Evidence of impairment of normal inflammatory reaction by a high-fat diet.

The murine dorsal air pouch model is a valuable tool for studying acute peripheral inflammatory reactions. We used this model to study the effect of diet on the onset of acute inflammation. Mice were fed a normal or a high-fat diet (HFD) for 5 weeks. Air pouches were raised and injected with non-stimulating (saline) or stimulating solution (saline containing lipopolysaccharides). After 4 h, leukocytes in the pouch fluid were enumerated, sorted and their viability measured. Cytokine/chemokine levels in the cell-free fluid were measured using a cytometric bead assay. Gene expression level was measured in leukocytes and in lining tissues using comparative real-time PCR. Leukocyte migration and cytokine/chemokine secretion were decreased substantially in mice fed the HFD. In contrast, leptin levels were elevated. Gene expression profiles in leukocytes recovered from the pouch and in the pouch-lining tissue (believed to have an important role in the initiation of granulocyte recruitment) were depressed. Genes encoding CC and CXC family chemokines were among the most negatively affected. These results suggest that a HFD can alter peripheral tissue activation as well as leukocyte recruitment and response, thereby affecting the development of an effective local immune response, which could have deleterious consequences.

Unstable insertion in the 5' flanking region of the cystatin B gene is the most common mutation in progressive myoclonus epilepsy type 1, EPM1.

Progressive myoclonus epilepsy type 1 (EPM1, also known as Unverricht-Lundborg disease) is an autosomal recessive disorder characterized by progressively worsening myoclonic jerks, frequent generalized tonic-clonic seizures, and a slowly progressive decline in cognition. Recently, two mutations in the cystatin B gene (also known as stefin B, STFB) mapping to 21q22.3 have been implicated in the EPM1 phenotype: a G-->C substitution in the last nucleotide of intron 1 that was predicted to cause a splicing defect in one family, and a C-->T substitution that would change an Arg codon (CGA) to a stop codon (TGA) at amino acid position 68, resulting in a truncated cystatin B protein in two other families. A fourth family showed undetectable amounts of STFB mRNA by northern blot analysis in an affected individual. We present haplotype and mutational analyses of our collection of 20 unrelated EPM1 patients and families from different ethnic groups. We identify four different mutations, the most common of which consists of an unstable approximately 600-900 bp insertion which is resistant to PCR amplification. This insertion maps to a 12-bp polymorphic tandem repeat located in the 5' flanking region of the STFB gene, in the region of the promoter. The size of the insertion varies between different EPM1 chromosomes sharing a common haplotype and a common origin, suggesting some level of meiotic instability over the course of many generations. This dynamic mutation, which appears distinct from conventional trinucleotide repeat expansions, may arise via a novel mechanism related to the instability of tandemly repeated sequences.

Granulocyte/macrophage colony-stimulating factor stimulates the expression of the 5-lipoxygenase-activating protein (FLAP) in human neutrophils.

The synthesis of leukotrienes in human blood neutrophils chiefly relies on the activity of two enzymes, phospholipase A2 and 5-lipoxygenase (5-LO). In turn, the activation of the 5-LO requires the participation of a recently characterized membrane-bound protein, the 5-LO-activating protein (FLAP). In this study, we have investigated conditions under which FLAP expression in neutrophils may be modulated. Of several cytokines tested, only granulocyte/macrophage colony-stimulating factor (GM-CSF) (and to a lesser extent tumor necrosis factor alpha) significantly increased expression of FLAP. GM-CSF increased FLAP mRNA steady-state levels in a time- and dose-dependent manner. The stimulatory effect of GM-CSF on FLAP mRNA was inhibited by prior treatment of the cells with the transcription inhibitor, actinomycin D, and pretreatment of the cells with the protein synthesis inhibitor, cycloheximide, failed to prevent the increase in FLAP mRNA induced by GM-CSF. The accumulation of newly synthesized FLAP, as determined by immunoprecipitation after incorporation of 35S-labeled amino acids, was also increased after incubation of neutrophils with GM-CSF. In addition, the total level of FLAP protein was increased in GM-CSF-treated neutrophils, as determined by two-dimensional gel electrophoresis, followed by Western blot. GM-CSF did not alter the stability of the FLAP protein, indicating that the effect of GM-CSF on FLAP accumulation was the consequence of increased de novo synthesis as opposed to decreased degradation of FLAP. Finally, incubation of neutrophils with the synthetic glucocorticoid dexamethasone directly stimulated the upregulation of FLAP mRNA and protein, and enhanced the effect of GM-CSF. Taken together, these data demonstrate that FLAP expression may be upmodulated after appropriate stimulation of neutrophils. The increase in FLAP expression induced by GM-CSF in inflammatory conditions could confer upon neutrophils a prolonged capacity to synthesize leukotrienes.

Lipoxin (LX)A4 and aspirin-triggered 15-epi-LXA4 inhibit tumor necrosis factor 1alpha-initiated neutrophil responses and trafficking: regulators of a cytokine-chemokine axis.

The impact of lipoxin A4 (LXA4) and aspirin-triggered lipoxins (ATLs) was investigated in tumor necrosis factor (TNF)-alpha-initiated neutrophil (polymorphonuclear leukocyte) responses in vitro and in vivo using metabolically stable LX analogues. At concentrations as low as 1-10 nM, the LXA4 and ATL analogues each inhibited TNF-alpha-stimulated superoxide anion generation and IL-1beta release by human polymorphonuclear leukocytes. These LXA4-ATL actions were time and concentration dependent and proved selective for TNF-alpha, as these responses were not altered with either GM-CSF- or zymosan-stimulated cells. TNF-alpha-induced IL-1beta gene expression was also regulated by both anti-LXA4 receptor antibodies and LXA4-ATL analogues. In murine air pouches, 15R/S-methyl-LXA4 dramatically inhibited TNF-alpha-stimulated leukocyte trafficking, as well as the appearance of both macrophage inflammatory peptide 2 and IL-1beta, while concomitantly stimulating IL-4 in pouch exudates. Together, these results indicate that both LXA4 and ATL regulate TNF-alpha-directed neutrophil actions in vitro and in vivo and stimulate IL-4 in exudates, playing a pivotal role in immune responses.

Expanded Characterization of a Hemi-Body Shielded Göttingen Minipig Model of Radiation-induced Gastrointestinal Injury Incorporating Oral Dosing Procedures.

In collaboration with the Biomedical Advanced Research and Development Authority (BARDA), the authors recently conducted a pilot study in a hemi-body shielded model of radiation-induced gastrointestinal (GI) injury in Göttingen minipigs following exposure to radiation dose levels between 8-16 Gy. Herein, the impact of oral dosing procedures is assessed, as well as the specific causes of death in animals exposed to radiation doses of 14 and 16 Gy (n = 64; 32 male, 32 female, between 6 and 8 mo of age). Oral dosing using a 2-tablet placebo system comprised of both immediate release and enteric-coated tablets starting 24 h post-irradiation resulted in inhibited gastric emptying of the enteric-coated tablets, which were found to be retained in the stomach and/or regurgitated. This finding appears to be species-specific, as similar findings have not been reported for other large animal species (e.g., non-human primates). Mortality was primarily dictated by decreased activity, body weight loss (>35%), and/or respiratory distress, despite shielding of the lung. The cause of respiratory distress in animals that were pre-terminally euthanized varied according to the timing of death, with interstitial inflammation and extensive fibrosis observed >20 days post-irradiation. Kidney damage was also identified in most animals after day 10. Changes in the GI tract were consistent with previous studies and included collagen deposition/fibrosis. Observations of inflammatory infiltrates and interstitial inflammation/fibrosis in both shielded and unshielded organs support a strong secondary inflammatory syndrome post-irradiation.

Pilot Study of Radiation-induced Gastrointestinal Injury in a Hemi-body Shielded Göttingen Minipig Model.

Development of medical countermeasures (MCMs) for gastrointestinal (GI) injury following acute radiation exposure requires well-characterized models that can assess not only survival but also secondary endpoints, including structural and functional characteristics of GI damage and recovery that ultimately contribute to long-term survival. The authors conducted a pilot study in a hemi-body shielded Göttingen minipig model of radiation-induced GI injury that enables radiation damage to the GI tract to be evaluated and reduces the potential for hemorrhage and/or damage in other more sensitive organ systems. With shielding of the head, chest, and front legs, radiation dose levels of 14 Gy were required to see significant GI-related morbidity, while dose levels of 16 Gy resulted in significant mortality by day 45 post-irradiation. Periodic scheduled necropsies showed significant reduction in and slow recovery of intestinal crypt count at 14 and 16 Gy. Intestinal proliferative activity was initially increased and then gradually decreased over the course of the study. Histological evidence of marked inflammatory infiltrates was noted in the GI tract at day 5, while collagen deposition, indicative of fibrosis, was observed as early as day 15, peaking at day 30. The radiation dose-responsive indicators of GI damage identified in this model (i.e., intestinal crypt count and proliferative activity) may serve as useful endpoints for evaluation of the efficacy of potential MCMs.

Effects of pyrrophenone, an inhibitor of group IVA phospholipase A2, on eicosanoid and PAF biosynthesis in human neutrophils.

BACKGROUND AND PURPOSE: The biosynthesis of leukotrienes (LT) and platelet-activating factor (PAF) involves the release of their respective precursors, arachidonic acid (AA) and lyso-PAF by the group IVA PLA2 (cPLA2alpha). This paper aims at characterizing the inhibitory properties of the cPLA2alpha inhibitor pyrrophenone on eicosanoids and PAF in human neutrophils (PMN). EXPERIMENTAL APPROACH: Freshly isolated human PMN were activated with physiological and pharmacological agents (fMLP, PAF, exogenous AA, A23187 and thapsigargin) in presence and absence of the cPLA2alpha inhibitor pyrrophenone and biosynthesis of LT, PAF, and PGE2 was measured. KEY RESULTS: Pyrrophenone potently inhibited LT, PGE2 and PAF biosynthesis in PMN with IC50s in the range of 1-20 nM. These inhibitory effects of pyrrophenone were specific (the consequence of substrate deprivation), as shown by the reversal of inhibition by exogenous AA and lyso-PAF. Comparative assessment of pyrrophenone, methyl-arachidonoyl-fluoro-phosphonate (MAFP) and arachidonoyl-trifluoromethylketone (AACOCF3) demonstrated that pyrrophenone was more specific and 100-fold more potent than MAFP and AACOCF3 for the inhibition of LT biosynthesis in A23187-activated PMN. The inhibitory effect of pyrrophenone on LT biosynthesis was reversible as LT biosynthesis was recovered when pyrrophenone-treated PMN were washed with autologous plasma. No alteration of phospholipase D (PLD) activity in fMLP-activated PMN was observed with up to 10 microM pyrrophenone, suggesting that the cPLA2alpha inhibitor does not directly inhibit PLD. CONCLUSIONS AND IMPLICATIONS: Pyrrophenone is a more potent and specific cPLA2alpha inhibitor than MAFP and AACOCF3 and represents an excellent pharmacological tool to investigate the biosynthesis and the biological roles of eicosanoids and PAF.

Citrulline as a Biomarker for Gastrointestinal-Acute Radiation Syndrome: Species Differences and Experimental Condition Effects.

Animal models of hematopoietic and gastrointestinal acute radiation syndromes (ARS) have been characterized to develop medical countermeasures. Acute radiation-induced decrease of intestinal absorptive function has been correlated to a decrease in the number of intestinal crypt cells resulting from apoptosis and enterocyte mass reduction. Citrulline, a noncoded amino acid, is produced almost exclusively by the enterocytes of the small intestine. Citrullinemia has been identified as a simple, sensitive and suitable biomarker for radiation-induced injury associated with gastrointestinal ARS (GI-ARS). Here we discuss the effect of radiation on plasma citrulline levels in three different species, C57BL/6 mice, Göttingen minipigs and rhesus nonhuman primates (NHPs), measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). The effects of experimental study conditions such as feeding and anesthesia were also examined on plasma citrulline levels in the NHPs. Both the mice and Göttingen minipigs were partial-body irradiated (PBI) with doses from 13-17 Gy and 8-16 Gy, respectively, whereas NHPs were total-body irradiated (TBI) with doses from 6.72-13 Gy. Blood samples were taken at different time points and plasma citrulline levels were measured in the three species at baseline and after irradiation. Basal plasma citrulline concentrations (mean ± SEM) in mice and minipigs were 57.8 ± 2.8 µM and 63.1 ± 2.1 µM, respectively. NHPs showed a basal plasma citrulline concentration of 32.6 ± 0.7 µM, very similar to that of humans (∼40 µM). Plasma citrulline progressively decreased after irradiation, reaching nadir values between day 3.5 and 7. The onset of citrulline recovery was observed earlier at lower radiation doses, while only partial citrulline recovery was noted at higher radiation doses in minipigs and NHPs, complete recovery was noted in mice at all doses. Plasma citrulline levels in NHPs anesthetized with ketamine and acepromazine significantly decreased by 35.5% (P = 0.0017), compared to unanesthetized NHPs. In the postprandial state, citrulline concentrations in NHPs were slightly but significantly decreased by 12.2% (P = 0.0287). These results suggest that plasma citrulline is affected by experimental conditions such as anesthesia and feeding.

Visceral obesity in men. Associations with glucose tolerance, plasma insulin, and lipoprotein levels.

The relations of regional adipose tissue (AT) distribution measured by computed tomography (CT) to plasma insulin-glucose homeostasis and lipoprotein-lipid levels were studied in 58 obese and 29 lean control men. In the group of obese men, the visceral AT area measured by CT was positively correlated with fasting plasma triglyceride and insulin levels and with glucose and insulin areas under the curves measured during a 75-g oral glucose tolerance test. Visceral AT area was also negatively associated with plasma high-density lipoprotein (HDL) and HDL2 cholesterol levels. The relative accumulation of abdominal fat, estimated by the ratio of abdominal to femoral AT areas obtained by CT, was also a significant correlate of indices of carbohydrate metabolism and was the best univariate correlate of plasma lipoprotein levels. No significant associations were observed between the visceral AT area, the ratio of abdominal to femoral AT areas, and indices of carbohydrate and lipoprotein metabolism in the group of lean men. On the other hand, the subcutaneous abdominal AT area was a significant correlate of the glucose area under the curve in both groups of men, but this association was not independent from the percentage of total body fat. No relationship was observed between the femoral AT area and indices of carbohydrate metabolism in either lean or obese groups. In obese men, however, the femoral AT area was negatively correlated with plasma triglyceride concentration and positively correlated with plasma HDL and HDL2 cholesterol levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein E polymorphism modifies relation of hyperinsulinemia to hypertriglyceridemia.

The effect of apolipoprotein E polymorphism on the established relationships between glucose tolerance, plasma insulin levels, and plasma lipoprotein concentrations were investigated in a sample of women defined on the basis of apolipoprotein E phenotypes. In women with the apolipoprotein E epsilon 2 allele (n = 22), fasting plasma insulin and glucose and insulin areas under the curve measured during an oral glucose tolerance test were positively correlated with plasma triglyceride levels (0.48 < or = r < or = 0.70; P < 0.05). In this group, very-low-density lipoprotein cholesterol and very-low-density lipoprotein triglyceride concentrations were positively correlated with fasting insulin levels, the insulin area, and with the ratio of insulin area to glucose area. In women (n = 24) homozygous for the apolipoprotein E epsilon 3 allele (the most common allele), essentially similar associations were found. In contrast, in women (n = 17) with the apolipoprotein E epsilon 4 allele, no association was found between glucose tolerance, fasting and postglucose plasma insulin levels, and plasma lipid and lipoprotein levels. These results suggest that apolipoprotein E polymorphism substantially modifies the associations between glucose tolerance, plasma insulin levels, and plasma lipoprotein concentrations. Additional analysis of the data revealed that apolipoprotein E polymorphism did not alter the relationships between body fat distribution and fasting insulin and postglucose insulin levels, but no correlation was observed between fatness indexes and glucose tolerance among apolipoprotein E epsilon 2 carriers.(ABSTRACT TRUNCATED AT 250 WORDS)

Estimation of deep abdominal adipose-tissue accumulation from simple anthropometric measurements in men.

Equations have been developed for the prediction of deep abdominal adipose-tissue (AT) accumulation from anthropometric measurements in a sample of 110 men. An equation including the waist circumference and age could predict 74% of the variance in the amount of deep abdominal AT with an SEE of 29.6 cm2 (29.2% of the mean deep abdominal AT value), whereas another equation including the sagittal diameter, the waist-to-hip ratio (WHR), and age explained 76.6% of its variance with an SEE of 28.1 cm2 (27.7%). Equations excluding age as an independent variable were also developed. These results indicate that equations in which simple anthropometric measurements are used can provide further information in the assessment of the risk of cardiovascular disease in men. However, we must remember that our ability to predict the amount of deep abdominal AT from anthropometry is limited.

Waist circumference and abdominal sagittal diameter: best simple anthropometric indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women.

The amount of abdominal visceral adipose tissue measured by computed tomography is a critical correlate of the potentially "atherogenic" metabolic disturbances associated with abdominal obesity. In this study conducted in samples of 81 men and 70 women, data are presented on the anthropometric correlates of abdominal visceral adipose tissue accumulation and related cardiovascular disease risk factors (triglyceride and high-density lipoprotein cholesterol levels, fasting and postglucose insulin and glucose levels). Results indicate that the waist circumference and the abdominal sagittal diameter are better correlates of abdominal visceral adipose tissue accumulation than the commonly used waist-to-hip ratio (WHR). In women, the waist circumference and the abdominal sagittal diameter also appeared more closely related to the metabolic variables than the WHR. When the samples were divided into quintiles of waist circumference, WHR or abdominal sagittal diameter, it was noted that increasing values of waist circumference and abdominal sagittal diameter were more consistently associated with increases in fasting and postglucose insulin levels than increasing values of WHR, especially in women. These findings suggest that the waist circumference or the abdominal sagittal diameter, rather than the WHR, should be used as indexes of abdominal visceral adipose tissue deposition and in the assessment of cardiovascular risk. It is suggested from these data that waist circumference values above approximately 100 cm, or abdominal sagittal diameter values > 25 cm are most likely to be associated with potentially "atherogenic" metabolic disturbances.

Analytic clinical chemistry precision and medical needs. The Canadian Interlab Program (CIP).

Precision obtained with two different serum pools used daily as internal quality-control specimens by 130 laboratories throughout Canada (Canadian Interlab Program) is reported for 14 analytes assayed by either manual or automated methods over a period of 16 months. Precision criteria set by Barnett to meet medical needs were not met for calcium, glucose, phosphorus, and urea nitrogen by more than 10% of the laboratories studied. Specific guidelines for laboratory precision are suggested for optimal and minimal performance in the assays of albumin, bilirubin, calcium, chloride, cholesterol, creatinine, glucose, phosphorus, potassium, sodium, total protein, triglyceride, urea nitrogen, and uric acid.

Computed tomography-measured trunk fat and plasma lipoprotein levels in nonobese women.

The associations between total adiposity, adipose tissue distribution measured by computed axial tomography (CAT), regional variation in fat cell size, and plasma lipoprotein levels were studied in a sample of 22 premenopausal healthy nonobese women aged 34.6 +/- 3.1 years (mean +/- SD) (% body fat, 27.8 +/- 5.8). In these nonobese women, no associations were found between total adiposity, adipose tissue distribution, and plasma triglyceride or very-low-density lipoprotein levels. However, total adiposity (as reflected by the body density-derived fat mass and by the adipose tissue volume measured by CAT), as well as the total trunk fat areas (measured at the abdominal and thoracic levels) were positively correlated with plasma low-density lipoprotein (LDL) cholesterol (.05 greater than P less than .01) and LDL apolipoprotein (apo) B (.05 greater than P less than .0005) levels. Because of these associations with LDL-C and LDL apo B levels, these body fatness indicators were negatively correlated with the HDL-cholesterol/LDL-cholesterol and HDL-apo A-I/LDL-apo B ratios. However, few significant associations were observed between the proportion of abdominal fat estimated by the waist/hip circumference ratio (WHR) and the lipoprotein-lipid profile (r = .45 and r = .44, P less than .05 with HDL triglyceride (TG) and LDL-apo B/LDL-cholesterol ratio, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Is body fat loss a determinant factor in the improvement of carbohydrate and lipid metabolism following aerobic exercise training in obese women?

Thirty-one obese, premenopausal women aged 35.4 +/- 5.1 (SD) years exercised for 90 minutes at approximately 55% of maximal aerobic power (VO2max) four to five times a week for a period of 6 months. The training program induced a significant increase in VO2max (P < .001) and significant improvements in carbohydrate and lipid metabolism, as reflected by decreased plasma insulin (INS) concentrations measured in the fasting state and after glucose (GLU) ingestion (INS area, P < .001), by reduced plasma cholesterol (C) and low-density lipoprotein cholesterol (LDL-C) levels (P < .001), and by increased ratios of high-density lipoprotein cholesterol (HDL-C)/LDL-C and HDL2-C/HDL3-C (P < .05 and P < .001, respectively). Changes in body fat mass were positively associated with changes in the INS area/GLU area ratio (r = .49, P < .05) and with changes in very-low-density lipoprotein triglycerides ([VLDL-TG] r = .49, P < .05). Furthermore, changes in the INS area were positively associated with changes in VLDL-TG (r = .51, P < .05). Although no significant mean change in body composition was observed, important individual variation was noted. Twenty women showed a reduction in body fat mass (mean reduction, 2.63 +/- 2.2 kg), whereas 11 women showed an increase in adipose mass (mean increase, 2.79 +/- 2.36 kg). Comparable increases in VO2max were observed between the two groups. The group that showed a decrease in body fat mass with exercise also had significant improvements in carbohydrate and lipid metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlates of plasma very-low-density lipoprotein concentration and composition in premenopausal women.

Potential correlates of plasma very-low-density lipoprotein (VLDL) concentration and composition were studied in a sample of 75 premenopausal women. Fasting plasma free fatty acid (FFA) levels, as well as plasma glucose and insulin levels in the fasting state and during an oral glucose tolerance test, displayed significant positive correlations with plasma triglyceride (TG) and VLDL-TG levels (P less than .005). Plasma post-heparin lipoprotein lipase (LPL) activity, measured in a subsample of 31 women from the original sample, was negatively correlated with plasma TG, VLDL-cholesterol (CHOL), VLDL-TG, and VLDL-apolipoprotein (apo) B concentrations (.005 greater than P less than .05). Multivariate analyses showed that, after LPL was considered, the insulin area was the only other metabolic variable studied that was significantly correlated with VLDL-apo B concentration, whereas fasting FFA levels were significantly correlated with plasma TG and VLDL-TG levels. ANOVA revealed that plasma VLDL-CHOL, VLDL-TG, and VLDL-apo B levels were not associated with the glucose area, but were significantly associated with the insulin area (P less than .005). When the effect of insulin area was controlled for, the plasma FFA levels did not contribute significantly to the variance in VLDL-CHOL and VLDL-apo B, but showed an independent effect on VLDL-TG levels (P less than .05). Finally, stepwise multiple regression analyses indicated that once the variance explained by plasma LPL activity and by the insulin area was considered, no other metabolic variable could account for the variation in VLDL-CHOL and VLDL-apo B levels, whereas fasting FFA levels explained a further 5% of the VLDL-TG variance and one third of the variance observed in the VLDL-TG/apo B ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Critical evaluation of the logit-log plot for the radio assay of vitamin B12.

The dose-response calculation for radio assay of vitamin B12 is carried out using a straight line and a third degree curve to fit the experimentally obtained calibration points. It is shown that high dispersion of the calibration points with respect to the regression line can lead to errors in the calculation of the response. The calculation of the mean dispersion sx with respect to the regression line turns out to be a good criterion for checking the accuracy of the results.

Normalization of the metabolic profile in obese women by exercise and a low fat diet.

This study was performed to evaluate the additive effect of exercise and a low fat diet on body weight, body composition, and the metabolic profile in four obese women who were previously exercise-trained for 15 months. This study therefore included regular aerobic exercise for 15 months and a low fat diet plus exercise for an additional period of 14 months. After 15 months, mean body weight and fat losses corresponded to 6.4 and 8.4 kg, respectively. Significant reductions (P less than 0.05) in plasma insulin, cholesterol, apo B, and LDL-C were also observed. Following the second part of the study, mean cumulative body weight and fat losses were 11.0 and 11.3 kg, respectively. At this time, the subjects were still overweight, but their plasma glucose and insulin during an oral glucose tolerance test were essentially similar to values obtained in a sample of 22 nonobese women. With the exception of plasma apo B and HDL-C levels, plasma lipid and lipoprotein levels were also comparable to those observed in nonobese controls. These results thus indicate that aerobic exercise-training and a low fat diet can normalize the metabolic profile of obese women, even if their adiposity remains higher than that of lean women.

Uniaxial compression of thermal gels based on microfluidized blends of WPI and heat-denatured WPI.

The effect of heat-denatured whey protein isolate (dWPI)/whey protein isolate (WPI) ratio (0-0.6), microfluidization pressure (0-1000 bar), and number of passes (1-10) on the uniaxial shear stress at 10% (sigma(10)) and 80% (sigma(80)) relative deformation of dWPI/WPI heat-induced gels (14% total protein, w/w) was studied. No correlation between the average diameter of aggregates and the dWPI/WPI ratio, microfluidization pressure, or number of passes was found. However, increasing the microfluidization pressure or the number of passes resulted in a narrower size distribution of aggregates. Increasing the dWPI/WPI ratio and the number of passes resulted in a decrease and an increase of gel hardness, respectively. The results were interpreted in terms of more random aggregation/gelation of proteins in the presence of aggregates that could result in localized heterogeneities into gels and more dissipation of the deformation energy during compression. The positive effect of the number of passes on the gel hardness was also considered to be due to a more homogeneous aggregation/gelation of proteins in the presence of smaller aggregates.