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Biological & Pharmaceutical Bulletin Jun 2008The effects of pantothenic acid-supplementation on the adrenal secretion of corticosterone and progesterone in male rats were investigated using an in vitro cell culture...
The effects of pantothenic acid-supplementation on the adrenal secretion of corticosterone and progesterone in male rats were investigated using an in vitro cell culture system. Male rats at 21 d of age were given 0.03% pantothenic acid in their drinking water for 9 weeks. After 9 weeks of treatment, the animals were decapitated, and adrenal cells were cultured in the absence or presence of rat adrenocorticotropic hormone (ACTH; 10(-15) to 10(-10) M) and/or ovine prolactin (oPRL; 10(-9) to 10(-7) M) for 4 h. Adrenal cells in pantothenic acid-treated rats exhibited higher basal levels of corticosterone and progesterone than control rats. The response of ACTH and/or PRL on corticosterone and progesterone release was higher in the pantothenic acid-treated rats than in the control rats. In addition, PRL increased the stimulatory effect of ACTH-induced corticosterone secretion in both normal and pantothenic acid-treated rats. These results clearly demonstrated that pantothenic acid supplementation stimulates the ability of adrenal cells in male rats to secrete corticosterone and progesterone. Additionally, these results also showed that pantothenic acid supplementation induced adrenal hyperresponsiveness to ACTH stimulation, and PRL further stimulated adrenal sensitivity to ACTH.
Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Body Weight; Corticosterone; Culture Media; Dietary Supplements; Male; Organ Size; Pantothenic Acid; Prolactin; Radioimmunoassay; Rats; Rats, Wistar; Steroids
PubMed: 18520055
DOI: 10.1248/bpb.31.1205 -
Chemistry (Weinheim An Der Bergstrasse,... Nov 2018Access to vitamin B [(R)-pantothenic acid] and both diastereoisomers of α-methyl-substituted vitamin B [(R)- and...
Access to vitamin B [(R)-pantothenic acid] and both diastereoisomers of α-methyl-substituted vitamin B [(R)- and (S)-3-((R)-2,4-dihydroxy-3,3-dimethylbutanamido)-2-methylpropanoic acid] was achieved using a modular three-step biocatalytic cascade involving 3-methylaspartate ammonia lyase (MAL), aspartate-α-decarboxylase (ADC), β-methylaspartate-α-decarboxylase (CrpG) or glutamate decarboxylase (GAD), and pantothenate synthetase (PS) enzymes. Starting from simple non-chiral dicarboxylic acids (either fumaric acid or mesaconic acid), vitamin B and both diastereoisomers of α-methyl-substituted vitamin B , which are valuable precursors for promising antimicrobials against Plasmodium falciparum and multidrug-resistant Staphylococcus aureus, can be generated in good yields (up to 70 %) and excellent enantiopurity (>99 % ee). This newly developed cascade process may be tailored and used for the biocatalytic production of various vitamin B derivatives by modifying the pantoyl or β-alanine moiety.
Topics: Adenosine Triphosphate; Ammonia-Lyases; Anti-Infective Agents; Biocatalysis; Escherichia coli; Glutamate Decarboxylase; Methicillin-Resistant Staphylococcus aureus; Pantothenic Acid; Peptide Synthases; Plasmodium falciparum; Stereoisomerism; beta-Alanine
PubMed: 30192043
DOI: 10.1002/chem.201804151 -
Future Microbiology Oct 2022Our main objectives were to compare the effects of Rejuveinix (RJX), dexamethasone (DEX) and their combination on the severity of sepsis and survival outcome in an...
Our main objectives were to compare the effects of Rejuveinix (RJX), dexamethasone (DEX) and their combination on the severity of sepsis and survival outcome in an animal model of fatal sepsis. We used the LPS plus D-galactosamine mouse model of sepsis to compare the anti-inflammatory activities of RJX, dexamethasone and a combination of RJX plus DEX. Additionally, we examined the clinical feasibility and tolerability of combining RJX with DEX in COVID-19 patients in a clinical phase I study. Data were analyzed using standard methods. RJX exhibited potent anti-inflammatory activity in the murine sepsis model. The combination of RJX plus DEX was more effective than either agent alone, decreased the inflammatory cytokine responses and associated organ damage, and improved the survival outcome in mice. In the phase I clinical study, RJX plus DEX was well tolerated by COVID-19 patients.
Topics: Animals; Anti-Inflammatory Agents; Ascorbic Acid; Dexamethasone; Disease Models, Animal; Drug Combinations; Magnesium Sulfate; Mice; Niacinamide; Pantothenic Acid; Pyridoxine; Riboflavin; Sepsis; Thiamine; COVID-19 Drug Treatment
PubMed: 36052743
DOI: 10.2217/fmb-2022-0044 -
Movement Disorders : Official Journal... Jun 2021Pantothenate kinase-associated neurodegeneration (PKAN) currently has no approved treatments. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pantothenate kinase-associated neurodegeneration (PKAN) currently has no approved treatments.
OBJECTIVES
The Fosmetpantotenate Replacement Therapy pivotal trial examined whether treatment with fosmetpantotenate improves PKAN symptoms and stabilizes disease progression.
METHODS
This randomized, double-blind, placebo-controlled, multicenter study evaluated fosmetpantotenate, 300 mg oral dose three times daily, versus placebo over a 24-week double-blind period. Patients with pathogenic variants of PANK2, aged 6 to 65 years, with a score ≥6 on the PKAN-Activities of Daily Living (PKAN-ADL) scale were enrolled. Patients were randomized to active (fosmetpantotenate) or placebo treatment, stratified by weight and age. The primary efficacy endpoint was change from baseline at week 24 in PKAN-ADL.
RESULTS
Between July 23, 2017, and December 18, 2018, 84 patients were randomized (fosmetpantotenate: n = 41; placebo: n = 43); all 84 patients were included in the analyses. Six patients in the placebo group discontinued treatment; two had worsening dystonia, two had poor compliance, and two died of PKAN-related complications (aspiration during feeding and disease progression with respiratory failure, respectively). Fosmetpantotenate and placebo group PKAN-ADL mean (standard deviation) scores were 28.2 (11.4) and 27.4 (11.5) at baseline, respectively, and were 26.9 (12.5) and 24.5 (11.8) at week 24, respectively. The difference in least square mean (95% confidence interval) at week 24 between fosmetpantotenate and placebo was -0.09 (-1.69 to 1.51; P = 0.9115). The overall incidence of treatment-emergent serious adverse events was similar in the fosmetpantotenate (8/41; 19.5%) and placebo (6/43; 14.0%) groups.
CONCLUSIONS
Treatment with fosmetpantotenate was safe but did not improve function assessed by the PKAN-ADL in patients with PKAN. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Activities of Daily Living; Double-Blind Method; Humans; Pantothenate Kinase-Associated Neurodegeneration; Pantothenic Acid
PubMed: 33200489
DOI: 10.1002/mds.28392 -
PloS One 2017A novel, selective and sensitive single-ion monitoring (SIM) gas chromatography-mass spectrometry (GCMS) method was developed and validated for the determination of...
A novel, selective and sensitive single-ion monitoring (SIM) gas chromatography-mass spectrometry (GCMS) method was developed and validated for the determination of energy metabolites related to glycolysis, the tricarboxylic acid (TCA) cycle, glutaminolysis, and fatty acid β-oxidation. This assay used N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA) containing 1% tert-butyldimethylchlorosilane (TBDMCS) as derivatizing reagent and was highly reproducible, sensitive, specific and robust. The assay was used to analyze liver tissue and serum from C57BL/6N obese mice fed a high-fat diet (HFD) and C57BL/6N mice fed normal chow for 8 weeks. HFD-fed mice serum displayed statistically significantly reduced concentrations of pyruvate, citrate, succinate, fumarate, and 2-oxoglutarate, with an elevated concentration of pantothenic acid. In liver tissue, HFD-fed mice exhibited depressed levels of glycolysis end-products pyruvate and lactate, glutamate, and the TCA cycle intermediates citrate, succinate, fumarate, malate, and oxaloacetate. Pantothenate levels were 3-fold elevated accompanied by a modest increased gene expression of Scl5a6 that encodes the pantothenate transporter SLC5A6. Since both glucose and fatty acids inhibit coenzyme A synthesis from pantothenate, it was concluded that these data were consistent with downregulated fatty acid β-oxidation, glutaminolysis, glycolysis, and TCA cycle activity, due to impaired anaplerosis. The novel SIM GCMS assay provided new insights into metabolic effects of HFD in mice.
Topics: Animals; Blood Chemical Analysis; Citric Acid; Diet, High-Fat; Energy Metabolism; Fatty Acids; Gas Chromatography-Mass Spectrometry; Glutamic Acid; Lactic Acid; Male; Metabolome; Mice; Mice, Inbred C57BL; Obesity; Pantothenic Acid; Pyruvic Acid; Symporters
PubMed: 28520815
DOI: 10.1371/journal.pone.0177953 -
Folia Histochemica Et Cytobiologica 2016The available immunohistochemical techniques have documented restricted distribution of vitamins in the mammalian brain. The aim of the study was to develop a highly...
INTRODUCTION
The available immunohistochemical techniques have documented restricted distribution of vitamins in the mammalian brain. The aim of the study was to develop a highly specific antiserum directed against pantothenic acid to explore the presence of this vitamin in the mammalian brain.
MATERIAL AND METHODS
According to ELISA tests, the anti-pantothenic acid antiserum used showed a good affinity (10-8 M) and specificity. The antiserum was raised in rabbits. Using an indirect immunoperoxidase technique, the mapping of pantothenic acid-immunoreactive structures was carried out in the rat brain.
RESULTS
Pantothenic acid-immunoreactive perikarya were exclusively found in the intermediate part of the lateral septal nucleus. These cells were generally small, round, fusiform or pyramidal and showed 2-3 long (50-100 μm) immunoreactive dendrites. Any immunoreactive axons containing pantothenic acid were detected.
CONCLUSIONS
The very restricted anatomical distribution of the pantothenic acid suggests that this vitamin could be involved in some specific neurophysiological mechanisms.
Topics: Animals; Antibodies; Antibody Formation; Antibody Specificity; Axons; Brain; Enzyme-Linked Immunosorbent Assay; Immune Sera; Immunoenzyme Techniques; Immunohistochemistry; Male; Neurons; Pantothenic Acid; Rabbits; Rats; Rats, Wistar; Septal Nuclei
PubMed: 27966211
DOI: 10.5603/FHC.a2016.0024 -
Structure (London, England : 1993) Nov 2022Fungal infections are the leading cause of mortality by eukaryotic pathogens, with an estimated 150 million severe life-threatening cases and 1.7 million deaths reported...
Fungal infections are the leading cause of mortality by eukaryotic pathogens, with an estimated 150 million severe life-threatening cases and 1.7 million deaths reported annually. The rapid emergence of multidrug-resistant fungal isolates highlights the urgent need for new drugs with new mechanisms of action. In fungi, pantothenate phosphorylation, catalyzed by PanK enzyme, is the first step in the utilization of pantothenic acid and coenzyme A biosynthesis. In all fungi sequenced so far, this enzyme is encoded by a single PanK gene. Here, we report the crystal structure of a fungal PanK alone as well as with high-affinity inhibitors from a single chemotype identified through a high-throughput chemical screen. Structural, biochemical, and functional analyses revealed mechanisms governing substrate and ligand binding, dimerization, and catalysis and helped identify new compounds that inhibit the growth of several Candida species. The data validate PanK as a promising target for antifungal drug development.
Topics: Antifungal Agents; Phosphotransferases (Alcohol Group Acceptor); Pantothenic Acid; Fungi
PubMed: 36167065
DOI: 10.1016/j.str.2022.09.001 -
International Journal of Experimental... Aug 2022Wound healing is a dynamic process initiated in response to injury. There are many factors that have detrimental effects on the wound healing process. Numerous studies... (Comparative Study)
Comparative Study
Wound healing is a dynamic process initiated in response to injury. There are many factors that have detrimental effects on the wound healing process. Numerous studies have been conducted for improving wound healing processes. Dexpanthenol is widely used to accelerate wound healing. Sucralfate is used for the treatment of peptic ulcers. We aimed to compare the efficacy of topical Dexpanthenol and Sucralfate in an experimental wound model in rats via histopathological examinations and immune histochemical determinations, as well, to evaluate their effects on EGF levels. Three different groups were formed: the Control Group, the Dexpanthenol Group and the Sucralfate Group. Full-thickness skin wounds were created on the back of each rat and isotonic saline was applied to the wounds of the rats in the control group, Bepanthol cream was applied in Dexpanthenol Group and 10% Sucralfate cream was applied in Sucralfate Group, once a day. On the 7th, 14th and 21st days the wounds were measured and seven rats from each group were sacrificed and the wounds were excised for histopathological examination. Sucralfate increased wound healing rates by increasing neovascularization, fibroblast activation, reepithelialization and collagen density, as well as dexpanthenol. Our study revealed that the dexpanthenol and sucralfate groups were better than the control group in terms of their effects on wound healing, however there was no statistically significant difference among these two groups. Sucralfate improves EGF expression in skin wounds and has positive results on skin wound healing comparable to dexpanthenol.
Topics: Animals; Epidermal Growth Factor; Pantothenic Acid; Rats; Sucralfate; Wound Healing
PubMed: 35441448
DOI: 10.1111/iep.12441 -
Poultry Science May 1978The biotin, folic acid, and pantothenic acid requirements of Mycoplasma meleagridis were determined in vitro by examining the growth and survival of the organism in the... (Comparative Study)
Comparative Study
The biotin, folic acid, and pantothenic acid requirements of Mycoplasma meleagridis were determined in vitro by examining the growth and survival of the organism in the presence of varying concentrations of these factors. Growth and survival were also studied in the presence of aminopterin and methotrexate which prevent utilization of folic acid, and in the presence of avidin, a known biotin antagonist. Whereas pantothenate appeared to have no obvious effect on growth or survival, folate was marginally stimulatory at only the highest concentration tested. Aminopterin exerted a slight, but not significant, inhibitory effect at four of the five concentrations tested. In contrast, the inhibition seen with methotrexate increased, dependent on dose. Biotin exerted a pronounced stimulatory effect at the two highest concentrations tested. Avidin inhibited growth only at one of the concentrations tested; however, this concentration did not correspond to the greatest amount of avidin. The possible significance of the avidin-biotin relationship to the etiology of Turkey Syndrome 1965 is explored on the basis of these in vitro observations and previous in vivo findings.
Topics: Aminopterin; Avidin; Biotin; Culture Media; Folic Acid; Methotrexate; Mycoplasma; Pantothenic Acid
PubMed: 674043
DOI: 10.3382/ps.0570611 -
Microbial Cell Factories Apr 2023Coenzyme A (CoA) is a carrier of acyl groups. This cofactor is synthesized from pantothenic acid in five steps. The phosphorylation of pantothenate is catalyzed by...
BACKGROUND
Coenzyme A (CoA) is a carrier of acyl groups. This cofactor is synthesized from pantothenic acid in five steps. The phosphorylation of pantothenate is catalyzed by pantothenate kinase (CoaA), which is a key step in the CoA biosynthetic pathway. To determine whether the enhancement of the CoA biosynthetic pathway is effective for producing useful substances, the effect of elevated acetyl-CoA levels resulting from the introduction of the exogenous coaA gene on poly(3-hydroxybutyrate) [P(3HB)] synthesis was determined in Escherichia coli, which express the genes necessary for cyanobacterial polyhydroxyalkanoate synthesis (phaABEC).
RESULTS
E. coli containing the coaA gene in addition to the pha genes accumulated more P(3HB) compared with the transformant containing the pha genes alone. P(3HB) production was enhanced by precursor addition, with P(3HB) content increasing from 18.4% (w/w) to 29.0% in the presence of 0.5 mM pantothenate and 16.3%-28.2% by adding 0.5 mM β-alanine. Strains expressing the exogenous coaA in the presence of precursors contained acetyl-CoA in excess of 1 nmol/mg of dry cell wt, which promoted the reaction toward P(3HB) formation. The amount of acetate exported into the medium was three times lower in the cells carrying exogenous coaA and pha genes than in the cells carrying pha genes alone. This was attributed to significantly enlarging the intracellular pool size of CoA, which is the recipient of acetic acid and is advantageous for microbial production of value-added materials.
CONCLUSIONS
Enhancing the CoA biosynthetic pathway with exogenous CoaA was effective at increasing P(3HB) production. Supplementing the medium with pantothenate facilitated the accumulation of P(3HB). β-Alanine was able to replace the efficacy of adding pantothenate.
Topics: 3-Hydroxybutyric Acid; Acetyl Coenzyme A; Escherichia coli; Pantothenic Acid; Acetic Acid; Polyesters
PubMed: 37081440
DOI: 10.1186/s12934-023-02083-5