Intralipid™ administration attenuates the hypotensive effects of acute intravenous amiodarone overdose in a swine model.

PURPOSE: To investigate whether a lipid emulsion could counteract the hypotensive effects of amiodarone overdose after an acute intravenous administration and improve 4 h survival in an established model of swine cardiovascular research. METHODS: Twenty pigs were intubated and instrumented to measure aortic pressures and central venous pressures (CVP). After allowing the animals to stabilize for 60 minutes, amiodarone overdose (1 mg/kg/min) was initiated for a maximum of 20 minutes. Afterwards, the animals were randomized into 2 groups. Group A (n = 10) received 0.9% Normal Saline (NS) and Group B (n = 10) received 20% Intralipid® (ILE). A bolus dose of 2 ml/kg in over 2 min time was initially administered in both groups followed by a 45 min infusion (0.2 ml/kg/min) of either NS or ILE. RESULTS: All animals survived the overdose and all animals survived the monitoring period of 4 hours. Systolic aortic pressure (SpthAorta) (6.90 vs 14.10 mmHg, P = .006) and mean arterial pressure (MAP) (6.10 vs 14.90 mmHg, P = .001) were higher in the ILE group 2 min after the bolus ILE infusion. This difference was maintained for 15 min after ILE infusion for both SpthAorta (7.85 vs 13.15 mmHg, P = .044) and MAP (7.85 vs 13.15 mmHg, P = .042). Animals that received ILE had higher CVP (11.6 vs 15.7 mmHg, P = .046), an effect which was attenuated 2 and 4 hours post administration. Animals receiving ILE were more acidotic (7.21 vs 7.38, P = .048) in the monitoring period compared to animals receiving NS. CONCLUSIONS: Intralipid attenuated the hypotensive effects of amiodarone toxicity for a period of 15 minutes compared to animals receiving NS.

Quadriceps muscle blood flow and oxygen availability during repetitive bouts of isometric exercise in simulated sailing.

In this study, we wished to determine whether the observed reduction in quadriceps muscle oxygen availability, reported during repetitive bouts of isometric exercise in simulated sailing efforts (i.e. hiking), is because of restricted muscle blood flow. Six national-squad Laser sailors initially performed three successive 3-min hiking bouts followed by three successive 3-min cycling tests sustained at constant intensities reproducing the cardiac output recorded during each of the three hiking bouts. The blood flow index (BFI) was determined from assessment of the vastus lateralis using near-infrared spectroscopy in association with the light-absorbing tracer indocyanine green dye, while cardiac output was determined from impedance cardiography. At equivalent cardiac outputs (ranging from 10.3±0.5 to 14.8±0.86 L · min(-1)), the increase from baseline in vastus lateralis BFI across the three hiking bouts (from 1.1±0.2 to 3.1±0.6 nM · s(-1)) was lower (P = 0.036) than that seen during the three cycling bouts (from 1.1±0.2 to 7.2±1.4 nM · s(-1)) (Cohen's d: 3.80 nM · s(-1)), whereas the increase from baseline in deoxygenated haemoglobin (by ∼17.0±2.9 µM) (an index of tissue oxygen extraction) was greater (P = 0.006) during hiking than cycling (by ∼5.3±2.7 µM) (Cohen's d: 4.17 µM). The results suggest that reduced vastus lateralis muscle oxygen availability during hiking arises from restricted muscle blood flow in the isometrically acting quadriceps muscles.

Synergistic effect of cold atmospheric pressure plasma and free or liposomal doxorubicin on melanoma cells.

The aim of the present study was to investigate combined effects of cold atmospheric plasma (CAP) and the chemotherapeutic drug doxorubicin (DOX) on murine and human melanoma cells, and normal cells. In addition to free drug, the combination of CAP with a liposomal drug (DOX-LIP) was also studied for the first time. Thiazolyl blue tetrazolium bromide (MTT) and Trypan Blue exclusion assays were used to evaluate cell viability; the mechanism of cell death was evaluated by flow cytometry. Combined treatment effects on the clonogenic capability of melanoma cells, was also tested with soft agar colony formation assay. Furthermore the effect of CAP on the cellular uptake of DOX or DOX-LIP was examined. Results showed a strong synergistic effect of CAP and DOX or DOX-LIP on selectively decreasing cell viability of melanoma cells. CAP accelerated the apoptotic effect of DOX (or DOX-LIP) and dramatically reduced the aggressiveness of melanoma cells, as the combination treatment significantly decreased their anchorage independent growth. Moreover, CAP did not result in increased cellular uptake of DOX under the present experimental conditions. In conclusion, CAP facilitates DOX cytotoxic effects on melanoma cells, and affects their metastatic potential by reducing their clonogenicity, as shown for the first time.

Real-Time Overlapping of Indocyanine Green-Video Angiography With White Light Imaging for Vascular Neurosurgery: Technique, Implementation, and Clinical Experience.

BACKGROUND: Fluorescent-guided techniques in vascular neurosurgery can be demonstrated via black and white indocyanine green videoangiography (ICG-VA). Multispectral imaging (MFL) is a new method, which overlaps fluorescence with the white light and provides a fluorescent white light augmented reality image to the surgeon. OBJECTIVE: To investigate (a) whether MFL can enhance the visualization of the blood-flow with simultaneous visualization of the anatomic structures and (b) if MFL can ergonomically improve the microvascular surgical treatment compared to ICG-VA. METHODS: A digital imaging of the blood flow after intravenous injection of ICG on 7 pigs was performed in real time under white light, standard fluorescence, and MFL. The blood flow was interrupted with a surgical clip, demonstrating the blockage of the blood flow. We prospectively included 30 patients with vascular deformities. The vasculature was visualized on the microscope's monitor and through the microscope's eyepiece. RESULTS: In the animal experiment, the visualization of the anatomy and the blood flow under MFL produced high resolution images. The occlusion of blood vessels demonstrated sufficiently the blockage of tissue perfusion and its reperfusion after clip removal. During all 30 surgical cases, the MFL technique and the direct delivery of the pseudo-colored image through the eyepiece allowed for enhanced anatomic and dynamic data. CONCLUSION: MFL was shown to be superior to the classic ICG-VA, delivering enhanced data and notably improving the workflow due to the simultaneous and precise white light visualization of the blood flow and the surrounding anatomic structures.

Confocal-Assisted Multispectral Fluorescent Microscopy for Brain Tumor Surgery.

Optimal surgical therapy for brain tumors is the combination of complete resection with minimal invasion and damage to the adjacent normal tissue. To achieve this goal, we need advanced imaging techniques on a scale from macro- to microscopic resolution. In the last decade, the development of fluorescence-guided surgery has been the most influential breakthrough, marginally improving outcomes in brain tumor surgery. Multispectral fluorescence microscopy (MFL) is a novel imaging technique that allows the overlapping of a fluorescent image and a white light image in real-time, with delivery of the merged image to the surgeon through the eyepieces of a surgical microscope. MFL permits the detection and characterization of brain tumors using fluorescent molecular markers such as 5-aminolevulinic acid (5-ALA) or indocyanine green (ICG), while simultaneously obtaining high definition white light images to create a pseudo-colored composite image in real-time. Limitations associated with the use of MFL include decreased light imaging intensity and decreased levels of magnification that may compromise maximal tumor resection on a cellular scale. Confocal laser endomicroscopy (CLE) is another novel advanced imaging technique that is based on miniaturization of the microscope imaging head in order to provide the possibility of in vivo microscopy at the cellular level. Clear visualization of the cellular cytoarchitecture can be achieved with 400-fold-1,000-fold magnification. CLE allows on the one hand the intra-operative detection and differentiation of single tumor cells (without the need for intra-operative histologic analysis of biopsy specimens) as well as the definition of borders between tumor and normal tissue at a cellular level, dramatically improving the accuracy of surgical resection. The application and implementation of CLE-assisted surgery in surgical oncology increases not only the number of options for real-time diagnostic imaging, but also the therapeutic options by extending the resection borders of cancer at a cellular level and, more importantly, by protecting the functionality of normal tissue in the adjacent areas of the human brain. In this article, we describe our experience using these new techniques of confocal-assisted fluorescent surgery including analysis on the technology, usability, indications, limitations, and further developments.

Human respiratory muscle blood flow measured by near-infrared spectroscopy and indocyanine green.

Measurement of respiratory muscle blood flow (RMBF) in humans has important implications for understanding patterns of blood flow distribution during exercise in healthy individuals and those with chronic disease. Previous studies examining RMBF in humans have required invasive methods on anesthetized subjects. To assess RMBF in awake subjects, we applied an indicator-dilution method using near-infrared spectroscopy (NIRS) and the light-absorbing tracer indocyanine green dye (ICG). NIRS optodes were placed on the left seventh intercostal space at the apposition of the costal diaphragm and on an inactive control muscle (vastus lateralis). The primary respiratory muscles within view of the NIRS optodes include the internal and external intercostals. Intravenous bolus injection of ICG allowed for cardiac output (by the conventional dye-dilution method with arterial sampling), RMBF, and vastus lateralis blood flow to be quantified simultaneously. Esophageal and gastric pressures were also measured to calculate the work of breathing and transdiaphragmatic pressure. Measurements were obtained in five conscious humans during both resting breathing and three separate 5-min bouts of constant isocapnic hyperpnea at 27.1 +/- 3.2, 56.0 +/- 6.1, and 75.9 +/- 5.7% of maximum minute ventilation as determined on a previous maximal exercise test. RMBF progressively increased (9.9 +/- 0.6, 14.8 +/- 2.7, 29.9 +/- 5.8, and 50.1 +/- 12.5 ml 100 ml(-1) min(-1), respectively) with increasing levels of ventilation while blood flow to the inactive control muscle remained constant (10.4 +/- 1.4, 8.7 +/- 0.7, 12.9 +/- 1.7, and 12.2 +/- 1.8 ml 100 ml(-1) min(-1), respectively). As ventilation rose, RMBF was closely and significantly correlated with 1) cardiac output (r = 0.994, P = 0.006), 2) the work of breathing (r = 0.995, P = 0.005), and 3) transdiaphragmatic pressure (r = 0.998, P = 0.002). These data suggest that the NIRS-ICG technique provides a feasible and sensitive index of RMBF at different levels of ventilation in humans.

Smoking habits of Greek preschool children's parents.

BACKGROUND: Smoking is Greece's largest public health threat. Greece has the highest adult smoking prevalence among all E.U countries, which in turn possibly predisposes Greek children and adolescents to smoke. The purpose of our study was to research into the smoking habits of preschool children's parents since children of that age could be vulnerable to parental negative role modeling and to investigate into the necessity of conducting a public health awareness programme aimed at the general population. METHODS: A cross-sectional study was performed on the parents of children enrolled in kindergarten in western Crete-Greece (2809 parents), and interviewed during the 2004-2005 Cretan school health promotion programme. RESULTS: 63% of households had at least one parent a current smoker and in 26% both parents were found to be current smokers. Smoking prevalence among adults with preschool children was estimated at 44% (52% of fathers and 36% of mothers). Paternal education and nationality were statistically significantly related to smoking (p < 0.001), unlike place of residence (p = 0.862) and level of maternal education (p = 0.132). CONCLUSION: Smoking prevalence is high even among parents with preschool children. Taking into account the parents' significant primary role in the children's upbringing and the effect that parental induced passive smoking has on children's health and health attitude; one can deduce that the health of Greek children is under threat. It is of major importance that educational and policy intervention measures are implemented to reduce such a situation that could contribute to promoting the initiation of smoking among Greek adolescents.

Recent Findings in Alzheimer Disease and Nutrition Focusing on Epigenetics.

Alzheimer disease (AD) is a chronic neurodegenerative disease with no effective cure so far. The current review focuses on the epigenetic mechanisms of AD and how nutrition can influence the course of this disease through regulation of gene expression, according to the latest scientific findings. The search strategy was the use of scientific databases such as PubMed and Scopus in order to find relative research or review articles published in the years 2012-2015. By showing the latest data of various nutritional compounds, this study aims to stimulate the scientific community to recognize the value of nutrition in this subject. Epigenetics is becoming a very attractive subject for researchers because it can shed light on unknown aspects of complex diseases like AD. DNA methylation, histone modifications, and microRNAs are the principal epigenetic mechanisms involved in AD pathophysiology. Nutrition is an environmental factor that is related to AD through epigenetic pathways. Vitamin B-12, for instance, can alter the one-carbon metabolism and thus interfere in the DNA methylation process. The research results might seem ambiguous about the clinical role of nutrition, but there is strengthening evidence that proper nutrition can not only change epigenetic biomarker levels but also prevent the development of late-onset AD and attenuate cognition deficit. Nutrition might grow to become a preventive and even therapeutic alternative against AD, especially if combined with other antidementia interventions, brain exercise, physical training, etc. Epigenetic biomarkers can be a very helpful tool to help researchers find the exact nutrients needed to create specific remedies, and perhaps the same biomarkers can be used even in patient screening in the future.

Comparative analysis of phase difference estimation methods quantifying asynchronies between compartmental chest wall volume signals.

Asynchronous breathing movements may be observed in the presence of pulmonary disease, such as chronic obstructive pulmonary disease (COPD). This study was undertaken in an attempt to propose a reliable methodology to quantify this asynchrony. Five methods for estimating phase differences between two signals, based on the phase angle of the Fourier Transform (PhD(FT)), paradoxical motion (PhD(PM)), the Lissajous figure (PhD(LF)), maximal linear correlation (PhD(P)) and least-squares filtering (PhD(LS)), were compared. Frequency-modulated signals, simulating compartmental chest wall volumes, were used to evaluate the methods. Breathing asynchrony was quantified in two ways; by estimating (a) a single PhD value for the entire recording and (b) time-varying PhDs, representing non-stationarities of human breathing. PhD(PM) and PhD(LF) had the lowest average errors (4%), and PhD(LS) had a slightly higher error. PhD(FT) had zero error when estimating a single PhD value but a considerable error when estimating time-varying PhDs. PhD(P) presented the highest errors in all cases. An application of this methodology is proposed in real compartmental chest wall volume signals of normal and COPD subjects. Preliminary results indicate that the methodology is promising in quantifying differences in asynchronous breathing between thoracic volumes of COPD patients and healthy controls.

Effects of hypoxia on diaphragmatic fatigue in highly trained athletes.

Previous work suggests that exercise-induced arterial hypoxaemia (EIAH), causing only moderate arterial oxygen desaturation (SaO2 : 92 +/- 1%), does not exaggerate diaphragmatic fatigue exhibited by highly trained endurance athletes. Since changes in arterial O2 tension have a significant effect on the rate of development of locomotor muscle fatigue during strenuous exercise, the present study investigated whether hypoxia superimposed on EIAH exacerbates the exercise-induced diaphragmatic fatigue in these athletes. Eight trained cyclists (VO2max : 67.0 +/- 2.6 ml kg(-1) min(-1); mean +/- S.E.M.) completed in balanced order four 5 min exercise tests leading to different levels of end-exercise SaO2 (64 +/- 2, 83 +/- 1, 91 +/- 1 and 96 +/- 1%) via variations in inspired O2 fraction (FiO2 : 0.13, 0.17, 0.21 and 0.26, respectively). Measurements were made at corresponding intensities (65 +/- 3, 80 +/- 3, 85 +/- 3 and 90 +/- 3% of normoxic maximal work rate, respectively) in order to produce the same tidal volume, breathing frequency and respiratory muscle load at each FiO2. The mean pressure time product of the diaphragm did not differ across the four exercise tests and ranged between 312 +/- 28 and 382 +/- 22 cmH2O s min(-1). Ten minutes into recovery, twitch transdiaphragmatic pressure (P(di,tw)) determined by bilateral phrenic nerve stimulation, was significantly (P = 0.0001) reduced after all tests. After both hypoxic tests (FiO2 : 0.13, 0.17) the degree of fall in P(di,tw) (by 26.9 +/- 2.7 and 27.4 +/- 2.6%, respectively) was significantly greater (P < 0.05) than after the normoxic test (by 20.1 +/- 3.4%). The greater amount of diaphragmatic fatigue in hypoxia at lower leg work rates (presumably requiring smaller leg blood flow compared with normoxia at higher leg work rates), suggests that when ventilatory muscle load is similar between normoxia and hypoxia, hypoxia exaggerates diaphragmatic fatigue in spite of potentially greater respiratory muscle blood flow availability.

Biomarkers of passive smoking among Greek preschool children.

BACKGROUND: Greece has the highest adult smoking prevalence in the European Union, affecting not only those who smoke but also threatening the health of those who are involuntarily exposed to passive smoke, especially young Greek children. OBJECTIVE: The aim of this study was to quantify passive smoking biomarkers (serum nicotine and cotinine levels) among preschool children in Crete in relation to parental smoking habits. METHODS: All children enrolled in kindergarten in western Crete (1,757 preschool children and 2,809 parents) were interviewed during the 2004-2005 Cretan health promotion programme out of which a sample of 81 children was randomly selected according to parental smoking status and blood samples for cotinine and nicotine assay were taken. RESULTS: The geometric means of serum nicotine values in children with both parents current smokers and in those with both parents non-smokers were 0.71 ng/ml (95%CI 0.62, 0.80) and 0.59 ng/ml (95%CI 0.49, 0.69), respectively, (p=0.073). Cotinine geometric mean values were found at 1.69 ng/ml (95%CI 0.93, 3.06) and 0.15 ng/ml (95%CI 0.09, 0.28), respectively, (p<0.001). Girls with smoker parents had also greater cotinine geometric mean values than boys (3.35 versus 0.85 ng/ml, respectively, p=0.018). CONCLUSION: Our findings prove that Greek preschool children, especially young girls, are exposed to substantial levels of passive smoke which therefore stresses the need for immediate action so as to prevent the predisposition and early addiction of Greek preschool children to tobacco.