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Production and Radioprotective Effects of Pyrroloquinoline Quinone  [PDF]
Xiang-Hua Xiong,Yan Zhao,Xin Ge,Shou-Jun Yuan,Jian-Hua Wang,Jing-Juan Zhi,Yan-Xin Yang,Bao-Hua Du,Wan-Jun Guo,Shan-Shan Wang,De-Xuan Yang,Wei-Cai Zhang
International Journal of Molecular Sciences , 2011, DOI: 10.3390/ijms12128913
Abstract: Pyrroloquinoline quinone (PQQ) was produced by fermentation of the M ethylovorus sp. MP688 strain and purified by ion-exchange chromatography, crystallization and recrystallization. The yield of PQQ reached approximately 125 mg/L and highly pure PQQ was obtained. To determine the optimum dose of PQQ for radioprotection, three doses (2 mg/kg, 4 mg/kg, 8 mg/kg) of PQQ were orally administrated to the experimental animals subjected to a lethal dose of 8.0 Gy in survival test. Survival of mice in the irradiation + PQQ (4 mg/kg) group was found to be significantly higher in comparison with the irradiation and irradiation + nilestriol (10 mg/kg) groups. The numbers of hematocytes and bone marrow cells were measured for 21 days after sublethal 4 Gy gamma-ray irradiation with per os of 4 mg/kg of PQQ. The recovery of white blood cells, reticulocytes and bone marrow cells in the irradiation + PQQ group was faster than that in the irradiation group. Furthermore, the recovery of bone marrow cell in the irradiation + PQQ group was superior to that in irradiation + nilestriol group. Our results clearly indicate favourable effects on survival under higher lethal radiation doses and the ability of pyrroloquinoline quinine to enhance haemopoietic recovery after sublethal radiation exposure.
Crystal structure and characterization of pyrroloquinoline quinone disodium trihydrate
Kazuto Ikemoto, Hitoshi Sakamoto, Masahiko Nakano
Chemistry Central Journal , 2012, DOI: 10.1186/1752-153x-6-57
Abstract: We prepared a crystal of PQQ disodium trihydrate in a solution of ethanol and water, studied its structure, and analyzed its properties. In the prepared crystal, the sodium atom interacted with the oxygen atom of two carboxylic acids as well as two quinones of the PQQ disodium trihydrate. In addition, the hydration water of the prepared crystal was less than that of the conventional PQQ disodium crystal. From the results of this study, it was found that the color and the near-infrared (NIR) spectrum of the prepared crystal changed depending on the water content in the dried samples.The water content in the dried samples was restored to that in the trihydrate crystal by placing the samples in a humid environment. In addition, the results of X-ray diffraction (XRD) and X-ray diffraction-differential calorimetry (XRD-DSC) analyses show that the phase of the trihydrate crystal changed when the crystallization water was eliminated. The dried crystal has two crystalline forms that are restored to the original trihydrate crystals in 20% relative humidity (RH). This crystalline (PQQ disodium trihydrate) is stable under normal environment.Pyrroloquinoline quinone (PQQ; 4,5-dihydro-4,5-dioxo-1 H-pyrrolo[2,3-f]quinoline- 2,7,9-tricarboxylic acid) (Figure 1a) is a water-soluble quinone that was first identified as a non-covalently prosthetic group in some bacterial glucose- or alcohol dehydrogenases [1,2]. It is interesting to note that trace amounts of PQQ have been found not only in microorganisms but also in humans and in the organs and tissues of rats, with the highest amount being found in human milk [3,4]. In addition, trace amounts of PQQ have also been found in daily foods and beverages [5,6]. In recent years, PQQ has been receiving considerable attention owing to its several interesting physiological functions [7,8]. PQQ stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and an increase in PGC-1α expression [9,10]. In addi
The pyrroloquinoline quinone biosynthesis pathway revisited: A structural approach
Sandra Puehringer, Moritz Metlitzky, Robert Schwarzenbacher
BMC Biochemistry , 2008, DOI: 10.1186/1471-2091-9-8
Abstract: New structural data of some PQQ biosynthesis proteins and their homologues provide new insights and functional assignments of the proteins in the pathway. Based on sequence analysis and homology models we propose the role and catalytic function for each enzyme involved in this intriguing biosynthesis pathway.PQQ is derived from the two amino acids glutamate and tyrosine encoded in the precursor peptide PqqA. Five reactions are necessary to form this quinone cofactor. The PqqA peptide is recognised by PqqE, which links the C9 and C9a, afterwards it is accepted by PqqF which cuts out the linked amino acids. The next reaction (Schiff base) is spontaneous, the following dioxygenation is catalysed by an unknown enzyme. The last cyclization and oxidation steps are catalysed by PqqC. Taken together the known facts of the different proteins we assign a putative function to all six proteins in PQQ biosynthesis pathway.Pyrroloquinoline quinone (4,5-dihydro-4,5-dioxo-1H-pyrrolo-[2,3-f]quinoline-2,7,9-tricarboxylic acid: PQQ) is a water soluble, heat-stable, tricyclic ortho-quinone. It serves as redox cofactor for various bacterial dehydrogenases[1] providing unique redox-features. Among the best known examples of enzymes that utilize PQQ as a noncovalent cofactor are methanol dehydrogenase [2] and glucose dehydrogenase [3]. In general, ortho-quinone cofactors are involved in various biological reactions that range from oxidative deaminations to free-radical redox reactions [4]. PQQ was the first cofactor to be found in this cofactor-family, followed by the identification of tryptophan tryptophylquinone (TTQ), trihydroxyphenylalanyl quinone (topaquinone or TPQ), lysine tyrosylquinone (LTQ) and the copper-complexed cysteinyltyrosyl radical. This family is the third family of cofactors following pyridine nucleotide- and flavin-dependent cofactors [5]. Among the quinone family PQQ is unique in that it features a high mid point redox potential, in the range of 90 mV, as compared to
Screening of Peptide Ligands for Pyrroloquinoline Quinone Glucose Dehydrogenase Using Antagonistic Template-Based Biopanning  [PDF]
Koichi Abe,Wataru Yoshida,Kotaro Terada,Yukiko Yagi-Ishii,Stefano Ferri,Kazunori Ikebukuro,Koji Sode
International Journal of Molecular Sciences , 2013, DOI: 10.3390/ijms141223244
Abstract: We have developed a novel method, antagonistic template-based biopanning, for screening peptide ligands specifically recognizing local tertiary protein structures. We chose water-soluble pyrroloquinoline quinone (PQQ) glucose dehydrogenase (GDH-B) as a model enzyme for this screening. Two GDH-B mutants were constructed as antagonistic templates; these have some point mutations to induce disruption of local tertiary structures within the loop regions that are located at near glucose-binding pocket. Using phage display, we selected 12-mer peptides that specifically bound to wild-type GDH-B but not to the antagonistic templates. Consequently, a peptide ligand showing inhibitory activity against GDH-B was obtained. These results demonstrate that the antagonistic template-based biopanning is useful for screening peptide ligands recognizing the specific local tertiary structure of proteins.
Altering Pyrroloquinoline Quinone Nutritional Status Modulates Mitochondrial, Lipid, and Energy Metabolism in Rats  [PDF]
Kathryn Bauerly,Calliandra Harris,Winyoo Chowanadisai,James Graham,Peter J. Havel,Eskouhie Tchaparian,Mike Satre,Joel S. Karliner,Robert B. Rucker
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0021779
Abstract: We have reported that pyrroloquinoline quinone (PQQ) improves reproduction, neonatal development, and mitochondrial function in animals by mechanisms that involve mitochondrial related cell signaling pathways. To extend these observations, the influence of PQQ on energy and lipid relationships and apparent protection against ischemia reperfusion injury are described herein. Sprague-Dawley rats were fed a nutritionally complete diet with PQQ added at either 0 (PQQ?) or 2 mg PQQ/Kg diet (PQQ+). Measurements included: 1) serum glucose and insulin, 2) total energy expenditure per metabolic body size (Wt3/4), 3) respiratory quotients (in the fed and fasted states), 4) changes in plasma lipids, 5) the relative mitochondrial amount in liver and heart, and 6) indices related to cardiac ischemia. For the latter, rats (PQQ? or PQQ+) were subjected to left anterior descending occlusions followed by 2 h of reperfusion to determine PQQ's influence on infarct size and myocardial tissue levels of malondialdehyde, an indicator of lipid peroxidation. Although no striking differences in serum glucose, insulin, and free fatty acid levels were observed, energy expenditure was lower in PQQ? vs. PQQ+ rats and energy expenditure (fed state) was correlated with the hepatic mitochondrial content. Elevations in plasma di- and triacylglyceride and β-hydroxybutryic acid concentrations were also observed in PQQ? rats vs. PQQ+ rats. Moreover, PQQ administration (i.p. at 4.5 mg/kg BW for 3 days) resulted in a greater than 2-fold decrease in plasma triglycerides during a 6-hour fast than saline administration in a rat model of type 2 diabetes. Cardiac injury resulting from ischemia/reperfusion was more pronounced in PQQ? rats than in PQQ+ rats. Collectively, these data demonstrate that PQQ deficiency impacts a number of parameters related to normal mitochondrial function.
Sleep, Fatigue, and Functional Health in Psychotic Patients  [PDF]
Flavie Waters,Neepa Naik,Daniel Rock
Schizophrenia Research and Treatment , 2013, DOI: 10.1155/2013/425826
Abstract: This study sought to examine the association between sleep, fatigue, and functional health in psychotic patients. Participants included 93 psychotic inpatients ( with schizophrenia) who completed the Chalder Fatigue Scale (ChFS), the Fatigue Symptom Inventory (FSI), the Pittsburgh Sleep Quality Index (PSQI), and the SF36 Health Survey. Patients were classified on the basis of their performance on sleep and fatigue measures: 60% reported significant levels of fatigue and 67% significant sleep disturbances. 28.4% reported both, suggesting that fatigue and sleep dysfunctions do not necessarily cooccur. A closer examination of patterns showed that fatigue was only related to qualitative aspects of sleep and not quantifiable aspects of sleep disturbances. The results also showed that functional health was the lowest in patients with high levels of fatigue, compared to patients with sleep problems only or patients with neither symptom. A regression analysis further showed that the size of the contribution of fatigue onto functional health was twice as much as that of sleep dysfunctions. In conclusion, the results show that (i) dissatisfaction with sleep—and not sleep itself—is related to fatigue symptoms and that (ii) fatigue is particularly detrimental to functional health, regardless of the presence of sleep dysfunctions. 1. Introduction Fatigue is a condition characterised by persistent weakness or exhaustion and a combination of symptoms that feature self-reported impairments in some of the following: impaired attention and concentration, headaches, unrefreshing sleep, and/or musculoskeletal pain [1]. Fatigue is an experiential state typically diagnosed on the basis of self-reports and is a common complaint in the general population [2, 3]. It is usually associated with middle age, being female, and having lower education and occupation attainment [4]. Fatigue is common in psychiatric conditions such as anxiety and depression (25–36%) [5–7] and in chronic medical conditions such as cancer, Parkinson’s disease, multiple sclerosis, diabetes, and viral infection [8–12]. Fatigue worsens with increasing physical disease severity [10] and is independent of medication suggesting that medication itself is not responsible for fatigue. Studies of fatigue in patients with psychotic disorders such as schizophrenia or bipolar disorder are currently lacking. Yet several reasons support an investigation into fatigue symptoms in these individuals. First, the functional impairments associated with fatigue include considerable impairments and disability [13, 14] pointing
Evaluat on of Sleep Quality and Fatigue in Hospitalized Patients  [PDF]
Ayla ünsal,G?k?e Demir
International Journal of Caring Sciences , 2012,
Abstract: Background: Hospitalization can significantly disrupt sleeping patterns. Insomnia in the hospitalized patient leads to increased fatigue.Aims and Objectives: The aim of this study was to evaluate and compare sleep quality and fatigue of the hospitalized patients and match healthy controls.Methodology: This is a descriptive cross-sectional study. A total of 150 hospitalized patients (internal clinics=75, surgical clinics=75) and 50 healthy controls constituted the sample. As the data gatheringtools, a questionnaire form, Pittsburgh Sleep Quality Index, and Visual Analogue Scale for Fatigue were used. The data was evaluated after transferring to SPSS 11.0 database in percentage, mean, independent group’s t-test, one way-ANOVA, LSD post hoc, chi-square, cronbach’s alpha coefficient, pearson product-moment correlation.Results: We found worse sleep quality and more fatigue in patients compared to controls. Female patients reported greater sleep disturbances and more severe fatigue than did male patients. It was found that the severity of fatigue was significantly correlated to sleep quality score.Conclusions: These results suggest that sleep quality and fatigue of inpatients is worse than healthy persons; there are significant relationships between sleep quality and fatigue, indicating the need for more individualized supportive nursing care. Patients with hospitalized need professional support from nurse. It is expected that nurses should have the basic knowledge about sleeping problems and fatigue in hospitalized patients when providing care to patients because of possible interactions with other treatments.
Melatonin Supplementation in Patients with Complete Tetraplegia and Poor Sleep  [PDF]
Jo Spong,Gerard A. Kennedy,Douglas J. Brown,Stuart M. Armstrong,David J. Berlowitz
Sleep Disorders , 2013, DOI: 10.1155/2013/128197
Abstract: People with complete tetraplegia have interrupted melatonin production and commonly report poor sleep. Whether the two are related is unclear. This pilot study investigated whether nightly supplementation of 3?mg melatonin would improve objective and subjective sleep in tetraplegia. Five participants with motor and sensory complete tetraplegia ingested 3?mg melatonin (capsule) two hours prior to usual sleep time for two weeks. Full portable sleep studies were conducted in participants’ homes on the night before commencing melatonin supplementation (baseline) and on the last night of the supplementation period. Endogenous melatonin levels were determined by assaying saliva samples collected the night of (just prior to sleep) and morning after (upon awakening) each sleep study. Prior to each sleep study measures of state sleepiness and sleep behaviour were collected. The results showed that 3?mg of melatonin increased salivary melatonin from near zero levels at baseline in all but one participant. A delay in time to Rapid Eye Movement sleep, and an increase in stage 2 sleep were observed along with improved subjective sleep experience with a reduction in time to fall asleep, improved quality of sleep and fewer awakenings during the night reported. Daytime sleepiness increased however. A randomised, placebo controlled trial with a larger sample is required to further explore and confirm these findings. 1. Introduction For people living with tetraplegia, excessive daytime sleepiness, disturbed and poor quality sleep are a common problem [1]. A number of factors contribute to disturbed sleep in people with tetraplegia with the absence of increase in evening endogenous melatonin production after a complete cervical spinal cord injury (SCI) [2, 3] potentially being one. Melatonin is secreted nocturnally by the pineal gland and is believed to play a major modulatory role in the timing of circadian rhythms including the sleep-wake cycle [4]. The daily rhythm of melatonin secretion is regulated by an endogenous pacemaker, the suprachiasmatic nucleus (SCN, “circadian clock”) which signals the pineal gland via a circuitous route involving other hypothalamic nuclei, brain stem nuclei, the spinal cord, and peripheral sympathetic neurons from the superior cervical ganglion (SCG) [4]. Melatonin levels typically begin to increase two to three hours before sleep with peak levels between 02:00 and 04:00 and trough levels during the day [4]. Melatonin secretion following a SCI is low or abolished in those with complete tetraplegia, but relatively normal in those with
The State of Fatigue and Sleep among Clinical Nurses in Japan  [PDF]
Naomi Sumi, Naotaka Sugimura, Yuko Yoshida, Rika Yano
Open Journal of Nursing (OJN) , 2017, DOI: 10.4236/ojn.2017.712104
The objective of this study was to investigate the state of fatigue and sleep among clinical nurses in Japan. This descriptive cross-sectional study was conducted from December 2015 to January 2016. The participants were nurses who worked in public hospitals with 500 beds in the major cities and regional cities of Hokkaido. Fatigue was quantitatively assessed using the Cumulative Fatigue Symptoms Index (CFSI). Among nurses in their twenties, the rate of complaints about anxiety and decrease in vitality were high, which was replaced with complaints about irritability among nurses in their thirties. The most popular complaint among nurses in their forties was general fatigue. There was no difference in complaint ratios concerning the workplace location among nurses in their twenties and thirties, nurses in their forties working in suburban areas complained about fatigue more than their urban area. Nurses with sleep problems related to anxiety have a significantly higher complaint rate for all the eight items of CFSI compared with the nurses who do not have such problems (p < 0.001). This is an intermediate report and is part of a study that aims to develop a health management program for hospital nurses regarding fatigue and sleep.
Sleep structure and sleepiness in chronic fatigue syndrome with or without coexisting fibromyalgia
Fumiharu Togo, Benjamin H Natelson, Neil S Cherniack, Jennifer FitzGibbons, Carmen Garcon, David M Rapoport
Arthritis Research & Therapy , 2008, DOI: 10.1186/ar2425
Abstract: We compared sleep structures and subjective scores on visual analog scales for sleepiness and fatigue in CFS patients with or without coexisting fibromyalgia (n = 12 and 14, respectively) with 26 healthy subjects. None had current major depressive disorder, and all were studied at the same menstrual phase.CFS patients had significant differences in polysomnograpic findings from healthy controls and felt sleepier and more fatigued than controls after a night's sleep. CFS patients as a group had less total sleep time, lower sleep efficiency, and less rapid eye movement sleep than controls. A possible explanation for the unrefreshing quality of sleep in CFS patients was revealed by stratification of patients into those who reported more or less sleepiness after a night's sleep (a.m. sleepier or a.m. less sleepy, respectively). Those in the sleepier group reported that sleep did not improve their symptoms and had poorer sleep efficiencies and shorter runs of sleep than both controls and patients in the less sleepy group; patients in the less sleepy group reported reduced fatigue and pain after sleep and had relatively normal sleep structures. This difference in sleep effects was due primarily to a decrease in the length of periods of uninterrupted sleep in the a.m. sleepier group.CFS patients had significant differences in polysomnographic findings from healthy controls and felt sleepier and more fatigued than controls after a night's sleep. This difference was due neither to diagnosable sleep disorders nor to coexisting fibromyalgia but primarily to a decrease in the length of periods of uninterrupted sleep in the patients with more sleepiness in the morning than on the night before. This sleep disruption may explain the overwhelming fatigue, report of unrefreshing sleep, and pain in this subgroup of patients.Chronic fatigue syndrome (CFS) is a medically unexplained condition occurring mostly in women and is characterized by persistent or relapsing fatigue that lasts a
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