Les taux des amino-acides libres dans le liquide cérébro-spinal chez les nourrissons trisomiques 21

Résumé Nous avons testé les taux des AA libres dans le LCS chez 22 nourrrissons trisomiques 21 en comparaison avec 10 nourrissons témoins. Les dosages ont été réalisés par chromatographie sur colonne.Nos résultats ont montré une augmentation des acides dicarboxyliques et d'autres modifications (rapport phénylalanine/tyrosine, glycine/alanine, lysine, histidine, valine, méthionine). Du point de vue statistique les résultats ont été reproductibles. Les variations trouvées sur les acides dicarboxyliques peuvent être liées soit à l'augmentation des synthèses intraneuronales, soit au passage accru à travers la BHM.Il est difficile de conclure que la présence d'un chromosome 21 surnuméraire est la cause des modifications constatées. Des épreuves de surcharge sont envisagées.

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Free amino-acids levels of cerebrospinal fluid in baby infants with down's syndrome

Summary The amino-acid levels of cerebrospinal fluid have been determined in 22 babies with Down's syndrome. Our study utilized an automatic aminoacid analyzer.Elevated levels of dicarboxylic acids were found, and modification of (phenylalanine/tyrosine and glycine/alanine ratio, lysine, histidine, valine, and methionine levels). The results are statistically reproducible.The relation of these findings to increase of intraneuronal synthesis or passage through the blood-brain barrier are discussed.It is difficult to attribute these modifications of amino-acid levels to the presence of a extra chromosome 21. Loading tests will be carried out.

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Zusammenfassung Bei 12 Säuglingen mit Down-Syndrom und 10 Kontrollen wurden durch Säulenchromatographie die Aminosäuren der Cerebrospinalflüssigkeit gemessen.Folgende statistisch signifikante Veränderungen wurden beim Down-Syndrom festgestellt: Vermehrung der Dicarbonsäuren sowie Veränderungen der Mengenverhältnisse von Phenylalanin/Tyrosin und Glycin/Alanin. Verändert waren ebenfalls die Mengen von Lysin, Histidin, Valin und Methionin.Zur Deutung der Befunde werden erhöhte intraneuronale Synthese und vermehrter Transport durch die Blut-Hirn-Schranke diskutiert. Zur weiteren Klärung sind Aminosäurebelastungsversuche geplant.Es erscheint fraglich, ob die beobachteten Veränderungen eine direkte Folge der Vermehrung des Chromosomenmaterials sind.

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Abréviations utilisées dans le texte LCS liquide cérébro-spinal - AA amino-acide(s) - BHM barrière hémo-méningée     

Receipt of Glucose Testing and Performance of Two US Diabetes Screening Guidelines, 2007–2012

Background

Screening guidelines are used to help identify prediabetes and diabetes before implementing evidence-based prevention and treatment interventions. We examined screening practices benchmarking against two US guidelines, and the capacity of each guideline to identify dysglycemia.

Methods

Using 2007–2012 National Health and Nutrition Examination Surveys, we analyzed nationally-representative, cross-sectional data from 5,813 fasting non-pregnant adults aged ≥20 years without self-reported diabetes. We examined proportions of adults eligible for diagnostic glucose testing and those who self-reported receiving testing in the past three years, as recommended by the American Diabetes Association (ADA) and the US Preventive Services Task Force (USPSTF-2008) guidelines. For each screening guideline, we also assessed sensitivity, specificity, and positive (PPV) and negative predictive values in identifying dysglycemia (defined as fasting plasma glucose ≥100 mg/dl or hemoglobin A1c ≥5.7%).

Results

In 2007–2012, 73.0% and 23.7% of US adults without diagnosed diabetes met ADA and USPSTF-2008 criteria for screening, respectively; and 91.5% had at least one major risk factor for diabetes. Of those ADA- or USPSTF-eligible adults, about 51% reported being tested within the past three years. Eligible individuals not tested were more likely to be lower educated, poorer, uninsured, or have no usual place of care compared to tested eligible adults. Among adults with ≥1 major risk factor, 45.7% reported being tested, and dysglycemia yields (i.e., PPV) ranged from 45.8% (high-risk ethnicity) to 72.6% (self-reported prediabetes). ADA criteria and having any risk factor were more sensitive than the USPSTF-2008 guideline (88.8–97.7% vs. 31.0%) but less specific (13.5–39.7% vs. 82.1%) in recommending glucose testing, resulting in lower PPVs (47.7–54.4% vs. 58.4%).

Conclusion

Diverging recommendations and variable performance of different guidelines may be impeding national diabetes prevention and treatment efforts. Efforts to align screening recommendations may result in earlier identification of adults at high risk for prediabetes and diabetes.     

Acute hemorrhagic shock decreases airway resistance in anesthetized rat

We studied the relation between changes in pulmonary and systemic hemodynamics to those in the airway resistance, respiratory tissue mechanics, and thoracic gas volume (TGV) following acute hemorrhage and blood reinfusion in rats. Forced oscillation technique was used to measure airway resistance (Raw), respiratory tissue damping, and elastance at baseline and after stepwise 1-ml blood withdrawals up to 5 ml total, followed by stepwise reinfusion up to full restoration. Mean systemic (Pam) and pulmonary arterial pressures and suprarenal aortic blood flow were measured at each step. In supplemental animals, plethysmographic TGV, Pam, and respiratory mechanics measurements were performed. Blood volume loss (BVL) led to proportional decreases in Raw (66.5 ± 8.8 vs. 44.8 ± 9.0 cmH(2)O·s·l(-1) with 5 ml, P < 0.001), Pam, and aortic blood flow. In contrast, tissue damping increased significantly (1,070 ± 91 vs. 1,235 ± 105 cmH(2)O/l, P = 0.009 with 5 ml BVL), whereas tissue elastance did not change significantly. TGV significantly increased with acute BVL (3.7 ± 0.2 vs. 4.2 ± 0.2 ml, P = 0.01). Stepwise reinfusions produced opposite changes in the above parameters, with Raw reaching a higher value than baseline (P = 0.001) upon full volume restoration. Both adrenalin (P = 0.015) and noradrenalin levels were elevated (P = 0.010) after 5-ml blood withdrawal. Our data suggest that the decreases in Raw following BVL may be attributed to the following: 1) an increased TGV enhancing airway parenchymal tethering forces; and 2) an increase in circulating catecholamines. The apparent beneficial effect of a reduction in Raw in acute hemorrhagic shock is counteracted by an increase in dead space and the appearance of peripheral mechanical heterogeneities due to de-recruitment of the pulmonary vasculature.     

The bariatric surgery patient: lost to follow-up; from morbid obesity to severe malnutrition

ObjectiveTo describe the potential long-term risk of malnutrition after Roux-en-Y gastric bypass (GBP) through an uncommon occurrence of inflammatory bowel disease (IBD) postoperatively, which posed a serious threat to the nutritional status and the life of the patient.MethodWe present a case report of a 44-year-old woman in whom Crohn disease developed 4 years after she had undergone GBP. The double insult of IBD and GBP resulted in severe malnutrition, with a serum albumin concentration of 0.9 g/dL (reference range, 3.5 to 5.0), weight loss, and watery diarrhea necessitating 6 hospital admissions during a period of 7 months.ResultUltimately, the administration of total parenteral nutrition with aggressive macronutrient, vitamin, and mineral repletion resulted in substantial improvement in the patient’s strength, function, and quality of life, in parallel with diminished symptoms of IBD.ConclusionRarely, IBD develops after GBP, but the relationship between the 2 conditions remains unclear. Regardless, in addition to the altered anatomy after bariatric surgery, the further insult of IBD poses a severe threat to the nutritional status of affected patients. Malnutrition needs to be recognized and aggressively treated. Nutritional markers should be followed closely in this population of bariatric patients in an effort to avert the onset of severe malnutrition. (Endocr Pract. 2012;18:e21-e25)     

Determination of glibenclamide in human plasma by liquid chromatography and atmospheric pressure chemical ionization/MS-MS detection

A simple and fast method intended for large-scale bioequivalence studies for the determination of glibenclamide in plasma samples is presented. The chromatographic separation was achieved on a monolithic octadecyl chemically modified silicagel column and a mobile phase containing 42% aqueous 0.1% HCOOH solution (v/v) and 58% acetonitrile, at a flow rate of 1 mL/min, in isocratic conditions. Preparation of plasma samples was based on protein precipitation with acetonitrile. Gliquidone was used as internal standard. The target analytes were transferred into an ion trap mass analyzer via an atmospheric pressure chemical ionization interface. The precursor ions with mass 494 a.m.u. for glibenclamide and 528 a.m.u. for gliquidone were isolated, while in the second MS stage product ions 369 a.m.u. and 403 a.m.u., respectively, were monitored. The analytical process was characterized by a low limit of quantitation of 1.5 ng/mL. The mean recovery for glibenclamide was 98.1+/-2.8% over a concentration interval ranging from 1 to 500 ng/mL. Intra-day and inter-day precision calculated over 2-400 ng/mL concentration interval ranged from 15.4% to 3.4%. Inter-sequence accuracy expressed as % bias from theoretical concentration values over the concentration interval of 10-400 ng/mL fall within -13.9% and +14.6%. The method was applied for evaluation of the bioequivalence between two formulations containing 3.5mg glibenclamide per dose.     

Phosphorylation and biosynthesis of high molecular weight proteins of tumor nuclear matrix

INTRODUCTIONAsearlyasin1948wehavefr8CtionatedisolatednucleifromnormalandtumorcellsbyextractionwithiMNaCIanddilutealkali[1].Thenuclearresiduewasthenstudiedmorethoroughly[2,3].Lateron,sillillarproteinousnuclearresidueswereisolatedbyotherworkers[46]andasstud…     

Algorithms and software for support of gene identification experiments

MOTIVATION: Gene annotation is the final goal of gene prediction algorithms. However, these algorithms frequently make mistakes and therefore the use of gene predictions for sequence annotation is hardly possible. As a result, biologists are forced to conduct time-consuming gene identification experiments by designing appropriate PCR primers to test cDNA libraries or applying RT-PCR, exon trapping/amplification, or other techniques. This process frequently amounts to 'guessing' PCR primers on top of unreliable gene predictions and frequently leads to wasting of experimental efforts. RESULTS: The present paper proposes a simple and reliable algorithm for experimental gene identification which bypasses the unreliable gene prediction step. Studies of the performance of the algorithm on a sample of human genes indicate that an experimental protocol based on the algorithm's predictions achieves an accurate gene identification with relatively few PCR primers. Predictions of PCR primers may be used for exon amplification in preliminary mutation analysis during an attempt to identify a gene responsible for a disease. We propose a simple approach to find a short region from a genomic sequence that with high probability overlaps with some exon of the gene. The algorithm is enhanced to find one or more segments that are probably contained in the translated region of the gene and can be used as PCR primers to select appropriate clones in cDNA libraries by selective amplification. The algorithm is further extended to locate a set of PCR primers that uniformly cover all translated regions and can be used for RT-PCR and further sequencing of (unknown) mRNA.      

Intranasal vaccination using interleukin-12 and cholera toxin subunit B as adjuvants to enhance mucosal and systemic immunity to human immunodeficiency virus type 1 glycoproteins

We have investigated the induction of protective mucosal immunity to human immunodeficiency virus type 1 (HIV-1) isolate 89.6 by intranasal (i.n.) immunization of mice with gp120 and gp140 together with interleukin-12 (IL-12) and cholera toxin subunit B (CTB) as adjuvants. It was found that both IL-12 and CTB were required to elicit mucosal antibody responses and that i.n. immunization resulted in increased total, immunoglobulin G1 (IgG1), and IgG2a anti-HIV-1 antibody levels in serum; increased total, IgG1, IgG2a, and IgA antibody expression in bronchoalveolar lavage fluids; and increased IgA antibody levels in vaginal washes. Levels of anti-HIV-1 antibodies in both sera and secretions were higher in groups immunized with gp140 than in those immunized with gp120. However, only gp120-specific mucosal antibodies demonstrated neutralizing activity against HIV-1 89.6. Taken together, the results show that IL-12 and CTB act synergistically to enhance both systemic and local mucosal antibody responses to HIV-1 glycoproteins and that even though gp140 induces higher antibody titers than gp120, only gp120-specific mucosal antibodies interfere with virus infectivity.     

Increased systemic and adipose tissue cytokines in patients with HIV-associated lipodystrophy

The lipodystrophy syndrome (adipose tissue redistribution and metabolic abnormalities) observed with highly active antiretroviral therapy (HAART) during human immunodeficiency virus (HIV) infection may be related to increased proinflammatory cytokine activity. We measured acute cytokine (TNF-alpha, IL-6, leptin), glycerol, and lactate secretion from abdominal subcutaneous adipose tissue (SAT), and systemic cytokine levels, in HIV-infected subjects with and without lipodystrophy (HIVL+ and HIVL-, respectively) and healthy non-HIV controls. Lipodystrophy was confirmed and characterized as adipose tissue redistribution in HIVL+ compared with HIVL- and controls, by dual-energy X-ray absorptiometry and by whole body MRI. TNF-alpha secretion from abdominal SAT and circulating levels of IL-6, soluble TNF receptors I and II, and insulin were elevated in HIVL+ relative to HIVL- and/or controls, particularly in HIVL+ undergoing HAART. In the HIV-infected group as a whole, IL-6 secretion from abdominal SAT and serum IL-6 were positively associated with visceral fat and were negatively associated with the relative amount of lower limb adipose tissue (P < 0.01). Decreased leptin and increased lactate secretion from abdominal SAT were specifically associated with HAART. In conclusion, increased cytokine secretion from adipose tissue and increased systemic proinflammatory cytokine activity may play a significant role in the adipose tissue remodeling and/or the metabolic abnormalities associated with the HIV-lipodystrophy syndrome in patients undergoing HAART.