Dietary pantothenic acid depressed the gill immune and physical barrier function via NF-κB, TOR, Nrf2, p38MAPK and MLCK signaling pathways in grass carp (Ctenopharyngodon idella).

This study explored the effects of pantothenic acid (PA) on the immune and physical barrier function, and relative mRNA levels of signaling molecules in the gill of grass carp (Ctenopharyngodon idella). The results indicated that compared with optimal PA supplementation, PA deficiency (1.31 mg/kg diet) decreased gill interleukin 10, transforming growth factor ß1, inhibitor of κBα (IκBα), eIF4E-binding protein 2, Claudin b and ZO-1 mRNA levels; anti-superoxide anion activity, and activities and mRNA levels of copper/zinc superoxide dismutase, manganese superoxide dismutase, glutathione peroxidase, glutathione reductase and NF-E2-related factor (P < 0.05). Additionally, PA deficiency and excess (75.08 mg/kg diet) decreased gill complement 3 and glutathione contents, lysozyme and acid phosphatase, anti-hydroxy radical, catalase and glutathione S-transferases activities, and liver-expression antimicrobial peptide 2, hepcidin, Claudin 3, Claudin c and Occludin mRNA levels (P < 0.05). Conversely, PA deficiency increased gill reactive oxygen species and protein carbonyl contents, and interferon γ2, interleukin 8, nuclear factor kappa B P65, Claudin 15a, Kelch-like ECH-associating protein 1a and Kelch-like ECH-associating protein 1b mRNA levels (P<0.05). Moreover, PA deficiency and excess increased gill malondialdehyde content, and tumor necrosis factor α, interleukin 1ß, IκB kinase α, IκB kinase ß, IκB kinase γ, target of rapamycin and ribosomal S6 protein kinase1 p38 mitogen-activated protein kinases and myosin light-chain kinase mRNA levels (P<0.05). In conclusion, PA deficiency decreased immune and physical barrier function, and regulated relative mRNA levels of signaling molecules in fish gill. Based on the quadratic regression analysis of gill lysozyme activity, the optimal PA levels in grass carp (253.44-745.25 g) were estimated to be 36.97 mg/kg diet.

Dietary pantothenic acid deficiency and excess depress the growth, intestinal mucosal immune and physical functions by regulating NF-κB, TOR, Nrf2 and MLCK signaling pathways in grass carp (Ctenopharyngodon idella).

This study investigated the effects of dietary pantothenic acid (PA) on the growth, intestinal mucosal immune and physical barrier, and relative mRNA levels of signaling molecules in the intestine of grass carp (Ctenopharyngodon idella). A total of 540 grass carp (253.44 ± 0.69 g) were fed six diets with graded levels of PA (PA1, PA15, PA30, PA45, PA60 and PA75 diets) for 8 weeks. The results indicated that compared with PA deficiency (PA1 diet) and excess (PA75 diet) groups, optimal PA supplementation increased (P < 0.05): (1) percent weight gain (PWG), feed intake and feed efficiency; (2) lysozyme activity, complement 3 content, liver-expressed antimicrobial peptide 2 and hepcidin, interleukin 10, transforming growth factor ß1 and inhibitor of κBα mRNA levels in some intestinal segments; (3) activities and mRNA levels of copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferases and glutathione reductase, and NF-E2-related factor 2 (Nrf2) mRNA level in the whole intestine; (4) Claudin b, Claudin 3, Claudin c, Occludin and ZO-1 mRNA levels in some intestinal segments of grass carp. Conversely, optimal PA supplementation decreased (P < 0.05): (1) tumor necrosis factor α, interleukin 1ß, interferon γ2, interleukin 8, nuclear factor κB P65 (NF-κB P65), IκB kinase α, IκB kinase ß, IκB kinase γ and target of rapamycin (TOR) mRNA expression levels in some intestinal segments; (2) reactive oxygen species, malondialdehyde and protein carbonyl contents, and Kelch-like ECH-associating protein 1a, Kelch-like ECH-associating protein 1b in the intestine; (3) Claudin 12, Claudin 15a and myosin light-chain kinase (MLCK) mRNA levels in some intestinal segments of grass carp. In conclusion, optimum PA promoted growth, intestinal mucosal immune and physical function, as well as regulated mRNA levels of signaling molecules NF-κB P65, TOR, Nrf2 and MLCK in grass carp intestine. Based on the quadratic regression analysis of PWG and intestinal lysozyme activity, the optimal PA levels in grass carp (253.44-745.25 g) were estimated to be 37.73 mg/kg and 41.38 mg/kg diet, respectively.

Increased physical activity not decreased energy intake is associated with inpatient medical treatment for anorexia nervosa in adolescent females.

There is a dearth of data regarding changes in dietary intake and physical activity over time that lead to inpatient medical treatment for anorexia nervosa (AN). Without such data, more effective nutritional therapies for patients cannot be devised. This study was undertaken to describe changes in diet and physical activity that precede inpatient medical hospitalization for AN in female adolescents. This data can be used to understand factors contributing to medical instability in AN, and may advance rodent models of AN to investigate novel weight restoration strategies. It was hypothesized that hospitalization for AN would be associated with progressive energy restriction and increased physical activity over time. 20 females, 11-19 years (14.3±1.8 years), with restricting type AN, completed retrospective, self-report questionnaires to assess dietary intake and physical activity over the 6 month period prior to inpatient admission (food frequency questionnaire, Pediatric physical activity recall) and 1 week prior (24 hour food recall, modifiable activity questionnaire). Physical activity increased acutely prior to inpatient admission without any change in energy or macronutrient intake. However, there were significant changes in reported micronutrient intake causing inadequate intake of Vitamin A, Vitamin D, and pantothenic acid at 1 week versus high, potentially harmful, intake of Vitamin A over 6 months prior to admission. Subject report of significantly increased physical activity, not decreased energy intake, were associated with medical hospitalization for AN. Physical activity and Vitamin A and D intake should be carefully monitored following initial AN diagnosis, as markers of disease progression as to potentially minimize the risk of medical instability.

Preparation of a γ-glutamylcysteine-enriched yeast extract from a newly developed GSH2-deficient strain.

Gamma-glutamylcysteine (γ-GC), the precursor of glutathione (GSH), may have significant health benefits as a dietary supplement, but there are few cost-effective methods available for its large-scale production. We developed an efficient method for producing γ-GC in a mutant yeast strain using a three-step breeding procedure and a unique cultivation process. In the first breeding step, we prepared a glutathione synthetase (GSH2)-deficient yeast mutant. In the second step, selenate (SeO(4)(2-)) sensitivity was introduced by crossing the GSH2-deficient mutant with a strain harboring the met30 mutation. In the final step, pantothenic acid auxotrophy was introduced by ethyl methanesulfonate mutagenesis. The isolated strain displayed significantly enhanced cellular γ-GC when cultivated in synthetic medium without pantothenic acid, reaching a maximum level of 4.39% of dry cell weight. Using this strain, we were able to prepare a yeast extract containing approximately 13% γ-GC (w/w), which is markedly higher than the reported value (0.3%) of commercially available yeast extracts. The present method may facilitate large-scale γ-GC production for investigating the nutritive value and other benefits of dietary γ-GC.

[The separate and combined effects of calcium pantothenate deficiency and cadmium intoxication on rat reproductive function].

The publication presents investigation evaluated of separate and combined effects of calcium pantothenate deficiency and cadmium (Cd2+) intoxication on rat reproductive function. The experi-ments were performed on 280 adult and 890 offspring of Wistar rats. Reproductive function was estimated by fertility study, prenatal and postnatal development of offspring. The separate and combined effects of and cadmium intoxication during the mating period and pregnancy had no effect on fertility and fecundity of rats, pre-and postimplantation loss, the survival of offspring, and not caused the abnormal development of skeleton and internal organs. However, in prenatal ontogeny of this effect was manifested by lower body weight and fetal growth, postnatal - underdevelopment of rat pups in all morphological and functional studied parameters and increasing number of stillbirths in the offspring.

Pantothenic acid in health and disease.

In summary, the vitamin pantothenic acid is an integral part of the acylation carriers, CoA and acyl carrier protein (ACP). The vitamin is readily available from diverse dietary sources, a fact which is underscored by the difficulty encountered in attempting to induce pantothenate deficiency. Although pantothenic acid deficiency has not been linked with any particular disease, deficiency of the vitamin results in generalized malaise clinically. In view of the fact that pantothenate is required for the synthesis of CoA, it is surprising that tissue CoA levels are not altered in pantothenate deficiency. This suggests that the cell is equipped to conserve its pantothenate content, possibly by a recycling mechanism for utilizing pantothenate obtained from degradation of pantothenate-containing molecules. Although the steps involved in the conversion of pantothenate to CoA have been characterized, much remains to be done to understand the regulation of CoA synthesis. In particular, in view of what is known about the in vitro regulation of pantothenate kinase, it is surprising that the enzyme is active in vivo, since factors that are known to inhibit the enzyme are present in excess of the concentrations known to inhibit the enzyme. Thus, other physiological regulatory factors (which are largely unknown) must counteract the effects of these inhibitors, since the pantothenate-to-CoA conversion is operative in vivo. Another step in the biosynthetic pathway that may be rate limiting is the conversion of 4'-phosphopantetheine (4'-PP) to dephospho-CoA, a step catalyzed by 4'-phosphopantetheine adenylyl-transferase. In mammalian systems, this step may occur in the mitochondria or in the cytosol. The teleological significance of these two pathways remains to be established, particularly since mitochondria are capable of transporting CoA from the cytosol. Altered homeostasis of CoA has been observed in diverse disease states including starvation, diabetes, alcoholism, Reye syndrome (RS), medium-chain acyl CoA dehydrogenase deficiency, vitamin B12 deficiency, and certain tumors. Hormones, such as glucocorticoids, insulin, and glucagon, as well as drugs, such as clofibrate, also affect tissue CoA levels. It is not known whether the abnormal metabolism observed in these conditions is the result of altered CoA metabolism or whether CoA levels change in response to hormonal or nonhormonal perturbations brought about in these conditions. In other words, a cause-effect relation remains to be elucidated. It is also not known whether the altered CoA metabolism (be it cause or result of abnormal metabolism) can be implicated in the manifestations of a disease. Besides CoA, pantothenic acid is also an integral part of the ACP molecule.(ABSTRACT TRUNCATED AT 400 WORDS)

[Metabolism of pantothenic acid and its derivatives in animals deficient in this enzyme]. / Metabolizm pantotenovoi kisloty i ee proizvodnykh u zhivotnykh s nedostatochnost'iu étogo vitamina.

Distribution of [14C]labelled metabolites of pantothenic acid (PAA) has been studied in tissues of normal and PAA-deficient rats-weaners 6 h after single injection of the calcium pantothenate (PAA-Ca), calcium 4'-phosphopantothenate (PAA-Ca) or pantethine (PT) preparations. Essential differences in the intertissue distribution of vitamin derivatives to be injected are revealed against a background of a higher vitamin-retaining ability of the PAA-deficient tissues. A degree of radionuclides' biotransformation into CoA permits them to be arranged in the series: PPA-Ca greater than PAA-Ca greater than PT. In PAA-deficient animals which were injected labelled PPA-Ca up to 41% of the liver radioactivity is concentrated in the CoA fraction and the quantity of label in the composition of PAA-protein cytosolium complexes increases considerably. It is supposed that there is a special PAA-depositing system which provides the intracellular CoA biosynthesis.

[Acid-soluble CoA and free amino acid levels in the liver of pantothenic acid-deficient albino rats after separate and combined administration of panthotenic acid and cysteine]. / Uroven' kislotorastvorimogo KoA i svobodnykh aminokislot pecheni pantotenatdefitsitnykh belykh krys pri razdel'nom i sochetannom vvedenii pantotenata i tsisteina.

The feeding of white rats with a synthetic diet deprived of pantothenic acid (PAA) for 10 weeks led to a decrease in the content of acid-soluble CoA (AS-CoA) and to an increase in the liver taurine and glycine concentration. One hour after pantothenate injection (30 mg/kg) to PAA-deficient animals the level of AS-CoA rose by 96%, whereas after administration of an equimolar dose of cystein by 63%. Combined administration of CoA precursors did not result in summation of the effects. In all the cases of cystein injections, substantial changes were recorded in the structure of the liver amino acid pool, which were less marked if cystein was combined with pantothenate. It is assumed that the metabolism of cystein, glycine and, probably, that of alanine may depend on the changes in the CoA pool in hepatocytes.

Pantothenic acid, coenzyme A, and human chronic ulcerative and granulomatous colitis.

To investigate further an apparent relationship between chronic ulcerative and granulomatous colitis and pantothenic acid deficiency, colonic tissues obtained at the time of colectomy in 29 patients with these disorders were assayed for pantothenic acid and for coenzyme A (CoA) activity. For comparison, normal colonic tissues free of pathological lesions were obtained from 31 patients having colectomy for carcinoma or diverticulitis. Plasma, red blood cells, and colonic mucosa were assayed microbiologically for free and total pantothenic acid. The activity of CoA in colonic mucosa was determined by assaying the acetylation of sulfanilamide. Concentrations of free, bound, and total pantothenic acid in blood and in colonic mucosa did not differ between the two groups of patients. Bound pantothenic acid increased linearly with total pantothenic acid. Colonic mucosa concentrated free pantothenic acid to about 50 times the level of blood, and pantothenic acid in red cells was similar to the concentration in plasma. Compared to normal gut mucosa, CoA activity was markedly low in mucosa from patients with chronic ulcerative or granulomatous disease despite the presence of normal amounts of free and bound pantothenic acid. A block in the conversion of bound pantothenic acid to CoA in diseased mucosa is suggested.