Kinetic of body nitrogen loss during a whole day infusion and withdrawal of glucose and insulin in injured patients

Objective To investigate the kinetics of body nitrogen (N) excretion during 24 h glucose infusion (relating glycemia with insulin supply) and during subsequent 24 h saline infusion in injured patients during a full blown stress reaction. To define the lag time between the start or the withdrawal of glucose and insulin infusion, and the modification in the N loss from the body, and the time span to reach the maximum effect and its size. The knowledge of these variables is mandatory to plan short term studies in critically ill patients, while assuring the stability of the metabolic condition during the study period, and also to assess the possible weaning of the effect on protein breakdown during prolonged glucose and insulin infusion. Design 24\u201336 h after injury, patients were fasted (<100 g glucose) for 24 h (basal day). Thereafter, a 24 h glucose infusion in amount corresponding to measured fasting energy production rate (EPR), clamping glycemia at normal level with insulin supply followed by 24 h saline infusion, was performed. Total N, urea and 3-methyl-histidine (3-MH) in urine were measured on 4 h samples starting from 20th h of the basal day. Setting Multipurpose ICU in University Hospital. Patients 6 consecutive patients who underwent accidental and/or surgical injury, immediately admitted for respiratory assistance (FIO2<0.4). Excluded patients were those with abnormal nutritional status, cardiovascular compromise and organ failures. Main results Patients showed a 33% increase in measured versus predicted fasting EPR and a consistent increase in N and 3-MH urinary loss. An infusion of glucose at 5.95\ub10.53 mg/kg\ub7min (97.20\ub10.03% of the fasting measured EPR) with 1.22\ub10.18 mU/kg\ub7min insulin infusion reduced N and 3-MH loss after a time lag of 12 h. The peak decrease in body N ( 1236%) and 3-MH loss ( 1238%) was reached during the first 12 h of glucose withdrawal period. Thereafter, during the following 12 h, the effect completely vanished confirming that it is therapy-dependent and that the metabolic environment of the patients did not change during the three days study period. Conclusion 24 h glucose withdrawal reduces N and 3-MH loss in injured patients, the drug-like effect is maintained during the first 12 h of withdrawal and thereafter disappears. The study suggests that at least a 24 h study period is necessary when planning studies exploring energy-protein metabolism relationship in injured patients, and, again 24 h before changing protocol in a crossover stud

Determinazione della digossina nel siero: confronto tra metodi

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Peripheral, visceral and body nitrogen balance of catabolic patients, without and with parenteral nutrition

The effect of major trauma and sepsis on skeletal muscle, central tissue and whole body nitrogen (N) metabolism was investigated in 5 patients before and during TPN (30 kcal, 0.30 g N kg-1 day-1). Fasting 3-methylhistidine (MEH) urinary excretion was elevated (407.9 +/- 67.6 mumol m-2 day-1), muscle and body N balances (NB) were markedly negative (-28.2 +/- 4.6 g m-2 day-1 and -15.7 +/- 3.1 g m-2 day-1), while central tissue NB was positive (13.0 +/- 2.4 g m-2 day-1). TPN effected a reduction in MEH excretion (261.8 +/- 27.5 mmol m-2 day-1 - p less than 0.05) and decreased the release of almost all amino acids from muscle tissue, some of them acting as catabolic markers. Muscle (-7.2 +/- 1.2 g m-2 day-1 - p less than 0.01) as well as body NB (-4.8 +/- 1.4 g m-2 day-1 - p less than 0.01) improved, whilst central tissue NB worsened, even though still positive (3.1 +/- 1.6 g m-2 day-1 - p less than 0.05). Gathering fasting and TPN data MEH excretion was significantly related to both body (r = 0.89) and muscle (r = 0.73) NB, that were highly related to each other (r = 0.93), being muscle always worse than body NB. In conclusion, the anticatabolic activity of TPN is confirmed, although our setting did not achieve muscle NB, it was consistently improved and seems to be the major determinant of body NB, in contrast central NB and central N utilization (46.4% +/- 5.4 vs 15.8% +/- 8.4 - p less than 0.05) worsened

Simultaneous mining of linkage and linkage disequilibrium to fine-map QTL in outbred half-sib pedigrees: revisiting the location of a QTL with major effect on milk production on bovine chromosome 14

v2002o

The rate of de novo structural variation is increased in in vitro-produced offspring and preferentially affects the paternal genome.

peer reviewedAssisted reproductive technologies (ARTs), including in vitro maturation and fertilization (IVF), are increasingly used in human and animal reproduction. Whether these technologies directly affect the rate of de novo mutation (DNM), and to what extent, has been a matter of debate. Here we take advantage of domestic cattle, characterized by complex pedigrees that are ideally suited to detect DNMs and by the systematic use of ART, to study the rate of de novo structural variation (dnSV) in this species and how it is impacted by IVF. By exploiting features of associated de novo point mutations (dnPMs) and dnSVs in clustered DNMs, we provide strong evidence that (1) IVF increases the rate of dnSV approximately fivefold, and (2) the corresponding mutations occur during the very early stages of embryonic development (one- and two-cell stage), yet primarily affect the paternal genome.DAMON

Highly effective SNP-based association mapping and management of recessive defects in livestock.

The widespread use of elite sires by means of artificial insemination in livestock breeding leads to the frequent emergence of recessive genetic defects, which cause significant economic and animal welfare concerns. Here we show that the availability of genome-wide, high-density SNP panels, combined with the typical structure of livestock populations, markedly accelerates the positional identification of genes and mutations that cause inherited defects. We report the fine-scale mapping of five recessive disorders in cattle and the molecular basis for three of these: congenital muscular dystony (CMD) types 1 and 2 in Belgian Blue cattle and ichthyosis fetalis in Italian Chianina cattle. Identification of these causative mutations has an immediate translation into breeding practice, allowing marker assisted selection against the defects through avoidance of at-risk matings

Variants modulating the expression of a chromosome domain encompassing PLAG1 influence bovine stature.

We report mapping of a quantitative trait locus (QTL) with a major effect on bovine stature to a approximately 780-kb interval using a Hidden Markov Model-based approach that simultaneously exploits linkage and linkage disequilibrium. We re-sequenced the interval in six sires with known QTL genotype and identified 13 clustered candidate quantitative trait nucleotides (QTNs) out of >9,572 discovered variants. We eliminated five candidate QTNs by studying the phenotypic effect of a recombinant haplotype identified in a breed diversity panel. We show that the QTL influences fetal expression of seven of the nine genes mapping to the approximately 780-kb interval. We further show that two of the eight candidate QTNs, mapping to the PLAG1-CHCHD7 intergenic region, influence bidirectional promoter strength and affect binding of nuclear factors. By performing expression QTL analyses, we identified a splice site variant in CHCHD7 and exploited this naturally occurring null allele to exclude CHCHD7 as single causative gene