Protective effects of antioxidant medications on limb ischemia reperfusion injury

BACKGROUND: N-acetylcysteine, beta-glucan, and coenzyme Q(10) were shown to have antioxidant and anti-inflammatory effects on reperfusion injury. The aim of our study was to determine and evaluate the effects of these agents on ischemia reperfusion injury of limb. MATERIAL AND METHOD: Forty-four New Zealand white rabbits, all female, weighing between 2.3 to 4.2 (mean 3.8) kg, were used in the study. Four study groups were arranged of 11 animals each, by randomization. The first group was the control group (Group C), the other groups were the Group Q, which was medicated with coenzyme Q10, the Group betaG, which was medicated with beta-glucan, and the Group N, medicated with N-acetylcysteine. After baseline measurements, for the ischemia-reperfusion experiments, common iliac artery was clamped and collateral flow was occluded by a rubber arterial tourniquet wrapped around the thigh at the proximal third of the leg. After 60 min of transient ischemic period, the limb was perfused for 180 min. After perfusion, biopsy was taken from the adductor magnus muscle. Second blood sampling was done after reperfusion period. Blood and tissue analysis were done and evaluated statistically. RESULTS: Baseline and post-reperfusion levels of glutathione peroxidase (GPx), super oxide dismutase (SOD), malonyldialdehyde (MDA), and nitric oxide (NO) changed significantly. While MDA levels increased in the control group, it decreased in the other study groups. The increase in GPx and SOD levels were significant in all groups except the control group. Levels of NO were found to have decreased in the control group, whereas it had increased in the other groups. CONCLUSION: Antioxidant medication may help lowering limb ischemia reperfusion injury. All mentioned medications in our study are shown to be able to have an effective role for preventing ischemia reperfusion injury to some extent through their antioxidant properties.     

Assessment of atrial conduction time by tissue Doppler echocardiography and P-wave dispersion in patients with mitral annulus calcification

The aim of our study was to investigate atrial conduction time in patients with mitral annulus calcification (MAC) using P-wave dispersion (PWD) and electromechanical coupling measured with the surface electrocardiogram and the tissue Doppler echocardiography. Fifty-nine patients with MAC and 43 control subjects underwent resting the surface electrocardiogram and tissue Doppler echocardiography. The difference between the maximum (Pmax) and minimum P-wave durations was calculated and defined as PWD. Interatrial and intraatrial electromechanical delays were measured with tissue Doppler echocardiography. Both Pmax and PWD were higher in patients with MAC compared with controls (111.4 ± 15.8 vs 97.3 ± 18.8 milliseconds; P < .0001 and 46.4 ± 14.6 vs 31.4 ± 13.1 milliseconds; P < .0001, respectively). Both interatrial and intraatrial conduction time were also delayed in patients with MAC compared with controls (29.8 ± 13.3 vs 17.6 ± 12.5 milliseconds; P < .0001; 9.4 ± 5.1 vs 6.8 ± 4.0 milliseconds; P < .008, respectively). Left atrial (LA) diameter was significantly higher in patients with MAC compared with controls (35.4 ± 5.0 mm vs 32.3 ± 4.2 mm; P < .001). The LA diameter correlated significantly with both interatrial conduction times and PWD (r = 0.56; P < .0001 and r = 0.47; P < .0001, respectively). There is a delay in both intraatrial and interatrial electromechanical coupling intervals in patients with MAC.     

Long-term effect of varicocele repair on intratesticular arterial resistance index

PURPOSE: To investigate the long-term effect of varicocele repair on ipsilateral intratesticular arterial resistance index (RI) using color Doppler sonography (CDS). METHODS: A total of 26 infertile patients with left varicocele who underwent a testicular artery and lymphatic-sparing subinguinal varicocelectomy were examined with CDS for intratesticular flow parameters before and at least 6 months after surgery. We also evaluated preoperative and postoperative semen parameters. RESULTS: The mean values of RI, end-diastolic velocity and pulsatility index decreased significantly after surgery, whereas no significant change was observed in peak systolic velocity. Repair of the varicocele resulted in a statistically significant increase in the total sperm count, motility, morphology, and total motile sperm count. However, no significant correlation was found between sperm parameters and RI values (p > 0.05). CONCLUSIONS: Our data show that a significant improvement occurs in testicular blood supply and sperm parameters after surgical varicocele repair, without significant correlation between these 2 changes.     

Effects of diffuse fatty infiltration of the liver on portal vein flow hemodynamics

PURPOSE: To investigate the effects of various degrees of diffuse fatty infiltration of the liver on portal vein blood flow with Doppler sonography. METHODS: One hundred forty subjects were examined with color and spectral Doppler sonography. The subjects were divided into 4 groups of 35 subjects each according to the degree (normal, grade 1, grade 2 and grade 3) of hepatic fatty infiltration assessed on gray-scale images. The portal vein pulsatility index (VPI) and time-averaged mean flow velocity (MFV) were calculated for each subject. VPI was calculated as (peak maximum velocity - peak minimum velocity) / peak maximum velocity. RESULTS: VPI and MFV values were, respectively, 0.32 +/- 0.06 and 16.8 +/- 2.6 cm/second in the normal group, 0.27 +/- 0.07 and 14.2 +/- 2.2 cm/second in the group with grade 1 fatty infiltration, 0.22 +/- 0.06 and 12.2 +/- 1.8 cm/second in the group with grade 2 fatty infiltration, and 0.18 +/- 0.04 and 10.8 +/- 1.5 cm/second in the group with grade 3 fatty infiltration. There was a negative inverse correlation between the grade of fatty infiltration and both VPI (f = 55.3, p < 0.001) and MFV (f = 43.9, p < 0.001). CONCLUSION: The pulsatility index and mean velocity of the portal vein blood flow decrease as the severity of fatty infiltration increases.     

Clinical course of hepatitis C virus infection in renal transplant recipients

Patients with end-stage renal disease are at high risk for exposure to hepatitis C virus (HCV) infection. Although both viral replication and liver disease progression are accelerated after renal transplantation, the long-term impact of chronic HCV infection is unclear. Our aim was to analyze the course of HCV infection in renal transplant recipients and the effects of HCV reactivation on patient and graft survival. METHODS: We retrospectively examined the 21-year (1985-2006) data of 1274 renal transplant recipients, 43 of whom were anti-HCV positive at the time of transplantation. RESULTS: The mean posttransplant follow-up of 43 patients was 62.0 +/- 7.3 months. At the time of transplantation, HCV RNA was positive in 11 (25.6%) patients and negative in 32 (74.4%) patients. HCV reactivation was seen in 19 (45.2%) patients at a mean time of 20.8 +/- 5.7 months. In 31 (72%) patients, acute rejection occurred, whereas graft loss occurred in 10 (23%) patients. Three (7%) patients died. Among 43 patients, 22 (51.2%) were treated with interferon before transplantation. There was a statistically significant association between pretransplant interferon therapy and pretransplant HCVRNA level (P=.024), but no significant association of HCV reactivation and graft rejection, mortality, or kidney survival. CONCLUSION: HCV reactivation occurred in nearly half of the renal transplant recipients, mostly in the second year. Patient survival and graft survival were not affected by HCV reactivation. Anti-HCV positivity should not preclude chronic renal failure patients from renal transplantation.     

The indirect NMDAR antagonist acamprosate induces postischemic neurologic recovery associated with sustained neuroprotection and neuroregeneration

Cerebral ischemia stimulates N-methyl-d-aspartate receptors (NMDARs) resulting in increased calcium concentration and excitotoxicity. Yet, deactivation of NMDAR failed in clinical studies due to poor preclinical study designs or toxicity of NMDAR antagonists. Acamprosate is an indirect NMDAR antagonist used for patients with chronic alcohol dependence. We herein analyzed the therapeutic potential of acamprosate on brain injury, neurologic recovery and their underlying mechanisms. Mice were exposed to cerebral ischemia, treated with intraperitoneal injections of acamprosate or saline (controls), and allowed to survive until 3 months. Acamprosate yielded sustained neuroprotection and increased neurologic recovery when given no later than 12 hours after stroke. The latter was associated with increased postischemic angioneurogenesis, albeit acamprosate did not stimulate angioneurogenesis itself. Rather, increased angioneurogenesis was due to inhibition of calpain-mediated pro-injurious signaling cascades. As such, acamprosate-mediated reduction of calpain activity resulted in decreased degradation of p35, increased abundance of the pro-survival factor STAT6, and reduced N-terminal-Jun-kinase activation. Inhibition of calpain was associated with enhanced stability of the blood–brain barrier, reduction of oxidative stress and cerebral leukocyte infiltration. Taken into account its excellent tolerability, its sustained effects on neurologic recovery, brain tissue survival, and neural remodeling, acamprosate is an intriguing candidate for adjuvant future stroke treatment.     

Uterine preservation and vaginal reconstruction in a patient with congenital vaginal agenesis presenting with cyclic menouria

Herein we report the case of a patient with primary amenorrhea and cyclic menouria. The patient was a 20-year-old woman with primary amenorrhea and inability to achieve sexual intercourse. Clinical examination revealed normally developed labia majora and minora, clitoris, and external urethral orifice, but no vaginal opening. A mature female pubic hair pattern was present, and axillary hair development was normal. Breasts were normally developed. Abdominopelvic magnetic resonance imaging demonstrated a remnant upper vagina and unicornuate uterus filled with fluid, and left-sided renal agenesis. Intraoperatively, a congenital vesicouterine fistulous tract was observed. The fistulous tract was completely resected. Vaginal reconstruction using a sigmoid colon pedicled flap was performed. The proximal part of the neovagina was connected to the remnant cervix, and a Foley catheter was left in the uterine cavity for 7 days to prevent obstruction. The patient has been menstruating regularly since the operation. Menouria might be an early sign of congenital vesicouterine fistula. Resection of the fistulous tract with uterine preservation might be considered in patients with vaginal agenesis.     

Prognostic value of plasma soluble CD40 ligand in patients with chronic non-valvular atrial fibrillation.

AIMS: We aimed to clarify whether determination of levels of soluble CD40 ligand (sCD40L) could predict subsequent thrombo-embolic events in patients with non-valvular atrial fibrillation (NVAF). METHODS AND RESULTS: Forty-four consecutive outpatients (mean age: 58 +/- 6 years, 20 male) with chronic NVAF who were not receiving aspirin and had no thrombus or spontaneous echo contrast (SEC) on left atrium (LA) or left atrial appendage (LAA) were included in the study. The patients had no history of an embolic event and were followed up 24 +/- 2 months for thrombo-embolic events. sCD40L was determined at the enrollment. All patients were evaluated by means of SEC and thrombus formation by transoesophageal echocardiography at the end of follow-up period. Twelve (27%) patients had SEC and 2 (5%) patients had thrombus on LAA. Ischaemic stroke occurred in 2 (4.5%) patients and transient ischaemic attack developed in 4 (9%) patients during follow-up. sCD40L was significantly higher in patients with LASEC (0.41 +/- 0.05 vs. 0.16 +/- 0.04 ng/mL, P = 0.02) and embolic events (0.74 +/- 0.05 vs. 0.19 +/- 0.03 ng/mL, P = 0.001) than in those without. sCD40L levels were significantly related to the LASEC grade (R = 0.377, P = 0.02). In multivariable analysis, while independent variables for SEC or thrombus formation were LA diameter, sCD40L levels, and the duration of AF, independent variables for cerebrovascular events were the existence of SEC or thrombus formation on LAA, and sCD40L level. CONCLUSION: Plasma sCD40L may prospectively predict stroke in AF. sCD40L may provide useful marker to identify patients at high thrombo-embolic risk with NVAF.