The earliest unambiguous Neanderthal engravings on cave walls: La Roche-Cotard, Loire Valley, France.

Here we report on Neanderthal engravings on a cave wall at La Roche-Cotard (LRC) in central France, made more than 57±3 thousand years ago. Following human occupation, the cave was completely sealed by cold-period sediments, which prevented access until its discovery in the 19th century and first excavation in the early 20th century. The timing of the closure of the cave is based on 50 optically stimulated luminescence ages derived from sediment collected inside and from around the cave.

Does acute glutamine depletion enhance the response of glutamine synthesis to fasting in muscle in adult and old rats?

Background And Aims: In earlier studies, skeletal muscle glutamine synthetase (GS) activity was shown to be enhanced by fasting and glucocorticoids, and inhibited by exogenous glutamine (Gln) supplementation. The current study was designed to determine whether phenylbutyrate (PhiB), a Gln-chelating agent in humans, (1) could trap Gln and produce a decline in plasma Gln in rats, as it does in humans, and (2) if so, whether (Phi)B would further enhance the response of muscle GS activity to fasting in rats.

Methods: Adult (6-8 months) and aged (20-21 months) rats were fasted for 5 days and received two doses of 0.

Effect of medroxyprogesterone acetate on the efficiency of an oral protein-rich nutritional support in HIV-infected patients.

We have examined the effect of a medroxyprogesterone therapy in HIV-infected patients under appropriate nutrition for anabolism. The experiments were performed on 12 men (mean age 40 y), HIV seropositive but free of any clinically active opportunistic infection for at least one month. The patients underwent a 2-week baseline diet period (1.

Leucine-supplemented meal feeding for ten days beneficially affects postprandial muscle protein synthesis in old rats.

Acute leucine supplementation of the diet has been shown to blunt defects in postprandial muscle protein metabolism in old rats. This study was undertaken to determine whether the effect of leucine persists in a 10-d experiment. For this purpose, adult (9 mo) and old (21 mo) rats were fed a semiliquid 18.

Pulse protein feeding pattern restores stimulation of muscle protein synthesis during the feeding period in old rats.

Muscle loss during aging could be related to a lower sensitivity of muscle protein synthesis to feeding. To overcome this decrease without increasing protein intake, we proposed to modulate the daily protein feeding pattern. We showed that consuming 80% of dietary proteins at noon (pulse pattern) improved nitrogen balance in elderly women.

Postprandial stimulation of muscle protein synthesis in old rats can be restored by a leucine-supplemented meal.

Aging is characterized by a progressive loss of muscle mass. A decrease of muscle protein synthesis stimulation has been detected in the postprandial state and correlated to a decrease of muscle protein synthesis sensitivity to leucine in vitro. This study was undertaken to examine the effect of a leucine-supplemented meal on postprandial (PP) muscle protein synthesis during aging.

The response of liver albumin synthesis to infection in rats varies with the phase of the inflammatory process.

To discriminate between the effects of infection and of anorexia associated with infection, liver albumin synthesis was measured in well-fed rats, in rats injected with live Escherichia coli and in pair-fed rats at different stages of the inflammatory response (1, 6 and 10 days after infection) using a large dose of l-[1-(14)C]valine. Albuminaemia and albumin mRNA levels were unchanged following food restriction. However, absolute albumin synthesis was decreased in pair-fed rats compared with control animals after 1 day of food restriction, and had returned to normal values by day 10 when food intake was restored.

Synthesis rate of plasma albumin is a good indicator of liver albumin synthesis in sepsis.

Plasma albumin is well known to decrease in response to inflammation. The rate of albumin synthesis from both liver and plasma was measured in vivo by use of a large dose of L-[(2)H(3)-(14)C]valine in rats injected intravenously with live Escherichia coli and in pair-fed control rats during the acute-phase period (2 days postinfection). The plasma albumin concentration was reduced by 50% in infected rats compared with pair-fed animals.

Protein turnover modifications induced by the protein feeding pattern still persist after the end of the diets.

This study was undertaken to determine whether the protein feeding pattern could induce chronic adaptation of protein turnover. After a 15-day adaptive period, elderly (68 yr) and young (26 yr) women received, for 14 days, a diet providing 200 KJ x kg fat-free mass (FFM)(-1) x day(-1), where the daily protein intake (1.7 g protein x kg FFM(-1) x day(-1)) was either spread over 4 meals in the spread pattern or mainly (80%) consumed at noon in the pulse pattern.

Response of leucine metabolism to hyperinsulinemia in hypothyroid patients before and after thyroxine replacement.

We have investigated the effect of hypothyroidism and insulin on protein metabolism in humans. Six hypothyroid patients were studied in a postabsorptive state before and after 5 months of regular treatment for hypothyroidism (153 +/- 17 microg/day of L-T4). The effect of insulin was assessed under hyperinsulinemic euglycemic and eukalemic conditions.

Diazoxide-induced insulin deficiency greatly reduced muscle protein synthesis in rats: involvement of eIF4E.

We have investigated the effect of a postprandial acute insulin deficiency induced by diazoxide injection on rat skeletal muscle protein synthesis. Diazoxide administration lowered plasma insulin >85% within 3 h after injection, whereas other hormones (insulin-like growth factor I, glucagon, corticosterone) involved in the regulation of muscle protein synthesis were not altered significantly compared with control animals. The fractional rate of muscle protein synthesis, measured in vivo, was reduced significantly (P < 0.

Threonine and methionine are limiting amino acids for protein synthesis in patients with AIDS.

This study was conducted to identify the most rate-limiting amino acids for whole-body protein synthesis in acquired immunodeficiency syndrome (AIDS) patients. We postulated that an essential amino acid that would be rate limiting in AIDS should have a low basal plasma concentration and should remain at a low level during amino acid infusion. Seven male AIDS patients (median age 37 y, CD4 cell count: 76 mm-3) without any clinically active opportunistic infection during the month before the experiment were infused intravenously with a complete amino acid-glucose mixture for 2.

Sustained modifications of protein metabolism in various tissues in a rat model of long-lasting sepsis.

1. Sepsis was induced in rats by an intravenous injection of live bacteria. Infected and pair-fed animals were studied before the infection, in an acute septic phase (day 2 post-infection), in a chronic septic phase (day 6) and in a late septic phase (day 10).

Contribution of proteolysis and de novo synthesis to alanine production in diabetic rat skeletal muscle: a 15N/1H nuclear magnetic resonance study.

To assess the role of leucine as a precursor of alanine alpha-amino nitrogen in skeletal muscle during diabetes, extensor digitorum longus muscles from control (n = 7 experiments) and streptozotocin-diabetic rats (n = 8 experiments) were isolated and superfused with [15N]leucine (3 mmol/l) in the presence of glucose (10 mmol/l) for 2 h. Muscle perchloric acid extraction was performed at the end of superfusion in order to quantify newly synthesized alanine by 15N/1H nuclear magnetic resonance. Release of [15N]alanine in the superfusion medium was also measured.

Rapid detection of Pneumocystis carinii in bronchoalveolar lavage specimens from human immunodeficiency virus-infected patients: use of a simple DNA extraction procedure and nested PCR.

We report on the development of a rapid nested PCR protocol for the detection of Pneumocystis carinii DNA in bronchoalveolar lavage (BAL) specimens in which the protocol included the use of a commercially available DNA extraction kit (GeneReleaser). GeneReleaser enabled us to obtain amplification-ready DNA within 20 min without requiring the purification of the DNA. The nested PCR was performed with the primers pAZ102-E, pAZ102-H, and pAZ102-L2 (A.

Detection of Pneumocystis carinii DNA by PCR amplification in various rat organs in experimental pneumocystosis.

Pneumocystosis is usually a disease of the lungs, but the number of cases of extrapulmonary pneumocystosis has greatly increased during the AIDS epidemic. Much remains unknown about the frequency and mechanisms of dissemination. In the present study, a systematic search for Pneumocystis carinii by PCR with primers specific for mitochondrial rRNA was performed in the lung, liver, spleen and kidney of 12 immunosuppressed rats and two immunocompetent rats.

The effect of a high dose of 3-hydroxy-3-methylbutyrate on protein metabolism in growing lambs.

The effect of a high dose of 3-hydroxy-3-methylbutyrate (HMB, a leucine catabolite) on protein metabolism was investigated in growing male lambs fed on hay and concentrate. Concentrate was supplemented with either Ca(HMB)2 (4 g/kg) or Ca(CO3)2 in experimental (HMB) and control groups respectively. Both groups consisted of six 2-month old lambs.

Response of leucine metabolism to hyperinsulinemia under amino acid replacement in experimental hyperthyroidism.

We investigated the responsiveness of protein metabolism to insulin as a mediator of the protein catabolic response to hyperthyroidism in humans. Six healthy volunteers were studied in a postabsorptive state before and after oral intake of thyroid hormones (2 micrograms.kg-1.

Effect of hyperinsulinemia and hyperaminoacidemia on muscle and liver protein synthesis in lactating goats.

The experiment was carried out to clarify the roles of insulin and amino acids on protein synthesis in fed lactating goats (30 days postpartum). Protein synthesis in the liver and various skeletal muscles was assessed after an intravenous injection of a large dose of unlabeled valine containing a tracer dose of L-[2,3,4-3H]valine. The animals were divided into three groups.

Leucine metabolism in lactating and dry goats: effect of insulin and substrate availability.

Early lactating goats show insulin resistance with respect to extramammary glucose utilization. However, much less is known about the two major factors, insulin and plasma amino acid concentration, that regulate protein metabolism in lactating goats. To examine this question, the in vivo effect of acute insulin was studied in goats during early lactation (12-31 days postpartum), midlactation (98-143 days postpartum), and the dry period (approximately 1 yr postpartum).

Effect of amino acids alone or with insulin on muscle and liver protein synthesis in adult and old rats.

This study was carried out to analyze age-related changes on amino acid and insulin effects on muscle and liver protein synthesis. Conscious male rats, aged 12 (adult) and 24 (old) mo, were infused for 90 min with either saline, amino acids, or amino acids with insulin and glucose. Protein synthesis was measured during the last 15 min of infusion (flooding dose of valine with L-[2,3,4-3H]valine).

In vivo longitudinal variations in protein synthesis in developing ovine intestines.

Changes in fractional rates of protein synthesis (Ks) were investigated at different small and large intestinal sites in 1-, 5-, and 8-wk-old milk-fed and 8-wk-old weaned lambs, a species with early intestinal maturation similar to most domestic animals and humans, with the use of a flooding dose of L-[3H]valine. Between 1 and 8 wk of age, Ks did not change significantly in the duodenum, the cecum, or the colon of milk-fed lambs, but was depressed by 30% in the jejunum and by 39% in the ileum. This was because of reduced ribosomal capacity, i.

Effect of insulin in conjunction with glucose, amino acids and potassium on net metabolism of glucose and amino acids in the goat mammary gland.

The hyperinsulinaemic euglycaemic insulin clamp technique was used to study the effect of insulin on the arterio-venous concentration differences of glucose and amino acids across the mammary gland in dairy goats. Insulin was given in conjunction with K to prevent insulin hypokalaemia. Appropriate amino acid infusion was used to blunt insulin-induced hypoaminoacidaemia or to create hyperaminoacidaemia and maintain this state under insulin treatment.

Altered partition of threonine metabolism in pigs by protein-free feeding or starvation.

Kinetic aspects of threonine (Thr) metabolism were examined in growing pigs fed a well-balanced diet (C), an isocaloric protein-free diet (PF), or starved (S) for 48 h. With the use of continuous simultaneous infusion of L-[1-13C]Thr, [1-14C]sarcosine, and 2-[1-14C]ketobutyrate (KB) for 10 h, estimates were made of rates of Thr incorporated into protein (S), released from body proteins (B), and oxidized through the catabolic pathways of L-Thr 3-dehydrogenase (TDG) and threonine dehydratase (TDH). In the C group S was 185, B was 138, Thr disposal to glycine (DRThr-Gly) was 47, and Thr disposal to KB (DRThr-KB) was 7 mumol.