George Koliakos

Serum Ghrelin, Leptin and Adiponectin Levels before and after Weight Loss: Comparison of Three Methods of Treatment – A Prospective Study

Background: Ghrelin is a peptide hormone with orexigenic properties, primarily produced by the stomach. Leptin and adiponectin are the two adiposity products that participate in body weight control. Leptin always decreases and adiponectin increases after weight loss. Different changes in fasting ghrelin levels have been reported following bariatric surgery. In this study, we compare the changes in fasting ghrelin, leptin and adiponectin levels in 3 groups of patients who achieved weight loss by either diet, MacLean vertical banded gastroplasty (VBG) or biliopancreatic diversion with duodenal switch (BPD-DS). Methods: Serum fasting ghrelin, leptin and adiponectin concentration was measured in 40 obese patients who achieved weight loss by either diet (n=14), VBG (n=13) or BPD-DS (n=13), before and after weight loss. The follow-up period was 18 months for BPD-DS and VBG and 6 months for diet. Serum ghrelin level was measured by ELISA. Results: BMI was significantly decreased in all 3 groups: 9.2±2.4% (P<0.01) following diet, 38.47±7.26% (P<0.01) after VBG, and 42.88±9.09% after BPD-DS (P<0.01). Serum fasting ghrelin level increased after diet (110.45±117.84%, P=0.002) and VBG (65.48±92.93%, P=0.001),but decreased after BPD-DS (−21.63±28.63%, P=0.019). Leptin concentration decreased and adiponectin increased in all groups. Conclusions: Unlike after diet or gastric restrictive surgery, BPD-DS is associated with markedly suppressed ghrelin levels, possibly contributing to the weight-reducing effect of this operation. Sleeve gastrectomy seems to be the main cause of this reduction.

A prospective, non-randomized, no placebo-controlled, phase Ib clinical trial to study the safety of the adipose derived stromal cells-stromal vascular fraction in idiopathic pulmonary fibrosis

IntroductionRegenerative medicine and particular adult stem cells represent an alternative option with several fruitful therapeutic applications in patients suffering from chronic lung diseases including idiopathic pulmonary fibrosis (IPF). Nevertheless, lack of knowledge regarding the origin and the potential of mesenchymal stem cells (MSCs) to differentiate into fibroblasts has limited their use for the treatment of this dismal disease.Patients and methodsTo this end, we conducted a phase Ib, non-randomized, clinical trial to study the safety of three endobronchial infusions of autologous adipose derived stromal cells (ADSCs)-stromal vascular fraction (SVF) (0.5 million cells per kgr of body weight per infusion) in patients with IPF (n=14) of mild to moderate disease severity (forced vital capacity –FVC>50% predicted value and diffusion lung capacity for carbon monoxide-DLCO>35% of predicted value). Our primary end-point was incidence of treatment emergent adverse events within 12 months. Alterations of functional, exercise capacity and quality of life parameters at serial time points (baseline, 6 and 12 months after first infusion) were exploratory secondary end-points.ResultsNo cases of serious or clinically meaningful adverse events including short-term infusional toxicities as well as long-term ectopic tissue formation were recorded in all patients. Detailed safety monitoring through several time-points indicated that cell-treated patients did not deteriorate in both functional parameters and indicators of quality of life.ConclusionsThe clinical trial met its primary objective demonstrating an acceptable safety profile of endobronchially administered autologous ADSCs-SVF. Our findings accelerate the rapidly expanded scientific knowledge and indicate a way towards future efficacy trials.

Prooxidant-antioxidant balance as a new risk factor in patients with angiographically defined coronary artery disease.

OBJECTIVES Determination of the prooxidant-antioxidant balance (PAB) in patients with angiographically defined coronary artery disease (CAD+) by a modified PAB assay and presentation of PAB value as a novel cardiovascular risk factor. DESIGN AND METHODS For 61 patients with CAD+ and 63 healthy volunteers, the PAB were measured and its correlation was determined with anthropological and clinical parameters. RESULTS A significant increase of the PAB value was observed in patients in comparison to control group. A correlation, which is not quite significant, was noted between angiographic finding (number of diseased vessel) and the PAB values in patients. A significant positive correlation was established between the PAB value and systolic blood pressure, diastolic blood pressure, smoking, fasting blood sugar and serum urea concentration; and a significant negative correlation was established between PAB value and serum creatinine and bilirubin. CONCLUSIONS This study shows that the PAB value may be considered as a cardiovascular risk factor. Further clinical research is needed to substantiate the potency of the PAB value as a cardiovascular risk factor.

The Effect of Biliopancreatic Diversion with Pylorus-Preserving Sleeve Gastrectomy and Duodenal Switch on Fasting Serum Ghrelin, Leptin and Adiponectin Levels: Is there a Hormonal Contribution to the Weight-Reducing Effect of this Procedure?

Background: Ghrelin is a peptide hormone with orexigenic properties, primarily produced by the stomach. Different changes in fasting ghrelin levels have been reported following bariatric surgery. In this study, we investigate the hypothesis that because ghrelin is mainly produced by the fundus of the stomach, biliopancreatic diversion with sleeve gastrectomy with total resection of the gastric fundus and duodenal switch (BPD-DS) will cause substantial decrease in circulating ghrelin levels. Methods: Serum fasting ghrelin, leptin and adiponectin concentrations were measured by ELISA in 13 patients with morbid obesity who achieved weight loss by BPD-DS, before the operation and 18 months after. Results: After BPD-DS, BMI decreased significantly, from 59.15±15.82 kg/m2 to 32.91±6.46 kg/m2 (P=0.001). Serum fasting ghrelin level decreased from 1.44±0.77 ng/ml to 0.99±0.35 ng/ml (P=0.019). Serum leptin level decreased from 1.81±0.38 ng/ml to 1.65±0.32 ng/ml, (P=0.196), and adiponectin level increased from 37.85±11.24 μg/ml to 39.84±16.27 μg/ml (P=0.422). Conclusions: BPD-DS is associated with markedly suppressed ghrelin levels, possibly contributing to the longlasting weight-reducing effect of the procedure. Leptin levels decreased and adiponectin increased, as expected, after weight loss. Sleeve gastrectomy with resection of the gastric fundus seems to be the main cause of the postoperative reduction in ghrelin levels.

Fibrinogen β-Chain Tyrosine Nitration Is a Prothrombotic Risk Factor

Elevated levels of circulating fibrinogen are associated with an increased risk of atherothrombotic diseases although a causative correlation between high levels of fibrinogen and cardiovascular complications has not been established. We hypothesized that a potential mechanism for an increased prothrombotic state is the post-translational modification of fibrinogen by tyrosine nitration. Mass spectrometry identified tyrosine residues 292 and 422 at the carboxyl terminus of the β-chain as the principal sites of fibrinogen nitration in vivo. Immunoelectron microscopy confirmed the incorporation of nitrated fibrinogen molecules in fibrin fibers. The nitration of fibrinogen in vivo resulted in four distinct functional consequences: increased initial velocity of fibrin clot formation, altered fibrin clot architecture, increased fibrin clot stiffness, and reduced rate of clot lysis. The rate of fibrin clot formation and clot architecture was restored upon depletion of the tyrosine-nitrated fibrinogen molecules. An enhanced response to the knob “B” mimetic peptides Gly-His-Arg-Proam and Ala-His-Arg-Proam suggests that incorporation of nitrated fibrinogen molecules accelerates fibrin lateral aggregation. The data provide a novel biochemical risk factor that could explain epidemiological associations of oxidative stress and inflammation with thrombotic complications.

Ascorbic acid concentration is reduced in the aqueous humor of patients with exfoliation syndrome

PURPOSE To investigate whether there is a role for ascorbic acid in the development of exfoliation syndrome (XFS). DESIGN A case-control study was undertaken that included consecutive patients with and without XFS in whom cataract surgery was indicated. Patients with ophthalmic conditions other than XFS and conditions that may influence ascorbic acid levels were excluded. METHODS A prospective institutional study was undertaken. A small volume of aqueous humor was aspirated at the beginning of phacoemulsification cataract surgery. Eighty aqueous samples, 40 samples from 40 eyes of 40 cataract patients with XFS and 40 samples from 40 eyes of 40 age matched cataract patients without XFS, were collected and analyzed. Ascorbic acid concentration was evaluated in the aqueous samples with a microplate assay method. RESULTS The mean +/- SD concentration of ascorbic acid in the aqueous from patients with XFS (0.86 +/- 0.43 mM; range, 0.12 to 1.7 mM) was significantly lower than the concentration of ascorbic acid found in the aqueous of age-matched control patients (1.15 +/- 0.50 mM; range 0.42 to 3.1 mM; P =.0068). Total mean protein concentration was found to be significantly higher in the XFS group (481.1 +/- 196.8 pg/dl versus 336.3 +/- 86.4 pg/dl in the controls; P <.0001). Nevertheless, no correlation could be established between ascorbic level and protein concentration. CONCLUSIONS A significantly reduced mean level of ascorbic acid was observed in the aqueous humor of patients with XFS. In view of the fact that ascorbic acid is a major protective factor against free radical action, a role for free radical action is possible in the pathobiology of XFS.

Endothelin-1 concentration is increased in the aqueous humour of patients with exfoliation syndrome.

Background/aim: Endothelin 1 (ET-1) is considered the most potent vasoconstrictor in the body and the eye. This molecule may play a significant role in the pathobiology of exfoliation syndrome (XFS), a disorder characterised by a progressive iris vasculopathy. The purpose of this study was to investigate the concentration of ET-1 in the aqueous humour of cataract patients with and without XFS. Methods: Aqueous humour samples were obtained from 25 consecutive eyes of 25 cataract patients with XFS and an equal number of age matched controls during phacoemulsification cataract surgery. None of the subjects had elevated intraocular pressure or glaucoma. ET-1 concentration in the aqueous was measured using a specific immunoassay with 100% immunoreactivity for ET-1. Total aqueous humour protein concentration was measured with a microplate Coomassie blue based method and was correlated with ET-1 concentration. Results: Mean ET-1 concentration in the XFS aqueous samples (4.6 (SD 2.3) pg/ml) was significantly higher than that measured in the age matched control samples (2.8 (SD 1.71) pg/ml); (p = 0.006). Although total protein concentration was significantly elevated in the XFS samples (0.380 (SD 0.159) v 0.279 (SD 0.144) mg/ml in the controls); (p = 0.023), no correlation was found between aqueous ET-1 and total protein concentration (p = 0.730). Conclusion: The increased concentration of ET-1 in the aqueous humour of XFS patients suggests that ET-1 may play a role in the pathobiology of XFS.

Isolation of mesenchymal stem cells using the total length of umbilical cord for transplantation purposes

Background: Umbilical cord (UC) mesenchymal cells have the ability to differentiate into various cell types, which make them an easily obtainable source for therapeutic uses. Different approaches have been used to isolate mesenchymal stem cells (MSC).

N-Terminal Pro-Brain Natriuretic Peptide Levels Are Elevated in Patients with Acute Ischemic Stroke

Brain natriuretic peptide (BNP) is a counterregulatory hormone released by the ventricles of the heart. Its main actions are natriuresis and vasodilation. The authors studied N-terminal pro-brain natriuretic peptide (NT-proBNP) levels soon after an acute ischemic stroke. They compared plasma NT-proBNP concentrations in 30 patients with an acute ischemic stroke with those of 30 controls. The 2 groups were adjusted for age and gender, and there were no significant differences in vascular risk factors and left ventricular systolic and diastolic function. Venous samples were collected within the first 11.8 ±1.2 hours after the onset of symptoms and again on day 6. Brain computed tomography/magnetic resonance imaging (CT/MRI) was performed on the same days (day 0 and day 6) in order to assess the site (carotid or vertebrobasilar), cause (atherothrombotic, cardioembolic, or lacunar), and size (large, medium, or small) of the brain infarct. NT-proBNP levels were elevated in patients with acute stroke (129.9 ±9.9 fmol/mL) compared with the controls (90.8 ±6.3 fmol/mL, p<0.05). These levels remained elevated at day 6 (113.5 ±13.0 fmol/mL). NT-proBNP at admission was significantly higher in cardioembolic compared with atherothrombotic infarctions. There was no correlation between circulating NT-proBNP and stroke topography, infarct size, or severity as assessed by the National Institutes of Health Stroke Scale (NIHSS) at any of the 2 time points (admission and day 6). NT-proBNP levels were raised in patients with acute ischemic stroke; this effect persisted until day 6. The authors suggest that neurohumoral activation occurs in patients with acute ischemic stroke, either reflecting a counterbalancing vasodilating response to the cerebral ischemia or direct myocardial dysfunction.

Treatment of non-healing wounds with autologous bone marrow cells, platelets, fibrin glue and collagen matrix

BACKGROUND AIMS Recalcitrant diabetic wounds are not responsive to the most common treatments. Bone marrow-derived stem cell transplantation is used for the healing of chronic lower extremity wounds. METHODS We report on the treatment of eight patients with aggressive, refractory diabetic wounds. The marrow-derived cells were injected/applied topically into the wound along with platelets, fibrin glue and bone marrow-impregnated collagen matrix. RESULTS Four weeks after treatment, the wound was completely closed in three patients and significantly reduced in the remaining five patients. CONCLUSIONS Our study suggests that the combination of the components mentioned can be used safely in order to synergize the effect of chronic wound healing.