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Influence of dietary protein on motor fluctuations in Parkinson's disease.

On a nearly zero protein diet, 11 patients with Parkinson's disease with the "on-off" effect demonstrated great sensitivity to levodopa (L-dopa)-carbidopa and reduced fluctuations. Eight patients required a 41% reduction in total L-dopa dosage and discontinuation of all adjuvant therapy to reduce the preponderance of chorea. On a high-protein diet, all patients were immobilized by bradykinesia for most of the day. A low-protein dietary regimen during the daytime offers an important technique for the control of fluctuations in patients with Parkinson's disease who are receiving L-dopa-carbidopa.

Aged↗

Adequate protein dietary restriction in diabetic and nondiabetic patients with chronic renal failure.

OBJECTIVE: To evaluate whether a dietary protein restriction is useful for slowing the progression of chronic renal failure (CRF) in diabetic and nondiabetic patients and to analyze the possible risk of malnutrition after such a dietary regimen. DESIGN: Prospective, randomized case-control clinical trial. SETTING: Nephrology outpatients. PATIENTS AND OTHER PARTICIPANTS: A total of 169 patients, 89 affected with CRF and chronic hypertension and 80 affected with overt diabetic nephropathy (24 suffering from type 1 and 56 from type 2 diabetes) and chronic hypertension. INTERVENTION: Diabetic patients and nondiabetic patients were randomly divided into 2 groups: 40 diabetic patients received a low-protein diet (0.8 g/kg/day) and 40 were maintained on a free protein diet; similarly, 44 nondiabetic patients received a low-protein diet (0.6 g/kg/day) and 45 were maintained on a free protein diet. The investigation lasted 1 year. MAIN OUTCOME MEASURE: Renal function and nutritional status. RESULTS: At the end of the study, there were no statistically significant differences in renal function between treated and nontreated diabetic patients, whereas treated nondiabetic patients showed a lower decrease in renal function compared with the nontreated group. In both diabetic and nondiabetic patients, the mean body weight and obesity index decreased significantly in treated patients compared with nontreated ones. Serum albumin and prealbumin were stable in all patients during the whole study time, and there were no other signs of malnutrition. CONCLUSION: An adequate dietary protein restriction is accepted by patients, and it is well tolerated during a 12-month follow-up. Without any sign of malnutrition, it is possible to get near the ideal body weight and to reduce the obesity index and the body mass index, which are both well-established risk factors for developing cardiovascular pathology. In nondiabetic patients only, we observed a significant slowing of the progression of renal damage.

Adult↗

Evidence that pretranslational and translational defects decrease serum insulin-like growth factor-I concentrations during dietary protein restriction.

Dietary protein restriction causes GH resistance and decreases serum insulin-like growth factor-I (IGF-I) concentrations. To determine whether pretranslational or translational defects are involved in the decline of serum IGF-I concentrations during protein restriction, we measured hepatic IGF-I mRNA abundance together with the serum IGF-I peptide response to exogenous GH after 1 week of protein restriction (5% casein in diet; P5) in hypophysectomized rats. We compared these responses with those of hypophysectomized rats fed a protein-sufficient diet (15% casein in diet; P15) and given exogenous GH. A single injection of rat GH (200 micrograms/100 g BW) produced a comparable IGF-I mRNA increment in both groups (at 6 h, 7.8 +/- 1.1 arbitrary units in P5 vs. 8.2 +/- 1.1 in P15), but failed to raise serum IGF-I normally in the P5 group (at 6 h, 90 +/- 15 ng/ml in P5 vs. 216 +/- 63 in P15; P less than 0.01). The post-GH decline of the 7.5-kilobase (kb) IGF-I mRNA abundance was faster in P5 than in P15 animals. In another experiment in intact rats subjected to protein restriction, injections of pharmacological doses of rat GH (400 micrograms/100 g BW.day) for 1 week restored liver IGF-I mRNA abundance to normal without normalization of serum IGF-I (403 +/- 91 vs. 713 +/- 53 ng/ml; P less than 0.01). Our data suggest that 1) the machinery involved in the transcription of the liver IGF-I gene is intact in protein-restricted rats, because these animals retain the ability to muster normal IGF-I mRNA responses to high doses of exogenous GH; 2) the stability of the 7.5-kb IGF-I mRNA is probably decreased by the protein restriction, as suggested by the faster decline of the 7.5-kb transcript in P5 than in P15 hypophysectomized rats; and 3) the discrepancy between normal liver IGF-I mRNA abundance and low serum and liver IGF-I peptide concentrations suggests that translational stalling of the IGF-I mRNAs or increased serum IGF-I clearance is involved in the low serum IGF-I concentrations during dietary protein restriction.

Animals↗

Variations in dietary protein but not in dietary fat plus cellulose or carbohydrate levels affect cysteine metabolism in rat isolated hepatocytes.

To determine if previously observed effects of dietary protein on hepatic cysteine metabolism were due specifically to increases in dietary protein or to the accompanying decreases in dietary carbohydrate, two experiments were conducted. In one experiment, rats were fed diets that contained different levels of protein vs. an isocaloric mixture of fat + cellulose and a constant amount of carbohydrate. In the other, rats were fed diets that contained a constant amount of protein but different levels of carbohydrate vs. an isocaloric mixture of fat+cellulose. Diets were fed for 2-3 wk and hepatocytes were then isolated. Hepatic cysteine dioxygenase activity increased and cysteinesulfinate decarboxylase and gamma-glutamylcysteine synthetase activities decreased in a stepwise manner when protein was added to the diet at the expense of fat + cellulose. Changes in cysteine dioxygenase, cysteinesulfinate decarboxylase and gamma-glutamylcysteine synthetase activities were consistent with changes in rates of cysteine catabolism, taurine production and glutathione synthesis, respectively, by intact hepatocytes incubated with 0.2 mmol/L cysteine. When the carbohydrate to fat+ cellulose ratio was varied, but the protein level was held constant, little or no change in enzyme activities or levels of metabolite production was observed. Regulation of the activities of enzymes involved in cysteine metabolism is predominantly due to changes in dietary protein intake and not to the associated changes in intake of other dietary macronutrients.

Adenosine Triphosphate↗

Further investigation of the dietary protein level-monensin interrelationship in broiler chicks: influence of dietary protein source and type of anticoccidial drug.

Three experiments were conducted to evaluate the influence of dietary protein source on the monensin response in healthy chicks fed diets varying in CP. The interrelationship between dietary CP level and four different anticoccidial drugs was evaluated in a fourth experiment. The experiments were conducted from 8 to 21 or 22 days posthatching. In Experiment 1, crossbred chicks were fed corn-soybean meal (SBM) diets containing either 24 or 16% CP or casein-dextrose diets containing 20, 15, or 10% CP in the presence or absence of 160 mg/kg monensin. When CP level was decreased in the corn-SBM treatments, the resulting monensin-induced growth depression was greater. However, this interaction was not observed in chicks fed casein-dextrose diets. Experiments 2 and 3 were conducted to determine if the monensin-protein level interrelationship is influenced by the source of dietary soybean protein or by high levels of animal protein (AP). Monensin at 140 mg/kg produced a much greater growth depression at 16 than at 24% CP in chicks fed a corn-SBM diet, whereas amounts of monensin depression in chicks fed a corn-isolated soy protein diet were similar for both CP levels. As dietary protein was reduced from 24 to 16% in Experiment 3, 140 mg/kg monensin caused growth depressions of 10 and 40%, and 14 and 28%, respectively, in broiler chicks fed corn-SBM and corn-AP diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Vasodilation to vascular endothelial growth factor in the uterine artery of the pregnant rat is blunted by low dietary protein intake.

Pregnancy is associated with a substantial increase in uterine artery blood flow, which may in part result from dilation in response to vascular endothelial growth factor (VEGF). Uterine blood flow is reported to be reduced in globally diet-restricted pregnant rats. Both global and protein dietary restriction in pregnancy produce programmed effects in offspring. In this study we hypothesized that protein restriction in pregnancy impairs maternal uterine artery responses to VEGF. Vascular responses to VEGF were determined in isolated uterine arteries of pregnant (18 or 19 d of gestation) Wistar rats fed a diet containing either 18% or 9% casein throughout pregnancy. For comparison, responses to phenylephrine, potassium chloride, and acetylcholine were determined. In addition, the response of the mesenteric artery to VEGF was studied in the same animals. A significant reduction of the maximal relaxation to VEGF (p = 0.041) and in the overall response (p = 0.004) to VEGF was found in uterine arteries of the 9% compared with the 18% group, but responses to all other agonists were similar. The VEGF response was reduced by cyclooxygenase inhibition (indomethacin) in both groups. In the 18%, but not the 9%, group it was further reduced by nitric oxide synthase inhibition (Nomega-nitro-L-arginine methyl ester). VEGF was shown to dilate the mesenteric artery but this effect was not significantly altered by the low-protein diet. These results show an attenuated uterine artery vasodilator response to VEGF produced by a low-protein diet in pregnancy, partly because of a reduction of the nitric oxide component of VEGF-mediated relaxation.

Acetylcholine↗

Dietary protein enterocolitis.

Dietary protein enterocolitis generally presents in the 1st year of life with diarrhea, emesis, and irritability. When there is a delay in diagnosis, persistent exposure to the offending dietary antigen leads to increasing enteric inflammation manifesting as bloody diarrhea, anemia, dehydration, and failure to sustain normal patterns of weight gain and growth. The extent of enteric inflammation may be limited to mild proctitis, pancolitis, or true enterocolitis with esophagitis, gastritis, enteropathy, and colitis. The offending antigen is usually cow's milk protein or soy protein. A significant number of the infants are exclusively breast fed, especially those with proctitis. In older children, a wide variety of dietary proteins have been implicated. The inconsistency between allergists and gastroenterologists in the clinical definition of the syndrome remains a significant problem. To the allergist, the definition is based on clinical criteria, allergy testing, and response to double-blind food challenge, whereas to the gastroenterologist, it is defined by histologic criteria and the response of clinical and histologic manifestations to elimination diets. To further complicate the issue, European studies have emphasized the alterations in enteric permeability noted in both enteropathy and enterocolitis. In an effort to establish a unified approach, the International Life Sciences Institute sponsored a workshop in late 1998, which resulted in a document entitled "Classification of Gastrointestinal Disease of Infants and Children Due to Adverse Immunologic Reactions."

Child Welfare↗

Protein supply from undegraded dietary protein.

A summary of in vivo estimates of the amount of dietary protein from individual feedstuffs that escapes microbial degradation in the rumen is presented. Values range from approximately 20% for protein in barley, oats, wheat, and alfalfa silage to 65 to 70% for protein in fish meal and animal by-products. In vitro or in situ methods for estimating protein degradation can be used, but at this stage of development, the methodology is more useful in providing a relative ranking of feedstuffs on the basis of protein degradation than in providing absolute estimates of protein degradation. A number of factors influence protein breakdown in the rumen, including extent of crosslinking in the protein (disulfide bonds), retention time in the rumen, protein solubility, and processing and storage effects on protein. It is important to consider the amino acid content of the undegraded dietary protein, particularly lysine and methionine, two amino acids likely to be limiting for milk production. Strategies for using protected proteins in dairy cattle diets are discussed.

Animals↗

Net protein oxidation is adapted to dietary protein intake in domestic cats (Felis silvestris catus).

Cats have a requirement for dietary protein two to three times that of omnivores and herbivores. This was reported to be due to the hepatic catabolic enzymes of this species being set to a permanently high level and, therefore, showing little adaptation to low dietary protein. A major mechanism for adapting to dietary protein in other species is amino acid oxidation (hereafter referred to as protein oxidation), and the objective of this study was to determine whether protein oxidation in cats was correlated with protein intake. Net protein and net fat oxidation in six adult cats were studied directly from gas exchanges using indirect calorimetry, after feeding moderate protein (MP; 35% energy) and high protein (HP; 52% energy) diets. Protein oxidation was significantly higher (P < 0.05) when cats were fed the HP diet (28.4 plus minus 0.7 mg/min) rather than the MP diet (20.4 plus minus 0.8 mg/min). Fat oxidation was significantly higher (P < 0.05) when cats consumed the MP diet (9.0 plus minus 0.7 mg/min) rather than the HP diet (4.7 plus minus 0.5 mg/min). Protein oxidation was significantly correlated (linear regression, R(2) = 46.0, P < 0.05) with protein intake such that the mean ratio of 18-h oxidation: 18-h intake was 1.2 on both diets. Fat oxidation was significantly correlated (linear regression, R(2) = 18.9, P < 0.05) with fat intake such that the mean ratio of 18-h fat oxidation: 18-h fat intake was 1.1 (MP) and 0.9 (HP). This study demonstrated that cats adapt net protein oxidation at these levels of protein intake, and the reason for the high dietary protein requirement of this species is, therefore, unclear.

Animal Nutritional Physiological Phenomena↗

Two dimensional non equilibrium pH gel electrophoresis mapping of cytosolic protein changes caused by dietary protein depletion in mouse liver.

Two-dimensional non-equilibrium pH gel electrophoresis (2D-NEPHGE) analysis was used to evaluate the effects of dietary protein depletion on the protein composition of mouse liver cytosol. Analysing the cytosol from both normal and protein depleted liver, the position in gels of more than three hundred protein spots was determined. After 5 days of protein depletion, about 20% of the spots either increased or decreased more than 2 fold. Five spots of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were recognised by specific antibodies. The glutathione S-transferase (GSTs) subunits Ybl, Yc and Yf were identified by the simultaneous analysis of both glutathione-binding cytosolic proteins and the corresponding standards. As estimated by internal optical density (IOD) of spots, the changes caused by protein depletion in GAPDH and GST subunit contents were similar to those obtained by other methods. By means of mass spectrometric analysis of tryptic peptides generated from spots and/or comparison of two-dimensional gel electrophoretic patterns, carbonic anhydrase III (CAIII), Cu, Zn superoxide dismutase (CuZnSOD) and a cytochrome P450 cytosolic protein (cyt P450) were identified. These three proteins, as well as GSTs, are related with intracellular detoxification and free radical scavenging systems. Their contents were regulated by dietary protein restriction in a manner indicative of diminished liver defence against oxidising agents.

Animals↗

Effects of level of feeding and ruminally undegraded protein on ruminal bacterial protein synthesis, escape of dietary protein, intestinal amino acid profile, and performance of dairy cows.

Six cannulated lactating cows were used in two replicated, concurrently run 3 x 3 Latin square experiment to study the interaction between level of feeding and diets differing in ruminally undegraded protein (RUP) on bacterial protein synthesis, ruminal escape of dietary protein, and flow of total and individual amino acids (AA) to the small intestine. Treatments consisted of three diets formulated to contain 69 g (HL), 53 g (HH), and 48 g (LL) of RUP per kilogram of DM, respectively. Measurements were made in early lactation, at high feeding level (19.3 kg DM/d), and repeated at late lactation (9.8 kg DM/d, low feeding level) with the same animals and diets. Decreasing feed intake increased (P < .05) the apparent digestibility of OM, NDF, and ADF in the rumen and the total tract, decreased (P < .05) ruminal liquid and particulate passage rate and total ruminal VFA concentration, and increased ruminal pH and ammonia concentration. Decreased level of intake reduced the (P < .05) efficiency of bacterial N synthesis (28.1 vs 23.7 g bacterial N/kg OM truly digested in the rumen) and decreased (P < .05) ruminal protein degradation rate measured with an in situ method. Duodenal flow of nonammonia nitrogen (NAN), and total AA were highest (P < .05) for the HL diet and lowest (P < .05) for the LL diet at the high feeding level. However, at the low feeding level, diet composition did not affect the amount of NAN or total AA passing to the small intestine. Diet HL increased the proportion of Met, His (P < .05), and Arg (P < .07) in the duodenal digesta at both feeding levels. When purines were used to calculate bacterial N synthesis, no differences between diets were detected. However, when diaminopimelic acid was used, highest bacterial N synthesis was detected for diet HH at the high feeding level. Diet HL supported the highest (P < .05) milk protein production at the high feeding level, and the highest (P < .05) milk protein content at the low feeding level. In conclusion, level of feeding and amount of RUP altered the amount and composition of AA presented to the cows.

Amino Acids↗

Response of storage protein levels to variation in dietary protein levels.

Storage proteins have been found to play a major role in insect metamorphosis and egg production and are accumulated during the actively feeding larval stage. Yet few studies have focused on how nutrition affects storage protein levels. Three storage proteins were identified in male and female Heliothis virescens pupae, one arylphorin and two putative high-methionine hexamers. Storage proteins were quantified in early pupae and in pharate adults. Storage protein levels peaked in 48-h pupae and were more abundant in females across all stages. Both male and female pharate adults retained a portion of total storage protein levels and females retained greater levels overall. In females, post-eclosion protein reserves will likely be used toward egg manufacturing, while the role of protein reserves in males remains speculative. In our previous study of H. virescens larvae, we found that protein-derived growth in females progressively increased as dietary protein levels increased. Our present data show that levels of storage protein also increased progressively along with dietary protein levels. This suggests that females allocated protein, in excess of adult tissue formation needs, toward storage protein. Our study is the first to demonstrate how responsive storage protein levels can be in face of varying levels of dietary protein.

Journal Article↗

The role of glucagon in regulating chicken hepatic malic enzyme and histidase messenger ribonucleic acid expression in response to an increase in dietary protein intake.

Increased dietary protein intake rapidly (3 h) decreases hepatic malic enzyme and increases hepatic histidase mRNA expression in broiler chicks. A series of experiments was conducted to determine the role that glucagon or a specific mixture of dietary amino acids might have in regulating the rapid changes in mRNA expression of these enzymes, when dietary protein intake is increased. Three hours after the injection of glucagon (240 microg/kg of BW) into the brachial vein of broiler chicks, hepatic malic enzyme mRNA expression was significantly lower and hepatic histidase mRNA expression was significantly greater than the level detected in saline-injected chicks. In addition, broiler chicks fed a high (40 g/ 100 g of diet) protein diet had significantly higher plasma glucagon levels at 1 and 3 h after initial access to this diet than broiler chicks fed a basal (22 g/100 g of diet) protein diet. The plasma glucagon concentration, however, was not different between the chicks fed the 2 dietary protein levels at 2 h after the initial access to the 2 diets. When a mixture of indispensable or dispensable amino acids was added to the basal diet to equal the concentrations of the individual indispensable or dispensable amino acids in the high protein diet, hepatic mRNA expression of malic enzyme and histidase were intermediate to the expression found in chicks fed the basal and high protein diet. The results indicate that glucagon may mediate the changes in the mRNA expression of malic enzyme and histidase in response to dietary protein intake and that total amino acid intake rather than the ingestion of specific amino acids regulates the mRNA expression of malic enzyme and histidase in chicks.

Animals↗

Higher KT/V urea associated with greater protein catabolic rate and dietary protein intake in children treated with CCPD compared to CAPD. Mid-European Pediatric CPD Study Group (MPCS).

Being more suitable to children's lifestyle habits, continuous cycling peritoneal dialysis (CCPD) is becoming the treatment modality of first choice in the pediatric CPD population. In order to establish whether these regimens, prescribed on an empirical basis, provide an equally effective dialysis as does standard continuous ambulatory peritoneal dialysis (CAPD), we performed a cross-sectional analysis of dialysate and residual renal small molecule clearances in 85 children aged 3 months to 20 years, who were treated in 16 pediatric dialysis centers. Forty-three children were on CAPD and 42 were on CCPD. The two patient groups did not differ in age, body size, duration of dialysis, underlying disease distribution, or residual renal function. The CAPD patients achieved an average daily drain volume of 159 +/- 40 mL/kg body weight, as compared to 208 +/- 95 mL/kg in the CCPD group (p < 0.005). Average serum creatinine and BUN values were similar in both groups. While the (total) creatinine clearance did not differ, the KT/V urea was significantly higher in the patients treated with CCPD (0.35 +/- 0.12 vs 0.28 +/- 0.13, p < 0.05). The estimated protein catabolic rate (PCR) was significantly higher in the CCPD group (1.39 +/- 0.6 g/kg d) than in the CAPD patients (1.08 +/- 0.48 g/kg d, p < 0.05). Three-day dietary histories, available in 20 patients, showed a similar difference in dietary protein intake between CCPD and CAPD patients. We conclude that CCPD treatment regimens, at the dose currently prescribed in Mid-European pediatric dialysis centers, provide a higher clearance of urea and, possibly, other small molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Gene expression of cellular retinol-binding protein I (CRBP I) is affected by dietary proteins in the rat liver.

The effect of dietary proteins and vitamin A status on the gene expression of cellular retinol-binding protein I (CRBP I) was studied in the rat liver. The gene expression was estimated as amounts of transcript (mRNA) by Northern blot analysis using rat CRBP I cDNA. Though vitamin A status is known to positively regulate the gene expression of CRBP I in the extrahepatic tissues, in the present study we observed that the amount of the CRBP I transcript in liver was neither reduced by vitamin A-deficiency, nor affected by replenishment with an excess dose of all-trans retinoic acid. These results indicate that in the liver, different from the extrahepatic tissues, the gene expression of CRBP I may not be controlled by vitamin A. However, when the rats were fed on the diets that differed in dietary proteins, the gene expression of CRBP I in liver was enhanced by higher quality and quantity of dietary proteins, though no effect of dietary proteins was observed upon the hepatic contents of retinol. The concentrations of serum retinol were almost proportional to the mRNA levels of CRBP I. In contrast, the hepatic gene expression of another retinol-binding protein, RBP, and one subtype of retinoic acid receptor, RAR alpha was not influenced in the nutritional condition tested here. Our findings suggest that the gene expression of CRBP I in liver may be under control of the intake of dietary proteins. Thus, it is likely that in the light of the function of CRBP I on cellular transport and metabolism of retinol, dietary proteins may affect the actions of vitamin A in the extrahepatic tissues through changing the amounts of CRBP I in liver.

Animals↗

Body protein and energy accretion in response to dietary protein level in mice from weaning to maturity.

The accumulation of body protein and body energy in mice from weaning to maturity as a response to dietary protein level was studied. Seven groups of ddY male mice were fed for 75 d purified diets with a range of 15-70% protein concentration, calculated on a gross energy basis. The food intake and body weight data were analyzed by nonlinear regression to Parks' feeding and growth equation, and data of body protein (%) and body energy (kcal/g) were analyzed using stepwise multiple regression. Body protein (approximately 17%) was independent of both dietary protein level and age. Body energy, as a function of time after weaning, increased to a plateau at about 30 d after weaning. At every dietary protein level the accumulation of body protein and energy increased with age asymptotically to a plateau at approximately 40 d and approximately 30 d after weaning, respectively. At every dietary protein level, the protein accretion rose rapidly with age to attain a maximum at about 7 d after weaning, when it depended on the dietary protein level, then decreased markedly to where differences due to dietary protein level became negligible. It is clearly shown in this study that manipulation of dietary protein level has a greater effect on protein growth and energy gain during the pre-peak part of the body protein accretion and body energy accretion curves than during other portions of those curves.

Aging↗