An antioxidant resveratrol significantly enhanced replication of hepatitis C virus

AIM:To elucidate the effect of antioxidants,resveratrol (RVT)and astaxanthin(AXN),on hepatitis C virus(HCV) replication. METHODS:We investigated the effect of recent popular antioxidant supplements on replication of the HCV replicon system OR6.RVT is a strong antioxidant and a kind of polyphenol that inhibits replication of various viruses.AXN is also a strong antioxidant.The replication of HCV RNA was assessed by the luciferase reporter assay.An additive effect of antioxidants on antiviral effects of inter...     

Retinal vein thrombosis associated with chronic hepatitis C: a case series and review of the literature

The role of procoagulant autoantibodies in hepatitis C virus (HCV) infection is unclear. Three individuals with HCV infection and a unique genetic hypercoagulable state developed retinal vein thrombosis (RVT) in association with interferon-alpha (IFN-alpha) therapy. It is probable that a combination of active HCV infection in a genetically susceptible individual receiving IFN-alpha accounted for the observed RVT.     

Protective effects of resveratrol against acetaminophen-induced toxicity in mice.

This investigation elucidates the role of free radicals in acetaminophen (AA)-induced toxicity and the possible protection by resveratrol (RVT). BALB-c mice were injected with a single dose of 900mg/kg AA to induce toxicity, while RVT administred in a dose of 30mg/kg i.p. following AA. Mice were sacrificed 4h after AA injection to determine serum ALT, AST and tumor necrosis factor-alpha (TNF-alpha) levels in blood, and glutathione (GSH), malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and collagen contents in liver tissues. Formation of reactive oxygen species in hepatic tissue samples was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probe. ALT, AST levels and TNF-alpha were increased significantly after AA treatment, and reduced with RVT. AA caused a significant decrease in GSH levels while MDA levels and MPO activity were increased in liver tissues. On the other hand when RVT administered following AA, depletion of GSH and accumulation of MDA and neutrophil infiltration were reversed back to control. Furthermore increased luminol and lucigenin CL levels in the AA group reduced by RVT treatment. Our results implicate that AA causes oxidative damage in hepatic tissues and RVT, by its potent antioxidant effects protects the liver tissue. These data suggest that RVT may be of therapeutic use in preventing hepatic oxidative injury due to AA toxicity.     

Right ventricular abnormalities assessed by myocardial single-photon emission computed tomography using technetium-99m sestamibi/tetrofosmin in right ventricle-originated ventricular tachyarrhythmias

OBJECTIVES: We sought to determine whether right ventricular (RV) perfusion imaging with technetium-99m (Tc-99m) sestamibi or tetrofosmin single-photon emission computed tomography has diagnostic benefit for RV-originated ventricular tachyarrhythmias (RVT). BACKGROUND: Identification of RV abnormalities is clinically important to establish RVT etiology. METHODS: Forty-seven patients with RVT (23 with idiopathic and 24 with organic RVT due to arrhythmogenic RV or dilated cardiomyopathy, cardiac sarcoidosis or myocarditis) were compared to 25 control subjects. Right ventricular uptake score, as assessed by modified tomographic imaging, and regional RV count relative to peak left ventricular (LV) count (RV/LV count ratio) were compared with RV regional and global function. RESULTS: Regional RV uptake score correlated well with the RV/LV count ratio, and segmental abnormality was more frequently (p = 0.001) detected in the organic RVT group (22 [92%] of 24 patients) than in the idiopathic RVT group (4 [17%] of 23 patients) or the control group (8 [32%] of 25 patients). The total RV score (8.4+/-3.8) in the organic RVT group was significantly lower than that in the idiopathic RVT group (15.6+/-1.6) or the control group (15.1+/-1.8). The total RV score correlated with RV EF (r = 0.702, p<0.001). A total RV score <12 differentiated the organic RVT group from the other two groups, with a sensitivity of 79% and a specificity of 100%. The asynergic RV regions had a significantly lower RV/LV count ratio and RV score as compared with the nonasynergic regions and were identified by RV assessment, with a sensitivity of 76.1% and a specificity of 76.6%. CONCLUSIONS: Right ventricular perfusion tomography using a Tc-99m-labeled tracer is clinically useful for the noninvasive detection of RV myocardial damage in patients with RVT and for differentiating organic from idiopathic RVT.     

Residual vein thrombosis for assessing duration of anticoagulation after unprovoked deep vein thrombosis of the lower limbs: the extended DACUS study

The safest duration of anticoagulation after idiopathic deep vein thrombosis (DVT) is unknown. We conducted a prospective study to assess the optimal duration of vitamin K antagonist (VKA) therapy considering the risk of recurrence of thrombosis according to residual vein thrombosis (RVT). Patients with a first unprovoked DVT were evaluated for the presence of RVT after 3 months of VKA administration; those without RVT suspended VKA, while those with RVT continued oral anticoagulation for up to 2 years. Recurrent thrombosis and/or bleeding events were recorded during treatment (RVT group) and 1 year after VKA withdrawal (both groups). Among 409 patients evaluated for unprovoked DVT, 33.2% (136 of 409 patients) did not have RVT and VKA was stopped. The remaining 273 (66.8%) patients with RVT received anticoagulants for an additional 21 months; during this period of treatment, recurrent venous thromboembolism and major bleeding occurred in 4.7% and 1.1% of patients, respectively. After VKA suspension, the rates of recurrent thrombotic events were 1.4% and 10.4% in the no-RVT and RVT groups, respectively (relative risk = 7.4; 95% confidence interval = 4.9-9.9). These results indicate that in patients without RVT, a short period of treatment with a VKA is sufficient; in those with persistent RVT, treatment extended to 2 years substantially reduces, but does not eliminate, the risk of recurrent thrombosis.     

Resveratrol and its synthetic derivatives exert opposite effects on mesothelial cell-dependent angiogenesis via modulating secretion of VEGF and IL-8/CXCL8

We examined the effect of resveratrol (RVT) and its two derivatives (3,3',4,4'-tetrahydroxy-trans-stilbene and 3,3',4,4',5,5'-hexahydroxy-trans-stilbene) on human peritoneal mesothelial cell (HPMC)-dependent angiogenesis in vitro. To this end, angiogenic activity of endothelial cells (HUVEC, HMVEC, and HMEC-1) was monitored upon their exposure to conditioned medium (CM) from young and senescent HPMCs treated with stilbenes or to stilbenes themselves. Results showed that proliferation and migration of endothelial cells were inhibited in response to indirect (HPMC-dependent) or direct RVT activity. This effect was associated with decreased secretion of VEGF and IL-8/CXCL8 by HPMCs treated with RVT, which confirmed the experiments with recombinant forms of these angiogenic agents. Angiogenic activity of endothelial cells treated with CM from HPMCs exposed to RVT analogues was more effective. Improved migration was particularly evident in cells exposed to CM from senescent HPMCs. Upon direct treatment, RVT derivatives stimulated proliferation (but not migration) of HUVECs, and failed to affect the behaviour of HMVEC and HMEC-1 cells. These compounds stimulated production of VEGF and IL-8/CXCL8 by HPMCs. Studies with neutralizing antibodies against angiogenic factors revealed that augmented angiogenic reactions of endothelial cells exposed to CM from HPMC treated with RVT analogues were related to enhanced production of VEGF and IL-8/CXCL8. Collectively, these findings indicate that RVT and its synthetic analogues divergently alter the secretion of the angiogenic factors by HPMCs, and thus modulate HPMC-dependent angiogenic responses in the opposite directions. This may have implications for the attempts of practical employment of the stilbenes for treatment of pathologies proceeding with abnormal vascularisation of the peritoneal tissue.     

Renal vein thrombosis in nephrotic syndrome--a prospective study of 54 cases

Recent advance of radiographic technique makes antemortem diagnosis of renal vein thrombosis (RVT) possible. However the incidence of RVT in patients with nephrotic syndrome(NS) is still not known. This study was designed to investigate the incidence, clinical presentation and radiological features of RVT in NS patients in China. A prospective study including clinical, and pathological examination as well as renal venogram was carried out in all our hospitalized NS patients except those having contradiction for renal venogram. RVT was found in 23 of the 54 cases (42%) and there was obstruction in 34 renal vein branches. RVT was more common in left (19) than right side (15), in upper (19) than middle and lower branches (10). It is interesting that in our group not only membranous but also minimal change as well as mesangium proliferative glomerulonephritis had high incidence of RVT (47%, 45% and 36% respectively) Only 6 cases (26%) had a typical acute presentation with severe loin pain, significant increase of urinary protein, enlargement of involved kidney. Occasionally fever, deterioration of renal function and sterile urinary white cells were also present. The remaining patients (74%) had latent onset of RVT which could hardly be identified in the clinical course of the underlying NS. For the high incidence and atypical clinical course of RVT shown in our study, it is recommended that due attention should be paid of this complication during management of NS and interpretation of therapeutic response.     

The coagulogram in patients with nephrotic syndrome

The coagulogram done in half of the 100 cases of nephrotic patients admitted into our hospital from 1986 to 1988 was studied. It is shown that the patients of either the renal vein thrombosis (RVT) positive or negative group were in hypercoagulability state. 46 patients in this series had RVT proved by renography. The mechanism of RVT and the clinical significance of the changes of these hemostatic data are discussed.     

Oxidative stress modulation in hepatitis C virus infected cells

Hepatitis C virus(HCV) replication is associated with the endoplasmic reticulum, where the virus can induce cellular stress. Oxidative cell damage plays an important role in HCV physiopathology. Oxidative stress is triggered when the concentration of oxygen species in the extracellular or intracellular environment exceeds antioxidant defenses. Cells are protected and modulate oxidative stress through the interplay of intracellular antioxidant agents, mainly glutathione system(GSH) and thioredoxin; and antioxidant enzyme systems such as superoxide dismutase, catalase, GSH peroxidase, and heme oxygenase-1. Also, the use of natural and synthetic antioxidants(vitamin C and E, N-acetylcysteine, glycyrrhizin, polyenylphosphatidyl choline, mitoquinone, quercetin, S-adenosylmethionine and silymarin) has already shown promising results as co-adjuvants in HCV therapy. Despite all the available information, it is not known how different agents with antiviral activity can interfere with the modulation of the cell redox state induced by HCV and decrease viral replication. This review describes an evidence-based consensus on molecular mechanisms involved in HCV replication and their relationship with cell damage induced by oxidative stress generated by the virus itself and cell antiviral machinery. It also describes some molecules that modify the levels of oxidative stress in HCV-infected cells.     

Residual vein thrombosis to establish duration of anticoagulation after a first episode of deep vein thrombosis: the Duration of Anticoagulation based on Compression UltraSonography (DACUS) study

Residual vein thrombosis (RVT) indicates a prothrombotic state and is useful for evaluating the optimal duration of oral anticoagulant treatment (OAT). Patients with a first episode of deep vein thrombosis, treated with OAT for 3 months, were managed according to RVT findings. Those with RVT were randomized to either stop or continue anticoagulants for 9 additional months, whereas in those without RVT, OAT was stopped. Outcomes were recurrent venous thromboembolism and/or major bleeding. Residual thrombosis was detected in 180 (69.8%) of 258 patients; recurrent events occurred in 27.2% of those who discontinued (25/92; 15.2% person-years) and 19.3% of those who continued OAT (17/88; 10.1% person-years). The relative adjusted hazard ratio (HR) was 1.58 (95% confidence interval [CI], 0.85-2.93; P = .145). Of the 78 (30.2%) patients without RVT, only 1 (1.3%; 0.63% person-years) had a recurrence. The adjusted HR of patients with RVT versus those without was 24.9 (95% CI, 3.4-183.6; P = .002). One major bleeding event (1.1%; 0.53% person-years) occurred in patients who stopped and 2 occurred (2.3%; 1.1% person-years) in those who continued OAT. Absence of RVT identifies a group of patients at very low risk for recurrent thrombosis who can safely stop OAT. This trial was registered at http://www.ClinicalTrials.gov as no. NCT00438230.     

Abdominal venous thrombosis in neonates and infants: role of prothrombotic risk factors - a multicentre case-control study. For the Childhood Thrombophilia Study Group

The factor V (FV) G1691A mutation, the prothrombin (PT) G20210A variant, the methylenetetrahydrofolate reductase (MTHFR) T677T genotype, together with fasting homocysteine (HCY) concentration, lipoprotein (Lp)(a), anti-thrombin (AT), protein C (PC), protein S (PS) and anti-cardiolipin antibodies were investigated in 65 consecutively recruited infants (neonate to < 12 months) with renal venous thrombosis (RVT; n = 31), portal vein thrombosis (PVT; n = 24) or hepatic vein thrombosis (HVT n = 10), and 100 age- and sex-matched healthy controls. FV G1691A was found in 14 babies (heterozygous: RVT n = 9, PVT n = 4; homozygous HVT n = 1) and five controls, the MTHFR TT677 genotype together with increased HCY in four infants with thrombosis (RVT n = 2; PVT n = 1; HVT n = 1) compared with one control, and the PT G20210A variant was present in one control only. PC type I deficiency was diagnosed in three patients (RVT n = 2; PVT n = 1) and AT deficiency in two patients (RVT n = 1; PVT n = 1). Three neonates with spontaneous thrombosis showed FV G1691A combined with Lp(a) and the FV G1691A was combined with the PT G20210A genotype in two infants. Additional triggering factors were reported in 27 patients (41.5%). The overall odds ratios (ORs) and 95% confidence intervals (CIs) with respect to the different thrombosis locations were: RVT (OR/CI: 10.9/3.85-31.1; P < 0.0001), PVT (5.47/1.7-17.6; P < 0.0007) and HVT (3.3/0.58-18.7; P = 0.18). The data presented here suggest that genetic prothrombotic risk factors also play an important role in abdominal venous thrombosis during infancy.     

Renal Vein Thrombosis in a Newborn With Abnormal Factor VIII Level: Clinical Case Report

Renal vein thrombosis (RVT) in neonates is a rare condition of low mortality but significant morbidity due to renal impairment.We report the case of a male term newborn with left RVT and elevated serum factor VIII (FVIII).The main symptoms of the patient and the important clinical findings: prompt diagnosis of RVT was possible because the classic clinical presentation of macroscopic hematuria, thrombocytopenia, and palpable flank mass were present in this newborn infant.The main diagnoses: finally, the reason of RVT was established when the infant was 3 months of age: the increased level of FVIII was confirmed. We discuss the diagnosis, therapy, and outcome of the patient and compare with the literature.Therapeutics interventions: however, despite anticoagulant therapy the left kidney developed areas of scarring and then atrophy.Conclusions and outcomes: Prothrombotic defects should be considered in all patients with perinatal RVT. Elevated factor VIII as a reason of RVT in neonatal period is particularly rare. Given a poor renal outcome in children associated with elevated levels of factor VIII, consideration could be given to more aggressive antithrombotic therapy in such cases.     

Renal vein thrombosis: a case report

The presenting symptoms of acute renal vein thrombosis (RVT) can often be confused with those of nephrolithiasis. Delayed diagnosis and treatment of RVT can result in catastrophic complications, including loss of renal function and pulmonary embolism. A high clinical suspicion and early imaging with computed tomography or magnetic resonance imaging will allow early initiation of therapy and prevention of thrombus extension in patients with RVT.     

Antioxidant supplementation attenuates oxidative stress in chronic hepatitis C patients

Reactive oxygen species (ROS) overgeneration is involved in the pathogenesis of hepatitis C. The aim of this study was to evaluate the antioxidant status in the blood of HCV infected patients treated or not with standard therapy before and after supplementation of vitamins E, C and zinc. Biomarkers of oxidative stress were evaluated in the blood of three groups of patients: group 1 - controls; group 2 - HCV patients without treatment examined before and after a daily antioxidant supplementation (vitamin E 800 mg, C 500 mg and zinc 40 mg) for 6 months; and group 3 - HCV patients treated with pegylated interferon combined with ribavirin, also examined before and after the same antioxidant supplementation. Before antiviral treatment HCV patients showed enhanced superoxide dismutase, catalase and glutathione peroxidase activities and decreased glutathione reductase activity, while lipoperoxidation was increased and reduced glutathione showed decreased levels compared to controls. Treatment with standard therapy enhanced the activities of catalase and glutathione S-transferase, increased contents of protein carbonyl and promoted further reduced glutathione depletion. After antioxidant supplementation, decreased catalase and glutathione S-transferase activities, decreased lipoperoxidation in group 2, and increased reduced glutathione contents in both supplemented groups were detected. Before antioxidant supplementation, alanine aminotransferase and gamma glutamyl transferase contents showed significant increases in group 2. CONCLUSION: Untreated HCV patients and also those treated with the standard therapy are coping with a systemic oxidative stress. The antioxidant supplementation conferred an antioxidant protection to both supplemented groups attenuating oxidation processes related to the disease.     

Undefined hypercoaguable state associated with massive right ventricular thrombus and embolism in a previously healthy 17-year-old male

A right ventricular thrombus (RVT) is an unusual finding on echocardiography. We describe a healthy young male patient who developed RVT with subsequent pulmonary embolism (PE), the etiology of which remains uncertain.     

Antioxidant therapy for chronic hepatitis C after failure of interferon: Results of phase Ⅱ randomized, double-blind placebo controlled clinical trial

AIM: To assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus (HCV) infection. METHODS: One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo, or oral treatment alone. Primary end points were liver enzymes, HCV-RNA levels and histology. RESULTS: Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo (P = 0.05). Histology activity index (HAI) score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo (P = 0.21). HCV-RNA levels decreased by 1-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo (P = NS). In part Ⅱ of the trial, oral administration of antioxidants was not associated with significant alterations in any of the end points. CONCLUSION: Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients.     

Antioxidant therapy for chronic hepatitis C after failure of interferon： Results of phase Ⅱ randomized,double-blind placebo controlled clinical trial

AIM： TO assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus （HCV） infection.
METHODS： One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo, or oral treatment alone, Primary end points were liver enzymes, HCV-RNA levels and histology.
RESULTS： Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo （P = 0.05）. Histology activity index （HAI） score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo （P = 0.21）. HCV-RNA levels decreased by l-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo （P = NS）. In part 11 of the trial, oral administration of antioxidants was not associated with significant alterations in any of the end points.
CONCLUSION： Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients.     

Catheter‐directed therapy for acute renal vein thrombosis in systemic lupus erythematosus: A case report

We report our experience using catheter‐directed thrombectomy/thrombolysis (CDT) to treat a patient with acute renal vein thrombosis (RVT) associated with systemic lupus erythematosus (SLE). A 34‐year‐old woman presented with persistent left flank pain, and a renal ultrasonography examination revealed an enlarged left kidney. Contrast‐enhanced computed tomography confirmed the presence of acute left RVT. Because medical treatment failed to relieve her pain and the renal function was deteriorating, we attempted to salvage the occluded left renal vein using an endovascular approach. The pain was completely relieved after a CDT and an overnight urokinase infusion. A follow‐up computed tomography examination revealed the complete resolution of the thrombus. The creatinine level returned to normal (1.7–0.4 mg/dL), along with contrast enhancement in the left kidney, and this suggested the preservation of renal function. To our knowledge, this is the first report utilizing CDT to treat SLE‐associated RVT. When the renal function is deteriorating, CDT is worth considering for RVT if conventional medical treatment has failed. © 2016 Wiley Periodicals, Inc.     

Acute kidney injury as the first sign of spontaneous renal vein thrombosis: report of 2 cases

Spontaneous renal vein thrombosis (RVT) is very rare in the absence of nephrotic syndrome. It is more common in newborns and infants. RVT should always be included in the differential diagnosis of flank pain and hematuria, and because RVT can induce acute renal injury. A 19-year-old man was admitted to our hospital because he complained of right flank pain and oliguria for 3 days. Another patient, a 24-year-old man, complained of a severe and sudden onset of bilateral flank pain and anuria for a day. They were both healthy before they developed the described symptoms and had different levels of decrease in renal function when they visited the hospital. Color Doppler ultrasonography revealed RVT in both the patients. The patients received therapy, including anticoagulation and thrombolysis, following their diagnoses, and they recovered in a few days.