Effects of Lactobacillus hilgardii 4785 and Lactobacillus buchneri 40788 on the bacterial community, fermentation and aerobic stability of high-moisture corn silage.

AIMS: To evaluate the capacity of Lactobacillus hilgardii and Lactobacillus buchneri on modifying the bacterial community and improving fermentation and aerobic stability of high-moisture corn (HMC). METHODS AND RESULTS: High-moisture corn was untreated (CTR), treated with L. hilgardii (LH) or L. buchneri (LB) at 600 000 CFU per gram fresh weight, or with L. hilgardii and L. buchneri at 300 000 CFU per gram fresh weight each (LHLB), and stored for 10, 30 or 92 days. Compared to CTR, inoculated silages had higher Lactobacillaceae relative abundance, lower yeasts numbers and higher aerobic stability. Treatment with LHLB resulted in a higher acetic acid concentration than LH and higher 1,2 propanediol concentration than LB, such differences were numerically greater at 10 and 30 days but statistically greater at 92 days. At 10 days, all inoculated silages were more stable than CTR, but LHLB was even more stable than LB or LH. CONCLUSIONS: The combination of L. hilgardii and L. buchneri had a synergistic effect on yeast inhibition, leading to greater improvements in aerobic stability as early as 10 days after ensiling. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus hilgardii, especially in combination with L. buchneri, can improve the aerobic stability of HMC after a very short period of ensiling.

Fatigue-independent alterations in muscle activation and effort perception during forearm exercise: role of local oxygen delivery.

The oxygen-conforming response (OCR) of skeletal muscle refers to a downregulation of muscle force for a given muscle activation when oxygen delivery (O2D) is reduced, which is rapidly reversed when O2D is restored. We tested the hypothesis that the OCR exists in voluntary human exercise and results in compensatory changes in muscle activation to maintain force output, thereby altering perception of effort. In eight men and eight women, electromyography (EMG), oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb), forearm blood flow (FBF), and task effort awareness (TEA) were measured. Participants completed two nonfatiguing rhythmic handgrip tests consisting of 5-min steady state (SS) followed by two bouts of 2-min brachial artery compression to reduce FBF by ~50% of SS (C1 and C2), separated by 2 min of no compression (NC1) and ending with 2 min of no compression (NC2). When FBF was compromised during C1, EMG/Force (1.58 ± 0.39) increased compared with SS (1.31 ± 0.33, P = 0.001). However, EMG/Force was not restored upon FBF restoration at NC1 (1.48 ± 0.38, P = 0.479), consistent with C1 evoking skeletal muscle fatigue. When FBF was compromised during C2, EMG/Force increased (1.73 ± 0.50) compared with NC1 (1.48 ± 0.38, P = 0.013). EMG/Force returned to NC1 levels during NC2 (1.50 ± 0.39, P = 0.016), consistent with an OCR in C2. TEA (SS 2.2 ± 2.3, C1 3.9 ± 2.5, NC1 3.4 ± 2.7, C2 4.6 ± 2.7, NC2 3.9 ± 2.8) mirrored changes in EMG. It is noteworthy that during the second compromise and then restoration of muscle oxygenation EMG and TEA were rapidly restored to precompromise levels. We interpreted these findings to support the existence of an OCR and its ability to rapidly modify perception of effort during voluntary exercise. NEW & NOTEWORTHY In healthy individuals, when force output is maintained during rhythmic handgrip exercise, muscle activation and perception of effort rapidly increase with compromised muscle oxygen delivery (O2D) and then return to precompromised levels when muscle O2D is restored. These findings suggest that an oxygen-conforming response (OCR) exists and is able to modify perception of effort during voluntary exercise. Therefore, similar to fatigue, an OCR may have implications for exercise tolerance.

Silage review: Unique challenges of silages made in hot and cold regions.

Silage making can be conveniently divided into field, ensiling, storage, and feed-out phases. In all of these stages, controllable and uncontrollable components can affect silage quality. For instance, silages produced in hot or cold regions are strongly influenced by uncontrollable climate-related factors. In hot regions, crops for silage are influenced by (1) high temperatures negatively affecting corn yield (whole-crop and grain) and nutritive value, (2) butyric and alcoholic fermentations in warm-season grasses (Panicum, Brachiaria, and Pennisetum genera) and sugarcane, respectively, and (3) accelerated aerobic deterioration of silages. Ensiling expertise and economic factors that limit mechanization also impair silage production and utilization in hot environments. In cold regions, a short and cool growing season often limits the use of crops sensitive to cool temperature, such as corn. The fermentation triggered by epiphytic and inoculated microorganisms can also be functionally impaired at lower temperature. Although the use of silage inoculants has increased in Northern Europe, acid-based additives are still a good option in difficult weather conditions to ensure good fermentation quality, nutritive value, and high intake potential of silages. Acid-based additives have enhanced the quality of round bale silage, which has become a common method of forage preservation in Northern Europe. Although all abiotic factors can affect silage quality, the ambient temperature is a factor that influences all stages of silage making from production in the field to utilization at the feed bunk. This review identifies challenges and obstacles to producing silages under hot and cold conditions and discusses strategies for addressing these challenges.

Silage review: Mycotoxins in silage: Occurrence, effects, prevention, and mitigation.

Ensiled forage, particularly corn silage, is an important component of dairy cow diets worldwide. Forages can be contaminated with several mycotoxins in the field pre-harvest, during storage, or after ensiling during feed-out. Exposure to dietary mycotoxins adversely affects the performance and health of livestock and can compromise human health. Several studies and surveys indicate that ruminants are often exposed to mycotoxins such as aflatoxins, trichothecenes, ochratoxin A, fumonisins, zearalenone, and many other fungal secondary metabolites, via the silage they ingest. Problems associated with mycotoxins in silage can be minimized by preventing fungal growth before and after ensiling. Proper silage management is essential to reduce mycotoxin contamination of dairy cow feeds, and certain mold-inhibiting chemical additives or microbial inoculants can also reduce the contamination levels. Several sequestering agents also can be added to diets to reduce mycotoxin levels, but their efficacy varies with the type and level of mycotoxin contamination. This article gives an overview of the types, prevalence, and levels of mycotoxin contamination in ensiled forages in different countries, and describes their adverse effects on health of ruminants, and effective prevention and mitigation strategies for dairy cow diets. Future research priorities discussed include research efforts to develop silage additives or rumen microbial innocula that degrade mycotoxins.

Silage review: Using molecular approaches to define the microbial ecology of silage.

Ensiling of forages was recognized as a microbial-driven process as early as the late 1800s, when it was associated with the production of "sweet" or "sour" silage. Classical microbiological plating techniques defined the epiphytic microbial populations associated with fresh forage, the pivotal role of lactic acid-producing bacteria in the ensiling process, and the contribution of clostridia, bacilli, yeast, and molds to the spoilage of silage. Many of these classical studies focused on the enumeration and characterization of a limited number of microbial species that could be readily isolated on selective media. Evidence suggested that many of the members of these microbial populations were viable but unculturable, resulting in classical studies underestimating the true microbial diversity associated with ensiling. Polymerase chain reaction-based techniques, including length heterogeneity PCR, terminal RFLP, denaturing gradient gel electrophoresis, and automated ribosomal intergenic spacer analysis, were the first molecular methods used to study silage microbial communities. Further advancements in whole comparative genomic, metagenomic, and metatranscriptomic sequencing have or are in the process of superseding these methods, enabling microbial communities during ensiling to be defined with a degree of detail that is impossible using classical microbiology. These methods have identified new microbial species in silage, as well as characterized shifts in microbial communities with forage type and composition, ensiling method, and in response to aerobic exposure. Strain- and species-specific primers have been used to track the persistence and contribution of silage inoculants to the ensiling process and the role of specific species of yeast and fungi in silage spoilage. Sampling and the methods used to isolate genetic materials for further molecular analysis can have a profound effect on results. Primer selection for PCR amplification and the presence of inhibitors can also lead to biases in the interpretation of sequence data. Bioinformatic analyses are reliant on the integrity and presence of sequence data within established databases and can be subject to low taxonomic resolution. Despite these limitations, advancements in molecular biology are poised to revolutionize our current understanding of the microbial ecology of silage.

Effect of temperature (5-25°C) on epiphytic lactic acid bacteria populations and fermentation of whole-plant corn silage.

AIMS: The objective of this study was to investigate the effect of temperature (5-25°C) on epiphytic lactic acid bacteria (LAB) populations during 60 days of fermentation of whole-plant corn silage. METHODS AND RESULTS: Vacuum bag mini-silos of chopped whole-plant corn were incubated at five different temperatures (5, 10, 15, 20 and 25°C), according to a completely randomized design with four repetitions. The silos were opened and sampled on day 0, 1, 2, 3, 7, 28 and 60. At 20 and 25°C, Lactobacillus plantarum- and Pediococcus  pentosaceus-related operational taxonomic units (OTU) dominated the fermentation within 1 day. After 7 days, the OTU related to the heterofermentative species Lactobacillus buchneri began to appear and it eventually dominated silages incubated at these temperatures. Population dynamic of LAB at 5 and 10°C was different. At these temperatures, Leuconostoc citreum OTU was identified at the beginning of the fermentation. Thereafter, Lactobacillus sakei- and Lactobacillus curvatus-related OTU appeared and quickly prevailed. Corn silage at 15°C acted as a transition between 20-25°C and 5-10°C, in terms of LAB diversity and succession. CONCLUSION: The conditions of silage incubation temperature affect species diversity of LAB population with notable difference along the temperature gradient. Colder temperature conditions (5 and 10°C) have led to the identification of LAB species never observed in corn silage. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated the impact of temperature gradient on the diversity and some important population shift of lactic acid bacteria communities during fermentation of corn silage.

Screening histories and contact with physicians as determinants of cervical cancer risk in Montreal, Quebec.

BACKGROUND: Cervical cancer (cca) is largely a preventable disease if women receive regular screening, which allows for the detection and treatment of preinvasive lesions before they become invasive. Having been inadequately screened is a common finding among women who develop cca. Our primary objective was to determine the Pap screening histories of women diagnosed with cca in Montreal, Quebec. Secondary objectives were to determine the characteristics of women at greatest risk of cca and to characterize the level of physician contact those women had before developing cca. METHODS: The Invasive Cervical Cancer Study, a population-based case-control study, consisted of Greater Montreal residents diagnosed with histologically confirmed cca between 1998 and 2004. Respondents to the 2003 Canadian Community Health Survey and a sample of women without cca obtained from Quebec medical billing records served as controls. RESULTS: During the period of interest, 568 women were diagnosed with cca. Immigrants and women speaking neither French nor English were at greatest risk of cca. Most of the women in the case group had been screened at least once during their lifetime (84.8%-90.4%), but they were less likely to have been screened within 3 years of diagnosis. Having received care from a family physician or a medical specialist other than a gynecologist within the 5 years before diagnosis was associated with a greater risk of cca development. CONCLUSIONS: Our findings provide evidence of the need for an organized population-based screening program. They also underscore the need for provider education to prevent missed opportunities for cca screening when at-risk women seek medical attention.

Independent measurement of the total active 8B solar neutrino flux using an array of 3He proportional counters at the Sudbury Neutrino Observatory.

The Sudbury Neutrino Observatory (SNO) used an array of 3He proportional counters to measure the rate of neutral-current interactions in heavy water and precisely determined the total active (nu_x) 8B solar neutrino flux. This technique is independent of previous methods employed by SNO. The total flux is found to be 5.54_-0.31;+0.33(stat)-0.34+0.36(syst)x10(6) cm(-2) s(-1), in agreement with previous measurements and standard solar models. A global analysis of solar and reactor neutrino results yields Deltam2=7.59_-0.21;+0.19x10(-5) eV2 and theta=34.4_-1.2;+1.3 degrees. The uncertainty on the mixing angle has been reduced from SNO's previous results.

Gliclazide modified release: results of a 2-year study in patients with type 2 diabetes.

AIM: To evaluate the efficacy and safety of gliclazide modified release (MR), alone or combined with other oral antidiabetic drug(s) over 2 years in type 2 diabetic patients. METHODS: Two consecutive periods: (i) a 10-month, double-blind comparative study, where 800 type 2 diabetic patients were randomized either to gliclazide MR (30-120 mg) once daily or to gliclazide (80-320 mg) twice daily. All the patients were then treated with gliclazide MR for a 2-month switch period; (ii) 549 patients were subsequently enrolled in a 12-month, open-label period on gliclazide MR alone or in combination according to glycaemic control, 507 of whom completed the study. RESULTS: Glycated haemoglobin (HbA1c) significantly decreased from baseline over 2 years by -0.46 +/- 1.08% in the whole cohort of 2-year completed patients, -0.95% in the subgroup of diet-failed patients and by -0.34% in the subgroup of patients pretreated with one oral antidiabetic drug. HbA1c was reduced by -0.43 +/- 1.02% and by -0.51 +/- 1.16%, when gliclazide MR was used in monotherapy and in combination therapy, respectively. The overall incidence of symptoms suggestive of hypoglycaemia was 4.8 episodes/100 patient-year, with no severe episode. This incidence was similarly low in elderly patients and patients with impaired renal function. CONCLUSION: Gliclazide MR alone or in combination with another oral antidiabetic drug significantly improved glycaemic control in type 2 diabetic patients over 2 years with a very good safety profile, notably in the elderly and in patients with impaired renal function.

Effects of orlistat on obesity-related diseases - a six-month randomized trial.

AIM: To assess the effect of orlistat on body weight and concomitant diseases in patients with body mass index (BMI) of > 28 kg/m2 and poorly controlled type 2 diabetes, hypertension or hypercholesterolaemia. METHODS: This trial was a six-month, randomized, double-blind, placebo-controlled study of orlistat 120 mg three times daily plus a mildly reduced-calorie diet. 1004 obese patients (BMI 28-40 kg/m2) were included by 253 private endocrinologists and received orlistat (n = 499) or placebo (n = 505). Patients were stratified by concomitant disorder (type 2 diabetes, n = 193; hypertension, n = 614; hypercholesterolaemia, n = 197). Body weight, anthropometry, lipid and glycaemic control parameters and blood pressure. RESULTS: After six months, orlistat produced a significantly greater weight loss than placebo in type 2 diabetes (-4.2% vs. -1.4%), hypertension (-6.2% vs. -1.9%) and hypercholesterolaemia (-5.5% vs. -2.3%) groups (p < 0.0001 for all). There was a greater decrease in HbA(1c) in the type 2 diabetes group (-0.54 vs. -0.18%; p = 0.002) and low-density lipoprotein (LDL)-cholesterol in the hypercholesterolaemia group (-11.7% vs. -4.5%; p = 0.004) with orlistat vs. placebo. Early weight loss (> or = 5% at 12 weeks) was associated with the highest weight loss in each group, and the highest decreases in HbA1c, LDL-cholesterol and diastolic blood pressure in patients with type 2 diabetes, hypercholesterolaemia and hypertension, respectively, at six months. The incidence of adverse events was similar for orlistat and placebo, except for certain generally well-tolerated gastrointestinal events that were more common with orlistat. CONCLUSION: Orlistat plus a mildly reduced-calorie diet produced clinically meaningful weight loss and improvements in risk factors in overweight and obese patients with poorly controlled type 2 diabetes, hypertension or hypercholesterolaemia.

A decision-support system for Salmonella in broiler-chicken flocks.

We built a decision-support system to assess the risk of contamination of chicken-broiler flocks by Salmonella at the end of the rearing period. This system was developed from the survey data from 85 chicken-broiler flocks located in western France. First, we estimated the probability of contamination of the house by Salmonella before placement of day-old chicks via a cleansing inspection using a visual-inspection grid, a decontamination evaluation using count-plates, and risk factors for Salmonella persistence in the barn after cleansing and disinfection. Second, we estimated (using a logistic model) the probability of prevalent contamination of the flock by Salmonella at the end of the rearing period. Validation was carried out on 60 flocks selected from seven production companies in western France. The risk estimated by the model was compared to the Salmonella status of the flock (gold standard) assessed by samples taken from the environment of the broilers and analysed with classical bacteriological methods. The sensitivity was 97.8% and the specificity 64.3%.

Fatty acid abnormalities in chronic pancreatitis: effect of concomitant diabetes mellitus.

OBJECTIVE: Patients with chronic pancreatitis suffer from malabsorption and nutritional deficiencies. However there is little data available concerning the fatty acid profile in chronic pancreatitis. Diabetes mellitus, a common complication of this disease, could interfere with the metabolism of fatty acids. SUBJECTS: We therefore compared the fatty acid composition of LDL from four groups of male patients with (a) chronic pancreatitis without diabetes (ND-CP; n=12), (b) diabetes secondary to chronic pancreatitis and insulin-treated (CP-D; n=35); (c) type 1 diabetes (n=25); and (d) controls (n=20). RESULTS: The patients in both groups of chronic pancreatitis (ND-CP and CP-D) had lower mean values for linoleic acid than that seen in the type 1 DM and control groups, whereas monounsaturated fatty acids (MUFA; 18 : 1(n-9) and (16 : 1(n-7)) were significantly increased in these two groups (ND-CP and CP-D). Docosa-hexaenoic-acid (22 : 6(n-3)) was significantly decreased in the CP-D group (P>0.05), a response that could be explained by the effects of diabetes mellitus and by selenium deficiency. In this way, diabetes was associated with a decrease in the docosa-hexaenoic-acid (22 : 6(n-3); r=0.30, P=0.005), and selenium was correlated with DHA (r=0.28, P=0.029) and with the 22 : 6(n-3)/20 : 5(n-3) ratio (evaluating the delta 4 desaturation); r=0.31, P=0.022), independently of the diabetes effect. Selenium was negatively correlated with 20 : 4(n-6)/20 : 3(n-6) ratio (evaluating the delta 5 desaturase; r=-0.30; P=0.025). These results suggest that these two factors may have a role in the regulation of the desaturation process. If we consider that a ratio of 16 : 1(n-7)/18 : 2(n-6) greater than 0.086 in plasma indicates an EFAn-6 deficiency, 40% of our CP patients, 57.6% of CP-D patients and 13.6% of type 1 DM patients were involved. CONCLUSIONS: The consequences of these deficiencies are not evaluated in this disease. However, correction of the fundamental deficiencies in essential fatty acids and in selenium seems desirable in chronic pancreatitis.

Self-monitoring of blood glucose significantly improves metabolic control in patients with type 2 diabetes mellitus: the Auto-Surveillance Intervention Active (ASIA) study.

OBJECTIVE: Self monitoring of blood glucose (SMBG) in type 2 diabetes is a topic of current interest (imbalance between increased health-care costs and improvement in compliance with treatment and diet). An open label randomized prospective study was designed to compare changes in metabolic control over 6 months in patients managed with usual recommendations alone (conventional assessment group) or combined with SMBG. RESEARCH DESIGN AND METHODS: Patients not treated with insulin or previously self monitored, 40 to 75 years of age, with a diagnosis of type 2 diabetes > 1 year and standardized HbA(1c) level > =7.5 and< =11% were randomized to either a control group or SMBG group. They were followed up every 6 weeks over 24 weeks. Patients in the SMBG group were given the same device (Ascensia Esprit Discmeter, Bayer) and were required to perform at least 6 capillary assays a week (3 different days of the week, including weekend). Management of patients was standardized, including drugs, diet and physical activity. The primary efficacy criterion was change in HbA(1c) level in Intent To Treat (ITT) patients. Assays were performed at baseline, at 3 and 6 months using the calibrated DCA 2000(R) device (Bayer). RESULTS: Two hundred sixty five general practitioners randomized 988 patients (ITT Population), but 689 patients were evaluable for the primary criterion. At the endpoint, HbA(1c) was lower in the SMBG group (8.1 +/- 1.6%) than in the conventional treatment group (8.4 +/- 1.4%, P=0.012). The change in HbA(1c) levels between baseline and endpoint was classified into two classes: improvement if a change > 0.5% occurred, stability or worsening in case of a change< =0.5%; 57.1% of patients in the SMBG group vs 46.8% in the control group had an improvement in HbA(1c) level (P=0.007) after 3 months. A steady state was reached during the last 3 months. A multivariate logistic regression analysis was performed and identified factors predictive of improvement in HbA(1c) levels: HbA(1c) at baseline: odd ratio (OR)=1.749 (P<0.001), SMBG group (reference value: SMBG group): OR=0.665 (P=0.015), duration of diabetes: OR=0.953 (P=0.001) and BMI: OR=0.962 (P=0.039). CONCLUSIONS: This study is the first multicenter, controlled, prospective trial conducted on a large number of patients demonstrating that SMBG was statistically associated with a better quality of metabolic control than usual traditional recommendations alone in type 2 diabetes.

Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix.

PURPOSE: To test the hypothesis that cisplatin (CDDP) administered concurrently with standard radiotherapy (RT) would improve pelvic control and survival in patients with advanced squamous cell cancer of the cervix. PATIENTS AND METHODS: A total of 259 patients with International Federation of Gynecology and Obstetrics stage IB to IVA squamous cell cervical cancer with central disease greater-than-or-equal 5 cm or histologically confirmed pelvic lymph node involvement were randomized to receive RT (external-beam RT plus brachytherapy) plus weekly CDDP chemotherapy (40 mg/m(2)) (arm 1) or the same RT without chemotherapy (arm 2). RESULTS: A total of 253 patients were available for analysis. Median follow-up was 82 months. No significant difference was found in progression-free survival (P =.33). No significant difference in 3- and 5-year survival rates was found (69% v 66% and 62% v 58%, respectively; P =.42). The hazard ratio for survival (arm 2 to arm 1) was 1.10 (95% confidence interval, 0.75 to 1.62). CONCLUSION: This study did not show a benefit to either pelvic control or survival by adding concurrent weekly CDDP chemotherapy in a dose of 40 mg/m(2) to radical RT as given in this trial. Careful attention to RT details is important for achieving optimum outcome for patients with this disease.

Which are the insulin treatment regimens used in France? The "Schema survey".

OBJECTIVE: To examine how insulin therapy is used in France under real life conditions for type 1 and insulin-treated type 2 patients. MATERIAL AND METHODS: The "Schema survey" was a cross-sectional survey carried out for all the insulin-treated patients seen by participating physicians on a given day. All registered diabetologists in France were invited to participate, 934 initially agreed, 450 returned at least one questionnaire. These 450 physicians appeared to be representative of the whole. The reasons for which 484 physicians who had initially agreed to participate did not were collected by telephone and do not seem to introduce a bias. 1,263 patients were included in the analysis, type 1: 57.6%, type 2: 36.8%. RESULTS: Over 54% of type 1 patients were treated with 3 or more insulin injections per day. Among type 1 patients treated with 2 injections per day, 30% were younger than 18. Over 82% type 2 patients were treated with 1 or 2 insulin injections per day. A regimen combining oral agents and bed time NPH was used in 18% of type 2 patients. Premixed insulins were used by 45.5% of type 2 and 39.5% of type 1 patients. For patients under 3 or more injections per day, over 30 different regimens were identified. About 40% of patients, either type 1 or 2, were poorly controlled (HbA1c > 8.5%). The frequency of blood glucose monitoring appears to comply with recommendations. CONCLUSIONS: Under real life conditions, a majority of French type 1 patients are treated with intensified multiple injections but a lot are not, despite inadequate metabolic control. Only few type 2 patients are treated with intensified therapy.

Effect of the inflammation, chronic hyperglycemia, or malabsorption on the apolipoprotein A-IV concentration in type 1 diabetes mellitus and in diabetes secondary to chronic pancreatitis.

The metabolism of apolipoprotein (apo) A-IV in diabetes mellitus (DM) is poorly understood. Several factors, such as dietary fat intake, fat malabsorption, acute inflammation, and hormonal dysregulation can disturb the plasma apo A-IV concentration. We have compared the plasma apo A-IV concentrations in patients with type 1 DM and DM secondary to chronic pancreatitis to determine the effects of combinations of these factors. We examined 4 groups of male patients with chronic pancreatitis without diabetes (ND-CP) (n = 12), diabetes secondary to chronic pancreatitis and insulin-treated (CP-DM) (n = 32), type 1 diabetes (n = 25), and controls (n = 20). Plasma apo A-IV was significantly lower in the chronic pancreatitis patients (ND-CP and CP-DM) than in the other patients. Inflammatory proteins (fibrinogen, ceruloplasmin, and haptoglobin) were significantly elevated in the 2 chronic pancreatitis groups. The apo A-IV concentration was positively correlated with hemoglobin A(1c) (HbA(1c)) percentage in each group of diabetic patients (CP-DM, r =.35; P =.046; type 1 DM, r =.53; P =.010), in both groups of diabetic patients (r =.472; P <.0001) and negatively correlated with ceruloplasmin concentration in each group of diabetic patients (CP-DM, r = -.48; P =.0052; type 1 DM, r = -.66; P =.003), in both groups of diabetic patients (r = -.561; P <.0001), and in the whole population (r = -.463; P <.0001). Apo A-IV was also negatively correlated with haptoglobin in type 1 DM patients (r = -.434; P =.0435), in the both groups of diabetic patients (r = -.349; P =.0154), and in the whole population (r = -.351; P =.0019). Multiple linear regression analysis revealed that only HbA(1c) and ceruloplasmin were independent explanatory variables. Plasma apo A-IV is positively correlated with HbA(1c) suggesting that hyperglycemia per se selectively affects apo A-IV metabolism. The correlation between the concentrations of inflammatory protein and apo A-IV suggest a link between chronic inflammation and apo A-IV synthesis or catabolism. As apo A-IV is involved in reverse cholesterol transport, its low level in CP-DM may contribute to the accelerated development of atherosclerosis in these patients.

Endothelial dysfunction and type 2 diabetes. Part 1: physiology and methods for exploring the endothelial function.

Coronary artery, cerebrovascular and peripheral vascular disease, are the principal causes of morbidity and mortality in type 2 diabetes mellitus. The accelerated macrovascular disease in type 2 diabetes mellitus is due partly to the increased incidence of cardiovascular risk factors, such as hypertension, obesity and dyslipidemia. Advanced glycation end products, glycoxidised and oxidized low-density lipoproteins and reactive oxygen species linked to hyperglycemia have all been identified in type 2 diabetes mellitus and could accelerate macroangiopathy. Hence, the resistance to insulin is an additional independent risk factor, in association with oxidant stress, dyslipidemias, and prothrombic/hypofibrinolytic states. The endothelium is a major organ involved by cardiovascular risk factors, such as hypercholesterolemia, hypertension, inflammation, ageing, postmenopausal status, and smoking. Changes in endothelium function may lead to the coronary artery circulation being unable to cope with the increased metabolism of myocardial muscle independently of a reduced coronary artery diameter. The way endothelial function is altered in diabetic patients is not yet fully understood, but the loss of normal endothelial function could be involved in the pathogenesis of diabetic angiopathy, as endothelial dysfunction is associated with diabetic microangiopathy and macroangiopathy. Finally, recent reports indicate that an improved metabolic control in diabetic patients, whatever the treatment used, is associated with near normalization or restoration of normal endothelial function.

Endothelial dysfunction and type 2 diabetes. Part 2: altered endothelial function and the effects of treatments in type 2 diabetes mellitus.

Coronary artery, cerebrovascular and peripheral vascular disease, are the principal causes of morbidity and mortality in type 2 diabetes mellitus. The accelerated macrovascular disease in type 2 diabetes mellitus is due partly to the increased incidence of cardiovascular risk factors, such as hypertension, obesity and dyslipidemia. Advanced glycation end products, glycoxidised and oxidized low-density lipoproteins and reactive oxygen species linked to hyperglycemia have all been identified in type 2 diabetes mellitus and could accelerate macroangiopathy. Hence, the resistance to insulin is an additional independent risk factor, in association with oxidant stress, dyslipidemias, and prothrombic/hypofibrinolytic states. The endothelium is a major organ involved by cardiovascular risk factors, such as hypercholesterolemia, hypertension, inflammation, ageing, postmenopausal status, and smoking. Changes in endothelium function may lead to the coronary artery circulation being unable to cope with the increased metabolism of myocardial muscle independently of a reduced coronary artery diameter. The way endothelial function is altered in diabetic patients is not yet fully understood, but the loss of normal endothelial function could be involved in the pathogenesis of diabetic angiopathy, as endothelial dysfunction is associated with diabetic microangiopathy and macroangiopathy. Finally, recent reports indicate that an improved metabolic control in diabetic patients, whatever the treatment used, is associated with near normalization or restoration of normal endothelial function.

Analysis of the postprandial lipid metabolism: use of a 3-point test.

OBJECTIVES: The oral fat load tests used to study postprandial lipemia are complex and costly and time consuming. A simplified fat load test could be more convenient and more appropriate in routine clinical practice because of the number of lipid determinations required. RESEARCH DESIGN AND METHODS: We evaluated the capacity of a postprandial test model that reduced the number of blood samples taken in thirty three normal weight controls and 17 normotriglyceridemic obese patients (study 1), 10 normolipidemic type 2 diabetic patients and 7 healthy controls (study 2), and 10 hyperlipidemic type 2 diabetic patients studied before and after hypolipidemic therapy (study 3). Blood samples were taken before and up to 8 hours after giving the oral fat load containing retinol. Triglyceride (TG) and retinyl palmitate (RP) concentrations in the plasma, chylomicrons (CM) and non-chylomicron (nCM) fractions were measured. Postprandial lipid responses using conventional area under the curves (AUCc using 5 to 7 lipid determinations) were compared to a 3-point test that uses only three sample points to predict the area under the curve (AUCp: triglycerides at T0, triglycerides at average peak-time (T4), and triglycerides at T8). RESULTS: The AUCc and AUCp for triglycerides and retinyl palmitate were highly correlated in each of the groups and whatever the lipid subfraction (r=0.664 - 0.995, p<0.0001). When incremental AUC (iAUC) were used, the coefficients of correlation for triglycerides remained highly significant between iAUCc and iAUCp (r=0.718 - 0.979, p<0.01 - 0.0001). The same trend of differences was found between cases and controls when AUCp was used instead of AUCc. The means of differences between AUCc and AUCp for triglyceride values were small (0.34 - 0.74 mmol/L.h), and the confidence intervals were acceptable considering the range of the AUCs values (5.60 to 79.8 mmol/L.h for plasma triglycerides). CONCLUSIONS: We found that data obtained with a simplified model of AUC using only 3 points to analyse postprandial lipemia are well correlated with those obtained by conventional AUC, and that the AUCp allows to the same conclusions as AUCc when healthy subjects were compared to patients with altered postprandial metabolism. Thus AUCp may be a good evaluation of the AUCc, and the simplified 3-point protocol may well be used and suitable for studies on large groups of subjects who are eligible for an oral fat load test.