Severe protein deficiency induces hepatic expression and systemic level of FGF21 but inhibits its hypothalamic expression in growing rats.

To study, in young growing rats, the consequences of different levels of dietary protein deficiency on food intake, body weight, body composition, and energy balance and to assess the role of FGF21 in the adaptation to a low protein diet. Thirty-six weanling rats were fed diets containing 3%, 5%, 8%, 12%, 15% and 20% protein for three weeks. Body weight, food intake, energy expenditure and metabolic parameters were followed throughout this period. The very low-protein diets (3% and 5%) induced a large decrease in body weight gain and an increase in energy intake relative to body mass. No gain in fat mass was observed because energy expenditure increased in proportion to energy intake. As expected, Fgf21 expression in the liver and plasma FGF21 increased with low-protein diets, but Fgf21 expression in the hypothalamus decreased. Under low protein diets (3% and 5%), the increase in liver Fgf21 and the decrease of Fgf21 in the hypothalamus induced an increase in energy expenditure and the decrease in the satiety signal responsible for hyperphagia. Our results highlight that when dietary protein decreases below 8%, the liver detects the low protein diet and responds by activating synthesis and secretion of FGF21 in order to activate an endocrine signal that induces metabolic adaptation. The hypothalamus, in comparison, responds to protein deficiency when dietary protein decreases below 5%.

Very low-density lipoprotein receptor increases in a liver-specific manner due to protein deficiency but does not affect fatty liver in mice.

Very low-density lipoprotein receptor (VLDLR) is a member of the LDL receptor family that is involved in the uptake of VLDL into cells. Increased hepatic VLDLR under endoplasmic reticulum (ER) stress has been shown to cause fatty liver. In this study, the effect of dietary protein restriction on hepatic VLDLR and the role of VLDLR in fatty liver were investigated using Vldlr knockout (KO) mice. Growing wild-type (WT) and KO mice were fed a control diet containing 20% ​​protein or a low protein diet containing 3% protein for 11 days. In WT mice, the amount of hepatic Vldlr mRNA and VLDLR protein increased by approximately 8- and 7-fold, respectively, due to protein restriction. Vldlr mRNA and protein levels increased in both type 1 and type 2 VLDLR. However, neither Vldlr mRNA nor protein levels were significantly increased in heart, muscle, and adipose tissue, demonstrating that VLDLR increase due to protein restriction occurred in a liver-specific manner. Increased liver triglyceride levels during protein restriction occurred in KO mice to the same extent as in WT mice, indicating that increased VLDLR during protein restriction was not the main cause of fatty liver, which was different from the case of ER stress.

Circulating fatty acid profiles are associated with protein energy wasting in maintenance hemodialysis patients: a cross-sectional study.

The metabolic impact of circulating fatty acids (FAs) in patients requiring hemodialysis (HD) is unknown. We investigated the associations between plasma triglyceride (TG) FAs and markers of inflammation, insulin resistance, nutritional status and body composition. Plasma TG-FAs were measured using gas chromatography in 341 patients on HD (age = 55.2 ± 14.0 years and 54.3% males). Cross-sectional associations of TG-FAs with 13 markers were examined using multivariate linear regression adjusted for potential confounders. Higher levels of TG saturated fatty acids were associated with greater body mass index (BMI, r = 0.230), waist circumference (r = 0.203), triceps skinfold (r = 0.197), fat tissue index (r = 0.150), serum insulin (r = 0.280), and homeostatic model assessment of insulin resistance (r = 0.276), but lower malnutrition inflammation score (MIS, r = - 0.160). Greater TG monounsaturated fatty acid levels were associated with lower lean tissue index (r = - 0.197) and serum albumin (r = - 0.188), but higher MIS (r = 0.176). Higher levels of TG n-3 polyunsaturated fatty acids (PUFAs) were associated with lower MIS (r = - 0.168) and interleukin-6 concentrations (r = - 0.115). Higher levels of TG n-6 PUFAs were associated with lower BMI (r = - 0.149) but greater serum albumin (r = 0.112). In conclusion, TG monounsaturated fatty acids were associated with poor nutritional status, while TG n-3 PUFAs were associated with good nutritional status. On the other hand, TG saturated fatty acids and TG n-6 PUFAs had both favorable and unfavorable associations with nutritional parameters.

1H NMR metabolomic and transcriptomic analyses reveal urinary metabolites as biomarker candidates in response to protein undernutrition in adult rats.

Protein undernutrition contributes to the development of various diseases in broad generations. Urinary metabolites may serve as non-invasive biomarkers of protein undernutrition; however, this requires further investigation. We aimed to identify novel urinary metabolites as biomarker candidates responsive to protein undernutrition. Adult rats were fed control (CT; 14 % casein) or isoenergetic low-protein (LP; 5 % casein) diets for 4 weeks. 1H NMR metabolomics was applied to urine, plasma and liver samples to identify metabolites responsive to protein undernutrition. Liver samples were subjected to mRNA microarray and quantitative PCR analyses to elucidate the mechanisms causing fluctuations in identified metabolites. Urinary taurine levels were significantly lower in the LP group than in the CT group at week 1 and remained constant until week 4. Hepatic taurine level and gene expression level of cysteine dioxygenase type 1 were also significantly lower in the LP group than in the CT group. Urinary trimethylamine N-oxide (TMAO) levels were significantly higher in the LP group than in the CT group at week 2 and remained constant until week 4. Hepatic TMAO level and gene expression levels of flavin-containing mono-oxygenase 1 and 5 were also significantly higher in the LP group than in the CT group. In conclusion, urinary taurine and TMAO levels substantially responded to protein undernutrition. Furthermore, changes in hepatic levels of these metabolites and gene expressions associated with their metabolic pathways were also reflected in their fluctuating urinary levels. Thus, taurine and TMAO could act as non-invasive urinary biomarker candidates to detect protein undernutrition.

Impairment of G-CSF receptor on granulocytic progenitor cells causes neutropenia in protein malnutrition.

OBJECTIVE: It is well known that protein malnutrition (PM) states can affect hematopoiesis, leading to severe leukopenia and reduced number of granulocytes, which act as the first line of defense, and are important to the innate immune response. The aim of this study was to elucidate some of the mechanisms involved in the impairment of granulopoiesis in PM. METHODS: Male C57BL/6 mice were submitted to PM with a low-protein diet containing 2% protein. Control mice were fed a 12% protein-containing diet. Bone marrow histology and the percentage of granulocytic progenitors were evaluated after in vivo granulocyte-colony stimulating factor (G-CSF) stimulus. Cell proliferation, STAT3 signaling, and the expression of G-CSF receptor were evaluated in hematopoietic progenitor cells. RESULTS: Malnourished animals presented with leukopenia associated with reduced number of granulocytes and reduced percentage of granulocytic progenitors; however, no differences were observed in the regulatory granulopoietic cytokine G-CSF. Additionally, the malnourished group presented with impaired response to in vivo G-CSF stimulus compared with control animals. PM was implicated in decreased ability of c-Kit+ cells to differentiate into myeloid progenitor cells and downregulated STAT3 signaling. Furthermore, the malnourished group exhibited reduced expression of G-CSF receptor on granule-monocytic progenitors. This reduced expression was not completely reversible with G-CSF treatment. CONCLUSIONS: This study implies that PM promotes intrinsic alterations to hematopoietic precursors, which result in hematologic changes, mainly neutropenia, observed in peripheral blood in PM states.

Plasma Transthyretin as A Biomarker of Sarcopenia in Elderly Subjects.

Skeletal muscle (SM) mass, the chief component of the structural compartment belonging to lean body mass (LBM), undergoes sarcopenia with increasing age. Decreased SM in elderly persons is a naturally occurring process that may be accelerated by acute or chronic nutritional deficiencies and/or inflammatory disorders, declining processes associated with harmful complications. A recently published position paper by European experts has provided an overall survey on the definition and diagnosis of sarcopenia in elderly persons. The present review describes the additional contributory role played by the noninvasive transthyretin (TTR) micromethod. The body mass index (BMI) formula is currently used in clinical studies as a criterion of good health to detect, prevent, and follow up on the downward trend of muscle mass. The recent upsurge of sarcopenic obesity with its multiple subclasses has led to a confused stratification of SM and fat stores, prompting workers to eliminate BMI from screening programs. As a result, investigators are now focusing on indices of protein status that participate in SM growth, maturation, and catabolism that might serve to identify sarcopenia trajectories. Plasma TTR is clearly superior to all other hepatic biomarkers, showing the same evolutionary patterns as those displayed in health and disease by both visceral and structural LBM compartments. As a result, this TTR parameter maintains positive correlations with muscle mass downsizing in elderly persons. The liver synthesis of TTR is downregulated in protein-depleted states and suppressed in cytokine-induced inflammatory disorders. TTR integrates the centrally-mediated regulatory mechanisms governing the balance between protein accretion and protein breakdown, emerging as the ultimate indicator of LBM resources. This review proposes the adoption of a gray zone defined by cut-off values ranging from 200 mg/L to 100 mg/L between which TTR plasma values may fluctuate and predict either the best or the worst outcome. The best outcome occurs when appropriate dietary, medicinal and surgical decisions are undertaken, resuming TTR synthesis which manifests rising trends towards pre-stress levels. The worst occurs when all therapeutic means fail to succeed, leading inevitably to complete exhaustion of LBM and SM metabolic resources with an ensuing fatal outcome. Some patients may remain unresponsive in the middle of the gray area, combining steady clinical states with persistent stagnant TTR values. Using the serial measurement of plasma TTR values, these last patients should be treated with the most aggressive and appropriate therapeutic strategies to ensure the best outcome.

A Novel Concept of Amino Acid Supplementation to Improve the Growth of Young Malnourished Male Rats.

BACKGROUNDS/AIMS: This study was aimed at understanding the relationship between plasma amino acids and protein malnutrition and at determining whether amino acid supplementation associated with malnutrition and growth improves linear growth in growing rats. METHODS: Body length and plasma amino acids were measured in young male rats that were fed the following diet for 3 weeks, mimicking a low and imbalanced protein diets based on maize, a major staple consumed in developing countries: a 70% calorically restricted cornmeal-based diet (C), C + micronutrients (CM), CM + casein (CMC), CM + soy protein (CMS) or CMS + 0.3% lysine. RESULTS: A correlation analysis of linear growth and plasma amino acids indicated that lysine, tryptophan, branched-chain amino acids, methionine, and phenylalanine significantly correlated with body length. Supplementation with these 5 amino acids (AA1) significantly improved the body length in rats compared to CMC treatment whereas, nitrogen-balanced amino acid supplemented controls (AA2) did not (CM +1.2 ± 0.2, CMC +2.7 ± 0.3, CMS +2.1 ± 0.3, AA1 +2.8 ± 0.2, and AA2 +2.5 ± 0.3 cm). CONCLUSION: With securing proper amino acid balance, supplementing growth-related amino acids is more effective in improving linear growth in malnourished growing male rats. Analysis of the correlation between plasma amino acids and growth represents a powerful tool to determine candidate amino acids for supplementation to prevent malnutrition. This technology is adaptable to children in developing countries.

Protein and micronutrient deficiencies in patients with radiation cystitis and outcome after hyperbaric oxygen therapy.

BACKGROUND & AIMS: Haemorrhagic radiation cystitis (HRC) is a late complication of pelvic radiotherapy. Severe cases are difficult to treat due to persistent or recurrent bleeding, despite urological and hyperbaric oxygen therapy (HBOT). However, wound healing requires a good nutritional status. In this respect, we aimed at analysing the nutritional status of patients with HRC prior to the onset of HBOT and at highlighting predictive nutritional factors of outcome. METHODS: Data were retrospectively collected from a cohort of 179 patients with HRC (between 2011 and 2015). Haematuria was graded according to the Subjective, Objective, Management, Analytic scale (SOMA): grade-4 (n = 46) was compared with grade-3 (n = 56), and with grades 1 and 2 (n = 77). S-albumin, prealbumin, vitamins C, D and B6, zinc, selenium, and essential fatty acids were evaluated before HBOT. HBOT response was measured at 3 months according to the haematuria SOMA grade. The Mann-Whitney test, Fisher's exact test and principal-component analysis were used to compare groups. RESULTS: Patients with higher haematuria grades (3 and 4) harboured significant deficiencies in S-albumin, prealbumin, vitamins C, D and B6, zinc, selenium and essential fatty acids. Moreover, grade-4 patients without improvement after 3 months of HBOT had significant lower initial levels of S-albumin, vitamin C, selenium and linoleic acid. Vitamin C levels <2.5 mg/L were strongly associated with HBOT non-response (OR 23.14, 95% CI 3.73-143.69, p = 0.002). CONCLUSIONS: Our analyses show serious nutritional deficiencies associated with higher grades of HRC and worse prognoses. Patients with haemorrhagic cystitis might benefit from an adequate dietary supplementation to support healing of their bladder mucosa.

The reduced/oxidized state of plasma albumin is modulated by dietary protein intake partly via albumin synthesis rate in rats.

The reduced/oxidized state of plasma albumin is influenced by many factors, including chronic diseases and strenuous training. Recently, the reduced/oxidized state has also been shown to be associated with dietary protein and energy intakes in rats. We hypothesized that dietary protein intake may modulate the reduced/oxidized state of plasma albumin by altering the rate of albumin synthesis and that the reduced/oxidized state could therefore serve as a novel marker of protein undernutrition. We tested this hypothesis by examining male growing rats placed on a low-protein or energy-restriction diet. In the 4-week experiment, animals fed a low-protein diet (3% casein), whose dietary intakes were lower than those fed control diet (20% casein), showed significant decreases in plasma albumin level and the ratio of the reduced form of albumin to total albumin. Animals given the same amount of control diet as the low-protein diet group (approximately 30% energy restriction) also showed the above decreases, albeit to much more limited extents. The ratio of reduced to total plasma albumin correlated significantly with plasma albumin fractional synthesis rate. When animals were maintained on the low-protein diet for as long as 12 weeks and then fed the control diet for 1 week, the decreased ratio of reduced to total plasma albumin, but not plasma albumin level, resolved rapidly. The reduced/oxidized state of plasma albumin would thus reflect dietary protein status via plasma albumin turnover including the fractional synthesis rate and could prove useful as a sensitive marker of protein undernutrition.

Nutritional and Protein Deficiencies in the Short Term following Both Gastric Bypass and Gastric Banding.

BACKGROUND: The number of morbidly obese patients undergoing bariatric surgery (BS) has increased dramatically in recent years. Therefore, monitoring food intake and its consequences in terms of nutritional status is necessary to prevent nutritional deficiencies. The aim of this study was to analyze the effect of food restriction on nutritional parameters in the short-term (≤3 months) period after BS in morbid obesity. METHOD: In a prospective study, we followed 22 obese women who underwent Roux-en-Y gastric bypass (GBP) or adjustable gastric banding (AGB) at baseline (T0) and 1 (T1) and 3 (T3) months after surgery. We evaluated food intake, nutrient adequacy and serum concentrations of vitamins and minerals known to be at risk for deficiency following BS. RESULTS: Before surgery, we observed suboptimal food intakes, leading to a risk of micronutrient deficiencies. Serum analysis confirmed nutritional deficiencies for iron and thiamine for 27 and 23% of the patients, respectively. The drastic energy and food reduction seen in the short term led to very low probabilities of adequacy for nutrients equivalent across both surgeries. Serum analysis demonstrated a continuous decrease in prealbumin during the follow-up, indicating mild protein depletion in 21 and 57% of GBP patients and 50 and 63% of AGB patients, respectively, at T1 and T3. Regarding vitamins and minerals, systematic supplementation after GBP prevented most nutritional deficiencies. By contrast, AGB patients, for whom there is no systematic supplementation, developed such deficiencies. CONCLUSIONS: Our results suggest that cautious monitoring of protein intake after BS is mandatory. Furthermore, AGB patients might also benefit from systematic multivitamin and mineral supplementation at least in the short term.

Change in skeletal muscle mass after administering entecavir in patients with hepatitis B.

OBJECTIVE: Cachexia, or disease-related loss of muscle mass, is a complication of chronic liver disease that modifies its clinical course. The aim of this study was to determine whether improvement in liver function and cachexia through control of the hepatitis B virus (HBV) increases skeletal muscle mass. METHODS: The blood tests and cross-sectional area (mm(2)) of the psoas major muscle on computed tomography were measured before and after long-term entecavir therapy (median, 39 mo; range, 14-76 mo) in patients with hepatitis B (17 men, 13 women; mean age, 63 ± 13 y). RESULTS: The anti-HBV effect was good in 30 patients given entecavir, and most patients had undetectable serum HBV-DNA levels (93%) and alanine aminotransferase normalization (83%) within a median of 32 mo. Overall, no significant change in the area of the psoas major muscle was seen in any of the patients, although a significant increase was seen when limited to cases of protein malnutrition defined as serum albumin (Alb) <4 g/dL. A positive correlation was seen for the amount of change (Δ) in the psoas major muscle and the amount of change (Δ) in Alb. CONCLUSIONS: The present findings suggest that skeletal muscle mass may fluctuate in parallel with Alb levels. An improvement in low muscle mass may thus be expected from antiviral therapy for viral liver disease, especially in patients with cachexia.

Evaluation of biochemical, hematological and parasitological parameters of protein-deficient hamsters infected with Ancylostoma ceylanicum.

BACKGROUND: Hookworms infect millions of people worldwide and can cause severe clinical symptoms in their hosts. Prospective cohort studies in Brazil show high rates of hookworm reinfection in malnourished children compared to well-nourished children, despite previous treatment. Additionally, soil-transmitted helminth (STH) infections can worsen the nutritional status of affected populations. Therefore, this study aims to clarify the effects of host malnutrition during Ancylostoma ceylanicum infection and how this infection affects host physiological parameters using a hamster model. METHODOLOGY/PRINCIPAL FINDINGS: Hamsters were divided into four experimental groups: normal diet or low-protein diet (also referred to as "malnourished") and A. ceylanicum infection or no infection. More severe pathogenesis was observed in the infected malnourished group, as demonstrated by significant decreases in the hemoglobin concentration, erythrocyte number and packed-cell volume compared to the non-infected malnourished group. Greater numbers of adult parasites and eggs were observed in the malnourished group compared to the control group; however, the oviposition rate was lower in the malnourished group. In general, greater values of total lipids were observed in malnourished animals compared to control animals, including lipids excreted in the stool. CONCLUSIONS: In this work, we have demonstrated that animals fed an isocaloric low-protein diet presented more severe pathogenesis when infected with A. ceylanicum. The increased lipid concentration in the liver and blood is related to the conversion of the excess carbohydrate into fatty acids that increase the concentration of triglycerides in general. Triglycerides were excreted in the feces, indicating that infection associated with malnutrition caused a greater loss of these molecules for this group of animals and confirming the hypothesis that both nutrition and infection are responsible for the malabsorption syndrome. Taken together, the results found in this work confirm the hypothesis that the nutritional condition of the host greatly influences the course of the infection.

Zinc status and dietary intake of pregnant women, Alexandria, Egypt.

BACKGROUND AND OBJECTIVES: Deficiencies of protein, energy, and micronutrients are highly prevalent in developing countries and have major effects on pregnancy outcome. Low dietary intake is the most common reason for zinc deficiency. The present research is part of a larger double-blind randomized-controlled trial to evaluate the effect of zinc supplementation on the pregnancy outcome. The aim of the present study was to assess the zinc status and dietary intake of zinc and other macronutrients and micronutrients among pregnant women in Alexandria, Egypt. PARTICIPANTS AND METHODS: Participants were pregnant women attending two antenatal care centers that serve low-income and middle-income pregnant populations. A total of 1055 healthy pregnant women aged 20-45 years were assessed for eligibility. Of these, only 675 had serum zinc level below the median for the gestational age. They were assigned randomly to one of three parallel groups. Zinc supplements were provided from 16 weeks until delivery. A subsample of 100 women was assessed for their dietary intake. A questionnaire interview was used to collect basic socioeconomic and data on current pregnancy and labor. Dietary data were collected using the 24-h recall method and a food frequency questionnaire. The nutritive value of the daily diet was computed using the Egyptian food composition tables. The blood hemoglobin level, serum zinc level, and fasting blood sugar were determined. RESULTS: Zinc deficiency was detected among 53.5% of the sample. Dietary intake of zinc was low, representing 59.4, 59.4, and 62% of the recommended dietary allowance (RDA) for the zinc group, zinc plus multivitamins, and the placebo group, respectively. The iron intake was below 50% of the RDA. Protein intake was less than 70% of the RDA. The mean intakes of fat were 191.97, 211.8, and 196.3 g/day for the three groups. The mean energy intake represented 51.1, 53.5, and 49.8% of the RDA. CONCLUSION AND RECOMMENDATIONS: Except for carbohydrate intake, the dietary intake of all macronutrients and micronutrients was low. The lowest intake was of iron (below 50% of the RDA). Zinc and protein intake represented less than 70% of the RDA. The overall energy intake was around 50% of the RDA. Nutritional health education should be used as a preventive approach to allow the large sector of the low-income population to maximize the use of the limited resources in the best way. In women at high risk of zinc deficiency, zinc supplementation should be added to the routine supplements.

Hematologic and bone marrow changes in children with protein-energy malnutrition.

BACKGROUND: All systems in an organism are affected by protein-energy malnutrition (PEM), but one of the worst affected is the hematopoietic system. Today PEM remains a very serious problem in developing countries. We examined the relationships between clinical features, hematological, and bone marrow changes with severe PEM from Turkey. METHOD: We evaluated 34 (11 females and 23 males) consecutive cases of severe PEM, with no underlying diseases aged 3-20 months. The clinical nutritional conditions of the patients were determined using the Wellcome-Trust PEM classification. Ten of the patients were in the Marasmic-Kwashiorkor (M-K) group, 10 were in the Kwashiorkor (KW) group, and 14 were in the Marasmic (M) group. Full blood count, protein, albumin, serum iron (SI), iron-binding capacity (TIBC), ferritin, vitamin B12, folic acid, complement-3 (C3), complement-4 (C4), and bone marrow were investigated in all groups. RESULTS: Anemia was detected in 97% of patients. We determined serum iron levels were low in 67.6% of the patients, TS levels were low in 76.4% of the patients and ferritin levels were low in 20.5%. The level of vitamin B12 was normal in all patients. Bone marrow analysis showed erythroid series hypoplasia in 28.5% of patients in the M group, 50% in the KW group, and 30% in the M-K group. Marrow iron was absent in 58.8% of patients. CONCLUSION: The most common hematologic change in the children with PEM was anemia and major cause of anemia was iron deficiency in this study. Patients with severe PEM have normal Vit B12 and serum folate levels. Most of the patients with severe PEM had normal cellularity with megaloblastic and dysplastic changes in bone marrow due to the inadequate and imbalanced intake of protein and energy.

Is there any interaction of resistin and adiponectin levels with protein-energy wasting among patients with chronic kidney disease.

The aim of this study was to evaluate the effects of adipocytokines including adiponectin, leptin, resistin, neuropeptide Y and ghrelin in chronic kidney disease (CKD) patients on appearance of protein-energy wasting (PEW). One hundred fifty patients with mean age of 45.4 ± 15.9 years, without active infections or chronic inflammatory conditions were recruited into the study. Study groups were control group (consisting of 30 healthy volunteers with normal kidney functions), hemodialysis group, predialysis group, peritoneal dialysis group and kidney transplant group. Fasting morning serum leptin, ghrelin, acylated ghrelin, neuropeptide Y, adiponectin, resistin levels of all of the groups were measured. Anthropometric and nutritional assessments of all patients were obtained. Diagnosis of PEW was made according to definition recommended by the International Society of Renal Nutrition and Metabolism. Presence of PEW in hemodialysis (23.3%) and peritoneal dialysis (26.7%) groups were significantly higher than those of predialysis (3.3%), and transplantation (0%) groups. Adiponectin and resistin levels in predialysis, peritoneal dialysis and hemodialysis patients were significantly higher than control group (p: 0.0001). This study had given significant positive correlations between presence of PEW and serum resistin (r: 0.267, p: 0.001), and serum adiponectin levels (r: 0.349, p: 0.0001). There were no relationship between presence of PEW and ghrelin, acylated-ghrelin, neuropeptide Y, and leptin levels of the groups. CKD patients except transplant patients had higher adiponectin and resistin levels than control group. PEW was found to be linearly correlated with resistin and adiponectin. High serum resistin and adiponectin levels might have a role in development of PEW among dialysis patients.

[Activity of the marker liver enzymes under the conditions of toxic hepatitis and alimentary deprivation of protein].

The activity of the sorbitoldehydrogenase (SDH), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in the blood serum of rats with acetaminophen-induced hepatitis under the conditions of alimentary deprivation of protein was studied. The animals were divided into 3 groups: 1--rats with acute acetaminophen-induced hepatitis, maintained on the full ration; 2--rats with acute acetaminophen-induced hepatitis, maintained under the conditions of alimentary deprivation of protein; 3--control. The activity of the sorbitol dehydrogenase in blood serum was determined by the kinetic method, activity of the alanine aminotransferase and alkaline phosphatase - photometrically. It is shown, that in animals with the model hepatitis the activity of sorbitol dehydrogenase in blood serum increases 20-fold, wherein statistical significance between animals with hepatitis maintained under the conditions of full ration and those of low-protein diet is not established. In the group of animals with acetaminophen-induced hepatitis the preservation on the control level of the alkaline phosphatase activity on the base of the increase of alanine aminotransferase by 2.2 times and ratio ALT/ALP>5 testifies about hepatocellular liver injury. In the group of animals with drug-induced hepatitis and alimentary deprivation of protein, the increase of the alkaline phosphatase and alanine aminotransferase activity is observed, herewith the ratio ALT/ALP ranges from 2 to 5 and testifies about mixed liver injury. The conclusion was made, that alimentary deprivation of protein is the critical factor for the development of the disturbances of functional and structural liver integrity, and the therapeutic approaches to the correction of the drug-induced liver injury should be different depending on the value of protein ration in the anamnesis, taking into account the different types of liver injury.

Relative contributions of inflammation and inadequate protein intake to hypoalbuminemia in patients on maintenance hemodialysis.

PURPOSE: Serum albumin is one of the strongest mortality predictors in maintenance hemodialysis (MHD) patients. Yet, the degree to which serum albumin represents dietary protein intake or an inflammatory state, among others, is not clear. We hypothesize that these inadequate protein intake and inflammation contribute somewhat equally to hypoalbuminemia. METHODS: In a cross-sectional analysis, we examined correlates of low serum albumin, <3.8 g/dL, in 812 MHD patients in whom interleukin-6 (IL-6) and normalized protein nitrogen appearance (nPNA), also known as normalized protein catabolic rate (nPCR), were also measured. Logistic regression estimated odds ratios were employed, and spline models were plotted to examine the likelihood of relatively low serum albumin <3.8 g/dL. RESULTS: Mean age (±SD) of patients was 54 ± 15 years; 53 % of patients were men, 50 % Hispanic, 31 % African-American, and 55 % diabetic. The mean dialysis vintage was 31 ± 34 months (median: 19, inter-quartile range: 7-44 months). The baseline serum albumin, averaged over a 3-month period (mean ± SD), was 3.88 ± 0.38 g/mL. The unadjusted correlation coefficients of l IL-6 and nPNA with serum albumin were -0.36 and +0.20, respectively (p < 0.001 for each comparison). The likelihood for an albumin <3.8 gr/dL increased linearly with decreasing nPNA and rising serum IL-6. This trend was steeper with increasing serum IL-6 up to a concentration of 30 ng/mL. CONCLUSIONS: Both low protein intakes and a high state of inflammation are associated with low serum albumin in MHD patients.

High-carbohydrate/low-protein-induced hyperinsulinemia does not improve protein balance in children after cardiac surgery.

OBJECTIVE: In pediatric cardiac surgery, fluid-restricted low-protein (LoProt) diets account for cumulative protein deficits with increased morbidity. In this setting, we aimed to inhibit proteolysis by a high-carbohydrate (HiCarb)-intake-induced hyperinsulinemia and improve protein balance. METHODS: The effect of a HiCarb/LoProt (glucose 10 mg · kg(-1) · min(-1)/protein 0.7 g · kg(-1) · d(-1)) versus a normal-carbohydrate (NormCarb)/LoProt (glucose 7.5 mg · kg(-1) · min(-1)/protein 0.3 g · kg(-1) · d(-1)) enteral diet on whole-body protein breakdown and balance was compared in a prospective, randomized, single-blinded trial in 24 children after cardiac surgery. On the second postoperative day, plasma insulin and amino acid concentrations, protein breakdown (endogenous rate of appearance of valine), protein synthesis (non-oxidative disposal of valine), protein balance, and the rate of appearance of urea were measured by using an isotopic infusion of [1-(13)C]valine and [(15)N(2)]urea. RESULTS: The HiCarb/LoProt diet led to a serum insulin concentration that was three times higher than the NormCarb/LoProt diet (596 pmol/L, 80-1833, and 198 pmol/L, 76-1292, respectively, P = 0.02), without differences in plasma glucose concentrations. There were no differences in plasma amino acid concentrations, non-oxidative disposal of valine, and endogenous rate of appearance of valine between the groups, with a negative valine balance in the two groups (-0.65 µmol · kg(-1) · min(-1), -1.91 to 0.01, and -0.58 µmol · kg(-1) · min(-1), -2.32 to -0.07, respectively, P = 0.71). The serum cortisol concentration in the HiCarb/LoProt group was lower compared with the NormCarb/LoProt group (204 nmol/L, 50-544, and 532 nmol/L, 108-930, respectively, P = 0.02). CONCLUSION: In children with fluid restriction after cardiac surgery, a HiCarb/LoProt diet compared with a NormCarb/LoProt diet stimulates insulin secretion but does not inhibit proteolysis further and therefore cannot be advocated for this purpose.

Relative and combined effects of ethanol and protein deficiency on bone manganese and copper.

Both manganese and copper may affect bone synthesis. Bone content of both metals can be altered in alcoholics, although controversy exists regarding this matter. To analyse the relative and combined effects of ethanol and a low protein diet on bone copper and manganese, and their relationships with bone structure and metabolism, including trabecular bone mass (TBM), osteoid area (OA), osteocalcin (OCN), insulin-like growth factor-1 (IGF-1), parathyroid hormone (PTH), urinary hydroxyproline (uHP) and vitamin D. Adult male Sprague-Dawley rats were divided into four groups. The control rats received a 18% protein-containing diet; a second group, an isocaloric, 2% protein-containing diet; a third one, an isocaloric, 36% ethanol-containing diet and a fourth, an isocaloric diet containing 2% protein and 36% ethanol. After sacrifice, TBM and OA were histomorphometrically assessed; bone and serum manganese and copper were determined by atomic absorption spectrophotometry, and serum OCN, IGF-1, PTH, uHP and vitamin D by radioimmunoassay. Ethanol-fed rats showed decreased TBM and bone manganese. Significant relationships existed between bone manganese and TBM, serum IGF-1 and OCN. Ethanol leads to a decrease in bone manganese, related to decreased bone mass and bone synthesis. No alterations were found in bone copper.

Vegetarianism produces subclinical malnutrition, hyperhomocysteinemia and atherogenesis.

OBJECTIVE: To explain why vegetarian subjects develop morbidity and mortality from cardiovascular diseases unrelated to vitamin B status and Framingham criteria. METHODS: A study of 24 rural male subjects 18 to 30 y old and 15 urban male controls was conducted in the Sahel region of Chad. Food consumption was determined from a dietary questionnaire, and overall health status was assessed by body weight, body mass index, serum albumin, plasma transthyretin, urinary nitrogen, and creatinine. Plasma lipids, vitamins B6, B9 and B12, homocysteine, and related sulfur amino acids were measured as selected cardiovascular disease risk factors. RESULTS: Body weight, body mass index, blood, and urinary markers of protein status were significantly lower, with an estimated 10% decrease of lean body mass in the study group compared with urban controls. Neither lipid fractions nor plasma levels of vitamins B6, B9, and B12 were significantly different between the two groups. Although the mean consumption of sulfur amino acids (10.4 mg·kg(-1)·d(-1)) by rural subjects was significantly below the recommended dietary allowances (13 mg·kg(-1)·d(-1)), plasma methionine values were similar in the two groups. In contrast, homocysteine concentration was significantly increased (18.6 µmol/L, P < 0.001), and the levels of cysteine and glutathione were significantly decreased in the study group, demonstrating inhibition of the trans-sulfuration pathway. The strong negative correlation (r = -0.71) between transthyretin and homocysteine implicated lean body mass as a critical determinant of hyperhomocysteinemia. CONCLUSION: The low dietary intake of protein and sulfur amino acids by a plant-eating population leads to subclinical protein malnutrition, explaining the origin of hyperhomocysteinemia and the increased vulnerability of these vegetarian subjects to cardiovascular diseases.