Multi-tissue transcriptomic study reveals the main role of liver in the chicken adaptive response to a switch in dietary energy source through the transcriptional regulation of lipogenesis.

BACKGROUND: Because the cost of cereals is unstable and represents a large part of production charges for meat-type chicken, there is an urge to formulate alternative diets from more cost-effective feedstuff. We have recently shown that meat-type chicken source is prone to adapt to dietary starch substitution with fat and fiber. The aim of this study was to better understand the molecular mechanisms of this adaptation to changes in dietary energy sources through the fine characterization of transcriptomic changes occurring in three major metabolic tissues - liver, adipose tissue and muscle - as well as in circulating blood cells. RESULTS: We revealed the fine-tuned regulation of many hepatic genes encoding key enzymes driving glycogenesis and de novo fatty acid synthesis pathways and of some genes participating in oxidation. Among the genes expressed upon consumption of a high-fat, high-fiber diet, we highlighted CPT1A, which encodes a key enzyme in the regulation of fatty acid oxidation. Conversely, the repression of lipogenic genes by the high-fat diet was clearly associated with the down-regulation of SREBF1 transcripts but was not associated with the transcript regulation of MLXIPL and NR1H3, which are both transcription factors. This result suggests a pivotal role for SREBF1 in lipogenesis regulation in response to a decrease in dietary starch and an increase in dietary PUFA. Other prospective regulators of de novo hepatic lipogenesis were suggested, such as PPARD, JUN, TADA2A and KAT2B, the last two genes belonging to the lysine acetyl transferase (KAT) complex family regulating histone and non-histone protein acetylation. Hepatic glycogenic genes were also down-regulated in chickens fed a high-fat, high-fiber diet compared to those in chickens fed a starch-based diet. No significant dietary-associated variations in gene expression profiles was observed in the other studied tissues, suggesting that the liver mainly contributed to the adaptation of birds to changes in energy source and nutrients in their diets, at least at the transcriptional level. Moreover, we showed that PUFA deposition observed in the different tissues may not rely on transcriptional changes. CONCLUSION: We showed the major role of the liver, at the gene expression level, in the adaptive response of chicken to dietary starch substitution with fat and fiber.

Metal-binding hydrogel particles alleviate soil toxicity and facilitate healthy plant establishment of the native metallophyte grass Astrebla lappacea in mine waste rock and tailings.

Soil contaminants are potentially a major threat to human and ecosystem health and sustainable production of food and energy where mineral processing wastes are discharged into the environment. In extreme conditions, metal concentrations in wastes often exceed even the metal tolerance thresholds of metallophytes (metal-tolerant plants) and sites remain barren with high risks of contaminant leaching and dispersion into the environment via erosion. A novel soil amendment based on micron-size thiol functional cross-linked acrylamide polymer hydrogel particles (X3) binds toxic soluble metals irreversibly and significantly reduces their concentrations in the soil solution to below the phytotoxicity thresholds. X3 mixed into the top 50mm of phytotoxic mine waste materials in pots in glasshouse conditions reduced total soluble concentrations of toxic contaminants by 90.3-98.7% in waste rock, and 88.6-96.4% in tailings immediately after application. After 61 days, quality of unamended bottom layer of X3-treated pots was also significantly improved in both wastes. Combination of X3 and metallophytes was more efficient at improving soil solution quality than X3 alone. Addition of X3 to substrates increased substrate water retention and water availability to plants by up to 108% and 98% for waste rock and tailings respectively. Soil quality improvement by X3 allowed successful early establishment of the native metallophyte grass Astrebla lappacea on both wastes where plants failed to establish otherwise.

Pleiotropic effects of polymorphism of the gene diacylglycerol-O-transferase 1 (DGAT1) in the mammary gland tissue of dairy cows.

Microarray analysis was used to identify genes whose expression in the mammary gland of Holstein-Friesian dairy cows was affected by the nonconservative Ala to Lys amino acid substitution at position 232 in exon VIII of the diacylglycerol-O-transferase 1 (DGAT1) gene. Mammary gland biopsies of 9 homozygous Ala cows, 13 heterozygous cows (Ala/Lys), and 4 homozygous Lys cows in midlactation were taken. Microarray ANOVA and factor analysis for multiple testing methods were used as statistical methods to associate the expression level of the genes present on Affymetrix bovine genome arrays (Affymetrix Inc., Santa Clara, CA) with the DGAT1 gene polymorphism. The data was also analyzed at the level of functional modules by gene set enrichment analysis. In this small-scale experimental setting, DGAT1 gene polymorphism did not modify milk yield and composition significantly, although expected changes occurred in the yields of C14:0, cis-9 C16:1, and long-chain fatty acids. Diacylglycerol-O-transferase 1 gene polymorphism affected the expression of 30 annotated genes related to cell growth, proliferation, and development, remodeling of the tissue, cell signaling and immune system response. Furthermore, the main affected functional modules were related to energy metabolism (lipid biosynthesis, oxidative phosphorylation, electron transport chain, citrate cycle, and propanoate metabolism), protein degradation (proteosome-ubiquitin pathways), and the immune system. We hypothesize that the observed differences in transcriptional activity reflect counter mechanisms of mammary gland tissue to respond to changes in milk fatty acid concentration or composition, or both.

[Global therapy management of chronic heart failure during cardiac rehabilitation]. / Prise en charge globale de l'insuffisance cardiaque en réadaptation.

Heart failure is a complex syndrome, whose treatment associates diet, medicine, educational sessions, exercise training, psychological and social help. During cardiac rehabilitation, heart failure patients start exercise training against reconditioning and wasting muscle tissues: segmental rehabilitation, steady state exercise or interval training, breathing physiotherapy, swimming pool, low frequency electric muscle stimulation, according to individualized training program, in association with salt free diet and fight against cardiovascular risk factors. Rehabilitation also helps to increase the dose of drugs according to international recommendations, looking after clinical and biological parameters, and allows including patients in educational sessions. These two last points seem to be a key role of rehabilitation. Thanks to these many actions, hold by multidisciplinary team trained to take care of chronic heart failure patients and to lead therapeutic education, cardiac rehabilitation is very useful for chronic heart failure patients, to help hospital and liberal management therapy of chronic heart failure and reduce medical cost. Rehabilitation counsels should be carried on in home-based program.

[Value of pulsed Doppler tissue imaging for early detection of myocardial dysfunction with anthracyclines]. / Intérêt du Doppler tissulaire pulsé pour le dépistage précoce de l'altération de la fonction myocardique aux anthracyclines.

The cumulative and definitive nature of chronic cardiotoxicity of anthracyclines requires a preventive strategy of early diagnosis. The authors undertook a prospective study of the association of echocardiography, mitral Doppler and pulsed Doppler tissue imaging of the left ventricular lateral and posterior walls in the context of this problem in 20 patients without cardiac disease undergoing cancer chemotherapy including anthracyclines. Doppler echocardiography was performed before the first session of chemotherapy and at the end of treatment, 6 +/- 4 months later. After a total cumulative dose of 227 +/- 91 mg/m2 of doxorubicine, there were no changes in left ventricular ejection fraction but a significant decrease in mitral E wave velocity (p = 0.04) and in E/A ratio (p = 0.01), suggesting early changes in left ventricular relaxation. The Doppler tissue examination confirmed the presence of radial and longitudinal abnormalities in myocardial relaxation (decreases in myocardial E wave velocities of the posterior and lateral walls of the left ventricle, p = 0.02 and p = 0.01, respectively). The peak velocity of the myocardial systolic wave (Sm) was significantly decreased in the lateral wall (p = 0.02) and approached statistical significance in the posterior wall (p = 0.07). These results suggest concomitant changes in myocardial systolic and diastolic function with moderate doses of anthracyclines. Therefore, pulsed Doppler tissue examination enables earlier detection of left ventricular cardiotoxicity with anthracyclines than classical echocardiographic parameters.

[Fusarium onychomycosis]. / Onychomycose à Fusarium.

INTRODUCTION: A 69-year-old man with an uneventful past history consulted for a proximal subungueal leukonychia and associated paronychia of the right greater toe. Macroscopic examination and culture lead to the diagnosis of Fusarium oxysporum. Local treatment with bifonazol and cyclopirox was effective. DISCUSSION: Fungal onychomycoses are uncommon and usually present as superficial leukonychia. The association of a proximal localization with paronychia would suggest possible Fusarium infection. Though no specific treatment protocol is well-established, this case emphasizes the importance of effective treatment since invasive fusariosis is described in immunosuppressed patients with ungueal localizations can be an important portal for infection.

[Histopathology of exogenous and idiopathic lucites and provocation phototests]. / Histopathologie des lucites exogénes et idiopathiques et des phototests de provocation.

OBJECTIVE: Provocative phototests are used regularly to explore photobiology in patients with photodermatoses. Our objective was to determine the reliability of the phototest in the diagnosis of idiopathic and exogenous light eruption in order to identify the ideal date for the histological examination by correlation between the histological aspects of light- triggered and spontaneous lesions. PATIENTS AND METHODS: Among 66 patients, there were 48 with polymorphous light eruptions, 13 with exogenous eruptions and 5 with chronic actinodermatitis. The histological findings of the provocative phototests were correlated with the clinical aspect, the date of biopsy and the histological aspect of the spontaneous lesions. RESULTS: In polymorphous light eruptions (48 cases) this test triggered a photoallergic reaction in 48% of the patients. There was a good correlation between the histological findings and clinical features in 96% of the cases. The histological image of the light-triggered lesion on day 6 was the closest to that of the spontaneous lesion. In exogenous eruptions and chronic actinodermatitis (18 cases), only 33% of the clinically positive phototests were also positive at histological examination. The histological image was the same for the provocative tests whether they were clinically positive or negative, with signs of epidermal phototoxicity, regeneration acanthosis and moderate perivascular lymphocyte infiltration of the superficial dermal layer. CONCLUSIONS: Our findings confirmed that the phototest provides a good correlation between histological findings and clinical presentation in idiopathic polymorphous light eruptions, justifying simple clinical interpretation, but did not demonstrate a rate of positive results as high as reported in the literature. Day 6 is the ideal date for a phototest biopsy. In exogenous light eruptions, the phototest is less reliable since the correlation between histology and clinical presentation is weaker. It is difficult to reproduce spontaneous lesions with the phototest, but if used, the phototest biopsy should be done on day 18.

[Recurrent phototriggered summer light eruption of the axillary and inguinal area: an atypical topographic form of benign summer lucitis]. / Eruption estivale photodeclenchée récidivante des régions axillaires et inguinales: une forme topographique atypique de lucite estivale bénigne.

UNLABELLED: INTRODUCTION This case report of benign summer light eruption emphasizes the importance of phototests in the diagnosis of photosensitive dermatoses. CASE REPORT: A 25-year-old man, phototype II, had experienced a pruriginous papulovesicular erythematous eruption of the axillary and inguinal regions each summer for 12 years. A high-dose UV phototest (40 J/cm2 x 3 days) directed on the right posterior axillary area and a whole body exposure test (4 J/cm2 UVA, 20 mJ/cm2 UVB x 3 days) were positive both clinically and histologically on day 4. DEM B was normal at 26 mJ/cm2. Iterative polychromatic phototest (DEM x 3 days) in the area usually involved (left posterior axillary region) was negative. The simple UVA (13 J/cm2) and iterative phototests performed on the back were negative. The results of the phototests led to the diagnosis of benign light eruption despite the unusual localization. DISCUSSION: The diagnosis of benign light eruption is generally clinical. Phototests are unnecessary in most cases. Benign light eruption can be triggered by high-dose iterative UVA exposure of the susceptible area or whole body phototests (UVA-UVB). These specific phototests are indicated in atypical forms or localizations in order to determine the course of benign light eruption and to uncover simulations.

Comparison of three advanced chromatographic techniques for cannabis identification.

The development of chromatography technology, with the increasing availability of easier-to-use mass spectrometers combined with gas chromatography (GC), the use of diode-array or programmable variable-wavelength ultraviolet absorption detectors in conjunction with high-performance liquid chromatography (HPLC), and the availability of scanners capable of reading thin-layer chromatography (TLC) plates in the ultraviolet and visible regions, has made for easier, quicker and more positive identification of cannabis samples that standard analytical laboratories are occasionally required to undertake in the effort to combat drug addiction. At laboratories that do not possess the technique of GC combined with mass spectrometry, which provides an irrefutable identification, the following procedure involving HPLC or TLC techniques may be used: identification of the chromatographic peaks corresponding to each of the three main cannabis constituents-cannabidiol (CBD), delta-9-tetrahydrocannabinol (delta-9-THC) and cannabinol (CBN)-by comparison with published data in conjunction with a specific absorption spectrum for each of those constituents obtained between 200 and 300 nm. The collection of the fractions corresponding to the three major cannabinoids at the HPLC system outlet and the cross-checking of their identity in the GC process with flame ionization detection can further corroborate the identification and minimize possible errors due to interference.

[Therapeutic potential of Ro 5-3335. New active benzodiazepine in vitro against HIV-1 viruses resistant or non-resistant to AZT]. / Potentiel thérapeutique du Ro 5-3335. Une nouvelle benzodiazépine active in vitro contre les virus HIV-1 résistants ou non à l'AZT.

Ro 5-3335 is a new benzodiazepine highly active in vitro (IC50 = 0.1-1.0 microM [corrected]) against HIV-1 viruses of AIDS resistant or non-resistant to zidovudine (AZT). It is also active against HIV-2. Ro 5-3335 is original by its mechanism of action, acting on the trans-activation factor of transcription (TAT) and non on the reverse transcriptase. Such as, it could prevent proviral DNA to express in both evolutive and silent AIDS resistant or non-resistant to AZT or to other anti-reverse transcriptase series. In addition, in antagonizing extracellular TAT's actions, Ro 5-3335 could alleviate the syndrome commonly associated with AIDS as Kaposi's syndrome. In rodent test, Ro 5-3335 has no diazepam-like central effects and presents in comparison to AZT a more favorable therapeutic index. In dog, the elimination half-life, peak concentration and availability are 2 h, 0.8 microM and 85% respectively, after a 1 mg.kg-1 oral dose of Ro 5-3335. Theoretically, Ro 5-3335 and now its analogue Ro 24-7429 seem to possess all virtues to antagonize evolutive and latent AIDS. Its arrival is timely to cope with the ever increasing resistance phenomena, lengthy development of AIDS vaccines, exponential contamination of populations worldwide and last but not least possibly to impede evolutions of the disease. Ability to manipulate TAT-mediated activation of HIV-1 genes paves the ways to study conceivable corrections of abnormal gene expressions of neurotransmitters, hormones, oncogenes and key enzymes.

Serum digoxin levels related to plasma propafenone levels during concomitant treatment.

Nine patients with supraventricular rhythm disorders were treated during 5-day periods with different oral doses (300, 450, 600, and 900 mg daily) of propafenone concomitantly to long-term digoxin treatment. A poor correlation (r = .398; P less than .05) was obtained when the difference between the mean digoxin serum level (calculated with the Cmin data determined each of the 5 days) observed during a given propafenone dose and the mean digoxin serum level observed before propafenone treatment, was correlated with the dose of propafenone; but an evident correlation (r = .778; P less than .01) was found when the difference in digoxin level was correlated with the plasma propafenone concentration. The propafenone effect of increasing digoxin blood levels was thus concluded to be poorly dose dependent but strongly concentration dependent. The association of propafenone to a long-term digoxin treatment can be considered with a low risk of toxicity when plasma propafenone concentration does not exceed about 1000 ng/mL. Propafenone plasma levels are unpredictable in view of their wide interindividual variation for a given dose, so their measurement is advised to detect high levels and consequently to prevent a rise in digoxin serum concentrations with the possibility of toxicity. In clinical practice, when propafenone concentration determinations are not readily available, digoxin serum levels at least have to be carefully monitored.

Pharmacokinetics of fluconazole in patients undergoing continuous ambulatory peritoneal dialysis.

The pharmacokinetics of fluconazole given orally (100 mg) or intraperitoneally (50 and 150 mg) were determined in 15 patients with chronic renal failure who were undergoing continuous ambulatory peritoneal dialysis. The half-life (72 to 85 hours) was intermediate between values obtained in healthy volunteers and in patients with renal insufficiency studied during an interhaemodialysis period. The peritoneal clearance, 0.26 to 0.33 L/h, led to an 18% recovery of administered drug in the dialysates after 48 hours. The peritoneal absorption was slow (time to peak plasma concentration 7 hours) but the peritoneal bioavailability was excellent at 87 +/- 5%. The mean concentrations of fluconazole up to 24 hours were 770 and 1900 micrograms/L after single intraperitoneal doses of 50 and 150 mg, respectively. The volume of distribution (40 to 60 L) did not differ from that determined in patients with normal renal function. In the case of fungal peritonitis essentially attributed to Candida spp., a 6-hour intraperitoneal infusion of fluconazole 150 mg every 2 days appears to be a good regimen to rapidly exceed minimum inhibitory concentrations and treat infection without risk of systemic dissemination of fungi or toxicity.

Clinical pharmacokinetics after repeated intrapleural bupivacaine administration.

Patients (n = 14) who underwent thoracotomy during surgery of the oesophagus for cancer received an initial intrapleural dose of 10 ml bupivacaine hydrochloride 2.5 mg/ml followed by repeated administration every 8 hours from the first to the fourth postoperative day. The mean (+/- SD) peak plasma drug concentration (Cmax) [352 +/- 120 micrograms/L], time to peak (tmax) [0.83 +/- 0.51 h], and first-order absorption rate constant (ka) [5.46 +/- 4.95 h-1] after the twelfth dose were significantly different from the Cmax (206 +/- 81 micrograms/L), tmax (1.8 +/- 1.2h), and ka (1.8 +/- 1.47 h-1) determined after the first dose. Half-life (3.5 +/- 2.2h) and mean concentration (204 +/- 105 micrograms/L) were not significantly different on the fourth day from those on the first (4.1 +/- 2.6h and 142 +/- 71 micrograms/L, respectively). No sharp peak corresponding to systemic toxicity and no accumulation could be expected with these low doses, administered at short intervals and providing good pain relief in this surgical series.

Quinidine disposition in relation to antipyrine elimination and debrisoquine phenotype in alcoholic patients with and without cirrhosis.

Single dose disposition of oral quinidine (400 mg sulfate) was studied in a control group of subjects (No. = 6) and in hospitalized alcoholic patients involving one group with (No. = 6) and one group without (No. = 11) hepatic cirrhosis. All subjects also underwent an antipyrine and a debrisoquine test. Patients with cirrhosis had a prolonged elimination half-life (29.5 +/- 5.9 h) and low clearance (24 +/- 7 ml.kg-1.h-1) of antipyrine and also a considerably higher debrisoquine metabolic ratio (18.8 +/- 3.3) than the controls, whereas the alcoholics without cirrhosis had metabolic patterns for these two test compounds comparable to those seen in the controls (antipyrine half-life: 8.8 +/- 1.1 h and 9.8 +/- 2.0 h; debrisoquine metabolic ratio: 3.6 +/- 0.7 and 3.8 +/- 1.2 for alcoholics and controls respectively). In patients with cirrhosis the apparent elimination half-life of quinidine was longer (12.8 +/- 1.8 h) whereas after oral administration clearance of quinidine (15.6 +/- 3.5 l.h-1) and quinidine/3-hydroxyquinidine ratio (9.9 +/- 2.1) were not different from controls (quinidine clearance: 13.45 +/- 1.9 l.h-1; quinidine/3-hydroxyquinidine: 10.3 +/- 2.7). A possible change in distribution patterns of quinidine in cirrhotics may explain these findings.

[Adrenergic therapy and vigilance: beta-2 sympathomimetic aerosols in asthma]. / Médicaments adrénergiques et pharmacovigilance: les aérosols de bêta-2 sympathomimétiques dans l'asthme.

It has been established that the use of beta-2 sympathomimetic aerosols is a safe and efficacious treatment of asthma. Unexpected cases of sudden death amongst insufficiently-treated patients or patients who stopped their treatment are not linked with the use of these drugs. To assess the risk of possible "receptor desensitization" it is necessary to notify these accidents to the Committee on Safety of Drugs and to take into consideration the opposite results of further administration and termination of treatment.