The determination of nutritional requirements in rats: mathematical modeling of sigmoidal, inhibited nutrient-response curves.

The Saturation Kinetics Model (SKM) is useful in describing many physiological responses as functions of a limiting dietary nutrient. However, as nutrients are fed at higher dietary concentrations, responses become inhibited and diminish from their usual plateaus. By adding an inhibition constant (Ks) to the SKM in a manner consistent with substrate inhibition (based on enzyme kinetics), it becomes possible to predict the inhibited portions of the nutrient-response curve. To test this, rats were fed diets of graded levels of casein (0-75%) or lysine (0-6.2%), and weight gains and food intakes were measured daily for up to 2 wk. The inhibition form of the SKM was able to predict the complete response range of each experiment, producing a Ks (weight gain) at a dietary level of 50.60% for casein and 7.56% for lysine. It was also possible to set up an upper and lower dietary nutrient concentration that encompassed the 100% response range for each response, thereby giving an inhibition or toxicity index of 2.02 for casein and 4.98 for lysine. This index allows one to set nutritional requirement levels precisely, optimizing responses without moving into inhibiting or toxic ranges of nutrients. Based on growth response curves, requirements were 25.61% for casein and 1.97% for lysine.

Influence of dietary protein deficiency on lead-copper interaction in rats.

The influence of dietary protein deficiency on the effects of exposure to lead or its combination with copper was investigated in rats. The administration of lead (100 ppm in drinking water) inhibited the activity of blood delta-aminolevulinic acid dehydratase; decreased hemoglobin, brain dopamine, and 5-hydroxytryptamine; and increased urinary excretion of delta-aminolevulinic acid, blood zinc protoporphyrin, and tissue accumulation of lead more markedly in animals fed a protein-deficient diet (10% casein) than in those fed a normal diet (21% casein). The simultaneous supplementation of copper (100 ppm in diet) reduced some of the lead-induced alterations and body uptake of lead more efficiently in animals fed a normal diet than in those fed a protein-deficient diet, which shows that the beneficial effects of copper in lead toxicity are adversely affected by low dietary protein.

Effects on the fetus of maternal benomyl exposure in the protein-deprived rat.

The separate and combined effects of protein deprivation and benomyl [(methyl 1-butylcarbomoyl)-2-benzimidazole carbamate] exposure were studied in the pregnant rat fed a diet containing 24% (control) or 8% (deficient) casein throughout gestation. Within each diet group, subgroups were gavaged at 31.2 mg/kg body weight with benomyl or corn-oil carrier only on d 7-16 or 7-21 of gestation. No effects on the skeleton were seen. Benomyl exposure in the last 2 wk in dams fed the 24% casein diet resulted in a high incidence of fetal brain anomalies. This effect did not occur in those with benomyl exposure during the period of organogenesis only and was reduced in groups fed the protein-deficient diet. Exposure to benomyl in the last 2 wk in the protein-deprived rat resulted in a decrease in the weight of the fetal heart in excess of that attributable to diet alone. Lungs were a smaller portion of body weight in fetuses of benomyl-treated dams in both diet groups. The teratogenic effect on the brain in animals exposed to benomyl in wk 2 and 3 of gestation suggests that screening for teratogenic effects during organogenesis only may be insufficient.

Effects of postnatal protein undernutrition on myelination in rat brain.

Pups were subjected, from birth, to protein undernutrition by feeding the lactating dams 8% casein (CS) or 8% soy protein (SP) diet up to weaning; the weanlings were fed the same diets until 6 weeks of age. At 3 and 6 weeks of age, myelin was isolated from the brains and characterized. The quantities of myelin and its content of cholesterol, galactolipids and phospholipids, were significantly depressed in the 8% CS and 8% SP groups but not when soy protein was fed at the same level as casein (25%) in the control. Furthermore, the severity of the deficits in myelination showed a differential pattern depending on the type of dietary protein fed. At weaning, the deficits with the 8% SP diet were 1.5-2.0-times greater than with the corresponding casein diet. A more pronounced retardation in the initiation, progression and capacity of myelination in postnatal soy protein undernutrition was indicated.

Variación en niveles de hormonas tiroideas circulantes en ratas sometidas a dietas de restricción alimenticia y a dietas hipoproteicas de caseína / Variation in thyroid hormones circulating levels in rats subjected to food restriction and low protein diets of casein

Grupos de ratas sometidas durante 20 días, a dieta de restricción alimenticia, en las cuales se redujo en contenido total de alimento suministrado a 8 gr diarios de Ratarina, fueron comparados con contoles con dieta ad libitum, observándose una reducción significativa de los valores plasmáticos de T3 y T4 en los grupos con restricción alimenticia. En grupos de ratas que fueron realimentadas ad libitum después de 20 días de dieta, se observó después de 5 días, una recuperación de los valores de T4, los cuales se aproximaron a los valores basales, no así para T3 que muestra una recuperación más lenta. Las dietas hipopoteicas ad libitum de caseina al 5 y 10%, ricas en hidratos de carbono, muestran valores significativamente aumentados de T3, en relación con el alto contenido de hidratos de carbono de la dieta, y su bajo contenido de proteinas (Caseina). Ratas tiroidectomizadas sirvieron de control para valores bajos de función tiroidea en los parámetros estudiados, los cuales incluyeron además, control de peso, talla, ingesta de agua y alimento y excreción de orina. Se midió el peso de la glándula tiroides, su captación de I-3- y los resultados de estos últimos, sometidos a discusión en relación a los valores obtenidos de hormonas tiroideas circulantes

Alteration of cell-mediated immunity to Listeria monocytogenes in protein-malnourished mice treated with thymosin fraction V.

Cell-mediated immune reactivity, measured by lymphocyte responsiveness to phytohemagglutinin, was higher in both young or aged mice fed a 4% casein diet compared with age-matched controls. Treatment in vivo with bovine thymosin fraction V decreased the responsiveness to phytohemagglutinin of lymphocytes from mice fed either the control or moderately protein-deficient diets when compared with mice treated in vivo with saline. Resistance against Listeria monocytogenes, known to be a cell-mediated immune function, was impaired in young and aged mice which were fed the low-protein diet. Treatment with thymosin was able to significantly improve the cell-mediated immune resistance to L. monocytogenes of moderately protein-malnourished mice. Thymosin treatment impaired the resistance to L. monocytogenes of young or aged mice fed the control diet. The splenic natural killer cell cytotoxicity of protein-malnourished mice was impaired compared with that of mice fed the control diet. Treatment with thymosin did not restore the natural killer cell cytotoxic activity in protein-malnourished mice, but did enhance that activity in control mice.

The effect of a low protein diet on the immunogenic activity of murine peritoneal macrophages.

The activity of resident and exudate peritoneal macrophages from mice maintained on a low protein diet (4% casein initiated at weaning) was assessed in a variety of assay systems which examined aspects of macrophage 'immunogenic' function in vivo and in vitro. Antigen-pulsed macrophages from malnourished mice triggered secondary IgE and IgG responses following intraperitoneal inoculation into pre-immunized syngeneic recipients. Similarly, intraperitoneal transfer of low numbers of these cells successfully primed immunologically naive syngeneic mice; in both cases, the activity of macrophages from malnourished mice could not be distinguished from these derived from normal animals. Examination of uptake and breakdown of radio-labelled antigen revealed normal rates of phagocytosis, and a brief lag in the early phase of degradation, relative to control macrophages. Antigen-pulsed macrophages from malnourished mice were severely impaired in their capacity to trigger the proliferation of antigen-primed T cells in vitro.