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Pre- and post-natal protein deficiency in albino rats. I. Weight progression analysis.

Alterations in periodontal tissue were analyzed histologically in rats who had received a protein-deficient diet during intra-uterine life due to inadequate nutrition of the mothers and during the post-natal period due to the continuity of poor nutrition. The animals were weighed at sacrifice: 0, 1, 4, 11, 17, 21, 42, 50 and 105 days. Histological data comparing the undernourished and control groups will be the objective of a future publication. This first part reports the statistical analysis of weight progression of the two groups, concerning not only the mean weight, but also the individual weight of each animal at the various sacrifice periods. Weight progression was gradual and proportional in each group, despite the fact that the control group had accentuated weight gain, deviating, with time, from the weight of the undernourished group of the same age.

Age Factors↗

Sodium cyanate alters glutathione homeostasis in rodent brain: relationship to neurodegenerative diseases in protein-deficient malnourished populations in Africa.

Sodium cyanate, a neurotoxic chemical in rodents, primates and humans, is implicated in neurodegenerative disorders in protein-deficient populations subsisting in parts of Africa on the cyanogenic plant cassava. The molecular and cellular mechanisms of cyanate neurotoxicity are not understood. This study investigates the effect of sodium cyanate on glutathione (GSH) homeostasis in rodent brain and liver in vitro and in vivo. GSH levels in mouse brain were rapidly, time- and dose-dependently decreased following intraperitoneal administration of 100, 200 or 300 mg/kg sodium cyanate. By contrast, GSH disulfide (GSSG) levels were increased and GSH/GSSG ratios were decreased in a dose-dependent manner in rat brain. Sodium cyanate depleted GSH levels in all regions of mouse brain. Brain glutathione reductase activity was dose-dependently inhibited, while glutathione peroxidase activity was not affected by sodium cyanate. The disruption of GSH homeotasis, as evidenced by reduced tissue GSH/GSSG ratios, likely results from cyanate-induced inhibition of glutathione reductase activity. The results of this study suggest that cyanate neurotoxicity, and perhaps cassava-associated neurodegenerative diseases, are mediated in part by disruption of glutathione homeostasis in neural tissue.

Africa↗

Effect of selenium and protein deficiency on selenium and glutathione peroxidase in rats.

Twenty-four weanling male Wistar rats were divided into four groups fed diets containing adequate or deficient levels of selenium (0.5 ppm [+Se] or < 0.02 ppm [-Se] and protein (15% [+Pro] or 5% [-Pro]), but adequate levels of all other nutrients for 4 wk to determine the effects of Se deficiency and protein deficiency on tissue Se and glutathione peroxidase (GSHPx) activity in rats. Plasma, heart, liver, and kidney Se and GSHPx were significantly lower in Se-deficient groups in relation to Se-sufficient groups. In Se-deficient groups, Se and GSHPx were significantly higher in -Se-Pro rats in heart, liver, and kidney. Data analysis showed that there were significant interaction effects between dietary Se and protein on Se and GSHPx of rats. It is assumed that under the condition of Se deficiency, a low level of protein may decrease Se and GSHPx utilization, increase GSHPx synthesis, and result in Se redistribution. This could account for high levels of Se and GSHPx in the -Se-Pro rats compared to -Se+Pro rats.

Analysis of Variance↗

Partial hypoparathyroidism associated with mitochondrial trifunctional protein deficiency.

The mitochondrial trifunctional protein (MTP) catalyzes the last three steps in the long-chain fatty acid beta-oxidation pathway. We report herein a patient with an inherited MTP deficiency and hypoparathyroidism that were both revealed at 4 months of age. Although parathyroid function appeared to be normalized following nutritional management of the fatty acid beta-oxidation defect, persistent gland dysfunction was suggested by frequent mild episodes of hypocalcaemia without increase in plasma intact parathyroid hormone (iPTH) levels during recurrent fasting-induced episodes of rhabdomyolysis and by our finding of a bilateral cataract at 5 years of age. An acute provocation test conducted to stimulate iPTH release with sodium bicarbonate infusion resulted in a subnormal rise in iPTH release, which further supported a partial hypoparathyroidism. This case is the third report of inherited MTP deficiency associated with hypoparathyroidism, thus raising the possibility of a link between these two rare disorders.

Calcium↗

Lymphopoiesis in protein deficiency. Stathmokinetic and tritiated thymidine uptake studies of the mesenteric lymph node of the guinea pig.

In view of the depressed immunity in protein malnutrition, an assessment of the lymphoproliferative activity of the constantly stimulated mesenteric lymph node of the guinea pig was undertaken. A significant reduction of this activity was observed in protein deficiency. a) The germinal centers were reduced in number and size; new formation in the medulla was rarely seen. Lymphoid cells showed lowering of mitotic index and mitotic rate and prolongation of mitotic duration and turnover time. Nuclear labeling with (3)H-thymidine was focal and localized to the peripheral zone. b) Mitotic activity and nuclear labeling were less pronounced in the outer cortex and medulla and least in the paracortical area. Specific uptake of (3)H-thymidine paralleled the low labeling index. c) No appreciable reduction in the number of plasma cells in the medulla was observed. Serum gamma-globulin levels were not significantly altered, but albumin levels were consistently reduced. This was suggestive of preferential preservation of plasma cell activity in the malnourished host. d) There were significant lymphopenia and neutropenia with relative increase of neutrophils in the peripheral blood. This might indicate more severe involvement of lymphopoiesis than myelopoiesis in protein malnutrition.

Animals↗

Acetylcholinesterase activity in Nippostrongylus brasiliensis during the course of a primary infection in normal and in protein-deficient rats.

Acetylcholinesterase (AChE) activity was measured in Nippostrongylus brasiliensis recovered during the course of a primary infection in normal and in protein-deficient rats. In well-nourished rats the amount of AChE present in N. brasiliensis increased as the infection progressed, concomitant with the development of the humoral response. In malnourished rats, there was a similar and parallel increase in the amount of AChE synthesized by worms between days 7 and 13 of the infection but as the infection progressed enzyme production decreased so that, by day 26 of the infection, the nematodes contained approximately the same amount of AChE as 8-day-old worms. The possible reasons for this change in enzyme production are discussed.

Acetylcholinesterase↗

Marginal protein deficiency in pregnant rats. Changes in offspring body composition.

The influence of protein on some biochemical parameters in the liver, brain and plasma of rats at weaning was studied. The tissue parameters studied were the amounts of DNA, RNA and protein in the liver and brain. For the plasma, the parameters studied were the total amount of protein and the ratio of non-essential to essential amino acids (ratio NE/E). During the gestation and lactation period, the rats were divided into three groups according to the diet received: group 1, 20% casein; group 2, 8% casein; and group 3, 8% corn. As a result we can assert that groups 2 and 3, fed on hypoprotein diets, were seriously compromised in body weight and in the biochemical parameters and these alteration were enhanced by the corn diet. These results suggest that the alterations depend on the duration and intensity of the malnourishment and that the quality of the protein is an important factor to be considered.

Animals↗

Growth hormone responses in isolated protein deficiency state in rhesus monkey.

We have longitudinally studied the effects of protein-deficient diet on serum growth hormone (GH) concentration in rhesus monkey. A biphasic basal GH response and a phenomenon of failure to suppress GH levels after glucose administration were observed in animals fed diet lacking proteins. GH levels remained consistently elevated in protein-deprived monkeys. Whether these elevations in GH will have any deleterious influence on the host remains to be seen.

Animals↗

Dietary protein deficiency and Mycobacterium bovis BCG affect interleukin-2 activity in experimental pulmonary tuberculosis.

Inbred strain 2 guinea pigs were vaccinated with Mycobacterium bovis BCG or were left unvaccinated. They were maintained for 6 weeks on defined, isocaloric diets containing either 30% (control animals) or 10% (animals receiving low protein) ovalbumin as the sole protein source. Animals were challenged by the respiratory route with a low dose of virulent M. tuberculosis H37Rv and killed 4 weeks later. Protein-malnourished animals were not protected by previous vaccination with BCG. Lymphocytes isolated from various tissues were tested in vitro for proliferative responses to mitogen (concanavalin A) and antigen (purified protein derivative [PPD]), production of interleukin-2 (IL-2), and response to exogenous recombinant IL-2 (rIL-2). Protein-malnourished guinea pigs responded only weakly to PPD skin tests, and their blood and lymph node lymphocytes exhibited impaired proliferation when cultured with PPD in vitro. IL-2 levels were consistently low in cultures of stimulated blood and spleen lymphocytes from protein-deprived animals. BCG vaccination of nutritionally normal guinea pigs, on the other hand, induced significantly more IL-2 production by PPD- and concanavalin A-stimulated lymphocytes. The addition of exogenous mouse rIL-2 (40 and 80 U/ml) in vitro to PPD-stimulated blood and lymph node cells from nonvaccinated, protein-deprived guinea pigs resulted in no improvement of the proliferative response. Previous vaccination of malnourished guinea pigs did not consistently enhance the response of PPD-stimulated lymphocytes to added rIL-2. Dietary protein deficiency and BCG vaccination appear to modulate antigen-driven cellular immunity in animals with tuberculosis by altering the production of, and the response to, IL-2 by PPD-stimulated lymphocytes.

Animals↗

Carbohydrate absorption in the young of protein-deficient rats.

The absorption of 3-O-methylglucose (TMG) and of lactose has been studied in the young of female rats fed a protein-deficient diet during pregnancy. Postnatally, these young were suckled by stock diet-fed dams. Intestines of newborn, 4-day and 12-day old pups were infused in situ with 5% TMG or 3.5% lactose. The mean amount retained per enterocyte was measured as well as the mean amount absorbed from the lumen and transferred from the enterocyte. Absorption of lactose was reduced in the enterocytes of newborn prenatally protein-deprived (PPD) young but not postnatally, while TMG absorption was normal at birth and 12 days but reduced at 4 days. The amount of carbohydrates absorbed in total or per unit intestinal weight seemed to vary with changes in the number of absorptive cells. It is suggested that reduced absorption in PPD pups is primarily related to the smaller number of absorptive cells in these young. There is a greater increase in numbers of cells and in absorption per cell between birth and 12 days in PPD young than in controls, indicating that the effect on the intestine of prenatal protein deprived young is at least partially reversible.

Age Factors↗

Osteopontin upregulation and polymerization by transglutaminase 2 in calcified arteries of Matrix Gla protein-deficient mice.

Matrix Gla protein (MGP) is a potent inhibitor of soft tissue calcification, and Mgp gene deletion in mice results in arterial calcification. Our aim was to examine osteopontin (OPN) expression and localization, and posttranslational processing of OPN by the crosslinking enzyme transglutaminase 2 (TG2), in the calcified aorta of Mgp-deficient (Mgp(-/-)) mice. Using immunohistochemistry and light and electron microscopy, we report that following mineralization occurring in the arterial media of Mgp(-/-) aortas, OPN is upregulated and accumulates at the surface of the calcified elastic lamellae. Macrophages were observed in direct contact with this OPN-rich layer. Western blot analysis of extracted Mgp(-/-) aortas revealed that the majority of the OPN was in high molecular mass protein complexes, indicating modification by a crosslinking enzyme. Consistent with this observation, TG2 expression and gamma-glutamyl-epsilon-lysyl crosslink levels were also increased in Mgp(-/-) aortas. In addition to the mineral-inhibiting actions of OPN, and based on data linking OPN and TG2 with cell adhesion in various cell types including monocytes and macrophages, we propose that TG2 interactions with OPN lead to protein polymerization that facilitates macrophage adhesion to the calcified elastic lamellae to promote clearance of the ectopic mineral deposits.

Animals↗

Relationship between protein deficiency in the ration of rats during early ontogeny and function of enzyme systems of digestive and non-digestive organs in adult life.

Low protein content in the ration of rat pups during transfer from mixed to definitive nutrition (days 21-30 of life) has a negative impact on digestive function of the small intestine and trophic and barrier functions of the large intestine, liver, and kidneys and increases (sucrase, glycyl-L-leucin dipeptidase) or decreases (alkaline phosphatase, aminopeptidase M, glycyl-L-leucine dipeptidase) enzyme activities in these organs in 6-month-old rats. Protein deficiency during the early ontogeny modulates functioning of the enzyme systems in digestive and non-digestive organs in adult life, which can lead to the development of not only gastrointestinal, but other visceral diseases.

Alkaline Phosphatase↗

Lipid absorption in the young of protein-deficient rats.

The effect of reduced protein in the diet during pregnancy on the subsequent absorption of triolein and of oleic acid which were infused into the intestine of the young was studied. Pregnant rats were fed diets containing either 24% or 4% casein as the sole source of protein. Control and prenatally protein-deprived (PPD) young were studied at birth before and after suckling, and at 4, 8, and 12 days. Both body weight and the weight and length of intestine were reduced in PPD young. Uptake of triolein from the lumen and retention in enterocytes increased on suckling in newborn control pups, but the amount transferred from or metabolized by the cells did not change. In suckled PPD young, transfer of triolein increased through the enterocyte as well. Unsuckled PPD pups had reduced absorption and retention per enterocyte, per g body weight, per cm gut, and in total. In intestines of control and PPD suckled newborn and postnatal pups, absorption per cell did not differ. Blood lipid levels were increased markedly between 0 and 14 days and tended to decrease to newborn levels by 12 days in both diet groups. Oleic acid absorption in newborn and 12-day PPD pups were reduced in total, per g body weight and per cm of gut. The individual enterocytes were shown to be equally capable of absorption and transfer of triolein and oleic acid. Differences in absorption are related primarily to the numbers of absorptive cells.

Aging↗

[Enzymes of the oral mucosa in rats with protein deficiency].

In rats receiving a protein-poor diet for 60 days (4% caloric share of casein) the activity of beta-galactosidase, beta-N-acetyl glucose aminidase, acid proteinases, acid phosphatase, acetyl estherase, catalase, glutathione reductase, monoamine oxidase (MAO), glucose-6-phosphate dehydrogenase, and the content of malonic dialdehyde (MDA) were measured in the oral cavity mucosa. The authors observed the significant increase in MAO activity, and decrease in activities of beta-N-acetyl glucose aminidase, acetyl estherase, catalase, glutathione reductase, increased MDA contents. The changes in enzymatic activities had, to a several extent, an adaptive nature and were related to their reduced biosynthesis.

Animals↗