Low protein

About: Low protein is a research topic. Over the lifetime, 8139 publications have been published within this topic receiving 213225 citations.

Early programming of glucose–insulin metabolism

Abstract: Epidemiological studies have revealed strong inverse relationships between birthweight and the risk of developing type 2 diabetes mellitus (T2DM) and the metabolic syndrome. The mechanistic basis of these relationships remains the subject of research and debate. Evidence for the importance of the fetal environment has been obtained from both human and rodent studies. Studies of monozygotic twins have shown that genetic effects cannot explain these relationships entirely, if at all. Fetal and early postnatal growth restriction produced by feeding a reduced protein diet to rat dams leads to T2DM in old male offspring and, if combined with an obesity-inducing diet after weaning, to all the features of the metabolic syndrome.

Pharmacokinetics and pharmacodynamics of the nitroimidazole antimicrobials.

Abstract: Metronidazole, the prototype nitroimidazole antimicrobial, was originally introduced to treat Trichomonas vaginalis, but is now used for the treatment of anaerobic and protozoal infections. The nitroimidazoles are bactericidal through toxic metabolites which cause DNA strand breakage. Resistance, both clinical and microbiological, has been described only rarely. Metronidazole given orally is absorbed almost completely, with bioavailability > 90% for tablets; absorption is unaffected by infection. Rectal and intravaginal absorption are 67 to 82%, and 20 to 56%, of the dose, respectively. Metronidazole is distributed widely and has low protein binding (< 20%). The volume of distribution at steady state in adults is 0.51 to 1.1 L/kg. Metronidazole reaches 60 to 100% of plasma concentrations in most tissues studied, including the central nervous system, but does not reach high concentrations in placental tissue. Metronidazole is extensively metabolised by the liver to 5 metabolites. The hydroxy metabolite has biological activity of 30 to 65% and a longer elimination half-life than the parent compound. The majority of metronidazole and its metabolites are excreted in urine and faeces, with less than 12% excreted unchanged in urine. The pharmacokinetics of metronidazole are unaffected by acute or chronic renal failure, haemodialysis, continuous ambulatory peritoneal dialysis, age, pregnancy or enteric disease. Renal dysfunction reduces the elimination of metronidazole metabolites; however, no toxicity has been documented and dosage alterations are unnecessary. Liver disease leads to a decreased clearance of metronidazole and dosage reduction is recommended. Recent pharmacodynamic studies of metronidazole have demonstrated activity for 12 to 24 hours after administration of metronidazole 1 g. The post-antibiotic effect of metronidazole extends beyond 3 hours after the concentration falls below the minimum inhibitory concentration (MIC). The concentration-dependent bactericidal activity, prolonged half-life and sustained activity in plasma support the clinical evaluation of higher doses of metronidazole given less frequently. Metronidazole-containing regimens for Helicobacter pylori in combination with proton pump inhibitors demonstrate higher success rates than antimicrobial regimens alone. The pharmacokinetics of metronidazole in gastric fluid appear contradictory to these results, since omeprazole reduces peak drug concentration and area under the concentration-time curve for metronidazole and its hydroxy metabolite; however, concentrations remain above the MIC. Other members of this class include tinidazole, ornidazole and secnidazole. They are also well absorbed and distributed after oral administration. Their only distinguishing features are prolonged half-lives compared with metronidazole. The choice of nitroimidazole may be influenced by the longer administration intervals possible with other members of this class; however, metronidazole remains the predominant antimicrobial for anaerobic and protozoal infections.

Down‐regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet

Abstract: Intrauterine growth restriction (IUGR) represents an important risk factor for perinatal complications and for adult disease. IUGR is associated with a down-regulation of placental amino acid transporters; however, whether these changes are primary events directly contributing to IUGR or a secondary consequence is unknown. We investigated the time course of changes in placental and fetal growth, placental nutrient transport in vivo and the expression of placental nutrient transporters in pregnant rats subjected to protein malnutrition, a model for IUGR. Pregnant rats were given either a low protein (LP) diet (n = 64) or an isocaloric control diet (n = 66) throughout pregnancy. Maternal insulin, leptin and IGF-I levels decreased, whereas maternal amino acid concentrations increased moderately in response to the LP diet. Fetal and placental weights in the LP group were unaltered compared to control diet at gestational day (GD) 15, 18 and 19 but significantly reduced at GD 21. Placental system A transport activity was reduced at GD 19 and 21 in response to a low protein diet. Placental protein expression of SNAT2 was decreased at GD 21. In conclusion, placental amino acid transport is down-regulated prior to the development of IUGR, suggesting that these placental transport changes are a cause, rather than a consequence, of IUGR. Reduced maternal levels of insulin, leptin and IGF-1 may link maternal protein malnutrition to reduced fetal growth by down-regulation of key placental amino acid transporters.

A natively unfolded yeast prion monomer adopts an ensemble of collapsed and rapidly fluctuating structures

Abstract: The yeast prion protein Sup35 is a translation termination factor, whose activity is modulated by sequestration into a self-perpetuating amyloid. The prion-determining domain, NM, consists of two distinct regions: an amyloidogenic N terminus domain (N) and a charged solubilizing middle region (M). To gain insight into prion conversion, we used single-molecule fluorescence resonance energy transfer (SM-FRET) and fluorescence correlation spectroscopy to investigate the structure and dynamics of monomeric NM. Low protein concentrations in these experiments prevented the formation of obligate on-pathway oligomers, allowing us to study early folding intermediates in isolation from higher-order species. SM-FRET experiments on a dual-labeled amyloid core variant (N21C/S121C, retaining wild-type prion behavior) indicated that the N region of NM adopts a collapsed form similar to “burst-phase” intermediates formed during the folding of many globular proteins, even though it lacks a typical hydrophobic core. The mean distance between residues 21 and 121 was ≈43 Å. This increased with denaturant in a noncooperative fashion to ≈63 Å, suggesting a multitude of interconverting species rather than a small number of discrete monomeric conformers. Fluorescence correlation spectroscopy analysis of singly labeled NM revealed fast conformational fluctuations on the 20- to 300-ns time scale. Quenching from proximal and distal tyrosines resulted in distinct fast and slower fluctuations. Our results indicate that native monomeric NM is composed of an ensemble of structures, having a collapsed and rapidly fluctuating N region juxtaposed with a more extended M region. The stability of such ensembles is likely to play a key role in prion conversion.