Search PubMed⌕ Search

Biomedical subjects

A Sorribas

Publications and source records attributed to A Sorribas.

27 records · Page 2Linked to original sources
PubMed1989

A comparison of variant theories of intact biochemical systems. II. Flux-oriented and metabolic control theories.

In the past two decades, several theories, all ultimately based upon the same power-law formalism, have been proposed to relate the behavior of intact biochemical systems to the properties of their underlying determinants. Confusion concerning the relatedness of these alternatives has become acute because the implications of these theories have never been compared. In the preceding paper we characterized a specific system involving enzyme-enzyme interactions for reference in comparing alternative theories. We also analyzed the reference system by using an explicit variant that involves the S-system representation within biochemical systems theory (BST). We now analyze the same reference system according to two other variants within BST. First, we carry out the analysis by using an explicit variant that involves the generalized mass action representation, which includes the flux-oriented theory of Crabtree and Newsholme as a special case. Second, we carry out the analysis by using an implicit variant that involves the generalized mass action representation, which includes the metabolic control theory of Kacser and his colleagues as a special case. The explicit variants are found to provide a more complete characterization of the reference system than the implicit variants. Within each of these variant classes, the S-system representation is shown to be more mathematically tractable and accurate than the generalized mass action representation. The results allow one to make clear distinctions among the variant theories.

Biochemical Phenomena↗
PubMed1989

Strategies for representing metabolic pathways within biochemical systems theory: reversible pathways.

The search for systematic methods to deal with the integrated behavior of complex biochemical systems has over the past two decades led to the proposal of several theories of biochemical systems. Among the most promising is biochemical systems theory (BST). Recent comparisons of this theory with several others that have recently been proposed have demonstrated that all are variants of BST and share a common underlying formalism. Hence, the different variants can be precisely related and ranked according to their completeness and operational utility. The original and most fruitful variant within BST is based on a particular representation, called an S-system (for synergistic and saturable systems), that exhibits many advantages not found among alternative representations. Even within the preferred S-system representation there are options, depending on the method of aggregating fluxes, that become especially apparent when one considers reversible pathways. In this paper we focus on the paradigm situation and clearly distinguish the two most common strategies for generating an S-system representation. The first is called the "reversible" strategy because it involves aggregating incoming fluxes separately from outgoing fluxes for each metabolite to define a net flux that can be positive, negative, or zero. The second is the "irreversible" strategy, which involves aggregating forward and reverse fluxes through each reaction to define a net flux that is always positive. This second strategy has been used almost exclusively in all variants of BST. The principal results of detailed analyses are the following: (1) All S-system representations predict the same changes in dependent concentrations for a given change in an independent concentration. (2) The reversible strategy is superior to the irreversible on the basis of several criteria, including accuracy in predicting steady-state flux, accuracy in predicting transient responses, and robustness of representation. (3) Only the reversible strategy yields a representation that is able to capture the characteristic feature of amphibolic pathways, namely, the reversal of nets flux under physiological conditions. Finally, the results document the wide range of variation over which the S-system representation can accurately predict the behavior of intact biochemical systems and confirm similar results of earlier studies [Voit and Savageau, Biochemistry 26: 6869-6880 (1987)].

Biochemical Phenomena↗
PubMed1989

Correlation of plasma lipid fractions with colorimetrically determined glycated hemoglobin in a nondiabetic population.

To evaluate the incidence of protein glycation (measured as glycated hemoglobin) on plasma lipid levels in a free-living population, a colorimetric method has been used to detect 5-hydroxymethylforfural (HMF) released from glycated hemoglobin (GHb) and enzymatic methods have been used to evaluate total cholesterol, high-density lipoprotein (HDL) cholesterol, fasting glycemia, and total plasma triacylglycerides. These results have been used to calculate low-density lipoprotein-(LDL) cholesterol levels with the Friedewald formula. Results show that a positive correlation exists in men, but not in premenopausal women, between GHb and fasting glycemia (P less than 10(-14], GHb and total plasma cholesterol (P less than .001), GHb and LDL cholesterol (P less than .0001), and GHb with the atherogenic index total/HDL cholesterol (P less than .0001), whereas a negative correlation was shown between GHb and HDL cholesterol (P less than .05). Fasting glycemia does not correlate with cholesterol lipoprotein fractions, but correlates well with total triacylglycerides. These correlations are significant when they are adjusted by age and body mass index. It has also been observed that the positive correlation between glycation of hemoglobin and total cholesterol occurs constantly at all glycohemoglobin levels, and affects all cholesterol fractions analyzed. This suggests an increased atherogenicity with increasing glycohemoglobin levels. Comparisons between groups with high and low GHb levels show variations in the order of 6.5% of total cholesterol levels and a major proportion in the different cholesterol fractions. The higher-range "glycated" populations show total cholesterol, LDL cholesterol and HDL cholesterol values significantly different from the lower-range "glycated" population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Apolipoprotein C subtype distribution in type 2 diabetes mellitus.

Plasma lipid levels and apolipoprotein C (apo C) composition of VLDL were investigated in a group of Type 2 diabetic patients at first attendance at the outpatient clinic and before any therapeutic intervention. Patients were distributed into two groups of 26 individuals, normo- and hyperlipidaemic, respectively, and compared with two matched control groups. Normolipidaemic diabetic patients had higher serum triglycerides, VLDL cholesterol, and lower HDL cholesterol than matched normolipidaemic control subjects. While hyperlipidaemic non-diabetic individuals showed increased apo C II and decreased apo C III-1 percentages when compared with normolipidaemic non-diabetic individuals (12.1 +/- 4.9 vs 8.5 +/- 3.2% and 44.0 +/- 6.7 vs 48.1 +/- 7.0%, respectively, mean +/- SD, both with p less than 0.05), the relative distribution of apo C III isoforms and apo C II was similar in both normo- and hyperlipidaemic diabetic patients.

Apolipoproteins C↗
PubMed1986

Theoretical analysis of the flux control properties of a substrate cycle.

Substrate cycles are able to increase the flux control of a non-equilibrium reaction in a wide range of situations related to the effects of the metabolites involved in the cycle on the reaction producing them. No limit exists for that amplification if appropriate conditions are attained if those effects are positive. In all cases, the ratio between the rate of the reverse reaction and the net flux through the pathway plays an important role in defining the final amplification.

Enzymes↗
PubMed1983

[Assessment of cardiovascular tests in the diagnosis of diabetic autonomic neuropathies].

Eight tests for cardiovascular reflex function were evaluated in a group of 140 diabetic patients. The sensitivity, reproducibility and normal values of each test were previously assessed in a group of 70 normal controls. The measure of the R-R interval variation during six cycles of deep breathing (expiration/inspiration ratio) proved to be the most sensitive test, and was selected for screening. The Valsalva ratio, the bradycardia/tachycardia ratio post-standing and the blood pressure response to standing and to sustained handgrip served as a confirmatory test of autonomic neuropathy and were related to the severity of the lesion. The R-R interval variation during one deep breathing cycle, the post-standing tachycardia, and the R-R 30/15 standing ratio proved to be of little or not value in assessing cardiovascular neuropathy. Cardiovascular autonomic neuropathy was diagnosed in 38.5% of our diabetic population, predominantly in patients with other clinical evidence of autonomic neuropathy. In a few asymptomatic patients, abnormal cardiovascular responses were the first evidence of autonomic lesion.

Adolescent↗
PubMedDate not supplied

[Application of artificial neural networks for risk stratification of hospital mortality].

OBJECTIVE: To compare the ability of an artificial neural network (ANN) to predict hospital mortality with that of the Acute Physiology and Chronic Health Evaluation II (APACHE II) system and multiple logistic regression (LR). A secondary objective was to compare the allocation of individual probability among the models. METHOD: The variables required for calculating the APACHE II were prospectively collected. A total of 1146 patients were divided (randomly 70% and 30%) into the Development (800) and the Validation (346) sets. With the same variables an LR model and an ANN were carried out (a 3-layer perceptron trained by algorithm backpropagation with bootstrap resampling and with 9 nodes in the hidden layer) in the Development set. The models developed were contrasted with the Validation set and their discrimination properties were evaluated using the area under the ROC curve (AUC [95% CI]) and calibration with the Hosmer-Lemeshow C (HLC) test. Differences between the probabilities were evaluated using the Bland-Altman test. RESULTS: The Validation set showed an APACHE II with an AUC = 0.79 (0.75-0.84) and HLC = 11 (p = 0.329); LR model AUC = 0.81 (0.76-0.85) and HLC = 29 (p = 0.0001) and an ANN AUC = 0.82 (0.77-0.86) and HLC = 10 (p = 0.404). The patients with the most important differences in the allocation of probability between LR and ANN (8% of the total) were neurological. The worst results were found in trauma patients with an AUC of not greater than 0.75 in all the models. In respiratory patients, the ANN achieved the best AUC = 0.87 (0.78-0.91). CONCLUSIONS: The ANN was able to stratify hospital mortality risk by using the APACHE II system variables. The ANN tended to achieve better results than LR, since, in order to work, it does not require lineal restrictions or independent variables. Allocation of individual probability differed in each model.

Female↗