Visión de los funcionarios/as de Teletón Valparaíso sobre el perfil de competencias de inclusión social a desarrollar en jóvenes viviendo en situación de discapacidad egresados de la institución: un estudio cualitativo / Teletón Valparaíso's staff member's vision on a profile of social inclusion skills to be developed by children and youngersters with disabilities, who exit the instruction: a qualitative study

Introduction: The definition of skill has its origin in the mid 60's and early 70's, througth the development of organizational and industrial psychology. The concept reached since the educational field, and later on was applied in general to individuals in their everyday life and to specific performance. In the process of rehabilitation, the development of "social inclusion skills", both as a hypothetical construct and as therapeutic practice, has been long unexplored. At Chile's Teletón Institutes, there is no explicit formulation of the skills that are expected to be learned during the rehabilitation process. Purpose: The purpose of this study was to build an initial exiting skills profile based on the child and/or youngster's general skills, and thus, direct our rehabilitation practices to greater effectiveness and efficiency. Method: A qualitative approach based on the Grounded Theory's method was used. Semi-structured interviews were conducted with 83 (96.5 percent) staff members of Valparaíso's Teletón Institute. The information was analyzed with Atlas-T software. Results: An initial exiting skills profile with 50 skills was obtained, which showed a tendency to autonomy with procedural and attitudinal components. Other elements, associated to the Institute's rehabilitation process were also indentified. Conclusions: This profile defies social inclusion skills which should invite us to practice more in depth the rehabilitation process, within a bio-psychosocial model.

Introducción: El concepto de competencia tiene su origen en trabajos de la psicología industrial y organizacional en la década de 1960 y principios de 1970, extendiéndose al mundo educativo y en general a las personas en su desempeño cotidiano y/o específico. En el área de la rehabilitación, el desarrollo de competencias es un campo inexplorado, tanto en su constructo "Competencias de Inclusión Social", como en el desarrollo de éstas en el proceso. En Teletón Chile, no existe una formulación explícita de las competencias que se pretenden apoyar durante el proceso rehabilitador. Objetivos: Levantar un perfil inicial de egreso basado en competencias generales y de inclusión social del niño/a y/o del Instituto Teletón Valparaíso. Tiene como propósito, orientar prácticas de rehabilitación de mayor eficiencia y eficacia. Metodología: Abordaje cualitativo basado en el método de la teoría fundamentada, usando la técnica de entrevistas individuales semi-estructuradas, aplicadas a 83/86 funcionarios (96,5 por ciento) de Teletón Valparaíso. Para el procesamiento de la información, se utilizó el software Atlas-ti. Resultados: Se obtuvo un perfil inicial de egreso con 50 competencias, observándose una tendencia hacia el funcionamiento autónomo, con componentes procedimentales y actitudinales. Se identificaron además elementos relacionados con el proceso de rehabilitación que se lleva a cabo en el Instituto. Conclusión: Este perfil define competencias de inclusión social invitándonos a un mayor grado de practicidad en el quehacer rehabilitador dentro de un modelo de atención biopsicosocial.

Effect of parvoviral enteritis on plasma citrulline concentration in dogs.

BACKGROUND: Plasma citrulline concentration is a reliable marker of global enterocyte mass in humans and is markedly decreased in diffuse small intestinal diseases. However, the relationship between acute intestinal damage and plasma citrulline concentration in dogs has never been documented. HYPOTHESIS: That dogs with parvoviral enteritis have a lower plasma citrulline concentration than healthy dogs and that plasma citrulline concentration is a predictor of death in puppies with parvoviral enteritis. ANIMALS: Sixty-one dogs with spontaneous parvoviral enteritis and 14 healthy age-matched control dogs. METHODS: Observational cohort study. Plasma citrulline concentration was measured by liquid chromatography and tandem mass spectrometry in blood samples collected at admission and each day until death or discharge from the hospital. Parvovirus enteritis was confirmed by electron microscopy on a fecal sample. RESULTS: Median (interquartile range) plasma citrulline concentrations at admission were 2.8 µmol/L (range: 0.3, 49.0; P < .001 versus controls) in survivors (n = 49), 2.1 µmol/L (range: 0.5, 6.4, P < .001 versus controls) in nonsurvivors (n = 12) and 38.6 µmol/L (range: 11.4, 96.1) in controls (n = 14), respectively. There was no significant difference in plasma citrulline concentration between survivors and nonsurvivors within the parvovirus-infected puppies, and plasma citrulline concentration was not significantly associated with outcome in parvoviral enteritis. There were no significant changes in plasma citrulline concentration over the 8-day follow-up period. CONCLUSION AND CLINICAL IMPORTANCE: Parvovirus enteritis is associated with a severe decrease in plasma citrulline concentration that does not appear to have any significant prognostic value.

Non-surgical alternatives to invasive procedures in mice.

We have developed and validated catheterization protocols in mice that allow for simultaneous infusion and sampling. A sampling catheter was inserted in the lateral vein of the tail, while the animals were infused either intravenously or intragastrically through a second catheter placed in the contralateral lateral vein or via an intragastric catheter, respectively. The applicability of these methods of infusion and blood sampling were validated by conducting urea kinetics utilizing stable isotopes. These non-surgical procedures are non-invasive, inexpensive, fast to perform and animals do not require a recovery period before their use.

The low oxygen-carrying capacity of Krebs buffer causes a doubling in ventricular wall thickness in the isolated heart.

The buffer-perfused Langendorff heart is significantly vasodilated compared with the in vivo heart. In this study, we employed ultrasound to determine if this vasodilation translated into changes in left ventricular wall thickness (LVWT), and if this effect persisted when these hearts were switched to the "working" mode. To investigate the effects of perfusion pressure, vascular tone, and oxygen availability on cardiac dimensions, we perfused hearts (from male Wistar rats) in the Langendorff mode at 80, 60, and 40 cm H2O pressure, and infused further groups of hearts with either the vasoconstrictor endothelin-1 (ET-1) or the blood substitute FC-43. Buffer perfusion induced a doubling in diastolic LVWT compared with the same hearts in vivo (5.4 +/- 0.2 mm vs. 2.6 +/- 0.2 mm, p < 0.05) that was not reversed by switching hearts to "working" mode. Perfusion pressures of 60 and 40 cm H2O resulted in an increase in diastolic LVWT. ET-1 infusion caused a dose-dependent decrease in diastolic LVWT (6.6 +/- 0.4 to 4.8 +/- 0.4 mm at a concentration of 10(-9) mol/L, p < 0.05), with a concurrent decrease in coronary flow. FC-43 decreased diastolic LVWT from 6.7 +/- 0.5 to 3.8 +/- 0.7 mm (p < 0.05), with coronary flow falling from 16.1 +/- 0.4 to 8.1 +/- 0.4 mL/min (p < 0.05). We conclude that the increased diastolic LVWT observed in buffer-perfused hearts is due to vasodilation induced by the low oxygen-carrying capacity of buffer compared with blood in vivo, and that the inotropic effect of ET-1 in the Langendorff heart may be the result of a reversal of this wall thickening. The implications of these findings are discussed.

Acute alcohol administration inhibits the refeeding response after starvation in rat skeletal muscle.

This study determined whether an acute alcohol dose could inhibit the refeeding response in starved muscle. Rats starved for 24 h were pretreated with alcohol or saline before refeeding by intragastric or intravenous infusion of enteral diet (ENT), total parenteral nutrition (TPN), or saline. Refeeding by TPN or ENT stimulated increases in the fractional rate of protein synthesis (k(s)) in skeletal muscle. Alcohol prevented the increase in k(s) when refeeding occurred intragastrically (TPN or ENT) (P < 0.001) but not intravenously (TPN). Upon intragastric refeeding, alcohol inhibited the increase in both eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) and p70 S6 kinase (p70(S6K)) phosphorylation in plantaris but caused only partial inhibition in soleus muscle (ENT only). When rats were refed intravenously, alcohol had no effect on the increased 4E-BP1 or p70(S6K) phosphorylation in either muscle. Plasma insulin levels were augmented by alcohol. Alcohol-related changes in plasma amino acid concentrations were similar irrespective of the route of feeding, whereas IGF-I levels showed differential changes. This is the first study to demonstrate that acute alcohol ingestion impedes the starved-to-fed response in skeletal muscle.

Response of in vivo protein synthesis in T lymphocytes and leucocytes to an endotoxin challenge in healthy volunteers.

In vivo determination of protein synthesis in immune cells reflects metabolic activity and immunological activation. An intravenous injection of endotoxin to healthy volunteers was used as a human sepsis model, and in vivo protein synthesis of T lymphocytes and leucocytes was measured. The results were related to plasma concentrations of selected cytokines, peripheral cell counts and subpopulations of immune cells. The subjects (n = 8 + 8) were randomized to an endotoxin (4 ng/kg) or a saline group. In vivo protein synthesis was determined twice: before and 1-2.5 h after the endotoxin/saline injection. Protein synthesis decreased in isolated T lymphocytes, but increased in leucocytes. Plasma levels of TNF-alpha, IL-8, IL-6, IL-1 ra and IL-10 were elevated, whereas IL-2 and IFN-gamma, produced predominantly by T lymphocytes, did not change in response to endotoxin. Neutrophils increased, whereas lymphocytes and monocytes decreased 2.5 h after the endotoxin injection. Flow cytometry revealed a drop in total CD3+ T lymphocytes and CD56+ natural killer cells, accompanied by an increase in CD15+ granulocytes. In summary, in vivo protein synthesis decreased in T lymphocytes, while the total leucocyte population showed a concomitant increase immediately after the endotoxin challenge. The changes in protein synthesis were accompanied by alterations in immune cell subpopulations and in plasma cytokine levels.

Acute metabolic acidosis decreases muscle protein synthesis but not albumin synthesis in humans.

Chronic metabolic acidosis induces negative nitrogen balance by either increased protein breakdown or decreased protein synthesis. Few data exist regarding effects of acute metabolic acidosis on protein synthesis. We investigated fractional synthesis rates (FSRs) of muscle protein and albumin, plasma concentrations of insulin-like growth factor-I (IGF-I), thyroid-stimulating hormone (TSH), and thyroid hormones (free thyroxin [fT(4)] and triiodothyronine [fT(3)]) in seven healthy human volunteers after a stable controlled metabolic period of 5 days and again 48 hours later after inducing metabolic acidosis by oral ammonium chloride intake (4.2 mmol/kg/d divided in six daily doses). Muscle and albumin FSRs were obtained by the [(2)H(5)ring]phenylalanine flooding technique. Ammonium chloride induced a significant decrease in pH (7.43 +/- 0.02 versus 7.32 +/- 0.04; P < 0.0001) and bicarbonate concentration (24.6 +/- 1.6 versus 16.0 +/- 2.7 mmol/L; P < 0.0001) within 48 hours. Nitrogen balance decreased significantly on the second day of acidosis. The FSR of muscle protein decreased (1.94 +/- 0.25 versus 1.30 +/- 0.39; P < 0.02), whereas the FSR of albumin remained constant. TSH levels increased significantly (1.1 +/- 0.5 versus 1.9 +/- 1.1 mU/L; P = 0.03), whereas IGF-I, fT(4), and fT(3) levels showed no significant change. We conclude that acute metabolic acidosis for 48 hours in humans induces a decrease in muscle protein synthesis, which contributes substantially to a negative nitrogen balance. In contrast to prolonged metabolic acidosis of 7 days, a short period of acidosis in the present study did not downregulate albumin synthesis.

A combined stress hormone infusion decreases in vivo protein synthesis in human T lymphocytes in healthy volunteers.

In vivo protein synthesis decreases in mononuclear cells following a combined stress hormone infusion given to healthy volunteers as a human trauma model. Here, the purpose was to further investigate this finding and to measure in vivo protein synthesis in isolated T lymphocytes. Furthermore, the effects of stress hormones on the lymphocyte subpopulations and mononuclear cells, characterized by flow cytometry and phytohemagglutinin (PHA)-induced and unstimulated proliferative responses in vitro, were elucidated. Healthy volunteers (n = 16) were randomized into 2 groups to receive either a stress hormone or a saline infusion for 6 hours. In vivo protein synthesis was studied before and after the treatment by measuring the incorporation of stable isotopically-labeled phenylalanine into lymphocyte and mononuclear cell proteins. Protein synthesis decreased after stress hormone infusion in both cell populations: in T lymphocytes from 13.0% +/- 0.7%/d (mean +/- SD) to 8.6% +/- 2.1%/d (P <.01) and in mononuclear cells from 13.3% +/- 1.2%/d to 6.3 +/- 2.0%/d (P <.001). No change in proliferative responsiveness in vitro was observed. The stress hormone infusion produced a decrease in the percentage of T helper CD3/CD4 from 41% to 18% (P <.001), T cytotoxic CD3/CD8 from 27% to 15% (P <.001), as well as total T CD3 cells from 69% to 35% (P <.001). There was an increase in the percentage of natural killer (NK) cells CD16/CD56 from 17% to 55% (P <.001). Determination of phenotypes expressed on activated T lymphocytes showed that CD3/HLA-DR was unchanged and CD3/CD25 decreased from 14% to 7% (P <.01) in the stress hormone group. The study showed that the decrease of in vivo protein synthesis was 34% in T lymphocytes as compared with 53% in mononuclear cells, when determined immediately after a 6-hour stress hormone infusion. This change was associated with a pronounced decrease in all lymphocyte subpopulations, except for the NK cells, which increased substantially.

Lymphocyte protein synthesis is increased with the progression of HIV-associated disease to AIDS.

HIV infection has been shown to affect lymphocyte function and to reduce lymphocyte responsiveness in vitro to mitogenic stimulation, but little is known about lymphocyte metabolism in vivo and how it is affected during the course of the disease. This study investigated the metabolic activity of lymphocytes in vivo through the progression of HIV-associated disease. Lymphocyte protein synthesis was measured with L-[(2)H(5)]phenylalanine (45 mg/kg body weight) in healthy volunteers (n=7), in patients who were HIV-positive (n=7) but asymptomatic, and in patients with AIDS (n=8). The rates of lymphocyte protein synthesis [expressed as a percentage of lymphocyte protein, i.e. fractional synthesis rate (FSR)] were not altered in HIV-positive patients compared with healthy controls (7.9+/-1.28% and 9.1+/-0.53%/day respectively), but were significantly elevated in AIDS patients (14.0+/-1.16%/day; P<0.05). The serum concentration of the cytokine tumour necrosis factor-alpha (TNF-alpha) increased with the progression of the disease, and TNF-alpha levels were significantly higher in AIDS patients (6.81+/-0.88 ng/l) than in healthy controls (3.09+/-0.27 ng/l; P<0.05). Lymphocyte protein FSR was positively correlated with serum TNF-alpha concentration (r=0.55, P=0.009) and negatively correlated with CD4(+) lymphocyte count (r=-0.70, P=0.004). The elevation of lymphocyte protein synthesis in AIDS patients suggests a higher rate of turnover of lymphocytes. This may be associated with a generalized activation of the immune system, which is also reflected by the elevated serum TNF-alpha concentration in the late stages of HIV-associated disease.

Assessment of the safety of glutamine and other amino acids.

Glutamine is used to supplement intravenous and enteral feeding. Although there have been many human studies of its efficacy, there have been very few studies with safety as a primary goal. This article analyzes the literature on the safety of glutamine and also examines the available information on high intakes of total protein and other amino acids, so that additional indicators of potentially adverse effects can be suggested. Four studies that specifically addressed glutamine safety were identified, from which it was concluded that glutamine is safe in adults and in preterm infants. However, the published studies of safety have not fully taken account of chronic consumption by healthy subjects of all age groups. To help identify potential undetected hazards of glutamine intake, the literature on adverse effects of high dietary intake of protein and other amino acids was examined. High protein is reputed to cause nausea, vomiting and ultimately death in adults, and has been shown to result in neurological damage in preterm infants. Individual amino acids cause a variety of adverse effects, some of them potentially fatal, but neurological effects were the most frequently observed. Because glutamine is metabolized to glutamate and ammonia, both of which have neurological effects, psychological and behavioral testing may be especially important.

Abnormal glucose handling by the kidney in response to hypoglycemia in type 1 diabetes.

The frequent occurrence of hypoglycemia in people with type 1 diabetes is attributed to abnormalities in the blood glucose counterregulatory response. In view of recent findings indicating that the kidney contributes to prevent and correct hypoglycemia in healthy subjects, we decided to investigate the role of renal glucose handling in hypoglycemia in type 1 diabetes. Twelve type 1 diabetic patients and 14 age-matched normal individuals were randomized to hyperinsulinemic-euglycemic (n = 6 diabetic subjects and n = 8 control subjects) or hypoglycemic (n = 6 each) clamps with blood glucose maintained either stable near 100 mg/dl (5.6 mmol/l) or reduced to 54 mg/dl (3.0 mmol/l). All study subjects had their renal vein catheterized under fluoroscopy, and net renal glucose balance and renal glucose production and utilization rates were measured using a combination of arteriovenous concentration difference with stable isotope dilution technique. Blood glucose and insulin were comparable in both groups in all studies. In patients with diabetes, elevations in plasma glucagon, epinephrine, and norepinephrine were blunted, and both the compensatory rise in endogenous glucose production and in the net glucose output by the kidney seen in normal subjects with equivalent hypoglycemia were absent. Renal glucose balance switched from a mean +/- SE baseline net uptake of 0.6 +/- 0.4 to a net output of 4.5 +/- 1.3 micromol x kg(-1) x min(-1) in normal subjects, but in patients with diabetes there was no net renal contribution to blood glucose during similar hypoglycemia (mean +/- SE net glucose uptake [baseline 0.7 +/- 0.4] remained at 0.4 +/- 0.3 micromol x kg(-1) x min(-1) in the final 40 min of hypoglycemia; P < 0.01 between groups). We conclude that adrenergic stimulation of glucose output by the kidney, which represents an additional defense mechanism against hypoglycemia in normal subjects, is impaired in patients with type 1 diabetes and contributes to defective glucose counterregulation.

Growth hormone does not affect albumin synthesis in the critically ill.

OBJECTIVE: To study the effect of growth hormone (GH) on albumin synthesis in critically ill patients. DESIGN: Prospective randomized controlled study. SETTING: Two intensive care units, university hospital and county hospital, respectively. PATIENTS: Twenty-two critically ill patients in the intensive care unit. INTERVENTIONS: Albumin synthesis was measured twice in each patient, with a 5-day interval. The patients in the control group (n = 11) received standard intensive care unit (ICU) treatment between measurements, whereas those in the GH group (n = 11) also received 0.3 U/kg daily of human recombinant GH. MEASUREMENTS AND RESULTS: Albumin synthesis was measured by labeling with L-[2H5]phenylalanine. In the control group, the fractional synthesis rate (FSR) of albumin was 16.3+/-4.1%/day (mean and SD) in the first measurement and 15.7+/-4.2%/day 5 days later (NS), whereas in the GH group the corresponding values were 17.0+/-4.7%/day and 16.7+/-5.5%/day (NS). The calculated absolute synthesis rates of albumin, based on FSR and intravascular albumin mass, also showed no effect of GH. CONCLUSION: Albumin synthesis rates were consistently higher in the two groups of critically ill patients than previously reported values in healthy subjects. However, GH treatment for 5 days neither stimulated nor inhibited albumin synthesis rates in these critically ill patients.

Growth hormone together with glutamine-containing total parenteral nutrition maintains muscle glutamine levels and results in a less negative nitrogen balance after surgical trauma.

BACKGROUND: Muscle protein catabolism, reflected by a decrease in glutamine (GLN), a decrease in muscle protein synthesis, and a negative nitrogen balance can be reduced by either administration of GLN or growth hormone (GH). In this study, the effects of a combination of GH and GLH were studied. METHODS: Patients (n = 16) undergoing abdominal operation were given total parenteral nutrition (TPN) containing either GLN alone or GLN together with GH (GH/GLN) during 3 postoperative days. The amino acid concentration and protein synthesis in muscle tissue and the nitrogen balance were measured. RESULTS: GH/GLN reduced nitrogen losses compared with GLN alone (-5.8 +/- 1.4 g nitrogen versus -10.6 +/- 1.1 g nitrogen, P <.05). GH/GLN maintained muscle GLN at preoperative levels compared with a 47.5% +/- 6.3% decline in the GLN group. A similar decrease was seen in the fractional synthesis rate of muscle protein postoperatively in both groups. CONCLUSIONS: GH has an additive effect given together with GLN on muscle amino acid metabolism, preventing the decrease in the GLN concentration in skeletal muscle and diminishing the loss of whole body nitrogen. However, the improvements in muscle amino acid concentrations and nitrogen loss were not associated with differences between the groups in muscle protein synthesis postoperatively.

Increased concentration of tracee affects estimates of muscle protein synthesis.

Muscle protein synthesis was measured by infusion of L-[2H(5)]phenylalanine in two groups of anesthetized dogs, before and during infusion of insulin with euaminoacidemia, and with differing concentrations of unlabeled phenylalanine (tracee). With the infusion of insulin, muscle protein synthesis increased 39 +/- 12% based on phenylalanyl-tRNA. Calculation with plasma phenylalanine enrichment overestimated insulin stimulation by 40% (56 +/- 12 vs. 39 +/- 12%). Raising the concentration of plasma phenylalanine twofold during infusion of insulin further increased the apparent stimulation of muscle protein synthesis based on plasma relative to phenylalanyl-tRNA by 225% (65 +/- 19 vs. 20 +/- 14%, P < 0.001). In both experiments, the stimulation of synthesis rates calculated from phenylalanine enrichment within the muscle was closer to that from phenylalanyl-tRNA (48 +/- 19%, experiment 1; 30 +/- 14%, experiment 2). Results indicate that the enrichment of a labeled amino acid within plasma and tissue amino acid pools is affected by the concentration of tracee infused. Increasing the concentration of tracee overestimates the insulin-mediated stimulation of muscle protein synthesis when amino acid pools other than aminoacyl-tRNA are used as the precursor enrichment.

Effects of smoking and abstention from smoking on fibrinogen synthesis in humans.

Cigarette smoking and hyperfibrinogenaemia are both significant risk factors for the development of cardiovascular disease. Two studies are described here which aimed to establish the metabolic mechanism responsible for the raised plasma fibrinogen concentration observed in smokers. Chronic smokers had a significantly elevated absolute rate of fibrinogen synthesis (ASR) compared with non-smokers (22.7 +/- 1.3 mg/kg per day versus 16.0 +/- 1.3 mg/kg per day; means +/- S.E.M., P < 0.01), with plasma levels of fibrinogen significantly correlated with fibrinogen synthesis (r = 0.65, P = 0.04). Unlike fibrinogen, plasma albumin concentrations were lower in smokers than in non-smokers (45 +/- 0.4 versus 47 +/- 0.7 g/l, P < 0.05), but there was no difference in rates of albumin synthesis between the two groups. Two weeks cessation from smoking by previously chronic smokers was associated with a rapid and marked fall in plasma fibrinogen concentration (from 3.06 +/- 0.11 g/l to 2.49 +/- 0.14 g/l, P < 0.001), and a significant reduction in ASR (a 33% reduction, from 24.1 +/- 1.7 to 16.1 +/- 1.0 mg/kg per day, P < 0.001). These studies suggest a primary role for increased synthesis in producing the hyperfibrinogenaemia associated with smoking. Moreover, abstention from smoking for a period of only 2 weeks induces a significant decrease in the rate of fibrinogen synthesis by the liver, with a concomitant reduction in the plasma fibrinogen concentration.

Stimulation of human albumin synthesis and gene expression by growth hormone treatment.

BACKGROUND AND AIMS: In this study the effects of acute (5 h) and short-term (5 days) GH treatment on albumin synthesis rates in man were investigated and related to changes in the availability of hepatic albumin mRNA. METHODS: 30 patients undergoing elective laparoscopic cholecystectomy were randomized into controls (n=10) or GH-treatment (12 U/dose) for 5 h or 5 days (n=10 in each group). Albumin mRNA levels (in liver biopsy specimens) were measured employing a quantitative polymerase chain reaction assay developed specifically for this purpose, whereas albumin synthesis was measured using [(2)H(5)]phenylalanine. RESULTS: The fractional synthesis rate of albumin was 6.0+/-0.9 %/day in the control group and 8.0+/-1.8 %/day and 8.3+/-1.7 %/day in the GH-treated groups, respectively (P<0.05 vs controls in both cases). The corresponding values for the concentration of albumin mRNA were 2.6+/-1.1 ng/microg total RNA, 2.9+/-0.8 ng/microg total RNA (NS) and 4.7+/-1.8 ng/microg total RNA in the "GH 5" group (P<0.01 vs controls). The changes in albumin synthesis were only partly explained by the differences in hepatic albumin mRNA levels (r=0.5, P<0.01). CONCLUSION: These results suggest that GH may induce a quick, gene expression-independent increase in albumin synthesis, which is sustained by a later-occurring increase in albumin gene expression.

Enhanced synthesis of albumin and fibrinogen at high altitude.

The acute effects of active and passive ascent to high altitude on plasma volume (PV) and rates of synthesis of albumin and fibrinogen have been examined. Measurements were made in two groups of healthy volunteers, initially at low altitude (550 m) and again on the day after ascent to high altitude (4,559 m). One group ascended by helicopter (air group, n = 8), whereas the other group climbed (foot group, n = 9), so that the separate contribution of physical exertion to the response could be delineated. PV was measured by dilution of (125)I-labeled albumin, whereas synthesis rates of albumin and fibrinogen were determined from the incorporation of isotope into protein after injection of [ring-(2)H(5)]phenylalanine. In the air group, there was no change in PV at high altitude, whereas, in the foot group, there was a 10% increase in PV (P < 0.01). Albumin synthesis (mg. kg(-1). day(-1)) increased by 13% in the air group (P = 0.058) and by 32% in the foot group (P < 0.001). Fibrinogen synthesis (mg. kg(-1). day(-1)) increased by 40% in the air group (P = 0.068) and by 100% in the foot group (P < 0.001). Hypoxia and alkalosis at high altitude did not differ between the groups. Plasma interleukin-6 was increased modestly in both groups but C-reactive protein was not changed in either group. It is concluded that increases in PV and plasma protein synthesis at high altitude result mainly from the physical exercise associated with climbing. However, a small stimulation of albumin and fibrinogen synthesis may be attributable to hypobaric hypoxia alone.

Penetrance and expressivity of genes involved in the development of epilepsy in the genetically epilepsy-prone rat (GEPR).

In order to understand the level of complexity of the epileptic phenotype in the two strains of Genetically Epilepsy-Prone Rats (GEPRs), we determined two important measures of genetic complexity, penetrance and expressivity. Penetrance is the percentage of animals of a specific genotype who express the phenotype associated with that underlying genotype. Expressivity refers to the degree that a particular genotype is expressed as a phenotype within an individual. Incomplete penetrance and variable expressivity are caused by genetic and environmental variation. In this paper we have studied the epileptic phenotype for 20,373 rats. Animals were tested on three occasions for audiogenic seizure and given an audiogenic response score (on a scale of 0-9, 0 being no seizure and 9 being the most severe). The GEPR-3 and GEPR-9 animals both show incomplete penetrance and variable expressivity of the underlying genetic predisposition. The GEPR-9 strain has more animals that have variable levels of seizure predisposition (as measured by a scoring system that denotes the severity of generalized tonic/clonic seizures) and a greater percentage of animals that exhibit no susceptibility to such seizures induced by sound. Both strains have a number of animals that are not susceptible to sound-induced GTCSs and that exhibit some variability in seizure severity. The GEPR-9 males show greater differences in expressivity and penetrance compared to GEPR-9 females. The GEPR-3 animals also show sex-associated variable penetrance and expressivity of the epileptic phenotype, although the differences are much smaller. These findings are the first step toward the mapping of the underlying quantitative trait loci (QTL) for seizure in these animals.

Effect of hemodialysis on protein synthesis.

BACKGROUND: Earlier studies have shown that hemodialysis (HD) treatment stimulates net protein catabolism. Several factors associated with HD affect protein catabolism, such as an inflammatory effect due to blood-membrane contact and loss of amino acids and glucose into the dialysate. SUBJECTS, MATERIAL AND METHODS: We have studied protein synthesis in skeletal muscle of healthy volunteers (n = 9) before and after a single heparin-free HD. Protein synthesis (PS) was studied, using 2 independent techniques: the incorporation of labeled 2H5-phenylalanine into muscle protein, which gives a quantitative measure of the fractional synthesis rate of muscle proteins, and the concentration and size distribution of ribosomes, which gives a qualitative estimate of protein synthesis. Furthermore, free amino acid concentrations were determined in muscle and plasma. RESULTS: The rate of PS, expressed as the fractional synthesis rate, decreased by 13% during HD (p < 0.02). The capacity for PS, as reflected by the total concentration of ribosomes, was reduced by 22% (p < 0.02) and the activity of PS, expressed as the relative proportion of polyribosomes, decreased from 48.4 +/- 0.9% to 44.8 +/- 0.8% after dialysis (p < 0.01). There was a total loss of 5.8 +/- 0.3 g amino acid to the dialysate. Plasma and muscle free amino acid concentrations were determined at four time points; before and after the phenylalanine incorporation period, before dialysis and before and after the second incorporation period after dialysis. Immediately after dialysis, there was a decrease in plasma asparagine, histidine, alanine, taurine, valine and tryptophane. In muscle, no changes occurred except for a slight increase in leucine after dialysis. In blood, the glucose concentration decreased and the total amount of glucose lost to the dialysate was 21 +/- 3.0 g. In summary, one single hemodialysis treatment decreases fractional protein synthesis rate in skeletal muscle. CONCLUSION: The results demonstrate substantial losses of amino acids and glucose to the dialysate and decreased amino acid concentrations in plasma, but only minimal changes in the intracellular amino acid concentrations in muscle, suggesting that the decreased PS is caused not by lack of amino acid precursors at the site of the synthesis activity, but by other mechanisms.