Distinct Roles of Apolipoproteins A1 and E in the Modulation of High-Density Lipoprotein Composition and Function.

In addition to high-density lipoprotein cholesterol (HDL-C) levels, HDL quality also appears to be very important for atheroprotection. Analysis of various clinical paradigms suggests that the lipid and apolipoprotein composition of HDL defines its size, shape, and functions and may determine its beneficial effects on human health. Previously, we reported that like apolipoprotein A-I (Apoa1), apolipoprotein E (Apoe) is also capable of promoting the de novo biogenesis of HDL with the participation of ATP binding cassette A lipid transporter member 1 (Abca1) and plasma enzyme lecithin:cholesterol acyltransferase (Lcat), in a manner independent of a functional Apoa1. Here, we performed a comparative analysis of the functions of these HDL subpopulations. Specifically, Apoe and Apoa1 double-deficient (Apoe(-/-) × Apoa1(-/-)) mice were infected with APOA1- or APOE3-expressing adenoviruses, and APOA1-containing HDL (APOA1-HDL) and APOE3-containing HDL (APOE3-HDL), respectively, were isolated and analyzed by biochemical and physicochemical methods. Western blot and lipidomic analyses indicated significant differences in the apolipoprotein and lipid composition of the two HDL species. Moreover APOE3-HDL presented a markedly reduced antioxidant potential and Abcg1-mediated cholesterol efflux capacity. Surprisingly, APOE3-HDL but not APOA1-HDL attenuated LPS-induced production of TNFα in RAW264.7 cells, suggesting that the anti-inflammatory effects of APOA1 are dependent on APOE expression. Taken together, our data indicate that APOA1 and APOE3 recruit different apolipoproteins and lipids on the HDL particle, leading to structurally and functionally distinct HDL subpopulations. The distinct role of these two apolipoproteins in the modulation of HDL functionality may pave the way toward the development of novel pharmaceuticals that aim to improve HDL functionality.

Scavenger Receptor Class B Type I Regulates Plasma Apolipoprotein E Levels and Dietary Lipid Deposition to the Liver.

Scavenger receptor class B type I (SR-BI) is primarily responsible for the selective uptake of cholesteryl esters (CE) of high-density lipoprotein (HDL) by the liver and other tissues. In the present study, we show that SR-BI-deficient (scarb1(-/-)) mice are resistant to diet-induced obesity, hepatic lipid deposition, and glucose intolerance after 24 weeks of being fed a western-type diet. No differences in energy expenditure or mitochondrial function could account for the observed phenotype. Kinetic and gene expression analyses suggested reduced de novo fatty acid synthesis in scarb1(-/-) mice. Furthermore, adenosine monophosphate-activated protein kinase (AMPK)-stimulated hepatic FFA catabolism was reduced in these mice, leaving direct dietary lipid uptake from plasma as the major modulator of hepatic lipid content. Analysis of the apolipoprotein composition of plasma lipoproteins revealed a significant accumulation of apolipoprotein E (ApoE)-containing HDL and TG-rich lipoproteins in scarb1(-/-) mice that correlated with reduced plasma LpL activity. Our data suggest that scarb1(-/-) mice fed a western-type diet for 24 weeks accumulate CE- and ApoE-rich HDL of abnormal density and size. The elevated HDL-ApoE levels inhibit plasma LpL activity, blocking the clearance of triglyceride-rich lipoproteins and preventing the shuttling of dietary lipids to the liver.

Novice surgeons: do they benefit from 3D laparoscopy?

In this study, the impact of two-dimensional (2D) and three-dimensional (3D) vision on laparoscopic performance of novice surgeons is examined. Twenty-five novice surgeons were directed to complete four basic tasks from European Training in Basic Laparoscopic Urological Skills (E-BLUS) with both 2D and 3D systems in a random order: task 1: needle guidance, task 2: cutting a circle, task 3: laparoscopic suturing, and task 4: pegs transfer. Quality and quantity scores for each task were measured. Participants completed all of the tasks in one modality of vision and than switched to the other. NASA Task Load Index was used for subjective workload assessment. Statistically significant differences in favor of 3D vision were detected in tasks 1 and 4 both in terms of quality and quantity. In task 2 and task 3, a significantly better performance was observed with the 3D vision only in quantity assessment. The participants who started the tasks in the 3D vision were better in performing the skills in 2D when compared to the participants who started with 2D vision. Overall, the participants reported a better perception of depth and spatial orientation with the 3D mode. Subjective work load was also lower for the tasks performed in 3D. Novice surgeons tended to perform better and felt much more comfortable with 3D in comparison to 2D laparoscopy. Even though previous task experience seemed to have an important impact on laparoscopic performance regardless of imaging modality, 3D laparoscopy seemed to facilitate the learning for novice surgeons.

Background adjustment of cDNA microarray images by Maximum Entropy distributions.

Many empirical studies have demonstrated the exquisite sensitivity of both traditional and novel statistical and machine intelligence algorithms to the method of background adjustment used to analyze microarray datasets. In this paper we develop a statistical framework that approaches background adjustment as a classic stochastic inverse problem, whose noise characteristics are given in terms of Maximum Entropy distributions. We derive analytic closed form approximations to the combined problem of estimating the magnitude of the background in microarray images and adjusting for its presence. The proposed method reduces standardized measures of log expression variability across replicates in situations of known differential and non-differential gene expression without increasing the bias. Additionally, it results in computationally efficient procedures for estimation and learning based on sufficient statistics and can filter out spot measures with intensities that are numerically close to the background level resulting in a noise reduction of about 7%.

Factors affecting the long-term response to tacrolimus in renal transplant patients: pharmacokinetic and pharmacogenetic approach.

BACKGROUND: The aim of our study was to determine the impact of CYP3A5*1 and CYP3A5*3 on the kinetics of tacrolimus in renal transplant recipients. MATERIAL AND METHODS: Forty kidney recipients were selected to participate. Maintenance scheme consisted of tacrolimus, a purine inhibitor and a steroid. CYP3A5 genotyping was performed with PCR and RFLP. Pharmacokinetic model was developed with Linear Regression and General Linear Model repeated measures approach. The impact of sex, CYP3A5*1 allele, age at transplantation, hepatic and renal function on tacrolimus kinetics was examined. RESULTS: The frequency of CYP3A5*3/*3 and CYP3A5*1/*3 genotype was 35/40 and 5/40, respectively. No CYP3A5*1/*1 was detected. CYP3A5*1 variant was associated with significant lower TAC dose adjusted concentration at 3, 6, 12 and 36 months after transplantation. Hepatic and renal function showed a significant effect on tacrolimus dose adjusted concentration 3 months after transplantation (p=0.000 and 0.028, respectively). Sex did not show a significant impact on tacrolimus kinetics. Carriers of CYP3A5*1 allele had lower predicted measures for tacrolimus dose adjusted concentration and higher predicted measures for volume of distribution. CONCLUSION: We proved that CYP3A5*1 carriers need higher tacrolimus dose than CYP3A5*3 homozygotes to achieve the target blood concentration.

Bayesian clustering of flow cytometry data for the diagnosis of B-chronic lymphocytic leukemia.

In the rapidly advancing field of flow cytometry, methodologies facilitating automated clinical decision support are increasingly needed. In the case of B-chronic lymphocytic leukemia (B-CLL), discrimination of the various subpopulations of blood cells is an important task. In this work, our objective is to provide a useful paradigm of computer-based assistance in the domain of flow-cytometric data analysis by proposing a Bayesian methodology for flow cytometry clustering. Using Bayesian clustering, we replicate a series of (unsupervised) data clustering tasks, usually performed manually by the expert. The proposed methodology is able to incorporate the expert's knowledge, as prior information to data-driven statistical learning methods, in a simple and efficient way. We observe almost optimal clustering results, with respect to the expert's gold standard. The model is flexible enough to identify correctly non canonical clustering structures, despite the presence of various abnormalities and heterogeneities in data; it offers an advantage over other types of approaches that apply hierarchical or distance-based concepts.

A perspective for biomedical data integration: design of databases for flow cytometry.

BACKGROUND: The integration of biomedical information is essential for tackling medical problems. We describe a data model in the domain of flow cytometry (FC) allowing for massive management, analysis and integration with other laboratory and clinical information. The paper is concerned with the proper translation of the Flow Cytometry Standard (FCS) into a relational database schema, in a way that facilitates end users at either doing research on FC or studying specific cases of patients undergone FC analysis RESULTS: The proposed database schema provides integration of data originating from diverse acquisition settings, organized in a way that allows syntactically simple queries that provide results significantly faster than the conventional implementations of the FCS standard. The proposed schema can potentially achieve up to 8 orders of magnitude reduction in query complexity and up to 2 orders of magnitude reduction in response time for data originating from flow cytometers that record 256 colours. This is mainly achieved by managing to maintain an almost constant number of data-mining procedures regardless of the size and complexity of the stored information. CONCLUSION: It is evident that using single-file data storage standards for the design of databases without any structural transformations significantly limits the flexibility of databases. Analysis of the requirements of a specific domain for integration and massive data processing can provide the necessary schema modifications that will unlock the additional functionality of a relational database.

Influence of blood transfusions and preoperative anemia on long-term survival in patients operated for non-small cell lung cancer.

It has been postulated that transfusions have immunosuppressive effects that promote tumor growth and metastasis. Moreover perioperative anemia is considered an independent prognostic factor on outcome in patients operated for malignancy. We evaluated the influence of red blood cell (RBC) transfusions and perioperative anemia on survival in non-small cell lung carcinoma (NSCLC) patients. From 1999 through 2005, 331 consecutive patients, male/female=295/36 (mean age 64+/-9 years), who underwent radical surgery for NSCLC were prospectively enrolled in this cohort and followed up for a mean of 27.2 months. The overall survival of patients was analyzed in relation to RBC transfusions and perioperative anemia. These parameters were analyzed in the whole cohort of patients and separately for stage I patients. Patients were divided according to perioperative transfusion, into Group A (transfused) and Group B (non-transfused) and according to the preoperative haemoglobin (Hb) level into Group 1(Hb<12g/dl) and Group 2(Hb> or =12g/dl), respectively. The overall transfusion rate was 25.7%. Univariate analysis showed that in the whole cohort of patients overall survival was significantly shorter in Group A (mean 33.6 months, 5-year survival 25.1%) compared to Group B (mean 48.0 months, 5-year survival 37.3%) (p=0.001). It also showed that patients with preoperative Hb level <12g/dl (Group 1), (mean of 33.0 months, 5-year survival 21.3%) had shorter survival compared to Group 2 patients (mean 49.3 months and 5-year survival 40.0%), respectively (p=0.002). Multivariate analysis in the whole cohort of patients showed that preoperative anemia was an independent risk factor for survival while RBC transfusion was not. In particular for stage I patients, it was shown that RBC transfusion was an independent prognostic factor for long-term survival as detected by multivariate analysis (p=0.043), while anemia was not. RBC transfusions affect adversely the survival of stage I NSCLC patients, while do not exert any effect on survival of patients with surgically resectable more advanced disease, where preoperative anemia is an independent negative prognostic factor. These findings indicate that RBC transfusion might exert an immunomodulatory effect on patients with early disease while in more advanced stages this effect is not apparent.

Molecular imaging and the unification of multilevel mechanisms and data in medical physics.

Molecular imaging (MI) constitutes a recently developed approach of imaging, where modalities and agents have been reinvented and used in novel combinations in order to expose and measure biologic processes occurring at molecular and cellular levels. It is an approach that bridges the gap between modalities acquiring data from high (e.g., computed tomography, magnetic resonance imaging, and positron-emitting isotopes) and low (e.g., PCR, microarrays) levels of a biological organization. While data integration methodologies will lead to improved diagnostic and prognostic performance, interdisciplinary collaboration, triggered by MI, will result in a better perception of the underlying biological mechanisms. Toward the development of a unifying theory describing these mechanisms, medical physicists can formulate new hypotheses, provide the physical constraints bounding them, and consequently design appropriate experiments. Their new scientific and working environment calls for interventions in their syllabi to educate scientists with enhanced capabilities for holistic views and synthesis.

Nursing workload associated with fever in the general intensive care unit.

BACKGROUND: Fever in a patient in the intensive care unit necessitates several nursing tasks. Moreover, factors associated with increased patient care needs may be associated with fever. OBJECTIVE: To identify relationships between fever and characteristics of fever and nursing workload at the patient level. METHODS: A prospective study was conducted in a medical-surgical intensive care unit. The sample consisted of 361 patients consecutively admitted from October 2005 to August 2006. Each patient's body temperature was measured by using a tympanic membrane or an axillary thermometer. The Therapeutic Intervention Scoring System-28 was used to measure nursing workload. RESULTS: A total of 188 patients (52.1%) had fever. Mean daily scores on the Therapeutic Intervention Scoring System and on 5 of its 7 categories were significantly higher for febrile patients than for nonfebrile patients. Fever was an independent predictor of the mean daily scores for all patients (P < .001). Peak body temperature but not duration of fever also was an independent predictor of mean daily scores for febrile patients (P < .001). CONCLUSION: In a general intensive care unit, fever in patients should be taken into consideration for the proper allocation of nursing personnel.

Association between nursing workload and mortality of intensive care unit patients.

PURPOSE: To investigate differences in mortality of intensive care unit (ICU) patients according to the ratio between total patient care demands and nurse staffing. DESIGN: Observational, prospective study. Patients consecutively admitted in the medical-surgical ICU of a Greek hospital over a 1-year period were enrolled. METHODS: The Therapeutic Intervention Scoring System (TISS)-28 was used for measuring patient care demands. Daily sum of TISS-28 of patients and daily number of nurses were considered for estimating median and peak patient exposure to nursing workload. According to the values of median and peak patient exposure to nursing workload, patients were divided into three groups (low, medium, and high). Logistic regression was used for evaluating the associations between mortality during ICU length of stay and median or peak patient exposure to nursing workload, after adjusting for patient clinical severity. FINDINGS: 396 patients were included and 102 died. Differences in ICU mortality between high and low groups of median and peak patient exposure to nursing workload, although not statistically significant, were clinically remarkable, both when all patients were studied and when medical and surgical patients were separately studied. CONCLUSIONS: Consideration of individual differences in patient acuity might add sensitivity to the detection of associations between nurse understaffing and ICU mortality. CLINICAL RELEVANCE: The findings indicate that not only differences among nurse characteristics, but also differences in patient care demands, are important when investigating the effect of nurse understaffing on mortality of ICU patients. Proper nurse staffing levels should be based on the estimation of total patient acuity, rather than on the absolute number of patients.

Adaptable pattern recognition system for discriminating Melanocytic Nevi from Malignant Melanomas using plain photography images from different image databases.

OBJECTIVE: The aim of this study was to propose features that evaluate pictorial differences between melanocytic nevus (mole) and melanoma lesions by computer-based analysis of plain photography images and to design a cross-platform, tunable, decision support system to discriminate with high accuracy moles from melanomas in different publicly available image databases. MATERIAL AND METHODS: Digital plain photography images of verified mole and melanoma lesions were downloaded from (i) Edinburgh University Hospital, UK, (Dermofit, 330moles/70 melanomas, under signed agreement), from 5 different centers (Multicenter, 63moles/25 melanomas, publicly available), and from the Groningen University, Netherlands (Groningen, 100moles/70 melanomas, publicly available). Images were processed for outlining the lesion-border and isolating the lesion from the surrounding background. Fourteen features were generated from each lesion evaluating texture (4), structure (5), shape (4) and color (1). Features were subjected to statistical analysis for determining differences in pictorial properties between moles and melanomas. The Probabilistic Neural Network (PNN) classifier, the exhaustive search features selection, the leave-one-out (LOO), and the external cross-validation (ECV) methods were used to design the PR-system for discriminating between moles and melanomas. RESULTS: Statistical analysis revealed that melanomas as compared to moles were of lower intensity, of less homogenous surface, had more dark pixels with intensities spanning larger spectra of gray-values, contained more objects of different sizes and gray-levels, had more asymmetrical shapes and irregular outlines, had abrupt intensity transitions from lesion to background tissue, and had more distinct colors. The PR-system designed by the Dermofit images scored on the Dermofit images, using the ECV, 94.1%, 82.9%, 96.5% for overall accuracy, sensitivity, specificity, on the Multicenter Images 92.0%, 88%, 93.7% and on the Groningen Images 76.2%, 73.9%, 77.8% respectively. CONCLUSION: The PR-system as designed by the Dermofit image database could be fine-tuned to classify with good accuracy plain photography moles/melanomas images of other databases employing different image capturing equipment and protocols.

Level of consciousness as a conditioning factor of F wave generation in stroke patients.

OBJECTIVE: The current study aimed to investigate whether the level of consciousness influenced the F wave generation, as an independent factor. METHODS: Forty three patients with acute stroke were divided according to their level of consciousness in two groups; to those with Glasgow scale (GCS) score 3-7 indicating coma (group I) and those with GCS score 8-15 (group II). A series of 40 electrical stimuli were delivered to the ulnar nerve bilaterally in order to obtain F waves. The following variables were estimated and then compared between groups: F persistence, F wave latency, amplitude and duration. All studies were performed within 3 days from the onset of the stroke symptoms. RESULTS: The main finding to emerge was the significantly reduced F wave persistence in the group of patients with low GCS score as opposed to patients allocated in the group with GCS score 8-15. This result is referred to F waves obtained from both the affected and unaffected limb. F wave minimum latency was also prolonged in the group with low GCS score, whilst the comparison of all other F wave variables revealed no significant differences between groups I and II. F wave persistence measurements did not differ between the affected and unaffected sides. Stroke location and type (ischemic or hemorrhagic) were not associated with alterations of F wave measurements. CONCLUSIONS: Our results on stroke patients suggest that generation of F waves, expressed by the F wave persistence is associated with the level of consciousness. SIGNIFICANCE: F wave study may be useful as an objective measure in documenting the severity of consciousness impairment.

Identification of iodine deficiency in the field by the rapid urinary iodide test: comparison with the classic Sandell-Kolthoff reaction method.

The two traditional methods for the assessment of iodine deficiency in a given area are the estimation of urinary excretion of iodine, and the prevalence of goiter. In field studies, the estimation of urinary iodine excretion (UIE) in random urine specimens provides an adequate assessment of a population's iodine nutrition. The recommended method is the classic one, based on Sandell-Kolthoff reaction (Method A). Recently, a new semi-quantitative method has been introduced (rapid urinary iodide test [RUIT]). We performed a field study in a developing country (Azerbaijan) in order to compare the classic Method A to RUIT. The study included 942 schoolchildren, to whom UIE was estimated by RUIT. Comparing the two methods, (n = 260), the sensitivity of RUIT using as gold standard Method A, was 96% and the specificity was 61%. The correlation between median values UIE estimated by RUIT and by Method A was excellent (r = 0.98, p < 0.001). An agreement in iodine deficiency classification according to the World Health Organization-United Nations Children's Fund-International Council for the Control of Iodine-Deficiency Disorders (WHO-UNICEF-ICCIDD) between the two methods was observed in eight of nine areas. In conclusion, RUIT is a suitable method for UIE estimation in field studies of suspected iodine deficiency. The test is relatively inexpensive, easy to perform, and does not require sophisticated instruments.

CT angiography with three-dimensional techniques for the early diagnosis of intracranial aneurysms. Comparison with intra-arterial DSA and the surgical findings.

INTRODUCTION: Cerebral CT angiography (CTA) is an established method applied to both the detection and treatment planning of intracranial aneurysms. The aim of our study was to compare CTA and digital subtraction angiography (DSA) findings with the surgical results mainly in patients with acute SAH and to evaluate the clinical usefulness of CTA. MATERIALS AND METHODS: During the last 2 years, 82 consecutive patients were admitted under clinical symptoms and signs suggestive of harboring an intracranial aneurysm. CT angiography performed immediately afterwards the plain CT, while DSA was performed within the first 48 h of admission. All aneurysms detected were confirmed during surgery or endovascular embolization. Repeat DSA was performed in all patients having both the initial CTA and the DSA 15 days after the onset of symptoms negative. CT angiograms and conventional angiographies were studied by a consensus of two radiologists for each technique, who performed aneurysm detection, morphological features characterization and evaluation of the technique. RESULTS: Surgical or/and endovascular treatment was performed in 45 patients and 53 aneurysms were confirmed. Using 3D-CT angiography, we detected 47 aneurysms in 42 patients. Conventional angiography depicted 43 aneurysms in 39 patients. The sensitivity of CTA for the detection of all aneurysms versus surgery was 88.7%, the specificity 100%, the positive predictive value (PPV) 100%, the negative predictive value (NPV) 80.7% and the accuracy 92.3%. Accordingly, the sensitivity of DSA was 87.8%, the specificity 98%, the PPV 97.7%, the NPV 89.1% and the accuracy 92.9%. Considering aneurysms > or =3 mm, CTA showed a sensitivity ranging from 93.3 to 100%, equal to that of DSA. CONCLUSION: Cerebral CT angiography has an equal sensitivity to DSA in the detection of intracranial aneurysms >3 mm. It has also 100% detection rate in AcoA and MCA bifurcation aneurysms, while some locations, like posterior communicating artery aneurysms, remain problematic. The delineating features of each aneurysm are better depicted with CTA due to 3D visualization. The use of digital subtraction angiography as a diagnostic tool can be limited in equivocal cases.

Motor unit number estimation and quantitative needle electromyography in stroke patients.

OBJECTIVE: To evaluate the effect of upper motor neuron damage upon motor units' function by means of two separate and supplementary electrophysiological methods. METHODS: The abductor digiti minimi muscle of the non-paretic and the paretic side was studied in forty-six stroke patients with (a) motor unit number estimation (MUNE) - adapted multiple point stimulation method and (b) computerized quantitative needle electromyography (EMG) assessing the configuration of voluntary recruited motor unit potentials. Main outcome comparisons were focused on differences between non-paretic and paretic side. RESULTS: On the affected hands mean MUNE value was significantly lower and mean area of the surface recorded single motor unit potentials was significantly larger than the corresponding ones on the non-paretic hands. EMG findings did not reveal remarkable differences between the two sides. Neither severity nor chronicity of stroke was related to MUNE or EMG parameters. DISCUSSION: MUNE results, which suggested reduced motor unit numbers in stroke patients, in conjunction with the normal EMG features in these same muscles has given rise to different interpretations. In a clinical setting, reinnervation type changes in the EMG similar to that occurring in neuronopathies or axonal neuropathies should not be expected in muscles with central neurogenic lesion.

Pregnancy outcomes and nutritional indices after 3 types of bariatric surgery performed at a single institution.

BACKGROUND: Nutritional status during pregnancy and the effects of nutritional deficiencies on pregnancy outcomes after bariatric surgery is an important issue that warrants further study. The objective of this study was to investigate pregnancy outcomes and nutritional indices after restrictive and malabsorptive procedures. METHODS: We investigated pregnancy outcomes of 113 women who gave birth to 150 children after biliopancreatic diversion (BPD), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) between June 1994 and December 2011. Biochemical indices and pregnancy outcomes were compared among the different types of surgery and to overall 20-year hospital data, as well as to 56 presurgery pregnancies in 36 women of the same group. RESULTS: Anemia was observed in 24.2% and 15.6% of pregnancies after BPD and RYGB, respectively. Vitamin B12 levels decreased postoperatively in all groups, with no further decrease during pregnancy; however, low levels were observed not only after BPD (11.7%) and RYGB (15.6%), but also after SG (13.3%). Folic acid levels increased. Serum albumin levels decreased in all groups during pregnancy, but hypoproteinemia was seen only after BPD. Neonates after BPD had significantly lower average birth weight without a higher frequency of low birth weight defined as<2500 g. A comparison of neonatal data between babies born before surgery and siblings born after surgery (AS) showed that AS newborns had lower average birth weight with no significant differences in body length or head circumference and no cases of macrosomia. CONCLUSION: Our study showed reasonably good pregnancy outcomes in this sample population after all types of bariatric surgery provided nutritional supplement guidelines are followed. Closer monitoring is required in pregnancies after malabsorptive procedures especially regarding protein nutrition.

Improved levothyroxine pharmacokinetics after bariatric surgery.

BACKGROUND: The absorption of levothyroxine (LT4) is affected by many factors. Bariatric surgery is recommended in severely obese patients. The aim of this study was to determine the consequences of bariatric surgery on LT4 pharmacokinetic parameters, and to identify the regions of the gastrointestinal tract where LT4 is absorbed in patients with severe obesity before and after surgery. METHODS: We studied 32 severely obese nonhypothyroid patients who underwent sleeve gastrectomy (SG; n=10), Roux-en-Y gastric bypass (RYGBP; n=7), or biliopancreatic diversion with long limbs (BPD-LL; n=15). Before surgery, from 8:00 a.m., blood samples were collected before and every 30 minutes after the oral administration of a solution of 600 µg of LT4. The same procedure was repeated 35 days after surgery. We estimated the pharmacokinetic parameters of LT4 before and after surgery, including the area under the curve (AUC), the peak thyroxine concentration (Cmax), and the time to peak thyroxine concentration (Tmax). RESULTS: Following surgery, in the SG group, the mean AUC was higher than it was before surgery (18.97±6.01 vs. 25.048±6.47 [µg/dL]·h; p<0.01), whereas the values of Cmax and Tmax were similar to those before surgery. In the RYGBP group, mean AUC, Cmax, and Tmax were similar before and after surgery. In the BPD-LL group, mean AUC and Cmax were higher after surgery than before (14.18±5.64 vs. 25.51±9.1 [µg/dL]·h, p<0.001; 5.62±1.34 vs. 8.16±2.57 µg/dL, p<0.001, respectively), whereas Tmax was similar. CONCLUSIONS: The pharmacokinetic parameters of LT4 absorption are improved following SG and BPD-LL types of bariatric procedures. We conclude that the stomach, the duodenum, and the upper part of the jejunum are not sites for LT4 absorption, because in the above-mentioned bariatric procedures these are bypassed or removed.

The effect of prolonged aerobic exercise on serum adipokine levels during an ultra-marathon endurance race.

OBJECTIVE: To evaluate the effect of prolonged intensive aerobic exercise and acute energy deficit (180 km ultra-marathon race) on serum leptin, adiponectin, resistin and visfatin levels and their association and interaction with serum cortisol and insulin levels in highly trained ultra-endurance runners. DESIGN: The study included 17 highly trained ultra-endurance male athletes (mean age 51.29±6.84 years and body mass index (ΒΜΙ) 23.51±1.90) participating in the 5th Olympian Race held in Greece on May 2010. Anthropometric values were assessed; Serum cortisol, insulin, leptin, adiponectin, resistin and visfatin levels were measured at baseline, post-exercise and ~20 hours after the end of the race. RESULTS: All hormonal values of the post-exercise and recovery status were corrected for plasma volume changes. The estimated energy deficit during the ultra-endurance event was about 5000 Kcal. At the end of the race serum resistin levels were elevated (p<0.001) and serum leptin levels were reduced (p<0.001) and failed to reach pre-exercise levels, although showing a tendency towards restoration. No significant changes were noted in serum adiponectin and visfatin levels. CONCLUSIONS: Ultra-endurance aerobic exercise and acute negative energy balance lead to an up-regulation of serum resistin levels and a down-regulation of serum leptin levels.

Qualitative characteristics of HDL in young patients of an acute myocardial infarction.

AIM: Recently, the concept that high density lipoprotein (HDL) quality is an important parameter for atheroprotection is gaining ground, though little data exists so far to support it. In an attempt to identify measurable qualitative parameters of HDL associated with increased risk for premature myocardial infarction (MI), we studied the structural characteristics of HDL from patients who survived an MI at a young age (≤35 years). METHODS AND RESULTS: We studied 20 MI patients and 20 healthy control subjects. HDL of patients had reduced apolipoprotein A-I (apoA-I), apolipoprotein M, and paraoxonase 1 levels and significantly elevated apolipoprotein C-III (apoCIII) levels (all p<0.05). Specifically, the HDL apoA-I/apoC-III ratio was 0.24±0.01 in patients versus 4.88±0.90 in controls (p<0.001). These structural alterations correlated with increased oxidation potential of HDL of the MI group compared to controls (2.5-fold, p=0.026). Electron microscopy showed no significant difference in average HDL particle diameter between the two groups though a significant difference existed in HDL diameter distribution, suggesting the presence of different HDL subpopulations in MI and control subjects. Indeed, non-denaturing two-dimensional electrophoresis revealed that MI patients had reduced pre-ß1(α), pre-ß1(b) and α(2), and elevated α(1), α(3), and pre-α(4) HDL. CONCLUSIONS: Reduction in the HDL apoA-I/apoC-III ratio, changes in the HDL subpopulation distribution and an increase in HDL oxidation potential correlated with the development of MI in young patients. The possibility that such changes may serve as markers for the early identification of young individuals at high risk for an acute coronary event should be further explored.