Acid Deficiency Research Articles

Relationships between dietary ascorbic acid status and deficiency, weight gain and brain neurotransmitter levels in juvenile rainbow trout,Salmo gairdneri

A study was conducted to determine the interrelationships between dietary ascorbic acid (AA) concentrations, brain neurotransmitter levels and weight gain in juvenile rainbow trout. At the end of 4 weeks and until the end of 12 weeks of feeding test diets of varying AA concentrations (0-320 mg AA/kg diet), increased weight gain was noted in fish fed the AA-free diet. However, by the end of 13 weeks and until the end of the experiment this phenomenon was no longer evident; instead the fish showed the more classical deficiency signs of anorexia and decreased weight gain. After 12 and 24 weeks, there were no significant differences in brain serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE) or dopamine (DA) between fish reared on the different test diets. However, after 12 weeks of feeding the test diets, brain 5-HT, brain AA and weight gain were significantly correlated with one another. No such relationships were found for brain NE or brain DA. After 24 weeks of feeding the diets, the relationships between brain 5-HT, brain AA and weight gain were no longer apparent. Similarly, after 24 weeks brain NE and DA were also unrelated to brain AA and weight gain. These results provide evidence that in very young rainbow trout, AA deficiency, brain 5-HT levels and weight gain were related. However in fish reared on the diets for 24 weeks these relationships were no longer evident.

Lung injury caused by cobra venom factor is reduced in rats raised on an essential fatty acid-deficient diet

Arachidonate metabolites appear to be involved in lung injury caused by cobra venom factor (CVF)-induced complement and polymorphonuclear leukocyte (PMN) activation. These studies were designed to assess the effects of a dietary-induced deficiency of arachidonic acid on CVF-induced lung injury. Rats raised on an essential fatty acid-deficient (EFAD) diet exhibited the expected changes in fatty acid composition including decreased plasma levels of arachidonic acid and increased levels of 5,8,11-eicosatrienoic acid. In intact rats raised on the EFAD diet, CVF-induced lung injury was attenuated. When blood and excised lungs from rats raised on the normal diet were used, CVF caused pulmonary vascular constriction and acute lung injury, as evidenced by increased 125I-labeled bovine serum albumin accumulation in lung parenchyma and alveolar lavage fluid. The CVF-induced pulmonary artery pressor response and lung injury were reduced when blood perfusate or blood perfusate and excised lungs were obtained from rats raised on the EFAD diet. The pulmonary vascular constriction and lung injury were not attenuated when the blood perfusate was obtained from rats raised on the normal diet, irrespective of whether the excised lungs were obtained from rats raised on the normal or EFAD diet. PMNs obtained from rats raised on the EFAD diet demonstrated decreased superoxide production as well as impaired random migration and chemotaxis in vitro. In contrast, beta-glucuronidase release was quantitatively similar to PMNs from control rats. These data indicate that the EFAD diet-induced attenuation of CVF-induced pulmonary hypertension and acute lung injury is due to defective effector cells in blood rather than modified pulmonary target tissue.

Anorexia of rats for a diet with deficiency of an essential l-amino acid, lysine, and its appetite

Anorexia of rats for a diet with deficiency of an essential l-amino acid, lysine, and its appetite

Increased plasma triglyceride secretion in EFA-deficient rats fed diets with or without saturated fat.

Metabolic responses to essential fatty acid-deficiency in rats include an increased rate of triglyceride secretion into the plasma, a large reduction in the HDL1 plasma lipoprotein concentration, and increased concentrations of liver triacylglycerols and cholesteryl esters. Because of differences in the types of EFA-deficient diets used, it is not clear whether these responses were solely due to the absence of EFA from the diet or whether saturated fat, or differences in acyl group chain length in this fat, might be responsible. Therefore, we fed rats diets differing only in amounts and kinds of fat, and measured triacylglycerol secretion rates and liver concentrations of triacylglycerols and cholesteryl esters, for comparison with our earlier measurements of plasma high density lipoprotein subpopulations in rats fed exactly the same diets. The purified diets contained either no fat, 5% by weight hydrogenated coconut oil, 5% hydrogenated cottonseed oil, or each of these three diets supplemented with 1% safflower oil, or 5% corn oil. We also fed some rats a nonpurified stock diet for comparison with literature reports. The present results indicate that the metabolic responses to essential fatty acid deficiency described above are definitely due to essential fatty acid-deficiency and not to the presence or chain length of acyl groups in saturated fat in the diet.

Two Cases of Cystic Fibrosis in Japanese Children: Studies on the Essential Fatty Acid and Prostaglandin Metabolism

We describe the fatty acid (FA) and prostaglandin (PG) metabolism in two Japanese cases of cystic fibrosis (CF) with or without pancreatic insufficiency (PI). The diagnosis of CF was based on the elevated sweat chloride concentration by pilocarpine iontophoresis. A 1-month-old boy (case 1) showed poor weight gain, steatorrhea and scaly dermatitis, but no respiratory symptoms were noted. He had decreased levels of serum linoleate and arachidonate, and increased palmitoleate and oleate levels, indicating essential fatty acid (EFA) deficiency. Supplementation of fat-emulsion improved his skin lesions and the altered FA pattern within a few months, associated with the definite reduction of the urinary PG F2 alpha levels. Until two years of age, he has been free from respiratory symptoms. A 12-year-old girl (case 2) had had recurrent respiratory tract infections due to Pseudomonas aeruginosa and Staphylococcus aureus for several years, and her pancreatic functions were preserved. The FA patterns of her serum lipid were almost within the normal range. These results indicate that 1) the altered FA composition appeared to be a secondary consequence of PI commonly complicating CF and 2) the correction of the altered FA and PG metabolism might have a beneficial effect on the respiratory function of CF patients with EFA deficiency.

The effects of fishmeal and postruminal glucose on the intake and digestion of low-quality herbages by grazing cattle in southern Australia

The intake and digestion of barley stubble and mature pasture were studied in grazing cattle given no supplement or supplements of fishmeal (800 g day-1 per rumen) or fishmeal (800 g day-1 per rumen) plus glucose (500 g day-1 per abomasum). Herbage intake was unaffected by supplements but was greater on pasture than stubble (P<0.001). While fishmeal increased ammonia levels above the basal level of 90 mg 1-1 , the flow of bacterial nitrogen was not increased. Bacterial efficiency (g bacterial nitrogen per kg dry matter apparently digested in the rumen) was 26 and 15 at pasture and stubble, respectively (P< 0.008), and was uninfluenced by supplementation with fishmeal. Similarly, the bacterial nitrogen content and the ratio of diaminopimelic acid to total nitrogen in the bacteria was unaffected by supplementation. Total non-ammonia nitrogen flow and the flow of essential amino acids from the rumen were greater at pasture than stubble (P<0.003) and were increased by fishmeal supplement (P<0.01). Plasma glucose was significantly affected by herbage type but not by supplement (P>0.05). Plasma insulin was not significantly altered by either herbage or supplement. It is concluded that large quantities of postruminal energy and protein supplements can be given to grazing cattle with no detrimental effects on herbage intake and utilization. Further work should be conducted to identify the cause of an apparent inefficiency of bacterial efficiency in cattle on low-quality stubble. It did not appear to result from a deficiency of either ammonia or branch-chain fatty acids.

Evidence for an increased secretory capacity for dehydroepiandrosterone-sulphate in the pantothenic acid-deficient rat associated with an impaired adrenal cholesterol deposition.

The adrenal capacity to store cholesterol and to secrete corticosterone, androstenedione, and dehydroepiandrosterone-sulphate (DHEA-S) was investigated following long- and short-term adrenocor-ticotropic hormone (ACTH) stimulation of growing male rats kept on a pantothenic acid-deficient (PAD) diet for about two months. After chronic treatment with ACTH1-24, the pantothenic acid-deficient rats revealed a drastic impairment in adrenal cholesterol storage compared with ad libitum and pair-weight fed control groups. However, corticosteroid plasma responses to short-term as well as to prolonged ACTH stimulation were normal or in the case of DHEA-S, even significantly increased in pantothenic acid deficiency. The elevated secretory capacity for this androgen sulphate was also discernible in an exaggerated renal DHEA-S excretion in PAD rats under ACTH1-24 hyperstimulation. According to the results of a further hormonal study involving metyrapone administration, a PAD-associated increase in specific enzyme activities of the post-pregnenolone pathway of androgen synthesis was excluded as the reason for the DHEA-S hypersecretion. The experimental findings are discussed with regard to a PAD-induced tissue CoA decrease and its consequences for adrenal cholesterol metabolism and steroid hormone secretion. A concept is presented that takes into account the functional differences in the zona fasciculata and the zona reticularis of the adrenal cortex in order to explain the phenomenon of the abnormal capacity of rats to secrete DHEA-S in pantothenic acid deficiency.

Purification and Characterization of an Incompletely Glycosylated Form of Human Chorionic Gonadotropin from Human Placenta*

A small form of hCG (SP-hCG) was purified from an acetone powder preparation of human first trimester placenta by repeated gel filtration and ion exchange chromatography on a Q-Sepharose or FPLC Mono Q column. The estimated mol wt (Mr) of the small hCG by gel filtration is 43K compared to 58K for authentic hCG. The pI of SP-hCG is 10.0, suggesting deficiency of sialic acids. SP-hCG dissociates into subunits when treated with 6 M guanidine-HCl or analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Two beta-subunits of SP-hCG were found with estimated Mr of 23K and 20K. Both are distinctly smaller than authentic hCG beta. A single alpha-subunit was found, with an estimated Mr of 21 K. The immunoactivity (8,900-10,000 IU/mg) of highly purified SP-hCG was comparable to that of reference hCG (CR119) determined by a RIA method using anti-hCG antibodies. The hCG/LH receptor-binding activity of SP-hCG is equivalent to that of reference hCG (CR119). Its biological activity is lower than that of reference hCG (approximately 30% or more) assayed by the in vitro stimulation of rat Leydig cells to produce testosterone and cAMP. A high dose is required to attain the same level of stimulation as reference hCG. The amino acid composition of SP-hCG is similar to that of reference hCG, whereas its hexsamine content is significantly lower. Its glucosamine content is about half that in reference hCG, while it completely lacks galactosamine. These findings suggest that SP-hCG is deficient in O-linked oligosaccharide chain in the beta-subunit, and that the N-linked oligosaccharide chains of both subunits are shortened. SP-hCG is one of the principal forms of the hormone present in first trimester placenta and may be a key intermediate in the posttranslational biosynthesis of hCG. Although it lacks O-linked sugar chains and shortened N-linked sugar chains, it possesses substantial biological activity. To have full biological activity, the hCG molecule must contain the complete complement of sugar chains.

Deficiency of ascorbic acid in experimental diabetes. Relationship with collagen and polyol pathway abnormalities

Deficiency of ascorbic acid in experimental diabetes. Relationship with collagen and polyol pathway abnormalities

Increased vascular reactivity induced by essential fatty acid deficiency in rat autoperfused hindquarters

The effects of essential fatty acid deficiency (EFAD) on vascular reactivity to vasoconstrictor stimuli were studied in rat autoperfused hindquarters. Weanling male Sprague-Dawley rats (aged 21 days) were fed diets containing 8% (weight/weight) of stearax plus 2% safflower oil (control diet) or 10% stearax (EFAD diet) for 8 weeks. There was no difference in systemic blood pressure or body weight between the two groups. Basal production of immunoreactive 6-keto-PGF1 alpha by aortic segments was much less in EFAD aortae than in control aortae. In contrast, immunoreactive 6-keto-PGF1 alpha produced by incubating aortic segments with exogenous arachidonic acid (12 mumol/l) was much greater in EFAD aortae than in control aortae. Moreover, conversion of [14C]-arachidonate to [14C]-6-keto-PGF1 alpha was more pronounced in EFAD aortae than in control aortae. Vasoconstrictor responses to noradrenaline (0.01-1.0 mumol/l) and angiotensin II (0.001-1.0 mumol/l) infused into the blood perfused hindquarters were then examined. The rats on the EFAD diet were more sensitive to both noradrenaline and angiotensin II than rats on the control diet (P less than 0.05, two-way ANOVA). Thus, a deficiency of essential fatty acids can lead to increased vascular sensitivity to vasoconstrictor stimuli. Deficiency of arachidonic acid in phospholipid stores is also accompanied by augmented cyclo-oxygenase activity in the vessel wall, similar to that observed previously in spontaneously hypertensive rats (SHR) and rats with one kidney renovascular hypertension.

Effects of dietary supplement of methionine and lysine on blood parameters and fur quality in blue fox during low-protein feeding

Four groups of blue fox (Alopex Lagopus) were fed from weaning to pelting with feed of two different protein levels. The metabolizable energy (ME) from protein amounted to 35/30 % in the control group and to 22/18 % in three low-protein groups during the early and late growth period, respectively. One of the low-protein groups received an unsupplemented diet. The second low-protein diet was fortified with methionine, and the third with methionine and lysine to the same level as in the control diet. Hematological values, urea and creatinine were lower in all low-protein groups as compared to the control group. The activities of amino acid metabolizing enzymes ASAT, ALAT and GOT in plasma were lower in the low-protein groups although the relative sizes of the liver and kidneys were greater. The lowered protein content in the feed was sufficient for growth, and only a slight negative effect on fur characteristics was observed. The dietary supplementation of methionine and lysine yielded no improvement in the fur quality or other parameters as compared to the unsupplemented low-protein feed, indicating that there was no deficiency of these amino acids in these low-protein feeds.

Ascorbic acid requirement and assessment of ascorbate status in the common marmoset (Callithrix jacchus).

Marmosets can tolerate an ascorbic acid (AA) deficiency for several weeks without clinical symptoms. After being fed an AA-free diet for 3 months, nonspecific deficiency symptoms became obvious. Different dietary levels of AA resulted in corresponding serum ascorbate levels. The kidney threshold of AA in marmosets is comparable to that in humans. When the minimal AA requirement is defined as the amount that is necessary to maintain a serum AA level above the kidney threshold, then about 20 mg AA/kg body weight is needed. This intake was achieved in our trial with a diet containing 500 ppm AA. Thus, the AA requirement of marmosets is severalfold higher than the AA requirement of humans.

Plasma and erythrocyte essential fatty acids during total parenteral nutrition in infants: effects of a cutaneous supply.

In order to prevent essential fatty acid (EFA) deficiency induced by fat-free total parenteral nutrition (TPN), 10 infants on TPN were rubbed three times daily for 20 days using oenethera oil (80% EFA). Total EFA amount provided cutaneously was 1900 mg/kg/d. Plasma and red blood cells phospholipids were determined on days 1 and 20 in these 10 treated and six untreated infants on TPN and compared with those of normal control infants. On day 1, plasma nonessential FA including 20:3 n-9(p less than 0.01) were increased in both TPN groups while 18:2 n-6 and 18:3 n-3 (p less than 0.001 and p less than 0.01) were decreased. On the 20th day, EFA deficiency had worsened with a decrease in plasma level of 20:4 n-6 (p less than 0.02) and a higher than normal triene/tetraene ratio : 3.4 +/- 1.1 and 2.3 +/- 0.6 vs 0.1 +/- 0.1 (p less than 0.02). As for red blood cells phospholipids, 16:0 was increased and 18:2 n-6 and 20:3 n-6 were decreased (p less than 0.05) on day 1. On day 20, these FA were more abnormal while 20:3 n-9 became significantly increased (p less than 0.05). No difference was observed between the TPN groups at any time. These results show that cutaneous application of large amounts of EFA-rich oil is unable to prevent or cure TPN induced EFA deficiency.

Influence of Selected Amino Acid Deficiencies on Somatomedin, Growth and Glycosaminoglycan Metabolism in Weanling Rats

The effects of lysine-, methionine- or histidine-deficient diets compared to a control diet fed ad libitum or 15, 10 or 5 g/d were studied in weanling rats. Feed intake was 5–7 g/d for the amino acid-deficient animals. After 3 wk, all amino acid-deficient rats had lost more weight (P < 0.01) than the controls fed at comparable energy levels. Serum somatomedin (Sm) activity was significantly decreased in lysine- (0.55 U/ml), methionine- (0.32 U/ml) and histidine-deficient (0.38 U/ml) rats compared to rats fed the control diet ad libitum (1.6 U/ml). Differences between amino acid-deficient and calorie-restricted animals were not significant. A similar response was observed in 35SO4 uptake by cartilage glycosaminoglycans (GAG). Caloric restriction and amino acid deficiency each resulted in lower 35SO4 uptake by cartilage GAG than occurred with ad libitum feeding, but there were no significant differences between the rats fed amino acid-deficient diets and those fed 5 or 10 g of the control diet. Compared to rats fed the control diet ad libitum, plasma growth hormone (GH) concentrations were lower in the rats fed 5 or 10 g of control diet per day and in those fed amino acid-deficient diets (P < 0.05), but GH concentrations were not consistent with the growth retardation observed. The results confirm that Sm and GAG activities are reduced in protein-energy restriction independent of GH. However, changes could not be attributed to specific deficiencies of lysine, methionine and/or histidine.

Elevated Levels of Dietary Ascorbic Acid Increase Immune Responses in Channel Catfish

Channel catfish fingerlings were fed purified diets containing 0 to 3000 mg/kg of ascorbic acid until external signs of scurvy were seen in the fish fed the ascorbic acid-deficient diet. At this time, resistance to bacterial infection, antibody production, complement activity and phagocytic activity were assessed for fish from the various dietary treatments. Mortality rates of fish experimentally infected with Edwardsiella ictaluri, the bacterium causing enteric septicemia in channel catfish, decreased with increases in dietary ascorbic acid doses, ranging from 100% for fish fed the ascorbic acid-deficient diet to 15% for fish fed 300 mg ascorbic acid per kilogram diet and 0 for fish fed 3000 mg ascorbic acid per kilogram diet. Antibody response to E. ictaluri antigen, hemolysis of sensitized sheep erythrocytes by complement activity and phagocytic engulfment of E. ictaluri by peripheral phagocytes were each impaired in fish fed the diet without supplemental ascorbic acid; intracellular bactericidal activity of the phagocytes was not affected by ascorbic acid deficiency. There were no differences in antibody production, complement activity, or phagocytic activities among fish fed diets containing 30–300 mg ascorbic acid/kg of diet. However, the dose level of 3000 mg ascorbic acid/kg significantly enhanced antibody production and complement activity.

Serum lipids and fatty acid composition of tissues in rats on total parenteral nutrition (TPN)

The modulating effect of energy and exogenous triglyceride supply on serum lipids and fatty acid composition of liver, tibialis anterior muscle, subcutaneous and peri-epididymal fat was assessed in rats using Total Parenteral Nutrition (TPN). Nutrients were infused continuously for 10 days through a central vein catheter. Four levels of fat were tested: No fat, Low fat (6% non-protein calories), Medium fat (30%) and High fat (60%), at 2 energy levels (270 kcal and 350 kcal/kg X day). An isonitrogenous supply was given to all groups as 0.9 g N/kg X day. At the highest level of fat intake (20.4 g/kg) at the high energy level triglycerides, cholesterol and phospholipids of serum were elevated. Biochemical signs of essential fatty acid (EFA) deficiency were observed as rising levels of eicosatrienoic acid and lowered concentrations of linoleic and arachidonic acid, mostly in the liver and the muscle in the No fat groups. EFA levels were reduced significantly in the No fat and Low fat groups and more pronounced at the high energy level. In conclusion, our study suggests that when energy intake is increased the EFA status becomes more critical. It seems evident that more EFA is required in absolute values when hypercaloric diets are given.

GM1-Gangliosidosis: a molecular abnormality of acid beta-galactosidase in fibroblasts.

G~l-Gangliosidosis is an inherited lysosomal disease with a deficiency of acid ~-gatactosidase activity causing generalized accumulation of ganglioside GM~ in somatic cells (Okada and O'Brien, 1968). The molecular structure of [3-galactosidase A was reported to be altered in this disease since liver samples from patients contained more than normal quantities of cross-reacting materials to antinormal liver [3-galactosidase A antibodies (Meisler and Rattazzi, 1974; O'Brien, 1975; BenYoseph et al., 1977). Recently, acid [3-galactosidase from human placenta was found to have highly reactive sulphydryl groups in the molecule closely associated with the enzyme activity (Furuya et al., unpublished data). Subsequently, a purification procedure was developed with Hg-agarose affinity chromatography utilizing a specific affinity to sulphydryl groups of this enzyme molecule. In this report acid J3-galactosidase was studied in GM1gangliosidosis fibroblasts with regard to -SH specificity for the investigation of molecular abnormality in this disease.

Lung surfactant and fatty acid composition of lung tissue and lavage of rats fed diets containing different lipids.

Two nutritional models, essential fatty acid (EFA) deficiency and the feeding of saturated vs unsaturated fats, were used to determine the effects of dietary lipids on the fatty acid composition of rat lung and lavage. Semipurified diets containing 7% corn oil, 7% hydrogenated coconut oil (EFA-deficient), 10% butter or 10% safflower oil were fed to dams during lactation and thereafter to their offspring for a total of 24 weeks. Lipids were extracted from the lung lavage and lung tissue and their fatty acid composition was determined. The content of dipalmitoylphosphatidylcholine (DPPC), the main surfactant in the lungs, was also determined. The results show that the levels of DPPC in the lungs of rats fed 10% butter decreased although the decrease in the EFA-deficient rats was greater. Comparing rats fed butter with those fed corn oil, there were also modifications in the fatty acid composition of the total lipids and phospholipids of lung tissue and lavage as well as in phosphatidyl-choline, phosphatidylethanolamine and phosphatidylinositol + phosphatidylserine fractions isolated from the lung tissue. The changes in fatty acid composition were somewhat fewer in rats fed butter then in those fed an EFA-deficient diet. The results suggest that a marginal EFA deficiency produced in rats by long-term feeding of 10% butter may account for the reduction in DPPC levels and in the changes in fatty acid composition in the lung tissue and lavage.

Physiological impairment in linoleic acid deficiency of rats and the effect of n-3 polyunsaturated fatty acids.

Some impairments related to membrane function were found in linoleic acid-deficient rats and the effects of fish oil feeding were investigated. In linoleic acid-deficient rats, glucose transport into erythrocytes was decreased. The concentrations of plasma free fatty acids were significantly reduced in the animals. Further, epinephrine-stimulated lipase was remarkably less sensitive to epinephrine in the deficient rat than in the corn oil-fed control rat. However, these impairments were relieved by fish oil feeding. Therefore, the impairments may be ascribed to the decrease of arachidonic acid as a polyunsaturated fatty acid in membrane phospholipids, since n-3 polyunsaturated fatty acids appear to take the place of arachidonic acid.

Effect of essential fatty acid deficiency on the epidermal sphingolipids of the rat

The epidermal sphingolipids from rats maintained on either a rat stock diet or a fat-free diet have been analyzed. Thin-layer Chromatographic analyses have revealed glucosylceramides, acylglucosylceramides and four fractions of ceramides, one of which proved to be an acylceramide. The relative amounts of the glucosylceramides, acylglucosylceramides and acylceramides were increased in the essential fatty acid-deficient epidermis while one ceramide fraction was diminished. The other two ceramide fractions remained unchanged. The acylceramides and acylglucosylceramides from normal rat epidermis both contained long-chain ω-hydroxy acids in amide linkage to sphingosine bases and high proportions of linoleic acid in ester linkage. The linoleate, which is known to be crucial for the formation and maintenance of the epidermal water barrier, was replaced by oleate in the essential fatty acid-deficient rats.