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The Journal of Biological Chemistry Aug 1951
Topics: Pantothenic Acid
PubMed: 14861196
DOI: No ID Found -
Auris, Nasus, Larynx Jun 2020Limited data exist on the clinical benefits of nasal applications for moistening the nasal mucosa. We therefore investigated the effects of hyaluronic acid, hyaluronic... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomised trial on performance, safety and clinical benefit of hyaluronic acid, hyaluronic acid plus dexpanthenol and isotonic saline nasal sprays in patients suffering from dry nose symptoms.
OBJECTIVE
Limited data exist on the clinical benefits of nasal applications for moistening the nasal mucosa. We therefore investigated the effects of hyaluronic acid, hyaluronic acid plus dexpanthenol and isotonic saline nasal sprays in patients suffering from dry nose symptoms in an otorhinolaryngological outpatient setting.
METHODS
240 patients were randomised into this prospective, three-armed clinical trial with two assessment points (baseline and 4 weeks later). Patients received either hyaluronic acid, hyaluronic acid plus dexpanthenol or isotonic saline nasal spray over a period of four weeks. Rhinitis Sicca Symptom Score (RSSS) was assessed as primary endpoint, and individual symptoms and tolerability of all treatments as secondary endpoints. Patient perceptions after first application of the allocated nasal spray were recorded using the Nasal Spray Sensory Scale. Treatment effects were analysed for each study arm first and subsequently compared against each other.
RESULTS
RSSS (hyaluronic acid: mean difference = 8.90 [98.33% CI = 7.34/10.45]; hyaluronic acid plus dexpanthenol: mean difference = 8.42 [98.33% CI = 6.91/9.94]; isotonic saline: mean difference = 8.94 [98.33% CI = 7.33/10.54]), individual symptoms and Endoscopy Score improved significantly (p < 0.001) in all treatment arms. Tolerability was assessed as "flawless" in more than 85% of all treatments, which is reflected in overall high rankings in the Nasal Spray Sensory Scale. Perception of nasal moisturisation was reported to be significantly higher in patients receiving hyaluronic acid plus dexpanthenol as compared to patients receiving hyaluronic acid or isotonic saline. No further significant differences were observed between the three treatments.
CONCLUSION
All three tested sprays (hyaluronic acid, hyaluronic acid plus dexpanthenol and isotonic saline) proved to be suitable treatments for patients suffering from dry nose symptoms. (DRKS-ID: DRKS00013357).
Topics: Administration, Intranasal; Adult; Drug Therapy, Combination; Female; Humans; Hyaluronic Acid; Male; Middle Aged; Nasal Mucosa; Pantothenic Acid; Prospective Studies; Rhinitis; Saline Solution; Sjogren's Syndrome
PubMed: 32067777
DOI: 10.1016/j.anl.2020.01.008 -
Biomedicine & Pharmacotherapy =... Sep 2021Here, we demonstrate that the two distinct formulations of our anti-sepsis drug candidate Rejuveinix (RJX), have a very favorable safety profile in Wistar Albino rats at...
Here, we demonstrate that the two distinct formulations of our anti-sepsis drug candidate Rejuveinix (RJX), have a very favorable safety profile in Wistar Albino rats at dose levels comparable to the projected clinical dose levels. 14-day treatment with RJX-P (RJX PPP.18.1051) or RJX-B (RJX-B200702-CLN) similarly elevated the day 15 tissue levels of the antioxidant enzyme superoxide dismutase (SOD) as well as ascorbic acid in both the lungs and liver in a dose-dependent fashion. The activity of SOD and ascorbic acid levels were significantly higher in tissues of RJX-P or RJX-B treated rats than vehicle-treated control rats (p < 0.0001). There was no statistically significant difference between tissue SOD activity or ascorbic acid levels of rats treated with RJX-P vs. rats treated with RJX-B (p > 0.05). The observed elevations of the SOD and ascorbic acid levels were transient and were no longer detectable on day 28 following a 14-day recovery period. These results demonstrate that RJX-P and RJX-B are bioequivalent relative to their pharmacodynamic effects on tissue SOD and ascorbic acid levels. Furthermore, both formulations showed profound protective activity in a mouse model of sepsis. In agreement with the PD evaluations in rats and their proposed mechanism of action, both RJX-P and RJX-B exhibited near-identical potent and dose-dependent anti-oxidant and anti-inflammatory activity in the LPS-GalN model of ARDS and multi-organ failure in mice.
Topics: Animals; Female; Male; Rats; Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Dose-Response Relationship, Drug; Drug Combinations; Drug Compounding; Lipopolysaccharides; Magnesium Sulfate; Mice, Inbred BALB C; Niacinamide; Oxidative Stress; Pantothenic Acid; Pyridoxine; Rats, Sprague-Dawley; Rats, Wistar; Riboflavin; Sepsis; Superoxide Dismutase; Thiamine; Mice
PubMed: 34147902
DOI: 10.1016/j.biopha.2021.111823 -
Antimicrobial Agents and Chemotherapy Nov 2005The growth and proliferation of the human malaria parasite Plasmodium falciparum are dependent on the parasite's ability to obtain essential nutrients. One nutrient for...
The growth and proliferation of the human malaria parasite Plasmodium falciparum are dependent on the parasite's ability to obtain essential nutrients. One nutrient for which the parasite has an absolute requirement is the water-soluble vitamin pantothenic acid (vitamin B5). In this study, a series of pantothenic acid analogs which retain the 2,4-dihydroxy-3,3-dimethylbutyramide core of pantothenic acid but deviate in structure from one another and from pantothenic acid in the nature of the substituent attached to the amide nitrogen were synthesized using an efficient single-step synthetic route. Eight of 10 analogs tested inhibited the proliferation of intraerythrocytic P. falciparum parasites in vitro, doing so with 50% inhibitory concentrations between 15 and 200 microM. The compounds were generally selective, inhibiting the proliferation of a human cell line (the Jurkat cell line) only at concentrations severalfold higher than those required for inhibition of parasite growth. It was demonstrated that compounds in this series inhibited the phosphorylation of pantothenic acid by pantothenate kinase, the first step in the parasite's biosynthesis of the essential enzyme cofactor coenzyme A, doing so competitively, with K(i) values in the nanomolar range.
Topics: Animals; Antimalarials; Enzyme Inhibitors; Humans; Jurkat Cells; Kinetics; Pantothenic Acid; Parasitic Sensitivity Tests; Phosphorylation; Phosphotransferases (Alcohol Group Acceptor); Plasmodium falciparum; Structure-Activity Relationship
PubMed: 16251308
DOI: 10.1128/AAC.49.11.4649-4657.2005 -
Trends in Parasitology Mar 2007Vitamins are essential components of the human diet. By contrast, the malaria parasite Plasmodium falciparum and related apicomplexan parasites synthesize certain... (Review)
Review
Vitamins are essential components of the human diet. By contrast, the malaria parasite Plasmodium falciparum and related apicomplexan parasites synthesize certain vitamins de novo, either completely or in parts. The various biosynthesis pathways are specific to different apicomplexan parasites and emphasize the distinct requirements of these parasites for nutrients and growth factors. The absence of vitamin biosynthesis in humans implies that inhibition of the parasite pathways might be a way to interfere specifically with parasite development. However, the roles of biosynthesis and uptake of vitamins in the regulation of vitamin homeostasis in parasites needs to be established first. In this article, the procurement of vitamins B(1), B(5) and B(6) by Plasmodium and other apicomplexan parasites is discussed.
Topics: Animals; Apicomplexa; Ascorbic Acid; Biotin; Humans; Pantothenic Acid; Plasmodium; Plasmodium falciparum; Species Specificity; Thiamine; Vitamin A; Vitamin B 6; Vitamins
PubMed: 17276140
DOI: 10.1016/j.pt.2007.01.009 -
PloS One 2015Four groups of juvenile Megalobrama amblycephala were fed three times daily with six semi-purified diets containing 3.39 (PA unsupplied diet), 10.54, 19.28, 31.04, 48.38...
Effects of dietary pantothenic acid on growth, intestinal function, anti-oxidative status and fatty acids synthesis of juvenile blunt snout bream Megalobrama amblycephala.
Four groups of juvenile Megalobrama amblycephala were fed three times daily with six semi-purified diets containing 3.39 (PA unsupplied diet), 10.54, 19.28, 31.04, 48.38 and 59.72 mg kg(-1) calcium D-pantothenate. The results showed that survival rate, final weight, specific growth rate, protein efficiency ratio and nitrogen retention efficiency all increased significantly (P<0.01) as dietary PA levels increased from 3.39 to 19.28 mg kg(-1), whereas the opposite was true for feed conversion ratio. Whole-body crude protein increased as dietary PA levels increased, while the opposite pattern was found for the crude lipid content. Intestinal α-amylase, lipase, protease, Na+-K+-ATPase, alkaline phosphatase and gamma-glutamyl transferase activities were all elevated in fish fed PA-supplemented diets. Hepatic catalase activities improved with increases in dietary PA, while the opposite was true for malondialdehyde contents. The liver PA concentration and coenzyme A content rose significantly (P<0.01), up to 31.04 mg kg(-1), with increasing dietary PA levels and then plateaued. The percentage of hepatic saturated fatty acids increased significantly (P<0.01) as dietary PA levels increased, while the percentages of monounsaturated fatty acids and polyunsaturated fatty acid (PUFA) decreased as dietary PA increased. Fish fed diets containing 19.28 and 31.04 mg kg(-1) PA exhibited higher (P<0.01) docosahexaenoic acid and PUFA percentages in muscle than those fed with other diets. The expression of the gene encoding pantothenate kinase was significantly up-regulated (P<0.01) in fish fed PA-supplemented diets. Hepatic Acetyl-CoA carboxylase α, fatty acid synthetase, stearoyl regulatory element-binding protein 1 and X receptor α genes all increased significantly (P<0.01) as dietary PA levels increased from 3.39 to 31.04 mg kg(-1). Based on broken-line regression analyses of weight gain, liver CoA concentrations and PA contents against dietary PA levels, the optimal dietary PA requirements of juvenile blunt snout bream were estimated to be 24.08 mg kg(-1).
Topics: Animals; Antioxidants; Cyprinidae; Dietary Supplements; Fatty Acids; Intestines; Pantothenic Acid
PubMed: 25781913
DOI: 10.1371/journal.pone.0119518 -
Journal of Bacteriology Jan 1983Structural genes have been identified for all of the enzymes involved in the biosynthesis of pantothenic acid in Salmonella typhimurium and Escherichia coli K-12, with...
Structural genes have been identified for all of the enzymes involved in the biosynthesis of pantothenic acid in Salmonella typhimurium and Escherichia coli K-12, with the exception of ketopantoic acid reductase, which catalyzes the conversion of alpha-ketopantoate to pantoate. The acetohydroxy acid isomeroreductase from S. typhimurium efficiently bound alpha-ketopantoate (K(m) = 0.25 mM) and catalyzed its reduction at 1/20 the rate at which alpha-acetolactate was reduced. Since two enzymes could apparently participate in the synthesis of pantoate, a S. typhimurium ilvC8 strain was mutagenized to derive strains completely blocked in the conversion of alpha-ketopantoate to pantoate. Several isolates were obtained that grew in isoleucine-valine medium supplemented with either pantoate or pantothenate, but not in the same medium supplemented with alpha-ketopantoate or beta-alanine. The mutations that conferred pantoate auxotrophy (designated panE) to these isolates appeared to be clustered, but were not linked to panB or panC. All panE strains tested had greatly reduced levels of ketopantoic acid reductase (3 to 12% of the activity present in DU201). The capacity of the isomeroreductase to synthesize pantoate in vivo was assessed by determining the growth requirements of ilvC(+) derivatives of panE ilvC8 strains. These strains required either alpha-ketopantoate, pantoate, or pantothenate when the isomeroreductase was present at low levels; when the synthesis of isomeroreductase was induced, panE ilvC(+) strains grew in unsupplemented medium. These phenotypes indicate that a high level of isomeroreductase is sufficient for the synthesis of pantoate. panE ilvC(+) strains also grew in medium supplemented with lysine and methionine. This phenotype resembles that of some S. typhimurium ilvG mutants (e.g., DU501) which are partially blocked in the biosynthesis of coenzyme A and are limited for succinyl coenzyme A. panE ilvC(+) strains which lack the acetohydroxy acid synthases required only methionine for growth (in the presence of leucine, isoleucine, and valine). This and other evidence suggested that the synthesis of pantoic acid by isomeroreductase was blocked by the alpha-acetohydroxy acids and that pantoic acid synthesis was enhanced in the absence of these intermediates, even when the isomeroreductase was at low levels. panE ilvC(+) strains reverted to pantothenate independence. Several of these revertants were shown to have elevated isomeroreductase levels under noninduced and induced conditions; the suppressing mutation in each revertant was shown to be closely linked to ilvC by P22 transduction. This procedure presents a means for obtaining mutants with altered regulation of isomeroreductase.
Topics: 2-Acetolactate Mutase; Alcohol Oxidoreductases; Chromosome Mapping; Chromosomes, Bacterial; Genes, Regulator; Hydroxybutyrates; Isomerases; Ketol-Acid Reductoisomerase; Lysine; Methionine; Mutation; Pantothenic Acid; Salmonella typhimurium
PubMed: 6401279
DOI: 10.1128/jb.153.1.259-269.1983 -
Biomolecules Sep 2022Coenzyme A (CoA) is an essential co-factor at the intersection of diverse metabolic pathways. Cellular CoA biosynthesis is regulated at the first committed...
Coenzyme A (CoA) is an essential co-factor at the intersection of diverse metabolic pathways. Cellular CoA biosynthesis is regulated at the first committed step-phosphorylation of pantothenic acid-catalyzed by pantothenate kinases (PANK1,2,3 in humans, PANK3 being the most highly expressed). Despite the critical importance of CoA in metabolism, the differential roles of PANK isoforms remain poorly understood. Our investigations of PANK proteins as potential precision oncology collateral lethality targets ( is co-deleted as part of the locus in some highly aggressive cancers) were severely hindered by a dearth of commercial antibodies that can reliably detect endogenous PANK3 protein. While we successfully validated commercial antibodies for PANK1 and PANK2 using CRISPR knockout cell lines, we found no commercial antibody that could detect endogenous PANK3. We therefore set out to generate a mouse monoclonal antibody against human PANK3 protein. We demonstrate that a clone (Clone MDA-299-62A) can reliably detect endogenous PANK3 protein in cancer cell lines, with band-specificity confirmed by CRISPR PANK3 knockout and knockdown cell lines. Sub-cellular fractionation shows that PANK3 is overwhelmingly cytosolic and expressed broadly across cancer cell lines. PANK3 monoclonal antibody MDA-299-62A should prove a valuable tool for researchers investigating this understudied family of metabolic enzymes in health and disease.
Topics: Animals; Antibodies, Monoclonal; Coenzyme A; Humans; Mice; Neoplasms; Pantothenic Acid; Precision Medicine; Protein Isoforms
PubMed: 36139163
DOI: 10.3390/biom12091323 -
Maternal & Child Nutrition Apr 2010Weaning formulas served in hospitals and care facilities in Japan should conform to dietary reference intakes (DRIs). We examined whether the DRI for breastfed infants...
Formulas providing adequate pantothenic acid, vitamin D, manganese, iron and vitamin A for infants fed with mother's milk (aged 6-11 months) according to the Japanese Dietary Reference Intakes prepared by the Ministry of Health, Labour and Welfare (2005 edition).
Weaning formulas served in hospitals and care facilities in Japan should conform to dietary reference intakes (DRIs). We examined whether the DRI for breastfed infants aged 6-11 months can be satisfied in dietary practice, with a particular focus on the fulfilment rates for vitamins, minerals, trace elements and electrolytes in weaning formulas containing energy and protein at levels either greater than or equal to the DRIs, as well as on the dietary profiles of weaning formulas to achieve the DRI for every nutrient. The results showed that no weaning formulas examined in this study fulfilled the DRI for pantothenic acid (5 mg), vitamin D (4 microg), manganese (1.2 mg) or iron (5.5 mg). Furthermore, their vitamin A content exceeded the DRI (350 microg RE). The discrepancy between the guidelines and actual dietary practice is probably because of the fact that the estimated reference values poorly reflect the actual dietary intake in the target population; for example, the pantothenic acid and manganese DRIs for breastfed infants aged 6-11 months were set based on the breast milk intake of younger infants (0-5 months) in combination with the breast milk contents. Our results suggest that dietary guidance for infants should include information to promote proper intakes of vitamins A and D, and iron by reducing the amount of vitamin A-rich foods and utilizing dietary vitamin D and iron supplements including government-approved specified health foods.
Topics: Dietary Supplements; Female; Food, Fortified; Humans; Infant; Infant Food; Infant Formula; Infant Nutritional Physiological Phenomena; Iron; Japan; Male; Milk, Human; Nutrition Policy; Nutritional Requirements; Pantothenic Acid; Vitamin A; Vitamin D; Weaning
PubMed: 20624211
DOI: 10.1111/j.1740-8709.2009.00192.x -
BMC Geriatrics Apr 2023During biological aging, significant metabolic dysregulation in the central nervous system may lead to cognitive decline and neurodegeneration. However, the metabolomics...
BACKGROUND
During biological aging, significant metabolic dysregulation in the central nervous system may lead to cognitive decline and neurodegeneration. However, the metabolomics of the aging process in cerebrospinal fluid (CSF) has not been thoroughly explored.
METHODS
In this cohort study of CSF metabolomics using liquid chromatography-mass spectrometry (LC-MS), fasting CSF samples collected from 92 cognitively unimpaired adults aged 20-87 years without obesity or diabetes were analyzed.
RESULTS
We identified 37 metabolites in these CSF samples with significant positive correlations with aging, including cysteine, pantothenic acid, 5-hydroxyindoleacetic acid (5-HIAA), aspartic acid, and glutamate; and two metabolites with negative correlations, asparagine and glycerophosphocholine. The combined alterations of asparagine, cysteine, glycerophosphocholine, pantothenic acid, sucrose, and 5-HIAA showed a superior correlation with aging (AUC = 0.982). These age-correlated changes in CSF metabolites might reflect blood-brain barrier breakdown, neuroinflammation, and mitochondrial dysfunction in the aging brain. We also found sex differences in CSF metabolites with higher levels of taurine and 5-HIAA in women using propensity-matched comparison.
CONCLUSIONS
Our LC-MS metabolomics of the aging process in a Taiwanese population revealed several significantly altered CSF metabolites during aging and between the sexes. These metabolic alterations in CSF might provide clues for healthy brain aging and deserve further exploration.
Topics: Female; Humans; Male; Aging; Asparagine; Chromatography, Liquid; Cohort Studies; Cysteine; Hydroxyindoleacetic Acid; Pantothenic Acid; Tandem Mass Spectrometry; Healthy Volunteers; Metabolome; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over; Cognition; Fasting
PubMed: 37020298
DOI: 10.1186/s12877-023-03939-6