Nikolaos Panagopoulos

Thiol redox state (TRS) and oxidative stress in the mouse hippocampus after pentylenetetrazol-induced epileptic seizure

In this study we evaluated oxidative stress (lipid peroxidation and protein oxidation) and thiol redox state [TRS: glutathione (GSH), glutathione disulfide (GSSG), cysteine (CSH), protein (P) thiols (PSH) and protein and non-protein (NP) mixed/symmetric disulfides (PSSR, NPSSR, NPSSC, PSSP)] in hippocampus after pentylenetetrazol (PTZ) administration at convulsive and subconvulsive dose. The significant decrease in PSH, CSH and NPSSC, as well as the increase in PSSP, NPSSR, lipid peroxidation and protein oxidation levels after PTZ-induced seizure indicate increased oxidative damage in hippocampus, although the levels of GSH and GSSG do not change significantly.

Effect of pentylenetetrazol-induced epileptic seizure on thiol redox state in the mouse cerebral cortex.

In the present study we examined the effects of pentylenetetrazol (PTZ) administration on the thiol redox state (TRS), lipid peroxidation and protein oxidation in left and right mouse cerebral cortex in order (a) to quantitate the major components of the thiol redox state and relate them with oxidative stress and cortical laterality, and (b) to investigate whether neuronal activation without synchronization, induced by subconvulsive doses of PTZ, can cause similar qualitative effects on the thiol redox state. Specifically, we examined the TRS components [glutathione (GSH), glutathione disulfide (GSSG), cysteine (CSH), protein (P) thiols (PSH) and protein and non-protein (NP) mixed/symmetric disulfides (PSSR, NPSSR, NPSSC, PSSP)]. At 15 min after seizure, GSH, GSSG, CSH, NPSSC, PSSR and PSSC levels are decreased in left (14-50%) and right (11-53%) cortex while PSSP levels are increased in both left (1400%) and right (1600%) cortex. At 30 min after seizure, GSSG, CSH, NPSSC, PSSR and PSSC levels are decreased in left (14-51%) and right (18-56%) cortex while PSSP and protein carbonyl levels are increased in left (2300% and 20%, respectively) and right (2800% and 21%, respectively) cortex. At 24 h after seizure, the TRS components return to normal and protein carbonyl levels are decreased in left (16%) and right (20%) cortex. The significant decrease in GSH, GSSG, CSH, NPSSC, PSSR and PSSC, as well as the increase in protein carbonyl and the high increase in PSSP levels after PTZ-induced seizure indicate increased oxidative stress in cerebral cortex of mice, and of similar magnitude and TRS-component profiles between left and right cerebral cortex.

Fatal stroke after completion pneumonectomy for torsion of left upper lobe following left lower lobectomy

BackgroundThe lobar torsion after lung surgery is a rare complication with an incidence of 0.09 to 0.4 %. It may occur after twisting of the bronchovascular pedicle of the remaining lobe after lobectomy, usually on the right side. The 180-degree rotation of the pedicle produces an acute obstruction of the lobar bronchus (atelectasis) and of the lobar vessels as well. Without prompt treatment it progresses to lobar ischemia, pulmonary infarction and finally fatal gangrene.Case PresentationA 62 years old female patient was admitted for surgical treatment of lung cancer. She underwent elective left lower lobectomy for squamous cell carcinoma (pT2 N0). The operation was unremarkable, and the patient was extubated in the operating room. After eight hours the patient established decrease of pO2 and chest x-ray showed atelectasis of the lower lobe. To establish diagnosis, bronchoscopy was performed, demonstrating obstructed left lobar bronchus. The patient was re-intubated, and admitted to the operating room where reopening of the thoracotomy was performed. Lobar torsion was diagnosed, with the diaphragmatic surface of the upper lobe facing in an anterosuperior orientation. A completion pneumonectomy was performed. At the end of the procedure the patient developed a right pupil dilatation, presumably due to a cerebral embolism. A subsequent brain angio-CT scan established the diagnosis. She died at the intensive care unit 26 days later.ConclusionThe thoracic surgeon should suspect this rare early postoperative complication after any thoracic operation in every patient with atelectasis of the neighboring lobe. High index of suspicion and prompt diagnosis may prevent catastrophic consequences, such as, infarction or gangrene of the pulmonary lobe. During thoracic operations, especially whenever the lung or lobe hilum is full mobilized, fixation of the remaining lobe may prevent this life threatening complication.

High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology

BackgroundBcl-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. Bcl-2 has been investigated as a prognostic factor in non small cell lung cancer (NSCLC) patients with conflicting results.MethodsHere, we quantitatively assessed Bcl-2 expression in two large and independent cohorts to investigate the impact of Bcl-2 on survival. AQUA®, a fluorescent-based method for analysis of in situ protein expression, was used to measure Bcl-2 protein levels and classify tumors by Bcl-2 expression in a cohort of 180 NSCLC patients. An independent cohort of 354 NSCLC patients was used to validate Bcl-2 classification and evaluate outcome.ResultsFifty % and 52% of the cases were classified as high expressers in training and validation cohorts respectively. Squamous cell carcinomas were more likely to be high expressers compared to adenocarcinomas (63% vs. 45%, p = 0.002); Bcl-2 was not associated with other clinical or pathological characteristics. Survival analysis showed that patients with high BCL-2 expression had a longer median survival compared to low expressers (22 vs. 17.5 months, log rank p = 0.014) especially in the subset of non-squamous tumors (25 vs. 13.8 months, log rank p = 0.04). Multivariate analysis revealed an independent lower risk for all patients with Bcl-2 expressing tumors (HR = 0.53, 95% CI 0.37-0.75, p = 0.0003) and for patients with non-squamous tumors (HR = 0.5, 95% CI 0.31-0.81, p = 0.005).ConclusionsBcl-2 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of NSCLC patients.

Thiol redox state and lipid and protein oxidation in the mouse striatum after pentylenetetrazol-induced epileptic seizure

Summary:  Purpose: In the present study, we examined the effects of pentylenetetrazol (PTZ) administration on the thiol redox state (TRS), lipid peroxidation, and protein oxidation in the mouse striatum to (a) quantitate the major components of TRS and relate them to oxidative stress, and (b) investigate whether neuronal activation without synchronization, induced by subconvulsive doses of PTZ, can cause similar qualitative effects on TRS in this brain area. Specifically, we examined the TRS components glutathione (GSH), glutathione disulfide (GSSG), cysteine (CSH), protein thiols (PSH), and the protein (P) and nonprotein (NP/R) disulfides PSSR, NPSSR, NPSSC, and PSSP.

Thiol redox state and oxidative stress in midbrain and striatum of weaver mutant mice, a genetic model of nigrostriatal dopamine deficiency

In this study we measured thiol redox state (TRS) and the oxidative stress indicator lipid peroxidation in midbrain and striatum of adult (4 months old) male control (+/+) and weaver (wv/wv) mice in order to relate them with oxidative stress in conditions of progressive and severe (approximately 70%) nigrostriatal dopaminergic neurodegeneration. Specifically, we measured the specific TRS components glutathione (GSH), glutathione disulfide (GSSG), cysteine (CSH), and the general classes of TRS components. The latter are the protein thiols (PSH) and the disulfides between (a) protein (P) and protein thiols (PSSP), (b) protein and non-protein (NP/R) thiols (PSSR, PSSC) and (c) non-protein and non-protein thiols (NPSSR, NPSSC). In addition, the main product of lipid peroxidation malonyl dialdehyde (MDA) was estimated. In the midbrain of wv/wv, GSH and NPSSC levels are decreased (44% and 64%, respectively) and GSSG, NPSSR, CSH, PSH, PSSP, PSSR and MDA levels are increased (23%, 660%, 110%, 51%, 68%, 18% and 44%, respectively). In the striatum of male wv/wv, protein and non-protein thiol/disulfide and MDA levels do not change, possibly due to the high decrease in striatal dopamine level versus midbrain. Our data show that the high degeneration of the dopaminergic nigrostriatal neurons in male adult wv/wv mice is accompanied by significant changes in TRS and an increase in lipid peroxidation in the midbrain, suggesting involvement of oxidative stress in the degeneration of dopaminergic neurons. They also strengthen the possible use of thiol antioxidants for the development of new neuroprotective therapeutic strategies for neurodegenerative diseases, such as Parkinsons disease.

Prognostic factors of atrial fibrillation following elective coronary artery bypass grafting: the impact of quantified intraoperative myocardial ischemia

BackgroundAtrial fibrillation (AF) occurs in 28-33% of the patients undergoing coronary artery revascularization (CABG). This study focuses on both pre- and peri-operative factors that may affect the occurrence of AF. The aim is to identify those patients at higher risk to develop AF after CABG.Patients and methodsTwo patient cohorts undergoing CABG were retrospectively studied. The first group (group A) consisted of 157 patients presenting AF after elective CABG. The second group (group B) consisted of 191 patients without AF postoperatively.ResultsPreoperative factors presenting significant correlation with the incidence of post-operative AF included: 1) age > 65 years (p = 0.029), 2) history of AF (p = 0.022), 3) chronic obstructive pulmonary disease (p = 0.008), 4) left ventricular dysfunction with ejection fraction < 40% (p = 0.015) and 5) proximal lesion of the right coronary artery (p = 0.023). The intraoperative factors that appeared to have significant correlation with the occurrence of postoperative AF were: 1) CPB-time > 120 minutes (p = 0.011), 2) myocardial ischemia index < 0.27 ml.m2/Kg.min (p = 0.011), 3) total positive fluid-balance during ICU-stay (p < 0.001), 4) FiO2/PO2 > 0, 4 after extubation and during the ICU-stay (p = 0.021), 5) inotropic support with doses 15-30 μg/Kg/min (p = 0.016), 6) long ICU-stay recovery for any reason (p < 0.001) and perioperative myocardial infarction (p < 0.001).ConclusionsOur results suggest that the incidence of post-CABG atrial fibrillation can be predicted by specific preoperative and intraoperative measures. The intraoperative myocardial ischemia can be sufficiently quantified by the myocardial ischemia index. For those patients at risk we would suggest an early postoperative precautionary anti-arrhythmic treatment.

Influence of ultra-low dose Aprotinin on thoracic surgical operations: a prospective randomized trial

BackgroundThe blood saving effect of aprotinin has been well documented in cardiac surgery. In thoracic surgery, very few recent studies, using rather high doses of aprotinin, have shown a similar result. In a randomized prospective trial, we have tested the influence of aprotinin using an ultra-low dose drug regime.MethodsFifty-nine patients, mean age 58 ± 13.25 years (mean ± SD) undergoing general thoracic procedures were randomized into placebo (Group A) and treatment group (Group B). The group B (n = 29) received 500.000 IU of aprotinin after induction to anesthesia and a repeat dose immediately after chest closure. A detailed protocol with several laboratory parameters was recorded. Patients were transfused when perioperative Ht was less than 26%.ResultsThe two groups were similar in terms of age, gender, diagnosis, pathology, co-morbidity and operations performed. The mean drainage of the first and second postoperative day in group B was significantly reduced (412.6 ± 199.2 vs. 764.3 ± 213.9 ml, p < 0.000, and 248.3 ± 178.5 vs. 455.0 ± 274.6, p < 0.001). Similarly, the need for fresh frozen plasma transfusion was lower in group B, p < 0.035. Both the operation time and the hospital stay were also less for group B but without reaching statistical significance (84.6 ± 35.2 vs 101.2 ± 52.45 min. and 5.8 ± 1.6 vs 7.2 ± 3.6 days respectively, p < 0.064). The overall transfusion rate did not differ significantly. No side effects of aprotinin were noted.ConclusionThe perioperative ultra-low dose aprotinin administration was associated with a reduction of total blood losses and blood product requirements. We therefore consider the use of aprotinin safe and effective in major thoracic surgery.

VATS bullectomy and apical pleurectomy for spontaneous pneumothorax in a young patient with Swyer-James-Mc Leod syndrome: case report presentation and literature review focusing on surgically treated cases

BackgroundSwyer-James-McLeod Syndrome (SJMS) is an uncommon, emphysematous disease characterized by radiologic hyperlucency of pulmonary parenchyma due to loss of the pulmonary vascular structure and to alveolar overdistension.Case reportWe herein describe a 15-year-old Caucasian patient with well-established SJMS since childhood who presented with spontaneous pneumothorax. Video-assisted thoracoscopic bullectomy with apical pleurectomy was performed. Since SJMS is considered an on-going inflammatory process, the patient one year after surgery exhibits excellent quality of life with no pneumothorax recurrence.

17β-Estradiol/N-acetylcysteine interaction enhances the neuroprotective effect on dopaminergic neurons in the weaver model of dopamine deficiency.

The weaver mouse, is a phenocopy of Parkinsons disease (PD) in which dopaminergic neurons degenerate gradually during development, reaching at P21 a neurodegeneration of 55%. Thus, the weaver mouse constitutes an appropriate in vivo PD model for investigating the effect of neuroprotective agents. In the present study, long-term treatment (from P1 to P21) with 17β-estradiol (17β-estradiol) significantly protected the dopaminergic neurons in the substantia nigra (SN) of weaver mouse by 54%, as was detected by immunohistochemical experiments, using the specific antibody against tyrosine hydroxylase (TH). This dopaminergic neuroprotection is in line with our biochemical results showing that 17β-estradiol treatment significantly decreased the high lipid peroxidation levels seen in the SN of weaver mouse, indicating high oxidative stress. Interestingly, co-administration of 17β-estradiol with N-acetylcysteine (NAC, precursor molecule of glutathione (GSH)) further significantly increased the survival of dopaminergic neurons in the SN (by 85%), with a parallel further decrease of lipid peroxidation to normal levels. Our results show the in vivo neuroprotective effect of 17β-estradiol, which is strongly enhanced by co administration of NAC, indicating a strong synergistic effect of the two drugs. Furthermore, the main mechanism underlying this neuroprotective action seems to be the reversal of the oxidative stress shown by the high peroxidation levels. These results could be of clinical relevance since both drugs are already used separately in the clinic, 17β-estradiol for treatment of PD and NAC as a mucolytic agent and for the treatment of several disorders.