Covertly active and progressing neurochemical abnormalities in suppressed HIV infection.

Science.gov (United States)

Cysique, Lucette A; Jugé, Lauriane; Gates, Thomas; Tobia, Michael; Moffat, Kirsten; Brew, Bruce J; Rae, Caroline

2018-01-01

To assess whether HIV-related brain injury is progressive in persons with suppressed HIV infection. Seventy-three HIV+ virally suppressed men and 35 HIV- men, screened for psychiatric and alcohol/drug use disorders, underwent neuropsychological evaluation and proton magnetic resonance spectroscopy ( 1 H-MRS) at baseline and after and 23 ± 5 months. 1 H-MRS included brain regions known to be vulnerable to HIV and aging: frontal white matter (FWM), posterior cingulate cortex (PCC), and caudate area (CA). Major brain metabolites such as creatine (Cr: marker of cellular energy), N -acetyl aspartate (NAA: marker of neuronal integrity), choline (marker of cellular membrane turnover), glutamate/glutamine (excitatory/inhibitory neurotransmitter), and myo -Inositol (mI: marker of neuroinflammation) were calculated with reference to water signal. Neurocognitive decline was corrected for practice effect and baseline HIV-associated neurocognitive disorder (HAND) status. Across the study period, 44% had intact cognition, 42% stable HAND (including the single case that improved), 10% progressing HAND, and 4% incident HAND. When analyzing the neurochemical data per neurocognitive trajectories, we found decreasing PCC Cr in all subgroups compared with controls ( p < 0.002). In addition, relative to the HIV- group, stable HAND showed decreasing FWM Cr, incident HAND showed steep FWM Cr reduction, whereas progressing HAND had a sharply decreasing PCC NAA and reduced but stable CA NAA. When analyzing the neurochemical data at the group level (HIV+ vs HIV- groups), we found stable abnormal metabolite concentrations over the study period: decreased FWM and PCC Cr (both p < 0.001), decreased PCC NAA and CA NAA (both p < 0.05) and PCC mI increase ( p < 0.05). HIV duration and historical HAND had modest effects on metabolite changes. Our study reveals covertly active or progressing HIV-related brain injury in the majority of this virally suppressed cohort, reflecting ongoing

Prediction of Relative In Vivo Metabolite Exposure from In Vitro Data Using Two Model Drugs: Dextromethorphan and Omeprazole

Science.gov (United States)

Lutz, Justin D.

2012-01-01

Metabolites can have pharmacological or toxicological effects, inhibit metabolic enzymes, and be used as probes of drug-drug interactions or specific cytochrome P450 (P450) phenotypes. Thus, better understanding and prediction methods are needed to characterize metabolite exposures in vivo. This study aimed to test whether in vitro data could be used to predict and rationalize in vivo metabolite exposures using two model drugs and P450 probes: dextromethorphan and omeprazole with their primary metabolites dextrorphan, 5-hydroxyomeprazole (5OH-omeprazole), and omeprazole sulfone. Relative metabolite exposures were predicted using metabolite formation and elimination clearances. For dextrorphan, the formation clearances of dextrorphan glucuronide and 3-hydroxymorphinan from dextrorphan in human liver microsomes were used to predict metabolite (dextrorphan) clearance. For 5OH-omeprazole and omeprazole sulfone, the depletion rates of the metabolites in human hepatocytes were used to predict metabolite clearance. Dextrorphan/dextromethorphan in vivo metabolite/parent area under the plasma concentration versus time curve ratio (AUCm/AUCp) was overpredicted by 2.1-fold, whereas 5OH-omeprazole/omeprazole and omeprazole sulfone/omeprazole were predicted within 0.75- and 1.1-fold, respectively. The effect of inhibition or induction of the metabolite's formation and elimination on the AUCm/AUCp ratio was simulated. The simulations showed that unless metabolite clearance pathways are characterized, interpretation of the metabolic ratios is exceedingly difficult. This study shows that relative in vivo metabolite exposure can be predicted from in vitro data and characterization of secondary metabolism of probe metabolites is critical for interpretation of phenotypic data. PMID:22010218

Muscle-tendon-related abnormalities detected by ultrasonography are common in symptomatic hip dysplasia

DEFF Research Database (Denmark)

Jacobsen, Julie Sandell; Bolvig, Lars; Hölmich, Per

2018-01-01

INTRODUCTION: Hip dysplasia is characterized by reduced acetabular coverage of the femoral head leading to an increased mechanical load on the hip joint and the acting hip muscles. Potentially, the muscles and tendons functioning close to the hip joint may present with overuse......-related ultrasonography findings. The primary aim was to report the prevalence of muscle-tendon-related abnormalities detected by ultrasonography in 100 patients with symptomatic hip dysplasia. The secondary aim was to investigate correlations between muscle-tendon-related abnormalities detected by ultrasonography......-tendon-related abnormalities detected by ultrasonography in the hip and groin region are common in patients with symptomatic hip dysplasia, and the ultrasonography findings of the iliopsoas and gluteus medius/minimus tendons are weakly to moderately correlated to pain related to muscles and tendons in these structures. Both...

Relation between the level of self-mutilation and theconcentration of fecal metabolites of glucocorticoids incaptive chimpanzees (Pan troglodytes

Directory of Open Access Journals (Sweden)

Cristiane S. Pizzutto

2015-01-01

Full Text Available The influence of stress in an environment, according with the behavioral and endocrine variables of primates, are increasingly being studied by a diversity of authors, and have shown that abnormal behaviors associated with increased glucocorticoids may be directly related with the impairment of their well-being. In this work were used 22 adult chimpanzees (Pan troglodytes, 11 males and 11 females, kept in captivity in three different institutions. All animals had their behavior registered by focal session using a 30 seconds sample interval, during six months, totaling 4,800 registries per each animal. During this period, fecal samples were collected 3 times a week for the extraction and measurement of the concentration of fecal metabolites of glucocorticoid by radioimmunoassay. Of the total observed, stereotypical behaviors represented 13,45±2.76%, and among them, self-mutilation represented 38.28±3.98 %. The animals were classified into three different scores, according with the percentage of body surface with alopecia due to self-mutilation. It was found a positive correlation of high intensity between the scores of alopecia due to the observed mutilation and the average concentrations of fecal metabolites of glucocorticoids. This result strongly suggests that this measurement of self-mutilation in a chimpanzee can be used as an important auxiliary tool to evaluate de conditions of adaptation of an animal in captivity, functioning as a direct indicator of the presence of chronic stress.

Motility abnormalities in esophageal body in GERD: are they truly related to reflux?

Science.gov (United States)

Ciriza de los Ríos, C; García Menéndez, L; Díez Hernández, A; Fernández Eroles, A L; Vega Fernández, A; Enguix Armada, A

2005-03-01

Esophageal motility abnormalities have been observed in patients with gastroesophageal reflux disease. The aim of the present study was to determine if esophageal motor disorders in patients with a positive response to the omeprazole test are related to the existence of reflux or they are concomitant findings. A 24-hour pH monitoring and a stationary manometry were performed on 128 patients: 49 of them had normal manometry, 31 hypotensive lower esophageal sphincter, 29 motor disorder in esophageal body, and 19 hypotensive lower esophageal sphincter and motor disorder in esophageal body. We found an association between the presence of abnormal reflux and motor disorder in esophageal body (chi test; P esophageal motility was the disorder most strongly related to reflux, whereas the hypercontractile disorders were not clearly attributed to it. Esophageal manometric abnormalities should be considered cautiously before considering a motor disorder as a consequence of abnormal reflux.

The nature of white matter abnormalities in blast-related mild traumatic brain injury

Directory of Open Access Journals (Sweden)

Jasmeet P. Hayes

2015-01-01

Full Text Available Blast-related traumatic brain injury (TBI has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI. The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI - LOC group, and blast-related mTBI with LOC (mTBI + LOC group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1 a region-specific analysis and 2 a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of

A new paradigm for known metabolite identification in metabonomics/metabolomics: metabolite identification efficiency.

Science.gov (United States)

Everett, Jeremy R

2015-01-01

A new paradigm is proposed for assessing confidence in the identification of known metabolites in metabonomics studies using NMR spectroscopy approaches. This new paradigm is based upon the analysis of the amount of metabolite identification information retrieved from NMR spectra relative to the molecular size of the metabolite. Several new indices are proposed including: metabolite identification efficiency (MIE) and metabolite identification carbon efficiency (MICE), both of which can be easily calculated. These indices, together with some guidelines, can be used to provide a better indication of known metabolite identification confidence in metabonomics studies than existing methods. Since known metabolite identification in untargeted metabonomics studies is one of the key bottlenecks facing the science currently, it is hoped that these concepts based on molecular spectroscopic informatics, will find utility in the field.

A New Paradigm for Known Metabolite Identification in Metabonomics/Metabolomics: Metabolite Identification Efficiency

Directory of Open Access Journals (Sweden)

Jeremy R. Everett

2015-01-01

Full Text Available A new paradigm is proposed for assessing confidence in the identification of known metabolites in metabonomics studies using NMR spectroscopy approaches. This new paradigm is based upon the analysis of the amount of metabolite identification information retrieved from NMR spectra relative to the molecular size of the metabolite. Several new indices are proposed including: metabolite identification efficiency (MIE and metabolite identification carbon efficiency (MICE, both of which can be easily calculated. These indices, together with some guidelines, can be used to provide a better indication of known metabolite identification confidence in metabonomics studies than existing methods. Since known metabolite identification in untargeted metabonomics studies is one of the key bottlenecks facing the science currently, it is hoped that these concepts based on molecular spectroscopic informatics, will find utility in the field.

Ventricular shape and relative position abnormalities in preterm neonates

Directory of Open Access Journals (Sweden)

N. Paquette

2017-01-01

Full Text Available Recent neuroimaging findings have highlighted the impact of premature birth on subcortical development and morphological changes in the deep grey nuclei and ventricular system. To help characterize subcortical microstructural changes in preterm neonates, we recently implemented a multivariate tensor-based method (mTBM. This method allows to precisely measure local surface deformation of brain structures in infants. Here, we investigated ventricular abnormalities and their spatial relationships with surrounding subcortical structures in preterm neonates. We performed regional group comparisons on the surface morphometry and relative position of the lateral ventricles between 19 full-term and 17 preterm born neonates at term-equivalent age. Furthermore, a relative pose analysis was used to detect individual differences in translation, rotation, and scale of a given brain structure with respect to an average. Our mTBM results revealed broad areas of alterations on the frontal horn and body of the left ventricle, and narrower areas of differences on the temporal horn of the right ventricle. A significant shift in the rotation of the left ventricle was also found in preterm neonates. Furthermore, we located significant correlations between morphology and pose parameters of the lateral ventricles and that of the putamen and thalamus. These results show that regional abnormalities on the surface and pose of the ventricles are also associated with alterations on the putamen and thalamus. The complementarity of the information provided by the surface and pose analysis may help to identify abnormal white and grey matter growth, hinting toward a pattern of neural and cellular dysmaturation.

Movement-related cortical potentials in paraplegic patients: abnormal patterns and considerations for BCI-rehabilitation

Directory of Open Access Journals (Sweden)

Ren eXu

2014-08-01

Full Text Available Non-invasive EEG-based Brain-Computer Interfaces (BCI can be promising for the motor neuro-rehabilitation of paraplegic patients. However, this shall require detailed knowledge of the abnormalities in the EEG signatures of paraplegic patients. The association of abnormalities in different subgroups of patients and their relation to the sensorimotor integration are relevant for the design, implementation and use of BCI systems in patient populations. This study explores the patterns of abnormalities of movement related cortical potentials (MRCP during motor imagery tasks of feet and right hand in patients with paraplegia (including the subgroups with/without central neuropathic pain and complete/incomplete injury patients and the level of distinctiveness of abnormalities in these groups using pattern classification. The most notable observed abnormalities were the amplified execution negativity and its slower rebound in the patient group. The potential underlying mechanisms behind these changes and other minor dissimilarities in patients’ subgroups, as well as the relevance to BCI applications, are discussed. The findings are of interest from a neurological perspective as well as for BCI-assisted neuro-rehabilitation and therapy.

Abnormal tyrosine and phenylalanine metabolism in patients with tyrosyluria and phenylketonuria; gas-liquid chromatographic analysis of urinary metabolites

NARCIS (Netherlands)

Wadman, S.K.; Heiden, C. van der; Ketting, D.; Sprang, F.J. van

Gas-liquid chromatographic methods have been developed for the analysis of: urinary phenylalanine metabolites (I) in patients with phenylketonuria, tyrosine metabolites (II) in patients with a disturbed tyrosine metabolism at the level of p-hydroxyphenylpyruvate hydroxylase, and homogentisic acid in

Prevalence of abnormal birth weight and related factors in Northern region, Ghana

OpenAIRE

Abubakari, Abdulai; Kynast-Wolf, Gisela; Jahn, Albrecht

2015-01-01

Background: Birth weight is a crucial determinant of the development potential of the newborn. Abnormal newborn weights are associated with negative effects on the health and survival of the baby and the mother. Therefore, this study was designed to determine the prevalence of abnormal birth weight and related factors in Northern region, Ghana. Methods: The study was a facility-based cross-sectional survey in five hospitals in Northern region, Ghana. These hospitals were selected based on t...

Effect of pistachio consumption on the modulation of urinary gut microbiota-related metabolites in prediabetic subjects.

Science.gov (United States)

Hernández-Alonso, Pablo; Cañueto, Daniel; Giardina, Simona; Salas-Salvadó, Jordi; Cañellas, Nicolau; Correig, Xavier; Bulló, Mònica

2017-07-01

The specific nutritional composition of nuts could affect different metabolic pathways involved in a broad range of metabolic diseases. We therefore investigated whether chronic consumption of pistachio nuts modifies the urine metabolome in prediabetic subjects. We designed a randomized crossover clinical trial in 39 prediabetic subjects. They consumed a pistachio-supplemented diet (PD, 50% carbohydrates, 33% fat, including 57 g/d of pistachios daily) and a control diet (CD, 55% carbohydrates, 30% fat) for 4 months each, separated by a 2-week wash-out. Nuclear magnetic resonance (NRM) was performed to determine changes in 24-h urine metabolites. Significant changes in urine metabolites according to the different intervention periods were found in uni- and multivariate analysis. Score plot of the first two components of the multilevel partial least squares discriminant analysis (ML-PLS-DA) showed a clear separation of the intervention periods. Three metabolites related with gut microbiota metabolism (i.e., hippurate, p-cresol sulfate and dimethylamine) were found decreased in PD compared with CD (Ppistachio consumption may modulate some urinary metabolites related to gut microbiota metabolism and the TCA cycle; all associated with metabolic derangements associated with insulin resistance and Type 2 diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

Dupuytren's disease metabolite analyses reveals alterations following initial short-term fibroblast culturing.

NARCIS (Netherlands)

Rehman, S.; Xu, Y.; Dunn, W.B.; Day, P.J.; Westerhoff, H.V.; Goodacre, R.; Bayat, A.

2012-01-01

Dupuytren's disease (DD) is an ill-defined fibroproliferative disorder affecting the palm of the hand, resulting in progressive and irreversible digital contracture. In view of the abnormal gene dysregulation found in DD, and its potential effect on metabolites at a functional level, we chose to

ST-T Abnormalities on ECG in Relation to Cardiovascular Risk Factors

Directory of Open Access Journals (Sweden)

Yuko Chinushi, MD

2011-01-01

Conclusions: ST-T abnormalities without apparent heart diseas may be considered to be nonspecific but this cross-sectional study showed that they are related to CVRs and may be used as an early marker of preclinical cardiac damage by CVRs.

MRI abnormalities and related risk factors of the brain in patients with neuromyelitis optica

International Nuclear Information System (INIS)

Xiao Hui; Ma Lin; Lou Xin; Cai Youquan; Wang Yulin; Wang Yan; Wu Lei; Wu Weiping

2011-01-01

Objective: To investigate the MRI features of the brain in patients with neuromyelitis optica (NMO), and to evaluate the correlation between the brain abnormalities and related risk factors. Methods: Fifty-four patients with definite NMO according to 2006 Wingerchuk diagnosis criteria were enrolled in this study. MRI scanning of the brain was performed in these patients. Distribution and signal features of all the lesions were analyzed. A Logistic regression analysis was used to evaluate the risk factors of brain abnormalities. Results: Twenty-four NMO patients (44.4%) showed unremarkable findings and thirty (55.6%) showed abnormalities on brain MRI. Multiple and non-specific small lesions in the subcortical white matter and grey-white matter junction were the most frequent abnormalities on brain MRI (13/30, 43.3%). Typical lesion locations included corpus callosum, subependyma of ventricles, hypothalamus and brain stem. The lesions showed punctate, patchy and linear abnormal signals. Post-contrast MRI showed no abnormal enhancement in 16 cases. Logistic regression analysis showed that coexisting autoimmune disease or infection. history had correlations with abnormalities of the brain on MRI (OR=3.519, P<0.05). Conclusions: There was a high incidence of brain abnormalities in NMO. Subependymal white matter, corpus callosum, hypothalamus and brain stem were often involved in NMO. NMO patients with coexisting autoimmune disease and infection history had higher risk of brain abnormalities. (authors)

Thyroid abnormalities among first-degree relatives of children with congenital hypothyroidism: an ultrasound survey.

Science.gov (United States)

Adibi, Atoosa; Haghighi, Mahshid; Hosseini, Seyed Reza; Hashemipour, Mahin; Amini, Massoud; Hovsepian, Silva

2008-01-01

Congenital hypothyroidism (CH) is caused by thyroid dysgenesis and dyshormonogenesis. Evidence suggests the presence of genetic factors in both types of pathogenesis. We investigated whether an increased incidence of thyroid abnormalities could be shown by ultrasonography among first-degree relatives of children with CH. In this case-control study the presence of both developmental and non-developmental thyroid abnormalities was studied among first-degree relatives of CH patients and healthy children. Assessments included neck ultrasonography and thyroid function tests. The data obtained from parents, siblings and children were compared in the case and control groups. In the case group, 92 patients, 172 parents and 57 siblings, and in the control group, 82 healthy children, 160 parents and 39 siblings were studied. Thyroid developmental abnormalities were more prevalent among parents (3.5 vs. 0%, p = 0.03) and siblings (10.5 vs. 0, p = 0.01) of CH patients than the control group. Non-developmental abnormalities were not significantly different between the case and control groups (17 vs. 13%, p = 0.3). Thyroid developmental abnormalities were more prevalent among parents and siblings of CH patients than the control group, confirming the familial component of this entity. Copyright 2008 S. Karger AG, Basel.

Congenital abnormalities associated with hemivertebrae in relation to hemivertebrae location.

Science.gov (United States)

Bollini, Gerard; Launay, Franck; Docquier, Pierre-Louis; Viehweger, Elke; Jouve, Jean-Luc

2010-01-01

Numerous congenital abnormalities have been reported in association with hemivertebrae (HV). No data exist about their incidence depending on the location of the HV. From 1980 to 2003, 75 patients with 80 HV responsible for evolutive congenital scoliosis were managed by HV resection using a double approach and short anterior and posterior convex fusion. The associated abnormalities were evaluated with MRI, echocardiography and renal ultrasound. Associated genitourinary abnormalities were found in 24% of patients, cardiac abnormalities in 8% and intrathecal abnormalities in 15%. Medullar abnormalities were more frequent in case of vertebral malformations at lumbosacral level.

Urinary phthalate metabolite concentrations in relation to history of infertility and use of assisted reproductive technology.

Science.gov (United States)

Alur, Snigdha; Wang, Hongyue; Hoeger, Kathy; Swan, Shanna H; Sathyanarayana, Sheela; Redmon, Bruce J; Nguyen, Ruby; Barrett, Emily S

2015-11-01

To examine urinary phthalate metabolite concentrations in pregnant women with planned pregnancies in relation to history of infertility and use of assisted reproductive technology (ART). Phthalate metabolite concentrations were measured in first-trimester urine samples collected from women participating in a prospective pregnancy cohort study. Prenatal clinics. A total of 750 women, of whom 86 had a history of infertility. Forty-one women used ART to conceive. None. Primary outcomes were concentrations of four metabolites of diethylhexyl phthalate (DEHP) and their molar sum (∑DEHP). Multivariable analyses compared phthalate metabolite levels in [1] women reporting a history of infertility vs. those who did not (comparison group); and [2] those who used ART to conceive the index pregnancy vs. women with a history of infertility who did not use ART. Among women with a history of infertility, ∑DEHP was significantly lower in women who conceived after ART compared with those who did not (geometric mean ratio: 0.83; 95% confidence interval 0.71-0.98). Similar significant associations were observed for all of the individual DEHP metabolites. There were no differences in DEHP metabolite concentrations between women with a history of infertility and the comparison group. Women who used ART to conceive had lower first-trimester phthalate metabolite concentrations than women with a history of infertility who did not use ART. Further research is needed to explore whether those pursuing fertility treatments take precautions to avoid exposure to environmental toxins, to improve treatment outcomes. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Prioritizing Candidate Disease Metabolites Based on Global Functional Relationships between Metabolites in the Context of Metabolic Pathways

Science.gov (United States)

Yang, Haixiu; Xu, Yanjun; Han, Junwei; Li, Jing; Su, Fei; Zhang, Yunpeng; Zhang, Chunlong; Li, Dongguo; Li, Xia

2014-01-01

Identification of key metabolites for complex diseases is a challenging task in today's medicine and biology. A special disease is usually caused by the alteration of a series of functional related metabolites having a global influence on the metabolic network. Moreover, the metabolites in the same metabolic pathway are often associated with the same or similar disease. Based on these functional relationships between metabolites in the context of metabolic pathways, we here presented a pathway-based random walk method called PROFANCY for prioritization of candidate disease metabolites. Our strategy not only takes advantage of the global functional relationships between metabolites but also sufficiently exploits the functionally modular nature of metabolic networks. Our approach proved successful in prioritizing known metabolites for 71 diseases with an AUC value of 0.895. We also assessed the performance of PROFANCY on 16 disease classes and found that 4 classes achieved an AUC value over 0.95. To investigate the robustness of the PROFANCY, we repeated all the analyses in two metabolic networks and obtained similar results. Then we applied our approach to Alzheimer's disease (AD) and found that a top ranked candidate was potentially related to AD but had not been reported previously. Furthermore, our method was applicable to prioritize the metabolites from metabolomic profiles of prostate cancer. The PROFANCY could identify prostate cancer related-metabolites that are supported by literatures but not considered to be significantly differential by traditional differential analysis. We also developed a freely accessible web-based and R-based tool at http://bioinfo.hrbmu.edu.cn/PROFANCY. PMID:25153931

Cerebral metabolic abnormalities in congestive heart failure detected by proton magnetic resonance spectroscopy.

Science.gov (United States)

Lee, C W; Lee, J H; Kim, J J; Park, S W; Hong, M K; Kim, S T; Lim, T H; Park, S J

1999-04-01

Using proton magnetic resonance spectroscopy, we investigated cerebral metabolism and its determinants in congestive heart failure (CHF), and the effects of cardiac transplantation on these measurements. Few data are available about cerebral metabolism in CHF. Fifty patients with CHF (ejection fraction OGM) and parietal white matter (PWM). Absolute levels of the metabolites (N-acetylaspartate, creatine, choline, myo-inositol) were calculated. In PWM only creatine level was significantly lower in CHF than in control subjects, but in OGM all four metabolite levels were decreased in CHF. The creatine level was independently correlated with half-recovery time and duration of heart failure symptoms in PWM (r = -0.56, p OGM (r = 0.58, p < 0.05). Cerebral metabolic abnormalities were improved after successful cardiac transplantation. This study shows that cerebral metabolism is abnormally deranged in advanced CHF and it may serve as a potential marker of the disease severity.

Induction of phenolic metabolites and physiological changes in chamomile plants in relation to nitrogen nutrition.

Science.gov (United States)

Kováčik, Jozef; Klejdus, Bořivoj

2014-01-01

Alternative tools, such as the manipulation of mineral nutrition, may affect secondary metabolite production and thus the nutritional value of food/medicinal plants. We studied the impact of nitrogen (N) nutrition (nitrate/NO3(-) or ammonium/NH4(+) nitrogen) and subsequent nitrogen deficit on phenolic metabolites and physiology in Matricaria chamomilla plants. NH4(+)-fed plants revealed a strong induction of selected phenolic metabolites but, at the same time, growth, Fv/Fm, tissue water content and soluble protein depletion occurred in comparison with NO3(-)-fed ones. On the other hand, NO3(-)-deficient plants also revealed an increase in phenolic metabolites but growth depression was not observed after the given exposure period. Free amino acids were more accumulated in NH4(+)-fed shoots (strong increase in arginine and proline mainly), while the pattern of roots' accumulation was independent of N form. Among phenolic acids, NH4(+) strongly elevated mainly the accumulation of chlorogenic acid. Within flavonoids, flavonols decreased while flavones strongly increased in response to N deficiency. Coumarin-related metabolites revealed a similar increase in herniarin glucosidic precursor in response to N deficiency, while herniarin was more accumulated in NO3(-)- and umbelliferone in NH4(+)-cultured plants. These data indicate a negative impact of NH4(+) as the only source of N on physiology, but also a higher stimulation of some valuable phenols. Nitrogen-induced changes in comparison with other food/crop plants are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Abnormalities in alternative splicing of angiogenesis-related genes and their role in HIV-related cancers

Directory of Open Access Journals (Sweden)

Mthembu NN

2017-03-01

Full Text Available Nonkululeko N Mthembu,1 Zukile Mbita,2 Rodney Hull,1 Zodwa Dlamini1 1Research, Innovation and Engagements, Mangosuthu University of Technology, Durban, 2Department of Biochemistry, Microbiology and Biotechnology, University of Limpopo, Sovenga, South Africa Abstract: Alternative splicing of mRNA leads to an increase in proteome biodiversity by allowing the generation of multiple mRNAs, coding for multiple protein isoforms of various structural and functional properties from a single primary pre-mRNA transcript. The protein isoforms produced are tightly regulated in normal development but are mostly deregulated in various cancers. In HIV-infected individuals with AIDS, there is an increase in aberrant alternative splicing, resulting in an increase in HIV/AIDS-related cancers, such as Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and cervical cancer. This aberrant splicing leads to abnormal production of protein and is caused by mutations in cis-acting elements or trans-acting factors in angiogenesis-related genes. Restoring the normal regulation of alternative splicing of angiogenic genes would alter the expression of protein isoforms and may confer normal cell physiology in patients with these cancers. This review highlights the abnormalities in alternative splicing of angiogenesis-related genes and their implication in HIV/AIDS-related cancers. This allows us to gain an insight into the pathogenesis of HIV/AIDS-related cancer and in turn elucidate the therapeutic potential of alternatively spliced genes in HIV/AIDS-related malignancies. Keywords: vascular endothelial growth factor, oncogenic viruses, hypoxia induced factor 1, Kaposi’s sarcoma, non-Hodgkin’s lymphoma, therapies targeting alternative splicing

Use of Ulipristal Acetate for the Management of Fibroid-Related Acute Abnormal Uterine Bleeding.

Science.gov (United States)

Arendas, Kristina; Leyland, Nicholas A

2016-01-01

Episodes of acute abnormal uterine bleeding related to uterine fibroids can cause significant morbidity. Traditional management with high-dose hormonal regimens may not be as effective when used in women with fibroids. A 32-year-old woman with a 12 cm uterine fibroid presented with an episode of acute abnormal uterine bleeding requiring blood transfusion. In lieu of using a hormonal maintenance regimen after the bleeding had stabilized, the patient was treated with ulipristal acetate 5 mg daily for three months. Amenorrhea was induced rapidly and the patient had no further episodes of acute excessive uterine bleeding. She subsequently underwent a laparoscopic myomectomy with a satisfactory outcome. Ulipristal acetate has been shown to induce amenorrhea rapidly in women with uterine fibroids, and it can be a useful treatment in the emergency management of fibroid-related acute abnormal uterine bleeding. Copyright © 2016 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

Confirmatory analysis method for zeranol, its metabolites and related mycotoxins in urine by liquid chromatography-negative ion electrospray tandem mass spectrometry

NARCIS (Netherlands)

Bennekom, van E.O.; Brouwer, L.; Laurant, E.H.M.; Hooijerink, H.; Nielen, M.W.F.

2002-01-01

The determination of the banned anabolic substance zeranol and the metabolites taleranol and zearalanone in bovine urine is complicated by the occurrence of the structurally-related mycotoxin zearalenone and the corresponding - and -zearalenol metabolites which possess similar estrogenic properties.

Identification of phenylbutyrate-generated metabolites in Huntington disease patients using parallel liquid chromatography/electrochemical array/mass spectrometry and off-line tandem mass spectrometry.

Science.gov (United States)

Ebbel, Erika N; Leymarie, Nancy; Schiavo, Susan; Sharma, Swati; Gevorkian, Sona; Hersch, Steven; Matson, Wayne R; Costello, Catherine E

2010-04-15

Oral sodium phenylbutyrate (SPB) is currently under investigation as a histone deacetylation (HDAC) inhibitor in Huntington disease (HD). Ongoing studies indicate that symptoms related to HD genetic abnormalities decrease with SPB therapy. In a recently reported safety and tolerability study of SPB in HD, we analyzed overall chromatographic patterns from a method that employs gradient liquid chromatography with series electrochemical array, ultraviolet (UV), and fluorescence (LCECA/UV/F) for measuring SPB and its metabolite phenylacetate (PA). We found that plasma and urine from SPB-treated patients yielded individual-specific patterns of approximately 20 metabolites that may provide a means for the selection of subjects for extended trials of SPB. The structural identification of these metabolites is of critical importance because their characterization will facilitate understanding the mechanisms of drug action and possible side effects. We have now developed an iterative process with LCECA, parallel LCECA/LCMS, and high-performance tandem MS for metabolite characterization. Here we report the details of this method and its use for identification of 10 plasma and urinary metabolites in treated subjects, including indole species in urine that are not themselves metabolites of SPB. Thus, this approach contributes to understanding metabolic pathways that differ among HD patients being treated with SPB. Copyright 2010 Elsevier Inc. All rights reserved.

Metabolites related to renal function, immune activation, and carbamylation are associated with muscle composition in older adults.

Science.gov (United States)

Lustgarten, Michael S; Fielding, Roger A

2017-12-15

Reduced skeletal muscle density in older adults is associated with insulin resistance, decreased physical function, and an increased all-cause mortality risk. To elucidate mechanisms that may underlie the maintenance of skeletal muscle density, we conducted a secondary analysis of previously published muscle composition and serum metabolomic data in 73 older adults (average age, 78y). Multivariable-adjusted linear regression was used to examine associations between 321 metabolites with muscle composition, defined as the ratio between normal density (NDM) with low density (LDM) thigh muscle cross sectional area (NDM/LDM). Sixty metabolites were significantly (p≤0.05 and qMetabolites that were significantly associated with muscle composition were then tested for their association with circulating markers of renal function (blood urea nitrogen, creatinine, uric acid), and with the immune response (neutrophils/lymphocytes) and activation (kynurenine/tryptophan). 43 significant NDM/LDM metabolites (including urea) were co-associated with at least 1 marker of renal function; 23 of these metabolites have been previously identified as uremic solutes. The neutrophil/lymphocyte ratio was significantly associated with NDM/LDM (β±SE: -0.3±0.1, p=0.01, q=0.04). 35 significant NDM/LDM metabolites were co-associated with immune activation. Carbamylation (defined as homocitrulline/lysine) was identified as a pathway that may link renal function and immune activation with muscle composition, as 29 significant NDM/LDM metabolites were co-associated with homocitrulline/lysine, with at least 2 markers of renal function, and with kynurenine/tryptophan. When considering that elevated urea and uremic metabolites have been linked with an increased systemic microbial burden, that antimicrobial defense can be reduced in the presence of carbamylation, and that adipocytes can promote host defense, we propose the novel hypothesis that the age-related increase in adipogenesis within muscle

Relationship between Pesticide Metabolites, Cytokine Patterns, and Asthma-Related Outcomes in Rural Women Workers

Directory of Open Access Journals (Sweden)

Hussein H. Mwanga

2016-09-01

Full Text Available The objective of this study was to investigate the relationship between exposure to organophosphate (OP and pyrethroid (PYR pesticides with serum cytokine patterns and asthma-related outcomes among rural women workers. A cross-sectional study was conducted among rural women (n = 211, including those working and living on farms and nearby town dwellers. Pesticide exposure was assessed using urinary metabolite concentrations of OP and PYR pesticides. Health outcome assessment was ascertained through the European Community Respiratory Health Survey (ECRHS questionnaire, fractional exhaled nitric oxide (FeNO, and serum cytokines associated with asthma. The prevalence of doctor-diagnosed asthma was 11%, adult-onset asthma 9%, and current asthma 6%. In this population, the proportion of T helper type 2 (Th2 cytokines (interleukin (IL-4, IL-5, and IL-13 detectable in subjects was between 18% and 40%, while the proportion of non-Th2 cytokines (IL-6, IL-8, IL-10, IL-17, and interferon gamma was between 35% and 71%. Most Th2 and non-Th2 cytokines were positively associated with either OP or PYR metabolites. Non-Th2 cytokines showed much stronger associations with OP metabolites (Dimethyl phosphate OR = 4.23; 95% CI: 1.54–11.65 than Th2 cytokines (Dimethyl phosphate OR = 1.69; 95% CI: 0.83–3.46. This study suggests that exposure to most OP and some PYR pesticides may be associated with asthma-related cytokines, with non-Th2 cytokines demonstrating consistently stronger relationships.

Morphostructural MRI Abnormalities Related to Neuropsychiatric Disorders Associated to Multiple Sclerosis

Directory of Open Access Journals (Sweden)

Simona Bonavita

2013-01-01

Full Text Available Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD, obsessive-compulsive disorder (OCD, bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS, euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions, which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS.

Association between Metabolite Profiles, Metabolic Syndrome and Obesity Status

Directory of Open Access Journals (Sweden)

Bénédicte Allam-Ndoul

2016-05-01

Full Text Available Underlying mechanisms associated with the development of abnormal metabolic phenotypes among obese individuals are not yet clear. Our aim is to investigate differences in plasma metabolomics profiles between normal weight (NW and overweight/obese (Ov/Ob individuals, with or without metabolic syndrome (MetS. Mass spectrometry-based metabolite profiling was used to compare metabolite levels between each group. Three main principal components factors explaining a maximum of variance were retained. Factor 1’s (long chain glycerophospholipids metabolite profile score was higher among Ov/Ob with MetS than among Ov/Ob and NW participants without MetS. This factor was positively correlated to plasma total cholesterol (total-C and triglyceride levels in the three groups, to high density lipoprotein -cholesterol (HDL-C among participants without MetS. Factor 2 (amino acids and short to long chain acylcarnitine was positively correlated to HDL-C and negatively correlated with insulin levels among NW participants. Factor 3’s (medium chain acylcarnitines metabolite profile scores were higher among NW participants than among Ov/Ob with or without MetS. Factor 3 was negatively associated with glucose levels among the Ov/Ob with MetS. Factor 1 seems to be associated with a deteriorated metabolic profile that corresponds to obesity, whereas Factors 2 and 3 seem to be rather associated with a healthy metabolic profile.

Rationalization and prediction of in vivo metabolite exposures: The role of metabolite kinetics, clearance predictions and in vitro parameters

Science.gov (United States)

Lutz, Justin D.; Fujioka, Yasushi; Isoherranen, Nina

2010-01-01

Importance of the field Due to growing concerns over toxic or active metabolites, significant efforts have been focused on qualitative identification of potential in vivo metabolites from in vitro data. However, limited tools are available to quantitatively predict their human exposures. Areas covered in this review Theory of clearance predictions and metabolite kinetics is reviewed together with supporting experimental data. In vitro and in vivo data of known circulating metabolites and their parent drugs was collected and the predictions of in vivo exposures of the metabolites were evaluated. What the reader will gain The theory and data reviewed will be useful in early identification of human metabolites that will circulate at significant levels in vivo and help in designing in vivo studies that focus on characterization of metabolites. It will also assist in rationalization of metabolite-to-parent ratios used as markers of specific enzyme activity. Take home message The relative importance of a metabolite in comparison to the parent compound as well as other metabolites in vivo can only be predicted using the metabolites in vitro formation and elimination clearances, and the in vivo disposition of a metabolite can only be rationalized when the elimination pathways of that metabolite are known. PMID:20557268

Light microscopy morphological characteristics of the sperm flagellum may be related to axonemal abnormalities.

Science.gov (United States)

Mitchell, V; Sigala, J; Ballot, C; Jumeau, F; Barbotin, A L; Duhamel, A; Rives, N; Rigot, J M; Escalier, D; Peers, M C

2015-03-01

Although electron microscopy provides a detailed analysis of ultrastructural abnormalities, this technique is not available in all laboratories. We sought to determine whether certain characteristics of the flagellum as assessed by light microscopy were related to axonemal abnormalities. Forty-one patients with an absence of outer dynein arms (type I), a lack of a central complex (type III) and an absence of peripheral doublets (type IV) were studied. Sperm morphology was scored according to David's modified classification. Flagella with an irregular thickness were classified as being of normal length, short or broken. There were correlations between missing outer dynein arms and abnormal, short or coiled flagellum. Type III patients showed the highest flagellar defects (a short (P = 0.0027) or an absent flagellum (P = 0.011)). Just over 68% of the irregular flagella were short in Type III patients, whereas this value was only 34.5% in type I and 26.4% in type IV (P = 0.002). There was a negative correlation between misassembly and spermatozoa of irregular flagella (r = -0.79; P = 0.019). It is concluded that light microscopy analysis of flagellum abnormalities may help provide a correct diagnosis, identify sperm abnormalities with fertility potentials and outcomes in assisted reproduction technologies and assess the genetic risk. © 2014 Blackwell Verlag GmbH.

Ozone effects on radish (Raphanus sativus L. cv. Cherry Belle): foliar sensitivity as related to metabolite levels and cell architecture

Energy Technology Data Exchange (ETDEWEB)

Athanassious, R.

1980-01-01

The development of the first four leaves of radish (Raphanus sativus L. cv. Cherry Belle) was followed to determine the relationship between foliar sensitivity to ozone as related to selected soluble metabolites and leaf-cell arrangement. Although relatively high metabolite (protein, sugars, phenols) levels and compact cell arrangement may be advanced as factors contributing to the resistance of young leaves (L/sub 3,4/ of 21-day old plants) these same parameters do not explain the resistance of old leaves (L/sub 1,2/ of 30-day old plants). 16 references, 4 figures, 1 table.

Urinary Metabolite Profiling Offers Potential for Differentiation of Liver-Kidney Yin Deficiency and Dampness-Heat Internal Smoldering Syndromes in Posthepatitis B Cirrhosis Patients

Directory of Open Access Journals (Sweden)

Xiaoning Wang

2015-01-01

Full Text Available Zheng is the basic theory and essence of traditional Chinese medicine (TCM in diagnosing diseases. However, there are no biological evidences to support TCM Zheng differentiation. In this study we elucidated the biological alteration of cirrhosis with TCM “Liver-Kidney Yin Deficiency (YX” or “Dampness-Heat Internal Smoldering (SR” Zheng and the potential of urine metabonomics in TCM Zheng differentiation. Differential metabolites contributing to the intergroup variation between healthy controls and liver cirrhosis patients were investigated, respectively, and mainly participated in energy metabolism, gut microbiota metabolism, oxidative stress, and bile acid metabolism. Three metabolites, aconitate, citrate, and 2-pentendioate, altered significantly in YX Zheng only, representing the abnormal energy metabolism. Contrarily, hippurate and 4-pyridinecarboxylate altered significantly in SR Zheng only, representing the abnormalities of gut microbiota metabolism. Moreover, there were significant differences between two TCM Zhengs in three metabolites, glycoursodeoxycholate, cortolone-3-glucuronide, and L-aspartyl-4-phosphate, among all differential metabolites. Metabonomic profiling, as a powerful approach, provides support to the understanding of biological mechanisms of TCM Zheng stratification. The altered urinary metabolites constitute a panel of reliable biological evidence for TCM Zheng differentiation in patients with posthepatitis B cirrhosis and may be used for the potential biomarkers of TCM Zheng stratification.

Metabolite coupling in genome-scale metabolic networks

Directory of Open Access Journals (Sweden)

Palsson Bernhard Ø

2006-03-01

Full Text Available Abstract Background Biochemically detailed stoichiometric matrices have now been reconstructed for various bacteria, yeast, and for the human cardiac mitochondrion based on genomic and proteomic data. These networks have been manually curated based on legacy data and elementally and charge balanced. Comparative analysis of these well curated networks is now possible. Pairs of metabolites often appear together in several network reactions, linking them topologically. This co-occurrence of pairs of metabolites in metabolic reactions is termed herein "metabolite coupling." These metabolite pairs can be directly computed from the stoichiometric matrix, S. Metabolite coupling is derived from the matrix ŜŜT, whose off-diagonal elements indicate the number of reactions in which any two metabolites participate together, where Ŝ is the binary form of S. Results Metabolite coupling in the studied networks was found to be dominated by a relatively small group of highly interacting pairs of metabolites. As would be expected, metabolites with high individual metabolite connectivity also tended to be those with the highest metabolite coupling, as the most connected metabolites couple more often. For metabolite pairs that are not highly coupled, we show that the number of reactions a pair of metabolites shares across a metabolic network closely approximates a line on a log-log scale. We also show that the preferential coupling of two metabolites with each other is spread across the spectrum of metabolites and is not unique to the most connected metabolites. We provide a measure for determining which metabolite pairs couple more often than would be expected based on their individual connectivity in the network and show that these metabolites often derive their principal biological functions from existing in pairs. Thus, analysis of metabolite coupling provides information beyond that which is found from studying the individual connectivity of individual

Evaluating Metabolite-Related DNA Oxidation and Adduct Damage from Aryl Amines Using a Microfluidic ECL Array.

Science.gov (United States)

Bist, Itti; Bhakta, Snehasis; Jiang, Di; Keyes, Tia E; Martin, Aaron; Forster, Robert J; Rusling, James F

2017-11-21

Damage to DNA from the metabolites of drugs and pollutants constitutes a major human toxicity pathway known as genotoxicity. Metabolites can react with metal ions and NADPH to oxidize DNA or participate in S N 2 reactions to form covalently linked adducts with DNA bases. Guanines are the main DNA oxidation sites, and 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG) is the initial product. Here we describe a novel electrochemiluminescent (ECL) microwell array that produces metabolites from test compounds and measures relative rates of DNA oxidation and DNA adduct damage. In this new array, films of DNA, metabolic enzymes, and an ECL metallopolymer or complex assembled in microwells on a pyrolytic graphite wafer are housed in dual microfluidic chambers. As reactant solution passes over the wells, metabolites form and can react with DNA in the films to form DNA adducts. These adducts are detected by ECL from a RuPVP polymer that uses DNA as a coreactant. Aryl amines also combine with Cu 2+ and NADPH to form reactive oxygen species (ROS) that oxidize DNA. The resulting 8-oxodG was detected selectively by ECL-generating bis(2,2'-bipyridine)-(4-(1,10-phenanthrolin-6-yl)-benzoic acid)Os(II). DNA/enzyme films on magnetic beads were oxidized similarly, and 8-oxodG determined by LC/MS/MS enabled array standardization. The array limit of detection for oxidation was 720 8-oxodG per 10 6 nucleobases. For a series of aryl amines, metabolite-generated DNA oxidation and adduct formation turnover rates from the array correlated very well with rodent 1/TD 50 and Comet assay results.

Neuropharmacology of 3,4-Methylenedioxypyrovalerone (MDPV), Its Metabolites, and Related Analogs.

Science.gov (United States)

Baumann, Michael H; Bukhari, Mohammad O; Lehner, Kurt R; Anizan, Sebastien; Rice, Kenner C; Concheiro, Marta; Huestis, Marilyn A

2017-01-01

3,4-Methylenedioxypyrovalerone (MDPV) is a psychoactive component of so-called bath salts products that has caused serious medical consequences in humans. In this chapter, we review the neuropharmacology of MDPV and related analogs, and supplement the discussion with new results from our preclinical experiments. MDPV acts as a potent uptake inhibitor at plasma membrane transporters for dopamine (DAT) and norepinephrine (NET) in nervous tissue. The MDPV formulation in bath salts is a racemic mixture, and the S isomer is much more potent than the R isomer at blocking DAT and producing abuse-related effects. Elevations in brain extracellular dopamine produced by MDPV are likely to underlie its locomotor stimulant and addictive properties. MDPV displays rapid pharmacokinetics when injected into rats (0.5-2.0 mg/kg), with peak plasma concentrations achieved by 10-20 min and declining quickly thereafter. MDPV is metabolized to 3,4-dihydroxypyrovalerone (3,4-catechol-PV) and 4-hydroxy-3-methoxypyrovalerone (4-OH-3-MeO-PV) in vivo, but motor activation produced by the drug is positively correlated with plasma concentrations of parent drug and not its metabolites. 3,4-Catechol-PV is a potent uptake blocker at DAT in vitro but has little activity after administration in vivo. 4-OH-3-MeO-PV is the main MDPV metabolite but is weak at DAT and NET. MDPV analogs, such as α-pyrrolidinovalerophenone (α-PVP), display similar ability to inhibit DAT and increase extracellular dopamine concentrations. Taken together, these findings demonstrate that MDPV and its analogs represent a unique class of transporter inhibitors with a high propensity for abuse and addiction.

Brain metabolites in the hippocampus-amygdala region and cerebellum in autism: an 1H-MR spectroscopy study

International Nuclear Information System (INIS)

Otsuka, H.; Harada, M.; Hisaoka, S.; Nishitani, H.; Mori, K.

1999-01-01

Histological abnormalities of the brain in autism have been investigated extensively. We studied metabolites in the hippocampusamygdala (HA) region and cerebellum. We examined the right HA region and left cerebellar hemisphere of 27 autistic patients 2-18 years old, 21 boys and 6 girls and 10 normal children 6-14 years old, 4 boys and 6 girls, using the STEAM sequence. This sequence was used to minimise the influence of relaxation times. The N-acetyl aspartate (NAA) concentration was significantly lower (P=0.042) in autistic patients than in normal children (9.37 and 10.95 mM, respectively). There was no significant difference in other metabolites. The correlation coefficient (r value) of NAA between the HA region and cerebellum was 0.616. The decreased NAA concentration may be due to neuronal hypofunction or immature neurons. The NAA concentration in the HA region and cerebellum may be related, because of neuronal circuits or networks. (orig.)

Differential impact of hyponatremia and hepatic encephalopathy on health-related quality of life and brain metabolite abnormalities in cirrhosis.

Science.gov (United States)

Ahluwalia, Vishwadeep; Wade, James B; Thacker, Leroy; Kraft, Kenneth A; Sterling, Richard K; Stravitz, R Todd; Fuchs, Michael; Bouneva, Iliana; Puri, Puneet; Luketic, Velimir; Sanyal, Arun J; Gilles, Hochong; Heuman, Douglas M; Bajaj, Jasmohan S

2013-09-01

Hyponatremia (HN) and hepatic encephalopathy (HE) together can impair health-related quality of life (HRQOL) and cognition in cirrhosis. We aimed at studying the effect of hyponatremia on cognition, HRQOL, and brain MR spectroscopy (MRS) independent of HE. Four cirrhotic groups (no HE/HN, HE alone, HN alone (sodium <130 mEq/L), HE+HN) underwent cognitive testing, HRQOL using Sickness Impact Profile (SIP: higher score is worse; has psychosocial and physical sub-scores) and brain MRS (myoinositol (mI) and glutamate+glutamine (Glx)), which were compared across groups. A subset underwent HRQOL testing before/after diuretic withdrawal. 82 cirrhotics (30 no HE/HN, 25 HE, 17 HE+HN, and 10 HN, MELD 12, 63% hepatitis C) were included. Cirrhotics with HN alone and without HE/HN had better cognition compared to HE groups (median abnormal tests no-HE/HN: 3, HN: 3.5, HE: 6.5, HE+HN: 7, p=0.008). Despite better cognition, HN only patients had worse HRQOL in total and psychosocial SIP while both HN groups (with/without HE) had a significantly worse physical SIP (p<0.0001, all comparisons). Brain MRS showed the lowest Glx in HN and the highest in HE groups (p<0.02). mI levels were comparably decreased in the three affected (HE, HE+HN, and HN) groups compared to no HE/HN and were associated with poor HRQOL. Six HE+HN cirrhotics underwent diuretic withdrawal which improved serum sodium and total/psychosocial SIP scores. Hyponatremic cirrhotics without HE have poor HRQOL despite better cognition than those with concomitant HE. Glx levels were lowest in HN without HE but mI was similar across affected groups. HRQOL improved after diuretic withdrawal. Hyponatremia has a complex, non-linear relationship with brain Glx and mI, cognition and HRQOL. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

RaMP: A Comprehensive Relational Database of Metabolomics Pathways for Pathway Enrichment Analysis of Genes and Metabolites.

Science.gov (United States)

Zhang, Bofei; Hu, Senyang; Baskin, Elizabeth; Patt, Andrew; Siddiqui, Jalal K; Mathé, Ewy A

2018-02-22

The value of metabolomics in translational research is undeniable, and metabolomics data are increasingly generated in large cohorts. The functional interpretation of disease-associated metabolites though is difficult, and the biological mechanisms that underlie cell type or disease-specific metabolomics profiles are oftentimes unknown. To help fully exploit metabolomics data and to aid in its interpretation, analysis of metabolomics data with other complementary omics data, including transcriptomics, is helpful. To facilitate such analyses at a pathway level, we have developed RaMP (Relational database of Metabolomics Pathways), which combines biological pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, WikiPathways, and the Human Metabolome DataBase (HMDB). To the best of our knowledge, an off-the-shelf, public database that maps genes and metabolites to biochemical/disease pathways and can readily be integrated into other existing software is currently lacking. For consistent and comprehensive analysis, RaMP enables batch and complex queries (e.g., list all metabolites involved in glycolysis and lung cancer), can readily be integrated into pathway analysis tools, and supports pathway overrepresentation analysis given a list of genes and/or metabolites of interest. For usability, we have developed a RaMP R package (https://github.com/Mathelab/RaMP-DB), including a user-friendly RShiny web application, that supports basic simple and batch queries, pathway overrepresentation analysis given a list of genes or metabolites of interest, and network visualization of gene-metabolite relationships. The package also includes the raw database file (mysql dump), thereby providing a stand-alone downloadable framework for public use and integration with other tools. In addition, the Python code needed to recreate the database on another system is also publicly available (https://github.com/Mathelab/RaMP-BackEnd). Updates for databases in RaMP will be

Methionine Metabolites in Patients With Sepsis.

Science.gov (United States)

Wexler, Orren; Gough, Michael S; Morgan, Mary Anne M; Mack, Cynthia M; Apostolakos, Michael J; Doolin, Kathleen P; Mooney, Robert A; Arning, Erland; Bottiglieri, Teodoro; Pietropaoli, Anthony P

2018-01-01

Sepsis is characterized by microvascular dysfunction and thrombophilia. Several methionine metabolites may be relevant to this sepsis pathophysiology. S-adenosylmethionine (SAM) serves as the methyl donor for trans-methylation reactions. S-adenosylhomocysteine (SAH) is the by-product of these reactions and serves as the precursor to homocysteine. Relationships between plasma total homocysteine concentrations (tHcy) and vascular disease and thrombosis are firmly established. We hypothesized that SAM, SAH, and tHcy levels are elevated in patients with sepsis and associated with mortality. This was a combined case-control and prospective cohort study consisting of 109 patients with sepsis and 50 control participants without acute illness. The study was conducted in the medical and surgical intensive care units of the University of Rochester Medical Center. Methionine, SAM, SAH, and tHcy concentrations were compared in patients with sepsis versus control participants and in sepsis survivors versus nonsurvivors. Patients with sepsis had significantly higher plasma SAM and SAH concentrations than control participants (SAM: 164 [107-227] vs73 [59-87 nM], P sepsis patients compared to healthy control participants (4 [2-6]) vs 7 [5-9] μM; P = .04). In multivariable analysis, quartiles of SAM, SAH, and tHcy were independently associated with sepsis ( P = .006, P = .05, and P Sepsis nonsurvivors had significantly higher plasma SAM and SAH concentrations than survivors (SAM: 223 [125-260] vs 136 [96-187] nM; P = .01; SAH: 139 [81-197] vs 86 [55-130] nM, P = .006). Plasma tHcy levels were similar in survivors vs nonsurvivors. The associations between SAM or SAH and hospital mortality were no longer significant after adjusting for renal dysfunction. Methionine metabolite concentrations are abnormal in sepsis and linked with clinical outcomes. Further study is required to determine whether these abnormalities have pathophysiologic significance.

Metabolite-Sensing G Protein-Coupled Receptors-Facilitators of Diet-Related Immune Regulation.

Science.gov (United States)

Tan, Jian K; McKenzie, Craig; Mariño, Eliana; Macia, Laurence; Mackay, Charles R

2017-04-26

Nutrition and the gut microbiome regulate many systems, including the immune, metabolic, and nervous systems. We propose that the host responds to deficiency (or sufficiency) of dietary and bacterial metabolites in a dynamic way, to optimize responses and survival. A family of G protein-coupled receptors (GPCRs) termed the metabolite-sensing GPCRs bind to various metabolites and transmit signals that are important for proper immune and metabolic functions. Members of this family include GPR43, GPR41, GPR109A, GPR120, GPR40, GPR84, GPR35, and GPR91. In addition, bile acid receptors such as GPR131 (TGR5) and proton-sensing receptors such as GPR65 show similar features. A consistent feature of this family of GPCRs is that they provide anti-inflammatory signals; many also regulate metabolism and gut homeostasis. These receptors represent one of the main mechanisms whereby the gut microbiome affects vertebrate physiology, and they also provide a link between the immune and metabolic systems. Insufficient signaling through one or more of these metabolite-sensing GPCRs likely contributes to human diseases such as asthma, food allergies, type 1 and type 2 diabetes, hepatic steatosis, cardiovascular disease, and inflammatory bowel diseases.

Metabolites of cannabidiol identified in human urine.

Science.gov (United States)

Harvey, D J; Mechoulam, R

1990-03-01

1. Urine from a dystonic patient treated with cannabidiol (CBD) was examined by g.l.c.-mass spectrometry for CBD metabolites. Metabolites were identified as their trimethylsilyl (TMS), [2H9]TMS, and methyl ester/TMS derivatives and as the TMS derivatives of the product of lithium aluminium deuteride reduction. 2. Thirty-three metabolites were identified in addition to unmetabolized CBD, and a further four metabolites were partially characterized. 3. The major metabolic route was hydroxylation and oxidation at C-7 followed by further hydroxylation in the pentyl and propenyl groups to give 1"-, 2"-, 3"-, 4"- and 10-hydroxy derivatives of CBD-7-oic acid. Other metabolites, mainly acids, were formed by beta-oxidation and related biotransformations from the pentyl side-chain and these were also hydroxylated at C-6 or C-7. The major oxidized metabolite was CBD-7-oic acid containing a hydroxyethyl side-chain. 4. Two 8,9-dihydroxy compounds, presumably derived from the corresponding epoxide were identified. 5. Also present were several cyclized cannabinoids including delta-6- and delta-1-tetrahydrocannabinol and cannabinol. 6. This is the first metabolic study of CBD in humans; most observed metabolic routes were typical of those found for CBD and related cannabinoids in other species.

Impact of secondary metabolites and related enzymes in flax ...

African Journals Online (AJOL)

Changes in various physiological defenses including secondary metabolites, proline, total soluble protein and antioxidant enzymes were investigated in leaves and stems of 18 flax lines either resistant or susceptible to powdery mildew. The results showed that the total alkaloids content in flax stems was significantly ...

Brain metabolites in the hippocampus-amygdala region and cerebellum in autism: an {sup 1}H-MR spectroscopy study

Energy Technology Data Exchange (ETDEWEB)

Otsuka, H; Harada, M; Hisaoka, S; Nishitani, H [Dept. of Radiology, Univ. of Tokushima, Tokushima City (Japan); Mori, K [Dept. of Pediatrics, Univ. of Tokushima (Japan)

1999-07-01

Histological abnormalities of the brain in autism have been investigated extensively. We studied metabolites in the hippocampusamygdala (HA) region and cerebellum. We examined the right HA region and left cerebellar hemisphere of 27 autistic patients 2-18 years old, 21 boys and 6 girls and 10 normal children 6-14 years old, 4 boys and 6 girls, using the STEAM sequence. This sequence was used to minimise the influence of relaxation times. The N-acetyl aspartate (NAA) concentration was significantly lower (P=0.042) in autistic patients than in normal children (9.37 and 10.95 mM, respectively). There was no significant difference in other metabolites. The correlation coefficient (r value) of NAA between the HA region and cerebellum was 0.616. The decreased NAA concentration may be due to neuronal hypofunction or immature neurons. The NAA concentration in the HA region and cerebellum may be related, because of neuronal circuits or networks. (orig.)

Neurochemical metabolites in prefrontal cortex in patients with mild/moderate levels in first-episode depression

Directory of Open Access Journals (Sweden)

Sozeri-Varma G

2013-08-01

Full Text Available Gülfizar Sözeri-Varma,1 Nalan Kalkan-Oğuzhanoglu,1 Muharrem Efe,1 Yilmaz Kiroglu,2 Taçlan Duman11Department of Psychiatry, 2Department of Radiology, Faculty of Medicine, Pamukkale University, Denizli, TurkeyBackground: Previous studies have determined the neurochemical metabolite abnormalities in major depressive disorder (MDD. The results of studies are inconsistent. Severity of depression may relate to neurochemical metabolic changes. The aim of this study is to investigate neurochemical metabolite levels in the prefrontal cortex (PFC of patients with mild/moderate MDD.Methods: Twenty-one patients with mild MDD, 18 patients with moderate MDD, and 16 matched control subjects participated in the study. Patients had had their first episode. They had not taken treatment. The severity of depression was assessed by the Hamilton Rating Scale for Depression (HAM-D. Levels of N-acetyl aspartate (NAA, choline-containing compounds (Cho, and creatine-containing compounds (Cr were measured using proton magnetic resonance spectroscopy (1H-MRS at 1.5 T, with an 8-cm3 single voxel placed in the right PFC.Results: The moderate MDD patients had lower NAA/Cr levels than the control group. No differences were found in neurochemical metabolite levels between the mild MDD and control groups. No correlation was found between the patients’ neurochemical metabolite levels and HAM-D scores.Conclusion: Our findings suggest that NAA/Cr levels are low in moderate-level MDD in the PFC. Neurochemical metabolite levels did not change in mild depressive disorder. Our results suggest that the severity of depression may affect neuronal function and viability. Studies are needed to confirm this finding, including studies on severely depressive patients.Keywords: major depressive disorder, magnetic resonance spectroscopy, N-acetyl aspartate, creatine, choline

Detection of driver metabolites in the human liver metabolic network using structural controllability analysis

Science.gov (United States)

2014-01-01

Background Abnormal states in human liver metabolism are major causes of human liver diseases ranging from hepatitis to hepatic tumor. The accumulation in relevant data makes it feasible to derive a large-scale human liver metabolic network (HLMN) and to discover important biological principles or drug-targets based on network analysis. Some studies have shown that interesting biological phenomenon and drug-targets could be discovered by applying structural controllability analysis (which is a newly prevailed concept in networks) to biological networks. The exploration on the connections between structural controllability theory and the HLMN could be used to uncover valuable information on the human liver metabolism from a fresh perspective. Results We applied structural controllability analysis to the HLMN and detected driver metabolites. The driver metabolites tend to have strong ability to influence the states of other metabolites and weak susceptibility to be influenced by the states of others. In addition, the metabolites were classified into three classes: critical, high-frequency and low-frequency driver metabolites. Among the identified 36 critical driver metabolites, 27 metabolites were found to be essential; the high-frequency driver metabolites tend to participate in different metabolic pathways, which are important in regulating the whole metabolic systems. Moreover, we explored some other possible connections between the structural controllability theory and the HLMN, and find that transport reactions and the environment play important roles in the human liver metabolism. Conclusion There are interesting connections between the structural controllability theory and the human liver metabolism: driver metabolites have essential biological functions; the crucial role of extracellular metabolites and transport reactions in controlling the HLMN highlights the importance of the environment in the health of human liver metabolism. PMID:24885538

Fibrillin abnormalities and prognosis in Marfan syndrome and related disorders

Energy Technology Data Exchange (ETDEWEB)

Aoyama, T.; Furthmayr, H.; Francke, U.; Gasner, C. [Stanford Univ. Medical Center, CA (United States)

1995-08-28

Marfan syndrome (MFS), a multisystem autosomal-dominant disorder, is characterized by mutations of the fibrillin-1 (FBN1) gene and by abnormal patterns of synthesis, secretion, and matrix deposition of the fibrillin protein. To determine the sensitivity and specificity of fibrillin protein abnormalities in the diagnosis of MFS, we studied dermal fibroblasts from 57 patients with classical MFS, 15 with equivocal MFS, 8 with single-organ manifestations, and 16 with other connective tissue disorders including homocystinuria and Ehlers-Danlos syndrome. Abnormal fibrillin metabolism was identified in 70 samples that were classified into four different groups based on quantitation of fibrillin synthesis and matrix deposition. Significant correlations were found for phenotypic features including arachnodactyly, striae distensae, cardiovascular manifestations, and fibrillin groups II and IV, which included 70% of the MFS patients. In addition, these two groups were associated with shortened {open_quotes}event-free{close_quotes} survival and more severe cardiovascular complications than groups I and III. The latter included most of the equivocal MFS/single manifestation patients with fibrillin abnormalities. Our results indicate that fibrillin defects at the protein level per se are not specific for MFS, but that the drastically reduced fibrillin deposition, caused by a dominant-negative effect of abnormal fibrillin molecules in individuals defined as groups II and IV, is of prognostic and possibly diagnostic significance. 25 refs., 3 figs., 6 tabs.

Biochemical and secondary metabolites changes under moisture ...

African Journals Online (AJOL)

The study showed the importance of carbohydrate and nitrogen cycle related metabolites in mediating tolerance in cassava by affecting their phenotypic expression in the plant. Keywords: Hydrothermal stress, bio-chemicals, pigments, secondary metabolites, cassava. African Journal of Biotechnology, Vol 13(31) 3173-3186 ...

Age-related differences in metabolites in the posterior cingulate cortex and hippocampus of normal ageing brain: A 1H-MRS study

International Nuclear Information System (INIS)

Reyngoudt, Harmen; Claeys, Tom; Vlerick, Leslie; Verleden, Stijn; Acou, Marjan; Deblaere, Karel; De Deene, Yves; Audenaert, Kurt; Goethals, Ingeborg; Achten, Eric

2012-01-01

Objective: To study age-related metabolic changes in N-acetylaspartate (NAA), total creatine (tCr), choline (Cho) and myo-inositol (Ins). Materials and methods: Proton magnetic resonance spectroscopy ( 1 H-MRS) was performed in the posterior cingulate cortex (PCC) and the left hippocampus (HC) of 90 healthy subjects (42 women and 48 men aged 18–76 years, mean ± SD, 48.4 ± 16.8 years). Both metabolite ratios and absolute metabolite concentrations were evaluated. Analysis of covariance (ANCOVA) and linear regression were used for statistical analysis. Results: Metabolite ratios Ins/tCr and Ins/H 2 O were found significantly increased with age in the PCC (P 2 O was only observed in the PCC (P 1 H-MRS results in these specific brain regions can be important to differentiate normal ageing from age-related pathologies such as mild cognitive impairment (MCI) and Alzheimer's disease.

Production of Secondary Metabolites in Extreme Environments: Food- and Airborne Wallemia spp. Produce Toxic Metabolites at Hypersaline Conditions

DEFF Research Database (Denmark)

Jančič, Sašo; Frisvad, Jens Christian; Kocev, Dragi

2016-01-01

the genome data analysis of W. mellicola (previously W. sebi sensu lato) and W. ichthyophaga revealed a low number of secondary metabolites clusters, a substantial number of secondary metabolites were detected at different conditions. Machine learning analysis of the obtained dataset showed that NaCl has...... of salt or sugar. In relation to food safety, the effect of high salt and sugar concentrations on the production of secondary metabolites by this toxigenic fungus was investigated. The secondary metabolite profiles of 30 strains of the listed species were examined using general growth media, known...... to support the production of secondary metabolites, supplemented with different concentrations of NaCl, glucose and MgCl2. In more than two hundred extracts approximately one hundred different compounds were detected using high-performance liquid chromatography-diode array detection (HPLC-DAD). Although...

Secondary metabolite profiles and antifungal drug susceptibility of Aspergillus fumigatus and closely related species, Aspergillus lentulus, Aspergillus udagawae, and Aspergillus viridinutans.

Science.gov (United States)

Tamiya, Hiroyuki; Ochiai, Eri; Kikuchi, Kazuyo; Yahiro, Maki; Toyotome, Takahito; Watanabe, Akira; Yaguchi, Takashi; Kamei, Katsuhiko

2015-05-01

The incidence of Aspergillus infection has been increasing in the past few years. Also, new Aspergillus fumigatus-related species, namely Aspergillus lentulus, Aspergillus udagawae, and Aspergillus viridinutans, were shown to infect humans. These fungi exhibit marked morphological similarities to A. fumigatus, albeit with different clinical courses and antifungal drug susceptibilities. The present study used liquid chromatography/time-of-flight mass spectrometry to identify the secondary metabolites secreted as virulence factors by these Aspergillus species and compared their antifungal susceptibility. The metabolite profiles varied widely among A. fumigatus, A. lentulus, A. udagawae, and A. viridinutans, producing 27, 13, 8, and 11 substances, respectively. Among the mycotoxins, fumifungin, fumiquinazoline A/B and D, fumitremorgin B, gliotoxin, sphingofungins, pseurotins, and verruculogen were only found in A. fumigatus, whereas auranthine was only found in A. lentulus. The amount of gliotoxin, one of the most abundant mycotoxins in A. fumigatus, was negligible in these related species. In addition, they had decreased susceptibility to antifungal agents such as itraconazole and voriconazole, even though metabolites that were shared in the isolates showing higher minimum inhibitory concentrations than epidemiological cutoff values were not detected. These strikingly different secondary metabolite profiles may lead to the development of more discriminative identification protocols for such closely related Aspergillus species as well as improved treatment outcomes. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Plant abnormality inspection device

International Nuclear Information System (INIS)

Takenaka, Toshio.

1990-01-01

The present invention concerns a plant abnormality inspection device for conducting remote or automatic patrolling inspection in a plant and, more particularly, relates to such a device as capable of detecting abnormal odors. That is, the device comprises a moving device for moving to a predetermined position in the plant, a plurality of gas sensors for different kind of gases to be inspected mounted thereon, a comparator for comparing the concentration of a gas detected by the gas sensor with the normal gas concentration at the predetermined position and a judging means for judging the absence or presence of abnormality depending on the combination of the result of the comparison and deliverying a signal if the state is abnormal. As a result, a slight amount of gas responsible to odors released upon abnormality of the plant can be detected by a plurality of gas sensors for different kinds gases to rapidly and easily find abnormal portions in the plant. (I.S.)

Utilizing relative potency factors (RPF) and threshold of toxicological concern (TTC) concepts to assess hazard and human risk assessment profiles of environmental metabolites: a case study.

Science.gov (United States)

Terry, C; Rasoulpour, R J; Knowles, S; Billington, R

2015-03-01

There is currently no standard paradigm for hazard and human risk assessment of environmental metabolites for agrochemicals. Using an actual case study, solutions to challenges faced are described and used to propose a generic concept to address risk posed by metabolites to human safety. A novel approach - built on the foundation of predicted human exposures to metabolites in various compartments (such as food and water), the threshold of toxicological concern (TTC) and the concept of comparative toxicity - was developed for environmental metabolites of a new chemical, sulfoxaflor (X11422208). The ultimate aim was to address the human safety of the metabolites with the minimum number of in vivo studies, while at the same time, ensuring that human safety would be considered addressed on a global regulatory scale. The third component, comparative toxicity, was primarily designed to determine whether the metabolites had the same or similar toxicity profiles to their parent molecule, and also to one another. The ultimate goal was to establish whether the metabolites had the potential to cause key effects - such as cancer and developmental toxicity, based on mode-of-action (MoA) studies - and to develop a relative potency factor (RPF) compared to the parent molecule. Collectively, the work presented here describes the toxicology programme developed for sulfoxaflor and its metabolites, and how it might be used to address similar future challenges aimed at determining the relevance of the metabolites from a human hazard and risk perspective. Sulfoxaflor produced eight environmental metabolites at varying concentrations in various compartments - soil, water, crops and livestock. The MoA for the primary effects of the parent molecule were elucidated in detail and a series of in silico, in vitro, and/or in vivo experiments were conducted on the environmental metabolites to assess relative potency of their toxicity profiles when compared to the parent. The primary metabolite

Tinnitus perception and distress is related to abnormal spontaneous brain activity as measured by magnetoencephalography.

Directory of Open Access Journals (Sweden)

2005-06-01

Full Text Available BACKGROUND: The neurophysiological mechanisms underlying tinnitus perception are not well understood. Surprisingly, there have been no group studies comparing abnormalities in ongoing, spontaneous neuronal activity in individuals with and without tinnitus perception. METHODS AND FINDINGS: Here, we show that the spontaneous neuronal activity of a group of individuals with tinnitus (n = 17 is characterised by a marked reduction in alpha (8-12 Hz power together with an enhancement in delta (1.5-4 Hz as compared to a normal hearing control group (n = 16. This pattern was especially pronounced for temporal regions. Moreover, correlations with tinnitus-related distress revealed strong associations with this abnormal spontaneous activity pattern, particularly in right temporal and left frontal areas. Overall, effects were stronger for the alpha than for the delta frequency band. A data stream of 5 min, recorded with a whole-head neuromagnetometer under a resting condition, was sufficient to extract the marked differences. CONCLUSIONS: Despite some limitations, there are arguments that the regional pattern of abnormal spontaneous activity we found could reflect a tinnitus-related cortical network. This finding, which suggests that a neurofeedback approach could reduce the adverse effects of this disturbing condition, could have important implications for the treatment of tinnitus.

Prevalence of Abnormal Papanicolaou Test Results and Related Factors among Women Living in Zanjan, Iran.

Science.gov (United States)

Maleki, Azam; Ahmadnia, Elahe; Avazeh, Azar; Mazloomzadeh, Saeideh; Molaei, Behnaz; Jalilvand, Ahmad

2015-01-01

Currently, a comprehensive program for screening and early detection of cervical cancer does not exist in Iran. This study aimed to determine the prevalence of abnormal Papanicolaou (Pap) smears and some related factors among women living in Zanjan, Iran. This cross-sectional study was conducted in 2012 in Zanjan on 4274 married women aged 20-65 years. The study participants were selected through two-stage cluster sampling. After obtaining written consent, demographic and fertility questionnaires were completed. Samples from cervix were obtained through a standard method using the Rover Cervex- Brush. Evaluation and interpretation of the samples were reported using the Bethesda 2001 method. Data were statistically analyzed using chi-square and logistic regression models. Most inflammatory changes in the samples were mild (37.4%). Abnormal atypical changes in the epithelial cells were found in 4.04%. The highest percentage of abnormal changes in the epithelial cells was atypical squamous cells of undetermined significance (ASCUS) (1.9%). Abnormal results of Pap smear was significantly and independently associated with age, papillomavirus infection, and lack of awareness about Pap smear tests. Given the high prevalence of inflammatory and precancerous changes in this study, compared to other studies in Iran and other Muslim countries, and the effect of demographic variables and individual factors on abnormal results, increasing the awareness of women and their families regarding the risk factors for cervical cancer, preventive measures such as screening, and timely treatment seem necessary.

Study of Blood Metabolites Changes of Purebred Ghezel and Crossbred Arkhar Merinos × Ghezel Ewes during Late Pregnancy

Directory of Open Access Journals (Sweden)

Leila Ahmadzadeh

2016-11-01

, which may originate from genetic potential of these two groups. These differences revealed that hybrid ewes are more resistant against blood metabolite changes during late pregnancy. Study of fluctuations in the blood metabolites during several stages of pregnancy can help us to determine abnormal metabolic cases and prediction of metabolic disorders such as pregnancy toxemia or ketosis, fatty liver syndrome and disease relating to fetus and ewe metabolism.

Drug repositioning for enzyme modulator based on human metabolite-likeness.

Science.gov (United States)

Lee, Yoon Hyeok; Choi, Hojae; Park, Seongyong; Lee, Boah; Yi, Gwan-Su

2017-05-31

Recently, the metabolite-likeness of the drug space has emerged and has opened a new possibility for exploring human metabolite-like candidates in drug discovery. However, the applicability of metabolite-likeness in drug discovery has been largely unexplored. Moreover, there are no reports on its applications for the repositioning of drugs to possible enzyme modulators, although enzyme-drug relations could be directly inferred from the similarity relationships between enzyme's metabolites and drugs. We constructed a drug-metabolite structural similarity matrix, which contains 1,861 FDA-approved drugs and 1,110 human intermediary metabolites scored with the Tanimoto similarity. To verify the metabolite-likeness measure for drug repositioning, we analyzed 17 known antimetabolite drugs that resemble the innate metabolites of their eleven target enzymes as the gold standard positives. Highly scored drugs were selected as possible modulators of enzymes for their corresponding metabolites. Then, we assessed the performance of metabolite-likeness with a receiver operating characteristic analysis and compared it with other drug-target prediction methods. We set the similarity threshold for drug repositioning candidates of new enzyme modulators based on maximization of the Youden's index. We also carried out literature surveys for supporting the drug repositioning results based on the metabolite-likeness. In this paper, we applied metabolite-likeness to repurpose FDA-approved drugs to disease-associated enzyme modulators that resemble human innate metabolites. All antimetabolite drugs were mapped with their known 11 target enzymes with statistically significant similarity values to the corresponding metabolites. The comparison with other drug-target prediction methods showed the higher performance of metabolite-likeness for predicting enzyme modulators. After that, the drugs scored higher than similarity score of 0.654 were selected as possible modulators of enzymes for

Comparison of DDT and its metabolites concentrations in cow milk from agricultural and industrial areas.

Science.gov (United States)

Kuba, Jarosław; Tomza-Marciniak, Agnieszka; Pilarczyk, Bogumiła; Tarasewicz, Natalia; Pilarczyk, Renata; Ligocki, Marek

2015-01-01

The risk of pesticidal intoxication in humans is severe, especially because of the strongly negative impact on human health. The consequences of the exposure to these substances may include cancerogenesis or endocrine abnormalities resulting for example in decreased fertility. Therefore, the aim of our study was to evaluate the content of dichlorodiphenyltrichloroethane (DDT) and its metabolites in cow milk from two regions of Poland, varying by level of industrialization. Samples were collected from agricultural (n = 25) and industrial (n = 25) areas, and the concentrations of DDT and its metabolites were evaluated by gas chromatography. Residues of DDT were detected in all the milk samples tested, mostly in the samples from the agricultural area, where a total DDT median concentration reached 0.336 μg L(-1). In the milk samples from the industrial area, the median concentration was lower, at 0.131 μg L(-1). 4,4'-DDT was the main metabolite, constituting 83% of total DDT metabolites. Although none of the samples exceeded the level above which they should be considered dangerous, the results showed that the problem of DDT had not diminished and so should be constantly monitored.

Morphine metabolites

DEFF Research Database (Denmark)

Christrup, Lona Louring

1997-01-01

, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) are the major metabolites of morphine. The metabolism of morphine occurs not only in the liver, but may also take place in the brain and the kidneys. The glucuronides are mainly eliminated via bile and urine. Glucuronides as a rule...... are considered as highly polar metabolites unable to cross the blood-brain barrier. Although morphine glucuronidation has been demonstrated in human brain tissue, the capacity is very low compared to that of the liver, indicating that the M3G and M6G concentrations observed in the cerebrospinal fluid (CSF) after...... systemic administration reflect hepatic metabolism of morphine and that the morphine glucuronides, despite their high polarity, can penetrate into the brain. Like morphine, M6G has been shown to be relatively more selective for mu-receptors than for delta- and kappa-receptors while M3G does not appear...

Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition

Directory of Open Access Journals (Sweden)

Zhu Zhu

2016-01-01

Full Text Available Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice by altering exposure to light. C57 BL/6J mice (C57 mice and ApoE-KO mice (ApoE-KO mice exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1 levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

Gaucher disease: plasmalogen levels in relation to primary lipid abnormalities and oxidative stress.

Science.gov (United States)

Moraitou, Marina; Dimitriou, Evangelia; Dekker, Nick; Monopolis, Ioannis; Aerts, Johannes; Michelakakis, Helen

2014-01-01

Plasmalogens represent a unique class of phospholipids. Reduced red blood cell plasmalogen levels in Gaucher disease patients were reported, correlating to total disease burden. The relation between plasmalogen abnormalities in Gaucher disease patients and primary glycosphingolipid abnormalities, malonyldialdehyde levels, an indicator of lipid peroxidation, and the total antioxidant status was further investigated. Significant reduction of C16:0 and C18:0 plasmalogens in red blood cells of Gaucher disease patients was confirmed. In parallel, a significant increase in the glucosylceramide/ceramide ratio in red blood cell membranes, as well as an average 200-fold increase in plasma glucosylsphingosine levels was observed. Red blood cell malonyldialdehyde levels were significantly increased in patients, whereas their total antioxidant status was significantly reduced. A negative correlation between plasmalogen species and glucosylceramide, ceramide, glucosylceramide/ceramide ratio, glucosylsphingosine and malonyldialdehyde, significant for the C16:0 species and all the above parameters with the exception of malonyldialdehyde levels, was found along with a positive non-significant correlation with the total antioxidant status. Our results indicate that increased lipid peroxidation and reduced total antioxidant status exist in Gaucher disease patients. They demonstrate a clear link between plasmalogen levels and the primary glycolipid abnormalities characterizing the disorder and an association with the increased oxidative stress observed in Gaucher disease patients. Copyright © 2014 Elsevier Inc. All rights reserved.

White matter abnormalities in tuberous sclerosis complex

Energy Technology Data Exchange (ETDEWEB)

Griffiths, P.D. [Sheffield Univ. (United Kingdom). Academic Dept. of Radiology; Bolton, P. [Cambridge Univ. (United Kingdom). Section of Developmental Psychiatry; Verity, C. [Addenbrooke`s NHS Trust, Cambridge (United Kingdom). Dept. of Paediatric Radiology

1998-09-01

The aim of this study was to investigate and describe the range of white matter abnormalities in children with tuberous sclerosis complex by means of MR imaging. Material and Methods: A retrospective cross-sectional study was performed on the basis of MR imaging findings in 20 cases of tuberous sclerosis complex in children aged 17 years or younger. Results: White matter abnormalities were present in 19/20 (95%) cases of tuberous sclerosis complex. These were most frequently (19/20 cases) found in relation to cortical tubers in the supratentorial compartment. White matter abnormalities related to tubers were found in the cerebellum in 3/20 (15%) cases. White matter abnormalities described as radial migration lines were found in relation to 5 tubers in 3 (15%) children. In 4/20 (20%) cases, white matter abnormalities were found that were not related to cortical tubers. These areas had the appearance of white matter cysts in 3 cases and infarction in the fourth. In the latter case there was a definable event in the clinical history, supporting the diagnosis of stroke. Conclusion: A range of white matter abnormalities were found by MR imaging in tuberous sclerosis complex, the commonest being gliosis and hypomyelination related to cortical tubers. Radial migration lines were seen infrequently in relation to cortical tubers and these are thought to represent heterotopic glia and neurons along the expected path of cortical migration. (orig.)

Abnormal occipital event-related potentials in Parkinson's disease with concomitant REM sleep behavior disorder.

Science.gov (United States)

Gaudreault, Pierre-Olivier; Gagnon, Jean-François; Montplaisir, Jacques; Vendette, Mélanie; Postuma, Ronald B; Gagnon, Katia; Gosselin, Nadia

2013-02-01

Rapid eye movement sleep behavior disorder is found in 33-46% of patients with Parkinson's disease and was shown to be associated with cognitive deficits. Our goal was to improve our understanding of the role of this sleep disorder in cerebral dysfunction occurring in Parkinson's disease using a visual cognitive task and event-related potentials. Sixteen patients with Parkinson's disease and rapid eye movement sleep behavior disorder, 15 patients with Parkinson's disease without rapid eye movement sleep behavior disorder and 16 healthy control subjects were included. The amplitude and latency of event-related potentials were compared between groups. No group differences were found for reaction times or accuracy. A Group effect was found for P2 wave amplitude; patients with rapid eye movement sleep behavior disorder had increased P2 in comparison with the control group (p disorder were associated with abnormal visual P2 component of event-related potentials. Although patients with Parkinson's disease alone were not significantly different from patients with combined Parkinson's disease and rapid eye movement sleep behavior disorder, their P2 amplitudes were not sufficiently abnormal to differ from that of control subjects. This study confirms that rapid eye movement sleep behavior disorder accentuates cerebral dysfunctions in Parkinson's disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

Detecting beer intake by unique metabolite patterns

DEFF Research Database (Denmark)

Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian

2016-01-01

Evaluation of health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern...... representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1) 18 participants were given one at a time four different test beverages: strong, regular and non-alcoholic beers and a soft drink. Four participants were...... assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e. N-methyl tyramine sulfate and the sum...

Late-onset Rise of 6-MMP Metabolites in IBD Patients on Azathioprine or Mercaptopurine.

Science.gov (United States)

Munnig-Schmidt, Erik; Zhang, Mei; Mulder, Chris J; Barclay, Murray L

2018-03-19

The thiopurines azathioprine and mercaptopurine remain pivotal maintenance treatments in inflammatory bowel disease (IBD); however, up to 15%-20% of patients preferentially produce the hepatotoxic metabolite 6-methylmercaptopurine (6MMP) at the expense of the therapeutic 6-thioguanine nucleotides (6TGN). This metabolic shunting usually begins within 3 months of therapy. We noted patients developing shunting many months or years after starting treatment and aimed to determine how often this late shunting occurs and whether this could be explained by patient factors or concomitant medications. The New Zealand database of thiopurine metabolite results from 2002 to 2016 (19085 6TGN/6MMP pairs from 7130 patients) was interrogated to identify patients developing a 6MMP/6TGN ratio >20 after at least 4 months treatment. Dosing history, concomitant therapy, and comorbidity data were assessed. Fifteen percent of database patients developed preferential 6-MMP production, and of these, 29 patients had late-onset shunting with sufficient data available for validation. This extrapolates to 90 patients in total, representing 1.7% of IBD patients on thiopurines, or 10% of all those with preferential 6-MMP production. Time from starting therapy to shunting was 5 months to 10.4 years (median, 21 months). Eleven patients had abnormal liver function when shunting was recognized, all with 6MMP >5900 pmol/8 × 108 red blood cells. No common factors were found to explain the late onset. Some IBD patients develop preferential 6MMP production many months or years after commencing therapy. This is important when considering frequency of metabolite monitoring, failure of therapy, or abnormal liver function. 10.1093/ibd/izx081_video1izx081.video15746667546001.

Di-(2-ethylhexyl phthalate metabolites in urine show age-related changes and associations with adiposity and parameters of insulin sensitivity in childhood.

Directory of Open Access Journals (Sweden)

Arianna Smerieri

Full Text Available Phthalates might be implicated with obesity and insulin sensitivity. We evaluated the levels of primary and secondary metabolites of Di-(2-ethylhexyl phthalate (DEHP in urine in obese and normal-weight subjects both before and during puberty, and investigated their relationships with auxological parameters and indexes of insulin sensitivity.DEHP metabolites (MEHP, 6-OH-MEHP, 5-oxo-MEHP, 5-OH-MEHP, and 5-CX-MEHP, were measured in urine by RP-HPLC-ESI-MS. Traditional statistical analysis and a data mining analysis using the Auto-CM analysis were able to offer an insight into the complex biological connections between the studied variables.The data showed changes in DEHP metabolites in urine related with obesity, puberty, and presence of insulin resistance. Changes in urine metabolites were related with age, height and weight, waist circumference and waist to height ratio, thus to fat distribution. In addition, clear relationships in both obese and normal-weight subjects were detected among MEHP, its products of oxidation and measurements of insulin sensitivity.It remains to be elucidated whether exposure to phthalates per se is actually the risk factor or if the ability of the body to metabolize phthalates is actually the key point. Further studies that span from conception to elderly subjects besides further understanding of DEHP metabolism are warranted to clarify these aspects.

Identification, quantification, and relative concentrations of carotenoids and their metabolites in human milk and serum.

Science.gov (United States)

Khachik, F; Spangler, C J; Smith, J C; Canfield, L M; Steck, A; Pfander, H

1997-05-15

Thirty-four carotenoids, including 13 geometrical isomers and eight metabolites, in breast milk and serum of three lactating mothers have been separated, identified, quantified, and compared by high-performance liquid chromatography (HPLC)-photodiode array (PDA) detection-mass spectrometry (MS). Among the metabolites were two oxidation products of lycopene and four of lutein/ zeaxanthin. In addition, two metabolites of lutein, formed as a result of dehydration of this dihydroxycarotenoid under acidic conditions similar to those of the stomach, have also been identified in plasma and breast milk. The oxidative metabolites of lycopene with a novel five-membered-ring end group have been identified as epimeric 2,6-cyclolycopene-1,5-diols by comparison of their HPLC-UV/visible-MS profiles with those of fully characterized (1H- and 13C-NMR spectroscopy) synthetic compounds. The HPLC procedures employed also detected vitamin A, two forms of vitamin E (gamma- and alpha-tocopherol), and two non-carotenoid food components, i.e., piperine and caffeine, in serum and breast milk.

Prevalence of abnormal birth weight and related factors in Northern region, Ghana.

Science.gov (United States)

Abubakari, Abdulai; Kynast-Wolf, Gisela; Jahn, Albrecht

2015-12-15

Birth weight is a crucial determinant of the development potential of the newborn. Abnormal newborn weights are associated with negative effects on the health and survival of the baby and the mother. Therefore, this study was designed to determine the prevalence of abnormal birth weight and related factors in Northern region, Ghana. The study was a facility-based cross-sectional survey in five hospitals in Northern region, Ghana. These hospitals were selected based on the different socio-economic backgrounds of their clients. The data on birth weight and other factors were derived from hospital records. It was observed that low birth weight is still highly prevalent (29.6%), while macrosomia (10.5%) is also increasingly becoming important. There were marginal differences in low birth weight observed across public hospitals but marked difference in low birth weight was observed in Cienfuegos Suglo Specialist Hospital (Private hospital) as compared to the public hospitals. The private hospital also had the highest prevalence of macrosomia (20.1%). Parity (0-1) (p malnutrition phenomenon, which is currently being experienced by developing and transition counties. Both low birth weight and macrosomia are risk factors, which could contribute considerably to the current and future burden of diseases. This may overstretch the already fragile health system in Ghana. Therefore, it is prudent to recommend that policies aiming at reducing diet related diseases should focus on addressing malnutrition during pregnancy and early life.

The Arabidopsis-related halophyte Thellungiella halophila: boron tolerance via boron complexation with metabolites?

Science.gov (United States)

Lamdan, Netta Li; Attia, Ziv; Moran, Nava; Moshelion, Menachem

2012-04-01

Tolerance to boron (B) is still not completely understood. We tested here the hypothesis that Thellungiella halophila, an Arabidopsis thaliana-related 'extremophile' plant, with abundance of B in its natural environment, is tolerant to B, and examined the potential mechanisms of this tolerance. With 1-10 mm B applied ([B](ext)) to Thellungiella and Arabidopsis grown in hydroponics, the steady-state accumulated B concentration ([B](int)) in the root was below [B](ext), and was similar in both, suggesting both extrude B actively. Whether grown in soil or hydroponically, the shoot [B](int) was higher in Arabidopsis than in Thellungiella, suggesting more effective net B exclusion by Thellungiella root. Arabidopsis exhibited toxicity symptoms including reduced shoot fresh weight (FW), but Thellungiella was not affected, even at similar levels of shoot-accumulated [B](int) (about 10 to 40 mm B in 'shoot water'), suggesting additional B tolerance mechanism in Thellungiella shoot. At [B](ext) = 5 mm, the summed shoot concentration of the potentially B-binding polyhydroxyl metabolites (malic acid, fructose, glucose, sucrose and citric acid) in Arabidopsis was below [B](int) , but in Thellungiella it was over twofold higher than [B](int) , and therefore likely to allow appreciable 1:2 boron-metabolite complexation in the shoot. This, we suggest, is an important component of Thellungiella B tolerance mechanism. © 2011 Blackwell Publishing Ltd.

The effectiveness of osteopathic manipulative treatment in an abnormal uterine bleeding related pain and health related quality of life (HR-QoL) - A case report.

Science.gov (United States)

Goyal, Kanu; Goyal, Manu; Narkeesh, Kanimozhi; John Samuel, Asir; Sharma, Sorabh; Chatterjee, Subhasish; Arumugam, Narkeesh

2017-07-01

Abnormal uterine bleeding is characterized by painful and/or excessive menorrhea, chronic pelvic pain due to the endometriosis (Em). Osteopathic treatment is commonly used in the gynecological dysfunctions. The aim of the present case study was to explore the effect of osteopathic treatment (OT) for a woman with abnormal uterine bleeding related pain and quality of life (QoL). We reported a case of 29 year old female who presented with chief complaints of increased flow during periods, lower abdominal pain, leukorrhoea, lower back pain and with occasional constipation for the last 3 years. Patient is a mother of 6 years old male child born with normal delivery. On diagnostic ultrasonography the uterus was found bulky with insignificant endometriosis and no other abnormality was detected. She did not have any relevant past medical and surgical history. The pre and post osteopathic treatment measurements were measured using Visual Analog Scale (VAS) and the health related quality of life (HR-QoL) questionnaire called short form Endometriosis Health Profile Questionnaire (EHP) - 5. In the present case the pain due to the endometriosis was treated with the osteopathic treatment consists of all the major diaphragms' release (release of pelvic diaphragm, abdominal diaphragm, thoracic outlet release and hyoid diaphragm) during the first session and in the second session gastro-esophageal (GE) junction release, sigmoid colon release, cranial therapy to the occiput, sacral release and dural tube rocking. Following that improvement of pain from VAS 8.3/10 to 3.9/10 and QoL improvement from EHP-5, 72/100 to 26/100 was noted. Osteopathic manipulative approach (OMA) in the patient with Em might improve the abnormal uterine bleeding related pain and health related quality of life (HR-QoL). Copyright © 2016 Elsevier Ltd. All rights reserved.

Battery-Free Smart Sock for Abnormal Relative Plantar Pressure Monitoring.

Science.gov (United States)

Lin, Xiaoyou; Seet, Boon-Chong

2017-04-01

This paper presents a new design of a wearable plantar pressure monitoring system in the form of a smart sock for sensing abnormal relative pressure changes. One advantage of this approach is that with a battery-free design, this system can be powered solely by radio frequency (RF) energy harvested from a radio frequency identification (RFID) reader unit hosted on a smartphone of the wearer. At the same time, this RFID reader can read foot pressure values from an embedded sensor-tag in the sock. A pressure sensing matrix made of conductive fabric and flexible piezo-resistive material is integrated into the sock during the knitting process. Sensed foot pressures are digitized and stored in the memory of a sensor-tag, thus allowing relative foot pressure values to be tracked. The control unit of the smart sock is assembled on a flexible printed circuit board (FPC) that can be strapped to the lower limb and detached easily when it is not in use. Experiments show that the system can operate reliably in both tasks of RF energy harvesting and pressure measurement.

Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders.

Science.gov (United States)

Kang, Dae-Wook; Ilhan, Zehra Esra; Isern, Nancy G; Hoyt, David W; Howsmon, Daniel P; Shaffer, Michael; Lozupone, Catherine A; Hahn, Juergen; Adams, James B; Krajmalnik-Brown, Rosa

2018-02-01

Evidence supporting that gut problems are linked to ASD symptoms has been accumulating both in humans and animal models of ASD. Gut microbes and their metabolites may be linked not only to GI problems but also to ASD behavior symptoms. Despite this high interest, most previous studies have looked mainly at microbial structure, and studies on fecal metabolites are rare in the context of ASD. Thus, we aimed to detect fecal metabolites that may be present at significantly different concentrations between 21 children with ASD and 23 neurotypical children and to investigate its possible link to human gut microbiome. Using 1 H-NMR spectroscopy and 16S rRNA gene amplicon sequencing, we examined metabolite profiles and microbial compositions in fecal samples, respectively. Of the 59 metabolites detected, isopropanol concentrations were significantly higher in feces of children with ASD after multiple testing corrections. We also observed similar trends of fecal metabolites to previous studies; children with ASD have higher fecal p-cresol and possibly lower GABA concentrations. In addition, Fisher Discriminant Analysis (FDA) with leave-out-validation suggested that a group of metabolites-caprate, nicotinate, glutamine, thymine, and aspartate-may potentially function as a modest biomarker to separate ASD participants from the neurotypical group (78% sensitivity and 81% specificity). Consistent with our previous Arizona cohort study, we also confirmed lower gut microbial diversity and reduced relative abundances of phylotypes most closely related to Prevotella copri in children with ASD. After multiple testing corrections, we also learned that relative abundances of Feacalibacterium prausnitzii and Haemophilus parainfluenzae were lower in feces of children with ASD. Despite a relatively short list of fecal metabolites, the data in this study support that children with ASD have altered metabolite profiles in feces when compared with neurotypical children and warrant further

Changes in hippocampal metabolites after effective treatment for fibromyalgia: a case study.

Science.gov (United States)

Wood, Patrick B; Ledbetter, Christina R; Patterson, James C

2009-01-01

Fibromyalgia has been associated with disrupted hippocampal brain metabolite ratios by studies using single voxel magnetic resonance spectroscopy (1H-MRS). Exposure to stress is considered a risk factor for the development and exacerbation of fibromyalgia symptoms. Basic science has demonstrated the hippocampus to be exquisitely sensitive to the effects of stressful experience, which results in changes including alterations in metabolite content and frank atrophy. This report details the case of a 47-year-old woman with fibromyalgia who was originally found to have a profound depression of the ratio of N-acetylaspartate to creatine in her right hippocampus during participation in a study to assess brain metabolite disturbances in fibromyalgia utilizing single voxel proton magnetic resonance spectroscopy. An individualized treatment strategy was developed based both on physiological abnormalities associated with the disorder and symptoms that characterized the patient's unique clinical profile. Clinical and spectroscopic evaluation following nine months of treatment demonstrated both an improvement in her clinical profile and normalization of the NAA/Cr ratio within her right hippocampus. Therapeutic strategies aimed at demonstrable lesions associated with fibromyalgia appear to represent rational targets for pharmacological intervention. The rationale for development of novel pharmacotherapies for this unusual disorder is discussed.

Serum concentrations of phthalate metabolites are related to abdominal fat distribution two years later in elderly women

Directory of Open Access Journals (Sweden)

Lind P Monica

2012-04-01

Full Text Available Abstract Background Phthalates, commonly used to soften plastic goods, are known PPAR-agonists affecting lipid metabolism and adipocytes in the experimental setting. We evaluated if circulating concentrations of phthalates were related to different indices of obesity using data from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS study. Data from both dual-energy X-ray absorptiometry (DXA and abdominal magnetic resonance imaging (MRI were used. Methods 1,016 subjects aged 70 years were investigated in the PIVUS study. Four phthalate metabolites were detected in the serum of almost all subjects (> 96% by an API 4000 liquid chromatograph/tandem mass spectrometer. Abdominal MRI was performed in a representative subsample of 287 subjects (28%, and a dual-energy X-ray absorptiometry (DXA-scan was obtained in 890 (88% of the subjects two year following the phthalate measurements. Results In women, circulating concentrations of mono-isobutyl phthalate (MiBP were positively related to waist circumference, total fat mass and trunk fat mass by DXA, as well as to subcutaneous adipose tissue by MRI following adjustment for serum cholesterol and triglycerides, education, smoking and exercise habits (all p Conclusions The present evaluation shows that especially the phthalate metabolite MiBP was related to increased fat amount in the subcutaneous abdominal region in women measured by DXA and MRI two years later.

Neurochemical abnormalities in brains of renal failure patients treated by repeated hemodialysis.

Science.gov (United States)

Perry, T L; Yong, V W; Kish, S J; Ito, M; Foulks, J G; Godolphin, W J; Sweeney, V P

1985-10-01

We examined autopsied brain from 10 patients with end-stage renal failure who had undergone repeated hemodialysis. Eight had classic symptoms, and two had suggestive symptoms of dialysis encephalopathy. Findings were compared with those in autopsied brain from control adults who had never been hemodialyzed. Mean gamma-aminobutyric acid (GABA) contents were significantly reduced in frontal and occipital cortex, cerebellar cortex, dentate nucleus, caudate nucleus, and medial-dorsal thalamus of the hemodialyzed patients, the reduction being greater than 40% in cerebral cortex and thalamus. Choline acetyltransferase activity was reduced by 25-35% in three cortical regions in the hemodialyzed patients. These two abnormalities were observed in the brain of each hemodialyzed patient, regardless of whether or not the patient died with unequivocal dialysis encephalopathy. Pyridoxal phosphate contents were substantially reduced in brains of the hemodialyzed patients, but metabolites of noradrenaline, 3,4-dihydroxyphenylethylamine (dopamine), and 5-hydroxytryptamine (serotonin) were present in normal amounts. Aluminum levels were abnormally high in frontal cortical gray matter in the hemodialyzed patients. Although this study does not clarify the role played by aluminum toxicity in the pathogenesis of dialysis encephalopathy, the abnormalities we found suggest the need for further neurochemical investigations in this disorder.

Novel pyrazine metabolites found in polymyxin biosynthesis by Paenibacillus polymyxa

DEFF Research Database (Denmark)

Beck, Hans Christian; Hansen, Anne M; Lauritsen, Frants R

2003-01-01

A complex mixture of methyl-branched alkyl-substituted pyrazines was found in the growth medium of the polymyxin-producing bacterium Paenibacillus polymyxa, and of these, seven are new natural compounds. A total of 19 pyrazine metabolites were identified. The dominant metabolite was 2...... supplementation. The other pyrazine metabolites, all related pyrazines with either one, two or three alkyl substituents, were identified by means of their mass spectral data and/or co-elution with authentic standards....

Parkinsonian abnormality of foot strike: a phenomenon of ageing and/or one responsive to levodopa therapy?

Science.gov (United States)

Hughes, J R; Bowes, S G; Leeman, A L; O'Neill, C J; Deshmukh, A A; Nicholson, P W; Dobbs, S M; Dobbs, R J

1990-01-01

1. Normally during walking, the heel strikes the ground before the forefoot. Abnormalities of foot strike in idiopathic Parkinson's disease may be amenable to therapy: objective measurements may reveal response which is not clinically apparent. Occult changes in foot strike leading to instability may parallel the normal, age-related loss of striatal dopamine. 2. The nature of foot strike was studied using pedobarography in 160 healthy volunteers, aged 15 to 91 years. Although 16% of strikes were made simultaneously by heel and forefoot, there were no instances of the forefoot preceding the heel. No significant effect of age on an index of normality of foot strikes was detected (P greater than 0.3). 3. The effect on foot strike of substituting placebo for a morning dose of a levodopa/carbidopa combination was studied in a double-blind, cross-over trial in 14 patients, aged 64 to 88 years, with no overt fluctuations in control of their idiopathic Parkinson's disease in relation to dosing. On placebo treatment there was a highly significant (P = 0.004) reduction in the number of more normal strikes, i.e. heel strikes plus simultaneous heel and forefoot strikes. The effect appeared unrelated to the corresponding difference between active and placebo treatments in plasma concentration of levodopa or a metabolite of long half-time, 3-O-methyldopa (3OMD). However, it correlated negatively (P less than 0.05) with the mean of the 3OMD concentrations. 4. It appears that some abnormalities of foot strike due to Parkinson's disease are reversible. Employing test conditions, designed to provoke abnormalities of foot strike, might be useful in screening for pre-clinical Parkinson's disease. PMID:2306409

Mu receptor binding of some commonly used opioids and their metabolites

International Nuclear Information System (INIS)

Chen, Zhaorong; Irvine, R.J.; Somogyi, A.A.; Bochner, F.

1991-01-01

The binding affinity to the μ receptor of some opioids chemically related to morphine and some of their metabolites was examined in rat brain homogenates with 3 H-DAMGO. The chemical group at position 6 of the molecule had little effect on binding. Decreasing the length of the alkyl group at position 3 decreased the K i values (morphine < codeine < ethylmorphine < pholcodine). Analgesics with high clinical potency containing a methoxyl group at position 3 had relatively weak receptor binding, while their O-demethylated metabolites had much stronger binding. Many opioids may exert their pharmacological actions predominantly through metabolites

Mu receptor binding of some commonly used opioids and their metabolites

Energy Technology Data Exchange (ETDEWEB)

Chen, Zhaorong; Irvine, R.J. (Univ. of Adelaide (Australia)); Somogyi, A.A.; Bochner, F. (Univ. of Adelaide (Australia) Royal Adelaide Hospital (Australia))

1991-01-01

The binding affinity to the {mu} receptor of some opioids chemically related to morphine and some of their metabolites was examined in rat brain homogenates with {sup 3}H-DAMGO. The chemical group at position 6 of the molecule had little effect on binding. Decreasing the length of the alkyl group at position 3 decreased the K{sub i} values (morphine < codeine < ethylmorphine < pholcodine). Analgesics with high clinical potency containing a methoxyl group at position 3 had relatively weak receptor binding, while their O-demethylated metabolites had much stronger binding. Many opioids may exert their pharmacological actions predominantly through metabolites.

Radiation-Induced Growth Retardation and Microstructural and Metabolite Abnormalities in the Hippocampus.

Science.gov (United States)

Rodgers, Shaefali P; Zawaski, Janice A; Sahnoune, Iman; Leasure, J Leigh; Gaber, M Waleed

2016-01-01

Cranial radiotherapy (CRT) increases survival in pediatric brain-tumor patients but can cause deleterious effects. This study evaluates the acute and long-term impact of CRT delivered during childhood/adolescence on the brain and body using a rodent model. Rats received CRT, either 4 Gy fractions × 5 d (fractionated) or a cumulative dose of 20 Gy (single dose) at 28 d of age. Animals were euthanized 1 d, 5 d, or 3.5 mo after CRT. The 3.5 mo group was imaged prior to euthanasia. At 3.5 mo, we observed significant growth retardation in irradiated animals, versus controls, and the effects of single dose on brain and body weights were more severe than fractionated. Acutely single dose significantly reduced body weight but increased brain weight, whereas fractionation significantly reduced brain but not body weights, versus controls. CRT suppressed cell proliferation in the hippocampal subgranular zone acutely. Fractional anisotropy (FA) in the fimbria was significantly lower in the single dose versus controls. Hippocampal metabolite levels were significantly altered in the single dose animals, reflecting a heightened state of inflammation that was absent in the fractionated. Our findings indicate that despite the differences in severity between the doses they both demonstrated an effect on cell proliferation and growth retardation, important factors in pediatric CRT.

Complicating factors in safety testing of drug metabolites: Kinetic differences between generated and preformed metabolites

International Nuclear Information System (INIS)

Prueksaritanont, Thomayant; Lin, Jiunn H.; Baillie, Thomas A.

2006-01-01

This paper aims to provide a scientifically based perspective on issues surrounding the proposed toxicology testing of synthetic drug metabolites as a means of ensuring adequate nonclinical safety evaluation of drug candidates that generate metabolites considered either to be unique to humans or are present at much higher levels in humans than in preclinical species. We put forward a number of theoretical considerations and present several specific examples where the kinetic behavior of a preformed metabolite given to animals or humans differs from that of the corresponding metabolite generated endogenously from its parent. The potential ramifications of this phenomenon are that the results of toxicity testing of the preformed metabolite may be misleading and fail to characterize the true toxicological contribution of the metabolite when formed from the parent. It is anticipated that such complications would be evident in situations where (a) differences exist in the accumulation of the preformed versus generated metabolites in specific tissues, and (b) the metabolite undergoes sequential metabolism to a downstream product that is toxic, leading to differences in tissue-specific toxicity. Owing to the complex nature of this subject, there is a need to treat drug metabolite issues in safety assessment on a case-by-case basis, in which a knowledge of metabolite kinetics is employed to validate experimental paradigms that entail administration of preformed metabolites to animal models

1D-¹H-nuclear magnetic resonance metabolomics reveals age-related changes in metabolites associated with experimental venous thrombosis.

Science.gov (United States)

Obi, Andrea T; Stringer, Kathleen A; Diaz, Jose A; Finkel, Michael A; Farris, Diana M; Yeomans, Larisa; Wakefield, Thomas; Myers, Daniel D

2016-04-01

Age is a significant risk factor for the development of venous thrombosis (VT), but the mechanism(s) that underlie this risk remain(s) undefined and poorly understood. Aging is known to adversely influence inflammation and affect metabolism. Untargeted metabolomics permits an agnostic assessment of the physiological landscape and lends insight into the mechanistic underpinnings of clinical phenotypes. The objective of this exploratory study was to test the feasibility of a metabolomics approach for identifying potential metabolic mechanisms of age-related VT. We subjected whole blood samples collected from young and old nonthrombosed controls and VT mice 2 days after thrombus induction using the electrolytic inferior vena cava, to a methanol:chloroform extraction and assayed the resulting aqueous fractions using 1D-(1)H- nuclear magnetic resonance. Normalized mouse metabolite data were compared across groups using analysis of variance (ANOVA) with Holm-Sidak post-testing. In addition, associations between metabolite concentrations and parameters of thrombosis such as thrombus and vein wall weights, and markers of inflammation, vein wall P- and E-selectin levels, were assessed using linear regression. The relatedness of the found significant metabolites was visually assessed using a bioinformatics tool, Metscape, which generates compound-reaction-enzyme-gene networks to aid in the interpretation of metabolomics data. Old mice with VT had a greater mean vein wall weight compared with young mice with VT (P metabolomics as a new approach to furthering knowledge about the mechanisms of age-related VT. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Semen phthalate metabolites, semen quality parameters and serum reproductive hormones: A cross-sectional study in China.

Science.gov (United States)

Wang, Yi-Xin; Zeng, Qiang; Sun, Yang; Yang, Pan; Wang, Peng; Li, Jin; Huang, Zhen; You, Ling; Huang, Yue-Hui; Wang, Cheng; Li, Yu-Feng; Lu, Wen-Qing

2016-04-01

Exposure to phthalates has been found to have adverse effects on male reproductive function in animals. However, the findings from human studies are inconsistent. Here we examined the associations of phthalate exposure with semen quality and reproductive hormones in a Chinese population using phthalate metabolite concentrations measured in semen as biomarkers. Semen (n = 687) and blood samples (n = 342) were collected from the male partners of sub-fertile couples who presented to the Reproductive Center of Tongji Hospital in Wuhan, China. Semen quality parameters and serum reproductive hormone levels were determined. Semen concentrations of 8 phthalate metabolites were assessed using high-performance liquid chromatography and tandem mass spectrometry. Associations of the semen phthalate metabolites with semen quality parameters and serum reproductive hormones were assessed using confounder-adjusted linear and logistic regression models. Semen phthalate metabolites were significantly associated with decreases in semen volume [mono-n-butyl phthalate (MBP), mono-(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)], sperm curvilinear velocity [monobenzyl phthalate (MBzP), MEHP, the percentage of di-(2-ethylhexyl)-phthalate metabolites excreted as MEHP (%MEHP)], and straight-line velocity (MBzP, MEHP, %MEHP), and also associated with an increased percentage of abnormal heads and tails (MBzP) (all p for trend hormones. Our findings suggest that environmental exposure to phthalates may impair human semen quality. Copyright © 2015 Elsevier Ltd. All rights reserved.

A bell pepper cultivar tolerant to chilling enhanced nitrogen allocation and stress-related metabolite accumulation in the roots in response to low root-zone temperature.

Science.gov (United States)

Aidoo, Moses Kwame; Sherman, Tal; Lazarovitch, Naftali; Fait, Aaron; Rachmilevitch, Shimon

2017-10-01

Two bell pepper (Capsicum annuum) cultivars, differing in their response to chilling, were exposed to three levels of root-zone temperatures. Gas exchange, shoot and root phenology, and the pattern of change of the central metabolites and secondary metabolites caffeate and benzoate in the leaves and roots were profiled. Low root-zone temperature significantly inhibited gaseous exchange, with a greater effect on the sensitive commercial pepper hybrid (Canon) than on the new hybrid bred to enhance abiotic stress tolerance (S103). The latter was less affected by the treatment with respect to plant height, shoot dry mass, root maximum length, root projected area, number of root tips and root dry mass. More carbon was allocated to the leaves of S103 than nitrogen at 17°C, while in the roots at 17°C, more nitrogen was allocated and the ratio between C/N decreased. Metabolite profiling showed greater increase in the root than in the leaves. Leaf response between the two cultivars differed significantly. The roots accumulated stress-related metabolites including γ-aminobutyric acid (GABA), proline, galactinol and raffinose and at chilling (7°C) resulted in an increase of sugars in both cultivars. Our results suggest that the enhanced tolerance of S103 to root cold stress, reflected in the relative maintenance of shoot and root growth, is likely linked to a more effective regulation of photosynthesis facilitated by the induction of stress-related metabolism. © 2017 Scandinavian Plant Physiology Society.

Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders

Energy Technology Data Exchange (ETDEWEB)

Kang, Dae-Wook; Ilhan, Zehra Esra; Isern, Nancy G.; Hoyt, David W.; Howsmon, Daniel P.; Shaffer, Michael; Lozupone, Catherine A.; Hahn, Juergen; Adams, James B.; Krajmalnik-Brown, Rosa

2018-02-01

Evidence supporting that gut problems are linked to ASD symptoms has been accumulating both in humans and animal models of ASD. Gut microbes and their metabolites may be linked not only to GI problems but also to ASD behavior symptoms. Despite this high interest, most previous studies have looked mainly at microbial structure, and studies on fecal metabolites are rare in the context of ASD. Thus, we aimed to detect fecal metabolites that may be present at significantly different concentrations between 21 children with ASD and 23 neurotypical children and to investigate its possible link to human gut microbiome. Using NMR spectroscopy and 16S rRNA gene amplicon sequencing, we examined metabolite profiles and microbial compositions in fecal samples, respectively. Of the 59 metabolites detected, isopropanol concentrations were significantly higher in feces of children with ASD after multiple testing corrections. We also observed similar trends of fecal metabolites to previous studies; children with ASD have higher fecal p-cresol and possibly lower GABA concentrations. In addition, Fisher Discriminant Analysis (FDA) with leave-out-validation suggested that a group of metabolites- caprate, nicotinate, glutamine, thymine, and aspartate- may potentially function as a biomarker to separate ASD participants from the neurotypical group (78% sensitivity and 81% specificity). Consistent with our previous Arizona cohort study, we also confirmed lower gut microbial diversity and reduced relative abundances of Prevotella copri in children with ASD. After multiple testing corrections, we also learned that relative abundances of Feacalibacterium prausnitzii and Haemophilus parainfluenzae were lower in feces of children with ASD. Despite a relatively short list of fecal metabolites, the data in this study support that children with ASD have altered metabolite profiles in feces when compared with neurotypical children and warrant further investigation of metabolites in larger cohorts.

Abnormal Selective Attention Normalizes P3 Amplitudes in PDD

Science.gov (United States)

Hoeksma, Marco R.; Kemner, Chantal; Kenemans, J. Leon; van Engeland, Herman

2006-01-01

This paper studied whether abnormal P3 amplitudes in PDD are a corollary of abnormalities in ERP components related to selective attention in visual and auditory tasks. Furthermore, this study sought to clarify possible age differences in such abnormalities. Children with PDD showed smaller P3 amplitudes than controls, but no abnormalities in…

MSD-MAP: A Network-Based Systems Biology Platform for Predicting Disease-Metabolite Links.

Science.gov (United States)

Wathieu, Henri; Issa, Naiem T; Mohandoss, Manisha; Byers, Stephen W; Dakshanamurthy, Sivanesan

2017-01-01

Cancer-associated metabolites result from cell-wide mechanisms of dysregulation. The field of metabolomics has sought to identify these aberrant metabolites as disease biomarkers, clues to understanding disease mechanisms, or even as therapeutic agents. This study was undertaken to reliably predict metabolites associated with colorectal, esophageal, and prostate cancers. Metabolite and disease biological action networks were compared in a computational platform called MSD-MAP (Multi Scale Disease-Metabolite Association Platform). Using differential gene expression analysis with patient-based RNAseq data from The Cancer Genome Atlas, genes up- or down-regulated in cancer compared to normal tissue were identified. Relational databases were used to map biological entities including pathways, functions, and interacting proteins, to those differential disease genes. Similar relational maps were built for metabolites, stemming from known and in silico predicted metabolite-protein associations. The hypergeometric test was used to find statistically significant relationships between disease and metabolite biological signatures at each tier, and metabolites were assessed for multi-scale association with each cancer. Metabolite networks were also directly associated with various other diseases using a disease functional perturbation database. Our platform recapitulated metabolite-disease links that have been empirically verified in the scientific literature, with network-based mapping of jointly-associated biological activity also matching known disease mechanisms. This was true for colorectal, esophageal, and prostate cancers, using metabolite action networks stemming from both predicted and known functional protein associations. By employing systems biology concepts, MSD-MAP reliably predicted known cancermetabolite links, and may serve as a predictive tool to streamline conventional metabolomic profiling methodologies. Copyright© Bentham Science Publishers; For any

Mutagenic azide metabolite is azidoalanine

International Nuclear Information System (INIS)

Owais, W.M.; Rosichan, J.L.; Ronald, R.C.; Kleinhofs, A.; Nilan, R.A.

1981-01-01

Sodium axide produces high mutation rates in a number of species. Azide mutagenicity is mediated through a metabolite in barley and bacteria. Many studies showed that azide affects the L-cysteine biosynthesis pathway. Cell-free extracts of Salmonella typhimurium convert azide and O-acetylserine to the mutagenic metabolite. O-acetylserine sulfhydrylase was identified as the enzyme responsible for the metabolite biosynthesis. To confirm the conclusion that the azide metabolite is formed through the β-substitution pathway of L-cysteine, we radioactively labeled the azide metabolite using 14 C-labeled precursors. Moreover, the mutagenic azide metabolite was purified and identified as azidoalanine based on mass spectroscopy and elemental analysis. 26 refs., 3 figs., 1 tab

Chromosomal abnormalities and autism

Directory of Open Access Journals (Sweden)

Farida El-Baz

2016-01-01

Conclusion: Chromosomal abnormalities were not detected in the studied autistic children, and so the relation between the genetics and autism still needs further work up with different study methods and techniques.

Semen phthalate metabolites, semen quality parameters and serum reproductive hormones: A cross-sectional study in China

International Nuclear Information System (INIS)

Wang, Yi-Xin; Zeng, Qiang; Sun, Yang; Yang, Pan; Wang, Peng; Li, Jin; Huang, Zhen; You, Ling; Huang, Yue-Hui; Wang, Cheng; Li, Yu-Feng; Lu, Wen-Qing

2016-01-01

Exposure to phthalates has been found to have adverse effects on male reproductive function in animals. However, the findings from human studies are inconsistent. Here we examined the associations of phthalate exposure with semen quality and reproductive hormones in a Chinese population using phthalate metabolite concentrations measured in semen as biomarkers. Semen (n = 687) and blood samples (n = 342) were collected from the male partners of sub-fertile couples who presented to the Reproductive Center of Tongji Hospital in Wuhan, China. Semen quality parameters and serum reproductive hormone levels were determined. Semen concentrations of 8 phthalate metabolites were assessed using high-performance liquid chromatography and tandem mass spectrometry. Associations of the semen phthalate metabolites with semen quality parameters and serum reproductive hormones were assessed using confounder-adjusted linear and logistic regression models. Semen phthalate metabolites were significantly associated with decreases in semen volume [mono-n-butyl phthalate (MBP), mono-(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)], sperm curvilinear velocity [monobenzyl phthalate (MBzP), MEHP, the percentage of di-(2-ethylhexyl)-phthalate metabolites excreted as MEHP (%MEHP)], and straight-line velocity (MBzP, MEHP, %MEHP), and also associated with an increased percentage of abnormal heads and tails (MBzP) (all p for trend <0.05). These associations remained suggestive or significant after adjustment for multiple testing. There were no significant associations between semen phthalate metabolites and serum reproductive hormones. Our findings suggest that environmental exposure to phthalates may impair human semen quality. - Highlights: • We quantified 8 phthalate metabolites in the semen samples from 687 adult men. • We assessed associations of the metabolites with semen quality and serum hormones. �

Abnormal error monitoring in math-anxious individuals: evidence from error-related brain potentials.

Directory of Open Access Journals (Sweden)

Macarena Suárez-Pellicioni

Full Text Available This study used event-related brain potentials to investigate whether math anxiety is related to abnormal error monitoring processing. Seventeen high math-anxious (HMA and seventeen low math-anxious (LMA individuals were presented with a numerical and a classical Stroop task. Groups did not differ in terms of trait or state anxiety. We found enhanced error-related negativity (ERN in the HMA group when subjects committed an error on the numerical Stroop task, but not on the classical Stroop task. Groups did not differ in terms of the correct-related negativity component (CRN, the error positivity component (Pe, classical behavioral measures or post-error measures. The amplitude of the ERN was negatively related to participants' math anxiety scores, showing a more negative amplitude as the score increased. Moreover, using standardized low resolution electromagnetic tomography (sLORETA we found greater activation of the insula in errors on a numerical task as compared to errors in a non-numerical task only for the HMA group. The results were interpreted according to the motivational significance theory of the ERN.

Detecting Beer Intake by Unique Metabolite Patterns.

Science.gov (United States)

Gürdeniz, Gözde; Jensen, Morten Georg; Meier, Sebastian; Bech, Lene; Lund, Erik; Dragsted, Lars Ove

2016-12-02

Evaluation of the health related effects of beer intake is hampered by the lack of accurate tools for assessing intakes (biomarkers). Therefore, we identified plasma and urine metabolites associated with recent beer intake by untargeted metabolomics and established a characteristic metabolite pattern representing raw materials and beer production as a qualitative biomarker of beer intake. In a randomized, crossover, single-blinded meal study (MSt1), 18 participants were given, one at a time, four different test beverages: strong, regular, and nonalcoholic beers and a soft drink. Four participants were assigned to have two additional beers (MSt2). In addition to plasma and urine samples, test beverages, wort, and hops extract were analyzed by UPLC-QTOF. A unique metabolite pattern reflecting beer metabolome, including metabolites derived from beer raw material (i.e., N-methyl tyramine sulfate and the sum of iso-α-acids and tricyclohumols) and the production process (i.e., pyro-glutamyl proline and 2-ethyl malate), was selected to establish a compliance biomarker model for detection of beer intake based on MSt1. The model predicted the MSt2 samples collected before and up to 12 h after beer intake correctly (AUC = 1). A biomarker model including four metabolites representing both beer raw materials and production steps provided a specific and accurate tool for measurement of beer consumption.

Immune regulation by microbiome metabolites.

Science.gov (United States)

Kim, Chang H

2018-03-22

Commensal microbes and the host immune system have been co-evolved for mutual regulation. Microbes regulate the host immune system, in part, by producing metabolites. A mounting body of evidence indicates that diverse microbial metabolites profoundly regulate the immune system via host receptors and other target molecules. Immune cells express metabolite-specific receptors such as P2X 7 , GPR41, GPR43, GPR109A, aryl hydrocarbon receptor precursor (AhR), pregnane X receptor (PXR), farnesoid X receptor (FXR), TGR5 and other molecular targets. Microbial metabolites and their receptors form an extensive array of signals to respond to changes in nutrition, health and immunological status. As a consequence, microbial metabolite signals contribute to nutrient harvest from diet, and regulate host metabolism and the immune system. Importantly, microbial metabolites bidirectionally function to promote both tolerance and immunity to effectively fight infection without developing inflammatory diseases. In pathogenic conditions, adverse effects of microbial metabolites have been observed as well. Key immune-regulatory functions of the metabolites, generated from carbohydrates, proteins and bile acids, are reviewed in this article. © 2018 John Wiley & Sons Ltd.

New Methodology for Known Metabolite Identification in Metabonomics/Metabolomics: Topological Metabolite Identification Carbon Efficiency (tMICE).

Science.gov (United States)

Sanchon-Lopez, Beatriz; Everett, Jeremy R

2016-09-02

A new, simple-to-implement and quantitative approach to assessing the confidence in NMR-based identification of known metabolites is introduced. The approach is based on a topological analysis of metabolite identification information available from NMR spectroscopy studies and is a development of the metabolite identification carbon efficiency (MICE) method. New topological metabolite identification indices are introduced, analyzed, and proposed for general use, including topological metabolite identification carbon efficiency (tMICE). Because known metabolite identification is one of the key bottlenecks in either NMR-spectroscopy- or mass spectrometry-based metabonomics/metabolomics studies, and given the fact that there is no current consensus on how to assess metabolite identification confidence, it is hoped that these new approaches and the topological indices will find utility.

A novel scoring system to measure radiographic abnormalities and related spirometric values in cured pulmonary tuberculosis.

Directory of Open Access Journals (Sweden)

Renata Báez-Saldaña

Full Text Available BACKGROUND: Despite chemotherapy, patients with cured pulmonary tuberculosis may result in lung functional impairment. OBJECTIVE: To evaluate a novel scoring system based on the degree of radiographic abnormalities and related spirometric values in patients with cured pulmonary tuberculosis. METHODS: One hundred and twenty seven patients with cured pulmonary tuberculosis were prospectively enrolled in a referral hospital specializing in respiratory diseases. Spirometry was performed and the extent of radiographic abnormalities was evaluated twice by each of two readers to generate a novel quantitative score. Scoring reproducibility was analyzed by the intra-class correlation coefficient (ICC and the Bland-Altman method. Multiple linear regression models were performed to assess the association of the extent of radiographic abnormalities with spirometric values. RESULTS: The intra-observer agreement for scoring of radiographic abnormalities (SRA showed an ICC of 0.81 (CI:95%, 0.67-0.95 and 0.78 (CI:95%, 0.65-0.92, for reader 1 and 2, respectively. Inter-observer reproducibility for the first measurement was 0.83 (CI:95%, 0.71-0.95, and for the second measurement was 0.74 (CI:95%, 0.58-0.90. The Bland-Altman analysis of the intra-observer agreement showed a mean bias of 0.87% and -0.55% and an inter-observer agreement of -0.35% and -1.78%, indicating a minor average systematic variability. After adjustment for age, gender, height, smoking status, pack-years of smoking, and degree of dyspnea, the scoring degree of radiographic abnormalities was significantly and negatively associated with absolute and percent predicted values of FVC: -0.07 (CI:95%, -0.01 to -0.04; -2.48 (CI:95%, -3.45 to -1.50; and FEV1 -0.07 (CI:95%, -0.10 to -0.05; -2.92 (CI:95%, -3.87 to -1.97 respectively, in the patients studied. CONCLUSION: The extent of radiographic abnormalities, as evaluated through our novel scoring system, was inversely associated with spirometric values

A Novel Scoring System to Measure Radiographic Abnormalities and Related Spirometric Values in Cured Pulmonary Tuberculosis

Science.gov (United States)

Báez-Saldaña, Renata; López-Arteaga, Yesenia; Bizarrón-Muro, Alma; Ferreira-Guerrero, Elizabeth; Ferreyra-Reyes, Leticia; Delgado-Sánchez, Guadalupe; Cruz-Hervert, Luis Pablo; Mongua-Rodríguez, Norma; García-García, Lourdes

2013-01-01

Background Despite chemotherapy, patients with cured pulmonary tuberculosis may result in lung functional impairment. Objective To evaluate a novel scoring system based on the degree of radiographic abnormalities and related spirometric values in patients with cured pulmonary tuberculosis. Methods One hundred and twenty seven patients with cured pulmonary tuberculosis were prospectively enrolled in a referral hospital specializing in respiratory diseases. Spirometry was performed and the extent of radiographic abnormalities was evaluated twice by each of two readers to generate a novel quantitative score. Scoring reproducibility was analyzed by the intra-class correlation coefficient (ICC) and the Bland-Altman method. Multiple linear regression models were performed to assess the association of the extent of radiographic abnormalities with spirometric values. Results The intra-observer agreement for scoring of radiographic abnormalities (SRA) showed an ICC of 0.81 (CI:95%, 0.67–0.95) and 0.78 (CI:95%, 0.65–0.92), for reader 1 and 2, respectively. Inter-observer reproducibility for the first measurement was 0.83 (CI:95%, 0.71–0.95), and for the second measurement was 0.74 (CI:95%, 0.58–0.90). The Bland-Altman analysis of the intra-observer agreement showed a mean bias of 0.87% and -0.55% and an inter-observer agreement of -0.35% and -1.78%, indicating a minor average systematic variability. After adjustment for age, gender, height, smoking status, pack-years of smoking, and degree of dyspnea, the scoring degree of radiographic abnormalities was significantly and negatively associated with absolute and percent predicted values of FVC: -0.07 (CI:95%, -0.01 to -0.04); -2.48 (CI:95%, -3.45 to -1.50); and FEV1 -0.07 (CI:95%, -0.10 to -0.05); -2.92 (CI:95%, -3.87 to -1.97) respectively, in the patients studied. Conclusion The extent of radiographic abnormalities, as evaluated through our novel scoring system, was inversely associated with spirometric values, and

Circulating metabolites and general cognitive ability and dementia: Evidence from 11 cohort studies.

Science.gov (United States)

van der Lee, Sven J; Teunissen, Charlotte E; Pool, René; Shipley, Martin J; Teumer, Alexander; Chouraki, Vincent; Melo van Lent, Debora; Tynkkynen, Juho; Fischer, Krista; Hernesniemi, Jussi; Haller, Toomas; Singh-Manoux, Archana; Verhoeven, Aswin; Willemsen, Gonneke; de Leeuw, Francisca A; Wagner, Holger; van Dongen, Jenny; Hertel, Johannes; Budde, Kathrin; Willems van Dijk, Ko; Weinhold, Leonie; Ikram, M Arfan; Pietzner, Maik; Perola, Markus; Wagner, Michael; Friedrich, Nele; Slagboom, P Eline; Scheltens, Philip; Yang, Qiong; Gertzen, Robert E; Egert, Sarah; Li, Shuo; Hankemeier, Thomas; van Beijsterveldt, Catharina E M; Vasan, Ramachandran S; Maier, Wolfgang; Peeters, Carel F W; Jörgen Grabe, Hans; Ramirez, Alfredo; Seshadri, Sudha; Metspalu, Andres; Kivimäki, Mika; Salomaa, Veikko; Demirkan, Ayşe; Boomsma, Dorret I; van der Flier, Wiesje M; Amin, Najaf; van Duijn, Cornelia M

2018-01-06

Identifying circulating metabolites that are associated with cognition and dementia may improve our understanding of the pathogenesis of dementia and provide crucial readouts for preventive and therapeutic interventions. We studied 299 metabolites in relation to cognition (general cognitive ability) in two discovery cohorts (N total = 5658). Metabolites significantly associated with cognition after adjusting for multiple testing were replicated in four independent cohorts (N total = 6652), and the associations with dementia and Alzheimer's disease (N = 25,872) and lifestyle factors (N = 5168) were examined. We discovered and replicated 15 metabolites associated with cognition including subfractions of high-density lipoprotein, docosahexaenoic acid, ornithine, glutamine, and glycoprotein acetyls. These associations were independent of classical risk factors including high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, and apolipoprotein E (APOE) genotypes. Six of the cognition-associated metabolites were related to the risk of dementia and lifestyle factors. Circulating metabolites were consistently associated with cognition, dementia, and lifestyle factors, opening new avenues for prevention of cognitive decline and dementia. Copyright © 2018 the Alzheimer's Association. All rights reserved.

Co-evolution of secondary metabolite gene clusters and their host

DEFF Research Database (Denmark)

Kjærbølling, Inge; Vesth, Tammi Camilla; Frisvad, Jens Christian

Secondary metabolite gene cluster evolution is mainly driven by two events: gene duplication and annexation and horizontal gene transfer. Here we use comparative genomics of Aspergillus species to investigate the evolution of secondary metabolite (SM) gene clusters across a wide spectrum of speci....... We investigate the dynamic evolutionary relationship between the cluster and the host by examining the genes within the cluster and the number of homologous genes found within the host and in closely related species.......Secondary metabolite gene cluster evolution is mainly driven by two events: gene duplication and annexation and horizontal gene transfer. Here we use comparative genomics of Aspergillus species to investigate the evolution of secondary metabolite (SM) gene clusters across a wide spectrum of species...

Regional cerebral metabolic rate for glucose and cerebrospinal fluid monoamine metabolites in subacute sclerosing panencephalitis

International Nuclear Information System (INIS)

Yanai, Kazuhiko; Miyabayashi, Shigeaki; Iinuma, Kazuie; Tada, Keiya; Fukuda, Hiroshi; Ito, Masatoshi; Matsuzawa, Taiju.

1987-01-01

Regional cerebral metabolic rate for glucose (rCMRglu) and cerebrospinal fluid monoamine metabolites were measured in two cases of subacute sclerosing panencephalitis (SSPE) with different clinical courses. A marked decrease in rCMRglu was found in the cortical gray matter of a patient with rapidly developing SSPE (3.6 - 4.2 mg/100 g brain tissue/min). However, the rCMRglu was preserved in the caudate and lenticular nuclei of the patient (7.7 mg/100 g/min). The rCMRglu in a patient with slowly developing SSPE revealed patterns and values similar to those of the control. Cerebrospinal fluid monoamine metabolites ; homovanilic acid and 5-hydroxyindoleacetic acid, were decreased in both rapidly and slowly developing SSPE. These data indicated that rCMRglu correlated better with the neurological and psychological status and that dopaminergic and serotonergic abnormalities have been implicated in pathophysiology of SSPE. (author)

Developmental social isolation affects adult behavior, social interaction, and dopamine metabolite levels in zebrafish.

Science.gov (United States)

Shams, Soaleha; Amlani, Shahid; Buske, Christine; Chatterjee, Diptendu; Gerlai, Robert

2018-01-01

The zebrafish is a social vertebrate and an excellent translational model for a variety of human disorders. Abnormal social behavior is a hallmark of several human brain disorders. Social behavioral problems can arise as a result of adverse early social environment. Little is known about the effects of early social isolation in adult zebrafish. We compared zebrafish that were isolated for either short (7 days) or long duration (180 days) to socially housed zebrafish, testing their behavior across ontogenesis (ages 10, 30, 60, 90, 120, 180 days), and shoal cohesion and whole-brain monoamines and their metabolites in adulthood. Long social isolation increased locomotion and decreased shoal cohesion and anxiety in the open-field in adult. Additionally, both short and long social isolation reduced dopamine metabolite levels in response to social stimuli. Thus, early social isolation has lasting effects in zebrafish, and may be employed to generate zebrafish models of human neuropsychiatric conditions. © 2017 Wiley Periodicals, Inc.

Engineering Microbial Metabolite Dynamics and Heterogeneity.

Science.gov (United States)

Schmitz, Alexander C; Hartline, Christopher J; Zhang, Fuzhong

2017-10-01

As yields for biological chemical production in microorganisms approach their theoretical maximum, metabolic engineering requires new tools, and approaches for improvements beyond what traditional strategies can achieve. Engineering metabolite dynamics and metabolite heterogeneity is necessary to achieve further improvements in product titers, productivities, and yields. Metabolite dynamics, the ensemble change in metabolite concentration over time, arise from the need for microbes to adapt their metabolism in response to the extracellular environment and are important for controlling growth and productivity in industrial fermentations. Metabolite heterogeneity, the cell-to-cell variation in a metabolite concentration in an isoclonal population, has a significant impact on ensemble productivity. Recent advances in single cell analysis enable a more complete understanding of the processes driving metabolite heterogeneity and reveal metabolic engineering targets. The authors present an overview of the mechanistic origins of metabolite dynamics and heterogeneity, why they are important, their potential effects in chemical production processes, and tools and strategies for engineering metabolite dynamics and heterogeneity. The authors emphasize that the ability to control metabolite dynamics and heterogeneity will bring new avenues of engineering to increase productivity of microbial strains. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Methodological considerations for measuring glucocorticoid metabolites in feathers

Science.gov (United States)

Berk, Sara A.; McGettrick, Julie R.; Hansen, Warren K.; Breuner, Creagh W.

2016-01-01

In recent years, researchers have begun to use corticosteroid metabolites in feathers (fCORT) as a metric of stress physiology in birds. However, there remain substantial questions about how to measure fCORT most accurately. Notably, small samples contain artificially high amounts of fCORT per millimetre of feather (the small sample artefact). Furthermore, it appears that fCORT is correlated with circulating plasma corticosterone only when levels are artificially elevated by the use of corticosterone implants. Here, we used several approaches to address current methodological issues with the measurement of fCORT. First, we verified that the small sample artefact exists across species and feather types. Second, we attempted to correct for this effect by increasing the amount of methanol relative to the amount of feather during extraction. We consistently detected more fCORT per millimetre or per milligram of feather in small samples than in large samples even when we adjusted methanol:feather concentrations. We also used high-performance liquid chromatography to identify hormone metabolites present in feathers and measured the reactivity of these metabolites against the most commonly used antibody for measuring fCORT. We verified that our antibody is mainly identifying corticosterone (CORT) in feathers, but other metabolites have significant cross-reactivity. Lastly, we measured faecal glucocorticoid metabolites in house sparrows and correlated these measurements with corticosteroid metabolites deposited in concurrently grown feathers; we found no correlation between faecal glucocorticoid metabolites and fCORT. We suggest that researchers should be cautious in their interpretation of fCORT in wild birds and should seek alternative validation methods to examine species-specific relationships between environmental challenges and fCORT. PMID:27335650

Sensorimotor integration and psychopathology: motor control abnormalities related to psychiatric disorders.

Science.gov (United States)

Velasques, Bruna; Machado, Sergio; Paes, Flávia; Cunha, Marlo; Sanfim, Antonio; Budde, Henning; Cagy, Mauricio; Anghinah, Renato; Basile, Luis F; Piedade, Roberto; Ribeiro, Pedro

2011-12-01

Recent evidence is reviewed to examine relationships among sensorimotor and cognitive aspects in some important psychiatry disorders. This study reviews the theoretical models in the context of sensorimotor integration and the abnormalities reported in the most common psychiatric disorders, such as Alzheimer's disease, autism spectrum disorder and squizophrenia. The bibliographical search used Pubmed/Medline, ISI Web of Knowledge, Cochrane data base and Scielo databases. The terms chosen for the search were: Alzheimer's disease, AD, autism spectrum disorder, and Squizophrenia in combination with sensorimotor integration. Fifty articles published in English and were selected conducted from 1989 up to 2010. We found that the sensorimotor integration process plays a relevant role in elementary mechanisms involved in occurrence of abnormalities in most common psychiatric disorders, participating in the acquisition of abilities that have as critical factor the coupling of different sensory data which will constitute the basis of elaboration of consciously goal-directed motor outputs. Whether these disorders are associated with an abnormal peripheral sensory input or defective central processing is still unclear, but some studies support a central mechanism. Sensorimotor integration seems to play a significant role in the disturbances of motor control, like deficits in the feedforward mechanism, typically seen in AD, autistic and squizophrenic patients.

Age-related and 224Ra-induced abnormalities in the teeth of male mice

International Nuclear Information System (INIS)

Humphreys, E.R.; Stones, V.A.

1985-01-01

A high incidence of incisor abnormalities was found in aged control and aged 224 Ra-treated male CBA mice. Visual examination of the abnormalities in both controls and treated mice revealed extreme shortening of the upper incisors and hypoplastic, grooved or undulating enamel. The administration of 865 or 1730 nCi of 224 Ra hastened the onset of incisor abnormalities although no specific feature was attributable solely to radium toxicity. Radiography and histology revealed corrugated incisors, obliteration of the pulp cavity, extension and disorganized growth of incisors basally, secondary incisors, open pulp and fractures within the alveoli. There was a statistically-significant reduction in the number of molars present in animals given 432, 865 or 1730 nCi 224 Ra. (author)

Syringomyelia and Craniocervical Junction Abnormalities in Chihuahuas.

Science.gov (United States)

Kiviranta, A-M; Rusbridge, C; Laitinen-Vapaavuori, O; Hielm-Björkman, A; Lappalainen, A K; Knowler, S P; Jokinen, T S

2017-11-01

Chiari-like malformation (CM) and syringomyelia (SM) are widely reported in Cavalier King Charles Spaniels and Griffon Bruxellois dogs. Increasing evidence indicates that CM and SM also occur in other small and toy breed dogs, such as Chihuahuas. To describe the presence of SM and craniocervical junction (CCJ) abnormalities in Chihuahuas and to evaluate the possible association of CCJ abnormalities with SM. To describe CM/SM-related clinical signs and neurologic deficits and to investigate the association of CM/SM-related clinical signs with signalment, SM, or CCJ abnormalities. Fifty-three client-owned Chihuahuas. Prospective study. Questionnaire analyses and physical and neurologic examinations were obtained before magnetic resonance and computed tomography imaging. Images were evaluated for the presence of SM, CM, and atlantooccipital overlapping. Additionally, medullary kinking, dorsal spinal cord compression, and their sum indices were calculated. Scratching was the most common CM/SM-related clinical sign and decreased postural reaction the most common neurologic deficit in 73 and 87% of dogs, respectively. Chiari-like malformation and SM were present in 100 and 38% of dogs, respectively. Syringomyelia was associated with the presence of CM/SM-related clinical signs (P = 0.034), and medullary kinking and sum indices were higher in dogs with clinical signs (P = 0.016 and P = 0.007, respectively). Syringomyelia and CCJ abnormalities are prevalent in Chihuahuas. Syringomyelia was an important factor for the presence of CM/SM-related clinical signs, but many dogs suffered from similar clinical signs without being affected by SM, highlighting the clinical importance of CCJ abnormalities in Chihuahuas. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Caffeine metabolites not caffeine protect against riboflavin photosensitized oxidative damage related to skin and eye health

DEFF Research Database (Denmark)

Scurachio, R. S.; Mattiucci, F.; Santos, W. G.

2016-01-01

. Caffeine metabolites rather than caffeine seem accordingly important for the observed protective effect against cutaneous melanoma identified for drinkers of regular but not of decaffeinated coffee. The caffeine metabolites, but not caffeine, were by time resolved single photon counting found to quench...... singlet excited riboflavin through exothermic formation of ground-state precursor complexes indicating importance of hydrogen bounding through keto-enol tautomer's for protection of oxidizable substrates and sensitive structures against riboflavin photosensitization....

Abnormal imaging findings of the breast related to hormone replacement therapy: analysis of surgically excised cases

Energy Technology Data Exchange (ETDEWEB)

Moon, Woo Kyung; Cha, Joo Hee; Cho, Kyung Soo; Choi, Een Wan; Lee, Yu Jin; Im, Jung Gi [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of); Kim, Hyung Seok [Wooridul Spine Hospital, Seoul (Korea, Republic of); Chung, Sun Yang [Bundang CHA General Hospital, Sungnam (Korea, Republic of); Cho, Nariya [Gil Medical Center, Incheon (Korea, Republic of)

2004-02-01

To correlate the mammographic and ultrasonographic findings with the pathologic results in women undergoing hormone replacement therapy (HRT), and to determine the characteristic clinical, mammographic or histologic findings of breast cancer in these patients. Twenty-five breast lesions in 25 patients aged 44-65 (mean, 55.5) years undergoing HRT were surgically removed due to abnormal mammographic findings or the presence of palpable masses. Mammograms in all patients and ultrasonograms in 23 were retrospectively analyzed in terms of the shape and margin of the mass, and microcalcifications, and the imaging findings were correlated with the pathologic results. As a control group, 45 cancer patients not undergoing HRT were selected. Using the student t test, detection methods, tumor size, mammographic findings, and the proportion of intraductal cancers were compared between to two groups. Surgical excision revealed ten benign lesions (four fibroadenomas and six cases of fibrocystic change) and 15 cancers (three intraductal and twelve invasive ductal cancers). Abnormal findings at mammography were a mass in 16 cases, clustered microcalcifications in seven, and a mass with microcalcifications in two. Mammography showed that all four circumscribed masses were benign. Five of seven ill-defined masses (71%) and all six spiculated masses were malignant. Three of seven cases (43%) with microcalcifications, and both with a mass and microcalcification, were malignant. In two cases in which ultrasonography revealed cystic lesions, histologic examination showed that fibrocystic change had occurred. Compared to non-HRT-related cancers, HRT-related cancers were more often detected by mammography (60% vs 16%; p<0.001), smaller (17 mm vs 24 mm, p<0.01), showed microcalcification only (20% vs 13%; p<0.05), and were intraductal (20% vs 7%; p<0.01). In patients with HRT, mammographic findings of an ill-defined or spiculated mass, or one with microcalcifications, were associated with

Abnormal imaging findings of the breast related to hormone replacement therapy: analysis of surgically excised cases

International Nuclear Information System (INIS)

Moon, Woo Kyung; Cha, Joo Hee; Cho, Kyung Soo; Choi, Een Wan; Lee, Yu Jin; Im, Jung Gi; Kim, Hyung Seok; Chung, Sun Yang; Cho, Nariya

2004-01-01

To correlate the mammographic and ultrasonographic findings with the pathologic results in women undergoing hormone replacement therapy (HRT), and to determine the characteristic clinical, mammographic or histologic findings of breast cancer in these patients. Twenty-five breast lesions in 25 patients aged 44-65 (mean, 55.5) years undergoing HRT were surgically removed due to abnormal mammographic findings or the presence of palpable masses. Mammograms in all patients and ultrasonograms in 23 were retrospectively analyzed in terms of the shape and margin of the mass, and microcalcifications, and the imaging findings were correlated with the pathologic results. As a control group, 45 cancer patients not undergoing HRT were selected. Using the student t test, detection methods, tumor size, mammographic findings, and the proportion of intraductal cancers were compared between to two groups. Surgical excision revealed ten benign lesions (four fibroadenomas and six cases of fibrocystic change) and 15 cancers (three intraductal and twelve invasive ductal cancers). Abnormal findings at mammography were a mass in 16 cases, clustered microcalcifications in seven, and a mass with microcalcifications in two. Mammography showed that all four circumscribed masses were benign. Five of seven ill-defined masses (71%) and all six spiculated masses were malignant. Three of seven cases (43%) with microcalcifications, and both with a mass and microcalcification, were malignant. In two cases in which ultrasonography revealed cystic lesions, histologic examination showed that fibrocystic change had occurred. Compared to non-HRT-related cancers, HRT-related cancers were more often detected by mammography (60% vs 16%; p<0.001), smaller (17 mm vs 24 mm, p<0.01), showed microcalcification only (20% vs 13%; p<0.05), and were intraductal (20% vs 7%; p<0.01). In patients with HRT, mammographic findings of an ill-defined or spiculated mass, or one with microcalcifications, were associated with

Nuclear abnormalities in cells from nasal epithelium: a promising assay to evaluate DNA damage related to air pollution in infants

Directory of Open Access Journals (Sweden)

Michelle Mergener

2014-12-01

Full Text Available OBJECTIVES: This study intends to provide a quick, easy, and inexpensive way to assess nuclear abnormalities such as micronuclei and bud frequencies; binucleated, karyorrhectic, karyolytic, pycnotic, and condensed chromatin cells in nasal scrapings of infants, which are particularly important for conducting genotoxic studies related to the inhaled atmosphere in pediatric populations. METHODS: Nasal swab samples were collected from 40 infants under 12 months of age using a small cytobrush. 2,000 cells from each infant sample were analyzed and classified according to the frequency of nuclear abnormalities. RESULTS: Rates of nuclear abnormalities found agree with values reported in other studies of neonates and children. This study found 0.13% of cells with micronuclei; 1.20% karyorrhexis; 0.03% pyknosis; 10.85% karyolysis; 1.11% condensed chromatin; 0.54 binucleated cells; and 0.02% nuclear bud. Differences were not observed between genders or environmental passive smoking, nor was any age correlation found. CONCLUSION: The assay proposed here is suitable for assessing the frequency of nuclear abnormalities from nasal cells in infants.

Metabolite Profiling of Red Sea Corals

KAUST Repository

Ortega, Jovhana Alejandra

2016-12-01

Looking at the metabolite profile of an organism provides insights into the metabolomic state of a cell and hence also into pathways employed. Little is known about the metabolites produced by corals and their algal symbionts. In particular, corals from the central Red Sea are understudied, but interesting study objects, as they live in one of the warmest and most saline environments and can provide clues as to the adjustment of corals to environmental change. In this study, we applied gas chromatography – mass spectrometry (GC–MS) metabolite profiling to analyze the metabolic profile of four coral species and their associated symbionts: Fungia granulosa, Acropora hemprichii, Porites lutea, and Pocillopora verrucosa. We identified and quantified 102 compounds among primary and secondary metabolites across all samples. F. granulosa and its symbiont showed a total of 59 metabolites which were similar to the 51 displayed by P. verrucosa. P. lutea and A. hemprichii both harbored 40 compounds in conjunction with their respective isolated algae. Comparing across species, 28 metabolites were exclusively present in algae, while 38 were exclusive to corals. A principal component and cluster analyses revealed that metabolite profiles clustered between corals and algae, but each species harbored a distinct catalog of metabolites. The major classes of compounds were carbohydrates and amino acids. Taken together, this study provides a first description of metabolites of Red Sea corals and their associated symbionts. As expected, the metabolites of coral hosts differ from their algal symbionts, but each host and algal species harbor a unique set of metabolites. This corroborates that host-symbiont species pairs display a fine-tuned complementary metabolism that provide insights into the specific nature of the symbiosis. Our analysis also revealed aquatic pollutants, which suggests that metabolite profiling might be used for monitoring pollution levels and assessing

Fetal exposure to PCBs and their hydroxylated metabolites in a Dutch cohort

NARCIS (Netherlands)

Soechitram, S.D.; Athanasiadou, M.; Hovander, L.; Bergman, A.; Sauer, P. J. J.

2004-01-01

Polychlorinated biphenyls (PCBs) are still the most abundant pollutants in wildlife and humans. Hydroxylated PCB metabolites (OH-PCBs) are known to be formed in humans and wildlife. Studies in animals show that these metabolites cause endocrine-related toxicity. The health effects in humans have not

Perturbational Profiling of Metabolites in Patient Fibroblasts Implicates α-Aminoadipate as a Potential Biomarker for Bipolar Disorder

Science.gov (United States)

Huang, Joanne H.; Berkovitch, Shaunna S.; Iaconelli, Jonathan; Watmuff, Bradley; Park, Hyoungjun; Chattopadhyay, Shrikanta; McPhie, Donna; Öngür, Dost; Cohen, Bruce M.; Clish, Clary B.; Karmacharya, Rakesh

2016-01-01

Many studies suggest the presence of aberrations in cellular metabolism in bipolar disorder. We studied the metabolome in bipolar disorder to gain insight into cellular pathways that may be dysregulated in bipolar disorder and to discover evidence of novel biomarkers. We measured polar and nonpolar metabolites in fibroblasts from subjects with bipolar I disorder and matched healthy control subjects, under normal conditions and with two physiologic perturbations: low-glucose media and exposure to the stress-mediating hormone dexamethasone. Metabolites that were significantly different between bipolar and control subjects showed distinct separation by principal components analysis methods. The most statistically significant findings were observed in the perturbation experiments. The metabolite with the lowest p value in both the low-glucose and dexamethasone experiments was α-aminoadipate, whose intracellular level was consistently lower in bipolar subjects. Our study implicates α-aminoadipate as a possible biomarker in bipolar disorder that manifests under cellular stress. This is an intriguing finding given the known role of α-aminoadipate in the modulation of kynurenic acid in the brain, especially as abnormal kynurenic acid levels have been implicated in bipolar disorder. PMID:27606323

Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities induced by brain-disease-related genetic risk factors

Science.gov (United States)

Haziza, Simon; Mohan, Nitin; Loe-Mie, Yann; Lepagnol-Bestel, Aude-Marie; Massou, Sophie; Adam, Marie-Pierre; Le, Xuan Loc; Viard, Julia; Plancon, Christine; Daudin, Rachel; Koebel, Pascale; Dorard, Emilie; Rose, Christiane; Hsieh, Feng-Jen; Wu, Chih-Che; Potier, Brigitte; Herault, Yann; Sala, Carlo; Corvin, Aiden; Allinquant, Bernadette; Chang, Huan-Cheng; Treussart, François; Simonneau, Michel

2017-05-01

Brain diseases such as autism and Alzheimer's disease (each inflicting >1% of the world population) involve a large network of genes displaying subtle changes in their expression. Abnormalities in intraneuronal transport have been linked to genetic risk factors found in patients, suggesting the relevance of measuring this key biological process. However, current techniques are not sensitive enough to detect minor abnormalities. Here we report a sensitive method to measure the changes in intraneuronal transport induced by brain-disease-related genetic risk factors using fluorescent nanodiamonds (FNDs). We show that the high brightness, photostability and absence of cytotoxicity allow FNDs to be tracked inside the branches of dissociated neurons with a spatial resolution of 12 nm and a temporal resolution of 50 ms. As proof of principle, we applied the FND tracking assay on two transgenic mouse lines that mimic the slight changes in protein concentration (∼30%) found in the brains of patients. In both cases, we show that the FND assay is sufficiently sensitive to detect these changes.

Secondary metabolites from marine microorganisms.

Science.gov (United States)

Kelecom, Alphonse

2002-03-01

After 40 years of intensive research, chemistry of marine natural products has become a mature field. Since 1995, there are signals of decreased interest in the search of new metabolites from traditional sources such as macroalgae and octocorals, and the number of annual reports on marine sponges stabilized. On the contrary, metabolites from microorganisms is a rapidly growing field, due, at least in part, to the suspicion that a number of metabolites obtained from algae and invertebrates may be produced by associated microorganisms. Studies are concerned with bacteria and fungi, isolated from seawater, sediments, algae, fish and mainly from marine invertebrates such as sponges, mollusks, tunicates, coelenterates and crustaceans. Although it is still to early to define tendencies, it may be stated that the metabolites from microorganisms are in most cases quite different from those produced by the invertebrate hosts. Nitrogenated metabolites predominate over acetate derivatives, and terpenes are uncommon. Among the latter, sesquiterpenes, diterpenes and carotenes have been isolated; among nitrogenated metabolites, amides, cyclic peptides and indole alkaloids predominate.

Secondary metabolites from marine microorganisms

Directory of Open Access Journals (Sweden)

KELECOM ALPHONSE

2002-01-01

Full Text Available After 40 years of intensive research, chemistry of marine natural products has become a mature field. Since 1995, there are signals of decreased interest in the search of new metabolites from traditional sources such as macroalgae and octocorals, and the number of annual reports on marine sponges stabilized. On the contrary, metabolites from microorganisms is a rapidly growing field, due, at least in part, to the suspicion that a number of metabolites obtained from algae and invertebrates may be produced by associated microorganisms. Studies are concerned with bacteria and fungi, isolated from seawater, sediments, algae, fish and mainly from marine invertebrates such as sponges, mollusks, tunicates, coelenterates and crustaceans. Although it is still to early to define tendencies, it may be stated that the metabolites from microorganisms are in most cases quite different from those produced by the invertebrate hosts. Nitrogenated metabolites predominate over acetate derivatives, and terpenes are uncommon. Among the latter, sesquiterpenes, diterpenes and carotenes have been isolated; among nitrogenated metabolites, amides, cyclic peptides and indole alkaloids predominate.

Prognostic value of proton magnetic resonance spectroscopy findings in near drowning patients: reversibility of the early metabolite abnormalities relates with a good outcome Valor prognóstico da espectroscopia de prótons em vítimas de quase-afogamento: reversibilidade das anormalidades metabólicas precoces relacionou-se com bom prognóstico

Directory of Open Access Journals (Sweden)

Maria de Fátima Vasco Aragão

2009-03-01

Full Text Available In two children with near drowning hypoxic encephalopathy and normal-appearing structural MRI, acute proton magnetic resonance spectroscopy (¹H MRS showed biochemical alterations that correctly indicated prognosis and helped to guide management decisions. Elevation of the lipid-lactate and glutamine-glutamate peaks, on the early (72 hour ¹H MRS, predicts a poor prognosis. Absence of lipid-lactate and glutamine-glutamate peaks on the early ¹H MRS and reversibility of early mild metabolite abnormalities on follow up examination relates with good outcome.Em duas criancas vítimas de quase-afogamento com encefalopatia hipóxico-isquêmica, que apresentaram ressonância magnética por imagem normal, a espectroscopia de prótons por ressonância magnética (¹H MRS na fase aguda mostrou alterações bioquímicas que corretamente indicaram o prognóstico e ajudaram a guiar o manejo terapêutico. Elevação dos picos de lipídeo-lactato e glutamina-glutamato na ¹H MRS precoce realizada com 72 horas previu um mau prognóstico. Relacionaram-se com bom prognóstico; a ausência dos picos de lipídeo-lactato e glutamina-glutamato na ¹H MRS precoce, e a reversibilidade no exame de controle (3 meses das discretas anormalidades metabólicas encontradas no primeiro exame.

[Research of gestrinone-related abnormal uterine bleeding and the intervention in the treatment: a multi-center, randomized, controlled clinical trial].

Science.gov (United States)

Duan, H; Wang, S; Hao, M; Chen, L; Tang, J; Wang, X; Peng, Y Z; Zhang, S C; Cao, L R; Yu, J J

2016-02-01

To investigate the incidence, influencing factors and intervention of gestrinone-related abnormal uterine bleeding at different dosage of gestrinone in the clinical treatment. This was a multicenter, randomized, control study of 195 Chinese women with endometriosis or adenomyosis from June 2011 to November 2013. The subjects were randomized into three groups with oral administration of gestrinone, 2.5 mg dose at one time; twice a week group: 67 cases with oral administration twice a week last three months; double dose first month group: 67 cases with oral administration triple times a week at first month, then twice a week for two months; three times a week group: 61 cases with oral administration three times a week last three months. The improvement of the abnormal uterine bleeding, the changes in estrogen, liver function and blood coagulation were evaluated. At the same time, B-ultrasound examination evaluation were performed. (1) Three months later, the incidence of abnormal uterine bleeding in twice a week group was 30% (20/67), in double dose first month group and three times a week group were 7%(5/67) and 16% (10/61) respectively, there were significant difference between three groups (Pabnormal uterine bleeding (OR=0.461,P= 0.003;OR=0.303,P=0.016); logistic regression analysis demonstrated that the risk of abnormal uterine bleeding in double dose first month group was the lowest when compared with twice a week group and three times a week group, the risk in twice a week group was 5-fold higher than that in double dose first month group (OR=0.211,P=0.011). The incidence of abnormal uterine bleeding in participants with abnormal ovarian volume results from ovarian cyst or ovarian surgery was significantly lower than those with normal ovarian volume (OR=0.304,P=0.018). (3) After the treatment of three months, there were no significant difference in alanine transaminase level between the groups (P>0.05). The body mass index significantly increased in three group

High-performance liquid chromatography and inductively coupled plasma mass spectrometry (HPLC-ICP-MS) for the analysis of xenobiotic metabolites in rat urine: application to the metabolites of 4-bromoaniline.

Science.gov (United States)

Nicholson, J K; Lindon, J C; Scarfe, G; Wilson, I D; Abou-Shakra, F; Castro-Perez, J; Eaton, A; Preece, S

2000-02-01

The use of HPLC-ICP-MS for the profiling and quantification of the metabolites of 4-bromoaniline following reversed-phase gradient chromatography is demonstrated. In the 0-8 h post dose sample, which contained the highest concentrations of compound-related material, it was possible to detect at least 16 metabolites of the compound. The methodology described offers the possibility of obtaining metabolite profiles and quantification for drugs and other xenobiotics in biological fluids and excreta without the requirement for radiolabelled tracers.

[Effect of electro-acupuncture on metabolites in the cerebral cortex of ulcerative colitis rats based on Pi/Wei-brain related theory].

Science.gov (United States)

Yang, Yang; Zhao, Ji-lan; Hou, Tian-shu; Han, Xiao-xia; Zhao, Zheng-yu; Peng, Xiao-hua; Wu, Qiao-Feng

2014-10-01

To study the effect of electro-acupuncture (EA) at points along Foot Yangming Channel on metabolite of ulcerative colitis (UC) rats' cerebral cortex and to identify key metabolites by referring to Pi/Wei-brain related theory in Chinese medicine (CM). The UC rat model was set up by dextran sulfate sodium (DSS) method. Male SD rats were randomly divided into the model group and the EA group, 13 in each group. Another 13 rats were recruited as the blank control group. Rats in the blank control group and the model group received no EA. EA was performed at Zusanli (ST36), Shangjuxu (ST37), and Tianshu (ST25) for 5 days by using disperse-dense wave. Then all rats were sacrificed. Their recto-colon and the ileocecal junction were pathomorphologically observed by light microscope and transmission electron microscope (TEM). Cerebral cortexes were extracted. Water-soluble and lipid-soluble brain tissue metabolites were respectively extracted for metabolic research using 1H nuclear magnetic resonance (1H-NMR). EA could obviously improve the general condition of UC model rats, decrease the value of DAI, reduce the infiltration of inflammatory cells in the intestinal tract, stabilize structures such as mitochondria, endoplasmic reticulum and so on (P theory.

An integrated scheme for the simultaneous determination of biogenic amines, precursor amino acids, and related metabolites by liquid chromatography with electrochemical detection.

Science.gov (United States)

Oka, K; Kojima, K; Togari, A; Nagatsu, T; Kiss, B

1984-06-08

A new method using high-performance liquid chromatography with electrochemical detection (HPLC-ED) for the simultaneous determination of monoamines, their precursor amino acids, and related major metabolites in small samples of brain tissue weighing from 0.5 to 50 mg is described. The method is based on the preliminary isolation of monoamines (dopamine, norepinephrine, epinephrine, and serotonin), their precursor amino acids (tyrosine, 3,4-dihydroxyphenylalanine, tryptophan and 5-hydroxytryptophan), and their major metabolites (3-methoxytyramine, normetanephrine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, vanillylmandelic acid, 3-methoxy-4-hydroxyphenylethyleneglycol, and 5-hydroxyindoleacetic acid) by chromatography on small columns of Amberlite CG-50 and Dowex 50W, and by ethyl acetate extraction. All the compounds in the four isolated fractions were measured by HPLC-ED on a reversed-phase column under four different conditions. The sensitivity was from 0.1 to 40 pmol, depending on the substances analysed. This newly established method was applied to the study of the effects of an aromatic L-amino acid decarboxylase inhibitor (NSD-1015) and a monoamine oxidase inhibitor (pargyline) on the levels of monoamines, their precursor amino acids and their major metabolites in brain regions of mice.

Integrating Multiple Analytical Datasets to Compare Metabolite Profiles of Mouse Colonic-Cecal Contents and Feces.

Science.gov (United States)

Zeng, Huawei; Grapov, Dmitry; Jackson, Matthew I; Fahrmann, Johannes; Fiehn, Oliver; Combs, Gerald F

2015-09-11

The pattern of metabolites produced by the gut microbiome comprises a phenotype indicative of the means by which that microbiome affects the gut. We characterized that phenotype in mice by conducting metabolomic analyses of the colonic-cecal contents, comparing that to the metabolite patterns of feces in order to determine the suitability of fecal specimens as proxies for assessing the metabolic impact of the gut microbiome. We detected a total of 270 low molecular weight metabolites in colonic-cecal contents and feces by gas chromatograph, time-of-flight mass spectrometry (GC-TOF) and ultra-high performance liquid chromatography, quadrapole time-of-flight mass spectrometry (UPLC-Q-TOF). Of that number, 251 (93%) were present in both types of specimen, representing almost all known biochemical pathways related to the amino acid, carbohydrate, energy, lipid, membrane transport, nucleotide, genetic information processing, and cancer-related metabolism. A total of 115 metabolites differed significantly in relative abundance between both colonic-cecal contents and feces. These data comprise the first characterization of relationships among metabolites present in the colonic-cecal contents and feces in a healthy mouse model, and shows that feces can be a useful proxy for assessing the pattern of metabolites to which the colonic mucosum is exposed.

Integrating Multiple Analytical Datasets to Compare Metabolite Profiles of Mouse Colonic-Cecal Contents and Feces

Directory of Open Access Journals (Sweden)

Huawei Zeng

2015-09-01

Full Text Available The pattern of metabolites produced by the gut microbiome comprises a phenotype indicative of the means by which that microbiome affects the gut. We characterized that phenotype in mice by conducting metabolomic analyses of the colonic-cecal contents, comparing that to the metabolite patterns of feces in order to determine the suitability of fecal specimens as proxies for assessing the metabolic impact of the gut microbiome. We detected a total of 270 low molecular weight metabolites in colonic-cecal contents and feces by gas chromatograph, time-of-flight mass spectrometry (GC-TOF and ultra-high performance liquid chromatography, quadrapole time-of-flight mass spectrometry (UPLC-Q-TOF. Of that number, 251 (93% were present in both types of specimen, representing almost all known biochemical pathways related to the amino acid, carbohydrate, energy, lipid, membrane transport, nucleotide, genetic information processing, and cancer-related metabolism. A total of 115 metabolites differed significantly in relative abundance between both colonic-cecal contents and feces. These data comprise the first characterization of relationships among metabolites present in the colonic-cecal contents and feces in a healthy mouse model, and shows that feces can be a useful proxy for assessing the pattern of metabolites to which the colonic mucosum is exposed.

Exploring traditional aus-type rice for metabolites conferring drought tolerance.

Science.gov (United States)

Casartelli, Alberto; Riewe, David; Hubberten, Hans Michael; Altmann, Thomas; Hoefgen, Rainer; Heuer, Sigrid

2018-01-25

Traditional varieties and landraces belonging to the aus-type group of rice (Oryza sativa L.) are known to be highly tolerant to environmental stresses, such as drought and heat, and are therefore recognized as a valuable genetic resource for crop improvement. Using two aus-type (Dular, N22) and two drought intolerant irrigated varieties (IR64, IR74) an untargeted metabolomics analysis was conducted to identify drought-responsive metabolites associated with tolerance. The superior drought tolerance of Dular and N22 compared with the irrigated varieties was confirmed by phenotyping plants grown to maturity after imposing severe drought stress in a dry-down treatment. Dular and N22 did not show a significant reduction in grain yield compared to well-watered control plants, whereas the intolerant varieties showed a significant reduction in both, total spikelet number and grain yield. The metabolomics analysis was conducted with shoot and root samples of plants at the tillering stage at the end of the dry-down treatment. The data revealed an overall higher accumulation of N-rich metabolites (amino acids and nucleotide-related metabolites allantoin and uridine) in shoots of the tolerant varieties. In roots, the aus-type varieties were characterised by a higher reduction of metabolites representative of glycolysis and the TCA cycle, such as malate, glyceric acid and glyceric acid-3-phosphate. On the other hand, the oligosaccharide raffinose showed a higher fold increase in both, shoots and roots of the sensitive genotypes. The data further showed that, for certain drought-responsive metabolites, differences between the contrasting rice varieties were already evident under well-watered control conditions. The drought tolerance-related metabolites identified in the aus-type varieties provide a valuable set of protective compounds and an entry point for assessing genetic diversity in the underlying pathways for developing drought tolerant rice and other crops.

Transportable hyperpolarized metabolites

Science.gov (United States)

Ji, Xiao; Bornet, Aurélien; Vuichoud, Basile; Milani, Jonas; Gajan, David; Rossini, Aaron J.; Emsley, Lyndon; Bodenhausen, Geoffrey; Jannin, Sami

2017-01-01

Nuclear spin hyperpolarization of 13C-labelled metabolites by dissolution dynamic nuclear polarization can enhance the NMR signals of metabolites by several orders of magnitude, which has enabled in vivo metabolic imaging by MRI. However, because of the short lifetime of the hyperpolarized magnetization (typically <1 min), the polarization process must be carried out close to the point of use. Here we introduce a concept that markedly extends hyperpolarization lifetimes and enables the transportation of hyperpolarized metabolites. The hyperpolarized sample can thus be removed from the polarizer and stored or transported for use at remote MRI or NMR sites. We show that hyperpolarization in alanine and glycine survives 16 h storage and transport, maintaining overall polarization enhancements of up to three orders of magnitude. PMID:28072398

Biomarker discovery in biological specimens (plasma, hair, liver and kidney) of diabetic mice based upon metabolite profiling using ultra-performance liquid chromatography with electrospray ionization time-of-flight mass spectrometry.

Science.gov (United States)

Tsutsui, Haruhito; Maeda, Toshio; Min, Jun Zhe; Inagaki, Shinsuke; Higashi, Tatsuya; Kagawa, Yoshiyuki; Toyo'oka, Toshimasa

2011-05-12

the chromatograms. N-acetyl-L-leucine is an endogenous compound included in all biological specimens (plasma, hair, liver and kidney). Therefore, this metabolite appears to be a potential biomarker candidate related to diabetes. Although the structures of other biomarker candidates have still not yet determined, the present approach based upon a metabolite profiling study using UPLC-ESI-TOF-MS could be helpful for understanding the abnormal state of various diseases. Copyright © 2010 Elsevier B.V. All rights reserved.

Microsomal metabolism of trenbolone acetate metabolites ...

Science.gov (United States)

Trenbolone acetate (TBA) is a synthetic growth promoter widely used in animal agriculture, and its metabolites are suspected endocrine disrupting compounds in agriculturally impacted receiving waters. However, beyond the three widely recognized TBA metabolites (17-trenbolone, 17-trenbolone and trendione), little is known about other metabolites formed in vivo and subsequently discharged into the environment, with some evidence suggesting these unknown metabolites comprise a majority of the TBA mass dosed to the animal. Here, we explored the metabolism of the three known TBA metabolites using rat liver microsome studies. All TBA metabolites are transformed into a complex mixture of monohydroxylated products. Based on product characterization, the majority are more polar than the parent metabolites but maintain their characteristic trienone backbone. A minor degree of interconversion between known metabolites was also observed, as were higher order hydroxylated products with a greater extent of reaction. Notably, the distribution and yield of products were generally comparable across a series of variably induced rat liver microsomes, as well as during additional studies with human and bovine liver microsomes. Bioassays conducted with mixtures of these transformation products suggest that androgen receptor (AR) binding activity is diminished as a result of the microsomal treatment, suggesting that the transformation products are generally less potent than

Effect of competition on the production and activity of secondary metabolites in Aspergillus species

DEFF Research Database (Denmark)

Losada, L.; Ajayi, O.; Frisvad, Jens Christian

2009-01-01

and in the presence of other fungal species. However, it is not known whether secreted secondary metabolites provide a competitive advantage over other fungal species, or whether competition has any effect on the production of those metabolites. Here, we have performed co-cultivation competition assays among......Secondary metabolites are of intense interest to humans due to their pharmaceutical and/or toxic properties. Also, these metabolites are clinically relevant because of their importance in fungal pathogenesis. Aspergillus species secrete secondary metabolites when grown individually...... different species of Aspergillus to determine relative species fitness in culture, and to analyze the presence of possible antifungal activity of secondary metabolites in extracts. The results show that, for the most part, at 30C only one species is able to survive direct competition with a second species...

Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

Science.gov (United States)

Fernald, Charles D.

1980-01-01

Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

Global Prioritization of Disease Candidate Metabolites Based on a Multi-omics Composite Network

Science.gov (United States)

Yao, Qianlan; Xu, Yanjun; Yang, Haixiu; Shang, Desi; Zhang, Chunlong; Zhang, Yunpeng; Sun, Zeguo; Shi, Xinrui; Feng, Li; Han, Junwei; Su, Fei; Li, Chunquan; Li, Xia

2015-01-01

The identification of disease-related metabolites is important for a better understanding of metabolite pathological processes in order to improve human medicine. Metabolites, which are the terminal products of cellular regulatory process, can be affected by multi-omic processes. In this work, we propose a powerful method, MetPriCNet, to predict and prioritize disease candidate metabolites based on integrated multi-omics information. MetPriCNet prioritized candidate metabolites based on their global distance similarity with seed nodes in a composite network, which integrated multi-omics information from the genome, phenome, metabolome and interactome. After performing cross-validation on 87 phenotypes with a total of 602 metabolites, MetPriCNet achieved a high AUC value of up to 0.918. We also assessed the performance of MetPriCNet on 18 disease classes and found that 4 disease classes achieved an AUC value over 0.95. Notably, MetPriCNet can also predict disease metabolites without known disease metabolite knowledge. Some new high-risk metabolites of breast cancer were predicted, although there is a lack of known disease metabolite information. A predicted disease metabolic landscape was constructed and analyzed based on the results of MetPriCNet for 87 phenotypes to help us understand the genetic and metabolic mechanism of disease from a global view. PMID:26598063

Myocardial metabolic abnormalities in hypertrophic cardiomyopathy assessed by iodine-123-labeled beta-methyl-branched fatty acid myocardial scintigraphy and its relation to exercise-induced ischemia

International Nuclear Information System (INIS)

Matsuo, Shinro; Nakamura, Yasuyuki; Takahashi, Masayuki; Mitsunami, Kenichi; Kinoshita, Masahiko

1998-01-01

Reversible thallium-201 ( 201 Tl) abnormalities during exercise stress have been used as markers of myocardial ischemia in hypertrophic cardiomyopathy (HCM) and are most likely to identify relatively underperfused myocardium. Although metabolic abnormalities in HCM were reported, the relationship between impaired energy metabolism and exercise-induced ischemia has not been fully elucidated as yet. To assess the relationship between myocardial perfusion abnormalities and fatty acid metabolic abnormalities, 28 patients with HCM underwent exercise 201 Tl and rest 123 I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) scintigraphy. Perfusion abnormalities were observed by exercise 201 Tl in 19/28 patients with HCM. 123 I-BMIPP uptake was decreased compared with delayed 201 Tl in 106/364 (29%) of the total myocardial segments (p 123 I-BMIPP and 201 Tl was observed more often in the 49/75 (65%) segments with reversible exercise 201 Tl defects (p 123 I-BMIPP and 201 Tl suggests that myocardial ischemia may play an important role in metabolic abnormalities in HCM. (author)

Abnormalities of Early “Memory-Scanning” Event-Related Potentials in Patients with Temporal Lobe Epilepsy

Directory of Open Access Journals (Sweden)

A. Grippo

1994-01-01

Full Text Available We have recorded auditory event-related potentials (ERPs evoked by the “memory-scanning” (digit-probe identification/matching paradigm that was originally described by Sternberg (1966, in 17 patients with complex partial seizures (temporal lobe epilepsy and in 17 matched healthy control subjects. The patients, who had all complained spontaneously of memory difficulties, had significantly reduced scores on psychological tests of memory with relatively intact digit span and cognition. Their performance of the memory-scanning task was characterized by a higher error rate, longer reaction times and an increased slope of the reaction time/set size relationship. The associated ERPs in both patients and controls showed there were significant effects of memory load on several major components, but only a reduced amplitude of the N170 and a prolonged latency of the N290 waves distinguished the patients. In addition, the N170 wave in the patients decreased further as memory load increased. The prolonged N290 latency in the patients appeared to reflect the slowed processing time. This study has shown that ERPs generated by a short-term memory task are abnormal in patients with temporal lobe epilepsy who have neuropsychologically documented cognitive and memory deficits. Some of the significant waveform alterations occur earlier than those reported in previous ERP studies and provide electrophysiological support for the hypothesis that abnormalities of the early stages of short-term memory processing may contribute to the memory difficulties experienced by patients with temporal lobe epilepsy.

Circulating Metabolites Associated with Alcohol Intake in the European Prospective Investigation into Cancer and Nutrition Cohort

Directory of Open Access Journals (Sweden)

Eline H. van Roekel

2018-05-01

Full Text Available Identifying the metabolites associated with alcohol consumption may provide insights into the metabolic pathways through which alcohol may affect human health. We studied associations of alcohol consumption with circulating concentrations of 123 metabolites among 2974 healthy participants from the European Prospective Investigation into Cancer and Nutrition (EPIC study. Alcohol consumption at recruitment was self-reported through dietary questionnaires. Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQTM p180 kit. Data were randomly divided into discovery (2/3 and replication (1/3 sets. Multivariable linear regression models were used to evaluate confounder-adjusted associations of alcohol consumption with metabolite concentrations. Metabolites significantly related to alcohol intake in the discovery set (FDR q-value < 0.05 were further tested in the replication set (Bonferroni-corrected p-value < 0.05. Of the 72 metabolites significantly related to alcohol intake in the discovery set, 34 were also significant in the replication analysis, including three acylcarnitines, the amino acid citrulline, four lysophosphatidylcholines, 13 diacylphosphatidylcholines, seven acyl-alkylphosphatidylcholines, and six sphingomyelins. Our results confirmed earlier findings that alcohol consumption was associated with several lipid metabolites, and possibly also with specific acylcarnitines and amino acids. This provides further leads for future research studies aiming at elucidating the mechanisms underlying the effects of alcohol in relation to morbid conditions.

Abnormal interhemispheric connectivity in male psychopathic offenders.

Science.gov (United States)

Hoppenbrouwers, Sylco S; De Jesus, Danilo R; Sun, Yinming; Stirpe, Tania; Hofman, Dennis; McMaster, Jeff; Hughes, Ginny; Daskalakis, Zafiris J; Schutter, Dennis J L G

2014-01-01

Psychopathic offenders inevitably violate interpersonal norms and frequently resort to aggressive and criminal behaviour. The affective and cognitive deficits underlying these behaviours have been linked to abnormalities in functional interhemispheric connectivity. However, direct neurophysiological evidence for dysfunctional connectivity in psychopathic offenders is lacking. We used transcranial magnetic stimulation combined with electroencephalography to examine interhemispheric connectivity in the dorsolateral and motor cortex in a sample of psychopathic offenders and healthy controls. We also measured intracortical inhibition and facilitation over the left and right motor cortex to investigate the effects of local cortical processes on interhemispheric connectivity. We enrolled 17 psychopathic offenders and 14 controls in our study. Global abnormalities in right to left functional connectivity were observed in psychopathic offenders compared with controls. Furthermore, in contrast to controls, psychopathic offenders showed increased intracortical inhibition in the right, but not the left, hemisphere. The relatively small sample size limited the sensitivity to show that the abnormalities in interhemispheric connectivity were specifically related to the dorsolateral prefrontal cortex in psychopathic offenders. To our knowledge, this study provides the first neurophysiological evidence for abnormal interhemispheric connectivity in psychopathic offenders and may further our understanding of the disruptive antisocial behaviour of these offenders.

Detection of Volatile Metabolites of Garlic in Human Breast Milk

Science.gov (United States)

Scheffler, Laura; Sauermann, Yvonne; Zeh, Gina; Hauf, Katharina; Heinlein, Anja; Sharapa, Constanze; Buettner, Andrea

2016-01-01

The odor of human breast milk after ingestion of raw garlic at food-relevant concentrations by breastfeeding mothers was investigated for the first time chemo-analytically using gas chromatography−mass spectrometry/olfactometry (GC-MS/O), as well as sensorially using a trained human sensory panel. Sensory evaluation revealed a clear garlic/cabbage-like odor that appeared in breast milk about 2.5 h after consumption of garlic. GC-MS/O analyses confirmed the occurrence of garlic-derived metabolites in breast milk, namely allyl methyl sulfide (AMS), allyl methyl sulfoxide (AMSO) and allyl methyl sulfone (AMSO2). Of these, only AMS had a garlic-like odor whereas the other two metabolites were odorless. This demonstrates that the odor change in human milk is not related to a direct transfer of garlic odorants, as is currently believed, but rather derives from a single metabolite. The formation of these metabolites is not fully understood, but AMSO and AMSO2 are most likely formed by the oxidation of AMS in the human body. The excretion rates of these metabolites into breast milk were strongly time-dependent with large inter-individual differences. PMID:27275838

Semen quality in Peruvian pesticide applicators: association between urinary organophosphate metabolites and semen parameters

Directory of Open Access Journals (Sweden)

Gasco Manuel

2008-11-01

Full Text Available Abstract Background Organophosphates are broad class of chemicals widely used as pesticides throughout the world. We performed a cross-sectional study of associations between dialkylphosphate metabolites of organophosphates and semen quality among pesticide applicators in Majes (Arequipa, Peru. Methods Thirty-one men exposed to organophosphate (OP pesticides and 31 non-exposed were recruited (age, 20–60 years. In exposed subjects, semen and a blood sample were obtained one day after the last pesticide application. Subjects were grouped according to levels of OP metabolites in urine. Semen samples were analyzed for sperm concentration, percentage of sperm motility, percentage of normal morphology, semen leucocytes and concentrations of fructose and zinc. Exposure to OP was assessed by measuring six urinary OP metabolites (dimethyl and diethyl phosphates and thiophosphates by gas chromatography using a single flame photometric detector. Results Diethyldithiophosphate (p = 0.04 and diethylthiophosphate (p = 0.02 better reflected occupational pesticide exposure than other OP metabolites. Semen analysis revealed a significant reduction of semen volume and an increase in semen pH in men with OP metabolites. Multiple regression analysis showed that both occupational exposure to pesticides and the time of exposure to pesticides were more closely related to alterations in semen quality parameters than the single measurement of OP metabolites in urine. Conclusion The study demonstrated that occupational exposure to OP pesticides was more closely related to alterations in semen quality than a single measurement of urine OP metabolites. Current measurement of OP metabolites in urine may not reflect the full risk.

[Amyoplasia congenita: a serious congenital abnormality with a relatively favorable prognosis

NARCIS (Netherlands)

Petru, R.; Verrips, A.; Ravenswaaij-Arts, C.M.A. van

2002-01-01

After an uneventful pregnancy a girl was born with serious joint contractures and several fractures of the long bones. The family history was negative for congenital abnormalities. Based on the distinct clinical presentation the diagnosis was 'amyoplasia', which is a partial aplasia of skeletal

Abnormal Metabolite in Alcoholic Subjects,

Science.gov (United States)

1982-01-01

this study included alcoholic hepatitis or cirrhosis of the liver in 29. of the alcoholic subjects; diabetes mellitus in 8 and Korsakoff’s syndrome in 6...evidence of -7- Korsakoff’s syndrome and the presence or absence of 2,3-butanediol. There was, however, a suggestive correlation with independently...Gamma GT 193, SGPT 29 b 0 0.023 0.05 51a F.B. 22 M 28 0.029 0.14 b 0 ɘ.01 0.12 77 J.N.S. 52 M 0 0.027 0.11 57 JJ.S 45 m 4. 0.25 .35 Korsakoff ’s

DISTRIBUTION OF MONOAMINES AND THEIR METABOLITES IN BOTH SIDES OF THE RAT BRAIN AND ITS RELATION WITH FUNCTIONAL MOTOR ASYMMETRY

OpenAIRE

E.D. Morenkov; V.S. Kudrin

2013-01-01

The purpose of this neurochemical study was to quantitatively determine the regional distribution of monoamines (DA, 5HT, and NE) and their metabolites (DOPAC, HVA, and 5HIAA) in paired brain structures (the frontomedial cortex, hypothalamus, amygdala, hippocampus, striatum, and brainstem tegmentum) of the rat by performing HPLC/ED assays. Further, we aimed to relate these distributions to neuronal mechanisms of lateralized motor behavior. We found differences in monoamine levels and their...

Discrimination between leukaemia and non-leukaemia-related chromosomal abnormalities in the patient's lymphocytes

International Nuclear Information System (INIS)

Lucas, J.N.; Hill, F.; Burk, C.; Straume, T.; Swansbury, G.; Clutterbuck, R.

1994-01-01

The inability to measure precancer-related genetic damage accurately in blood cells of patients with leukaemia or lymphoma has prevented the use in such patients of available biodosimetric methods to determine prior exposure to clastogenic agents. This is because a substantial amount of disease-related genetic damage appears in the blood cells of these patients, thus masking genetic damage that may have been caused prior to the disease. We describe a new approach that may be used to measure pre-cancer-related chromosomal aberrations in such patients by totally separating the affected T lymphocytes from the malignant B lymphocytes. The approach employs stable chromosome translocations and will detect prior exposures above the detection limit of ∼ 0.05-0.1 Gy. The utility of this approach is illustrated by using blood lymphocytes from a nuclear dockyard worker who claims his B cell leukaemia was induced by work-related radiation exposures. Blood lymphocytes were obtained after diagnosis of the disease, but prior to therapy, and measurements were made of the frequency of chromosomal abnormalities in PHA-stimulated lymphocytes without prior separation of T and B cells and in T lymphocytes after complete separation from B cells using a rosetting technique. Results show that the separation of T cells prior to PHA stimulation eliminates the cancer-related chromosomal damage and thus appears to facilitate biodosimetry of pre-cancer in such patients. (Author)

Duodenal L cell density correlates with features of metabolic syndrome and plasma metabolites

Directory of Open Access Journals (Sweden)

Annieke C G van Baar

2018-05-01

Full Text Available Background: Enteroendocrine cells are essential for the regulation of glucose metabolism, but it is unknown whether they are associated with clinical features of metabolic syndrome (MetS and fasting plasma metabolites. Objective: We aimed to identify fasting plasma metabolites that associate with duodenal L cell, K cell and delta cell densities in subjects with MetS with ranging levels of insulin resistance. Research design and methods: In this cross-sectional study, we evaluated L, K and delta cell density in duodenal biopsies from treatment-naïve males with MetS using machine-learning methodology. Results: We identified specific clinical biomarkers and plasma metabolites associated with L cell and delta cell density. L cell density was associated with increased plasma metabolite levels including symmetrical dimethylarginine, 3-aminoisobutyric acid, kynurenine and glycine. In turn, these L cell-linked fasting plasma metabolites correlated with clinical features of MetS. Conclusions: Our results indicate a link between duodenal L cells, plasma metabolites and clinical characteristics of MetS. We conclude that duodenal L cells associate with plasma metabolites that have been implicated in human glucose metabolism homeostasis. Disentangling the causal relation between L cells and these metabolites might help to improve the (small intestinal-driven pathophysiology behind insulin resistance in human obesity.

Relation of metabolic syndrome with endometrial pathologies in patients with abnormal uterine bleeding.

Science.gov (United States)

Özdemir, Suna; Batmaz, Gonca; Ates, Seda; Celik, Cetin; Incesu, Feyzanur; Peru, Celalettin

2015-01-01

We aimed to investigate the association of metabolic syndrome and metabolic risk factors with endometrial hyperplasia and carcinoma among women with abnormal uterine bleeding (AUB). This study included 199 patients who had undergone endometrial curettage due to abnormal uterine bleeding. We divided the patients into two groups according to whether they had an abnormal (n = 53) or normal endometrium (n = 146). Waist circumference, blood pressure, fasting glucose and serum lipid levels were measured and statistically analyzed. The women in each group were matched with regard to mean age, gravidity, parity and menopausal status. We found increased prevalence of metabolic syndrome, diabetes, general and abdominal obesity, hypertension, elevated levels of glucose, total cholesterol and LDL-cholesterol and reduced levels of HDL-cholesterol among women with endometrial carcinoma and hyperplasia. These results were detected particularly in postmenopausal (>50 years) women compared to pre-menopausal cases (<50 years). All metabolic parameters were similar between hyperplasia and cancer groups. Metabolic syndrome and its components have been shown to have profound impacts on initiation and progession of endometrial pathology, particularly during post-menopausal period.

Detection of Cardiopulmonary Activity and Related Abnormal Events Using Microsoft Kinect Sensor.

Science.gov (United States)

Al-Naji, Ali; Chahl, Javaan

2018-03-20

Monitoring of cardiopulmonary activity is a challenge when attempted under adverse conditions, including different sleeping postures, environmental settings, and an unclear region of interest (ROI). This study proposes an efficient remote imaging system based on a Microsoft Kinect v2 sensor for the observation of cardiopulmonary-signal-and-detection-related abnormal cardiopulmonary events (e.g., tachycardia, bradycardia, tachypnea, bradypnea, and central apnoea) in many possible sleeping postures within varying environmental settings including in total darkness and whether the subject is covered by a blanket or not. The proposed system extracts the signal from the abdominal-thoracic region where cardiopulmonary activity is most pronounced, using a real-time image sequence captured by Kinect v2 sensor. The proposed system shows promising results in any sleep posture, regardless of illumination conditions and unclear ROI even in the presence of a blanket, whilst being reliable, safe, and cost-effective.

Detection of Cardiopulmonary Activity and Related Abnormal Events Using Microsoft Kinect Sensor

Directory of Open Access Journals (Sweden)

Ali Al-Naji

2018-03-01

Full Text Available Monitoring of cardiopulmonary activity is a challenge when attempted under adverse conditions, including different sleeping postures, environmental settings, and an unclear region of interest (ROI. This study proposes an efficient remote imaging system based on a Microsoft Kinect v2 sensor for the observation of cardiopulmonary-signal-and-detection-related abnormal cardiopulmonary events (e.g., tachycardia, bradycardia, tachypnea, bradypnea, and central apnoea in many possible sleeping postures within varying environmental settings including in total darkness and whether the subject is covered by a blanket or not. The proposed system extracts the signal from the abdominal-thoracic region where cardiopulmonary activity is most pronounced, using a real-time image sequence captured by Kinect v2 sensor. The proposed system shows promising results in any sleep posture, regardless of illumination conditions and unclear ROI even in the presence of a blanket, whilst being reliable, safe, and cost-effective.

Maternal phenylketonuria: Embryotoxicity in vitro of PKU-related metabolites and of human PKU-sera

NARCIS (Netherlands)

Piersma AH; Verhoef A; Hamers AM; van den Ham WA; Jansen EHJM

1993-01-01

Mothers with untreated phenylketonuria (PKU) have an increased risk of bearing children with congenital malformations. PKU causes accumulation of phenylalanine (PHE) and its metabolites in urine and blood, and this condition may contribute to the developmental problems. In the present study we

Seed metabolomic study reveals significant metabolite variations and correlations among different soybean cultivars.

Science.gov (United States)

Lin, Hong; Rao, Jun; Shi, Jianxin; Hu, Chaoyang; Cheng, Fang; Wilson, Zoe A; Zhang, Dabing; Quan, Sheng

2014-09-01

Soybean [Glycine max (L.) Merr.] is one of the world's major crops, and soybean seeds are a rich and important resource for proteins and oils. While "omics" studies, such as genomics, transcriptomics, and proteomics, have been widely applied in soybean molecular research, fewer metabolomic studies have been conducted for large-scale detection of low molecular weight metabolites, especially in soybean seeds. In this study, we investigated the seed metabolomes of 29 common soybean cultivars through combined gas chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry. One hundred sixty-nine named metabolites were identified and subsequently used to construct a metabolic network of mature soybean seed. Among the 169 detected metabolites, 104 were found to be significantly variable in their levels across tested cultivars. Metabolite markers that could be used to distinguish genetically related soybean cultivars were also identified, and metabolite-metabolite correlation analysis revealed some significant associations within the same or among different metabolite groups. Findings from this work may potentially provide the basis for further studies on both soybean seed metabolism and metabolic engineering to improve soybean seed quality and yield. © 2014 Institute of Botany, Chinese Academy of Sciences.

Seed metabolomic study reveals significant metabolite variations and correlations among different soybean cultivars

Institute of Scientific and Technical Information of China (English)

Hong Lin; Jun Rao; Jianxin Shi; Chaoyang Hu; Fang Cheng; Zoe AWilson; Dabing Zhang; Sheng Quan

2014-01-01

Soybean [Glycine max (L.) Merr.] is one of the world’s major crops, and soybean seeds are a rich and important resource for proteins and oils. While “omics”studies, such as genomics, transcriptomics, and proteomics, have been widely applied in soybean molecular research, fewer metabolomic studies have been conducted for large-scale detection of low molecular weight metabolites, especial y in soybean seeds. In this study, we investigated the seed metabolomes of 29 common soybean cultivars through combined gas chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry. One hundred sixty-nine named metabolites were identified and subsequently used to construct a metabolic network of mature soybean seed. Among the 169 detected metabolites, 104 were found to be significantly variable in their levels across tested cultivars. Metabolite markers that could be used to distinguish genetical y related soybean cultivars were also identified, and metabolite-metabolite correlation analysis revealed some significant associations within the same or among different metabolite groups. Findings from this work may potentially provide the basis for further studies on both soybean seed metabolism and metabolic engineering to improve soybean seed quality and yield.

Unknown and abnormal accumulation in the chest in bone scintigraphy

International Nuclear Information System (INIS)

Maruyama, Toshiaki; Takeuchi, Masashi; Tokunaga, Koji; Maeda, Yoichi; Hasegawa, Kazuhiko.

1979-01-01

In scintigraphies of forty patients with hemiplegia following appoplexia, focal abnormal accumulations in the chest region were seen in bone scintigraphies of four patients. These hot accumulations could be neither rib fracture, rib metastases, nor abnormal calcium accumulation. A mechanism of these accumulation remains to undicided. We believe that this phenomena is related to abnormal bone metabolism in hemiplegial condition. (author)

Chemical transformations of characteristic hop secondary metabolites in relation to beer properties and the brewing process: a review.

Science.gov (United States)

Steenackers, Bart; De Cooman, Luc; De Vos, Dirk

2015-04-01

The annual production of hops (Humulus lupulus L.) exceeds 100,000 mt and is almost exclusively consumed by the brewing industry. The value of hops is attributed to their characteristic secondary metabolites; these metabolites are precursors which are transformed during the brewing process into important bittering, aromatising and preservative components with rather low efficiency. By selectively transforming these components off-line, both their utilisation efficiency and functionality can be significantly improved. Therefore, the chemical transformations of these secondary metabolites will be considered with special attention to recent advances in the field. The considered components are the hop alpha-acids, hop beta-acids and xanthohumol, which are components unique to hops, and alpha-humulene and beta-caryophyllene, sesquiterpenes which are highly characteristic of hops. Copyright © 2014 Elsevier Ltd. All rights reserved.

Coagulation abnormalities in patients with chronic liver disease in Pakistan

International Nuclear Information System (INIS)

Siddiqui, S.A.; Ghani, M.H.; Ghori, M.A.; Ahmed, M.

2011-01-01

Objective: To determine the coagulation abnormalities and relationship between abnormal clotting tests and the risk of gastrointestinal bleeding (GI) among chronic liver disease (CLD) patients admitted at a tertiary care hospital in Pakistan. Methods: Adult CLD patients admitted at Liaquat University Hospital Jamshoro, during Nov 2004 - Oct 2005, were included in the study. The patients blood were tested for coagulation abnormalities including prothrombin time (PT), activated partial thromboplastin time (aPTT), platelet count and plasma fibrinogen. Association was seen between the abnormal clotting tests and the gastrointestinal bleeding by calculating relative risk (RR) with 95% confidence interval. Results: PT was prolonged in 88% and aPTT was raised in 71% cases of CLD. Both PT and aPTT were prolonged in 67% CLD cases. Approximately 37% CLD cases had decreased platelet count and 15% cases had decreased serum fibrinogen level. Relative risk of GI bleeding with abnormal clotting tests in CLD cases were weakly positive for PT (RR = 1.02; 95% CI, 0.49-2.10), negative for aPTT (RR=0.83; 95% CI, 0.47-1.45), strongly positive for decreased platelet counts (RR = 1.96; 95% CI, 1.08-3.56) and also for decreased fibrinogen level (RR = 1.47; 95% CI, 0.64-3.35). Conclusion: Coagulation abnormalities were profound in CLD. Decrease platelet counts and fibrinogen levels were related with GI bleeding but PT and aPTT were not significantly related with GI bleeding in patients with chronic liver disease. Nevertheless, these parameters (PT and aPTT) were still used as prognostic markers. (author)

Relations Among Detection of Syllable Stress, Speech Abnormalities, and Communicative Ability in Adults With Autism Spectrum Disorders.

Science.gov (United States)

Kargas, Niko; López, Beatriz; Morris, Paul; Reddy, Vasudevi

2016-04-01

To date, the literature on perception of affective, pragmatic, and grammatical prosody abilities in autism spectrum disorders (ASD) has been sparse and contradictory. It is interesting to note that the primary perception of syllable stress within the word structure, which is crucial for all prosody functions, remains relatively unexplored in ASD. Thus, in the current study, we explored syllable stress perception sensitivity and its relationship to speech production abnormalities and communicative ability in adults with ASD. A same-different syllable stress perception task using pairs of identical 4-syllable words was delivered to 42 adults with/without high-functioning ASD, matched for age, to investigate primary speech perception ability in ASD. Speech production and communicative ability in ASD was measured using the Autism Diagnostic Observation Schedule (Lord et al., 2000). As predicted, the results showed that adults with ASD were less sensitive in making judgments about syllable stress relative to controls. Also, partial correlations revealed a key association of speech production abnormalities with stress perception sensitivity, rather than communicative ability. Our findings provide empirical evidence for deficits on primary syllable stress perception in ASD and its role on sociocommunicative difficulties. This information could facilitate the development of effective interventions for speech and language therapy and social communication.

Diverticular Disease of the Colon: Neuromuscular Function Abnormalities.

Science.gov (United States)

Bassotti, Gabrio; Villanacci, Vincenzo; Bernardini, Nunzia; Dore, Maria P

2016-10-01

Colonic diverticular disease is a frequent finding in daily clinical practice. However, its pathophysiological mechanisms are largely unknown. This condition is likely the result of several concomitant factors occurring together to cause anatomic and functional abnormalities, leading as a result to the outpouching of the colonic mucosa. A pivotal role seems to be played by an abnormal colonic neuromuscular function, as shown repeatedly in these patients, and by an altered visceral perception. There is recent evidence that these abnormalities might be related to the derangement of the enteric innervation, to an abnormal distribution of mucosal neuropeptides, and to low-grade mucosal inflammation. The latter might be responsible for the development of visceral hypersensitivity, often causing abdominal pain in a subset of these patients.

The radioimmunological determination of glibenclamide and its metabolites in serum

International Nuclear Information System (INIS)

Glogner, P.; Heni, N.; Nissen, L.

1977-01-01

This report describes a sensitive and specific radio-immunological method for determining serum levels of the 1-(p-[2- (5-chloro-2-methoxybenzamido) -ethyl]-benzenesulfonyl) -3-cyclohexylurea (clibenclamide) and its metabolites. The antigen was prepared by coupling a metabolite to bovine serum albumin. Antibodies could be demonstrated in serum after immunisation of rabbits. The separation of free and antibody-bound glibenclamide was achieved by a dextran-charcoal suspension. Presence of serum did not influence the binding characteristics. The limit of detection was 20 ng/ml. The affinity of the metabolites differed only slightly from that of glibenclamide. The presence of related drugs from the sulfonylurea series such as tolbutamide, glibornuride and the sulfonamide sulfamethoxazol did not affect the determination. Only closely related substances showed a variable degree of affinity towards antibodies. As an example of the possible application of this method, the serum concentration of glibenclamide was determined over a period of 8 h after single i.v. injection to a volunteer. The data are in close accordance with the results of authors using radioactive glibenclamide. (orig.) [de

Study on the radiation-induced biological responses based on the analysis of metabolites

International Nuclear Information System (INIS)

Jo, Sungkee; Jung, Uhee; Park, Haeran; Roh, Changhyun; Shin, Heejune; Ryu, Dongkyoung

2013-01-01

1. Objectives □ Establishment of basis of biological radiation response study by metabolite analysis 2. Project results □ Establishment of analytical basis of radiation-responsive metabolites in biological samples - Large scale collection of tissue samples from irradiated animal for radiation metabolomics research - Establishment of mass spectromety (GC MS, LC MS-MS) analysis methods of biological samples - 3 Standard Operation Protocols (SOP) for ultra high resolution mass spectrometry (FT-ICR MS, Q-TOF MS) analysis of metabolites from biological samples - Establishment of database for radiation metabolites □ Basic research on radiation-responsive metabolites and the interpretation of their functions - Validation of spermidine as a candidate biomarker of acute radiation response in mouse blood - Verification of 5 radiation-responsive steroid hormones and alteration of their metabolic enzyme activities in mouse blood - Verification of 13 radiation-responsive amino acids (related to oxidative stress, neurotransmission, energy metabolism) in regional mouse brain -Verification of 10 radiation-responsive amino acids (related to oxidative stress, neurotransmission, energy metabolism) in regional mouse brain - Verification of 74 radiation-responsive metabolites in whole rat brain by ultra high resolution FT-ICR MS and Q-TOF MS analysis 3. Expected benefits and plan of application □ Establishment of research basis of radiation metabolomics in Korea □ Provision of core technology in radiation bioscience and safety field by application of radiation metabolomics results to the technology development in radiation biodosimetry, and radiation response evaluation and modulation

Study on the radiation-induced biological responses based on the analysis of metabolites

Energy Technology Data Exchange (ETDEWEB)

Jo, Sungkee; Jung, Uhee; Park, Haeran; Roh, Changhyun; Shin, Heejune; Ryu, Dongkyoung

2013-01-15

1. Objectives □ Establishment of basis of biological radiation response study by metabolite analysis 2. Project results □ Establishment of analytical basis of radiation-responsive metabolites in biological samples - Large scale collection of tissue samples from irradiated animal for radiation metabolomics research - Establishment of mass spectromety (GC MS, LC MS-MS) analysis methods of biological samples - 3 Standard Operation Protocols (SOP) for ultra high resolution mass spectrometry (FT-ICR MS, Q-TOF MS) analysis of metabolites from biological samples - Establishment of database for radiation metabolites □ Basic research on radiation-responsive metabolites and the interpretation of their functions - Validation of spermidine as a candidate biomarker of acute radiation response in mouse blood - Verification of 5 radiation-responsive steroid hormones and alteration of their metabolic enzyme activities in mouse blood - Verification of 13 radiation-responsive amino acids (related to oxidative stress, neurotransmission, energy metabolism) in regional mouse brain -Verification of 10 radiation-responsive amino acids (related to oxidative stress, neurotransmission, energy metabolism) in regional mouse brain - Verification of 74 radiation-responsive metabolites in whole rat brain by ultra high resolution FT-ICR MS and Q-TOF MS analysis 3. Expected benefits and plan of application □ Establishment of research basis of radiation metabolomics in Korea □ Provision of core technology in radiation bioscience and safety field by application of radiation metabolomics results to the technology development in radiation biodosimetry, and radiation response evaluation and modulation.

Monoamine related functional gene variants and relationships to monoamine metabolite concentrations in CSF of healthy volunteers

Directory of Open Access Journals (Sweden)

Propping Peter

2004-03-01

Full Text Available Abstract Background Concentrations of monoamine metabolites in human cerebrospinal fluid (CSF have been used extensively as indirect estimates of monoamine turnover in the brain. CSF monoamine metabolite concentrations are partly determined by genetic influences. Methods We investigated possible relationships between DNA polymorphisms in the serotonin 2C receptor (HTR2C, the serotonin 3A receptor (HTR3A, the dopamine D4 receptor (DRD4, and the dopamine β-hydroxylase (DBH genes and CSF concentrations of 5-hydroxyindolacetic acid (5-HIAA, homovanillic acid (HVA, and 3-methoxy-4-hydroxyphenylglycol (MHPG in healthy volunteers (n = 90. Results The HTR3A 178 C/T variant was associated with 5-HIAA levels (p = 0.02. The DBH-1021 heterozygote genotype was associated with 5-HIAA (p = 0.0005 and HVA (p = 0.009 concentrations. Neither the HTR2C Cys23Ser variant, nor the DRD4 -521 C/T variant were significantly associated with any of the monoamine metabolites. Conclusions The present results suggest that the HTR3A and DBH genes may participate in the regulation of dopamine and serotonin turnover rates in the central nervous system.

Confirmatory analysis method for zeranol, its metabolites and related mycotoxins in urine by liquid chromatography-negative ion electrospray tandem mass spectrometry

International Nuclear Information System (INIS)

Bennekom, E.O. van; Brouwer, L.; Laurant, E.H.M.; Hooijerink, H.; Nielen, M.W.F.

2002-01-01

The determination of the banned anabolic substance zeranol and the metabolites taleranol and zearalanone in bovine urine is complicated by the occurrence of the structurally-related mycotoxin zearalenone and the corresponding α- and β-zearalenol metabolites which possess similar estrogenic properties. A liquid chromatography-negative ion electrospray tandem mass spectrometric method is presented for the confirmatory analysis of all six resorcylic acid lactones ('zeranols') in urine samples using deuterium-labelled internal standards. The method was validated as a confirmatory method for bovine urine samples according to new draft EU guidelines and showed good precision and linearity, and CCα and CCβ values of 0.02-0.30 and -1 , respectively. The applicability was demonstrated by comparing the results of an incurred sample with previous results on the same sample obtained by gas chromatography high resolution mass spectrometry. Preliminary data show that following a simple matrix solid phase dispersion clean-up, liver samples from poultry will be amenable to this method as well

Syringomyelia and Craniocervical Junction Abnormalities in Chihuahuas

OpenAIRE

Kiviranta, A.‐M.; Rusbridge, C.; Laitinen‐Vapaavuori, O.; Hielm‐Björkman, A.; Lappalainen, A.K.; Knowler, S.P.; Jokinen, T.S.

2017-01-01

Background: Chiari-like malformation (CM) and syringomyelia (SM) are widely reported in Cavalier King Charles Spaniels and Griffon Bruxellois dogs. Increasing evidence indicates that CM and SM also occur in other small and toy breed dogs, such as Chihuahuas. Objectives: To describe the presence of SM and craniocervical junction (CCJ) abnormalities in Chihuahuas and to evaluate the possible association of CCJ abnormalities with SM. To describe CM/SM-related clinical signs and neuro...

Identification of drug metabolites in human plasma or serum integrating metabolite prediction, LC-HRMS and untargeted data processing

NARCIS (Netherlands)

Jacobs, P.L.; Ridder, L.; Ruijken, M.; Rosing, H.; Jager, N.G.L.; Beijnen, J.H.; Bas, R.R.; Dongen, W.D. van

2013-01-01

Background: Comprehensive identification of human drug metabolites in first-in-man studies is crucial to avoid delays in later stages of drug development. We developed an efficient workflow for systematic identification of human metabolites in plasma or serum that combines metabolite prediction,

Neurological abnormalities predict disability

DEFF Research Database (Denmark)

Poggesi, Anna; Gouw, Alida; van der Flier, Wiesje

2014-01-01

To investigate the role of neurological abnormalities and magnetic resonance imaging (MRI) lesions in predicting global functional decline in a cohort of initially independent-living elderly subjects. The Leukoaraiosis And DISability (LADIS) Study, involving 11 European centres, was primarily aimed...... at evaluating age-related white matter changes (ARWMC) as an independent predictor of the transition to disability (according to Instrumental Activities of Daily Living scale) or death in independent elderly subjects that were followed up for 3 years. At baseline, a standardized neurological examination.......0 years, 45 % males), 327 (51.7 %) presented at the initial visit with ≥1 neurological abnormality and 242 (38 %) reached the main study outcome. Cox regression analyses, adjusting for MRI features and other determinants of functional decline, showed that the baseline presence of any neurological...

Steady-state metabolite concentrations reflect a balance between maximizing enzyme efficiency and minimizing total metabolite load.

Directory of Open Access Journals (Sweden)

Naama Tepper

Full Text Available Steady-state metabolite concentrations in a microorganism typically span several orders of magnitude. The underlying principles governing these concentrations remain poorly understood. Here, we hypothesize that observed variation can be explained in terms of a compromise between factors that favor minimizing metabolite pool sizes (e.g. limited solvent capacity and the need to effectively utilize existing enzymes. The latter requires adequate thermodynamic driving force in metabolic reactions so that forward flux substantially exceeds reverse flux. To test this hypothesis, we developed a method, metabolic tug-of-war (mTOW, which computes steady-state metabolite concentrations in microorganisms on a genome-scale. mTOW is shown to explain up to 55% of the observed variation in measured metabolite concentrations in E. coli and C. acetobutylicum across various growth media. Our approach, based strictly on first thermodynamic principles, is the first method that successfully predicts high-throughput metabolite concentration data in bacteria across conditions.

Functional metabolite assemblies—a review

Science.gov (United States)

Aizen, Ruth; Tao, Kai; Rencus-Lazar, Sigal; Gazit, Ehud

2018-05-01

Metabolites are essential for the normal operation of cells and fulfill various physiological functions. It was recently found that in several metabolic disorders, the associated metabolites could self-assemble to generate amyloid-like structures, similar to canonical protein amyloids that have a role in neurodegenerative disorders. Yet, assemblies with typical amyloid characteristics are also known to have physiological function. In addition, many non-natural proteins and peptides presenting amyloidal properties have been used for the fabrication of functional nanomaterials. Similarly, functional metabolite assemblies are also found in nature, demonstrating various physiological roles. A notable example is the structural color formed by guanine crystals or fluorescent crystals in feline eyes responsible for enhanced night vision. Moreover, some metabolites have been used for the in vitro fabrication of functional materials, such as glycine crystals presenting remarkable piezoelectric properties or indigo films used to assemble organic semi-conductive electronic devices. Therefore, we believe that the study of metabolite assemblies is not only important in order to understand their role in normal physiology and in pathology, but also paves a new route in exploring the fabrication of organic, bio-compatible materials.

Studies on the application of tryptophan metabolites as indicators of acute radiation damage and their modification

International Nuclear Information System (INIS)

Streffer, C.

1979-01-01

It has been the aim of the investigations to continue earlier studies on the amplication of tryptophan metabolites as biochemical indicators after irradiation. These metabolites are of interest as they apparently indicate radiation effects in contrast to other metabolites like taurine and deoxycytidine in a dose range which leads to acute radiation sickness with the consequence of death. This assumption has been confirmed by the results of these studies. Measurements in the urine of rats demonstrate that the excretion of kynurenic acid and of xanthurenic acid as well as especially the ratio of kynurenic acid/anthranilic acid increases considerably in those animals which die some days later. The excretion of the surviving anilic acid increases considerably in those animals which die some days later. The excretion of the surviving animals is characteristical different. This abnormal excretion is induced by changes of specific, hepatic enzyme activities. The investigations have shown that the effects on the enzyme activities apppear not only after X-rays irradiation but also after neutrons. The studies, which have been performed with human material on the NAD-metabolism, demonstrate that with respect to the enzyme activities in the spleen as well as to the urinary excretion the same or similar effects, which have been found with animal experiments, can be expected. (orig.) 891 MG/orig. 892 CKA [de

Metabolite Profiling of Root Exudates of Common Bean under Phosphorus Deficiency

Directory of Open Access Journals (Sweden)

Keitaro Tawaraya

2014-07-01

Full Text Available Root exudates improve the nutrient acquisition of plants and affect rhizosphere microbial communities. The plant nutrient status affects the composition of root exudates. The purpose of this study was to examine common bean (Phaseolus vulgaris L. root exudates under phosphorus (P deficiency using a metabolite profiling technique. Common bean plants were grown in a culture solution at P concentrations of 0 (P0, 1 (P1 and 8 (P8 mg P L−1 for 1, 10 and 20 days after transplanting (DAT. Root exudates were collected, and their metabolites were determined by capillary electrophoresis time-of-flight mass spectrometry (CE-TOF MS. The shoot P concentration and dry weight of common bean plants grown at P0 were lower than those grown at P8. One hundred and fifty-nine, 203 and 212 metabolites were identified in the root exudates, and 16% (26/159, 13% (26/203 and 9% (20/212 of metabolites showed a P0/P8 ratio higher than 2.0 at 1, 10 and 20 DAT, respectively. The relative peak areas of several metabolites, including organic acids and amino acids, in root exudates were higher at P0 than at P8. These results suggest that more than 10% of primary and secondary metabolites are induced to exude from roots of common bean by P deficiency.

Metabolism of albendazole, ricobendazole and flubendazole in Haemonchus contortus adults: Sex differences, resistance-related differences and the identification of new metabolites

Directory of Open Access Journals (Sweden)

Lucie Raisová Stuchlíková

2018-04-01

Full Text Available Haemonchus contortus (family Trichostrongylidae, Nematoda, a hematophagous gastrointestinal parasite found in small ruminants, has a great ability to develop resistance to anthelmintic drugs. We studied the biotransformation of the three benzimidazole anthelmintics: albendazole (ABZ, ricobendazole (albendazole S-oxide; RCB and flubendazole (FLU in females and males of H. contortus in both a susceptible ISE strain and resistant IRE strain. The ex vivo cultivation of living nematodes in culture medium with or without the anthelmintics was used. Ultrasensitive UHPLC/MS/MS analysis revealed 9, 7 and 12 metabolites of ABZ, RCB and FLU, respectively, with most of these metabolites now described in the present study for the first time in H. contortus. The structure of certain metabolites shows the presence of biotransformation reactions not previously reported in nematodes. There were significant qualitative and semi-quantitative differences in the metabolites formed by male and female worms. In most cases, females metabolized drugs more extensively than males. Adults of the IRE strain were able to form many more metabolites of all the drugs than adults of the ISE strain. Some metabolites were even found only in adults of the IRE strain. These findings suggest that increased drug metabolism may play a role in resistance to benzimidazole drugs in H. contortus. Keywords: Drug resistance, Drug metabolism, Anthelmintics, Benzimidazole, Nematode

Metabolite damage and repair in metabolic engineering design

Energy Technology Data Exchange (ETDEWEB)

Sun, Jiayi; Jeffryes, James G.; Henry, Christopher S.; Bruner, Steven D.; Hanson, Andrew D.

2017-11-01

The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields, and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects.

Diagnosis and treatment of abnormal dental pain

OpenAIRE

Fukuda, Ken-ichi

2016-01-01

Most dental pain is caused by an organic problem such as dental caries, periodontitis, pulpitis, or trauma. Diagnosis and treatment of these symptoms are relatively straightforward. However, patients often also complain of abnormal dental pain that has a non-dental origin, whose diagnosis is challenging. Such abnormal dental pain can be categorized on the basis of its cause as referred pain, neuromodulatory pain, and neuropathic pain. When it is difficult to diagnose a patient's dental pain, ...

Detection of 191 Taxifolin Metabolites and Their Distribution in Rats Using HPLC-ESI-IT-TOF-MSn

Directory of Open Access Journals (Sweden)

Ping Yang

2016-09-01

Full Text Available Taxifolin is a ubiquitous bioactive constituent of foods and herbs. To thoroughly explore its metabolism in vivo, an HPLC-ESI-IT-TOF-MSn method combined with specific metabolite detection strategy was used to detect and identify the metabolites of taxifolin in rats. Of the 191 metabolites tentatively identified, 154 were new metabolites, 69 were new compounds and 32 were dimers. This is the first report of the in vivo biotransformation of a single compound into more than 100 metabolites. Furthermore, acetylamination and pyroglutamic acid conjugation were identified as new metabolic reactions. Seventeen metabolites were found to have various taxifolin-related bioactivities. The potential targets of taxifolin and 63 metabolites were predicted using PharmMapper, with results showing that more than 60 metabolites have the same five targets. Metabolites with the same fragment pattern may have the same pharmacophore. Thus these metabolites may exert the same pharmacological effects as taxifolin through an additive effect on the same drug targets. This observation indicates that taxifolin is bioactive not only in the parent form, but also through its metabolites. These findings enhance understanding of the metabolism and effective forms of taxifolin and may provide further insight of the beneficial effects of taxifolin and its derivatives.

Tracer kinetic modelling of receptor data with mathematical metabolite correction

International Nuclear Information System (INIS)

Burger, C.; Buck, A.

1996-01-01

Quantitation of metabolic processes with dynamic positron emission tomography (PET) and tracer kinetic modelling relies on the time course of authentic ligand in plasma, i.e. the input curve. The determination of the latter often requires the measurement of labelled metabilites, a laborious procedure. In this study we examined the possibility of mathematical metabolite correction, which might obviate the need for actual metabolite measurements. Mathematical metabilite correction was implemented by estimating the input curve together with kinetic tissue parameters. The general feasibility of the approach was evaluated in a Monte Carlo simulation using a two tissue compartment model. The method was then applied to a series of five human carbon-11 iomazenil PET studies. The measured cerebral tissue time-activity curves were fitted with a single tissue compartment model. For mathematical metabolite correction the input curve following the peak was approximated by a sum of three decaying exponentials, the amplitudes and characteristic half-times of which were then estimated by the fitting routine. In the simulation study the parameters used to generate synthetic tissue time-activity curves (K 1 -k 4 ) were refitted with reasonable identifiability when using mathematical metabolite correciton. Absolute quantitation of distribution volumes was found to be possible provided that the metabolite and the kinetic models are adequate. If the kinetic model is oversimplified, the linearity of the correlation between true and estimated distribution volumes is still maintained, although the linear regression becomes dependent on the input curve. These simulation results were confirmed when applying mathematical metabolite correction to the 11 C iomazenil study. Estimates of the distribution volume calculated with a measured input curve were linearly related to the estimates calculated using mathematical metabolite correction with correlation coefficients >0.990. (orig./MG)

Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells

Directory of Open Access Journals (Sweden)

Peng Liu

2018-05-01

Full Text Available Sulforaphane (SFN exhibits chemopreventive effects through various mechanisms. However, few studies have focused on the bioactivities of its metabolites. Here, three metabolites derived from SFN were studied, known as sulforaphane glutathione, sulforaphane cysteine and sulforaphane-N-acetylcysteine. Their effects on cell viability, DNA damage, tumorigenicity, cell migration and adhesion were measured in human hepatoma HepG2 cells, and their anti-angiogenetic effects were determined in a 3D co-culture model of human umbilical vein endothelial cells (HUVECs and pericytes. Results indicated that these metabolites at high doses decreased cancer cell viability, induced DNA damage and inhibited motility, and impaired endothelial cell migration and tube formation. Additionally, pre-treatment with low doses of SFN metabolites protected against H2O2 challenge. The activation of the nuclear factor E2-related factor 2 (Nrf2-antioxidant response element (ARE pathway and the induction of intracellular glutathione (GSH played an important role in the cytoprotective effects of SFN metabolites. In conclusion, SFN metabolites exhibited similar cytotoxic and cytoprotective effects to SFN, which proves the necessity to study the mechanisms of action of not only SFN but also of its metabolites. Based on the different tissue distribution profiles of these metabolites, the most relevant chemical forms can be selected for targeted chemoprevention.

Urinary excretion of androgen metabolites, comparison with excretion of radioactive metabolites after injection of [4-14C]testosterone

International Nuclear Information System (INIS)

Deslypere, J.P.; Sayed, A.; Vermeulen, A.; Wiers, P.W.

1981-01-01

The influence of age on the metabolic pattern of [4- 14 C]testosterone was studied in 20 young and 8 elderly males and compared to the metabolic pattern of endogenous androgens; the latter was also studied in 16 young and 8 elderly women. In both young and elderly males, androsterone and aetiocholanolone glucuronide represent 65% of [4- 14 C]testosterone metabolites: together with their suephoconjugates as well as with 5α- and 5β-androstane-3α, 17β-diol they represent even more than 75% of total urinary metabolites. The 5α/5β ratio of metabolites of [4- 14 C]testosterone was significantly (P 14 C]testosterone metabolites was generally higher than the ratio of metabolites of endogenous androgens, suggesting that the transformation of T to ring A saturated metabolites occurs at least partially in another compartment than the transformation of DHEA to these metabolites. For both [4- 14 C]testosterone and endogenous androgen metabolites we observed a statistically significant reduction of the 5α/5β ratio with age, a general phenomenon in both males and females. This reduction concern also 11-OH-androst-4-ene-3.17-dione metabolism. Neither sex hormone levels, nor specific binding seems to determine this age dependent shift; neither is there convincing evidence for latent hypothyroisism or liver dysfunction in the elderly. An age associated primary decrease of the 5α-reductase activity seems the most likely explanation. (author)

Measurement of hydroxylated PCB metabolites for Slovakia maternal blood serums

Energy Technology Data Exchange (ETDEWEB)

Park, J.S.; Athanasiadou, M; Bergman, A. [Stockholm Univ., Stockholm (Sweden); Charles, J.; Zhao, G.; Hertz-Picciotto, I. [California Univ., Sacramento, CA (United States); Petrik, J.; Kocan, A; Trnovec, T. [Bratislava Inst. of Preventive and Clinical Medicine, Bratislava (Slovakia)

2005-07-01

Although it is known that polychlorinated biphenyls (PCBs) have adverse impacts on human health, it is not clear if human health impacts are caused by the PCBs or their related hydroxylated (OH) PCB metabolite compounds. This study measured OH-PCB metabolites in the maternal blood serum specimens from the Svidnik and Michalovce areas in eastern Slovakia where PCBs were intensively produced and inadequately disposed. The aim of the study was to characterize and quantify levels of specific OH-PCB metabolites in Slovakian maternal serums exposed to high environmental PCB levels. All specimens were analyzed for PCBs, and a subset of the samples was analyzed for OH-PCB metabolites. The Wallenburg blood extraction method was adopted to separate the OH-PCBs from the blood serums. Final eluates and calibration standards were spiked with PCB209 as an injection standard before gas chromatography (GC) analysis. OH-PCBs in the samples range from 75{+-}9 per cent to 101{+-}11 per cent. Median concentrations of OH-PCB metabolites of Michalovce samples were approximately twice as high as for the Svidnik samples. Concentrations of OH-PCBs of Michalovce blood samples were comparable to samples obtained from northern Canadian female Inuit and Faroe Island females, and were considered to be among the highest OH-PCB concentrations obtained in human blood. It was concluded that further research is needed to understand the placental transfer of OH-PCBs to the fetus, as well as epidemiological approaches to determine the relationship between the exposure of OH-PCB metabolites and child development. 12 refs., 2 figs.

Metabolite profiling of somatic embryos of Cyclamen persicum in comparison to zygotic embryos, endosperm and testa

Directory of Open Access Journals (Sweden)

Traud eWinkelmann

2015-08-01

Full Text Available Somatic embryogenesis has been shown to be an efficient in vitro plant regeneration system for many crops such as the important ornamental plant Cyclamen persicum, for which this regeneration pathway of somatic embryogenesis is of interest for the vegetative propagation of parental lines as well as elite plants. However, somatic embryogenesis is not commercially used in many crops due to several unsolved problems, such as malformations, asynchronous development, deficiencies in maturation and germination of somatic embryos. In contrast, zygotic embryos in seeds develop and germinate without abnormalities in most cases. Instead of time-consuming and labor-intensive experiments involving tests of different in vitro culture conditions and plant growth regulator supplements, we follow a more directed approach. Zygotic embryos served as a reference and were compared to somatic embryos in metabolomic analyses allowing the future optimization of the in vitro system. The aims of this study were to detect differences in the metabolite profiles of torpedo stage somatic and zygotic embryos of C. persicum. Moreover, major metabolites in endosperm and testa were identified and quantified.Two sets of extracts of two to four biological replicates each were analyzed. In total 52 metabolites were identified and quantified in the different tissues. One of the most significant differences between somatic and zygotic embryos was that the proline concentration in the zygotic embryos was about 40 times higher than that found in somatic embryos. Epicatechin, a scavenger for reactive oxygen species, was found in highest abundance in the testa. Sucrose, the most abundant metabolite was detected in significantly higher concentrations in zygotic embryos. Also, a yet unknown trisaccharide, was significantly enriched in zygotic embryos.

Investigation on Abnormal Iron Metabolism and Related Inflammation in Parkinson Disease Patients with Probable RBD

Science.gov (United States)

Hu, Yang; Yu, Shu-Yang; Zuo, Li-Jun; Piao, Ying-Shan; Cao, Chen-Jie; Wang, Fang; Chen, Ze-Jie; Du, Yang; Lian, Teng-Hong; Liu, Gai-Fen; Wang, Ya-Jie; Chan, Piu; Chen, Sheng-Di; Wang, Xiao-Min; Zhang, Wei

2015-01-01

Objective To investigate potential mechanisms involving abnormal iron metabolism and related inflammation in Parkinson disease (PD) patients with probable rapid eye movement sleep behavior disorder (PRBD). Methods Total 210 PD patients and 31 controls were consecutively recruited. PD patients were evaluated by RBD Screening Questionnaire (RBDSQ) and classified into PRBD and probable no RBD (NPRBD) groups. Demographics information were recorded and clinical symptoms were evaluated by series of rating scales. Levels of iron and related proteins and inflammatory factors in cerebrospinal fluid (CSF) and serum were detected. Comparisons among control, NPRBD and PRBD groups and correlation analyses between RBDSQ score and levels of above factors were performed. Results (1)The frequency of PRBD in PD patients is 31.90%. (2)PRBD group has longer disease duration, more advanced disease stage, severer motor symptoms and more non-motor symptoms than NPRBD group. (3)In CSF, levels of iron, transferrin, NO and IL–1β in PRBD group are prominently increased. RBDSQ score is positively correlated with the levels of iron, transferrin, NO and IL–1β in PD group. Iron level is positively correlated with the levels of NO and IL–1β in PD group. (4)In serum, transferrin level is prominently decreased in PRBD group. PGE2 level in PRBD group is drastically enhanced. RBDSQ score exhibits a positive correlation with PGE2 level in PD group. Conclusions PRBD is common in PD patients. PRBD group has severer motor symptoms and more non-motor symptoms. Excessive iron in brain resulted from abnormal iron metabolism in central and peripheral systems is correlated with PRBD through neuroinflammation. PMID:26431210

Vascular alterations in PDAPP mice after anti-Aβ immunotherapy: Implications for amyloid-related imaging abnormalities.

Science.gov (United States)

Zago, Wagner; Schroeter, Sally; Guido, Teresa; Khan, Karen; Seubert, Peter; Yednock, Ted; Schenk, Dale; Gregg, Keith M; Games, Dora; Bard, Frédérique; Kinney, Gene G

2013-10-01

Clinical studies of β-amyloid (Aβ) immunotherapy in Alzheimer's disease (AD) patients have demonstrated reduction of central Aβ plaque by positron emission tomography (PET) imaging and the appearance of amyloid-related imaging abnormalities (ARIA). To better understand the relationship between ARIA and the pathophysiology of AD, we undertook a series of studies in PDAPP mice evaluating vascular alterations in the context of central Aβ pathology and after anti-Aβ immunotherapy. We analyzed PDAPP mice treated with either 3 mg/kg/week of 3D6, the murine form of bapineuzumab, or isotype control antibodies for periods ranging from 1 to 36 weeks and evaluated the vascular alterations in the context of Aβ pathology and after anti-Aβ immunotherapy. The number of mice in each treatment group ranged from 26 to 39 and a total of 345 animals were analyzed. The central vasculature displayed morphological abnormalities associated with vascular Aβ deposits. Treatment with 3D6 antibody induced clearance of vascular Aβ that was spatially and temporally associated with a transient increase in microhemorrhage and in capillary Aβ deposition. Microhemorrhage resolved over a time period that was associated with a recovery of vascular morphology and a decrease in capillary Aβ accumulation. These data suggest that vascular leakage events, such as microhemorrhage, may be related to the removal of vascular Aβ. With continued treatment, this initial susceptibility period is followed by restoration of vascular morphology and reduced vulnerability to further vascular leakage events. The data collectively suggested a vascular amyloid clearance model of ARIA, which accounts for the currently known risk factors for the incidence of ARIA in clinical studies. Copyright © 2013. Published by Elsevier Inc.

Online effects of transcranial direct current stimulation on prefrontal metabolites in gambling disorder.

Science.gov (United States)

Dickler, Maya; Lenglos, Christophe; Renauld, Emmanuelle; Ferland, Francine; Edden, Richard A; Leblond, Jean; Fecteau, Shirley

2018-03-15

Gambling disorder is characterized by persistent maladaptive gambling behaviors and is now considered among substance-related and addictive disorders. There is still unmet therapeutic need for these clinical populations, however recent advances indicate that interventions targeting the Glutamatergic/GABAergic system hold promise in reducing symptoms in substance-related and addictive disorders, including gambling disorder. There is some data indicating that transcranial direct current stimulation may hold clinical benefits in substance use disorders and modulate levels of brain metabolites including glutamate and GABA. The goal of the present work was to test whether this non-invasive neurostimulation method modulates key metabolites in gambling disorder. We conducted a sham-controlled, crossover, randomized study, blinded at two levels in order to characterize the effects of transcranial direct current stimulation over the dorsolateral prefrontal cortex on neural metabolites levels in sixteen patients with gambling disorder. Metabolite levels were measured with magnetic resonance spectroscopy from the right dorsolateral prefrontal cortex and the right striatum during active and sham stimulation. Active as compared to sham stimulation elevated prefrontal GABA levels. There were no significant changes between stimulation conditions in prefrontal glutamate + glutamine and N-acetyl Aspartate, or in striatal metabolite levels. Results also indicated positive correlations between metabolite levels during active, but not sham, stimulation and levels of risk taking, impulsivity and craving. Our findings suggest that transcranial direct current stimulation can modulate GABA levels in patients with gambling disorder which may represent an interesting future therapeutic avenue. Copyright © 2017 Elsevier Ltd. All rights reserved.

Secondary metabolites in fungus-plant interactions

Science.gov (United States)

Pusztahelyi, Tünde; Holb, Imre J.; Pócsi, István

2015-01-01

Fungi and plants are rich sources of thousands of secondary metabolites. The genetically coded possibilities for secondary metabolite production, the stimuli of the production, and the special phytotoxins basically determine the microscopic fungi-host plant interactions and the pathogenic lifestyle of fungi. The review introduces plant secondary metabolites usually with antifungal effect as well as the importance of signaling molecules in induced systemic resistance and systemic acquired resistance processes. The review also concerns the mimicking of plant effector molecules like auxins, gibberellins and abscisic acid by fungal secondary metabolites that modulate plant growth or even can subvert the plant defense responses such as programmed cell death to gain nutrients for fungal growth and colonization. It also looks through the special secondary metabolite production and host selective toxins of some significant fungal pathogens and the plant response in form of phytoalexin production. New results coming from genome and transcriptional analyses in context of selected fungal pathogens and their hosts are also discussed. PMID:26300892

Widespread occurrence of neuro-active pharmaceuticals and metabolites in 24 Minnesota rivers and wastewaters

Science.gov (United States)

Writer, Jeffrey; Ferrer, Imma; Barber, Larry B.; Thurman, E. Michael

2013-01-01

Concentrations of 17 neuro-active pharmaceuticals and their major metabolites (bupropion, hydroxy-bupropion, erythro-hydrobupropion, threo-hydrobupropion, carbamazepine, 10,11,-dihydro-10,11,-dihydroxycarbamazepine, 10-hydroxy-carbamazepine, citalopram, N-desmethyl-citalopram, fluoxetine, norfluoxetine, gabapentin, lamotrigine, 2-N-glucuronide-lamotrigine, oxcarbazepine, venlafaxine and O-desmethyl-venlafaxine), were measured in treated wastewater and receiving surface waters from 24 locations across Minnesota, USA. The analysis of upstream and downstream sampling sites indicated that the wastewater treatment plants were the major source of the neuro-active pharmaceuticals and associated metabolites in surface waters of Minnesota. Concentrations of parent compound and the associated metabolite varied substantially between treatment plants (concentrations ± standard deviation of the parent compound relative to its major metabolite) as illustrated by the following examples; bupropion and hydrobupropion 700 ± 1000 ng L−1, 2100 ± 1700 ng L−1, carbamazepine and 10-hydroxy-carbamazepine 480 ± 380 ng L−1, 360 ± 400 ng L−1, venlafaxine and O-desmethyl-venlafaxine 1400 ± 1300 ng L−1, 1800 ± 2300 ng L−1. Metabolites of the neuro-active compounds were commonly found at higher or comparable concentrations to the parent compounds in wastewater effluent and the receiving surface water. Neuro-active pharmaceuticals and associated metabolites were detected only sporadically in samples upstream from the effluent outfall. Metabolite to parent ratios were used to evaluate transformation, and we determined that ratios in wastewater were much lower than those reported in urine, indicating that the metabolites are relatively more labile than the parent compounds in the treatment plants and in receiving waters. The widespread occurrence of neuro-active pharmaceuticals and metabolites in Minnesota effluents and surface waters indicate that

SPE-NMR metabolite sub-profiling of urine

NARCIS (Netherlands)

Jacobs, D.M.; Spiesser, L.; Garnier, M.; Roo, de N.; Dorsten, van F.; Hollebrands, B.; Velzen, van E.; Draijer, R.; Duynhoven, van J.P.M.

2012-01-01

NMR-based metabolite profiling of urine is a fast and reproducible method for detection of numerous metabolites with diverse chemical properties. However, signal overlap in the (1)H NMR profiles of human urine may hamper quantification and identification of metabolites. Therefore, a new method has

Metabolite damage and repair in metabolic engineering design.

Science.gov (United States)

Sun, Jiayi; Jeffryes, James G; Henry, Christopher S; Bruner, Steven D; Hanson, Andrew D

2017-11-01

The necessarily sharp focus of metabolic engineering and metabolic synthetic biology on pathways and their fluxes has tended to divert attention from the damaging enzymatic and chemical side-reactions that pathway metabolites can undergo. Although historically overlooked and underappreciated, such metabolite damage reactions are now known to occur throughout metabolism and to generate (formerly enigmatic) peaks detected in metabolomics datasets. It is also now known that metabolite damage is often countered by dedicated repair enzymes that undo or prevent it. Metabolite damage and repair are highly relevant to engineered pathway design: metabolite damage reactions can reduce flux rates and product yields, and repair enzymes can provide robust, host-independent solutions. Herein, after introducing the core principles of metabolite damage and repair, we use case histories to document how damage and repair processes affect efficient operation of engineered pathways - particularly those that are heterologous, non-natural, or cell-free. We then review how metabolite damage reactions can be predicted, how repair reactions can be prospected, and how metabolite damage and repair can be built into genome-scale metabolic models. Lastly, we propose a versatile 'plug and play' set of well-characterized metabolite repair enzymes to solve metabolite damage problems known or likely to occur in metabolic engineering and synthetic biology projects. Copyright © 2017 International Metabolic Engineering Society. All rights reserved.

Trophic transfer of pyrene metabolites between aquatic invertebrates

International Nuclear Information System (INIS)

Carrasco Navarro, V.; Leppänen, M.T.; Kukkonen, J.V.K.; Godoy Olmos, S.

2013-01-01

The trophic transfer of pyrene metabolites was studied using Gammarus setosus as a predator and the invertebrates Lumbriculus variegatus and Chironomus riparius as prey. The results obtained by liquid scintillation counting confirmed that the pyrene metabolites produced by the aquatic invertebrates L. variegatus and C. riparius were transferred to G. setosus through the diet. More detailed analyses by liquid chromatography discovered that two of the metabolites produced by C. riparius appeared in the chromatograms of G. setosus tissue extracts, proving their trophic transfer. These metabolites were not present in chromatograms of G. setosus exclusively exposed to pyrene. The present study supports the trophic transfer of PAH metabolites between benthic macroinvertebrates and common species of an arctic amphipod. As some PAH metabolites are more toxic than the parent compounds, the present study raises concerns about the consequences of their trophic transfer and the fate and effects of PAHs in natural environments. - Highlights: ► The trophic transfer of pyrene metabolites between invertebrates was evaluated. ► Biotransformation of pyrene by L. variegatus and C. riparius is different. ► Metabolites produced by L. variegatus and C. riparius are transferred to G. setosus. ► Specifically, two metabolites produced by C. riparius were transferred. - Some of the pyrene metabolites produced by the model invertebrates L. variegatus and C. riparius are transferred to G. setosus through the diet, proving their trophic transfer.

Correlative analysis of metabolite profiling of Danggui Buxue Tang in rat biological fluids by rapid resolution LC-TOF/MS.

Science.gov (United States)

Li, Chang-Yin; Qi, Lian-Wen; Li, Ping

2011-04-28

In this work, the metabolite profiles of Danggui Buxue Tang (DBT) in rat bile and plasma were qualitatively described, and the possible metabolic pathways of DBT were subsequently proposed. Emphasis was put on correlative analysis of metabolite profiling in different biological fluids. After oral administration of DBT, bile and plasma samples were collected and pretreated by solid phase extraction. Rapid resolution liquid chromatography coupled to time-of-flight mass spectrometry (RRLC-TOFMS) was used for characterization of DBT-related compounds (parent compounds and metabolites) in biological matrices. A total of 142 metabolites were detected and tentatively identified from the drug-containing bile and plasma samples. Metabolite profiling shows that rat bile contained relatively more glutathione-derived conjugates, more saponins compounds and more diverse forms of metabolites than urine. The metabolite profile in plasma revealed that glucuronide conjugates of isoflavonoids, dimmers, acetylcysteine conjugates and parent form of phthalides, as well as saponin aglycones were the major circulating forms of DBT. Collectively, the metabolite profile analysis of DBT in different biological matrices provided a comprehensive understanding of the in vivo metabolic fates of constituents in DBT. Copyright © 2011 Elsevier B.V. All rights reserved.

Race and sex differences in small-molecule metabolites and metabolic hormones in overweight and obese adults.

Science.gov (United States)

Patel, Mahesh J; Batch, Bryan C; Svetkey, Laura P; Bain, James R; Turer, Christy Boling; Haynes, Carol; Muehlbauer, Michael J; Stevens, Robert D; Newgard, Christopher B; Shah, Svati H

2013-12-01

In overweight/obese individuals, cardiometabolic risk factors differ by race and sex categories. Small-molecule metabolites and metabolic hormone levels might also differ across these categories and contribute to risk factor heterogeneity. To explore this possibility, we performed a cross-sectional analysis of fasting plasma levels of 69 small-molecule metabolites and 13 metabolic hormones in 500 overweight/obese adults who participated in the Weight Loss Maintenance trial. Principal-components analysis (PCA) was used for reduction of metabolite data. Race and sex-stratified comparisons of metabolite factors and metabolic hormones were performed. African Americans represented 37.4% of the study participants, and females 63.0%. Of thirteen metabolite factors identified, three differed by race and sex: levels of factor 3 (branched-chain amino acids and related metabolites, phormones regulating body weight homeostasis. Among overweight/obese adults, there are significant race and sex differences in small-molecule metabolites and metabolic hormones; these differences may contribute to risk factor heterogeneity across race and sex subgroups and should be considered in future investigations with circulating metabolites and metabolic hormones.

Abnormalities in Functional Connectivity in Collegiate Football Athletes with and without a Concussion History: Implications and Role of Neuroactive Kynurenine Pathway Metabolites.

Science.gov (United States)

Meier, Timothy B; Lancaster, Melissa A; Mayer, Andrew R; Teague, T Kent; Savitz, Jonathan

2017-02-15

There is a great need to identify potential long-term consequences of contact sport exposure and to identify molecular pathways that may be associated with these changes. We tested the hypothesis that football players with (Ath-mTBI) (n = 25) and without a concussion history (Ath) (n = 24) have altered resting state functional connectivity in regions with previously documented structural changes relative to healthy controls without football or concussion history (HC) (n = 27). As a secondary aim, we tested the hypothesis that group differences in functional connectivity are moderated by the relative ratio of neuroprotective to neurotoxic metabolites of the kynurenine pathway. Ath-mTBI had significantly increased connectivity of motor cortex to the supplementary motor area relative to Ath and HC. In contrast, both Ath-mTBI and Ath had increased connectivity between the left orbital frontal cortex and the right lateral frontal cortex, and between the left cornu ammonis areas 2 and 3/dentate gyrus (CA2-3/DG) of the hippocampus and the middle and posterior cingulate cortices, relative to HC. The relationship between the ratio of plasma concentrations of kynurenic acid to quinolinic acid (KYNA/QUIN) and left pregenual anterior cingulate cortex connectivity to multiple regions as well as KYNA/QUIN and right CA2-3/DG connectivity to multiple regions differed significantly according to football and concussion history. The results suggest that football exposure with and without concussion history can have a significant effect on intrinsic brain connectivity and implicate the kynurenine metabolic pathway as one potential moderator of functional connectivity dependent on football exposure and concussion history.

The incidence of associated abnormalities in patients with sacrococcygeal teratoma.

Science.gov (United States)

Kremer, Marijke E B; Althof, Jessica F; Derikx, Joep P M; van Baren, Robertine; Heij, Hugo A; Wijnen, Marc H W A; Wijnen, René M H; van der Zee, David C; van Heurn, L W Ernest

2018-01-31

Gross genetic causes for SCT are unknown; however, it might be associated with other abnormalities. We assessed the incidence of associated abnormalities in a large national cohort of neonates with SCT and aimed to identify predictive risk factors. The medical records were reviewed of 235 consecutive neonates with SCT treated at the six pediatric surgical centers in the Netherlands from 1970 to 2010. Potential risk factors for associated abnormalities analyzed included sex, gestational age, tumor-volume/histology and Altman-classification. In 76 patients (32.3%) at least one associated abnormality was diagnosed, with hydronephrosis as the most common (16.2%) and hip dysplasia in 4.3%. Multiple abnormalities were documented for 21 (9.0%). Prematurity and Altman type IV SCT were associated with an increased risk of any associated abnormality. No association between increased tumor-volume and hydronephrosis or hip dysplasia was found. Patients with type IV Altman SCT had a fourfold risk of suffering from hydronephrosis compared to Altman type I SCT. SCT was associated with other abnormalities in one-third of children. Some were tumor-related while others were related to prematurity or occurred sporadically. In contrast to clinically obvious anomalies, hip dysplasia or hydronephrosis might be latently present with more subtle clinical presentation. We therefore suggest renal- and hip-ultrasound in all patients, certainly those with Altman type IV SCT. Level II (retrospective study). Copyright © 2018. Published by Elsevier Inc.

Are ECG abnormalities in Noonan syndrome characteristic for the syndrome?

Science.gov (United States)

Raaijmakers, R; Noordam, C; Noonan, J A; Croonen, E A; van der Burgt, C J A M; Draaisma, J M T

2008-12-01

Of all patients with Noonan syndrome, 50-90% have one or more congenital heart defects. The most frequent occurring are pulmonary stenosis (PS) and hypertrophic cardiomyopathy. The electrocardiogram (ECG) of a patient with Noonan syndrome often shows a characteristic pattern, with a left axis deviation, abnormal R/S ratio over the left precordium, and an abnormal Q wave. The objective of this study was to determine if these ECG characteristics are an independent feature of the Noonan syndrome or if they are related to the congenital heart defect. A cohort study was performed with 118 patients from two university hospitals in the United States and in The Netherlands. All patients were diagnosed with definite Noonan syndrome and had had an ECG and echocardiography. Sixty-nine patients (58%) had characteristic abnormalities of the ECG. In the patient group without a cardiac defect (n = 21), ten patients had a characteristic ECG abnormality. There was no statistical relationship between the presence of a characteristic ECG abnormality and the presence of a cardiac defect (p = 0.33). Patients with hypertrophic cardiomyopathy had more ECG abnormalities in total (p = 0.05), without correlation with a specific ECG abnormality. We conclude that the ECG features in patients with Noonan syndrome are characteristic for the syndrome and are not related to a specific cardiac defect. An ECG is very useful in the diagnosis of Noonan syndrome; every child with a Noonan phenotype should have an ECG and echocardiogram for evaluation.

Bayesian deconvolution and quantification of metabolites in complex 1D NMR spectra using BATMAN.

Science.gov (United States)

Hao, Jie; Liebeke, Manuel; Astle, William; De Iorio, Maria; Bundy, Jacob G; Ebbels, Timothy M D

2014-01-01

Data processing for 1D NMR spectra is a key bottleneck for metabolomic and other complex-mixture studies, particularly where quantitative data on individual metabolites are required. We present a protocol for automated metabolite deconvolution and quantification from complex NMR spectra by using the Bayesian automated metabolite analyzer for NMR (BATMAN) R package. BATMAN models resonances on the basis of a user-controllable set of templates, each of which specifies the chemical shifts, J-couplings and relative peak intensities for a single metabolite. Peaks are allowed to shift position slightly between spectra, and peak widths are allowed to vary by user-specified amounts. NMR signals not captured by the templates are modeled non-parametrically by using wavelets. The protocol covers setting up user template libraries, optimizing algorithmic input parameters, improving prior information on peak positions, quality control and evaluation of outputs. The outputs include relative concentration estimates for named metabolites together with associated Bayesian uncertainty estimates, as well as the fit of the remainder of the spectrum using wavelets. Graphical diagnostics allow the user to examine the quality of the fit for multiple spectra simultaneously. This approach offers a workflow to analyze large numbers of spectra and is expected to be useful in a wide range of metabolomics studies.

Urinary estrogen metabolites and breast cancer

DEFF Research Database (Denmark)

Dallal, Cher M; Stone, Roslyn A; Cauley, Jane A

2013-01-01

Background: Circulating estrogens are associated with increased breast cancer risk, yet the role of estrogen metabolites in breast carcinogenesis remains unclear. This combined analysis of 5 published studies evaluates urinary 2-hydroxyestrone (2-OHE1), 16a-hydroxyestrone (16a-OHE1......), and their ratio (2:16a-OHE1) in relation to breast cancer risk. ¿Methods: Primary data on 726 premenopausal women (183 invasive breast cancer cases and 543 controls) and 1,108 postmenopausal women (385 invasive breast cancer cases and 723 controls) were analyzed. Urinary estrogen metabolites were measured using...... premenopausal 2:16a-OHE1 was suggestive of reduced breast cancer risk overall (study-adjusted ORIIIvsI=0.80; 95% CI: 0.49-1.32) and for estrogen receptor negative (ER-) subtype (ORIIIvsI=0.33; 95% CI: 0.13-0.84). Among postmenopausal women, 2:16a-OHE1 was unrelated to breast cancer risk (study-adjusted ORIIIvs...

Secondary metabolites from Ganoderma.

Science.gov (United States)

Baby, Sabulal; Johnson, Anil John; Govindan, Balaji

2015-06-01

Ganoderma is a genus of medicinal mushrooms. This review deals with secondary metabolites isolated from Ganoderma and their biological significance. Phytochemical studies over the last 40years led to the isolation of 431 secondary metabolites from various Ganoderma species. The major secondary compounds isolated are (a) C30 lanostanes (ganoderic acids), (b) C30 lanostanes (aldehydes, alcohols, esters, glycosides, lactones, ketones), (c) C27 lanostanes (lucidenic acids), (d) C27 lanostanes (alcohols, lactones, esters), (e) C24, C25 lanostanes (f) C30 pentacyclic triterpenes, (g) meroterpenoids, (h) farnesyl hydroquinones (meroterpenoids), (i) C15 sesquiterpenoids, (j) steroids, (k) alkaloids, (l) prenyl hydroquinone (m) benzofurans, (n) benzopyran-4-one derivatives and (o) benzenoid derivatives. Ganoderma lucidum is the species extensively studied for its secondary metabolites and biological activities. Ganoderma applanatum, Ganoderma colossum, Ganoderma sinense, Ganoderma cochlear, Ganoderma tsugae, Ganoderma amboinense, Ganoderma orbiforme, Ganoderma resinaceum, Ganoderma hainanense, Ganoderma concinna, Ganoderma pfeifferi, Ganoderma neo-japonicum, Ganoderma tropicum, Ganoderma australe, Ganoderma carnosum, Ganoderma fornicatum, Ganoderma lipsiense (synonym G. applanatum), Ganoderma mastoporum, Ganoderma theaecolum, Ganoderma boninense, Ganoderma capense and Ganoderma annulare are the other Ganoderma species subjected to phytochemical studies. Further phytochemical studies on Ganoderma could lead to the discovery of hitherto unknown biologically active secondary metabolites. Copyright © 2015 Elsevier Ltd. All rights reserved.

Abnormal uterine bleeding

Science.gov (United States)

Anovulatory bleeding; Abnormal uterine bleeding - hormonal; Polymenorrhea - dysfunctional uterine bleeding ... ACOG committee opinion no. 557: Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women. Reaffirmed 2015. www. ...

Antioxidant status, immune system, blood metabolites and carcass ...

African Journals Online (AJOL)

This experiment was conducted to evaluate the effects of dietary turmeric rhizome powder (TP) on performance, blood metabolite, immune system, antioxidant status, and relative weight of organs in pre and post heat stressed broilers. Two hundred and sixty-four (264) day-old male Arian broiler chicks were randomly ...

Confirmatory analysis method for zeranol, its metabolites and related mycotoxins in urine by liquid chromatography-negative ion electrospray tandem mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Bennekom, E.O. van; Brouwer, L.; Laurant, E.H.M.; Hooijerink, H.; Nielen, M.W.F

2002-11-25

The determination of the banned anabolic substance zeranol and the metabolites taleranol and zearalanone in bovine urine is complicated by the occurrence of the structurally-related mycotoxin zearalenone and the corresponding {alpha}- and {beta}-zearalenol metabolites which possess similar estrogenic properties. A liquid chromatography-negative ion electrospray tandem mass spectrometric method is presented for the confirmatory analysis of all six resorcylic acid lactones ('zeranols') in urine samples using deuterium-labelled internal standards. The method was validated as a confirmatory method for bovine urine samples according to new draft EU guidelines and showed good precision and linearity, and CC{alpha} and CC{beta} values of 0.02-0.30 and <1.0 ng ml{sup -1}, respectively. The applicability was demonstrated by comparing the results of an incurred sample with previous results on the same sample obtained by gas chromatography high resolution mass spectrometry. Preliminary data show that following a simple matrix solid phase dispersion clean-up, liver samples from poultry will be amenable to this method as well.

Down's syndrome and related abnormalities in an area of high background radiation in coastal Kerala

International Nuclear Information System (INIS)

Kochupillai, N.; Verma, I.C.; Grewal, M.S.; Ramalingaswami, V.

1976-01-01

It is stated that in a coastal area of Kerala, Southern India, the background radiation is between 1500 and 3000 mR/yr, this being due to the presence of Th-containing monazite mineral in the soil. During an epidemiological study of modular lesions of the thyroid in this area an apparently high prevalence of Down's syndrome and other forms of severe mental retardation was observed. A house-to-house survey of relevant abnormalities in this area was made, and also in a comparable control area without high background radiation. The frequency of chromosome aberrations in a sample of the population in the study and control areas was also investigated. The observations support the view that radiation induces genetic anomalies occur with above average frequency in the population living in the area with high background radiation. Only gross abnormalities evident in clinical examination were recorded. The study and control populations were similar in age and sex structure and general sociologic conditions. Severe mental retardation was the commonest abnormality encountered, and 85% of the abnormalities detected in the study population were genetic in origin, compared with 56% in the control population. Prevalence of Down's syndrome was 0.93 per 1000 in the study population. (U.K.)

Urine - abnormal color

Science.gov (United States)

... medlineplus.gov/ency/article/003139.htm Urine - abnormal color To use the sharing features on this page, please enable JavaScript. The usual color of urine is straw-yellow. Abnormally colored urine ...

Tooth - abnormal colors

Science.gov (United States)

... medlineplus.gov/ency/article/003065.htm Tooth - abnormal colors To use the sharing features on this page, please enable JavaScript. Abnormal tooth color is any color other than white to yellowish- ...

Acute administration of fluoxetine normalizes rapid eye movement sleep abnormality, but not depressive behaviors in olfactory bulbectomized rats.

Science.gov (United States)

Wang, Yi-Qun; Tu, Zhi-Cai; Xu, Xing-Yuan; Li, Rui; Qu, Wei-Min; Urade, Yoshihiro; Huang, Zhi-Li

2012-01-01

In humans, depression is associated with altered rapid eye movement (REM) sleep. However, the exact nature of the relationship between depressive behaviors and sleep abnormalities is debated. In this study, bilateral olfactory bulbectomy (OBX) was carried out to create a model of depression in rats. The sleep-wake profiles were assayed using a cutting-edge sleep bioassay system, and depressive behaviors were evaluated by open field and forced swimming tests. The monoamine content and monoamine metabolite levels in the brain were determined by a HPLC-electrochemical detection system. OBX rats exhibited a significant increase in REM sleep, especially between 15:00 and 18:00 hours during the light period. Acute treatment with fluoxetine (10 mg/kg, i.p.) immediately abolished the OBX-induced increase in REM sleep, but hyperactivity in the open field test and the time spent immobile in the forced swimming test remained unchanged. Neurochemistry studies revealed that acute administration of fluoxetine increased serotonin (5-HT) levels in the hippocampus, thalamus, and midbrain and decreased levels of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA). The ratio of 5-HIAA to 5-HT decreased in almost all regions of the brain. These results indicate that acute administration of fluoxetine can reduce the increase in REM sleep but does not change the depressive behaviors in OBX rats, suggesting that there was no causality between REM sleep abnormalities and depressive behaviors in OBX rats. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Inhibition of Endothelial p53 Improves Metabolic Abnormalities Related to Dietary Obesity

Directory of Open Access Journals (Sweden)

Masataka Yokoyama

2014-06-01

Full Text Available Accumulating evidence has suggested a role for p53 activation in various age-associated conditions. Here, we identified a crucial role of endothelial p53 activation in the regulation of glucose homeostasis. Endothelial expression of p53 was markedly upregulated when mice were fed a high-calorie diet. Disruption of endothelial p53 activation improved dietary inactivation of endothelial nitric oxide synthase that upregulated the expression of peroxisome proliferator-activated receptor-γ coactivator-1α in skeletal muscle, thereby increasing mitochondrial biogenesis and oxygen consumption. Mice with endothelial cell-specific p53 deficiency fed a high-calorie diet showed improvement of insulin sensitivity and less fat accumulation, compared with control littermates. Conversely, upregulation of endothelial p53 caused metabolic abnormalities. These results indicate that inhibition of endothelial p53 could be a novel therapeutic target to block the vicious cycle of cardiovascular and metabolic abnormalities associated with obesity.

Report to Congress on abnormal occurrences, October-December 1981. Quarterly report

International Nuclear Information System (INIS)

1982-05-01

During the report period, there were two abnormal occurrences at the nuclear power plants licensed to operate. One involved a generic concern pertaining to blockage of coolant flow to safety-related systems. The other involved seismic design errors at Diablo Canyon Nuclear Power Plant with subsequent suspension of the fuel load and low power operating license for Unit 1. There were no abnormal occurrences for the other NRC licensees during the report period; the Agreement States reported no abnormal occurrences to the NRC. The report also contains information updating a previously reported abnormal occurrence

Hemorheological abnormalities in human arterial hypertension

Science.gov (United States)

Lo Presti, Rosalia; Hopps, Eugenia; Caimi, Gregorio

2014-05-01

Blood rheology is impaired in hypertensive patients. The alteration involves blood and plasma viscosity, and the erythrocyte behaviour is often abnormal. The hemorheological pattern appears to be related to some pathophysiological mechanisms of hypertension and to organ damage, in particular left ventricular hypertrophy and myocardial ischemia. Abnormalities have been observed in erythrocyte membrane fluidity, explored by fluorescence spectroscopy and electron spin resonance. This may be relevant for red cell flow in microvessels and oxygen delivery to tissues. Although blood viscosity is not a direct target of antihypertensive therapy, the rheological properties of blood play a role in the pathophysiology of arterial hypertension and its vascular complications.

Swimming exercise reverses aging-related contractile abnormalities of female heart by improving structural alterations.

Science.gov (United States)

Ozturk, Nihal; Olgar, Yusuf; Er, Hakan; Kucuk, Murathan; Ozdemir, Semir

2017-01-01

The objective of this study was to examine the effect of swimming exercise on aging-related Ca2+ handling alterations and structural abnormalities of female rat heart. For this purpose, 4-month and 24-month old female rats were used and divided into three following groups: sedentary young (SY), sedentary old (SO), and exercised old (Ex-O). Swimming exercise was performed for 8 weeks (60 min/day, 5 days/week). Myocyte shortening, L-type Ca2+ currents and associated Ca2+ transients were measured from ventricular myocytes at 36 ± 1°C. NOX-4 levels, aconitase activity, glutathione measurements and ultrastructural examination by electron microscopy were conducted in heart tissue. Swimming exercise reversed the reduced shortening and slowed kinetics of aged cardiomyocytes. Although the current density was similar for all groups, Ca2+ transients were higher in SO and Ex-O myocytes with respect to the SY group. Caffeine-induced Ca2+ transients and the integrated NCX current were lower in cardiomyocytes of SY rats compared with other groups, suggesting an increased sarcoplasmic reticulum Ca2+ content in an aged heart. Aging led to upregulated cardiac NOX-4 along with declined aconitase activity. Although it did not reverse these oxidative parameters, swimming exercise achieved a significant increase in glutathione levels and improved structural alterations of old rats' hearts. We conclude that swimming exercise upregulates antioxidant defense capacity and improves structural abnormalities of senescent female rat heart, although it does not change Ca2+ handling alterations further. Thereby, it improves contractile function of aged myocardium by mitigating detrimental effects of oxidative stress.

An expert system for prevention of abnormal event recurrence

International Nuclear Information System (INIS)

Nishiyama, Takuya

1990-01-01

A huge amount of information related to abnormal events occurring in nuclear power plants in Japan and abroad is collected and accumulated in the Nuclear Information Center at CRIEPI. This information contains a variety of knowledge which may be useful for prevention of similar trouble. An expert system named, 'Consultation System for Prevention of Abnormal-Event Recurrence (CSPAR) is being developed with the objective of preventing recurrence of similar abnormal events by offering an effective means of utilizing such knowledge. This paper presents the key points in designing and constructing the system, the system functional outline, and some demonstration examples. (author)

Yeast synthetic biology for high-value metabolites.

Science.gov (United States)

Dai, Zhubo; Liu, Yi; Guo, Juan; Huang, Luqi; Zhang, Xueli

2015-02-01

Traditionally, high-value metabolites have been produced through direct extraction from natural biological sources which are inefficient, given the low abundance of these compounds. On the other hand, these high-value metabolites are usually difficult to be synthesized chemically, due to their complex structures. In the last few years, the discovery of genes involved in the synthetic pathways of these metabolites, combined with advances in synthetic biology tools, has allowed the construction of increasing numbers of yeast cell factories for production of these metabolites from renewable biomass. This review summarizes recent advances in synthetic biology in terms of the use of yeasts as microbial hosts for the identification of the pathways involved in the synthesis, as well as for the production of high-value metabolites. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

Nonparametric Change Point Diagnosis Method of Concrete Dam Crack Behavior Abnormality

OpenAIRE

Li, Zhanchao; Gu, Chongshi; Wu, Zhongru

2013-01-01

The study on diagnosis method of concrete crack behavior abnormality has always been a hot spot and difficulty in the safety monitoring field of hydraulic structure. Based on the performance of concrete dam crack behavior abnormality in parametric statistical model and nonparametric statistical model, the internal relation between concrete dam crack behavior abnormality and statistical change point theory is deeply analyzed from the model structure instability of parametric statistical model ...

Intracellular metabolite profiling of Saccharomyces cerevisiae evolved under furfural.

Science.gov (United States)

Jung, Young Hoon; Kim, Sooah; Yang, Jungwoo; Seo, Jin-Ho; Kim, Kyoung Heon

2017-03-01

Furfural, one of the most common inhibitors in pre-treatment hydrolysates, reduces the cell growth and ethanol production of yeast. Evolutionary engineering has been used as a selection scheme to obtain yeast strains that exhibit furfural tolerance. However, the response of Saccharomyces cerevisiae to furfural at the metabolite level during evolution remains unknown. In this study, evolutionary engineering and metabolomic analyses were applied to determine the effects of furfural on yeasts and their metabolic response to continuous exposure to furfural. After 50 serial transfers of cultures in the presence of furfural, the evolved strains acquired the ability to stably manage its physiological status under the furfural stress. A total of 98 metabolites were identified, and their abundance profiles implied that yeast metabolism was globally regulated. Under the furfural stress, stress-protective molecules and cofactor-related mechanisms were mainly induced in the parental strain. However, during evolution under the furfural stress, S. cerevisiae underwent global metabolic allocations to quickly overcome the stress, particularly by maintaining higher levels of metabolites related to energy generation, cofactor regeneration and recovery from cellular damage. Mapping the mechanisms of furfural tolerance conferred by evolutionary engineering in the present study will be led to rational design of metabolically engineered yeasts. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Autophagy-Related Direct Membrane Import from ER/Cytoplasm into the Vacuole or Apoplast: A Hidden Gateway also for Secondary Metabolites and Phytohormones?

Directory of Open Access Journals (Sweden)

Ivan Kulich

2014-04-01

Full Text Available Transportation of low molecular weight cargoes into the plant vacuole represents an essential plant cell function. Several lines of evidence indicate that autophagy-related direct endoplasmic reticulum (ER to vacuole (and also, apoplast transport plays here a more general role than expected. This route is regulated by autophagy proteins, including recently discovered involvement of the exocyst subcomplex. Traffic from ER into the vacuole bypassing Golgi apparatus (GA acts not only in stress-related cytoplasm recycling or detoxification, but also in developmentally-regulated biopolymer and secondary metabolite import into the vacuole (or apoplast, exemplified by storage proteins and anthocyanins. We propose that this pathway is relevant also for some phytohormones’ (e.g., auxin, abscisic acid (ABA and salicylic acid (SA degradation. We hypothesize that SA is not only an autophagy inducer, but also a cargo for autophagy-related ER to vacuole membrane container delivery and catabolism. ER membrane localized enzymes will potentially enhance the area of biosynthetic reactive surfaces, and also, abundant ER localized membrane importers (e.g., ABC transporters will internalize specific molecular species into the autophagosome biogenesis domain of ER. Such active ER domains may create tubular invaginations of tonoplast into the vacuoles as import intermediates. Packaging of cargos into the ER-derived autophagosome-like containers might be an important mechanism of vacuole and exosome biogenesis and cytoplasm protection against toxic metabolites. A new perspective on metabolic transformations intimately linked to membrane trafficking in plants is emerging.

Comparative Pharmacokinetics of Chlorpyrifos versus its Major Metabolites Following Oral Administration in the Rat

Energy Technology Data Exchange (ETDEWEB)

Busby-Hjerpe, Andrea L.; Campbell, James A.; Smith, Jordan N.; Lee, Sookwang; Poet, Torka S.; Barr, Dana; Timchalk, Charles

2010-01-31

Chlorpyrifos (CPF) is a commonly used diethylphosphorothionate organophosphorus (OP) insecticide. Diethylphosphate (DEP), diethylthiophosphate (DETP) and 3,5,6-trichloro-2-pyridinol (TCPy) are products of in vivo metabolism and environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. Hence, urinary biomonitoring of TCPy, DEP and DETP may be reflective of an individual’s contact with both the parent pesticide and exposure to these metabolites. In the current study, simultaneous dosing of 13C- or 2H- isotopically labeled CPF (13Clabeled CPF, 5 13C on the TCPy ring; or 2H-labeled CPF, diethyl-D10 (deuterium labeled) on the side chain) were exploited to directly compare the pharmacokinetics and metabolism of CPF with TCPy, and DETP. Individual metabolites were co-administered (oral gavage) with the parent compound at equal molar doses (14 μmol/kg; ~5mg/kg CPF). The key objective in the current study was to quantitatively evaluate the pharmacokinetics of the individual metabolites relative to their formation following a dose of CPF. Major differences in the pharmacokinetics between CPF and metabolites doses were observed within the first 3 h of exposure, due to the required metabolism of CPF to initially form TCPy and DETP. Nonetheless, once a substantial amount of CPF has been metabolized (≥ 3 h post-dosing) pharmacokinetics for both treatment groups and metabolites were very comparable. Urinary excretion rates for orally administered TCPy and DETP relative to 13C-CPF or 2H-CPF derived 13C-TCPy and 2H-DETP were consistent with blood pharmacokinetics, and the urinary clearance of metabolite dosed groups were comparable with the results for the 13C- and 2H-CPF groups. Since the pharmacokinetics of the individual metabolites were not modified by co-exposure to 3 CPF; it suggests that environmental exposure to low dose mixtures of pesticides and metabolites will not impact the pharmacokinetics of either.

Application of a new procedure for liquid chromatography/mass spectrometry profiling of plasma amino acid-related metabolites and untargeted shotgun proteomics to identify mechanisms and biomarkers of calcific aortic stenosis.

Science.gov (United States)

Olkowicz, Mariola; Debski, Janusz; Jablonska, Patrycja; Dadlez, Michal; Smolenski, Ryszard T

2017-09-29

Calcific aortic valve stenosis (CAS) increasingly affects our ageing population, but the mechanisms of the disease and its biomarkers are not well established. Recently, plasma amino acid-related metabolite (AA) profiling has attracted attention in studies on pathology and development of biomarkers of cardiovascular diseases, but has not been studied in CAS. To evaluate the potential relationship between CAS and AA metabolome, a new ion-pairing reversed-phase liquid chromatography-tandem mass spectrometry (IP-RPLC-MS/MS) method has been developed and validated for simultaneous determination of 43 AAs in plasma of stenotic patients and age-matched control subjects. Furthermore, untargeted mass spectrometry-based proteomic analysis and confirmatory ELISA assays were performed. The method developed offered high accuracy (intra-assay imprecision averaged 4.4% for all compounds) and sensitivity (LOQ within 0.01-0.5μM). We found that 22 AAs and three AA ratios significantly changed in the CAS group as compared to control. The most pronounced differences were observed in urea cycle-related AAs and branched-chain AA (BCAA)-related AAs. The contents of asymmetric dimethylarginine (ADMA) and its monomethylated derivative (NMMA) were increased by 30-64% with CAS. The arginine/ADMA and Fischer's ratios as well as arginine, homoarginine, ADMA, symmetric dimethylarginine, hydroxyproline, betaine and 3-methylhistidine correlated with cardiac function-related parameters and concomitant systemic factors in the CAS patients. The results of proteomic analysis were consistent with involvement of inflammation, lipid abnormalities, hemostasis and extracellular matrix remodeling in CAS. In conclusion, changes in plasma AA profile and protein pattern that we identified in CAS provide information relevant to pathomechanisms and may deliver new biomarkers of the disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of metabolites of the tryptase inhibitor CRA-9249: observation of a metabolite derived from an unexpected hydroxylation pathway.

Science.gov (United States)

Yu, Walter; Dener, Jeffrey M; Dickman, Daniel A; Grothaus, Paul; Ling, Yun; Liu, Liang; Havel, Chris; Malesky, Kimberly; Mahajan, Tania; O'Brian, Colin; Shelton, Emma J; Sperandio, David; Tong, Zhiwei; Yee, Robert; Mordenti, Joyce J

2006-08-01

The metabolites of the tryptase inhibitor CRA-9249 were identified after exposure to liver microsomes. CRA-9249 was found to be degraded rapidly in liver microsomes from rabbit, dog, cynomolgus monkey, and human, and less rapidly in microsomes from rat. The key metabolites included cleavage of an aryl ether, in addition to an unexpected hydroxylation of the amide side chain adjacent to the amide nitrogen. The chemical structures of both metabolites were confirmed by synthesis and comparison to material isolated from the liver microsomes. Several suspected hydroxylated metabolites were also synthesized and analyzed as part of the structure identification process.

Hydrophobicity and charge shape cellular metabolite concentrations.

Directory of Open Access Journals (Sweden)

Arren Bar-Even

2011-10-01

Full Text Available What governs the concentrations of metabolites within living cells? Beyond specific metabolic and enzymatic considerations, are there global trends that affect their values? We hypothesize that the physico-chemical properties of metabolites considerably affect their in-vivo concentrations. The recently achieved experimental capability to measure the concentrations of many metabolites simultaneously has made the testing of this hypothesis possible. Here, we analyze such recently available data sets of metabolite concentrations within E. coli, S. cerevisiae, B. subtilis and human. Overall, these data sets encompass more than twenty conditions, each containing dozens (28-108 of simultaneously measured metabolites. We test for correlations with various physico-chemical properties and find that the number of charged atoms, non-polar surface area, lipophilicity and solubility consistently correlate with concentration. In most data sets, a change in one of these properties elicits a ~100 fold increase in metabolite concentrations. We find that the non-polar surface area and number of charged atoms account for almost half of the variation in concentrations in the most reliable and comprehensive data set. Analyzing specific groups of metabolites, such as amino-acids or phosphorylated nucleotides, reveals even a higher dependence of concentration on hydrophobicity. We suggest that these findings can be explained by evolutionary constraints imposed on metabolite concentrations and discuss possible selective pressures that can account for them. These include the reduction of solute leakage through the lipid membrane, avoidance of deleterious aggregates and reduction of non-specific hydrophobic binding. By highlighting the global constraints imposed on metabolic pathways, future research could shed light onto aspects of biochemical evolution and the chemical constraints that bound metabolic engineering efforts.

New metabolites of hongdenafil, homosildenafil and hydroxyhomosildenafil.

Science.gov (United States)

Yeo, Miseon; Park, Yujin; Lee, Heesang; Choe, Sanggil; Baek, Seung-Hoon; Kim, Hye Kyung; Pyo, Jae Sung

2018-02-05

Recently, illegal sildenafil analogues have emerged, causing serious social issues. In spite of the importance of sildenafil analogues, their metabolic profiles or clinical effects have not been reported yet. In this study, new metabolites of illegal sildenafil analogues such as hongdenafil, homosildenafil, and hydroxyhomosildenafil were determined using liquid chromatography quadrupole-time of flight mass spectrometry (LC-Q-TOF-MS) and tandem mass spectrometry (LC-Q-TOF-MS/MS). To prepare metabolic samples, in vitro and in vivo studies were performed. For in vivo metabolites analysis, urine and feces samples of rats treated with sildenafil analogues were analyzed. For in vitro metabolites analysis, human liver microsomes incubated with sildenafil analogues were extracted and analyzed. All metabolites were characterized by LC-Q-TOF-MS and LC-Q-TOF-MS/MS. As a result, five, six, and seven metabolites were determined in hongdenafil, homosildenafil, and hydroxyhomosildenafil treated samples, respectively. These results could be applied to forensic science and other analytical fields. Moreover, these newly identified metabolites could be used as fundamental data to determine the side effect and toxicity of illegal sildenafil analogues. Copyright © 2017 Elsevier B.V. All rights reserved.

Dysbiosis of gut microbiota and microbial metabolites in Parkinson's Disease.

Science.gov (United States)

Sun, Meng-Fei; Shen, Yan-Qin

2018-04-26

Gut microbial dysbiosis and alteration of microbial metabolites in Parkinson's disease (PD) have been increasingly reported. Dysbiosis in the composition and abundance of gut microbiota can affect both the enteric nervous system and the central nervous system (CNS), indicating the existence of a microbiota-gut-brain axis and thereby causing CNS diseases. Disturbance of the microbiota-gut-brain axis has been linked to specific microbial products that are related to gut inflammation and neuroinflammation. Future directions should therefore focus on the exploration of specific gut microbes or microbial metabolites that contribute to the development of PD. Microbiota-targeted interventions, such as antibiotics, probiotics and fecal microbiota transplantation, have been shown to favorably affect host health. In this review, recent findings regarding alterations and the role of gut microbiota and microbial metabolites in PD are summarized, and potential molecular mechanisms and microbiota-targeted interventions in PD are discussed. Copyright © 2018. Published by Elsevier B.V.

Abnormal pressures as hydrodynamic phenomena

Science.gov (United States)

Neuzil, C.E.

1995-01-01

So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author

Diagnostic accuracy of post mortem MRI for abdominal abnormalities in foetuses and children

Energy Technology Data Exchange (ETDEWEB)

Arthurs, Owen J., E-mail: owen.arthurs@gosh.nhs.uk [Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); Institute of Child Health, UCL, London (United Kingdom); Thayyil, Sudhin, E-mail: s.thayyil@imperial.ac.uk [Perinatal Neurology and Neonatology, Imperial College London, London (United Kingdom); Owens, Catherine M., E-mail: Catherine.owens@gosh.nhs.uk [Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); Centre for Cardiovascular Imaging, UCL Institute of Cardiovascular Science, London (United Kingdom); Cardiorespiratory Division, Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); Olsen, Oystein E., E-mail: oystein.olsen@gosh.nhs.uk [Department of Radiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); Institute of Child Health, UCL, London (United Kingdom); Wade, Angie, E-mail: a.wade@ucl.ac.uk [Clinical Epidemiology, Nutrition and Biostatistics Section, UCL Institute of Child health, London (United Kingdom); Addison, Shea, E-mail: shea.addison@imperial.ac.uk [Perinatal Neurology and Neonatology, Imperial College London, London (United Kingdom); Jones, Rod, E-mail: rod.jones@gosh.nhs.uk [Centre for Cardiovascular Imaging, UCL Institute of Cardiovascular Science, London (United Kingdom); Cardiorespiratory Division, Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); Norman, Wendy, E-mail: wendy.norman@gosh.nhs.uk [Centre for Cardiovascular Imaging, UCL Institute of Cardiovascular Science, London (United Kingdom); Cardiorespiratory Division, Great Ormond Street Hospital for Children NHS Foundation Trust, London (United Kingdom); Scott, Rosemary J., E-mail: rosemary.scott@uclh.nhs.uk [Department of Histopathology, University College London Hospital NHS Trust, London (United Kingdom); and others

2015-03-15

Highlights: •Postmortem MR imaging (PMMR) has high overall accuracy for abdominal pathology in foetuses, newborns and children. •PMMR is particularly good at detecting renal abnormalities, and relatively poor at detecting intestinal abnormalities. •In clinical practice, PMMR may be a useful alternative or adjunct to conventional autopsy in foetuses and children for detecting abdominal abnormalities. -- Abstract: Background: To compare the diagnostic accuracy of post-mortem magnetic resonance imaging (PMMR) specifically for abdominal pathology in foetuses and children, compared to conventional autopsy. Methods: Institutional ethics approval and parental consent was obtained. 400 unselected foetuses and children underwent PMMR using a 1.5 T Siemens Avanto MR scanner before conventional autopsy. PMMR images and autopsy findings were reported blinded to the other data respectively. Results: Abdominal abnormalities were found in 70/400 (12%) autopsies. Overall sensitivity and specificity (95% confidence interval) of PMMR for abdominal pathology was 72.5% (61.0, 81.6) and 90.8% (87.0, 93.6), with positive (PPV) and negative predictive values (NPV) of 64.1% (53.0, 73.9) and 93.6% (90.2, 95.8) respectively. PMMR was good at detecting renal abnormalities (sensitivity 80%), particularly in foetuses, and relatively poor at detecting intestinal abnormalities (sensitivity 50%). Overall accuracy was 87.4% (83.6, 90.4). Conclusions: PMMR has high overall accuracy for abdominal pathology in foetuses, newborns and children. PMMR is particularly good at detecting renal abnormalities, and relatively poor at detecting intestinal abnormalities. In clinical practice, PMMR may be a useful alternative or adjunct to conventional autopsy in foetuses and children for detecting abdominal abnormalities.

Diagnostic accuracy of post mortem MRI for abdominal abnormalities in foetuses and children

International Nuclear Information System (INIS)

Arthurs, Owen J.; Thayyil, Sudhin; Owens, Catherine M.; Olsen, Oystein E.; Wade, Angie; Addison, Shea; Jones, Rod; Norman, Wendy; Scott, Rosemary J.

2015-01-01

Highlights: •Postmortem MR imaging (PMMR) has high overall accuracy for abdominal pathology in foetuses, newborns and children. •PMMR is particularly good at detecting renal abnormalities, and relatively poor at detecting intestinal abnormalities. •In clinical practice, PMMR may be a useful alternative or adjunct to conventional autopsy in foetuses and children for detecting abdominal abnormalities. -- Abstract: Background: To compare the diagnostic accuracy of post-mortem magnetic resonance imaging (PMMR) specifically for abdominal pathology in foetuses and children, compared to conventional autopsy. Methods: Institutional ethics approval and parental consent was obtained. 400 unselected foetuses and children underwent PMMR using a 1.5 T Siemens Avanto MR scanner before conventional autopsy. PMMR images and autopsy findings were reported blinded to the other data respectively. Results: Abdominal abnormalities were found in 70/400 (12%) autopsies. Overall sensitivity and specificity (95% confidence interval) of PMMR for abdominal pathology was 72.5% (61.0, 81.6) and 90.8% (87.0, 93.6), with positive (PPV) and negative predictive values (NPV) of 64.1% (53.0, 73.9) and 93.6% (90.2, 95.8) respectively. PMMR was good at detecting renal abnormalities (sensitivity 80%), particularly in foetuses, and relatively poor at detecting intestinal abnormalities (sensitivity 50%). Overall accuracy was 87.4% (83.6, 90.4). Conclusions: PMMR has high overall accuracy for abdominal pathology in foetuses, newborns and children. PMMR is particularly good at detecting renal abnormalities, and relatively poor at detecting intestinal abnormalities. In clinical practice, PMMR may be a useful alternative or adjunct to conventional autopsy in foetuses and children for detecting abdominal abnormalities

Familial Resemblance for Serum Metabolite Concentrations

NARCIS (Netherlands)

Draisma, H.H.M.; Beekman, M.; Pool, R.; van Ommen, G.J.B; Vaarhorst, A.A.M.; de Craen, A.J.; Willemsen, G.; Slagboom, P.E.; Boomsma, D.I.

2013-01-01

Metabolomics is the comprehensive study of metabolites, which are the substrates, intermediate, and end products of cellular metabolism. The heritability of the concentrations of circulating metabolites bears relevance for evaluating their suitability as biomarkers for disease. We report aspects of

Metabolite Depletion Affects Flux Profiling of Cell Lines

DEFF Research Database (Denmark)

Nilsson, A.; Haanstra, J. R.; Teusink, B.

2018-01-01

Quantifying the rate of consumption and release of metabolites (i.e., flux profiling) has become integral to the study of cancer. The fluxes as well as the growth of the cells may be affected by metabolite depletion during cultivation.......Quantifying the rate of consumption and release of metabolites (i.e., flux profiling) has become integral to the study of cancer. The fluxes as well as the growth of the cells may be affected by metabolite depletion during cultivation....

The relevance of "non-relevant metabolites" from plant protection products (PPPs) for drinking water: the German view.

Science.gov (United States)

Dieter, Hermann H

2010-03-01

"Non-relevant metabolites" are those degradation products of plant protection products (PPPs), which are devoid of the targeted toxicities of the PPP and devoid of genotoxicity. Most often, "non-relevant metabolites" have a high affinity to the aquatic environment, are very mobile within this environment, and, usually, are also persistent. Therefore, from the point of drinking water hygiene, they must be characterized as "relevant for drinking water" like many other hydrophilic/polar environmental contaminants of different origins. "Non-relevant metabolites" may therefore penetrate to water sources used for abstraction of drinking water and may thus ultimately be present in drinking water. The presence of "non-relevant metabolites" and similar trace compounds in the water cycle may endanger drinking water quality on a long-term scale. During oxidative drinking water treatment, "non-relevant metabolites" may also serve as the starting material for toxicologically relevant transformation products similar to processes observed by drinking water disinfection with chlorine. This hypothesis was recently confirmed by the detection of the formation of N-nitroso-dimethylamine from ozone and dimethylsulfamide, a "non-relevant metabolite" of the fungicide tolylfluanide. In order to keep drinking water preferably free of "non-relevant metabolites", the German drinking water advisory board of the Federal Ministry of Health supports limiting their penetration into raw and drinking water to the functionally (agriculturally) unavoidable extent. On this background, the German Federal Environment Agency (UBA) recently has recommended two health related indication values (HRIV) to assess "non-relevant metabolites" from the view of drinking water hygiene. Considering the sometimes incomplete toxicological data base for some "non-relevant metabolites", HRIV also have the role of health related precautionary values. Depending on the completeness and quality of the toxicological

Metabolite profiling of Alzheimer's disease cerebrospinal fluid.

Directory of Open Access Journals (Sweden)

Christian Czech

Full Text Available Alzheimer's disease (AD is a neurodegenerative disorder characterized by progressive loss of cognitive functions. Today the diagnosis of AD relies on clinical evaluations and is only late in the disease. Biomarkers for early detection of the underlying neuropathological changes are still lacking and the biochemical pathways leading to the disease are still not completely understood. The aim of this study was to identify the metabolic changes resulting from the disease phenotype by a thorough and systematic metabolite profiling approach. For this purpose CSF samples from 79 AD patients and 51 healthy controls were analyzed by gas and liquid chromatography-tandem mass spectrometry (GC-MS and LC-MS/MS in conjunction with univariate and multivariate statistical analyses. In total 343 different analytes have been identified. Significant changes in the metabolite profile of AD patients compared to healthy controls have been identified. Increased cortisol levels seemed to be related to the progression of AD and have been detected in more severe forms of AD. Increased cysteine associated with decreased uridine was the best paired combination to identify light AD (MMSE>22 with specificity and sensitivity above 75%. In this group of patients, sensitivity and specificity above 80% were obtained for several combinations of three to five metabolites, including cortisol and various amino acids, in addition to cysteine and uridine.

Urinary phthalate metabolites and their biotransformation products: predictors and temporal variability among men and women

Science.gov (United States)

Meeker, John D.; Calafat, Antonia M.; Hauser, Russ

2012-01-01

Most epidemiology studies investigating potential adverse health effects in relation to phthalates measure the urinary concentration of the free plus glucuronidated species of phthalate metabolites (i.e., total concentration) to estimate exposure. However, the free species may represent the biologically relevant dose. In this study, we collected 943 urine samples from 112 men and 157 women and assessed the between- and within-person variability and predictors of a) the free and total urinary concentrations of phthalate metabolites, and b) the percentage of free phthalate metabolites (a potential phenotypic indicator of individual susceptibility). We also explored the proportion of urinary di-(2-ethylhexyl) phthalate (DEHP) metabolites contributed to by the bioactive mono-2-ethylhexyl phthalate (MEHP), considered a possible indicator of susceptibility to phthalate exposure. The percentage of phthalate metabolites present in the free form were less stable over time than the total metabolite concentration, and, therefore, it is not likely a useful indicator of metabolic susceptibility. Thus, the added costs and effort involved in the measurement of free in addition to total metabolite concentrations in large-scale studies may not be justified. Conversely, the proportion of DEHP metabolites contributed to by MEHP was more stable within individuals over time and may be a promising indicator of susceptibility if time of day of sample collection is carefully considered. PMID:22354176

Simvastatin (SV) metabolites in mouse tissues

International Nuclear Information System (INIS)

Duncan, C.A.; Vickers, S.

1990-01-01

SV, a semisynthetic analog of lovastatin, is hydrolyzed in vivo to its hydroxy acid (SVA), a potent inhibitor of HMG CoA reductase (HR). Thus SV lowers plasma cholesterol. SV is a substrate for mixed function oxidases whereas SVA undergoes lactonization and β-oxidation. Male CD-1 mice were dosed orally with a combination of ( 14 C)SV and ( 3 H)SVA at 25 mg/kg of each, bled and killed at 0.5, 2 and 4 hours. Labeled SV, SVA, 6'exomethylene SV (I), 6'CH 2 OH-SV (II), 6'COOH-SV (III) and a β-oxidized metabolite (IV) were assayed in liver, bile, kidneys, testes and plasma by RIDA. Levels of potential and active HR inhibitors in liver were 10 to 40 fold higher than in other tissues. II and III, in which the configuration at 6' is inverted, may be 2 metabolites of I. Metabolites I-III are inhibitors of HR in their hydroxy acid forms. Qualitatively ( 14 C)SV and ( 3 H)SVA were metabolized similarly (consistent with their proposed interconversion). However 3 H-SVA, I-III (including hydroxy acid forms) achieved higher concentrations than corresponding 14 C compounds (except in gall bladder bile). Major radioactive metabolites in liver were II-IV (including hydroxy acid forms). These metabolites have also been reported in rat tissues. In bile a large fraction of either label was unidentified polar metabolites. The presence of IV indicated that mice (like rats) are not good models for SV metabolism in man

Case control study of dry eye and related ocular surface abnormalities in Ibadan, Nigeria.

Science.gov (United States)

Bekibele, C O; Baiyeroju, A M; Ajaiyeoba, A; Akang, E E U; Ajayi, B G K

2010-02-01

Tear instability is associated with symptoms of ocular discomfort and irritation. Many patients with dry eyes remain untreated due to improper diagnoses. To identify symptoms and surface abnormalities associated with dry eyes. One hundred and fifty-six eyes of 78 subjects attending the Eye Clinic of the University College Hospital Ibadan were screened for dry eyes/tear instability using rose Bengal stain (graded 0-9), tear break-up time (TBUT), Schirmer's 1 tests, tear meniscus height and a standardised symptoms questionnaire. Grades 4-9 rose Bengal staining were considered as positive dry eye and were compared with grades 0-3 staining eyes as negative controls. Mean tear meniscus height, Schirmer's test and TBUT were lower among cases than their corresponding control eyes. The difference between the mean Schirmer's test values of cases and their controls were statistically significant (P = 0.00 for right eyes and P = 0.002 for left eyes). Rose Bengal grades were inversely correlated with the mean Schirmer's values (Pearson correlation -0.429, P = 0.05 for right eyes and -0.335, P = 0.03 for left eyes) and TBUT (Pearson correlation -0.316, P = 0.05 for right eyes and -0.212, P = 0.06 for left eyes). About 95.8% of the cases were symptomatic, as opposed to 70.4% of the controls (P = 0.01, Fisher's exact test) and 95.8% of dry right eyes compared to 61.1% of their controls had ocular surface abnormalities (P = 0.001), while 89.5% of dry left eyes compared to 62.7% of controls had surface abnormalities (P = 0.07). A close relationship exists between ocular irritation symptoms, surface abnormalities and functional evidence of tear instability. Such patients should be treated empirically or screened for dry eyes.

A systems biology approach to predict and characterize human gut microbial metabolites in colorectal cancer.

Science.gov (United States)

Wang, QuanQiu; Li, Li; Xu, Rong

2018-04-18

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths. It is estimated that about half the cases of CRC occurring today are preventable. Recent studies showed that human gut microbiota and their collective metabolic outputs play important roles in CRC. However, the mechanisms by which human gut microbial metabolites interact with host genetics in contributing CRC remain largely unknown. We hypothesize that computational approaches that integrate and analyze vast amounts of publicly available biomedical data have great potential in better understanding how human gut microbial metabolites are mechanistically involved in CRC. Leveraging vast amount of publicly available data, we developed a computational algorithm to predict human gut microbial metabolites for CRC. We validated the prediction algorithm by showing that previously known CRC-associated gut microbial metabolites ranked highly (mean ranking: top 10.52%; median ranking: 6.29%; p-value: 3.85E-16). Moreover, we identified new gut microbial metabolites likely associated with CRC. Through computational analysis, we propose potential roles for tartaric acid, the top one ranked metabolite, in CRC etiology. In summary, our data-driven computation-based study generated a large amount of associations that could serve as a starting point for further experiments to refute or validate these microbial metabolite associations in CRC cancer.

Importance of microbial pest control agents and their metabolites In relation to the natural microbiota on strawberry

DEFF Research Database (Denmark)

Jensen, Birgit; Knudsen, Inge M. B.; Jensen, Dan Funck

control. A series of laboratory, growth chamber, semi-field and field experiments using strawberry as a model plant focusing on commercial microbial pest control products (MPCPs) or laboratory MPCAs expected to be on the market within 10 years served as our experimental platform. Initially the background...... level of indigenous microbial communities and their mycotoxins/metabolites on strawberries was examined in a field survey with 4 conventional and 4 organic growers with different production practise and geographic distribution. Culturable bacteria, yeasts and filamentous fungi were isolated...... and identified using both chemotaxonomy (fatty acids and metabolite profiling) and morphological characteristics. Microbial communities on strawberries were complex including potential plant pathogens, opportunistic human pathogens, plant disease biocontrol agents and mycotoxin producers. Bacteria were the most...

Cassava brown streak disease effects on leaf metabolites and ...

African Journals Online (AJOL)

Cassava brown streak disease effects on leaf metabolites and pigment accumulation. ... Total reducing sugar and starch content also dropped significantly (-30 and -60%, respectively), much as NASE 14 maintained a relatively higher amount of carbohydrates. Leaf protein levels were significantly reduced at a rate of 0.07 ...

Abnormal sound detection device

International Nuclear Information System (INIS)

Yamada, Izumi; Matsui, Yuji.

1995-01-01

Only components synchronized with rotation of pumps are sampled from detected acoustic sounds, to judge the presence or absence of abnormality based on the magnitude of the synchronized components. A synchronized component sampling means can remove resonance sounds and other acoustic sounds generated at a synchronously with the rotation based on the knowledge that generated acoustic components in a normal state are a sort of resonance sounds and are not precisely synchronized with the number of rotation. On the other hand, abnormal sounds of a rotating body are often caused by compulsory force accompanying the rotation as a generation source, and the abnormal sounds can be detected by extracting only the rotation-synchronized components. Since components of normal acoustic sounds generated at present are discriminated from the detected sounds, reduction of the abnormal sounds due to a signal processing can be avoided and, as a result, abnormal sound detection sensitivity can be improved. Further, since it is adapted to discriminate the occurrence of the abnormal sound from the actually detected sounds, the other frequency components which are forecast but not generated actually are not removed, so that it is further effective for the improvement of detection sensitivity. (N.H.)

Effects of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) metabolites on cricket (Acheta domesticus) survival and reproductive success

Energy Technology Data Exchange (ETDEWEB)

Zhang Baohong [Institute of Environmental and Human Health (TIEHH), and Department of Environmental Toxicology, Texas Tech University, Box 41163, Lubbock, TX 79409-1163 (United States); Freitag, Christina M. [Institute of Environmental and Human Health (TIEHH), and Department of Environmental Toxicology, Texas Tech University, Box 41163, Lubbock, TX 79409-1163 (United States); Canas, Jaclyn E. [Institute of Environmental and Human Health (TIEHH), and Department of Environmental Toxicology, Texas Tech University, Box 41163, Lubbock, TX 79409-1163 (United States); Cheng Qiuqiong [Institute of Environmental and Human Health (TIEHH), and Department of Environmental Toxicology, Texas Tech University, Box 41163, Lubbock, TX 79409-1163 (United States); Anderson, Todd A. [Institute of Environmental and Human Health (TIEHH), and Department of Environmental Toxicology, Texas Tech University, Box 41163, Lubbock, TX 79409-1163 (United States)]. E-mail: todd.anderson@tiehh.ttu.edu

2006-11-15

The effect of two major hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) metabolites, hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX), on cricket (Acheta domesticus) survival and reproduction was studied. RDX metabolites did not have adverse effects on cricket survival, growth, and egg production. However, MNX and TNX did affect egg hatching. MNX and TNX were more toxic in spiked-sand than in topical tests. TNX was more toxic to egg than MNX. Developmental stage and exposure time affected hatching. After 30 days exposure to MNX or TNX, the EC{sub 2}, EC{sub 5}, and EC{sub 95} were 47, 128, and 247 {mu}g/g for TNX, and 65, 140, and 253 {mu}g/g for MNX in topical tests. The ECs for 20, 50, and 95 were 21, 52, and 99 {mu}g/g for MNX, and 12, 48, and 97 {mu}g/g for TNX in sand. No gross abnormalities in cricket nypmhs were observed in all experiments indicating that neither TNX or MNX is teratogenic in this assay. - RDX metabolites did not have adverse effects on cricket survival, growth, and egg production, but adversely affected egg hatching.

Effects of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) metabolites on cricket (Acheta domesticus) survival and reproductive success

International Nuclear Information System (INIS)

Zhang Baohong; Freitag, Christina M.; Canas, Jaclyn E.; Cheng Qiuqiong; Anderson, Todd A.

2006-01-01

The effect of two major hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) metabolites, hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX), on cricket (Acheta domesticus) survival and reproduction was studied. RDX metabolites did not have adverse effects on cricket survival, growth, and egg production. However, MNX and TNX did affect egg hatching. MNX and TNX were more toxic in spiked-sand than in topical tests. TNX was more toxic to egg than MNX. Developmental stage and exposure time affected hatching. After 30 days exposure to MNX or TNX, the EC 2 , EC 5 , and EC 95 were 47, 128, and 247 μg/g for TNX, and 65, 140, and 253 μg/g for MNX in topical tests. The ECs for 20, 50, and 95 were 21, 52, and 99 μg/g for MNX, and 12, 48, and 97 μg/g for TNX in sand. No gross abnormalities in cricket nypmhs were observed in all experiments indicating that neither TNX or MNX is teratogenic in this assay. - RDX metabolites did not have adverse effects on cricket survival, growth, and egg production, but adversely affected egg hatching

Comparison of Expression of Secondary Metabolite Biosynthesis Cluster Genes in Aspergillus flavus, A. parasiticus, and A. oryzae

OpenAIRE

Ehrlich, Kenneth C.; Mack, Brian M.

2014-01-01

Fifty six secondary metabolite biosynthesis gene clusters are predicted to be in the Aspergillus flavus genome. In spite of this, the biosyntheses of only seven metabolites, including the aflatoxins, kojic acid, cyclopiazonic acid and aflatrem, have been assigned to a particular gene cluster. We used RNA-seq to compare expression of secondary metabolite genes in gene clusters for the closely related fungi A. parasiticus, A. oryzae, and A. flavus S and L sclerotial morphotypes. The data help ...

Urinary Estrogen Metabolites, Active and Sedentary Behaviors, and Breast Cancer Risk

Science.gov (United States)

A cross-sectional study of approximately 600 postmenopausal controls in the Breast Cancer Case-Control Study in Poland to assess urinary estrogen metabolites in relation to accelerometer-based measures of active and sedentary behaviors

ABA and GA3 regulate the synthesis of primary and secondary metabolites related to alleviation from biotic and abiotic stresses in grapevine.

Science.gov (United States)

Murcia, Germán; Fontana, Ariel; Pontin, Mariela; Baraldi, Rita; Bertazza, Gianpaolo; Piccoli, Patricia N

2017-03-01

Plants are able to synthesize a large number of organic compounds. Among them, primary metabolites are known to participate in plant growth and development, whereas secondary metabolites are mostly involved in defense and other facultative processes. In grapevine, one of the major fruit crops in the world, secondary metabolites, mainly polyphenols, are of great interest for the wine industry. Even though there is an extensive literature on the content and profile of those compounds in berries, scarce or no information is available regarding polyphenols in other organs. In addition, little is known about the effect of plant growth regulators (PGRs), ABA and GA 3 (extensively used in table grapes) on the synthesis of primary and secondary metabolites in wine grapes. In table grapes, cultural practices include the use of GA 3 sprays shortly before veraison, to increase berry and bunch size, and sugar content in fruits. Meanwhile, ABA applications to the berries on pre-veraison improve the skin coloring and sugar accumulation, anticipating the onset of veraison. Accordingly, the aim of this study was to assess and characterize primary and secondary metabolites in leaves, berries and roots of grapevine plants cv. Malbec at veraison, and changes in compositions after ABA and GA 3 aerial sprayings. Metabolic profiling was conducted using GC-MS, GC-FID and HPLC-MWD. A large set of metabolites was identified: sugars, alditols, organic acids, amino acids, polyphenols (flavonoids and non-flavonoids) and terpenes (mono-, sesqui-, di- and triterpenes). The obtained results showed that ABA applications elicited synthesis of mono- and sesquiterpenes in all assessed tissues, as well as L-proline, acidic amino acids and anthocyanins in leaves. Additionally, applications with GA 3 elicited synthesis of L-proline in berries, and mono- and sesquiterpenes in all the tissues. However, treatment with GA 3 seemed to block polyphenol synthesis, mainly in berries. In conclusion, ABA and GA

Secondary metabolites from the endophytic fungus Talaromyces pinophilus.

Science.gov (United States)

Vinale, F; Nicoletti, R; Lacatena, F; Marra, R; Sacco, A; Lombardi, N; d'Errico, G; Digilio, M C; Lorito, M; Woo, S L

2017-08-01

Endophytic fungi have a great influence on plant health and growth, and are an important source of bioactive natural compounds. Organic extracts obtained from the culture filtrate of an endophytic strain of Talaromyces pinophilus isolated from strawberry tree (Arbutus unedo) were studied. Metabolomic analysis revealed the presence of three bioactive metabolites, the siderophore ferrirubin, the platelet-aggregation inhibitor herquline B and the antibiotic 3-O-methylfunicone. The latter was the major metabolite produced by this strain and displayed toxic effects against the pea aphid Acyrthosiphon pisum (Homoptera Aphidiidae). This toxicity represents an additional indication that the widespread endophytic occurrence of T. pinophilus may be related to a possible role in defensive mutualism. Moreover, the toxic activity on aphids could promote further study on 3-O-methylfunicone, or its derivatives, as an alternative to synthetic chemicals in agriculture.

Structural brain abnormalities in Cushing's syndrome.

Science.gov (United States)

Bauduin, Stephanie E E C; van der Wee, Nic J A; van der Werff, Steven J A

2018-05-08

Alongside various physical symptoms, patients with Cushing's disease and Cushing's syndrome display a wide variety of neuropsychiatric and cognitive symptoms, which are indicative of involvement of the central nervous system. The aim of this review is to provide an overview of the structural brain abnormalities that are associated with Cushing's disease and Cushing's syndrome and their relation to behavioral and cognitive symptomatology. In this review, we discuss the gray matter structural abnormalities found in patients with active Cushing's disease and Cushing's syndrome, the reversibility and persistence of these changes and the white matter structural changes related to Cushing's syndrome. Recent findings are of particular interest because they provide more detailed information on localization of the structural changes as well as possible insights into the underlying biological processes. Active Cushing's disease and Cushing's syndrome is related to volume reductions of the hippocampus and in a prefrontal region involving the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG). Whilst there are indications that the reductions in hippocampal volume are partially reversible, the changes in the ACC and MFG appear to be more persistent. In contrast to the volumetric findings, changes in white matter connectivity are typically widespread involving multiple tracts.

(1) H-MRS processing parameters affect metabolite quantification

DEFF Research Database (Denmark)

Bhogal, Alex A; Schür, Remmelt R; Houtepen, Lotte C

2017-01-01

investigated the influence of model parameters and spectral quantification software on fitted metabolite concentration values. Sixty spectra in 30 individuals (repeated measures) were acquired using a 7-T MRI scanner. Data were processed by four independent research groups with the freedom to choose their own...... + NAAG/Cr + PCr and Glu/Cr + PCr, respectively. Metabolite quantification using identical (1) H-MRS data was influenced by processing parameters, basis sets and software choice. Locally preferred processing choices affected metabolite quantification, even when using identical software. Our results......Proton magnetic resonance spectroscopy ((1) H-MRS) can be used to quantify in vivo metabolite levels, such as lactate, γ-aminobutyric acid (GABA) and glutamate (Glu). However, there are considerable analysis choices which can alter the accuracy or precision of (1) H-MRS metabolite quantification...

Changes of brain metabolite concentrations during maturation in different brain regions measured by chemical shift imaging

International Nuclear Information System (INIS)

Bueltmann, Eva; Lanfermann, Heinrich; Naegele, Thomas; Klose, Uwe

2017-01-01

We examined the effect of maturation on the regional distribution of brain metabolite concentrations using multivoxel chemical shift imaging. From our pool of pediatric MRI examinations, we retrospectively selected patients showing a normal cerebral MRI scan or no pathologic signal abnormalities at the level of the two-dimensional 1H MRS-CSI sequence and an age-appropriate global neurological development, except for focal neurological deficits. Seventy-one patients (4.5 months-20 years) were identified. Using LC Model, spectra were evaluated from voxels in the white matter, caudate head, and corpus callosum. The concentration of total N-acetylaspartate increased in all regions during infancy and childhood except in the right caudate head where it remained constant. The concentration of total creatine decreased in the caudate nucleus and splenium and minimally in the frontal white matter and genu. It remained largely constant in the parietal white matter. The concentration of choline-containing compounds had the tendency to decrease in all regions except in the parietal white matter where it remained constant. The concentration of myoinositol decreased slightly in the splenium and right frontal white matter, remained constant on the left side and in the caudate nucleus, and rose slightly in the parietal white matter and genu. CSI determined metabolite concentrations in multiple cerebral regions during routine MRI. The obtained data will be helpful in future pediatric CSI measurements deciding whether the ratios of the main metabolites are within the range of normal values or have to be considered as probably pathologic. (orig.)

Changes of brain metabolite concentrations during maturation in different brain regions measured by chemical shift imaging.

Science.gov (United States)

Bültmann, Eva; Nägele, Thomas; Lanfermann, Heinrich; Klose, Uwe

2017-01-01

We examined the effect of maturation on the regional distribution of brain metabolite concentrations using multivoxel chemical shift imaging. From our pool of pediatric MRI examinations, we retrospectively selected patients showing a normal cerebral MRI scan or no pathologic signal abnormalities at the level of the two-dimensional 1H MRS-CSI sequence and an age-appropriate global neurological development, except for focal neurological deficits. Seventy-one patients (4.5 months-20 years) were identified. Using LC Model, spectra were evaluated from voxels in the white matter, caudate head, and corpus callosum. The concentration of total N-acetylaspartate increased in all regions during infancy and childhood except in the right caudate head where it remained constant. The concentration of total creatine decreased in the caudate nucleus and splenium and minimally in the frontal white matter and genu. It remained largely constant in the parietal white matter. The concentration of choline-containing compounds had the tendency to decrease in all regions except in the parietal white matter where it remained constant. The concentration of myoinositol decreased slightly in the splenium and right frontal white matter, remained constant on the left side and in the caudate nucleus, and rose slightly in the parietal white matter and genu. CSI determined metabolite concentrations in multiple cerebral regions during routine MRI. The obtained data will be helpful in future pediatric CSI measurements deciding whether the ratios of the main metabolites are within the range of normal values or have to be considered as probably pathologic.

Changes of brain metabolite concentrations during maturation in different brain regions measured by chemical shift imaging

Energy Technology Data Exchange (ETDEWEB)

Bueltmann, Eva; Lanfermann, Heinrich [Hannover Medical School, Institute of Diagnostic and Interventional Neuroradiology, Hannover (Germany); Naegele, Thomas [University of Tuebingen, Department of Diagnostic and Interventional Neuroradiology, Radiological University Hospital, Tuebingen (Germany); Klose, Uwe [University of Tuebingen, Section of Experimental MR of the CNS, Department of Neuroradiology, Radiological University Hospital, Tuebingen (Germany)

2017-01-15

We examined the effect of maturation on the regional distribution of brain metabolite concentrations using multivoxel chemical shift imaging. From our pool of pediatric MRI examinations, we retrospectively selected patients showing a normal cerebral MRI scan or no pathologic signal abnormalities at the level of the two-dimensional 1H MRS-CSI sequence and an age-appropriate global neurological development, except for focal neurological deficits. Seventy-one patients (4.5 months-20 years) were identified. Using LC Model, spectra were evaluated from voxels in the white matter, caudate head, and corpus callosum. The concentration of total N-acetylaspartate increased in all regions during infancy and childhood except in the right caudate head where it remained constant. The concentration of total creatine decreased in the caudate nucleus and splenium and minimally in the frontal white matter and genu. It remained largely constant in the parietal white matter. The concentration of choline-containing compounds had the tendency to decrease in all regions except in the parietal white matter where it remained constant. The concentration of myoinositol decreased slightly in the splenium and right frontal white matter, remained constant on the left side and in the caudate nucleus, and rose slightly in the parietal white matter and genu. CSI determined metabolite concentrations in multiple cerebral regions during routine MRI. The obtained data will be helpful in future pediatric CSI measurements deciding whether the ratios of the main metabolites are within the range of normal values or have to be considered as probably pathologic. (orig.)

Sulfate metabolites as alternative markers for the detection of 4-chlorometandienone misuse in doping control.

Science.gov (United States)

Balcells, Georgina; Gómez, Cristina; Garrostas, Lorena; Pozo, Óscar J; Ventura, Rosa

2017-07-01

Sulfate metabolites have been described as long-term metabolites for some anabolic androgenic steroids (AAS). 4-chlorometandienone (4Cl-MTD) is one of the most frequently detected AAS in sports drug testing and it is commonly detected by monitoring metabolites excreted free or conjugated with glucuronic acid. Sulfation reactions of 4Cl-MTD have not been studied. The aim of this work was to evaluate the sulfate fraction of 4Cl-MTD metabolism by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to establish potential long-term metabolites valuable for doping control purposes. 4Cl-MTD was administered to two healthy male volunteers and urine samples were collected up to 8 days after administration. A theoretical selected reaction monitoring (SRM) method working in negative mode was developed. Ion transitions were based on ionization and fragmentation behaviour of sulfate metabolites as well as specific neutral losses (NL of 15 Da and NL of 36 Da) of compounds with related chemical structure. Six sulfate metabolites were detected after the analysis of excretion study samples. Three of the identified metabolites were characterized by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS). Results showed that five out of the six identified sulfate metabolites were detected in urine up to the last collected samples from both excretion studies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A case of refractory anemia with chromosomal abnormality (5q-) in Nagasaki atomic bomb survivor

International Nuclear Information System (INIS)

Kusano, Miyuki; Ikeda, Shuichi; Tomonaga, Yu; Sadamori, Naoki; Matsunaga, Masako

1978-01-01

Although assumed to be almost free from the effect of A-bomb radiation on the basis of the estimated dose, this case had progressive anemia with a specific manifestation and disclosed a clone with chromosomal abnormality (5q - ). In pure leukemia, a clone of abnormal chromosome is considered exactly that of leukemia. However, the presence of clones with chromosomal abnormality which are found in polycythemia vera or myelofibrosis do not always denote the leukemic changes. There is no established theory as to the significance of the clones with chromosomal abnormality in refractory anemia. Thus the interpretation of chromosomal abnormality in blood diseases is very difficult. Therefore analysis of chromosomes will be made actively in leukemia and related diseases as well as refractory anemia and preleukemia, and those will be compared in detail to search the relation between on occurrence of leukemia and chromosomal abnormality and also that between chromosomal abnormality and exposure to radiation. (Ueda, J.)

Global gene expression profiling related to temperature-sensitive growth abnormalities in interspecific crosses between tetraploid wheat and Aegilops tauschii.

Directory of Open Access Journals (Sweden)

Ryusuke Matsuda

Full Text Available Triploid wheat hybrids between tetraploid wheat and Aegilops tauschii sometimes show abnormal growth phenotypes, and the growth abnormalities inhibit generation of wheat synthetic hexaploids. In type II necrosis, one of the growth abnormalities, necrotic cell death accompanied by marked growth repression occurs only under low temperature conditions. At normal temperature, the type II necrosis lines show grass-clump dwarfism with no necrotic symptoms, excess tillers, severe dwarfism and delayed flowering. Here, we report comparative expression analyses to elucidate the molecular mechanisms of the temperature-dependent phenotypic plasticity in the triploid wheat hybrids. We compared gene and small RNA expression profiles in crown tissues to characterize the temperature-dependent phenotypic plasticity. No up-regulation of defense-related genes was observed under the normal temperature, and down-regulation of wheat APETALA1-like MADS-box genes, considered to act as flowering promoters, was found in the grass-clump dwarf lines. Some microRNAs, including miR156, were up-regulated, whereas the levels of transcripts of the miR156 target genes SPLs, known to inhibit tiller and branch number, were reduced in crown tissues of the grass-clump dwarf lines at the normal temperature. Unusual expression of the miR156/SPLs module could explain the grass-clump dwarf phenotype. Dramatic alteration of gene expression profiles, including miRNA levels, in crown tissues is associated with the temperature-dependent phenotypic plasticity in type II necrosis/grass-clump dwarf wheat hybrids.

Secondary metabolites from Bacillus amyloliquefaciens isolated from soil can kill Burkholderia pseudomallei.

Science.gov (United States)

Boottanun, Patcharaporn; Potisap, Chotima; Hurdle, Julian G; Sermswan, Rasana W

2017-12-01

Bacillus species are Gram-positive bacteria found in abundance in nature and their secondary metabolites were found to possess various potential activities, notably antimicrobial. In this study, Bacillus amyloliquefaciens N2-4 and N3-8 were isolated from soil and their metabolites could kill Burkholderia pseudomallei, a Gram-negative pathogenic bacterium also found in soil in its endemic areas. Moreover, the metabolites were able to kill drug resistant isolates of B. pseudomallei and also inhibit other pathogenic bacteria such as Staphylococcus aureus, Escherichia coli and Acinetobacter baumannii but not the non-pathogenic Burkholderia thailandensis, which is closely related to B. pseudomallei. Since the antimicrobial activity of N3-8 was not partially decreased or abolished when treated with proteolytic enzymes or autoclaved, but N2-4 was, these two strains should have produced different compounds. The N3-8 metabolites with antimicrobial activity consisted of both protein and non-protein compounds. The inhibition spectrum of the precipitated proteins compared to the culture supernatant indicated a possible synergistic effect of the non-protein and peptide compounds of N3-8 isolates against other pathogens. When either N2-4 or N3-8 isolates was co-cultured with B. pseudomallei the numbers of the bacteria decreased by 5 log 10 within 72 h. Further purification and characterization of the metabolites is required for future use of the bacteria or their metabolites as biological controls of B. pseudomallei in the environment or for development as new drugs for problematic pathogenic bacteria.

R-Limonene metabolism in humans and metabolite kinetics after oral administration.

Science.gov (United States)

Schmidt, Lukas; Göen, Thomas

2017-03-01

We studied the R-limonene (LMN) metabolism and elimination kinetics in a human in vivo study. Four volunteers were orally exposed to a single LMN dose of 100-130 µg kg -1 bw. In each case, one pre-exposure and subsequently all 24 h post-exposure urine samples were collected. From two subjects, blood samples were drawn up to 5 h after exposure. The parent compound was analysed in blood using headspace GC-MS. The metabolites cis- and trans-carveol (cCAR), perillyl alcohol (POH), perillic acid (PA), limonene-1,2-diol (LMN-1,2-OH), and limonene-8,9-diol (LMN-8,9-OH) were quantified in both blood and urine using GC-PCI-MS/MS. Moreover, GC-PCI-MS full-scan experiments were applied for identification of unknown metabolites in urine. In both matrices, metabolites reached maximum concentrations 1-2 h post-exposure followed by rapid elimination with half-lives of 0.7-2.5 h. In relation to the other metabolites, LMN-1,2-OH was eliminated slowest. Nonetheless, overall renal metabolite elimination was completed within the 24-h observation period. The metabolite amounts excreted via urine corresponded to 0.2 % (cCAR), 0.2 % (tCAR), <0.1 % (POH), 2.0 % (PA), 4.3 % (LMN-1,2-OH), and 32 % (LMN-8,9-OH) of the orally administered dose. GC-PCI-MS full-scan analyses revealed dihydroperillic acid (DHPA) as an additional LMN metabolite. DHPA was estimated to account for 5 % of the orally administered dose. The study revealed that human LMN metabolism proceeds fast and is characterised by oxidation mainly of the exo-cyclic double bond but also of the endo-cyclic double bond and of the methyl side chain. The study results may support the prediction of the metabolism of other terpenes or comparable chemical structures.

Abnormal shortened diastolic time length at increasing heart rates in patients with abnormal exercise-induced increase in pulmonary artery pressure

Directory of Open Access Journals (Sweden)

Bombardini Tonino

2011-11-01

Full Text Available Abstract Background The degree of pulmonary hypertension is not independently related to the severity of left ventricular systolic dysfunction but is frequently associated with diastolic filling abnormalities. The aim of this study was to assess diastolic times at increasing heart rates in normal and in patients with and without abnormal exercise-induced increase in pulmonary artery pressure (PASP. Methods. We enrolled 109 patients (78 males, age 62 ± 13 years referred for exercise stress echocardiography and 16 controls. The PASP was derived from the tricuspid Doppler tracing. A cut-off value of PASP ≥ 50 mmHg at peak stress was considered as indicative of abnormal increase in PASP. Diastolic times and the diastolic/systolic time ratio were recorded by a precordial cutaneous force sensor based on a linear accelerometer. Results At baseline, PASP was 30 ± 5 mmHg in patients and 25 ± 4 in controls. At peak stress the PASP was normal in 95 patients (Group 1; 14 patients (Group 2 showed an abnormal increase in PASP (from 35 ± 4 to 62 ± 12 mmHg; P Conclusion The first and second heart sound vibrations non-invasively monitored by a force sensor are useful for continuously assessing diastolic time during exercise. Exercise-induced abnormal PASP was associated with reduced diastolic time at heart rates beyond 100 beats per minute.

Electrocardiographic abnormalities in opiate addicts.

Science.gov (United States)

Wallner, Christina; Stöllberger, Claudia; Hlavin, Anton; Finsterer, Josef; Hager, Isabella; Hermann, Peter

2008-12-01

To determine in a cross-sectional study the prevalence of electrocardiographic (ECG) abnormalities in opiate addicts who were therapy-seeking and its association with demographic, clinical and drug-specific parameters. In consecutive therapy-seeking opiate addicts, a 12-lead ECG was registered within 24 hours after admission and evaluated according to a pre-set protocol between October 2004 and August 2006. Additionally, demographic, clinical and drug-specific parameters were recorded. Included were 511 opiate-addicts, 25% female, with a mean age of 29 years (range 17-59 years). One or more ECG abnormalities were found in 314 patients (61%). In the 511 patients we found most commonly ST abnormalities (19%), QTc prolongation (13%), tall R- and/or S-waves (11%) and missing R progression (10%). ECG abnormalities were more common in males than in females (64 versus 54%, P seizures less often (16 versus 27%, P opiate addicts. The most frequent ECG abnormalities are ST abnormalities, QTc prolongation and tall R- and/or S-waves. ST abnormalities are associated with cannabis, and QTc prolongation with methadone and benzodiazepines.

Roentgenologic abnormalities in Down's syndrome

Energy Technology Data Exchange (ETDEWEB)

Higuchi, Takehiko; Russell, W J; Komatsuda, Michio; Neriishi, Shotaro

1968-07-25

Roentgenograms of 28 patients with Down's syndrome were reviewed with emphasis on all previously reported abnormalities and any possible additional ones. Most of the abnormalities occurred with the same frequency as previously reported, but some less frequently reported findings were also seen. One abnormal vertebral measurement found in this series may be an additional stigma of Down's syndrome. All of the 27 cases studied cytogenetically had chromosomal abnormalities consistent with this disease. This study emphasizes the need for roentgenologic norms for the Japanese, and the desirability of combining chromosome studies with roentgenological abnormalities and clinical observations in diagnosing Down's syndrome. 19 references, 2 figures, 5 tables.

A Decade in the MIST: Learnings from Investigations of Drug Metabolites in Drug Development under the "Metabolites in Safety Testing" Regulatory Guidance.

Science.gov (United States)

Schadt, Simone; Bister, Bojan; Chowdhury, Swapan K; Funk, Christoph; Hop, Cornelis E C A; Humphreys, W Griffith; Igarashi, Fumihiko; James, Alexander D; Kagan, Mark; Khojasteh, S Cyrus; Nedderman, Angus N R; Prakash, Chandra; Runge, Frank; Scheible, Holger; Spracklin, Douglas K; Swart, Piet; Tse, Susanna; Yuan, Josh; Obach, R Scott

2018-06-01

Since the introduction of metabolites in safety testing (MIST) guidance by the Food and Drug Administration in 2008, major changes have occurred in the experimental methods for the identification and quantification of metabolites, ways to evaluate coverage of metabolites, and the timing of critical clinical and nonclinical studies to generate this information. In this cross-industry review, we discuss how the increased focus on human drug metabolites and their potential contribution to safety and drug-drug interactions has influenced the approaches taken by industry for the identification and quantitation of human drug metabolites. Before the MIST guidance was issued, the method of choice for generating comprehensive metabolite profile was radio chromatography. The MIST guidance increased the focus on human drug metabolites and their potential contribution to safety and drug-drug interactions and led to changes in the practices of drug metabolism scientists. In addition, the guidance suggested that human metabolism studies should also be accelerated, which has led to more frequent determination of human metabolite profiles from multiple ascending-dose clinical studies. Generating a comprehensive and quantitative profile of human metabolites has become a more urgent task. Together with technological advances, these events have led to a general shift of focus toward earlier human metabolism studies using high-resolution mass spectrometry and to a reduction in animal radiolabel absorption/distribution/metabolism/excretion studies. The changes induced by the MIST guidance are highlighted by six case studies included herein, reflecting different stages of implementation of the MIST guidance within the pharmaceutical industry. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

GPCR-Mediated Signaling of Metabolites

DEFF Research Database (Denmark)

Husted, Anna Sofie; Trauelsen, Mette; Rudenko, Olga

2017-01-01

microbiota target primarily enteroendocrine, neuronal, and immune cells in the lamina propria of the gut mucosa and the liver and, through these tissues, the rest of the body. In contrast, metabolites from the intermediary metabolism act mainly as metabolic stress-induced autocrine and paracrine signals...... and obesity. The concept of key metabolites as ligands for specific GPCRs has broadened our understanding of metabolic signaling significantly and provides a number of novel potential drug targets....

Diclofenac toxicity in human intestine ex vivo is not related to the formation of intestinal metabolites

NARCIS (Netherlands)

Niu, Xiaoyu; de Graaf, Inge A. M.; Langelaar-Makkinje, Miriam; Horvatovich, Peter; Groothuis, Geny M. M.

The use of diclofenac (DCF), a nonsteroidal anti-inflammatory drug, is associated with a high prevalence of gastrointestinal side effects. In vivo studies in rodents suggested that reactive metabolites of DCF produced by the liver or the intestine might be responsible for this toxicity. In the

NMR Spectroscopy Identifies Metabolites Translocated from Powdery Mildew Resistant Rootstocks to Susceptible Watermelon Scions.

Science.gov (United States)

Mahmud, Iqbal; Kousik, Chandrasekar; Hassell, Richard; Chowdhury, Kamal; Boroujerdi, Arezue F

2015-09-16

Powdery mildew (PM) disease causes significant loss in watermelon. Due to the unavailability of a commercial watermelon variety that is resistant to PM, grafting susceptible cultivars on wild resistant rootstocks is being explored as a short-term management strategy to combat this disease. Nuclear magnetic resonance-based metabolic profiles of susceptible and resistant rootstocks of watermelon and their corresponding susceptible scions (Mickey Lee) were compared to screen for potential metabolites related to PM resistance using multivariate principal component analysis. Significant score plot differences between the susceptible and resistant groups were revealed through Mahalanobis distance analysis. Significantly different spectral buckets and their corresponding metabolites (including choline, fumarate, 5-hydroxyindole-3-acetate, and melatonin) have been identified quantitatively using multivariate loading plots and verified by volcano plot analyses. The data suggest that these metabolites were translocated from the powdery mildew resistant rootstocks to their corresponding powdery mildew susceptible scions and can be related to PM disease resistance.

Abnormal ventilation scans in middle-aged smokers. Comparison with tests of overall lung function

International Nuclear Information System (INIS)

Barter, S.J.; Cunningham, D.A.; Lavender, J.P.; Gibellino, F.; Connellan, S.J.; Pride, N.B.

1985-01-01

The uniformity of regional ventilation during tidal breathing has been assessed using continuous inhalation of krypton-81m in 43 male, lifelong nonsmokers and 46 male, current cigarette smokers (mean daily consumption 24.1 cigarettes/day) between 44 and 61 yr of age and with mild or no respiratory symptoms. All subjects had normal chest radiographs. The results of the ventilation scans were compared with tests of overall lung function (spirometry, maximal expiratory flow-volume curves, and single-breath N2 test). Diffuse abnormalities of the ventilation scan were found in 19 (41%) of the 46 smokers but in none of the nonsmokers. Focal abnormalities were found in 7 smokers and 3 nonsmokers. Smokers showed the expected abnormalities in overall lung function (reduced FEV1 and VC, increased single-breath N2 slope, and closing volume), but in individual smokers there was only a weak relation between the severity of abnormality of overall lung function and an abnormal ventilation scan. Abnormal scans could be found when overall lung function was normal and were not invariably found when significant abnormalities in FEV1/VC or N2 slope were present. There was no relation between the presence of chronic expectoration and an abnormal scan. The prognostic significance of an abnormal ventilation scan in such smokers remains to be established

Gene expression and metabolite changes during Tuber magnatum fruiting body storage.

Science.gov (United States)

Zampieri, Elisa; Guzzo, Flavia; Commisso, Mauro; Mello, Antonietta; Bonfante, Paola; Balestrini, Raffaella

2014-11-01

The aim of this study was to investigate the impact of different 4 °C post-harvest storage periods on the quality of the white truffle Tuber magnatum. The expression of selected genes and the profiles of non-volatile metabolites have been analyzed. The up-regulation of genes related to cell wall metabolism and to a putative laccase points to cell wall modifications and browning events during cold storage. Time course RT-qPCR experiments have demonstrated that such transcription events probably depend on the ripening status, since this is delayed in partially ripe fruiting bodies. Changes in the concentrations of linoleate-derived metabolites occur during the first 3 days of considered cold storage, while the other metabolites, such as the amino acids, do not change. Taken together, the results demonstrate that complex molecular events occur in white truffles in the post-harvest period and before they are used as fresh products.

Automated pathway and reaction prediction facilitates in silico identification of unknown metabolites in human cohort studies.

Science.gov (United States)

Quell, Jan D; Römisch-Margl, Werner; Colombo, Marco; Krumsiek, Jan; Evans, Anne M; Mohney, Robert; Salomaa, Veikko; de Faire, Ulf; Groop, Leif C; Agakov, Felix; Looker, Helen C; McKeigue, Paul; Colhoun, Helen M; Kastenmüller, Gabi

2017-12-15

Identification of metabolites in non-targeted metabolomics continues to be a bottleneck in metabolomics studies in large human cohorts. Unidentified metabolites frequently emerge in the results of association studies linking metabolite levels to, for example, clinical phenotypes. For further analyses these unknown metabolites must be identified. Current approaches utilize chemical information, such as spectral details and fragmentation characteristics to determine components of unknown metabolites. Here, we propose a systems biology model exploiting the internal correlation structure of metabolite levels in combination with existing biochemical and genetic information to characterize properties of unknown molecules. Levels of 758 metabolites (439 known, 319 unknown) in human blood samples of 2279 subjects were measured using a non-targeted metabolomics platform (LC-MS and GC-MS). We reconstructed the structure of biochemical pathways that are imprinted in these metabolomics data by building an empirical network model based on 1040 significant partial correlations between metabolites. We further added associations of these metabolites to 134 genes from genome-wide association studies as well as reactions and functional relations to genes from the public database Recon 2 to the network model. From the local neighborhood in the network, we were able to predict the pathway annotation of 180 unknown metabolites. Furthermore, we classified 100 pairs of known and unknown and 45 pairs of unknown metabolites to 21 types of reactions based on their mass differences. As a proof of concept, we then looked further into the special case of predicted dehydrogenation reactions leading us to the selection of 39 candidate molecules for 5 unknown metabolites. Finally, we could verify 2 of those candidates by applying LC-MS analyses of commercially available candidate substances. The formerly unknown metabolites X-13891 and X-13069 were shown to be 2-dodecendioic acid and 9

A Rough Guide to Metabolite Identification Using High Resolution Liquid Chromatography Mass Spectrometry in Metabolomic Profiling in Metazoans

Directory of Open Access Journals (Sweden)

David G Watson

2013-01-01

Full Text Available Compound identification in mass spectrometry based metabolomics can be a problem but sometimes the problem seems to be presented in an over complicated way. The current review focuses on metazoans where the range of metabolites is more restricted than for example in plants. The focus is on liquid chromatography with high resolution mass spectrometry where it is proposed that most of the problems in compound identification relate to structural isomers rather than to isobaric compounds. Thus many of the problems faced relate to separation of isomers, which is usually required even if fragmentation is used to support structural identification. Many papers report the use of MS/MS or MS2 as an adjunct to the identification of known metabolites but there a few examples in metabolomics studies of metazoans of complete structure elucidation of novel metabolites or metabolites where no authentic standards are available for comparison.

Abnormal Events for Emergency Trip in HANARO

Energy Technology Data Exchange (ETDEWEB)

Ahn, Guk Hun; Choi, M. J.; Park, S. I.; Kim, H. W.; Kim, S. J.; Park, J. H.; Kwon, I. C

2006-12-15

This report gathers abnormal events related to emergency trip of HANARO that happened during its operation over 10 years since the first criticality on February 1995. The collected examples will be utilized to the HANARO's operators as a useful guide.

Cluster structure in the correlation coefficient matrix can be characterized by abnormal eigenvalues

Science.gov (United States)

Nie, Chun-Xiao

2018-02-01

In a large number of previous studies, the researchers found that some of the eigenvalues of the financial correlation matrix were greater than the predicted values of the random matrix theory (RMT). Here, we call these eigenvalues as abnormal eigenvalues. In order to reveal the hidden meaning of these abnormal eigenvalues, we study the toy model with cluster structure and find that these eigenvalues are related to the cluster structure of the correlation coefficient matrix. In this paper, model-based experiments show that in most cases, the number of abnormal eigenvalues of the correlation matrix is equal to the number of clusters. In addition, empirical studies show that the sum of the abnormal eigenvalues is related to the clarity of the cluster structure and is negatively correlated with the correlation dimension.

In Vivo Detection of Perinatal Brain Metabolite Changes in a Rabbit Model of Intrauterine Growth Restriction (IUGR.

Directory of Open Access Journals (Sweden)

Rui V Simões

Full Text Available Intrauterine growth restriction (IUGR is a risk factor for abnormal neurodevelopment. We studied a rabbit model of IUGR by magnetic resonance imaging (MRI and spectroscopy (MRS, to assess in vivo brain structural and metabolic consequences, and identify potential metabolic biomarkers for clinical translation.IUGR was induced in 3 pregnant rabbits at gestational day 25, by 40-50% uteroplacental vessel ligation in one horn; the contralateral horn was used as control. Fetuses were delivered at day 30 and weighted. A total of 6 controls and 5 IUGR pups underwent T2-w MRI and localized proton MRS within the first 8 hours of life, at 7T. Changes in brain tissue volumes and respective contributions to each MRS voxel were estimated by semi-automated registration of MRI images with a digital atlas of the rabbit brain. MRS data were used for: (i absolute metabolite quantifications, using linear fitting; (ii local temperature estimations, based on the water chemical shift; and (iii classification, using spectral pattern analysis.Lower birth weight was associated with (i smaller brain sizes, (ii slightly lower brain temperatures, and (iii differential metabolite profile changes in specific regions of the brain parenchyma. Specifically, we found estimated lower levels of aspartate and N-acetylaspartate (NAA in the cerebral cortex and hippocampus (suggesting neuronal impairment, and higher glycine levels in the striatum (possible marker of brain injury. Our results also suggest that the metabolic changes in cortical regions are more prevalent than those detected in hippocampus and striatum.IUGR was associated with brain metabolic changes in vivo, which correlate well with the neurostructural changes and neurodevelopment problems described in IUGR. Metabolic parameters could constitute non invasive biomarkers for the diagnosis and abnormal neurodevelopment of perinatal origin.

MetRxn: a knowledgebase of metabolites and reactions spanning metabolic models and databases

Directory of Open Access Journals (Sweden)

Kumar Akhil

2012-01-01

Full Text Available Abstract Background Increasingly, metabolite and reaction information is organized in the form of genome-scale metabolic reconstructions that describe the reaction stoichiometry, directionality, and gene to protein to reaction associations. A key bottleneck in the pace of reconstruction of new, high-quality metabolic models is the inability to directly make use of metabolite/reaction information from biological databases or other models due to incompatibilities in content representation (i.e., metabolites with multiple names across databases and models, stoichiometric errors such as elemental or charge imbalances, and incomplete atomistic detail (e.g., use of generic R-group or non-explicit specification of stereo-specificity. Description MetRxn is a knowledgebase that includes standardized metabolite and reaction descriptions by integrating information from BRENDA, KEGG, MetaCyc, Reactome.org and 44 metabolic models into a single unified data set. All metabolite entries have matched synonyms, resolved protonation states, and are linked to unique structures. All reaction entries are elementally and charge balanced. This is accomplished through the use of a workflow of lexicographic, phonetic, and structural comparison algorithms. MetRxn allows for the download of standardized versions of existing genome-scale metabolic models and the use of metabolic information for the rapid reconstruction of new ones. Conclusions The standardization in description allows for the direct comparison of the metabolite and reaction content between metabolic models and databases and the exhaustive prospecting of pathways for biotechnological production. This ever-growing dataset currently consists of over 76,000 metabolites participating in more than 72,000 reactions (including unresolved entries. MetRxn is hosted on a web-based platform that uses relational database models (MySQL.

Abnormality diagnosis device for nuclear reactor

Energy Technology Data Exchange (ETDEWEB)

Utsunomiya, Kazuhiro; Oyama, Shinmi; Sakaba, Hideo

1989-02-21

According to the present invention, abnormality such as abnormal increase of temperature in a nuclear reactor is detected to send a signal to control rod drives, etc. thereby stopping the operation of the nuclear reactor. Receiving/transmission device transmits a signal for conducting normal operation of an abnormality information section, as well as receives an echo signal from the abnormality information section to transmit an abnormal signal to a reactor protection system. The abnormality information section is disposed to fuel assemblies, receives a signal from the receiving/transmission device for conducting the normal operation to transmit a normal echo signal, as well as changes the echo signal when detecting the nuclear reactor abnormality. By the foregoing method, since the abnormality information section is disposed to the fuel assemblies, various effects can be attained such as: (1) there is no response delay from the occurrence of abnormality to emergency counter measure after detection, (2) high burnup degree for fuels can thus be possible to improve the economical property, (3) the abnormality information section can be taken out from the reactor container together with fuel assemablies by an existent take-out mechanism and (4) since wireless transmission and reception are established between the receiving/transmission device and the abnormality information section, cables are not required in the container. (K.M.).

A unique automation platform for measuring low level radioactivity in metabolite identification studies.

Directory of Open Access Journals (Sweden)

Joel Krauser

Full Text Available Generation and interpretation of biotransformation data on drugs, i.e. identification of physiologically relevant metabolites, defining metabolic pathways and elucidation of metabolite structures, have become increasingly important to the drug development process. Profiling using (14C or (3H radiolabel is defined as the chromatographic separation and quantification of drug-related material in a given biological sample derived from an in vitro, preclinical in vivo or clinical study. Metabolite profiling is a very time intensive activity, particularly for preclinical in vivo or clinical studies which have defined limitations on radiation burden and exposure levels. A clear gap exists for certain studies which do not require specialized high volume automation technologies, yet these studies would still clearly benefit from automation. Use of radiolabeled compounds in preclinical and clinical ADME studies, specifically for metabolite profiling and identification are a very good example. The current lack of automation for measuring low level radioactivity in metabolite profiling requires substantial capacity, personal attention and resources from laboratory scientists. To help address these challenges and improve efficiency, we have innovated, developed and implemented a novel and flexible automation platform that integrates a robotic plate handling platform, HPLC or UPLC system, mass spectrometer and an automated fraction collector.

A Unique Automation Platform for Measuring Low Level Radioactivity in Metabolite Identification Studies

Science.gov (United States)

Krauser, Joel; Walles, Markus; Wolf, Thierry; Graf, Daniel; Swart, Piet

2012-01-01

Generation and interpretation of biotransformation data on drugs, i.e. identification of physiologically relevant metabolites, defining metabolic pathways and elucidation of metabolite structures, have become increasingly important to the drug development process. Profiling using 14C or 3H radiolabel is defined as the chromatographic separation and quantification of drug-related material in a given biological sample derived from an in vitro, preclinical in vivo or clinical study. Metabolite profiling is a very time intensive activity, particularly for preclinical in vivo or clinical studies which have defined limitations on radiation burden and exposure levels. A clear gap exists for certain studies which do not require specialized high volume automation technologies, yet these studies would still clearly benefit from automation. Use of radiolabeled compounds in preclinical and clinical ADME studies, specifically for metabolite profiling and identification are a very good example. The current lack of automation for measuring low level radioactivity in metabolite profiling requires substantial capacity, personal attention and resources from laboratory scientists. To help address these challenges and improve efficiency, we have innovated, developed and implemented a novel and flexible automation platform that integrates a robotic plate handling platform, HPLC or UPLC system, mass spectrometer and an automated fraction collector. PMID:22723932

Production of Bioactive Secondary Metabolites by Marine Vibrionaceae

Directory of Open Access Journals (Sweden)

Lone Gram

2011-08-01

Full Text Available Bacteria belonging to the Vibrionaceae family are widespread in the marine environment. Today, 128 species of vibrios are known. Several of them are infamous for their pathogenicity or symbiotic relationships. Despite their ability to interact with eukaryotes, the vibrios are greatly underexplored for their ability to produce bioactive secondary metabolites and studies have been limited to only a few species. Most of the compounds isolated from vibrios so far are non-ribosomal peptides or hybrids thereof, with examples of N-containing compounds produced independent of nonribosomal peptide synthetases (NRPS. Though covering a limited chemical space, vibrios produce compounds with attractive biological activities, including antibacterial, anticancer, and antivirulence activities. This review highlights some of the most interesting structures from this group of bacteria. Many compounds found in vibrios have also been isolated from other distantly related bacteria. This cosmopolitan occurrence of metabolites indicates a high incidence of horizontal gene transfer, which raises interesting questions concerning the ecological function of some of these molecules. This account underlines the pending potential for exploring new bacterial sources of bioactive compounds and the challenges related to their investigation.

21 CFR 862.3250 - Cocaine and cocaine metabolite test system.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cocaine and cocaine metabolite test system. 862... Test Systems § 862.3250 Cocaine and cocaine metabolite test system. (a) Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine metabolite...

Non-invasive quantitation of phosphorus metabolites in human brain and brain tumors by magnetic resonance spectroscopy

International Nuclear Information System (INIS)

Naruse, Shoji; Higuchi, Toshihiro; Horikawa, Yoshiharu; Tanaka, Chuzo; Roth, K.; Hubesch, B.; Meyerhoff, D.J.; Weiner, M.W.

1989-01-01

In obtaining localized magnetic resonance spectra in the clinical setting, the exact determination of volume of interest (VOI), the relative sensitivity of detection within the VOI, the inhomogeneity of B 1 field, the Q factor of the coil, and saturation factors should be considered. Taking these items into account, a quantitative method for calculating the absolute amount of phosphorus metabolites was developed. Using this method, phosphorus metabolites in the brain were determined in 15 patients with brain tumors - meningioma (8) and astrocytoma (7), and 10 normal volunteers. The integrals for metabolite signals were determined by using the curve-fitting software. The concentrations for ATP, PCr, PDE, inorganic orthophosphate (Pi), and phosphomonosters (PME) were 2.5, 4.9, 11.3, 1.9 and 3.9 mM, respectively, in the normal brain. For the brain tumors, phosphorus metabolites were decreased, except for Pi and PME. These results encourage the clinical use of this method in the quantitative analysis of metabolites of the diseased brain. (Namekawa, K)

Urinary excretion of androgen metabolites, comparison with excretion of radioactive metabolites after injection of (4-/sup 14/C)testosterone. Influence of age

Energy Technology Data Exchange (ETDEWEB)

Deslypere, J P; Sayed, A; Vermeulen, A [Department of Internal Medicine, Section of Endocrinology, State University Academic Hospital, De Pintelaan, 135, Ghent, Belgium; Wiers, P W [Department of Internal Medicine, Section of Pneumology, State University Academic Hospital, The Netherlands

1981-01-01

The influence of age on the metabolic pattern of (4-/sup 14/C)testosterone was studied in 20 young and 8 elderly males and compared to the metabolic pattern of endogenous androgens; the latter was also studied in 16 young and 8 elderly women. In both young and elderly males, androsterone and aetiocholanolone glucuronide represent 65% of (4-/sup 14/C)testosterone metabolites: together with their suephoconjugates as well as with 5..cap alpha..- and 5..beta..-androstane-3..cap alpha.., 17..beta..-diol they represent even more than 75% of total urinary metabolites. The 5..cap alpha../5..beta.. ratio of metabolites of (4-/sup 14/C)testosterone was significantly (P<0.01) correlated with the 5..cap alpha../5..beta.. ratio of the metabolites of the endogenous androgens, mainly dehydroepiandrosterone and androstenedione. The 5..cap alpha../5..beta.. ratio of (4-/sup 14/C)testosterone metabolites was generally higher than the ratio of metabolites of endogenous androgens, suggesting that the transformation of T to ring A saturated metabolites occurs at least partially in another compartment than the transformation of DHEA to these metabolites. For both (4-/sup 14/C)testosterone and endogenous androgen metabolites we observed a statistically significant reduction of the 5..cap alpha../5..beta.. ratio with age, a general phenomenon in both males and females. This reduction concern also 11-OH-androst-4-ene-3.17-dione metabolism. Neither sex hormone levels, nor specific binding seems to determine this age dependent shift; neither is there convincing evidence for latent hypothyroisism or liver dysfunction in the elderly. An age associated primary decrease of the 5..cap alpha..-reductase activity seems the most likely explanation.

Multi-Omics Analysis Reveals a Correlation between the Host Phylogeny, Gut Microbiota and Metabolite Profiles in Cyprinid Fishes

Science.gov (United States)

Li, Tongtong; Long, Meng; Li, Huan; Gatesoupe, François-Joël; Zhang, Xujie; Zhang, Qianqian; Feng, Dongyue; Li, Aihua

2017-01-01

Gut microbiota play key roles in host nutrition and metabolism. However, little is known about the relationship between host genetics, gut microbiota and metabolic profiles. Here, we used high-throughput sequencing and gas chromatography/mass spectrometry approaches to characterize the microbiota composition and the metabolite profiles in the gut of five cyprinid fish species with three different feeding habits raised under identical husbandry conditions. Our results showed that host species and feeding habits significantly affect not only gut microbiota composition but also metabolite profiles (ANOSIM, p ≤ 0.05). Mantel test demonstrated that host phylogeny, gut microbiota, and metabolite profiles were significantly related to each other (p ≤ 0.05). Additionally, the carps with the same feeding habits had more similarity in gut microbiota composition and metabolite profiles. Various metabolites were correlated positively with bacterial taxa involved in food degradation. Our results shed new light on the microbiome and metabolite profiles in the gut content of cyprinid fishes, and highlighted the correlations between host genotype, fish gut microbiome and putative functions, and gut metabolite profiles. PMID:28367147

Parenchymal abnormalities associated with developmental venous anomalies

Energy Technology Data Exchange (ETDEWEB)

San Millan Ruiz, Diego; Gailloud, Philippe [Johns Hopkins Hospital, Division of Interventional Neuroradiology, Baltimore, MD (United States); Delavelle, Jacqueline [Geneva University Hospital, Neuroradiology Section, Department of Radiology and Medical Informatics, Geneva (Switzerland); Yilmaz, Hasan; Ruefenacht, Daniel A. [Geneva University Hospital, Section of Interventional Neuroradiology, Department of Clinical Neurosciences, Geneva (Switzerland); Piovan, Enrico; Bertramello, Alberto; Pizzini, Francesca [Verona City Hospital, Service of Neuroradiology, Verona (Italy)

2007-12-15

To report a retrospective series of 84 cerebral developmental venous anomalies (DVAs), focusing on associated parenchymal abnormalities within the drainage territory of the DVA. DVAs were identified during routine diagnostic radiological work-up based on magnetic resonance imaging (MRI) (60 cases), computed tomography (CT) (62 cases) or both (36 cases). Regional parenchymal modifications within the drainage territory of the DVA, such as cortical or subcortical atrophy, white matter density or signal alterations, dystrophic calcifications, presence of haemorrhage or a cavernous-like vascular malformation (CVM), were noted. A stenosis of the collecting vein of the DVA was also sought for. Brain abnormalities within the drainage territory of a DVA were encountered in 65.4% of the cases. Locoregional brain atrophy occurred in 29.7% of the cases, followed by white matter lesions in 28.3% of MRI investigations and 19.3% of CT investigations, CVMs in 13.3% of MRI investigations and dystrophic calcification in 9.6% of CT investigations. An intracranial haemorrhage possibly related to a DVA occurred in 2.4% cases, and a stenosis on the collecting vein was documented in 13.1% of cases. Parenchymal abnormalities were identified for all DVA sizes. Brain parenchymal abnormalities were associated with DVAs in close to two thirds of the cases evaluated. These abnormalities are thought to occur secondarily, likely during post-natal life, as a result of chronic venous hypertension. Outflow obstruction, progressive thickening of the walls of the DVA and their morphological organization into a venous convergence zone are thought to contribute to the development of venous hypertension in DVA. (orig.)

Olfaction in Eating Disorders and Abnormal Eating Behaviour: A Systematic Review

Directory of Open Access Journals (Sweden)

Mohammed Anisul eIslam

2015-09-01

Full Text Available The study provides a systematic review that explores the current literature on olfactory capacity in abnormal eating behavior to present a basis for discussion on whether research in olfaction in eating disorders may offer additional insights with regard to the complex etiopathology of ED and abnormal eating behaviors. Electronic databases (Medline, PsycINFO, PubMed, Science Direct and Web of Science were searched using the components in relation to olfaction and combining them with the components related to abnormal eating behavior. Out of 1,352 articles, 14 articles were selected (820 patients and 385 control participants for this review. The highest number of existing literature on olfaction in ED were carried out with AN patients (78.6% followed by BN (35.7% and obesity (14.3%. The general findings support that olfaction is altered in AN and Obesity and indicates towards there being no differences in olfactory capacity between BN patients and the general population. Due to the limited number of studies and heterogeneity this review stresses on the importance of more research on olfaction and abnormal eating behavior.

Urinary Concentrations of Phthalate Metabolites and Pregnancy Loss Among Women Conceiving with Medically Assisted Reproduction.

Science.gov (United States)

Messerlian, Carmen; Wylie, Blair J; Mínguez-Alarcón, Lidia; Williams, Paige L; Ford, Jennifer B; Souter, Irene C; Calafat, Antonia M; Hauser, Russ

2016-11-01

Animal studies demonstrate that several phthalates are embryofetotoxic and are associated with increased pregnancy loss and malformations. Results from human studies on phthalates and pregnancy loss are inconsistent. We examined pregnancy loss prospectively in relation to urinary phthalate metabolite concentrations among women undergoing medically assisted reproduction. We used data from 256 women conceiving 303 pregnancies recruited between 2004 and 2012 from the Massachusetts General Hospital Fertility Center. We quantified 11 phthalate metabolite concentrations and calculated the molar sum of four di(2-ethylhexyl) phthalate (DEHP) metabolites (ΣDEHP). We estimated risk ratios (RRs) and 95% confidence intervals for biochemical loss and total pregnancy loss (assisted reproduction.

SECONDARY METABOLITES FROM MARINE PENICILLIUM BREVICOMPACTUM

OpenAIRE

ROVIROSA, JUANA; DIAZ-MARRERO, ANA; DARIAS, JOSE; PAINEMAL, KARIN; SAN MARTIN, AURELIO

2006-01-01

In a screening of Basidiomycete cultures isolated from marine invertebrates collected along the Chilean coastline for the production of antibiotics we identified a Penicillium brevicompactum strain as a producer of metabolites inhibiting the growth of bacteria and fungi. Bioactivity guided purification resulted in the isolation of four known metabolites. Their structures were elucidated by spectroscopic methods.

Plant metabolites and nutritional quality of vegetables.

Science.gov (United States)

Hounsome, N; Hounsome, B; Tomos, D; Edwards-Jones, G

2008-05-01

Vegetables are an important part of the human diet and a major source of biologically active substances such as vitamins, dietary fiber, antioxidants, and cholesterol-lowering compounds. Despite a large amount of information on this topic, the nutritional quality of vegetables has not been defined. Historically, the value of many plant nutrients and health-promoting compounds was discovered by trial and error. By the turn of the century, the application of chromatography, mass spectrometry, infrared spectrometry, and nuclear magnetic resonance allowed quantitative and qualitative measurements of a large number of plant metabolites. Approximately 50000 metabolites have been elucidated in plants, and it is predicted that the final number will exceed 200000. Most of them have unknown function. Metabolites such as carbohydrates, organic and amino acids, vitamins, hormones, flavonoids, phenolics, and glucosinolates are essential for plant growth, development, stress adaptation, and defense. Besides the importance for the plant itself, such metabolites determine the nutritional quality of food, color, taste, smell, antioxidative, anticarcinogenic, antihypertension, anti-inflammatory, antimicrobial, immunostimulating, and cholesterol-lowering properties. This review is focused on major plant metabolites that characterize the nutritional quality of vegetables, and methods of their analysis.

β-Orcinol Metabolites from the Lichen Hypotrachyna revoluta

Directory of Open Access Journals (Sweden)

Panagiota Papadopoulou

2007-05-01

Full Text Available Four new β-orcinol metabolites, hypotrachynic acid (1, deoxystictic acid (2, cryptostictinolide (3 and 8 ́-methylconstictic acid (4 along with the metabolites 8 ́-methylstictic acid (5, 8 ́-methylmenegazziaic acid (6, stictic acid (7, 8 ́-ethylstictic acid (8 and atranorin (9, that have been previously described, were isolated for the first time from the tissue extracts of the lichen Hypotrachyna revoluta (Flörke Hale. The structures of the new metabolites were elucidated on the basis of extensive spectroscopic analyses. Radical scavenging activity (RSA of the metabolites isolated in adequate amounts, was evaluated using luminol chemiluminescence and comparison with Trolox®.

Association of plasma IL-6 and Hsp70 with HRV at different levels of PAHs metabolites.

Directory of Open Access Journals (Sweden)

Jian Ye

Full Text Available Exposure to polycyclic aromatic hydrocarbons (PAHs is associated with reduced heart rate variability (HRV, a strong predictor of cardiovascular diseases, but the mechanism is not well understood.We hypothesized that PAHs might induce systemic inflammation and stress response, contributing to altered cardiac autonomic function.HRV indices were measured using a 3-channel digital Holter monitor in 800 coke oven workers. Plasma levels of interleukin-6 (IL-6 and heat shock protein 70 (Hsp70 were determined using ELISA. Twelve urinary PAHs metabolites (OH-PAHs were measured by gas chromatography-mass spectrometry.We found that significant dose-dependent relationships between four urinary OH-PAHs and IL-6 (all Ptrend<0.05; and an increase in quartiles of IL-6 was significantly associated with a decrease in total power (TP and low frequency (LF (Ptrend = 0.014 and 0.006, respectively. In particular, elevated IL-6 was associated in a dose-dependent manner with decreased TP and LF in the high-PAHs metabolites groups (all Ptrend<0.05, but not in the low-PAHs metabolites groups. No significant association between Hsp70 and HRV in total population was found after multivariate adjustment. However, increased Hsp70 was significantly associated with elevated standard deviation of NN intervals (SDNN, TP and LF in the low-PAHs metabolites groups (all Ptrend<0.05. We also observed that both IL-6 and Hsp70 significantly interacted with multiple PAHs metabolites in relation to HRV.In coke oven workers, increased IL-6 was associated with a dose-response decreased HRV in the high-PAHs metabolites groups, whereas increase of Hsp70 can result in significant dose-related increase in HRV in the low-PAHs metabolites groups.

Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study.

Directory of Open Access Journals (Sweden)

Vijay R Varma

2018-01-01

Full Text Available The metabolic basis of Alzheimer disease (AD is poorly understood, and the relationships between systemic abnormalities in metabolism and AD pathogenesis are unclear. Understanding how global perturbations in metabolism are related to severity of AD neuropathology and the eventual expression of AD symptoms in at-risk individuals is critical to developing effective disease-modifying treatments. In this study, we undertook parallel metabolomics analyses in both the brain and blood to identify systemic correlates of neuropathology and their associations with prodromal and preclinical measures of AD progression.Quantitative and targeted metabolomics (Biocrates AbsoluteIDQ [identification and quantification] p180 assays were performed on brain tissue samples from the autopsy cohort of the Baltimore Longitudinal Study of Aging (BLSA (N = 44, mean age = 81.33, % female = 36.36 from AD (N = 15, control (CN; N = 14, and "asymptomatic Alzheimer's disease" (ASYMAD, i.e., individuals with significant AD pathology but no cognitive impairment during life; N = 15 participants. Using machine-learning methods, we identified a panel of 26 metabolites from two main classes-sphingolipids and glycerophospholipids-that discriminated AD and CN samples with accuracy, sensitivity, and specificity of 83.33%, 86.67%, and 80%, respectively. We then assayed these 26 metabolites in serum samples from two well-characterized longitudinal cohorts representing prodromal (Alzheimer's Disease Neuroimaging Initiative [ADNI], N = 767, mean age = 75.19, % female = 42.63 and preclinical (BLSA (N = 207, mean age = 78.68, % female = 42.63 AD, in which we tested their associations with magnetic resonance imaging (MRI measures of AD-related brain atrophy, cerebrospinal fluid (CSF biomarkers of AD pathology, risk of conversion to incident AD, and trajectories of cognitive performance. We developed an integrated blood and brain endophenotype score that summarized the relative importance of

Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study

Science.gov (United States)

Oommen, Anup M.; Varma, Sudhir; Casanova, Ramon; An, Yang; O’Brien, Richard; Pletnikova, Olga; Kastenmueller, Gabi; Doraiswamy, P. Murali; Kaddurah-Daouk, Rima; Thambisetty, Madhav

2018-01-01

Background The metabolic basis of Alzheimer disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD pathogenesis are unclear. Understanding how global perturbations in metabolism are related to severity of AD neuropathology and the eventual expression of AD symptoms in at-risk individuals is critical to developing effective disease-modifying treatments. In this study, we undertook parallel metabolomics analyses in both the brain and blood to identify systemic correlates of neuropathology and their associations with prodromal and preclinical measures of AD progression. Methods and findings Quantitative and targeted metabolomics (Biocrates AbsoluteIDQ [identification and quantification] p180) assays were performed on brain tissue samples from the autopsy cohort of the Baltimore Longitudinal Study of Aging (BLSA) (N = 44, mean age = 81.33, % female = 36.36) from AD (N = 15), control (CN; N = 14), and “asymptomatic Alzheimer’s disease” (ASYMAD, i.e., individuals with significant AD pathology but no cognitive impairment during life; N = 15) participants. Using machine-learning methods, we identified a panel of 26 metabolites from two main classes—sphingolipids and glycerophospholipids—that discriminated AD and CN samples with accuracy, sensitivity, and specificity of 83.33%, 86.67%, and 80%, respectively. We then assayed these 26 metabolites in serum samples from two well-characterized longitudinal cohorts representing prodromal (Alzheimer’s Disease Neuroimaging Initiative [ADNI], N = 767, mean age = 75.19, % female = 42.63) and preclinical (BLSA) (N = 207, mean age = 78.68, % female = 42.63) AD, in which we tested their associations with magnetic resonance imaging (MRI) measures of AD-related brain atrophy, cerebrospinal fluid (CSF) biomarkers of AD pathology, risk of conversion to incident AD, and trajectories of cognitive performance. We developed an integrated blood and brain endophenotype score that

Analysis of Intracellular Metabolites from Microorganisms: Quenching and Extraction Protocols.

Science.gov (United States)

Pinu, Farhana R; Villas-Boas, Silas G; Aggio, Raphael

2017-10-23

Sample preparation is one of the most important steps in metabolome analysis. The challenges of determining microbial metabolome have been well discussed within the research community and many improvements have already been achieved in last decade. The analysis of intracellular metabolites is particularly challenging. Environmental perturbations may considerably affect microbial metabolism, which results in intracellular metabolites being rapidly degraded or metabolized by enzymatic reactions. Therefore, quenching or the complete stop of cell metabolism is a pre-requisite for accurate intracellular metabolite analysis. After quenching, metabolites need to be extracted from the intracellular compartment. The choice of the most suitable metabolite extraction method/s is another crucial step. The literature indicates that specific classes of metabolites are better extracted by different extraction protocols. In this review, we discuss the technical aspects and advancements of quenching and extraction of intracellular metabolite analysis from microbial cells.

Marine metabolites: The sterols of soft coral

Digital Repository Service at National Institute of Oceanography (India)

Sarma, N.S.; Krishna, M.S.; Pasha, Sk.G.; Rao, T.S.P.; Venkateswarlu, Y.; Parameswaran, P.S.

Sterols constitute a major group of secondary metabolites of soft corals. Several of these compounds have the 'usual' 3 beta-hydroxy, delta sup(5) (or delta sup(0)) cholestane skeleton, a large number of these metabolites are polar sterols...

MIDAS: a database-searching algorithm for metabolite identification in metabolomics.

Science.gov (United States)

Wang, Yingfeng; Kora, Guruprasad; Bowen, Benjamin P; Pan, Chongle

2014-10-07

A database searching approach can be used for metabolite identification in metabolomics by matching measured tandem mass spectra (MS/MS) against the predicted fragments of metabolites in a database. Here, we present the open-source MIDAS algorithm (Metabolite Identification via Database Searching). To evaluate a metabolite-spectrum match (MSM), MIDAS first enumerates possible fragments from a metabolite by systematic bond dissociation, then calculates the plausibility of the fragments based on their fragmentation pathways, and finally scores the MSM to assess how well the experimental MS/MS spectrum from collision-induced dissociation (CID) is explained by the metabolite's predicted CID MS/MS spectrum. MIDAS was designed to search high-resolution tandem mass spectra acquired on time-of-flight or Orbitrap mass spectrometer against a metabolite database in an automated and high-throughput manner. The accuracy of metabolite identification by MIDAS was benchmarked using four sets of standard tandem mass spectra from MassBank. On average, for 77% of original spectra and 84% of composite spectra, MIDAS correctly ranked the true compounds as the first MSMs out of all MetaCyc metabolites as decoys. MIDAS correctly identified 46% more original spectra and 59% more composite spectra at the first MSMs than an existing database-searching algorithm, MetFrag. MIDAS was showcased by searching a published real-world measurement of a metabolome from Synechococcus sp. PCC 7002 against the MetaCyc metabolite database. MIDAS identified many metabolites missed in the previous study. MIDAS identifications should be considered only as candidate metabolites, which need to be confirmed using standard compounds. To facilitate manual validation, MIDAS provides annotated spectra for MSMs and labels observed mass spectral peaks with predicted fragments. The database searching and manual validation can be performed online at http://midas.omicsbio.org.

Chromosomal abnormalities in a psychiatric population

Energy Technology Data Exchange (ETDEWEB)

Lewis, K.E.; Lubetsky, M.J.; Wenger, S.L.; Steele, M.W. [Univ. of Pittsburgh Medical Center, PA (United States)

1995-02-27

Over a 3.5 year period of time, 345 patients hospitalized for psychiatric problems were evaluated cytogenetically. The patient population included 76% males and 94% children with a mean age of 12 years. The criteria for testing was an undiagnosed etiology for mental retardation and/or autism. Cytogenetic studies identified 11, or 3%, with abnormal karyotypes, including 4 fragile X positive individuals (2 males, 2 females), and 8 with chromosomal aneuploidy, rearrangements, or deletions. While individuals with chromosomal abnormalities do not demonstrate specific behavioral, psychiatric, or developmental problems relative to other psychiatric patients, our results demonstrate the need for an increased awareness to order chromosomal analysis and fragile X testing in those individuals who have combinations of behavioral/psychiatric, learning, communication, or cognitive disturbance. 5 refs., 1 fig., 2 tabs.

Physical activity, sedentary behavior, and vitamin D metabolites.

Science.gov (United States)

Hibler, Elizabeth A; Sardo Molmenti, Christine L; Dai, Qi; Kohler, Lindsay N; Warren Anderson, Shaneda; Jurutka, Peter W; Jacobs, Elizabeth T

2016-02-01

Physical activity is associated with circulating 25-hydroxyvitamin D (25(OH)D). However, the influence of activity and/or sedentary behavior on the biologically active, seco-steroid hormone 1α,25-dihydroxyvitamin D (1,25(OH)2D) is unknown. We conducted a cross-sectional analysis among ursodeoxycholic acid (UDCA) randomized trial participants (n=876) to evaluate associations between physical activity, sedentary behavior, and circulating vitamin D metabolite concentrations. Continuous vitamin D metabolite measurements and clinical thresholds were evaluated using multiple linear and logistic regression models, mutually adjusted for either 1,25(OH)2D or 25(OH)D and additional confounding factors. A statistically significant linear association between 1,25(OH)2D and moderate-vigorous physical activity per week was strongest among women (β (95% CI): 3.10 (1.51-6.35)) versus men (β (95% CI): 1.35 (0.79-2.29)) in the highest tertile of activity compared to the lowest (p-interaction=0.003). Furthermore, 25(OH)D was 1.54ng/ml (95% CI 1.09-1.98) higher per hour increase in moderate-vigorous activity (p=0.001) and odds of sufficient 25(OH)D status was higher among physically active participants (p=0.001). Sedentary behavior was not significantly associated with either metabolite in linear regression models, nor was a statistically significant interaction by sex identified. The current study identified novel associations between physical activity and serum 1,25(OH)2D levels, adjusted for 25(OH)D concentrations. These results identify the biologically active form of vitamin D as a potential physiologic mechanism related to observed population-level associations between moderate-vigorous physical activity with bone health and chronic disease risk. However, future longitudinal studies are needed to further evaluate the role of physical activity and vitamin D metabolites in chronic disease prevention. Copyright © 2015 Elsevier Inc. All rights reserved.

Pharmacologically active plant metabolites as survival strategy products.

Science.gov (United States)

Attardo, C; Sartori, F

2003-01-01

The fact that plant organisms produce chemical substances that are able to positively or negatively interfere with the processes which regulate human life has been common knowledge since ancient times. One of the numerous possible examples in the infusion of Conium maculatum, better known as Hemlock, a plant belonging to the family umbelliferae, used by the ancient Egyptians to cure skin diseases. The current official pharmacopoeia includes various chemical substances produced by secondary plant metabolisms. For example, the immunosuppressive drugs used to prevent organ transplant rejection and the majority of antibiotics are metabolites produced by fungal organisms, pilocarpin, digitalis, strophantus, salicylic acid and curare are examples of plant organism metabolites. For this reason, there has been an increase in research into plants, based on information on their medicinal use in the areas where they grow. The study of plants in relation to local culture and traditions is known as "ethnobotany". Careful study of the behaviour of sick animals has also led to the discovery of medicinal plants. The study of this subject is known as "zoopharmacognosy". The aim of this article is to discuss the fact that "ad hoc" production of such chemical substances, defined as "secondary metabolites", is one of the modes in which plant organisms respond to unfavourable environmental stimuli, such as an attack by predatory phytophagous animals or an excessive number of plant individuals, even of the same species, in a terrain. In the latter case, the plant organisms produce toxic substances, called "allelopathic" which limit the growth of other individuals. "Secondary metabolites" are produced by metabolic systems that are shunts of the primary systems which, when required, may be activated from the beginning, or increased to the detriment of others. The study of the manner in which such substances are produced is the subject of a new branch of learning called "ecological

Imaging mass spectrometry visualizes ceramides and the pathogenesis of dorfman-chanarin syndrome due to ceramide metabolic abnormality in the skin.

Directory of Open Access Journals (Sweden)

Naoko Goto-Inoue

Full Text Available Imaging mass spectrometry (IMS is a useful cutting edge technology used to investigate the distribution of biomolecules such as drugs and metabolites, as well as to identify molecular species in tissues and cells without labeling. To protect against excess water loss that is essential for survival in a terrestrial environment, mammalian skin possesses a competent permeability barrier in the stratum corneum (SC, the outermost layer of the epidermis. The key lipids constituting this barrier in the SC are the ceramides (Cers comprising of a heterogeneous molecular species. Alterations in Cer composition have been reported in several skin diseases that display abnormalities in the epidermal permeability barrier function. Not only the amounts of different Cers, but also their localizations are critical for the barrier function. We have employed our new imaging system, capable of high-lateral-resolution IMS with an atmospheric-pressure ionization source, to directly visualize the distribution of Cers. Moreover, we show an ichthyotic disease pathogenesis due to abnormal Cer metabolism in Dorfman-Chanarin syndrome, a neutral lipid storage disorder with ichthyosis in human skin, demonstrating that IMS is a novel diagnostic approach for assessing lipid abnormalities in clinical setting, as well as for investigating physiological roles of lipids in cells/tissues.

Comparative metabolite profiling of Solanum tuberosum against six wild Solanum species with Colorado potato beetle resistance.

Science.gov (United States)

Tai, Helen H; Worrall, Kraig; Pelletier, Yvan; De Koeyer, David; Calhoun, Larry A

2014-09-10

The Colorado potato beetle Leptinotarsa decemlineata (Say) (CPB) is a coleopteran herbivore that feeds on the foliage on Solanum species, in particular, potato. Six resistant wild Solanum species were identified, and two of these species had low levels of glycoalkaloids. Comparative analysis of the untargeted metabolite profiles of the foliage using UPLC-qTOF-MS was done to find metabolites shared between the wild species but not with Solanum tuberosum (L.) to identify resistance-related metabolites. It was found that only S. tuberosum produced the triose glycoalkaloids solanine and chaconine. Instead, the six wild species produced glycoalkaloids that shared in common tetrose sugar side chains. Additionally, there were non-glycoalkaloid metabolites associated with resistance including hydroxycoumarin and a phenylpropanoid, which were produced in all wild species but not in S. tuberosum.

Use of prokaryotic transcriptional activators as metabolite biosensors in eukaryotic cells

DEFF Research Database (Denmark)

2018-01-01

The present invention relates to the use of transcriptional activators from prokaryotic organisms for use in eukaryotic cells, such as yeast as sensors of intracellular and extracellular accumulation of a ligand or metabolite specifically activating this transcriptional activator in a eukaryot...

40 CFR 159.179 - Metabolites, degradates, contaminants, and impurities.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Metabolites, degradates, contaminants.../Benefit Information § 159.179 Metabolites, degradates, contaminants, and impurities. (a) Metabolites and... degradation of less than 10 percent in a 30-day period. (b) Contaminants and impurities. The presence in any...

Analysis of Intracellular Metabolites from Microorganisms: Quenching and Extraction Protocols

Directory of Open Access Journals (Sweden)

Farhana R. Pinu

2017-10-01

Full Text Available Sample preparation is one of the most important steps in metabolome analysis. The challenges of determining microbial metabolome have been well discussed within the research community and many improvements have already been achieved in last decade. The analysis of intracellular metabolites is particularly challenging. Environmental perturbations may considerably affect microbial metabolism, which results in intracellular metabolites being rapidly degraded or metabolized by enzymatic reactions. Therefore, quenching or the complete stop of cell metabolism is a pre-requisite for accurate intracellular metabolite analysis. After quenching, metabolites need to be extracted from the intracellular compartment. The choice of the most suitable metabolite extraction method/s is another crucial step. The literature indicates that specific classes of metabolites are better extracted by different extraction protocols. In this review, we discuss the technical aspects and advancements of quenching and extraction of intracellular metabolite analysis from microbial cells.

Abnormalities on diffusion-weighted magnetic resonance imaging in patients with transient ischemic attack

Energy Technology Data Exchange (ETDEWEB)

Nakamura, Tomomi; Shibagaki, Yasuro [Ushiku Aiwa General Hospital, Ibaraki (Japan); Uchiyama, Shinichiro; Iwata, Makoto [Tokyo Women' s Medical Coll. (Japan)

2003-03-01

We studied abnormalities on diffusion-weighted magnetic resonance imaging (DWI) in patients with transient ischemic attack (TIA). Out of 18 consecutive TIA patients, 9 patients had relevant focal abnormalities on DWI. Among TIA patients, six patients were associated with atrial fibrillation (Af), and all of these patients had focal abnormalities on DWI as well. TIA patients with Af had significantly more frequent focal abnormalities on DWI than those without Af (p=0.009; Fisher's exact probability test). In addition, the duration of TIA symptoms was not related to the presence of focal abnormalities on DWI. These results indicate that embolic mechanism may cause focal abnormalities on DWI. DWI was more sensitive to detect responsible ischemic lesions in these patients than T2-weighted image or fluid-attenuated inversion recovery image. (author)

Abnormalities on diffusion-weighted magnetic resonance imaging in patients with transient ischemic attack

International Nuclear Information System (INIS)

Nakamura, Tomomi; Shibagaki, Yasuro; Uchiyama, Shinichiro; Iwata, Makoto

2003-01-01

We studied abnormalities on diffusion-weighted magnetic resonance imaging (DWI) in patients with transient ischemic attack (TIA). Out of 18 consecutive TIA patients, 9 patients had relevant focal abnormalities on DWI. Among TIA patients, six patients were associated with atrial fibrillation (Af), and all of these patients had focal abnormalities on DWI as well. TIA patients with Af had significantly more frequent focal abnormalities on DWI than those without Af (p=0.009; Fisher's exact probability test). In addition, the duration of TIA symptoms was not related to the presence of focal abnormalities on DWI. These results indicate that embolic mechanism may cause focal abnormalities on DWI. DWI was more sensitive to detect responsible ischemic lesions in these patients than T2-weighted image or fluid-attenuated inversion recovery image. (author)

Investigation of metabolites for estimating blood deposition time.

Science.gov (United States)

Lech, Karolina; Liu, Fan; Davies, Sarah K; Ackermann, Katrin; Ang, Joo Ern; Middleton, Benita; Revell, Victoria L; Raynaud, Florence J; Hoveijn, Igor; Hut, Roelof A; Skene, Debra J; Kayser, Manfred

2018-01-01

Trace deposition timing reflects a novel concept in forensic molecular biology involving the use of rhythmic biomarkers for estimating the time within a 24-h day/night cycle a human biological sample was left at the crime scene, which in principle allows verifying a sample donor's alibi. Previously, we introduced two circadian hormones for trace deposition timing and recently demonstrated that messenger RNA (mRNA) biomarkers significantly improve time prediction accuracy. Here, we investigate the suitability of metabolites measured using a targeted metabolomics approach, for trace deposition timing. Analysis of 171 plasma metabolites collected around the clock at 2-h intervals for 36 h from 12 male participants under controlled laboratory conditions identified 56 metabolites showing statistically significant oscillations, with peak times falling into three day/night time categories: morning/noon, afternoon/evening and night/early morning. Time prediction modelling identified 10 independently contributing metabolite biomarkers, which together achieved prediction accuracies expressed as AUC of 0.81, 0.86 and 0.90 for these three time categories respectively. Combining metabolites with previously established hormone and mRNA biomarkers in time prediction modelling resulted in an improved prediction accuracy reaching AUCs of 0.85, 0.89 and 0.96 respectively. The additional impact of metabolite biomarkers, however, was rather minor as the previously established model with melatonin, cortisol and three mRNA biomarkers achieved AUC values of 0.88, 0.88 and 0.95 for the same three time categories respectively. Nevertheless, the selected metabolites could become practically useful in scenarios where RNA marker information is unavailable such as due to RNA degradation. This is the first metabolomics study investigating circulating metabolites for trace deposition timing, and more work is needed to fully establish their usefulness for this forensic purpose.

Regional cerebral blood flow abnormalities in late-life depression. Relation to refractoriness and chronification

Energy Technology Data Exchange (ETDEWEB)

Awata, Shuichi; Konno, Michiko; Sato, Mitsumoto [Tohoku Univ., Sendai (Japan). School of Medicine; Ito, Hiroshi; Ono, Shuichi; Kawashima, Ryuta; Fukuda, Hiroshi

1998-02-01

We examined patterns of regional cerebral blood flow (rCBF) abnormalities in 18 patients with major depressive disorder in late life using single photon emission computed tomography (SPECT) and {sup 99m}Tc-hexamethyl-propylenamine oxime ({sup 99m}Tc-HMPAO). Compared with 13 age-matched controls, relative rCBF was significantly decreased bilaterally in the anterior cingulate gyrus, the prefrontal cortex, the temporal cortex, the parietal cortex, the hippocampus and the caudate nucleus. However, it was not correlated with the severity of depression or global cognitive dysfunction. In 10 patients with a prolonged depressive episode or prolonged residual symptoms (the refractory subgroup), robust and extensive decreases in rCBF were found compared with controls and the rCBF decreased significantly in the anterior cingulate gyrus and the prefrontal cortex compared with that in the non-refractory subgroup. In the non-reflactory subgroup, rCBF decreased significantly in the caudate nucleus and tended to decrease in the anterior cingulate gyrus compared with controls. These findings indicate that dysfunction of the limbic system, the cerebral association cortex and the caudate nucleus may be implicated in late-life depression and that robust and extensive hypoperfusion, especially in the anterior cingulate and the prefrontal regions, may relate to refractoriness or chronification of depression. (author). 60 refs.

Regional cerebral blood flow abnormalities in late-life depression. Relation to refractoriness and chronification

International Nuclear Information System (INIS)

Awata, Shuichi; Konno, Michiko; Sato, Mitsumoto; Ito, Hiroshi; Ono, Shuichi; Kawashima, Ryuta; Fukuda, Hiroshi

1998-01-01

We examined patterns of regional cerebral blood flow (rCBF) abnormalities in 18 patients with major depressive disorder in late life using single photon emission computed tomography (SPECT) and 99m Tc-hexamethyl-propylenamine oxime ( 99m Tc-HMPAO). Compared with 13 age-matched controls, relative rCBF was significantly decreased bilaterally in the anterior cingulate gyrus, the prefrontal cortex, the temporal cortex, the parietal cortex, the hippocampus and the caudate nucleus. However, it was not correlated with the severity of depression or global cognitive dysfunction. In 10 patients with a prolonged depressive episode or prolonged residual symptoms (the refractory subgroup), robust and extensive decreases in rCBF were found compared with controls and the rCBF decreased significantly in the anterior cingulate gyrus and the prefrontal cortex compared with that in the non-refractory subgroup. In the non-reflactory subgroup, rCBF decreased significantly in the caudate nucleus and tended to decrease in the anterior cingulate gyrus compared with controls. These findings indicate that dysfunction of the limbic system, the cerebral association cortex and the caudate nucleus may be implicated in late-life depression and that robust and extensive hypoperfusion, especially in the anterior cingulate and the prefrontal regions, may relate to refractoriness or chronification of depression. (author). 60 refs

Hidden State Conditional Random Field for Abnormal Activity Recognition in Smart Homes

Directory of Open Access Journals (Sweden)

Yu Tong

2015-03-01

Full Text Available As the number of elderly people has increased worldwide, there has been a surge of research into assistive technologies to provide them with better care by recognizing their normal and abnormal activities. However, existing abnormal activity recognition (AAR algorithms rarely consider sub-activity relations when recognizing abnormal activities. This paper presents an application of the Hidden State Conditional Random Field (HCRF method to detect and assess abnormal activities that often occur in elderly persons’ homes. Based on HCRF, this paper designs two AAR algorithms, and validates them by comparing them with a feature vector distance based algorithm in two experiments. The results demonstrate that the proposed algorithms favorably outperform the competitor, especially when abnormal activities have same sensor type and sensor number as normal activities.

Cognition and brain abnormalities on MRI in pituitary patients

International Nuclear Information System (INIS)

Brummelman, Pauline; Sattler, Margriet G.A.; Meiners, Linda C.; Berg, Gerrit van den; Klauw, Melanie M. van der; Elderson, Martin F.; Dullaart, Robin P.F.; Koerts, Janneke; Werumeus Buning, Jorien; Tucha, Oliver; Wolffenbuttel, Bruce H.R.; Bergh, Alfons C.M. van den; Beek, André P. van

2015-01-01

Highlights: • Cognitive impairments are frequently observed in treated NFA patients. • NFA patients with cognitive impairments do not show brain abnormalities on MRI more frequently than patients without cognitive impairments. • The absence of brain abnormalities on brain MRI does not exclude impairments of cognition. - Abstract: Purpose: The extent to which cognitive dysfunction is related to specific brain abnormalities in patients treated for pituitary macroadenoma is unclear. Therefore, we compared brain abnormalities seen on Magnetic Resonance Imaging (MRI) in patients treated for nonfunctioning pituitary macroadenoma (NFA) with or without impairments in cognitive functioning. Methods: In this cross-sectional design, a cohort of 43 NFA patients was studied at the University Medical Center Groningen. White matter lesions (WMLs), cerebral atrophy, (silent) brain infarcts and abnormalities of the temporal lobes and hippocampi were assessed on pre-treatment and post-treatment MRI scans. Post-treatment cognitive examinations were performed using a verbal memory and executive functioning test. We compared our patient cohort with large reference populations representative of the Dutch population. Results: One or more impairments on both cognitive tests were frequently observed in treated NFA patients. No treatment effects were found with regard to the comparison between patients with and without impairments in executive functioning. Interestingly, in patients with one or more impairments on verbal memory function, treatment with radiotherapy had been given more frequently (74% in the impaired group versus 40% in the unimpaired group, P = 0.025). Patients with or without any brain abnormality on MRI did not differ in verbal memory or executive functioning. Conclusions: Brain abnormalities on MRI are not observed more frequently in treated NFA patients with impairments compared to NFA patients without impairments in verbal memory or executive functioning

Cognition and brain abnormalities on MRI in pituitary patients

Energy Technology Data Exchange (ETDEWEB)

Brummelman, Pauline [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Sattler, Margriet G.A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen (Netherlands); Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Meiners, Linda C. [Department of Radiology, University of Groningen, University Medical Center Groningen (Netherlands); Berg, Gerrit van den; Klauw, Melanie M. van der [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Elderson, Martin F. [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); LifeLines Cohort Study and Biobank, University of Groningen, University Medical Center Groningen (Netherlands); Dullaart, Robin P.F. [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Koerts, Janneke [Department of Clinical and Developmental Neuropsychology, University of Groningen, Groningen (Netherlands); Werumeus Buning, Jorien, E-mail: j.werumeus.buning@umcg.nl [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); Tucha, Oliver [Department of Clinical and Developmental Neuropsychology, University of Groningen, Groningen (Netherlands); Wolffenbuttel, Bruce H.R. [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands); LifeLines Cohort Study and Biobank, University of Groningen, University Medical Center Groningen (Netherlands); Bergh, Alfons C.M. van den [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen (Netherlands); Beek, André P. van, E-mail: a.p.van.beek@umcg.nl [Department of Endocrinology, University of Groningen, University Medical Center Groningen (Netherlands)

2015-02-15

Highlights: • Cognitive impairments are frequently observed in treated NFA patients. • NFA patients with cognitive impairments do not show brain abnormalities on MRI more frequently than patients without cognitive impairments. • The absence of brain abnormalities on brain MRI does not exclude impairments of cognition. - Abstract: Purpose: The extent to which cognitive dysfunction is related to specific brain abnormalities in patients treated for pituitary macroadenoma is unclear. Therefore, we compared brain abnormalities seen on Magnetic Resonance Imaging (MRI) in patients treated for nonfunctioning pituitary macroadenoma (NFA) with or without impairments in cognitive functioning. Methods: In this cross-sectional design, a cohort of 43 NFA patients was studied at the University Medical Center Groningen. White matter lesions (WMLs), cerebral atrophy, (silent) brain infarcts and abnormalities of the temporal lobes and hippocampi were assessed on pre-treatment and post-treatment MRI scans. Post-treatment cognitive examinations were performed using a verbal memory and executive functioning test. We compared our patient cohort with large reference populations representative of the Dutch population. Results: One or more impairments on both cognitive tests were frequently observed in treated NFA patients. No treatment effects were found with regard to the comparison between patients with and without impairments in executive functioning. Interestingly, in patients with one or more impairments on verbal memory function, treatment with radiotherapy had been given more frequently (74% in the impaired group versus 40% in the unimpaired group, P = 0.025). Patients with or without any brain abnormality on MRI did not differ in verbal memory or executive functioning. Conclusions: Brain abnormalities on MRI are not observed more frequently in treated NFA patients with impairments compared to NFA patients without impairments in verbal memory or executive functioning

Terpene metabolic engineering via nuclear or chloroplast genomes profoundly and globally impacts off-target pathways through metabolite signalling.

Science.gov (United States)

Pasoreck, Elise K; Su, Jin; Silverman, Ian M; Gosai, Sager J; Gregory, Brian D; Yuan, Joshua S; Daniell, Henry

2016-09-01

The impact of metabolic engineering on nontarget pathways and outcomes of metabolic engineering from different genomes are poorly understood questions. Therefore, squalene biosynthesis genes FARNESYL DIPHOSPHATE SYNTHASE (FPS) and SQUALENE SYNTHASE (SQS) were engineered via the Nicotiana tabacum chloroplast (C), nuclear (N) or both (CN) genomes to promote squalene biosynthesis. SQS levels were ~4300-fold higher in C and CN lines than in N, but all accumulated ~150-fold higher squalene due to substrate or storage limitations. Abnormal leaf and flower phenotypes, including lower pollen production and reduced fertility, were observed regardless of the compartment or level of transgene expression. Substantial changes in metabolomes of all lines were observed: levels of 65-120 unrelated metabolites, including the toxic alkaloid nicotine, changed by as much as 32-fold. Profound effects of transgenesis on nontarget gene expression included changes in the abundance of 19 076 transcripts by up to 2000-fold in CN; 7784 transcripts by up to 1400-fold in N; and 5224 transcripts by as much as 2200-fold in C. Transporter-related transcripts were induced, and cell cycle-associated transcripts were disproportionally repressed in all three lines. Transcriptome changes were validated by qRT-PCR. The mechanism underlying these large changes likely involves metabolite-mediated anterograde and/or retrograde signalling irrespective of the level of transgene expression or end product, due to imbalance of metabolic pools, offering new insight into both anticipated and unanticipated consequences of metabolic engineering. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Ruta graveolens Extracts and Metabolites against Spodoptera frugiperda.

Science.gov (United States)

Ayil-Gutiérrez, Benjamin A; Villegas-Mendoza, Jesús M; Santes-Hernndez, Zuridai; Paz-González, Alma D; Mireles-Martínez, Maribel; Rosas-García, Ninfa M; Rivera, Gildardo

2015-11-01

The biological activity of Ruta graveolens leaf tissue extracts obtained with different solvents (ethyl acetate, ethanol, and water) and metabolites (psoralen, 2- undecanone and rutin) against Spodoptera frugiperda was evaluated. Metabolites levels in extracts were quantified by HPLC and GC. Ethyl acetate and ethanol extracts showed 94% and 78% mortality, respectively. Additionally, psoralen metabolite showed a high mortality as cypermethrin. Metabolite quantification in extracts shows the presence of 2-undecanone (87.9 µmoles mg(-1) DW), psoralen (3.6 µmoles mg(-1) DW) and rutin (0.001 pmoles mg(-1) DW). We suggest that these concentrations of 2-undecanone and psoralen in R. graveolens leaf tissue extracts could be responsible for S. frugiperda mortality.

Abnormal expression of blood group-related antigens in uterine endometrial cancers.

Science.gov (United States)

Tsukazaki, K; Sakayori, M; Arai, H; Yamaoka, K; Kurihara, S; Nozawa, S

1991-08-01

The expression of A, B, and H group antigens, Lewis group antigens (Lewis(a), Lewis(b), Lewis(x), and Lewis(y)), and Lc4 and nLc4 antigens, the precursor antigens of both groups, was examined immunohistochemically with monoclonal antibodies in 9 normal endometria, 6 endometrial hyperplasias, and 31 endometrial cancers. 1) A, B and/or H antigens were detected in endometrial cancers at an incidence of 51.6%, while no distinct localization of these antigens was observed in normal endometria. H antigen, the precursor of A and B antigens, was particularly frequently detected in endometrial cancers. 2) An increased rate of expression of Lewis group antigens, particularly Lewis(b) antigen, was observed in endometrial cancers compared with its expression in normal endometria. 3) Lc4 and nLc4 antigens were detected in endometrial cancers at rates of 41.9% and 38.7%, respectively, these expressions being increased compared with those in normal endometria. 4) These results suggest that a highly abnormal expression of blood group-related antigens in endometrial cancers occurs not only at the level of A, B, and H antigens and Lewis group antigens, but also at the level of their precursor Lc4 and nLc4 antigens. 5) Lewis(a), Lewis(b), and Lc4 antigens, built on the type-1 chain, are more specific to endometrial cancers than their respective positional isomers, Lewis(x), Lewis(y), and nLc4 antigens, built on the type-2 chain.

Comparison of expression of secondary metabolite biosynthesis cluster genes in Aspergillus flavus, A. parasiticus, and A. oryzae.

Science.gov (United States)

Ehrlich, Kenneth C; Mack, Brian M

2014-06-23

Fifty six secondary metabolite biosynthesis gene clusters are predicted to be in the Aspergillus flavus genome. In spite of this, the biosyntheses of only seven metabolites, including the aflatoxins, kojic acid, cyclopiazonic acid and aflatrem, have been assigned to a particular gene cluster. We used RNA-seq to compare expression of secondary metabolite genes in gene clusters for the closely related fungi A. parasiticus, A. oryzae, and A. flavus S and L sclerotial morphotypes. The data help to refine the identification of probable functional gene clusters within these species. Our results suggest that A. flavus, a prevalent contaminant of maize, cottonseed, peanuts and tree nuts, is capable of producing metabolites which, besides aflatoxin, could be an underappreciated contributor to its toxicity.

[11C]Flumazenil metabolite measurement in plasma is not necessary for accurate brain benzodiazepine receptor quantification

International Nuclear Information System (INIS)

Sanabria-Bohorquez, S.M.; Veraart, C.; Labar, D.; Bol, A.; Volder, A.G. de; Michel, C.; Leveque, P.

2000-01-01

In this work, a mathematical correction for metabolites has been validated which estimates the relative amount of [ 11 C]flumazenil ([ 11 C]FMZ) in the total plasma curve from the tissue kinetic data without the need for direct metabolite measurement in blood plasma samples. Kinetic data were obtained using a 90-min three-injection protocol on five normal volunteers. First, the relative amount of [ 11 C]FMZ in plasma was modelled by a two-parameter exponential function. The parameters were estimated either directly by fitting this model to the blood plasma metabolite measurements, or indirectly from the simultaneous fitting of tissue time activity curves from several brain regions with a non-linear FMZ kinetic model. Second, the direct and indirect metabolite corrections were fixed and the FMZ compartmental parameters were determined on a regional basis in the brain. The validation was performed by comparing the regional values of benzodiazepine receptor density B max and equilibrium dissociation constant K d obtained with the direct metabolite correction with those values obtained with the indirect correction. For B max , the correlation coefficient r 2 was above 0.97 for all subjects and the slope values of the linear regression were within the interval [0.97, 1.2]. For K d , r 2 was above 0.96, and the slope values of the linear regression were within the interval [0.99, 1.1]. Simulation studies were performed in order to evaluate whether this metabolite correction method could be used in a clinical protocol where only a single [ 11 C]FMZ injection and a linear compartmental model are used. The resulting [ 11 C]FMZ distribution volume estimates were found to be linearly correlated with the true values, with r 2 =1.0 and a slope value of 1.1. The mathematical metabolite correction proved to be a feasible and reliable method to estimate the relative amount of [ 11 C]FMZ in plasma and the compartmental model parameters for three-injection protocols. Although

Normal and abnormal growth plate

International Nuclear Information System (INIS)

Kumar, R.; Madewell, J.E.; Swischuk, L.E.

1987-01-01

Skeletal growth is a dynamic process. A knowledge of the structure and function of the normal growth plate is essential in order to understand the pathophysiology of abnormal skeletal growth in various diseases. In this well-illustrated article, the authors provide a radiographic classification of abnormal growth plates and discuss mechanisms that lead to growth plate abnormalities

Role of scintigraphy in focally abnormal sonograms of fatty livers

International Nuclear Information System (INIS)

Lisbona, R.; Mishkin, S.; Derbekyan, V.; Novales-Diaz, J.A.; Roy, A.; Sanders, L.

1988-01-01

Fatty infiltration of the liver may cause a range of focal abnormalities on hepatic sonography which may simulate hepatic nodular lesions. Discrete deposits of fat or islands of normal tissue which are uninvolved by fatty infiltration may stand out as potential space-occupying lesions on the sonograms. Twelve patients with such focally abnormal ultrasound images were referred for liver scintigraphy with 133 Xe and /sup 99m/Tc colloidal SPECT studies to clarify the issue. These examinations helped identify, in nine of 12 patients, the innocent nature of the sonographic abnormalities which were simply related to the fat deposition process. Further, [/sup 99m/Tc]RBC scans defined the additional pathologic process in three patients in whom actual space-occupying lesions were indeed present in the liver. Scintigraphy has an important role to play in the understanding of focal hepatic ultrasound abnormalities particularly in unsuspected hepatic steatosis

Role of scintigraphy in focally abnormal sonograms of fatty livers

Energy Technology Data Exchange (ETDEWEB)

Lisbona, R.; Mishkin, S.; Derbekyan, V.; Novales-Diaz, J.A.; Roy, A.; Sanders, L.

1988-06-01

Fatty infiltration of the liver may cause a range of focal abnormalities on hepatic sonography which may simulate hepatic nodular lesions. Discrete deposits of fat or islands of normal tissue which are uninvolved by fatty infiltration may stand out as potential space-occupying lesions on the sonograms. Twelve patients with such focally abnormal ultrasound images were referred for liver scintigraphy with /sup 133/Xe and /sup 99m/Tc colloidal SPECT studies to clarify the issue. These examinations helped identify, in nine of 12 patients, the innocent nature of the sonographic abnormalities which were simply related to the fat deposition process. Further, (/sup 99m/Tc)RBC scans defined the additional pathologic process in three patients in whom actual space-occupying lesions were indeed present in the liver. Scintigraphy has an important role to play in the understanding of focal hepatic ultrasound abnormalities particularly in unsuspected hepatic steatosis.

Prospective study of blood metabolites associated with colorectal cancer risk.

Science.gov (United States)

Shu, Xiang; Xiang, Yong-Bing; Rothman, Nathaniel; Yu, Danxia; Li, Hong-Lan; Yang, Gong; Cai, Hui; Ma, Xiao; Lan, Qing; Gao, Yu-Tang; Jia, Wei; Shu, Xiao-Ou; Zheng, Wei

2018-02-26

Few prospective studies, and none in Asians, have systematically evaluated the relationship between blood metabolites and colorectal cancer risk. We conducted a nested case-control study to search for risk-associated metabolite biomarkers for colorectal cancer in an Asian population using blood samples collected prior to cancer diagnosis. Conditional logistic regression was performed to assess associations of metabolites with cancer risk. In this study, we included 250 incident cases with colorectal cancer and individually matched controls nested within two prospective Shanghai cohorts. We found 35 metabolites associated with risk of colorectal cancer after adjusting for multiple comparisons. Among them, 12 metabolites were glycerophospholipids including nine associated with reduced risk of colorectal cancer and three with increased risk [odds ratios per standard deviation increase of transformed metabolites: 0.31-1.98; p values: 0.002-1.25 × 10 -10 ]. The other 23 metabolites associated with colorectal cancer risk included nine lipids other than glycerophospholipid, seven aromatic compounds, five organic acids and four other organic compounds. After mutual adjustment, nine metabolites remained statistically significant for colorectal cancer. Together, these independently associated metabolites can separate cancer cases from controls with an area under the curve of 0.76 for colorectal cancer. We have identified that dysregulation of glycerophospholipids may contribute to risk of colorectal cancer. © 2018 UICC.

Hysterosalpingographic abnormalities in women with infertility in a ...

African Journals Online (AJOL)

Background: Structural tubal abnormalities are responsible for infertility in significant proportion of infertile couples. Hysterosalpingography (HSG) being a simple, less invasive, relatively inexpensive, and reproducible rapid diagnostic test provides valuable information about the uterine cavity and tubal architecture.

Report to Congress on abnormal occurrences, January--March 1988

International Nuclear Information System (INIS)

1988-07-01

Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event which the Nuclear Regulatory Commission determines to be significant from the standpoint of public health or safety and requires a quarterly report of such events to be made to Congress. This report covers the period from January 1 to March 31, 1988. For this reporting period, there were three abnormal occurrences at nuclear power plants licensed to operate: a potential for common mode failure of safety-related components due to a degraded instrument air system at Fort Calhoun; common mode failures of main steam isolation valves at Perry Unit 1; and a cracked pipe weld in a safety injection system at Farley Unit 2. There were six abnormal occurrences at other NRC licensees: a diagnostic medical misadministration; a breakdown in management controls at the Georgia Institute of Technology reactor facility; release of polonium-210 from static elimination devices manufactured by the 3M Company; two therapeutic medical misadministrationS; and a significant widespread breakdown in the radiation safety program at Case Western Reserve University research laboratories. There was one abnormal occurrence reported by an Agreement State (Texas) involving radiation injury to two radiographers. The report also contains information updating some previously reported abnormal occurrences. 43 refs

Age-related clinical and biological features of PTEN abnormalities in T-cell acute lymphoblastic leukaemia.

Science.gov (United States)

Tesio, M; Trinquand, A; Ballerini, P; Hypolite, G; Lhermitte, L; Petit, A; Ifrah, N; Baruchel, A; Dombret, H; Macintyre, E; Asnafi, V

2017-12-01

The tumour suppressor gene PTEN is commonly altered in T-cell acute lymphoblastic leukaemia but its prognostic impact is still debated. We screened a cohort of 573 fully characterised adult and paediatric T-cell acute lymphoblastic leukaemia (T-ALL) patients for genomic PTEN abnormalities. PTEN-inactivating mutations and/or deletions were identified in 91 cases (16%), including 18% of paediatric (49/277) and 14% of adult cases (42/296). Thirty-four patients harboured only mutations, 12 cases demonstrated only large deletions and 9 only microdeletions. About 36 patients had combined alterations. Different mechanisms of PTEN inactivation predicted differences in the clinical outcome for both adult and paediatric patients treated according to the GRAALL03/05 and FRALLE2000 protocols. Whereas large deletions predicted lower 5-year overall survival (P=0.0053 in adults, P=0.001 in children) and disease-free survival (P=0.0009 in adults, P=0.0002 in children), mutations were not associated with a worse prognosis. The prognostic impact of PTEN loss is therefore linked to the underlying type of genomic abnormality, both in adult and paediatric T-ALLs, demonstrating that detailed analysis of the type of abnormality type would be useful to refine risk stratification.

Rapid analysis of fungal cultures and dried figs for secondary metabolites by LC/TOF-MS

Energy Technology Data Exchange (ETDEWEB)

Senyuva, Hamide Z. [Ankara Test and Analysis Laboratory, Scientific and Technological Research Council of Turkey, Ankara 06330 (Turkey)], E-mail: hamide.senyuva@tubitak.gov.tr; Gilbert, John [Central Science Laboratory, Sand Hutton, York YO41 1LZ (United Kingdom); Oztuerkoglu, Sebnem [Ankara Test and Analysis Laboratory, Scientific and Technological Research Council of Turkey, Ankara 06330 (Turkey)

2008-06-09

A liquid chromatography-time-of-flight mass spectrometry (LC/TOF-MS) method has been developed for profiling fungal metabolites. The performance of the procedure in terms of mass accuracy, selectivity (specificity) and repeatability was established by spiking aflatoxins, ochratoxins, trichothecenes and other metabolites into blank growth media. After extracting, and carrying out LC/TOF-MS analysis, the standards were correctly identified by searching a specially constructed database of 465 secondary metabolites. To demonstrate the viability of this approach 11 toxigenic and four non-toxigenic fungi from reference collections were grown on various media, for 7-14 days. The method was also applied to two toxigenic fungi, A. flavus (200-138) and A. parasiticus (2999-465) grown on gamma radiation sterilised dried figs, for 7-14 days. The fungal hyphae plus a portion of growth media or portions of dried figs were solvent extracted and analysed by LC/TOF-MS using a rapid resolution microbore LC column. Data processing based on cluster analysis, showed that electrospray ionization (ESI)-TOF-MS could be used to unequivocally identify metabolites in crude extracts. Using the elemental metabolite database, it was demonstrated that from culture collection isolates, anticipated metabolites. The speed and simplicity of the method has meant that levels of these metabolites could be monitored daily in sterilised figs. Over a 14-day period, levels of aflatoxins and kojic acid maximised at 5-6 days, whilst levels of 5-methoxysterigmatocystin remained relatively constant. In addition to the known metabolites expected to be produced by these fungi, roquefortine A, fumagillin, fumigaclavine B, malformins (peptides), aspergillic acid, nigragillin, terrein, terrestric acid and penicillic acid were also identified.

Nonparametric Change Point Diagnosis Method of Concrete Dam Crack Behavior Abnormality

Directory of Open Access Journals (Sweden)

Zhanchao Li

2013-01-01

Full Text Available The study on diagnosis method of concrete crack behavior abnormality has always been a hot spot and difficulty in the safety monitoring field of hydraulic structure. Based on the performance of concrete dam crack behavior abnormality in parametric statistical model and nonparametric statistical model, the internal relation between concrete dam crack behavior abnormality and statistical change point theory is deeply analyzed from the model structure instability of parametric statistical model and change of sequence distribution law of nonparametric statistical model. On this basis, through the reduction of change point problem, the establishment of basic nonparametric change point model, and asymptotic analysis on test method of basic change point problem, the nonparametric change point diagnosis method of concrete dam crack behavior abnormality is created in consideration of the situation that in practice concrete dam crack behavior may have more abnormality points. And the nonparametric change point diagnosis method of concrete dam crack behavior abnormality is used in the actual project, demonstrating the effectiveness and scientific reasonableness of the method established. Meanwhile, the nonparametric change point diagnosis method of concrete dam crack behavior abnormality has a complete theoretical basis and strong practicality with a broad application prospect in actual project.

The Neurological Significance of Abnormal Natural Killer Cell Activity in Chronic Toxigenic Mold Exposures

Directory of Open Access Journals (Sweden)

Ebere Anyanwu

2003-01-01

Full Text Available Toxigenic mold activities produce metabolites that are either broad-spectrum antibiotics or mycotoxins that are cytotoxic. Indoor environmental exposure to these toxigenic molds leads to adverse health conditions with the main outcome measure of frequent neuroimmunologic and behavioral consequences. One of the immune system disorders found in patients presenting with toxigenic mold exposure is an abnormal natural killer cell activity. This paper presents an overview of the neurological significance of abnormal natural killer cell (NKC activity in chronic toxigenic mold exposure. A comprehensive review of the literature was carried out to evaluate and assess the conditions under which the immune system could be dysfunctionally interfered with leading to abnormal NKC activity and the involvement of mycotoxins in these processes. The functions, mechanism, the factors that influence NKC activities, and the roles of mycotoxins in NKCs were cited wherever necessary. The major presentations are headache, general debilitating pains, nose bleeding, fevers with body temperatures up to 40�C (104�F, cough, memory loss, depression, mood swings, sleep disturbances, anxiety, chronic fatigue, vertigo/dizziness, and in some cases, seizures. Although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system, it could be disturbed by mycotoxins. Most likely, mycotoxins exert some rigorous effects on the circadian rhythmic processes resulting in sleep deprivation to which an acute and transient increase in NKC activity is observed. Depression, psychological stress, tissue injuries, malignancies, carcinogenesis, chronic fatigue syndrome, and experimental allergic encephalomyelitis could be induced at very low physiological concentrations by mycotoxin-induced NKC activity. In the light of this review, it is concluded that chronic exposures to toxigenic mold could lead to abnormal NKC activity with a wide

Neural mechanisms of oculomotor abnormalities in the infantile strabismus syndrome.

Science.gov (United States)

Walton, Mark M G; Pallus, Adam; Fleuriet, Jérome; Mustari, Michael J; Tarczy-Hornoch, Kristina

2017-07-01

Infantile strabismus is characterized by numerous visual and oculomotor abnormalities. Recently nonhuman primate models of infantile strabismus have been established, with characteristics that closely match those observed in human patients. This has made it possible to study the neural basis for visual and oculomotor symptoms in infantile strabismus. In this review, we consider the available evidence for neural abnormalities in structures related to oculomotor pathways ranging from visual cortex to oculomotor nuclei. These studies provide compelling evidence that a disturbance of binocular vision during a sensitive period early in life, whatever the cause, results in a cascade of abnormalities through numerous brain areas involved in visual functions and eye movements. Copyright © 2017 the American Physiological Society.

The genetic and environmental determinants of the association between brain abnormalities and schizophrenia: the schizophrenia twins and relatives consortium.

Science.gov (United States)

van Haren, Neeltje E M; Rijsdijk, Fruhling; Schnack, Hugo G; Picchioni, Marco M; Toulopoulou, Timothea; Weisbrod, Matthias; Sauer, Heinrich; van Erp, Theo G; Cannon, Tyrone D; Huttunen, Matti O; Boomsma, Dorret I; Hulshoff Pol, Hilleke E; Murray, Robin M; Kahn, Rene S

2012-05-15

Structural brain abnormalities are consistently found in schizophrenia (Sz) and have been associated with the familial risk for the disorder. We aim to define the relative contributions of genetic and nongenetic factors to the association between structural brain abnormalities and Sz in a uniquely powered cohort (Schizophrenia Twins and Relatives consortium). An international multicenter magnetic resonance imaging collaboration was set up to pool magnetic resonance imaging scans from twin pairs in Utrecht (The Netherlands), Helsinki (Finland), London (United Kingdom), and Jena (Germany). A sample of 684 subjects took part, consisting of monozygotic twins (n = 410, with 51 patients from concordant and 52 from discordant pairs) and dizygotic twins (n = 274, with 39 patients from discordant pairs). The additive genetic, common, and unique environmental contributions to the association between brain volumes and risk for Sz were estimated by structural equation modeling. The heritabilities of most brain volumes were significant and ranged between 52% (temporal cortical gray matter) and 76% (cerebrum). Heritability of cerebral gray matter did not reach significance (34%). Significant phenotypic correlations were found between Sz and reduced volumes of the cerebrum (-.22 [-.30/-.14]) and white matter (-.17 [-.25/-.09]) and increased volume of the third ventricle (.18 [.08/.28]). These were predominantly due to overlapping genetic effects (77%, 94%, and 83%, respectively). Some of the genes that transmit the risk for Sz also influence cerebral (white matter) volume. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Secondary metabolites from Eurotium species, Aspergillus calidoustus and A. insuetus common in Canadian homes with a review of their chemistry and biological activities.

Science.gov (United States)

Slack, Gregory J; Puniani, Eva; Frisvad, Jens C; Samson, Robert A; Miller, J David

2009-04-01

As part of studies of metabolites from fungi common in the built environment in Canadian homes, we investigated metabolites from strains of three Eurotium species, namely E. herbariorum, E. amstelodami, and E. rubrum as well as a number of isolates provisionally identified as Aspergillus ustus. The latter have been recently assigned as the new species A. insuetus and A. calidoustus. E. amstelodami produced neoechinulin A and neoechinulin B, epiheveadride, flavoglaucin, auroglaucin, and isotetrahydroauroglaucin as major metabolites. Minor metabolites included echinulin, preechinulin and neoechinulin E. E. rubrum produced all of these metabolites, but epiheveadride was detected as a minor metabolite. E. herbariorum produced cladosporin as a major metabolite, in addition to those found in E. amstelodami. This species also produced questin and neoechinulin E as minor metabolites. This is the first report of epiheveadride occurring as a natural product, and the first nonadride isolated from Eurotium species. Unlike strains from mainly infection-related samples, largely from Europe, neither ophiobolins G and H nor austins were detected in the Canadian strains of A. insuetus and A. calidoustus tested, all of which had been reported from the latter species. TMC-120 A, B, C and a sesquiterpene drimane are reported with certainty for the first time from indoor isolates, as well as two novel related methyl isoquinoline alkaloids.

MARSI: metabolite analogues for rational strain improvement

DEFF Research Database (Denmark)

Cardoso, João G. R.; Zeidan, Ahmad A; Jensen, Kristian

2018-01-01

reactions in an organism can be used to predict effects of MAs on cellular phenotypes. Here, we present the Metabolite Analogues for Rational Strain Improvement (MARSI) framework. MARSI provides a rational approach to strain improvement by searching for metabolites as targets instead of genes or reactions...

Abundant Rodent Furan-Derived Urinary Metabolites Are Associated with Tobacco Smoke Exposure in Humans.

Science.gov (United States)

Grill, Alex E; Schmitt, Thaddeus; Gates, Leah A; Lu, Ding; Bandyopadhyay, Dipankar; Yuan, Jian-Min; Murphy, Sharon E; Peterson, Lisa A

2015-07-20

Furan, a possible human carcinogen, is found in heat treated foods and tobacco smoke. Previous studies have shown that humans are capable of converting furan to its reactive metabolite, cis-2-butene-1,4-dial (BDA), and therefore may be susceptible to furan toxicity. Human risk assessment of furan exposure has been stymied because of the lack of mechanism-based exposure biomarkers. Therefore, a sensitive LC-MS/MS assay for six furan metabolites was applied to measure their levels in urine from furan-exposed rodents as well as in human urine from smokers and nonsmokers. The metabolites that result from direct reaction of BDA with lysine (BDA-N(α)-acetyllysine) and from cysteine-BDA-lysine cross-links (N-acetylcysteine-BDA-lysine, N-acetylcysteine-BDA-N(α)-acetyllysine, and their sulfoxides) were targeted in this study. Five of the six metabolites were identified in urine from rodents treated with furan by gavage. BDA-N(α)-acetyllysine, N-acetylcysteine-BDA-lysine, and its sulfoxide were detected in most human urine samples from three different groups. The levels of N-acetylcysteine-BDA-lysine sulfoxide were more than 10 times higher than that of the corresponding sulfide in many samples. The amount of this metabolite was higher in smokers relative to that in nonsmokers and was significantly reduced following smoking cessation. Our results indicate a strong relationship between BDA-derived metabolites and smoking. Future studies will determine if levels of these biomarkers are associated with adverse health effects in humans.

Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain.

Directory of Open Access Journals (Sweden)

Erwin van Vliet

Full Text Available Intrauterine Growth Restriction (IUGR due to placental insufficiency occurs in 5-10% of pregnancies and is a major risk factor for abnormal neurodevelopment. The perinatal diagnosis of IUGR related abnormal neurodevelopment represents a major challenge in fetal medicine. The development of clinical biomarkers is considered a promising approach, but requires the identification of biochemical/molecular alterations by IUGR in the fetal brain. This targeted metabolomics study in a rabbit IUGR model aimed to obtain mechanistic insight into the effects of IUGR on the fetal brain and identify metabolite candidates for biomarker development.At gestation day 25, IUGR was induced in two New Zealand rabbits by 40-50% uteroplacental vessel ligation in one horn and the contralateral horn was used as control. At day 30, fetuses were delivered by Cesarian section, weighed and brains collected for metabolomics analysis. Results showed that IUGR fetuses had a significantly lower birth and brain weight compared to controls. Metabolomics analysis using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS and database matching identified 78 metabolites. Comparison of metabolite intensities using a t-test demonstrated that 18 metabolites were significantly different between control and IUGR brain tissue, including neurotransmitters/peptides, amino acids, fatty acids, energy metabolism intermediates and oxidative stress metabolites. Principle component and hierarchical cluster analysis showed cluster formations that clearly separated control from IUGR brain tissue samples, revealing the potential to develop predictive biomarkers. Moreover birth weight and metabolite intensity correlations indicated that the extent of alterations was dependent on the severity of IUGR.IUGR leads to metabolic alterations in the fetal rabbit brain, involving neuronal viability, energy metabolism, amino acid levels, fatty acid profiles and oxidative stress

Profiling of Intracellular Metabolites: An Approach to Understanding the Characteristic Physiology of Mycobacterium leprae.

Science.gov (United States)

Miyamoto, Yuji; Mukai, Tetsu; Matsuoka, Masanori; Kai, Masanori; Maeda, Yumi; Makino, Masahiko

2016-08-01

Mycobacterium leprae is the causative agent of leprosy and also known to possess unique features such as inability to proliferate in vitro. Among the cellular components of M. leprae, various glycolipids present on the cell envelope are well characterized and some of them are identified to be pathogenic factors responsible for intracellular survival in host cells, while other intracellular metabolites, assumed to be associated with basic physiological feature, remain largely unknown. In the present study, to elucidate the comprehensive profile of intracellular metabolites, we performed the capillary electrophoresis-mass spectrometry (CE-MS) analysis on M. leprae and compared to that of M. bovis BCG. Interestingly, comparison of these two profiles showed that, in M. leprae, amino acids and their derivatives are significantly accumulated, but most of intermediates related to central carbon metabolism markedly decreased, implying that M. leprae possess unique metabolic features. The present study is the first report demonstrating the unique profiles of M. leprae metabolites and these insights might contribute to understanding undefined metabolism of M. leprae as well as pathogenic characteristics related to the manifestation of the disease.

Smaller Dentate Gyrus and CA2 and CA3 Volumes Are Associated with Kynurenine Metabolites in Collegiate Football Athletes.

Science.gov (United States)

Meier, Timothy B; Savitz, Jonathan; Singh, Rashmi; Teague, T Kent; Bellgowan, Patrick S F

2016-07-15

An imbalance in kynurenine pathway metabolism is hypothesized to be associated with dysregulated glutamatergic neurotransmission, which has been proposed as a mechanism underlying the hippocampal volume loss observed in a variety of neurological disorders. Pre-clinical models suggest that the CA2-3 and dentate gyrus hippocampal subfields are particularly susceptible to excitotoxicity after experimental traumatic brain injury. We tested the hypothesis that smaller hippocampal volumes in collegiate football athletes with (n = 25) and without (n = 24) a concussion history would be most evident in the dentate gyrus and CA2-3 subfields relative to nonfootball healthy controls (n = 27). Further, we investigated whether the concentration of peripheral levels of kynurenine metabolites are altered in football athletes. Football athletes with and without a self-reported concussion history had smaller dentate gyrus (p Football athletes with and without a concussion history had a trend toward lower (p history had greater levels of quinolinic acid compared with athletes without a concussion history (p football athletes with a concussion history (p football athletes without a concussion history (p < 0.05). Our results raise the possibility that abnormalities of the kynurenine metabolic pathway constitute a mechanism for hippocampal volume differences in the context of sports-related brain injury.

Metabolite identification through multiple kernel learning on fragmentation trees.

Science.gov (United States)

Shen, Huibin; Dührkop, Kai; Böcker, Sebastian; Rousu, Juho

2014-06-15

Metabolite identification from tandem mass spectrometric data is a key task in metabolomics. Various computational methods have been proposed for the identification of metabolites from tandem mass spectra. Fragmentation tree methods explore the space of possible ways in which the metabolite can fragment, and base the metabolite identification on scoring of these fragmentation trees. Machine learning methods have been used to map mass spectra to molecular fingerprints; predicted fingerprints, in turn, can be used to score candidate molecular structures. Here, we combine fragmentation tree computations with kernel-based machine learning to predict molecular fingerprints and identify molecular structures. We introduce a family of kernels capturing the similarity of fragmentation trees, and combine these kernels using recently proposed multiple kernel learning approaches. Experiments on two large reference datasets show that the new methods significantly improve molecular fingerprint prediction accuracy. These improvements result in better metabolite identification, doubling the number of metabolites ranked at the top position of the candidates list. © The Author 2014. Published by Oxford University Press.

Pyometra in Bitches Induces Elevated Plasma Endotoxin and Prostaglandin F2α Metabolite Levels

Directory of Open Access Journals (Sweden)

Hagman R

2006-03-01

Full Text Available Endotoxemia in bitches with pyometra can cause severe systemic effects directly or via the release of inflammatory mediators. Plasma endotoxin concentrations were measured in ten bitches suffering from pyometra with moderately to severely deteriorated general condition, and in nine bitches admitted to surgery for non-infectious reasons. Endotoxin samples were taken on five occasions before, during and after surgery. In addition, urine and uterine bacteriology was performed and hematological, blood biochemical parameters, prostaglandin F2α metabolite 15-ketodihydro-PGF2α (PG-metabolite, progesterone and oestradiol (E2-17β levels were analysed. The results confirm significantly increased plasma levels of endotoxin in bitches with pyometra and support previous reports of endotoxin involvement in the pathogenesis of the disease. Plasma concentrations of PG-metabolite were elevated in pyometra bitches and provide a good indicator of endotoxin release since the concentrations were significantly correlated to the endotoxin levels and many other hematological and chemistry parameters. The γ-globulin serum protein electrophoresis fraction and analysis of PG-metabolite can be valuable in the diagnosis of endotoxin involvement if a reliable, rapid and cost-effective test for PG-metabolite analysis becomes readily available in the future. Treatment inhibiting prostaglandin biosynthesis and related compounds could be beneficial for bitches suffering from pyometra.

Effects of dietary sodium on metabolites: the Dietary Approaches to Stop Hypertension (DASH)-Sodium Feeding Study.

Science.gov (United States)

Derkach, Andriy; Sampson, Joshua; Joseph, Justin; Playdon, Mary C; Stolzenberg-Solomon, Rachael Z

2017-10-01

Background: High sodium intake is known to increase blood pressure and is difficult to measure in epidemiologic studies. Objective: We examined the effect of sodium intake on metabolites within the DASH (Dietary Approaches to Stop Hypertension Trial)-Sodium Trial to further our understanding of the biological effects of sodium intake beyond blood pressure. Design: The DASH-Sodium Trial randomly assigned individuals to either the DASH diet (low in fat and high in protein, low-fat dairy, and fruits and vegetables) or a control diet for 12 wk. Participants within each diet arm received, in random order, diets containing high (150 nmol or 3450 mg), medium (100 nmol or 2300 mg), and low (50 nmol or 1150 mg) amounts of sodium for 30 d (crossover design). Fasting blood samples were collected at the end of each sodium intervention. We measured 531 identified plasma metabolites in 73 participants at the end of their high- and low-sodium interventions and in 46 participants at the end of their high- and medium-sodium interventions ( N = 119). We used linear mixed-effects regression to model the relation between each log-transformed metabolite and sodium intake. We also combined the resulting P values with Fisher's method to estimate the association between sodium intake and 38 metabolic pathways or groups. Results: Six pathways were associated with sodium intake at a Bonferroni-corrected threshold of 0.0013 (e.g., fatty acid, food component or plant, benzoate, γ-glutamyl amino acid, methionine, and tryptophan). Although 82 metabolites were associated with sodium intake at a false discovery rate ≤0.10, only 4-ethylphenylsufate, a xenobiotic related to benzoate metabolism, was significant at a Bonferroni-corrected threshold ( P Sodium intake is associated with changes in circulating metabolites, including gut microbial, tryptophan, plant component, and γ-glutamyl amino acid-related metabolites. This trial was registered at clinicaltrials.gov as NCT00000608. © 2017

Linoleic acid participates in the response to ischemic brain injury through oxidized metabolites that regulate neurotransmission.

Science.gov (United States)

Hennebelle, Marie; Zhang, Zhichao; Metherel, Adam H; Kitson, Alex P; Otoki, Yurika; Richardson, Christine E; Yang, Jun; Lee, Kin Sing Stephen; Hammock, Bruce D; Zhang, Liang; Bazinet, Richard P; Taha, Ameer Y

2017-06-28

Linoleic acid (LA; 18:2 n-6), the most abundant polyunsaturated fatty acid in the US diet, is a precursor to oxidized metabolites that have unknown roles in the brain. Here, we show that oxidized LA-derived metabolites accumulate in several rat brain regions during CO 2 -induced ischemia and that LA-derived 13-hydroxyoctadecadienoic acid, but not LA, increase somatic paired-pulse facilitation in rat hippocampus by 80%, suggesting bioactivity. This study provides new evidence that LA participates in the response to ischemia-induced brain injury through oxidized metabolites that regulate neurotransmission. Targeting this pathway may be therapeutically relevant for ischemia-related conditions such as stroke.

Do metabolites that are produced during resistance exercise enhance muscle hypertrophy?

Science.gov (United States)

Dankel, Scott J; Mattocks, Kevin T; Jessee, Matthew B; Buckner, Samuel L; Mouser, J Grant; Loenneke, Jeremy P

2017-11-01

Many reviews conclude that metabolites play an important role with respect to muscle hypertrophy during resistance exercise, but their actual physiologic contribution remains unknown. Some have suggested that metabolites may work independently of muscle contraction, while others have suggested that metabolites may play a secondary role in their ability to augment muscle activation via inducing fatigue. Interestingly, the studies used as support for an anabolic role of metabolites use protocols that are not actually designed to test the importance of metabolites independent of muscle contraction. While there is some evidence in vitro that metabolites may induce muscle hypertrophy, the only study attempting to answer this question in humans found no added benefit of pooling metabolites within the muscle post-exercise. As load-induced muscle hypertrophy is thought to work via mechanotransduction (as opposed to being metabolically driven), it seems likely that metabolites simply augment muscle activation and cause the mechanotransduction cascade in a larger proportion of muscle fibers, thereby producing greater muscle growth. A sufficient time under tension also appears necessary, as measurable muscle growth is not observed after repeated maximal testing. Based on current evidence, it is our opinion that metabolites produced during resistance exercise do not have anabolic properties per se, but may be anabolic in their ability to augment muscle activation. Future studies are needed to compare protocols which produce similar levels of muscle activation, but differ in the magnitude of metabolites produced, or duration in which the exercised muscles are exposed to metabolites.

Effects of 3,4-methylenedioxymethamphetamine (MDMA) and its main metabolites on cardiovascular function in conscious rats.

Science.gov (United States)

Schindler, Charles W; Thorndike, Eric B; Blough, Bruce E; Tella, Srihari R; Goldberg, Steven R; Baumann, Michael H

2014-01-01

The cardiovascular effects produced by 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy') contribute to its acute toxicity, but the potential role of its metabolites in these cardiovascular effects is not known. Here we examined the effects of MDMA metabolites on cardiovascular function in rats. Radiotelemetry was employed to evaluate the effects of s.c. administration of racemic MDMA and its phase I metabolites on BP, heart rate (HR) and locomotor activity in conscious male rats. MDMA (1-20 mg·kg(-1)) produced dose-related increases in BP, HR and activity. The peak effects on HR occurred at a lower dose than peak effects on BP or activity. The N-demethylated metabolite, 3,4-methylenedioxyamphetamine (MDA), produced effects that mimicked those of MDMA. The metabolite 3,4-dihydroxymethamphetamine (HHMA; 1-10 mg·kg(-1)) increased HR more potently and to a greater extent than MDMA, whereas 3,4-dihydroxyamphetamine (HHA) increased HR, but to a lesser extent than HHMA. Neither dihydroxy metabolite altered motor activity. The metabolites 4-hydroxy-3-methoxymethamphetamine (HMMA) and 4-hydroxy-3-methoxyamphetamine (HMA) did not affect any of the parameters measured. The tachycardia produced by MDMA and HHMA was blocked by the β-adrenoceptor antagonist propranolol. Our results demonstrate that HHMA may contribute significantly to the cardiovascular effects of MDMA in vivo. As such, determining the molecular mechanism of action of HHMA and the other hydroxyl metabolites of MDMA warrants further study. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Metabolite fingerprinting, pathway analyses, and bioactivity correlations for plant species belonging to the Cornaceae, Fabaceae, and Rosaceae families.

Science.gov (United States)

Son, Su Young; Kim, Na Kyung; Lee, Sunmin; Singh, Digar; Kim, Ga Ryun; Lee, Jong Seok; Yang, Hee-Sun; Yeo, Joohong; Lee, Sarah; Lee, Choong Hwan

2016-09-01

A multi-parallel approach gauging the mass spectrometry-based metabolite fingerprinting coupled with bioactivity and pathway evaluations could serve as an efficacious tool for inferring plant taxonomic orders. Thirty-four species from three plant families, namely Cornaceae (7), Fabaceae (9), and Rosaceae (18) were subjected to metabolite profiling using gas chromatography-time-of-flight-mass spectrometry (GC-TOF-MS) and ultrahigh performance liquid chromatography-linear trap quadrupole-ion trap-mass spectrometry (UHPLC-LTQ-IT-MS/MS), followed by multivariate analyses to determine the metabolites characteristic of these families. The partial least squares discriminant analysis (PLS-DA) revealed the distinct clustering pattern of metabolites for each family. The pathway analysis further highlighted the relatively higher proportions of flavonols and ellagitannins in the Cornaceae family than in the other two families. Higher levels of phenolic acids and flavan-3-ols were observed among species from the Rosaceae family, while amino acids, flavones, and isoflavones were more abundant among the Fabaceae family members. The antioxidant activities of plant extracts were measured using ABTS, DPPH, and FRAP assays, and indicated that extracts from the Rosaceae family had the highest activity, followed by those from Cornaceae and Fabaceae. The correlation map analysis positively links the proportional concentration of metabolites with their relative antioxidant activities, particularly in Cornaceae and Rosaceae. This work highlights the pre-eminence of the multi-parallel approach involving metabolite profiling and bioactivity evaluations coupled with metabolic pathways as an efficient methodology for the evaluation of plant phylogenies.

Study on the abnormal image appeared in radiographs of welds, 3

International Nuclear Information System (INIS)

Hayashi, Morihiro; Sugimura, Seiichi; Umemura, Kunio; Imamura, Senji; Kanno, Munekazu.

1984-01-01

On the abnormal images arising at times in the X-ray radiographs of austenitic stainless steel welded parts, the cause of occurrence was clarified before. In this study, the authors made the welded parts of austenitic stainless steel SUS 304 and SUS 316 with abnormal images of different clearness by making heat input into respective layers of welds large or small, and compared the static and dynamic strength. Moreover, the relation of the form of abnormal images in radiographs to metal structures was studied. The welding method employed was TIG welding and submerged arc welding. The images of X-ray radiographs and the metal structures of the welded parts tested are shown. The mechanical strength test was carried out by tension, bending and impact. Also fatigue test was performed. In the welded parts of SUS 304 and SUS 316, even if abnormal images appeared in radiographs, when sound welding was made, they possessed sufficient strength statically and dynamically. In the macroscopic and microscopic cross-sectional structures of the welded parts with remarkable abnormal images, defect was not observed at all. The cause of abnormal image appearance is the diffraction of X-ray. (Kako, I.)

Concentrations, patterns and metabolites of organochlorine pesticides in relation to xenobiotic phase I and II enzyme activities in ringed seals (Phoca hispida) from Svalbard and the Baltic Sea

International Nuclear Information System (INIS)

Routti, Heli; Bavel, Bert van; Letcher, Robert J.; Arukwe, Augustine; Chu Shaogang; Gabrielsen, Geir W.

2009-01-01

The present study investigates the concentrations and patterns of organochlorine pesticides (OCPs) and their metabolites in liver and plasma of two ringed seal populations (Phoca hispida): lower contaminated Svalbard population and more contaminated Baltic Sea population. Among OCPs, p,p'-DDE and sum-chlordanes were the highest in concentration. With increasing hepatic contaminant concentrations and activities of xenobiotic-metabolizing enzymes, the concentrations of 3-methylsulfonyl-p,p'-DDE and the concentration ratios of pentachlorophenol/hexachlorobenzene increased, and the toxaphene pattern shifted more towards persistent Parlar-26 and -50 and less towards more biodegradable Parlar-44. Relative concentrations of the chlordane metabolites, oxychlordane and -heptachlorepoxide, to sum-chlordanes were higher in the seals from Svalbard compared to the seals from the Baltic, while the trend was opposite for cis- and trans-nonachlor. The observed differences in the OCP patterns in the seals from the two populations are probably related to the catalytic activity of xenobiotic-metabolizing enzymes, and also to differences in dietary exposure. - Contrasting patterns of organochlorine pesticides in two ringed seal populations.

Concentrations, patterns and metabolites of organochlorine pesticides in relation to xenobiotic phase I and II enzyme activities in ringed seals (Phoca hispida) from Svalbard and the Baltic Sea

Energy Technology Data Exchange (ETDEWEB)

Routti, Heli, E-mail: heli.routti@npolar.n [Norwegian Polar Institute, Polar Environmental Centre, 9296 Tromso (Norway); Centre of Excellence in Evolutionary Genetics and Physiology, Department of Biology, University of Turku, 20014 Turku (Finland); Bavel, Bert van [MTM Research Centre, Orebro University, 70182 Orebro (Sweden); Letcher, Robert J. [Wildlife Toxicology and Disease Program, Wildlife and Landscape Science Directorate, Science and Technology Branch, Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, Ontario K1A 0H3 (Canada); Arukwe, Augustine [Department of Biology, Norwegian University of Science and Technology, 7491 Trondheim (Norway); Chu Shaogang [Wildlife Toxicology and Disease Program, Wildlife and Landscape Science Directorate, Science and Technology Branch, Environment Canada, National Wildlife Research Centre, Carleton University, Ottawa, Ontario K1A 0H3 (Canada); Gabrielsen, Geir W. [Norwegian Polar Institute, Polar Environmental Centre, 9296 Tromso (Norway)

2009-08-15

The present study investigates the concentrations and patterns of organochlorine pesticides (OCPs) and their metabolites in liver and plasma of two ringed seal populations (Phoca hispida): lower contaminated Svalbard population and more contaminated Baltic Sea population. Among OCPs, p,p'-DDE and sum-chlordanes were the highest in concentration. With increasing hepatic contaminant concentrations and activities of xenobiotic-metabolizing enzymes, the concentrations of 3-methylsulfonyl-p,p'-DDE and the concentration ratios of pentachlorophenol/hexachlorobenzene increased, and the toxaphene pattern shifted more towards persistent Parlar-26 and -50 and less towards more biodegradable Parlar-44. Relative concentrations of the chlordane metabolites, oxychlordane and -heptachlorepoxide, to sum-chlordanes were higher in the seals from Svalbard compared to the seals from the Baltic, while the trend was opposite for cis- and trans-nonachlor. The observed differences in the OCP patterns in the seals from the two populations are probably related to the catalytic activity of xenobiotic-metabolizing enzymes, and also to differences in dietary exposure. - Contrasting patterns of organochlorine pesticides in two ringed seal populations.

Defining Abnormally Low Tenders

DEFF Research Database (Denmark)

Ølykke, Grith Skovgaard; Nyström, Johan

2017-01-01

The concept of an abnormally low tender is not defined in EU public procurement law. This article takes an interdisciplinary law and economics approach to examine a dataset consisting of Swedish and Danish judgments and verdicts concerning the concept of an abnormally low tender. The purpose...

Metabolite Profiles in Leaves and Spikes of Wheat under Constrasting Field-growing Environments Are Derived from Hyperspectral Readings

Science.gov (United States)

Vergara-Diaz, O.; Obata, T., Sr.; Kefauver, S. C.; Fernie, A., Sr.; Araus, J. L.

2017-12-01

The advance on metabolomics has led to a better understanding of plant-environment interactions and how the levels of specific metabolites may be used as indicators of plant performance. In cereals, the accumulation of certain metabolites -such as proline and sugars- has been related with water stress and drought tolerance/susceptibility, even revealing significant relationships with yield. On the other hand, recent studies relating plant biochemicals with spectral reflectance open the door to a deep assessment of plant status which would have implications on plant breeding and ecosystem studies. In this study, we investigated in durum wheat the relationship between the reflectance in the visible and near infrared regions (400-2500 µm wavelength) of the spectrum of the flag leaf, the ears and canopy levels with their respective metabolite profiles as well as its relationship with yield. To this aim, five durum wheat genotypes grown in four environments in the field were examined. PLS regression models indicated a strong determination of yield by using the spectrum of either leaves, ears and canopy. Additionally, grain yield was strongly predicted by the metabolite content of leaves and ears with multivariate regression analysis. Further preliminary results showed a promising performance of hyperspectral remote-proximal sensing for the calibration of plant metabolite content.

Chemotaxonomic Metabolite Profiling of 62 Indigenous Plant Species and Its Correlation with Bioactivities

Directory of Open Access Journals (Sweden)

Sarah Lee

2015-11-01

Full Text Available Chemotaxonomic metabolite profiling of 62 indigenous Korean plant species was performed by ultrahigh performance liquid chromatography (UHPLC-linear trap quadrupole-ion trap (LTQ-IT mass spectrometry/mass spectrometry (MS/MS combined with multivariate statistical analysis. In partial least squares discriminant analysis (PLS-DA, the 62 species clustered depending on their phylogenetic family, in particular, Aceraceae, Betulaceae, and Fagaceae were distinguished from Rosaceae, Fabaceae, and Asteraceae. Quinic acid, gallic acid, quercetin, quercetin derivatives, kaempferol, and kaempferol derivatives were identified as family-specific metabolites, and were found in relatively high concentrations in Aceraceae, Betulaceae, and Fagaceae. Fagaceae and Asteraceae were selected based on results of PLS-DA and bioactivities to determine the correlation between metabolic differences among plant families and bioactivities. Quinic acid, quercetin, kaempferol, quercetin derivatives, and kaempferol derivatives were found in higher concentrations in Fagaceae than in Asteraceae, and were positively correlated with antioxidant and tyrosinase inhibition activities. These results suggest that metabolite profiling was a useful tool for finding the different metabolic states of each plant family and understanding the correlation between metabolites and bioactivities in accordance with plant family.

MR imaging of abnormal synovial processes

International Nuclear Information System (INIS)

Quinn, S.F.; Sanchez, R.; Murray, W.T.; Silbiger, M.L.; Ogden, J.; Cochran, C.

1987-01-01

MR imaging can directly image abnormal synovium. The authors reviewed over 50 cases with abnormal synovial processes. The abnormalities include Baker cysts, semimembranous bursitis, chronic shoulder bursitis, peroneal tendon ganglion cyst, periarticular abscesses, thickened synovium from rheumatoid and septic arthritis, and synovial hypertrophy secondary to Legg-Calve-Perthes disease. MR imaging has proved invaluable in identifying abnormal synovium, defining the extent and, to a limited degree, characterizing its makeup

Secondary Metabolites from Higher Fungi: Discovery, Bioactivity, and Bioproduction

Science.gov (United States)

Zhong, Jian-Jiang; Xiao, Jian-Hui

Medicinal higher fungi such as Cordyceps sinensis and Ganoderma lucidum have been used as an alternative medicine remedy to promote health and longevity for people in China and other regions of the world since ancient times. Nowadays there is an increasing public interest in the secondary metabolites of those higher fungi for discovering new drugs or lead compounds. Current research in drug discovery from medicinal higher fungi involves a multifaceted approach combining mycological, biochemical, pharmacological, metabolic, biosynthetic and molecular techniques. In recent years, many new secondary metabolites from higher fungi have been isolated and are more likely to provide lead compounds for new drug discovery, which may include chemopreventive agents possessing the bioactivity of immunomodulatory, anticancer, etc. However, numerous challenges of secondary metabolites from higher fungi are encountered including bioseparation, identification, biosynthetic metabolism, and screening model issues, etc. Commercial production of secondary metabolites from medicinal mushrooms is still limited mainly due to less information about secondary metabolism and its regulation. Strategies for enhancing secondary metabolite production by medicinal mushroom fermentation include two-stage cultivation combining liquid fermentation and static culture, two-stage dissolved oxygen control, etc. Purification of bioactive secondary metabolites, such as ganoderic acids from G. lucidum, is also very important to pharmacological study and future pharmaceutical application. This review outlines typical examples of the discovery, bioactivity, and bioproduction of secondary metabolites of higher fungi origin.

Analytical method for urinary metabolites of the fluorine-containing pyrethroids metofluthrin, profluthrin and transfluthrin by gas chromatography/mass spectrometry.

Science.gov (United States)

Yoshida, Toshiaki

2013-01-15

An analytical method was developed for measurement of the major urinary metabolites in rats administered fluorine-containing pyrethroids (metofluthrin, profluthrin and transfluthrin) which are widely used recently as mosquito repellents or mothproof repellents. Eight metabolites, 2,3,5,6-tetrafluorobenzoic acid, 4-methyl-2,3,5,6-tetrafluorobenzoic acid, 2,2-dimethyl-3-(1-propenyl)-cyclopropanecarboxylic acid, 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid (carboxylic metabolites), 2,3,5,6-tetrafluorobenzyl alcohol, 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol, 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol and 4-hydroxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (alcoholic metabolites), were extracted from enzymatic hydrolyzed urine using toluene and then concentrated. After transformation to their tert-butyldimethylsilyl derivatives for carboxylic metabolites or their trimethylsilyl derivatives for alcoholic metabolites, analysis was conducted by gas chromatography/mass spectrometry in the electron impact ionization mode. The calibration curves for each metabolite were linear over the concentration range of 0-20μg/ml in urine, and the quantification limits were between 0.009 and 0.03μg/ml. The relative errors and the relative standard deviations on replicate assays were less than 6% and 5%, respectively, for all concentrations studied. The measurements were accurate and precise. The collected urine samples could be stored for up to 1 month at -20°C in a freezer. The proposed method was applied to the analysis of several urine samples collected from rats treated with these pyrethroids. Copyright © 2012 Elsevier B.V. All rights reserved.

Pharmaceutically active secondary metabolites of marine actinobacteria.

Science.gov (United States)

Manivasagan, Panchanathan; Venkatesan, Jayachandran; Sivakumar, Kannan; Kim, Se-Kwon

2014-04-01

Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinobacteria from terrestrial sources have been studied and screened since the 1950s, for many important antibiotics, anticancer, antitumor and immunosuppressive agents. However, frequent rediscovery of the same compounds from the terrestrial actinobacteria has made them less attractive for screening programs in the recent years. At the same time, actinobacteria isolated from the marine environment have currently received considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. They are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic, cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral, antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the current status of research on marine actinobacteria yielding pharmaceutically active secondary metabolites. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens. With the increasing advancement in science and technology, there would be a greater demand for new bioactive compounds synthesized by actinobacteria from various marine sources in future. Copyright © 2013 Elsevier GmbH. All rights reserved.

Metabolites in vertebrate Hedgehog signaling.

Science.gov (United States)

Roberg-Larsen, Hanne; Strand, Martin Frank; Krauss, Stefan; Wilson, Steven Ray

2014-04-11

The Hedgehog (HH) signaling pathway is critical in embryonic development, stem cell biology, tissue homeostasis, chemoattraction and synapse formation. Irregular HH signaling is associated with a number of disease conditions including congenital disorders and cancer. In particular, deregulation of HH signaling has been linked to skin, brain, lung, colon and pancreatic cancers. Key mediators of the HH signaling pathway are the 12-pass membrane protein Patched (PTC), the 7-pass membrane protein Smoothened (SMO) and the GLI transcription factors. PTC shares homology with the RND family of small-molecule transporters and it has been proposed that it interferes with SMO through metabolites. Although a conclusive picture is lacking, substantial efforts are made to identify and understand natural metabolites/sterols, including cholesterol, vitamin D3, oxysterols and glucocorticoides, that may be affected by, or influence the HH signaling cascade at the level of PTC and SMO. In this review we will elaborate the role of metabolites in HH signaling with a focus on oxysterols, and discuss advancements in modern analytical approaches in the field. Copyright © 2014 Elsevier Inc. All rights reserved.

Amelioration of behavioral abnormalities in BH(4-deficient mice by dietary supplementation of tyrosine.

Directory of Open Access Journals (Sweden)

Sang Su Kwak

Full Text Available This study reports an amelioration of abnormal motor behaviors in tetrahydrobiopterin (BH4-deficient Spr (-/- mice by the dietary supplementation of tyrosine. Since BH4 is an essential cofactor for the conversion of phenylalanine into tyrosine as well as the synthesis of dopamine neurotransmitter within the central nervous system, the levels of tyrosine and dopamine were severely reduced in brains of BH4-deficient Spr (-/- mice. We found that Spr (-/- mice display variable 'open-field' behaviors, impaired motor functions on the 'rotating rod', and dystonic 'hind-limb clasping'. In this study, we report that these aberrant motor deficits displayed by Spr (-/- mice were ameliorated by the therapeutic tyrosine diet for 10 days. This study also suggests that dopamine deficiency in brains of Spr (-/- mice may not be the biological feature of aberrant motor behaviors associated with BH4 deficiency. Brain levels of dopamine (DA and its metabolites in Spr (-/- mice were not substantially increased by the dietary tyrosine therapy. However, we found that mTORC1 activity severely suppressed in brains of Spr (-/- mice fed a normal diet was restored 10 days after feeding the mice the tyrosine diet. The present study proposes that brain mTORC1 signaling pathway is one of the potential targets in understanding abnormal motor behaviors associated with BH4-deficiency.

TARGETED, LCMS-BASED METABOLOMICS FOR QUANTITATIVE MEASUREMENT OF NAD+ METABOLITES

Directory of Open Access Journals (Sweden)

Samuel AJ Trammell

2013-01-01

Full Text Available Nicotinamide adenine dinucleotide (NAD+ is a coenzyme for hydride transfer reactions and a substrate for sirtuins and other NAD+-consuming enzymes. The abundance of NAD+, NAD+ biosynthetic intermediates, and related nucleotides reflects the metabolic state of cells and tissues. High performance liquid chromatography (HPLC followed by ultraviolet-visible (UV-Vis spectroscopic analysis of NAD+ metabolites does not offer the specificity and sensitivity necessary for robust quantification of complex samples. Thus, we developed a targeted, quantitative assay of the NAD+ metabolome with the use of HPLC coupled to mass spectrometry. Here we discuss NAD+ metabolism as well as the technical challenges required for reliable quantification of the NAD+ metabolites. The new method incorporates new separations and improves upon a previously published method that suffered from the problem of ionization suppression for particular compounds.

Prototype of an intertwined secondary-metabolite supercluster

Science.gov (United States)

Phillipp Wiemann; Chun-Jun. Guo; Jonathan M. Palmer; Relebohile Sekonyela; Clay C.C. Wang; Nancy P. Keller

2013-01-01

The hallmark trait of fungal secondary-metabolite gene clusters is well established, consisting of contiguous enzymatic and often regulatory gene(s) devoted to the production of a metabolite of a specific chemical class. Unexpectedly, we have found a deviation from this motif in a subtelomeric region of Aspergillus fumigatus. This region, under the...

Recent Advances in Mass Spectrometry for the Identification of Neuro-chemicals and their Metabolites in Biofluids.

Science.gov (United States)

Kailasa, Suresh Kumar; Wu, Hui-Fen

2013-07-01

Recently, mass spectrometric related techniques have been widely applied for the identification and quantification of neurochemicals and their metabolites in biofluids. This article presents an overview of mass spectrometric techniques applied in the detection of neurological substances and their metabolites from biological samples. In addition, the advances of chromatographic methods (LC, GC and CE) coupled with mass spectrometric techniques for analysis of neurochemicals in pharmaceutical and biological samples are also discussed.

Abnormalities of resting state functional connectivity are related to sustained attention deficits in MS.

Directory of Open Access Journals (Sweden)

Marisa Loitfelder

Full Text Available OBJECTIVES: Resting state (RS functional MRI recently identified default network abnormalities related to cognitive impairment in MS. fMRI can also be used to map functional connectivity (FC while the brain is at rest and not adhered to a specific task. Given the importance of the anterior cingulate cortex (ACC for higher executive functioning in MS, we here used the ACC as seed-point to test for differences and similarities in RS-FC related to sustained attention between MS patients and controls. DESIGN: Block-design rest phases of 3 Tesla fMRI data were analyzed to assess RS-FC in 31 patients (10 clinically isolated syndromes, 16 relapsing-remitting, 5 secondary progressive MS and 31 age- and gender matched healthy controls (HC. Participants underwent extensive cognitive testing. OBSERVATIONS: In both groups, signal changes in several brain areas demonstrated significant correlation with RS-activity in the ACC. These comprised the posterior cingulate cortex (PCC, insular cortices, the right caudate, right middle temporal gyrus, angular gyri, the right hippocampus, and the cerebellum. Compared to HC, patients showed increased FC between the ACC and the left angular gyrus, left PCC, and right postcentral gyrus. Better cognitive performance in the patients was associated with increased FC to the cerebellum, middle temporal gyrus, occipital pole, and the angular gyrus. CONCLUSION: We provide evidence for adaptive changes in RS-FC in MS patients compared to HC in a sustained attention network. These results extend and partly mirror findings of task-related fMRI, suggesting FC may increase our understanding of cognitive dysfunction in MS.

[Identification of saponins from Panax notoginseng in metabolites of rats].

Science.gov (United States)

Shen, Wen-Wen; Zhang, Yin; Qiu, Shou-Bei; Zhu, Fen-Xia; Jia, Xiao-Bin; Tang, Dao-Quan; Chen, Bin

2017-10-01

UPLC-QTOF-MS/MS was used to identify metabolites in rat blood, urine and feces after the administration of n-butanol extract derived from steamed notoginseng. The metabolic process of saponins came from steamed notoginseng was analyzed. The metabolites were processed by PeakView software, and identified according to the structural characteristics of prototype compounds and the accurate qualitative and quantitative changes of common metabolic pathways. Four saponins metabolites were identified based on MS/MS information of metabolites, namely ginsenoside Rh₄, Rk₃, Rk₁, Rg₅,and their 15 metabolites were verified. The metabolic pathways of the four ginsenosides in n-butanol extract included glucuronidation, desugar, sulfation, dehydromethylation, and branch loss. The metabolites of main active saponin components derived from steamed Panax notoginseng were analyzed from the perspective of qualitative analysis. And the material basis for the efficacy of steamed notoginseng was further clarified. Copyright© by the Chinese Pharmaceutical Association.

Variants of Insulin-Signaling Inhibitor Genes in Type 2 Diabetes and Related Metabolic Abnormalities

Directory of Open Access Journals (Sweden)

Carlo de Lorenzo

2013-01-01

Full Text Available Insulin resistance has a central role in the pathogenesis of several metabolic diseases, including type 2 diabetes, obesity, glucose intolerance, metabolic syndrome, atherosclerosis, and cardiovascular diseases. Insulin resistance and related traits are likely to be caused by abnormalities in the genes encoding for proteins involved in the composite network of insulin-signaling; in this review we have focused our attention on genetic variants of insulin-signaling inhibitor molecules. These proteins interfere with different steps in insulin-signaling: ENPP1/PC-1 and the phosphatases PTP1B and PTPRF/LAR inhibit the insulin receptor activation; INPPL1/SHIP-2 hydrolyzes PI3-kinase products, hampering the phosphoinositide-mediated downstream signaling; and TRIB3 binds the serine-threonine kinase Akt, reducing its phosphorylation levels. While several variants have been described over the years for all these genes, solid evidence of an association with type 2 diabetes and related diseases seems to exist only for rs1044498 of the ENPP1 gene and for rs2295490 of the TRIB3 gene. However, overall the data recapitulated in this Review article may supply useful elements to interpret the results of novel, more technically advanced genetic studies; indeed it is becoming increasingly evident that genetic information on metabolic diseases should be interpreted taking into account the complex biological pathways underlying their pathogenesis.

Biochemical, histopathological and morphological profiling of a rat model of early immune stimulation: relation to psychopathology.

Directory of Open Access Journals (Sweden)

Anna Kubesova

Full Text Available Perinatal immune challenge leads to neurodevelopmental dysfunction, permanent immune dysregulation and abnormal behaviour, which have been shown to have translational validity to findings in human neuropsychiatric disorders (e.g. schizophrenia, mood and anxiety disorders, autism, Parkinson's disease and Alzheimer's disease. The aim of this animal study was to elucidate the influence of early immune stimulation triggered by systemic postnatal lipopolysaccharide administration on biochemical, histopathological and morphological measures, which may be relevant to the neurobiology of human psychopathology. In the present study of adult male Wistar rats we examined the brain and plasma levels of monoamines (dopamine, serotonin, their metabolites, the levels of the main excitatory and inhibitory neurotransmitters glutamate and γ-aminobutyric acid and the levels of tryptophan and its metabolites from the kynurenine catabolic pathway. Further, we focused on histopathological and morphological markers related to pathogenesis of brain diseases--glial cell activation, neurodegeneration, hippocampal volume reduction and dopaminergic synthesis in the substantia nigra. Our results show that early immune stimulation in adult animals alters the levels of neurotransmitters and their metabolites, activates the kynurenine pathway of tryptophan metabolism and leads to astrogliosis, hippocampal volume reduction and a decrease of tyrosine hydroxylase immunoreactivity in the substantia nigra. These findings support the crucial pathophysiological role of early immune stimulation in the above mentioned neuropsychiatric disorders.

Benzene: a case study in parent chemical and metabolite interactions.

Science.gov (United States)

Medinsky, M A; Kenyon, E M; Schlosser, P M

1995-12-28

Benzene, an important industrial solvent, is also present in unleaded gasoline and cigarette smoke. The hematotoxic effects of benzene in humans are well documented and include aplastic anemia and pancytopenia, and acute myelogenous leukemia. A combination of metabolites (hydroquinone and phenol for example) is apparently necessary to duplicate the hematotoxic effect of benzene, perhaps due in part to the synergistic effect of phenol on myeloperoxidase-mediated oxidation of hydroquinone to the reactive metabolite benzoquinone. Since benzene and its hydroxylated metabolites (phenol, hydroquinone and catechol) are substrates for the same cytochrome P450 enzymes, competitive interactions among the metabolites are possible. In vivo data on metabolite formation by mice exposed to various benzene concentrations are consistent with competitive inhibition of phenol oxidation by benzene. In vitro studies of the metabolic oxidation of benzene, phenol and hydroquinone are consistent with the mechanism of competitive interaction among the metabolites. The dosimetry of benzene and its metabolites in the target tissue, bone marrow, depends on the balance of activation processes such as enzymatic oxidation and deactivation processes such as conjugation and excretion. Phenol, the primary benzene metabolite, can undergo both oxidation and conjugation. Thus, the potential exists for competition among various enzymes for phenol. However, zonal localization of Phase I and Phase II enzymes in various regions of the liver acinus regulates this competition. Biologically-based dosimetry models that incorporate the important determinants of benzene flux, including interactions with other chemicals, will enable prediction of target tissue doses of benzene and metabolites at low exposure concentrations relevant for humans.

Sleep and Sex: What Can Go Wrong? A Review of the Literature on Sleep Related Disorders and Abnormal Sexual Behaviors and Experiences

Science.gov (United States)

Schenck, Carlos H.; Arnulf, Isabelle; Mahowald, Mark W.

2007-01-01

Study Objectives: To formulate the first classification of sleep related disorders and abnormal sexual behaviors and experiences. Design: A computerized literature search was conducted, and other sources, such as textbooks, were searched. Results: Many categories of sleep related disorders were represented in the classification: parasomnias (confusional arousals/sleepwalking, with or without obstructive sleep apnea; REM sleep behavior disorder); sleep related seizures; Kleine-Levin syndrome (KLS); severe chronic insomnia; restless legs syndrome; narcolepsy; sleep exacerbation of persistent sexual arousal syndrome; sleep related painful erections; sleep related dissociative disorders; nocturnal psychotic disorders; miscellaneous states. Kleine-Levin syndrome (78 cases) and parasomnias (31 cases) were most frequently reported. Parasomnias and sleep related seizures had overlapping and divergent clinical features. Thirty-one cases of parasomnias (25 males; mean age, 32 years) and 7 cases of sleep related seizures (4 males; mean age, 38 years) were identified. A full range of sleep related sexual behaviors with self and/or bed partners or others were reported, including masturbation, sexual vocalizations, fondling, sexual intercourse with climax, sexual assault/rape, ictal sexual hyperarousal, ictal orgasm, and ictal automatism. Adverse physical and/or psychosocial effects from the sleepsex were present in all parasomnia and sleep related seizure cases, but pleasurable effects were reported by 5 bed partners and by 3 patients with sleep related seizures. Forensic consequences were common, occurring in 35.5% (11/31) of parasomnia cases, with most (9/11) involving minors. All parasomnias cases reported amnesia for the sleepsex, in contrast to 28.6% (2/7) of sleep related seizure cases. Polysomnography (without penile tumescence monitoring), performed in 26 of 31 parasomnia cases, documented sexual moaning from slow wave sleep in 3 cases and sexual intercourse during

Plant protein and secondary metabolites influence diet selection in a mammalian specialist herbivore

Science.gov (United States)

Amy C. Ulappa; Rick G. Kelsey; Graham G. Frye; Janet L. Rachlow; LIsa A. Shipley; Laura Bond; Xinzhu Pu; Jennifer Sorensen. Forbey

2014-01-01

For herbivores, nutrient intake is limited by the relatively low nutritional quality of plants and high concentrations of potentially toxic defensive compounds (plant secondary metabolites [PSMs]) produced by many plants. In response to phytochemical challenges, some herbivores selectively forage on plants with higher nutrient and lower PSM concentrations relative to...

Basal ganglia impairments in autism spectrum disorder are related to abnormal signal gating to prefrontal cortex.

Science.gov (United States)

Prat, Chantel S; Stocco, Andrea; Neuhaus, Emily; Kleinhans, Natalia M

2016-10-01

Research on the biological basis of autism spectrum disorder has yielded a list of brain abnormalities that are arguably as diverse as the set of behavioral symptoms that characterize the disorder. Among these are patterns of abnormal cortical connectivity and abnormal basal ganglia development. In attempts to integrate the existing literature, the current paper tests the hypothesis that impairments in the basal ganglia's function to flexibly select and route task-relevant neural signals to the prefrontal cortex underpins patterns of abnormal synchronization between the prefrontal cortex and other cortical processing centers observed in individuals with autism spectrum disorder (ASD). We tested this hypothesis using a Dynamic Causal Modeling analysis of neuroimaging data collected from 16 individuals with ASD (mean age=25.3 years; 6 female) and 17 age- and IQ-matched neurotypical controls (mean age=25.6, 6 female), who performed a Go/No-Go test of executive functioning. Consistent with the hypothesis tested, a random-effects Bayesian model selection procedure determined that a model of network connectivity in which basal ganglia activation modulated connectivity between the prefrontal cortex and other key cortical processing centers best fit the data of both neurotypicals and individuals with ASD. Follow-up analyses suggested that the largest group differences were observed for modulation of connectivity between prefrontal cortex and the sensory input region in the occipital lobe [t(31)=2.03, p=0.025]. Specifically, basal ganglia activation was associated with a small decrease in synchronization between the occipital region and prefrontal cortical regions in controls; however, in individuals with ASD, basal ganglia activation resulted in increased synchronization between the occipital region and the prefrontal cortex. We propose that this increased synchronization may reflect a failure in basal ganglia signal gating mechanisms, resulting in a non-selective copying

Secondary metabolites from Eremostachys laciniata

DEFF Research Database (Denmark)

Calis, Ihsan; Güvenc, Aysegül; Armagan, Metin

2008-01-01

), and forsythoside B (18), and five flavone derivatives, luteolin (19), luteolin 7-O-β-D-glucopyranoside (20), luteolin 7-O-(6''-O-β-D-apiofuranosyl)-β-D-glucopyranoside (21), apigenin 7-O-β-D-glucopyranoside (22), and apigenin 7-O-(6''-O-p-coumaroyl)-β-D-glucopyranoside (23). The structures of the metabolites were...... elucidated from spectroscopic (UV, IR, 1D- and 2D-NMR) and ESI-MS evidence, as well as from their specific optical rotation. The presence of these metabolites of three different classes strongly supports the close relationship of the genera Eremostachys and Phlomis....

Cyanobacteria as Cell Factories to Produce Plant Secondary Metabolites

OpenAIRE

Xue, Yong; He, Qingfang

2015-01-01

Cyanobacteria represent a promising platform for the production of plant secondary metabolites. Their capacity to express plant P450 proteins, which have essential functions in the biosynthesis of many plant secondary metabolites, makes cyanobacteria ideal for this purpose, and their photosynthetic capability allows cyanobacteria to grow with simple nutrient inputs. This review summarizes the advantages of using cyanobacteria to transgenically produce plant secondary metabolites. Some techniq...

An update on organohalogen metabolites produced by basidiomycetes

NARCIS (Netherlands)

Field, J.A.; Wijnberg, J.B.P.A.

2003-01-01

Basidiomycetes are an ecologically important group of higher fungi known for their widespread capacity to produce organohalogen metabolites. To date, 100 different organohalogen metabolites (mostly chlorinated) have been identified from strains in 70 genera of Basidiomycetes. This manuscript

Metabolome analysis - mass spectrometry and microbial primary metabolites

DEFF Research Database (Denmark)

Højer-Pedersen, Jesper Juul

2008-01-01

, and therefore sample preparation is critical for metabolome analysis. The three major steps in sample preparation for metabolite analysis are sampling, extraction and concentration. These three steps were evaluated for the yeast Saccharomyces cerevisiae with primary focus on analysis of a large number...... of metabolites by one method. The results highlighted that there were discrepancies between different methods. To increase the throughput of cultivation, S. cerevisiae was grown in microtitier plates (MTPs), and the growth was found to be comparable with cultivations in shake flasks. The carbon source was either...... a theoretical metabolome. This showed that in combination with the specificity of MS up to 84% of the metabolites can be identified in a high-accuracy ESI-spectrum. A total of 66 metabolites were systematically analyzed by positive and negative ESI-MS/MS with the aim of initiating a spectral library for ESI...

Serotonergic neurotoxic metabolites of ecstasy identified in rat brain.

Science.gov (United States)

Jones, Douglas C; Duvauchelle, Christine; Ikegami, Aiko; Olsen, Christopher M; Lau, Serrine S; de la Torre, Rafael; Monks, Terrence J

2005-04-01

The selective serotonergic neurotoxicity of 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) depends on their systemic metabolism. We have recently shown that inhibition of brain endothelial cell gamma-glutamyl transpeptidase (gamma-GT) potentiates the neurotoxicity of both MDMA and MDA, indicating that metabolites that are substrates for this enzyme contribute to the neurotoxicity. Consistent with this view, glutathione (GSH) and N-acetylcysteine conjugates of alpha-methyl dopamine (alpha-MeDA) are selective neurotoxicants. However, neurotoxic metabolites of MDMA or MDA have yet to be identified in brain. Using in vivo microdialysis coupled to liquid chromatography-tandem mass spectroscopy and a high-performance liquid chromatography-coulometric electrode array system, we now show that GSH and N-acetylcysteine conjugates of N-methyl-alpha-MeDA are present in the striatum of rats administered MDMA by subcutaneous injection. Moreover, inhibition of gamma-GT with acivicin increases the concentration of GSH and N-acetylcysteine conjugates of N-methyl-alpha-MeDA in brain dialysate, and there is a direct correlation between the concentrations of metabolites in dialysate and the extent of neurotoxicity, measured by decreases in serotonin (5-HT) and 5-hydroxyindole acetic (5-HIAA) levels. Importantly, the effects of acivicin are independent of MDMA-induced hyperthermia, since acivicin-mediated potentiation of MDMA neurotoxicity occurs in the context of acivicin-mediated decreases in body temperature. Finally, we have synthesized 5-(N-acetylcystein-S-yl)-N-methyl-alpha-MeDA and established that it is a relatively potent serotonergic neurotoxicant. Together, the data support the contention that MDMA-mediated serotonergic neurotoxicity is mediated by the systemic formation of GSH and N-acetylcysteine conjugates of N-methyl-alpha-MeDA (and alpha-MeDA). The mechanisms by which such metabolites access the brain and produce selective

Steroid receptor profiling of vinclozolin and its primary metabolites

International Nuclear Information System (INIS)

Molina-Molina, Jose-Manuel; Hillenweck, Anne; Jouanin, Isabelle; Zalko, Daniel; Cravedi, Jean-Pierre; Fernandez, Mariana-Fatima; Pillon, Arnaud; Nicolas, Jean-Claude; Olea, Nicolas; Balaguer, Patrick

2006-01-01

Several pesticides and fungicides commonly used to control agricultural and indoor pests are highly suspected to display endocrine-disrupting effects in animals and humans. Endocrine disruption is mainly caused by the interference of chemicals at the level of steroid receptors: it is now well known that many of these chemicals can display estrogenic effects and/or anti-androgenic effects, but much less is known about the interaction of these compounds with other steroid receptors. Vinclozolin, a dicarboximide fungicide, like its primary metabolites 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), is known to bind androgen receptor (AR). Although vinclozolin and its metabolites were characterized as anti-androgens, relatively little is known about their effects on the function of the progesterone (PR), glucocorticoid (GR), mineralocorticoid (MR) or estrogen receptors (ERα and ERβ). Objectives of the study were to determine the ability of vinclozolin and its two primary metabolites to activate AR, PR, GR, MR and ER. For this purpose, we used reporter cell lines bearing luciferase gene under the control of wild type or chimeric Gal4 fusion AR, PR, GR, MR or ERs. We confirmed that all three were antagonists for AR, whereas only M2 was found a partial agonist. Interestingly, M2 was also a PR, GR and MR antagonist (MR >> PR > GR) while vinclozolin was an MR and PR antagonist. Vinclozolin, M1 and M2 were agonists for both ERs with a lower affinity for ERβ. Although the potencies of the fungicide and its metabolites are low when compared to natural ligands, their ability to act via more than one mechanism and the potential for additive or synergistic effect must be taken into consideration in the risk assessment process

Steroid receptor profiling of vinclozolin and its primary metabolites.

Science.gov (United States)

Molina-Molina, José-Manuel; Hillenweck, Anne; Jouanin, Isabelle; Zalko, Daniel; Cravedi, Jean-Pierre; Fernández, Mariana-Fátima; Pillon, Arnaud; Nicolas, Jean-Claude; Olea, Nicolás; Balaguer, Patrick

2006-10-01

Several pesticides and fungicides commonly used to control agricultural and indoor pests are highly suspected to display endocrine-disrupting effects in animals and humans. Endocrine disruption is mainly caused by the interference of chemicals at the level of steroid receptors: it is now well known that many of these chemicals can display estrogenic effects and/or anti-androgenic effects, but much less is known about the interaction of these compounds with other steroid receptors. Vinclozolin, a dicarboximide fungicide, like its primary metabolites 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), is known to bind androgen receptor (AR). Although vinclozolin and its metabolites were characterized as anti-androgens, relatively little is known about their effects on the function of the progesterone (PR), glucocorticoid (GR), mineralocorticoid (MR) or estrogen receptors (ERalpha and ERbeta). Objectives of the study were to determine the ability of vinclozolin and its two primary metabolites to activate AR, PR, GR, MR and ER. For this purpose, we used reporter cell lines bearing luciferase gene under the control of wild type or chimeric Gal4 fusion AR, PR, GR, MR or ERs. We confirmed that all three were antagonists for AR, whereas only M2 was found a partial agonist. Interestingly, M2 was also a PR, GR and MR antagonist (MR>PR>GR) while vinclozolin was an MR and PR antagonist. Vinclozolin, M1 and M2 were agonists for both ERs with a lower affinity for ERbeta. Although the potencies of the fungicide and its metabolites are low when compared to natural ligands, their ability to act via more than one mechanism and the potential for additive or synergistic effect must be taken into consideration in the risk assessment process.

Special report on abnormal climate in 2010

International Nuclear Information System (INIS)

2010-12-01

This reports on abnormal climate in 2010 with impact on the each field. It is comprised of four chapters, which deal with Introduction with purpose of publish and background, current situation and cause of abnormal climate in 2010 on abnormal climate around the world and Korea, Action and impact against abnormal climate in 2010 to agriculture, industry and energy, prevention of disasters, forest, fishery products, environment and health, Evaluation and policy proposal. It also has an appendix about occurrence and damage on abnormal climate of the world in 2010 and media reports on abnormal climate in Korea in 2010.

[Cytogenetic Abnormalities and Outcomes of 117 Patients with Multiple Myeloma Detected by FISH].

Science.gov (United States)

Zhai, Bing; Zou, Dan-Dan; Yan, Jian-Jun; Wang, Nan; Wang, Li-Li; Zhu, Hong-Li; Huang, Wen-Rong; Yu, Li

2016-02-01

To analyze the cytogenetic abnormalities and prognostic outcomes of patients with multiple myeloma (MM) detected by fluorescence in situ hybridization (FISH). The clinical record of 117 newly-diagnosed patients with MM treated in department of hematology and geriatric hematology of our hospital for 7 years were collected, and their molecular cytogenetic abnormalities detected by FISH and the clinical outcome were analyzed retrospectively. The detected rate of cytogenetic abnormality was 76.9%(90/117), the most common abnormality deteted by FISH was 1q21+ (71.1%), followed by 13q- (56.6%). The cross comparison method showed that 13q- and 17p13-, t(11;14) and t(4;14) were related respectively. All the patients with cytogenetic abnormalities showed no significant difference in the overall survival from cytogenetic normal patients. The positive rate of molecular cytogenetic abnormalities detected by FISH in MM patients is high, but data from larger and longer studies are needed to evaluate the prognostic outcomes.

Motor-related brain abnormalities in HIV-infected patients. A multimodal MRI study

Energy Technology Data Exchange (ETDEWEB)

Zhou, Yawen; Wang, Xiaoxiao; Miao, Hui; Wei, Yarui; Ali, Rizwan [University of Science and Technology of China, Centers for Biomedical Engineering, Hefei, Anhui (China); Li, Ruili; Li, Hongjun [Capital Medical University, Department of Radiology, Beijing Youan Hospital, Beijing (China); Qiu, Bensheng [University of Science and Technology of China, Centers for Biomedical Engineering, Hefei, Anhui (China); Anhui Computer Application Institute of Traditional Chinese Medicine, Hefei, Anhui (China)

2017-11-15

It is generally believed that HIV infection could cause HIV-associated neurocognitive disorders (HAND) across a broad range of functional domains. Some of the most common findings are deficits in motor control. However, to date no neuroimaging studies have evaluated basic motor control in HIV-infected patients using a multimodal approach. In this study, we utilized high-resolution structural imaging and task-state functional magnetic resonance imaging (fMRI) to assess brain structure and motor function in a homogeneous cohort of HIV-infected patients. We found that HIV-infected patients had significantly reduced gray matter (GM) volume in cortical regions, which are involved in motor control, including the bilateral posterior insula cortex, premotor cortex, and supramarginal gyrus. Increased activation in bilateral posterior insula cortices was also demonstrated by patients during hand movement tasks compared with healthy controls. More importantly, the reduced GM in bilateral posterior insula cortices was spatially coincident with abnormal brain activation in HIV-infected patients. In addition, the results of partial correlation analysis indicated that GM reduction in bilateral posterior insula cortices and premotor cortices was significantly correlated with immune system deterioration. This study is the first to demonstrate spatially coincident GM reduction and abnormal activation during motor performance in HIV-infected patients. Although it remains unknown whether the brain deficits can be recovered, our findings may yield new insights into neurologic injury underlying motor dysfunction in HAND. (orig.)

Motor-related brain abnormalities in HIV-infected patients. A multimodal MRI study

International Nuclear Information System (INIS)

Zhou, Yawen; Wang, Xiaoxiao; Miao, Hui; Wei, Yarui; Ali, Rizwan; Li, Ruili; Li, Hongjun; Qiu, Bensheng

2017-01-01

It is generally believed that HIV infection could cause HIV-associated neurocognitive disorders (HAND) across a broad range of functional domains. Some of the most common findings are deficits in motor control. However, to date no neuroimaging studies have evaluated basic motor control in HIV-infected patients using a multimodal approach. In this study, we utilized high-resolution structural imaging and task-state functional magnetic resonance imaging (fMRI) to assess brain structure and motor function in a homogeneous cohort of HIV-infected patients. We found that HIV-infected patients had significantly reduced gray matter (GM) volume in cortical regions, which are involved in motor control, including the bilateral posterior insula cortex, premotor cortex, and supramarginal gyrus. Increased activation in bilateral posterior insula cortices was also demonstrated by patients during hand movement tasks compared with healthy controls. More importantly, the reduced GM in bilateral posterior insula cortices was spatially coincident with abnormal brain activation in HIV-infected patients. In addition, the results of partial correlation analysis indicated that GM reduction in bilateral posterior insula cortices and premotor cortices was significantly correlated with immune system deterioration. This study is the first to demonstrate spatially coincident GM reduction and abnormal activation during motor performance in HIV-infected patients. Although it remains unknown whether the brain deficits can be recovered, our findings may yield new insights into neurologic injury underlying motor dysfunction in HAND. (orig.)

Chest computed tomography-based scoring of thoracic sarcoidosis: Inter-rater reliability of CT abnormalities

Energy Technology Data Exchange (ETDEWEB)

Heuvel, D.A.V. den; Es, H.W. van; Heesewijk, J.P. van; Spee, M. [St. Antonius Hospital Nieuwegein, Department of Radiology, Nieuwegein (Netherlands); Jong, P.A. de [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Zanen, P.; Grutters, J.C. [University Medical Center Utrecht, Division Heart and Lungs, Utrecht (Netherlands); St. Antonius Hospital Nieuwegein, Center of Interstitial Lung Diseases, Department of Pulmonology, Nieuwegein (Netherlands)

2015-09-15

To determine inter-rater reliability of sarcoidosis-related computed tomography (CT) findings that can be used for scoring of thoracic sarcoidosis. CT images of 51 patients with sarcoidosis were scored by five chest radiologists for various abnormal CT findings (22 in total) encountered in thoracic sarcoidosis. Using intra-class correlation coefficient (ICC) analysis, inter-rater reliability was analysed and reported according to the Guidelines for Reporting Reliability and Agreement Studies (GRRAS) criteria. A pre-specified sub-analysis was performed to investigate the effect of training. Scoring was trained in a distinct set of 15 scans in which all abnormal CT findings were represented. Median age of the 51 patients (36 men, 70 %) was 43 years (range 26 - 64 years). All radiographic stages were present in this group. ICC ranged from 0.91 for honeycombing to 0.11 for nodular margin (sharp versus ill-defined). The ICC was above 0.60 in 13 of the 22 abnormal findings. Sub-analysis for the best-trained observers demonstrated an ICC improvement for all abnormal findings and values above 0.60 for 16 of the 22 abnormalities. In our cohort, reliability between raters was acceptable for 16 thoracic sarcoidosis-related abnormal CT findings. (orig.)

Chest computed tomography-based scoring of thoracic sarcoidosis: Inter-rater reliability of CT abnormalities

International Nuclear Information System (INIS)

Heuvel, D.A.V. den; Es, H.W. van; Heesewijk, J.P. van; Spee, M.; Jong, P.A. de; Zanen, P.; Grutters, J.C.

2015-01-01

To determine inter-rater reliability of sarcoidosis-related computed tomography (CT) findings that can be used for scoring of thoracic sarcoidosis. CT images of 51 patients with sarcoidosis were scored by five chest radiologists for various abnormal CT findings (22 in total) encountered in thoracic sarcoidosis. Using intra-class correlation coefficient (ICC) analysis, inter-rater reliability was analysed and reported according to the Guidelines for Reporting Reliability and Agreement Studies (GRRAS) criteria. A pre-specified sub-analysis was performed to investigate the effect of training. Scoring was trained in a distinct set of 15 scans in which all abnormal CT findings were represented. Median age of the 51 patients (36 men, 70 %) was 43 years (range 26 - 64 years). All radiographic stages were present in this group. ICC ranged from 0.91 for honeycombing to 0.11 for nodular margin (sharp versus ill-defined). The ICC was above 0.60 in 13 of the 22 abnormal findings. Sub-analysis for the best-trained observers demonstrated an ICC improvement for all abnormal findings and values above 0.60 for 16 of the 22 abnormalities. In our cohort, reliability between raters was acceptable for 16 thoracic sarcoidosis-related abnormal CT findings. (orig.)

New secondary metabolites of phenylbutyrate in humans and rats.

Science.gov (United States)

Kasumov, Takhar; Brunengraber, Laura L; Comte, Blandine; Puchowicz, Michelle A; Jobbins, Kathryn; Thomas, Katherine; David, France; Kinman, Renee; Wehrli, Suzanne; Dahms, William; Kerr, Douglas; Nissim, Itzhak; Brunengraber, Henri

2004-01-01

Phenylbutyrate is used to treat inborn errors of ureagenesis, malignancies, cystic fibrosis, and thalassemia. High-dose phenylbutyrate therapy results in toxicity, the mechanism of which is unexplained. The known metabolites of phenylbutyrate are phenylacetate, phenylacetylglutamine, and phenylbutyrylglutamine. These are excreted in urine, accounting for a variable fraction of the dose. We identified new metabolites of phenylbutyrate in urine of normal humans and in perfused rat livers. These metabolites result from interference between the metabolism of phenylbutyrate and that of carbohydrates and lipids. The new metabolites fall into two categories, glucuronides and phenylbutyrate beta-oxidation side products. Two questions are raised by these data. First, is the nitrogen-excreting potential of phenylbutyrate diminished by ingestion of carbohydrates or lipids? Second, does competition between the metabolism of phenylbutyrate, carbohydrates, and lipids alter the profile of phenylbutyrate metabolites? Finally, we synthesized glycerol esters of phenylbutyrate. These are partially bioavailable in rats and could be used to administer large doses of phenylbutyrate in a sodium-free, noncaustic form.

Novel urinary metabolite of d-delta-tocopherol in rats

International Nuclear Information System (INIS)

Chiku, S.; Hamamura, K.; Nakamura, T.

1984-01-01

A novel metabolite of d-delta-tocopherol was isolated from the urine of rats given d-3,4-[ 3 H 2 ]-delta-tocopherol intravenously. The metabolite was collected from the urine of rats given d-delta-tocopherol in the same manner as that of the labeled compound. It was found that the metabolites consisted of sulfate conjugates. The portion of the major metabolite released with sulfatase was determined to be 2,8-dimethyl-2-(2'-carboxyethyl)-6-chromanol by infrared spectra, nuclear magnetic resonance spectra, and mass spectra. The proposed structure was confirmed by comparing the analytical results with those of a synthetically derived compound. As a result of the structural elucidation of this novel metabolite, a pathway for the biological transformation of delta-tocopherol is proposed which is different from that of alpha-tocopherol. A characteristic feature of the pathway is the absence of any opening of the chroman ring throughout the sequence

Circulating prostacyclin metabolites in the dog

International Nuclear Information System (INIS)

Taylor, B.M.; Shebuski, R.J.; Sun, F.F.

1983-01-01

The present study was designed to determine the concentration of prostacyclin (PGI2) metabolites in the blood of the dog. After a bolus i.v. dose of [11 beta- 3 H]PGI2 (5 micrograms/kg) into each of five dogs, blood samples were withdrawn at 0.33, 0.67, 1, 3, 5, 20, 30, 60 and 120 min postdrug administration. Plasma samples were extracted and the radioactive components were analyzed by two-dimensional thin-layer chromatography with autoradiofluorography and radio-high-performance liquid chromatography. The compounds were identified by comparing their mobility with synthetic standards; only parallel responses observed in both tests constituted positive identification. Seven metabolites were identified by these two techniques: 6-keto-prostaglandin (PG)F1 alpha; 6-keto-PGE1; 2,3-dinor-6-keto-PGF 1 alpha; 2,3-dinor-13,14-dihydro-6,15-diketo-20-carboxyl PGF 1 alpha; and 2,3,18,19-tetranor-13,14-dihydro-6,15-diketo-20-carboxyl PGF 1 alpha. Several additional compounds, both polar and nonpolar in nature, which did not co-chromatograph with any of our standards were also detected. Early samples consisted predominantly of 6-keto-PGF 1 alpha and other 20-carbon metabolites. By 30 min, the predominant metabolites were the 16- and 18-carbon dicarboxylic acids. By 60 min, 85% of the radioactivity was associated with two unidentified polar compounds. The evidence suggests that 6-keto-PGF 1 alpha probably reflects only the transient levels of freshly entering PGI2 in the circulation, whereas levels of the most polar metabolites (e.g., dihydro-diketo-carboxyl tetranor-PGF 2 alpha) may be a better measure of the overall PGI2 presence due to its longer half-life in circulation

Growth regulator induced mobilization of 14C-metabolites into sunflower heads

International Nuclear Information System (INIS)

Prasad, T.G.; Udaykumar, M.; Rama Rao, S.; Krishna Sastry, K.S.

1977-01-01

Effect of exogenous application of mixtures of NAA, Ga and BA to the head in sunflower, after pollination and fertilization, on the mobilization of 14 C-metabolites was studied. Application of such mixtures increased mobilization and altered the pattern of translocation. TIBA applied to the head when the ray florets only had commenced opening also caused an increase in mobilization of 14 C-metabolites. Percent activity in relation to the activity fixed by the leaf increased from 36.8 in control to 63 in TIBA treated head. Field experiments conducted for 2 seasons also confirmed effectiveness of TIBA application in increasing percent seed filling and also 1000 grain weight. In sunflower it was possible to increase the sink capacity by application of growth regulators. (author)

Olfaction in eating disorders and abnormal eating behavior: a systematic review.

Science.gov (United States)

Islam, Mohammed A; Fagundo, Ana B; Arcelus, Jon; Agüera, Zaida; Jiménez-Murcia, Susana; Fernández-Real, José M; Tinahones, Francisco J; de la Torre, Rafael; Botella, Cristina; Frühbeck, Gema; Casanueva, Felipe F; Menchón, José M; Fernandez-Aranda, Fernando

2015-01-01

The study provides a systematic review that explores the current literature on olfactory capacity in abnormal eating behavior. The objective is to present a basis for discussion on whether research in olfaction in eating disorders may offer additional insight with regard to the complex etiopathology of eating disorders (ED) and abnormal eating behaviors. Electronic databases (Medline, PsycINFO, PubMed, Science Direct, and Web of Science) were searched using the components in relation to olfaction and combining them with the components related to abnormal eating behavior. Out of 1352 articles, titles were first excluded by title (n = 64) and then by abstract and fulltext resulting in a final selection of 14 articles (820 patients and 385 control participants) for this review. The highest number of existing literature on olfaction in ED were carried out with AN patients (78.6%) followed by BN patients (35.7%) and obese individuals (14.3%). Most studies were only conducted on females. The general findings support that olfaction is altered in AN and in obesity and indicates toward there being little to no difference in olfactory capacity between BN patients and the general population. Due to the limited number of studies and heterogeneity this review stresses on the importance of more research on olfaction and abnormal eating behavior.

Prevalence and distribution of congenital abnormalities in Turkey: differences between the prenatal and postnatal periods.

Science.gov (United States)

Oztarhan, Kazim; Gedikbasi, Ali; Yildirim, Dogukan; Arslan, Oguz; Adal, Erdal; Kavuncuoglu, Sultan; Ozbek, Sibel; Ceylan, Yavuz

2010-12-01

The aim of this study was to determine the distribution of cases associated with congenital abnormalities during the following three periods: pregnancy, birth, and the neonatal period. This was a retrospective study of cases between 2002 and 2006. All abnormal pregnancies, elective terminations of pregnancies, stillbirths, and births with congenital abnormalities managed in the Neonatology Unit were classified based on the above distribution scheme. During the 5-year study period, 1906 cases with congenital abnormalities were recruited, as follows: 640 prenatally detected and terminated cases, with most abnormalities related to the central nervous system, chromosomes, and urogenital system (56.7%, 12.7%, and 8.9%, respectively); 712 neonates with congenital abnormalities (congenital heart disease [49.2%], central nervous system abnormalities [14.7%], and urogenital system abnormalities [12.9%]); and hospital stillbirths, of which 34.2% had malformations (220 prenatal cases [34.4%] had multiple abnormalities, whereas 188 liveborn cases [26.4%] had multiple abnormalities). The congenital abnormalities rate between 2002 and 2006 was 2.07%. Systematic screening for fetal anomalies is the primary means for identification of affected pregnancies. © 2010 The Authors. Congenital Anomalies © 2010 Japanese Teratology Society.

Identification of differential metabolites in liquid diet fermented with Bacillus subtilis using gas chromatography time of flight mass spectrometry

Directory of Open Access Journals (Sweden)

Yuyong He

2016-12-01

Full Text Available Growth and health responses of pigs fed fermented liquid diet are not always consistent and causes for this issue are still not very clear. Metabolites produced at different fermentation time points should be one of the most important contributors. However, currently no literatures about differential metabolites of fermented liquid diet are reported. The aim of this experiment was to explore the difference of metabolites in a fermented liquid diet between different fermentation time intervals. A total of eighteen samples that collected from Bacillus subtilis fermented liquid diet on days 7, 21 and 35 respectively were used for the identification of metabolites by gas chromatography time of flight mass spectrometry (GC-TOF-MS. Fifteen differential metabolites including melibiose, sortitol, ribose, cellobiose, maltotriose, sorbose, isomaltose, maltose, fructose, d-glycerol-1-phosphate, 4-aminobutyric acid, beta-alanine, tyrosine, pyruvic acid and pantothenic acid were identified between 7-d samples and 21-d samples. The relative level of melibiose, ribose, maltotriose, d-glycerol-1-phosphate, tyrosine and pyruvic acid in samples collected on day 21 was significantly higher than that in samples collected on day 7 (P < 0.01, respectively. Eight differential metabolites including ribose, sorbose, galactinol, cellobiose, pyruvic acid, galactonic acid, pantothenic acid and guanosine were found between 21-d samples and 35-d samples. Samples collected on day 35 had a higher relative level of ribose than that in samples collected on day 21 (P < 0.01. In conclusion, many differential metabolites which have important effects on the growth and health of pigs are identified and findings contribute to explain the difference in feeding response of fermented liquid diet.

Development of a novel artificial medium based on utilization of algal photosynthetic metabolites by symbiotic heterotrophs.

Science.gov (United States)

Watanabe, K; Imase, M; Aoyagi, H; Ohmura, N; Saiki, H; Tanaka, H

2008-09-01

(i) Quantitative and qualitative analyses of photosynthetic metabolites of Chlorella sorokiniana and elucidation of the mechanism of their utilization by algal symbionts. (ii) Development of artificial medium that imitates photoautotroph-heterotroph interaction and investigation of its suitability for isolation of novel microbes from the environment. Various components, including free dissolved carbohydrates, nitrogenous compounds and vitamin, were detected and together contributed 11.1% (as carbon content) of the total photosynthetic metabolites in the medium. Utilization of these photosynthetic metabolites in algal culture broth by algal symbionts was studied. Many symbionts showed specific utilization patterns. A novel artificial extracellular released organic carbon medium, which imitated the nutritional conditions surrounding algae, was developed based on the pattern of utilization of the algal metabolites by the symbiotic heterotrophs. About 42.9% of the isolates were closely related to photoautotrophic-dependent and oligotrophic bacteria. With the novel artificial medium, it was possible to selectively isolate some bacterial strains. Synthetic bacterial growth medium is an important and basic tool for bacterial isolation from environmental samples. The current study shows that preferential separation of typical bacterial subset can be achieved by using artificial medium that mimics photosynthetic metabolites.

EEG changes and neuroimaging abnormalities in relevance to ...

African Journals Online (AJOL)

Background: Autism is currently viewed as a genetically determined neurodevelopmental disorder although its defi nite underlying etiology remains to be established. Aim of the Study: Our purpose was to assess autism related morphological neuroimaging changes of the brain and EEG abnormalities in correlation to the ...

Pharmacokinetics of ifosfamide and some metabolites in children

NARCIS (Netherlands)

Kaijser, G. P.; de Kraker, J.; Bult, A.; Underberg, W. J.; Beijnen, J. H.

1998-01-01

The pharmacokinetics of ifosfamide and some metabolites in children was investigated. The patients received various doses of ifosfamide, mostly by continuous infusion, over several days. The penetration of ifosfamide and its metabolites into the cerebrospinal fluid was also studied in four cases.

Concentrations of phthalates and DINCH metabolites in pooled urine from Queensland, Australia.

Science.gov (United States)

Gomez Ramos, M J; Heffernan, A L; Toms, L M L; Calafat, A M; Ye, X; Hobson, P; Broomhall, S; Mueller, J F

2016-03-01

Dialkyl phthalate esters (phthalates) are ubiquitous chemicals used extensively as plasticizers, solvents and adhesives in a range of industrial and consumer products. 1,2-Cyclohexane dicarboxylic acid, diisononyl ester (DINCH) is a phthalate alternative introduced due to a more favourable toxicological profile, but exposure is largely uncharacterised. The aim of this study was to provide the first assessment of exposure to phthalates and DINCH in the general Australian population. De-identified urine specimens stratified by age and sex were obtained from a community-based pathology laboratory and pooled (n=24 pools of 100). Concentrations of free and total species were measured using online solid phase extraction isotope dilution high performance liquid chromatography tandem mass spectrometry. Concentrations ranged from 2.4 to 71.9ng/mL for metabolites of di(2-ethylhexyl)phthalate, and from <0.5 to 775ng/mL for all other metabolites. Our data suggest that phthalate metabolites concentrations in Australia were at least two times higher than in the United States and Germany; and may be related to legislative differences among countries. DINCH metabolite concentrations were comparatively low and consistent with the limited data available. Ongoing biomonitoring among the general Australian population may help assess temporal trends in exposure and assess the effectiveness of actions aimed at reducing exposures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Abnormal brain activation in excoriation (skin-picking) disorder

DEFF Research Database (Denmark)

Odlaug, Brian L.; Hampshire, Adam; Chamberlain, Samuel R

2016-01-01

Background: Excoriation (skin-picking) disorder (SPD) is a relatively common psychiatric condition whose neurobiological basis is unknown. Aims: To probe the function of fronto-striatal circuitry in SPD. Method: Eighteen participants with SPD and 15 matched healthy controls undertook an executive...... encompassing bilateral dorsal striatum (maximal in right caudate), bilateral anterior cingulate and right medial frontal regions. These abnormalities were, for the most part, outside the dorsal planning network typically activated by executive planning tasks. Conclusions: Abnormalities of neural regions...... involved in habit formation, action monitoring and inhibition appear involved in the pathophysiology of SPD. Implications exist for understanding the basis of excessive grooming and the relationship of SPD with putative obsessive-compulsive spectrum disorders....

Maternal urinary tract infection and related drug treatments during pregnancy and risk of congenital abnormalities in the offspring.

Science.gov (United States)

Bánhidy, F; Acs, N; Puhó, E H; Czeizel, A E

2006-12-01

The association between urinary tract infection (UTI) of pregnant women and preterm birth/low birthweight is known, but the possible association between UTI and congenital abnormalities (CAs) was evaluated rarely. Only one study showed an association with atrial septal defect, thus we decided to check this possible association. The population-based large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA); most maternal UTIs were based on medically recorded data. SETTING The HCCSCA, 1980-1996, contained 22 843 newborns or fetuses with CAs and 38 151 matched controls, i.e. newborn infants without any HCAs. Hungarian informative offspring: live births, stillbirths and prenatally diagnosed malformed fetuses. Case-control pair analysis. Twenty-five CA groups. A total of 1542 (6.75%) mothers in the case group had UTI during entire pregnancy compared with 2188 (5.74%) mothers in the control group (adjusted prevalence odds ratios [POR] with 95% CI: 1.15, 1.06-1.24). We did not find a higher prevalence of UTI during the second and/or third months of pregnancy in total case group (adjusted POR with 95% CI: 1.1, 0.9-1.2) and in any group of CAs including atrial septal defect type II. No evidence for the teratogenic effect of maternal UTI and related drug treatments during early pregnancy.

Association between plasma metabolites and gene expression profiles in five porcine endocrine tissues

Directory of Open Access Journals (Sweden)

Bassols Anna

2011-07-01

Full Text Available Abstract Background Endocrine tissues play a fundamental role in maintaining homeostasis of plasma metabolites such as non-esterified fatty acids and glucose, the levels of which reflect the energy balance or the health status of animals. However, the relationship between the transcriptome of endocrine tissues and plasma metabolites has been poorly studied. Methods We determined the blood levels of 12 plasma metabolites in 27 pigs belonging to five breeds, each breed consisting of both females and males. The transcriptome of five endocrine tissues i.e. hypothalamus, adenohypophysis, thyroid gland, gonads and backfat tissues from 16 out of the 27 pigs was also determined. Sex and breed effects on the 12 plasma metabolites were investigated and associations between genes expressed in the five endocrine tissues and the 12 plasma metabolites measured were analyzed. A probeset was defined as a quantitative trait transcript (QTT when its association with a particular metabolic trait achieved a nominal P value Results A larger than expected number of QTT was found for non-esterified fatty acids and alanine aminotransferase in at least two tissues. The associations were highly tissue-specific. The QTT within the tissues were divided into co-expression network modules enriched for genes in Kyoto Encyclopedia of Genes and Genomes or gene ontology categories that are related to the physiological functions of the corresponding tissues. We also explored a multi-tissue co-expression network using QTT for non-esterified fatty acids from the five tissues and found that a module, enriched in hypothalamus QTT, was positioned at the centre of the entire multi-tissue network. Conclusions These results emphasize the relationships between endocrine tissues and plasma metabolites in terms of gene expression. Highly tissue-specific association patterns suggest that candidate genes or gene pathways should be investigated in the context of specific tissues.

Novel pyrazine metabolites found in polymyxin biosynthesis by Paenibacillus polymyxa

DEFF Research Database (Denmark)

Beck, Hans Christian; Hansen, Anne M; Lauritsen, Frants R

2003-01-01

A complex mixture of methyl-branched alkyl-substituted pyrazines was found in the growth medium of the polymyxin-producing bacterium Paenibacillus polymyxa, and of these, seven are new natural compounds. A total of 19 pyrazine metabolites were identified. The dominant metabolite was 2,5-diisoprop......A complex mixture of methyl-branched alkyl-substituted pyrazines was found in the growth medium of the polymyxin-producing bacterium Paenibacillus polymyxa, and of these, seven are new natural compounds. A total of 19 pyrazine metabolites were identified. The dominant metabolite was 2...

Assessing the associations of blood metabolites with osteoporosis: a Mendelian randomization study.

Science.gov (United States)

Liu, Li; Wen, Yan; Zhang, Lei; Xu, Peng; Liang, Xiao; Du, Yanan; Li, Ping; He, Awen; Fan, QianRui; Hao, Jingcan; Wang, Wenyu; Guo, Xiong; Shen, Hui; Tian, Qing; Zhang, Feng; Deng, Hong-Wen

2018-03-01

Osteoporosis is a metabolic bone disease. The impact of blood metabolites on the development of osteoporosis remains elusive now. To explore the relationship between blood metabolites and osteoporosis. We used 2,286 unrelated Caucasian subjects as discovery samples and 3,143 unrelated Caucasian subjects from the Framingham heart study (FHS) as replication samples. Bone mineral density (BMD) were measured using dual-energy X-ray absorptiometry. Genome-wide SNP genotyping was performed using Affymetrix Human SNP Array 6.0 (for discovery samples) and Affymetrix SNP 500K and 50K array (for FHS replication samples). The SNP sets significantly associated with blood metabolites were obtained from a published whole-genome sequencing study. For each subject, the genetic risk score (GRS) of metabolite was calculated from the genotype data of metabolite associated SNP sets. Pearson correlation analysis was conducted to evaluate the potential impact of blood metabolites on the variations bone phenotypes. 10,000 permutations were conducted to calculate the empirical P value and false discovery rate (FDR). 481 blood metabolites were analyzed in this study. We identified multiple blood metabolites associated with hip BMD, such as 1,5-anhydroglucitol(1,5-AG) (Pdiscovery metabolites on the variations of BMD, and identified several candidate blood metabolites for osteoporosis.

Metabolites of alectinib in human: their identification and pharmacological activity

Directory of Open Access Journals (Sweden)

Mika Sato-Nakai

2017-07-01

Full Text Available Two metabolites (M4 and M1b in plasma and four metabolites (M4, M6, M1a and M1b in faeces were detected through the human ADME study following a single oral administration of [14C]alectinib, a small-molecule anaplastic lymphoma kinase inhibitor, to healthy subjects. In the present study, M1a and M1b, which chemical structures had not been identified prior to the human ADME study, were identified as isomers of a carboxylate metabolite oxidatively cleaved at the morpholine ring. In faeces, M4 and M1b were the main metabolites, which shows that the biotransformation to M4 and M1b represents two main metabolic pathways for alectinib. In plasma, M4 was a major metabolite and M1b was a minor metabolite. The contribution to in vivo pharmacological activity of these circulating metabolites was assessed from their in vitro pharmacological activity and plasma protein binding. M4 had a similar cancer cell growth inhibitory activity and plasma protein binding to that of alectinib, suggesting its contribution to the antitumor activity of alectinib, whereas the pharmacological activity of M1b was insignificant.

Metabolomics and Cheminformatics Analysis of Antifungal Function of Plant Metabolites.

Science.gov (United States)

Cuperlovic-Culf, Miroslava; Rajagopalan, NandhaKishore; Tulpan, Dan; Loewen, Michele C

2016-09-30

Fusarium head blight (FHB), primarily caused by Fusarium graminearum , is a devastating disease of wheat. Partial resistance to FHB of several wheat cultivars includes specific metabolic responses to inoculation. Previously published studies have determined major metabolic changes induced by pathogens in resistant and susceptible plants. Functionality of the majority of these metabolites in resistance remains unknown. In this work we have made a compilation of all metabolites determined as selectively accumulated following FHB inoculation in resistant plants. Characteristics, as well as possible functions and targets of these metabolites, are investigated using cheminformatics approaches with focus on the likelihood of these metabolites acting as drug-like molecules against fungal pathogens. Results of computational analyses of binding properties of several representative metabolites to homology models of fungal proteins are presented. Theoretical analysis highlights the possibility for strong inhibitory activity of several metabolites against some major proteins in Fusarium graminearum , such as carbonic anhydrases and cytochrome P450s. Activity of several of these compounds has been experimentally confirmed in fungal growth inhibition assays. Analysis of anti-fungal properties of plant metabolites can lead to the development of more resistant wheat varieties while showing novel application of cheminformatics approaches in the analysis of plant/pathogen interactions.

Metabolite Profiling of Candidatus Liberibacter Infection in Hamlin Sweet Oranges.

Science.gov (United States)

Hung, Wei-Lun; Wang, Yu

2018-04-18

Huanglongbing (HLB), also known as citrus greening disease, caused by Candidatus Liberibacter asiaticus (CLas), is considered the most serious citrus disease in the world. CLas infection has been shown to greatly affect metabolite profiles in citrus fruits. However, because of uneven distribution of CLas throughout the tree and a minimum bacterial titer requirement for polymerase chain reaction (PCR) detection, the infected trees may test false negative. To prevent this, metabolites of healthy Hamlin oranges (CLas-) obtained from the citrus undercover protection systems (CUPS) were investigated. Comparison of the metabolite profile of juice obtained from CLas- and CLas+ (asymptomatic and symptomatic) trees revealed significant differences in both volatile and nonvolatile metabolites. However, no consistent pattern could be observed in alcohols, esters, sesquiterpenes, sugars, flavanones, and limonoids as compared to previous studies. These results suggest that CLas may affect metabolite profiles of citrus fruits earlier than detecting infection by PCR. Citric acid, nobiletin, malic acid, and phenylalanine were identified as the metabolic biomarkers associated with the progression of HLB. Thus, the differential metabolites found in this study may serve as the biomarkers of HLB in its early stage, and the metabolite signature of CLas infection may provide useful information for developing a potential treatment strategy.

Modules of co-regulated metabolites in turmeric (Curcuma longa) rhizome suggest the existence of biosynthetic modules in plant specialized metabolism.

Science.gov (United States)

Xie, Zhengzhi; Ma, Xiaoqiang; Gang, David R

2009-01-01

Turmeric is an excellent example of a plant that produces large numbers of metabolites from diverse metabolic pathways or networks. It is hypothesized that these metabolic pathways or networks contain biosynthetic modules, which lead to the formation of metabolite modules-groups of metabolites whose production is co-regulated and biosynthetically linked. To test whether such co-regulated metabolite modules do exist in this plant, metabolic profiling analysis was performed on turmeric rhizome samples that were collected from 16 different growth and development treatments, which had significant impacts on the levels of 249 volatile and non-volatile metabolites that were detected. Importantly, one of the many co-regulated metabolite modules that were indeed readily detected in this analysis contained the three major curcuminoids, whereas many other structurally related diarylheptanoids belonged to separate metabolite modules, as did groups of terpenoids. The existence of these co-regulated metabolite modules supported the hypothesis that the 3-methoxyl groups on the aromatic rings of the curcuminoids are formed before the formation of the heptanoid backbone during the biosynthesis of curcumin and also suggested the involvement of multiple polyketide synthases with different substrate selectivities in the formation of the array of diarylheptanoids detected in turmeric. Similar conclusions about terpenoid biosynthesis could also be made. Thus, discovery and analysis of metabolite modules can be a powerful predictive tool in efforts to understand metabolism in plants.

Direct coupling of electromembrane extraction to mass spectrometry - Advancing the probe functionality toward measurements of zwitterionic drug metabolites.

Science.gov (United States)

Rye, Torstein Kige; Fuchs, David; Pedersen-Bjergaard, Stig; Petersen, Nickolaj Jacob

2017-08-29

A triple-flow electromembrane extraction (EME) probe was developed and coupled directly to electrospray-ionization mass spectrometry (ESI-MS). Metabolic reaction mixtures (pH 7.4) containing drug substances and related metabolites were continuously drawn (20 μL/min) into the EME probe in one flow channel, and mixed inside the probe with 7.5 μL min -1 of 1 M formic acid as make-up flow from a second flow channel. Following this acidification, the drug substances and their related metabolites were continuously extracted by EME at 400 V, across a supported liquid membrane (SLM) comprising 2-nitrophenyl octyl ether (and for some experiments containing 30% triphenyl phosphate (TPP)), and into 20 μL min -1 of formic acid as acceptor phase, which was introduced through a third flow channel. The acceptor phase was pumped directly to the MS system, and the ion intensity of extracted analytes was followed continuously as function of time. The triple-flow EME probe was used for co-extraction of positively charged parent drugs and their zwitterionic drug metabolites (hydroxyzine and its carboxylic acid metabolite cetirizine; and vortioxetine and its carboxylic acid metabolite Lu AA34443). While the zwitterionic metabolites could not be extracted at pH 7.4, it was shown that by acidifying the sample solution the zwitterionic metabolites could be extracted effectively. Various extraction parameters like make-up flow, extraction voltage and SLM composition were optimized for simultaneous extraction of parent drugs and metabolites. It was found that TPP added to the SLM improved extraction efficiencies of certain drug metabolites. Finally the optimized and characterized triple-flow EME probe was used for online studying the in-vitro metabolism of hydroxyzine and vortioxetine by rat liver microsomes. Due to the automated pre-extraction acidification of the rat liver microsomal solutions, it was possible to continuously monitor formation of the zwitterionic drug

Metabolite Profiles of Lactic Acid Bacteria in Grass Silage▿

OpenAIRE

Broberg, Anders; Jacobsson, Karin; Ström, Katrin; Schnürer, Johan

2007-01-01

The metabolite production of lactic acid bacteria (LAB) on silage was investigated. The aim was to compare the production of antifungal metabolites in silage with the production in liquid cultures previously studied in our laboratory. The following metabolites were found to be present at elevated concentrations in silos inoculated with LAB strains: 3-hydroxydecanoic acid, 2-hydroxy-4-methylpentanoic acid, benzoic acid, catechol, hydrocinnamic acid, salicylic acid, 3-phenyllactic acid, 4-hydro...

Treatments for Biomedical Abnormalities Associated with Autism Spectrum Disorder

Directory of Open Access Journals (Sweden)

Richard Eugene Frye

2014-06-01

Full Text Available Recent studies point to the effectiveness of novel treatments that address physiological abnormalities associated with autism spectrum disorder (ASD. This is significant because safe and effective treatments for ASD remain limited. These physiological abnormalities as well as studies addressing treatments of these abnormalities are reviewed in this article. Treatments commonly used to treat mitochondrial disease have been found to improve both core and associated ASD symptoms. Double-blind, placebo-controlled studies have investigated L-carnitine and a multivitamin containing B vitamins, antioxidants, vitamin E, and coenzyme Q10 while non-blinded studies have investigated ubiquinol. Controlled and uncontrolled studies using folinic acid, a reduced form of folate, have reported marked improvements in core and associated ASD symptoms in some children with ASD and folate related pathways abnormities. Treatments that could address redox metabolism abnormalities include methylcobalamin with and without folinic acid in open-label studies and vitamin C and N-acetyl-L-cysteine in double-blind, placebo-controlled studies. These studies have reported improved core and associated symptoms with these treatments. Lastly, both open-label and double-blind, placebo-controlled studies have reported improvement in core and associated ASD symptoms with tetrahydrobiopterin. Overall, these treatments were generally well tolerated without significant adverse effects for most children, although we review the reported adverse effects in detail. This review provides evidence for potential safe and effective treatments for core and associated symptoms of ASD that target underlying known physiological abnormalities associated with ASD. Further research is needed to define subgroups of children with ASD in which these treatments may be most effective as well as confirm their efficacy in double-blind, placebo-controlled, large-scale multicenter studies.

Correcting ligands, metabolites, and pathways

Directory of Open Access Journals (Sweden)

Vriend Gert

2006-11-01

Full Text Available Abstract Background A wide range of research areas in bioinformatics, molecular biology and medicinal chemistry require precise chemical structure information about molecules and reactions, e.g. drug design, ligand docking, metabolic network reconstruction, and systems biology. Most available databases, however, treat chemical structures more as illustrations than as a datafield in its own right. Lack of chemical accuracy impedes progress in the areas mentioned above. We present a database of metabolites called BioMeta that augments the existing pathway databases by explicitly assessing the validity, correctness, and completeness of chemical structure and reaction information. Description The main bulk of the data in BioMeta were obtained from the KEGG Ligand database. We developed a tool for chemical structure validation which assesses the chemical validity and stereochemical completeness of a molecule description. The validation tool was used to examine the compounds in BioMeta, showing that a relatively small number of compounds had an incorrect constitution (connectivity only, not considering stereochemistry and that a considerable number (about one third had incomplete or even incorrect stereochemistry. We made a large effort to correct the errors and to complete the structural descriptions. A total of 1468 structures were corrected and/or completed. We also established the reaction balance of the reactions in BioMeta and corrected 55% of the unbalanced (stoichiometrically incorrect reactions in an automatic procedure. The BioMeta database was implemented in PostgreSQL and provided with a web-based interface. Conclusion We demonstrate that the validation of metabolite structures and reactions is a feasible and worthwhile undertaking, and that the validation results can be used to trigger corrections and improvements to BioMeta, our metabolite database. BioMeta provides some tools for rational drug design, reaction searches, and

Report on abnormal climate in 2011

International Nuclear Information System (INIS)

2011-12-01

This paper reports of impact on abnormal climate in 2011. It has Introduction with purpose and background of publish and summary of this report. The cause and current state on abnormal climate of the world and Korea in 2011, Measurement and impact against abnormal climate in 2011 to agriculture, land and maritime, industry and energy, prevention of disasters, environment and health, assessment and advice on the policy. It lists the appendix about occurrence and damage on abnormal climate of the world and Korea in 2011 and media report data.

Pregnancy Complications: Umbilical Cord Abnormalities

Science.gov (United States)

... Umbilical cord abnormalities Umbilical cord abnormalities Now playing: E-mail to a friend Please fill in all fields. ... blood supply) to the baby. The two arteries transport waste from the baby to the placenta (where ...

SPERM MORPHOLOGICAL ABNORMALITIES AS INDICATORS OF DNA FRAGMENTATION AND FERTILIZATION IN ASSISTED REPRODUCTION

Directory of Open Access Journals (Sweden)

Barbara Dariš

2018-02-01

Full Text Available Background. To determine the relationship between sperm morphological abnormalities, DNA fragmentation and fertilization rate in IVF and ICSI. Methods. Sperm samples from 10 IVF and 20 ICSI cycles were analyzed. Morphology was assessed according to strict criteria, and DNA fragmentation was measured by terminal deoxynucleotidyl transferase (TdT-mediated fluorescein-dUTP nick end labelling (TUNEL using a flow cytometry. Results. There was a significant difference in the amount of morphological abnormalities between sperm samples with low (< 20 % and high (≥ 20 % degree of DNA fragmentation. The percentages of amorphous heads (10 vs. 4 % and overall head abnormalities (42 vs. 30 % were significantly higher in sperm samples with elevated degree of DNA fragmentation. No correlation was found between sperm DNA fragmentation and fertilization rate after IVF and ICSI. When the predominant morphological abnormality in sperm samples was determined, a negative correlation was found between the percentage of spermatozoa with elongated heads and fertilization rate in ICSI (r = –0.45, P < 0.05. The fertilization rate after IVF was lower in the case of acrosomal abnormalities (35.3 %, compared to the cases of other predominant morphological abnormalities. Conclusions. Head abnormalities, especially amorphous heads, are related to elevated degree of DNA fragmentation. Predominant abnormal form in sperm samples, such as elongated heads and acrosomal abnormalities, may affect fertilization in ART.

Aspergillus flavus secondary metabolites: more than just aflatoxins

Science.gov (United States)

Aspergillus flavus is best known for producing the family of potent carcinogenic secondary metabolites known as aflatoxins. However, this opportunistic plant and animal pathogen also produces numerous other secondary metabolites, many of which have also been shown to be toxic. While about forty of t...

Gray matter abnormalities in patients with narcissistic personality disorder.

Science.gov (United States)

Schulze, Lars; Dziobek, Isabel; Vater, Aline; Heekeren, Hauke R; Bajbouj, Malek; Renneberg, Babette; Heuser, Isabella; Roepke, Stefan

2013-10-01

Despite the relevance of narcissistic personality disorder (NPD) in clinical settings, there is currently no empirical data available regarding the neurobiological correlates of NPD. In the present study, we performed a voxel-based morphometric analysis to provide initial insight into local abnormalities of gray matter (GM) volume. Structural brain images were obtained from patients with NPD (n = 17) and a sample of healthy controls (n = 17) matched regarding age, gender, handedness, and intelligence. Groups were compared with regard to global brain tissue volumes and local abnormalities of GM volume. Regions-of-interest analyses were calculated for the anterior insula. Relative to the control group, NPD patients had smaller GM volume in the left anterior insula. Independent of group, GM volume in the left anterior insula was positively related to self-reported emotional empathy. Complementary whole-brain analyses yielded smaller GM volume in fronto-paralimbic brain regions comprising the rostral and median cingulate cortex as well as dorsolateral and medial parts of the prefrontal cortex. Here we provide the first empirical evidence for structural abnormalities in fronto-paralimbic brain regions of patients with NPD. The results are discussed in the context of NPD patients' restricted ability for emotional empathy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Fetal magnetic resonance imaging in prenatal diagnosis of central nervous system abnormalities

International Nuclear Information System (INIS)

Morioka, Takato; Hashiguchi, Kimiaki; Kawamura, Tadao; Mihara, Futoshi; Hikino, Shunji; Nagata, Hideaki; Iwaki, Toru; Sasaki, Tomio

2005-01-01

The diagnostic value of fetal magnetic resonance imaging (MRI), performed in 42 pregnant women whose fetuses had structural abnormalities of the central nervous system identified with transabdominal ultrasonography from 1995 through 2002, was analyzed retrospectively. Half-Fourier acquisition single-shot turbo spin-echo (HASTE) T 2 -weighted imaging clearly delineated the cerebrospinal fluid (CSF) space and the malformed brain and spinal cord and provided valuable information for the diagnosis of structural abnormalities related to the CSF space, such as spina bifida with Chiari type II malformation (7 cases), colpocephaly with agenesis of the corpus callosum (7 cases), holoprosencephaly (6 cases), porencephaly (2 cases), lissencephaly with hydrocephalus (2 cases), and middle fossa arachnoid cyst (1 case). However, some difficulty was encountered in the diagnosis of rare pathologic conditions that were not related to the CSF space, such as epignathus, multiple arteriovenous fistulae, trapped suboccipital meningocele, and Turner syndrome. We conclude that HASTE T 2 -weighted imaging, which provides useful diagnostic images in a reasonable time, is a useful adjunct to ultrasonography to confirm or exclude certain abnormalities related to the CSF space. (author)

Esophagogastric junction outflow obstruction is often associated with coexistent abnormal esophageal body motility and abnormal bolus transit.

Science.gov (United States)

Zheng, E; Gideon, R M; Sloan, J; Katz, P O

2017-10-01

Currently, the diagnosis of esophageal motility disorders is in part based upon a hierarchical algorithm in which abnormalities of the esophagogastric junction (EGJ) is prioritized. An important metric in evaluating the EGJ is the integrated relaxation pressure (IRP). Patients who do not have achalasia but are found to have an elevated IRP are diagnosed with EGJ outflow obstruction. It has been our observation that a subset of these patients also has a second named motility disorder and may also have abnormal bolus transit. The aim of this study is to determine the frequency of abnormal body motility and or abnormal bolus movement in patients with EGJ outflow obstruction. Further, in an effort to evaluate the potential clinical value in measuring bolus transit as a complement to esophageal manometry, specifically in patients with EGJ outflow obstruction, we analyzed the presenting symptoms of these patients. A total of 807 patients with a mean age of 53 years completed esophageal function testing with impedance monitoring and high-resolution manometry between January 2012 and October 2016. There were 74 patients with achalasia who were excluded from the study. Of the remaining 733 patients, 138 (19%) had an elevated IRP and were given a diagnosis of EGJ outflow obstruction. Among these patients, 56 (40%) were diagnosed with an abnormal motility pattern to liquids (ineffective esophageal motility = 28, distal esophageal spasm = 19, Jackhammer = 6), of which 44 (76%) had abnormal bolus transit to liquids, viscous, or both. In contrast, there were 82 patients with EGJ outflow obstruction and normal esophageal motility, of which 33 (40%) had abnormal bolus transit. Patients with preserved esophageal motility and EGJ outflow obstruction were then evaluated. Of the 733 patients, 299 (40%) had intact esophageal motility. Of the 299 patients with normal esophageal motility, 56 patients had an elevated IRP, of which 16 (28%) had abnormal bolus transit. There were 243 (33

Direct detection of glucuronide metabolites of lidocaine in sheep urine.

Science.gov (United States)

Doran, Gregory S; Smith, Alistair K; Rothwell, Jim T; Edwards, Scott H

2018-02-15

The anaesthetic lidocaine is metabolised quickly to produce a series of metabolites, including several hydroxylated metabolites, which are further metabolised by addition of a glucuronic acid moiety. Analysis of these glucuronide metabolites in urine is performed indirectly by cleaving the glucuronic acid group using β-glucuronidase. However, direct analysis of intact glucuronide conjugates is a more straightforward approach as it negates the need for long hydrolysis incubations, and minimises the oxidation of sensitive hydrolysis products, while also distinguishing between the two forms of hydroxylated metabolites. A method was developed to identify three intact glucuronides of lidocaine in sheep urine using LC-MS/MS, which was further confirmed by the synthesis of glucuronide derivatives of 3OH-MEGX and 4OH-LIDO. Direct analysis of urine allowed the detection of the glucuronide metabolites of hydroxylidocaine (OH-LIDO), hydroxyl-monoethylglycinexylidide (OH-MEGX), and hydroxy-2,6-xylidine (OH-XYL). Analysis of urine before and after β-glucuronidase digestion showed that the efficiency of hydrolysis of these glucuronide metabolites may be underestimated in some studies. Analysis of urine in the current study from three different sheep with similar glucuronide metabolite concentrations resulted in different hydrolysis efficiencies, which may have been a result of different levels of substrate binding by matrix components, preventing enzyme cleavage. The use of direct analysis of intact glucuronides has the benefit of being less influenced by these matrix effects, while also allowing analysis of unstable metabolites like 4OH-XYL, which rapidly oxidises after hydrolysis. Additionally, direct analysis is less expensive and less time consuming, while providing more information about the status of hydroxylated metabolites in urine. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Exercises to Improve Gait Abnormalities

Science.gov (United States)

... Articles Directories Videos Resources Contact Exercises to Improve Gait Abnormalities Home » Article Categories » Exercise and Fitness Font Size: A A A A Exercises to Improve Gait Abnormalities Next Page The manner of how a ...

Tissue distribution of berberine and its metabolites after oral administration in rats.

Directory of Open Access Journals (Sweden)

Xiang-Shan Tan

Full Text Available Berberine (BBR has been confirmed to have multiple bioactivities in clinic, such as cholesterol-lowering, anti-diabetes, cardiovascular protection and anti- inflammation. However, BBR's plasma level is very low; it cannot explain its pharmacological effects in patients. We consider that the in vivo distribution of BBR as well as of its bioactive metabolites might provide part of the explanation for this question. In this study, liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MS(n-IT-TOF as well as liquid chromatography that coupled with tandem mass spectrometry (LC-MS/MS was used for the study of tissue distribution and pharmacokinetics of BBR in rats after oral administration (200 mg/kg. The results indicated that BBR was quickly distributed in the liver, kidneys, muscle, lungs, brain, heart, pancreas and fat in a descending order of its amount. The pharmacokinetic profile indicated that BBR's level in most of studied tissues was higher (or much higher than that in plasma 4 h after administration. BBR remained relatively stable in the tissues like liver, heart, brain, muscle, pancreas etc. Organ distribution of BBR's metabolites was also investigated paralleled with that of BBR. Thalifendine (M1, berberrubine (M2 and jatrorrhizine (M4, which the metabolites with moderate bioactivity, were easily detected in organs like the liver and kidney. For instance, M1, M2 and M4 were the major metabolites in the liver, among which the percentage of M2 was up to 65.1%; the level of AUC (0-t (area under the concentration-time curve for BBR or the metabolites in the liver was 10-fold or 30-fold higher than that in plasma, respectively. In summary, the organ concentration of BBR (as well as its bioactive metabolites was higher than its concentration in the blood after oral administration. It might explain BBR's pharmacological effects on human diseases in clinic.

Report to Congress on abnormal occurrences

International Nuclear Information System (INIS)

1993-06-01

Section 208 of the Energy Reorganization Act of 1974 identifies an abnormal occurrence as an unscheduled incident or event that the Nuclear Regulatory Commission determines to be significant from the standpoint of public health and safety and requires a quarterly report of such events to be made to Congress. This report covers the period January through March 1993. There is one abnormal occurrence at a nuclear power plant disposed in this report that involved a steam generator tube rupture at Palo Verde Unit 2, and none for fuel cycle facilities. Three abnormal occurrences involving medical misadminstrations (two therapeutic and one diagnostic) at NRC-licensed facilities are also discussed in this report. No abnormal occurrences were reported by NRC's Agreement States. The report also contains information updating previously reported abnormal occurrences

Abnormal lung function at preschool age asthma in adolescence?

Science.gov (United States)

Lajunen, Katariina; Kalliola, Satu; Kotaniemi-Syrjänen, Anne; Sarna, Seppo; Malmberg, L Pekka; Pelkonen, Anna S; Mäkelä, Mika J

2018-05-01

Asthma often begins early in childhood. However, the risk for persistence is challenging to evaluate. This longitudinal study relates lung function assessed with impulse oscillometry (IOS) in preschool children to asthma in adolescence. Lung function was measured with IOS in 255 children with asthma-like symptoms aged 4-7 years. Baseline measurements were followed by exercise challenge and bronchodilation tests. At age 12-16 years, 121 children participated in the follow-up visit, when lung function was assessed with spirometry, followed by a bronchodilation test. Asthma symptoms and medication were recorded by a questionnaire and atopy defined by skin prick tests. Abnormal baseline values in preschool IOS were significantly associated with low lung function, the need for asthma medication, and asthma symptoms in adolescence. Preschool abnormal R5 at baseline (z-score ≥1.645 SD) showed 9.2 odds ratio (95%CI 2.7;31.7) for abnormal FEV1/FVC, use of asthma medication in adolescence, and 9.9 odds ratio (95%CI 2.9;34.4) for asthma symptoms. Positive exercise challenge and modified asthma-predictive index at preschool age predicted asthma symptoms and the need for asthma medication, but not abnormal lung function at teenage. Abnormal preschool IOS is associated with asthma and poor lung function in adolescence and might be utilised for identification of asthma persistence. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Changes of Enzymes Activity and Production of Secondary Metabolites of Artemisia aucheri in Different Altitudes and Its Relation to Adaptation

Directory of Open Access Journals (Sweden)

Hassan Zare-maivan

2014-08-01

Full Text Available Artemisia plants are the most abundant plants species in Iran which contain strong antioxidant properties and as such, have medicinal and economic value. Despite wide distribution of Artemisisa species, ecophysiology of its adaptation to changes in altitude and soil property had not been investigated. In this study, the relationships between ecophysiological and adaptation capabilities of A. aucheri to altitude changes through measuring changes in the activity of its antioxidant enzymes and secondary metabolites in situ was investigated based on a completely randomized experiment. The enzyme activities of superoxide dismutase, catalase, peroxidase, and the amount of total phenolics, flavonoids, anthocyanins, malondialdehyde and chlorophylls A and B were measured in A. aucheri plants growing in three different altitudes at and above the 36° latitude on the southern slopes of Eastern Alborz Mountain ranges in triplicate 10*10 m quadrates. Statistical analysis of data showed that soil type was loamy significantly becoming more sandy- loam with lowering in altitude and the soil contained greater amounts of oxides of silicone, aluminum, magnesium, sodium, potassium and phosphorus in upper altitude except calcium which was present in greater quantity in lower altitude. With increasing altitude, activity of superoxide dismutase and quantities of chlorophylls and total phenols in leaves increased. Some biochemical factors in A. aucheri showed significant positive correlation(P ≤ 0.05 between them. Adaptation of A. aucheri to changes in altitude occurred through changing its antioxidant enzymes activity and production of secondary metabolites in response to factors related to the altitude including soil type and texture, moisture level, temperature and most importantly radiation

Production of secondary metabolites by some terverticillate penicillia on carbohydrate-rich and meat substrates.

Science.gov (United States)

Núñez, Félix; Westphal, Carmen D; Bermúdez, Elena; Asensio, Miguel A

2007-12-01

Most terverticillate penicillia isolated from dry-cured meat products are toxigenic, but their ability to produce hazardous metabolites on meat-based substrates is not well known. The production of extrolites by selected terverticillate penicillia isolated from dry-cured ham has been studied on carbohydrate-rich media (malt extract agar, Czapek yeast autolysate agar, rice extract agar, and rice), meat extract triolein salt agar, and ham slices. Chloroform extracts from the selected strains grown on malt extract agar were toxic for the brine shrimp (Artemia salina) larvae and VERO cells at a concentration of 2 mg/ml, but 0.02 mg/ml produced no toxic effect. Analysis by high-pressure liquid chromatography (HPLC) coupled with photodiode array detection (DAD) or with mass spectrometry (MS) and an atmospheric pressure chemical ionization (APCI) source revealed different biologically active metabolites: cyclopiazonic acid and rugulovasine A from Penicillium commune; verrucosidin, anacine, puberuline, verrucofortine, and viridicatols from Penicillium polonicum; arisugacin and viridicatols from Penicillium echinulatum; and compactin and viridicatols from Penicillium solitum. Most of these metabolites, including the amino acid-derived compounds, were produced in the media containing high levels of carbohydrates. High concentrations of nitrogen compounds in the medium does not imply a greater production of the metabolites studied, not even those derived from the amino acids. However, molds growing on dry-cured ham are able to synthesize limited amounts of some secondary metabolites, a fact not previously reported. The combination of HPLC coupled with DAD and MS-APCI was useful for identification of closely related terverticillate Penicillium species from dry-cured ham. These techniques could be used to characterize the risk associated with the potential production of secondary metabolites in cured meats.

Antioxidant properties and global metabolite screening of the probiotic yeast Saccharomyces cerevisiae var. boulardii.

Science.gov (United States)

Datta, Suprama; Timson, David J; Annapure, Uday S

2017-07-01

Saccharomyces cerevisiae var. boulardii is the only yeast species with probiotic properties. It is considered to have therapeutic significance in gastrointestinal disorders. In the present study, a comparative physiological study between this yeast and Saccharomyces cerevisiae (BY4742) was performed by evaluating two prominent traits of probiotic species, responses to different stress conditions and antioxidant capacity. A global metabolite profile was also developed aiming to identify which therapeutically important secondary metabolites are produced. Saccharomyces cerevisiae var. boulardii showed no significant difference in growth patterns but greater stress tolerance compared to S. cerevisiae. It also demonstrated a six- to 10-fold greater antioxidant potential (judged by the 1,1-diphenyl-2-picrylhydrazyl assay), with a 70-fold higher total phenolic content and a 20-fold higher total flavonoid content in the extracellular fraction. These features were clearly differentiated by principal component analysis and further indicated by metabolite profiling. The extracellular fraction of the S. cerevisiae var. boulardii cultures was found to be rich in polyphenolic metabolites: vanillic acid, cinnamic acid, phenyl ethyl alcohol (rose oil), erythromycin, amphetamine and vitamin B 6 , which results in the antioxidant capacity of this strain. The present study presents a new perspective for differentiating the two genetically related strains of yeast, S. cerevisiae and S. cerevisiae var. boulardii by assessing their metabolome fingerprints. In addition to the correlation of the phenotypic properties with the secretory metabolites of these two yeasts, the present study also emphasizes the potential to exploit S. cerevisiae var. boulardii in the industrial production of these metabolites. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Metabolite characterization in serum samples from normal healthy ...

African Journals Online (AJOL)

Metabolite characterization in serum samples from normal healthy human subjects by 1H and 13C NMR spectroscopy. D Misra, U Bajpai. Abstract. One and two dimensional NMR spectroscopy has been employed to characterize the various metabolites of serum control healthy samples. Two dimensional heteronuclear ...

UV-guided isolation of fungal metabolites by HSCCC

DEFF Research Database (Denmark)

Dalsgaard, P.W.; Nielsen, K.F.; Larsen, Thomas Ostenfeld

2005-01-01

Analytical standardised reversed phase liquid chromatography (RPLC) data can be helpful in finding a suitable solvent combination for isolation of fungal metabolites by high-speed counter current chromatography. Analysis of the distribution coefficient (K-D) of fungal metabolites in a series...... peptides from a crude fungal extract....

Effect of metabolites produced by Trichoderma species against ...

African Journals Online (AJOL)

Metabolites released from Trichoderma viride, T. polysporum, T. hamatum and T. aureoviride were tested in culture medium against Ceratocystis paradoxa, which causes black seed rot in oil palm sprouted seeds. The Trichoderma metabolites had similar fungistatic effects on the growth of C. paradoxa except those from T.

Cortical thickness abnormalities associated with dyslexia, independent of remediation status

Science.gov (United States)

Ma, Yizhou; Koyama, Maki S.; Milham, Michael P.; Castellanos, F. Xavier; Quinn, Brian T.; Pardoe, Heath; Wang, Xiuyuan; Kuzniecky, Ruben; Devinsky, Orrin; Thesen, Thomas; Blackmon, Karen

2014-01-01

Abnormalities in cortical structure are commonly observed in children with dyslexia in key regions of the “reading network.” Whether alteration in cortical features reflects pathology inherent to dyslexia or environmental influence (e.g., impoverished reading experience) remains unclear. To address this question, we compared MRI-derived metrics of cortical thickness (CT), surface area (SA), gray matter volume (GMV), and their lateralization across three different groups of children with a historical diagnosis of dyslexia, who varied in current reading level. We compared three dyslexia subgroups with: (1) persistent reading and spelling impairment; (2) remediated reading impairment (normal reading scores), and (3) remediated reading and spelling impairments (normal reading and spelling scores); and a control group of (4) typically developing children. All groups were matched for age, gender, handedness, and IQ. We hypothesized that the dyslexia group would show cortical abnormalities in regions of the reading network relative to controls, irrespective of remediation status. Such a finding would support that cortical abnormalities are inherent to dyslexia and are not a consequence of abnormal reading experience. Results revealed increased CT of the left fusiform gyrus in the dyslexia group relative to controls. Similarly, the dyslexia group showed CT increase of the right superior temporal gyrus, extending into the planum temporale, which resulted in a rightward CT asymmetry on lateralization indices. There were no group differences in SA, GMV, or their lateralization. These findings held true regardless of remediation status. Each reading level group showed the same “double hit” of atypically increased left fusiform CT and rightward superior temporal CT asymmetry. Thus, findings provide evidence that a developmental history of dyslexia is associated with CT abnormalities, independent of remediation status. PMID:25610779

Memetics clarification of abnormal behavior

Institute of Scientific and Technical Information of China (English)

无

2007-01-01

AIM: Biological medicine is hard to fully and scientifically explain the etiological factor and pathogenesis of abnormal behaviors; while, researches on philosophy and psychology (including memetics) are beneficial to better understand and explain etiological factor and pathogenesis of abnormal behaviors. At present, the theory of philosophy and psychology is to investigate the entity of abnormal behavior based on the views of memetics.METHODS: Abnormal behavior was researched in this study based on three aspects, including instinctive behavior disorder, poorly social-adapted behavior disorder and mental or body disease associated behavior disorder. Most main viewpoints of memetics were derived from "The Meme Machine", which was written by Susan Blackmore. When questions about abnormal behaviors induced by mental and psychological diseases and conduct disorder of teenagers were discussed, some researching achievements which were summarized by authors previously were added in this study, such as aggressive behaviors, pathologically aggressive behaviors, etc.RESULTS: The abnormal behaviors mainly referred to a part of people's substandard behaviors which were not according with the realistic social environment, culture background and the pathologic behaviors resulted from people's various psychological diseases. According to the theory of "meme", it demonstrated that the relevant behavioral obstacles of various psychological diseases, for example, the unusual behavior of schizophrenia, were caused, because the old meme was destroyed thoroughly but the new meme was unable to establish; psychoneurosis and personality disorder were resulted in hard establishment of meme; the behavioral obstacles which were ill-adapted to society, for example, various additional and homosexual behaviors, were because of the selfish replications and imitations of "additional meme" and "homosexual meme"; various instinct behavioral and congenital intelligent obstacles were not significance

Neurologic abnormalities in murderers.

Science.gov (United States)

Blake, P Y; Pincus, J H; Buckner, C

1995-09-01

Thirty-one individuals awaiting trial or sentencing for murder or undergoing an appeal process requested a neurologic examination through legal counsel. We attempted in each instance to obtain EEG, MRI or CT, and neuropsychological testing. Neurologic examination revealed evidence of "frontal" dysfunction in 20 (64.5%). There were symptoms or some other evidence of temporal lobe abnormality in nine (29%). We made a specific neurologic diagnosis in 20 individuals (64.5%), including borderline or full mental retardation (9) and cerebral palsy (2), among others. Neuropsychological testing revealed abnormalities in all subjects tested. There were EEG abnormalities in eight of the 20 subjects tested, consisting mainly of bilateral sharp waves with slowing. There were MRI or CT abnormalities in nine of the 19 subjects tested, consisting primarily of atrophy and white matter changes. Psychiatric diagnoses included paranoid schizophrenia (8), dissociative disorder (4), and depression (9). Virtually all subjects had paranoid ideas and misunderstood social situations. There was a documented history of profound, protracted physical abuse in 26 (83.8%) and of sexual abuse in 10 (32.3%). It is likely that prolonged, severe physical abuse, paranoia, and neurologic brain dysfunction interact to form the matrix of violent behavior.

Somatosensory abnormalities in knee OA.

Science.gov (United States)

Wylde, Vikki; Palmer, Shea; Learmonth, Ian D; Dieppe, Paul

2012-03-01

The aim of this study was to use quantitative sensory testing (QST) to explore the range and prevalence of somatosensory abnormalities demonstrated by patients with advanced knee OA. One hundred and seven knee OA patients and 50 age- and sex-matched healthy participants attended a 1-h QST session. Testing was performed on the medial side of the knee and the pain-free forearm. Light-touch thresholds were assessed using von Frey filaments, pressure pain thresholds using a digital pressure algometer, and thermal sensation and pain thresholds using a Thermotest MSA. Significant differences in median threshold values from knee OA patients and healthy participants were identified using Mann-Whitney U-tests. The z-score transformations were used to determine the prevalence of the different somatosensory abnormalities in knee OA patients. Testing identified 70% of knee OA patients as having at least one somatosensory abnormality. Comparison of median threshold values between knee OA patients and healthy participants revealed that patients had localized thermal and tactile hypoaesthesia and pressure hyperalgesia at the osteoarthritic knee. Tactile hypoaesthesia and pressure hyperalgesia were also present at the pain-free forearm. The most prevalent somatosensory abnormalities were tactile hypoaesthesia and pressure hyperalgesia, evident in between 20 and 34% of patients. This study found that OA patients demonstrate an array of somatosensory abnormalities, of which the most prevalent were tactile hypoaesthesia and pressure hyperalgesia. Further research is now needed to establish the clinical implications of these somatosensory abnormalities.

Enhanced photo(geno)toxicity of demethylated chlorpromazine metabolites

Energy Technology Data Exchange (ETDEWEB)

Palumbo, Fabrizio [Instituto de Tecnología Química UPV-CSIC/Departamento de Química, Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia (Spain); Garcia-Lainez, Guillermo [Instituto de Investigación Sanitaria (IIS) La Fe, Hospital Universitari i Politècnic La Fe, Avenida de Fernando Abril Martorell 106, 46026 Valencia (Spain); Limones-Herrero, Daniel [Instituto de Tecnología Química UPV-CSIC/Departamento de Química, Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia (Spain); Coloma, M. Dolores; Escobar, Javier [Instituto de Investigación Sanitaria (IIS) La Fe, Hospital Universitari i Politècnic La Fe, Avenida de Fernando Abril Martorell 106, 46026 Valencia (Spain); Jiménez, M. Consuelo [Instituto de Tecnología Química UPV-CSIC/Departamento de Química, Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia (Spain); Miranda, Miguel A., E-mail: mmiranda@qim.upv.es [Instituto de Tecnología Química UPV-CSIC/Departamento de Química, Universitat Politècnica de València, Camino de Vera s/n, 46022 Valencia (Spain); and others

2016-12-15

Chlorpromazine (CPZ) is an anti-psychotic drug widely used to treat disorders such as schizophrenia or manic-depression. Unfortunately, CPZ exhibits undesirable side effects such as phototoxic and photoallergic reactions in humans. In general, the influence of drug metabolism on this type of reactions has not been previously considered in photosafety testing. Thus, the present work aims to investigate the possible photo(geno)toxic potential of drug metabolites, using CPZ as an established reference compound. In this case, the metabolites selected for the study are demethylchlorpromazine (DMCPZ), didemethylchlorpromazine (DDMCPZ) and chlorpromazine sulfoxide (CPZSO). The demethylated CPZ metabolites DMCPZ and DDMCPZ maintain identical chromophore to the parent drug. In this work, it has been found that the nature of the aminoalkyl side chain modulates the hydrophobicity and the photochemical properties (for instance, the excited state lifetimes), but it does not change the photoreactivity pattern, which is characterized by reductive photodehalogenation, triggered by homolytic carbon-chlorine bond cleavage with formation of highly reactive aryl radical intermediates. Accordingly, these metabolites are phototoxic to cells, as revealed by the 3T3 NRU assay; their photo-irritation factors are even higher than that of CPZ. The same trend is observed in photogenotoxicity studies, both with isolated and with cellular DNA, where DMCPZ and DDMCPZ are more active than CPZ itself. In summary, side-chain demethylation of CPZ, as a consequence of Phase I biotransformation, does not result a photodetoxification. Instead, it leads to metabolites that exhibit in an even enhanced photo(geno)toxicity. - Highlights: • Demethylated CPZ metabolites are phototoxic to cells, as revealed by the NRU assay. • Single cell electrophoresis (Comet Assay) confirms the photodamage to cellular DNA. • DNA single strand breaks formation is observed on agarose gel electrophoresis. �

Enhanced photo(geno)toxicity of demethylated chlorpromazine metabolites

International Nuclear Information System (INIS)

Palumbo, Fabrizio; Garcia-Lainez, Guillermo; Limones-Herrero, Daniel; Coloma, M. Dolores; Escobar, Javier; Jiménez, M. Consuelo; Miranda, Miguel A.

2016-01-01

Chlorpromazine (CPZ) is an anti-psychotic drug widely used to treat disorders such as schizophrenia or manic-depression. Unfortunately, CPZ exhibits undesirable side effects such as phototoxic and photoallergic reactions in humans. In general, the influence of drug metabolism on this type of reactions has not been previously considered in photosafety testing. Thus, the present work aims to investigate the possible photo(geno)toxic potential of drug metabolites, using CPZ as an established reference compound. In this case, the metabolites selected for the study are demethylchlorpromazine (DMCPZ), didemethylchlorpromazine (DDMCPZ) and chlorpromazine sulfoxide (CPZSO). The demethylated CPZ metabolites DMCPZ and DDMCPZ maintain identical chromophore to the parent drug. In this work, it has been found that the nature of the aminoalkyl side chain modulates the hydrophobicity and the photochemical properties (for instance, the excited state lifetimes), but it does not change the photoreactivity pattern, which is characterized by reductive photodehalogenation, triggered by homolytic carbon-chlorine bond cleavage with formation of highly reactive aryl radical intermediates. Accordingly, these metabolites are phototoxic to cells, as revealed by the 3T3 NRU assay; their photo-irritation factors are even higher than that of CPZ. The same trend is observed in photogenotoxicity studies, both with isolated and with cellular DNA, where DMCPZ and DDMCPZ are more active than CPZ itself. In summary, side-chain demethylation of CPZ, as a consequence of Phase I biotransformation, does not result a photodetoxification. Instead, it leads to metabolites that exhibit in an even enhanced photo(geno)toxicity. - Highlights: • Demethylated CPZ metabolites are phototoxic to cells, as revealed by the NRU assay. • Single cell electrophoresis (Comet Assay) confirms the photodamage to cellular DNA. • DNA single strand breaks formation is observed on agarose gel electrophoresis. �

Reparation and Immunomodulating Properties of Bacillus sp. Metabolites from Permafrost.

Science.gov (United States)

Kalenova, L F; Melnikov, V P; Besedin, I M; Bazhin, A S; Gabdulin, M A; Kolyvanova, S S

2017-09-01

An ointment containing metabolites of Bacillus sp. microorganisms isolated from permafrost samples was applied onto the skin wound of BALB/c mice. Metabolites isolated during culturing of Bacillus sp. at 37°C produced a potent therapeutic effect and promoted wound epithelialization by 30% in comparison with the control (ointment base) and by 20% in comparison with Solcoseryl. Treatment with Bacillus sp. metabolites stimulated predominantly humoral immunity, reduced the time of wound contraction and the volume of scar tissue, and promoted complete hair recovery. These metabolites can be considered as modulators of the wound process with predominance of regeneration mechanisms.

Quantification of homocysteine-related metabolites and the role of betaine-homocysteine S-methyltransferase in HepG2 cells

Czech Academy of Sciences Publication Activity Database

Kořínek, M.; Šístek, V.; Mládková, Jana; Mikeš, P.; Jiráček, Jiří; Selicharová, Irena

2013-01-01

Roč. 27, č. 1 (2013), s. 111-121 ISSN 0269-3879 R&D Projects: GA ČR(CZ) GAP207/10/1277 Institutional support: RVO:61388963 Keywords : homocysteine * BHMT * LC-MS/MS * HepG2 * metabolites Subject RIV: CE - Biochemistry Impact factor: 1.662, year: 2013

Role of Cereal Secondary Metabolites Involved in Mediating the Outcome of Plant-Pathogen Interactions

Directory of Open Access Journals (Sweden)

Lauren A. Du Fall

2011-12-01

Full Text Available Cereal crops such as wheat, rice and barley underpin the staple diet for human consumption globally. A multitude of threats to stable and secure yields of these crops exist including from losses caused by pathogens, particularly fungal. Plants have evolved complex mechanisms to resist pathogens including programmed cell death responses, the release of pathogenicity-related proteins and oxidative bursts. Another such mechanism is the synthesis and release of secondary metabolites toxic to potential pathogens. Several classes of these compounds have been identified and their anti-fungal properties demonstrated. However the lack of suitable analytical techniques has hampered the progress of identifying and exploiting more of these novel metabolites. In this review, we summarise the role of the secondary metabolites in cereal crop diseases and briefly touch on the analytical techniques that hold the key to unlocking their potential in reducing yield losses.

Extracellular Metabolites from Industrial Microalgae and Their Biotechnological Potential

Directory of Open Access Journals (Sweden)

Lu Liu

2016-10-01

Full Text Available Industrial microalgae, as a big family of promising producers of renewable biomass feedstock, have been commercially exploited for functional food, living feed and feed additives, high-value chemicals in nutraceuticals, cosmeceuticals, and chemical reagents. Recently, microalgae have also been considered as a group that might play an important role in biofuel development and environmental protection. Almost all current products of industrial microalgae are derived from their biomass; however, large amounts of spent cell-free media are available from mass cultivation that is mostly unexploited. In this contribution we discuss that these media, which may contain a remarkable diversity of bioactive substances are worthy to be recovered for further use. Obviously, the extracellular metabolites from industrial microalgae have long been neglected in the development of production methods for valuable metabolites. With the advances in the last ten years, more and more structures and properties from extracellular metabolites have been identified, and the potential utilization over wide fields is attracting attention. Some of these extracellular metabolites can be potentially used as drugs, antioxidants, growth regulators or metal chelators. The purpose of this review is to provide an overview of the known extracellular metabolites from industrial microalgae which might be of commercial interest. The attention mainly focuses on the reports of extracellular bioactive metabolites and their potential application in biotechnology.

Metabolites from inhalation of aerosolized S-8 synthetic jet fuel in rats.

Science.gov (United States)

Tremblay, Raphael T; Martin, Sheppard A; Fisher, Jeffrey W

2011-01-01

Alternative fuels are being considered for civilian and military uses. One of these is S-8, a replacement jet fuel synthesized using the Fischer-Tropsch process, which contains no aromatic compounds and is mainly composed of straight and branched alkanes. Metabolites of S-8 fuel in laboratory animals have not been identified. The goal of this study was to identify metabolic products from exposure to aerosolized S-8 and a designed straight-chain alkane/polyaromatic mixture (decane, undecane, dodecane, tridecane, tetradecane, pentadecane, naphthalene, and 2-methylnaphthalene) in male Fischer 344 rats. Collected blood and tissue samples were analyzed for 70 straight and branched alcohols and ketones ranging from 7 to 15 carbons. No fuel metabolites were observed in the blood, lungs, brain, and fat following S-8 exposure. Metabolites were detected in the liver, urine, and feces. Most of the metabolites were 2- and 3-position alcohols and ketones of prominent hydrocarbons with very few 1- or 4-position metabolites. Following exposure to the alkane mixture, metabolites were observed in the blood, liver, and lungs. Interestingly, heavy metabolites (3-tridecanone, 2-tridecanol, and 2-tetradecanol) were observed only in the lung tissues possibly indicating that metabolism occurred in the lungs. With the exception of these heavy metabolites, the metabolic profiles observed in this study are consistent with previous studies reporting on the metabolism of individual alkanes. Further work is needed to determine the potential metabolic interactions of parent, primary, and secondary metabolites and identify more polar metabolites. Some metabolites may have potential use as biomarkers of exposure to fuels.

Selective mutism and abnormal electroencephalography (EEG) tracings.

Science.gov (United States)

Politi, Keren; Kivity, Sara; Goldberg-Stern, Hadassa; Halevi, Ayelet; Shuper, Avinoam

2011-11-01

Epileptic discharges are not considered a part of the clinical picture of selective mutism, and electroencephalography is generally not recommended in its work-up. This report describes 6 children with selective mutism who were found to have a history of epilepsy and abnormal interictal or subclinical electroencephalography recordings. Two of them had benign epilepsy of childhood with centro-temporal spikes. The mutism was not related in time to the presence of active seizures. While seizures could be controlled in all children by medications, the mutism resolved only in 1. Although the discharges could be coincidental, they might represent a co-morbidity of selective mutism or even play a role in its pathogenesis. Selective mutism should be listed among the psychiatric disorders that may be associated with electroencephalographic abnormalities. It can probably be regarded as a symptom of a more complicated organic brain disorder.

Prevalence of vaginal candidiasis among pregnant women with abnormal vaginal discharge in Maiduguri.

Science.gov (United States)

Ibrahim, S M; Bukar, M; Mohammed, Y; Mohammed, B; Yahaya, M; Audu, B M; Ibrahim, H M; Ibrahim, H A

2013-01-01

Pregnancy represents a risk factor in the occurrence of vaginal candidiasis. To determine the prevalence and clinical features associated with abnormal vaginal discharge and C. albicans infection in pregnant women. High vaginal swab samples and data on epidemiological characteristics were collected from 400 pregnant women with complaints of abnormal vaginal discharge at booking clinic of University of Maiduguri Teaching Hospital. The data was analysed using SPSS 16.0 statistical software. The prevalence of abnormal vaginal discharge in pregnancy was 31.5%. The frequency of abnormal vaginal discharge was 183 (45.8%) among those aged 20-24 years, 291 (72.8%) in multipara, 223 (55.8%) in those with Primary education and 293 (73.2%) in unemployed. Vulval pruritus 300 (75.0%) was significantly related to abnormal vaginal discharge (P candidiasis were 151 (50.3%), 14 (56.0%) and 75 (75.0%) respectively (P vaginal discharge in pregnancy was high in this study and C. albicans was the commonest cause. It is recommended that a pregnant woman complaining of abnormal vaginal discharge be assessed and Laboratory diagnosis done in order to give appropriate treatment.

Structural requirements for bioactivation of anticonvulsants to cytotoxic metabolites in vitro.

Science.gov (United States)

Riley, R J; Kitteringham, N R; Park, B K

1989-01-01

The formation of cytotoxic metabolites from the anticonvulsants phenytoin and carbamazepine was investigated in vitro using a hepatic microsomal enzyme system and human mononuclear leucocytes as target cells. Both drugs were metabolised to cytotoxic products. In order to assess the structural requirements for this bioactivation, a series of structurally related compounds was investigated. It was found that molecules which contain either an amide function or an aryl ring may undergo activation in vitro, but only the metabolism-dependent toxicity of the latter is potentiated by pre-treatment of the target cells with an epoxide hydrolase inhibitor. Taken collectively, these data are consistent with the concept that reactive epoxide metabolites of both phenytoin and carbamazepine may produce toxicity in individuals with an inherited deficiency in epoxide hydrolase. PMID:2590607

Plasma metabolite score correlates with Hypoxia time in a newly born piglet model for asphyxia

Directory of Open Access Journals (Sweden)

Julia Kuligowski

2017-08-01

Full Text Available Hypoxic-ischemic encephalopathy (HIE secondary to perinatal asphyxia is a leading cause of mortality and acquired long-term neurologic co-morbidities in the neonate. The most successful intervention for the treatment of moderate to severe HIE is moderate whole body hypothermia initiated within 6 h from birth. The objective and prompt identification of infants who are at risk of developing moderate to severe HIE in the critical first hours still remains a challenge. This work proposes a metabolite score calculated based on the relative intensities of three metabolites (choline, 6,8-dihydroxypurine and hypoxanthine that showed maximum correlation with hypoxia time in a consolidated piglet model for neonatal hypoxia-ischemia. The metabolite score's performance as a biomarker for perinatal hypoxia and its usefulness for clinical grading and decision making have been assessed and compared to the performance of lactate which is currently considered the gold standard. For plasma samples withdrawn before and directly after a hypoxic insult, the metabolite score performed similar to lactate. However, it provided an enhanced predictive capacity at 2 h after resuscitation. The present study evidences the usefulness of the metabolite score for improving the early assessment of the severity of the hypoxic insult based on serial determinations in a minimally invasive biofluid. The applicability of the metabolite score for clinical diagnosis and patient stratification for hypothermia treatment has to be confirmed in multicenter trials involving newborns suffering from HIE. Keywords: Hypoxia, Perinatal asphyxia, Newborn, Metabolic biomarker, Neonatal piglet model, Liquid Chromatography – Time-of-Flight Mass Spectrometry (LC-TOF-MS

Diagnosis and treatment of abnormal dental pain.

Science.gov (United States)

Fukuda, Ken-Ichi

2016-03-01

Most dental pain is caused by an organic problem such as dental caries, periodontitis, pulpitis, or trauma. Diagnosis and treatment of these symptoms are relatively straightforward. However, patients often also complain of abnormal dental pain that has a non-dental origin, whose diagnosis is challenging. Such abnormal dental pain can be categorized on the basis of its cause as referred pain, neuromodulatory pain, and neuropathic pain. When it is difficult to diagnose a patient's dental pain, these potential alternate causes should be considered. In this clinical review, we have presented a case of referred pain from the digastric muscle (Patient 1), of pulpectomized (Patient 2), and of pulpectomized pain (Patient 3) to illustrate referred, neuromodulatory, and neuropathic pain, respectively. The Patient 1 was advised muscle stretching and gentle massage of the trigger points, as well as pain relief using a nonsteroidal anti-inflammatory and the tricyclic antidepressant amitriptyline. The pain in Patient 2 was relieved completely by the tricyclic antidepressant amitriptyline. In Patient 3, the pain was controlled using either a continuous drip infusion of adenosine triphosphate or intravenous Mg2+ and lidocaine administered every 2 weeks. In each case of abnormal dental pain, the patient's diagnostic chart was used (Fig.2 and 3). Pain was satisfactorily relieved in all cases.

Abnormalities of hippocampal signal intensity in patients with familial mesial temporal lobe epilepsy

Directory of Open Access Journals (Sweden)

Coan A.C.

2004-01-01

Full Text Available Mesial temporal lobe epilepsy (MTLE is associated with hippocampal atrophy and hippocampal signal abnormalities. In our series of familial MTLE (FMTLE, we found a high proportion of hippocampal abnormalities. To quantify signal abnormalities in patients with FMTLE we studied 152 individuals (46 of them asymptomatic with FMTLE. We used NIH-Image® for volumetry and signal quantification in coronal T1 inversion recovery and T2 for all cross-sections of the hippocampus. Values diverging by 2 or more SD from the control mean were considered abnormal. T2 hippocampal signal abnormalities were found in 52% of all individuals: 54% of affected subjects and 48% of asymptomatic subjects. T1 hippocampal signal changes were found in 34% of all individuals: 42.5% of affected subjects and 15% of asymptomatic subjects. Analysis of the hippocampal head (first three slices revealed T2 abnormalities in 73% of all individuals (74% of affected subjects and 72% of asymptomatic subjects and T1 abnormalities in 59% (67% of affected subjects and 41% of asymptomatic subjects. Affected individuals had smaller volumes than controls (P < 0.0001. There was no difference in hippocampal volumes between asymptomatic subjects and controls, although 39% of asymptomatic patients had hippocampal atrophy. Patients with an abnormal hippocampal signal (133 individuals had smaller ipsilateral volume, but no linear correlation could be determined. Hippocampal signal abnormalities in FMTLE were more frequently found in the hippocampal head in both affected and asymptomatic family members, including those with normal volumes. These results indicate that subtle abnormalities leading to an abnormal hippocampal signal in FMTLE are not necessarily related to seizures and may be determined by genetic factors.

Metabolite production by species of Stemphylium

DEFF Research Database (Denmark)

Olsen, Kresten Jon Kromphardt; Rossman, Amy; Andersen, Birgitte

2018-01-01

metabolites were found to be important for distinguishing species, while some unknown metabolites were also found to have important roles in distinguishing species of Stemphylium. This study is the first of its kind to investigate the chemical potential of Stemphylium across the whole genus.......Morphology and phylogeny has been used to distinguish members of the plant pathogenic fungal genus Stemphylium. A third method for distinguishing species is by chemotaxonomy. The main goal of the present study was to investigate the chemical potential of Stemphylium via HPLC-UV-MS analysis, while...

Abnormal functional motor lateralization in healthy siblings of patients with schizophrenia.

Science.gov (United States)

Altamura, Mario; Fazio, Leonardo; De Salvia, Michela; Petito, Annamaria; Blasi, Giuseppe; Taurisano, Paolo; Romano, Raffaella; Gelao, Barbara; Bellomo, Antonello; Bertolino, Alessandro

2012-07-30

Earlier neuroimaging studies of motor function in schizophrenia have demonstrated reduced functional lateralization in the motor network during motor tasks. Here, we used event-related functional magnetic resonance imaging during a visually guided motor task in 18 clinically unaffected siblings of patients with schizophrenia and 24 matched controls to investigate if abnormal functional lateralization is related to genetic risk for this brain disorder. Whereas activity associated with motor task performance was mainly contralateral with only a marginal ipsilateral component in healthy participants, unaffected siblings had strong bilateral activity with significantly greater response in ipsilateral and contralateral premotor areas as well as in contralateral subcortical motor regions relative to controls. Reduced lateralization in siblings was also identified with a measure of laterality quotient. These findings suggest that abnormal functional lateralization of motor circuitry is related to genetic risk of schizophrenia. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

T wave abnormalities, high body mass index, current smoking and high lipoprotein (a levels predict the development of major abnormal Q/QS patterns 20 years later. A population-based study

Directory of Open Access Journals (Sweden)

Sundstrom Johan

2006-03-01

Full Text Available Abstract Background Most studies on risk factors for development of coronary heart disease (CHD have been based on the clinical outcome of CHD. Our aim was to identify factors that could predict the development of ECG markers of CHD, such as abnormal Q/QS patterns, ST segment depression and T wave abnormalities, in 70-year-old men, irrespective of clinical outcome. Methods Predictors for development of different ECG abnormalities were identified in a population-based study using stepwise logistic regression. Anthropometrical and metabolic factors, ECG abnormalities and vital signs from a health survey of men at age 50 were related to ECG abnormalities identified in the same cohort 20 years later. Results At the age of 70, 9% had developed a major abnormal Q/QS pattern, but 63% of these subjects had not been previously hospitalized due to MI, while 57% with symptomatic MI between age 50 and 70 had no major Q/QS pattern at age 70. T wave abnormalities (Odds ratio 3.11, 95% CI 1.18–8.17, high lipoprotein (a levels, high body mass index (BMI and smoking were identified as significant independent predictors for the development of abnormal major Q/QS patterns. T wave abnormalities and high fasting glucose levels were significant independent predictors for the development of ST segment depression without abnormal Q/QS pattern. Conclusion T wave abnormalities on resting ECG should be given special attention and correlated with clinical information. Risk factors for major Q/QS patterns need not be the same as traditional risk factors for clinically recognized CHD. High lipoprotein (a levels may be a stronger risk factor for silent myocardial infarction (MI compared to clinically recognized MI.

Identification of Unique Metabolites of the Designer Opioid Furanyl Fentanyl.

Science.gov (United States)

Goggin, Melissa M; Nguyen, An; Janis, Gregory C

2017-06-01

The illicit drug market has seen an increase in designer opioids, including fentanyl and methadone analogs, and other structurally unrelated opioid agonists. The designer opioid, furanyl fentanyl, is one of many fentanyl analogs clandestinely synthesized for recreational use and contributing to the fentanyl and opioid crisis. A method has been developed and validated for the analysis of furanyl fentanyl and furanyl norfentanyl in urine specimens from pain management programs. Approximately 10% of samples from a set of 500 presumptive heroin-positive urine specimens were found to contain furanyl fentanyl, with an average concentration of 33.8 ng/mL, and ranging from 0.26 to 390 ng/mL. Little to no furanyl norfentanyl was observed; therefore, the furanyl fentanyl specimens were further analyzed by untargeted high-resolution mass spectrometry to identify other metabolites. Multiple metabolites, including a dihydrodiol metabolite, 4-anilino-N-phenethyl-piperidine (4-ANPP) and a sulfate metabolite were identified. The aim of the presented study was to identify the major metabolite(s) of furanyl fentanyl and estimate their concentrations for the purpose of toxicological monitoring. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Loss of metabolites from monkey striatum during PET with FDOPA

DEFF Research Database (Denmark)

Cumming, P; Munk, O L; Doudet, D

2001-01-01

diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate...... constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

Dietary Energy Source in Dairy Cows in Early Lactation: Metabolites and Metabolic Hormones

NARCIS (Netherlands)

Knegsel, van A.T.M.; Brand, van den H.; Graat, E.A.M.; Dijkstra, J.; Jorritsma, R.; Decuypere, M.P.; Tamminga, S.; Kemp, B.

2007-01-01

Negative energy balance-related metabolic disorders suggest that the balance between available lipogenic and glucogenic nutrients is important. The objectives of this study were to compare the effects of a glucogenic or a lipogenic diet on liver triacylglycerides (TAG), metabolites, and metabolic

Imaging findings of sternal abnormalities