Monocytic adhesion molecule expression and monocyte-endothelial cell dysfunction are increased in patients with peripheral vascular disease versus patients with abdominal aortic aneurysms

BackgroundStatin therapy is used in the medical management of patients with peripheral vascular disease (PVD) and abdominal aortic aneurysm (AAA) for the pleiotropic and anti-inflammatory benefits. We hypothesize that the inflammatory mechanisms of monocyte–endothelial cell interactions in endothelial barrier dysfunction are more significant in patients with PVD compared with those with AAA. The purpose of this study was to assess patient peripheral blood monocyte adhesion molecules by flow cytometry and monocyte-induced endothelial barrier dysfunction by using an in vitro endothelial cell layer and electric cell-substrate impedance sensing (ECIS) system.MethodsPeripheral blood was collected from patients with either PVD (ankle-brachial index <0.9, toe–arm index <0.8, or required lower extremity vascular intervention) or AAA (aortic diameter >3.0 cm). Monocytes were isolated from fresh whole blood using an accuspin-histopaque technique. The separated monocytes underwent flow cytometry analysis to evaluate the expression levels of the cell membrane adhesion molecules: CD18, CD11a/b/c, and very late antigen-4. Endothelial cell function was assessed by adding monocytes to an endothelial monolayer on ECIS arrays and coculturing overnight. Peak changes in transendothelial electrical resistance were measured and compared between patient groups.ResultsTwenty-eight monocyte samples were analyzed for adhesion molecules (PVD, 19 and AAA, 9) via flow cytometry, and 11 patients were evaluated for endothelial dysfunction (PVD, 7 and AAA, 4) via ECIS. There was no significant difference between risk factors among PVD and AAA patients except for age, where AAA patients were significantly older than PVD patients in both flow cytometry and ECIS groups (P = 0.02 and 0.01, respectively). There were significantly higher levels of adhesion molecules CD11a, CD18, and CD11c (averaged mean fluorescent intensity P values: 0.047, 0.038, and 0.014, respectively) in PVD patients compared with AAA patients. No significant difference was found for CD11b and very late antigen-4 expression (P = 0.21 and 0.15, respectively). There was significantly more monocyte–endothelial cell dysfunction in patients with PVD versus patients with AAA, with a maximal effect seen at 15 h after monocyte addition (P = 0.032).ConclusionsPatients with PVD have increased expression levels of certain monocyte adhesion molecules and greater monocyte-induced endothelial layer dysfunction compared with those with AAA. This may lead to other methods of targeted therapy to improve outcomes of these vascular patients.     

Impact of polyclonal anti-thymocyte globulins on the expression of adhesion and inflammation molecules after ischemia–reperfusion injury

BackgroundPolyclonal anti-thymocyte globulins (ATGs) are immunosuppressive agents used for the treatment and prevention of acute organ rejection after transplantation. ATGs induce apoptosis and complement-mediated cell death in peripheral T-lymphocytes and have shown a reduction of leukocyte adhesion after ischemia–reperfusion (IRI). We analyzed the impact of different ATGs upon the expression of adhesion and inflammation molecules after IRI.Materials and methodsThe major arteries and veins of the extremities of cynomolgus monkeys were surgically isolated and flushed with Ringer's lactate at 4 °C. After 60 min of ischemia the limbs were reperfused with matching human blood. ATGs were added to the blood 30 min prior to the reperfusion, forming four groups: Tecelac-ATG group (n = 16), Fresenius(S)-ATG group (n = 16), Thymoglobulin-ATG group (n = 12) and a control group (n = 16). Biopsies from muscular tissue were obtained after the experiments. The expression of adhesion (ICAM-1, VCAM, PECAM, CD11b, CD62E) and inflammation (IL-1, IL-6, TNF-α) molecules on endothelium, leukocytes, and reperfused tissue was analyzed by means of immunohistochemistry.ResultsThe expression of the studied adhesion molecules (ICAM-1, VCAM, PECAM, CD11b, and CD62E) was significantly increased in the control group when compared with the treated groups. The expression of IL-1, IL-6, and TNF-α was reduced in the ATG-groups in comparison to the control group.DiscussionOur results showed that ATGs caused a reduction of the expression of adhesion and inflammation molecules both in endothelium and reperfused tissue. The inhibition of the expression of molecules required for firm cellular adhesion, may contribute to decreasing cellular graft infiltration after post-ischemic reperfusion.     

A Biological Alternative to Alloplastic Grafts in Dialysis Therapy: Evaluation of an Autologised Bioartificial Haemodialysis Shunt Vessel in a Sheep Model

ObjectivesTo evaluate bioartificial haemodialysis access grafts in a sheep model with respect to patency and morphology.Material and methodsBovine internal thoracic arteries (n = 28) were decellularised. Fourteen grafts (DC grafts) were directly implanted as cervical AV shunts, the remaining were re-seeded with endothelial cells (ECs) derived from blood samples of the later ovine recipient (EC grafts) first. Following simulated punctures and duplex ultrasound scans to determine patency, grafts were explanted for immunohistochemical characterisation after 3 and 6 months, respectively. DC grafts underwent biomechanical testing for compliance (C), suture retention strength (SRT), and burst pressure (BP) before (n = 6) and after (n = 6) implantation.ResultsFollowing 3 and 6 months, the majority of EC (n = 6/6; n = 6/7) and DC grafts (n = 5/6; n = 5/7) were patent and not relevantly stenosed (peak systolic velocity: EC grafts = 76 cm s^?1 ± 4; DC grafts = 77 cm s^?1 ± 5). Simulated haemodialysis punctures revealed significantly shorter bleeding times in all bioartificial grafts than in native jugular veins (P > 0.001). Comparing native carotid arteries with DC grafts prior to and post-implantation, the latter differed significantly with respect to C (P > 0.001; P = 0.005), whereas only pre-implant DC grafts differed regarding BP (P = 0.002); no differences were observed for SRT. Histology revealed complete endothelial surface coverage of EC, but not DC grafts. Furthermore, DC grafts exhibited areas of pronounced tissue calcification.ConclusionThe preclinical development of a bioartificial haemodialysis access graft with promising mechanical and morphological properties in a sheep model is feasible.     

No differences of carotid intima-media thickness between young patients with ankylosing spondylitis and healthy controls

ObjectiveAccelerated atherosclerosis in inflammatory rheumatic diseases such as ankylosing spondylitis (AS) stands out among the leading causes of morbidity and mortality. We assessed the correlation between subclinical carotid atherosclerosis and its related clinical parameters in AS patients.MethodsTwenty-eight patients (23 males, 5 females) with AS and 27 sex- and age-matched controls were consecutively recruited to this study. We estimated the carotid intima–media thickness (IMT) and parameters related to arterial elastic properties, including the distensibility coefficient (DC), stiffness index (β), and incremental elastic modulus (E_inc) using high-resolution ultrasonography. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) were measured using enzyme-linked immunosorbent assay (ELISA).ResultsCarotid IMT values and arterial elastic parameters in AS patients showed no statistical significance compared to those of controls (0.57 ± 0.07 vs 0.55 ± 0.05, p = 0.387 for IMT, 28.45 ± 9.23 vs 31.93 ± 9.52, p = 0.175 for DC, 2.32 ± 0.18 vs 2.29 ± 0.15, p = 0.559 for stiffness index (β), and 0.14 ± 0.05 vs 0.12 ± 0.03, p = 0.116 for E_inc). The serum level of IL-6 in AS patients was significantly different compared with controls (p = 0.001), but not in serum levels of TNF-α and MCP-1 (p = 0.162, p = 0.087, respectively). Carotid IMT and all arterial elastic parameters calculated in this study were not found to be associated with serum levels of TNF-α, IL-6, and MCP-1.ConclusionThis cross-sectional study showed that carotid IMT and parameters related with arterial elastic properties in young AS patients without clinically evident cardiovascular risk factors were not different from those of sex- and age-matched healthy controls. Serum levels of TNF-α, IL-6, and MCP-1 did not reflect the degree of carotid subclinical atherosclerosis. However, these findings should be confirmed further in a larger population.     

Changes of serum Tau, GFAP, TNF-α and malonaldehyde after blast-related traumatic brain injury

Objective： To determine the changes of serum Tau protein, glial fibrillary acidic protein （GFAP）, tumor necrosis factor alpha （TNF-α）, and malonaldehyde （MDA） in rats after blast-related traumatic brain injury （BTBI） and to provide relative information for further studies on BTBI mechanism and seek specific biomarkers for BTBI. Methods： Ninety male Sprague-Dawley rats were randomly assigned into three groups： control group, moderate blast injury group, and severe blast injury group （n=30 for each）. Rats in the moderate and severe blast injury groups were respectively exposed to corresponding levels of BTBI. After explosion, serum levels of Tau, GFAP, TNF-α, and MDA in each group were determined by Elisa assay at different time points after injury （8 h, 24 h, 3 d, and 6 d）. The extent of brain damage was detected by Nissl staining and TUNEL assay. Results： Serum levels of Tau and GFAP rapidly increased and reached the peak at 24 h after either moderate or severe blast injury. All the values were significantly higher than control group at all time points （P〈0.05）. Serum TNF-α level of both injury groups peaked at 8 h after BTBI and stayed significantly higher than control group at all time points （P〈0.05）. Serum MDA of two injury groups began to significantly increase at 3 d and the level stayed significantly higher than control group until 6 d （P〈0.05）. Moreover, unlike the other biomarkers, serum MDA of severe blast injury group was significantly higher than moderate blast injury group at 6 d （P〈0.05）. Conclusion： The changes of serum Tau, GFAP, and TNF-α showed a good sensitivity at the acute phase after BTBI （within 24 h）. However, their specificity and correlation with the extent of injury were limited in this experiment. Moreover, although the change of serum MDA showed a poor sensitivity and specificity to the diagnosis of BTBI during the first few days, it can reflect the injury degree at 6 d after injury. Therefore, further studies are nee     

Low Molecular Weight Heparin Significantly Reduces Embolisation After Carotid Endarterectomy – A Randomised Controlled Trial

ObjectivesThe administration of unfractionated heparin (UFH) prior to carotid clamping during carotid endarterectomy (CEA) transiently increases the platelet aggregation response to arachidonic acid (AA) despite the use of aspirin. We hypothesized that this phenomenon might be reduced by using low molecular weight heparin (LMWH) resulting in fewer emboli in the early post-operative period.Methods183 aspirinated patients undergoing CEA were randomised to 5000 IU UFH (n = 91) or 2500 IU LMWH (dalteparin, n = 92) prior to carotid clamping. End-points were: transcranial Doppler (TCD) measurement of embolisation, effect on bleeding and platelet aggregation to AA and adenosine 5′-diphosphate (ADP).ResultsPatients randomised to UFH had twice the odds of experiencing a higher number of emboli in the first 3 h after CEA, than those randomised to LMWH (p = 0.04). This was not associated with increased bleeding (mean time from flow restoration to operation end: 23 min (UFH) vs. 24 min (LMWH), p = 0.18). Platelet aggregation to AA increased significantly following heparinisation, but was unaffected by heparin type (p = 0.90). The platelets of patients randomised to LMWH exhibited significantly lower aggregation to ADP compared to UFH (p < 0.0001).ConclusionsIntravenous LMWH is associated with a significant reduction in post-operative embolisation without increased bleeding. The higher rate of embolisation seen with UFH may be mediated by increased platelet aggregation to ADP, rather than to AA.     

Inflammatory and growth factor response to continuous and intermittent exercise in youth with cystic fibrosis

BackgroundChildren with cystic fibrosis (CF) tend to suffer from chronic systemic inflammation and may have impaired growth associated with muscle catabolism. Therefore, investigating which type of exercise can elicit an anabolic response with minimal inflammation is of clinical value.MethodsTwelve children with CF (mean ± SD; age: 14.7 ± 2.3 years, predicted FEV₁: 90.0 ± 21.6%) and biological age-matched controls (age: 13.9 ± 2.1 years) completed moderate-intensity, continuous exercise (MICE) and high-intensity, intermittent exercise (HIIE) on separate days. During each exercise, blood was drawn at various time points and analyzed for immune cells, inflammatory cytokines, and growth mediators.ResultsAt rest, children with CF had higher concentrations of neutrophils and IL-6 compared with controls. In children with CF, HIIE did not affect immune cell subsets or cytokines: TNF-α, IL-6, and tumor necrosis factor-like weak inducer of apoptosis (TWEAK). All immune cell subsets and IL-6 increased significantly with MICE in both groups. Growth hormone (GH) increased with both types of exercise, with a greater change from rest during MICE.ConclusionsHIIE was a sufficient stimulus to increase GH in children with CF, without affecting systemic inflammation.     

Protective effect of immunosuppressive treatment before orthotopic kidney autotransplantation

BackgroundIschemia reperfusion injury (IRI) is one of the risk factors for delayed graft function, acute rejection and long term allograft survival after kidney transplantation. IRI is an independent antigen inflammatory process that produces tissue damage. Our objective was to study the impact of immunosuppressive treatment (IS) on IRI applying only one dose of IS before orthotopic kidney autotransplantation.MethodsTwenty-four rats allocated in four groups were studied. One group served as control (G1: autotransplanted rats without IS) and the rest received IS 12 h before kidney autotransplantation (G2: Rapamycin, G3: Mycophenolate mofetil and G4: Tacrolimus).ResultsImproved renal function and systemic inflammatory response were found among IS groups compared to the control group (Delta Urea p < 0.0001; Delta Creatinine p < 0.0001; Delta C3 p < 0.001). The number of apoptotic nuclei in renal medulla in G1 was higher than in IS groups (p < 0.0001). Tubular damage was less severe in IS groups respecting G1 (p < 0.001). C3, TNF-α and IL-6 expression in kidney samples was reduced when IS was used compared to the control group. No differences were observed among the different immunosuppressive drugs tested. However, Heme oxygenase-1(HO-1) was increased only in Rapamycin treatment.ConclusionsThese data suggest that the use of IS administered before transplant attenuates the IRI process after kidney transplantation in an animal model.     

Mast cells activation contribute to small intestinal ischemia reperfusion induced acute lung injury in rats

BackgroundSmall intestinal ischemia-reperfusion (IIR) injury may lead to severe local and remote tissue injury, especially acute lung injury (ALI). Mast cell activation plays an important role in IIR injury. It is unknown whether IIR mediates lung injury via mast cell activation.MethodsAdult SD rats were randomized into sham operated group (S), sole IIR group (IIR) in which rats were subjected to 75 min of superior mesenteric artery occlusion followed by 4 h reperfusion, or IIR being respectively treated with the mast cell stabilizer Cromolyn Sodium (IIR + CS group), with the tryptase antagonist Protamine (IIR + P group), with the histamine receptor antagonist Ketotifen (IIR + K group), or with the mast cell degranulator Compound 48/80 (IIR + CP group). The above agents were, respectively, administrated intravenously 5 min before reperfusion. At the end of experiment, lung tissue was obtained for histologic assessment and assays for protein expressions of tryptase and mast cell protease 7(MCP7). Pulmonary mast cell number and levels of histamine, TNF-α and IL-8 were quantified.ResultsIIR resulted in lung injury evidenced as significant increases in lung histological scores (P < 0.05 IIR vs. S), accompanied with concomitant increases of mast cell counts and elevations in TNF-α and IL-8 concentrations and reductions in histamine levels (all P < 0.05 IIR vs. S). IIR also increased lung tissue tryptase and MCP7 protein expressions (all P < 0.05, IIR vs. S). Cromolyn Sodium, Ketotifen and Protamine significantly reduced whilst Compound 48/80 aggravated IIR mediated ALI and the above biochemical changes (P < 0.05).ConclusionsMast cells activation play a critical role in IIR mediated ALI.     

Clostridial collagenase aggravates the systemic inflammatory response in rats with partial-thickness burns

AimClostridial collagenase A (CCA) has been shown effective in degrading collagen in eschar tissue and promoting healing in partial-thickness burns. As there are also reports of fever, leukocytosis, increased C-reactive protein (CRP) levels and septic complications during treatment with CCA, we aimed to determine in rats whether CCA aggravates the systemic inflammatory response.MethodsRats with partial-thickness burns were randomly divided into groups with either no dressing (ND), povidone-iodine dressing (PID) or CCA dressing (CCAD). Body weights and temperatures, blood leukocyte counts, and serum levels of CRP, interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α), were measured at 0, 3, and 24 h and days 3 and 7 from burn. Wounds were cultured on days 1, 3 and 7 and burn depth was evaluated on day 1.ResultsBody weights for all groups were significantly lower after burn, with highest loss (25.5%) in the CCAD group. At 3 h a significant drop in rectal temperature was noted in all groups. The CCAD group had higher rectal temperature levels than the PID group on days 3 and 7 (p < 0.05). Changes in serum levels of CRP, IL-1β, IL-6 and TNF-α were not significant in the ND and PID groups; the CCAD group showed a significant rise in serum levels of CRP on day 1, of IL-6 on day 3 and of TNF-α on day 7. Wound infection was more common in CCAD group and increased on days 3 and 7, but this was insignificant.ConclusionCCA aggravated the systemic inflammatory response in rats with partial-thickness burns, which is accompanied by a higher risk of infection.     

The effectiveness of hypertonic saline and pentoxifylline (HTS-PTX) resuscitation in haemorrhagic shock and sepsis tissue injury: comparison with LR, HES, and LR-PTX treatments

PurposeTo compare lung and liver injury and laboratory results in haemorrhagic shock and sepsis models treated with combinations of lactated Ringer's solution (LR), 7.5% hypertonic saline (HTS), hydroxyethyl starch (HES), and pentoxifylline (PTX).MethodsMale Sprague-Dawley rats (200–290 g) were assigned randomly to one of four treatment groups (n = 16 per group): (1) LR; (2) HES; (3) LR–PTX; and (4) HTS–PTX. Each group was subdivided into (1) haemorrhagic shock (n = 8) and (2) sepsis (n = 8) model groups. A venous catheter was used to inject resuscitation fluids, and an arterial catheter was used to withdraw blood and monitor mean arterial pressure (MAP). Lung and liver histology, bronchoalveolar lavage (BAL) fluid, and cytokine levels were evaluated.ResultsThe mean lung injury score was 1.7. At 24 h after treatment, the total leucocyte count in the BAL fluid was significantly (p < 0.05) higher with LR treatment (10 × 10⁶ ± 0.8) than with other treatments in the sepsis model groups (HES, 6 × 10⁶ ± 1.2; LR–PTX, 5 × 10⁶ ± 1.5; HTS–PTX, 5 × 10⁶ ± 0.6). The higher total leucocyte count after LR treatment was attributable to a greater increase in the number of neutrophils (17 ± 1.5%) compared with increases after the other treatments (HES, 6 ± 0.8%; LR–PTX, 10 ± 1.3%; HTS–PTX, 5 ± 0.4%). In the sepsis model groups, the total hepatic injury score was also significantly (p < 0.05) higher with LR treatment (9.9 ± 0.5) than with the other treatments (HES, 6.7 ± 0.8; LR–PTX, 5.6 ± 0.7; HTS–PTX, 3.1 ± 0.9). This also occurred in the shock model (LR, 10.6 ± 2.1; HES, 5.8 ± 0.9; LR–PTX, 7.3 ± 0.9; HTS–PTX, 3.5 ± 0.9). As compared with LR treatment, HTS–PTX resuscitation resulted in a 49% decrease in TNF-α, 29% decrease in IL-1β, and 58% decrease in IL-6 in the shock model at 24 h (p < 0.05), and the respective decreases were 45, 24, and 35% in the sepsis model (p < 0.05).ConclusionHTS–PTX was superior to HES, LR–PTX, and LR for treating shock and sepsis, and LR–PTX and HES gave better results than LR therapy alone.     

TGF beta1 polymorphisms are candidate predictors of the clinical response to rituximab in rheumatoid arthritis

ObjectiveTo evaluate the association between several candidate single-nucleotide polymorphisms (SNPs) and responsiveness to rituximab in patients with rheumatoid arthritis (RA).MethodsSixty-three RA patients were included. Nine genes (13 SNPs) were subsequently analyzed, including those coding for cytokines involved in synovitis (IL10, LTA, TGFβ1, TNF-α, TNF receptor II) and genes associated with RA susceptibility (-C5 TRAF1, STAT4, TNFAIP3 and PTPN22).ResultsForty-four patients were defined as responders and 19 as nonresponders. TGFβ1 Codon 10 and TGFβ1 Codon 25 SNPs were both associated with clinical response (probability to respond to treatment with the Codon 10 C/T genotype: OR = 1.6; P = 0.002, and with the Codon 25 G/C genotype: OR = 1.6; P = 0.025). The probability to be a responder when the TGFβ Codon10 C/T and TGFβ Codon 25 G/C genotypes were co-inherited, doubled (OR = 2.6; P = 0.008).ConclusionThe TGFβ1 SNPs are associated with a good response to rituximab therapy and as such could be useful genetic biomarkers in predicting therapy outcome.     

25 mg etanercept once weekly in rheumatoid arthritis and spondylarthropathy

ObjectiveTo assess the clinical results at 6 months of etanercept 25 mg once weekly (half-dose), and etanercept 25 mg twice weekly (full-dose), in patients with rheumatoid arthritis or spondylarthropathy.MethodsCase records of all patients treated by etanercept for at least 6 months in the same rheumatoloy unit were retrospectively studied, to assess the mean values of DAS-28 and BASDAI, just before (J0), and after 6 months (M6) of treatment, in patients with rheumatoid arthritis or spondylarthropathy treated with etanercept 25 mg given either once or twice weekly.Results112 patients had been treated for at least 6 months (44 at half-dose, and 68 at full-dose). Values of DAS-28 or BASDAI both at J0 and M6 were available in 92 patients. DAS-28 dramatically improved both in the half-dose group (from 5.2 ± 0.8 to 3.5 ± 0.8) and in the full-dose group (from 5.5 ± 1.0 to 4.1 ± 1.0). BASDAI also strikingly improved both in the half-dose group (from 60 ± 13 to 25 ± 18), and in the full-dose group (from 58 ± 15 to 37 ± 23).ConclusionAlthough this was not a double-blind, prospective, randomised study, the strong improvement noticed in the half-dose group suggests that etanercept 25 mg once a week can induce major clinical and biological relief in some patients with RA or spondylarthropathy.     

Plasma levels of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) in familial Mediterranean fever

AimsTo assess the levels of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) in patients with familial Mediterranean fever (FMF).MethodsPlasma levels of sVEGFR-1 were investigated in 33 FMF patients in an attack-free period (mean age 30.8 years; males/females 10/23), in 15 patients with acute FMF attack (mean age 32.7 years; males/females 7/8), and 19 healthy controls (mean age 32 years; males/females 11/8). Levels of sVEGFR-1 were also compared among patients who were receiving colchicine and those who were not.ResultsPlasma sVEGFR-1 levels were 3.49 ± 1.10, 3.53 ± 1.02, and 0.37 ± 0.28 ng/ml for FMF patients in the attack-free period, FMF patients with acute attack, and healthy controls, respectively. Plasma sVEGFR-1 levels were significantly higher in FMF patients with and without acute attack compared to the control group (p < 0.05). sVEGFR-1 levels were not statistically significant between patients with acute attack and attack-free FMF patients (p > 0.05). The plasma levels of sVEGFR-1 were also comparable in colchicine treated and untreated patients.ConclusionOur data suggest that sVEGFR-1 may have a role in the ongoing inflammatory cascade in FMF.     

Linking systemic angiogenic factors (VEGF,angiogenin, TIMP-2) and Doppler ultrasound to anti-inflammatory treatment in rheumatoid arthritis

ObjectiveTo evaluate an association between synovial Doppler flow and serum levels of vascular endothelial growth factor (VEGF), angiogenin and TIMP-2 in patients with rheumatoid arthritis during anti-inflammatory treatment with glucocorticoids and TNF-α inhibitors.MethodsInflamed wrists of 15 patients with rheumatoid arthritis (RA) were examined by two independent ultrasound investigators prior to and at days 3, 7, 14 and 42 after the initiation of treatment with glucocorticoids in therapy-naïve patients or after the beginning of a therapy with a TNF-α inhibitor in patients with DMARD failure. Quantitative three-dimensional power Doppler ultrasonographic assessment of synovial vascularization was compared at each visit with serum levels of VEGF, angiogenin and TIMP-2.ResultsIn the glucocorticoid group, synovial Doppler signals decreased significantly at day 3 (?44%; P = 0.003) in comparison to a delayed decrease in the TNF-α inhibitor group after 6 weeks (?46%; P = 0.001). A significant reduction of serum VEGF levels could be determined with a delay of 1 week after the decrease of Doppler activity but no correlation was found between both parameters (rho: P = 0.7; r = ?0.03). Angiogenin concentrations decreased in the TNF group and increased in the GC group. Levels of TIMP-2 did not change significantly in both groups.ConclusionThe decrease of serum VEGF levels under treatment with glucocorticoids or TNF-α inhibitors followed the reduction of the intra-articular synovial Doppler flow. This result supports the idea that the reduction of synovial perfusion due to anti-inflammatory treatment is not regulated by systemic VEGF, but that the inflamed joints are the source for circulating VEGF.     

Perioperative anaesthetic management of high-order repeat caesarean section: audit of practice in a university-affiliated medical centre

BackgroundHigh-order (five or more) repeat caesarean sections (HORCS) are associated with increased rates of placenta praevia, placenta accreta and peripartum hysterectomy and prolonged surgical time secondary to intra-abdominal adhesions. This study summarizes our experience in the anaesthetic management of HORCS.MethodsThe files of all parturients undergoing HORCS between January 1995 and August 2007 were reviewed to determine surgical times, rates and causes of conversion from neuraxial to general anaesthesia and the need to supplement neuraxial anaesthesia with intravenous sedation.ResultsParturients (n = 108) were 35 ± 4.5 years old with a gestational age of 37.5 ± 1.5 weeks, weighed 88 ± 20 kg and had undergone 6 ± 1 caesarean sections. Eighty-six (80%) were elective. Initial anaesthetic techniques included spinal (n = 80, 74%), epidural (n = 9, 8%), combined spinal-epidural (n = 6, 6%) and general anaesthesia (n = 13, 12%). Surgery lasted 38 ± 19 min (median 34, range 9-120). Fourteen parturients (13%) underwent intraoperative manipulations other than caesarean section, including three hysterectomies for haemorrhage (two placenta accreta, one praevia). There were no ruptures or dehiscences of the uterine scar, intraoperative bladder/ bowel injuries or re-explorations. Apgar scores <9 at 1 (n = 9, 13%) and 5 (n = 6, 5%) min were related to non-anaesthetic causes. Anaesthesia was converted from neuraxial to general in five cases (5/95, 5%) but only two were due to haemorrhage. No epidural top-up doses or intravenous sedatives/analgesics were required for spinal anaesthesia.ConclusionHORCS is not necessarily an indication for general anaesthesia provided uterine and placental abnormalities are sought preoperatively. In our practice single-shot spinal anaesthesia sufficed for uncomplicated HORCS.     

Evaluation of magnetic resonance imaging and clinical outcome after tissue-engineered cartilage implantation: prospective 6-year follow-up study

BackgroundAutologous chondrocyte implantation (ACI) is an important procedure when repairing cartilage defects of the knee. We previously reported several basic studies on tissue-engineered cartilage, and conducted a multicenter clinical study in 2009. In this clinical study, we evaluated the patients' clinical scores and MRI findings before and after tissue-engineered cartilage implantation, and compared the data obtained at 1 year and approximately 6 years post-implantation.MethodsFourteen patients who underwent implantation of tissue-engineered cartilage to repair cartilage defects of the knee were evaluated. Tissue-engineered cartilage was produced by culturing autologous chondrocytes three dimensionally in atelocollagen gel. The patients were evaluated clinically using the Lysholm score, and the original knee-function score at pre-implantation and at 1 year and approximately 6 years post-implantation. MRI scans were obtained at the same observation periods. A modified magnetic resonance observation of cartilage repair tissue (MOCART) system was used to quantify clinical efficacy based on the MRI findings.ResultsIn approximately 6 years of follow-up, none of the 14 patients reported any subjective symptoms of concern. The mean Lysholm score and the original knee-function score (63.0 ± 10.1, 59.9 ± 5.7) significantly improved at 1 year after implantation (86.4 ± 11.8, 94.1 ± 9.2), and were maintained until 6 years after implantation (89.8 ± 6.2, 89.9 ± 11.2), although some patients showed deterioration of Lysholm and original knee scores between 1 year post-implantation and the final follow-up. The mean MOCART score was 13.2 ± 12.0 pre-implantation, and 62.5 ± 24.7 at 1 year and 70.7 ± 22.7 at approximately 6 years post-implantation. The MOCART scores at 1 year and 6 years were significantly higher than the pre-implantation score, but there was no significant difference between the scores at 1 and 6 years, indicating that the MRI results at 1 year after implantation were maintained for the next 5 years.ConclusionsThe clinical scores and MRI findings after implantation of tissue-engineered cartilage were improved at 1 year after implantation and were maintained until 6 years after implantation.     

Influence of acute ethanol intoxication on neuronal apoptosis and Bcl-2 protein expression after severe traumatic brain injury in rats

To study the influence and mechanism of acute ethanol intoxication (AEI) on rat neuronal apoptosis after severe traumatic brain injury (TBI).Methods:Ninety-six Sprague-Dawley rats were randomly divided...