Increased macrophage migration inhibitory factor (MIF) plasma levels in acute HIV-1 infection.

Considering macrophage migratory inhibitory factor (MIF) as a critical pro-inflammatory cytokine of the immune system, we evaluated plasma MIF levels in 89 HIV-infected adults. Plasma MIF levels were higher in HIV-infected than in HIV-negative individuals. Highest MIF levels were observed during acute HIV infection (AHI) whilst patients on antiretroviral therapy (ART) had lower MIF levels, regardless of ART efficacy. Our results suggest that MIF is an integral component of the cytokine storm characteristic of AHI.

Distribution of plasma levels of adiponectin and leptin in an adult Caucasian population.

OBJECTIVES: Little is known regarding the distribution and the determinants of leptin and adiponectin levels in the general population. DESIGN: Cross-sectional study. PATIENTS: Women (3004) and men (2552) aged 35-74 living in Lausanne, Switzerland. MEASUREMENTS: Plasma levels of leptin and adiponectin (ELISA measurement). RESULTS: Women had higher leptin and adiponectin levels than men. In both genders, leptin and adiponectin levels increased with age. After adjusting for fat mass, leptin levels were significantly and negatively associated with age in women: 18.1 +/- 0.3, 17.1 +/- 0.3, 16.7 +/- 0.3 and 15.5 +/- 0.4 ng/ml (adjusted mean +/- SE) for age groups [35-44], [45-54], [55-64] and [65-75], respectively, P < 0.001. A similar but nonsignificant trend was also found in men. Conversely, the age-related increase of adiponectin was unrelated to body fat in both genders. Post-menopausal women had higher leptin and adiponectin levels than premenopausal women, independently of hormone replacement therapy. Although body fat mass was associated with leptin and adiponectin, the associations were stronger with body mass index (BMI), waist and hip in both genders. Finally, after adjusting for age and anthropometry, no relationships were found between leptin or adiponectin levels with alcohol, caffeine consumption and physical activity, whereas smoking and diabetes decreased leptin and adiponectin levels in women only. CONCLUSIONS: The age-related increase in leptin levels is attributable to changes in fat mass in women and probably also in men. Leptin and adiponectin levels are more related to BMI than to body fat mass. The effects of smoking and diabetes appear to be gender-specific.

Variability of voriconazole plasma levels measured by new high-performance liquid chromatography and bioassay methods, [and] Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes

Rapport de synthèse1. Partie de laboratoireCette première étude décrit le développement et la validation, selon les standards internationaux, de deux techniques de mesure des concentrations sanguines de voriconazole, un nouvel agent antifongique à large spectre: 1) la chromatographic en phase liquide à haute pression et 2) le bio-essai utilisant une souche mutante de Candida hypersensible au voriconazole. Ce travail a aussi permis de mettre en évidence une importante et imprévisible variabilité inter- et intra-individuelle des concentrations sanguines de voriconazole malgré l'utilisation des doses recommandées par le fabriquant. Ce travail a été publié dans un journal avec "peer-review": "Variability of voriconazole plasma levels measured by new high- performance liquid chromatography and bioassay methods" by A. Pascual, V. Nieth, T. Calandra, J. Bille, S. Bolay, L.A. Decosterd, T. Buclin, P.A. Majcherczyk, D. Sanglard, 0. Marchetti. Antimicrobial Agents Chemotherapy, 2007; 51:137-432. Partie CliniqueCette deuxième étude a évalué de façon prospective l'impact clinique des concentrations sanguines de voriconazole sur l'efficacité et sécurité thérapeutique chez des patients atteints d'infections fongiques. Des concentrations sanguines élevées étaient significativement associés à la survenue d'une toxicité neurologique (encéphalopathie avec confusion, hallucinations et myoclonies) et des concentrations sanguines basses à une réponse insuffisante au traitement antifongique (persistance ou progression des signes cliniques et radiologiques de l'infection). Dans la majorité des cas, un ajustement de la dose de voriconazole, sur la base des concentrations mesurées, a abouti à une récupération neurologique complète ou à une résolution de l'infection, respectivement. Ce travail a été publié dans un journal avec "peer-review": " Voriconazole Therapeutic Drug Monitoring in Patients with Invasive Mycoses Improves Efficacy and Safety Outcomes" by A. Pascual, T. Calandra, S. Bolay, T. Buclin, J. Bille, and O. Marchetti. Clinical Infectious Diseases, 2008 January 15; 46(2): 201-11.Ces deux études, financées de façon conjointe par un "grant" international de la Société suisse d'infectiologie et la Société internationale de maladies infectieuses et par la Fondation pour le progrès en microbiologie médicale et maladies infectieuses (FAMMID, Lausanne), ont été réalisées au sein du Service des Maladies Infectieuses, Département de Médecine, au CHUV, en étroite collaboration avec la Division de Pharmacologie Clinique, Département de Médecine, au CHUV et l'Institut de Microbiologie du CHUV et de l'Université de Lausanne.

Genetic variants influencing circulating lipid levels and risk of coronary artery disease.

OBJECTIVE: Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. METHODS AND RESULTS: We combined genome-wide association data from 8 studies, comprising up to 17 723 participants with information on circulating lipid concentrations. We did independent replication studies in up to 37 774 participants from 8 populations and also in a population of Indian Asian descent. We also assessed the association between single-nucleotide polymorphisms (SNPs) at lipid loci and risk of CAD in up to 9 633 cases and 38 684 controls. We identified 4 novel genetic loci that showed reproducible associations with lipids (probability values, 1.6×10(-8) to 3.1×10(-10)). These include a potentially functional SNP in the SLC39A8 gene for HDL-C, an SNP near the MYLIP/GMPR and PPP1R3B genes for LDL-C, and at the AFF1 gene for triglycerides. SNPs showing strong statistical association with 1 or more lipid traits at the CELSR2, APOB, APOE-C1-C4-C2 cluster, LPL, ZNF259-APOA5-A4-C3-A1 cluster and TRIB1 loci were also associated with CAD risk (probability values, 1.1×10(-3) to 1.2×10(-9)). CONCLUSIONS: We have identified 4 novel loci associated with circulating lipids. We also show that in addition to those that are largely associated with LDL-C, genetic loci mainly associated with circulating triglycerides and HDL-C are also associated with risk of CAD. These findings potentially provide new insights into the biological mechanisms underlying lipid metabolism and CAD risk.

Cardiac hypertrophy, low blood pressure, and low aldosterone levels in mice devoid of the three circadian PAR bZip transcription factors DBP, HLF, and TEF.

The cardiovascular system is under the control of the circadian clock, and disturbed circadian rhythms can induce cardiovascular pathologies. This cyclic regulation is probably brought about by the circadian expression of genes encoding enzymes and regulators involved in cardiovascular functions. We have previously shown that the rhythmic transcription of output genes is, in part, regulated by the clock-controlled PAR bZip transcription factors DBP (albumin D-element Binding Protein), HLF (Hepatic Leukemia Factor), and TEF (Thyrotroph Embryonic Factor). The simultaneous deletion of all three PAR bZip transcription factors leads to increased morbidity and shortened life span. Here, we demonstrate that Dbp/Tef/Hlf triple knockout mice develop cardiac hypertrophy and left ventricular dysfunction associated with a low blood pressure. These dysfunctions are exacerbated by an abnormal response to this low blood pressure characterized by low aldosterone levels. The phenotype of PAR bZip knockout mice highlights the importance of circadian regulators in the modulation of cardiovascular functions.

Combining ability of maize grain yield under different levels of environmental stress

The objectives of this work were to caracterize the tropical maize germplasm and to compare the combining abilities of maize grain yield under different levels of environmental stress. A diallel was performed among tropical maize cultivars with wide adaptability, whose hybrid combinations were evaluated in two sowing dates, in two years. The significance of the environmental effect emphasized the environmental contrasts. Based on grain yield, the environments were classified as favorable (8,331 kg ha-1), low stress (6,637 kg ha-1), high stress (5,495 kg ha-1), and intense stress (2,443 kg ha-1). None of the genetic effects were significant in favorable and intense stress environments, indicating that there was low germplasm variability under these conditions. In low and high stresses, the specific combining ability effects (SCA) were significant, showing that the nonadditive genetic effects were the most important, and that it is possible to select parent pairs with breeding potential. SCA and grain yield showed significant correlations only between the closer environment pairs like favorable/low stress and high/intense stress. The genetic control of grain yield differed under contrasting stress environments for which maize cultivars with wide adaptability are not adequate.

Growth performance and body composition of giant trahira fingerlings fed diets with different protein and energy levels

The objective of this work was to determine the proper levels of protein and energy in diets of Hoplias lacerdae fingerlings. The dietary crude protein (CP) and gross energy (GE) levels for fingerlings of giant trahira were evaluated in a completely randomized 4x3 factorial design with 35, 39, 43 and 47% CP and 4,100, 4,300 and 4,500 kcal kg-1 of GE, and four replicates. The survival rate was 99.22%, and a linear improvement on the performance parameters was detected after increasing diet crude protein levels. Feed conversion ratio decreased with increasing levels of dietary protein and energy in the diets. A significant interaction between crude protein and gross energy was observed over body protein and mineral matter. Body lipid has increased linearly as gross energy in the diet increased. The retention of crude protein and energy showed a linear increasing with rising of crude protein levels in the diet. Crude protein level at 47% provides the best performance and energy retention, independently of the gross energy levels in the diet.

Production of annual winter forage sown before and after soybean harvest under different nitrogen fertilization levels

The objective of this work was to evaluate the effect on forage yield of sowing winter forage species before and after soybean harvest, at different nitrogen application levels. The experiment was set out in a randomized block design with a strip-split plot arrangement, and three replicates. Sowing methods (18 days before soybean harvest and six days after soybean harvest) were allocated in the main plots, and the combination among forage species (Avena strigosa cv. IAPAR 61 + Lolium multiflorum; A. strigosa cv. Comum + L. multiflorum; A. strigosa cv. Comum + L. multiflorum + Vicia villosa; A. strigosa cv. Comum + L. multiflorum + Raphanus sativus; and L. multiflorum) and nitrogen levels (0, 140, 280 and 420 kg ha-1) in the plots and subplots, respectively. Forage sowing before the soybean harvest made it possible to anticipate first grazing by 14 days, with satisfactory establishment of forage species without affecting forage production. This method permitted a longer grazing period, preventing the need for soil disking, besides allowing the use of no-tillage system. The mixture of forage species enables higher forage yield for pasture in relation to single species pastures, with response to nitrogen fertilization up to 360 kg ha-1.

Use of recovered frying oils in chicken and rabbit feeds: effect on the fatty acid and tocol composition and on the oxidation levels of meat, liver and plasma

The addition of some fat co- and by-products to feeds is usual nowadays; however, the regulations of their use are not always clear and vary between countries. For instance, the use of recycled cooking oils is not allowed in the European Union, but they are used in other countries. However, oils recovered from industrial frying processes could show satisfactory quality for this purpose. Here we studied the effects of including oils recovered from the frying industry in rabbit and chicken feeds (at 30 and 60 g/kg, respectively) on the fatty acid (FA) and tocol (tocopherol + tocotrienol) compositon of meat, liver and plasma, and on their oxidative stability. Three dietary treatments (replicated eight times) were compared: fresh non-used oil (LOX); oil discarded from the frying industry, having a high content of secondary oxidation compounds (HOX); and an intermediate level (MOX) obtained by mixing 50 : 50 of LOX and HOX. The FA composition of oil diets and tissues was assessed by GC, their tocol content by HPLC, the thiobarbituric acid value was used to assess tissue oxidation status, and the ferrous oxidation-xylenol orange method was used to assess the susceptibility of tissues to oxidation. Our results indicate that FA composition of rabbit and chicken meat, liver and plasma was scarcely altered by the addition of recovered frying oils to feed. Differences were encountered in the FA composition between species, which might be attributed mainly to differences in the FA digestion, absorption and metabolism between species, and to some physiological dietary factors (i.e. coprophagy in rabbits that involves fermentation with FA structure modification). The α-tocopherol (αT) content of tissues was reduced in response to the lower αT content in the recovered frying oil. Differences in the content of other tocols were encountered between chickens and rabbits, which might be attributable to the different tocol composition of their feeds, as well as to species differences in the digestion and metabolism of tocols. Tissue oxidation and susceptibility to oxidation were in general low and were not greatly affected by the degree of oxidation of the oil added to the feeds. The relative content of polyunsaturated fatty acids/αT in these types of samples would explain the differences observed between species in the susceptibility of each tissue to oxidation. According to our results, oils recovered from the frying industry could be useful for feed uses.

Intercepted solar radiation by maize crops subjected to different tillage systems and water availability levels

The objective of this work was to evaluate changes in the photosynthetic photon flux density (PPFD) interception efficiency and PPFD extinction coefficient for maize crop subjected to different soil tillage systems and water availability levels. Crops were subjected to no-tillage and conventional tillage systems combined with full irrigation and non-irrigation treatments. Continuous measurements of transmitted PPFD on the soil surface and incoming PPFD over the canopy were taken throughout the crop cycle. Leaf area index and soil water potential were also measured during the whole period. Considering a mean value over the maize cycle, intercepted PPFD was higher in the conventional tillage than in the no-tillage system. During the initial stages of plants, intercepted PPFD in the conventional tillage was double the PPFD interception in the no-tillage treatment. However, those differences were reduced up to the maximum leaf area index, close to tasseling stage. The lowest interception of PPFD occurred in the conventional tillage during the reproductive period, as leaf senescence progressed. Over the entire crop cycle, the interception of PPFD by the non-irrigated plants was about 20% lower than by the irrigated plants. The no-tillage system reduced the extinction coefficient for PPFD, which may have allowed a higher penetration of solar radiation into the canopy

Incidence and risk factors for chronic elevation of alanine aminotransferase levels in HIV-infected persons without hepatitis b or c virus co-infection.

BACKGROUND: Chronic liver disease in human immunodeficiency virus (HIV)-infected patients is mostly caused by hepatitis virus co-infection. Other reasons for chronic alanine aminotransferase (ALT) elevation are more difficult to diagnose. METHODS: We studied the incidence of and risk factors for chronic elevation of ALT levels (greater than the upper limit of normal at 2 consecutive semi-annual visits) in participants of the Swiss HIV Cohort Study without hepatitis B virus (HBV) or hepatitis C virus (HCV) infection who were seen during the period 2002-2008. Poisson regression analysis was used. RESULTS: A total of 2365 participants were followed up for 9972 person-years (median age, 38 years; male sex, 66%; median CD4+ cell count, 426/microL; receipt of antiretroviral therapy [ART], 56%). A total of 385 participants (16%) developed chronic elevated ALT levels, with an incidence of 3.9 cases per 100 person-years (95% confidence interval [CI], 3.5-4.3 cases per 100 person-years). In multivariable analysis, chronic elevated ALT levels were associated with HIV RNA level >100,000 copies/mL (incidence rate ratio [IRR], 2.23; 95% CI, 1.45-3.43), increased body mass index (BMI, defined as weight in kilograms divided by the square of height in meters) (BMI of 25-29.9 was associated with an IRR of 1.56 [95% CI, 1.24-1.96]; a BMI 30 was associated with an IRR of 1.70 [95% CI, 1.16-2.51]), severe alcohol use (1.83 [1.19-2.80]), exposure to stavudine (IRR per year exposure, 1.12 [95% CI, 1.07-1.17]) and zidovudine (IRR per years of exposure, 1.04 [95% CI, 1.00-1.08]). Associations with cumulative exposure to combination ART, nucleoside reverse-transcriptase inhibitors, and unboosted protease inhibitors did not remain statistically significant after adjustment for exposure to stavudine. Black ethnicity was inversely correlated (IRR, 0.52 [95% CI, 0.33-0.82]). Treatment outcome and mortality did not differ between groups with and groups without elevated ALT levels. CONCLUSIONS: Among patients without hepatitis virus co-infection, the incidence of chronic elevated ALT levels was 3.9 cases per 100 person-years, which was associated with high HIV RNA levels, increased BMI, severe alcohol use, and prolonged stavudine and zidovudine exposure. Long-term follow-up is needed to assess whether chronic elevation of ALT levels will result in increased morbidity or mortality.

Use of recovered frying oils in chicken and rabbit feeds: effect on the fatty acid and tocol composition and on the oxidation levels of meat, liver and plasma

The addition of some fat co- and by-products to feeds is usual nowadays; however, the regulations of their use are not always clear and vary between countries. For instance, the use of recycled cooking oils is not allowed in the European Union, but they are used in other countries. However, oils recovered from industrial frying processes could show satisfactory quality for this purpose. Here we studied the effects of including oils recovered from the frying industry in rabbit and chicken feeds (at 30 and 60 g/kg, respectively) on the fatty acid (FA) and tocol (tocopherol1tocotrienol) compositon of meat, liver and plasma, and on their oxidative stability. Three dietary treatments (replicated eight times) were compared: fresh non-used oil (LOX); oil discarded from the frying industry, having a high content of secondary oxidation compounds (HOX); and an intermediate level (MOX) obtained by mixing 50 : 50 of LOX and HOX. The FA composition of oil diets and tissues was assessed by GC, their tocol content by HPLC, the thiobarbituric acid value was used to assess tissue oxidation status, and the ferrous oxidation-xylenol orange method was used to assess the susceptibility of tissues to oxidation. Our results indicate that FA composition of rabbit and chicken meat, liver and plasma was scarcely altered by the addition of recovered frying oils to feed. Differences were encountered in the FA composition between species, which might be attributed mainly to differences in the FA digestion, absorption and metabolism between species, and to some physiological dietary factors (i.e. coprophagy in rabbits that involves fermentation with FA structure modification). The a-tocopherol (aT) content of tissues was reduced in response to the lower aT content in the recovered frying oil. Differences in the content of other tocols were encountered between chickens and rabbits, which might be attributable to the different tocol composition of their feeds, as well as to species differences in the digestion and metabolism of tocols. Tissue oxidation and susceptibility to oxidation were in general low and were not greatly affected by the degree of oxidation of the oil added to the feeds. The relative content of polyunsaturated fatty acids/aT in these types of samples would explain the differences observed between species in the susceptibility of each tissue to oxidation. According to our results, oils recovered from the frying industry could be useful for feed uses.

A need for determination of arsenic species at low levels in cereal-based food and infant cereals. Validation of a method by LC-ICPMS.

The present study arose from the need to determine inorganic arsenic (iAs) at low levels in cereal-based food. Validated methods with a low limit of detection (LOD) are required to analyse these kinds of food. An analytical method for the determination of iAs, methylarsonic acid (MA) and dimethylarsinic acid (DMA) in cereal-based food and infant cereals is reported. The method was optimised and validated to achieve low LODs. Ion chromatography-inductively coupled plasma mass spectrometry (LC-ICPMS) was used for arsenic speciation. The main quality parameters were established. To expand the applicability of the method, different cereal products were analysed: bread, biscuits, breakfast cereals, wheat flour, corn snacks, pasta and infant cereals. The total and inorganic arsenic content of 29 cereal-based food samples ranged between 3.7-35.6 and 3.1-26.0 microg As kg-1, respectively. The present method could be considered a valuable tool for assessing inorganic arsenic contents in cereal-based foods.