Showing papers on "Low protein published in 1991"

Protein adsorption to poly(ethylene oxide) surfaces.

Abstract: Surfaces containing poly(ethylene oxide) (PEO) are interesting biomaterials because they exhibit low degrees of protein adsorption and cell adhesion. In this study different molecular weight PEO molecules were covalently attached to poly(ethylene terephthalate) (PET) films using cyanuric chloride chemistry. Prior to the PEO immobilization, amino groups were introduced onto the PET films by exposing them to an allylamine plasma glow discharge. The amino groups on the PET film were next activated with cyanuric chloride and then reacted with bis-amino PEO. The samples were characterized by scanning electron microscopy, water contact angle measurements, gravimetric analysis, and electron spectroscopy for chemical analysis (ESCA). The adsorption of 125I-labeled baboon fibrinogen and bovine serum albumin was studied from buffer solutions. Gravimetric analysis indicated that the films grafted with the low-molecular-weight PEO contained many more PEO molecules than the surfaces grafted with higher-molecular-weight PEO. The high-molecular-weight PEO surfaces, however, exhibited greater wettability (lower water contact angles) and less protein adsorption than the low-molecular-weight PEO surfaces. Adsorption of albumin and fibrinogen to the PEO surfaces decreased with increasing PEO molecular weight up to 3500. A further increase in molecular weight resulted in only slight decreases in protein adsorption. Protein adsorption studies as a function of buffer ionic strength suggest that there may be an ionic interaction between the protein and the allylamine surface. The trends in protein adsorption together with the water contact angle results and the gravimetric analysis suggest that a kind of "cooperative" water structuring around the larger PEO molecules may create an "excluded volume" of the hydrated polymer coils. This may be an important factor contributing to the observed low protein adsorption behavior.

A kinetic study of the competition between renaturation and aggregation during the refolding of denatured-reduced egg white lysozyme.

Abstract: The recovery of proteins following denaturation is optimal at low protein concentrations. The decrease in yield at high concentrations has been explained by the kinetic competition of folding and "wrong aggregation". In the present study, the renaturation-reoxidation of hen and turkey egg white lysozyme was used as a model system to analyze the committed step in aggregate formation. The yield of renatured protein for both enzymes decreased with increasing concentration in the folding process. In addition, the yield decreased with increasing concentrations of the enzyme in the denatured state (i.e., prior to its dilution in the renaturation buffer). The kinetics of renaturation of turkey lysozyme were shown to be very similar to those of hen lysozyme, with a half-time of about 4.5 min at 20 degrees C. The rate of formation of molecular species that lead to formation of aggregates (and therefore fail to renature) was shown to be rapid. Most of the reaction occurred in less than 5 s after the transfer to renaturation buffer, and after 1 min, the reaction was essentially completed. Yet, by observing the effects of the delayed addition of denatured hen lysozyme to refolding turkey lysozyme, it was shown that folding intermediates become resistant to aggregation only much more slowly, with kinetics indistinguishable from those observed for the appearance of native molecules. The interactions leading to the formation of aggregates were nonspecific and do not involve disulfide bonds. These observations are discussed in terms of possible kinetic and structural aspects of the folding pathway.

Metabolic acidosis and skeletal muscle adaptation to low protein diets in chronic uremia.

Abstract: To maintain nitrogen equilibrium when prescribed a low protein diet (LPD), metabolic adaptations occur involving a reduction protein turnover, principally decreased muscle protein degradation. Studies suggest that in patients with chronic renal failure (CRF) uncomplicated by metabolic acidosis (MA), these adaptive responses are intact. Because MA stimulates muscle proteolysis, this study examined the hypothesis that in CRF complicated by MA, the adaptation to LPD may be impaired, inducing a nitrogen wasting state. Six adults with CRF (mean GFR: 12.8 +/- 1.5 ml/min) and MA (mean serum bicarbonate: 17.0 +/- 1.0 mM/liter) receiving an unrestricted diet (protein intake: 1.2 g/kg body wt/day) were converted to an isocaloric LPD (protein: 0.6 g/kg body wt/day). Two weeks later total urinary nitrogen losses decreased, but skeletal muscle protein catabolism (SMPC), assessed from the urinary 3-methyl histidine:creatinine ratio, increased, demonstrating impairment in the adaptive down-regulation of SMPC. The LPD was continued for a further two weeks and MA was corrected with oral sodium bicarbonate (mean serum bicarbonate: 24.3 +/- 1.2 mM/liter). Correcting MA decreased SMPC to a level below that measured prior to protein restriction. The decreased SMPC was paralleled by further decreases in urinary nitrogen losses, confirming that MA impaired nitrogen utilization. It is concluded that MA can override the expected metabolic adaptive response to a LPD. The associated impairment of nitrogen utilization not only diminishes the efficacy of the diet, but also accelerates the loss of lean body mass.

Short-term effects of substituting protein for carbohydrate in the diets of moderately hypercholesterolemic human subjects.

Abstract: The short-term effects of plasma lipoprotein lipids of substituting meat and dairy protein for carbohydrate in the diets of 10 free-living moderately hypercholesterolemic human subjects (four men, six women) were studied under closely supervised dietary control during the consumption of constant, low intakes of fat and cholesterol and the maintenance of stable body weight as well as constant fiber consumption. Subjects were randomly allocated to either the high or low protein diets (mean, 23% v 11% of energy as protein, 24% as fat, and 53% v 65% as carbohydrate) and then switched to the other diet for another 4 to 5 weeks. Mean fasting plasma high-density lipoprotein cholesterol (HDL-C) was significantly higher by 12% ± 4% (0.97 ± 0.08 v 0.89 ± 0.08 mmol/L, P < .01), whereas mean total cholesterol (TC) was lower by 6.5% ± 1.3% (5.7 ± 0.3 v 6.1 ± 0.3 mmol/L, P < .001), mean low-density lipoprotein-cholesterol (LDL-C) lower by 6.4% ± 2.0% (4.5 ± 0.2 v 4.8 ± 0.2 mmol/L, P < .02), mean total triglycerides (TG) lower by 23% ± 5% (1.7 ± 0.1 v 2.4 ± 0.3 mmol/L, P < .02), and mean very-low-density lipoprotein triglycerides (VLDL-TG) lower by 31% ± 9% (0.96 ± 0.15 v 1.48 ± 0.26 mmol/L, P < .05) on the high versus low protein diet. Mean values of LDL-C were significantly lower during weeks 3 to 5 of the high protien diet than during either weeks 1 to 5 or weeks 1 to 2 of the high protein diet (4.3 ± 0.3, 4.5 ± 0.2, and 4.7 ± 0.3 mmol/L, respectively, P < .05) and 11% ± 3% lower than on low protein diet, P < .005. The ratio of plasma LDL-C to HDL-C was consistently lower by 17% ± 3% during the high versus low protein diet (4.9 ± 0.5 v 5.8 ± 0.5, P < .001). Lowering plasma TC and LDL-C and total TG and VLDL-TG and increasing HDL-C by chronic isocaloric substitution of dietary protein for carbohydrate may enhance the cardiovascular risk reduction obtained by restriction of dietary fat and cholesterol.

Secretory responses in granular ducts and acini of submandibular glands in vivo to parasympathetic or sympathetic nerve stimulation in rats.

Abstract: The roles of sympathetic and parasympathetic nerves in the secretion of saliva from submandibular glands of rats have been tested by electrical stimulation of either nerve for 1 h unilaterally in separate animals. The flows of saliva thereby induced and their protein content were monitored. Structural changes in each gland were assessed by light- and electron microscopy and compared with the unstimulated contralateral control gland, and the extent of the changes was determined morphometrically. Sympathetic nerve stimulation induced a relatively low flow of saliva that was rich in protein and was accompanied by extensive degranulation from both acinar and granular duct cells. In contrast parasympathetic nerve stimulation induced a considerable flow of saliva that had a low protein content and no detectable degranulation occurred from the secretory cells. It is possible, therefore, that some protein in parasympathetic saliva may have arisen from a non-granular pathway.

Relationships between pork loin palatability traits and physical characteristics of cooked chops.

Abstract: Pork loins (n = 72) were selected so that marbling scores would range from "practically devoid" to "abundant" in the longissimus muscle. Loin chops were cooked and rated by a trained six-member sensory panel. Physical and chemical characteristics were stratified according to marbling level (divided into 10 subclasses), muscle structure, shear force, overall palatability, and juiciness (each divided into three subclasses). The highest ratings for overall palatability were assigned to chops with high reflectance (685 nm), low moisture (70.1%), high i.m. fat (9.1%; or, high marbling score), low protein (19.4%), and low cooking loss (25.9%). Chops with the highest percentage of cooking loss were high in moisture content (75.59%), low in i.m. fat (1.78%), and high in protein content (21.54%). Differences in muscle structure, shear force, overall palatability, and juiciness were associated with differences in percentages of protein, moisture (whole tissue basis [WTB]) and fat (WTB). Pork loins with marbling between "practically devoid-plus" and "small" had (P less than .05) more protein and less fat (WTB) than loins with marbling scores between "modest" and "abundant." Loins with overall palatability ratings between 4.0 and 6.0 had more moisture and protein (P less than .05) than did loins with palatability ratings of 6.1 to 8.0. Selecting pork loins with "small" or less marbling, extremely open structure, a juicy rating of "slightly juicy," and an overall palatability rating of "like slightly" would identify fresh loins that had lower fat and(or) higher protein content.

Cell-cycle-dependent protein accumulation by producer and nonproducer murine hybridoma cell lines: A population analysis

Abstract: Single-cell rates of accumulation of cellular protein have been determined as a function of total protein content using flow cytometry and population balance equations for exponentially growing murine hybridoma cells in the individual G(1), S(1) and G(2) + M cell cycle phases. A novel flow cytometric technique for the identification of hybridoma cells in mitosis was developed and implemented. The data were obtained from a producer cell line which synthesizes and secretes high levels of monoclonal antibodies, and from a nonproducer clone which does not synthesize and secrete substantial amounts of antibody. The results indicate that the kinetics of single-cell protein accumulation in these two cell lines are considerably different. In particular, low protein content G(1) phase producer cells were characterized by a rate of protein accumulation which was approximately five times higher than the mean rate observed for higher protein content producer cells cycle phase. In contrast, the rate of accumulation of protein increased continuously with total protein content for the G(1) phase nonproducer cells. S phase hybridoma cells were characterized by a considerably lower rate of protein accumulation which did not vary much with protein content for either cell line. Finally, G(2) + M phase producer cells demonstrated a negative rate of protein accumulation which indicates that the rates of protein synthesis. It was hypothesized that these differences in total protein accumulation are caused by differences in monoclonal antibody accumulation. The distribution of rates suggests the need for a segregated approach to the modeling of the kinetics of antibody production in hybridomas.

Influence of protein nutrition on the response of growing lambs to exogenous bovine growth hormone.

Abstract: Interactions between protein supply and the anabolic response to exogenous bovine (b) GH have been examined in two experiments using 28-35 kg lambs sustained entirely by intragastric infusion of volatile fatty acids (700 kJ/kg W 0.75 per day) into the rumen and the casein (600 mg (low protein; LP) or 1200 mg (high protein; HP)/kg W 0.75 per day) into the abomasum. Sheep received continuous i.v. infusions of bGH for 6 days in experiment 1 and for 18 days in experiment 2. Nitrogen balances were determined daily throughout both experiments and blood samples, from indwelling catheters, were assayed for GH, insulin-like growth factor-I (IGF-I), insulin and glucose. Infusion of bGH increased plasma GH concentration by five- to sixfold in all animals. There was an increase in N retention in both HP and LP animals over the first 2-3 days of GH administration. HP animals sustained higher N retentions (31%; P less than 0.05) throughout the GH administration but LP animals did not. In contrast, plasma IGF-I concentrations increased progressively over the first 72 to 96 h of GH administration in all sheep and thereafter remained significantly (P less than 0.05) elevated until termination of the GH infusion. In lambs which received both HP and LP infusion in experiment 1 the increase in IGF-I and LP infusions in experiment 1 the increase in IGF-I concentration by day 6 of GH administration was significantly (P less than 0.05) greater when they received the higher protein intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of lysine damage and calculation of lysine bio-availability in several processed foods.

Abstract: By analyzing lysine and furosine the amount of inactivated lysine in several food systems was determined and the values for available lysine and total lysine were calculated. Considerable heat damage was found in heated cereal products, and in heated milk products, including several formula for children and hospitalized patients. Some products contained more inactivated lysine than available lysine. This may have consequences for the nutrition in low protein consuming populations and leads to errors in predicting the protein quality, e.g., by the recently proposed "Protein Digestibility Corrected Amino Acid Score".

Failure of dietary protein and phosphate restriction to retard the rate of progression of chronic renal failure: a prospective, randomized, controlled trial.

Abstract: Ninety-five patients (63 male, 32 female), age 45 +/- 2 years (mean +/- SEM) with chronic renal failure of varied aetiology were randomized to receive either a conventional low protein diet (0.6 g/kg/day protein, 800 mg phosphate; n = 33), a low phosphate diet (providing approximately 1000 mg phosphate plus an orally administered phosphate binder, minimum protein intake 0.8 g/kg/day; n = 30) or to control (minimum protein intake 0.8 g/kg/day, no phosphate restriction; n = 32). Patients were reviewed for a minimum of 6 months before randomization and were withdrawn from the study if plasma creatinine exceeded 900 mumol/l, plasma phosphate was greater than 2.0 mmol/l or at the onset of uraemic symptoms. Following randomization patients were studied for an average of 19 +/- 3 months. Mean plasma creatinine rose from 398 +/- 33 to 600 +/- 50 mumol/l. Dietary protein intake was estimated at 0.69 +/- 0.02 g/kg/day in the low protein group, 1.02 +/- 0.05 in the low phosphate and 1.14 +/- 0.05 in the controls, phosphate intake was 815 +/- 43, 1000 +/- 47, and 1315 +/- 57 mg/day, respectively. Urinary urea excretion and protein catabolic rates were significantly reduced (p less than 0.01) only in those on protein restriction, at 213 +/- 9 mmol/24 hours and 0.71 g/kg/day, respectively. Phosphate excretion was significantly lower (p less than 0.05) in both the low protein group (17.9 +/- 0.8 mmol/24 hours) and the low phosphate group (18.6 +/- 1.0 mmol/24 hours) compared to controls. Changes in body weight, muscle mass and serum transferrin, albumin and immunoglobulins were comparable between the groups. Mean blood pressure following randomization was 150/89 +/- 3/1 (low protein), 148/87 +/- 3/1 (low phosphate) and 146/87 +/- 3/1 (controls). Progression of renal failure was analysed by rate of all of creatinine clearance (ml/min/1.73 m2/month), by rate of deterioration derived from reciprocal plasma creatinine against time plots (1/mmol/year) and to assess individual patient's response to treatment by two phase linear regression ('breakpoint') analysis of reciprocal plasma creatinine/time plots. Progression was analysed only in patients seen for at least 3 months following randomization. The rate of fall of creatinine clearance was not significantly different between the groups (ANOVA): 0.56 +/- 0.08 ml/min/1.73 m2/month (low protein, n = 28), 0.44 +/- 0.07 (low phosphate, n = 23) and 0.69 +/- 0.11 (control, n = 27).(ABSTRACT TRUNCATED AT 400 WORDS)

Biochemical ecology of the forest tent caterpillar: responses to dietary protein and phenolic glycosides.

Abstract: Interactions between quaking aspen (Populus tremuloides) and the forest tent caterpillar (Malacosoma disstria) are likely to be influenced by leaf protein and phenolic glycoside levels, and insect detoxication activity. We investigated the direct and interactive effects of dietary protein and phenolic glycosides on larval performance and midgut enzyme activity of forest tent caterpillars. We conducted bioassays with six artificial diets, using both first and fourth stadium larvae. Four of the diets comprised a 2×2 factorial design-two levels of protein, each with and without phenolic glycosides. Additionally, we assayed high protein diets containing S,S,S-tributylphosphorotrithioate (DEF, an esterase inhibitor) and DEF plus phenolic glycosides. Enzyme solutions were prepared from midguts of sixth instars and assayed for β-glucosidase, esterase and glutathione transferase activities. First instar mortality and development times were higher for larvae on diets low in protein or containing phenolic glycosides. Effects of phenolic glycosides were especially pronounced at low protein levels and when administered with DEF. Fourth instar development times were prolonged, and growth rates reduced, in response to consumption of low protein diets. Effects of phenolic glycosides on growth were less pronounced, although the effect for larvae on the low protein diet was nearly significant. Activity of each of the enzyme systems was reduced in larvae reared on low protein diets, and esterase activity was induced in larvae fed phenolic glycosides. Our results suggest that larval performance may be strongly affected by levels of protein and phenolic glycosides commonly occurring in aspen foliage, and that these factors may play a role in differential defoliation of aspen by forest tent caterpillars.

The effects of food protein content on the performance of pigs previously given foods with low or moderate protein contents

Abstract: An experiment was conducted to study the ability of the pig to recover from the effects of a period on a food deficient in crude protein (CP). Forty young pigs were given free and continuous access to foods with either 150 (L) or 252 (M) g CP per kg in period 1 of the experiment, from 6·3 kg to 13·4 and 12·3 kg live weight respectively. These live weights were expected to give equal lipid-free empty body weights. In period 2, four males and four females from each of the period 1 treatments were given access to either M or a food with 377 g CP per kg (H) to a live weight of 30 kg, when the 32 pigs were killed.Pigs on L took 11 (s.e. 0·6) days longer to complete period 1, and had, at the end of this period, 0·20 (s.e. 0·03) kg less protein and 1·20 (s.e. 0·06) kg more lipid in their bodies than the M pigs, at a common ash weight. In period 2, pigs from L grew at a faster rate (750 v. 633 (s.e.d. 20) g/day), ate food at the same rate (1115 v. 1085 (s.e.d. 35) g/day) and converted food more efficiently (0·676 v. 0·585 (s.e.d. 0·016) g gain per g food) than those from M. At 30·3 kg live weight the pigs from L had corrected their protein deficit relative to ash and reduced their fatness, so that they had the same protein: ash ratio and only 0·47 (s.e. 0·12) kg more lipid in their bodies than those from M. This was the result of a higher rate of gain of protein and water, a lower rate of lipid gain and similar rate of ash gain by the pigs from L than those from M. In the first 7 days of period 2 the pigs from L gained weight at 1·4 times the rate of those from M. In the final 7 days there was no significant effect of period 1 treatment on growth rate. The pigs from L given food H in period 2 were more efficient than those given M in period 2 (food conversion efficiency (FCE) values of 0·884 and 0·791 respectively; s.e.d. 0·027), but this difference was reversed in the final 7 days (FCE values of 0·521 and 0·603 respectively). t I is concluded from these results that a period of eating a food of low protein content produces a reduced protein: ash and an increased lipid: ash ratio in the body and reduced growth rate and efficiency. When subsequently pigs are given a food of sufficiently high protein content, the protein: ash and lipid: ash ratios return to normal. The repletion of labile protein reserves, with their associated water, leads to a substantial increase in the rate of live-weight gain. The lower lipid content of the gain leads to a high efficiency. The duration of these effects depends on the protein content of the food given.

The effect of antibody protein dose on the uniformity of tumor distribution of radioantibodies: an autoradiographic study.

Abstract: The inaccessibility of radiolabeled antibody to poorly vascularized regions of solid tumors may reduce the therapeutic efficacy of these macromolecules. Theoretical mathematical models have predicted that increasing the protein dose administered would reduce the heterogeneity of radioantibody distribution. This investigation was undertaken to evaluate this hypothesis in experimental animal models. We have utilized the technique of macroautoradiography to demonstrate an increase in tumor penetration of the lower-affinity 125I-labeled NP-4 or higher-affinity Immu-14 anti-carcinoembryonic antigen (anti-CEA) mAbs into small (60.25-0.4 g) and large (0.8-1.5 g) GW-39 and LS174T human colonic xenografts, grown subcutaneously in the nude mouse, when 400 micrograms unlabeled antibody is administered simultaneously with 10 micrograms (100 microCi) radioantibody. Further increases in protein to 800 micrograms result in a reduction in total tumor uptake of the antibody. These in a reduction in total tumor uptake of the antibody. These differences in mAb distribution could be visualized as early as 1 day after antibody injection. Improved mAb penetration was also achieved for the Mu-9 anti-CSAp (anti-mucin) antibody using 800 micrograms unlabeled antibody. An irrelevant antibody (AFP-7-31) was found to be homogeneously distributed 3 days after injection, even at a low protein dose. Attempts to improve mAb penetration by increasing the protein dose in the GS-2 colorectal tumor, a model that has low NP-4 accretion as a result physiological barriers separating antibody from antigen, were not successful. These results suggest that a more homogeneous distribution of radioantibody can be achieved by carefully selecting a dose of unlabeled antibody to coadminister. Work is currently in progress to determine the effect of improved tumor distribution of radioantibody on the therapeutic potential of a single dose of radioantibody.

Protein Requirements of Costa's Hummingbirds Calypte costae

Abstract: Captive Costa's hummingbirds (Calypte costae) were fed liquid purified diets containing 0%, 0.75%, 1.5%, or 3.0% protein (dry-matter basis). The birds were weighed and excreta samples were collected at days 5 and 10 of 10-d experimental periods. Body-mass maintenance data revealed that the hummingbirds require about 4.5 mg N/d, or 1.5% protein in their diets. Nitrogen balance analysis suggested that these birds should be in balance when ingesting only 1.11 mg N/d (0.4% protein), but this level did not maintain body mass. Similar positive N balances without growth have been documented in other avian and mammalian species, but the fate of this unaccounted N has not been explained. The bodymass data indicated that adult, nonreproducing hummingbirds have a low protein requirement. These results are compared with published time-budget studies of free-living hummingbirds, which have shown that the birds spend most of their feeding time foraging for nectar to meet their high energy needs.

Limiting amino acids in low protein maize-soyabean meal diets fed to broiler chicks from 3 to 7 weeks of age.

Abstract: 1. An experiment with separately housed male and female broiler chicks was carried out during the period of 3 to 7 weeks of age to determine the limiting amino acids (AA) in a low protein maize-soyabean meal diet. Chicks were fed on diets containing 170, 180, 190 and 200 g crude protein (CP)/kg with or without combined additions of L-threonine (Thr), L-tryptophan (Trp) and L-arginine (Arg) to those in the 180, 190 or 200 g CP/kg diets and a 170 g CP/kg diet with or without combined additions of Thr, Trp, Arg, L-isoleucine (Ile), L-leucine (Leu) and L-valine (Val) to those in the 190 g CP/kg diet. The diets were iso-energetic and contained the same concentrations of lysine (Lys) and sulphur-containing amino acids. 2. Decreasing the dietary CP had a significantly negative effect on performance. 3. No significant effects on performance were found when diets with 180 and 190 g CP/kg were supplemented with Thr, Trp and Arg to those in the 200 g CP/kg diet. 4. There were no significant differences in performance between the groups fed on the diets with 170, 180 and 190 g CP/kg when the 170 and 180 g CP/kg diets were supplemented with Thr, Trp and Arg to those in the 190 g CP/kg diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical transformation of wheat straw constituents after solid-state fermentation with selected lignocellulose-degrading fungi

Abstract: The changes in the composition of major straw constituents were studied after solid-state fermentation with ligninolytic and cellulolytic fungi in order to evaluate fungal treatments for biological upgrading of wheat straw. Species of Pleurotus and Trametes increased in vitro digestibility (attaining 60–70% of the straw dry wt) and the polysaccharide hexose/pentose ratio. Trametes versicolor caused large simultaneous degradation, but preferential removal of lignin was achieved with the Pleurotus species. The low protein content and the straw deficiency in certain amino acids was compensated by solid-state fermentation ( T. versicolor increased x 10 lysine content). Fungal alteration of lignin after the straw treatment with ligninolytic species was evidenced by non-destructive techniques and CuO alkaline degradation, the latter showing a decrease in the syringyl/guaiacyl ratio and in the cinnamic acid content.

Increased insulin action in the rat after protein malnutrition early in life.

Abstract: The effect of a limited period of low protein feeding in young rats on insulin secretion and insulin action during adult-age has been studied Four-week-old rats were maintained for 4 weeks on isocaloric diets containing 5% protein (low protein) or 15% protein (control) The low protein rats gained weight at a considerably lower rate than the control rats This was obtained in the absence of any decrease of spontaneous food intake Basal plasma insulin levels were decreased (p<001) by 40% in low protein rats However, the glucose-stimulated insulin secretion obtained in vivo after an iv glucose load remained normal The basal plasma glucose level in the low protein rats was only marginally decreased (by 20%) The tolerance to iv glucose was found to be slightly enhanced in the low protein rats as compared to the control rats as shown by a significantly increased K value (p}<001) In vivo insulin action in the low protein rats was investigated using the euglycaemic-hyperinsulinaemic clamp technique in conjunction with isotopic measurements of glucose turnover The overall glucose utilization rate was normal in the basal state but significantly increased (p<005) when measured at a submaximal plasma insulin level The basal hepatic glucose production in the low protein rats was similar to that in the control rats During the clamp studies, the suppression of endogenous glucose production was found to be similar in the low protein rats and the control rats but this was obtained at significantly lower (p<001) steady-state insulin levels in the low protein group than in the control group In conclusion, the current results indicate that the modest improvement of glucose tolerance which is revealed in the low protein rats results from changes in the insulin action upon the target tissues: both the insulin-mediated glucose uptake by peripheral tissues and the ability of insulin to suppress hepatic glucose output are enhanced

A sensitive enzyme immunoassay for the quantitation of human C5a/C5a(desArg) anaphylatoxin using a monoclonal antibody with specificity for a neoepitope.

Abstract: The direct quantitation of C5a/C5a(desArg) in human plasma was achieved by a specific and highly sensitive ELISA which is based on the neoepitope-specific monoclonal antibody C17/5. The error-prone removal of C5 from plasma prior to the assay is therefore not required. With a detection limit of 20 pg C5a/ml plasma, the sensitivity of this assay allowed to define normal ranges (1.94 +/- 1.49 ng C5a/nl, mean +/- SD) of C5a/C5a(desArg) in human blood plasma. This assay will also be applicable to the quantitation of C5a in specimens with low protein content where precipitation-based assays fail to accurately determine C5a. In addition, the mAb C17/5 turned out to efficiently block the binding of C5a/C5a (desArg) to its cellular receptor and therefore provides a valuable tool in the delineation of C5a effects in complex biologic systems in the presence of native C5, such as under in vivo conditions.

Mean-field and Monte Carlo simulation studies of the lateral distribution of proteins in membranes.

Abstract: Monte Carlo simulations and mean-field calculations have been applied to a statistical mechanical lattice model of lipid-protein interactions in membranes in order to investigate the phase equilibria as well as the state of aggregation of small integral membrane proteins in dipalmitoyl phosphatidylcholine bilayers. The model, which provides a detailed description of the pure lipid bilayer phase transition, incorporates hydrophobic matching between the lipid and protein hydrophobic thicknesses as a major contribution to the lipid-protein interactions. The model is analyzed in the regime of low protein concentration. It is found that a large mismatch between the lipid and protein hydrophobic thicknesses does not guarantee protein aggregation even though it strongly affects the phase behaviour. This result is consistent with experimental work (Lewis and Engelman 1983) considering the effect of lipid acyl-chain length on the planar organization of bacteriorhodopsin in fluid phospholipid bilayers. The model calculations predict that the lipid-mediated formation of protein aggregates in the membrane plane is mainly controlled by the strength of the direct lipid-protein hydrophobic attractive interaction but that direct protein-protein interactions are needed to induce substantial aggregation.

Quantifying hepatic function in the presence of liver disease with phenazone (antipyrine) and its metabolites.

Abstract: The disposition of phenazone (antipyrine), a low extraction compound with low protein binding, is known to be altered in the presence of various types of hepatic dysfunction. As such, its pharmacokinetics may be useful in the objective characterisation of altered liver function. Understanding the known effects of various liver disease states upon the disposition of this probe may provide insight into future applications. This article provides a review of background information about normal plasma phenazone pharmacokinetics, urinary metabolite disposition and tabulations of reported total body clearances of the drug in the presence of cirrhosis, fatty liver, hepatitis and cholestasis in humans. An estimate is made of the sensitivity and specificity of phenazone testing for the verification of the presence of cirrhosis based on this compiled literature.

The influence of protein containing meals on the pharmacokinetics of levodopa in healthy volunteers.

Abstract: 1 The pharmacokinetics of levodopa and paracetamol after single oral doses have been investigated in eight healthy young volunteers in the fasted state and following isocaloric meals containing either 105 g or 305 g of protein 2 The initial peak and maximum plasma drug concentrations and the times at which these occurred were not affected by food 3 The mean area under the plasma concentration-time curve (AUC) for paracetamol following an overnight fast did not differ significantly from that observed following the low and high protein meals 4 By contrast, the AUC for levodopa following the low protein meal (1939 +/- 157 micrograms ml-1 min) was significantly lower compared with administration in the fasted state (2165 +/- 261 micrograms ml-1 min) However, there were no significant differences in the kinetics of levodopa between the fasting state and following the high protein meal 5 There was no evidence that consumption of a meal containing 305 g of protein impaired either the rate or extent of absorption of levodopa Therefore the reported beneficial effects of a low protein diet in the treatment of patients with Parkinson's disease probably result from reduced competition for levodopa transport across the blood-brain barrier