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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.

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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.

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Background: Proteins having structural and various regulatory functions are essential components of all unicellular and multicellular organisms. The only source of proteins and their building blocks, amino acids, for human and many animals are the proteins and amino acids in their foods. Although qualitative and quantitative protein malnutrition are common problems in animals and men, the impacts of dietary proteins on serum electrolytes are still controversial. Materials, Methods & Results: Adult male Wistar rats were randomly divided into three groups of 6 or 7 animals serving as controls, and quantitative or qualitative protein malnutrition groups. Animals were held in metabolic cages individually in a conventional room with 12:12 h day/night cycle, 29°C temperature and 50-70% relative humidity. After a 10-day acclimation period controls (n = 7) were given rat chow diet consisting of 24% protein, while other groups received an almost N-free diet (quantitative malnutrition) or a diet containing 20% gelatin as protein source (qualitative malnutrition) for 35 days. Food and tap water were given animals ad libitum during acclimation period and throughout the experiment. At the end of experiment, blood samples were collected and Na+, K+ and Cl- concentrations in serum were determined. Data were analyzed by ANOVA, ANCOVA and Pearson's correlation test. Dietary interventions had significant effects on mean body weights of animals (P = 0.000), but not on their food consumptions. However, in the last week controls consumed significantly more food than both malnourished groups (P = 0.001). If row data were used for statistical evaluation, it was seen that qualitative and quantitative protein malnutrition affected only the serum K+, and Cl- concentrations significantly (P = 0.003, P = 0.000). Controls had higher K+ concentrations than those of gelatin-given group (P = 0.002) and N-free group had higher Cl- concentrations than control and gelatin-given groups (P = 0.001). However, if body-weight corrected electrolyte values were considered, compared to controls a two-fold increase in mean concentrations of all three electrolytes in sera of both malnourished groups were seen (P = 0.000). There were certain negative or positive correlations between different variables interested. Discussion: The findings of this study revealed that, on the basis of the row data, the dietary protein inanition increase serum Cl - concentration, while gelatin in the diet decrease the K+ concentration in sera of rats. Because of the body weights of malnourished animals decreased while controls continued to gain weight throughout the experiment, a substantial difference in body weights of malnourished animals and controls occurred. And, because of physiological variables are reflections of body weights, it was necessary to eliminate the possible effects of the body weights of animals. If the effect of the body weights of animals eliminated, a two-fold increase of all three electrolytes studied was seen. It was concluded that dietary proteins exert signifi cant control on the homeokinesis of serum electrolytes. If physiopathological conditions are questioned, standardization for comparison of the results from control and experimental groups in a study as well as from different studies is indispensible

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Malnutrition induces a decrease in immunity that affects the ability of the organism to deal with an infectious challenge. The clotting system is considered a branch of immunity and its activation is important in the pathogenesis of an infectious disease. This work was conducted to determine coagulation modifications in malnourished hosts before and during infection. Weaned mice were malnourished via a protein-free diet. Well-nourished control mice (WNC) consumed a balanced conventional diet. Malnourished mice (MN) and WNC were challenged intranasally with Streptococcus pneumoniae. Blood, bronchoalveolar lavages (BAL), and lung samples were taken at different times post infection. The results were that MN showed altered hemostatic tests and fibrin(ogen) deposits in the lung. Thus, an increase in thrombin-antithrombin complexes (TATc) in plasma and BAL was observed. In the MN group, infection induced a rise in TATc in plasma and BAL and increased plasma fibrinogen and fibrin(ogen) deposits in the lung. A decrease in activated protein C and antithrombin in BAL and an early decrease followed by an increase in plasma Factor VIII were also observed. Thus, malnourishment induced a procoagulant state increased by infection. This is the first work that presents results of an exhaustive study of coagulation in malnourished hosts before and during an infection.

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Protein malnutrition leads to functional impairment in several organs, which is not fully restored with nutritional recovery. Little is known about the role of oxidative stress in the genesis of these alterations. This study was designed to assess the sensitivity of blood oxidative stress biomarkers to a dietary protein restriction. Male Wistar rats were divided into two groups, according to the diet fed from weaning (21 days) to 60 day old: normal protein (17% protein) and low protein (6% protein). Serum protein, albumin, free fatty acid and liver glycogen and lipids were evaluated to assess the nutritional status. Blood glutathione reductase (GR) and catalase (CAT) activities, plasma total sulfhydryl groups concentration (TSG) as well as plasma thiobarbituric acid reactive substances (TBARs) and reactive carbonyl derivatives (RCD) were measured as biomarkers of the antioxidant system and oxidative damage, respectively. The glucose metabolism in soleus muscle was also evaluated as an index of stress severity imposed to muscular mass by protein malnutrition. No difference was observed in muscle glucose metabolism or plasma RCD concentration between both groups. However, our results showed that the low protein group had higher plasma TBARs (62%) concentration and lower TSG (44%) concentration than control group, indicating increased reactive oxygen species production in low protein group. The enhancement of erythrocyte GR (29%) and CAT (28%) activities in this group also suggest an adaptation to the stress generated by the protein deficiency. Taken together, the results presented here show that the biomarkers used were able to reflect the oxidative stress level induced by this specific protein deficient diet.

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OBJECTIVES: To study the role of protein sufficiency, age, calorie sufficiency, and phenylalanine levels in children with phenylketonuria (PKU) and determine how these affect linear growth. METHODS: Age, growth measures, plasma prealbumin, and mean phenylalanine levels were analyzed from a chart review of 38 children with early and continuously treated PKU. RESULTS: A regression model was calculated investigating the effects of prealbumin, age, body mass index, and mean phenylalanine level on height. In this model, plasma prealbumin of <20 was associated with a loss of 45 height percentiles, whereas age and body mass index also had smaller but statistically significant effects. Prealbumin was correlated with height and age such that children with lower prealbumin levels were shorter and younger. There was no significant correlation between age and height or mean plasma phenylalanine level and height. A prealbumin level of 20 mg/dL appeared to constitute a threshold level, below which height growth was very significantly impaired. CONCLUSIONS: There is a strong relation between protein insufficiency, as determined by plasma prealbumin levels, and linear growth impairment. We suggest that a plasma prealbumin level of at least 20 mg/dL is necessary for optimal growth in children with PKU.

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The aims of this work were to evaluate the effects of the deficient ingestion of protein and vitamin B on the biochemical and hematologic parameters and on the NADH- and NADPH-diaphorase positive myenteric neurons. The control animals (n=10) received commercial chow and the experimental rats (n=10) received chow with protein level reduced to 8% during 120 days. At the time of killing blood was collected for assessment of the blood and hematologic parameters and the ascending colon for quantitative analysis of the neurons of the myenteric plexus. It was observed that the reduction of the protein level to 8% coupled to the reduction of the levels of vitamin B in adult rats neither led to qualitative or quantitative changes on red or white blood cells, nor decreased globulin levels, induced the formation of edema or gave rise to clinical signs typical of protein or vitamin B deficiency. On the other hand, the experimental protocol led to less weight gain, change on the body composition with fat deposition; decrease of the values of serum total protein and albumin; reduction of the area of colon and density of nitrergic and NADH-diaphorase myenteric neurons inferior to the expected.

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The aims of this work were to evaluate the effects of the deficient ingestion of protein and vitamin B on the biochemical and hematologic parameters and on the NADH- and NADPH-diaphorase positive myenteric neurons. The control animals (n=10) received commercial chow and the experimental rats (n=10) received chow with protein level reduced to 8 percent during 120 days. At the time of killing blood was collected for assessment of the blood and hematologic parameters and the ascending colon for quantitative analysis of the neurons of the myenteric plexus. It was observed that the reduction of the protein level to 8 percent coupled to the reduction of the levels of vitamin B in adult rats neither led to qualitative or quantitative changes on red or white blood cells, nor decreased globulin levels, induced the formation of edema or gave rise to clinical signs typical of protein or vitamin B deficiency. On the other hand, the experimental protocol led to less weight gain, change on the body composition with fat deposition; decrease of the values of serum total protein and albumin; reduction of the area of colon and density of nitrergic and NADH-diaphorase myenteric neurons inferior to the expected

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The aim of the present work was to study the effect of nutritional rehabilitation with different concentration of dietary protein (6, 18 or 50%) of previously undernourished rats on serum Insulin-like growth factor-I (IGF-I) and Insulin-like growth factor binding proteins levels (IGFBPs). Undernutrition was induced by feeding rats with 0.5% casein diet for 5 weeks. Over this period, growth, serum total proteins, IGF-I levels and IGFBP-3/IGFBP-2 ratio were significantly decreased compared to the group fed ad libitum 18% casein diet. Nutritional rehabilitation for 21 days with 6% casein diet did not change any of these parameters. Nutritional rehabilitation with 18 or 50% casein diet for one day did not initiate the restoration of serum IGF-I levels and IGFBP-3/IGFBP-2 ratio. However, after 10 days with 18 or 50% casein diets, there was an increase of 12 fold in IGF-I levels and 7 fold in the IGFBP-3/IGFBP-2 ratio. Finally, rehabilitation for 21 days with 18 or 50% casein diet produced an increase of 21 and 26 fold in IGF-I levels, and 6.1 and 14.5 fold in the IGFBP-3/IGFBP-2 ratio respectively. These results suggest that nutritional rehabilitation with 18% casein and above were more effective than 6% casein diets to reestablish body weight. Serum IGF-I and IGFBP-3 concentrations were sensitive indicators of the evolution of the nutritional status of the rats depending of the protein concentration in the diet in previously undernourished rats.

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El propósito del presente trabajo fue estudiar el efecto de la rehabilitación nutricia con dietas que contenían diferente concentración de proteína (6, 18 o 50 por ciento) en ratas previamente desnutridas sobre los niveles del factor de crecimiento semejante a la insulina (IGF-I) y de las proteínas que unen al factor semejante a la insulina (IGFBPs). La desnutrición se indujo alimentando ratas en crecimiento con 0.5 por ciento de caseína por cinco semanas. En este periodo, el crecimiento, las proteínas totales en el suero, las concentraciones de IGF-I en suero y la relación IGFBP-3/IGFBP-2 se encontraron significativamente disminuidas comparados con el grupo con libre acceso a una dieta con 18 por ciento de caseína. La rehabilitación nutricia por 21 días con 6 por ciento de caseína no cambió ninguno de estos parámetros. La rehabilitación nutricia con una dieta con 18 o 50 por ciento de caseína por un día no inició el restablecimiento de las concentraciones de IGF-I y la relación IGFBP-3/IGFBP-2. Sin embargo, después de 10 días con dietas al 18 o 50 por ciento de caseína por un día no inició el restablecimiento de las concentraciones de IGF-I y la relación IGFBP-3/IGFBP-2. Sin embargo, después de 10 días con dietas al 18 o 50 por ciento de caseína, las ratas aumentaron 12 veces las concentraciones de IGF-I y siete veces la relación IGFBP-3/IGFBP-2. Finalmente, la rehabilitación por 21 días con 18 o 50 por ciento de caseína produjo un incremento de 21 y 16 veces en las concentraciones de IGF-I y 6.1 y 14.5 veces en la relación IGFBP-3/IGFBP-2 respectivamente. Estos resultados sugieren que la rehabilitación nutricia con 18 por ciento o 50 por ciento de caseína son más efectivas que dietas que contienen 6 por ciento de caseína para restablecer el peso corporal. Las concentraciones de IGF-I e IGFBP-3 fueron indicadores sensibles de la evolución del estado nutricio dependiendo de la concentración de proteína en la dieta

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The case of an 8-month-old male with heterozygous coagulation protein C deficiency is presented. Sepsis due to Salmonella typhi aggravated the protein C deficiency and resulted in arterial thrombosis of the distal third of the lower right limb. The patient was treated with both heparin and danazol, the levels of functional protein C increasing and the necrotic phenomenon resolving, thus making unnecessary amputation of the limb. The observation is discussed with the evidences of danazol being useful in the treatment of patients with protein C deficiency.

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Pregnant Wistar rats were fed ad libitum diets containing either 25% (control) or 8% casein (undernourished) from conception through the gestation and lactation periods. Rats from undernourished dams had lower birth weights than control rats and this difference persisted up to day 21 of postnatal life. Livers obtained from undernourished animals aged 10, 15 and 20 days weighed 50% less than control livers. Liver glycogen concentration was much higher in 7- and 10-day-old undernourished rats than in normal rats, but no differences were observed between groups aged 15 or 20 days. Malnutrition caused a decrease in glycemia from 10 days of age and an increase in ketonemia at 10 and 15 days of age. The results show that pre- and postnatal protein malnutrition causes changes in carbohydrate and lipid metabolism in rats during the period of brain growth spurt.

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A study was carried out to determine the effect of protein deficiency on the phagocytic function of blood neutrophils and of peritoneal exudate of rats. The deficient animals exhibited significantly lower leukocyte and neutrophil values, as well as NBT reduction and diminished peroxidase and bactericidal capacity. Englobement of S. aureus and latex particles was found to be normal in both groups. Alkaline phosphatase activity in the neutrophils appear to be increased in the deficient animals.

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Estudou-se os efeitos da carência proteica sobre a funçäo fagocitária de neutrófilos do sangue e do exsudato peritoneal de ratos. Os animais carentes apresentaram valores significativamente menores para o número de leucócitos e de neutrófilos, para testes de reduçäo do NBT, para a atividade da peroxidase e para a atividade bactericida. A ingestäo de S. aureus e de particulas inertes näo mostrou diferença entre os grupos. A fosfatase alcalina leucocitária apresentou-se aumentada nos neutrófilos dos animais deficientes

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Food intake, body weight changes, serum protein and amino acid concentrations were measured during the course of primary infections of Nippostrongylus brasiliensis in rats fed on either a 2% protein (casein) diet or a 16% protein diet (Oxoid 41 B). Total serum protein concentration declined from 77.84 +/- 5.35 mg/ml in uninfected well-nourished rats to 54 +/- 3.29 mg/ml in rats at 9 days post-infection (p.i.). A reduction from 47.80 +/- 2.78 to 40.38 +/- 5.62 mg/ml had occurred in protein-malnourished rats by day 6 p.i. The hypoproteinaemia was accompanied by significant hypoalbuminaemia in the protein-malnourished rats and concentrations fell from approximately 33 to 19 mg/ml at the time of peak infection. Six days after inoculation, a significant increase was detected in the concentration of serum amino acids in both well-nourished and protein-malnourished rats; the effect was more prolonged for non-essential than for essential amino acids. The results are discussed briefly in relation to recent work on the control of protein metabolism during malnutrition.

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The Nippostrongylus brasiliensis-rat model was used to determine whether iron and protein deficiency, which are commonly associated with parasitic infections, affected the pharmacokinetic behaviour of fenbendazole as measured by plasma concentrations and uptake by worms. Plasma 14C concentrations after [14C] fenbendazole administration were higher in iron and protein-deficient rats than in sufficient rats. However, the uptake of 14C by N. brasiliensis in iron and protein-deficient rats was significantly less than in worms from diet-sufficient rats. The reduced anthelmintic uptake by worms in protein and iron-deficient hosts may account, in part, for reduced anthelmintic efficacy under these circumstances. These findings are relevant to understanding variations in response to chemotherapy in populations of parasitised hosts containing malnourished individuals.

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Male adult rats of the Wistar strain were fed "ad libitum" either a protein-free or a 20% casein diet for a period of 28 to 32 days. At the end of the experimental procedure, the animals given the protein-free diet presented a marked loss of body weight plus low levels of plasma protein and albumin concentration. Their livers showed diffuse fatty changes; most of the animals had moderate to severe fatty liver infiltration. They had a negative cumulative nitrogen balance; on the contrary, rats fed the 20% casein diet showed nitrogen retention. The animals of one of the two protein-deficient groups had a significant lower food intake than its control group. However, when food intake was related to animal body weight (g/100 g), the rates of rats on the 20% casein diet and those on protein-free diet were not significantly different.

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