study, we examined the correlation between the ADAMTS5 gene polymorphism, rs226794, and knee osteoarthritis. We used a meta-analysis and trial sequential analysis to determine whether ADAMTS5 rs226794 expression increases susceptibility to osteoarthritis. METHODS: This study consisted of two parts: a case-control study and a meta-analysis. The case-control study included subjects who underwent knee radiography at the Health Examination Center of the Tri Service General Hospital from 2015 to 2019. The Kellgren-Lawrence (KL) grading system was used as diagnostic criteria. Patients with unsuccessful gene sequencing were excluded. There were 606 subjects in the knee osteoarthritis group (KL ≥ 2) and 564 in the control group (KL < 2). Gene sequencing was performed using iPLEX Gold to determine the association between the gene polymorphism of ADAMTS5 rs226794 and knee osteoarthritis. For the meta-analysis, databases such as PubMed, Embase, and Cochrane were queried to identify studies that examined the relationship between ADAMTS5 rs226794 and osteoarthritis. Next, the findings of the meta-analysis were incorporated with the results of the case-control study and samples from the published studies to estimate the association between the genetic polymorphism and osteoarthritis using an odds ratio and a 95% confidence interval. RESULTS: We found a non-significant association between the G allele and knee OA (crude-OR: 0.93 (95% CI: 0.79-1.10) and adjusted-OR: 1.02 (95% CI: 0.76-1.36) in the allele model) in the present study, and the analysis of other genetic models revealed a similar trend. After including five published studies and our case-control study, the results with 2866 Asians indicated a conclusively null association between ADAMTS5 rs226794 and knee OA) OR: 1.09 (95% CI: 0.93-1.26). The results for Caucasians also revealed a null association (OR: 1.21 (95% CI: 0.81-1.82)). CONCLUSIONS: This study indicates that the gene polymorphism, ADAMTS5 rs226794, is not significantly associated with knee osteoarthritis. Additionally, assuming that the cumulative sample size in the allele model is sufficient, we confirmed that the G allele is not a risk factor for osteoarthritis. This study integrated all available evidence to arrive at this conclusion, and it suggests that no additional studies are necessary.

Comparison of the Confluence-Initiated Neurogenic Differentiation Tendency of Adipose-Derived and Bone Marrow-Derived Mesenchymal Stem Cells.

Adipose-derived mesenchymal stem cells (ADSCs), which tended to neurogenically differentiate spontaneously after achieving high confluence, were observed. Human ADSCs reaching 80% confluence were cultured in DMEM without an inducing factor for 24 h and then maintained in DMEM plus 1% FBS medium for 7 days. The neurogenic, adipogenic, and osteogenic genes of the factor-induced and confluence-initiated differentiation of the ADSCs and bone marrow-derived mesenchymal stem cells (BMSCs) at passages 3 to 5 were determined and compared using RT-qPCR, and the neurogenic differentiation was confirmed using immunofluorescent staining. In vitro tests revealed that the RNA and protein expression of neuronal markers, including class III ß-tubulin (TUBB3), microtubule-associated protein 2 (MAP2), neurofilament medium polypeptide (NEFM), neurofilament heavy polypeptide (NEFH), and neurofilament light polypeptide (NEFL), had been enhanced in the confluence-initiated differentiation of the ADSCs. In addition, the expressions of neurotrophins, such as the nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-derived neurotrophic factor (GDNF), were also elevated in the confluence-initiated differentiation of the ADSCs. However, the confluent ADSCs did not show a tendency toward spontaneous adipogenic and osteogenic differentiation. Moreover, compared with the confluent ADSCs, the tendency of spontaneous neurogenic, adipogenic, and osteogenic differentiation of the confluent human bone marrow mesenchymal stem cells (BMSCs) was not observed. The results indicated that ADSCs had the potential to spontaneously differentiate into neuron-like cells during the confluent culture period; however, this tendency was not observed in BMSCs.

Polymorphism of rs6426749 at 1p36.12 is associated with the risk of osteoarthritis in Taiwanese female population.

BACKGROUND: Osteoarthritis (OA) is a multifactorial disease that is associated with several genetic factors. TFAP2A with a motif of C allele at rs6426749 demonstrates a higher binding ability, thereby increasing CDC42 expression, potentially affecting OA occurrence. In this study, we evaluated the role of rs6426749 polymorphisms on knee OA in a female Taiwanese population. METHODS: We performed a case-control study of 368 OA cases and 379 controls between March 2017 and October 2018. Knee OA was defined using the Kellgren-Lawrence grading system, and genotypes were determined using the Sequenom MassArray iPLEX Gold assay. Stratified sex and body mass index (BMI) analyses were performed using logistic regression to explore interactions between genes and the environment. We also used expression quantitative trait loci data from the genotype-tissue expression project to conduct functional analyses. RESULTS: The C allele of rs6426749 was associated with the risk of knee OA (odds ratio [OR] = 1.31, 95% confidence interval [CI], 1.01-1.71; p = 0.042), after adjusting for gender, age, and BMI. In addition, subgroup analyses indicated that females expressing C alleles showed an increased risk for knee OA (OR = 1.56; 95% CI, 1.12-2.18; p = 0.009). Females with a normal BMI and the C allele had the highest OA risk (OR = 1.73; 95% CI, 1.08-2.76; p = 0.022). CONCLUSION: Our findings indicated that rs6426749 may be related to OA susceptibility in the Taiwanese population. This was particularly true for women with normal BMI.

Prognostic factors and survival in conventional chondrosarcoma: A single institution review.

BACKGROUND: Chondrosarcoma is the second most common primary sarcoma of the bone. Surgery remains the gold standard for treatment due to chemotherapy and radiotherapy resistance in chondrosarcoma. The main aim of our study was to analyze patients with primary chondrosarcoma of the bone who were treated in a single tumor center. Our study team identified the prognostic factors for overall survival, metastasis-free survival, and recurrence-free survival. METHODS: From 1998 to 2012, 55 consecutive patients were treated surgically. All patients were followed for local recurrence or distant metastasis. Uni- and multivariate analyses were performed for overall, metastasis-free, and recurrence-free survival. RESULTS: Local recurrence developed in 29 of the 55 patients (52.7%). Recurrence-free survival in the multivariate analysis showed a significant association with the surgical margin, and high-grade lesions were an independent factor for local recurrence. In total, 11 patients died of the disease in the study, and the 5- and 10-year survival rates were 84.4% and 78.1%, respectively. The tumor grade and local recurrence were significant factors in the univariate analysis but were insignificant in the Cox regression with time-dependent covariates (p = 0.327 and p = 0.82, respectively). The development of distant metastasis was a significant poor prognostic factor in both the uni- and multivariate analyses. CONCLUSION: Chondrosarcoma of the bone is a disease with surgery-dependent outcomes; but, however, patients often develop subsequent recurrence of the disease. The surgical margins were statistically associated with the risk of subsequent local recurrence but did not predict survival. The development of distant metastases was an independent prognostic factor for poor survival.

Results of Fabry Disease Screening in Male Pre-End Stage Renal Disease Patients with Unknown Etiology Found Through the Platform of a Chronic Kidney Disease Education Program in a Northern Taiwan Medical Center.

BACKGROUND/AIMS: Fabry disease (FD), a rare x-lined genetic disorder is a cause of renal deterioration. The phenotype of FD is highly variable and nonspecific, and correct diagnosis has always been delayed. We aimed to explore the prevalence and clinical presentation of FD in this high-risk male population in a Northern Taiwan medical center. METHODS: This is the first study to survey the incidence of FD in this high-risk population through the platform of a chronic kidney disease (CKD) education program in Asia. A total of 1,012 male patients with unknown CKD causes were screened using an assay of alpha-galactosidase A activity (α-Gal A) by dried blood spots (DBS). A final GLA gene analysis was also done for those with low enzyme activity. RESULTS: We identified two new patients with classic FD and four patients with late-onset FD. One novel GLA mutation with c.413 G>A was found in one classic FD patient (index 5). The prevalence of FD is about 0.59 % (6 in 1,012) in the high-risk population group with CKD. The clinical symptoms of FD patients are nonspecific except in those with various degrees of renal failure. Those patients' correct diagnosis was delayed, taking years and even decades. Three patients received enzyme replacement therapy and one started regular hemodialysis due to persistent renal function deterioration. Another two patients were found from family screening through a new index. In addition, a false negative result occurred in one patient who was proved to have FD by his kidney pathology as determined by this screening. CONCLUSION: FD is not such as rare a disease and its prevalence is greater in this high-risk male population. Clinicians need to be aware that FD should be included in the differential diagnosis in CKD with unknown etiology.

Intralesional curettage of central low-grade chondrosarcoma: A midterm follow-up study.

BACKGROUND: The aim of this study was to review the experience of surgical treatment of low-grade chondrosarcoma and to assess the long-term oncological and functional outcomes between intralesional curettage and wide excision. METHODS: We included 11 patients with central low-grade chondrosarcoma lesions treated with intralesional curettage or wide excision from 1998 to 2013. Seven patients were treated with intralesional curettage and local adjuvant treatment (Group A), and four patients were treated with wide excision and reconstructive surgery (Group B). The mean age of patients was 43.8±17.6 years (range, 20-71 years), and the mean duration of follow-up was 84.4±47.6 months (range, 48-194 months). RESULTS: Group A had a significantly lower complication rate than Group B; three complications were documented in Group B (0% vs. 75%, p=0.024). The operative time (177.1 hours vs. 366.3 hours, p=0.010) and the hospital stay (6.6 days vs. 12.5 days, p=0.010) were significantly shorter in Group A. There was one local recurrence in Group A without statistical significance. Also, there were no differences between intralesional curettage and wide excision with respect to the blood loss. No metastasis disease occurred in either group during the follow-up period. The Musculoskeletal Tumor Society (MSTS) scores in Groups A and B were 99.0±2.5 and 94.2±4.2, respectively, with statistically significant difference (p=0.048). CONCLUSION: Extended intralesional curettage has the benefits of good MSTS score, shorter operative time, shorter hospital stay, and lower complication rate without increasing local recurrence in central low-grade chondrosarcoma. For central low-grade chondrosarcoma, we suggest extended curettage to decrease soft tissue damage and surgical risk.

Precursors of post-bout motion sickness in adolescent female boxers.

Athletic head trauma (both concussive and sub-concussive) is common among adolescents. Head trauma often is followed by motion sickness-like symptoms, by changes in cognitive performance, and by changes in standing body sway. We evaluated adolescent female boxers who did and did not report motion sickness after a bout (i.e., a boxing match), together with a control group of non-boxers. We asked whether pre-bout body sway would differ between boxers who experienced post-bout motion sickness and those who did not. In addition, we asked whether pre-bout cognitive performance would differ between non-boxers and boxers with and without post-bout motion sickness. Seven of twenty boxers reported motion sickness after a bout. Pre-bout measures of cognitive performance and body sway were different in boxers who reported post-bout motion sickness than in boxers without post-bout sickness or controls. The results suggest that susceptibility to motion sickness-like symptoms in adolescent female boxers may be manifested in characteristic patterns of body sway and cognitive performance. It may be possible to use pre-bout data to predict susceptibility to post-bout symptoms.

Motion control, motion sickness, and the postural dynamics of mobile devices.

Drivers are less likely than passengers to experience motion sickness, an effect that is important for any theoretical account of motion sickness etiology. We asked whether different types of control would affect the incidence of motion sickness, and whether any such effects would be related to participants' control of their own bodies. Participants played a video game on a tablet computer. In the Touch condition, the device was stationary and participants controlled the game exclusively through fingertip inputs via the device's touch screen. In the Tilt condition, participants held the device in their hands and moved the device to control some game functions. Results revealed that the incidence of motion sickness was greater in the Touch condition than in the Tilt condition. During game play, movement of the head and torso differed as a function of the type of game control. Before the onset of subjective symptoms of motion sickness, movement of the head and torso differed between participants who later reported motion sickness and those that did not. We discuss implications of these results for theories of motion sickness etiology.

Cognitive and postural precursors of motion sickness in adolescent boxers.

Athletic head trauma (both concussive and sub-concussive) is common among adolescents. Concussion typically is followed by motion sickness-like symptoms, by changes in cognitive performance, and by changes in standing body sway. We asked whether pre-bout body sway would differ between adolescent boxers who experienced post-bout motion sickness and those who did not. In addition, we asked whether pre-bout cognitive performance would differ as a function of adolescent boxers' post-bout motion sickness. Nine of nineteen adolescent boxers reported motion sickness after a bout. Pre-bout measures of cognitive performance and body sway differed between boxers who reported post-bout motion sickness and those who did not. The results suggest that susceptibility to motion sickness-like symptoms in adolescent boxers may be manifested in characteristic patterns of body sway and cognitive performance. It may be possible to use pre-bout data to predict susceptibility to post-bout symptoms.

Hemolysis-induced acute kidney injury following cardiac surgery: a case report and review of the literature.

Acute kidney injury is a common complication following cardiac surgery. Even small increases in creatinine levels are associated with increases in morbidity and mortality. Numerous factors such as hemolysis can contribute to the development of acute kidney injury after cardiac surgery. We present a rare case of severe hemolysis related to cardiopulmonary bypass resulting in kidney injury and requiring dialysis. The patient's renal function gradually recovered when hemolysis was improved. After follow-up for 3 months, his creatinine levels returned to normal. We discussed the pathogenesis of this hemolysis-related kidney dysfunction, the causes of hemolysis during cardiac surgery, and a new treatment option.

Pre-bout standing body sway differs between adult boxers who do and do not report post-bout motion sickness.

BACKGROUND: Motion sickness is characterized by subjective symptoms that include dizziness and nausea. Studies have shown that subjective symptoms of motion sickness are preceded by differences in standing body sway between those who experience the symptoms and those who are not. Boxers often report dizziness and nausea immediately after bouts. We predicted that pre-bout standing body sway would differ between boxers who experienced post-bout motion sickness and those who did not. METHODOLOGY/PRINCIPAL FINDINGS: We collected data on standing body sway before bouts. During measurement of body sway participants performed two visual tasks. In addition, we varied stance width (the distance between the heels). Postural testing was conducted separately before and after participants' regular warm-up routines. After bouts, we collected self-reports of motion sickness incidence and symptoms. Results revealed that standing body sway was greater after warm-up than before warm-up, and that wider stance width was associated with reduced sway. Eight of 15 amateur boxers reported motion sickness after a bout. Two statistically significant interactions revealed that standing body sway before bouts differed between participants who reported post-bout motion sickness and those who did not. CONCLUSIONS/SIGNIFICANCE: The results suggest that susceptibility to motion sickness in boxers may be manifested in characteristic patterns of body sway. It may be possible to use pre-bout data on postural sway to predict susceptibility to post-bout motion sickness.

DR-70 immunoassay for the surveillance of hepatocellular carcinoma.

BACKGROUND AND AIM: Although alpha-fetoprotein (AFP) is a widely used serological marker for hepatocellular carcinoma (HCC), its utility is limited due to its unsatisfactory sensitivity. Meanwhile, a newly developed immunoassay-DR-70-has been reported to have a good sensitivity for HCC in a small-scale study. The aim of this study was to determine the clinical value of DR-70 for the surveillance of HCC. METHODS: Serum levels of DR-70 and AFP were measured in 103 patients with HCC, 50 healthy volunteers, and 33 patients with chronic liver disease. In addition, we investigated the prognostic value of DR-70 in patients with HCC correlating with the clinical staging-Cancer of the Liver Italian Program (CLIP) score and Barcelona Clinic Liver Cancer (BCLC) classification. RESULTS: Based on the receiver operating characteristic curve with area under the curve of 0.836, the DR-70 cut-off value for detecting HCC was determined to be 0.75 µg/mL. DR-70 provided a sensitivity of 81.6% and a specificity of 77.1%, and correlated well with the CLIP score and BCLC classification. The combination of DR-70 and AFP increased the sensitivity to 91.2%. The prognosis for patients with HCC with DR-70 level > 0.75 µg/mL was worse than that for those with DR-70 ≤ 0.75 µg/mL. Among the patients with early stage HCC (CLIP score 0-2), DR-70 > 0.75 µg/mL independently predicted a poor survival. CONCLUSIONS: DR-70 immunoassay is complementary to AFP for the detection of HCC and has a good correlation with clinical staging and prognosis.

Urgency severity scale could predict urodynamic detrusor overactivity in patients with overactive bladder syndrome.

AIMS: To evaluate the correlation between an urgency severity scale (USS) based on a voiding diary with detrusor overactivity (DO) in a videourodynamic study in patients with an overactive bladder (OAB). METHODS: We prospectively enrolled 190 consecutive patients with OAB. All patients were assessed using a USS and completed a 3-day voiding diary that recorded urgency and urgency urinary incontinence (UUI) episodes and the degree of urgency severity. The highest recorded USS score in the voiding diary was considered as the USS score. A videourodynamic study was performed, and the presence of increased bladder sensation (IBS) or DO was recorded. These clinical findings and videourodynamic data were analyzed. RESULTS: This study enrolled 65 men and 125 women. The mean patient age was 66.4 years (21-88). Among them, 82.6% had urodynamic DO, 7.9% had IBS, and 9.5% had normal urodynamic findings. The prevalence of DO was 50%, 76%, and 94% in patients with a USS = 2, 3, and 4, respectively. Multivariate analysis indicated that OAB wet, high USS and UUI were significantly associated with the presence of DO. Urodynamic DO was present in most patients with OAB wet (94.1%) or USS = 4 (95.5%); however, only 63.9% of OAB dry patients had DO. In the OAB dry patients, 11/25 (44%) with USS = 2, 30/42 (71%) with USS = 3, and 5/5 (100%) with USS = 4 had DO. CONCLUSIONS: A high USS recorded in conjunction with a voiding diary and OAB wet were strongly associated with urodynamic DO.

Simvastatin effects on portal-systemic collaterals of portal hypertensive rats.

BACKGROUND AND AIM: Portal-systemic collateral vascular resistance and vasoconstrictor responsiveness are crucial in portal hypertension and variceal bleeding control. Statins enhance vasodilators production, but their influence on collaterals is unknown. This study aimed to survey the effect of simvastatin on collaterals. METHODS: Partially portal vein-ligated rats received oral simvastatin (20 mg/kg/day) or distilled water from -2 to +7 day of ligation. After hemodynamic measurements on the eighth postoperative day, baseline perfusion pressure (i.e. an index of collateral vascular resistance) and arginine vasopressin (AVP, 0.1 nM-0.1 microM) responsiveness were evaluated with an in situ perfusion model for collateral vascular beds. RT-PCR of endothelial NO synthase (eNOS), inducible NOS (iNOS), cyclooxygenase-1 (COX-1), COX-2, thromboxane A(2) synthase (TXA(2)-S) and prostacyclin synthase genes was performed in parallel groups for splenorenal shunt (SRS), the most prominent intra-abdominal collateral vessel. To determine the acute effects of simvastatin, collateral AVP response was assessed with vehicle or simvastatin. SRS RT-PCR of eNOS, iNOS, COX-1, COX-2 and TXA(2)-S, and measurements of perfusate nitrite/nitrate, 6-keto-PGF1(alpha) and TXB(2) levels were performed in parallel groups without AVP. RESULTS: Acute simvastatin administration enhanced SRS eNOS expression and elevated perfusate nitrite/nitrate and 6-keto-PGF1(alpha) concentrations. Chronic simvastatin treatment reduced baseline collateral vascular resistance and portal pressure and enhanced SRS eNOS, COX-2 and TXA(2)-S mRNA expression. Neither acute nor chronic simvastatin administration influenced collateral AVP responsiveness. CONCLUSION: Simvastatin reduces portal-systemic collateral vascular resistance and portal pressure in portal hypertensive rats. This may be related to the enhanced portal-systemic collateral vascular NO and prostacyclin activities.