Georgios Koliakos

8-Isoprostaglandin F2a and ascorbic acid concentration in the aqueous humour of patients with exfoliation syndrome

Background/aim: The authors investigated the concentrations of 8-isoprostaglandin F2a, a marker of oxidative stress in vivo, and ascorbic acid, a protectant against oxidative damage, in the aqueous humour of patients with exfoliation syndrome (XFS) and cataract and compared the results with those in age matched patients with cataract, but without XFS, to determine whether XFS is associated with increased oxidative stress. Methods: Aqueous humour was aspirated at the beginning of phacoemulsification cataract surgery from 27 eyes of 27 cataract patients with XFS and 27 eyes of 27 age matched cataract patients without XFS. 8-Isoprostaglandin F2aconcentration in the aqueous was determined with a commercial immunoassay; ascorbic acid concentration was measured with a microplate assay method. Results:. The mean concentration of 8-isoprostaglandin F2ain the aqueous from patients with XFS (2429 (SD 2940) pg/ml; range 400–10500 pg/ml) was significantly higher than that measured in the aqueous of age matched control patients (529.1 (226.8) pg/ml; range 325–1000 pg/ml); (p = 0.0028). Furthermore, mean ascorbic acid concentration in XFS patients (0.75 (0.39) mM; range 0.28–1.70 mM) was significantly lower than that found in control patients (1.19 (0.47) mM; range 0.53–2.4 mM); (p = 0.0005). There was a reverse correlation between 8-isoprostaglandin F2aand ascorbic acid concentration. Conclusion: 8-Isoprostaglandin F2awas significantly increased in the aqueous of patients with XFS, and ascorbic acid was decreased, providing evidence of a role for free radical induced oxidative damage in the pathobiology of XFS.

Early Detection of Cardiac Involvement in Systemic Sclerosis Assessed by Tissue-Doppler Echocardiography: Relationship with Neurohormonal Activation and Endothelial Dysfunction

Objective. Cardiopulmonary complications are common in patients with systemic sclerosis (SSc). We assessed cardiac involvement in patients with SSc using echocardiography and investigated the association of N-terminal pro-brain natriuretic peptide (NT-proBNP) and asymmetric dimethylarginine (ADMA) with echocardiographic measures of myocardial function in sera of patients with SSc who had no symptoms of heart failure. Methods. We prospectively studied 52 patients with SSc (mean age 55.7 ± 10.1 yrs, 51 women), with conventional and tissue-Doppler echocardiography. Plasma NT-proBNP and ADMA levels were measured in all patients. Data were compared with those obtained from 25 healthy controls comparable for age and sex. Results. Patients with SSc had impaired left ventricular (LV) and right ventricular diastolic function expressed by inverted ratio of peak early to peak late transmitral (Mit E/A) and transtricuspid velocity and increased left atrial diameter compared with controls. Peak systolic mitral lateral annular motion velocity and peak early diastolic mitral lateral annular motion velocity (LV Em) were lower, while LV E/Em ratio was higher, in patients with SSc compared to controls. ADMA was significantly related with LV Em and E/Em ratio. NT-proBNP was associated with Mit E, Mit E/A ratio and mitral deceleration time. Significant correlation was also observed between NT-proBNP and ADMA levels. Conclusion. Depressed cardiac function is common, even in asymptomatic patients with SSc. NT-proBNP and ADMA are significantly correlated with echocardiographic abnormalities, providing a potent link for cardiac function, neuroendocrine derangement, and endothelial dysfunction in patients with SSc who have cardiac disease.

Hybrid approach of ventricular assist device and autologous bone marrow stem cells implantation in end-stage ischemic heart failure enhances myocardial reperfusion

We challenge the hypothesis of enhanced myocardial reperfusion after implanting a left ventricular assist device together with bone marrow mononuclear stem cells in patients with end-stage ischemic cardiomyopathy. Irreversible myocardial loss observed in ischemic cardiomyopathy leads to progressive cardiac remodelling and dysfunction through a complex neurohormonal cascade. New generation assist devices promote myocardial recovery only in patients with dilated or peripartum cardiomyopathy. In the setting of diffuse myocardial ischemia not amenable to revascularization, native myocardial recovery has not been observed after implantation of an assist device as destination therapy. The hybrid approach of implanting autologous bone marrow stem cells during assist device implantation may eventually improve native cardiac function, which may be associated with a better prognosis eventually ameliorating the need for subsequent heart transplantation. The aforementioned hypothesis has to be tested with well-designed prospective multicentre studies.

Increased growth factor activity in the aqueous humour of patients with exfoliation syndrome

Abstract Background: To investigate the growth factor activity in the aqueous humour of patients with exfoliation syndrome (XFS). Methods: We collected 154 aqueous humour samples (69 from patients with XFS and 85 from age-matched controls) prior to routine extracapsular cataract surgery. Growth factor activity was investigated using a [3H]thymidine incorporation assay on McCoy cells that assesses DNA synthesis. Albumin concentration was measured by a radio-immunoassay as an index of blood aqueous barrier integrity. N-Acetylglucosaminidase (NAG) activity, a marker of cellular breakdown, was ascertained by a fluorometric method. Results: XFS aqueous samples exhibited significantly higher growth factor activity than to the control samples (P<0.001). Albumin concentration was also higher in the XFS group. NAG activity was similar in the two groups. No relationship between growth factor activity and the other parameters investigated was found. Conclusions: Increased growth factor activity was detected in the aqueous humour of patients with XFS. This finding may be re-lated to the pathogenesis of XFS.

Contribution of insulin-like growth factor I to the healing of colonic anastomoses in rats.

The aim of this experimental study was to investigate the contribution of insulin-like growth factor I (IGF)-I in the colonic healing process when injected intraperitoneally after colon resection. Forty male Wistar rats were used. Rats in the control group were injected with 3 mL of a solution of 0.9% NaCl intraperitoneally after the operation and on postoperative day 2, 4, and 6. Rats in the IGF-I group received recombinant human IGF-I in a dose of 2 mg/kg body weight intraperitoneally, immediately after the colonic anastomosis was performed and on postoperative day 2, 4, and 6. All rats were killed on postoperative day 7. The hydroxyproline tissue content was significantly higher in the IGF-1 group than in the control group. The bursting pressures were also significantly higher in IGF-1 group than in the control group. The weight change between the groups differed significantly; in the control group the average weight decreased about 5% postoperatively, while in the IGF-1 group the average weight increased about 6%. The average inflammatory cell infiltration score was significantly higher in the control group. Neoagiogenesis did not differ significantly between the two groups. The fibroblast activity differed significantly between the two groups, as the control group had significantly less fibroblasts compared to the IGF-1 group. In conclusion, IGF-I when given intraperitoneally stimulates the healing of colonic anastomoses in the rats. Further studies are required in order to determine whether this effect is dose related.

The Oxidative Effect of Prolonged CO2 Pneumoperitoneum A Comparative Study in Rats

BACKGROUND The current study evaluated the effect of time in the severity of the oxidative stress due to pneumoperitoneum. METHODS Forty Wistar rats were allocated randomly into 2 groups. The 1 h pneumoperitoneum (Pp) group, which was subjected to 60 min of pneumoperitoneum, and the 3 h Pp, to pneumoperitoneum for 180 min. The animals were divided in half. One half of the rats were left resting for 30 min after abdominal desufflation and the other for 8 h. After these two time periods, blood, liver, kidney, lung and small intestine were obtained for biochemical analysis and histopathological examination. RESULTS In the 3 h Pp, the associated oxidative stress was increased. There was an overt increase in blood and tissue MDA and blood PAB values. The MPO values were significantly higher in the 3 h Pp group in serum, kidneys, and intestine during the early phase of reperfusion and in liver after 8 h of reperfusion. These changes occurred in the presence of light microscopic evidence of greater tissue damage for the 3 h Pp, which were consistent with the fluctuation of the MPO values. CONCLUSION In our experimental model, we proved biochemically and histologically that time of maintenance of pneumoperitoneum is an additive factor that could cause increased oxidative stress in laparoscopic procedures.

Stem cells transplantation combined with long-term mechanical circulatory support enhances myocardial viability in end-stage ischemic cardiomyopathy

End-stage ischemic cardiomyopathy (ICM) with non-graftable coronary arteries is a common and debilitating problem. The ultimate therapeutic goal in such cases is cardiac transplantation which is restricted by donor availability. Alternatively, left ventricular assist devices (LVAD) are increasingly used as bridge to transplantation or more recently as destination therapy in non-transplant candidates. Although encouraging results with LVAD as a bridge to recovery have been reported from the Harefield group in patients with non-ischemic heart failure, myocardial recovery after mechanical circulatory support (MCS) rarely occurs in the severely failing ischemic heart [1]. Ischemic cardiomyopathy has the distinctiveness of irreversible myocardial damage with scar tissue formation and mainly impaired perfusion of the remaining viable myocardium. Widely used secondand third-generation continuous-flow LVAD offer symptomatic relief and prolong life. However, LV unloading rarely improves native heart function in ischemic hearts [2]. Because of this we sought after increasing myocardial viability and improving native cardiac function in a patient with end-stage ICM by injecting autologous bone marrow stem cells (BMSC) at the time of LVAD implantation.

The Effects of Irinotecan on the Healing of Colonic Anastomoses in Rats

Aim: The aim of this experimental study was to investigate the effects of intraperitoneally injected irinotecan on the healing of colonic anastomoses after colon resection. Methods: Thirty male Wistar rats were used. The rats were randomized into two groups of 15 rats each. Immediately after colonic anastomoses were performed, the rats were injected intraperitoneally with either 3 ml of 0.9% NaCl solution or ir- inotecan (3 mg/kg body weight) depending on their group. All rats were sacrificed on the eighth postoperative day. The anastomoses were examined macroscopically and histologically. The anastomotic bursting pressures were recorded. Results: Anastomotic dehiscence was noted in 3 rats of the irinotecan group. All anastomoses of the control group re- mained intact until sacrifice. The adhesion formation at the anastomotic sites and the average inflammatory cell infiltra- tion scores were significantly higher in the irinotecan group compared to the control group. The bursting pressures, the hydroxyproline tissue content, the fibroblast activity and the collagen deposition were significantly lower in the irinotecan group. Neoangiogenesis did not differ significantly between the groups. Conclusion: Irinotecan, when injected intraperitoneally, affects the healing of colonic anastomoses in rats.

Evaluation of intra-articular injection of autologous platelet lysate (PL) in horses with osteoarthritis of the distal interphalangeal joint

ABSTRACT Background: Regenerative medicine has become one of the most promising therapies of equine osteoarthritis. Platelet lysate (PL) is rich in bioactive proteins and growth factors that play a crucial role in tissue healing. Objective: To evaluate the efficacy of intra-articularly injected autologous PL in equine athletes with naturally occurring osteoarthritis. Animals and methods: Fifteen warmblood geldings aged 8–19 years with osteoarthritis of the distal interphalangeal joint were included in this study. They were randomly divided into two groups; 10 horses received intra-articular injections of PL and 5 of normal saline (controls). Before treatment, platelet-derived growth factor (PDGF) levels in basal plasma and prepared PL were estimated. Each joint was injected twice within a three-week period. Lameness was evaluated using the American Association of Equine Practitioners grading system, before treatment and 10 days after each intra-articular injection. Horses were examined fortnightly for one year. Radiographic examination was performed six months post-treatment. The generalized estimating equation test was used for statistical analysis. Results: Acceptable levels of PDGF were detected in PLs (mean ± SD: 258.0 ± 52.3 pg/ml). The majority of horses (9/10) responded positively to PL treatment presenting lower lameness grades (p < 0.0005) compared to controls 10 days after the second injection, and returned to normal athletic activity. Radiographs revealed no changes in osteoarthritis lesions six months after treatment. One year post-injections, however, all horses relapsed to their initial degree of lameness. Conclusion: Intra-articularly injected autologous PL is an efficient method for temporarily managing osteoarthritis of the distal interphalangeal joint in athletic horses.

The C‐terminal Region of HPNAP Activates Neutrophils and Promotes Their Adhesion to Endothelial Cells

Entire Helicobacter Pylori Neutrophil Activated Protein (HPNAP) and its truncated forms NH2‐terminal region HPNAP1–57 and C‐terminal region HPNAP58–144 after cloning into pET29c vector, purification and removal of LPS traces were subjected to human neutrophil activation. Our results revealed that the C‐terminal region of HPNAP is indispensable for human neutrophil stimulation and their further adhesion to endothelial cells – a step necessary to H. pylori inflammation – in a ratio equal to that exhibited by the entire protein.