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Burns : Journal of the International... Feb 2015The importance of cyanide toxicity as a component of inhalational injury in patients with burns is increasingly being recognised, and its prompt recognition and... (Review)
Review
The importance of cyanide toxicity as a component of inhalational injury in patients with burns is increasingly being recognised, and its prompt recognition and management is vital for optimising burns survival. The evidence base for the use of cyanide antidotes is limited by a lack of randomised controlled trials in humans, and in addition consideration must be given to the concomitant pathophysiological processes in patients with burns when interpreting the literature. We present a literature review of the evidence base for cyanide antidotes with interpretation in the context of patients with burns. We conclude that hydroxycobalamin should be utilised as the first-line antidote of choice in patients with burns with inhalational injury where features consistent with cyanide toxicity are present.
Topics: Adenosine; Amyl Nitrite; Burns; Chelating Agents; Cyanides; Edetic Acid; Humans; Hydroxocobalamin; Hyperbaric Oxygenation; Oxygen Inhalation Therapy; Poisoning; Pteridines; Smoke Inhalation Injury; Sodium Nitrite; Thiosulfates
PubMed: 24994676
DOI: 10.1016/j.burns.2014.06.001 -
Scientific Reports Oct 2020This study aimed to evaluate the possible changes of neopterin, biopterin levels and tryptophan degradation in diabetes and to compare the results within diabetes groups...
This study aimed to evaluate the possible changes of neopterin, biopterin levels and tryptophan degradation in diabetes and to compare the results within diabetes groups and with healthy subjects. Diabetes mellitus patients and healthy controls were recruited the study. Patients were further subgrouped according to their drug therapy. Serum neopterin concentrations were detected by ELISA. Urinary neopterin, biopterin, serum tryptophan (Trp) and kynurenine (Kyn) levels were detected by HPLC. There was no difference between controls and diabetes patients in serum neopterin, urinary neopterin and biopterin levels (p > 0.05, all). Serum Trp and Kyn levels were significantly different in type 1 diabetes (T1DM) patients compared to controls (p < 0.05, both). Serum neopterin levels were significantly higher in type 2 diabetes patients (T2DM) compared to T1DM (p < 0.05). Urinary biopterin levels of T2DM patients using both metformin and vildagliptin were significantly higher than T1DM patients (p < 0.05). The correlations between serum neopterin and urinary neopterin, Kyn and Kyn/Trp were statistically significant in control and patient groups (p < 0.05, all). The study showed that Kyn/Trp was altered in diabetes patients due to immune modulation. On the other hand, although xenobiotic exposure may change pteridine levels, metformin and/or vildagliptin use in T2DM patients did not have any effect on the measured parameters.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biopterins; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Kynurenine; Male; Metformin; Middle Aged; Neopterin; Tryptophan; Vildagliptin; Young Adult
PubMed: 33046801
DOI: 10.1038/s41598-020-74183-w -
Biochimica Et Biophysica Acta Jun 2015X-ray absorption (XAS) and X-ray emission spectroscopy (XES) provide element specific probes of the geometric and electronic structures of metalloprotein active sites.... (Review)
Review
X-ray absorption (XAS) and X-ray emission spectroscopy (XES) provide element specific probes of the geometric and electronic structures of metalloprotein active sites. As such, these methods have played an integral role in nitrogenase research beginning with the first EXAFS studies on nitrogenase in the late 1970s. Herein, we briefly explain the information that can be extracted from XAS and XES. We then highlight the recent applications of these methods in nitrogenase research. The influence of X-ray spectroscopy on our current understanding of the atomic structure and electronic structure of iron molybdenum cofactor (FeMoco) is emphasized. Contributions of X-ray spectroscopy to understanding substrate interactions and cluster biosynthesis are also discussed. This article is part of a Special Issue entitled: Fe/S proteins: Analysis, structure, function, biogenesis and diseases.
Topics: Coenzymes; Iron; Metalloproteins; Models, Molecular; Molecular Structure; Molybdenum Cofactors; Nitrogenase; Protein Conformation; Pteridines; Spectrometry, X-Ray Emission; X-Ray Absorption Spectroscopy
PubMed: 25486459
DOI: 10.1016/j.bbamcr.2014.11.027 -
Progress in Neuro-psychopharmacology &... Jan 2023Pteridines, such as neopterin, biopterin, and tetrahydrobiopterin (BH), may be involved in depression pathophysiology owing to their links to immune-inflammatory... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Pteridines, such as neopterin, biopterin, and tetrahydrobiopterin (BH), may be involved in depression pathophysiology owing to their links to immune-inflammatory response, oxidative and nitrosative stress, and monoaminergic transmission. Nonetheless, studies assessing pteridines in depression are inconsistent. We conducted a systematic review and meta-analysis of observational studies comparing blood pteridine concentrations between subjects with depression and healthy controls (HCs).
METHODS
We searched Embase, MEDLINE, and PsycInfo for articles indexed through November 2021. Study quality was appraised, evaluating age and gender comparability between groups, sample representativeness, and methods to assess depression. Random-effects meta-analyses were carried out, generating pooled standardized mean differences (SMDs). Heterogeneity across studies was estimated using the I statistic.
RESULTS
Twenty-four studies, involving 3075 subjects, were included. Individuals with depression showed blood neopterin concentrations higher than HCs (k = 19; SMD = 0.36; p < 0.001) with moderate heterogeneity across studies (I = 58.2%). No moderating role of age, gender, or type of blood sample was found. Sensitivity analyses showed no impact of inconsistency and quality of studies on findings. Neopterin concentrations were higher among individuals with major depressive disorder compared to HCs (SMD = 0.44; p < 0.001). This held true also when considering only drug-free subjects (SMD = 0.68; p = 0.003). No differences in biopterin concentrations were found between subjects with depression and HCs (k = 5; SMD = -0.35; p = 0.086), though this result was limited by inconsistency of findings (I = 77.9%) and quality of studies. Finally, no sufficient data were available for a meta-analysis on BH.
CONCLUSIONS
As a whole, our work partly supports the hypothesis of an imbalance of pteridine metabolism in depression.
Topics: Humans; Neopterin; Depression; Depressive Disorder, Major; Biopterins; Pteridines
PubMed: 36089162
DOI: 10.1016/j.pnpbp.2022.110633 -
International Journal of Molecular... Oct 2023Red coloration is considered an economically important trait in some fish species, including spotted scat, a marine aquaculture fish. Erythrophores are gradually covered...
Red coloration is considered an economically important trait in some fish species, including spotted scat, a marine aquaculture fish. Erythrophores are gradually covered by melanophores from the embryonic stage. Despite studies of black spot formation and melanophore coloration in the species, little is known about erythrophore development, which is responsible for red coloration. 1-phenyl 2-thiourea (PTU) is a tyrosinase inhibitor commonly used to inhibit melanogenesis and contribute to the visualization of embryonic development. In this study, spotted scat embryos were treated with 0.003% PTU from 0 to 72 h post fertilization (hpf) to inhibit melanin. Erythrophores were clearly observed during the embryonic stage from 14 to 72 hpf, showing an initial increase (14 to 36 hpf), followed by a gradual decrease (36 to 72 hpf). The number and size of erythrophores at 36 hpf were larger than those at 24 and 72 hpf. At 36 hpf, LC-MS and absorbance spectrophotometry revealed that the carotenoid content was eight times higher than the pteridine content, and β-carotene and lutein were the main pigments related to red coloration in spotted scat larvae. Compared with their expression in the normal hatching group, , , and related to retinol metabolism and and related to steroid hormone biosynthesis and steroid biosynthesis were significantly up-regulated in the PTU group, and associated with phototransduction was significantly down-regulated. By qRT-PCR, the expression levels of genes involved in carotenoid metabolism (, , , , , and ), pteridine synthesis (), and chromatophore differentiation ( and ) were significantly higher at 36 hpf than at 24 hpf and 72 hpf, except for . These gene expression profiles were consistent with the developmental changes of erythrophores. These findings provide insights into pigment cell differentiation and gene function in the regulation of red coloration and contribute to selective breeding programs for ornamental aquatic animals.
Topics: Animals; Larva; Fishes; Gene Expression Profiling; Carotenoids; Pteridines; Steroids
PubMed: 37895036
DOI: 10.3390/ijms242015356 -
Leukemia Jan 2015Owing to their integral involvement in cell cycle regulation, the Polo-like kinase (Plk) family, particularly Plk1, has emerged as an attractive therapeutic target in... (Review)
Review
Owing to their integral involvement in cell cycle regulation, the Polo-like kinase (Plk) family, particularly Plk1, has emerged as an attractive therapeutic target in oncology. In recent years, several Plk1 inhibitors have been developed, with some agents showing encouraging results in early-phase clinical trials. This review focuses on volasertib (BI 6727; an investigational agent), a potent and selective Plk inhibitor. Volasertib has shown promising activity in various cancer cell lines and xenograft models of human cancer. Trials performed to date suggest that volasertib has clinical efficacy in a range of malignancies, with the most promising results seen in patients with acute myeloid leukemia (AML). Encouragingly, recent phase II data have demonstrated that volasertib combined with low-dose cytarabine (LDAC) was associated with higher response rates and improved event-free survival than LDAC alone in patients with previously untreated AML. Based on these observations, and its presumably manageable safety profile, volasertib is currently in phase III development as a potential treatment for patients with AML who are ineligible for intensive remission induction therapy. Given that many patients with AML are of an older age and frail, this constitutes an area of major unmet need. In this review, we discuss the biologic rationale for Plk1 inhibitors in cancer, the clinical development of volasertib to date in solid tumors and AML, and the future identification of biomarkers that might predict response to volasertib and help determine the role of this agent in the clinic.
Topics: Humans; Neoplasms; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Pteridines
PubMed: 25027517
DOI: 10.1038/leu.2014.222 -
Journal of Insect Physiology Jan 2023Tetrahydrobiopterin (BH4) is produced from guanosine triphosphate (GTP) under catalyzation of GTP cyclohydrolase I (GTPCH), 6-pyruvoyltetrahydropterin synthase (PTPS)...
Tetrahydrobiopterin (BH4) is produced from guanosine triphosphate (GTP) under catalyzation of GTP cyclohydrolase I (GTPCH), 6-pyruvoyltetrahydropterin synthase (PTPS) and sepiapterin reductase (SR), among others. In Drosophila melanogaster, BH4 and other pteridines are required for cuticle tanning and eye pigmentation. In this study, two Hvgtpch (Hvgtpch-a and Hvgtpch-b), an Hvptps and an Hvsr transcripts were identified in a serious defoliator Henosepilachna vigintioctopunctata. Hvgtpch-a and Hvgtpch-b were highly expressed just before and/or right after the molt, in contrast to Hvptps and Hvsr. RNA interference (RNAi) by injection of a dsgtpch targeting the common fragment of Hvgtpch-a and Hvgtpch-b into the third instar larvae caused albino fourth-instar larvae and pupae. Around 80% of the Hvgtpch RNAi larvae failed to pupate. The remaining 20% of Hvgtpch RNAi pupated beetles did not completely remove the larval/pupal exuviae after emerged as adults and eventually died. Depletion of Hvgtpch at the fourth instar stage resulted in under-pigmented pupae and adults, with significantly low pupation and emergence rates. The Hvgtpch RNAi adults rarely moved and fed on plant leaves; they died within a week after emergence. Silence of Hvptps or Hvsr at the third- and fourth-instar stages led to similar but less serious phenotypes, with lowest influence in the Hvsr RNAi ladybirds. Moreover, RNAi of Hvgtpch, Hvptps or Hvsr did not affect coloration of the larval ocelli and pupal/adult compound eyes. Therefore, our results demonstrated that pteridines are involved in melanin formation but not in eye pigmentation in H. vigintioctopunctata. Moreover, our findings will enable the development of a dsgtpch-based pesticide to control H. vigintioctopunctata larvae.
Topics: Animals; Drosophila melanogaster; Coleoptera; Larva; Biopterins; Pigmentation; Pupa
PubMed: 36427533
DOI: 10.1016/j.jinsphys.2022.104457 -
BioFactors (Oxford, England) Jul 2017Molybdenum (Mo) is present in the active center of eukaryotic enzymes as a tricyclic pyranopterin chelate compound forming the Mo Cofactor (Moco). Four Moco containing... (Review)
Review
Molybdenum (Mo) is present in the active center of eukaryotic enzymes as a tricyclic pyranopterin chelate compound forming the Mo Cofactor (Moco). Four Moco containing enzymes are known in eukaryotes, nitrate reductase (NR), sulfite oxidase (SO), xanthine oxidoreductase (XOR), and aldehyde oxidase (AO). A fifth Moco enzyme has been recently identified. Because of the ability of this enzyme to convert by reduction several amidoximes prodrugs into their active amino forms, it was named mARC (mitochondrial Amidoxime Reducing Component). This enzyme is also able to catalyze the reduction of a broad range of N-hydroxylated compounds (NHC) as the base analogue 6-hydroxylaminopurine (HAP), as well as nitrite to nitric oxide (NO). All the mARC proteins need reducing power that is supplied by other proteins. The human and plants mARC proteins require a Cytochrome b5 (Cytb5) and a Cytochrome b5 reductase (Cytb5-R) to form an electron transfer chain from NADH to the NHC. Recently, plant mARC proteins were shown to be implicated in the reduction of nitrite to NO, and it was proposed that the electrons required for the reaction were supplied by NR instead of Cytochrome b5 components. This newly characterized mARC activity was termed NO Forming Nitrite Reductase (NOFNiR). Moonlighting proteins form a special class of multifunctional enzymes that can perform more than one function; if the extra function is not physiologically relevant, they are called promiscuous enzymes. In this review, we summarize the current knowledge on the mARC protein, and we propose that mARC is a new moonlighting enzyme. © 2017 BioFactors, 43(4):486-494, 2017.
Topics: Aldehyde Oxidase; Animals; Coenzymes; Cytochromes b5; Humans; Metalloproteins; Molybdenum Cofactors; Nitrate Reductase; Pteridines; Sulfite Oxidase; Xanthine Dehydrogenase
PubMed: 28497908
DOI: 10.1002/biof.1362 -
Medicinal Research Reviews Jul 2016Considering the important side effects of conventional microtubule targeting agents, more and more research focuses on regulatory proteins for the development of... (Review)
Review
Considering the important side effects of conventional microtubule targeting agents, more and more research focuses on regulatory proteins for the development of mitosis-specific agents. Polo-like kinase 1 (Plk1), a master regulator of several cell cycle events, has arisen as an intriguing target in this research field. The observed overexpression of Plk1 in a broad range of human malignancies has given rise to the development of several potent and specific small molecule inhibitors targeting the kinase. In this review, we focus on volasertib (BI6727), the lead agent in category of Plk1 inhibitors at the moment. Numerous preclinical experiments have demonstrated that BI6727 is highly active across a variety of carcinoma cell lines, and the inhibitor has been reported to induce tumor regression in several xenograft models. Moreover, volasertib has shown clinical efficacy in multiple tumor types. As a result, Food and Drug Administration (FDA) has recently awarded volasertib the Breakthrough Therapy status after significant benefit was observed in acute myeloid leukemia (AML) patients treated with the Plk1 inhibitor. Here, we discuss both preclinical and clinical data available for volasertib administered as monotherapy or in combination with other anticancer therapies in a broad range of tumor types.
Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cell Cycle Proteins; Humans; Neoplasms; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Pteridines; Randomized Controlled Trials as Topic; Polo-Like Kinase 1
PubMed: 27140825
DOI: 10.1002/med.21392 -
Journal of Pharmaceutical and... Jun 2024Type 1 diabetes (T1D) and its complications are known to be associated with oxidative stress. Pteridine derivatives and indoleamine 2,3-dioxygenase (IDO) activity can be...
AIM
Type 1 diabetes (T1D) and its complications are known to be associated with oxidative stress. Pteridine derivatives and indoleamine 2,3-dioxygenase (IDO) activity can be used as biomarkers in the evaluation of oxidative stress. In this study, our aim is to compare the concentrations of serum and urinary pteridine derivatives, as well as serum IDO activity, in children and adolescents diagnosed with T1D and those in a healthy control group.
METHOD
A cross-sectional study was performed and included 93 patients with T1D and 71 healthy children. Serum and urine biopterin, neopterin, monapterin, pterin, isoxanthopterin, and pterin-6-carboxylic acid (6PTC) and serum tryptophan and kynurenine levels were analyzed and compared with healthy controls. High-performance liquid chromatography was used for the analysis of pteridine derivatives, tryptophan, and kynurenine. Xanthine oxidase (XO) activity, a marker of oxidative stress, was defined by measurement of serum and urine isoxanthopterin. As an indicator of indolamine 2,3-dioxygenase (IDO) activity, the ratio of serum kynurenine/tryptophan was used.
RESULTS
Serum isoxanthopterin and tryptophan concentrations were increased, and serum 6PTC concentration was decreased in children with T1D (p=0.01, p=0.021, p<0.001, respectively). In children with T1D, IDO activity was not different from healthy controls (p>0.05). Serum neopterin level and duration of diabetes were weakly correlated (p=0.045, r=0.209); urine neopterin/creatinine and isoxanthopterin/creatinine levels were weakly correlated with HbA1c levels (p=0.005, r=0.305; p=0.021, r=0.249, respectively). Urine pterin/creatinine level negatively correlated with body mass index-SDS. (p=0.015, r=-0.208).
CONCLUSION
We found for the first time that isoxanthopterin levels increased and 6PTC levels decreased in children and adolescents with T1D. Elevated isoxanthopterin levels suggest that the XO activity is increased in TID. Increased XO activity may be an indicator of vascular complications reflecting T1D-related endothelial dysfunction.
Topics: Child; Adolescent; Humans; Tryptophan; Kynurenine; Diabetes Mellitus, Type 1; Neopterin; Creatinine; Cross-Sectional Studies; Pteridines; Xanthopterin
PubMed: 38437786
DOI: 10.1016/j.jpba.2024.116072