Sense of coherence, self-esteem, and health locus of control in subjects with type 1 diabetes mellitus with/without satisfactory metabolic control.

BACKGROUND: Despite intensive training, a few individuals with Type 1 diabetes mellitus (T1DM) fail to reach the desired metabolic targets. AIM: To evaluate the association between disease-related emotional and cognitive aspects and metabolic control in subjects with T1DM. SUBJECTS AND METHODS: Health locus of control (HLOC), sense of coherence (SOC), and self-esteem were assessed in T1DM subjects using validated questionnaires. Sixty-seven consecutive subjects who did not attain the desired HbA1c target (mean HbA1c, 8.3% [67 mmol/mol]) were compared with 30 cases in satisfactory metabolic control (HbA1c levels <7%-53 mmol/mol). RESULTS: In the overall population, SOC was negatively associated with BMI and average HbA1c, as was the association of self-esteem with HbA1c. Subjects attaining the desired metabolic target were characterized by higher SOC scores, higher Internal HLOC and prevalent Internal vs. Powerful-others HLOC. Compared to subjects in good metabolic control, subjects with unsatisfactory control had lower scores of SOC, Internal HLOC and Self-esteem, with no difference in Powerful others, or Chance HLOC. In the same group, SOC in the upper tertile was significantly associated with self-esteem (OR 1.35; 95% CI 1.08-1.69) and PHLOC (OR 1.24; 95% CI 1.03-1.49), after adjustment for age, sex, educational level, and comorbidities. CONCLUSIONS: Patients who fail to reach a satisfactory metabolic control tend to rely on significant others, trusting in the physicians' skills or on the efficiency of the health-care system. Strategies aimed at increasing self-efficacy and SOC, based on personal ability, are eagerly awaited to help patients improve diabetes care.

Sex differences in food choices, adherence to dietary recommendations and plasma lipid profile in type 2 diabetes - The TOSCA.IT study.

BACKGROUND AND AIMS: Diabetic women have a more adverse plasma lipid profile than men. Sex differences in dietary habits may play a role, but are little investigated. The study evaluates the quality of diet, adherence to the nutritional recommendations of the Diabetes and Nutrition Study Group and their relation with plasma lipid in men and women with diabetes. METHODS AND RESULTS: We studied 2573 people, aged 50-75, enrolled in the TOSCA.IT study (clinicaltrials.gov; NCT00700856). Plasma lipids were measured centrally. Diet was assessed with a semi-quantitative food frequency questionnaire. Women had a more adverse plasma lipid profile than men. Women consumed significantly more legumes, vegetables, fruits, eggs, milk, vegetable oils, and added sugar, whereas men consumed more starchy foods, soft drinks and alcoholic beverages. This stands for a higher proportion (%) of energy intake from saturated fat and added sugar (12.0 ± 2.4 vs 11.5 ± 2.5 and 3.4 ± 3.2 vs 2.3 ± 3.2, P < 0.04), and a higher intake of fiber (11.2 ± 2.8 vs 10.4 ± 2.6 g/1000 Kcal/day) in women. Adherence to the recommendations for saturated fat and fiber consumption was associated with significantly lower LDL-cholesterol regardless of sex. Adherence to the recommendations for added sugars was associated with significantly lower triglycerides and higher HDL-cholesterol in men and women. CONCLUSIONS: Men and women with diabetes show significant differences in adherence to nutritional recommendations, but sex differences in plasma lipid profile are unlikely to be explained by nutritional factors. Adherence to the nutritional recommendations is associated with a better plasma lipid profile regardless of sex, thus reinforcing the importance of substituting saturated for unsaturated fat sources, increasing fiber and reducing added sugar intake.

Dipyridamole-induced C-type natriuretic peptide mRNA overexpression in a minipig model of pacing-induced left ventricular dysfunction.

Dipyridamole (DP) restores ischemic tissue blood flow stimulating angiogenesis in eNOS-dependent pathways. C-type natriuretic peptide (CNP) is expected to mimic the migration-stimulatory effect of NO via a cGMP-dependent mechanism. Aim of this study was to assess the role of concomitant treatment with DP on CNP levels in blood and myocardial tissue of minipigs with left ventricular dysfunction (LVD) induced by pacing at 200bpm in the right ventricular apex. Minipigs with DP therapy (DP+, n=4) or placebo (DP-, n=4) and controls (C-SHAM, n=4) underwent 2D-EchoDoppler examination and blood collection before and after 4 weeks of pacing, when cardiac tissue was collected. Histological/immunohistochemical analyses were performed. CNP levels were determined by radioimmunoassay; cardiac CNP, BNP, natriuretic receptors expression by Real-Time PCR. After pacing, cardiac parameters resulted less impaired in DP+ compared to DP-. Histological sections presented normal morphology while the arteriolar density resulted: C-SHAM: 9.0±1.2; DP-: 4.9±0.3; DP+: 6.5±0.6number/mm(2); C-SHAM vs DP- and DP+ p=0.004, p=0.04, respectively. CNP mRNA resulted lower in DP- compared to C-SHAM and DP+ as well as NPR-B (p=0.011, DP- vs DP+). Both NPR-A/NPR-C mRNA expressions were significantly (p<0.001) lower both in DP- and DP+ compared to C-SHAM. BNP mRNA was higher in LVD. CNP plasma levels showed a similar trend with respect to gene expression (C-SHAM: 30.5±15; DP-: 18.6±5.5; DP+: 21.2±4.7pg/ml). These data suggest that DP may serve as a preconditioning agent to increase the protective CNP-mediated endocrine response in LVD. This response, mediated by its specific receptor NPR-B, may offer new insights into molecular targets for treatment of LVD.

Endothelin system mRNA variation in the heart of Zucker rats: evaluation of a possible balance with natriuretic peptides.

BACKGROUND AND AIMS: The deregulation of neurohormonal systems, including the natriuretic peptide (NP) and endothelin (ET) systems, may increase the possibility of developing obesity-related risk. The aim of our paper was to evaluate ET system mRNA variation in heart of the Zucker rat model together with the simultaneous evaluation of the NP system transcriptomic profile. In order to analyze the link between the ET-1 system and the inflammatory process, the cardiac expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α was also measured. METHODS AND RESULTS: Zucker rats of 11-13 weeks were subdivided into obese rats (O, n = 20) and controls (CO, n = 20): half of them were studied under fasting conditions (CO(fc)-O(fc)) and the remainder after the induction of acute hyperglycemia (CO(AH)-O(AH)). Cardiac mRNA expression of TNF-α, IL-6, and NP/ET-1 systems was evaluated by Real-Time polymerase chain reaction. No significant difference for pre-proET-1, ET-A, and ET-B mRNA expression was detected between O and CO, whereas significantly lower mRNA levels of the ECE-1 were observed in O (p = 0.02). Regarding NPs, only BNP mRNA expression decreased significantly in O with respect to CO (p = 0.01). A down-regulation of NPR-B and NPR-C and an up-regulation of NPR-A were observed in O. No significant difference for IL-6 and TNF-α mRNA was revealed. Subdividing into fasting and hyperglycemic rats, many of the genes studied maintained their mRNA expression pattern almost unchanged. CONCLUSIONS: The modulation of ET-1/NP systems in obesity could be a useful starting point for future studies aimed at identifying new therapeutic strategies for the treatment of cardiometabolic syndrome.

Back to the heart: the protective role of adiponectin.

Cardiovascular disease (CVD) is the leading cause of death worldwide and the prevalence of obesity and diabetes are increasing. In obesity, adipose tissue increases the secretion of bioactive mediators (adipokines) that may represent a key mechanism linking obesity to CVD. Adiponectin, extensively studied in metabolic diseases, exerts anti-diabetic, anti-atherogenic and anti-inflammatory activities. Due to these positive actions, the role of adiponectin in cardiovascular protection has been evaluated in recent years. In particular, for its potential therapeutic benefits in humans, adiponectin has become the subject of intense preclinical research. In the cardiovascular context, understanding of the cellular and molecular mechanisms underlying the adiponectin system, throughout its secretion, regulation and signaling, is critical for designing new drugs that target adiponectin system molecules. This review focused on recent advances regarding molecular mechanisms related to protective effects of the adiponectin system on both cardiac and vascular compartments and its potential use as a target for therapeutic intervention of CVD.

C-type natriuretic peptide plasma levels are reduced in obese adolescents.

The high prevalence of obesity in children may increase the magnitude of lifetime risk of cardiovascular disease (CD). At present, explicit data for recommending biomarkers as routine pre-clinical markers of CD in children are lacking. C-type natriuretic peptide (CNP) is assuming increasing importance in CD; in adults with heart failure, its plasma levels are related to clinical and functional disease severity. We have previously reported five different reference intervals for blood CNP as a function of age in healthy children; however, data on plasma CNP levels in obese children are still lacking. Aim of this study was to assess CNP levels in obese adolescents and verify whether they differ from healthy subjects. Plasma CNP was measured in 29 obese adolescents (age: 11.8 ± 0.4 years; BMI: 29.8 ± 0.82) by radioimmunoassay and compared with the reference values of healthy subjects. BNP was also measured. Both plasma CNP and BNP levels were significantly lower in the obese adolescents compared to the appropriate reference values (CNP: 3.4 ± 0.2 vs 13.6 ± 2.3 pg/ml, p<0.0001; BNP: 18.8 ± 2.6 vs 36.9 ± 5.5 pg/ml, p=0.003). There was no significant difference between CNP values in males and females. As reported in adults, we observed lower plasma CNP and BNP levels in obese children, suggesting a defective natriuretic peptide system in these patients. An altered regulation of production, clearance and function of natriuretic peptides, already operating in obese adolescents, may possibly contribute to the future development of CD. Thus, the availability of drugs promoting the action of natriuretic peptides may represent an attractive therapeutic option to prevent CD.

C-type natriuretic peptide transcriptomic profiling increases in human leukocytes of patients with chronic heart failure as a function of clinical severity.

The aim of this study was to evaluate the transcriptomic profiling of C-type natriuretic peptide (CNP) and of its specific receptor, NPR-B in human leukocytes of heart failure (HF) patients as a function of clinical severity, assessing the possible changes with respect to healthy subjects (C). mRNA expression was evaluated by Real-Time PCR and total RNA was extracted from leukocytes of C (n=8) and of HF patients (NYHA I-II, n=7; NYHA III-IV, n=13) with PAXgene Blood RNA Kit. Significantly higher levels of CNP mRNA expression were found in HF patients as a function of clinical severity (C=0.23±0.058, NYHA I-II=0.47±0.18, NYHA III-IV=2.58±0.71, p=0.005 C vs NYHA III-IV, p=0.017 NYHA I-II vs NYHA III-IV) and NPR-B transcript levels resulted down-regulated in HF patients with higher NYHA class (C=2.2±0.61, NYHA I-II=2.76±0.46, NYHA III-IV=0.29±0.13, p=0.001 C vs NYHA III-IV, p<0.0001 NYHA I-II vs NYHA III-IV). A significant negative correlation between CNP and NPR-B mRNA expression (r=0.5, p=0.03) was also observed. These results suggest a co-regulation of NPR-B and CNP expression supporting the relevance of this receptor in human disease characterized by a marked inflammatory/immune component and suggesting the possibility of manipulating inflammation via pharmacological agents selective for this receptor.

High concentration of C-type natriuretic peptide promotes VEGF-dependent vasculogenesis in the remodeled region of infarcted swine heart with preserved left ventricular ejection fraction.

BACKGROUND: Vasculogenesis is a hallmark of myocardial restoration. Post-ischemic late remodeling is associated with pathology and function worsening. At the same time, neo-vasculogenesis helps function improving and requires the release of vascular endothelial growth factor type A (VEGF-A). The vasculogenic role of C-type natriuretic peptide (CNP), a cardiac paracrine hormone, is unknown in infarcted hearts with preserved left ventricular (LV) ejection fraction (EF). We explored whether myocardial VEGF-dependent vasculogenesis is affected by CNP. METHODS AND RESULTS: To this end, infarcted swine hearts were investigated by magnetic resonance imaging (MRI), histological and molecular assays. At the fourth week, MRI showed that transmural myocardial infarction (MI) affected approximately 13% of the LV wall mass without impairing global function (LVEF>50%, n=9). Increased fibrosis, metalloproteases and capillary density were localized to the infarct border zone (BZ), and were associated with increased expression of CNP (p=0.03 vs. remote zone (RZ)), VEGF-A (p<0.001 vs. RZ), BNP, a marker of myocardial dysfunction (p<0.01 vs. RZ) and the endothelial marker, factor VIII-related antigen (p<0.01 vs. RZ). In vitro, CNP 1000 nM promoted VEGF-dependent vasculogenesis without affecting the cell growth and survival, although CNP 100 nM or a high concentration of VEGF-A halted vascular growth. CONCLUSIONS: CNP expression is locally increased in infarct remodeled myocardium in the presence of dense capillary network. The vasculogenic response requires the co-exposure to high concentration of CNP and VEGF-A. Our data will be helpful to develop combined myocardial delivery of CNP and VEGF-A genes in order to reverse the remodeling process.

IL-33/ST2 pathway and classical cytokines in end-stage heart failure patients submitted to left ventricular assist device support: a paradoxic role for inflammatory mediators?

BACKGROUND: Inflammation is a critical process contributing to heart failure (HF). We hypothesized that IL-33/ST2 pathway, a new mechanism regulated during cardiac stress, may be involved in the functional worsening of end-stage HF patients, candidates for left ventricular assist device (LVAD) implantation, and potentially responsible for their outcome. METHODS: IL-33, ST2, and conventional cytokines (IL-6, IL-8, and TNF-α) were determined in cardiac biopsies and plasma of 22 patients submitted to LVAD implantation (pre-LVAD) and compared with (1) control stable chronic HF patients on medical therapy at the moment of heart transplantation without prior circulatory support (HT); (2) patients supported by LVAD at the moment of LVAD weaning (post-LVAD). RESULTS: Cardiac expression of ST2/IL-33 and cytokines was lower in the pre-LVAD than in the HT group. LVAD determined an increase of inflammatory mediators comparable to levels of the HT group. Only ST2 correlated with outcome indices after LVAD implantation. CONCLUSIONS: IL-33/ST2 and traditional cytokines were involved in decline of cardiac function of ESHF patients as well as in hemodynamic recovery induced by LVAD. IL-33/ST2 pathway was also associated to severity of clinical course. Thus, a better understanding of inflammation is the key to achieving more favorable outcome by new specific therapies.

Relation between adiponectin and brain natriuretic peptide in healthy pediatric subjects: from birth through childhood.

BACKGROUND AND AIMS: New biomarkers potentially improve clinical management of cardiovascular disease, but there are gaps in understanding their role during childhood. Adiponectin regulates metabolism and exerts anti-inflammatory/anti-atherogenic effects. The aim of the study was to evaluate circulating levels of adiponectin during postnatal growth and its relationship with Brain Natriuretic Peptide (BNP) in healthy children, a marker of cardiac function known to be increased in childhood. METHODS AND RESULTS: Plasma adiponectin and BNP were measured in 131 healthy children divided into: 43 newborns (0-3 days), 29 neonates (4-30 days), 25 infants (1-12 months) and 34 children (1-12 years). A group of 33 healthy adult subjects (25-60 years) was also studied. Plasma adiponectin in the 131 children resulted significantly higher compared to adult subjects (p < 0.0001). The time-course of adiponectin suggests the design of three age-based intervals: the first until 1 month of age (median 29.07 µg/mL, 11.61-47.01 µg/mL 5°-95° percentiles), the second between 1 and 12 months of age (21.66 µg/mL, 8.83-59.81 µg/mL) and the third for age up to 12 years (13.81 µg/mL, 4.10-28.57 µg/mL). Both adiponectin and BNP exhibited the same trend of a progressive decrease during growth, showing a significant relationship (Spearman's rho = 0.403, p < 0.0001). CONCLUSION: Adiponectin plasma levels in a healthy pediatric population vary as a function of age. Three reference intervals for adiponectin in pediatric subjects have been indicated. The relationship between adiponectin and BNP suggests that the age-dependent profile of circulating adiponectin could also be due to BNP.

Gene expression of C-type natriuretic peptide and of its specific receptor NPR-B in human leukocytes of healthy and heart failure subjects.

C-type natriuretic peptide (CNP), a member of the family of natriuretic peptides, is synthesized and secreted from monocytes and macrophages that resulted to be a source of CNP at inflammatory sites. This suggests that special attention should be focused on the possible role of CNP in the immune system, in addition to its effects on the cardiovascular system. The aim of this study was to evaluate the possibility of measuring the mRNA expression of CNP and NPR-B, its specific receptor, in human whole blood samples of healthy (N; n=7) and heart failure (HF; n=7) subjects by Real-Time PCR (RT-PCR). Total RNA was extracted from leukocytes with QIAamp RNA Blood Kit and/or with PAXgene Blood RNA Kit. RT-PCR was performed and optimized for each primer. The experimental results were normalized with the three most stably expressed genes. CNP and NPR-B expression trend was similar in both fresh and frozen human whole blood. Significant higher levels of CNP and NPR-B mRNA expression were found in HF patients with respect to controls (CNP: N=1.23±0.33 vs. HF=6.54±2.09 p=0.027; NPR-B: N=0.85±0.23 vs. HF=5.31±1.98 p=0.04). A significant correlation between CNP and NPR-B (r=0.86, p<0.0001) was observed. Further studies are needed to clarify the pathophysiological properties of this peptide but the possibility to measure CNP and NPR-B mRNA expression in human leukocytes with a fast and easy procedure is a useful starting point for future investigation devoted to better understand the biomolecular processes associated to different diseases.

The natriuretic peptide time-course in end-stage heart failure patients supported by left ventricular assist device implant: focus on NT-proCNP.

This study aimed to evaluate left ventricular assist device (LVAD) effects on natriuretic peptide (NP) prohormone plasma levels in end-stage heart failure (HF) patients, especially NT-proCNP, in order to better characterize the NP system during hemodynamic recovery by LVAD. HF patients (n=17, NYHA III-IV) undergoing LVAD were studied: 6 died of multi-organ failure syndrome (NS) and 11 survived (S). Total sequential organ failure assessment (t-SOFA) score and blood samples were obtained at admission (T1) and at 24, 72h and 1, 2, 4 weeks (T2-T6) after LVAD. In S, NT-proANP and NT-proCNP significantly increased at 24h after implantation, reaching a reduction to basal levels at 4 weeks following LVAD [NT-proANP: T1 vs. T2 p=0.017, NT-proCNP: T1 vs. T2 p=0.028, T1 vs. T3 p=0.043]. Elevated NT-proBNP plasma levels were observed at all times. In NS, NP plasma levels sustained higher with respect to S. No statistical variation was observed for NT-proCNP and NT-proANP in S and NS while NT-proBNP reached significant differences at T4 in NS. Considering S+NS, only NT-proCNP strongly correlated with t-SOFA score at T1 (rho=0.554, p=0.04) while subdividing patients NT-proCNP positively correlated in NS with t-SOFA score (rho=0.988, p=0.002) only at T4. In NS a correlation between NT-proCNP and NT-proBNP at T1 was observed (rho=-0.900, p=0.037). Both IL-6 and TNF-alpha sustained higher in NS patients than in S; in particular, statistical significance was observed for IL-6. The study of new peptides, such as NT-proCNP, would provide additional information for identifying patients who are more likely to recover.

Plasma C-type natriuretic peptide levels in healthy children.

C-type natriuretic peptide (CNP) is assuming increasing importance in cardiovascular disease, and in adults its plasma levels are related to clinical and functional disease severity. Data are scarce regarding the reference values for CNP in infancy. Aim of this study was to assess the reference intervals for CNP in human healthy newborns and infants. Plasma CNP was measured in 121 healthy children divided into: 41 newborns (age 0-3 days), 24 newborns (4-30 days), 22 infants (1-12 months) and 32 children (1-12 years). A group of 32 healthy adult subjects (age 64 ± 1 years) was also studied. CNP was measured by a specific radioimmunoassay. Between- and within-assay variability resulted ≤ 30 and 20%, respectively and analytical sensitivity 0.77 ± 0.05 pg/tube. Plasma CNP resulted significantly higher in children than in adult subjects (13.6 ± 1.2 pg/ml vs. 7.4 ± 1.0 pg/ml, p=0.030). When the results were analyzed as a function of the age the reference intervals for plasma CNP resulted: 11.6 ± 2.1 pg/ml for newborns (0-3 days), 16.4 ± 3.7 pg/ml for newborns (4-30 days), 15.4 ± 2.7 pg/ml for infants (1-12 months), 13.6 ± 2.3 pg/ml for children (1-12 years) [p=0.01 newborns (4-30 days) vs. adults; p=0.03 infants (1-12 months) vs. adults]. CNP showed the highest concentrations after 12h of life with a peak between 4 and 5 days of life and with a progressive decline afterwards. According to these data at least five different reference intervals for CNP determinations should be used. These observations may be helpful for future clinical application of CNP in human children.

Expression of C-type natriuretic peptide and its receptor NPR-B in cardiomyocytes.

C-type natriuretic peptide (CNP) was recently found in myocardium at the mRNA and protein levels, but it is not known whether cardiomyocytes are able to produce CNP. The aim of this study was to determine the expression of CNP and its specific receptor NPR-B in cardiac cells, both in vitro and ex vivo. CNP, brain natriuretic peptide (BNP) and natriuretic peptide receptor (NPR)-B mRNA expression were examined by RT-PCR in the H9c2 rat cardiac myoblast cell line, in neonatal rat primary cardiomyocytes and in human umbilical vein endothelial cells (HUVECs) as control. CNP protein expression was probed in cardiac tissue sections obtained from adult male minipigs by immunohistochemistry, and in H9c2 cells both by immunocytochemistry and by specific radioimmunoassay. The results showed that cardiac cells as well as endothelial cells were able to produce CNP. Unlike cardiomyocytes, as expected, in endothelial cells expression of BNP was not detected. NPR-B mRNA expression was found in both cell types. Production of CNP in the heart muscle cells at protein level was confirmed by radioimmunological determination (H9c2: CNP=0.86 ± 0.083 pg/mg) and by immunocytochemistry studies. By immunostaining of tissue sections, CNP was detected in both endothelium and cardiomyocytes. Expression of CNP in cardiac cells at gene and protein levels suggests that the heart is actively involved in the production of CNP.

Sequencing and cardiac expression of natriuretic peptide receptors A and C in normal and heart failure pigs.

Pharmacological treatments able to activate natriuretic receptors (NPRs) and inhibit cardiac remodelling in heart failure (HF) patients, are currently under investigation. To better understand the therapeutic potential of the NPRs activation is necessary to dispose of experimental models devoid of confounding effects. The pig constitutes an animal model largely used but its genome is not completely sequenced. Aims of this study were to sequence NPR-A and NPR-C in Susscrofa and to evaluate ANP, BNP and NPRs mRNA expression in cardiac tissue of normal and HF minipigs in order to have a starting point for future studies devoted to check new potential drugs. Cardiac tissue was collected from adult male minipigs without (n=4) and with HF (n=5). Pig NPR-A (179bp) and NPR-C (203bp) mRNA were partially sequenced (GenBank n.: FJ518622, FJ518621). Compared to control, ANP and BNP gene expression resulted higher in all the cardiac chambers of HF heart. This increase is associated to a down-regulation of NPR-A and an up-regulation of NPR-C in HF. These sequences will provide a new tool to investigate the role of natriuretic peptides and of their receptors under physiological and pathological conditions and their response to therapeutic interventions.

Lymphatic delivery and in vitro pancreatic lipase hydrolysis of glycerol esters of conjugated linoleic acids in rats.

We examined the intestinal delivery of conjugated linoleic acids (CLA) given in their triacylglycerol form in the mesenteric lymph of rats. Emulsions containing a mixture of the trilinolein/triester of CLA (9:1) and a tri-[1-(14)C]-linoleyl-sn-glycerol tracer were administered by force-feeding. Lymph was collected over two time periods (0-6 and 6-24 h), and the apparent recovery of CLA was determined relative to that of [1-(14)C]-18:2(n-6). A mixture of CLA-triester/trilinolein (1:9), trilinolein or CLA-triester was separately subjected to pancreatic lipase hydrolysis in vitro to determine whether the lymphatic recovery of CLA was correlated with the initial step of digestion. Lymphatic recovery of CLA was similar to that of 18:2(n-6) (95.6+/-9.0% of the linoleic acid recovery), and isomer repartition was similar in lymph and in the oil fed, indicating that all the CLA isomers were equally absorbed by the enterocytes. Unexpectedly, the in vitro release of CLA into the absorbable forms (free fatty acids and 2-monoacyl-sn-glycerol) was consistently lower than that of 18:2(n-6). Moreover, the 9c, 11t-isomer of CLA was also released faster into the absorbable forms than its 10t,12c homolog (P = 0.05). We cannot ascribe a distinct cellular accumulation or a difference in the biological effects of different CLA isomers on the ground of a selective intestinal absorbability. Also, the physiological conditions prevailing in vivo in the digestive tract are likely to overcome the relative resistance of CLA ester bonds to pancreatic lipase hydrolysis and allow a lymphatic recovery of CLA similar to that of linoleic acid.

A comparison of the transition from first words to grammar in English and Italian.

Cross-linguistic similarities and differences in early lexical and grammatical development are reported for 1001 English-speaking children and 386 Italian-speaking children between 1;6 and 2;6. Parents completed the English or Italian versions of the MacArthur Communicative Development Inventory: Words and Sentences, a parent report instrument that provides information about vocabulary size, vocabulary composition and grammatical complexity across this age range. The onset and subsequent growth of nouns, predicates, function words and social terms proved to be quite similar in both languages. No support was found for the prediction that verbs would emerge earlier in Italian, although Italians did produce a higher proportion of social terms, and there were small but intriguing differences in the shape of the growth curve for grammatical function words. A strikingly similar nonlinear relationship between grammatical complexity and vocabulary size was observed in both languages, and examination of the order in which function words are acquired also yielded more similarities than differences. However, a comparison of the longest sentences reported for a subset of children demonstrates large cross-linguistic differences in the amount of morphology that has been acquired in children matched for vocabulary size. Discussion revolves around the interplay between language-specific variations in the input to young children, and universal cognitive and social constraints on language development.

Long-term adaptation to high-fat diets modifies the nature and output of postprandial intestinal lymph fatty acid in rats.

These studies were designed to investigate the lymph absorption of a lipid emulsion in rats prefed different long-term high-fat diets. Particular emphasis was placed on the consequences of endogenous fatty acid alteration on the lymph recovery of two labeled fatty acids. Male Wistar rats were fed a standard diet (LF) containing 3.5 g/100 g fat or high-fat diets containing 15 g/100 g sunflower oil (HSFO), menhaden oil (HMO) or medium-chain triglyceride oil (HMCT) for 4 wk. The lymph was collected for 3 h before and after the intraduodenal infusion of a 90 micromol lipid emulsion (30 micromol monopalmitin, 30 micromol oleic acid, 25 micromol linoleic acid, 5 micromol arachidonic acid) labeled with [3H] oleic (OA) and [14C] arachidonic (AA) acids. The [3H] OA and [14C] AA lymph recoveries were measured and the lymph samples were tested for fatty acid, phospholipid and triglyceride content. Prefeeding an HSFO or HMO diet led to a 65 or 32% greater total lymph fatty acid output, respectively, compared with rats prefed the LF diet. In rats prefed both the HSFO and HMO diets, lymph fatty acid characteristics provided evidence of a dilution of exogenous fatty acids coming from the emulsion by endogenous fatty acids. In rats prefed the HMCT diet, the total lymph fatty acid output after the infusion of the lipid emulsion was not greater than that of starved rats. Nevertheless, 27% [3H] OA and 21% [14C] AA were recovered in the lymph, suggesting a limited dilution of exogenous fatty acids by endogenous fatty acids. In rats prefed the HMCT diet, some exogenous long-chain fatty acids must have been transported by the portal vein in response to low biliary phopholipid production, as indicated by the proportions of [3H] OA and [14C] AA taken up by the mucosa and not recovered in the lymph. Thus we demonstrated that during absorption of a single long-chain fatty acid meal a dilution of exogenous fatty acids by endogenous fatty acids occurred. The nature and the quantity of these endogenous fatty acids could alter the absorption efficiency of long-chain fatty acids by the lymphatic pathway and modify the fatty acid characteristics of lymph lipoprotein.

Effect of cyclic fatty acid monomers on fat absorption and transport depends on their positioning within the ingested triacylglycerols.

We investigated the intestinal digestion of cyclic fatty acid monomers (CFAM) isolated from heated linseed oil and their effects upon fatty acid lymphatic transport and lipoprotein profile in lymph. These cyclic fatty acid monomers were acylated in specific positions in the glycerol backbone of triacylglycerols (sn-(1/3) position for the 1C oil, sn-2 position for the 2C oil and together in the sn-1,2, and 3 positions for the 3C oil) and administered intragastrically to lymph-canulated rats. Their lumenal digestibility was also assessed in vitro using a pancreatic lipase assay. The lipase activity was 1.9 to 6.6 less towards the triacylglycerols acylated with cyclic fatty acids compared to control. The lowest activity was with the 2C oil. In the hydrolytic products, the cyclic fatty acid contents were similar between the experimental groups. When absorbed as 2-monoacyl-sn-glycerol (2C oil), cyclic fatty acid monomers were better and unselectively recovered into the lymph than when absorbed as free fatty acids (1C oil). In that latter situation, the bulkier cyclic fatty acids (C6 and cis membered-ring CFAM) were transported into the lymph to a lesser extent. The appearance of the lymphatic chylomicrons was delayed in rats fed the 1C oil. Cyclic fatty acid monomers from the 2C oil only increased the lymphatic transport of saturated fatty acids (80%). Cyclic fatty acids from the 3C oil (absorbed as 2-monoacyl-sn-glycerol and free fatty acid) usually elicited intermediary effects. We conclude that the effects of cyclic fatty acid monomers upon the intestinal metabolism are greatly influenced by their positioning within the triacylglycerol and that the structure of the cyclic fatty acids influences their lymphatic recovery only when they are absorbed as free fatty acid.