Liver synthesis function in chronic asymptomatic or oligosymptomatic alcoholics: correlation with other liver tests

Liver function and its correlation with bilirubin and hepatic enzymes were evaluated in 30 male chronic asymptomatic or oligosymptomatic alcoholics admitted into the psychiatric hospital for detoxification and treatment of alcoholism. Hypoalbuminemia, lowered prothrombin activity, hypotransferrinemia and hypofibrinogenemia were detected in 32 %, 32 %, 28 %, and 24 % of patients, respectively. Transferrin was elevated in 8 %. Greater prevalence of hyperbilirubinemia was found in patients with lowered prothrombin activity, hypofibrinogenemia, or hypotransferrinemia. No correlation was found between serum bilirubin or aminotransferase levels and normal or elevated albumin levels, time or activity of prothrombin, and fibrinogen levels. Serum alkaline phosphatase was elevated in normoalbuminemics and gamma-glutamyltransferase in patients with lowered prothrombin activity. Hypoalbuminemia was associated with hypofibrinogenemia, hypotransferrinemia with elevated aspartate aminotransferase or gamma-glutamyltransferase, and hypertransferrinemia with elevation of alanine aminotransferase. These data indicated the occurrence of hepatic dysfunction due to liver damage caused directly by alcohol or by alcoholism-associated nutritional deficiencies.

Systematic study of the static electrical properties of the CO molecule: influence of the basis set size and correlation energy

The influence of the basis set size and the correlation energy in the static electrical properties of the CO molecule is assessed. In particular, we have studied both the nuclear relaxation and the vibrational contributions to the static molecular electrical properties, the vibrational Stark effect (VSE) and the vibrational intensity effect (VIE). From a mathematical point of view, when a static and uniform electric field is applied to a molecule, the energy of this system can be expressed in terms of a double power series with respect to the bond length and to the field strength. From the power series expansion of the potential energy, field-dependent expressions for the equilibrium geometry, for the potential energy and for the force constant are obtained. The nuclear relaxation and vibrational contributions to the molecular electrical properties are analyzed in terms of the derivatives of the electronic molecular properties. In general, the results presented show that accurate inclusion of the correlation energy and large basis sets are needed to calculate the molecular electrical properties and their derivatives with respect to either nuclear displacements or/and field strength. With respect to experimental data, the calculated power series coefficients are overestimated by the SCF, CISD, and QCISD methods. On the contrary, perturbation methods (MP2 and MP4) tend to underestimate them. In average and using the 6-311 + G(3df) basis set and for the CO molecule, the nuclear relaxation and the vibrational contributions to the molecular electrical properties amount to 11.7%, 3.3%, and 69.7% of the purely electronic μ, α, and β values, respectively

The daily energy expenditure in stable chronic obstructive pulmonary disease.

Resting energy expenditure is frequently increased in chronic obstructive pulmonary disease (COPD), but it is unknown if this hypermetabolism holds true over 24 h. The aim of this study was to measure the actual 24-h energy expenditure (24-h EE) in patients with stable COPD. Energy expenditure was measured by indirect calorimetry, using a metabolic chamber for 24-h EE and a canopy for basal metabolic rate (BMR). Physical activity was detected in the chamber by a radar system, and its duration was quantified. Two groups matched for age and height were studied: 16 male ambulatory patients with stable COPD and 12 male normal subjects. Body weight was 92 +/- 12% of ideal body weight in the group with COPD and 108 +/- 11% in the control group (p = 0.01). BMR was 120 +/- 7% of predicted in the group with COPD and 108 +/- 12% in the control group (p < 0.01). However, 24-h EE was similar in the two groups, amounting to 1,935 +/- 259 kcal in patients with COPD and 2,046 +/- 253 kcal in the control group (NS). This corresponded to 145% and 137% of predicted BMR, and to 121% and 126% of measured BMR in patients with COPD and the control group, respectively (NS). Patients were allowed to pursue their usual treatment within the chamber, and a positive correlation existed between 24-h EE and the daily dose of inhaled beta 2-agonists (p < 0.03). During daytime, physical activity was lower in patients with COPD. This study shows that patients with stable COPD are characterized by a normal daily energy expenditure in controlled conditions in spite of an increased basal metabolic rate. They appear to save energy by reducing their spontaneous level of physical activity.

Flow cytofluorometric analysis of the binding of Vicia villosa lectin to T lymphoblasts: lack of correlation with cytolytic function.

The relationship between the binding of Vicia villosa (VV) lectin and the expression of cytolytic function in T lymphoblasts has been investigated using flow cytofluorometric techniques. Spleen cells activated in vitro in 5-day mixed leukocyte cultures (MLC) were incubated sequentially with VV, rabbit anti-V antiserum, and fluoresceinated sheep anti-rabbit IgG. When these stained MLC cells were passed on a flow cytometer gated to exclude nonviable cells and small lymphocytes, a single heterogeneous peak of fluorescence was seen, as compared to control MLC cells that had not been incubated with VV. Fluorescence of lymphoblasts was dependent upon lectin dose and was eliminated when staining was performed in the presence of N-acetyl-D-galactosamine, the appropriate competitive sugar for VV. T cell blast populations activated against H-2, Mls, or parasite antigens all had comparable levels of fluorescence after staining with VV, although the cytolytic activity of these cells varied widely. Furthermore, when MLC lymphoblasts binding large or small amounts of VV were sorted on the basis of their relative fluorescence intensity and tested for cytolytic function, no appreciable difference in activity between the 2 populations was observed. These results are inconsistent with the hypothesis that VV binds selectively to cytolytic T lymphocytes.

Energy and structure of dilute hard- and soft-sphere gases

The energy and structure of dilute hard- and soft-sphere Bose gases are systematically studied in the framework of several many-body approaches, such as the variational correlated theory, the Bogoliubov model, and the uniform limit approximation, valid in the weak-interaction regime. When possible, the results are compared with the exact diffusion Monte Carlo ones. Jastrow-type correlation provides a good description of the systems, both hard- and soft-spheres, if the hypernetted chain energy functional is freely minimized and the resulting Euler equation is solved. The study of the soft-sphere potentials confirms the appearance of a dependence of the energy on the shape of the potential at gas paremeter values of x~0.001. For quantities other than the energy, such as the radial distribution functions and the momentum distributions, the dependence appears at any value of x. The occurrence of a maximum in the radial distribution function, in the momentum distribution, and in the excitation spectrum is a natural effect of the correlations when x increases. The asymptotic behaviors of the functions characterizing the structure of the systems are also investigated. The uniform limit approach is very easy to implement and provides a good description of the soft-sphere gas. Its reliability improves when the interaction weakens.

Effect of elective antibiotic therapy on resting energy expenditure and inflammation in cystic fibrosis.

Cystic fibrosis (CF) patients often present with malnutrition which may partly be due to increased resting energy expenditure (REE) secondary to inflammation. Both REE and tumour necrosis factor-alpha (TNF-alpha), as other markers of inflammation, are elevated during respiratory exacerbations and decrease after antibiotic treatment. However, the effect of antibiotic therapy on REE and inflammation in patients without respiratory exacerbation is not known. The aim of our study was to determine the effect of such an elective antibiotic therapy on REE, TNF-alpha, and other serum markers of inflammation. Twelve CF patients 5F/7M, age 15.9 +/- 6.1 years, weight for height ratio 89 +/- 8% without clinically obvious exacerbation and treated by intravenous antibiotics were studied. Both before (D0) and after (D14) treatment, pulmonary function tests were performed. REE was measured by indirect calorimetry and blood taken to measure inflammation parameters. Body weight increased by 1.1 kg from D0 to D14 (P < 0.001), composed of 0.3 kg fat mass and 0.8 kg fat-free mass (FFM). The forced expiratory volume at 1 s increased from 43 +/- 15% of predicted at D0 to 51 +/- 15% of predicted at D14 (P < 0.01). Mean REE was 41.1 +/- 7.6 kcal/kg FFM per day at D0 and did not change significantly at D14 (40.6 +/- 8.5 kcal/kg FFM per day). Serum markers of inflammation decreased from D0 to D14: C-reactive protein 17 +/- 17 mg/l to 4 +/- 7 mg/l (P < 0.05), elastase 62 +/- 29 microg/l to 45 +/- 18 microg/l (P < 0.02), orosomucoid acid 1.25 +/- 0.11 g/l to 0.80 +/- 0.15 g/l (P < 0.001), and TNF-alpha 37 +/- 14 pg/ml to 29 +/- 6 pg/ml (P = 0.05). Individual values showed a correlation between changes in REE and in TNF-alpha (P < 0.02). The contribution of inflammation to energy expenditure is possible but appears to be minimal in cystic fibrosis patients treated by antibiotics on a regular basis in the absence of clinically obvious exacerbation.

Food for thought: the importance of glucose and other energy substrates for sustaining brain function under varying levels of activity.

The brain requires a constant and substantial energy supply to maintain its main functions. For decades, it was assumed that glucose was the major if not the only significant source of energy for neurons. This view was supported by the expression of specific facilitative glucose transporters on cerebral blood vessels, as well as neurons. Despite the fact that glucose remains a key energetic substrate for the brain, growing evidence suggests a different scenario. Thus astrocytes, a major type of glial cells that express their own glucose transporter, play a critical role in coupling synaptic activity with glucose utilization. It was shown that glutamatergic activity triggers an enhancement of aerobic glycolysis in this cell type. As a result, lactate is provided to neurons as an additional energy substrate. Indeed, lactate has proven to be a preferential energy substrate for neurons under various conditions. A family of proton-linked carriers known as monocarboxylate transporters has been described and specific members have been found to be expressed by endothelial cells, astrocytes and neurons. Moreover, these transporters are subject to fine regulation of their expression levels and localization, notably in neurons, which suggests that lactate supply could be adjusted as a function of their level of activity. Considering the importance of energetics in the aetiology of several neurodegenerative diseases, a better understanding of its cellular and molecular underpinnings might have important implications for the future development of neuroprotective strategies.

Structural assessment of single amino acid mutations: application to TP53 function.

Single amino acid substitution is the type of protein alteration most related to human diseases. Current studies seek primarily to distinguish neutral mutations from harmful ones. Very few methods offer an explanation of the final prediction result in terms of the probable structural or functional effect on the protein. In this study, we describe the use of three novel parameters to identify experimentally-verified critical residues of the TP53 protein (p53). The first two parameters make use of a surface clustering method to calculate the protein surface area of highly conserved regions or regions with high nonlocal atomic interaction energy (ANOLEA) score. These parameters help identify important functional regions on the surface of a protein. The last parameter involves the use of a new method for pseudobinding free-energy estimation to specifically probe the importance of residue side-chains to the stability of protein fold. A decision tree was designed to optimally combine these three parameters. The result was compared to the functional data stored in the International Agency for Research on Cancer (IARC) TP53 mutation database. The final prediction achieved a prediction accuracy of 70% and a Matthews correlation coefficient of 0.45. It also showed a high specificity of 91.8%. Mutations in the 85 correctly identified important residues represented 81.7% of the total mutations recorded in the database. In addition, the method was able to correctly assign a probable functional or structural role to the residues. Such information could be critical for the interpretation and prediction of the effect of missense mutations, as it not only provided the fundamental explanation of the observed effect, but also helped design the most appropriate laboratory experiment to verify the prediction results.

Neutrophil function and metabolism in individuals with diabetes mellitus

Neutrophils act as first-line-of-defense cells and the reduction of their functional activity contributes to the high susceptibilityto and severity of infections in diabetes mellitus. Clinical investigations in diabetic patients and experimental studies in diabetic rats and mice clearly demonstrated consistent defects of neutrophil chemotactic, phagocytic and microbicidal activities. Other alterations that have been reported to occur during inflammation in diabetes mellitus include: decreased microvascular responses to inflammatory mediators such as histamine and bradykinin, reduced protein leakage and edema formation, reduced mast cell degranulation, impairment of neutrophil adhesionto the endothelium and migration to the site of inflammation, production of reactive oxygen species and reduced release of cytokines and prostaglandin by neutrophils, increased leukocyte apoptosis, and reduction in lymph node retention capacity. Since neutrophil function requires energy, metabolic changes (i.e., glycolytic and glutaminolytic pathways) may be involved in the reduction of neutrophil function observed in diabetic states. Metabolic routes by which hyperglycemia is linked to neutrophil dysfunction include the advanced protein glycosylation reaction, the polyol pathway, oxygen-free radical formation, the nitric oxide-cyclic guanosine-3'-5'monophosphate pathway, and the glycolytic and glutaminolytic pathways. Lowering of blood glucose levels by insulin treatment of diabetic patients or experimental animals has been reported to have significant correlation with improvement of neutrophil functional activity. Therefore, changes might be primarily linked to a continuing insulin deficiency or to secondary hyperglycemia occurring in the diabetic individual. Accordingly, effective control with insulin treatment is likely to be relevant during infection in diabetic patients.

Correlation between heart rate variability and pulmonary function adjusted by confounding factors in healthy adults

The autonomic nervous system maintains homeostasis, which is the state of balance in the body. That balance can be determined simply and noninvasively by evaluating heart rate variability (HRV). However, independently of autonomic control of the heart, HRV can be influenced by other factors, such as respiratory parameters. Little is known about the relationship between HRV and spirometric indices. In this study, our objective was to determine whether HRV correlates with spirometric indices in adults without cardiopulmonary disease, considering the main confounders (e.g., smoking and physical inactivity). In a sample of 119 asymptomatic adults (age 20-80 years), we evaluated forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). We evaluated resting HRV indices within a 5-min window in the middle of a 10-min recording period, thereafter analyzing time and frequency domains. To evaluate daily physical activity, we instructed participants to use a triaxial accelerometer for 7 days. Physical inactivity was defined as <150 min/week of moderate to intense physical activity. We found that FVC and FEV1, respectively, correlated significantly with the following aspects of the RR interval: standard deviation of the RR intervals (r =0.31 and 0.35), low-frequency component (r =0.38 and 0.40), and Poincaré plot SD2 (r =0.34 and 0.36). Multivariate regression analysis, adjusted for age, sex, smoking, physical inactivity, and cardiovascular risk, identified the SD2 and dyslipidemia as independent predictors of FVC and FEV1 (R2=0.125 and 0.180, respectively, for both). We conclude that pulmonary function is influenced by autonomic control of cardiovascular function, independently of the main confounders.

Synechococcus sp. PCC 7002 CpcB lyase null mutations alter phycocyanin chromophore function and, consequently, affect the redistribution of excitation energy via the light state transition /

Phycobilisomes are the major light harvesting complexes for cyanobacteria and phycocyanin is the primary phycobiliprotein of the phycobilisome rod. The phycocyanobilin lyases responsible for chromophorylating the phycocyanin p subunit (CpcB) have been recently identified in the cyanobacterium Synechococcus sp. PCC 7002. Surprisingly, mutants missing the CpcB lyases were nevertheless capable of producing pigmented phycocyanin. 10K absorbance measurements revealed that the energy states of the p phycocyanin chromophores were only subtly shifted; however, 77K steady state fluorescence emission spectroscopy showed excitation energy transfer involving the targeted chromophores to be highly disrupted. Such evidence suggests that phycobilin orientation within the binding domain is specifically modified. We hypothesized that alternate, less specific lyases are able to act on the p binding sites. A phycocyanin linker-polypeptide deficient mutant was similarly characterized. The light state transition, a short term adaptation of the photosynthetic light harvesting apparatus resulting in the redistribution of excitation energy among the photo systems, was shown to be dominated by the reallocation of phycocyanin-absorbed excitation energy. Treatment with a high M phosphate buffer effectively prevented the redistribution of both chlorophyll a- and phycobilisome- absorbed excitation energy, suggesting that the two effects are not strictly independent. The mutant strains required a larger redistribution of excitation energy between light states, perhaps to compensate for their loss in phycobilisome antenna function.

Electron energy loss spectroscopy assessment of cationic migration in La2/3Ca1/3MnO3 thin films

Màster en Nanociència i Nanotecnologia curs 2006-2007. Directors: Francesca Peiró i Martínez and Jordi Arbiol i Cobos

Ground state correlation energy of the Be-sequence for Z = 4-20 in MCDF approximation

The ground state (J = 0) electronic correlation energy of the 4-electron Be-sequence is calculated in the Multi-Configuration Dirac-Fock approximation for Z = 4-20. The 4 electrons were distributed over the configurations arising from the 1s, 2s, 2p, 3s, 3p and 3d orbitals. Theoretical values obtained here are in good agreement with experimental correlation energies.

Estimation of the ground state correlation energy for isoelectronic series of 2 to 20 electrons

Correlation energies for all isoelectronic sequences of 2 to 20 electrons and Z = 2 to 25 are obtained by taking differences between theoretical total energies of Dirac-Fock calculations and experimental total energies. These are pure relativistic correlation energies because relativistic and QED effects are already taken care of. The theoretical as well as the experimental values are analysed critically in order to get values as accurate as possible. The correlation energies obtained show an essentially consistent behaviour from Z = 2 to 17. For Z > 17 inconsistencies occur indicating errors in the experimental values which become very large for Z > 25.

Systematic study of the static electrical properties of the CO molecule: influence of the basis set size and correlation energy

The influence of the basis set size and the correlation energy in the static electrical properties of the CO molecule is assessed. In particular, we have studied both the nuclear relaxation and the vibrational contributions to the static molecular electrical properties, the vibrational Stark effect (VSE) and the vibrational intensity effect (VIE). From a mathematical point of view, when a static and uniform electric field is applied to a molecule, the energy of this system can be expressed in terms of a double power series with respect to the bond length and to the field strength. From the power series expansion of the potential energy, field-dependent expressions for the equilibrium geometry, for the potential energy and for the force constant are obtained. The nuclear relaxation and vibrational contributions to the molecular electrical properties are analyzed in terms of the derivatives of the electronic molecular properties. In general, the results presented show that accurate inclusion of the correlation energy and large basis sets are needed to calculate the molecular electrical properties and their derivatives with respect to either nuclear displacements or/and field strength. With respect to experimental data, the calculated power series coefficients are overestimated by the SCF, CISD, and QCISD methods. On the contrary, perturbation methods (MP2 and MP4) tend to underestimate them. In average and using the 6-311 + G(3df) basis set and for the CO molecule, the nuclear relaxation and the vibrational contributions to the molecular electrical properties amount to 11.7%, 3.3%, and 69.7% of the purely electronic μ, α, and β values, respectively