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Sample records for abilify aripiprazole metabolic

  1. Aripiprazole Injection

    ... of interest in life, and strong or inappropriate emotions). Aripiprazole injection (Abilify) is used to treat episodes ... street drugs or have overused prescription medication or alcohol or has or has ever had diabetes, obsessive ...

  2. Aripiprazole

    ... bipolar disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Aripiprazole is also used with an antidepressant to treat depression when symptoms cannot ... difficulty communicating and interacting with others). Aripiprazole may ...

  3. Neurological, Metabolic, and Psychiatric Adverse Events in Children and Adolescents Treated With Aripiprazole

    Jakobsen, Klaus Damgaard; Bruhn, Christina Hedegaard; Pagsberg, Anne-Katrine;

    2016-01-01

    insomnia, Parkinsonism, behavioral changes psychoses, and weight gain, whereas the adverse effects in the PS group was predominantly anxiety, convulsions, and neuroleptic malignant syndrome. Although aripiprazole is considered safe and well tolerated in children and adolescents, severe adverse events as...... neuroleptic malignant syndrome, extreme insomnia, and suicidal behavior has been reported to health authorities. Clinicians should pay attention to these possible hazards when prescribing aripiprazole to this vulnerable group of patients....

  4. Effects of switching from olanzapine to aripiprazole on the metabolic profiles of patients with schizophrenia and metabolic syndrome: a double-blind, randomized, open-label study

    Wani RA

    2015-03-01

    Full Text Available Rayees Ahmad Wani, Mansoor Ahmad Dar, Rajesh Kumar Chandel, Yasir Hassan Rather, Inaamul Haq, Arshad Hussain, Altaf Ahmad MallaDepartment of Psychiatry, Government Medical College, Srinagar, Jammu and Kashmir, IndiaBackground: Patients with schizophrenia suffer high rates of metabolic derangements on some antipsychotic medications that predispose them to cardiovascular diseases. Keeping this fact in mind, we planned this open-label study to see the effect on various metabolic parameters after switching stable schizophrenia subjects, who had developed metabolic syndrome on olanzapine, to aripiprazole.Methods: Sixty-two patients with schizophrenia who were stable on olanzapine and were fulfilling modified National Cholesterol Education Program (NCEP Adult Treatment Panel III (ATP-III criteria for the presence of metabolic syndrome were enrolled on the study. Patients were randomly assigned either to switch to aripiprazole or to stay on olanzapine, on a 1:1 basis. Cross-tapering over a period of 1 month was done while switching patients to aripiprazole. Laboratory assessment for metabolic parameters was done at baseline, 8 weeks, and 24 weeks after enrollment; efficacy assessment was done using the Positive and Negative Syndrome Scale (PANSS at baseline and 24 weeks, the Clinical Global Impressions severity subscale (CGI-S at baseline, and the Clinical Global Impressions improvement subscale (CGI-I at 24 weeks.Results: All parameters of metabolic syndrome (waist circumference, blood pressure, triglyceride level, fasting blood glucose, and high-density lipoprotein cholesterol kept deteriorating in the stay group, compared with a continuous improvement in the switch group over time. At the end of the study, 26 patients (100% from the stay group and 15 patients (42.8% from switch group met the modified NCEP ATP-III criteria for presence of metabolic syndrome (P<0.001. There were no statistically significant differences between groups in

  5. Neurological, Metabolic, and Psychiatric Adverse Events in Children and Adolescents Treated With Aripiprazole.

    Jakobsen, Klaus Damgaard; Bruhn, Christina Hedegaard; Pagsberg, Anne-Katrine; Fink-Jensen, Anders; Nielsen, Jimmi

    2016-10-01

    Aripiprazole is a partial dopamine agonist with only minor neurological and psychiatric adverse effects, making it a potential first-line drug for the treatment of psychiatric disorders. However, the evidence of its use in children and adolescents is rather sparse. The aim of this case study is to discuss adverse drug reaction (ADR) reports concerning aripiprazole-associated neurological and psychiatric events in children and adolescents. The ADR report database at Danish Medicines Agency was searched for all ADRs involving children and adolescents (disorders (PS group) and nonpsychotic disorders (non-PS group). The PS group consisted of 5 patients with schizophrenia and psychoses, not otherwise specified; and the non-PS group consisted of fourteen cases including autism spectrum disorders, attention deficit and hyperactivity disorder, obsessive-compulsive disorder, and Tourette syndrome. The main reported adverse effects in the non-PS group were chronic insomnia, Parkinsonism, behavioral changes psychoses, and weight gain, whereas the adverse effects in the PS group was predominantly anxiety, convulsions, and neuroleptic malignant syndrome. Although aripiprazole is considered safe and well tolerated in children and adolescents, severe adverse events as neuroleptic malignant syndrome, extreme insomnia, and suicidal behavior has been reported to health authorities. Clinicians should pay attention to these possible hazards when prescribing aripiprazole to this vulnerable group of patients. PMID:27504593

  6. Acanthosis nigricans during treatment with aripiprazole.

    Manu, Peter; Al-Dhaher, Zainab; Dargani, Navin; Correll, Christoph U

    2014-01-01

    Aripiprazole is typically regarded as a metabolically sparing agent, in contrast to other second-generation antipsychotics, which are widely known to lead to weight gain and increase the cardiometabolic risk. We report for the first time the emergence of Acanthosis nigricans, a dermatological correlate of insulin resistance, during treatment with aripiprazole in an adolescent with a family history of diabetes mellitus. PMID:23011171

  7. Studies of phase transitions in the aripiprazole solid dosage form.

    Łaszcz, Marta; Witkowska, Anna

    2016-01-01

    Studies of the phase transitions in an active substance contained in a solid dosage form are very complicated but essential, especially if an active substance is classified as a BCS Class IV drug. The purpose of this work was the development of sensitive methods for the detection of the phase transitions in the aripiprazole tablets containing initially its form III. Aripiprazole exhibits polymorphism and pseudopolymorphism. Powder diffraction, Raman spectroscopy and differential scanning calorimetry methods were developed for the detection of the polymorphic transition between forms III and I as well as the phase transition of form III into aripiprazole monohydrate in tablets. The study involved the initial 10 mg and 30 mg tablets, as well as those stored in Al/Al blisters, a triplex blister pack and HDPE bottles (with and without desiccant) under accelerated and long term conditions. The polymorphic transition was not observed in the initial and stored tablets but it was visible on the DSC curve of the Abilify(®) 10 mg reference tablets. The formation of the monohydrate was observed in the diffractograms and Raman spectra in the tablets stored under accelerated conditions. The monohydrate phase was not detected in the tablets stored in the Al/Al blisters under long term conditions. The results showed that the Al/Al blisters can be recommended as the packaging of the aripiprazole tablets containing form III. PMID:26397209

  8. Aripiprazole (Otsuka Pharmaceutical Co).

    Ozdemir, Vural; Fourie, Jeanne; Ozdener, Fatih

    2002-01-01

    Otsuka Pharmaceuticals in collaboration with Bristol-Myers Squibb is developing aripiprazole, a dual dopamine autoreceptor agonist and postsynaptic D2 receptor antagonist, for the potential treatment of psychoses including schizophrenia [281327], [340364]. A regulatory filing for schizophrenia in the US was submitted at the end of 2001 [340364]. The compound entered phase III trials in Japan in 1995 [192966]. Although presynaptic dopamine autoreceptor agonists may be efficacious in the treatment of schizophrenia, they may also potentially increase the risk for exacerbation of psychosis through stimulation of postsynaptic dopaminergic receptors [245791], [350478], [350479]. However, earlier neuropharmacology studies have shown that aripiprazole can act as a presynaptic D2 agonist while displaying an antagonistic effect at the postsynaptic D2 receptors [281327], [337126], [350479], [424587], [424588]. In animal models, aripiprazole inhibits the apomorphine-induced stereotypy, without causing catalepsy [281327], [337126]. Moreover, in contrast to classical antipsychotics that produce disabling movement disorders, aripiprazole does not cause an upregulation of D2 receptors or an increase in expression of the c-fos mRNA in the striatum, in agreement with the low risk for extrapyramidal side effects (EPS) during aripiprazole treatment [245781], [262096], [350481], [350483]. Collectively, aripiprazole is an important atypical antipsychotic candidate with a favorable safety profile. Moreover, the mechanism of action of aripiprazole differentiates it from both typical and atypical antipsychotics and hence, may provide important leads for pharmacotherapy of schizophrenia and other psychotic disorders. In January 2000, Lehman Brothers predicted peak sales of aripiprazole could reach US $500 million [357788]. In February 2001, Credit Suisse First Boston predicted sales of US $403 million in 2005 [399484]. PMID:12054061

  9. Retrospective Study of Japanese Patients with Schizophrenia Treated with Aripiprazole

    Tanioka, Tetsuya; Fuji, Syoko; Kataoka, Mika; King, Beth; Tomotake, Masahito; Yasuhara, Yuko; Locsin, Rozzano; Sekido, Keiko; Mifune, Kazushi

    2012-01-01

    Aim. The purpose of this retrospective study was to evaluate changes in clinical indicators which influence the quality of life (QOL) of patients with schizophrenia treated by antipsychotic therapy before and after switching to aripiprazole. Methods. A retrospective chart review of 27 patients diagnosed with schizophrenia and who were switched from one antipsychotic to aripiprazole was performed. Clinical indicators about the daily dosage of antipsychotics and antiparkinsonian drugs, psychiatric condition, and glucose/lipid metabolism, clinical evaluation by nursing observation were used to measure the responsiveness of subjects to aripiprazole. Results. Of the 27 subjects, 14 responded to the switch to aripiprazole with significant improvement of the Brief Psychiatric Rating Scale (BPRS) score (P = 0.04), significant decrease in dosage of antipsychotics in 71% of patients (P = 0.03), and tendency toward reduction in dosage of antiparkinsonian drugs (P = 0.07) and body mass index (BMI) (P = 0.06). However, 8 of 27 subjects had a significant increase in lipid levels after switching to aripiprazole (P = 0.01). Conclusion. QOL for subjects who responded to the switch to aripiprazole improved as indicated by lower doses of antipsychotic and antiparkinson medications, improvement in BPRS score, and a decrease in BMI. Results indicate little influence on patient's QOL. PMID:22970386

  10. Comparison the effectiveness of aripiprazole and risperidone for the treatment of acute bipolar mania

    Amir Akhavan Rezayat; Paria Hebrani; Fatemeh Behdani; Mohamad Salaran; Majid Nabizadeh Marvast

    2014-01-01

    Background: Second-generation antipsychotics, approved for the treatment of mania, are associated with adverse effects such as weight gain and metabolic disorders. Aripiprazole, a recently introduced second-generation antipsychotic, are thought to account for its low propensity for weight gain, metabolic disturbances and sedation. The purpose of this study was to investigate the effect of risperidone versus aripiprazole in the treatment of acute mania. Materials and Methods: Fifty patients wi...

  11. Antipsychotic treatments for the elderly: efficacy and safety of aripiprazole

    Izchak Kohen

    2010-03-01

    Full Text Available Izchak Kohen1, Paula E Lester2, Sum Lam31Division of Geriatric Psychiatry, Zucker-Hillside Hospital, Glen Oaks, NY, USA; 2Division of Geriatric Medicine, Winthrop University Hospital, Mineola, NY, USA; 3Division of Pharmacy and Geriatrics, St. John’s University College of Pharmacy and Allied Health Professions, Queens, NY, USAAbstract: Delusions, hallucinations and other psychotic symptoms can accompany a number of conditions in late life. As such, elderly patients are commonly prescribed antipsychotic medications for the treatment of psychosis in both acute and chronic conditions. Those conditions include schizophrenia, bipolar disorder, depression and dementia. Elderly patients are at an increased risk of adverse events from antipsychotic medications because of age-related pharmacodynamic and pharmacokinetic changes as well as polypharmacy. Drug selection should be individualized to the patient’s previous history of antipsychotic use, current medical conditions, potential drug interactions, and potential side effects of the antipsychotic. Specifically, metabolic side effects should be closely monitored in this population. This paper provides a review of aripiprazole, a newer second generation antipsychotic agent, for its use in a variety of psychiatric disorders in the elderly including schizophrenia, bipolar disorder, dementia, Parkinson’s disease and depression. We will review the pharmacokinetics and pharmacodynamics of aripiprazole as well as dosing, diagnostic indications, efficacy studies, and tolerability including its metabolic profile. We will also detail patient focused perspectives including quality of life, patient satisfaction and adherence.Keywords: aripiprazole, antipsychotics, elderly, adverse drug reaction

  12. Comparison the effectiveness of aripiprazole and risperidone for the treatment of acute bipolar mania

    Amir Akhavan Rezayat

    2014-01-01

    Full Text Available Background: Second-generation antipsychotics, approved for the treatment of mania, are associated with adverse effects such as weight gain and metabolic disorders. Aripiprazole, a recently introduced second-generation antipsychotic, are thought to account for its low propensity for weight gain, metabolic disturbances and sedation. The purpose of this study was to investigate the effect of risperidone versus aripiprazole in the treatment of acute mania. Materials and Methods: Fifty patients with acute episodes of mania were enrolled in this study, and they were randomly assigned into a risperidone group of 24 cases and an aripiprazole group of 26 cases. In group A, aripiprazole with a dose of 5-30 mg/day and in group B, risperidone with a dose of 2-8 mg/day was given to patients. The average dose of aripiprazole was 27 mg/day, and the average dose of risperidone was 6 mg/day. The effects of each drug for the treatment of acute mania were assessed on the 1 st day of admission and on days 2, 4, 6, 8 and at weeks 2, 4 and 6 after therapy using the young mania rating scale (YMRS and at the baseline and on weeks 3 and 6 after admission using the clinical global impression (CGI scale. Results: The mean age of the group of risperidone was 34 ± 8.6 years and in a group of aripiprazole it was 34 ± 9.1 years (P = 0.83. Comparison of YMRS scores over the period of 6 weeks revealed a statistically significant difference in both groups (P < 0.0001.There was also a statistically significant difference in YMRS scores between risperidone and aripiprazole at day 8 (P = 0.026 and weeks 2 (P = 0.035 and 4 (P = 0.042. There was also a statistically significant difference in CGI-Severity scale score at weeks 3 (P = 0.003 and 6 (P = 0.000 and in CGI-Improvement scale score at weeks 3 (P = 0.005 and 6 (P = 0.002. The most common side-effect observed in both groups was headache (0%15/4 in aripiprazole vs. %16/7 in risperidone Conclusion: Aripiprazole that is readily

  13. Aripiprazole for the Treatment of Tourette's Disorder

    Padala, Prasad R.; Qadri, S. Faiz; Madaan, Vishal

    2005-01-01

    Objective: Tourette's disorder is a neuropsychiatric syndrome that manifests with motor and vocal tics, including coprolalia. This article presents a report of successful treatment of these tics with aripiprazole in 2 consecutive patients with Tourette's disorder.

  14. 换用阿立哌唑对精神分裂症患者代谢的影响%Metabolic effects in treating schizophrenia patients after switching to aripiprazole

    程群; 朱怀轩

    2012-01-01

    目的:探讨换用阿立哌唑治疗后精神分裂症患者各项代谢指标的改善情况. 方法:选择43例换用阿立哌唑治疗的精神分裂症患者,分别在换药前和换药12周对患者的血糖、血脂和体质量等代谢指标进行检测. 结果:换用阿立哌唑12周,患者的体质量(t=3.38,P<0.01)和体质量指数(t=3.07,P<0.01)显著改善,空腹血糖(t=2.96,P<0.01)、2h血糖(=2.58,P<0.01)、糖化血红蛋白(t=3.50,P<0.01)、空腹胰岛素(t=19.71,P<0.01)、和稳态模型评估的胰岛素抵抗系数(t=2.70,P<0.05)均较治疗前显著降低,总胆固醇(t=2.78,P<0.01)、三酰甘油(t=4.38,P<0.01)和低密度脂蛋白(=2.81,P<0.01)亦有显著降低,代谢综合征的患病率(x2=19.07,P<0.01)显著降低. 结论:换用阿立哌唑治疗对精神分裂症患者的代谢有显著改善作用.%Objective: To evaluate extensively the metabolic improvements of switching to aripirzazole in the treatment of schizophrenia. Method :43 patients who had successfully switched to aripirazole with a schizophrenia diagnosis went through an extensive metabolic evaluation, including blood glucose, blood lipids and body weight test at baseline and at 12 weeks post switch. Results: There was significant decreases in body weight(t=3. 38, P< 0.01), body mass index(t =3. 07,P <0. 01) .fasting glucose(t =2. 96,P <0. 01) .glucose at 2 h(t = 2. 58,P<0. 01) .glycated hemoglobin(t = 3. 50, P < 0.01) .fasting insulin(t = 19. 71,P< 0.01),insulin resistance index(t =2. 70,P<0.05) .total cholesterol (t =2. 78,P <0.01), triglycerides (t = 4. 38,P<0.01) and low-density lipoprotein (t =2. 81 ,P<0.01) levels. There was also a significant reduction in the prevalence of metabolic syndrome(χ 2 = 19.07,P <0.01). Conclusion: Switching to aripiprazole can significantly improve metabolic abnormalities in treating schizophrenia.

  15. Adjunctive Aripiprazole Treatment for Risperidone-Induced Hyperprolactinemia: An 8-Week Randomized, Open-Label, Comparative Clinical Trial.

    Jingyuan Zhao

    Full Text Available The present study aimed to evaluate the efficacy and safety of adjunctive aripiprazole treatment in schizophrenia patients with risperidone-induced hyperprolactinemia.One hundred and thirteen patients who were receiving a stable dose of risperidone were randomly assigned to either adjunctive aripiprazole treatment (10 mg/day (aripiprazole group or no additional treatment (control group at a 1:1 ratio for 8 weeks. Schizophrenia symptoms were measured using the Positive and Negative Syndrome Scale (PANSS. Rating scales and safety assessments (RSESE, BARS, UKU were performed at baseline and at weeks 4 and 8. Serum levels of prolactin were determined at baseline and at weeks 2, 4, 6 and 8. Metabolic parameters were determined at baseline and again at weeks 4 and 8.One hundred and thirteen patients were enrolled in this study, and 107 patients completed the study (54 in the aripiprazole group, and 53 in the control group. PANSS-total scores in the aripiprazole group decreased significantly at week 4 (P = 0.003 and week 8 (P = 0.007 compared with the control group. PANSS-negative scores in the aripiprazole group also decreased significantly at week 4 (P = 0.005 and week 8 (P< 0.001 compared with the control group. Serum levels of prolactin in the aripiprazole group decreased significantly at week 2 (P< 0.001, week 4 (P< 0.001, week 6 (P< 0.001 and week 8 (P< 0.001 compared with the control group. There were no significant differences in changes of Fasting Plasma Glucose, Total cholesterol, Triglycerides and High Density Lipoprotein within each group at week 4 and 8 execpt low density lipoproteins. There was no significant difference in the incidence of adverse reactions between the two groups.Adjunctive aripiprazole treatment may be beneficial in reducing serum levels of prolactin and improving negative symptoms in schizophrenia patients with risperidone-induced hyperprolactinemia.chictr.org ChiCTR-IOR-15006278.

  16. Aripiprazole

    ... of interest in life, and strong or inappropriate emotions) in adults and teenagers 13 years of age ... street drugs or have overused prescription medication or alcohol or has or has ever had diabetes, obsessive ...

  17. Normalization of Risperidone-Induced Hyperprolactinemia with the Addition of Aripiprazole

    Shores, Larry E.

    2005-01-01

    The objective of this study was to monitor metabolic changes, including hyperprolactinemia, in adolescents medicated with atypical antipsychotics, especially when polypharmacy is involved. This study specifically followed risperidone-induced hyperprolactinemia in adolescents (14 male patients and 2 female patients) after aripiprazole was added to begin transitioning to another atypical antipsychotic. No other changes were made in the medication regimen. Risperidone was continued at the previo...

  18. Aripiprazole-Induced Parkinsonism: Report of Two Cases

    Çetin Kürşad Akpınar; Dursun Aygün; Hakan Doğru

    2015-01-01

    Aripiprazole is one of the recently introduced atypical antipsychotics used in the treatment of psychosis related to schizophrenia, depression, bipolar disorder, and Parkinson’s disease. Well-documented side effects associated with the use of aripiprazole include insomnia, anxiety, headache, nausea, vomiting, and somnolence. Aripiprazole is associated with infrequent extrapyramidal side effects. Parkinsonism is caused by some drugs that block dopamine receptors. The sign of dru...

  19. Two Cases of Hypersexuality Probably Associated with Aripiprazole

    Cheon, EunJin; Koo, Bon-Hoon; Seo, Sang Soo; Lee, Jun-Yeob

    2013-01-01

    Sexual dysfunction is a common side effect in patients treated with antipsychotics but significant differences exist across different compounds. We report hypersexuality symptoms in two female patients with schizophrenia who were receiving treatment with aripiprazole. The patients experienced more frequent sexual desire and greater sexual preoccupation after taking aripiprazole. We discuss the potential neuro-chemical mechanisms for this and argue that aripiprazole's unique pharmacological pr...

  20. Comparison of Short-term Metabolic Risk in First-episode Young-adult Schizophrenia Treated with Aripiprazole and Olanzapine%阿立哌唑与奥氮平对首发年轻成人精神分裂症患者短期内代谢风险的比较

    吴小立; 魏钦令; 钟智勇; 张晋碚

    2011-01-01

    摘要:[目的]比较阿立哌唑与奥氮平对首发年轻成人精神分裂症患者短期内的代谢风险.[方法]采用开放对照的临床观察方法,对符合美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)精神分裂症诊断标准的首发住院精神分裂症患者,分别使用阿立哌唑(21例)和奥氮平(42例)治疗,自然观察时间不低于2周,不大于4周,于治疗前后各检测一次体质量、腰围、空腹血脂血糖及胰岛素、C肽.[结果]观察结束时:阿立哌唑组的体质量、体质量指数(BMI)、腰围、腰臀比均有增高(P<0.05),糖脂改变无统计学差异,男女患者间各项代谢指标的变化无统计学差异(P>0.05);奥氮平组的体质量、体质量指数(BMI)、腰围、腰臀比、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、载脂蛋白AI和B100及脂蛋白LPa较治疗前增高(P<0.0l),且胰岛素(INS)水平和胰岛素抵抗指数(IR)增高(P<0.05),多元逐步回归分析显示胰岛素抵抗与甘油三脂的增高有关(R2 =0.107,P=0.007);奥氛平组男性患者的空腹胰岛素和C肽、胰岛素抵抗指数均增高(P<0.05),女性患者则没有.[结论]阿立哌唑和奥氮平对首发年轻成人精神分裂症患者短期内的代谢风险即有差异,性别差异可能影响着非典型抗精神病药物的代谢风险.%[Objective] To compare the short-term metabolic risk in the first-episode young-adult schizophrenia treated with Aripiprazole and Olanzapine. [ Methods] The open-lable, natural observed, compared method was designed for this study. All of these cases were diagnosed as first-episode schizophrenia in accordance with the DSM-IV diagnosis criteria and respectively allocated into two groups for either Aripiprazole or Olanzapine treatment. The natural observed period was from two weeks to four weeks. Weight, waist circumference, fasting glucose, and lipid concentration, fasting insulin and C peptide

  1. Adjunctive Aripiprazole Treatment for Risperidone-Induced Hyperprolactinemia: An 8-Week Randomized, Open-Label, Comparative Clinical Trial

    Zhao, Jingyuan; Song, Xueqin; Ai, Xiaoqing; Gu, Xiaojing; Huang, Guangbiao; Li, Xue; Pang, Lijuan; Ding, Minli; Ding, Shuang; Lv, Luxian

    2015-01-01

    Objective The present study aimed to evaluate the efficacy and safety of adjunctive aripiprazole treatment in schizophrenia patients with risperidone-induced hyperprolactinemia. Methods One hundred and thirteen patients who were receiving a stable dose of risperidone were randomly assigned to either adjunctive aripiprazole treatment (10 mg/day) (aripiprazole group) or no additional treatment (control group) at a 1:1 ratio for 8 weeks. Schizophrenia symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). Rating scales and safety assessments (RSESE, BARS, UKU) were performed at baseline and at weeks 4 and 8. Serum levels of prolactin were determined at baseline and at weeks 2, 4, 6 and 8. Metabolic parameters were determined at baseline and again at weeks 4 and 8. Results One hundred and thirteen patients were enrolled in this study, and 107 patients completed the study (54 in the aripiprazole group, and 53 in the control group). PANSS-total scores in the aripiprazole group decreased significantly at week 4 (P = 0.003) and week 8 (P = 0.007) compared with the control group. PANSS-negative scores in the aripiprazole group also decreased significantly at week 4 (P = 0.005) and week 8 (P< 0.001) compared with the control group. Serum levels of prolactin in the aripiprazole group decreased significantly at week 2 (P< 0.001), week 4 (P< 0.001), week 6 (P< 0.001) and week 8 (P< 0.001) compared with the control group. There were no significant differences in changes of Fasting Plasma Glucose, Total cholesterol, Triglycerides and High Density Lipoprotein within each group at week 4 and 8 execpt low density lipoproteins. There was no significant difference in the incidence of adverse reactions between the two groups. Conclusions Adjunctive aripiprazole treatment may be beneficial in reducing serum levels of prolactin and improving negative symptoms in schizophrenia patients with risperidone-induced hyperprolactinemia. Trial Registration chictr.org Chi

  2. Low-dose aripiprazole for refractory burning mouth syndrome.

    Umezaki, Yojiro; Takenoshita, Miho; Toyofuku, Akira

    2016-01-01

    We report a case of refractory burning mouth syndrome (BMS) ameliorated with low dose of aripiprazole. The patient was a 66-year-old female who had suffered from chronic burning pain in her tongue for 13 months. No abnormality associated with the burning sensation was detected in the laboratory tests and the oral findings. Considering the clinical feature and the history together, we diagnosed the burning sensation as BMS. The BMS pain was decreased by aripiprazole (powder) 1.0 mg/d, though no other antidepressants had satisfying pain relief. It could be supposed that the efficacy of aripiprazole is caused by dopamine stabilization in this case, and BMS might have a subtype that is reactive to aripiprazole. Further studies are needed to confirm the efficacy of aripiprazole for BMS. PMID:27279742

  3. Effects of switching to aripiprazole from current atypical antipsychotics on subsyndromal symptoms and tolerability in patients with bipolar disorder.

    Woo, Young Sup; Bahk, Won-Myong; Park, Young-Min; Chung, Sangkeun; Yoon, Bo-Hyun; Won, Seunghee; Lee, Jeong Goo; Lee, Hwang-Bin; Kim, Won; Jeong, Jong-Hyun; Lee, Kwanghun; Kim, Moon-Doo

    2016-09-01

    We evaluated the effectiveness of aripiprazole among bipolar patients who had switched to this medication as a result of difficulty maintaining on their prestudy atypical antipsychotics (AAPs) because of subsyndromal mood symptoms or intolerance. This study included 77 bipolar patients who were in syndromal remission with an AAP as monotherapy or with an AAP combined with a mood stabilizer(s) who needed to switch from their present AAP because of subsyndromal symptoms or intolerance. At 24 weeks after switching to aripiprazole, the remission rates on the Montgomery-Åsberg Depression Rating Scale (MADRS) and on both the MADRS and the Young Mania Rating Scale were increased significantly in the full sample and in the inefficacy subgroup. In the inefficacy subgroup, the MADRS score change was significant during the 24 weeks of study. Total cholesterol and prolactin decreased significantly after switching to aripiprazole. The proportion of patients who had abnormal values for central obesity and hypercholesterolemia decreased significantly from baseline to week 24. These findings suggest that a change from the current AAP to aripiprazole was associated with improvement in subsyndromal mood symptoms and several lipid/metabolic or safety profile parameters in patients with bipolar disorder with tolerability concerns or subsyndromal mood symptoms. PMID:27487259

  4. Behandling af Tourettes syndrom med aripiprazol

    Stenstrøm, Anne Dorte; Sindø, Ingrid

    2008-01-01

    Tourette's syndrome (TS) is a motoric disorder characterised by multiple motor and vocal tics. The treatment for patients with moderate to severe TS includes antipsychotic medication. A case report is described in which a 20 year-old male had taken antipsychotic medication since the age of five......, due to TS. The initial treatment consisted of pimozide and risperidone, both of which had an unsatisfactorily efficacy on tics and side effects in the form of weight gain and sedation. The patient is now treated with aripiprazole and there is a marked reduction of tics and no side effects...

  5. The prescribing pattern of a new antipsychotic: A descriptive study of aripiprazole for psychiatric in-patients

    Johansson, M.; Manniche, C.; Andersen, Stig Ejdrup

    2008-01-01

    -naive. In 25% aripiprazole, monotherapy was commenced whereas aripiprazole-antipsychotic combinations were initially prescribed in 75%. Overall, 85% of the patients received periods of antipsychotic polypharmacy and aripiprazole was combined with 17 different antipsychotics. Each patient received median...... three (range 0-8) psychoactive drugs parallel with aripiprazole. This study demonstrates reality in psychopharmacology and quote aripiprazole as example. In day-to-day practice, aripiprazole is used as part of highly individualized regimens comprising polypharmacy and excessive dosing. Although...

  6. ARIPIPRAZOLE VERSUS HALOPERIDOL TREATMENT IN EARLY-STAGE SCHIZOPHRENIA

    Girgis, Ragy R; Merrill, David B.; Vorel, Stanislav R.; Kim, Edward; Portland, Kimberly; You, Min; Pikalov, Andrei; Whitehead, Richard; Lieberman, Jeffrey A.

    2010-01-01

    We conducted a secondary analysis of a completed study of the differential efficacy and side effects of aripiprazole versus haloperidol in early-stage schizophrenia (ESS), a subpopulation of patients which does not include first episode or chronic patients. A subpopulation of 360 individuals with ESS were identified from a randomized, multi-center, double-blind study of 1294 individuals with schizophrenia at different stages of illness who were randomized to treatment with aripiprazole (ESS=2...

  7. Aripiprazole Augmentation in Treatment of Resistant Obsessive Compulsive Disorder

    Karim Abdel Aziz; Nisrin M El-Saadouni; Mohammed Hashim E. Elamin; Dina Aly El-Gabry; Hamdy F Moselhy

    2016-01-01

    Background: Aripiprazole is a novel antipsychotic medication that has been tried in the treatment of several psychiatric disorders. In an open clinical study, we evaluated the safety and efficacy of aripiprazole in patients with obsessive compulsive disorder resistant to normal regimen of treatment. Method: A total of nine hundred and sixty one patients were admitted over three year period of time (January 2012- December 2014) to the psychiatric department of Al Ain hospital, United Arab Emir...

  8. Low-dose aripiprazole for refractory burning mouth syndrome

    Umezaki Y

    2016-05-01

    Full Text Available Yojiro Umezaki,1 Miho Takenoshita,2 Akira Toyofuku2 1Psychosomatic Dentistry Clinic, Dental Hospital, 2Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan Abstract: We report a case of refractory burning mouth syndrome (BMS ameliorated with low dose of aripiprazole. The patient was a 66-year-old female who had suffered from chronic burning pain in her tongue for 13 months. No abnormality associated with the burning sensation was detected in the laboratory tests and the oral findings. Considering the clinical feature and the history together, we diagnosed the burning sensation as BMS. The BMS pain was decreased by aripiprazole (powder 1.0 mg/d, though no other antidepressants had satisfying pain relief. It could be supposed that the efficacy of aripiprazole is caused by dopamine stabilization in this case, and BMS might have a subtype that is reactive to aripiprazole. Further studies are needed to confirm the efficacy of aripiprazole for BMS. Keywords: burning mouth syndrome, low-dose aripiprazole, chronic pain

  9. Salivary and serum biomarkers for the study of side effects of aripiprazole coprescribed with mirtazapine in rats.

    Bogdan, Maria; Silosi, Isabela; Surlin, Petra; Tica, Andrei Adrian; Tica, Oana Sorina; Balseanu, Tudor-Adrian; Rauten, Anne-Marie; Camen, Adrian

    2015-01-01

    The aim of this study was to investigate whether the co-administration of aripiprazole and mirtazapine could determine weight gain and lipid metabolism disorders in Wistar rats, compared to the same side effects produced by mirtazapine alone, and the risk of hepatotoxicity due to the combination of the two substances. Tumor necrosis factor alpha (TNF-α), liver fatty acid binding protein (L-FABP/FABP1) and repulsive guidance molecule C/hemojuvelin (RGM-C/HJV) levels were determined in serum and in saliva. Also, serum levels for total cholesterol (TC), low and high-density lipoprotein (LDL, HDL), triglycerides (TG), aspartate aminotransferase (ASAT) and alanine amino transferase (ALAT) were assessed. We found positive and statistically significant correlations between serum and salivary levels of TNF-α, L-FABP/FABP1 and RGM-C/HJV. Mirtazapine determined significantly differences of TNF-α and L-FABP serum levels; final body weight; TC and LDL levels, leading to higher concentrations than its association with aripiprazole. Although not statistically significant, mirtazapine group experienced higher values for salivary levels of TNF-α, TG and ASAT, and lower values for HDL, compared to aripiprazole + mirtazapine group. The results suggest that aripiprazole might improve some of the disturbances caused by mirtazapine, and that the two drugs combination cause no additional alterations in liver function. Also, the findings indicate that TNF-α, L-FABP/FABP1 and RGM-C/HJV levels can be helpful as biomarkers for metabolic disturbances and impaired function of hepatocytes, and that their salivary determination can replace serum determination. PMID:26221370

  10. [Hypersexuality associated with aripiprazole: a new case and review of the literature].

    Vrignaud, Laura; Aouille, Jerémie; Mallaret, Michel; Durrieu, Geneviève; Jonville-Béra, Annie-Pierre

    2014-01-01

    We report the case of a patient with hypersexuality while he was treated with aripiprazole since 6 months. Clinical manifestations were an increased libido, unusual frequent masturbation and sexual instincts. All have resolved upon discontinuation of aripiprazole, and recurred after it was restarted. The partial dopaminergic agonist effect of aripiprazole could probably explain the occurrence of this compulsive behaviour. PMID:25293487

  11. Effect of combination of aripiprazole with carbamazepine and fluvoxamine on liver functions in experimental animals

    Chakrakodi S Shastry

    2013-01-01

    Conclusions: There would be an accumulation of aripiprazole when coadministered with fluvoxamine, a known inhibitor of CYP3A4, leading to hepatic damage and reduction in aripiprazole when administered along with carbamazepine. Therefore, aripiprazole with fluvoxamine and carbamazepine should be coprescribed with caution. The patients should be monitored for signs of adverse effects like hepatic damage or decreased efficacy of these drugs.

  12. Schizophrenia relapse and the clinical usefulness of once-monthly aripiprazole depot injection

    Wang SM

    2014-08-01

    Full Text Available Sheng-Min Wang,1 Changsu Han,2 Soo-Jung Lee,5 Ashwin A Patkar,3 Prakash S Masand,4 Chi-Un Pae3,5 1International Health Care Center, Seoul St Mary’s Hospital, The Catholic University of Korea, College of Medicine, Seoul, Republic of Korea; 2Department of Psychiatry, College of Medicine, Korea University, Seoul, Republic of Korea; 3Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, 4Global Medical Education, New York, NY, USA; 5Department of Psychiatry, Bucheon St Mary’s Hospital, The Catholic University of Korea, College of Medicine, Seoul, Republic of Korea Abstract: Improving medication adherence is critical to improving outcomes in patients with schizophrenia. A long-acting injectable (depot antipsychotic is one of the most effective methods for improving treatment adherence and decreasing rehospitalization rates in patients with schizophrenia. Until recently, only three second-generation antipsychotics were available in a long-acting injectable formulation (risperidone, paliperidone, and olanzapine. In this respect, the emergence of long-acting aripiprazole injection (ALAI, approved by the US Food and Drug Administration for the treatment of schizophrenia in 2013, is timely. ALAI is a lyophilized powder of aripiprazole, and the aripiprazole molecule is unmodified. The initial and target dosage of ALAI is 400 mg once monthly, but it could be reduced to 300 mg if adverse reactions occur with 400 mg. When first administering ALAI, it is recommended to continue treatment with oral aripiprazole (10–20 mg/day or another oral antipsychotic for 2 weeks in order to maintain therapeutic antipsychotic concentrations. The primary clearance route for ALAI is hepatic, ie, cytochrome P450 (CYP2D6 and CYP3A4, so dose adjustment is required in poor CYP2D6 metabolizers. The efficacy of ALAI was demonstrated in three studies. A randomized controlled trial that formed the basis for approval of ALAI in the

  13. Aripiprazole Improved Obsessive Compulsive Symptoms in Asperger's Disorder.

    Celik, Gonca; Tahiroglu, Aysegul Yolga; Firat, Sunay; Avci, Ayşe

    2011-12-01

    There are many comorbid disorders associated with autism spectrum disorders in child and adolescent population. Although obsessive compulsive disorder and autism spectrum disorders (ASD) comorbidity has common in clinical practice, there are few reports about psychopharmacological treatment for obsessive compulsive symptoms in children with ASD in the literacy. We report a successful treatment case with aripiprazole in Asperger's Disorder with obsessive compulsive symptoms. The Yale Brown Obsessive Compulsive Scale was performed to assess symptom variety. This case report supports the effectiveness of aripiprazole in treatment of obsessive compulsive symptoms in Asperger's Disorder or ASDs. Aripiprazole may be beneficial to obsessive compulsive disorder comorbid autism spectrum disorders in child and adolescent age group. PMID:23429759

  14. Aripiprazole for the management of schizophrenia in the Japanese population: a systematic review and meta-analysis of randomized controlled trials

    Kishi T

    2015-02-01

    Full Text Available Taro Kishi, Yuki Matsuda, Shinji Matsunaga, Nakao Iwata Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan Background: We conducted a systematic review and meta-analysis of randomized controlled trials comparing aripiprazole with pooled antipsychotics in Japanese patients with schizophrenia. Methods: We performed a literature search of data published in PubMed®, the Cochrane Library database, the Japan Medical Abstracts Society, and PsycINFO® up to January 5, 2014. The odds ratio (OR, number-needed-to-harm (NNH, and standardized mean difference (SMD based on a random effects model were calculated. Results: We identified five relevant studies (seven comparisons, n=684; one comparison each for haloperidol [n=243], mosapramine [n=238], olanzapine [n=39], quetiapine [n=42], perospirone [n=100], and two comparisons for risperidone [n=66]. There were no significant differences in the Positive and Negative Syndrome Scale (PANSS total, negative, and general scores (SMD=0.10, SMD=-0.09, SMD=0.10, respectively; discontinuation rate associated with all causes (OR=1.35; or side effects (OR=1.03 between aripiprazole and the pooled antipsychotics. Aripiprazole was inferior to the pooled antipsychotics in PANSS positive subscale scores (SMD=0.17 and discontinuation because of inefficacy (OR=2.21, NNH=11. However, aripiprazole had fewer side effects compared with the pooled antipsychotics (OR=0.21, NNH=20 for one or more side effects, including fatigue (OR=0.22, NNH=8, hyperprolactinemia (OR=0.00, NNH=1, extrapyramidal symptoms (OR=0.46, NNH=6, and weight gain (OR=0.36, NNH=7. Moreover, aripiprazole was associated with lower total cholesterol (SMD=-0.20 and triglyceride (SMD=-0.17 levels and body weight (SMD=-0.20 compared with the pooled antipsychotics. Conclusion: Although the discontinuation rate associated with inefficacy was higher with aripiprazole than with the pooled antipsychotics, aripiprazole was associated

  15. Adjunctive treatment with aripiprazole for risperidone-induced hyperprolactinemia

    Ranjbar F

    2015-03-01

    Full Text Available Fatemeh Ranjbar,1 Homayoun Sadeghi-Bazargani,2,3 Parisa Niari Khams,1 Asghar Arfaie,1 Azim Salari,4 Mostafa Farahbakhsh1 1Clinical Psychiatry Research Center, Tabriz University of Medical Sciences, Tabriz, East Azerbaijan, Iran; 2Road Traffic Injury Research Center, Department of Statistics & Epidemiology, Tabriz University of Medical Sciences, Tabriz, Iran; 3World Health Organization Collaborating Center on Community Safety Promotion, Karolinska Institute, Stockholm, Sweden; 4Emam Khomeini Hospital, Naghadeh, West Azerbaijan, Iran Background: Antipsychotics have been used for more than 50 years in the treatment of schizophrenia and many other psychiatric disorders. Prolactin levels usually increase in patients treated with risperidone. Aripiprazole, which has a unique effect as an antipsychotic, is a D2 receptor partial agonist. It is an atypical antipsychotic with limited extrapyramidal symptoms. Since it acts as an antagonist in hyperdopaminergic conditions and as an agonist in hypodopaminergic conditions, it does not have adverse effects on serum prolactin levels. The present study aimed to investigate the effect of aripiprazole on risperidone-induced hyperprolactinemia. Methods: This before-and-after clinical trial was performed in 30 patients. Baseline prolactin levels were measured in all patients who were candidates for treatment with risperidone. In subjects with elevated serum prolactin, aripiprazole was added to their treatment. Serum prolactin levels were measured during the first week, second week, and monthly thereafter for at least 3 months or until prolactin levels became normal. The data were analyzed using Stata version 11 software. Survival analysis and McNemar’s test were also performed. Results: The mean age of the participants was 30.8 years. Prolactin levels normalized in 23 (77% participants during the study, and menstrual disturbances normalized in 25 (83.3%. Prolactin levels normalized in most patients between days 50

  16. Effect of aripiprazole on mismatch negativity (MMN in schizophrenia.

    Zhenhe Zhou

    Full Text Available BACKGROUND: Cognitive deficits are considered core symptoms of the schizophrenia. Cognitive function has been found to be a better predictor of functional outcome than symptom levels. Changed mismatch negativity (MMN reflects abnormalities of early auditory processing in schizophrenia. Up to now, no studies for the effects of aripiprazole on MMN in schizophrenia have been reported. METHODOLOGY/PRINCIPAL FINDINGS: Subjects included 26 patients with schizophrenia, and 26 controls. Psychopathology was rated in patients with the Positive and Negative Syndrome Scale (PANSS at baseline, after 4- and 8-week treatments with aripiprazole. Auditory stimuli for ERP consisted of 100 millisecond/1000 Hz standards, intermixed with 100 millisecond/1500 Hz frequency deviants and 250 millisecond/1000 Hz duration deviants. EEG was recorded at Fz. BESA 5.1.8 was used to perform data analysis. MMN waveforms were obtained by subtracting waveforms elicited by standards from waveforms elicited by frequency- or duration-deviant stimuli. Aripiprazole decreased all PANSS. Patients showed smaller mean amplitudes of frequency and duration MMN at baseline than did controls. A repeated measure ANOVA with sessions (i.e., baseline, 4- and 8-week treatments and MMN type (frequency vs. duration as within-subject factors revealed no significant MMN type or MMN type × session main effect for MMN amplitudes. Session main effect was significant. LSD tests demonstrated significant differences between MMN amplitudes at 8 weeks and those at both baseline and 4 weeks. There was significant negative correlation between changes in amplitudes of frequency and duration MMN and changes in PANSS total scores at baseline and follow-up periods. CONCLUSIONS: Aripiprazole improved the amplitudes of MMN. MMN offers objective evidence that treatment with the aripiprazole may ameliorate preattentive deficits in schizophrenia.

  17. Aripiprazole Augmentation in Treatment of Resistant Obsessive Compulsive Disorder

    Karim Abdel Aziz

    2016-02-01

    Full Text Available Background: Aripiprazole is a novel antipsychotic medication that has been tried in the treatment of several psychiatric disorders. In an open clinical study, we evaluated the safety and efficacy of aripiprazole in patients with obsessive compulsive disorder resistant to normal regimen of treatment. Method: A total of nine hundred and sixty one patients were admitted over three year period of time (January 2012- December 2014 to the psychiatric department of Al Ain hospital, United Arab Emirates. All patients whose been fulfilled DSM-IV diagnosis of obsessive compulsive disorder (OCD (36 patients screened for further assessment. Patients with a diagnosis of schizophrenia (22 patients and one patient with eating disorder were excluded. Thirteen patients were contacted to be involved in the study. Participants were unstable although they were adherent to their medications (SSRIs when seen in the outpatient clinic two weeks after their discharge. One patient refused to participate in the study. A final number of 12 agreed to participate in the study. twelve patients aged 22 to 65 years who had DSM-IV diagnosis of OCD were treated with aripiprazole besides their normal treatment for a period of three months with daily doses ranging from ten to 20 mg daily. Results: a positive clinical response was noted in eight of the 12 patients within three months of study recruitment according to the Clinical Global Impression-Improvement scale. Aripiprazole was well tolerated by most of the patients. The most commonly reported side effect was headache. Conclusion: our findings suggest that aripiprazole may be an effective adjuvant and safe treatment for resistant OCD.

  18. Salivary and serum biomarkers for the study of side effects of aripiprazole coprescribed with mirtazapine in rats

    Bogdan, Maria; SILOSI, Isabela; SURLIN, PETRA; Tica, Andrei Adrian; Tica, Oana Sorina; Balseanu, Tudor-Adrian; Rauten, Anne-Marie; Camen, Adrian

    2015-01-01

    The aim of this study was to investigate whether the co-administration of aripiprazole and mirtazapine could determine weight gain and lipid metabolism disorders in Wistar rats, compared to the same side effects produced by mirtazapine alone, and the risk of hepatotoxicity due to the combination of the two substances. Tumor necrosis factor alpha (TNF-α), liver fatty acid binding protein (L-FABP/FABP1) and repulsive guidance molecule C/hemojuvelin (RGM-C/HJV) levels were determined in serum an...

  19. Aripiprazole-induced hyperprolactinemia in a young female with delusional disorder

    Sam Padamadan Joseph

    2016-01-01

    Full Text Available Hyperprolactinemia is a common adverse effect of antipsychotic medication. Switching over to aripiprazole or adjunctive aripiprazole has been advocated for optimal management of antipsychotic-induced hyperprolactinemia. Adjunctive treatment with aripiprazole has been shown to normalize prolactin levels without affecting already achieved improvements in psychotic symptoms. However, here, we present the case of a 36 year old female with delusional disorder who developed symptomatic hyperprolactinemia while on aripiprazole treatment. Dopamine acts as a tonic inhibitor of prolactin secretion through the tubero-infundibular dopaminergic system. Aripiprazole being a partial agonist has a lower intrinsic activity at the D2 receptor than dopamine, allowing it to act as both, a functional agonist and antagonist, depending on the surrounding levels of dopamine. Hence, in the absence of a competing D2 antagonist and the presence of dopamine (the natural agonist, aripiprazole could act as a functional antagonist and thus elevate prolactin levels.

  20. Aripiprazole-induced Hyperprolactinemia in a Young Female with Delusional Disorder.

    Joseph, Sam Padamadan

    2016-01-01

    Hyperprolactinemia is a common adverse effect of antipsychotic medication. Switching over to aripiprazole or adjunctive aripiprazole has been advocated for optimal management of antipsychotic-induced hyperprolactinemia. Adjunctive treatment with aripiprazole has been shown to normalize prolactin levels without affecting already achieved improvements in psychotic symptoms. However, here, we present the case of a 36 year old female with delusional disorder who developed symptomatic hyperprolactinemia while on aripiprazole treatment. Dopamine acts as a tonic inhibitor of prolactin secretion through the tubero-infundibular dopaminergic system. Aripiprazole being a partial agonist has a lower intrinsic activity at the D2 receptor than dopamine, allowing it to act as both, a functional agonist and antagonist, depending on the surrounding levels of dopamine. Hence, in the absence of a competing D2 antagonist and the presence of dopamine (the natural agonist), aripiprazole could act as a functional antagonist and thus elevate prolactin levels. PMID:27335526

  1. Treatment and prevention of mania in bipolar I disorder: focus on aripiprazole

    Muzina, David J.

    2009-01-01

    Aripiprazole is a second-generation antipsychotic with a unique pharmacologic receptor profile that has efficacy in the treatment and prevention of mania in bipolar I disorder. This article reviews the evidence supporting treatment of adults with bipolar I disorder using aripiprazole as monotherapy or adjunctively during acute mania and its utility as an intramuscular agent for agitation in manic patients. Results from one of the longest bipolar maintenance trials which support aripiprazole a...

  2. Use of Aripiprazole in Clozapine Induced Enuresis: Report of Two Cases

    Lee, Myung-Ji; Kim, Chul-Eung

    2010-01-01

    This report describes the efficacy of combined use of aripiprazole in the treatment of a patient with clozapine induced enuresis. Aripiprazole acts as a potential dopamine partial agonist and the dopamine blockade in the basal ganglia might be one of the causes of urinary incontinence and enuresis. We speculate that aripiprazole functioned as a D2 agonist in hypodopaminergic state of basal ganglia caused by clozapine and maintained dopamine level that would improve enuresis ultimately.

  3. Aripiprazole-induced hyperprolactinemia in a young female with delusional disorder

    Sam Padamadan Joseph

    2016-01-01

    Hyperprolactinemia is a common adverse effect of antipsychotic medication. Switching over to aripiprazole or adjunctive aripiprazole has been advocated for optimal management of antipsychotic-induced hyperprolactinemia. Adjunctive treatment with aripiprazole has been shown to normalize prolactin levels without affecting already achieved improvements in psychotic symptoms. However, here, we present the case of a 36 year old female with delusional disorder who developed symptomatic hyperprolact...

  4. Aripiprazole Augmentation in Childhood Obsessive-Compulsive Disorder: Three Case Reports

    Murat Yuce

    2013-01-01

    Aripiprazole is a third generation antipsychotic that has a partial dopamine agonistic activity. There is an increasing usage of aripiprazole in children and adolescents with schizophrenia, pervasive developmental disorders, and bipolar disorders. In these presentation, we aimed to present three pediatric obsessive%u2013compulsive disorder (OCD) cases who were resistant to two different selective serotonin reuptake inhibitor treatments and prescribed aripiprazole for augmentation therapy. Th...

  5. Increased Anxiety, Akathisia, and Suicidal Thoughts in Patients with Mood Disorder on Aripiprazole and Lamotrigine

    Milena Pereira Pondé; Antonio Carlos Cruz Freire

    2015-01-01

    Introduction. Akathisia affects around 18% of patients with bipolar disorder treated with aripiprazole and may worsen when aripiprazole is combined with lamotrigine and antidepressants. Case. This paper reports on two clinical cases involving patients with a diagnosis of mood disorder who developed severe akathisia, anxiety, and suicidal ideation while using a combination of aripiprazole, antidepressants, and lamotrigine. Discussion. We recommend that patients with a mood disorder taking mult...

  6. Successful treatment of a prolactinoma with the antipsychotic drug aripiprazole

    Ilse C A Bakker

    2016-06-01

    Full Text Available In this report, we describe a female patient with both prolactinoma and psychotic disorder who was successfully treated with aripiprazole, a partial dopamine 2 receptor agonist. During the follow-up of more than 10 years, her psychotic symptoms improved considerably, prolactin levels normalised and the size of the prolactinoma decreased. This observation may be of clinical relevance in similar patients who often are difficult to treat with the regular dopaminergic drugs.

  7. Successful treatment of a prolactinoma with the antipsychotic drug aripiprazole

    Bakker, Ilse C A; Schubart, Chris D.; Zelissen, Pierre M J

    2016-01-01

    Summary In this report, we describe a female patient with both prolactinoma and psychotic disorder who was successfully treated with aripiprazole, a partial dopamine 2 receptor agonist. During the follow-up of more than 10 years, her psychotic symptoms improved considerably, prolactin levels normalised and the size of the prolactinoma decreased. This observation may be of clinical relevance in similar patients who often are difficult to treat with the regular dopaminergic drugs. Learning poin...

  8. Hyperprolactinemia due to paliperidone palmitate and treatment with aripiprazole

    gokay alpak; ahmet unal; feridun bulbul; ihsan aksoy; bahadir demir; haluk asuman savas

    2014-01-01

    For all typical antipsychotics, potent D2 receptor antagonism and prolonged connection to the receptor causes increased secretion of prolactin. Among second-generation antipsychotics, risperidone and amisulpride increase prolactin levels similar to typical antipsychotics whereas clozapine, olanzapine, quetiapine, aripiprazole and ziprasidone do not increase prolactin levels significantly. It has been claimed that the ongoing D2 receptor blockage by active metabolites of antipsychotic drugs mi...

  9. Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice

    Jaqueline Nascimento PICADA; Viviane Minuzzo PONTES; Patrícia PEREIRA; Bruna de Jesus Neto DOS SANTOS; Franciele CELSO; Jéssica Dias MONTEIRO; Kelly Morais DA ROSA; Leandro Rosa CAMACHO; Luciana Rodrigues VIEIRA; Taís Madelon FREITAS; Tatiana Grasiela DASILVA

    2011-01-01

    Aim:Aripiprazole is an antipsychotic agent to treat schizophrenia,which acts through dopamine D2 partial agonism,serotonin 5-HT1A partial agonism and 5-HT2A antagonism.This study was designed to evaluate the neurobehavioral effects and genotoxic/mutagenic activities of the agent,as well as its effects on lipoperoxidation.Methods:Open field and inhibitory avoidance tasks were used.Thirty min before performing the behavioral tasks,adult male CF-1 mice were administered aripiprazole (1,3 or 10 mg/kg,ip) once for the acute treatment,or the same doses for 5 d for the subchronic treatment.Genotoxic effects were assessed using comet assay in the blood and brain tissues.Mutagenic effects were evaluated using bone marrow micronucleus test.Lipoperoxidation was assessed with thiobarbituric acid reactive substances (TBARS).Results:Acute and subchronic treatments significantly decreased the number of crossing and rearing in the open field task.Acute treatment significantly increased the step-down latency for both the short- and long-term memory in the inhibitory avoidance task.Subchronic treatments with aripiprazole (3 and 10 mg/kg) caused significant DNA strain-break damage in peripheral blood but not in the brain.Mutagenic effect was not detected in the acute and subchronic treatments.Nor TBARS levels in the liver were affected.Conclusion:Aripiprazole improved memory,but could impair motor activities in mice.The drug increased DNA damage in blood,but did not show mutagenic effects,suggesting that it might affect long-term genomic stability.

  10. Aripiprazole Improved Obsessive Compulsive Symptoms in Asperger's Disorder

    Celik, Gonca; Tahiroglu, Aysegul Yolga; Firat, Sunay; AVCI, Ayşe

    2011-01-01

    There are many comorbid disorders associated with autism spectrum disorders in child and adolescent population. Although obsessive compulsive disorder and autism spectrum disorders (ASD) comorbidity has common in clinical practice, there are few reports about psychopharmacological treatment for obsessive compulsive symptoms in children with ASD in the literacy. We report a successful treatment case with aripiprazole in Asperger's Disorder with obsessive compulsive symptoms. The Yale Brown Obs...

  11. Aripiprazole alone or in combination for acute mania

    Brown, Rachel; Taylor, Matthew; Geddes, John

    2013-01-01

    BackgroundBipolar disorder is a mental disorder characterised by episodes of elevated or irritable mood (manic or hypomanic episodes) and episodes of low mood and loss of energy (depressive episodes). Drug treatment is the first-line treatment for acute mania with the initial aim of rapid control of agitation, aggression and dangerous behaviour. Aripiprazole, an atypical antipsychotic, is used in the treatment of mania both as monotherapy and combined with other medicines. The British Associa...

  12. When to start aripiprazole therapy in patients with bipolar mania

    Sayyaparaju KK; Grunze H; Fountoulakis KN

    2014-01-01

    Kiran Kumar Sayyaparaju,1 Heinz Grunze,1 Kostas N Fountoulakis2 1Newcastle University, Institute of Neuroscience, Academic Psychiatry, Newcastle upon Tyne, UK; 23rd Department of Psychiatry, Division of Neurosciences, School of Medicine, Aristotle University of Thessaloniki, Greece Abstract: Aripiprazole is a third generation atypical antipsychotic with compelling evidence as a highly effective treatment option in the management of acute manic and mixed episodes of bipolar I disorders. It ha...

  13. Aripiprazole for acute mania in an elderly person

    Balaji Bharadwaj

    2011-01-01

    Full Text Available New-onset bipolar disorder is rare in the elderly. Symptom profile is similar to that in young adults but the elderly are more likely to have neurological co-morbidities. There are no case reports of elderly mania being treated with aripiprazole, an atypical antipsychotic. A 78-year-old gentleman presented to us with symptoms suggestive of mania of 1 month′s duration. He had similar history 3 years ago and a family history of postpartum psychosis in his mother. There were no neurological signs on examination and work-up for an organic etiology was negative except for age-related cerebral atrophy. He improved with aripiprazole and tolerated the medications well. The use of psychotropic medications in the elderly is associated with side-effects of sedation, increased cardiovascular risk, and greater risk of extra-pyramidal side-effects. The use of partial dopaminergic antagonists like aripiprazole may be useful in the balancing of effects and side-effects.

  14. The cardiac safety of aripiprazole treatment in patients at high risk for torsade

    Polcwiartek, Christoffer; Sneider, Benjamin; Graff, Claus;

    2015-01-01

    reviewed and cardiac safety data were extracted. Continuous and dichotomous QTc data were used in the meta-analysis. RESULTS: Preclinical studies suggested that aripiprazole has limited affinity for the delayed rectifier potassium current. TdP was reported in two case reports and SCD was reported in one...... case report and one case series. No clinical studies assessing aripiprazole's cardiac safety in patients at high risk for torsade were found. No thorough QT (TQT) study with aripiprazole was found. The meta-analysis revealed that the mean ΔQTc interval was decreased with aripiprazole and QTc...... factors. OBJECTIVES: Aripiprazole's cardiac safety has not been assessed in patients at high risk for torsade, where QTc prolongation risk is highly increased. METHODS: MEDLINE, Embase, and The Cochrane Library were searched for preclinical, clinical, and epidemiological studies. Eligible studies were...

  15. Adjunctive aripiprazole versus placebo for antipsychotic-induced hyperprolactinemia: meta-analysis of randomized controlled trials.

    Xianbin Li

    Full Text Available OBJECTIVE: To compare the safety and efficacy of adjunctive aripiprazole versus placebo for antipsychotic-induced hyperprolactinemia. METHODS: POPULATION: adult patients presenting with antipsychotic-induced hyperprolactinemia diagnosed by prolactin level with or without prolactin-related symptoms. INTERVENTIONS: adjunctive aripiprazole vs. adjunctive placebo. OUTCOME MEASURES: adverse events and efficacy of treatment. STUDIES: randomized controlled trials. RESULTS: Five randomized controlled trials with a total of 639 patients (326 adjunctive aripiprazole, 313 adjunctive placebo met the inclusion criteria. Adjunctive aripiprazole was associated with a 79.11% (125/158 prolactin level normalization rate. Meta-analysis of insomnia, headache, sedation, psychiatric disorder, extrapyramidal symptom, dry mouth, and fatigue showed no significant differences in the adjunctive aripiprazole treatment group compared with the placebo group (risk difference (Mantel-Haenszel, random or fixed -0.05 to 0.04 (95% confidence interval -0.13 to 0.16; I(2 =0% to 68%, P=0.20 to 0.70. However, sedation, insomnia, and headache were more frequent when the adjunctive aripiprazole dose was higher than 15 mg/day. Meta-analysis of the prolactin level normalization indicated adjunctive aripiprazole was superior to placebo (risk difference (Mantel-Haenszel, random 0.76 (95% confidence interval 0.67 to 0.85; I(2 =43%, P<0.00001. The subgroup analysis confirmed that the subjects who received adjunctive aripiprazole 5 mg/day showed a degree of prolactin normalization similar to that of all participants. No significant differences between groups in discontinuation and improvements of psychiatric symptoms. CONCLUSION: Adjunctive aripiprazole is both safe and effective as a reasonable choice treatment for patients with antipsychotic-induced hyperprolactinemia. The appropriate dose of adjunctive aripiprazole may be 5 mg/day.

  16. Treatment and prevention of mania in bipolar I disorder: focus on aripiprazole

    David J Muzina

    2009-05-01

    Full Text Available David J MuzinaCenter for Mood Disorders Treatment and Research, Cleveland Clinic Neurological Institute, Cleveland, Ohio, USAAbstract: Aripiprazole is a second-generation antipsychotic with a unique pharmacologic receptor profile that has efficacy in the treatment and prevention of mania in bipolar I disorder. This article reviews the evidence supporting treatment of adults with bipolar I disorder using aripiprazole as monotherapy or adjunctively during acute mania and its utility as an intramuscular agent for agitation in manic patients. Results from one of the longest bipolar maintenance trials which support aripiprazole as a prophylactic mood stabilizer, specifically against manic relapses, will be discussed as well as a post-hoc analysis that suggests efficacy for rapid cycling bipolar disorder. Safety and tolerability issues, patient-focused perspectives and aripiprazole’s place in therapy for bipolar mania will be covered.Keywords: bipolar disorder, mania, prevention, aripiprazole, rapid cycling

  17. Treatment and prevention of mania in bipolar I disorder: focus on aripiprazole

    Muzina, David J.

    2009-01-01

    David J MuzinaCenter for Mood Disorders Treatment and Research, Cleveland Clinic Neurological Institute, Cleveland, Ohio, USAAbstract: Aripiprazole is a second-generation antipsychotic with a unique pharmacologic receptor profile that has efficacy in the treatment and prevention of mania in bipolar I disorder. This article reviews the evidence supporting treatment of adults with bipolar I disorder using aripiprazole as monotherapy or adjunctively during acute mania and its utility as an intra...

  18. Adjunctive Aripiprazole Treatment for Risperidone-Induced Hyperprolactinemia: An 8-Week Randomized, Open-Label, Comparative Clinical Trial

    Jingyuan Zhao; Xueqin Song; Xiaoqing Ai; Xiaojing Gu; Guangbiao Huang; Xue Li; Lijuan Pang; Minli Ding; Shuang Ding; Luxian Lv

    2015-01-01

    Objective The present study aimed to evaluate the efficacy and safety of adjunctive aripiprazole treatment in schizophrenia patients with risperidone-induced hyperprolactinemia. Methods One hundred and thirteen patients who were receiving a stable dose of risperidone were randomly assigned to either adjunctive aripiprazole treatment (10 mg/day) (aripiprazole group) or no additional treatment (control group) at a 1:1 ratio for 8 weeks. Schizophrenia symptoms were measured using the Positive an...

  19. Aripiprazole Improves Depressive Symptoms and Immunological Response to Antiretroviral Therapy in an HIV-Infected Subject with Resistant Depression

    Chiara Cecchelli; Giacomo Grassi; Stefano Pallanti

    2010-01-01

    Aripiprazole is the first medication approved by the FDA as an add-on treatment for MDD. The impact of aripiprazole on the response to HIV is unknown. The patient we report on was diagnosed HIV-positive in 1997 and has been treated with antiretroviral therapy since then. In 2008, we diagnosed resistant major depression, hypochondria, and panic disorder. On that occasion, blood tests showed a significantly reduced CD4 count and a positive viral load. We treated this patient with aripiprazole...

  20. Index to Drug-Specific Information

    ... Y Z A Abacavir sulfate Abilify (aripiprazole) Abstral (fentanyl sublingual tablets) Acetaminophen Accupril (quinapril) Accutane (isotretinoin) Aceon ( ... Aciphex (rabeprazole sodium) Actimmune (interferon gamma-1b) Actiq (fentanyl submucosal lozenge) Actoplus Met (pioglitazone) Adalimumab Adcetris (brentuximab ...

  1. [Application of HPLC-UV method for aripiprazole determination in serum].

    Synowiec, Anna; Gomółka, Ewa; Zyss, Tomasz; Zieba, Andrzej; Florek, Ewa; Piekoszewski, Wojciech

    2012-01-01

    Aripiprazole is a new drug applied in schizophrenia treatment. There are not strict indications for aripiprazole therapeutic drug monitoring. Despite, serum aripiprazole measuring would help control the drug doses effectiveness. The drug monitoring can eliminate overdosing, adverse effects and let control proper drug ingestion. The aim of the paper was to develop a simple method for aripiprazole determination in serum for therapeutic drug monitoring. High performance liquid chromatography with spectrophotometric detection (HPLC-UV) was used. Resolution was performed on LC-8 column; moving phase was solution 0,025M trimethylammonium buffer: acetonitrile (62:38). Isocratic flow was 1,2 ml/min; internal standard (IS) was promazine; monitored wavelength was lambda=214 nm. The validation parameters were: limits of linearity (LOL) 100-800 ng/ml, limit of detection (LOD) 10 ng/ml, limit of quantity (LOQ) 100 ng/ml. Coefficient of variation (CV) describing accuracy and precision didn't cross 10%. The method was useful for therapeutic drug monitoring in serum of patients treated with aripiprazole. PMID:23421079

  2. Low dosage of aripiprazole induced neuroleptic malignant syndrome after interaction with other neuroleptic drugs

    Albino Petrone

    2013-09-01

    Full Text Available Aripiprazole is a 2nd generation antipsychotic medication, atypical neuroleptic used for treatment of schizophrenia improving symptoms such as hallucinations, delusions, and disorganized thinking. A potentially fatal symptom complex sometimes referred to as neuroleptic malignant syndrome (NMS has been reported in association with administration of antipsychotic drugs, including aripiprazole. Rare cases of NMS occurred during aripiprazole treatment in the worldwide clinical database. The disease is characterized by a distinctive clinical syndrome of mental status change, rigidity, fever, and dysautonomia. We report on a 63-year old woman with depression syndrome who developed neuroleptic malignant syndrome after twelve days of aripripazole 5 mg per day. Our case is added to the small number already described and suggests the need for caution when aripripazole is added to increase the effect of other antipsychotics.

  3. The effect of resveratrol on pharmacokinetics of aripiprazole in vivo and in vitro.

    Zhan, Yun-Yun; Liang, Bing-Qing; Li, Xiang-Yu; Gu, Er-Min; Dai, Da-Peng; Cai, Jian-Ping; Hu, Guo-Xin

    2016-05-01

    1. The objective of this study were to investigate the effect of orally administered resveratrol on the pharmacokinetics of aripiprazole (APZ) in rat, and the inhibitory effects of resveratrol on APZ dehydrogenation activity in liver microsomes and human cytochrome P450 3A4 and 2D6. 2. Twenty-five healthy male Sprague-Dawley rats were randomly divided into five groups: A (control group), B (multiple dose of 200 mg/kg resveratrol), C (multiple dose of 100 mg/kg resveratrol), D (a single dose of 200 mg/kg resveratrol) and E (a single dose of 100 mg/kg resveratrol). A single dose of 3 mg/kg APZ administered orally 30 min after administration of resveratrol. In addition, CYP2D6*1, CYP3A4*1, human and rat liver microsomes were performed to determine the effect of resveratrol on the metabolism of APZ in vitro. 3. The multiple dose of 200 or 100 mg/kg resveratrol significantly increased the AUC and Cmax of APZ. The resveratrol also obviously decreased the CL, but without any significant difference on t1/2 in vivo. On the other hand, resveratrol showed inhibitory effect on CYP3A4*1, CYP2D6*1, human and rat microsomes, the IC50 of resveratrol was 6.771, 87.87, 45.11 and 35.59 μmol l(-1), respectively. 4. Those results indicated more attention should be paid when APZ was administrated combined with resveratrol. PMID:26391142

  4. A review of aripiprazole in the treatment of patients with schizophrenia or bipolar I disorder

    Citrome, Leslie

    2006-01-01

    Aripiprazole has been approved by regulatory agencies for the treatment of schizophrenia and bipolar I disorder. Although it is a dopamine partial agonist, it also has substantial binding affinity for the serotonin 5HT2A receptor. Several double-blind randomized clinical trials have established the efficacy and tolerability of aripiprazole within the dose range of 10–30 mg/day for schizophrenia, and 15–30 mg/day for manic or mixed states associated with bipolar I disorder. Relatively few comp...

  5. Acute Dystonia Following a Switch in Treatment from Atomoxetine to Low-dose Aripiprazole

    Başay, Ömer; Basay, Burge Kabukcu; Öztürk, Önder; Yüncü, Zeki

    2016-01-01

    The present report describes the cases of a 17-year-old male patient and a 13-year-old female patient who developed acute dystonia following the administration of low-dose aripiprazole (5 mg/day) after the cessation of atomoxetine treatment. Although aripiprazole-induced dystonia has been previously reported in the literature, it is rare, and most of these cases were associated with doses higher than 5 mg/day. Furthermore, both of the patients in the present study discontinued atomoxetine pri...

  6. Aripiprazole as augmentation therapy in bipolar patients with current minor or subsyndromal mood symptoms

    Schweitzer, Isaac; Sarris, Jerome; Tuckwell, Virginia; Maguire, Kay; Smith, Deidre; Ng, Chee

    2013-01-01

    Background This study aims to evaluate the effectiveness of aripiprazole augmentation of maintenance treatment for bipolar disorder in patients with minor or subsyndromal mood episodes while on a stable dose of a mood stabiliser and/or antidepressant. Methods All subjects had a diagnosis of bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders-4th Edition, Text Revision). Open-label aripiprazole was given over 8 weeks initially. The starting dose was 5 to 15 mg/day w...

  7. The effect of brexpiprazole (OPC-34712) and aripiprazole in adult patients with acute schizophrenia: results from a randomized, exploratory study.

    Citrome, Leslie; Ota, Ai; Nagamizu, Kazuhiro; Perry, Pamela; Weiller, Emmanuelle; Baker, Ross A

    2016-07-01

    The aim of this study was to explore the effects of brexpiprazole and aripiprazole on efficacy, cognitive functioning, and safety in patients with acute schizophrenia. Patients who would benefit from hospitalization/continued hospitalization for acute relapse of schizophrenia were enrolled and randomized (2 : 1) to target doses of open-label brexpiprazole 3 mg/day or aripiprazole 15 mg/day for 6 weeks. Outcomes included change from baseline to week 6 in the Positive and Negative Syndrome Scale total score, Barratt Impulsiveness Scale 11-item score, and Cogstate computerized cognitive test battery scores. Patients treated with brexpiprazole (n=64) or aripiprazole (n=33) showed reductions in symptoms of schizophrenia as assessed by Positive and Negative Syndrome Scale total score (-22.9 and -19.4, respectively). A modest reduction in impulsivity was observed with brexpiprazole, but not aripiprazole (mean change in the Barratt Impulsiveness Scale 11-item total score: -2.7 and 0.1, respectively). No change in Cogstate scores was observed for either treatment. Brexpiprazole was well tolerated and the incidence of akathisia was lower in patients treated with brexpiprazole (9.4%) than aripiprazole (21.2%). Clinically relevant improvements in psychopathology were observed in patients with acute schizophrenia treated with brexpiprazole or aripiprazole. Brexpiprazole was well tolerated, with a lower incidence of akathisia than aripiprazole. PMID:26963842

  8. Metabolism

    ... also influenced by body composition — people with more muscle and less fat generally have higher BMRs. previous continue Things That Can Go Wrong With Metabolism Most of the time your metabolism works effectively ...

  9. Metabolism

    2008-01-01

    2008255 Serum adiponectin level declines in the elderly with metabolic syndrome.WU Xiaoyan(吴晓琰),et al.Dept Geriatr,Huashan Hosp,Fudan UnivShanghai200040.Chin J Geriatr2008;27(3):164-167.Objective To investigate the correlation between ser-um adiponectin level and metabolic syndrome in the elderly·Methods Sixty-one subjects with metabolic syndrome and140age matched subjects without metabolic

  10. Aripiprazole blocks acute self-administration of cocaine and is not self-administered in mice

    Sørensen, Gunnar; Sager, Thomas N; Petersen, Jørgen H;

    2008-01-01

    RATIONALE: The novel antipsychotic aripiprazole in use for treatment of schizophrenia is a partial agonist at dopamine D(2) receptors with actions at a variety of other receptors as well. Cocaine is believed to exert an important part of its rewarding effect by increasing extracellular levels of ...

  11. The Treatment of Adult Bipolar Disorder with Aripiprazole: A Systematic Review.

    Muneer, Ather

    2016-01-01

    Bipolar disorder is characterized by exacerbations of opposite mood polarity, ranging from manic to major depressive episodes. In the current nosological system of the Diagnostic and Statistical Manual - 5(th) edition (DSM-5), it is conceptualized as a spectrum disorder consisting of bipolar disorder type I, bipolar disorder type II, cyclothymic disorder, and bipolar disorder not otherwise specified. Treatment of all phases of this disorder is primarily with mood stabilizers, but many patients either show resistance to the conventional mood stabilizing medications or are intolerant to their side-effects. In this setting, second-generation antipsychotics have gained prominence as many bipolar subjects who are otherwise treatment refractory show response to these agents. Aripiprazole is a novel antipsychotic initially approved for the treatment of schizophrenia but soon found to be effective in bipolar disorder. This drug is well studied, as randomized controlled trials have been conducted in various phases of bipolar disorders. Aripiprazole exhibits the pharmacodynamic properties of partial agonism, functional selectivity, and serotonin-dopamine activity modulation - the new exemplars in the treatment of major psychiatric disorders. It is the first among a new series of psychotropic medications, which now also include brexpiprazole and cariprazine. The current review summarizes the data from controlled trials regarding the efficacy and safety of aripiprazole in adult bipolar patients. On the basis of this evidence, aripiprazole is found to be efficacious in the treatment and prophylaxis of manic and mixed episodes but has no effectiveness in acute and recurrent bipolar depression. PMID:27190727

  12. The Treatment of Adult Bipolar Disorder with Aripiprazole: A Systematic Review

    2016-01-01

    Bipolar disorder is characterized by exacerbations of opposite mood polarity, ranging from manic to major depressive episodes. In the current nosological system of the Diagnostic and Statistical Manual – 5th edition (DSM-5), it is conceptualized as a spectrum disorder consisting of bipolar disorder type I, bipolar disorder type II, cyclothymic disorder, and bipolar disorder not otherwise specified. Treatment of all phases of this disorder is primarily with mood stabilizers, but many patients either show resistance to the conventional mood stabilizing medications or are intolerant to their side-effects. In this setting, second-generation antipsychotics have gained prominence as many bipolar subjects who are otherwise treatment refractory show response to these agents. Aripiprazole is a novel antipsychotic initially approved for the treatment of schizophrenia but soon found to be effective in bipolar disorder. This drug is well studied, as randomized controlled trials have been conducted in various phases of bipolar disorders. Aripiprazole exhibits the pharmacodynamic properties of partial agonism, functional selectivity, and serotonin-dopamine activity modulation – the new exemplars in the treatment of major psychiatric disorders. It is the first among a new series of psychotropic medications, which now also include brexpiprazole and cariprazine. The current review summarizes the data from controlled trials regarding the efficacy and safety of aripiprazole in adult bipolar patients. On the basis of this evidence, aripiprazole is found to be efficacious in the treatment and prophylaxis of manic and mixed episodes but has no effectiveness in acute and recurrent bipolar depression.

  13. Aripiprazole and Risperidone for Treatment of Methamphetamine-Associated Psychosis in Chinese Patients.

    Wang, Gang; Zhang, Yao; Zhang, Sheng; Chen, Huijing; Xu, Zaifeng; Schottenfeld, Richard S; Hao, Wei; Chawarski, Marek Cezary

    2016-03-01

    We evaluated tolerability and efficacy of aripiprazole and risperidone for treatment of methamphetamine (METH) associated psychotic symptoms in China. Patients with acute METH-associated psychotic symptoms (N=42) and with Positive and Negative Syndrome Scale (PANSS) total score between 60 and 120 were randomized to aripiprazole (initial dose 5-10mg per day followed by flexible doses 5-15 mg per day) or risperidone (initial dose 2-4 mg per day followed by flexible doses 4-6 mg per day) from day 3 to 25 of inpatient hospital stay. Outcome measures included PANSS and Clinical Global Impressions-Severity of Illness scale (CGI-S), METH craving Visual Analogue Scale (VAS), Simpson Angus Scale (SAS), Barnes Assessments Akathasia Rating Scale (BARS), and self-reported adverse effects evaluated during treatment. Retention was evaluated using Kaplan-Meier survival analysis and the MIXED models procedure was used to compare the groups on measures of psychotic and extra-pyramidal symptoms. Patients in both aripiprazole and risperidone groups showed statistically significant reductions in psychotic symptomatology from baseline during treatment (p<0.001) with no statistically significant differences between the treatment groups (p=0.73 and p=0.15, respectively). Risperidone-treated patients reported significantly greater METH craving reductions (p<0.001). Overall, 71% of patients completed the entire study, but the aripiprazole group had a significantly lower retention than the risperidone group (p=0.007), primarily due to medication related adverse effects. Aripiprazole-treated patients also had significantly more akathisia (p=0.03) and agitation (p=0.02) than risperidone-treated patients. Patients in both groups who tolerated their medications and completed the entire study achieved comparable reductions of psychotic symptoms. PMID:26733277

  14. Profile of aripiprazole in the treatment of bipolar disorder in children and adolescents

    Kirino E

    2014-11-01

    Full Text Available Eiji Kirino1–3 1Department of Psychiatry, Juntendo University School of Medicine, 2Department of Psychiatry, Juntendo University Shizuoka Hospital, 3Juntendo Institute of Mental Health, Shizuoka, Japan Abstract: Bipolar disorder is a pernicious illness. Compared with the later-onset form, early onset bipolar disorder is associated with worse psychosocial outcomes, and is characterized by rapid cycling and increased risks of substance abuse and suicide attempts. Controlling mood episodes and preventing relapse in this group of pediatric patients requires careful treatment. Here, we review the effectiveness of aripiprazole for bipolar disorder in children and adolescents, with discussion of this drug's unique pharmacological profile and various clinical study outcomes. Aripiprazole acts as a serotonin 5-HT2A receptor antagonist, as well as a partial agonist of the serotonin 5-HT1A and dopamine D2 receptors. It can be safely used in children and adolescents, as it is highly tolerated and shows lower rates of the side effects typically observed with other antipsychotic drugs, including sedation, weight gain, hyperprolactinemia, and extrapyramidal syndrome. The presently reviewed randomized controlled trials (RCTs and non-RCTs generally reported aripiprazole to be effective and well-tolerated in children and adolescents with bipolar disorder. However, due to the limited number of RCTs, the present conclusions must be evaluated cautiously. Furthermore, aripiprazole cannot yet be considered a preferred treatment for children and adolescents with bipolar disorder, as there is not yet evidence that aripiprazole shows greater efficacy compared to other second-generation antipsychotics. Additional data are needed from future head-to-head comparison studies. Keywords: child, mania, mixed state

  15. Aripiprazole Improves Depressive Symptoms and Immunological Response to Antiretroviral Therapy in an HIV-Infected Subject with Resistant Depression

    Chiara Cecchelli

    2010-01-01

    Full Text Available Aripiprazole is the first medication approved by the FDA as an add-on treatment for MDD. The impact of aripiprazole on the response to HIV is unknown. The patient we report on was diagnosed HIV-positive in 1997 and has been treated with antiretroviral therapy since then. In 2008, we diagnosed resistant major depression, hypochondria, and panic disorder. On that occasion, blood tests showed a significantly reduced CD4 count and a positive viral load. We treated this patient with aripiprazole and citalopram. Mood, somatic symptoms, and occupational functioning progressively improved. The last blood examination showed an increase in the CD4 count and a negative viral load. On the basis of the present case study and the review of the literature concerning the effects of psychotropic agents on viral replication, we suggest that the use of aripiprazole in HIV-infected subjects warrants further research.

  16. No difference in frontal cortical activity during an executive functioning task after acute doses of aripiprazole and haloperidol

    Ingeborg eBolstad

    2015-05-01

    Full Text Available Background: Aripiprazole is an atypical antipsychotic drug that is characterized by partial dopamine D2 receptor agonism. Its pharmacodynamic profile is proposed to be beneficial in the treatment of cognitive impairment, which is prevalent in psychotic disorders. This study compared brain activation characteristics produced by aripiprazole with that of haloperidol, a typical D2 receptor antagonist, during a task targeting executive functioning.Methods: Healthy participants received an acute oral dose of haloperidol, aripiprazole or placebo before performing an executive functioning task while blood-oxygen-level-dependent (BOLD functional magnetic resonance imaging (fMRI was carried out. Results: There was a tendency towards reduced performance in the aripiprazole group compared to the two other groups. The image analysis yielded a strong task-related BOLD-fMRI response within each group. An uncorrected between-group analysis showed that aripiprazole challenge resulted in stronger activation in the frontal and temporal gyri and the putamen compared with haloperidol challenge, but after correcting for multiple testing there was no significant group difference. Conclusion: No significant group differences between aripiprazole and haloperidol in frontal cortical activation were obtained when corrected for multiple comparisons.This study is registered in ClinicalTrials.gov (identifier: 2009-016222-14; https://clinicaltrials.gov/.

  17. A retrospective study of predictive factors for effective aripiprazole augmentation of antidepressant therapy in treatment-resistant depression

    Sugawara H

    2016-05-01

    Full Text Available Hiroko Sugawara,1,2 Kaoru Sakamoto,1 Tsuyoto Harada,3 Satoru Shimizu,4 Jun Ishigooka1 1Department of Psychiatry, Tokyo Women’s Medical University, 2Support Center for Women Health Care Professionals and Researchers, Tokyo Women’s Medical University, Shinjuku-ku, 3Department of Psychiatry, Tokyo Women’s Medical University Medical Center East, Arakawa-ku, 4Department of Research, Medical Research Institute, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan Background: Several studies have evaluated the efficacy and tolerability of aripiprazole for augmentation of antidepressant therapy for treatment-resistant depression (TRD. Here, we investigated the efficacy of aripiprazole augmentation for TRD including both major depressive disorder and bipolar disorder and the clinical predictors of treatment efficacy in a Japanese population.  Methods: Eighty-five depressed Japanese patients who underwent aripiprazole augmentation therapy after failing to respond satisfactorily to antidepressant monotherapy were included in the study. Treatment responses were evaluated based on Clinical Global Impression Improvement scores assessed 8 weeks after initiation of aripiprazole administration. We compared demographic and diagnostic variables, psychiatric medication variables, and clinical variables between remission and nonremission groups.  Results: The aripiprazole augmentation remission rate was 36.5%. Multiple logistic regression analysis indicated that aripiprazole augmentation was significantly more effective for bipolar depression than for major depressive disorder, and both absence of comorbid anxiety disorders and current episode duration >3 months were significantly associated with the efficacy of aripiprazole augmentation.  Conclusion: Polarity of depression, comorbidity of anxiety disorders, and current episode duration may predict the efficacy of aripiprazole augmentation for TRD including both major depressive disorder and

  18. Metabolism

    ... a particular food provides to the body. A chocolate bar has more calories than an apple, so ... More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood ...

  19. Aripiprazole augmentation in poor insight obsessive-compulsive disorder: a case report

    Vinciguerra Valentina

    2008-12-01

    Full Text Available Abstract Background Obsessive-compulsive disorder is associated with a relevant impairment in social and interpersonal functioning and severe disability. This seems to be particularly true for the poor insight subtype, characterised by a lack of consciousness of illness and, consequently, compliance with treatment. Poor responsiveness to serotonergic drugs in poor insight obsessive-compulsive patients may also require an augmentation therapy with atypical antipsychotics. Methods We reviewed a case in which a patient with a long history of poor insight obsessive-compulsive disorder was treated with a high dosage of serotonin reuptake inhibitors. Results The treatment resulted in a poor outcome. This patient was therefore augmentated with aripiprazole. Conclusion Doctors should consider aripiprazole as a possible augmentation strategy for serotonergic poor responder obsessive-compulsive patients, but further research on these subjects is needed.

  20. Verbessert sich das Gedächtnis euthymer bipolarer Patienten durch die Behandlung mit Aripiprazol?

    Bellmann, Katharina

    2016-01-01

    BACKGROUND: Medical treatment in bipolar disorder has been more focused on dealing with the acute phase of the illness and preventing future relapse rather than treating cognitive dysfunctions. Cognitive impairment in bipolar patients is related to the central vulnerability of the dopaminergic and serotonergic system. Aripiprazole as a partial agonist at D2/D3- and 5HT1A- receptors includes activity in the dopaminergic and serotonergic systems. Previous studies on animals and schizophrenic pa...

  1. Aripiprazole and Haloperidol Activate GSK3β-Dependent Signalling Pathway Differentially in Various Brain Regions of Rats

    Bo Pan

    2016-03-01

    Full Text Available Aripiprazole, a dopamine D2 receptor (D2R partial agonist, possesses a unique clinical profile. Glycogen synthase kinase 3β (GSK3β-dependent signalling pathways have been implicated in the pathophysiology of schizophrenia and antipsychotic drug actions. The present study examined whether aripiprazole differentially affects the GSK3β-dependent signalling pathways in the prefrontal cortex (PFC, nucleus accumbens (NAc, and caudate putamen (CPu, in comparison with haloperidol (a D2R antagonist and bifeprunox (a D2R partial agonist. Rats were orally administrated aripiprazole (0.75 mg/kg, bifeprunox (0.8 mg/kg, haloperidol (0.1 mg/kg or vehicle three times per day for one week. The levels of protein kinase B (Akt, p-Akt, GSK3β, p-GSK3β, dishevelled (Dvl-3, and β-catenin were measured by Western Blots. Aripiprazole increased GSK3β phosphorylation in the PFC and NAc, respectively, while haloperidol elevated it in the NAc only. However, Akt activity was not changed by any of these drugs. Additionally, both aripiprazole and haloperidol, but not bifeprunox, increased the expression of Dvl-3 and β-catenin in the NAc. The present study suggests that activation of GSK3β phosphorylation in the PFC and NAc may be involved in the clinical profile of aripiprazole; additionally, aripiprazole can increase GSK3β phosphorylation via the Dvl-GSK3β-β-catenin signalling pathway in the NAc, probably due to its relatively low intrinsic activity at D2Rs.

  2. Aripiprazole and Haloperidol Activate GSK3β-Dependent Signalling Pathway Differentially in Various Brain Regions of Rats.

    Pan, Bo; Huang, Xu-Feng; Deng, Chao

    2016-01-01

    Aripiprazole, a dopamine D₂ receptor (D₂R) partial agonist, possesses a unique clinical profile. Glycogen synthase kinase 3β (GSK3β)-dependent signalling pathways have been implicated in the pathophysiology of schizophrenia and antipsychotic drug actions. The present study examined whether aripiprazole differentially affects the GSK3β-dependent signalling pathways in the prefrontal cortex (PFC), nucleus accumbens (NAc), and caudate putamen (CPu), in comparison with haloperidol (a D₂R antagonist) and bifeprunox (a D₂R partial agonist). Rats were orally administrated aripiprazole (0.75 mg/kg), bifeprunox (0.8 mg/kg), haloperidol (0.1 mg/kg) or vehicle three times per day for one week. The levels of protein kinase B (Akt), p-Akt, GSK3β, p-GSK3β, dishevelled (Dvl)-3, and β-catenin were measured by Western Blots. Aripiprazole increased GSK3β phosphorylation in the PFC and NAc, respectively, while haloperidol elevated it in the NAc only. However, Akt activity was not changed by any of these drugs. Additionally, both aripiprazole and haloperidol, but not bifeprunox, increased the expression of Dvl-3 and β-catenin in the NAc. The present study suggests that activation of GSK3β phosphorylation in the PFC and NAc may be involved in the clinical profile of aripiprazole; additionally, aripiprazole can increase GSK3β phosphorylation via the Dvl-GSK3β-β-catenin signalling pathway in the NAc, probably due to its relatively low intrinsic activity at D₂Rs. PMID:27043526

  3. Successful treatment of catatonic syndrome in bipolar I disorder adding aripiprazole to ECT: A case report

    Diego Hidalgo, MD

    2012-09-01

    Full Text Available Background and Objectives: Catatonic syndrome is a condition presenting in multiple ways, sharing many of them with the neuroleptic malignant syndrome and other diseases. This diagnostic challenge is the main cause of keep treating catatonic syndromes without neuroleptics. Methods: Review of the literature and a case report. Results: We present the case of a 19 years old bipolar I patient with a severe catatonic syndrome, with a torpid clinical evolution, partial response to benzodiazepines and ECT, which successfully resolved with intramuscular aripiprazole. We found through a systematic review (PubMed 2005-2010 that there are few but significant case reports of catatonic syndromes treated with new second generation antipsychotics for different reasons with good outcomes as ours. The pharmacological profile of aripiprazole and the low incidence of NMS reported make it a suitable option in treating this syndrome. Conclusions: We think that this case report could contribute to add more evidence for aripiprazole to be considered a good third-line option in the treatment of catatonic syndrome. However, this would require randomized controlled trials to confirm its effectiveness and safety.

  4. Drug: D01164 [KEGG MEDICUS

    Full Text Available D01164 Drug Aripiprazole (JAN/USAN/INN); Abilify (TN) C23H27Cl2N3O2 447.148 448.3854 D01164.gif ... JAN/USAN/INN) USP drug classification [BR:br08302] Antidepressants ... Antidepressants , Other Aripiprazole D01164 Aripipr ...

  5. Development of fixed dose combination tablets of aripiprazole plus divalproex sodium and their simultaneous determination using HPLC-UV.

    Ahmed, Zia; Subhan, Fazal; Ahmed, Saba; Abdur Rasheed, Qazi; Ahmed, Sagheer; Shahid, Muhammad; Farooq, Saeed

    2016-09-01

    A vast majority of psychiatric patients are effectively treated with combination of drugs to improve efficacy and adherence, but due to limited research and development in fixed dose combination (FDC) in psychiatry, these products are not commonly available. The aim of this study is to prepare cost effective FDC tablets containing aripiprazole and divalproex sodium. Two batches of fixed dose combination tablets, FDC1 and FDC2, were successfully prepared using wet granulation technique. Furthermore, aripiprazole tablets A1 and A2 and divalproex tablets D1 were also formulated as reference to compare the in vitro availability profile. An accurate and simple isocratic HPLC method was established and validated for the simultaneous quantification of aripiprazole and valproic acid in the FDC tablets. A reversed-phase C18 (250 × 4.6 mm) column in isocratic mode was used. The mobile phase consisted of acetonitrile and 0.32% KH2PO4 (60:40, v/v), flow rate was set at 1.0 mL/min and the detection was performed at 210 nm. Average percent recoveries of aripiprazole and valproic acid were 96.0 and 95.5%, respectively, meeting the official requirements. The newly developed FDC product may be used for the better therapeutic outcomes of combined use of aripiprazole and valproic acid, which may improve patient adherence. PMID:26727505

  6. Clinical Usefulness of Aripiprazole and Lamotrigine in Schizoaffective Presentation of Tuberous Sclerosis

    Lee, Seung-Yup; Min, Jung-Ah; Lee, In Goo; Kim, Jung Jin

    2016-01-01

    Tuberous sclerosis is not as rare as once thought and has high psychiatric comorbidities. However, bipolar or psychotic features associated with tuberous sclerosis have been rarely reported. This report first presents a tuberous sclerosis patient, resembling a schizoaffective disorder of bipolar type. A patient with known tuberous sclerosis displayed mood fluctuation and psychotic features. Her symptoms did not remit along with several psychiatric medications. After hospitalization, the patient responded well with lamotrigine and aripiprazole without exacerbation. As demonstrated in this case, tuberous sclerosis may also encompass bipolar affective or psychotic features. We would like to point out the necessity to consider bipolarity in evaluating and treating tuberous sclerosis. PMID:27489387

  7. Repeated administration of aripiprazole produces a sensitization effect in the suppression of avoidance responding and phencyclidine-induced hyperlocomotion and increases D2 receptor-mediated behavioral function

    Gao, Jun; Qin, Rongyin; Li, Ming

    2016-01-01

    The present study investigated how repeated administration of aripiprazole (a novel antipsychotic drug) alters its behavioral effects in two behavioral tests of antipsychotic activity and whether this alteration is correlated with an increase in dopamine D2 receptor function. Male adult Sprague-Dawley rats were first repeatedly tested with aripiprazole (3, 10 and 30 mg/kg, subcutaneously (sc)) or vehicle in a conditioned avoidance response (CAR) test or a phencyclidine (PCP) (3.20 mg/kg, sc)-induced hyperlocomotion test daily for five consecutive days. After 2–3 days of drug-free retraining or resting, all rats were then challenged with aripiprazole (1.5 or 3.0 mg/kg, sc). Repeated administration of aripiprazole progressively increased its inhibition of avoidance responding and PCP-induced hyperlocomotion. More importantly, rats previously treated with aripiprazole showed significantly lower avoidance response and lower PCP-induced hyperlocomotion than those previously treated with vehicle in the challenge tests. An increased sensitivity to quinpirole (a selective D2/3 agonist) in prior aripiprazole-treated rats was also found in the quinpirole-induced hyperlocomotion test, suggesting an enhanced D2/3-mediated function. These findings suggest that aripiprazole, despite its distinct receptor mechanisms of action, induces a sensitization effect similar to those induced by other antipsychotic drugs and this effect may be partially mediated by brain plasticity involving D2/3 receptor systems. PMID:25586399

  8. Unique Effects of Acute Aripiprazole Treatment on the Dopamine D2 Receptor Downstream cAMP-PKA and Akt-GSK3β Signalling Pathways in Rats

    Pan, Bo; Chen, Jiezhong; Lian, Jiamei; Huang, Xu-Feng; Deng, Chao

    2015-01-01

    Aripiprazole is a wide-used antipsychotic drug with therapeutic effects on both positive and negative symptoms of schizophrenia, and reduced side-effects. Although aripiprazole was developed as a dopamine D2 receptor (D2R) partial agonist, all other D2R partial agonists that aimed to mimic aripiprazole failed to exert therapeutic effects in clinic. The present in vivo study aimed to investigate the effects of aripiprazole on the D2R downstream cAMP-PKA and Akt-GSK3β signalling pathways in comparison with a D2R antagonist – haloperidol and a D2R partial agonist – bifeprunox. Rats were injected once with aripiprazole (0.75mg/kg, i.p.), bifeprunox (0.8mg/kg, i.p.), haloperidol (0.1mg/kg, i.p.) or vehicle. Five brain regions – the prefrontal cortex (PFC), nucleus accumbens (NAc), caudate putamen (CPu), ventral tegmental area (VTA) and substantia nigra (SN) were collected. The protein levels of PKA, Akt and GSK3β were measured by Western Blotting; the cAMP levels were examined by ELISA tests. The results showed that aripiprazole presented similar acute effects on PKA expression to haloperidol, but not bifeprunox, in the CPU and VTA. Additionally, aripiprazole was able to increase the phosphorylation of GSK3β in the PFC, NAc, CPu and SN, respectively, which cannot be achieved by bifeprunox and haloperidol. These results suggested that acute treatment of aripiprazole had differential effects on the cAMP-PKA and Akt-GSK3β signalling pathways from haloperidol and bifeprunox in these brain areas. This study further indicated that, by comparison with bifeprunox, the unique pharmacological profile of aripiprazole may be attributed to the relatively lower intrinsic activity at D2R. PMID:26162083

  9. Add-on effects of a low-dose aripiprazole in resolving hyperprolactinemia induced by risperidone or paliperidone.

    Qiao, Ying; Yang, Fuzhong; Li, Chunbo; Guo, Qian; Wen, Hui; Zhu, Suoyu; Ouyang, Qiong; Shen, Weidi; Sheng, Jianhua

    2016-03-30

    This study investigated the effects of a low-dose aripiprazole adjunctive treatment for risperidone- or paliperidone-induced hyperprolactinemia in Han Chinese women with schizophrenia. After 4 weeks of risperidone or paliperidone treatment, 60 out of 66 patients improved significantly and experienced hyperprolactinemia. They were randomly assigned to the treatment group (aripiprazole adjunctive treatment) (n=30) or control group (non-adjunctive treatment) (n=30). The dosage of risperidone and paliperidone were maintained; and aripiprazole was maintained at 5mg/day during the 8-week study period. The prolactin levels at the end of the 8th week were significantly lower in the treatment group than in the control group. The estradiol level correlated negatively with serum prolactin level both in the treatment group and the control group at the end of the 8th week and the 4th week respectively. The Positive and Negative Syndrome Scale score improved significantly during the 8-week study period in both groups. The incidence of treatment-emergent adverse event was similar in two groups. Low-dose aripiprazole adjunctive treatment is effective in relieving risperidone- and paliperidone-induced hyperprolactinemia in female schizophrenic patients without increasing adverse event. PMID:26921057

  10. A Placebo-Controlled, Fixed-Dose Study of Aripiprazole in Children and Adolescents with Irritability Associated with Autistic Disorder

    Marcus, Ronald N.; Owen, Randall; Kamen, Lisa; Manos, George; McQuade, Robert D.; Carson, William H.; Aman, Michael G.

    2009-01-01

    Objective: To evaluate the short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Method: Two hundred eighteen children and adolescents (aged 6-17 years) with a diagnosis of autistic disorder, and with behaviors such as tantrums, aggression, self-injurious behavior, or a…

  11. Perinatal use of aripiprazole: plasma levels, placental transfer, and child outcome in 3 new cases.

    Windhager, Elmar; Kim, Sung-Wan; Saria, Alois; Zauner, Katharina; Amminger, Paul G; Klier, Claudia M

    2014-10-01

    The use of new agents of second-generation antipsychotics in childbearing women is increasing and poses an unknown risk to the fetus; thus, information of pregnancy and child outcome are urgently needed. We reviewed the literature of 12 patients, 3 of them were exposed during the first trimester, and added 3 new cases of peripartum use of aripiprazole. No teratogenesis was observed despite all 3 women having received the substance during part or full first trimester. All 3 pregnancies were uncomplicated with spontaneous birth. Dosage had to be changed during the course of gestation from 2.5 to 15 mg and plasma levels (PL) were below recommended levels, although all 3 women remained in stable remission throughout pregnancy and postpartum period.The extent of placental transfer of aripiprazole (mean ratio of 56.2%) is comparable with that of other second-generation antipsychotics.Our observations have clinical implications: antipsychotic PLs show large-scale decreases, which may require dose adjustments during pregnancy. Pregnant women may require lower PLs. In our cases, a PL of one third of the previous effective PL was effective and safe. Repeated therapeutic drug monitoring during late gestation based on individual, previous effective PLs seems to be a feasible way for safe and effective antipsychotic therapy in unplanned pregnancy. PMID:24949701

  12. Effects of acute and chronic aripiprazole treatment on choice between cocaine self-administration and food under a concurrent schedule of reinforcement in rats

    Thomsen, Morgane; Fink-Jensen, Anders; Woldbye, David;

    2008-01-01

    the hypothesis that aripiprazole, both as acute and as chronic treatment, would preferentially decrease cocaine self-administration while sparing behavior maintained by a natural reinforcer, resulting in a shift in the allocation of behavior from cocaine-taking towards the alternative reinforcer. MATERIALS...... performance in the choice procedure was assessed daily. RESULTS: An intermediate dose of aripiprazole decreased cocaine self-administration and shifted the cocaine choice curve to the right as an acute treatment. However, as a chronic treatment, aripiprazole failed to decrease cocaine self-administration...... or cocaine choice, despite a dose-dependent decrease in overall response rates and food-maintained behavior. CONCLUSIONS: Our results confirm and extend earlier findings and indicate that acute administration of aripiprazole can decrease cocaine self-administration. However, based on the present data...

  13. Determining Whether a Definitive Causal Relationship Exists Between Aripiprazole and Tardive Dyskinesia and/or Dystonia in Patients With Major Depressive Disorder, Part 3: Clinical Trial Data.

    Preskorn, Sheldon H; Macaluso, Matthew

    2016-03-01

    This series of columns has 3 main goals: (1) to explain class warnings as used by the United States Food and Drug Administration, (2) to increase awareness of movement disorders that may occur in patients treated with antipsychotic medications, and (3) to understand why clinicians should refrain from immediately assuming a diagnosis of tardive dyskinesia/dystonia (TD) in patients who develop abnormal movements during treatment with antipsychotics. The first column in the series presented a patient who developed abnormal movements while being treated with aripiprazole as an augmentation strategy for major depressive disorder (MDD) and reviewed data concerning the historical background, incidence, prevalence, and risk factors for tardive and spontaneous dyskinesias, the clinical presentations of which closely resemble each other. The second column in the series reviewed the unique mechanism of action of aripiprazole and preclinical studies and an early-phase human translational study that suggest a low, if not absent, risk of TD with aripiprazole. This column reviews clinical trial data to assess whether those data support the conclusion that aripiprazole has a low to absent risk of causing TD when used as an augmentation strategy to treat MDD. To date, no randomized, placebo-controlled trials have established a definitive link between exposure to aripiprazole and TD in patients with MDD. One long-term, open-label, safety trial examined aripiprazole as an augmentation strategy in individuals with MDD and found a rare occurrence (4/987, 0.4%, the confidence interval of which overlaps with zero) of an adverse event termed TD. In all 4 cases, the observed movements resolved within weeks of aripiprazole discontinuation, suggesting that they were either amenable to treatment or represented an acute syndrome rather than TD. No cases of TD were reported in the registration trials for the MDD indication for aripiprazole. These data were presented in a pooled analysis of

  14. Repeated administration of aripiprazole produces a sensitization effect in the suppression of avoidance responding and phencyclidine-induced hyperlocomotion and increases D2 receptor-mediated behavioral function

    Gao, Jun; Qin, Rongyin; LI Ming

    2015-01-01

    The present study investigated how repeated administration of aripiprazole (a novel antipsychotic drug) alters its behavioral effects in two behavioral tests of antipsychotic activity and whether this alteration is correlated with an increase in dopamine D2 receptor function. Male adult Sprague-Dawley rats were first repeatedly tested with aripiprazole (3, 10 and 30 mg/kg, subcutaneously (sc)) or vehicle in a conditioned avoidance response (CAR) test or a phencyclidine (PCP) (3.20 mg/kg, sc)-...

  15. Determining Whether a Definitive Causal Relationship Exists Between Aripiprazole and Tardive Dyskinesia and/or Dystonia in Patients With Major Depressive Disorder, Part 4: Case Report Data.

    Macaluso, Matthew; Flynn, Alexandra; Preskorn, Sheldon

    2016-05-01

    This series of columns has 3 main goals: (1) to explain class warnings as used by the United States Food and Drug Administration, (2) to increase awareness of movement disorders that may occur in patients treated with antipsychotic medications, and (3) to understand why clinicians should refrain from immediately assuming a diagnosis of tardive dyskinesia/dystonia (TD) in patients who develop abnormal movements during treatment with antipsychotics. The first column in the series presented a patient who developed abnormal movements while being treated with aripiprazole as an augmentation strategy for major depressive disorder and reviewed data concerning the historical background, incidence, prevalence, and risk factors for tardive and spontaneous dyskinesias, the clinical presentations of which closely resemble each other. The second column in the series reviewed the unique mechanism of action of aripiprazole and reviewed preclinical studies and an early-phase human translational study that suggest a low, if not absent, risk of TD with aripiprazole. The third column in this series reviewed the registration trial data for aripiprazole across all of its indications and found a raw incidence of TD ranging from 0.004 (4 out of 987) in long-term studies of the drug as an augmentation strategy for major depressive disorder to 0.0016 (19 out of 11,897) based on all short-term (ie, weeks to <6 mo) and long-term (6 mo to 1 y) studies combined. This fourth column in the series reviews the "real-world" data on aripiprazole and assesses whether these data also support the conclusion that aripiprazole has a low to absent risk of causing TD. The "real-world" data consist of case reports from the medical literature and the United States Food and Drug Administration Adverse Event Reporting System (FAERS). We found 37 cases in the medical literature reporting what was termed TD in association with aripiprazole treatment as well as 27 case reports suggesting improvement in

  16. Safety and efficacy of aripiprazole for the treatment of pediatric Tourette syndrome and other chronic tic disorders

    Cox JH

    2016-06-01

    Full Text Available Joanna H Cox,1 Stefano Seri,2,3 Andrea E Cavanna,2,4,5 1Heart of England NHS Foundation Trust, 2School of Life and Health Sciences, Aston Brain Centre, Aston University, 3Children’s Epilepsy Surgery Programme, The Birmingham Children’s Hospital NHS Foundation Trust, 4Department of Neuropsychiatry, Birmingham and Solihull Mental Health NHS Foundation Trust, Birmingham, 5Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology and UCL, London, UK Abstract: Tourette syndrome is a childhood-onset chronic tic disorder characterized by multiple motor and vocal tics and often accompanied by specific behavioral symptoms ranging from obsessionality to impulsivity. A considerable proportion of patients report significant impairment in health-related quality of life caused by the severity of their tics and behavioral symptoms and require medical intervention. The most commonly used medications are antidopaminergic agents, which have been consistently shown to be effective for tic control, but are also associated with poor tolerability because of their adverse effects. The newer antipsychotic medication aripiprazole is characterized by a unique mechanism of action (D2 partial agonism, and over the last decade has increasingly been used for the treatment of tics. We conducted a systematic literature review to assess the available evidence on the efficacy and safety of aripiprazole in pediatric patients with Tourette syndrome and other chronic tic disorders (age range: 4–18 years. Our search identified two randomized controlled trials (involving 60 and 61 participants and ten open-label studies (involving between six and 81 participants. The majority of these studies used two validated clinician-rated instruments (Yale Global Tic Severity Scale and Clinical Global Impression scale as primary outcome measures. The combined results from randomized controlled trials and open-label studies showed that aripiprazole is an

  17. Dilemma of prescribing aripiprazole under the Taiwan health insurance program: a descriptive study

    Hsu YC

    2015-01-01

    Full Text Available Yi-Chien Hsu,1,2 Yu-Ching Chou,3 Hsin-An Chang,1,2,4 Yu-Chen Kao,1,2,5 San-Yuan Huang,1,2 Nian-Sheng Tzeng1,2,4 1Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan; 2School of Medicine, 3School of Public Health, 4Student Counseling Center, National Defense Medical Center, Taipei, Taiwan; 5Department of Psychiatry, Tri-Service General Hospital, Song-Shan Branch, Taipei, Taiwan Objectives: Refractory major depressive disorder (MDD is a serious problem leading to a heavy economic burden. Antipsychotic augmentation treatment with aripiprazole and quetiapine is approved for MDD patients and can achieve a high remission rate. This study aimed to examine how psychiatrists in Taiwan choose medications and how that choice is influenced by health insurance payments and administrative policy.Design: Descriptive study.Outcome measures: Eight questions about the choice of treatment strategy and atypical antipsychotics, and the reason to choose aripiprazole.Intervention: We designed an augmentation strategy questionnaire for psychiatrists whose patients had a poor response to antidepressants, and handed it out during the annual meeting of the Taiwanese Society of Psychiatry in October 2012. It included eight questions addressing the choice of treatment strategy and atypical antipsychotics, and the reason whether or not to choose aripiprazole as the augmentation antipsychotic.Results: Choosing antipsychotic augmentation therapy or switching to other antidepressant strategies for MDD patients with an inadequate response to antidepressants was common with a similar probability (76.1% vs 76.4%. The most frequently used antipsychotics were aripiprazole and quetiapine, however a substantial number of psychiatrists chose olanzapine, risperidone, and sulpiride. The major reason for not choosing aripiprazole was cost (52.1%, followed by insurance official policy audit and deletion in the claims review system (30.1%.Conclusion: The prescribing

  18. Aripiprazole Increases the PKA Signalling and Expression of the GABAA Receptor and CREB1 in the Nucleus Accumbens of Rats.

    Pan, Bo; Lian, Jiamei; Huang, Xu-Feng; Deng, Chao

    2016-05-01

    The GABAA receptor is implicated in the pathophysiology of schizophrenia and regulated by PKA signalling. Current antipsychotics bind with D2-like receptors, but not the GABAA receptor. The cAMP-responsive element-binding protein 1 (CREB1) is also associated with PKA signalling and may be related to the positive symptoms of schizophrenia. This study investigated the effects of antipsychotics in modulating D2-mediated PKA signalling and its downstream GABAA receptors and CREB1. Rats were treated orally with aripiprazole (0.75 mg/kg, ter in die (t.i.d.)), bifeprunox (0.8 mg/kg, t.i.d.), haloperidol (0.1 mg/kg, t.i.d.) or vehicle for 1 week. The levels of PKA-Cα and p-PKA in the prefrontal cortex (PFC), nucleus accumbens (NAc) and caudate putamen (CPu) were detected by Western blots. The mRNA levels of Gabrb1, Gabrb2, Gabrb3 and Creb1, and their protein expression were measured by qRT-PCR and Western blots, respectively. Aripiprazole elevated the levels of p-PKA and the ratio of p-PKA/PKA in the NAc, but not the PFC and CPu. Correlated with this elevated PKA signalling, aripiprazole elevated the mRNA and protein expression of the GABAA (β-1) receptor and CREB1 in the NAc. While haloperidol elevated the levels of p-PKA and the ratio of p-PKA/PKA in both NAc and CPu, it only tended to increase the expression of the GABAA (β-1) receptor and CREB1 in the NAc, but not the CPu. Bifeprunox had no effects on PKA signalling in these brain regions. These results suggest that aripiprazole has selective effects on upregulating the GABAA (β-1) receptor and CREB1 in the NAc, probably via activating PKA signalling. PMID:26894264

  19. Enhancement of encapsulation efficiency of nanoemulsion-containing aripiprazole for the treatment of schizophrenia using mixture experimental design

    Fard Masoumi HR

    2015-10-01

    Full Text Available Hamid Reza Fard Masoumi, Mahiran Basri, Wan Sarah Samiun, Zahra Izadiyan, Chaw Jiang Lim Nanodelivery Group, Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia Abstract: Aripiprazole is considered as a third-generation antipsychotic drug with excellent therapeutic efficacy in controlling schizophrenia symptoms and was the first atypical anti­psychotic agent to be approved by the US Food and Drug Administration. Formulation of nanoemulsion-containing aripiprazole was carried out using high shear and high pressure homo­genizers. Mixture experimental design was selected to optimize the composition of nanoemulsion. A very small droplet size of emulsion can provide an effective encapsulation for delivery system in the body. The effects of palm kernel oil ester (3–6 wt%, lecithin (2–3 wt%, Tween 80 (0.5–1 wt%, glycerol (1.5–3 wt%, and water (87–93 wt% on the droplet size of aripiprazole nanoemulsions were investigated. The mathematical model showed that the optimum formulation for preparation of aripiprazole nanoemulsion having the desirable criteria was 3.00% of palm kernel oil ester, 2.00% of lecithin, 1.00% of Tween 80, 2.25% of glycerol, and 91.75% of water. Under optimum formulation, the corresponding predicted response value for droplet size was 64.24 nm, which showed an excellent agreement with the actual value (62.23 nm with residual standard error <3.2%. Keywords: schizoaffective disorder, antipsychotic drug, bipolar I disorder, D-optimal mixture design, optimization formulation

  20. Aripiprazole Injection

    ... pressure, seizures, difficulty swallowing, a high level of fats (cholesterol and triglycerides) in your blood, or a medical condition that may affect you receiving an injection in your arm or buttocks. Tell your doctor ...

  1. Fluvoxamine for aripiprazole-associated akathisia in patients with schizophrenia: a potential role of sigma-1 receptors

    Hashimoto Kenji

    2010-03-01

    Full Text Available Abstract Background Second-generation antipsychotic drugs have been reported to cause fewer incidences of extrapyramidal side effects (EPSs than typical antipsychotic drugs, but adverse events such as akathisia have been observed even with atypical antipsychotic drugs. Although understanding of the pathophysiology of akathisia remains limited, it seems that a complex interplay of several neurotransmitter systems might play a role in its pathophysiology. The endoplasmic reticulum protein sigma-1 receptors are shown to regulate a number of neurotransmitter systems in the brain. Methods We report on two cases in which monotherapy of the selective serotonin reuptake inhibitor and sigma-1 receptor agonist fluvoxamine was effective in ameliorating the akathisia of patients with schizophrenia treated with the antipsychotic drug aripiprazole. Results The global score on the Barnes Akathisia Scale in the two patients with schizophrenia treated with aripiprazole decreased after fluvoxamine monotherapy. Conclusion Doctors may wish to consider fluvoxamine as an alternative approach in treating akathisia associated with antipsychotic drugs such as aripiprazole.

  2. Aripiprazole loaded poly(caprolactone) nanoparticles: Optimization and in vivo pharmacokinetics.

    Sawant, Krutika; Pandey, Abhijeet; Patel, Sneha

    2016-09-01

    In the present investigation, a Quality by Design strategy was applied for formulation and optimization of aripiprazole (APZ) loaded PCL nanoparticles (APNPs) using nanoprecipitation method keeping entrapment efficiency (%EE) and particle size (PS) as critical quality attributes. Establishment of design space was done followed by analysis of its robustness and sensitivity. Characterization of optimized APNPs was done using DSC, FT-IR, PXRD and TEM studies and was evaluated for drug release, hemocompatibility and nasal toxicity. PS, zeta potential and %EE of optimized APNPs were found to be 199.2±5.65nm, -21.4±4.6mV and 69.2±2.34% respectively. In vitro release study showed 90±2.69% drug release after 8h. Nasal toxicity study indicated safety of developed formulation for intranasal administration. APNPs administered via intranasal route facilitated the brain distribution of APZ incorporated with the AUC0→8 in rat brain approximately 2 times higher than that of APNPs administered via intravenous route. Increase in Cmax was observed which might help in dose reduction along with reduction in dose related side effects. The results of the study indicate that intranasally administered APZ loaded PCL NPs can potentially transport APZ via nose to brain and can serve as a non-invasive alternative for the delivery of APZ to brain. PMID:27207059

  3. Medication adherence and utilization in patients with schizophrenia or bipolar disorder receiving aripiprazole, quetiapine, or ziprasidone at hospital discharge: A retrospective cohort study

    Berger Ariel; Edelsberg John; Sanders Kafi N; Alvir Jose Ma J; Mychaskiw Marko A; Oster Gerry

    2012-01-01

    Abstract Background Schizophrenia and bipolar disorder are chronic debilitating disorders that are often treated with second-generation antipsychotic agents, such as aripiprazole, quetiapine, and ziprasidone. While patients who are hospitalized for schizophrenia and bipolar disorder often receive these agents at discharge, comparatively little information exists on subsequent patterns of pharmacotherapy. Methods Using a database linking hospital admission records to health insurance claims, w...

  4. Cognitive and psychomotor effects of adjunctive aripiprazole or paliperidone in patients of schizophrenia receiving olanzapine: a double blind placebo controlled clinical study

    Mayur M. Mayabhate

    2014-02-01

    Conclusions: The best augmenting strategy with for olanzapine nonresponsive patients will be D2 receptor partial agonist like aripiprazole rather than D2 antagonist like paliperidone and other atypical antipsychotic agents for better improvement in cognition and psychomotor domains. [Int J Basic Clin Pharmacol 2014; 3(1.000: 130-138

  5. An open-label pilot study of aripiprazole for male and female veterans with chronic post-traumatic stress disorder who respond suboptimally to antidepressants.

    Youssef, Nagy A; Marx, Christine E; Bradford, Daniel W; Zinn, Sandra; Hertzberg, Michael A; Kilts, Jason D; Naylor, Jennifer C; Butterfield, Marian I; Strauss, Jennifer L

    2012-07-01

    Emerging data suggest that second-generation antipsychotics such as aripiprazole may be effective in the treatment of post-traumatic stress disorder (PTSD). However, few clinical trials have used aripiprazole in PTSD, and data are limited on its use in Veterans with PTSD. The objective of this pilot trial was to investigate the safety and efficacy of aripiprazole in Veterans with PTSD. Ten individuals (five men and five women) meeting the Diagnostic and statistical manual of mental disorders, 4th ed., PTSD criteria participated in this 12-week, open-label, flexibly dosed monotherapy trial. The dose range of aripiprazole was 5-30 mg/day, titrated to tolerability and clinical response. The primary outcome measure was the Clinician-Administered PTSD Scale. Additional outcomes included the Short PTSD Rating Interview, the Treatment Outcome PTSD Scale (Top-8), the Davidson Trauma Scale, the Positive and Negative Syndrome Scale, the Beck Depression Inventory-Fast Screen, and Clinical Global Impressions-Improvement. Eight participants completed the study, and aripiprazole was generally well tolerated and associated with a significant improvement in PTSD symptoms, as measured by the Clinician-Administered PTSD Scale (primary outcome measure) and by the Short PTSD Rating Interview, the Treatment Outcome PTSD Scale, and the Davidson Trauma Scale. An improvement was also observed on all three Positive and Negative Syndrome Scale subscales and the Beck Depression Inventory-Fast Screen, and the average Clinical Global Impressions-Improvement ratings indicated that patients were 'much improved'. These promising initial results merit further investigation in a larger, randomized-controlled trial. PMID:22475888

  6. Adjunctive aripiprazole in the treatment of risperidone-induced hyperprolactinemia: A randomized, double-blind, placebo-controlled, dose-response study.

    Chen, Jing-Xu; Su, Yun-Ai; Bian, Qing-Tao; Wei, Li-He; Zhang, Rong-Zhen; Liu, Yan-Hong; Correll, Christoph; Soares, Jair C; Yang, Fu-De; Wang, Shao-Li; Zhang, Xiang-Yang

    2015-08-01

    Hyperprolactinemia is an unwanted adverse effect associated with several antipsychotics. The addition of partial dopamine receptor agonist aripiprazole may attenuate antipsychotic-induced hyperprolactinemia effectively. However, the ideal dosing regimen for this purpose is unknown. We aimed to evaluate the dose effects of adjunctive treatment with aripiprazole on prolactin levels and hyperprolactinemia in schizophrenia patients. Stable subjects 18-45 years old with schizophrenia and hyperprolactinemia (i.e., >24 ng/ml for females and >20 ng/ml for males) were randomly assigned to receive 8 weeks of placebo (n=30) or oral aripiprazole 5mg/day (n=30), 10mg/day (n=29), or 20mg/day (n=30) added on to fixed dose risperidone treatment. Serum prolactin levels were measured at baseline and after 2, 4 and 8 weeks; clinical symptoms and side effects were assessed at baseline and week 8 using the Positive and Negative Syndrome Scale, Clinical Global Impressions Severity scale, Barnes Akathisia Scale, Simpson-Angus Scale and UKU Side Effects Rating Scale. Of 119 randomized patients, 107 (89.9%) completed the 8-week study. At study end, all three aripiprazole doses resulted in significantly lower prolactin levels (beginning at week 2), higher response rates (≥30% prolactin reduction) and higher prolactin normalization rates than placebo. Effects were significantly greater in the 10 and 20mg/day groups than the 5mg/day group. No significant changes were observed in any treatment groups regarding psychopathology and adverse effect ratings. Adjunctive aripiprazole treatment was effective and safe for resolving risperidone-induced hyperprolactinemia, producing significant and almost maximal improvements by week 2 without significant effects on psychopathology and side effects. PMID:25981348

  7. The effect of antipsychotic medication on sexual function and serum prolactin levels in community-treated schizophrenic patients: results from the Schizophrenia Trial of Aripiprazole (STAR study (NCT00237913

    Pans Miranda

    2008-12-01

    Full Text Available Abstract Background The aim of this paper is to evaluate the effect of antipsychotics for the treatment of schizophrenia in a community based study on sexual function and prolactin levels comparing the use of aripiprazole and standard of care (SOC, which was a limited choice of three widely used and available antipsychotics (olanzapine, quetiapine or risperidone (The Schizophrenia Trial of Aripiprazole [STAR] study [NCT00237913]. Method This open-label, 26-week, multi-centre, randomised study compared aripiprazole to SOC (olanzapine, quetiapine or risperidone in patients with schizophrenia (DSM-IV-TR criteria. The primary effectiveness variable was the mean total score of the Investigator Assessment Questionnaire (IAQ at Week 26. The outcome research variables included the Arizona Sexual Experience scale (ASEX. This along with the data collected on serum prolactin levels at week 4, 8, 12, 18 and 26 will be the focus of this paper. Results A total of 555 patients were randomised to receive aripiprazole (n = 284 or SOC (n = 271. Both treatment groups experienced improvements in sexual function from baseline ASEX assessments. However at 8 weeks the aripiprazole treatment group reported significantly greater improvement compared with the SOC group (p = 0.007; OC. Although baseline mean serum prolactin levels were similar in the two treatment groups (43.4 mg/dL in the aripiprazole group and 42.3 mg/dL in the SOC group, p = NS at Week 26 OC, mean decreases in serum prolactin were 34.2 mg/dL in the aripiprazole group, compared with 13.3 mg/dL in the SOC group (p Conclusion The study findings suggest that aripiprazole has the potential to reduce sexual dysfunction, which in turn might improve patient compliance.

  8. A 64-week, multicenter, open-label study of aripiprazole effectiveness in the management of patients with schizophrenia or schizoaffective disorder in a general psychiatric outpatient setting

    Chiu Nan-Ying

    2010-09-01

    Full Text Available Abstract Objective To evaluate the overall long-term effectiveness of aripiprazole in patients with schizophrenia in a general psychiatric practice setting in Taiwan. Methods This was a prospective, open-label, multicenter, post-market surveillance study in Taiwanese patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV diagnosis of schizophrenia or schizoaffective disorder requiring a switch in antipsychotic medication because current medication was not well tolerated and/or clinical symptoms were not well controlled. Eligible patients were titrated to aripiprazole (5-30 mg/day over a 12-week switching phase, during which their previous medication was discontinued. Patients could then enter a 52-week, long-term treatment phase. Aripiprazole was flexibly dosed (5-30 mg/day at the discretion of the treating physicians. Efficacy was assessed using the Clinical Global Impression scale Improvement (CGI-I score, the Clinical Global Impression scale Severity (CGI-S score, The Brief Psychiatry Rating Scale (BPRS, and the Quality of Life (QOL scale, as well as Preference of Medicine (POM ratings by patients and caregivers. Safety and tolerability were also assessed. Results A total of 245 patients were enrolled and switched from their prior antipsychotic medications, and 153 patients entered the 52-week extension phase. In all, 79 patients (32.2% completed the study. At week 64, the mean CGI-I score was 3.10 and 64.6% of patients who showed response. Compared to baseline, scores of CGI-S, QOL, and BPRS after 64 weeks of treatment also showed significant improvements. At week 12, 65.4% of subjects and 58.9% of caregivers rated aripiprazole as better than the prestudy medication on the POM. The most frequently reported adverse events (AEs were headache, auditory hallucinations and insomnia. A total of 13 patients (5.3% discontinued treatment due to AEs. No statistically significant changes were noted with respect to

  9. Quetiapine versus aripiprazole in children and adolescents with psychosis--protocol for the randomised, blinded clinical Tolerability and Efficacy of Antipsychotics (TEA) trial

    Pagsberg, Anne Katrine; Jeppesen, Pia; Klauber, Dea Gowers;

    2014-01-01

    BACKGROUND: The evidence for choices between antipsychotics for children and adolescents with schizophrenia and other psychotic disorders is limited. The main objective of the Tolerability and Efficacy of Antipsychotics (TEA) trial is to compare the benefits and harms of quetiapine versus...... aripiprazole in children and adolescents with psychosis in order to inform rational, effective and safe treatment selections. METHODS/DESIGN: The TEA trial is a Danish investigator-initiated, independently funded, multi-centre, randomised, blinded clinical trial. Based on sample size estimation, 112 patients...... aged 12-17 years with psychosis, antipsychotic-naïve or treated for a limited period are, 1:1 randomised to a 12- week, double-blind intervention with quetiapine versus aripiprazole. Effects on psychopathology, cognition, health-related quality of life, and adverse events are assessed 2, 4, and 12...

  10. Using ASL Method for Monitoring of Brain Perfusion Changes in a Rat Model of Schizophrenia and After Chronic Administration of Aripiprazole

    Dražanová, Eva; Grossová, Lucie; Pistovčáková, J.; Khainar, A.; Demlová, R.; Kašpárek, T.; Starčuk jr., Zenon

    Bratislava: Institute of Measurement Science, SAS, 2015, s. 81-84. ISBN 978-80-969672-9-2. [International Conference on Measurement /10./. Smolenice (SK), 25.05.2015-28.05.2015] R&D Projects: GA MŠk(CZ) LO1212; GA MŠk ED0017/01/01 Institutional support: RVO:68081731 Keywords : ASL * schizophrenia * poly I:C animal model * rats * aripiprazole Subject RIV: BH - Optics, Masers, Lasers

  11. Cognitive and psychomotor effects of adjunctive aripiprazole or paliperidone in patients of schizophrenia receiving olanzapine: a double blind placebo controlled clinical study

    Mayur M. Mayabhate; Vandana A. Badar; Praveer Waradkar; Abhishek Somani

    2014-01-01

    Background: Emergence of atypical antipsychotics has revolutionized the treatment of schizophrenia by exploiting dual actions on serotonin as well as dopaminergic receptors. Still, monotherapy with these agents is insufficient to control cognitive and psychomotor as well as positive and negative symptoms. Hence combination therapy with antipsychotics is common in clinical practice. Objective of current study is to compare the effects of addition of aripiprazole or paliperidone on cognition an...

  12. Effects of Dopamine D2 Receptor Partial Agonist Antipsychotic Aripiprazole on Dopamine Synthesis in Human Brain Measured by PET with L-[β-11C]DOPA

    Ito, Hiroshi; Takano, Harumasa; Arakawa, Ryosuke; Takahashi, Hidehiko; Kodaka, Fumitoshi; Takahata, Keisuke; Nogami, Tsuyoshi; Suzuki, Masayuki; Suhara, Tetsuya

    2012-01-01

    Dopamine D2 receptor partial agonist antipsychotic drugs can modulate dopaminergic neurotransmission as functional agonists or functional antagonists. The effects of antipsychotics on presynaptic dopaminergic functions, such as dopamine synthesis capacity, might also be related to their therapeutic efficacy. Positron emission tomography (PET) was used to examine the effects of the partial agonist antipsychotic drug aripiprazole on presynaptic dopamine synthesis in relation to dopamine D2 rece...

  13. Determining Whether a Definitive Causal Relationship Exists Between Aripiprazole and Tardive Dyskinesia and/or Dystonia in Patients With Major Depressive Disorder, Part 2: Preclinical and Early Phase Human Proof of Concept Studies.

    Macaluso, Matthew; Flynn, Alexandra; Preskorn, Sheldon

    2016-01-01

    This series of columns has 3 main goals: (1) to explain class warnings as used by the United States Food and Drug Administration, (2) to increase awareness of movement disorders that may occur in patients treated with antipsychotic medications, and (3) to understand why clinicians should refrain from immediately assuming a diagnosis of tardive dyskinesia/dystonia (TD) in patients treated with antipsychotics. The first column in this series began with the case of a 76-year-old man with major depressive disorder who developed orofacial dyskinesias while being treated with aripiprazole as an antidepressant augmentation strategy. It was alleged that a higher than intended dose of aripiprazole (ie, 20 mg/d for 2 wk followed by 10 mg/d for 4 wk instead of the intended dose of 2 mg/d) was the cause of the dyskinetic movements in this man, and the authors were asked to review the case and give their opinion. The principal basis for this theory of causation was the class warning about TD in the package insert for aripiprazole. The rationale for concluding aripiprazole caused TD in the 76-year-old man led to this series of columns about aripiprazole, its potential--if any--to cause TD, and the presence of a class warning about TD in its package insert. The central point is to illustrate why class warnings exist and their implications for practice. The first column in this series focused on the historical background, incidence, prevalence, risk factors, and clinical presentations of tardive and spontaneous dyskinesias and concluded with a discussion of diagnostic considerations explaining why clinicians should avoid making a diagnosis of TD until a thorough differential diagnosis has been considered. This second column in the series reviews the pharmacology of aripiprazole and the preclinical and phase I translational human studies that suggest aripiprazole should have a low to nonexistent risk of causing TD compared with other antipsychotics. The third column in the series

  14. Medication adherence and utilization in patients with schizophrenia or bipolar disorder receiving aripiprazole, quetiapine, or ziprasidone at hospital discharge: A retrospective cohort study

    Berger Ariel

    2012-08-01

    Full Text Available Abstract Background Schizophrenia and bipolar disorder are chronic debilitating disorders that are often treated with second-generation antipsychotic agents, such as aripiprazole, quetiapine, and ziprasidone. While patients who are hospitalized for schizophrenia and bipolar disorder often receive these agents at discharge, comparatively little information exists on subsequent patterns of pharmacotherapy. Methods Using a database linking hospital admission records to health insurance claims, we identified all patients hospitalized for schizophrenia (ICD-9-CM diagnosis code 295.XX or bipolar disorder (296.0, 296.1, 296.4-296.89 between January 1, 2001 and September 30, 2008 who received aripiprazole, quetiapine, or ziprasidone at discharge. Patients not continuously enrolled for 6 months before and after hospitalization (“pre-admission” and “follow-up”, respectively were excluded. We examined patterns of use of these agents during follow-up, including adherence with treatment (using medication possession ratios [MPRs] and cumulative medication gaps [CMGs] and therapy switching. Analyses were undertaken separately for patients with schizophrenia and bipolar disorder, respectively. Results We identified a total of 43 patients with schizophrenia, and 84 patients with bipolar disorder. During the 6-month period following hospitalization, patients with schizophrenia received an average of 101 therapy-days with the second-generation antipsychotic agent prescribed at discharge; for patients with bipolar disorder, the corresponding value was 68 therapy-days. Mean MPR at 6 months was 55.1% for schizophrenia patients, and 37.3% for those with bipolar disorder; approximately one-quarter of patients switched to another agent over this period. Conclusions Medication compliance is poor in patients with schizophrenia or bipolar disorder who initiate treatment with aripiprazole, quetiapine, or ziprasidone at hospital discharge.

  15. Comparison of risperidone and aripiprazole in the treatment of preschool children with disruptive behavior disorder and attention deficit-hyperactivity disorder: A randomized clinical trial.

    Safavi, Parvin; Hasanpour-Dehkordi, Ali; AmirAhmadi, Maryam

    2016-01-01

    Although pharmacotherapy with atypical antipsychotics is common in child psychiatry, there has been little research on this issue. To compare the efficacy and safety of risperidone and aripiprazole in the treatment of preschool children with disruptive behavior disorders comorbid with attention deficit-hyperactivity disorder (ADHD). Randomized clinical trial conducted in a university-affiliated child psychiatry clinic in southwest Iran. Forty 3-6-year-old children, diagnosed with oppositional defiant disorder comorbid with ADHD, were randomized to an 8-week trial of treatment with risperidone or aripiprazole (20 patients in each group). Assessment was performed by Conners' rating scale-revised and clinical global impressions scale, before treatment, and at weeks 2, 4, and 8 of treatment. The data were analyzed by SPSS version 16. Mean scores between the two groups were compared by analysis of variance and independent and paired t-test. Mean scores of Conners rating scales were not different between two groups in any steps of evaluation. Both groups had significantly reduced scores in week 2 of treatment (P = 0.00), with no significant change in subsequent measurements. Rates of improvement, mean increase in weight (P = 0.894), and mean change in fasting blood sugar (P = 0.671) were not significantly different between two groups. Mean serum prolactin showed a significant increase in risperidone group (P = 0.00). Both risperidone and aripiprazole were equally effective in reducing symptoms of ADHD and oppositional defiant disorder, and relatively safe, but high rates of side effects suggest the cautious use of these drugs in children. PMID:27144151

  16. Comparison of risperidone and aripiprazole in the treatment of preschool children with disruptive behavior disorder and attention deficit-hyperactivity disorder: A randomized clinical trial

    Parvin Safavi

    2016-01-01

    Full Text Available Although pharmacotherapy with atypical antipsychotics is common in child psychiatry, there has been little research on this issue. To compare the efficacy and safety of risperidone and aripiprazole in the treatment of preschool children with disruptive behavior disorders comorbid with attention deficit-hyperactivity disorder (ADHD. Randomized clinical trial conducted in a university-affiliated child psychiatry clinic in southwest Iran. Forty 3-6-year-old children, diagnosed with oppositional defiant disorder comorbid with ADHD, were randomized to an 8-week trial of treatment with risperidone or aripiprazole (20 patients in each group. Assessment was performed by Conners′ rating scale-revised and clinical global impressions scale, before treatment, and at weeks 2, 4, and 8 of treatment. The data were analyzed by SPSS version 16. Mean scores between the two groups were compared by analysis of variance and independent and paired t-test. Mean scores of Conners rating scales were not different between two groups in any steps of evaluation. Both groups had significantly reduced scores in week 2 of treatment (P = 0.00, with no significant change in subsequent measurements. Rates of improvement, mean increase in weight (P = 0.894, and mean change in fasting blood sugar (P = 0.671 were not significantly different between two groups. Mean serum prolactin showed a significant increase in risperidone group (P = 0.00. Both risperidone and aripiprazole were equally effective in reducing symptoms of ADHD and oppositional defiant disorder, and relatively safe, but high rates of side effects suggest the cautious use of these drugs in children.

  17. Determining Whether a Definitive Causal Relationship Exists Between Aripiprazole and Tardive Dyskinesia and/or Dystonia in Patients With Major Depressive Disorder: Part 1.

    Preskorn, Sheldon; Flynn, Alexandra; Macaluso, Matthew

    2015-09-01

    This series of columns has 2 main goals: (1) to explain the use of class warnings by the US Food and Drug Administration and (2) to increase clinicians' awareness of movement disorders that may occur in patients being treated with antipsychotic medications and why it is appropriate and good practice to refrain from immediately assuming the diagnosis is tardive dyskinesia/dystonia (TD). This first column in the series will focus on the second goal, which will then serve as a case example for the first goal. Clinicians should refrain from jumping to a diagnosis of TD because a host of other causes need to be ruled out first before inferring iatrogenic causation. The causal relationship between chronic treatment with dopamine antagonists and TD is based on pharmacoepidemiology (ie, the prevalence of such movement disorders is higher in individuals receiving chronic treatment with such agents than in a control group). There is nothing pathognomonic about movement disorders, nor is there any test that can currently prove a drug caused a movement disorder in a specific individual. Another goal of this series is to describe the types of research that would be needed to establish whether a specific agent has a meaningful risk of causing TD. In this first column of the series, we present the case of a patient who developed orofacial dyskinesia while being treated with aripiprazole. In this case, the movement disorder was prematurely called TD, which led to a malpractice lawsuit. This case highlights a number of key questions clinicians are likely to encounter in day-to-day practice. We then review data concerning the historical background, incidence, prevalence, and risk factors for 2 movement disorders, TD and spontaneous dyskinesia. Subsequent columns in this series will review: (1) unique aspects of the psychopharmacology of aripiprazole, (2) the limited and inconsistent data in the literature concerning the causal relationship between aripiprazole and TD, (3) the use of

  18. 阿立哌唑治疗精神分裂症老年患者临床疗效观察%OBSERVATION ON THE CLINIC EFFICACY OF ARIPIPRAZOLE IN THE TREATMENT OF THE ELDERLY PATIENTS WITH SCHIZOPHRENIA

    阿怀红

    2011-01-01

    [目的] 研究阿立哌唑治疗精神分裂症老年患者的临床疗效和不良反应,为临床提供依据.[方法] 选择符合CCMD-3精神分裂症诊断标准、简明精神疾病评定量表(BPRS)>35分、年龄≥65岁的病例共60例.随机分为阿立哌唑组与奋乃静组各30例.治疗前及治疗8周后分别用简明精神病评定量表(BPRS)及阳性和阴性综合征量表(PANSS)评定疗效,用副反应量表(TESS)评定不良反应.[结果] 阿立哌唑在治疗精神分裂症老年患者总疗效和对情感障碍、意志障碍的改善明显优于奋乃静.阿立哌唑在行为毒性、神经系和植物神经系的副作用明显低于奋乃静.阿立哌唑副反应轻且相对安全、依从性高.[结论] 阿立哌唑治疗精神分裂症老年患者效果确切、安全性强、依从性高,能全面提高患者生活质量.%[Objective] To study the efficacy and side effect of aripiprazole in the treatment of the elderly patients with schizophrenia, and to provide the basis for the clinical. [Methodsl According to CCMD-3, 65 patients with BPRS score over 35 and aged above 60 years old were selected and randomly divided into two groups: 30 patients had heen given aripiprazole for 8 weeks, and 30 patients had been given perphenazine for 8 weeks, then all patients were assessed by BPRS, PANSS and TESS. [ Results) Both aripiprazole and perphenazine had same effect on Psychiatric symptams. Aripiprazole were much better than perphenazine in these respects: anxiety, depression and exceasive activity. Aripiprazole has less side effecta than perphenazine. Aripiprazole was Side-Light and relatively safe and high compliance. [Conclusion] Aripiprazole is an effective trealment of the elderly patients with schizophrenia, strong security and , high compliance, we can improve the overall quality of life of patients.

  19. Antagonism of the adenosine A2A receptor attenuates akathisia-like behavior induced with MP-10 or aripiprazole in a novel non-human primate model.

    Bleickardt, Carina J; Kazdoba, Tatiana M; Jones, Nicholas T; Hunter, John C; Hodgson, Robert A

    2014-03-01

    Akathisia is a subset of the larger antipsychotic side effect profile known as extrapyramidal syndrome (EPS). It is associated with antipsychotic treatment and is characterized as a feeling of inner restlessness that results in a compulsion to move. There are currently no primate models available to assess drug-induced akathisia; the present research was designed to address this shortcoming. We developed a novel rating scale based on both the Barnes Akathisia Rating Scale (BARS) and the Hillside Akathisia Scale (HAS) to measure the objective, observable incidence of antipsychotic-induced akathisia-like behavior in Cebus apella non-human primates (NHPs). To induce akathisia, we administered the atypical antipsychotic aripiprazole (1 mg/kg) or the selective phosphodiesterase 10A (PDE10A) inhibitor MP-10 (1-3 mg/kg). Treatment with both compounds produced significantly greater akathisia scores on the rating scale than vehicle treatment. Characteristic behaviors observed included vocalizations, stereotypies, teeth grinding, restless limb movements, and hyperlocomotion. Adenosine A2A receptor antagonists have previously been shown to be effective in blocking antipsychotic-induced EPS in primates. The selective A2A receptor antagonist, SCH 412348 (10-30 mg/kg), effectively reduced or reversed akathisia-like behavior induced by both aripiprazole and MP-10. This work represents the first NHP measurement scale of akathisia and demonstrates that NHPs are responsive to akathisia-inducing agents. As such, it provides a useful tool for the preclinical assessment of putative antipsychotics. In addition, these results provide further evidence of the utility of A2A receptor antagonists for the treatment of antipsychotic-induced movement disorders. PMID:24211858

  20. Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

    Piantato Ennio

    2009-05-01

    Full Text Available Abstract Background One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study. Methods/Design The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome. Discussion The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole

  1. Not all partial dopamine D2 receptor agonists are the same in treating schizophrenia. Exploring the effects of bifeprunox and aripiprazole using a computer model of a primate striatal dopaminergic synapse

    Athan Spiros

    2010-09-01

    Full Text Available Athan Spiros1, Robert Carr1, Hugo Geerts1,21In Silico Biosciences, Berwyn, PA, USA; 2School of Medicine, University of Pennsylvania, PA, USAAbstract: Species differences in physiology and unique active human metabolites contribute to the limited predictive value of preclinical rodent models for many central nervous system (CNS drugs. In order to explore possible drivers for this translational disconnect, we developed a computer model of a dopaminergic synapse that simulates the competition among three agents and their binding to pre- and postsynaptic receptors, based on the affinities for their targets and their actual concentrations. The model includes presynaptic autoreceptor effects on neurotransmitter release and modulation by presynaptic firing frequency and is calibrated with actual experimental data on free dopamine levels in the striatum of the rodent and the primate. Using this model, we simulated the postsynaptic dopamine D2 receptor activation levels of bifeprunox and aripiprazole, two relatively similar dopamine D2 receptor agonists. The results indicate a substantial difference in dose–response for the two compounds when applying primate calibration parameters as opposed to rodent calibration parameters. In addition, when introducing the major human and rodent metabolites of aripiprazole with their specific pharmacological activities, the model predicts that while bifeprunox would result in a higher postsynaptic D2 receptor antagonism in the rodent, aripiprazole would result in a higher D2 receptor antagonism in the primate model. Furthermore, only the highest dose of aripiprazole, but not bifeprunox, reaches postsynaptic functional D2 receptor antagonism similar to 4 mg haloperidol in the primate model. The model further identifies a limited optimal window of functionality for dopamine D2 receptor partial agonists. These results suggest that computer modeling of key CNS processes, using well-validated calibration paradigms, can

  2. Metabolic acidosis

    Acidosis - metabolic ... Metabolic acidosis occurs when the body produces too much acid. It can also occur when the kidneys are not ... the body. There are several types of metabolic acidosis. Diabetic acidosis develops when acidic substances, known as ...

  3. A controlled study between Aripiprazole combined with low-Dose of Clozapine and single Aripiprazole in the Treatment of Female Chronic Schizophrenia%阿立哌唑合用小剂量氯氮平与阿立哌唑单用治疗女性慢性精神分裂症对照研究

    陆德青; 肖刚

    2014-01-01

    Objective To investigate the clinical efficacy and adverse reaction of aripiprazole combined with low- dose of clozapine in the treatment of female patients with chronic schizophrenia.Methods The Study Group 20 cases were treated by aripiprazole combined with low-dose of clozapine treatment,20 cases in the control group only treated with aripiprazole,analyzed the assessment efficacy with the Brief Psychiatric Rating Scale(BPRS)and Scale for the Assessment of Negative Symptoms(SANS),applied the Treatment Emergent Symptom Scale(TESS)to analyze their adverse reactions.Results There was no significant difference between the BPRS scores of the two groups before treatment.After treatment,it showed Significant diference in depression and anxiety and thought disorder(P<0.05), in the activity and total scores,it showed a very significant difference(P<0.01);The same group before and after treatment,the difference is very significant(P<0.01).SANS scores of the two groups had no sign- ificant difference before treatment,After treatment,in lack of interest/social lack had significant differences(P<0.05); The same group before and after treatment,the difference is very significant(P<0.01).TESS statistics showed that two groups’Side reaction occurred with the same frequency.Conclusion Regardless of aripiprazole combined with smal dose of clozapine or single use of aripiprazole in female patients with chronic schizophrenia had a definite effect,aripiprazole combined with smal dose of clozapine has advantages in improvement activities,improve interest/social and so on ,and the adverse reactions were not increased.%目的:探讨阿立哌唑合用小剂量氯氮平与阿立哌唑单用治疗女性慢性精神分裂症患者的临床疗效和不良反应。方法研究组20例应用阿立哌唑合用小剂量氯氮平治疗,对照组20例仅应用阿立哌唑单独治疗,应用简明精神病评定量表(BPRS)和阴性症状量表(SANS)评定疗效,应用副反应

  4. Identification and quantification of the antipsychotics risperidone, aripiprazole, pipamperone and their major metabolites in plasma using ultra-high performance liquid chromatography-mass spectrometry.

    Wijma, Rixt A; van der Nagel, Bart C H; Dierckx, Bram; Dieleman, Gwen C; Touw, Daan J; van Gelder, Teun; Koch, Birgit C P

    2016-06-01

    The antipsychotics risperidone, aripiprazole and pipamperone are frequently prescribed for the treatment in children with autism. The aim of this study was to validate an ultra-high performance liquid chromatography-mass spectrometry method for the quantification of these antipsychotics in plasma. An ultra-high performance liquid chromatography-mass spectrometry assay was developed for the determination of the drugs and metabolites. Gradient elution was performed on a reversed-phase column with a mobile phase consisting of ammonium acetate, formic acid in methanol or in Milli-Q ultrapure water at a flow rate of 0.5 mL/min. The method was validated according to the US Food and Drug Administration guidelines. The analytes were found to be stable enough after reconstitution and injection of only 5 μL improved the accuracy and precision in combination with the internal standard. Calibration curves of all five analytes were linear. All analytes were stable for at least 72 h in the autosampler and the high quality control of 9-OH-risperidone was stable for 48 h. The method allows quantification of all analytes. The advantage of this method is the combination of a minimal injection volume, a short run-time, an easy sample preparation method and the ability to quantify all analytes in one run. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26447610

  5. Metabolic Disorders

    ... as your liver, muscles, and body fat. A metabolic disorder occurs when abnormal chemical reactions in your body ... that produce the energy. You can develop a metabolic disorder when some organs, such as your liver or ...

  6. Metabolic Syndrome

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These ... doctors agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  7. A clinical comparative study in first-onset schizophrenia patients treated with Aripiprazole and Quetiapine%阿立哌唑与喹硫平治疗首发精神分裂症的临床对照研究

    刘娜

    2012-01-01

    Objective To study the clinical effects of Aripiprazole and Quetiapine in the treatment of first -onset schizophrenia. Methods 63 adult patients who were diagnosed as schizophreniain accordance with the CCMD-3 diagnosis standard were recruited in this study. All the cases were randomized into two groups and were treated with Aripiprazole and Quetiapine for 8 weeks. The positive and negative syndrome scale (PANSS) and treatment emergent side effect scale (TESS) were used to evaluate efficacy and adverse effects respectively. Results The significant efficacy rates of Aripiprazole was 93.55%, Quetiapine was 90.63%, there was no significant difference (P > 0.05). Before and after treatment between Aripiprazole group and Quetiapine group, the PANSS score had no significant difference (P > 0.05). The level of LEP and TG was elevated which were treated by Aripiprazole, the difference was statistically significant (P < 0.05). The level of LEP, PRL, BG and TG was elevated which were treated by Quetiapine, the difference was statistically significant (P < 0.05). Conclusion The curative effect of first-onset schizophrenia between Aripiprazole and Quetiapine is quite, but the adverse reactions are different, the former is better than the latter.%目的 探讨阿立哌唑与喹硫平治疗首发精神分裂症的临床疗效.方法 63例首发精神分裂症患者,符合CCMD-3精神分裂症诊断标准,随机分成两组,分别使用阿立哌唑和喹硫平治疗,疗程共8周.采用阳性和阴性症状量表(PANSS)和不良反应症状量表(TESS)进行副反应评定.结果 阿立哌唑组总有效率为93.55%,喹硫平组总有效率为90.63%,差异无统计学意义(P>0.05).阿立哌唑组和喹硫平组两组患者治疗前后PANSS量表评分,差异无统计学意义(P>0.05);阿立哌唑组治疗前后相比,瘦素和三酰甘油水平升高,差异有统计学意义(P<0.05),喹硫平组治疗前后瘦素、催乳素、血糖和三酰甘油水平升

  8. Clinical efficacy comparison of escitalopram treatment combined with aripiprazole on obsessive compulsive disorder%艾司西酞普兰联合阿立哌唑治疗强迫症患者的疗效观察

    姜涛

    2011-01-01

    Objective; To investigate the effectiveness and safety of escitalopram with or without aripi-prazole in the treatment of obsessive-compulsive disorder. Method;60 patients with obsessive compulsive disorder were randomly assigned to receive escitalopram with or without aripiprazole. Effectiveness and adverse effect were assessed by Yale-Brown obsessive compulsive scale (Y-BOCS) and treatment emergent symptom scale ( TESS) , respectively. Results; Patients both received escitalopram and escitalopram with aripiprazole showed significant improvement by Y-BOCS scores after treatment,while the combination group showed a better outcome. There was no significant difference in TESS evaluation between the two groups. Conclusion; Escitalopram could effectively treat obsessive-compulsive disorder, while escitalopram combined with aripiprazole is more effective.%目的:探讨艾司西酞普兰与阿立哌唑联合治疗强迫症的疗效及不良反应.方法:对60例强迫症患者随机分为单用艾司西酞普兰组(单用组)及艾司西酞普兰与阿立哌唑联合用药组(合用组)治疗强迫症患者各30例进行开放、随机、对照研究,通过耶鲁布朗强迫量表(Y-BOCS)评定疗效,治疗中出现的症状量表(TESS)评定不良反应. 结果:艾司西酞普兰治疗后显著改善强迫症状,艾司西酞普兰联合阿立哌唑也能显著改善强迫症状,后者改善效果更好;两组不良反应轻微.结论:艾司西酞普兰联合阿立哌唑较单用艾司西酞普兰的抗强迫效果更好.

  9. A systematic review and meta-analysis of randomised controlled trials of treatments for clozapine-induced obesity and metabolic syndrome.

    Zimbron, Jorge; Khandaker, Golam M; Toschi, Chiara; Jones, Peter B; Fernandez-Egea, Emilio

    2016-09-01

    Metabolic complications are commonly found in people treated with clozapine. Reviews on the management of this problem have generally drawn conclusions by grouping different types of studies involving patients treated with various different antipsychotics. We carried out a systematic review and meta-analysis of pharmacological and non-pharmacological treatments for clozapine-induced obesity or metabolic syndrome. Two researchers independently searched PubMed and Embase for randomised controlled trials (RCTs) of treatments for clozapine-induced obesity or metabolic syndrome. All other types of studies were excluded. We only included RCTs where more than 50% of participants were taking clozapine. We identified 15 RCTs. Effective pharmacological treatments for clozapine-induced obesity and metabolic syndrome include metformin, aripiprazole, and Orlistat (in men only). Meta-analysis of three studies showed a robust effect of metformin in reducing body mass index and waist circumference but no effects on blood glucose, triglyceride levels, or HDL levels. In addition, there is limited evidence for combined calorie restriction and exercise as a non-pharmacological alternative for the treatment of clozapine-induced obesity, but only in an in-patient setting. Rosiglitazone, topiramate, sibutramine, phenylpropanolamine, modafinil, and atomoxetine have not shown to be beneficial, despite reports of efficacy in other populations treated with different antipsychotics. We conclude that randomised-controlled trial data support the use of metformin, aripiprazole, and Orlistat (in men only) for treating clozapine-induced obesity. Calorie restriction in combination with an exercise programme may be effective as a non-pharmacological alternative. Findings from trials in different populations should not be extrapolated to people being treated with clozapine. PMID:27496573

  10. Metabolic ecology.

    Humphries, Murray M; McCann, Kevin S

    2014-01-01

    Ecological theory that is grounded in metabolic currencies and constraints offers the potential to link ecological outcomes to biophysical processes across multiple scales of organization. The metabolic theory of ecology (MTE) has emphasized the potential for metabolism to serve as a unified theory of ecology, while focusing primarily on the size and temperature dependence of whole-organism metabolic rates. Generalizing metabolic ecology requires extending beyond prediction and application of standardized metabolic rates to theory focused on how energy moves through ecological systems. A bibliometric and network analysis of recent metabolic ecology literature reveals a research network characterized by major clusters focused on MTE, foraging theory, bioenergetics, trophic status, and generalized patterns and predictions. This generalized research network, which we refer to as metabolic ecology, can be considered to include the scaling, temperature and stoichiometric models forming the core of MTE, as well as bioenergetic equations, foraging theory, life-history allocation models, consumer-resource equations, food web theory and energy-based macroecology models that are frequently employed in ecological literature. We conclude with six points we believe to be important to the advancement and integration of metabolic ecology, including nomination of a second fundamental equation, complementary to the first fundamental equation offered by the MTE. PMID:24028511

  11. E fficacy of Aripiprazole and Risperidone on Memory Function in Patients with Schizophrenia%阿立哌唑和利培酮对首发精神分裂症患者记忆功能的影响

    胡茂荣; 姜淑珍; 占海燕; 胡斌; 鲍成; 余斌; 周朝雄; 吴慧玲

    2013-01-01

    Objective To explore the efficacy of aripiprazole and risperidone on memory function in patients with schizophrenia. Methods 112 first-episode patients with schizophrenia were random-ized to aripiprazole group(n=56) and risperidone group(n=56). All subjects were assessed with the Wechsler Memory Scale-ⅢSpatial Span Task(WMS-Ⅲ SST), the Hopkins Verbal Learning Test-Re-vised (HVLT-R) and The Brief Visuospatial Memory Test-Revised (BVMT-R).Results Both groups showed no statistical significance in WMS-Ⅲ SST, HVLT-R and BVMT-R scores in the baseline (P>0.05).The performances after 12 weeks of treatment in the both groups was higher than those in the baseline in all tests(P0.05).Aripiprazole group was increased significantly compared with before treatment after treatment WMS-Ⅲ SST score (P<0.05), and after treatment there was a statistical significance between the two groups (P<0.05).Conclusion Memory impairments in the patients with first-episode schizophrenia was im-proved by aripiprazole and risperidone, and effect of aripiprazole on certain memory functions was better than those of risperidone.%目的:探讨阿立哌唑和利培酮对首发精神分裂症患者记忆功能的影响。方法112例首发精神分裂症患者随机分成阿立哌唑组和利培酮组,每组56例。在治疗前和治疗12周末采用韦氏记忆量表-第三版的空间广度测验(WMS-Ⅲ SST)、霍普金斯词汇学习测验-修订版(HVLT-R)、简单视觉空间记忆测验-修订版(BVMT-R)分别对工作记忆、言语记忆和视觉记忆领域进行评定。结果在治疗前,两组的WMS-Ⅲ SST HVLT-R 和BVMT-R得分比较均无统计学意义(P>0.05)。在治疗12周后,两组的HVLT-R 和BVMT-R得分较治疗前比较均有统计学意义(P<0.05)而治疗后两组间比较无统计学意义(P>0.05);阿立哌唑组在治疗后的WMS-Ⅲ SST得分较治疗前显著增加(P<0.05),且治疗后两组间比较有统计学意义(P<0.05

  12. DRUG METABOLISM

    Deepak Singla

    2011-02-01

    Full Text Available The termmetabolism, derived from the Greek language, simply means change or transformation. It relates to various processes within the body that convert food and other substances into energy and other metabolic byproducts used by the body. Drug metabolism is the body’s way of transforming drugs, so they can be excreted from the body. Many drugs arenot active until they have been metabolized in the body by enzymes that transform them. Most drugs are lipophilic, meaning they pass through membranes to reach their target site. Most drugs are treated by the body like foreign substances, also known as xenobiotics. Humans have evolved a complex system for xenobiotic metabolism

  13. Metabolic neuropathies

    ... body ( sepsis ) Thyroid disease Vitamin deficiencies (including vitamins B12 , B6 , E , and B1 ) Some metabolic disorders are ... by injection. Abnormal blood sugar level or thyroid function may need medicines to correct the problem. For ...

  14. Metabolic syndrome

    Gogia Atul

    2006-02-01

    Full Text Available The Metabolic syndrome is a widely prevalent and multi-factorial disorder. The syndrome has been given several names, including- the metabolic syndrome, the insulin resistance syndrome, the plurimetabolic syndrome, and the deadly quartet. With the formulation of NCEP/ATP III guidelines, some uniformity and standardization has occurred in the definition of metabolic syndrome and has been very useful for epidemiological purposes. The mechanisms underlying the metabolic syndrome are not fully known; however resistance to insulin stimulated glucose uptake seems to modify biochemical responses in a way that predisposes to metabolic risk factors. The clinical relevance of the metabolic syndrome is related to its role in the development of cardiovascular disease. Management of the metabolic syndrome involves patient-education and intervention at various levels. Weight reduction is one of the main stays of treatment. In this article we comprehensively discuss this syndrome- the epidemiology, pathogenesis, clinical relevance and management. The need to do a comprehensive review of this particular syndrome has arisen in view of the ever increasing incidence of this entitiy. Soon, metabolic syndrome will overtake cigarette smoking as the number one risk factor for heart disease among the US population. Hardly any issue of any primary care medical journal can be opened without encountering an article on type 2 diabetes, dyslipidemia or hypertension. It is rare to see type 2 diabetes, dyslipidemia, obesity or hypertension in isolation. Insulin resistance and resulting hyperinsulinemia have been implicated in the development of glucose intolerance (and progression to type 2 diabetes, hypertriglyceridemia, hypertension, polycystic ovary yndrome, hypercoagulability and vascular inflammation, as well as the eventual development of atherosclerotic cardiovascular disease manifested as myocardial infarction, stroke and myriad end organ diseases. Conversely

  15. Lipid Metabolism

    2008-01-01

    2008393 Effects of angiotensin Ⅱ type 1 receptor blocker on triglyceride metabolism in the liver: experiment with Zucker fatty rats. RAN Jianmin(冉建民), et al. Dept Endocrinol, Guangzhou Red Cross Hosp, 4th Hosp Med Coll, Jinan Univ, Guangzhou 510220. Natl Med J China 2008;88(22):1557-1561. Objective To investigate the effects of angiotensin receptor blocker (ARB) on triglyceride (TG) metabolism and mechanism thereof.

  16. Animal metabolism

    Studies on placental transport included the following: clearance of tritiated water as a baseline measurement for transport of materials across perfused placentas; transport of organic and inorganic mercury across the perfused placenta of the guinea pig in late gestation; and transport of cadmium across the perfused placenta of the guinea pig in late gestation. Studies on cadmium absorption and metabolism included the following: intestinal absorption and retention of cadmium in neonatal rats; uptake and distribution of an oral dose of cadmium in postweanling male and female, iron-deficient and normal rats; postnatal viability and growth in rat pups after oral cadmium administration during gestation; and the effect of calcium and phosphorus on the absorption and toxicity of cadmium. Studies on gastrointestinal absorption and mineral metabolism included: uptake and distribution of orally administered plutonium complex compounds in male mice; gastrointestinal absorption of 144Ce in the newborn mouse, rat, and pig; and gastrointestinal absorption of 95Nb by rats of different ages. Studies on iodine metabolism included the following: influence of thyroid status and thiocyanate on iodine metabolism in the bovine; effects of simulated fallout radiation on iodine metabolism in dairy cattle; and effects of feeding iodine binding agents on iodine metabolism in the calf

  17. A Treatment-control Study of Aripiprazole and Ziprasidone in Female First-onset Schizophrenia%阿立哌唑与齐拉西酮治疗女性首发精神分裂症对照研究

    许爱琴; 尤加永; 赵长银

    2013-01-01

    Objective:To evaluate the efficacy and adverse reactions of aripiprazole and ziprasidone in female first-onset schizophrenia.Method:31 female first-onset schizophrenia patients met the CCMD-3 diagnosis of schizophrenia were randomly assigned to aripiprazole group (36 patients) and ziprasidone group (35 cases). Positive symptoms and negative syndrome scale(PANSS) and treatment Emergent Symptom Scale(TESS) were used to evaluate the efficacy and safety.Result:There was no significant difference in PANSS scores(P>0.05) before and after 2,4,8 week’treatment between two groups. The two groups had no serious adverse reactions.Conclusion:Aripiprazole and ziprasidone were effective and less adverse reactions in treatment of female first-onset schizophrenia.%目的:评价齐拉西酮与阿立哌唑治疗女性首发精神分裂症的疗效与不良反应。方法:31例符合CCMD-3精神分裂症诊断标准的女性首发患者随机分为阿立哌唑(博思清)组(36例)和齐拉西酮(思贝格)组(35例),采用阳性症状与阴性症状量表(positive symptoms and negative symptoms scale,PANSS)评定疗效,副反应量表(treatment Emergent Symptom Scale,TESS)评价药物安全性。结果:两组患者治疗前及治疗后2、4、8 PANSS评分差异无显著性(P>0.05),两组均无严重不良反应。结论:阿立哌唑和齐拉西酮治疗女性首发精神分裂症有效,且不良反应少。

  18. 阿立哌唑应用于老年精神分裂症临床治疗的疗效和安全性%The clinical therapeutic effect and safety of aripiprazole in clinical treatment of senile schizophrenia

    王琪

    2014-01-01

    目的:探讨阿立哌唑应用于老年精神分裂症临床治疗效果及安全性,总结其治疗经验。方法:2010年1月-2013年10月收治老年精神分裂症患者40例,采用阿立哌唑治疗,平均治疗剂量(18.5±5.5)mg/d,治疗8周后采用简明精神病评定量表(BPRS)评定临床疗效,不良反应量表(TESS)评定安全性。结果:显效率70.0%,有效率87.5%,无明显锥体外系反应,不良反应轻。结论:阿立哌唑应用于老年精神分裂症患者的治疗依从性好、安全性高,可以有效缓解老年精神分裂症的精神病症状,值得临床推广应用。%Objective:To explore the clinical therapeutic effect and safety of aripiprazole in clinical treatment of senile schizophrenia,to summarize the treatment experience.Methods:40 elderly patients with schizophrenia were selected from January 2010 to October 2013.They were treated with aripiprazole.Average dose was (18.5 ± 5.5)mg/day.At 8 weeks after treatment,the clinical efficacy was assessed by the brief psychiatric rating scale(BPRS),and security was assessed by side effects scale(TESS). Results:The significant efficiency rate was 70%,and the efficiency was 87.5%.There was no obvious extrapyramidal reaction,and adverse reaction was light.Conclusion:Treatment compliance of application of aripiprazole in clinical treatment of senile schizophrenia is good,and security is high.It can effectively alleviate psychotic symptoms of senile schizophrenia,and it is worth the clinical promotion.

  19. Comparative Study on Aripiprazole and Risperidone in the Treatment of Schizophrenia%阿立哌唑与利培酮治疗精神分裂症的对照研究

    彭红波

    2013-01-01

    目的比较阿立哌唑和利培酮对精神分裂症的疗效,为临床用药提供参考。方法以我院2011年1月~2012年9月收治的120例精神分裂症患者为研究对象,将患者随机分为治疗组和对照组,每组60例。对照组患者应用利培酮,治疗组患者服用阿立哌唑。观察两组的治疗效果以及不良反应。结果治疗组总有效率高于对照组,但是差异不具有统计学意义( P>0.05);两组患者PANSS总分、阳性症状分、阴性症状分、一般精神病理分治疗后明显比治疗前降低(P<0.05),但是组间比较差异不具有统计学意义(P>0.05);治疗组不良反应发生率明显低于对照组(P<0.05)。结论临床对精神分裂症采用阿立哌唑和利培酮治疗效果均较显著,两种药物疗效相似;但是采用阿立哌唑治疗的不良反应发生率少,因此阿立哌唑治可作为临床的首要选择。%Objective Objective To analyze effect of aripiprazole and risperidone in the treatment of schizo-phrenia ,and provide reference for clinical medication choice .Methods 120 cases with schizophrenia from in-patient department in January 2011 to September 2012 were selected .These patients were randomly di-vided into treatment group and control group , 60 cases in each group .Control group received risperidone , and treatment group received aripiprazole .Curative effect and adverse reaction for two groups were observed and compared .Results Total effective rate for treatment group was obviously higher than control group , but there were no significant difference ( P>0 .05 ) .PANSS score , positive symptoms score , negative symp-toms score and general psychopathology score after treatment were obviously lower than the score before treatment ( P0 .05 ) .Incidence of adverse effect was obviously lower than control group ( P<0.05 ) .Conclusion herapeutic effects of aripiprazole and risperi-done in the treatment of

  20. 阿立哌唑和利培酮治疗女性精神分裂症对照研究%Aripiprazole and Risperidone in the Treatment of Female Schizophrenia

    姜丽艳

    2014-01-01

    目的:研究女性精神分裂症患者运用阿立哌唑和利培酮治疗的临床效果。方法2012年4月~2013年4月间诊治的160例女性精神分裂症患者,将其分为两组,组1使用阿立哌唑进行治疗,组2使用利培酮进行治疗,比较两组患者的临床效果。结果通过对两组患者进行比较,组1有效率为87.5%,组2为90.0%,两组患者临床效果未见明…显差异,无统计学意义(P >0.05);但组2患者的体质量增加情况、椎体外系反应的发生率、泌乳以及月经紊乱情况均比组1高,两组患者差异显著,有统计学意义(P <0.05)。结论对于女性精神分裂症治疗上效果上阿立哌唑和利培酮基本一致,但是阿立哌唑更适合用于女性精神分裂症患者。%Objective To study the clinical effect of female schizophrenia with aripiprazole and risperidone in the treatment of patients with. Methods 160 cases of female spirit in 2012 April ~2013 April in the diagnosis and treatment of patients with schizophrenia,it is divided into two groups, group 1 were treated by aripiprazole risperidone group, 2 were treated by comparison of the clinical effects of two groups of patients. Results The two groups of patients were compared, the group has an efficiency of 1 for 87.5%, group 2 to 90%,The patients in the two groups no significant differences in clinical effect, no statistical significance (P>0.05), but the group of 2 patients with body mass increase, extrapyramidal reaction rate, lactation and menstrual disorders are 1 higher than group, the differences between the two groups were significant, with statistical significance (P<0.05). Conclusion For the treatment of female schizophrenia aripiprazole and risperidone effect on basically the same,but aripiprazole is more suitable for female patients with schizophrenia.

  1. Efficacy and safety of aripiprazole in treating negative symptoms of schizophrenia%阿立哌唑与利培酮治疗精神分裂症阴性症状的疗效和安全性观察

    贾天成

    2014-01-01

    目的:探讨阿立哌唑治疗精神分裂症阴性症状的疗效和安全性。方法80名精神分裂症患者随机分为研究组(阿立哌唑治疗)和对照组(利培酮治疗),每组40例,在治疗前及治疗的2、4、8周末分别采用潘氏阳性与阴性症状量表(PANSS)、阴性症状评定量表(SANS)评分,并记录治疗期间发生的不良反应。结果两组患者治疗后的 PANSS 量表总分及 SANS 总分均明显降低(P <0.05),但同一时期,两组患者间的 PANSS 量表总分及 SANS 量表评分差异无统计学意义(P >0.05)。在治疗后第4、8周,研究组患者“思维贫乏”及“意志缺乏”的因子分较对照组明显下降(P <0.05),而对照组患者“兴趣/社交缺乏”的评分则明显低于同期的研究组患者(P <0.05)。阿立哌唑不良反应发生率小于利培酮(P <0.05)。结论阿立哌唑与利培酮均能改善精神分裂症患者的阴性症状,且总体疗效相似,但阿立哌唑更善于改善患者的情感与认知症状,而利培酮则对患者的情感与行为症状更有效。阿立哌唑的用药安全性总体上优于利培酮。%Objective To explore the efficacy and safety of aripiprazole in treating negtive symptoms of schizophrenia.Methods Eighty patients with schizophrenia were randomly assigned to the experimental group(treated with aripiprazole)and the control group(treated with risperidone),with 40 cases in each group.Positive and Negative Syndrome Scale(PANSS)and Scale for Assessment of Negative Symptoms(SANS)were used before treatment,and at the weekend of 2nd,4th,8th after treatment respectively.Results The scores of PANSS and SANS in both groups were decreased in comparison with those pretreatment(P 0.05).At the 4th,8th weekends of post-treatment,the scores of“poverty of thought”and“abulia”in experimental group were decreased in comparison with those in the control group(P 0.05).The

  2. Metabolic microspheres

    Fox, Sidney W.

    1980-08-01

    A systematic review of catalytic activities in thermal proteinoids and microspheres aggregated therefrom yields some new inferences on the origins and evolution of metabolism. Experiments suggest that, instead of being inert, protocells were already biochemically and cytophysically competent. The emergence and refinement of metabolism ab initio is thus partly traced conceptually. When the principle of molecular self-instruction, as of amino acids in peptide synthesis, is taken into account as a concomitant of natural selection, an expanded theory of organismic evolution, including saltations, emerges.

  3. Metabolic Syndrome

    ... If you already have metabolic syndrome, making these healthy lifestyle choices can help reduce your risk of heart disease and other health problems. If lifestyle changes alone can’t control your ... to help. Maintain a healthy weight Your doctor can measure your body mass ...

  4. Nucleotide Metabolism

    Martinussen, Jan; Willemoës, M.; Kilstrup, Mogens

    2011-01-01

    Metabolic pathways are connected through their utilization of nucleotides as supplier of energy, allosteric effectors, and their role in activation of intermediates. Therefore, any attempt to exploit a given living organism in a biotechnological process will have an impact on nucleotide metabolis...

  5. Metabolic syndrome

    Charles Shaeffer

    2004-01-01

    @@ The emergence of cardiac disease as the number one world-wide cause of death justifies efforts to identify individuals at higher risk for preventive therapy. The metabolic syndrome, originally described by Reaven, 1 has been associated with higher cardiovascular disease risk. 2 Type Ⅱ diabetes is also a frequent sequela. 3

  6. Endocrine and Metabolic Adverse Effects of Psychotropic Drugs in Children and Adolescents

    Evrim Aktepe

    2011-12-01

    Full Text Available ABSTRACT Much as an increase in the use of psychotropic drugs is observed in children and adolescents over the last decade, the endocrine and metabolic side effects of these drugs can limit their use. Atypical antipsychotics can cause many side effects, which are not suitable for the developmental periods of children and adolescents, such as those related with thyroid, blood sugar, level of sex hormones, growth rate and bone metabolism. Children are under a more serious risk regarding the weight increasing effects of atypical antipsychotics and weight gain that is not proportionate with age is especially important due to the association between glucose or lipid abnormalities and cardiovascular mortality. Aripiprazole and ziprasidone are the least risky antipsychotic drugs when it comes to metabolic side affects. The antipsychotic drug that is associated with weight increase and diabetes in children and adolescents most is olanzapine. Even though there are no comparative long-term data concerning children, it is suggested by the currently available information that metabolic side effects including dyslipidemia and impaired glucose tolerance are at an alarming level when it comes to long-term treatment with antipsychotics. The most risky agents in terms of hyperglycemia and glucosuria development are olanzapine and clozapine. Use of risperidone and haloperidol should be undertaken with caution since it may bring about the risk of hyperprolactinemia. Among the antidepressants associated with weight loss and suppression of appetite are selective serotonin reuptake inhibitors, bupropion and venlafaxine. Thyroid functions can be affected by lithium, carbamazepine and valproate treatments. It is reported that the side effect most frequently associated with valproate is weight increase. The relationship between valproate treatment and the development of hyperandrogenism and polycystic ovary syndrome in young women should also be kept in mind. [TAF Prev

  7. Clinical Observation on Fluvoxamine and Aripiprazole as Adjunctive Therapy in the Treatment of Obsessive-compulsive Disorders%阿立哌唑辅助氟伏沙明治疗强迫障碍的临床观察

    魏宏强; 康瑞; 李爱玲; 赵秀娟

    2013-01-01

    Objective:To explore the efficacy and safety of fluvoxamine and aripiprazole as adjunctive therapy in the treatment of obsessive-compulsive disorders patients.Method:Total 54 obsessive-compulsive disorders patients were randomly divided into two groups:Fluvoxamine(250-300 mg/d)auxiliaried by aripiprazole(2.5-10 mg/d)group(study group)and fluvoxamine(250-300 mg/d)group(contral group),27 for each. Each group had a 8-week treatment.The efficacy were assessed and analyzed by Yale-Brown Obsessive Compulsive Scale(Y-BOCS) at baseline and at week 2,4,6 and 8. The side effects were assessed by Treatment Emergent Syptom Scale(TESS)during the treatment. Result:Study group and contral group had 1,2 case being off respectively. The obsession and compulsion scores of study group had all statistical difference at baseline and week 2,4 ,6,8 each other(P0.05). At week 4,in both groups,the compulsion scores had statistical difference(P0.05). Conclusion:Fluvoxamine and aripiprazole as adjunctive therapy can effectively continue to improve the compulsive symptoms in the treatment of obsessive-compulsive disorders patients,the rate of side effects is similar to that of simple fluvoxamine therapy.%  目的:探讨阿立哌唑辅助氟伏沙明治疗强迫障碍的临床疗效及安全性.方法:将54例强迫障碍患者随机分为两组(各27例):阿立哌唑(2.5~10 mg/d)辅助氟伏沙明(250~300 mg/d)组(研究组)、氟伏沙明(250~300 mg/d)组(对照组),治疗观察期均为8周.两组患者于基线及治疗2、4、6、8周末分别评定Yale-Brown强迫量表(Y-BOCS),并采用副反应量表(TESS)评定治疗期间的不良反应.结果:研究组、对照组分别脱落1例、2例.研究组的强迫思维和强迫行为评分在基线及2、4、6、8周末时点间比较差异均有统计学意义(P0.05);4周末时,两组间的强迫行为评分比较差异有统计学意义(P0.05).结论:阿立哌唑辅助氟伏沙明可有效、持续地改善强迫障

  8. A Comparative Study on Aripiprazole and Sulpiride in Treating Schizophrenia Negative Symptoms%阿立哌唑与舒必利治疗精神分裂症阴性症状对照研究

    陈妙扬; 肖垚南; 陈丁玲; 黎艳芳

    2014-01-01

    Objective To evaluate the efficacy and safety of aripiprazole and sulpiride in treatment of schizophrenia negative symptoms. Methods 120 cases of schizophrenia whose predominant clin-ical features were negative symptoms were randomly assigned to treat with either aripiprezole or sulpiride for 3 months each. They were all assessed by SANS and TESS. Results There was a significant difference in efficacy between the groups assessed by SANS. Side effects of aripiprezole were significantly fewer than sulpiride assessed by TESS. Conclusions Aripiprazole has better ef-fect on schizophrenia whose negative symptoms as target symptom and less side effects.%目的:比较阿立哌唑与舒必利治疗精神分裂症阴性症状的疗效和安全性。方法选取120例符合中国精神疾病诊断标准(CCMD3)诊断为精神分裂症且以阴性症状为主的患者,根据随机对照的方法分为研究组(60例)和对照组(60例),研究组应用阿立哌唑治疗,对照组舒必利治疗,疗程均为3个月;用阴性症状评定量表(SANS)、用药物副反应量表(TESS)进行评定。结果两组治疗前后1个月比较有显著性差异(P<0.05),治疗后2、3个月与治疗前比较亦有显著性差异(P<0.05);两组药物副反应比较,阿立哌唑组明显舒必利组少,有显著性差异(P<0.05)。结论阿立哌唑对分裂症阴性症状有较好的治疗效果,药物副反应少,使用安全较高。

  9. Blueberries and Metabolic Syndrome

    Metabolic Syndrome is a cluster of metabolic disorders that increase the risk of cardiovascular diseases. Type 2 diabetes, elevated blood pressure, and atherogenic dyslipidemia are among the metabolic alterations that predispose the individual to several adverse cardiovascular complications. The hea...

  10. Carbohydrate Metabolism Disorders

    ... in your body tissues. If you have a metabolic disorder, something goes wrong with this process. Carbohydrate metabolism disorders are a group of metabolic disorders. Normally your enzymes break carbohydrates down into glucose ( ...

  11. Immunomodulatory Pathways and Metabolism

    Bhargava, Prerna

    2012-01-01

    Energy metabolism plays a vital role in normal physiology, adaptive responses and host defense mechanisms. Research throughout the last decade has shown evidence that immune pathways communicate with metabolic pathways to alter the metabolic status in response to physiological or pathological signals. In this thesis, I will explore how immunomodulatory molecules affect metabolic homeostasis and conversely, how metabolic sensing pathways modulate immune responses. The first part my work utiliz...

  12. 阿立哌唑治疗双相障碍躁狂发作的临床疗效及安全性%The effects and safety of aripiprazole in the treatment of bipolar disorder typelmanic episode

    蒋正伟

    2016-01-01

    目的 探讨阿立哌唑治疗双相障碍躁狂发作的临床疗效及安全性.方法 选取 2014 年 1 月—2015年 1 月在徐州精神病院治疗的 94 例双相障碍躁狂发作患者,按照治疗药物的不同分为对照组 40 例和研究组 54 例,对照组患者采用丙戊酸钠缓释片治疗,研究组患者采用阿立派唑治疗,比较两组患者的临床疗效及不良反应发生情况.结果 杨氏躁狂评定量表(YMRS)评分时间和方法无交互作用(P > 0. 05),时间间比较,差异有统计学意义(P 0. 05),时间间比较,差异有统计学意义(P 0. 05),治疗 7、14d 两组患者 YMRS 和 CIG - S - BP 评分比较,差异有统计学意义(P 0. 05),comparison between time,the differences were statistically significant(P 0. 05),comparison between time,the differences were statistically significant(P 0. 05),7,14d after treatment YMRS and CGI - S - BP scores between the two groups showed significant differences(P < 0. 05). The incidence of extrapyramidal symptoms between the two groups showed significant differences(P < 0. 05). Conclusion Aripiprazole has sure effect in the treatment of bipolar disorder typelmanic episode,and has good safety

  13. Inborn errors of metabolism

    ... metabolism. A few of them are: Fructose intolerance Galactosemia Maple sugar urine disease (MSUD) Phenylketonuria (PKU) Newborn ... disorder. Alternative Names Metabolism - inborn errors of Images Galactosemia References Bodamer OA. Approach to inborn errors of ...

  14. Cancer stem cell metabolism

    Peiris-Pagès, Maria; Martinez-Outschoorn, Ubaldo E.; Pestell, Richard G.; Sotgia, Federica; Lisanti, Michael P

    2016-01-01

    Cancer is now viewed as a stem cell disease. There is still no consensus on the metabolic characteristics of cancer stem cells, with several studies indicating that they are mainly glycolytic and others pointing instead to mitochondrial metabolism as their principal source of energy. Cancer stem cells also seem to adapt their metabolism to microenvironmental changes by conveniently shifting energy production from one pathway to another, or by acquiring intermediate metabolic phenotypes. Deter...

  15. Metabolic Syndrome and Migraine

    Sachdev, Amit; Marmura, Michael J.

    2012-01-01

    Migraine and metabolic syndrome are highly prevalent and costly conditions. The two conditions coexist, but it is unclear what relationship may exist between the two processes. Metabolic syndrome involves a number of findings, including insulin resistance, systemic hypertension, obesity, a proinflammatory state, and a prothrombotic state. Only one study addresses migraine in metabolic syndrome, finding significant differences in the presentation of metabolic syndrome in migraineurs. However, ...

  16. Clinical efficacy and safety of lithium carbonate combined with aripiprazole in treatment of bipolar depression%碳酸锂联合阿立哌唑治疗双相障碍抑郁发作的疗效和安全性

    粟幼嵩; 陈俊; 李则挚; 王勇; 黄佳; 方贻儒; 王祖承

    2011-01-01

    目的 探讨碳酸锂联合阿立哌唑治疗双相障碍抑郁发作的疗效和安全性.方法 81例双相障碍抑郁发作患者随机分为联合用药组(n=42)和锂盐组(n=39),分别给予碳酸锂联合阿立哌唑治疗或单用碳酸锂治疗,持续8周.在基线期及治疗第1、2、4、8周末,采用17项汉密顿抑郁量表(HAMD-17)和Young躁狂评定量表(YMRS)评定疗效,计算治疗有效率,采用治疗时出现的症状量表(TESS)评定不良反应.结果 基线期两组HAMD-17评分差异无统计学意义(P>0.05),治疗第1、2、4周末联合用药组HAMD-17评分显著低于锂盐组(P<0.05或P<0.01);治疗第8周末联合用药组HAMD-17评分低于锂盐组,但差异无统计学意义(P>0.05).两组基线期及治疗各阶段的YMRS评分均<7.两组治疗有效率和不良反应发生率比较差异均无统计学意义(P>0.05).结论 与单用碳酸锂比较,碳酸锂联合阿立哌唑治疗双相障碍抑郁发作起效快,疗效相似,不良反应无明显增加.%Objective To investigate the clinical efficacy and safety of lithium carbonate combined with aripiprazole in treatment of bipolar depression. Methods Eighty-one patients with bipolar depression were randomly divided into lithium carbonate combined with aripiprazole group (re = 42) or lithium carbonate group ( n = 39), and were treated with lithium carbonate combined with aripiprazole and lithium carbonate for 8 weeks respectively. At the baseline and the end of fthe irst, second, fourth and eighth week of treatment, Hamilton Depression Scale-17 ( HAMD-17) and Young Mania Rating Scale (YMRS) were employed to evaluate the clinical efficacy, the effective rates were calculated, and Treatment Emergent Symptom Scale (TESS) was adopted to assess the side effects. Results There was no significant difference in HAMD-17 score between two group at the baseline (P>0.05), while HAMD-17 scores at the end of first, second and fourth week of treatment in lithium

  17. Metabolic Engineering X Conference

    Flach, Evan [American Institute of Chemical Engineers

    2015-05-07

    The International Metabolic Engineering Society (IMES) and the Society for Biological Engineering (SBE), both technological communities of the American Institute of Chemical Engineers (AIChE), hosted the Metabolic Engineering X Conference (ME-X) on June 15-19, 2014 at the Westin Bayshore in Vancouver, British Columbia. It attracted 395 metabolic engineers from academia, industry and government from around the globe.

  18. Mathematical modelling of metabolism

    Gombert, Andreas Karoly; Nielsen, Jens

    2000-01-01

    Mathematical models of the cellular metabolism have a special interest within biotechnology. Many different kinds of commercially important products are derived from the cell factory, and metabolic engineering can be applied to improve existing production processes, as well as to make new process...... availability of genomic information and powerful analytical techniques, mathematical models also serve as a tool for understanding the cellular metabolism and physiology.......Mathematical models of the cellular metabolism have a special interest within biotechnology. Many different kinds of commercially important products are derived from the cell factory, and metabolic engineering can be applied to improve existing production processes, as well as to make new processes...

  19. Integrative metabolic engineering

    George H McArthur IV

    2015-07-01

    Full Text Available Recent advances in experimental and computational synthetic biology are extremely useful for achieving metabolic engineering objectives. The integration of synthetic biology and metabolic engineering within an iterative design-build-test framework will improve the practice of metabolic engineering by relying more on efficient design strategies. Computational tools that aid in the design and in silico simulation of metabolic pathways are especially useful. However, software helpful for constructing, implementing, measuring and characterizing engineered pathways and networks should not be overlooked. In this review, we highlight computational synthetic biology tools relevant to metabolic engineering, organized in the context of the design-build-test cycle.

  20. Metabolic enzymes link morphine withdrawal with metabolic disorder

    Xi Jiang; Jing Li; Lan Ma

    2007-01-01

    @@ Energy metabolism is a fundamental biological process that is vital for the survival of all species. Disorders in the metabolic system result in deficiency or redundancy of certain nutrients, including carbohydrates, lipids, amino acids, etc. Abnormality of the energy metabolism system leads to a number of metabolic diseases, such as the metabolic syndrome. Broadly speaking, the term "metabolic diseases" now tends to be widened to the category that refers to all diseases with metabolism disorder.

  1. Metabolic syndrome and migraine

    Amit eSachdev

    2012-11-01

    Full Text Available Migraine and metabolic syndrome are highly prevaleirnt and costly conditions.The two conditions coexist, but it is unclear what relationship may exist between the two processes. Metabolic syndrome involves a number of findings, including insulin resistance, systemic hypertension, obesity, a proinflammatory state, and a prothrombotic state. Only one study addresses migraine in metabolic syndrome, finding significant differences in the presentation of metabolic syndrome in migraineurs. However, controversy exists regarding the contribution of each individual risk factor to migraine pathogensis and prevalence. It is unclear what treatment implications, if any, exist as a result of the concomitant diagnosis of migraine and metabolic syndrome. The cornerstone of migraine and metabolic syndrome treatments is prevention, relying heavily on diet modification, sleep hygiene, medication use, and exercise.

  2. Inflammasomes and metabolic disease.

    Henao-Mejia, Jorge; Elinav, Eran; Thaiss, Christoph A; Flavell, Richard A

    2014-01-01

    Innate immune response pathways and metabolic pathways are evolutionarily conserved throughout species and are fundamental to survival. As such, the regulation of whole-body and cellular metabolism is intimately integrated with immune responses. However, the introduction of new variables to this delicate evolutionarily conserved physiological interaction can lead to deleterious consequences for organisms as a result of inappropriate immune responses. In recent decades, the prevalence and incidence of metabolic diseases associated with obesity have dramatically increased worldwide. As a recently acquired human characteristic, obesity has exposed the critical role of innate immune pathways in multiple metabolic pathophysiological processes. Here, we review recent evidence that highlights inflammasomes as critical sensors of metabolic perturbations in multiple tissues and their role in the progression of highly prevalent metabolic diseases. PMID:24274736

  3. Engineering Cellular Metabolism

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds......, and pharmaceuticals. However, making cells into efficient factories is challenging because cells have evolved robust metabolic networks with hard-wired, tightly regulated lines of communication between molecular pathways that resist efforts to divert resources. Here, we will review the current status and challenges...... of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

  4. 阿立哌唑合并康复训练改善精神分裂症患者生活质量的临床研究%Clinical Study of Aripiprazole Combined with Rehabilitation Training to Improve the Quality of Life in Patients with Schizophrenia

    程闯; 张新风

    2013-01-01

    Objective:To explore the effect of aripiprazole combined with rehabilitation training in patients with schizophrenia quality of life of the spirit.Method:Met the Chinese classification and diagnostic criteria of mental disorders Third Edition(CCMD-3)criteria for the diagnosis of 90 patients with schizophrenia were randomly divided into two groups,aripiprazole and clozapine in the treatment of,a total of 8 weeks,two groups were psychiatric rehabilitation training. The positive and negative symptoms scale before and after treatment(PANSS)was introduced in June to assess the efficacy,the side effects scale(TESS)assessment of adverse reactions,the WHO quality of life scale(WHOQOL-100)assessment of quality of life.Result:Aripiprazole group and clozapine group markedly effective rate were 73.3%and 75.6%,with no significant difference between two groups(P>0.05);4,8 weeks after treatment,two groups of PANSS scale scores were decreased than that before treatment(P0.05);治疗后4、8周,两组PANSS量表各项因子分均较治疗前下降(P<0.05),但治疗后8周阿立哌唑组阴性症状及一般精神病理分较氯氮平组差异有统计学意义(P<0.05);阿立哌唑组不良反应发生率显著低于氯氮平组(P<0.05);治疗6个月后两组在(WHOQOL-100)量表各领域均较治疗前有统计学意义(P<0.05),但阿立哌唑组在生理领域、心理领域、社会关系领域、精神支柱、生活质量方面较氯氮平组差异有统计学意义(P<0.05)。结论:阿立哌唑治疗精神分裂症疗效与氯氮平相仿,不良反应少,合并精神康复治疗可显著改善精神分裂症患者的生活质量。

  5. 阿立哌唑合并抗抑郁药治疗抑郁症的临床疗效及安全性研究%Study on the clinical effect and safety of aripiprazole combined with antidepressants in the treatment of depression

    姜美俊

    2014-01-01

    目的:探讨阿立哌唑合并抗抑郁药(三环类抗抑郁剂阿米替林)治疗抑郁症的临床疗效及安全性。方法选择120例抑郁症患者随机分为研究组和对照组。对照组给予常规抗抑郁药物治疗,研究组在常规抗抑郁治疗基础上给予阿立哌唑。采用汉密尔顿抑郁量表和副反应量表对两组患者治疗前和治疗后进行评定。结果研究组治疗后的第1、2、4、6周汉密尔顿抑郁量表评分分别与对照组同期比较,差异有统计学意义(P0.05)。结论阿立哌唑能够提高抗抑郁药(三环类抗抑郁剂阿米替林)治疗抑郁症的临床治疗效果,可作为临床抗抑郁治疗的一种增效手段。%Objective To study clinical effect and safety of aripiprazole combined with antidepressants(tricyclic antidepressants amitriptyline) in the treatment of depression. Methods From January 2010 to December 2013, 120 patients with depression patients were selected and randomly divided into study group and control group , control group was given regular treatment of antidepressant drugs, study group was given aripiprazole combined with antidepressants(tricyclic antidepressants amitriptyline). The Hamilton Depression Scale (HAMD) and Treatment Emergent Symptom Scale (TESS) were used in the two group s of patients before and after treatment. Results Hamilton Depression Scale scores in the study group after treatment of the first week, second week, fourth week and sixth week of study group was compared with those in control group , the difference was statistically significant(P0.05). Conclusion Aripiprazole can improve the clinical efficacy of antidepressants (tricyclic antidepressants amitriptyline) in the treatment of depression, which can be one of the augmentations in the treatment of depression.

  6. What is Nutrition & Metabolism?

    Feinman Richard D; Hussain M Mahmood

    2004-01-01

    Abstract A new Open Access journal, Nutrition & Metabolism (N&M) will publish articles that integrate nutrition with biochemistry and molecular biology. The open access process is chosen to provide rapid and accessible dissemination of new results and perspectives in a field that is of great current interest. Manuscripts in all areas of nutritional biochemistry will be considered but three areas of particular interest are lipoprotein metabolism, amino acids as metabolic signals, and the effec...

  7. METABOLISM OF IRON STORES

    Saito, Hiroshi

    2014-01-01

    ABSTRACT Remarkable progress was recently achieved in the studies on molecular regulators of iron metabolism. Among the main regulators, storage iron, iron absorption, erythropoiesis and hepcidin interact in keeping iron homeostasis. Diseases with gene-mutations resulting in iron overload, iron deficiency, and local iron deposition have been introduced in relation to the regulators of storage iron metabolism. On the other hand, the research on storage iron metabolism has not advanced since th...

  8. N-dealkylation of arylpiperazine derivatives: disposition and metabolism of the 1-aryl-piperazines formed.

    Caccia, Silvio

    2007-08-01

    In recent years several arylpiperazine derivatives have reached the stage of clinical application, mainly for the treatment of depression, psychosis or anxiety. Examples are the pyrimidinylpiperazine buspirone, the chlorophenylpiperazine derivatives nefazodone and trazodone, the dichlorophenylpiperazine aripiprazole and the benzisothiazolyl derivatives perospirone and ziprasidone. Most of them undergo extensive pre-systemic and systemic metabolism including CYP3A4-dependent N-dealkylation to 1-aryl-piperazines. These metabolites are best known for the variety of serotonin receptor-related effects they cause in man and animals, although some have affinity for other neurotransmitter receptors; others, however, are still largely unexplored despite uncontrolled use as amphetamine-like designer drugs. Once formed they distribute extensively in tissues, including brain which is the target site of most arylpiperazine derivatives, and are then primarily biotransformed by CYP2D6-dependent oxidation to hydroxylates which are excreted as conjugates; only 1-(2-benzisothiazolyl)-piperazine is more susceptible to sulfur oxidation than to aromatic hydroxylation. In studies analysing animal brain and human blood, 1-aryl-piperazine concentrations were either higher or lower than the parent compound(s), although information is available only for some derivatives. At steady state, the metabolite-to-parent drug ratios varied widely among individuals taking the same dosage of the same arylpiperazine derivative. This is consistent with the known individual variability in the expression and activity of CYP3A4 and CYP2D6. This review also surveys current published information on physiological and pathological factors affecting the 1-aryl-piperazine-to-parent drug ratios and examines the potential role of 1-aryl-piperazine formation in the pharmacological actions of the arylpiperazine derivatives that are already or will shortly be available in major markets. PMID:17691920

  9. Mevalonate metabolism in cancer.

    Gruenbacher, Georg; Thurnher, Martin

    2015-01-28

    Cancer cells are characterized by sustained proliferative signaling, insensitivity to growth suppressors and resistance to apoptosis as well as by replicative immortality, the capacity to induce angiogenesis and to perform invasive growth. Additional hallmarks of cancer cells include the reprogramming of energy metabolism as well as the ability to evade immune surveillance. The current review focuses on the metabolic reprogramming of cancer cells and on the immune system's capacity to detect such changes in cancer cell metabolism. Specifically, we focus on mevalonate metabolism, which is a target for drug and immune based cancer treatment. PMID:24467965

  10. Fatty acid metabolism: target for metabolic syndrome

    Wakil, Salih J.; Abu-Elheiga, Lutfi A.

    2009-01-01

    Fatty acids are a major energy source and important constituents of membrane lipids, and they serve as cellular signaling molecules that play an important role in the etiology of the metabolic syndrome. Acetyl-CoA carboxylases 1 and 2 (ACC1 and ACC2) catalyze the synthesis of malonyl-CoA, the substrate for fatty acid synthesis and the regulator of fatty acid oxidation. They are highly regulated and play important roles in the energy metabolism of fatty acids in animals, including humans. They...

  11. Cold-induced metabolism

    Lichtenbelt, W. van Marken; Daanen, H.A.M.

    2003-01-01

    Purpose of review Cold response can be insulative (drop in peripheral temperature) or metabolic (increase in energy expenditure). Nonshivering thermogenesis by sympathetic, norepinephrine-induced mitochondrial heat production in brown adipose tissue is a well known component of this metabolic respon

  12. Metabolic syndrome and menopause

    Jouyandeh Zahra

    2013-01-01

    Full Text Available Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3 criteria to classify subjects as having metabolic syndrome. Results Total prevalence of metabolic syndrome among our subjects was 30.1%. Waist circumference, HDL-cholesterol, fasting blood glucose, diastolic blood pressure ,Systolic blood pressure, and triglyceride were significantly higher among women with metabolic syndrome (P-value Conclusions Our study shows that postmenopausal status is associated with an increased risk of metabolic syndrome. Therefore, to prevent cardiovascular disease there is a need to evaluate metabolic syndrome and its components from the time of the menopause.

  13. Metabolic Engineering VII Conference

    Kevin Korpics

    2012-12-04

    The aims of this Metabolic Engineering conference are to provide a forum for academic and industrial researchers in the field; to bring together the different scientific disciplines that contribute to the design, analysis and optimization of metabolic pathways; and to explore the role of Metabolic Engineering in the areas of health and sustainability. Presentations, both written and oral, panel discussions, and workshops will focus on both applications and techniques used for pathway engineering. Various applications including bioenergy, industrial chemicals and materials, drug targets, health, agriculture, and nutrition will be discussed. Workshops focused on technology development for mathematical and experimental techniques important for metabolic engineering applications will be held for more in depth discussion. This 2008 meeting will celebrate our conference tradition of high quality and relevance to both industrial and academic participants, with topics ranging from the frontiers of fundamental science to the practical aspects of metabolic engineering.

  14. Metabolism in cancer metastasis.

    Weber, Georg F

    2016-05-01

    Cancer metabolism has regained substantial research interest over recent years. The focus has been mostly on the primary tumor, while metabolic adjustments during dissemination have been less extensively researched. Deadhesion impairs glucose transport and brings about an ATP deficit that leads to apoptosis. To survive, metastasizing cancer cells need to increase ATP synthesis, which involves mitochondrial activity and is accomplished in part through peroxide signaling. This change in metabolism, associated with cancer spread, is different from the Warburg effect. Therefore it is important to distinguish between the metabolic adjustments in primary tumor cells and those in disseminating tumor cells. In general, it is likely that metabolic responses to environmental cues commonly occur in cell biology. PMID:26355498

  15. Regulation of lipid metabolism

    Peng LI

    2011-01-01

    @@ Lipids including cholesterol, phospholipids, fatty acids and triacylglycerols are important cellular constituents involved in membrane structure, energy homeostasis and many biological processes such as signal transduction, organelle development and cell differentiation.Recently, the area of lipid metabolism has drawn a great deal of attention due to its emerging role in the development of metabolic disorders such as obesity, diabetes, atherosclerosis and liver steatosis.We decided to organize a special issue of Frontiers in Biology focusing on our current understanding of lipid metabolism.

  16. NMR studies of metabolism

    In this paper, the authors present applications of NMR to the study of different aspects of metabolism. The authors begin with a brief outline of localization methods that are commonly used to obtain in vivo NMR spectra. The authors then describe in more detail metabolic information recently obtained by NMR of perfused organs, intact animals, and humans. Previous reviews have already covered the applications of NMR to the study of metabolism in microorganisms, isolated or cultivated cells, and tumors. NMR spectroscopy of the brain, and human in vivo NMR spectroscopy have also been reviewed

  17. Insect flight muscle metabolism

    Horst, D.J. van der; Beenakkers, A.M.Th.; Marrewijk, W.J.A. van

    1984-01-01

    The flight of an insect is of a very complicated and extremely energy-demanding nature. Wingbeat frequency may differ between various species but values up to 1000 Hz have been measured. Consequently metabolic activity may be very high during flight and the transition from rest to flight is accompanied by an increase of 50-100-fold in metabolic rate. Small mammals running at maximal speed and flying birds achieve metabolic rates exceeding resting levels by only 7-14-fold. The exaggerated meta...

  18. A Metabolic Switch

    Hjorth, Poul G.

    Our muscles are metabolically flexible, i.e., they are capable of `switching' between two types of oxidation: (1) when fasting, a predominantly lipid oxidation with high rates of fatty acid uptake, and (2) when fed, suppression of lipid oxidation in favour of increased glucose uptake, oxidation and...... storage, in response to insulin. One of the many manifestations of obesity and Type 2 diabetes is an insulin resistance of the skeletal muscles, which suppresses this metabolic switch. This talk describes recent development of a low-dimensional system of ODEs that model the metabolic switch, displaying a...

  19. Efeitos adversos metabólicos de antipsicóticos e estabilizadores de humor Metabolic side effects of antipsychotics and mood stabilizers

    Paulo José Ribeiro Teixeira

    2006-08-01

    use of lithium and valproic acid once again directed the attention to their metabolic effects. This study aims to review the medical literature with regard to metabolic side effects associated with the use of antipsychotics and mood stabilizers. METHOD: Research was carried out at MEDLINE and LILACS through October 2005. CONCLUSION: Metabolic side effects remain a major concern for psychopharmacology. Clinically relevant weight gain occurs frequently in patients taking antipsychotics and mood stabilizers, particularly clozapine, olanzapine, lithium, and valproic acid. Clozapine and olanzapine are also associated with higher incidence of diabetes mellitus and dyslipidemias, either due to weight gain or because of a direct deleterious action on glucose metabolism. Incidence of obesity and other metabolic disorders is lower with risperidone when compared to olanzapine or clozapine. Carbamazepine is associated with lower weight gain when compared to lithium or valproic acid. Drugs such as haloperidol, ziprasidone, aripiprazole and lamotrigine are not associated with significant weight gain or with higher incidence of diabetes mellitus. They are alternatives for patients more likely to develop these adverse effects.

  20. What is Metabolic Syndrome?

    ... becoming more common due to a rise in obesity rates among adults. In the future, metabolic syndrome may overtake smoking as the leading risk factor for heart disease. It is possible to prevent or delay ...

  1. Metabolism and Endocrinology

    2012-01-01

    2012040 Analysis of risk factors of metabolic syndrome in obese subjects:a follow-up study. ZHU Lüyun(朱旅云),et al.Dept Endocrinol,Bethune Internatl Peace Hosp,PLA,Shijiazhuang 050082.Chin JEndocrinol

  2. Engineering of metabolic control

    Liao, James C.

    2006-10-17

    The invention features a method of producing heterologous molecules in cells under the regulatory control of a metabolite and metabolic flux. The method can enhance the synthesis of heterologous polypeptides and metabolites.

  3. What is Nutrition & Metabolism?

    Feinman Richard D

    2004-08-01

    Full Text Available Abstract A new Open Access journal, Nutrition & Metabolism (N&M will publish articles that integrate nutrition with biochemistry and molecular biology. The open access process is chosen to provide rapid and accessible dissemination of new results and perspectives in a field that is of great current interest. Manuscripts in all areas of nutritional biochemistry will be considered but three areas of particular interest are lipoprotein metabolism, amino acids as metabolic signals, and the effect of macronutrient composition of diet on health. The need for the journal is identified in the epidemic of obesity, diabetes, dyslipidemias and related diseases, and a sudden increase in popular diets, as well as renewed interest in intermediary metabolism.

  4. Metabolic Engineering of Bacteria

    Kumar, Ravi R.; Prasad, Satish

    2011-01-01

    Yield and productivity are critical for the economics and viability of a bioprocess. In metabolic engineering the main objective is the increase of a target metabolite production through genetic engineering. Metabolic engineering is the practice of optimizing genetic and regulatory processes within cells to increase the production of a certain substance. In the last years, the development of recombinant DNA technology and other related technologies has provided new tools for approaching yield...

  5. Tobacco and metabolic syndrome

    Yatan Pal Singh Balhara

    2012-01-01

    Full Text Available Tobacco is a leading contributor to morbidity and mortality globally. Metabolic syndrome is a constellation of abdominal obesity, atherogenic dyslipidemia, raised blood pressure, insulin resistance (with and without glucose intolerance, pro-inflammatory state, and pro-thrombotic state. Tobacco use is associated with various core components of metabolic syndrome. It has been found to play a causal role in various pathways leading on to development this condition, the current article discusses various facets of this association.

  6. Oxidative metabolism in muscle.

    Ferrari, M; Binzoni, T.; Quaresima, V.

    1997-01-01

    Oxidative metabolism is the dominant source of energy for skeletal muscle. Near-infrared spectroscopy allows the non-invasive measurement of local oxygenation, blood flow and oxygen consumption. Although several muscle studies have been made using various near-infrared optical techniques, it is still difficult to interpret the local muscle metabolism properly. The main findings of near-infrared spectroscopy muscle studies in human physiology and clinical medicine are summarized. The advantage...

  7. Cold-induced metabolism

    Lichtenbelt, W. van Marken; Daanen, H.A.M.

    2003-01-01

    Purpose of review Cold response can be insulative (drop in peripheral temperature) or metabolic (increase in energy expenditure). Nonshivering thermogenesis by sympathetic, norepinephrine-induced mitochondrial heat production in brown adipose tissue is a well known component of this metabolic response in infants and several animal species. In adult humans, however, its role is less clear. Here we explore recent findings on the role and variability of nonshivering thermogenesis in adults. Rece...

  8. Obesity, metabolism, and hypertension.

    Landsberg, L

    1989-01-01

    The relationship between obesity and hypertension is complex and poorly understood. A developing body of information suggests that metabolic factors related to the obese state are importantly involved. The pertinent observations include: (1) Diet influences sympathetic nervous system activity. Fasting suppresses, while carbohydrate and fat feeding stimulate, sympathetic activity. (2) Dietary-induced changes in sympathetic activity contribute to the changes in metabolic rate that accompany cha...

  9. Hereditary and metabolic myelopathies.

    Hedera, Peter

    2016-01-01

    Hereditary and metabolic myelopathies are a heterogeneous group of neurologic disorders characterized by clinical signs suggesting spinal cord dysfunction. Spastic weakness, limb ataxia without additional cerebellar signs, impaired vibration, and positional sensation are hallmark phenotypic features of these disorders. Hereditary, and to some extent, metabolic myelopathies are now recognized as more widespread systemic processes with axonal loss and demyelination. However, the concept of predominantly spinal cord disorders remains clinically helpful to differentiate these disorders from other neurodegenerative conditions. Furthermore, metabolic myelopathies are potentially treatable and an earlier diagnosis increases the likelihood of a good clinical recovery. This chapter reviews major types of degenerative myelopathies, hereditary spastic paraplegia, motor neuron disorders, spastic ataxias, and metabolic disorders, including leukodystrophies and nutritionally induced myelopathies, such as vitamin B12, E, and copper deficiencies. Neuroimaging studies usually detect a nonspecific spinal cord atrophy or demyelination of the corticospinal tracts and dorsal columns. Brain imaging can be also helpful in myelopathies caused by generalized neurodegeneration. Given the nonspecific nature of neuroimaging findings, we also review metabolic or genetic assays needed for the specific diagnosis of hereditary and metabolic myelopathies. PMID:27430441

  10. Human metabolic atlas: an online resource for human metabolism

    Pornputtapong, Natapol; Nookaew, Intawat; Nielsen, Jens

    2015-01-01

    Human tissue-specific genome-scale metabolic models (GEMs) provide comprehensive understanding of human metabolism, which is of great value to the biomedical research community. To make this kind of data easily accessible to the public, we have designed and deployed the human metabolic atlas (HMA) website (http://www.metabolicatlas.org). This online resource provides comprehensive information about human metabolism, including the results of metabolic network analyses. We hope that it can also...

  11. Atypical antipsychotics are not all alike: side effects and risk assessment.

    Howland, Robert H

    2014-09-01

    Atypical antipsychotic drugs are not all alike with respect to their pharmacologies, therapeutic uses, and side eff ects, although many clinicians lump them together and do not distinguish among them. Risk assessment for the potential use of a drug, such as aripiprazole (Abilify), should not focus on any particular adverse effect, but rather should consider risk assessment in a broader context. Specifically, what are the alternatives, and what are their inherent risk profiles? What is the risk of no treatment? Side eff ects commonly associated with a particular drug or class of drugs can also occur with other drugs. For any drug prescribed for any reason, prescribers should document discussion about common and potentially serious adverse effects, as well as document clinical monitoring. Alternative treatments and their inherent risks, along with the risks of not taking medication for a particular condition, should also be discussed with patients and documented. PMID:25346958

  12. 喹硫平利培酮阿立哌唑对精神分裂症患者认知功能的影响%The effect of quetiapine,risperidone and aripiprazole on cog-nitive function of schizophrenia patients

    鞠康; 陈思路; 谢茹韵; 高炬; 孙祝平; 季卫东

    2015-01-01

    目的:探讨喹硫平、利培酮和阿立哌唑对精神分裂症患者临床疗效及认知功能的影响。方法将154例精神分裂症患者分为3组,分别口服喹硫平(65例)、利培酮(47例)和阿立哌唑(42例)治疗,观察24周。采用阳性与阴性症状量表评定临床疗效,重复性成套神经心理状态测验评定认知功能。结果治疗24周末3组阳性与阴性症状量表评分均有显著改善,但喹硫平组改善阳性症状显著优于利培酮组和阿立哌唑组(P<0.05);3组重复性成套神经心理状态测验的9个因子分比较差异有显著性( P<0.05或0.01),阿立哌唑组对8个因子分的改善优于其他2组。不同性别、文化程度患者的认知功能改善有显著性差异(P<0.05)。合并躯体疾病患者认知功能的改善显著差于单纯精神分裂症患者(P<0.05)。结论喹硫平、利培酮和阿立哌唑均能显著改善精神分裂症患者的各种精神症状及认知功能;合并躯体疾病的患者认知功能改善差于单纯精神分裂症患者,性别、文化程度是影响认知功能改变的重要因素。%Objective To explore the efficacy of quetiapine ,risperidone and aripiprazole in schizophrenia patients and their effects on cognitive functions .Methods A total of 154 schizophrenics were assigned to three groups taking orally quetiapine (n=65) ,risperidone (n=47) or aripiprazole (n=42) for 24 weeks . Efficacies were assessed with the Positive and Negative Syndrome Scale (PANSS) and cognitive functions with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) .Results In the 24th week the PANSS scores of 3 groups improved more significantly ,so did that in quetiapine than risperi‐done and aripiprazole group (P<0 .05);there were significant differences in 9 factor scores of the RBANS among 3 groups (P<0 .05 or 0 .01) ,8 factor scores improved more significantly in

  13. Robustness of metabolic networks

    Jeong, Hawoong

    2009-03-01

    We investigated the robustness of cellular metabolism by simulating the system-level computational models, and also performed the corresponding experiments to validate our predictions. We address the cellular robustness from the ``metabolite''-framework by using the novel concept of ``flux-sum,'' which is the sum of all incoming or outgoing fluxes (they are the same under the pseudo-steady state assumption). By estimating the changes of the flux-sum under various genetic and environmental perturbations, we were able to clearly decipher the metabolic robustness; the flux-sum around an essential metabolite does not change much under various perturbations. We also identified the list of the metabolites essential to cell survival, and then ``acclimator'' metabolites that can control the cell growth were discovered. Furthermore, this concept of ``metabolite essentiality'' should be useful in developing new metabolic engineering strategies for improved production of various bioproducts and designing new drugs that can fight against multi-antibiotic resistant superbacteria by knocking-down the enzyme activities around an essential metabolite. Finally, we combined a regulatory network with the metabolic network to investigate its effect on dynamic properties of cellular metabolism.

  14. Nutrition and metabolic syndrome.

    Albornoz López, Raúl

    2012-12-01

    Full Text Available The metabolic syndrome comprises a cluster of metabolic abnormalities that increase the risk for cardiovascular disease and type 2 diabetes mellitus. The exact etiology is unclear, although it is known thatthere is a complex interaction between genetic, metabolic and environmental factors. Among the environmental factors, dietary habits play an important role in the treatment and prevention of this condition. General classic recommendations include control of obesity, increased physical activity, decreased intake of saturated fat and cholesterol, reduced intake of simple sugars and increased intake of fruits and vegetables. It has been studied the influence of diets low in carbohydrates, diets rich in polyunsaturated and monounsaturated fatty acids, fiber intake, the Mediterranean diet and the glycemic index in relation to metabolic syndrome.Other nutrients recently studied are the micronutrients (magnesium and calcium, soy and other phytochemicals. Evidence suggests that a healthy diet like the Mediterranean protects against metabolic syndrome,caracterized for a low content in saturated and trans fat, high in monounsaturated and polyunsaturated fatty acids, balanced intake of carbohydrates and high in fiber, fruits and vegetables. There is more controversy about the type of diet of choice for the control ofmetabolic syndrome (low-carbohydrate diets or lowfat, needing more studies on the role of soy and other phytochemicals.

  15. Depleted uranium: Metabolic disruptor?

    The presence of uranium in the environment can lead to long-term contamination of the food chain and of water intended for human consumption and thus raises many questions about the scientific and societal consequences of this exposure on population health. Although the biological effects of chronic low-level exposure are poorly understood, results of various recent studies show that contamination by depleted uranium (DU) induces subtle but significant biological effects at the molecular level in organs including the brain, liver, kidneys and testicles. For the first time, it has been demonstrated that DU induces effects on several metabolic pathways, including those metabolizing vitamin D, cholesterol, steroid hormones, acetylcholine and xenobiotics. This evidence strongly suggests that DU might well interfere with many metabolic pathways. It might thus contribute, together with other man-made substances in the environment, to increased health risks in some regions. (authors)

  16. Myocardial energy metabolism

    Myocardial Energy Metabolism offers a scientific survey which may be looked upon as complementary to the classical haemodynamic view of the hart. Sections on Basic mechanisms, Models and techniques, and on Clinical implications make this book a worthwhile acquisition for cardiologists, cardiac surgeons, basic scientists in cardiovascular physiology, as well as for students with a more than average interest in the organ. Not all basic questions with regard to formation, breakdown and usage of energy (ATP) in the hart have been asked or answered, but invited experts from the fields of cardiac biochemistry, (electro)physiology, pharmacology, anaesthesiology and clinical cardiological research have covered the subject extensively from their own points of view. Furthermore, Myocardial Energy Metabolism shows how basic scientific knowledge may be integrated into cardiological practice. The potential that new techniques like NMR and PET-scanning may offer to the cardiologist of the near future becomes particularly clear when the heart is studied with regard to its energy metabolism

  17. Endocannabinoids and Metabolic Disorders.

    Gatta-Cherifi, Blandine; Cota, Daniela

    2015-01-01

    The endocannabinoid system (ECS) is known to exert regulatory control on essentially every aspect related to the search for, and the intake, metabolism and storage of calories, and consequently it represents a potential pharmacotherapeutic target for obesity, diabetes and eating disorders. While the clinical use of the first generation of cannabinoid type 1 (CB(1)) receptor blockers has been halted due to the psychiatric side effects that their use occasioned, recent research in animals and humans has provided new knowledge on the mechanisms of actions of the ECS in the regulation of eating behavior, energy balance, and metabolism. In this review, we discuss these recent advances and how they may allow targeting the ECS in a more specific and selective manner for the future development of therapies against obesity, metabolic syndrome, and eating disorders. PMID:26408168

  18. Nitrile Metabolizing Yeasts

    Bhalla, Tek Chand; Sharma, Monica; Sharma, Nitya Nand

    Nitriles and amides are widely distributed in the biotic and abiotic components of our ecosystem. Nitrile form an important group of organic compounds which find their applications in the synthesis of a large number of compounds used as/in pharmaceutical, cosmetics, plastics, dyes, etc>. Nitriles are mainly hydro-lyzed to corresponding amide/acid in organic chemistry. Industrial and agricultural activities have also lead to release of nitriles and amides into the environment and some of them pose threat to human health. Biocatalysis and biotransformations are increasingly replacing chemical routes of synthesis in organic chemistry as a part of ‘green chemistry’. Nitrile metabolizing organisms or enzymes thus has assumed greater significance in all these years to convert nitriles to amides/ acids. The nitrile metabolizing enzymes are widely present in bacteria, fungi and yeasts. Yeasts metabolize nitriles through nitrilase and/or nitrile hydratase and amidase enzymes. Only few yeasts have been reported to possess aldoxime dehydratase. More than sixty nitrile metabolizing yeast strains have been hither to isolated from cyanide treatment bioreactor, fermented foods and soil. Most of the yeasts contain nitrile hydratase-amidase system for metabolizing nitriles. Transformations of nitriles to amides/acids have been carried out with free and immobilized yeast cells. The nitrilases of Torulopsis candida>and Exophiala oligosperma>R1 are enantioselec-tive and regiospecific respectively. Geotrichum>sp. JR1 grows in the presence of 2M acetonitrile and may have potential for application in bioremediation of nitrile contaminated soil/water. The nitrilase of E. oligosperma>R1 being active at low pH (3-6) has shown promise for the hydroxy acids. Immobilized yeast cells hydrolyze some additional nitriles in comparison to free cells. It is expected that more focus in future will be on purification, characterization, cloning, expression and immobilization of nitrile metabolizing

  19. Toxic and Metabolic Myelopathies.

    Ramalho, Joana; Nunes, Renato Hoffmann; da Rocha, Antonio José; Castillo, Mauricio

    2016-10-01

    Myelopathy describes any neurologic deficit related to the spinal cord. It is most commonly caused by its compression by neoplasms, degenerative disc disease, trauma, or infection. Less common causes of myelopathy include spinal cord tumors, infection, inflammatory, neurodegenerative, vascular, toxic, and metabolic disorders. Conditions affecting the spinal cord must be recognized as early as possible to prevent progression that may lead to permanent disability. Biopsy is rarely performed, thus the diagnosis and management rely on patient׳s history, physical examination, laboratory results, and imaging findings. Here we review the clinical presentations, pathophysiological mechanisms, and magnetic resonance imaging findings of myelopathies related to metabolic or toxic etiologies. PMID:27616316

  20. Hypothyroidism in metabolic syndrome

    Sunil Kumar Kota

    2012-01-01

    Full Text Available Aim: Metabolic syndrome (MetS and hypothyroidism are well established forerunners of atherogenic cardiovascular disease. Considerable overlap occurs in the pathogenic mechanisms of atherosclerotic cardiovascular disease by metabolic syndrome and hypothyroidism. Insulin resistance has been studied as the basic pathogenic mechanism in metabolic syndrome. [1] This cross sectional study intended to assess thyroid function in patients with metabolic syndrome and to investigate the association between hypothyroidism and metabolic syndrome. Materials and Methods: One hundred patients with metabolic syndrome who fulfilled the National Cholesterol Education Program- Adult Treatment Panel (NCEP-ATP III criteria [ 3 out of 5 criteria positive namely blood pressure ≥ 130/85 mm hg or on antihypertensive medications, fasting plasma glucose > 100 mg/dl or on anti-diabetic medications, fasting triglycerides > 150 mg/dl, high density lipoprotein cholesterol (HDL-C 102 cms in men and 88 cms in women] were included in the study group. [2] Fifty patients who had no features of metabolic syndrome (0 out of 5 criteria for metabolic syndrome were included in the control group. Patients with liver disorders, renal disorders, congestive cardiac failure, pregnant women, patients on oral contraceptive pills, statins and other medications that alter thyroid functions and lipid levels and those who are under treatment for any thyroid related disorder were excluded from the study. Acutely ill patients were excluded taking into account sick euthyroid syndrome. Patients were subjected to anthropometry, evaluation of vital parameters, lipid and thyroid profile along with other routine laboratory parameters. Students t-test, Chi square test and linear regression, multiple logistic regression models were used for statistical analysis. P value < 0.05 was considered significant. Results: Of the 100 patients in study group, 55 were females (55% and 45 were males (45%. Of the 50

  1. Endocrinology and Metabolism

    2014-01-01

    2014429 Impact of obesity-related gene polymorphism on risk of obesity and metabolic disorder in childhood.ZHANG Meixian(张美仙),et al.Dept Epidemiol,Capital Instit Pediatrics,Beijing 100020.Chin J Prev Med 2014;48(9):776-783.Objective To examine the impact of single nucleotide polymorphisms in obesity-related genes on risk of obesity and metabolic disorder in childhood.Methods A total of 3 503 Chinese children aged 6 to 18 years participated in the study,including 1 229 obese,655 overweight and 1 619 normal weight children(diagnosed by

  2. Exercise metabolism in runners.

    Hardman, A E; Williams, C

    1983-01-01

    The purpose of this study was to re-examine the commonly accepted association between high maximum oxygen uptake (VO2 max) values and the characteristics of metabolic adaptation to endurance training. The metabolic responses of 9 active males and 8 endurance trained females were observed during one hour of treadmill running at two speeds. One speed was common to both groups (3.58 m s-1. Test 1) whereas the second speed represented approximately 62% VO2 max for each individual (Test 2). The VO...

  3. Metabolic Factors in Fatigue

    Mark Hargreaves

    2006-01-01

    Increased non-oxidative and oxidative ATP production via metabolic pathways in skeletal muscle is essential for the maintenance of force and power production during exercise. However, substrate depletion and accumulation of metabolic byproducts are potential causes of fatigue. Reduced PCr availability can limit power production during sprint exercise, whereas carbohydrate depletion is a major limitation to endurance performance. During sprint exercise increased Pi and H+ may contribute to fatigue, and during prolonged strenuous exercise, the accumulation of NH3, reactive oxygen species, and heat can limit performance. Appropriate training programs and nutritional interventions are potential strategies to enhance fatigue resistance and exercise performance.

  4. A control study of SVSRT plus aripiprazole in the treatment of manic episode of bipolar disorder%丙戊酸钠缓释片联合阿立哌唑治疗双相障碍躁狂发作对照研究

    李菲; 谭柏坚; 郭彦杨

    2016-01-01

    目的:探讨丙戊酸钠缓释片联合阿立哌唑治疗双相障碍躁狂发作的疗效和安全性。方法将81例双相障碍躁狂发作患者按照治疗方法不同分为观察组42例,对照组39例,均口服丙戊酸钠缓释片治疗,观察组联合阿立哌唑治疗,对照组联合喹硫平治疗,观察8周。采用Young躁狂评定量表评定躁狂状况、健康调查简表评定生活质量、匹兹堡睡眠质量指数量表评定睡眠质量、副反应量表评定不良反应。结果治疗后两组Young躁狂评定量表总分及匹兹堡睡眠质量指数量表各维度评分均较治疗前显著下降(P<0.01),观察组显著低于对照组(P<0.01);两组健康调查简表各维度评分均较治疗前显著升高(P<0.01),观察组显著高于对照组(P<0.01)。两组不良反应均较轻微,发生率比较差异无显著性(P>0.05)。结论丙戊酸钠缓释片联合阿立哌唑治疗双相障碍躁狂发作疗效显著,能有效改善患者的生活质量及睡眠质量,安全性高。%Objective To explore the efficacy and safety of sodium valproate sus‐tained release tablets (SVSRT ) plus aripiprazole in the treatment of manic episode of bipolar disorder . Methods Eighty‐one patients with manic episodes of bipolar disorder were assigned to observation (n=42) and control group (n=39) according to different treatment methods ,both groups took orally SVSRT , observation was plus aripiprazole and control group plus quetiapine for 8 weeks .Manic states were as‐sessed with Young Mania Rating Scale (YMRS) ,qualities of life with the Short Form 36 Health Survey Questionnaire (SF‐36) ,sleep qualities with the Pittsburgh Sleep Quality Index (PSQI) ,and adverse reac‐tions with the Treatment Emergent Symptom Scale (TESS) .Results After treatment the total score of the YMRS and each dimension score of the PSQI of both groups lowered more significantly (P0 .05) .Conclusion SVSRT

  5. Sleep and Metabolism: An Overview

    Sunil Sharma

    2010-01-01

    Full Text Available Sleep and its disorders are increasingly becoming important in our sleep deprived society. Sleep is intricately connected to various hormonal and metabolic processes in the body and is important in maintaining metabolic homeostasis. Research shows that sleep deprivation and sleep disorders may have profound metabolic and cardiovascular implications. Sleep deprivation, sleep disordered breathing, and circadian misalignment are believed to cause metabolic dysregulation through myriad pathways involving sympathetic overstimulation, hormonal imbalance, and subclinical inflammation. This paper reviews sleep and metabolism, and how sleep deprivation and sleep disorders may be altering human metabolism.

  6. Metabolism at Evolutionary Optimal States

    Iraes Rabbers

    2015-06-01

    Full Text Available Metabolism is generally required for cellular maintenance and for the generation of offspring under conditions that support growth. The rates, yields (efficiencies, adaptation time and robustness of metabolism are therefore key determinants of cellular fitness. For biotechnological applications and our understanding of the evolution of metabolism, it is necessary to figure out how the functional system properties of metabolism can be optimized, via adjustments of the kinetics and expression of enzymes, and by rewiring metabolism. The trade-offs that can occur during such optimizations then indicate fundamental limits to evolutionary innovations and bioengineering. In this paper, we review several theoretical and experimental findings about mechanisms for metabolic optimization.

  7. Macrophage Polarization in Metabolism and Metabolic Disease

    Anna Meiliana

    2013-08-01

    Full Text Available BACKGROUND: Obesity is now recognized as the main cause of the worldwide epidemic of type 2 diabetes. Obesity-associated chronic inflammation is a contributing key factor for type 2 diabetes and cardiovascular disease. Numbers of studies have clearly demonstrated that the immune system and metabolism are highly integrated. CONTENT: Macrophages are an essential component of innate immunity and play a central role in inflammation and host defense. Moreover, these cells have homeostatic functions beyond defense, including tissue remodeling in ontogenesis and orchestration of metabolic functions. Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to interferons (IFNs, toll-like receptor (TLR, or interleukin (IL-4/IL-13 signals, macrophages undergo M1 (classical or M2 (alternative activation. Progress has now been made in defining the signaling pathways, transcriptional networks, and epigenetic mechanisms underlying M1, M2 or M2-like polarized activation. SUMMARY: In response to various signals, macrophages may undergo classical M1 activation (stimulated by TLR ligands and IFN-γ or alternative M2 activation (stimulated by IL-4/IL-13; these states mirror the T helper (Th1–Th2 polarization of T cells. Pathology is frequently associated with dynamic changes in macrophage activation, with classically activated M1 cells implicate in initiating and sustaining inflammation, meanwhile M2 or M2-like activated cells associated with resolution or smoldering chronic inflammation. Identification of the mechanisms and molecules that are associated with macrophage plasticity and polarized activation provides a basis for macrophage centered diagnostic and therapeutic strategies. KEYWORDS: obesity, adipose tissue, inflammation, macrophage polarization.

  8. METABOLIC CORRECTIONOFNEUROLOGICALCOMPLICATIONS OFDIABETES MELLITUS

    Sof'ya Alekseevna Rumyantseva

    2009-01-01

    Full Text Available The concepts of the metabolic and vascular mechanisms responsible for the occurrence and progression of neurological complications of diabetes mellitus are presented. The results of some investigations demonstrating the efficacy of actovegin in the treatment of diabetic polyneuropathy, encephalopathy, and diabetic foot syndrome are given.

  9. ENDOCRINOLOGY AND METABOLISM

    2006-01-01

    2006162 Change of vascular endothelial function in patients with disorders of glucose metabolism. ZHANG Songjing,(张松菁),et al. Dept Endocrinol ,1st Hosp, Fujian Med Univ ,Fuzhou 350005. Chin J Endocrinol Metab 2006;22(1): 11 - 14. Objective: To observe the changes of the endothelium - dependent vasodilation ( EDF) and serum superoxide

  10. Sterol metabolism of insects

    Ritter, F.J.; Wientjens, W.H.J.M.

    1967-01-01

    This article surveys the present knowledge of the sterol metabolism of insects. It is emphasized that a high degree of purity of the dietary sterols and the climination of the influence of symbionts are essential to present ambiguity in interpreting results. It is pointed out that a sharp distinctio

  11. Prebiotic metabolic networks?

    Luisi, Pier Luigi

    2014-01-01

    A prebiotic origin of metabolism has been proposed as one of several scenarios for the origin of life. In their recent work, Ralser and colleagues (Keller et al, 2014) observe an enzyme‐free, metabolism‐like reaction network under conditions reproducing a possible prebiotic environment.

  12. Metabolism and Endocrinology

    2010-01-01

    2010410 Association of liver fat content with insulin resistance and islet β cell function in individuals with various statuses of glucose metabolism.BIAN Hua(卞华), etal.Dept Endocrinol & Metab, Zhongshan Hosp,Fudan Univ, Shanghai 200032.Chin J Endocrinol Metab 2010;26(7):535-540.

  13. Sucrose Metabolism in Plastids

    Gerrits, N.; Turk, S.C.H.J.; Dun, van K.P.M.; Hulleman, H.D.; Visser, R.G.F.; Weisbeek, P.J.; Smeekens, S.C.M.

    2001-01-01

    The question whether sucrose (Suc) is present inside plastids has been long debated. Low Suc levels were reported to be present inside isolated chloroplasts, but these were argued to be artifacts of the isolation procedures used. We have introduced Suc-metabolizing enzymes in plastids and our experi

  14. Starch metabolism in leaves.

    Orzechowski, Sławomir

    2008-01-01

    Starch is the most abundant storage carbohydrate produced in plants. The initiation of transitory starch synthesis and degradation in plastids depends mainly on diurnal cycle, post-translational regulation of enzyme activity and starch phosphorylation. For the proper structure of starch granule the activities of all starch synthase isoenzymes, branching enzymes and debranching enzymes are needed. The intensity of starch biosynthesis depends mainly on the activity of AGPase (adenosine 5'-diphosphate glucose pyrophosphorylase). The key enzymes in starch degradation are beta-amylase, isoamylase 3 and disproportionating enzyme. However, it should be underlined that there are some crucial differences in starch metabolism between heterotrophic and autotrophic tissues, e.g. is the ability to build multiprotein complexes responsible for biosynthesis and degradation of starch granules in chloroplasts. The observed huge progress in understanding of starch metabolism was possible mainly due to analyses of the complete Arabidopsis and rice genomes and of numerous mutants with altered starch metabolism in leaves. The aim of this paper is to review current knowledge on transient starch metabolism in higher plants. PMID:18787712

  15. Metabolic crosstalk between choline/1-carbon metabolism and energy homeostasis

    Zeisel, Steven H.

    2013-01-01

    There are multiple identified mechanisms involved in energy metabolism, insulin resistance and adiposity, but there are here-to-fore unsuspected metabolic factors that also influence these processes. Studies in animal models suggest important links between choline/1-carbon metabolism and energy homeostasis. Rodents fed choline deficient diets become hypermetabolic. Mice with deletions in one of several different genes of choline metabolism have phenotypes that include increa...

  16. How Is Metabolic Syndrome Treated?

    ... page from the NHLBI on Twitter. How Is Metabolic Syndrome Treated? Heart-healthy lifestyle changes are the first line of treatment for metabolic syndrome. If heart-healthy lifestyle changes aren’t enough, ...

  17. SIRT1 and energy metabolism

    Xiaoling Li

    2013-01-01

    Sirtuin 1 (SIRT1) is the most conserved mammalian NAD+-dependent protein deacetylase that has emerged as a key metabolic sensor in various metabolic tissues.In response to different environmental stimuli,SIRT1 directly links the cellular metabolic status to the chromatin structure and the regulation of gene expression,thereby modulating a variety of cellular processes such as energy metabolism and stress response.Recent studies have shown that SIRT1 controls both glucose and lipid metabolism in the liver,promotes fat mobilization and stimulates brown remodeling of the white fat in white adipose tissue,controls insulin secretion in the pancreas,senses nutrient availability in the hypothalamus,influences obesityinduced inflammation in macrophages,and modulates the activity of circadian clock in metabolic tissues.This review focuses on the role of SIRT1 in regulating energy metabolism at different metabolic tissues.

  18. Metabolic syndrome and periodontal disease

    Bharti Vipin; Khurana Pankaj

    2009-01-01

    It is important for a dentist to be well informed and updated on the latest research on the association of oral and systemic health. Of late, the metabolic syndrome has gained importance in dental literature, and metabolic syndrome and periodontal disease have been linked. Metabolic syndrome (MeS) is a group of three or more (up to five) interrelated metabolic abnormalities, which increases the risk of cardiovascular morbidity and mortality. Also, both MeS and periodontal disease may be linke...

  19. Impaired nitrazepam metabolism in hypothyroidism.

    Kenny, R. A.; Kafetz, K; Cox, M; Timmers, J.; Impallomeni, M

    1984-01-01

    Delayed metabolism of a number of drugs has been described in hypothyroid patients. We report an elderly hypothyroid female who had prolonged delay in the metabolism of a commonly-used sedative, nitrazepam, and discuss the importance of delayed drug metabolism in hypothyroidism.

  20. Links between metabolism and cancer

    Dang, Chi V.

    2012-01-01

    Excessive caloric intake is associated with increased risk for cancer, while the nonobese state may be protective through mechanisms that reduce oxidative stress. In this review, Dang discusses the links between metabolism and cancer, which range from the low incidence of cancer in large mammals with low specific metabolic rates to altered cancer cell metabolism resulting from mutated enzymes or cancer genes.

  1. Uncovering transcriptional regulation of metabolism by using metabolic network topology

    Patil, Kiran Raosaheb; Nielsen, Jens

    2005-01-01

    Cellular response to genetic and environmental perturbations is often reflected and/or mediated through changes in the metabolism, because the latter plays a key role in providing Gibbs free energy and precursors for biosynthesis. Such metabolic changes are often exerted through transcriptional...... changes induced by complex regulatory mechanisms coordinating the activity of different metabolic pathways. It is difficult to map such global transcriptional responses by using traditional methods, because many genes in the metabolic network have relatively small changes at their transcription level. We...... therefore developed an algorithm that is based on hypothesis-driven data analysis to uncover the transcriptional regulatory architecture of metabolic networks. By using information on the metabolic network topology from genome-scale metabolic reconstruction, we show that it is possible to reveal patterns in...

  2. Algebraic comparison of metabolic networks, phylogenetic inference, and metabolic innovation

    Hofacker Ivo L

    2006-02-01

    Full Text Available Abstract Background Comparison of metabolic networks is typically performed based on the organisms' enzyme contents. This approach disregards functional replacements as well as orthologies that are misannotated. Direct comparison of the structure of metabolic networks can circumvent these problems. Results Metabolic networks are naturally represented as directed hypergraphs in such a way that metabolites are nodes and enzyme-catalyzed reactions form (hyperedges. The familiar operations from set algebra (union, intersection, and difference form a natural basis for both the pairwise comparison of networks and identification of distinct metabolic features of a set of algorithms. We report here on an implementation of this approach and its application to the procaryotes. Conclusion We demonstrate that metabolic networks contain valuable phylogenetic information by comparing phylogenies obtained from network comparisons with 16S RNA phylogenies. The algebraic approach to metabolic networks is suitable to study metabolic innovations in two sets of organisms, free living microbes and Pyrococci, as well as obligate intracellular pathogens.

  3. Genetics of metabolic resistance.

    Richter, Otto; Langemann, Dirk; Beffa, Roland

    2016-09-01

    Herbicide resistance has become a major issue for many weeds. Metabolic resistance refers to the biochemical processes within organisms that degrade herbicides to less toxic compounds, resulting in a shift of the dose response curve. This type of resistance involves polygenic inheritance. A model is presented linking the biochemical pathway of amino acid synthesis and the detoxifying pathway of an inhibitor of the key enzyme ALS. From this model, resistance factors for each biotype are derived, which are then applied to a polygenic population genetic model for an annual weed plant. Polygenic inheritance is described by a new approach based on tensor products of heredity matrices. Important results from the model are that low dose regimes favour fast emergence of resistant biotypes and that the emergence of resistant biotypes occurs as abrupt outbreaks. The model is used to evaluate strategies for the management of metabolic resistance. PMID:27424952

  4. Surfactant phospholipid metabolism.

    Agassandian, Marianna; Mallampalli, Rama K

    2013-03-01

    Pulmonary surfactant is essential for life and is composed of a complex lipoprotein-like mixture that lines the inner surface of the lung to prevent alveolar collapse at the end of expiration. The molecular composition of surfactant depends on highly integrated and regulated processes involving its biosynthesis, remodeling, degradation, and intracellular trafficking. Despite its multicomponent composition, the study of surfactant phospholipid metabolism has focused on two predominant components, disaturated phosphatidylcholine that confers surface-tension lowering activities, and phosphatidylglycerol, recently implicated in innate immune defense. Future studies providing a better understanding of the molecular control and physiological relevance of minor surfactant lipid components are needed. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism. PMID:23026158

  5. Nuclear Sphingolipid Metabolism

    Lucki, Natasha C.; Sewer, Marion B.

    2014-01-01

    Nuclear lipid metabolism is implicated in various processes, including transcription, splicing, and DNA repair. Sphingolipids play roles in numerous cellular functions, and an emerging body of literature has identified roles for these lipid mediators in distinct nuclear processes. Different sphingolipid species are localized in various subnuclear domains, including chromatin, the nuclear matrix, and the nuclear envelope, where sphingolipids exert specific regulatory and structural functions. Sphingomyelin, the most abundant nuclear sphingolipid, plays both structural and regulatory roles in chromatin assembly and dynamics in addition to being an integral component of the nuclear matrix. Sphingosine-1-phosphate modulates histone acetylation, sphingosine is a ligand for steroidogenic factor 1, and nuclear accumulation of ceramide has been implicated in apoptosis. Finally, nuclear membrane–associated ganglioside GM1 plays a pivotal role in Ca2+ homeostasis. This review highlights research on the factors that control nuclear sphingolipid metabolism and summarizes the roles of these lipids in various nuclear processes. PMID:21888508

  6. Paracetamol metabolism in pregnancy.

    Miners, J O; Robson, R A; Birkett, D J

    1986-01-01

    Paracetamol disposition was studied in groups of pregnant and non-pregnant women of comparable age. Paracetamol apparent oral clearance was 58% higher and elimination half-life was 28% lower in the pregnant women compared to the control group. The higher clearance in the pregnant women was due to increased activity of the glucuronidation (75% higher) and oxidative (88% higher) pathways of paracetamol metabolism. There was no difference between the two groups in paracetamol sulphation or renal...

  7. Sleep and metabolic function

    Morselli, Lisa L.; Guyon, Aurore; Spiegel, Karine

    2011-01-01

    Evidence for the role of sleep on metabolic and endocrine function has been reported more than four decades ago. In the past 30 years, the prevalence of obesity and diabetes has greatly increased in industrialized countries, and self-imposed sleep curtailment, now very common, is starting to be recognized as a contributing factor, alongside with increased caloric intake and decreased physical activity. Furthermore, obstructive sleep apnea, a chronic condition characterized by recurrent upper ...

  8. Automated Microbial Metabolism Laboratory

    1973-01-01

    Development of the automated microbial metabolism laboratory (AMML) concept is reported. The focus of effort of AMML was on the advanced labeled release experiment. Labeled substrates, inhibitors, and temperatures were investigated to establish a comparative biochemical profile. Profiles at three time intervals on soil and pure cultures of bacteria isolated from soil were prepared to establish a complete library. The development of a strategy for the return of a soil sample from Mars is also reported.

  9. Scaling metabolic rate fluctuations

    Labra, Fabio A.; Marquet, Pablo A.; Bozinovic, Francisco

    2007-01-01

    Complex ecological and economic systems show fluctuations in macroscopic quantities such as exchange rates, size of companies or populations that follow non-Gaussian tent-shaped probability distributions of growth rates with power-law decay, which suggests that fluctuations in complex systems may be governed by universal mechanisms, independent of particular details and idiosyncrasies. We propose here that metabolic rate within individual organisms may be considered as an example of an emerge...

  10. Metabolic syndrome in children

    Melinda Morea; Nicolae Miu

    2013-01-01

    Objective: To determine the prevalence of the metabolic syndrome (MS) in children. Material and methods: We performed a cross sectional, retrospective study. A total of 395 children aged between 2-19 years old were examined.. The children have undergone physical examination; weight, height, waist circumference, blood pressure (BP) were measured. The nutritional status of the children was assessed by body mass index (BMI) and laboratory tests needed to diagnose MS were performed. IDF ...

  11. Surfactant phospholipid metabolism

    Agassandian, Marianna; Mallampalli, Rama K.

    2012-01-01

    Pulmonary surfactant is essential for life and is comprised of a complex lipoprotein-like mixture that lines the inner surface of the lung to prevent alveolar collapse at the end of expiration. The molecular composition of surfactant depends on highly integrated and regulated processes involving its biosynthesis, remodeling, degradation, and intracellular trafficking. Despite its multicomponent composition, the study of surfactant phospholipid metabolism has focused on two predominant compone...

  12. Iron and Iron Metabolism

    Melike Sezgin Evim; Birol Baytan; Adalet Meral Güneş

    2012-01-01

    Iron is an essential element for almost all living organisms except some bacteria. A great number of new articles related to the iron metabolism have been published in recent years explaining new findings. Hepsidine, a peptide hormon, that is recently found, regulates iron methabolism by effecting iron absorbsion from gut, secreting iron from hepatic store and flows iron from macrophages. Hepsidin blockes to effluxe iron from cells by bounding to ferroportin and by inducing ferroportin destru...

  13. Metabolic Model Generalization

    Zhukova, Anna

    2013-01-01

    International audience Genome-scale metabolic models for new organisms include thousands of reactions that are generated automatically: by inferring them from databases of reactions and pathways, existing models for similar organisms, etc. This process includes several iterations of the draft model analysis, error detection, and improvement; starting from more general issues and going deeper into details. Especially in the first iterations model evaluation by a human expert is important. B...

  14. Obesity and metabolic inflammation

    Xu, Haiyan

    2013-01-01

    Obesity epidemics affect 35.7% of adults and approximately 17% of children in the United States. Obesity has been associated with several health disorders, such as type 2 diabetes, cardiovascular diseases, fatty liver disease, and certain forms of cancer. Medical costs associated with obesity were estimated at $147 billion in 2008. Chronic tissue inflammation, particularly in adipose tissue, has been considered as a key underlying mechanism for the development of obesity-related metabolic syn...

  15. Connecting Myokines and Metabolism

    Ahima, Rexford S.; Park, Hyeong-Kyu

    2015-01-01

    Skeletal muscle is the largest organ of the body in non-obese individuals and is now considered to be an endocrine organ. Hormones (myokines) secreted by skeletal muscle mediate communications between muscle and liver, adipose tissue, brain, and other organs. Myokines affect muscle mass and myofiber switching, and have profound effects on glucose and lipid metabolism and inflammation, thus contributing to energy homeostasis and the pathogenesis of obesity, diabetes, and other diseases. In thi...

  16. Analytics for metabolic engineering

    Christopher J Petzold

    2015-09-01

    Full Text Available Realizing the promise of metabolic engineering has been slowed by challenges related to moving beyond proof-of-concept examples to robust and economically viable systems. Key to advancing metabolic engineering beyond trial-and-error research is access to parts with well-defined performance metrics that can be readily applied in vastly different contexts with predictable effects. As the field now stands, research depends greatly on analytical tools that assay target molecules, transcripts, proteins, and metabolites across different hosts and pathways. Screening technologies yield specific information for many thousands of strain variants while deep omics analysis provide a systems-level view of the cell factory. Efforts focused on a combination of these analyses yield quantitative information of dynamic processes between parts and the host chassis that drive the next engineering steps. Overall, the data generated from these types of assays aid better decision-making at the design and strain construction stages to speed progress in metabolic engineering research.

  17. Dysregulated lipid metabolism in cancer

    2012-01-01

    Alteration of lipid metabolism has been increasingly recognized as a hallmark of cancer cells. The changes of expression and activity of lipid metabolizing enzymes are directly regulated by the activity of oncogenic signals. The dependence of tumor cells on the dysregulated lipid metabolism suggests that proteins involved in this process are excellent chemotherapeutic targets for cancer treatment. There are currently several drugs under development or in clinical trials that are based on specifically targeting the altered lipid metabolic pathways in cancer cells. Further understanding of dysregulated lipid metabolism and its associated signaling pathways will help us to better design efficient cancer therapeutic strategy.

  18. 帕罗西汀合并不同剂量阿立哌唑治疗强迫症的临床观察%Observing the effect of Paroxetine combined with different doses of ariPiPrazole on obsessive-comPulsive disorder

    朱立毛; 舒菊红; 戴升太

    2014-01-01

    Objective:To investigate the effectiveness and safety of paroxetine combined with different doses of aripiprazole on obsessive-compulsive disorder. Method:One hundred and sixty-four patients with obsessive-compulsive disorder were randomly divided into 2 groups:the paroxetine only group( n = 33),the 2. 2 mg/ d group(n = 32),the 2 mg/ d group(n = 34),the 7. 2mg group(n = 32),the 10 mg/ d group(n = 33). Each group was treated with paroxetine 40 mg/ d combined with corresponding doses of aripiprazole for 8 weeks. Effectiveness and adverse effect were assessed respectively by Yale-Brown obsessive compulsive scale( Y-BOCS)and treatment emergent symptom scale(TESS). Results:After 8 weeks treatment,in the five groups, the scores of Y-BOCS significantly decreased(P ﹤ 0. 02 or P ﹤ 0. 01),the 2. 2 mg/ d group and the 2 mg group were more obvious(all P ﹤ 0. 01). The decreased score rate of Y-BOCS were significantly different between the paroxetine only group and the 2. 2 mg/ d group or the 2 mg group(all P ﹤ 0. 02). After 8 weeks treatment,no significant difference was found in the rates of adverse effect in 2. 2 mg/ d group and 2 mg/ d group compared with paroxetine only group;but in 7. 2 mg/ d group and 10 mg/ d group were sifnificantly higher than paroxetine only group(P ﹤ 0. 02 or P ﹤ 0. 01). Conclusion:The paroxetine combined the 2. 2-2 mg/ d aripiprazole trea-ting patients with obsessive compulsive disorder is more effective than the paroxetine combined the 7. 2-10 mg/d aripiprazole and paroxetine only.%目的:探讨盐酸帕罗西汀联合不同剂量阿立哌唑治疗强迫症的疗效及安全性。方法:164例强迫症患者随机分为帕罗西汀治疗(单药)组及帕罗西汀+阿立哌唑2.2 mg/ d 组、2 mg/ d 组、7.2 mg/d 组及10 mg/ d 组,每组给予帕罗西汀40 mg/ d 及相应剂量的阿立哌唑治疗8周。治疗前后进行耶鲁布朗强迫量表(Y-BOCS)及治疗过程中出现的症状量表

  19. Tumor Metabolism of Malignant Gliomas

    Deliang Guo

    2013-11-01

    Full Text Available Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation.

  20. Tumor Metabolism of Malignant Gliomas

    Ru, Peng; Williams, Terence M.; Chakravarti, Arnab; Guo, Deliang, E-mail: deliang.guo@osumc.edu [Department of Radiation Oncology, Ohio State University Comprehensive Cancer Center & Arthur G James Cancer Hospital, Columbus, OH 43012 (United States)

    2013-11-08

    Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a novel direction for drug development in oncology. In malignant gliomas, metabolism pathways of glucose, glutamine and lipid are significantly reprogrammed. Moreover, molecular mechanisms causing these metabolic changes are just starting to be unraveled. In this review, we will summarize recent studies revealing critical gene alterations that lead to metabolic changes in malignant gliomas, and also discuss promising therapeutic strategies via targeting the key players in metabolic regulation.

  1. Disturbances of lipoprotein metabolism in metabolic syndro

    Marta Czyżewska

    2010-01-01

    Full Text Available Dyslipidemia in metabolic syndrome (MS, called the atherogenic triad, includes elevated levels of plasma triglycerides (TGs, low levels of HDL-cholesterol (HDL-CH, and the presence of small dense low-density lipoproteins (sdLDLs with normal or slightly elevated LDL-CH levels. Insulin resistance drives the increase in the three main sources of TG for VLDL synthesis: fatty-acid flux from adipose tissue, de novo lipogenesis, and uptake of remnant lipoproteins. Overproduction of VLDL, predominantly triglyceride-rich large VLDL1 particles, induces the cascade of events which lead to abnormalities of other plasma lipoproteins. The accumulation of VLDL in plasma and decreased activity of lipoprotein lipase (LPL impair the catabolism of chylomicrons. Moreover, hyperinsulinemia induces increased intestinal production of chylomicrons. These factors cause augmented postprandial lipemia. Hepatic overproduction of VLDL leads to an increased level of VLDL remnants in plasma. Highly atherogenic sdLDLs are generated from VLDL1 particles by the action of LPL, cholesterol ester transfer protein (CETP, and hepatic lipase (HL. In the presence of hypertriglyceridemia, accelerated CETP-mediated lipid transfer generates TG-enriched HDL particles. This enhances HDL catabolism mediated by HL and endothelial lipase (EL. The assessment of risk of atherosclerotic cardiovascular disease in MS related to low HDL-CH and the presence of sdLDL particles may be improved by the incorporation of measurements of apolipoproteins (apo-B and apoA-I into clinical practice. In addition, the concentration of non-HDL-CH may be useful in quantifying apo-B-containing atherogenic lipoproteins.

  2. Metabolic Burden: Cornerstones in Synthetic Biology and Metabolic Engineering Applications.

    Wu, Gang; Yan, Qiang; Jones, J Andrew; Tang, Yinjie J; Fong, Stephen S; Koffas, Mattheos A G

    2016-08-01

    Engineering cell metabolism for bioproduction not only consumes building blocks and energy molecules (e.g., ATP) but also triggers energetic inefficiency inside the cell. The metabolic burdens on microbial workhorses lead to undesirable physiological changes, placing hidden constraints on host productivity. We discuss cell physiological responses to metabolic burdens, as well as strategies to identify and resolve the carbon and energy burden problems, including metabolic balancing, enhancing respiration, dynamic regulatory systems, chromosomal engineering, decoupling cell growth with production phases, and co-utilization of nutrient resources. To design robust strains with high chances of success in industrial settings, novel genome-scale models (GSMs), (13)C-metabolic flux analysis (MFA), and machine-learning approaches are needed for weighting, standardizing, and predicting metabolic costs. PMID:26996613

  3. Predicting metabolic pathways from metabolic networks with limited biological knowledge

    Leung, HCM; Yiu, SM; Chin, FYL; Leung, SY; Xiang, CL

    2010-01-01

    Understanding the metabolism of new species (e.g. endophytic fungi that produce fuel) have tremendous impact on human lives. Based on predicted proteins and existing reaction databases, one can construct the metabolic network for the species. Next is to identify critical metabolic pathways from the network. Existing computational techniques identify conserved pathways based on multiple networks of related species, but have the following drawbacks. Some do not rely on additional information, s...

  4. Metal metabolism and toxicity

    This research focuses on the role of pregnancy and lactation in susceptibility to the toxic effects of cadmium and lead. Responses under investigation include lead-induced changes in pathways for vitamin D and calcium metabolism and cadmium-induced alterations in kidney function and skeletal structure. The second area focuses on the gastrointestinal absorption of plutonium and other actinide elements. Studies currently being conducted in nonhuman primates to develop a procedure to determine GI absorption values of uranium and plutonium that does not require sacrifice of the animal. 6 refs

  5. Morphine metabolism in children.

    Choonara, I A; McKay, P; Hain, R; Rane, A.

    1989-01-01

    1. The metabolism of morphine was studied in 12 children and nine premature neonates on a continuous infusion of morphine (10-360 micrograms kg-1 h-1). 2. The mean plasma clearance of morphine was significantly higher in children than neonates (25.7 and 4.7 ml min-1 kg-1, respectively) (P less than 0.01). 3. All the neonates and children had detectable concentrations of morphine-3-glucuronide (M3G) in plasma. All the children and five neonates had detectable concentrations of morphine-6-glucu...

  6. Metabolic syndrome and pregnancy

    A V Khromilev

    2014-06-01

    Full Text Available Metabolic syndrome (MS is a major problem of public health and health care system, with rising prevalence in the world. There is evidence that obesity, as the main component of MS, is strongly associated with the presence of gestational complications: fetal growth retardation, fetal macrosomia, gestational diabetes, preeclampsia, preterm delivery, stillbirth and perinatal death. The underlying mechanisms of this association are actively investigated nowadays. The importance of MS in pregnancy is also determined by the increase of the risk of venous trombosis.

  7. Metabolism and Endocrinology

    2009-01-01

    2009039 A survey of glucose and lipid metabolism and concomitant diseases among inpatients in Guangdong province. TANG Kuanxiao(唐宽晓), et al. Dept Endocrinol, 3rd Affili Hosp, Sun Yat-sen Univ, Guangzhou 510630. Chin J Intern Med 2009;48(3):196-200. Objectives To investigate the epidemiological and clinical characteristics of dyslipidemia as well as its treatment and influence on accompanying diseases in impaired glucose status among inpatients. Methods A cross-sectional survey was conducted among the inpatients registered in ten university hospitals of Guangdong, China during the week before the Diabetes Day in 2004.

  8. [Heme metabolism and oxidative stress].

    Kaliman, P A; Barannik, T B

    2001-01-01

    The role of heme metabolism in oxidative stress development and defense reactions formation in mammals under different stress factors are discussed in the article. Heme metabolism is considered as the totality of synthesis, degradation, transport and exchange processes of exogenous heme and heme liberated from erythrocyte hemoglobin under erythrocyte aging and hemolysis. The literature data presented display normal heme metabolism including mammals heme-binding proteins and intracellular free heme pool and heme metabolism alterations under oxidative stress development. The main attention is focused to the prooxidant action of heme, the interaction of heme transport and lipid exchange, and to the heme metabolism key enzymes (delta-aminolevulinate synthase and heme oxygenase), serum heme-binding protein hemopexin and intracellular heme-binding proteins participating in metabolism adaptation under the action of factors, which cause oxidative stress. PMID:11599427

  9. Arginine metabolism in wounds

    Arginine metabolism in wounds was investigated in the rat in 1) lambda-carrageenan-wounded skeletal muscle, 2) Schilling chambers, and 3) subcutaneous polyvinyl alcohol sponges. All showed decreased arginine and elevated ornithine contents and high arginase activity. Arginase could be brought to the wound by macrophages, which were found to contain arginase activity. However, arginase was expressed by macrophages only after cell lysis and no arginase was released by viable macrophages in vitro. Thus the extracellular arginase of wounds may derive from dead macrophages within the injured tissue. Wound and peritoneal macrophages exhibited arginase deiminase activity as demonstrated by the conversion of [guanido-14C]arginine to radiolabeled citrulline during culture, the inhibition of this reaction by formamidinium acetate, and the lack of prokaryotic contamination of the cultures. These findings and the known metabolic fates of the products of arginase and arginine deiminase in the cellular populations of the wound suggest the possibility of cooperativity among cells for the production of substrates for collagen synthesis

  10. Metabolic topography of Parkinsonism

    Kim, Jae Seung [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2007-04-15

    Parkinson's disease is one of the most frequent neurodegenerative diseases, which mainly affects the elderly. Parkinson's disease is often difficult to differentiate from atypical parkinson disorder such as progressive supranuclear palsy, multiple system atrophy, dementia with Lewy body, and corticobasal ganglionic degeneration, based on the clinical findings because of the similarity of phenotypes and lack of diagnostic markers. The accurate diagnosis of Parkinson's disease and atypical Parkinson disorders is not only important for deciding on treatment regimens and providing prognosis, but also it is critical for studies designed to investigate etiology and pathogenesis of parkinsonism and to develop new therapeutic strategies. Although degeneration of the nigrostriatal dopamine system results in marked loss of striatal dopamine content in most of the diseases causing parkinsonism, pathologic studies revealed different topographies of the neuronal cell loss in Parkinsonism. Since the regional cerebral glucose metabolism is a marker of integrated local synaptic activity and as such is sensitive to both direct neuronal/synaptic damage and secondary functional disruption at synapses distant from the primary site of pathology, and assessment of the regional cerebral glucose metabolism with F-18 FDG PET is useful in the differential diagnosis of parkinsonism and evaluating the pathophysiology of Parkinsonism.

  11. Metabolic Syndrome: Hyperlipidemia.

    Bragg, Dee Ann Stults; Walling, Anne

    2015-08-01

    Metabolic syndrome is associated with an elevated risk of cardiovascular disease and premature mortality. When metabolic syndrome includes lipid abnormalities, management goals are weight loss and cardiovascular risk management through lifestyle modifications (eg, diet, exercise), and, when appropriate, lowering of lipid levels with pharmacotherapy. Healthy diets are recommended, particularly the Mediterranean diet. Patients also should set a goal of at least 30 minutes of moderate to vigorous exercise on most, preferably all, days of the week. Guidelines provide criteria for statin treatment based on overall cardiovascular risk. High-intensity statin treatment (eg, rosuvastatin 20 to 40 mg, atorvastatin 40 to 80 mg) typically is recommended unless the patient cannot tolerate therapy. Approximately 5% of patients experience statin-induced myalgia, in which case moderate-intensity treatment can be tried. Lipid levels should be reevaluated 4 to 12 weeks after initiating therapy; lipid levels can be measured without fasting. A lack of improvement often indicates nonadherence. Bile acid sequestrants, fibric acids, and niacin can be used if other drugs are not tolerated. The evidence to support use of integrative medicine is limited, but the strongest evidence of benefit is for garlic (Allium sativum). PMID:26280341

  12. Metabolic topography of Parkinsonism

    Parkinson's disease is one of the most frequent neurodegenerative diseases, which mainly affects the elderly. Parkinson's disease is often difficult to differentiate from atypical parkinson disorder such as progressive supranuclear palsy, multiple system atrophy, dementia with Lewy body, and corticobasal ganglionic degeneration, based on the clinical findings because of the similarity of phenotypes and lack of diagnostic markers. The accurate diagnosis of Parkinson's disease and atypical Parkinson disorders is not only important for deciding on treatment regimens and providing prognosis, but also it is critical for studies designed to investigate etiology and pathogenesis of parkinsonism and to develop new therapeutic strategies. Although degeneration of the nigrostriatal dopamine system results in marked loss of striatal dopamine content in most of the diseases causing parkinsonism, pathologic studies revealed different topographies of the neuronal cell loss in Parkinsonism. Since the regional cerebral glucose metabolism is a marker of integrated local synaptic activity and as such is sensitive to both direct neuronal/synaptic damage and secondary functional disruption at synapses distant from the primary site of pathology, and assessment of the regional cerebral glucose metabolism with F-18 FDG PET is useful in the differential diagnosis of parkinsonism and evaluating the pathophysiology of Parkinsonism

  13. Biochemical Hypermedia: Galactose Metabolism.

    J.K. Sugai

    2013-05-01

    Full Text Available Introduction: Animations of biochemical processes and virtual laboratory environments lead to true molecular simulations. The use of interactive software’s in education can improve cognitive capacity, better learning and, mainly, it makes information acquisition easier. Material and Methods: This work presents the development of a biochemical hypermedia to understanding of the galactose metabolism. It was developed with the help of concept maps, ISIS Draw, ADOBE Photoshop and FLASH MX Program. Results and Discussion: A step by step animation process shows the enzymatic reactions of galactose conversion to glucose-1-phosphate (to glycogen synthesis, glucose-6-phosphate (glycolysis intermediary, UDP-galactose (substrate to mucopolysaccharides synthesis and collagen’s glycosylation. There are navigation guide that allow scrolling the mouse over the names of the components of enzymatic reactions of via the metabolism of galactose. Thus, explanatory text box, chemical structures and animation of the actions of enzymes appear to navigator. Upon completion of the module, the user’s response to the proposed exercise can be checked immediately through text box with interactive content of the answer. Conclusion: This hypermedia was presented for undergraduate students (UFSC who revealed that it was extremely effective in promoting the understanding of the theme.

  14. Metabolic regulation of yeast

    Fiechter, A.

    1982-12-01

    Metabolic regulation which is based on endogeneous and exogeneous process variables which may act constantly or time dependently on the living cell is discussed. The observed phenomena of the regulation are the result of physical, chemical, and biological parameters. These parameters are identified. Ethanol is accumulated as an intermediate product and the synthesis of biomass is reduced. This regulatory effect of glucose is used for the aerobic production of ethanol. Very high production rates are thereby obtained. Understanding of the regulation mechanism of the glucose effect has improved. In addition to catabolite repression, several other mechanisms of enzyme regulation have been described, that are mostly governed by exogeneous factors. Glucose also affects the control of respiration in a third class of yeasts which are unable to make use of ethanol as a substrate for growth. This is due to the lack of any anaplerotic activity. As a consequence, diauxic growth behavior is reduced to a one-stage growth with a drastically reduced cell yield. The pulse chemostat technique, a systematic approach for medium design is developed and medium supplements that are essential for metabolic control are identified.

  15. [Metabolic bone disease osteomalacia].

    Reuss-Borst, M A

    2014-05-01

    Osteomalacia is a rare disorder of bone metabolism leading to reduced bone mineralization. Underlying vitamin D deficiency and a disturbed phosphate metabolism (so-called hypophosphatemic osteomalacia) can cause the disease. Leading symptoms are dull localized or generalized bone pain, muscle weakness and cramps as well as increased incidence of falls. Rheumatic diseases, such as polymyalgia rheumatica, rheumatoid arthritis, myositis and fibromyalgia must be considered in the differential diagnosis. Alkaline phosphatase (AP) is typically elevated in osteomalacia while serum phosphate and/or 25-OH vitamin D3 levels are reduced. The diagnosis of osteomalacia can be confirmed by an iliac crest bone biopsy. Histological correlate is reduced or deficient mineralization of the newly synthesized extracellular matrix. Treatment strategies comprise supplementation of vitamin D and calcium and for patients with intestinal malabsorption syndromes vitamin D and calcium are also given parenterally. In renal phosphate wasting syndromes substitution of phosphate is the treatment of choice, except for tumor-induced osteomalacia when removal of the tumor leads to a cure in most cases. PMID:24811356

  16. Tumor Metabolism of Malignant Gliomas

    Deliang Guo; Arnab Chakravarti; Williams, Terence M.; Peng Ru

    2013-01-01

    Constitutively activated oncogenic signaling via genetic mutations such as in the EGFR/PI3K/Akt and Ras/RAF/MEK pathways has been recognized as a major driver for tumorigenesis in most cancers. Recent insights into tumor metabolism have further revealed that oncogenic signaling pathways directly promote metabolic reprogramming to upregulate biosynthesis of lipids, carbohydrates, protein, DNA and RNA, leading to enhanced growth of human tumors. Therefore, targeting cell metabolism has become a...

  17. Gut Microbiota and Metabolic Disorders

    Kyu Yeon Hur

    2015-06-01

    Full Text Available Gut microbiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gut microbiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gut microbiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or insulin signaling. Several strategies have been developed to change gut microbiota such as prebiotics, probiotics, certain antidiabetic drugs or fecal microbiota transplantation, which have diverse effects on body metabolism and on the development of metabolic disorders.

  18. Can you boost your metabolism?

    ... NA, Blundell JE. The relationship between substrate metabolism, exercise, and appetite control: Does glycogen availability influence the motivation to eat, energy intake or food choice? Sports ...

  19. Metabolic Adaptation to Muscle Ischemia

    Cabrera, Marco E.; Coon, Jennifer E.; Kalhan, Satish C.; Radhakrishnan, Krishnan; Saidel, Gerald M.; Stanley, William C.

    2000-01-01

    Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

  20. [Regulation of terpene metabolism

    Croteau, R.

    1989-11-09

    Terpenoid oils, resins, and waxes from plants are important renewable resources. The objective of this project is to understand the regulation of terpenoid metabolism using the monoterpenes (C[sub 10]) as a model. The pathways of monoterpene biosynthesis and catabolism have been established, and the relevant enzymes characterized. Developmental studies relating enzyme levels to terpene accumulation within the oil gland sites of synthesis, and work with bioregulators, indicate that monoterpene production is controlled by terpene cyclases, the enzymes catalyzing the first step of the monoterpene pathway. As the leaf oil glands mature, cyclase levels decline and monoterpene biosynthesis ceases. Yield then decreases as the monoterpenes undergo catabolism by a process involving conversion to a glycoside and transport from the leaf glands to the root. At this site, the terpenoid is oxidatively degraded to acetate that is recycled into other lipid metabolites. During the transition from terpene biosynthesis to catabolism, the oil glands undergo dramatic ultrastructural modification. Degradation of the producing cells results in mixing of previously compartmentized monoterpenes with the catabolic enzymes, ultimately leading to yield decline. This regulatory model is being applied to the formation of other terpenoid classes (C[sub 15] C[sub 20], C[sub 30], C[sub 40]) within the oil glands. Preliminary investigations on the formation of sesquiterpenes (C[sub 15]) suggest that the corresponding cyclases may play a lesser role in determining yield of these products, but that compartmentation effects are important. From these studies, a comprehensive scheme for the regulation of terpene metabolism is being constructed. Results from this project wail have important consequences for the yield and composition of terpenoid natural products that can be made available for industrial exploitation.

  1. Renal metabolism of calcitonin

    The kidneys account for approximately two-thirds of the metabolism of calcitonin, but relatively little is known regarding the details thereof. To further characterize this process, we examined the renal handling and metabolism of human calcitonin (hCT) by the isolated perfused rat kidney. We also studied the degradation of radiolabeled salmon calcitonin (sCT) by subcellular fractions prepared from isolated rabbit proximal tubules. The total renal (organ) clearance of immunoreactive hCT by the isolated kidney was 1.96 +/- 0.18 ml/min. This was independent of the perfusate total calcium concentration from 5.5 to 10.2 mg/dl. Total renal clearance exceeded the glomerular filtration rate (GFR, 0.68 +/- 0.05 ml/min), indicating filtration-independent removal. Urinary calcitonin clearance as a fraction of GFR averaged 2.6%. Gel filtration chromatography of medium from isolated kidneys perfused with 125I-labeled sCT showed the principal degradation products to be low molecular weight forms eluting with monoiodotyrosine. Intermediate size products were not detected. In the subcellular fractionation experiments, when carried out at pH 5.0, calcitonin hydrolysis exclusively followed the activities of the lysosomal enzyme N-acetyl-beta-glucosaminidase. Typically, at pH 7.5, 42% of total degradation occurred in the region of the brush-border enzyme alanyl aminopeptidase and 29% occurred in the region of the cytosolic enzyme phosphoglucomutase. Although 9% of the calcitonin-degrading activity was associated with basolateral membrane fractions, most of this activity could be accounted for by the presence of brush-border membranes

  2. Lysophosphatidylinositol Signalling and Metabolic Diseases.

    Arifin, Syamsul A; Falasca, Marco

    2016-01-01

    Metabolism is a chemical process used by cells to transform food-derived nutrients, such as proteins, carbohydrates and fats, into chemical and thermal energy. Whenever an alteration of this process occurs, the chemical balance within the cells is impaired and this can affect their growth and response to the environment, leading to the development of a metabolic disease. Metabolic syndrome, a cluster of several metabolic risk factors such as abdominal obesity, insulin resistance, high cholesterol and high blood pressure, and atherogenic dyslipidaemia, is increasingly common in modern society. Metabolic syndrome, as well as other diseases, such as diabetes, obesity, hyperlipidaemia and hypertension, are associated with abnormal lipid metabolism. Cellular lipids are the major component of cell membranes; they represent also a valuable source of energy and therefore play a crucial role for both cellular and physiological energy homeostasis. In this review, we will focus on the physiological and pathophysiological roles of the lysophospholipid mediator lysophosphatidylinositol (LPI) and its receptor G-protein coupled receptor 55 (GPR55) in metabolic diseases. LPI is a bioactive lipid generated by phospholipase A (PLA) family of lipases which is believed to play an important role in several diseases. Indeed LPI can affect various functions such as cell growth, differentiation and motility in a number of cell-types. Recently published data suggest that LPI plays an important role in different physiological and pathological contexts, including a role in metabolism and glucose homeostasis. PMID:26784247

  3. Obesity, metabolic syndrome and adipocytes

    Obesity and metabolic syndrome are examples whereby excess energy consumption and energy flux disruptions are causative agents of increased fatness. Because other, as yet elucidated, cellular factors may be involved and because potential treatments of these metabolic problems involve systemic agents...

  4. Can you boost your metabolism?

    ... more calories than fat. So will building more muscle not boost your metabolism? Yes, but only by a small amount. Most ... you burn. Plus, when not in active use, muscles burn very few calories. Most ... most of your metabolism. What to do: Lift weights for stronger bones ...

  5. Metabolic exchanges within tumor microenvironment.

    Chiarugi, Paola; Cirri, Paolo

    2016-09-28

    Tumor progression toward malignancy often requires a metabolic rewiring of cancer cells to meet changes in metabolic demand to forefront nutrient and oxygen withdrawal, together with strong anabolic requests to match high proliferation rate. Tumor microenvironment highly contributes to metabolic rewiring of cancer cells, fostering complete nutrient exploitation, favoring OXPHOS of lipids and glutamine at the expense of glycolysis and enhancing exchanges via extracellular microvesicles or exosomes of proteins, lipids and small RNAs among tumor and stromal cells. Noteworthy, the same molecular drivers of metabolic reprogramming within tumor and stroma are also able to elicit motility, survival and self-renewal on cancer cells, thereby sustaining successful escaping strategies to circumvent the hostile hypoxic, acidic and inflammatory environment. This review highlights the emerging role of nutrients and vesicle-mediated exchanges among tumor and stromal cells, defining their molecular pathways and offering new perspectives to develop treatments targeting this complex metabolic rewiring. PMID:26546872

  6. Fetal Programming and Metabolic Syndrome

    Rinaudo, Paolo; Wang, Erica

    2014-01-01

    Metabolic syndrome is reaching epidemic proportions, particularly in developing countries. In this review, we explore the concept—based on the developmental-origin-of-health-and-disease hypothesis—that reprogramming during critical times of fetal life can lead to metabolic syndrome in adulthood. Specifically, we summarize the epidemiological evidence linking prenatal stress, manifested by low birth weight, to metabolic syndrome and its individual components. We also review animal studies that suggest potential mechanisms for the long-term effects of fetal reprogramming, including the cellular response to stress and both organ- and hormone-specific alterations induced by stress. Although metabolic syndrome in adulthood is undoubtedly caused by multiple factors, including modifiable behavior, fetal life may provide a critical window in which individuals are predisposed to metabolic syndrome later in life. PMID:21910625

  7. [Metabolic syndrome--psychosomatic associations].

    Kolesnikov, D B; Rapoport, S I

    2008-01-01

    According to epidemiological investigations data, 10 to 35% of all population suffers from metabolic syndrome. However, until now, in spite of researches, metabolic syndrome remains little-studied complex problem. The aim of the review is summarized analysis of the researches results, going out the limits of internal diseases clinics and reflecting more complicated, psychosomatic mechanisms of the syndrome development. The data of literature indicate the row of patterns in development of psyche and metabolic processes disturbances. Analysis of various directions in study of metabolic syndrome with concomitant mental disturbances is represented in the article. The authors propose to perform further investigation subject to "multisectorality" of the disease, marking out prevailing mechanisms of development of metabolic syndrome subject to somatic and mental factors. PMID:18368784

  8. [Hypertension and the metabolic syndrome.

    Olsen, Michael; Jeppesen, Jørgen; Larsen, Mogens

    2009-01-01

    The metabolic syndrome is a relatively prevalent condition characterized by co-existence of several metabolic and cardiovascular risk factors including hypertension. Patients with hypertension have an increased risk of developing the metabolic syndrome which, in turn, increases the cardiovascular...... risk associated with increased blood pressure. As the definition of the metabolic syndrome is based on dichotomization of cardiovascular risk factors with a continuously increasing risk, it cannot match risk stratification tools like the HeartScore for calculation of prognosis. However, the metabolic...... syndrome is of clinical importance as it makes the treating physician test for other elements of the syndrome in patients with one of the elements, e.g. hypertension. Udgivelsesdato: 2009-Jun-15...

  9. Vitamin A Metabolism: An Update

    William S. Blaner

    2011-01-01

    Full Text Available Retinoids are required for maintaining many essential physiological processes in the body, including normal growth and development, normal vision, a healthy immune system, normal reproduction, and healthy skin and barrier functions. In excess of 500 genes are thought to be regulated by retinoic acid. 11-cis-retinal serves as the visual chromophore in vision. The body must acquire retinoid from the diet in order to maintain these essential physiological processes. Retinoid metabolism is complex and involves many different retinoid forms, including retinyl esters, retinol, retinal, retinoic acid and oxidized and conjugated metabolites of both retinol and retinoic acid. In addition, retinoid metabolism involves many carrier proteins and enzymes that are specific to retinoid metabolism, as well as other proteins which may be involved in mediating also triglyceride and/or cholesterol metabolism. This review will focus on recent advances for understanding retinoid metabolism that have taken place in the last ten to fifteen years.

  10. Ethnic Considerations for Metabolic Surgery.

    Morton, John Magaña

    2016-06-01

    Obesity and diabetes represent twin health concerns in the developed world. Metabolic surgery has emerged as an established and enduring treatment for both obesity and diabetes. As the burden of obesity and diabetes varies upon the basis of ethnicity, it is also apparent that there may be differences for indications and outcomes for different ethnic groups after metabolic surgery. Whereas there appears to be evidence for variation in weight loss and complications for different ethnic groups, comorbidity remission particularly for diabetes appears to be free of ethnic disparity after metabolic surgery. The impacts of access, biology, culture, genetics, procedure, and socioeconomic status upon metabolic surgery outcomes are examined. Further refinement of the influence of ethnicity upon metabolic surgery outcomes is likely imminent. PMID:27222553

  11. Retinoid Metabolism and Diabetes Mellitus

    Eun-Jung Rhee

    2012-06-01

    Full Text Available Retinoid acid is a metabolite of vitamin A and functions as an important factor in cell survival, differentiation and death. Most previous studies on retinoid metabolism have focused on its association with cancer, hematologic and dermatologic disorders. Given the special concern over the recent increase in the prevalence of diabetes worldwide, the role of retinoid metabolism on glucose metabolism and insulin resistance in the human body is of marked importance. Therefore, in this issue, we review the literature on the association of retinoid metabolism with glucose tolerance, with regard to insulin secretion, pancreatic autoimmunity, insulin sensitivity and lipid metabolism. Further, we tried to assess the possibility of using retinoids as a novel therapeutic strategy for diabetes.

  12. Lipid Chaperones and Metabolic Inflammation

    Masato Furuhashi

    2011-01-01

    Full Text Available Over the past decade, a large body of evidence has emerged demonstrating an integration of metabolic and immune response pathways. It is now clear that obesity and associated disorders such as insulin resistance and type 2 diabetes are associated with a metabolically driven, low-grade, chronic inflammatory state, referred to as “metaflammation.” Several inflammatory cytokines as well as lipids and metabolic stress pathways can activate metaflammation, which targets metabolically critical organs and tissues including adipocytes and macrophages to adversely affect systemic homeostasis. On the other hand, inside the cell, fatty acid-binding proteins (FABPs, a family of lipid chaperones, as well as endoplasmic reticulum (ER stress, and reactive oxygen species derived from mitochondria play significant roles in promotion of metabolically triggered inflammation. Here, we discuss the molecular and cellular basis of the roles of FABPs, especially FABP4 and FABP5, in metaflammation and related diseases including obesity, diabetes, and atherosclerosis.

  13. Metabolic crosstalk between choline/1-carbon metabolism and energy homeostasis.

    Zeisel, Steven H

    2013-03-01

    There are multiple identified mechanisms involved in energy metabolism, insulin resistance and adiposity, but there are here-to-fore unsuspected metabolic factors that also influence these processes. Studies in animal models suggest important links between choline/1-carbon metabolism and energy homeostasis. Rodents fed choline deficient diets become hypermetabolic. Mice with deletions in one of several different genes of choline metabolism have phenotypes that include increased metabolic rate, decreased body fat/lean mass ratio, increased insulin sensitivity, decreased ATP production by mitochondria, or decreased weight gain on a high fat diet. In addition, farmers have recognized that the addition of a metabolite of choline (betaine) to cattle and swine feed reduces body fat/lean mass ratio. Choline dietary intake in humans varies over a > three-fold range, and genetic variation exists that modifies individual requirements for this nutrient. Although there are some epidemiologic studies in humans suggesting a link between choline/1-carbon metabolism and energy metabolism, there have been no controlled studies in humans that were specifically designed to examine this relationship. PMID:23072856

  14. Role of Dopamine 2 Receptor in Impaired Drug-Cue Extinction in Adolescent Rats.

    Zbukvic, Isabel C; Ganella, Despina E; Perry, Christina J; Madsen, Heather B; Bye, Christopher R; Lawrence, Andrew J; Kim, Jee Hyun

    2016-06-01

    Adolescent drug users display resistance to treatment such as cue exposure therapy (CET), as well as increased liability to relapse. The basis of CET is extinction learning, which involves dopamine signaling in the medial prefrontal cortex (mPFC). This system undergoes dramatic alterations during adolescence. Therefore, we investigated extinction of a cocaine-associated cue in adolescent and adult rats. While cocaine self-administration and lever-alone extinction were not different between the two ages, we observed that cue extinction reduced cue-induced reinstatement in adult but not adolescent rats. Infusion of the selective dopamine 2 receptor (D2R)-like agonist quinpirole into the infralimbic cortex (IL) of the mPFC prior to cue extinction significantly reduced cue-induced reinstatement in adolescents. This effect was replicated by acute systemic treatment with the atypical antipsychotic aripiprazole (Abilify), a partial D2R-like agonist. These data suggest that adolescents may be more susceptible to relapse due to a deficit in cue extinction learning, and highlight the significance of D2R signaling in the IL for cue extinction during adolescence. These findings inspire new tactics for improving adolescent CET, with aripiprazole representing an exciting potential pharmacological adjunct for behavioral therapy. PMID:26946126

  15. Structural correlations in bacterial metabolic networks

    Lizana Ludvig; Gerlee Philip; Bernhardsson Sebastian

    2011-01-01

    Abstract Background Evolution of metabolism occurs through the acquisition and loss of genes whose products acts as enzymes in metabolic reactions, and from a presumably simple primordial metabolism the organisms living today have evolved complex and highly variable metabolisms. We have studied this phenomenon by comparing the metabolic networks of 134 bacterial species with known phylogenetic relationships, and by studying a neutral model of metabolic network evolution. Results We consider t...

  16. Metabolic reprogramming during neuronal differentiation.

    Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G

    2016-09-01

    Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate-glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K-Akt-mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation. PMID:27058317

  17. Noise effect in metabolic networks

    Constraint-based models such as flux balance analysis (FBA) are a powerful tool to study biological metabolic networks. Under the hypothesis that cells operate at an optimal growth rate as the result of evolution and natural selection, this model successfully predicts most cellular behaviours in growth rate. However, the model ignores the fact that cells can change their cellular metabolic states during evolution, leaving optimal metabolic states unstable. Here, we consider all the cellular processes that change metabolic states into a single term 'noise', and assume that cells change metabolic states by randomly walking in feasible solution space. By simulating a state of a cell randomly walking in the constrained solution space of metabolic networks, we found that in a noisy environment cells in optimal states tend to travel away from these points. On considering the competition between the noise effect and the growth effect in cell evolution, we found that there exists a trade-off between these two effects. As a result, the population of the cells contains different cellular metabolic states, and the population growth rate is at suboptimal states. (cross-disciplinary physics and related areas of science and technology)

  18. Regulation of sphingomyelin metabolism.

    Bienias, Kamil; Fiedorowicz, Anna; Sadowska, Anna; Prokopiuk, Sławomir; Car, Halina

    2016-06-01

    Sphingolipids (SFs) represent a large class of lipids playing diverse functions in a vast number of physiological and pathological processes. Sphingomyelin (SM) is the most abundant SF in the cell, with ubiquitous distribution within mammalian tissues, and particularly high levels in the Central Nervous System (CNS). SM is an essential element of plasma membrane (PM) and its levels are crucial for the cell function. SM content in a cell is strictly regulated by the enzymes of SM metabolic pathways, which activities create a balance between SM synthesis and degradation. The de novo synthesis via SM synthases (SMSs) in the last step of the multi-stage process is the most important pathway of SM formation in a cell. The SM hydrolysis by sphingomyelinases (SMases) increases the concentration of ceramide (Cer), a bioactive molecule, which is involved in cellular proliferation, growth and apoptosis. By controlling the levels of SM and Cer, SMSs and SMases maintain cellular homeostasis. Enzymes of SM cycle exhibit unique properties and diverse tissue distribution. Disturbances in their activities were observed in many CNS pathologies. This review characterizes the physiological roles of SM and enzymes controlling SM levels as well as their involvement in selected pathologies of the Central Nervous System, such as ischemia/hypoxia, Alzheimer disease (AD), Parkinson disease (PD), depression, schizophrenia and Niemann Pick disease (NPD). PMID:26940196

  19. Carbohydrate metabolism in catfish

    Radiolabeled (U- 14C)-glucose was incorporated in diets and forced-fed to channel catfish and was observed for a 24 hour period. About 95% of fed labeled (U-14C)-glucose was absorbed by catfish, showing a high digestibility of glucose. The amounts of 14C excreted over 24 h as carbon dioxide were 49% and amounts excreted in urine were 3.5%. The amount retained as protein, fat glycogen and other organic compounds were 8.2, 1.2, 6.5 and 32.1 % respectively, for the 24 hour period. The blood concentration of 14 C reached a maximum 2.5 hour after feeding (U-14C)-glucose, then gradually decreased. Based on tissue concentrations of 14C, glycogen was an immediate storage site for absorbed glucose, but 14C- glycogen in liver decreased rapidly. Glucose was quickly and heavily converted into triglyceride, indicating that fat is an important intermediate in the metabolism of glucose in channel catfish. 14C-fat in the serum and liver were transferred to the adipose tissue in the muscle and mesentery about 10 hours after feeding. (Author)

  20. Metabolism of lorazepam.

    Elliott, H W

    1976-10-01

    The metabolism of lorazepam by man and four other species is reviewed. Lorazepam and its metabolites in blood, urine and faeces were identified by thin-layer and gas chromatography and by mass spectrometry. The principal metabolite in man, dog, pig and cat is the glucuronide, but the rat produces other metabolites after small doses of lorazepam, and significant amounts of the glucuronide only after high doses. Since all metabolites, except the glucuronide, occur in small quantities only in man, most studies in man have been confined to an estimation of gree and conjugated lorazepam. Blood concentrations of unconjugated lorazepam peak at 1-4 h, significant concentrations persisting for 24 h and decreasing slowly over the next 24 h. About 95% of a dose of lorazepam was accounted for in urine and faeces over a period of 5 days; 74.5% was excreted in the urine as lorazepam glucuronide and 13.5% as minor metabolites. The excretory half-life was 12 h. The blood concentrations and excretion rates are compatible with the clinical effects of lorazepam. PMID:10938

  1. [Regulation of terpene metabolism

    Croteau, R.

    1991-01-01

    During the last grant period, we have completed studies on the key pathways of monoterpene biosynthesis and catabolism in sage and peppermint, and have, by several lines of evidence, deciphered the rate-limiting step of each pathway. We have at least partially purified and characterized the relevant enzymes of each pathway. We have made a strong case, based on analytical, in vivo, and in vitro studies, that terpene accumulation depends upon the balance between biosynthesis and catabolism, and provided supporting evidence that these processes are developmentally-regulated and very closely associated with senescence of the oil glands. Oil gland ontogeny has been characterized at the ultrastructural level. We have exploited foliar-applied bioregulators to delay gland senescence, and have developed tissue explant and cell culture systems to study several elusive aspects of catabolism. We have isolated pure gland cell clusters and localized monoterpene biosynthesis and catabolism within these structures, and have used these preparations as starting materials for the purification to homogeneity of target regulatory'' enzymes. We have thus developed the necessary background knowledge, based on a firm understanding of enzymology, as well as the necessary experimental tools for studying the regulation of monoterpene metabolism at the molecular level. Furthermore, we are now in a position to extend our systematic approach to other terpenoid classes (C[sub 15]-C[sub 30]) produced by oil glands.

  2. Metabolic Syndrome – Epidemiological Problem?

    Gierach, Marcin; Junik, Roman

    2013-01-01

    The main components of the metabolic syndrome (MetS) are abdominal obesity, hypertension, lipid disorders such as aterogenic dyslipidemia and carbohydrates disorders such as impaired fasting glucose or diabetes mellitus type 2 The first definition of MetS was described by Reaven in 1988 and was named as syndrome X. In the United States of America, the metabolic syndrome affects about 25 % of US adults. In Poland, data based on NATPOL PLUS study, according to NCEP-ATP III criteria, metabolic s...

  3. Redesigned Human Metabolic Simulator

    Duffield, Bruce; Jeng, Frank; Lange, Kevin

    2008-01-01

    A design has been formulated for a proposed improved version of an apparatus that simulates atmospheric effects of human respiration by introducing controlled amounts of carbon dioxide, water vapor, and heat into the air. Denoted a human metabolic simulator (HMS), the apparatus is used for testing life-support equipment when human test subjects are not available. The prior version of the HMS, to be replaced, was designed to simulate the respiratory effects of as many as four persons. It exploits the catalytic combustion of methyl acetate, for which the respiratory quotient (the molar ratio of carbon dioxide produced to oxygen consumed) is very close to the human respiratory quotient of about 0.86. The design of the improved HMS provides for simulation of the respiratory effects of as many as eight persons at various levels of activity. The design would also increase safety by eliminating the use of combustion. The improved HMS (see figure) would include a computer that would exert overall control. The computer would calculate the required amounts of oxygen removal, carbon dioxide addition, water addition, and heat addition by use of empirical equations for metabolic profiles of respiration and heat. A blower would circulate air between the HMS and a chamber containing a life-support system to be tested. With the help of feedback from a mass flowmeter, the blower speed would be adjusted to regulate the rate of flow according to the number of persons to be simulated and to a temperature-regulation requirement (the air temperature would indirectly depend on the rate of flow, among other parameters). Oxygen would be removed from the circulating air by means of a commercially available molecular sieve configured as an oxygen concentrator. Oxygen, argon, and trace amounts of nitrogen would pass through a bed in the molecular sieve while carbon dioxide, the majority of nitrogen, and other trace gases would be trapped by the bed and subsequently returned to the chamber. If

  4. The metabolic syndrome in HIV

    Worm, Signe W; Lundgren, Jens D

    2011-01-01

    The metabolic syndrome (MS) is a term used to describe the clustering of risk factors for cardiovascular disease (CVD), including elevated triglyceride (TG), low high density lipoprotein cholesterol (HDL), hypertension, hyperglycemia/ insulin resistance and intra-abdominal obesity. This paper...

  5. Metabolism and biochemistry in hypogravity

    Leach, Carolyn S.

    1991-01-01

    The headward shift of body fluid and increase in stress-related hormones that occur in hypogravity bring about a number of changes in metabolism and biochemistry of the human body. Such alterations may have important effects on health during flight and during a recovery period after return to earth. Body fluid and electrolytes are lost, and blood levels of several hormones that control metabolism are altered during space flight. Increased serum calcium may lead to an increased risk of renal stone formation during flight, and altered drug metabolism could influence the efficacy of therapeutic agents. Orthostatic intolerance and an increased risk of fracturing weakened bones are concerns at landing. It is important to understand biochemistry and metabolism in hypogravity so that clinically important developments can be anticipated and prevented or ameliorated.

  6. Adipose Tissue Metabolism During Hypobaria

    D. P. Chattopadhyay

    1974-10-01

    Full Text Available Possible factors affecting the metabolism of adipose tissue under hypobaric conditions have been reviewed. The hormonal changes brought into play under hypoxic stress generally stress generally increase the adipose tissue lipolysis.

  7. Metabolic syndrome and periodontal disease

    Bharti Vipin

    2009-01-01

    Full Text Available It is important for a dentist to be well informed and updated on the latest research on the association of oral and systemic health. Of late, the metabolic syndrome has gained importance in dental literature, and metabolic syndrome and periodontal disease have been linked. Metabolic syndrome (MeS is a group of three or more (up to five interrelated metabolic abnormalities, which increases the risk of cardiovascular morbidity and mortality. Also, both MeS and periodontal disease may be linked through a common pathophysiological pathway. Some studies have been conducted to show such an association and additional studies are required to establish this association. A dental surgeon can play a major role in evaluating patients with MeS and thus prevent the development of overt cardiovascular disease.

  8. Metabolic pancreatitis: Etiopathogenesis and management

    Sunil Kumar Kota

    2013-01-01

    Full Text Available Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis. Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson′s disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis.

  9. Dietary Fats and Metabolic Syndrome

    Danijela Ristic-Medic

    2013-12-01

    Full Text Available The quantity and quality of fats consumed in the diet can have important effects on prevention and/or improvement clustering metabolic abnormalities of the metabolic syndrome. Fatty acids as food ingredients regulate cholesterol homeostasis and concentrations of blood lipoproteins, and affect the levels of other cardiometabolic risk factors, such as blood pressure, haemostasis, and body weight, through various mechanisms. There is convincing evidence that exchanging dietary saturated fat with monounsaturated fat produces beneficial effects on metabolic control, i.a. it lowers LDL-cholesterol concentrations, improves the postprandial lipid profile and lowers the blood pressure. Serum fatty acid composition mainly reflects dietary fat intake, but also endogenous fatty acid synthesis catalyzed by desaturases. Furthermore, high fat intake and serum fatty acid profile may influence the progression of obesity and insulin sensitivity. This review highlights current dietary guidance of fats quality recommendation in health and cardio metabolic risk.

  10. Complex systems in metabolic engineering.

    Winkler, James D; Erickson, Keesha; Choudhury, Alaksh; Halweg-Edwards, Andrea L; Gill, Ryan T

    2015-12-01

    Metabolic engineers manipulate intricate biological networks to build efficient biological machines. The inherent complexity of this task, derived from the extensive and often unknown interconnectivity between and within these networks, often prevents researchers from achieving desired performance. Other fields have developed methods to tackle the issue of complexity for their unique subset of engineering problems, but to date, there has not been extensive and comprehensive examination of how metabolic engineers use existing tools to ameliorate this effect on their own research projects. In this review, we examine how complexity affects engineering at the protein, pathway, and genome levels within an organism, and the tools for handling these issues to achieve high-performing strain designs. Quantitative complexity metrics and their applications to metabolic engineering versus traditional engineering fields are also discussed. We conclude by predicting how metabolic engineering practices may advance in light of an explicit consideration of design complexity. PMID:26319897

  11. Metabolic Resistance in Bed Bugs

    Omprakash Mittapalli

    2011-03-01

    Full Text Available Blood-feeding insects have evolved resistance to various insecticides (organochlorines, pyrethroids, carbamates, etc. through gene mutations and increased metabolism. Bed bugs (Cimex lectularius are hematophagous ectoparasites that are poised to become one of the major pests in households throughout the United States. Currently, C. lectularius has attained a high global impact status due to its sudden and rampant resurgence. Resistance to pesticides is one factor implicated in this phenomenon. Although much emphasis has been placed on target sensitivity, little to no knowledge is available on the role of key metabolic players (e.g., cytochrome P450s and glutathione S-transferases towards pesticide resistance in C. lectularius. In this review, we discuss different modes of resistance (target sensitivity, penetration resistance, behavioral resistance, and metabolic resistance with more emphasis on metabolic resistance.

  12. Context-dependent metabolic networks

    Beguerisse-Díaz, Mariano; Oyarzún, Diego; Picó, Jesús; Barahona, Mauricio

    2016-01-01

    Cells adapt their metabolism to survive changes in their environment. We present a framework for the construction and analysis of metabolic reaction networks that can be tailored to reflect different environmental conditions. Using context-dependent flux distributions from Flux Balance Analysis (FBA), we produce directed networks with weighted links representing the amount of metabolite flowing from a source reaction to a target reaction per unit time. Such networks are analyzed with tools from network theory to reveal salient features of metabolite flows in each biological context. We illustrate our approach with the directed network of the central carbon metabolism of Escherichia coli, and study its properties in four relevant biological scenarios. Our results show that both flow and network structure depend drastically on the environment: networks produced from the same metabolic model in different contexts have different edges, components, and flow communities, capturing the biological re-routing of metab...

  13. Dementia due to metabolic causes

    ... these chemical abnormalities cause permanent brain damage and dementia. ... Metabolic causes of dementia include: Endocrine disorders, such as Addison disease , Cushing disease Heavy metal exposure, such as to lead, arsenic, ...

  14. Glycogen metabolism in humans.

    Adeva-Andany, María M; González-Lucán, Manuel; Donapetry-García, Cristóbal; Fernández-Fernández, Carlos; Ameneiros-Rodríguez, Eva

    2016-06-01

    In the human body, glycogen is a branched polymer of glucose stored mainly in the liver and the skeletal muscle that supplies glucose to the blood stream during fasting periods and to the muscle cells during muscle contraction. Glycogen has been identified in other tissues such as brain, heart, kidney, adipose tissue, and erythrocytes, but glycogen function in these tissues is mostly unknown. Glycogen synthesis requires a series of reactions that include glucose entrance into the cell through transporters, phosphorylation of glucose to glucose 6-phosphate, isomerization to glucose 1-phosphate, and formation of uridine 5'-diphosphate-glucose, which is the direct glucose donor for glycogen synthesis. Glycogenin catalyzes the formation of a short glucose polymer that is extended by the action of glycogen synthase. Glycogen branching enzyme introduces branch points in the glycogen particle at even intervals. Laforin and malin are proteins involved in glycogen assembly but their specific function remains elusive in humans. Glycogen is accumulated in the liver primarily during the postprandial period and in the skeletal muscle predominantly after exercise. In the cytosol, glycogen breakdown or glycogenolysis is carried out by two enzymes, glycogen phosphorylase which releases glucose 1-phosphate from the linear chains of glycogen, and glycogen debranching enzyme which untangles the branch points. In the lysosomes, glycogen degradation is catalyzed by α-glucosidase. The glucose 6-phosphatase system catalyzes the dephosphorylation of glucose 6-phosphate to glucose, a necessary step for free glucose to leave the cell. Mutations in the genes encoding the enzymes involved in glycogen metabolism cause glycogen storage diseases. PMID:27051594

  15. [Metabolic intolerance to exercise].

    Arenas, J; Martín, M A

    2003-01-01

    Exercise intolerance (EI) is a frequent cause of medical attention, although it is sometimes difficult to come to a final diagnosis. However, there is a group of patients in whom EI is due to a metabolic dysfunction. McArdle's disease (type V glucogenosis) is due to myophosphorylase (MPL) deficiency. The ischemic exercise test shows a flat lactate curve. The most frequent mutations in the PYGM gene (MPL gene) in Spanish patients with MPL deficiency are R49X and W797R. Carnitine palmitoyltransferase (CPT) II deficiency is invariably associated to repetitive episodes of myoglobinuria triggered by exercise, cold, fever or fasting. The diagnosis depends on the demonstration of CPT II deficiency in muscle. The most frequent mutation in the CPT2 gene is the S113L. Patients with muscle adenylate deaminase deficiency usually show either a mild myopathy or no symptom. The diagnosis is based on the absence of enzyme activity in muscle and the lack of rise of ammonia in the forearm ischemic exercise test. The mutation Q12X in the AMPD1 gene is strongly associated with the disease. Exercise intolerance is a common complaint in patients with mitochondrial respiratory chain (MRC) deficiencies, although it is often overshadowed by other symptoms and signs. Only recently we have come to appreciate that exercise intolerance can be the sole presentation of defects in the mtDNA, particularly in complex I, complex III, complex IV, or in some tRNAs. In addition, myoglobinuria can be observed in patients under statin treatment, particularly if associated with fibrates, due to an alteration in the assembly of the complex IV of the MRC. PMID:12838448

  16. Metabolic Syndrome in Nurses

    María Escasany

    2014-01-01

    Full Text Available Objectives: To estimate the prevalence of metabolic syndrome (MS in female nurses in the Hospital Juan A. Fernandez (HJAF, Buenos Aires, Argentina, and to determine whether work, rest, diet, and health, are predictive of it.Materials and methods: For the first objective, a descriptive, observational and cross-sectional study was conducted, and for the second, a multivariate cross-sectional observational multivariate analysis was made comparing independent samples. A total of 192 nurses were studied between October 2008 and March 2009. They completed a questionnaire that include indicators that could be predictors of MS. Anthropometric measurements, including blood pressure were taken, was well as a blood sample to analyze fasting glucose, HDL-C and plasma triglycerides.Results: It was found that 35% and 41% of nurses were overweight and obese, respectively. A total of 92% had centro-abdominal obesity. The prevalence of MS found was 33.3% (95%CI, 26.7 to 40.5. Those who had this disease were between 53±9 years. Statistically significant differences were found in the bivariate analysis between MS and the variables, age, length of service, time worked during night shift, and academic studies.Conclusions: The prevalence of MS was 64/192 in HJAF nurses (33.3% I 95%CI, 26.7-40.5. There were no statistically significant differences with the indicators of, age, “time worked during night shift”, and “studies”. These results suggest that age is the most important variable in predicting the onset of MS in the population of nurses.

  17. Testosterone and metabolic syndrome

    Glenn R Cunningham

    2015-04-01

    Full Text Available Controversies surround the usefulness of identifying patients with the metabolic syndrome (MetS. Many of the components are accepted risk factors for cardiovascular disease (CVD. Although the MetS as defined includes many men with insulin resistance, insulin resistance is not universal. The low total testosterone (TT and sex hormone binding globulin (SHBG levels in these men are best explained by the hyperinsulinism and increased inflammatory cytokines that accompany obesity and increased waist circumference. It is informative that low SHBG levels predict future development of the MetS. Evidence is strong relating low TT levels to CVD in men with and without the MetS; however, the relationship may not be causal. The recommendations of the International Diabetes Federation for managing the MetS include cardiovascular risk assessment, lifestyle changes in diet, exercise, weight reduction and treatment of individual components of the MetS. Unfortunately, it is uncommon to see patients with the MetS lose and maintain a 10% weight loss. Recent reports showing testosterone treatment induced dramatic changes in weight, waist circumference, insulin sensitivity, hemoglobin A1c levels and improvements in each of the components of the MetS are intriguing. While some observational studies have reported that testosterone replacement therapy increases cardiovascular events, the Food and Drug Administration in the United States has reviewed these reports and found them to be seriously flawed. Large, randomized, placebo-controlled trials are needed to provide more definitive data regarding the efficacy and safety of this treatment in middle and older men with the MetS and low TT levels.

  18. Evolution of metabolic network organization

    Bonchev Danail

    2010-05-01

    Full Text Available Abstract Background Comparison of metabolic networks across species is a key to understanding how evolutionary pressures shape these networks. By selecting taxa representative of different lineages or lifestyles and using a comprehensive set of descriptors of the structure and complexity of their metabolic networks, one can highlight both qualitative and quantitative differences in the metabolic organization of species subject to distinct evolutionary paths or environmental constraints. Results We used a novel representation of metabolic networks, termed network of interacting pathways or NIP, to focus on the modular, high-level organization of the metabolic capabilities of the cell. Using machine learning techniques we identified the most relevant aspects of cellular organization that change under evolutionary pressures. We considered the transitions from prokarya to eukarya (with a focus on the transitions among the archaea, bacteria and eukarya, from unicellular to multicellular eukarya, from free living to host-associated bacteria, from anaerobic to aerobic, as well as the acquisition of cell motility or growth in an environment of various levels of salinity or temperature. Intuitively, we expect organisms with more complex lifestyles to have more complex and robust metabolic networks. Here we demonstrate for the first time that such organisms are not only characterized by larger, denser networks of metabolic pathways but also have more efficiently organized cross communications, as revealed by subtle changes in network topology. These changes are unevenly distributed among metabolic pathways, with specific categories of pathways being promoted to more central locations as an answer to environmental constraints. Conclusions Combining methods from graph theory and machine learning, we have shown here that evolutionary pressures not only affects gene and protein sequences, but also specific details of the complex wiring of functional modules

  19. Metabolic syndrome in androgenic alopecia

    Hima Gopinath; Gatha M Upadya

    2016-01-01

    Background: Androgenic alopecia has been associated with an increased risk of coronary heart disease in various studies. The relationship between androgenic alopecia and metabolic syndrome, a known risk factor for atherosclerotic cardiovascular disease, is still poorly understood. Aim: To study the association between metabolic syndrome and early-onset androgenic alopecia. Methods: A hospital-based analytical cross-sectional study was done on men in the age group of 18–55 years. Eighty five c...

  20. Gut Microbiota and Metabolic Disorders

    Kyu Yeon Hur; Myung-Shik Lee

    2015-01-01

    Gut microbiota plays critical physiological roles in the energy extraction and in the control of local or systemic immunity. Gut microbiota and its disturbance also appear to be involved in the pathogenesis of diverse diseases including metabolic disorders, gastrointestinal diseases, cancer, etc. In the metabolic point of view, gut microbiota can modulate lipid accumulation, lipopolysaccharide content and the production of short-chain fatty acids that affect food intake, inflammatory tone, or...

  1. Phase II metabolism of benzene.

    Schrenk, D.; Orzechowski, A.; Schwarz, L R; Snyder, R.; Burchell, B; Ingelman-Sundberg, M; K. W. DE BOCK

    1996-01-01

    The hepatic metabolism of benzene is thought to be a prerequisite for its bony marrow toxicity. However, the complete pattern of benzene metabolites formed in the liver and their role in bone marrow toxicity are not fully understood. Therefore, benzene metabolism was studied in isolated rodent hepatocytes. Rat hepatocytes released benzene-1,2-dihydrodiol, hydroquinone (HQ), catechol (CT), phenol (PH), trans-trans-muconic acid, and a number of phase II metabolites such as PH sulfate and PH glu...

  2. Intermediary metabolism of the lung.

    Fisher, A B

    1984-01-01

    The lung is a metabolically active organ that is engaged in secretion, clearance and other maintenance functions that require reducing potential, energy and substrates for biosynthesis. These metabolic requirements are met in part through uptake and catabolism of glucose which represents the major fuel utilized by lung tissues. Gluconeogenesis does not occur, and glycogen stores are limited so that the lung depends on the circulation for its glucose requirement. Other substrates can be metabo...

  3. Oxygen Regulates Tissue Nitrite Metabolism

    Curtis, Erin; Hsu, Lewis L.; Noguchi, Audrey C.; Geary, Lisa; Shiva, Sruti

    2012-01-01

    Aims: Once dismissed as an inert byproduct of nitric oxide (NO) auto-oxidation, nitrite (NO2-) is now accepted as an endocrine reservoir of NO that elicits biological responses in major organs. While it is known that tissue nitrite is derived from NO oxidation and the diet, little is known about how nitrite is metabolized by tissue, particularly at intermediate oxygen tensions. We investigated the rates and mechanisms of tissue nitrite metabolism over a range of oxygen concentrations. Results...

  4. Mitochondria in Cancer Energy Metabolism

    Kim, Aekyong

    2015-01-01

    Cancer is a disease characterized by uncontrolled growth. Metabolic demands to sustain rapid proliferation must be compelling since aerobic glycolysis is the first as well as the most commonly shared characteristic of cancer. During the last decade, the significance of metabolic reprogramming of cancer has been at the center of attention. Nonetheless, despite all the knowledge gained on cancer biology, the field is not able to reach agreement on the issue of mitochondria: Are damaged mitochon...

  5. Metabolic syndrome and cardiovascular risk

    Abdullah M Alshehri

    2010-11-01

    Full Text Available The constellation of dyslipidemia (hypertriglyceridemia and low levels of high-density lipoprotein cholesterol, elevated blood pressure, impaired glucose tolerance, and central obesity is now classified as metabolic syndrome, also called syndrome X. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria for use in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general, they include a combination of multiple and metabolic risk factors. The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics, commonly manifest a prothrombotic state as well as and a proinflammatory state. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB, increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C. The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of atherosclerotic cardiovascular disease (ASCVD risk factors, that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to the components of the syndrome present as well as the other, non-metabolic syndrome risk factors in a particular person.

  6. [Metabolic therapy for heart failure].

    Loiacono, Ferdinando; Alberti, Luca; Lauretta, Ludovica; Puccetti, Patrizia; Silipigni, Carmen; Margonato, Alberto; Fragasso, Gabriele

    2014-01-01

    Heart failure may promote metabolic changes such as insulin resistance, in part through neurohumoral activation, and determining an increased utilization of non-carbohydrate substrates for energy production. In fact, fasting blood ketone bodies as well as fat oxidation have been shown to be increased in patients with heart failure. The result is depletion of myocardial ATP, phosphocreatine and creatine kinase with decreased efficiency of mechanical work. A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilization by the failing heart. To date, the most effective metabolic treatments include several pharmacological agents that directly inhibit fatty acid oxidation. The results of current research are supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and toward glucose metabolism could be an effective adjunctive treatment in patients with heart failure. Trimetazidine is the most studied drug in this context. Several small studies have evidenced the usefulness of such additional therapeutic tools for heart failure. More specifically, recent meta-analyses and a multicenter retrospective study have shown that additional use of trimetazidine in patients with heart failure, along with symptoms and cardiac function improvement, also provides a significant protective effect on all-cause mortality, cardiovascular events and hospitalization due to cardiac causes. Nevertheless, the exact role of metabolic therapy in heart failure is yet to be established, and a large multicenter randomized trial is necessary. PMID:25072544

  7. A randomized,controlled study of lithium carbonate monotheraPy or combined ariPiPrazole theraPy in Patients with biPolar disorder tyPe I manic ePisode%碳酸锂单用与合并阿立哌唑治疗双相障碍I型躁狂发作患者的随机对照研究

    宋振华; 粟幼嵩; 王勇; 黄佳; 季曹珺; 吴彦; 王祖承

    2014-01-01

    目的:探讨碳酸锂单用及合并阿立哌唑治疗双相障碍 I 型躁狂发作患者的疗效和安全性。方法:86例门诊双相障碍 I 型躁狂发作患者被随机分为联合组(碳酸锂+阿立哌唑治疗)和单药组(碳酸锂单药治疗),疗程8周。分别在治疗前、治疗2、4、8周进行杨氏躁狂量表(YMRS)和汉密顿抑郁量表(HAMD)-17项评定,采用治疗中出现的症状量表( TESS)评定不良反应。结果:治疗前两组YMRS 评分差异无统计学意义;治疗2、4、8周后联合组 YMRS 减分值明显高于对照组(P ﹤0.05或 P ﹤0.01);治疗前后两组 HAMD 均﹤7分;两组 TESS 评分差异无统计学意义。结论:碳酸锂联合阿立哌唑治疗双相障碍 I 型躁狂发作较单用碳酸锂起效快,症状改善更明显,且未见不良反应明显增加。%To investigate the clinical efficacy and safety of lithium carbonate monotherapy or combined aripiprazole therapy in patients with bipolar disorder type I manic episode. Method:Eighty-six out-patients with bipolar disorder type I manic episode were randomly divided into combining therapy group( trea-ted with lithium carbonate + aripiprazole)and monotherapy guoup(treated with lithium carbonate only),the course was 8 weeks. The patients were assessed by Young′s manic scale(YMRS)and Hamilton depression scale items(HAMD)-17 before treatment and 2,4,8 weeks after treatment. The adverse reaction was evaluated by treatment emergent symptoms scale(TESS). Results:Before treatment,the score of YMRS between the two groups was not significantly different. At 2,4,8 weeks after treatment the subtraction scores of YMRS in the combining therapy group were more obvious than the monotherapy guoup(P ﹤ 0. 05 or P ﹤ 0. 01). The scores of HAMD at each time point in the both groups were ﹤ 7. The score of TESS between the two groups was not signifi-cantly different. Conclusion:Compared lithium carbonate monotherapy

  8. Symptoms and Diagnosis of Metabolic Syndrome

    ... Tools & Resources Stroke More Symptoms and Diagnosis of Metabolic Syndrome Updated:Aug 30,2016 What are the symptoms ... content was last reviewed on 05/14/2014. Metabolic Syndrome • Home • About Metabolic Syndrome • Why Metabolic Syndrome Matters • ...

  9. Analog regulation of metabolic demand

    Muskhelishvili Georgi

    2011-03-01

    Full Text Available Abstract Background The 3D structure of the chromosome of the model organism Escherichia coli is one key component of its gene regulatory machinery. This type of regulation mediated by topological transitions of the chromosomal DNA can be thought of as an analog control, complementing the digital control, i.e. the network of regulation mediated by dedicated transcription factors. It is known that alterations in the superhelical density of chromosomal DNA lead to a rich pattern of differential expressed genes. Using a network approach, we analyze these expression changes for wild type E. coli and mutants lacking nucleoid associated proteins (NAPs from a metabolic and transcriptional regulatory network perspective. Results We find a significantly higher correspondence between gene expression and metabolism for the wild type expression changes compared to mutants in NAPs, indicating that supercoiling induces meaningful metabolic adjustments. As soon as the underlying regulatory machinery is impeded (as for the NAP mutants, this coherence between expression changes and the metabolic network is substantially reduced. This effect is even more pronounced, when we compute a wild type metabolic flux distribution using flux balance analysis and restrict our analysis to active reactions. Furthermore, we are able to show that the regulatory control exhibited by DNA supercoiling is not mediated by the transcriptional regulatory network (TRN, as the consistency of the expression changes with the TRN logic of activation and suppression is strongly reduced in the wild type in comparison to the mutants. Conclusions So far, the rich patterns of gene expression changes induced by alterations of the superhelical density of chromosomal DNA have been difficult to interpret. Here we characterize the effective networks formed by supercoiling-induced gene expression changes mapped onto reconstructions of E. coli's metabolic and transcriptional regulatory network. Our

  10. Metabolic syndrome in androgenic alopecia

    Hima Gopinath

    2016-01-01

    Full Text Available Background: Androgenic alopecia has been associated with an increased risk of coronary heart disease in various studies. The relationship between androgenic alopecia and metabolic syndrome, a known risk factor for atherosclerotic cardiovascular disease, is still poorly understood. Aim: To study the association between metabolic syndrome and early-onset androgenic alopecia. Methods: A hospital-based analytical cross-sectional study was done on men in the age group of 18–55 years. Eighty five clinically diagnosed cases with early-onset (<35 years androgenic alopecia of Norwood grade III or above, and 85 controls without androgenic alopecia were included. Data collected included anthropometric measurements, arterial blood pressure and history of chronic diseases. Fasting blood and lipid profile were determined. Metabolic syndrome was diagnosed as per the new International Diabetes Federation criteria. Chi-square and Student's t-test were used for statistical analysis using Statistical Package for the Social Sciences (SPSS version 17.00. Results: Metabolic syndrome was seen in 19 (22.4% patients with androgenic alopecia and 8 (9.4% controls (P = 0.021. Abdominal obesity, hypertension and lowered high-density lipoprotein were significantly higher in patients with androgenic alopecia versus their respective controls. Limitations: The limitations of our study include small sample size in subgroups and the lack of evidence of a temporal relationship between metabolic syndrome and androgenic alopecia. Conclusion: A higher prevalence of metabolic syndrome is seen in men with early-onset androgenic alopecia. Early screening for metabolic syndrome and its components is beneficial in patients with early-onset androgenic alopecia.

  11. Flux-balance modelling of plant metabolism

    Lee James Sweetlove; R. George eRatcliffe

    2011-01-01

    Flux-balance modelling of plant metabolic networks provides an important complement to 13C-based metabolic flux analysis. Flux-balance modelling is a constraints-based approach in which steady-state fluxes in a metabolic network are predicted by using optimisation algorithms within an experimentally bounded solution space. In the last two years several flux-balance models of plant metabolism have been published including genome-scale models of Arabidopsis metabolism. In this review we conside...

  12. Clinical effect and influence in cognitive function of aripiprazole and risperidone in patients with schizophrenia%阿立哌唑与利培酮对精神分裂症患者的临床疗效及认知功能的影响

    刘旭; 程哲; 杨芳; 程传宝

    2013-01-01

    [Objective]To explore the clinical effect and safety of aripiprazole and risperidone in patients with schizophrenia, and the influence in cognitive function of patients. [ Methods] 156 schizophrenia patients were randomly divided into two groups, 78 cases in each group. The research group was treated with aripiprazole orally, and the control group was given risperidone, for 8 weeks. Before treatment and at the end of the 4th and 8th week of treatment, the clinical effect was assessed with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression ( CGIS) , and the adverse reactions were evaluated with the Treatment Emergent Symptom Scale (TESS). Before treatment and at the end of the 8th week of treatment, the cognitive functions of patients was assessed with the Wechsler Adult Intelligence Scale (WAIS) , the Wechsler memory scale (WMS) and the Wisconsin Card Sorting Test (WCST). The evaluation results of two groups were analyzed and compared. [ Results] At the end of 4th week of treatment, the total and each factors scores of PANSS, as well as CGIS score decreased significantly as compared with those before treatment (P 0.05). At the end of 8th week of treatment, the obvious effective rate and effective rate in the research group was 73.08% and 96.15% respectively, and that in the control group was 71. 79% and 92. 31% respectively, which showed no significantly difference (X2 = 0. 032, 0. 806,P >0.05). At the end of 8th week, the error answers and non-persistent error of WCST of two groups decreased significantly than those before treatment, while factor scores of WMS in the recognition, regeneration, comprehension, memory quotient were significantly higher than those before treatment (P 0.05). Adverse reactions of both groups were mild, and appeared at the beginning of treatment. The incidence rates of extrapyramidal reactions, menstrual disorders, lactation and weight gain in the research group were significantly lower than those in the

  13. Lipid metabolism in mitochondrial membranes.

    Mayr, Johannes A

    2015-01-01

    Mitochondrial membranes have a unique lipid composition necessary for proper shape and function of the organelle. Mitochondrial lipid metabolism involves biosynthesis of the phospholipids phosphatidylethanolamine, cardiolipin and phosphatidylglycerol, the latter is a precursor of the late endosomal lipid bis(monoacylglycero)phosphate. It also includes mitochondrial fatty acid synthesis necessary for the formation of the lipid cofactor lipoic acid. Furthermore the synthesis of coenzyme Q takes place in mitochondria as well as essential parts of the steroid and vitamin D metabolism. Lipid transport and remodelling, which are necessary for tailoring and maintaining specific membrane properties, are just partially unravelled. Mitochondrial lipids are involved in organelle maintenance, fission and fusion, mitophagy and cytochrome c-mediated apoptosis. Mutations in TAZ, SERAC1 and AGK affect mitochondrial phospholipid metabolism and cause Barth syndrome, MEGDEL and Sengers syndrome, respectively. In these disorders an abnormal mitochondrial energy metabolism was found, which seems to be due to disturbed protein-lipid interactions, affecting especially enzymes of the oxidative phosphorylation. Since a growing number of enzymes and transport processes are recognised as parts of the mitochondrial lipid metabolism, a further increase of lipid-related disorders can be expected. PMID:25082432

  14. DNA methylation in metabolic disorders

    Barres, Romain; Zierath, Juleen R

    2011-01-01

    have provided evidence that environmental factors at all ages could modify DNA methylation in somatic tissues, which suggests that DNA methylation is a more dynamic process than previously appreciated. Because of the importance of lifestyle factors in metabolic disorders, DNA methylation provides...... a mechanism by which environmental factors, including diet and exercise, can modify genetic predisposition to disease. This article considers the current evidence that defines a role for DNA methylation in metabolic disorders.......DNA methylation is a major epigenetic modification that controls gene expression in physiologic and pathologic states. Metabolic diseases such as diabetes and obesity are associated with profound alterations in gene expression that are caused by genetic and environmental factors. Recent reports...

  15. Cancer Metabolism: A Modeling Perspective

    Ghaffari, Pouyan; Mardinoglu, Adil; Nielsen, Jens

    2015-01-01

    . Cancer cells present in complex tumor tissues communicate with the surrounding microenvironment and develop traits which promote their growth, survival, and metastasis. Decoding the full scope and targeting dysregulated metabolic pathways that support neoplastic transformations and their preservation...... suggest that utilization of amino acids and lipids contributes significantly to cancer cell metabolism. Also recent progresses in our understanding of carcinogenesis have revealed that cancer is a complex disease and cannot be understood through simple investigation of genetic mutations of cancerous cells...... requires both the advancement of experimental technologies for more comprehensive measurement of omics as well as the advancement of robust computational methods for accurate analysis of the generated data. Here, we review cancer-associated reprogramming of metabolism and highlight the capability of genome...

  16. Cellular compartmentalization of secondary metabolism

    H. Corby eKistler

    2015-02-01

    Full Text Available Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g. amino acids, acetyl CoA, NADPH, enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported.

  17. Flux networks in metabolic graphs

    A metabolic model can be represented as a bipartite graph comprising linked reaction and metabolite nodes. Here it is shown how a network of conserved fluxes can be assigned to the edges of such a graph by combining the reaction fluxes with a conserved metabolite property such as molecular weight. A similar flux network can be constructed by combining the primal and dual solutions to the linear programming problem that typically arises in constraint-based modelling. Such constructions may help with the visualization of flux distributions in complex metabolic networks. The analysis also explains the strong correlation observed between metabolite shadow prices (the dual linear programming variables) and conserved metabolite properties. The methods were applied to recent metabolic models for Escherichia coli, Saccharomyces cerevisiae and Methanosarcina barkeri. Detailed results are reported for E. coli; similar results were found for other organisms

  18. Novel genes in LDL metabolism

    Christoffersen, Mette; Tybjærg-Hansen, Anne

    2015-01-01

    transporters G5 and G8, Niemann-Pick C1-Like protein 1, sortilin-1, ABO blood-group glycosyltransferases, myosin regulatory light chain-interacting protein and cholesterol 7α-hydroxylase have all consistently been associated with LDL cholesterol levels and/or coronary artery disease in GWAS. Whole......-exome sequencing and 'exome chip' studies have additionally suggested several novel genes in LDL metabolism including insulin-induced gene 2, signal transducing adaptor family member 1, lysosomal acid lipase A, patatin-like phospholipase domain-containing protein 5 and transmembrane 6 superfamily member 2. Most of...... cholesterol. Novel genes in LDL metabolism will improve our understanding of mechanisms in LDL metabolism, and may lead to the identification of new drug targets to reduce LDL cholesterol levels....

  19. Complexity of vitamin E metabolism.

    Schmölz, Lisa; Birringer, Marc; Lorkowski, Stefan; Wallert, Maria

    2016-02-26

    Bioavailability of vitamin E is influenced by several factors, most are highlighted in this review. While gender, age and genetic constitution influence vitamin E bioavailability but cannot be modified, life-style and intake of vitamin E can be. Numerous factors must be taken into account however, i.e., when vitamin E is orally administrated, the food matrix may contain competing nutrients. The complex metabolic processes comprise intestinal absorption, vascular transport, hepatic sorting by intracellular binding proteins, such as the significant α-tocopherol-transfer protein, and hepatic metabolism. The coordinated changes involved in the hepatic metabolism of vitamin E provide an effective physiological pathway to protect tissues against the excessive accumulation of, in particular, non-α-tocopherol forms. Metabolism of vitamin E begins with one cycle of CYP4F2/CYP3A4-dependent ω-hydroxylation followed by five cycles of subsequent β-oxidation, and forms the water-soluble end-product carboxyethylhydroxychroman. All known hepatic metabolites can be conjugated and are excreted, depending on the length of their side-chain, either via urine or feces. The physiological handling of vitamin E underlies kinetics which vary between the different vitamin E forms. Here, saturation of the side-chain and also substitution of the chromanol ring system are important. Most of the metabolic reactions and processes that are involved with vitamin E are also shared by other fat soluble vitamins. Influencing interactions with other nutrients such as vitamin K or pharmaceuticals are also covered by this review. All these processes modulate the formation of vitamin E metabolites and their concentrations in tissues and body fluids. Differences in metabolism might be responsible for the discrepancies that have been observed in studies performed in vivo and in vitro using vitamin E as a supplement or nutrient. To evaluate individual vitamin E status, the analytical procedures used for

  20. Methadone metabolism by human placenta.

    Nanovskaya, Tatiana N; Deshmukh, Sujal V; Nekhayeva, Ilona A; Zharikova, Olga L; Hankins, Gary D V; Ahmed, Mahmoud S

    2004-08-01

    Methadone pharmacotherapy is considered the standard for treatment of the pregnant heroin/opioid addict. One of the factors affecting the transfer kinetics of opioids across human placenta and their levels in the fetal circulation is their metabolism by the tissue. The aim of this investigation is to identify the enzyme(s) responsible for the metabolism of methadone, determine the kinetics of the reaction and the metabolites formed utilizing placental tissue obtained from term healthy pregnancies. Microsomal fractions of trophoblast tissue homogenates had the highest activity in catalyzing the metabolism of methadone. The product formed was identified by HPLC-UV as 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP). Inhibitors selective for cytochrome P450 (CYP) isozymes were used to identify the enzyme catalyzing the biotransformation of methadone. Aminoglutethimide and 4-hydroxyandrostenedione inhibited EDDP formation by 88 and 70%, respectively, suggesting that CYP19/aromatase is the enzyme catalyzing the reaction. This was confirmed by the effect of monoclonal antibodies raised against CYP19 that caused an 80% inhibition of the reaction. The apparent K(m) and V(max) values for the CYP19 catalyzed metabolism of methadone to EDDP were 424 +/- 92 microM and 420 +/- 89 pmol(mgprotein)(-1)min(-1), respectively. Kinetic analysis of a cDNA-expressed CYP19 for the metabolism of methadone to EDDP was identical to that by placental microsomes. Taken together, these data indicate that CYP19/aromatase is the major enzyme responsible for the metabolism of methadone to EDDP in term human placentas obtained from healthy pregnancies. PMID:15242824

  1. Epigenetic regulation of skeletal muscle metabolism.

    Howlett, Kirsten F; McGee, Sean L

    2016-07-01

    Normal skeletal muscle metabolism is essential for whole body metabolic homoeostasis and disruptions in muscle metabolism are associated with a number of chronic diseases. Transcriptional control of metabolic enzyme expression is a major regulatory mechanism for muscle metabolic processes. Substantial evidence is emerging that highlights the importance of epigenetic mechanisms in this process. This review will examine the importance of epigenetics in the regulation of muscle metabolism, with a particular emphasis on DNA methylation and histone acetylation as epigenetic control points. The emerging cross-talk between metabolism and epigenetics in the context of health and disease will also be examined. The concept of inheritance of skeletal muscle metabolic phenotypes will be discussed, in addition to emerging epigenetic therapies that could be used to alter muscle metabolism in chronic disease states. PMID:27215678

  2. 'Biomoleculas': cellular metabolism didactic software

    'Biomoleculas' is a software that deals with topics such as the digestion, cellular metabolism and excretion of nutrients. It is a pleasant, simple and didactic guide, made by and for students. In this program, each biomolecule (carbohydrates, lipids and proteins) is accompanied until its degradation and assimilation by crossing and interrelating the different metabolic channels to finally show the destination of the different metabolites formed and the way in which these are excreted. It is used at present as a teaching-learning process tool by the chair of Physiology and Biophysics at the Facultad de Ingenieria - Universidad Nacional de Entre Rios

  3. [Metabolic therapy of postperitoneal intoxication].

    Vlasov, A P; Anaskin, S G; Vlasova, T I; Chivisov, S M; Shibitov, V A; Potyanova, I V; Selentsov, P V

    2012-01-01

    This clinico-laboratory study showed that antihypoxant remaxol promoted normalization of lipid metabolism in acute peritonitis and significantly reduced membrane-destabilizing events. This resulted in rapid elimination of the inflammatory process in the abdominal cavity and lowering of the intensity of endogenous intoxication. This beneficial effect decreased the severity of myocardial lesions and resulted in the normalization of erythrocyte function. It is concluded that the regulatory action of remaxol on lipid metabolism is due to its ability to control free radicals in lipid peroxidation and reduce phospholipase A2 activity. PMID:23285765

  4. Metabolic origins of childhood asthma.

    Grasemann, Hartmut

    2015-12-01

    Childhood obesity and incidence of asthma are increasing globally. The parallel increase of the two suggests that obesity and asthma may be related and that abnormalities in the lipid and/or glucose metabolism may contribute to the pathogenesis of asthma. The clinical presentation of obese asthma is distinct from other asthma phenotypes and depending on age of onset of symptoms. Asthma in obese people tends to be more severe, not typically associated with allergy, and less responsive to standard anti-inflammatory therapy, including corticosteroids. Obesity and obesity-related comorbidities may lead to asthma via a number of mechanisms including changes in lung mechanics, the nitric oxide metabolism, and by causing inflammation. Furthermore, evidence suggests that nutrition during pregnancy contributes to intrauterine immune and metabolic programming in the offspring, which may have major influences on predisposition to cardiovascular, metabolic, and allergic diseases, including asthma, later in life. This review will highlight some suggested mechanistic links between obesity and diabetes with asthma. PMID:26542296

  5. Metabolic vulnerabilities in endometrial cancer.

    Byrne, Frances L; Poon, Ivan K H; Modesitt, Susan C; Tomsig, Jose L; Chow, Jenny D Y; Healy, Marin E; Baker, William D; Atkins, Kristen A; Lancaster, Johnathan M; Marchion, Douglas C; Moley, Kelle H; Ravichandran, Kodi S; Slack-Davis, Jill K; Hoehn, Kyle L

    2014-10-15

    Women with metabolic disorders, including obesity and diabetes, have an increased risk of developing endometrial cancer. However, the metabolism of endometrial tumors themselves has been largely understudied. Comparing human endometrial tumors and cells with their nonmalignant counterparts, we found that upregulation of the glucose transporter GLUT6 was more closely associated with the cancer phenotype than other hallmark cancer genes, including hexokinase 2 and pyruvate kinase M2. Importantly, suppression of GLUT6 expression inhibited glycolysis and survival of endometrial cancer cells. Glycolysis and lipogenesis were also highly coupled with the cancer phenotype in patient samples and cells. To test whether targeting endometrial cancer metabolism could be exploited as a therapeutic strategy, we screened a panel of compounds known to target diverse metabolic pathways in endometrial cells. We identified that the glycolytic inhibitor, 3-bromopyruvate, is a powerful antagonist of lipogenesis through pyruvylation of CoA. We also provide evidence that 3-bromopyruvate promotes cell death via a necrotic mechanism that does not involve reactive oxygen species and that 3-bromopyruvate impaired the growth of endometrial cancer xenografts. PMID:25205105

  6. Metabolic engineering in methanotrophic bacteria

    Kalyuzhnaya, MG; Puri, AW; Lidstrom, ME

    2015-05-01

    Methane, as natural gas or biogas, is the least expensive source of carbon for (bio)chemical synthesis. Scalable biological upgrading of this simple alkane to chemicals and fuels can bring new sustainable solutions to a number of industries with large environmental footprints, such as natural gas/petroleum production, landfills, wastewater treatment, and livestock. Microbial biocatalysis with methane as a feedstock has been pursued off and on for almost a half century, with little enduring success. Today, biological engineering and systems biology provide new opportunities for metabolic system modulation and give new optimism to the concept of a methane-based bio-industry. Here we present an overview of the most recent advances pertaining to metabolic engineering of microbial methane utilization. Some ideas concerning metabolic improvements for production of acetyl-CoA and pyruvate, two main precursors for bioconversion, are presented. We also discuss main gaps in the current knowledge of aerobic methane utilization, which must be solved in order to release the full potential of methane-based biosystems. (C) 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  7. Absorption and Metabolism of Xanthophylls

    Eiichi Kotake-Nara

    2011-06-01

    Full Text Available Dietary carotenoids, especially xanthophylls, have attracted significant attention because of their characteristic biological activities, including anti-allergic, anti-cancer, and anti-obese actions. Although no less than forty carotenoids are ingested under usual dietary habits, only six carotenoids and their metabolites have been found in human tissues, suggesting selectivity in the intestinal absorption of carotenoids. Recently, facilitated diffusion in addition to simple diffusion has been reported to mediate the intestinal absorption of carotenoids in mammals. The selective absorption of carotenoids may be caused by uptake to the intestinal epithelia by the facilitated diffusion and an unknown excretion to intestinal lumen. It is well known that β-carotene can be metabolized to vitamin A after intestinal absorption of carotenoids, but little is known about the metabolic transformation of non provitamin A xanthophylls. The enzymatic oxidation of the secondary hydroxyl group leading to keto-carotenoids would occur as a common pathway of xanthophyll metabolism in mammals. This paper reviews the absorption and metabolism of xanthophylls by introducing recent advances in this field.

  8. Metabolic Acceleration in Human Evolution.

    Isler, Karin

    2016-07-12

    Humans stand out among other primates by an unusual combination of a very large brain and high fertility. Pontzer et al. (2016a) present new data on daily energy expenditure in great apes and show that the metabolic rate increased during human evolution. PMID:27411003

  9. Antihypertensive drugs and glucose metabolism

    Christos; V; Rizos; Moses; S; Elisaf

    2014-01-01

    Hypertension plays a major role in the development and progression of micro-and macrovascular disease.Moreover,increased blood pressure often coexists with additional cardiovascular risk factors such as insulin resistance.As a result the need for a comprehensive management of hypertensive patients is critical.However,the various antihypertensive drug categories have different effects on glucose metabolism.Indeed,angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose homeostasis.Calcium channel blockers(CCBs)have an overall neutral effect on glucose metabolism.However,some members of the CCBs class such as azelnidipine and manidipine have been shown to have advantageous effects on glucose homeostasis.On the other hand,diuretics andβ-blockers have an overall disadvantageous effect on glucose metabolism.Of note,carvedilol as well as nebivolol seem to differentiate themselves from the rest of theβ-blockers class,being more attractive options regarding their effect on glucose homeostasis.The adverse effects of some blood pressure lowering drugs on glucose metabolism may,to an extent,compromise their cardiovascular protective role.As a result the effects on glucose homeostasis of the various blood pressure lowering drugs should be taken into account when selecting an antihypertensive treatment,especially in patients which are at high risk for developing diabetes.

  10. Does Metabolically Healthy Obesity Exist?

    Muñoz-Garach, Araceli; Cornejo-Pareja, Isabel; Tinahones, Francisco J.

    2016-01-01

    The relationship between obesity and other metabolic diseases have been deeply studied. However, there are clinical inconsistencies, exceptions to the paradigm of “more fat means more metabolic disease”, and the subjects in this condition are referred to as metabolically healthy obese (MHO).They have long-standing obesity and morbid obesity but can be considered healthy despite their high degree of obesity. We describe the variable definitions of MHO, the underlying mechanisms that can explain the existence of this phenotype caused by greater adipose tissue inflammation or the different capacity for adipose tissue expansion and functionality apart from other unknown mechanisms. We analyze whether these subjects improve after an intervention (traditional lifestyle recommendations or bariatric surgery) or if they stay healthy as the years pass. MHO is common among the obese population and constitutes a unique subset of characteristics that reduce metabolic and cardiovascular risk factors despite the presence of excessive fat mass. The protective factors that grant a healthier profile to individuals with MHO are being elucidated. PMID:27258304

  11. Conducting the metabolic syndrome orchestra

    Civelek, Mete; Lusis, Aldons J.

    2011-01-01

    Genetic and gene expression studies have suggested an important role for KLF14 in metabolic disease. A new study now identifies a network of genes whose expression is associated with KLF14 variation in trans, providing a framework for understanding how KLF14 influences disease risk.

  12. SIRT1 and metabolic syndrome

    Katarzyna Mac-Marcjanek

    2011-04-01

    Full Text Available Both obesity and type 2 diabetes mellitus, two major components of metabolic syndrome, become healthepidemics in the world. Over the past decade, advances in understanding the role of some regulators participatingin lipid and carbohydrate homeostasis have been made.Of them, SIRT1, the mammalian orthologue of the yeast Sir2 protein has been identified. SIRT1 is a nuclearNAD+-dependent deacetylase that targets many transcriptional modulators, including PPAR-α and -γ (peroxisomeproliferator-activated receptors α and γ, PGC-1α (PPAR-γ coactivator-1α, FOXO (forkhead box O proteins,and nuclear factor κB (NF-κB, thereby this enzyme mediates a wide range of physiological processes like apoptosis,fat metabolism, glucose homeostasis, and neurodegeneration.In this article, we discuss how SIRT1 regulates lipid and carbohydrate metabolism, and insulin secretion indifferent metabolic organs/tissue, including liver, muscle, pancreas, and fat. Additionally, the role of this enzymein reduction of inflammatory signalling is highlighted.

  13. Galactosemia: a treatable metabolic disorder

    Galactosemia is a rare metabolic disorder. It has good prognosis, if detected in neonatal period or early infancy. Two cases of classic galactosemia are presented. One case was detected in neonatal period. Early intervention has led to normal development till now. The second case was diagnosed at 1 year of age. Elimination of milk from diet is quite simple and effective treatment modality. (author)

  14. CHROMIUM, METABOLIC SYNDROME AND DIABESITY

    Suboptimal intakes of the essential nutrient, chromium, are characterized by elevated blood glucose, insulin resistance, obesity, hypertriglyceridemia, and low HDL. These are also signs and symptoms of the metabolic syndrome. Improvements due to increased intake of chromium are related to the degr...

  15. Photorespiratory glycolate-glyoxylate metabolism.

    Dellero, Younès; Jossier, Mathieu; Schmitz, Jessica; Maurino, Veronica G; Hodges, Michael

    2016-05-01

    Photorespiration is one of the major carbon metabolism pathways in oxygen-producing photosynthetic organisms. This pathway recycles 2-phosphoglycolate (2-PG), a toxic metabolite, to 3-phosphoglycerate when ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) uses oxygen instead of carbon dioxide. The photorespiratory cycle is in competition with photosynthetic CO2 fixation and it is accompanied by carbon, nitrogen and energy losses. Thus, photorespiration has become a target to improve crop yields. Moreover, during the photorespiratory cycle intermediate metabolites that are toxic to Calvin-Benson cycle and RuBisCO activities, such as 2-PG, glycolate and glyoxylate, are produced. Thus, the presence of an efficient 2-PG/glycolate/glyoxylate 'detoxification' pathway is required to ensure normal development of photosynthetic organisms. Here we review our current knowledge concerning the enzymes that carry out the glycolate-glyoxylate metabolic steps of photorespiration from glycolate production in the chloroplasts to the synthesis of glycine in the peroxisomes. We describe the properties of the proteins involved in glycolate-glyoxylate metabolism in Archaeplastida and the phenotypes observed when knocking down/out these specific photorespiratory players. Advances in our understanding of the regulation of glycolate-glyoxylate metabolism are highlighted. PMID:26994478

  16. The Evolution of Fungal Metabolic Pathways

    Wisecaver, Jennifer H.; Slot, Jason C.; Rokas, Antonis

    2014-01-01

    Fungi contain a remarkable range of metabolic pathways, sometimes encoded by gene clusters, enabling them to digest most organic matter and synthesize an array of potent small molecules. Although metabolism is fundamental to the fungal lifestyle, we still know little about how major evolutionary processes, such as gene duplication (GD) and horizontal gene transfer (HGT), have interacted with clustered and non-clustered fungal metabolic pathways to give rise to this metabolic versatility. We e...

  17. Species differences in the metabolism of benzene.

    Henderson, R F

    1996-01-01

    The pathways of metabolism of benzene appear to be qualitatively similar in all species studied thus far. However, there are quantitative differences in the fraction of benzene metabolized by the different pathways. These species differences become important for risk assessments based on animal data. Mice have a greater overall capacity to metabolize benzene than rats or primates, based on mass balance studies conducted in vivo using radiolabled benzene. Mice and monkeys metabolize more of th...

  18. Indolealkylamine metabolism: synthesis of deuterated indolealkylamines as metabolic probes

    The synthesis of the deuterium labeled, endogenously occurring, indolealkylamine hallucinogens N,N-dimethyltryptamine and 5-methoxy-N, N-dimethyltryptamine via reduction of amide intermediates with lithium aluminum deuteride is described. The compounds were characterized with 1H, 2H and 13C NMR. These compounds were synthesized for use as probes for investigating the metabolism of these compounds by MAO via the in vivo kinetic isotope effect. (Author)

  19. It must be my metabolism: Metabolic control of mind

    Dana M Small

    2014-07-01

    relationship between the reinforcing potency of sugared solutions and the metabolic effects that follow their consumption (16, also see the abstract of I. de Araujo. We therefore hypothesized that metabolic response provides the critical signal necessary to condition preference. To test this prediction in humans we designed a flavor nutrient conditioning study in which participants first rated their liking for novel flavored beverages and then, over a three week-long conditioning protocol, alternately ingested one of the flavored beverages with 112.5 kcal from maltodextrin, a tasteless and odorless polysaccharide that breaks down into glucose, and another flavored beverage with no calories added. Plasma glucose was measured before and after each of the drinks’ consumption as a proxy measure of metabolic response, assuming that glucose oxidation depends upon the level of circulating glucose. For each participant flavor-calorie pairings were held constant but the identity of the conditioned flavors were counterbalanced across participants. Following the exposure phase, participants’ liking of, and brain responses to, non-caloric versions of the flavors were assessed. We predicted that change in plasma glucose produced by beverage consumption during the exposure sessions would be associated with neural responses in dopamine source and target regions to the calorie predictive flavor. As predicted, response in the ventral striatum and hypothalamus to the calorie-predictive flavor (CS+ vs. non the noncaloric-predictive flavor (CS- was strongly associated with the changes in plasma glucose levels produced by ingestion of these same beverages when consumed previously either with (CS+ or without (CS- calories (17. Specifically, the greater the increase in circulating glucose occurring post ingestion of the beverage containing 112.5 kcal from maltodextrin versus the noncaloric drink, the stronger was the brain response to the CS+ compared to the CS- flavor. Importantly, because each

  20. Ketone body metabolism and cardiovascular disease

    Cotter, David G.; Schugar, Rebecca C.; Crawford, Peter A.

    2013-01-01

    Ketone bodies are metabolized through evolutionarily conserved pathways that support bioenergetic homeostasis, particularly in brain, heart, and skeletal muscle when carbohydrates are in short supply. The metabolism of ketone bodies interfaces with the tricarboxylic acid cycle, β-oxidation of fatty acids, de novo lipogenesis, sterol biosynthesis, glucose metabolism, the mitochondrial electron transport chain, hormonal signaling, intracellular signal transduction pathways, and the microbiome. ...

  1. Urban metabolism: A review of research methodologies

    Urban metabolism analysis has become an important tool for the study of urban ecosystems. The problems of large metabolic throughput, low metabolic efficiency, and disordered metabolic processes are a major cause of unhealthy urban systems. In this paper, I summarize the international research on urban metabolism, and describe the progress that has been made in terms of research methodologies. I also review the methods used in accounting for and evaluating material and energy flows in urban metabolic processes, simulation of these flows using a network model, and practical applications of these methods. Based on this review of the literature, I propose directions for future research, and particularly the need to study the urban carbon metabolism because of the modern context of global climate change. Moreover, I recommend more research on the optimal regulation of urban metabolic systems. Highlights: •Urban metabolic processes can be analyzed by regarding cities as superorganisms. •Urban metabolism methods include accounting, assessment, modeling, and regulation. •Research methodologies have improved greatly since this field began in 1965. •Future research should focus on carbon metabolism and optimal regulation. -- The author reviews research progress in the field of urban metabolism, and based on her literature review, proposes directions for future research

  2. Metabolism of phthalates in humans

    Frederiksen, Hanne; Skakkebaek, Niels E; Andersson, Anna-Maria

    2007-01-01

    the foetal testis and they are similar to those seen in humans with testicular dysgenesis syndrome. Therefore, exposure of the human foetus and infants to phthalates via maternal exposure is a matter of concern. The metabolic pathways of phthalate metabolites excreted in human urine are partly known......Phthalates are synthetic compounds widely used as plasticisers, solvents and additives in many consumer products. Several animal studies have shown that some phthalates possess endocrine disrupting effects. Some of the effects of phthalates seen in rats are due to testosterone lowering effects on...... for some phthalates, but our knowledge about metabolic distribution in the body and other biological fluids, including breast milk, is limited. Compared to urine, human breast milk contains relatively more of the hydrophobic phthalates, such as di-n-butyl phthalate and the longer-branched, di(2...

  3. Spontaneous emergence of a metabolism

    Bagley, R.J.; Farmer, J.D. (Los Alamos National Lab., NM (USA) Santa Fe Inst., NM (USA))

    1990-01-01

    Networks of catalyzed reactions with nonlinear feedback have been proposed to play an important role in the origin of life. We investigate this possibility in a polymer chemistry with catalyzed cleavage and condensation reactions. We study the properties of a well-stirred reactor driven away from equilibrium by the flow of mass. Under appropriate non-equilibrium conditions. The nonlinear feedback of the reaction network focuses the material of the system into a few specific polymer species. The network of catalytic reactions digests'' the material of its environment, incorporating it into its own form. We call the result an autocatalytic metabolism. Under some variations it persists almost unchanged, while in other cases it dies. We argue that the dynamical stability of autocatalytic metabolisms gives them regenerative properties that allow them to repair themselves and to propagate through time. 43 refs., 16 figs., 3 tabs.

  4. Bupropion metabolism by human placenta

    Wang, Xiaoming; Abdelrahman, Doaa R.; Zharikova, Olga L.; PATRIKEEVA, Svetlana L; Hankins, Gary D.V.; AHMED, Mahmoud S.; Nanovskaya, Tatiana N.

    2010-01-01

    Smoking during pregnancy is the largest modifiable risk factor for pregnancy-related morbidity and mortality. The success of bupropion for smoking cessation warrants its investigation for treatment of pregnant patients. Nevertheless, the use of bupropion for the treatment of pregnant smokers requires additional data on its biodisposition during pregnancy. Therefore, the aim of this investigation was to determine the metabolism of bupropion in placentas obtained from nonsmoking and smoking wom...

  5. Metabolism of pantethine in cystinosis.

    Wittwer, C T; Gahl, W.A.; Butler, J D; Zatz, M; Thoene, J G

    1985-01-01

    D-Pantethine is a conjugate of the vitamin pantothenic acid and the low-molecular-weight aminothiol cysteamine. Pantethine is an experimental hypolipemic agent and has been suggested as a source of cysteamine in the treatment of nephropathic cystinosis. We treated four cystinotic children with 70-1,000 mg/kg per d oral D-pantethine and studied its metabolism. Pantethine was rapidly hydrolyzed to pantothenic acid and cysteamine; we could not detect pantethine in plasma after oral administratio...

  6. Differential Diagnosis of Metabolic Alkalosis

    M Hafizi

    1995-07-01

    Full Text Available A 9-month old female infant with growth retardation, constipation and restlessness id presented. Laboratory findings revealed hypochloremic metabolic alkalosis with hypokalemia and hyponatremia. Clinical and laboratory findings led us to think of batter syndrome and cystic fibrosis. Serum and urine levels of chloride were low. This led to the estimation of sweat electrolytes, which showed high chloride levels. Taking also into account other laboratory and clinical parameters cystic fibrosis was the final diagnosis.

  7. Zinc metabolism in thyroid disease.

    Nishi, Y.; Kawate, R.; Usui, T

    1980-01-01

    This study was designed to evaluate the zinc metabolism in adults of both sexes with thyroid disease. Plasma and erythrocyte zinc concentration and urinary zinc excretion were investigated. The mean concentration of plasma zinc in hypothyroid patients and in euthyroid patients, previously either hyperthyroid or hypothyroid, was lower than that of control subjects, whereas no statistically significant differences were observed in plasma zinc values between hyperthyroid patients and control sub...

  8. Metabolism and toxicity of californium

    Metabolism of californium can be compared with that of other transplutonium elements. The most important points are as follows: a fast blood clearance and fast bone uptake more important than liver uptake, a relatively high urinary excretion and kidney retention. Blood clearance of californium can be compared with that of americium. Distribution of californium 252 nitrate after intramuscular injection in rats was studied. There are very few experimental data on acute or long term toxicity of californium. (28 references)

  9. Polyol metabolism by Rhizobium trifolii.

    Primrose, S. B.; Ronson, C W

    1980-01-01

    In Rhizobium trifolii 7000, the polyols myo-inositol, xylitol, ribitol, D-arabitol, D-mannitol, D-sorbital, and dulcitol are metabolized by inducible nicotinamide adenine dinucleotide-dependent polyol dehydrogenases. Five different polyol dehydrogenases were recognized: inositol dehydrogenase, specific for inositil; ribitol dehydrogenase, specific for ribitol; D-arabitol dehydrogenase, which oxidized D-arabitol, D-mannitol, and D-sorbitol; xylitol dehydrogenase, which oxidized xylitol and D-s...

  10. NAD metabolism in Vibrio cholerae.

    Foster, J. W.; Brestel, C

    1982-01-01

    Extracts of Vibrio cholerae were assayed for various enzymatic activities associated with pyridine nucleotide cycle metabolism. The activities measured include NAD glycohydrolase, nicotinamide deamidase, nicotinamide mononucleotide deamidase, and nicotinic acid phosphoribosyltransferase. The results obtained demonstrate the existence in V. cholerae of the five-membered pyridine nucleotide cycle and the potential for a four-membered pyridine nucleotide cycle. The data presented also suggest th...

  11. Metabolism addiction in pancreatic cancer

    Blum, R.; Kloog, Y

    2014-01-01

    Pancreatic ductal adenocarcinoma, an aggressively invasive, treatment-resistant malignancy and the fourth leading cause of cancer deaths in the United States, is usually detectable only when already inevitably fatal. Despite advances in genetic screening, mapping and molecular characterization, its pathology remains largely elusive. Renewed research interest in longstanding doctrines of tumor metabolism has led to the emergence of aberrant signaling pathways as critical factors modulating cen...

  12. Fine-tuning Metabolic Switches

    Breckenridge, Ross A.; Piotrowska, Izabela; Ng, Keat-Eng; Ragan, Timothy J.; West, James A.; Kotecha, Surendra; Towers, Norma; Bennett, Michael; Kienesberger, Petra C.; Smolenski, Ryszard T.; Siddall, Hillary K.; Offer, John L.; Mocanu, Mihaela M.; Yelon, Derek M.; Dyck, Jason R.B.

    2013-01-01

    Cardiomyocytes are vulnerable to hypoxia in the adult, but adapted to hypoxia in utero. Current understanding of endogenous cardiac oxygen sensing pathways is limited. Myocardial oxygen consumption is determined by regulation of energy metabolism, which shifts from glycolysis to lipid oxidation soon after birth, and is reversed in failing adult hearts, accompanying re-expression of several “fetal” genes whose role in disease phenotypes remains unknown. Here we show that hypoxia-controlled exp...

  13. Nutritional Aspect of Tryptophan Metabolism

    Tsutomu Fukuwatari; Katsumi Shibata

    2013-01-01

    Mammals, including humans, can synthesize the vitamin nicotinamide from tryptophan in the liver. The resultant nicotinamide is distributed to non-hepatic tissues. We have studied the effects of changes in tryptophan–nicotinamide metabolism on niacin nutritional status. The liver plays a critical role in nicotinamide supply. Animal studies showed that the tryptophan–nicotinamide pathway is affected by physiological conditions, the presence of disease, nutrients, hormones, and chemicals. Human ...

  14. Nutritional, metabolic, and endocrine disorders

    Osteoporosis is reduction in bone quantity, the actual quality of the bone remaining normal. Strictly interpreted, osteoporosis means increased porosity of bone. This is the most commonly encountered metabolic disease of bone. An all-encompassing term used to describe increased radiolucency in bone is ''osteopenia,'' meaning ''poverty of bone.'' It does not, however, imply an etiology for the decreased bone density. Osteoporosis is classified into three types - generalized, regional, and localized. They are described here

  15. Mitochondrial Metabolism in Aging Heart.

    Lesnefsky, Edward J; Chen, Qun; Hoppel, Charles L

    2016-05-13

    Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area, there is ≈50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction. PMID:27174952

  16. Metabolic engineering in methanotrophic bacteria.

    Kalyuzhnaya, Marina G; Puri, Aaron W; Lidstrom, Mary E

    2015-05-01

    Methane, as natural gas or biogas, is the least expensive source of carbon for (bio)chemical synthesis. Scalable biological upgrading of this simple alkane to chemicals and fuels can bring new sustainable solutions to a number of industries with large environmental footprints, such as natural gas/petroleum production, landfills, wastewater treatment, and livestock. Microbial biocatalysis with methane as a feedstock has been pursued off and on for almost a half century, with little enduring success. Today, biological engineering and systems biology provide new opportunities for metabolic system modulation and give new optimism to the concept of a methane-based bio-industry. Here we present an overview of the most recent advances pertaining to metabolic engineering of microbial methane utilization. Some ideas concerning metabolic improvements for production of acetyl-CoA and pyruvate, two main precursors for bioconversion, are presented. We also discuss main gaps in the current knowledge of aerobic methane utilization, which must be solved in order to release the full potential of methane-based biosystems. PMID:25825038

  17. Immunometabolism: Cellular Metabolism Turns Immune Regulator.

    Loftus, Róisín M; Finlay, David K

    2016-01-01

    Immune cells are highly dynamic in terms of their growth, proliferation, and effector functions as they respond to immunological challenges. Different immune cells can adopt distinct metabolic configurations that allow the cell to balance its requirements for energy, molecular biosynthesis, and longevity. However, in addition to facilitating immune cell responses, it is now becoming clear that cellular metabolism has direct roles in regulating immune cell function. This review article describes the distinct metabolic signatures of key immune cells, explains how these metabolic setups facilitate immune function, and discusses the emerging evidence that intracellular metabolism has an integral role in controlling immune responses. PMID:26534957

  18. Interplay between oxidant species and energy metabolism.

    Quijano, Celia; Trujillo, Madia; Castro, Laura; Trostchansky, Andrés

    2016-08-01

    It has long been recognized that energy metabolism is linked to the production of reactive oxygen species (ROS) and critical enzymes allied to metabolic pathways can be affected by redox reactions. This interplay between energy metabolism and ROS becomes most apparent during the aging process and in the onset and progression of many age-related diseases (i.e. diabetes, metabolic syndrome, atherosclerosis, neurodegenerative diseases). As such, the capacity to identify metabolic pathways involved in ROS formation, as well as specific targets and oxidative modifications is crucial to our understanding of the molecular basis of age-related diseases and for the design of novel therapeutic strategies. Herein we review oxidant formation associated with the cell's energetic metabolism, key antioxidants involved in ROS detoxification, and the principal targets of oxidant species in metabolic routes and discuss their relevance in cell signaling and age-related diseases. PMID:26741399

  19. Lipid metabolism in experimental animals

    Sánchez-Muñiz, Francisco J.

    1998-08-01

    Full Text Available Publications are scarce in the way in chich metabolic processes are affected by the ingestion of heated fats used to prepare food. Similarly studies measuring metabolic effects of the consumption on fried food are poorly known. The purpose of this presentation is to summarize information on frying fats and frying foods upon lipid metabolism in experimental animals. Food consumption is equivalent or even higher when oils or the fat content of frying foods are poorly alterated decreasing their acceptability when their alteration degree increase. After 4hr. experiment the digestibility and absorption coefficients of a single dosis of thermooxidized oils were significantly decreased in rats, however the digestive utilization of frying thermooxidized oils included in diets showed very little change in comparison with unused oils by feeding trials on rats. Feeding rats different frying fats induced a slight hypercholesterolemic effect being the magnitude of this effect related to the linoleic decrease in diet produced by frying. However HDL, the main rat-cholesterol carrier, also increased, thus the serum cholesterol/HDL-cholesterol ratio did not change. Results suggest that rats fed frying fats adapt their lipoprotein metabolism increasing the number of HDL particles. Deep fat frying deeply changed the fatty acid composition of foods, being possible to increase their n-9 or n-6 fatty acid and to decrease the saturated fatty acid contents by frying. When olive oil-and sunflower oil-fried sardines were used as the only protein and fat sources of rats-diets in order to prevent the dietary hypercholesterolemia it was provided that both fried-sardine diets showed a powerful check effect on the cholesterol raising effect induced by dietary cholesterol. The negative effect of feeding rats cholesterol plus bovine bile to induce hypercholesterolemia on some cell-damage markers such as lactate dehydrogenase, transaminases, alkaline phosphatase, was

  20. Metabolism

    2006-01-01

    4.1 Nutrition imbalance 2006024 Effect of multiple micronutrients supplementation on anti - oxidative activity and oxidized DNA damage of lymphocytes in children ZHANG Ming ( 张明), Nutrit Dept, Weifang People Hosp, Weifang 261041. Chin J Epidemiol 2005 ;26(4) :268 -272. Objective:To examine the effect of multiple micronutrients supplementation on anti - oxidative activity and decreasing oxidized DNA damage of lymphocytes in Chinese children. Methods:82 healthy children in rural areas, aged 9-11 years, were selected and randomized into group receiving supplements and control group with 41 in

  1. Ensemble Kinetic Modeling of Metabolic Networks from Dynamic Metabolic Profiles

    Gengjie Jia

    2012-11-01

    Full Text Available Kinetic modeling of metabolic pathways has important applications in metabolic engineering, but significant challenges still remain. The difficulties faced vary from finding best-fit parameters in a highly multidimensional search space to incomplete parameter identifiability. To meet some of these challenges, an ensemble modeling method is developed for characterizing a subset of kinetic parameters that give statistically equivalent goodness-of-fit to time series concentration data. The method is based on the incremental identification approach, where the parameter estimation is done in a step-wise manner. Numerical efficacy is achieved by reducing the dimensionality of parameter space and using efficient random parameter exploration algorithms. The shift toward using model ensembles, instead of the traditional “best-fit” models, is necessary to directly account for model uncertainty during the application of such models. The performance of the ensemble modeling approach has been demonstrated in the modeling of a generic branched pathway and the trehalose pathway in Saccharomyces cerevisiae using generalized mass action (GMA kinetics.

  2. Does methamphetamine affect bone metabolism?

    There is a close relationship between the central nervous system activity and bone metabolism. Therefore, methamphetamine (METH), which stimulates the central nervous system, is expected to affect bone turnover. The aim of this study was to investigate the role of METH in bone metabolism. Mice were divided into 3 groups, the control group receiving saline injections, and the 5 and 10 mg/kg METH groups (n = 6 in each group). All groups received an injection of saline or METH every other day for 8 weeks. Bone mineral density (BMD) was assessed by X-ray computed tomography. We examined biochemical markers and histomorphometric changes in the second cancellous bone of the left femoral distal end. The animals that were administered 5 mg/kg METH showed an increased locomotor activity, whereas those receiving 10 mg/kg displayed an abnormal and stereotyped behavior. Serum calcium and phosphorus concentrations were normal compared to the controls, whereas the serum protein concentration was lower in the METH groups. BMD was unchanged in all groups. Bone formation markers such as alkaline phosphatase and osteocalcin significantly increased in the 5 mg/kg METH group, but not in the 10 mg/kg METH group. In contrast, bone resorption markers such as C-terminal telopeptides of type I collagen and tartrate-resistant acid phosphatase 5b did not change in any of the METH groups. Histomorphometric analyses were consistent with the biochemical markers data. A significant increase in osteoblasts, especially in type III osteoblasts, was observed in the 5 mg/kg METH group, whereas other parameters of bone resorption and mineralization remained unchanged. These results indicate that bone remodeling in this group was unbalanced. In contrast, in the 10 mg/kg METH group, some parameters of bone formation were significantly or slightly decreased, suggesting a low turnover metabolism. Taken together, our results suggest that METH had distinct dose-dependent effects on bone turnover and that

  3. Anaerobic metabolism in Brassica seedlings

    Park, Myoung-Ryoul; Hasenstein, Karl H.

    Germination typically depends on oxidative respiration. The lack of convection under space conditions may create hypoxic or conditions during seed germination. We investigated the effect of reduced oxygen on seed germination and metabolism to understand how metabolic constraints affect seed growth and responsiveness to reorientation. Germination was completely inhibited when seeds were imbibed in the absence of oxygen; germination occurred at 5% oxygen and higher levels. Adding oxygen after 72 h resulted in immediate germination (protrusion of the radicle). Hypoxia typically activates alcohol dehydrogenase (ADH, EC 1.1.1.1) and lactate dehydrogenase (LDH, EC 1.1.1.27) which produce ethanol and/or L-lactate, respectively. We report on the expression of ADH1 and LDH1, and changes in total soluble sugars, starch, pH, and L-lactate in seedlings grown at 28°C in 0, 2.5, 5, 10% and ambient (21%) oxygen conditions as controls. The highest consumption (lowest level) of sugars was seen at 0% oxygen but the lowest level of starch occurred 24 h after imbibition under ambient condition. Expression levels of ADH1 in ambient oxygen condition increased within 24 h but increased threefold under hypoxic conditions; LDH1 increased up to 8-fold under hypoxia compared to controls but ADH1 and LDH1 were less expressed as the oxygen levels increased. The intracellular pH of seeds decreased as the content of L-lactate increased for all oxygen concentrations. These results indicate that germination of Brassica is sensitive to oxygen levels and that oxygen availability during germination is an important factor for metabolic activities. (Supported by NASA grant NNX10AP91G)

  4. Metabolic effects of contraceptive steroids.

    Sitruk-Ware, Regine; Nath, Anita

    2011-06-01

    Estrogen and progestins have been used by millions of women as effective combined contraceptives. The safety of hormonal contraceptives has been documented by years of follow-up and serious adverse events that may be related to their use are rare in the young population exposed to these agents. The balance between the benefits and the risks of contraceptive steroids is generally positive in particular when comparing to the risks of pregnancy and especially in women with risk factors. The metabolic changes induced by the synthetic steroids used in contraception, such as lipoprotein changes, insulin response to glucose, and coagulation factors have been considered as potential markers of cardiovascular and venous risk. Observations of these effects have led to modifications of the composition of hormonal contraceptive in order to minimize these changes and hence potentially decrease the risks. The synthetic estrogen Ethinyl-Estradiol (EE) exerts a stronger effect that natural estradiol (E2) on hepatic metabolism including estrogen-dependent markers such as liver proteins. This stronger hepatic impact of EE has been related to its 17α-ethinyl group which prevents the inactivation of the molecule and results in a more pronounced hepatic effect of EE as compared to estradiol. Due to its strong activity, administering EE via a non-oral route does not prevent its impact on liver proteins. In order to circumvent the metabolic changes induced by EE, newer products using more natural compounds such as estradiol (E2) and estradiol valerate (E2V) have been introduced. The synthetic progestins used for contraception are structurally related either to testosterone (T) (estranes and gonanes) or to progesterone (pregnanes and 19-norpregnanes). Several new progestins have been designed to bind more specifically to the progesterone receptor and to minimize side-effects related to androgenic, estrogenic or glucocorticoid receptor interactions. Dienogest (DNG), and drospirenone (DRSP

  5. [Prostate cancer and metabolic syndrome].

    Nagamatsu, Hirotaka; Teishima, Jun; Inoue, Shogo; Hayashi, Tetsutaro; Matsubara, Akio

    2016-01-01

    The prevalence of metabolic syndrome (MS) is increasing in Japan because of westernization of diet and lifestyle. Previous epidemiological studies have demonstrated MS to relate with the malignant potential of prostate cancer (PCa) while its relationship to the risk of PCa has been still controversial. Several pathologies involved in MS, such as insulin resistance, abnormality of secreted adipokines, chronic inflammation, alteration of sex hormones, have been reported to affect the progression of PCa. Based on these evidences, clinical studies for PCa patients have been tried for suppressing the progression of PCa through the management of MS. PMID:26793896

  6. Thiophene metabolism by E. coli

    Clark, D.P.

    1990-01-01

    The objective of this project is to investigate the mechanism of degradation of sulfur containing heterocyclic molecules such as those found in coal, by mutants of Escherichia coli K-12. We previously isolated multiple mutants of E. coli which were selected for improved oxidation of furan and thiophene derivatives. We have focused on the thdA mutation in our subsequent research as it appears to be of central importance in thiophene oxidation. We hope that analysis of the thd genes of E. coli will lead to improvement of our thiophene metabolizing bacterial strains. 1 tab.

  7. Thiophene metabolism by E. coli

    Clark, D.P.

    1990-01-01

    The objective of this project is to investigate the mechanism of degradation of sulfur containing heterocyclic molecules by mutants of Escherichia coli K-12. We previously isolated multiple mutants of E. coli which were selected for improved oxidation of furan and thiophene derivatives. We have focused on the thdA mutation in our subsequent research as it appears to be of central importance in thiophene oxidation. We hope that analysis of the thd gene of E. coli will lead to improvement of our thiophene metabolizing bacterial strains.

  8. Glucose metabolism in ischemic myocardium

    We determined the myocardial metabolic rate for glucose (MMRGlc) in the ischemic or infarcted myocardium using 18-F-fluorodeoxyglucose (18-FDG) with positron emission tomography (PET), and studied energy metabolism in the ischemic myocardium. In some cases, we compared glucose metabolism images by 18-FDG with myocardial blood flow images using 15-oxygen water. Two normal subjects, seven patients with myocardial infarction and four patients with angina pectoris were studied. Coronary angiography was performed within two weeks before or after the PET study to detect ischemic areas. PET studies were performed for patients who did not eat for 5 to 6 hours after breakfast. Cannulation was performed in the pedal artery to measure free fatty acid, blood sugar, and insulin. After recording the transmission scan for subsequent correction of photon attenuation, blood pool images were recorded for two min. after the inhalation of carbon monoxide (oxygen-15) which labeled the red blood cells in vivo. After 20 min., oxygen-15 water (15 to 20 mCi) was injected for dynamic scans, and flow images were obtained. Thirty min. after this procedure, 18-FDG (5 to 6 mCi) was injected, and 60 min later, a static scan was performed and glucose metabolism images were obtained. Arterial blood sampling for the time activity curve of the tracer was performed at the same time. According to the method of Phelps et al, MMRGlc was calculated in each of the region of interest (ROI) which was located in the left ventricular wall. MMRGlc obtained from each ROI was 0 to 17 mg/100 ml/min. In normal subjects MMRGlc was 0.4 to 7.3 mg/100 ml/min. In patients with myocardial infarction, it ranged from 3 to 5 mg/100 ml/min in the infarcted lesion. In patients with angina pectoris and subendocardial infarction, MMRGlc was 7 to 17 mg/100 ml/min in the ischemic lesion. In this lesion, myocardial blood flow was relatively low by oxygen-15 imagings (so-called mismatch). (J.P.N.)

  9. Sulfonates and Organotrophic Sulfite Metabolism

    Cook, Alasdair M.; Theo H. M. Smits; Denger, Karin

    2007-01-01

    One is used to considering sulfite oxidation as part of a lithotrophic process (e.g. SorAB or Sox system), much of which involves neutral or ionic inorganic sulfur species on the outer surface of the cytoplasmic membrane. In contrast, the processes referred to in this chapter involve organic compounds, which (1) include a highly stable sulfonate substituent (C−SO3−), (2) are involved in the organotrophic growth of the organism and (3) much of whose metabolism takes place in the cytoplasm. Man...

  10. C. elegans Metabolic Gene Regulatory Networks Govern the Cellular Economy

    Watson, Emma; Walhout, Albertha J.M.

    2014-01-01

    Diet greatly impacts metabolism in health and disease. In response to the presence or absence of specific nutrients, metabolic gene regulatory networks sense the metabolic state of the cell and regulate metabolic flux accordingly, for instance by the transcriptional control of metabolic enzymes. Here we discuss recent insights regarding metazoan metabolic regulatory networks using the nematode Caenorhabditis elegans as a model, including the modular organization of metabolic gene regulatory networks, the prominent impact of diet on the transcriptome and metabolome, specialized roles of nuclear hormone receptors in responding to dietary conditions, regulation of metabolic genes and metabolic regulators by microRNAs, and feedback between metabolic genes and their regulators. PMID:24731597

  11. Role of aripiprazole in treatment-resistant schizophrenia

    Mossaheb N; Kaufmann RM

    2012-01-01

    Nilufar Mossaheb,1 Rainer M Kaufmann21Department of Child and Adolescent Psychiatry, 2Department of Psychiatry and Psychotherapy, Medical University, Vienna, AustriaAbstract: About one third of patients with schizophrenia respond unsatisfactorily to antipsychotic treatment and are termed “treatment-resistant”. Clozapine is still the gold standard in these cases. However, 40%–70% of patients do not improve sufficiently on clozapine either. In the search for more e...

  12. Metabolic model for diversity-generating biosynthesis.

    Tianero, Ma Diarey; Pierce, Elizabeth; Raghuraman, Shrinivasan; Sardar, Debosmita; McIntosh, John A; Heemstra, John R; Schonrock, Zachary; Covington, Brett C; Maschek, J Alan; Cox, James E; Bachmann, Brian O; Olivera, Baldomero M; Ruffner, Duane E; Schmidt, Eric W

    2016-02-16

    A conventional metabolic pathway leads to a specific product. In stark contrast, there are diversity-generating metabolic pathways that naturally produce different chemicals, sometimes of great diversity. We demonstrate that for one such pathway, tru, each ensuing metabolic step is slower, in parallel with the increasing potential chemical divergence generated as the pathway proceeds. Intermediates are long lived and accumulate progressively, in contrast with conventional metabolic pathways, in which the first step is rate-limiting and metabolic intermediates are short-lived. Understanding these fundamental differences enables several different practical applications, such as combinatorial biosynthesis, some of which we demonstrate here. We propose that these principles may provide a unifying framework underlying diversity-generating metabolism in many different biosynthetic pathways. PMID:26831074

  13. Metabolic flux rewiring in mammalian cell cultures.

    Young, Jamey D

    2013-12-01

    Continuous cell lines (CCLs) engage in 'wasteful' glucose and glutamine metabolism that leads to accumulation of inhibitory byproducts, primarily lactate and ammonium. Advances in techniques for mapping intracellular carbon fluxes and profiling global changes in enzyme expression have led to a deeper understanding of the molecular drivers underlying these metabolic alterations. However, recent studies have revealed that CCLs are not necessarily entrenched in a glycolytic or glutaminolytic phenotype, but instead can shift their metabolism toward increased oxidative metabolism as nutrients become depleted and/or growth rate slows. Progress to understand dynamic flux regulation in CCLs has enabled the development of novel strategies to force cultures into desirable metabolic phenotypes, by combining fed-batch feeding strategies with direct metabolic engineering of host cells. PMID:23726154

  14. RNA Regulation of Lipotoxicity and Metabolic Stress.

    Caputa, George; Schaffer, Jean E

    2016-07-01

    Noncoding RNAs are an emerging class of nonpeptide regulators of metabolism. Metabolic diseases and the altered metabolic environment induce marked changes in levels of microRNAs and long noncoding RNAs. Furthermore, recent studies indicate that a growing number of microRNAs and long noncoding RNAs serve as critical mediators of adaptive and maladaptive responses through their effects on gene expression. The metabolic environment also has a profound impact on the functions of classes of noncoding RNAs that have been thought primarily to subserve housekeeping functions in cells-ribosomal RNAs, transfer RNAs, and small nucleolar RNAs. Evidence is accumulating that these RNAs are also components of an integrated cellular response to the metabolic milieu. This Perspective discusses the different classes of noncoding RNAs and their contributions to the pathogenesis of metabolic stress. PMID:27288006

  15. Simulating Metabolism with Statistical Thermodynamics

    Cannon, William R.

    2014-08-04

    Kinetic probabilities of state are usually based on empirical measurements, while thermodynamic state probabilities are based on the assumption that chemical species are distributed to according to a multinomial Boltzmann distribution. While the use of kinetic simulations is desirable, obtaining all the mass action rate constants necessary to carry out kinetic simulations is an overwhelming challenge. Here, the kinetic probability of a state is compared in depth to the thermodynamic probability of a state for sets of coupled reactions. The entropic and energetic contributions to thermodynamic stable states are described and compared to entropic and energetic contributions of kinetic steady states. It is shown that many kinetic steady states are possible for a system of coupled reactions depending on the relative values of the mass action rate constants, but only one of these corresponds to a thermodynamically stable state. Furthermore, the thermodynamic stable state corresponds to a minimum free energy state. The use of thermodynamic simulations of state to model metabolic processes is attractive, since metabolite levels and energy requirements of pathways can be evaluated using only standard free energies of formation as parameters in the probability distribution. In chemical physics, the assumption of a Boltzmann distribution is the basis of transition state theory for modeling transitory species. Application to stable species, such as those found in metabolic processes, is a less severe assumption that would enable the use of simulations of state.

  16. Metabolic fate of chlorinated paraffins

    The disposition of three [1-14C]-chlorododecanes (MCDD, PCDD I and PCDD II; 17.4%, 55.9%, and 68.5% chlorination) was studied in C57Bl mice. [1-14C]-lauric acid (LA) was studied as reference compound. Fifty-two percent (MCDD), 32% (PCDD I), and 8% (PCDD II) of the radioactive doses were exhaled as 14CO2 during 12 h after i.v. injection. Similar results were obtained after p.o. administration. In addition to a marked labelling of the liver and fat, the distribution patterns observed at 24 h after administration revealed an uptake of radioactivity in tissues with high cell turnover/high metabolic activity, e.g., intestinal mucosa, bone marrow, salivary glands and thymus. The concentration of radioactivity in these sites and the exhalation of 14CO2, which were inverse to the degree of chlorination, indicate that the chloroalkanes are degraded to metabolites which can be utilized in the intermediary metabolism. A similar, although more pronounced, distribution pattern and 14CO2-exhalation (70% of i.v. dose) was observed after LA administration. The long time retention of heptane-soluble radioactivity in liver and fat (indicating unmetabolized substance) increased with degree of chlorination. On the contrary, the administration of LA and the chlorododecanes MCDD and PCDD I, but not of PCDD II, resulted in a selective labelling of the central nervous system 30-60 days after injection. (orig.)

  17. Metabolic Syndrome: Polycystic Ovary Syndrome.

    Mortada, Rami; Williams, Tracy

    2015-08-01

    Polycystic ovary syndrome (PCOS) is a heterogeneous condition characterized by androgen excess, ovulatory dysfunction, and polycystic ovaries. It is the most common endocrinopathy among women of reproductive age, affecting between 6.5% and 8% of women, and is the most common cause of infertility. Insulin resistance is almost always present in women with PCOS, regardless of weight, and they often develop diabetes and metabolic syndrome. The Rotterdam criteria are widely used for diagnosis. These criteria require that patients have at least two of the following conditions: hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The diagnosis of PCOS also requires exclusion of other potential etiologies of hyperandrogenism and ovulatory dysfunction. The approach to PCOS management differs according to the presenting symptoms and treatment goals, particularly the patient's desire for pregnancy. Weight loss through dietary modifications and exercise is recommended for patients with PCOS who are overweight. Oral contraceptives are the first-line treatment for regulating menstrual cycles and reducing manifestations of hyperandrogenism, such as acne and hirsutism. Clomiphene is the first-line drug for management of anovulatory infertility. Metformin is recommended for metabolic abnormalities such as prediabetes, and a statin should be prescribed for cardioprotection if the patient meets standard criteria for statin therapy. PMID:26280343

  18. Bone metabolism in thyroidectomized patients

    The bone mineral content in the patients who had undergone operation for thyroid carcinoma was measured by quantitative CT. Thirty-eight cases were enrolled as the subjects. All cases were papillary adenocarcinoma of the thyroid. The totally thyroidectomized group consisted of 3 males and 14 females, and the non-totally thyroidectomized group (post-lobectomy) 3 males and 18 females. Thirty-eight healthy males and females were assigned to the control group. For evaluation of bone mineral content, quantitative CT was used and bone mineral content in the patient's lumbar vertebrae was measured. Concurrently, bone metabolic parameter in serum was determined. No significant difference was observed in the mean bone mineral content among the above three groups. To make correction by sex and age, BMC-index was defined as the value that the bone mineral content in each case was divided by the standard mean by the same age and sex. No significant difference was observed in BMC-index among the above three groups. No significant correlation was observed in serum calcitonin level with the bone mineral content and BMC-index. It suggests that no influence is exerted on bone metabolism if serum calcitonin is maintained in the physiological level. (author)

  19. Male hypogonadism and metabolic syndrome.

    Naifar, M; Rekik, N; Messedi, M; Chaabouni, K; Lahiani, A; Turki, M; Abid, M; Ayedi, F; Jamoussi, K

    2015-06-01

    The role of androgens in cardiovascular disease is still controversial in men. In this study, we investigated metabolic disorders in Tunisian hypogonadal men compared with healthy controls. Forty hypogonadal men and 80 control subjects were enrolled. Patients with a history of pre-existing panhypopituitarism, thyroid dysfunction or inflammatory disease were excluded. Glycaemia, glycated haemoglobin (HbA1c), high-sensitive C-reactive protein (hsCRP), lipid profile, insulin, testosterone and gonadotrophins were measured. Insulin resistance was assessed by homoeostasis model assessment of insulin resistance (Homa IR). Waist circumference, body mass index and blood pressure were significantly higher in patients compared with controls. Glycemia, HbA1c, fasting serum insulin and Homa IR were significantly increased among hypogonadal men. In univariate analysis, testosterone levels were inversely correlated with body mass index, waist circumference, blood pressure, glycaemia, HbA1C, insulin, Homa IR and hsCRP. In multivariate analysis including all significant variables, initial testosterone level was the only independent risk factor for developing dyslipidaemia. With logistic regression, male hypogonadism was an independent risk factor for MS (P < 0.001). We conclude that low testosterone level plays a central role in the development of metabolic syndrome. Further prospective data are required to establish the causative link. PMID:25040289

  20. Benzodiazepine metabolism: an analytical perspective.

    Mandrioli, Roberto; Mercolini, Laura; Raggi, Maria Augusta

    2008-10-01

    Benzodiazepines are currently among the most frequently prescribed drugs all over the world. They act as anxiolytics, sedatives, hypnotics, amnesics, antiepileptics and muscle relaxants. Despite their common chemical scaffold, these drugs differ in their pharmacokinetic and metabolic properties. In particular, they are biotransformed by different cytochrome P450 isoforms and also by different UDP-glucuronosyltransferase subtypes. The most important studies on the metabolic characteristics of several 1,4-benzodiazepines, carried out from 1998 onwards, are reported and briefly discussed in this review. Moreover, the analytical methods related to these studies are also described and commented upon and their most important characteristics are highlighted. Most methods are based on liquid chromatography, which provides wide applicability and good analytical performance granting high precision, accuracy and feasibility. Mass spectrometry is gaining widespread acceptance, particularly if the matrix is very complex and variable, such as human or animal blood. However, spectrophotometric detection is still used for this purpose and can grant sufficient selectivity and sensitivity when coupled to suitable sample pre-treatment procedures. A monograph is included for each of the following benzodiazepines: alprazolam, bromazepam, brotizolam, clotiazepam, diazepam, etizolam, flunitrazepam, lorazepam, midazolam, oxazepam and triazolam. PMID:18855614

  1. Carbohydrate metabolism in Spirochaeta stenostrepta.

    Hespell, R B; Canale-Parola, E

    1970-07-01

    The pathways of carbohydrate metabolism in Spirochaeta stenostrepta, a free-living, strictly anaerobic spirochete, were studied. The organism fermented glucose to ethyl alcohol, acetate, lactate, CO(2), and H(2). Assays of enzymatic activities in cell extracts, and determinations of radioactivity distribution in products formed from (14)C-labeled glucose indicated that S. stenostrepta degraded glucose via the Embden-Meyerhof pathway. The spirochete utilized a clostridial-type clastic reaction to metabolize pyruvate to acetyl-coenzyme A, CO(2), and H(2), without production of formate. Acetyl-coenzyme A was converted to ethyl alcohol by nicotinamide adenine dinucleotide-dependent acetaldehyde and alcohol dehydrogenase activities. Phosphotransacetylase and acetate kinase catalyzed the formation of acetate from acetyl-coenzyme A. Hydrogenase and lactate dehydrogenase activities were detected in cell extracts. A rubredoxin was isolated from cell extracts of S. stenostrepta. Preparations of this rubredoxin stimulated acetyl phosphate formation from pyruvate by diethylaminoethyl cellulose-treated extracts of S. stenostrepta, an indication that rubredoxin may participate in pyruvate cleavage by this spirochete. Nutritional studies showed that S. stenostrepta fermented a variety of carbohydrates, but did not ferment amino acids or other organic acids. An unidentified growth factor present in yeast extract was required by the organism. Exogenous supplements of biotin, riboflavin, and vitamin B(12) were either stimulatory or required for growth. PMID:5423371

  2. Metabolic consequences of sleep and circadian disorders

    Depner, Christopher M.; Stothard, Ellen R.; Wright, Kenneth P.

    2014-01-01

    Sleep and circadian rhythms modulate or control daily physiological patterns with importance for normal metabolic health. Sleep deficiencies associated with insufficient sleep schedules, insomnia with short-sleep duration, sleep apnea, narcolepsy, circadian misalignment, shift work, night eating syndrome and sleep-related eating disorder may all contribute to metabolic dysregulation. Sleep deficiencies and circadian disruption associated with metabolic dysregulation may contribute to weight g...

  3. Metabolism and metabolites of polychlorinated biphenyls (PCBs)

    Grimm, FA; Hu, D.; Kania-Korwel, I.; Lehmler, HJ; Ludewig, G; Hornbuckle, KC; Duffel, MW; Bergman, A; Robertson, LW

    2015-01-01

    The metabolism of polychlorinated biphenyls (PCBs) is complex and has an impact on toxicity and thereby assessment of PCB risks. A large number of reactive and stable metabolites are formed in the processes of biotransformation in biota in general and in humans in particular. The aim of this document is to provide an overview of PCB metabolism and to identify metabolites of concern and their occurrence. Emphasis is given to mammalian metabolism of PCBs and their hydroxyl, methylsulfonyl, and ...

  4. Fermentation metabolism and its evolution in algae

    Catalanotti, Claudia; Yang, Wenqiang; Posewitz, Matthew C.; Grossman, Arthur R.

    2013-01-01

    Fermentation or anoxic metabolism allows unicellular organisms to colonize environments that become anoxic. Free-living unicellular algae capable of a photoautotrophic lifestyle can also use a range of metabolic circuitry associated with different branches of fermentation metabolism. While algae that perform mixed-acid fermentation are widespread, the use of anaerobic respiration is more typical of eukaryotic heterotrophs. The occurrence of a core set of fermentation pathways among the algae ...

  5. Regional myocardial free fatty acid metabolism

    Experimental evidence to date has confirmed the potential value of radioactive labelled free fatty acid (FFA) and their analogs for the assessment of regional myocardial FFA metabolism despite a number of current limitations. It is emphasized that with these agents only one specific aspect of myocardial metabolism, that of FFA, can be tested and that with these compounds information on the overall metabolic state cannot always be obtained. (WU)

  6. Neuroprotection in Metabolism-Based Therapy

    Hartman, Adam L.

    2011-01-01

    Metabolism-based therapy has been used successfully in the treatment of seizures but study of its use in other neurodegenerative disorders is growing. Data demonstrating the use of different forms of metabolism-based therapy in human trials of Alzheimer disease and Parkinson disease are discussed. Animal and in vitro studies have shed light on metabolism-based therapy’s mechanisms in these diseases, as well as ALS, aging, ischemia, trauma and mitochondrial cytopathies. Additional insights may...

  7. Mitochondrial function adaptations to changed metabolic conditions

    Bakkman, Linda

    2010-01-01

    The skeletal muscle mitochondria play a decisive role for the metabolic capacity of the body. A capability to adapt to changed metabolic conditions and energy demands is crucial for weight control and physical exercise. The aim of this thesis was to describe how the mitochondria adapt its function to different environmental conditions and changed metabolic demands. In study I, the aim was to evaluate mitochondrial adaptations to hypoxic exercise. The effect of one-legged...

  8. Toxic metabolic syndrome associated with HAART

    Haugaard, Steen B

    2006-01-01

    (HAART) may encounter the HIV-associated lipodystrophy syndrome (HALS), which attenuates patient compliance to this treatment. HALS is characterised by impaired glucose and lipid metabolism and other risk factors for cardiovascular disease. This review depicts the metabolic abnormalities associated with...... HAART by describing the key cell and organ systems that are involved, emphasising the role of insulin resistance. An opinion on the remedies available to treat the metabolic abnormalities and phenotype of HALS is provided....

  9. Fifteen years experience: Egyptian metabolic lab

    Ekram M. Fateen

    2014-10-01

    Conclusion: This study illustrates the experience of the reference metabolic lab in Egypt over 15 years. The lab began metabolic disorder screening by using simple diagnostic techniques like thin layer chromatography and colored tests in urine which by time updated and upgraded the methods to diagnose a wide range of disorders. This study shows the most common diagnosed inherited inborn errors of metabolism among the Egyptian population.

  10. Controlling fluxes for microbial metabolic engineering

    Sachdeva, Gairik

    2014-01-01

    This thesis presents novel synthetic biology tools and design principles usable for microbial metabolic engineering. Controlling metabolic fluxes is essential for biological manufacturing of fuels, materials, and high value chemicals. Insulating the flow of metabolites is a successful natural strategy for metabolic flux regulation. Recently, approaches using scaffolds, both in vitro and in vivo, to spatially co-localize enzymes have reported significant gains in product yields. RNA is suitabl...

  11. Mapping of cerebral oxidative metabolism with MRI

    Mellon, Eric A.; Beesam, R. Shashank; Elliott, Mark A.; Reddy, Ravinder

    2010-01-01

    Using a T1ρ MRI based indirect detection method, we demonstrate the detection of cerebral oxidative metabolism and its modulation by administration of the mitochondrial uncoupling agent 2,4-dinitrophenol (DNP) in a large animal model with minimum utilization of gas. The study was performed by inhalation in swine during imaging on clinical MRI scanners. Metabolic changes in swine were determined by two methods. First, in a series of animals, increased metabolism caused by DNP injection was m...

  12. The Reset Hypothesis: Lactation and Maternal Metabolism

    Stuebe, Alison M.; Rich-Edwards, Janet W.

    2008-01-01

    For maternal metabolism, pregnancy ends not with delivery, but with weaning. In several recent epidemiological studies, authors have reported an association between duration of breast-feeding and reduced maternal risk of metabolic disease. These findings parallel data from animal models showing favorable changes in metabolism associated with lactation. During gestation, visceral fat accumulates, and insulin resistance and lipid and triglyceride levels increase. These changes appear to reverse...

  13. Highly optimised global organisation of metabolic networks

    Tanaka, R.; Csete, M.; Doyle, J.

    2005-01-01

    High-level, mathematically precise descriptions of the global organisation of complex metabolic networks are necessary for understanding the global structure of metabolic networks, the interpretation and integration of large amounts of biologic data (sequences, various -omics) and ultimately for rational design of therapies for disease processes. Metabolic networks are highly organised to execute their function efficiently while tolerating wide variation in their environment. These network...

  14. The metabolic pathway collection: an update.

    Galimova, M; Goryanin, I; Gretchkin, Y; Ivanova, N.; Komarov, Y; Maltsev, N.; Mikhailova, N.; Nenashev, V; Overbeek, R; Panyushkina, E; Pronevitch, L; Selkov, E

    1997-01-01

    The Metabolic Pathway Collection from EMP is an extraction of data from the larger Enzymes and Metabolic Pathways database (EMP). This extraction has been made publicly available in the hope that others will find it useful for a variety of purposes. The original release in October 1995 contained 1814 distinct pathways. The current collection contains 2180. Metabolic reconstructions for the first completely sequenced organisms-Haemophilus influenzae,Mycoplasma genitalium,Saccharomyces cerevisi...

  15. Metabolic responses to hypoglycemia in juvenile diabetics

    Hilsted, J; Madsbad, S; Krarup, T;

    1980-01-01

    Glucagon and metabolic responses to insulin-induced hypoglycemia were studied in seven juvenile diabetics, age 31 +/- 2 years (mean and S.E.M.), duration of diabetes 17 +/- 3 years, with diabetic autonomic neuropathy (decreased beat-to-beat variation in heart rate during hyperventilation and...... both patient groups. Metabolic responses to hypoglycemia were also similar in the two patient groups. In conclusion, diabetic autonomic neuropathy has no effect on glucagon and metabolic responses to hypoglycemia in juvenile, insulin-treated diabetics....

  16. Scaling of Metabolic Scaling within Physical Limits

    Douglas S. Glazier

    2014-10-01

    Full Text Available Both the slope and elevation of scaling relationships between log metabolic rate and log body size vary taxonomically and in relation to physiological or developmental state, ecological lifestyle and environmental conditions. Here I discuss how the recently proposed metabolic-level boundaries hypothesis (MLBH provides a useful conceptual framework for explaining and predicting much, but not all of this variation. This hypothesis is based on three major assumptions: (1 various processes related to body volume and surface area exert state-dependent effects on the scaling slope for metabolic rate in relation to body mass; (2 the elevation and slope of metabolic scaling relationships are linked; and (3 both intrinsic (anatomical, biochemical and physiological and extrinsic (ecological factors can affect metabolic scaling. According to the MLBH, the diversity of metabolic scaling relationships occurs within physical boundary limits related to body volume and surface area. Within these limits, specific metabolic scaling slopes can be predicted from the metabolic level (or scaling elevation of a species or group of species. In essence, metabolic scaling itself scales with metabolic level, which is in turn contingent on various intrinsic and extrinsic conditions operating in physiological or evolutionary time. The MLBH represents a “meta-mechanism” or collection of multiple, specific mechanisms that have contingent, state-dependent effects. As such, the MLBH is Darwinian in approach (the theory of natural selection is also meta-mechanistic, in contrast to currently influential metabolic scaling theory that is Newtonian in approach (i.e., based on unitary deterministic laws. Furthermore, the MLBH can be viewed as part of a more general theory that includes other mechanisms that may also affect metabolic scaling.

  17. METABOLIC SYNDROME – THEORY AND PRACTICE

    Ramic, Enisa; Prasko, Subhija; Mujanovic, Olivera Batic; Gavran, Larisa

    2016-01-01

    Introduction: Due to sedentary lifestyles and excessive calorie intake, metabolic syndrome is becoming increasingly common health problem in the world, as well as in our country, and it is estimated to occur in 30% of the population of middle and older age. The metabolic syndrome is a combination of disorders that include: obesity, insulin resistance, glucose intolerance, impaired regulation of body fat and high blood pressure. Complications resulting from metabolic syndrome significantly red...

  18. Dynamics in the Central Plant Cell Metabolism

    Ampofo-Asiama, Jerry

    2014-01-01

    As part of their development, plants have acquired adaptive mechanisms to cope with different stress situations they encounter in their environment. These adaptive mechanisms include the ability to alter their metabolism when faced with extreme environmental conditions such as low oxygen. In higher plants, oxygen (O2) availability is important for energy production through respiratory metabolism. Under conditions where O2 becomes limiting, respiratory metabolism can be impeded leading to impa...

  19. Metabolic Flexibility: Hibernation, Torpor, and Estivation.

    Staples, James F

    2016-01-01

    Many environmental conditions can constrain the ability of animals to obtain sufficient food energy, or transform that food energy into useful chemical forms. To survive extended periods under such conditions animals must suppress metabolic rate to conserve energy, water, or oxygen. Amongst small endotherms, this metabolic suppression is accompanied by and, in some cases, facilitated by a decrease in core body temperature-hibernation or daily torpor-though significant metabolic suppression can be achieved even with only modest cooling. Within some ectotherms, winter metabolic suppression exceeds the passive effects of cooling. During dry seasons, estivating ectotherms can reduce metabolism without changes in body temperature, conserving energy reserves, and reducing gas exchange and its inevitable loss of water vapor. This overview explores the similarities and differences of metabolic suppression among these states within adult animals (excluding developmental diapause), and integrates levels of organization from the whole animal to the genome, where possible. Several similarities among these states are highlighted, including patterns and regulation of metabolic balance, fuel use, and mitochondrial metabolism. Differences among models are also apparent, particularly in whether the metabolic suppression is intrinsic to the tissue or depends on the whole-animal response. While in these hypometabolic states, tissues from many animals are tolerant of hypoxia/anoxia, ischemia/reperfusion, and disuse. These natural models may, therefore, serve as valuable and instructive models for biomedical research. © 2016 American Physiological Society. Compr Physiol 6:737-7771, 2016. PMID:27065167

  20. Epigenetic methylations and their connections with metabolism.

    Chiacchiera, Fulvio; Piunti, Andrea; Pasini, Diego

    2013-05-01

    Metabolic pathways play fundamental roles in several processes that regulate cell physiology and adaptation to environmental changes. Altered metabolic pathways predispose to several different pathologies ranging from diabetes to cancer. Specific transcriptional programs tightly regulate the enzymes involved in cell metabolism and dictate cell fate regulating the differentiation into specialized cell types that contribute to metabolic adaptation in higher organisms. For these reasons, it is of extreme importance to identify signaling pathways and transcription factors that positively and negatively regulate metabolism. Genomic organization allows a plethora of different strategies to regulate transcription. Importantly, large evidence suggests that the quality of diet and the caloric regimen can influence the epigenetic state of our genome and that certain metabolic pathways are also epigenetically controlled reveling a tight crosstalk between metabolism and epigenomes. Here we focus our attention on methylation-based epigenetic reactions, on how different metabolic pathways control these activities, and how these can influence metabolism. Altogether, the recent discoveries linking these apparent distant areas reveal that an exciting field of research is emerging. PMID:23456257

  1. Supply–demand balance and metabolic scaling

    Banavar, Jayanth R.; Damuth, John; Maritan, Amos; Rinaldo, Andrea

    2002-01-01

    It is widely accepted that metabolic rates scale across species approximately as the 3/4 power of mass in most if not all groups of organisms. Metabolic demand per unit mass thus decreases as body mass increases. Metabolic rates reflect both the ability of the organism's transport system to deliver metabolites to the tissues and the rate at which the tissues use them. We show that the ubiquitous 3/4 power law for interspecific metabolic scaling arises from simple, general geometric properties...

  2. Modelling metabolism of the diatom Phaeodactylum tricornutum.

    Singh, Dipali; Carlson, Ross; Fell, David; Poolman, Mark

    2015-12-01

    Marine diatoms have potential as a biotechnological production platform, especially for lipid-derived products, including biofuels. Here we introduce some features of diatom metabolism, particularly with respect to photosynthesis, photorespiration and lipid synthesis and their differences relative to other photosynthetic eukaryotes. Since structural metabolic modelling of other photosynthetic organisms has been shown to be capable of representing their metabolic capabilities realistically, we briefly review the main approaches to this type of modelling. We then propose that genome-scale modelling of the diatom Phaeodactylum tricornutum, in response to varying light intensity, could uncover the novel aspects of the metabolic potential of this organism. PMID:26614658

  3. Effects of introducing heterologous pathways on microbial metabolism with respect to metabolic optimality

    Kim, Hyun Uk; Kim, Byoungjin; Seung, Do Young; Yup Lee, Sang

    2014-01-01

    Although optimality of microbial metabolism under genetic and environmental perturbations is well studied, the effects of introducing heterologous reactions on the overall metabolism are not well understood. This point is important in the field of metabolic engineering because heterologous...... reactions are more frequently introduced into various microbial hosts. The genome-scale metabolic simulations of Escherichia coli strains engineered to produce 1,4-butanediol, 1,3-propanediol, and amorphadiene suggest that microbial metabolism shows much different responses to the introduced heterologous...... can be considered as engineering targets in systems metabolic engineering strategies. To our knowledge, this study is the first attempt to quantitatively characterize microbial metabolisms with different heterologous reactions. The suggested potential reasons behind each strain’s different metabolic...

  4. Metabolism of stem tissue during growth and its inhibition. III. Nitrogen metabolism

    Christiansen, G.S.; Thimann, K.V.

    1950-01-01

    The nitrogen metabolism of isolated pea stem sections as affected by arsenite, fluoride, and iodoacetate growth inhibitors in auxin solutions was studied. The changes in growth and metabolism caused by these inhibitors are discussed.

  5. Relationship Between Metabolic Syndrome and Prostate Cancer

    Serkan Bas

    2014-12-01

    Full Text Available Aim: Metabolic syndrome has gained increased attention in the last century after researchers identified its important role in cardiovascular mortality and morbidity in developed countries. Despite limited research into the relationship between metabolic syndrome and prostate cancer (PCa, the precise relationship has not been elucidated due to lack of research into the specific factors associated with PCa. To fill this research gap, we evaluated the incidence of PCa in patients with metabolic syndrome and the relationship between metabolic syndrome and the parameters of PCa. Material and Method: We retrospectively evaluated the biochemical analyses of the serum parameters and pathological reports of 102 PCa patients diagnosed by transrectal ultrasound. After determining the incidence of metabolic syndrome in patients with PCa, we divided the patients into two groups, those with and without a diagnosis of metabolic syndrome. We then compared the serum PSA level, age, total prostate volume, Gleason score, triglyceride (TG level, high-density lipoprotein cholesterol level (HDL-C, blood pressure, and fasting glucose level of the two groups. Results: We included 102 patients with a diagnosis of prostate cancer in the present study. Among the 102 patients, 18 (17.6% were diagnosed with metabolic syndrome. While the PSA levels of the PCa patients were found to be significantly lower in those with metabolic syndrome compared to those without metabolic syndrome (P=0.04, no difference was found between the groups regarding the other components of PCa (P>0.05. Discussion: Serum PSA level was found to be significantly lower in those with metabolic syndrome. This result leads us to consider whether prostate biopsy should be performed in patients with metabolic syndrome who have lower PSA levels than the levels currently specified for biopsy. Further research into the parameters of PCa needs to be conducted to confirm our findings.

  6. Skeletal muscle metabolism in hypokinetic rats

    Tischler, Marc E.

    1993-01-01

    This grant focused on the mechanisms of metabolic changes associated with unweighting atrophy and reduced growth of hind limb muscles of juvenile rats. Metabolic studies included a number of different areas. Amino acid metabolic studies placed particular emphasis on glutamine and branched-chain amino acid metabolism. These studies were an outgrowth of understanding stress effects and the role of glucocorticoids in these animals. Investigations on protein metabolism were largely concerned with selective loss of myofibrillar proteins and the role of muscle proteolysis. These investigations lead to finding important differences from denervation and atrophy and to define the roles of cytosolic versus lysosomal proteolysis in these atrophy models. A major outgrowth of these studies was demonstrating an ability to prevent atrophy of the unweighted muscle for at least 24 hours. A large amount of work concentrated on carbohydrate metabolism and its regulation by insulin and catecholamines. Measurements focused on glucose transport, glycogen metabolism, and glucose oxidation. The grant was used to develop an important new in situ approach for studying protein metabolism, glucose transport, and hormonal effects which involves intramuscular injection of various agents for up to 24 hours. Another important consequence of this project was the development and flight of Physiological-Anatomical Rodent Experiment-1 (PARE-1), which was launched aboard Space Shuttle Discovery in September 1991. Detailed descriptions of these studies can be found in the 30 peer-reviewed publications, 15 non-reviewed publications, 4 reviews and 33 abstracts (total 82 publications) which were or are scheduled to be published as a result of this project. A listing of these publications grouped by area (i.e. amino acid metabolism, protein metabolism, carbohydrate metabolism, and space flight studies) are included.

  7. Nitrogen metabolism in the ruminant

    Selected aspects of nitrogen metabolism in the ruminant are discussed. Particular attention is paid to the effect of rumen ammonia concentration on protein synthesis in the rumen. In order to judge the suitability of microbial protein as a source of protein for the ruminant, it is necessary to be able to assess the amino-acid requirements of the ruminant accurately. Several methods of doing this are discussed. Available data would indicate that under many conditions methionine is the first limiting amino acid. Possible ways of increasing the supply of methionine at the duodenum are discussed. When the amino-acid requirements are fully met, it is to be expected that protein synthesis in the tissues will proceed at its maximal rate. Ways of determining the extent of tissue protein synthesis in vivo are briefly discussed. (author)

  8. Paraneoplastic endocrine-metabolic syndromes

    Marco Grandi

    2013-04-01

    Full Text Available BACKGROUND The paraneoplastic syndromes (PS are characterized by the presence of biochemical alterations, signs and symptoms expressive of cancer distance action into the patient’s organism. Sometimes these syndromes can precede the evidence of malignancy even of some years or can correspond to cancer relapse. PS, even being characterized by general symptoms (fever, anorexia, cachexia, may occur with neurological, rheumathological, osteoarticular, vascular, haematological, nephrological and endocrinological/metabolic symptoms; the latter ones are discussed in this article. AIM OF THE STUDY Here we will focus on the most common PS: paraneoplastic hypercalcemia, inappropriate secretion of antidiuretic hormone (SIADH and paraneoplastic Cushing syndrome. CONCLUSIONS Our work can be useful in the diagnosis and therapeutic management of paraneoplastic syndromes.

  9. Mammalian aquaglyceroporin function in metabolism.

    Laforenza, Umberto; Bottino, Cinzia; Gastaldi, Giulia

    2016-01-01

    Aquaglyceroporins are integral membrane proteins that are permeable to glycerol as well as water. The movement of glycerol from a tissue/organ to the plasma and vice versa requires the presence of different aquaglyceroporins that can regulate the entrance or the exit of glycerol across the plasma membrane. Actually, different aquaglyceroporins have been discovered in the adipose tissue, small intestine, liver, kidney, heart, skeletal muscle, endocrine pancreas and capillary endothelium, and their differential expression could be related to obesity and the type 2 diabetes. Here we describe the expression and function of different aquaglyceroporins in physiological condition and in obesity and type 2 diabetes, suggesting they are potential therapeutic targets for metabolic disorders. PMID:26456554

  10. Metabolic syndrome in South Asians

    Kaushik Pandit

    2012-01-01

    Full Text Available South Asia is home to one of the largest population of people with metabolic syndrome (MetS. The prevalence of MetS in South Asians varies according to region, extent of urbanization, lifestyle patterns, and socioeconomic/cultural factors. Recent data show that about one-third of the urban population in large cities in India has the MetS. All classical risk factors comprising the MetS are prevalent in Asian Indians residing in India. The higher risk in this ethnic population necessitated a lowering of the cut-off values of the risk factors to identify and intervene for the MetS to prevent diabetes and cardiovascular disease. Some pharmacological and nonpharmacological interventions are underway in MetS to assess the efficacy in preventing the diabetes and cardiovascular disease in this ethnic population.

  11. Water metabolism in Australian marsupials

    Several studies are discussed in which tritiated water (TOH) has been used to investigate water metabolism in Australian marsupials, particularly arid-zone species. Equilibration of injected TOH in large kangaroos was slower than in smaller marsupials and similar to that in ruminants and camels, presumably because of the high gut water space of all large forestomach fermenters. Loss of TOH in urine, faeces and insensible water during equilibration was also similar to that in ruminants. Total body water (TBW) was similar whether estimated by equilibration or extrapolation. TBW of small marsupial species (16 g to 6.5 kg body weight) was usually in the range found for small eutherian mammals (56 to 68% of body weight). However, in the larger kangaroos TBW ranged from 73 to 78% of body weight, possibly due to the low body fat content and the high ratio of gut contents to total body weight of kangaroos. In general, the water turnover rate of marsupials is about 30% below that of eutherians; this has been related to their lower metabolic rate. Nevertheless, significant differences in water turnover have been found between some species. It has been suggested that there may be a correlation between the water turnover rates measured under ad libitum water availability and the aridity of the animal's habitat. However, this is not always so; differences in behaviour and in the water content of the natural diet explain why some marsupials with high ad libitum water turnovers can survive in desert environments. The physiological state of the animals (e.g. lactation) has also been shown to affect water turnover, both in the laboratory and in the field. (author)

  12. Metabolism of stromal and immune cells in health and disease

    Ghesquière, Bart; Wong, Brian W.; Kuchnio, Anna; Carmeliet, Peter

    2014-01-01

    Cancer cells have been at the centre of cell metabolism research, but the metabolism of stromal and immune cells has received less attention. Nonetheless, these cells influence the progression of malignant, inflammatory and metabolic disorders. Here we discuss the metabolic adaptations of stromal and immune cells in health and disease, and highlight how metabolism determines their differentiation and function.

  13. Topics and Problems in Metabolic P Systems

    Manca, Vincenzo; Research Group on Natural Computing (Universidad de Sevilla) (Coordinador)

    2006-01-01

    P metabolic systems are a special class of P systems which seem to be adequate for expressing biological phenomena related to metabolism and signaling transduction in biological systems. We give the basic motivation for their introduction and some ideas about their applicability and development.

  14. Aspects of plasma triglyceride metabolism in children

    P.P. Forget

    1975-01-01

    textabstractThis thesis aimed at investigating some aspects of plasma triglyceride metabolism in children. In the introduction general aspects of plasma triglyceride metabolism are presented. Chapter 1 reviews recent litterature data on the intravenous fat tolerance test and on plasma postheparin li

  15. Metabolism and cancer mix in Madrid

    Shaw, Reuben J.

    2010-01-01

    The CNIO Cancer Conference ‘The Energy of Cancer' was a bridge between metabolic and cancer research, emphasizing the interdisciplinary nature of the field. The outlines of the main pathways involved in coordinating nutrient uptake and metabolism with cell growth have begun to emerge.

  16. Progress in Metabolic Engineering of Saccharomyces cerevisiae

    Nevoigt, Elke

    2008-01-01

    Summary: The traditional use of the yeast Saccharomyces cerevisiae in alcoholic fermentation has, over time, resulted in substantial accumulated knowledge concerning genetics, physiology, and biochemistry as well as genetic engineering and fermentation technologies. S. cerevisiae has become a platform organism for developing metabolic engineering strategies, methods, and tools. The current review discusses the relevance of several engineering strategies, such as rational and inverse metabolic...

  17. Mediterranean diet and the metabolic syndrome

    Bos, M.B.

    2009-01-01

    Mediterranean diet and the metabolic syndrome Background: The metabolic syndrome refers to a clustering of risk factors including abdominal obesity, hyperglycaemia, low HDL-cholesterol, hypertriglyceridaemia, and hypertension and it is a risk factor for diabetes mellitus type 2 and cardiovascula

  18. Glycogen metabolism in aerobic mixed cultures

    Dircks, Klaus; Beun, J.J.; van Loosdrecht, M.C.M.;

    2001-01-01

    In this study, the metabolism of glycogen storage and consumption in mixed cultures under aerobic conditions is described. The experimental results are used to calibrate a metabolic model, which as sole stoichiometric variables has the efficiency of oxidative phosphorylation (delta) and maintenan...

  19. Correlated FLIM and PLIM for cell metabolism

    Rück, A.; Breymayer, J.; Kalinina, S.

    2016-03-01

    Correlated imaging of phosphorescence and fluorescence lifetime parameters of metabolic markers is a challenge for direct investigating mechanisms related to cell metabolism and oxygen tension. A large variety of clinical phenotypes is associated with mitochondrial defects accomplished with changes in cell metabolism. In many cases the hypoxic microenvironment of cancer cells shifts metabolism from oxidative phosphorylation (OXPHOS) to anaerobic or aerobic glycolysis, a process known as "Warburg" effect. Also during stem cell differentiation a switch in cell metabolism is observed. A defective mitochondrial function associated with hypoxia has been invoked in many complex disorders such as type 2 diabetes, Alzheimers disease, cardiac ischemia/reperfusion injury, tissue inflammation and cancer. Cellular responses to oxygen tension have been studied extensively, optical imaging techniques based on time correlated single photon counting (TCSPC) to detect the underlying metabolic mechanisms are therefore of prominent interest. They offer the possibility by inspecting fluorescence decay characteristics of intrinsic coenzymes to directly image metabolic pathways. Moreover oxygen tension can be determined by considering the phosphorescence lifetime of a phosphorescent probe. The combination of both fluorescence lifetime imaging (FLIM) of coenzymes like NADH and FAD and phosphorescence lifetime (PLIM) of phosphorescent dyes could provide valuable information about correlation of metabolic pathways and oxygen tension.

  20. The metabolic syndrome - background and treatment

    van Zwieten, P. A.

    2006-01-01

    The metabolic syndrome (MBS) is characterised by a clustering of cardiovascular and metabolic risk factors. This syndrome is now widely recognised as a distinct pathological entity, and it is receiving a great deal of attention in the medical literature but also in the lay press.

  1. VITAMIN D AND THE METABOLIC SYNDROME

    The identification of vitamin D receptor (VDR) expression in different tissues suggests a widespread role for vitamin D action beyond its classical function in bone and mineral metabolism. Recently, the importance of vitamin D status as a risk factor in the development of metabolic syndrome has been...

  2. Effects of hyperammonemia on brain energy metabolism

    Schousboe, Arne; Waagepetersen, Helle S.; Leke, Renata; Bak, Lasse K

    2014-01-01

    The literature related to the effects of elevated plasma ammonia levels on brain energy metabolism is abundant, but heterogeneous in terms of the conclusions. Thus, some studies claim that ammonia has a direct, inhibitory effect on energy metabolism whereas others find no such correlation. In this...

  3. Metabolic connections during apoptotic cell engulfment

    Han, Claudia Z.; Ravichandran, Kodi S.

    2011-01-01

    Billions of cells die via apoptosis every day and are swiftly and efficiently removed. When a phagocyte engulfs an apoptotic cell, it essentially doubles its cellular contents, raising the question of how a phagocyte may manage the excess metabolic load. This review discusses phagocyte cellular metabolism, the digestion of the ingested apoptotic cell and the impact of these processes on engulfment.

  4. Marxism, social metabolism, and ecologically unequal exchange

    MARTÍNEZ ALIER, Joan

    2004-01-01

    Authors working on "industrial metabolism" or "social metabolism" look at the economy in terms of flows of energy and materials. Together with the ecological economists, they see the economy as a subsystem of a larger physical system. Marx and Engels followed with a few years' delay many of the remarkable scientific and technical novelties of their time.

  5. Regulation of intermediary metabolism by protein acetylation

    Guan, Kun-Liang; Xiong, Yue

    2010-01-01

    Extensive studies during the past four decades have identified important roles for lysine acetylation in the regulation of nuclear transcription. Recent proteomic analyses on protein acetylation uncovered a large number of acetylated proteins in the cytoplasm and mitochondria, including most enzymes involved in intermediate metabolism. Acetylation regulates metabolic enzymes by multiple mechanisms, including via enzymatic activation or inhibition, and by influencing protein stability. Convers...

  6. Optimization of cardiac metabolism in heart failure.

    Nagoshi, Tomohisa; Yoshimura, Michihiro; Rosano, Giuseppe M C; Lopaschuk, Gary D; Mochizuki, Seibu

    2011-12-01

    The derangement of the cardiac energy substrate metabolism plays a key role in the pathogenesis of heart failure. The utilization of non-carbohydrate substrates, such as fatty acids, is the predominant metabolic pathway in the normal heart, because this provides the highest energy yield per molecule of substrate metabolized. In contrast, glucose becomes an important preferential substrate for metabolism and ATP generation under specific pathological conditions, because it can provide greater efficiency in producing high energy products per oxygen consumed compared to fatty acids. Manipulations that shift energy substrate utilization away from fatty acids toward glucose can improve the cardiac function and slow the progression of heart failure. However, insulin resistance, which is highly prevalent in the heart failure population, impedes this adaptive metabolic shift. Therefore, the acceleration of the glucose metabolism, along with the restoration of insulin sensitivity, would be the ideal metabolic therapy for heart failure. This review discusses the therapeutic potential of modifying substrate utilization to optimize cardiac metabolism in heart failure. PMID:21933140

  7. Towards a metabolic therapy of cancer?

    Chiu, Martina; Ottaviani, Laura; Bianchi, Massimiliano G; Franchi-Gazzola, Renata; Bussolati, Ovidio

    2012-12-01

    It is increasingly appreciated that cancer cells must be endowed with specific metabolic adaptations to support enhanced growth and to ensure survival under stressful conditions. On the other hand, many oncogenic mutations of protooncogenes and tumor suppressor genes directly cause metabolic derangements and, conversely, mutations of enzymes have been found to underlie several forms of cancer. Thus, cancer-specific metabolic alterations are now considered among the hallmarks of malignant tumors. Most commonly, cancer cells exhibit enhanced glycolysis under aerobic conditions (the Warburg effect) but alterations in the metabolism of amino acids, such as glutamine, serine and proline are increasingly described as important metabolic features of selected tumor types. In theory, all these deranged cancer-specific metabolic pathways may constitute novel therapeutic targets, although the only "metabolic" drug in clinical use is still represented by the enzyme L-asparaginase. However, the increasing amount of experimental evidence, as well as the number of trials in progress, suggests that metabolic drugs will soon complement standard anti-cancer chemotherapy and modern biological drugs. PMID:23762991

  8. Medical management of metabolic dysfunction in PCOS

    Duleba, Antoni J.

    2011-01-01

    Polycystic ovary syndrome (PCOS) is associated with metabolic derangements including insulin resistance, dyslipidemia, systemic inflammation and endothelial dysfunction. There is a growing need to develop pharmacologic interventions to improve metabolic function in women with PCOS. Medications that have been tested in patients with PCOS include metformin, thiazolidinediones, acarbose, naltrexone, orlistat, vitamin D and statins.

  9. Swimming Performance and Metabolism of Golden Shiners

    The swimming ability and metabolism of golden shiners, Notemigonus crysoleucas, was examined using swim tunnel respirometery. The oxygen consumption and tail beat frequencies at various swimming speeds, an estimation of the standard metabolic rate, and the critical swimming speed (Ucrit) was determ...

  10. 2-Hydroxy Acids in Plant Metabolism

    Maurino, Veronica G.; Engqvist, Martin K. M.

    2015-01-01

    Glycolate, malate, lactate, and 2-hydroxyglutarate are important 2-hydroxy acids (2HA) in plant metabolism. Most of them can be found as D- and L-stereoisomers. These 2HA play an integral role in plant primary metabolism, where they are involved in fundamental pathways such as photorespiration, tricarboxylic acid cycle, glyoxylate cycle, methylglyoxal pathway, and lysine catabolism. Recent molecular studies in Arabidopsis thaliana have helped elucidate the participation of these 2HA in in plant metabolism and physiology. In this chapter, we summarize the current knowledge about the metabolic pathways and cellular processes in which they are involved, focusing on the proteins that participate in their metabolism and cellular/intracellular transport in Arabidopsis. PMID:26380567

  11. FXR: a metabolic regulator and cell protector

    Yan-Dong Wang; Wei-Dong Chen; David D Moore; Wendong Huang

    2008-01-01

    Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand-activated transcription fac-tors. As a metabolic regulator, FXR plays key roles in bile acid, cholesterol, lipid, and glucose metabolism. Therefore, FXR is a potential drug target for a number of metabolic disorders, especially those related to the metabolic syn-drome. More recently, our group and others have extended the functions of FXR to more than metabolic regulation, which include anti-bacterial growth in intestine, liver regeneration, and hepatocarcinogenesis. These new findings suggest that FXR has much broader roles than previously thought, and also higl light FXR as a drug target for mul-tiple diseases. This review summarizes the basic information of FXR but focuses on its new functions.

  12. [Abnormality in bone metabolism after burn].

    Gong, X; Xie, W G

    2016-08-20

    Burn causes bone metabolic abnormality in most cases, including the changes in osteoblasts and osteoclasts, bone mass loss, and bone absorption, which results in decreased bone mineral density. These changes are sustainable for many years after burn and even cause growth retardation in burned children. The mechanisms of bone metabolic abnormality after burn include the increasing glucocorticoids due to stress response, a variety of cytokines and inflammatory medium due to inflammatory response, vitamin D deficiency, hypoparathyroidism, and bone loss due to long-term lying in bed. This article reviews the pathogenesis and regularity of bone metabolic abnormality after burn, the relationship between bone metabolic abnormality and burn area/depth, and the treatment of bone metabolic abnormality, etc. and discusses the research directions in the future. PMID:27562160

  13. Energy metabolism and thermoregulation in old age

    Sacher, G. A.

    1979-01-01

    Over their life spans, mice and men alike show a 15 to 30% decrease in their minimum, or resting, levels of energy metabolism, and a 50 to 70% decrease in the metabolism of activity. This, together with age-decrements in the capacity to regulate heat loss, makes the old person more susceptible to hypothermia that the young. Two independent relations of length of life to metabolic rate have been found in mice. First, as average metabolic rate increases, survival time decreases, and second, as the fraction of metabolic energy available for activity increases, survival time increases. The second term is the important one, for it is the first experimental support for the efforts to maintain human health and vigor, and to extend life, by means of regimes of exercise and activity. If mice are good models for men in these respects, rapid progress in understanding is possible.

  14. Metabolic syndrome in fixed-shift workers

    Raquel Canuto

    2015-01-01

    Full Text Available OBJECTIVE To analyze if metabolic syndrome and its altered components are associated with demographic, socioeconomic and behavioral factors in fixed-shift workers. METHODS A cross-sectional study was conducted on a sample of 902 shift workers of both sexes in a poultry processing plant in Southern Brazil in 2010. The diagnosis of metabolic syndrome was determined according to the recommendations from Harmonizing the Metabolic Syndrome. Its frequency was evaluated according to the demographic (sex, skin color, age and marital status, socioeconomic (educational level, income and work shift, and behavioral characteristics (smoking, alcohol intake, leisure time physical activity, number of meals and sleep duration of the sample. The multivariate analysis followed a theoretical framework for identifying metabolic syndrome in fixed-shift workers. RESULTS The prevalence of metabolic syndrome in the sample was 9.3% (95%CI 7.4;11.2. The most frequently altered component was waist circumference (PR 48.4%; 95%CI 45.5;51.2, followed by high-density lipoprotein. Work shift was not associated with metabolic syndrome and its altered components. After adjustment, the prevalence of metabolic syndrome was positively associated with women (PR 2.16; 95%CI 1.28;3.64, workers aged over 40 years (PR 3.90; 95%CI 1.78;8.93 and those who reported sleeping five hours or less per day (PR 1.70; 95%CI 1.09;2.24. On the other hand, metabolic syndrome was inversely associated with educational level and having more than three meals per day (PR 0.43; 95%CI 0.26;0.73. CONCLUSIONS Being female, older and deprived of sleep are probable risk factors for metabolic syndrome, whereas higher educational level and higher number of meals per day are protective factors for metabolic syndrome in fixed-shift workers.

  15. Metabolic correlates of learning disability.

    Nyhan, W L; Wulfeck, B B; Tallal, P; Marsden, D L

    1989-01-01

    To summarize, the neuropsychologic findings in MSUD and MMA children in both groups demonstrated deficits in cognitive/language areas, but interesting individual differences existed. For example, a marked contrast in abilities existed between NT and GV, even taking into account the age difference between these children with MSUD. While NT's general intellectual functioning was within the low-average range, GV was severely impaired. In more specific areas of cognitive functioning, NT had an uneven performance profile with areas of strengths and weaknesses, while GV evidenced a flat profile with significant impairment in all areas. NT demonstrated mild delay in visual-spatial processing, articulation development, motor-speech abilities, and selective attention and concentration; however, his language and psychosocial development were within the broad range of normality. In contrast, GV exhibited severe dysfunction in speech, language, and perceptual/conceptual development. The three children with MMA also exhibited a range of disabilities in cognitive functioning. TJ and SH contrasted in the degree of developmental delay across language and cognitive domains. Both were distractible and exhibited very short attention spans but there was a measurable difference in the extent of their speech, language, visual-spatial development. CH was markedly delayed in all areas of cognitive development, which is consistent with global retardation. The severity of her disease and its probable impact on brain development were undoubtedly related to her intellectual impairment. These datasets illustrate the challenges we face, because within each group we see a range of impairment. Nevertheless, we are optimistic that our efforts to relate metabolic, anatomic and neuropsychologic findings for such children will lead to a better understanding of these disorders. We are hopeful that this will result in new advances in diagnosis and intervention, which will ultimately improve the

  16. Polymorphisms in oxidative drug metabolism: relationship to food preference.

    Britto, M R; McKean, H E; Bruckner, G G; Wedlund, P J

    1991-01-01

    To determine whether a correlation exists between polymorphisms of oxidative drug metabolism and dietary preference, 29 poor metabolizers of dextromethorphan, 18 poor metabolizers of mephenytoin and 134 extensive metabolizers of both drugs were screened for their preferences for various food items. Poor metabolizers of dextromethorphan showed a diminished stated preference for cauliflower and coconut, and poor metabolizers of mephenytoin showed a diminished stated preference for spinach and c...

  17. Metabolic Shifts during Aging and Pathology

    Ma, Yina; Li, Ji

    2016-01-01

    The heart is a very special organ in the body and has a high requirement for metabolism due to its constant workload. As a consequence, to provide a consistent and sufficient energy a high steady-state demand of metabolism is required by the heart. When delicately balanced mechanisms are changed by physiological or pathophysiological conditions, the whole system’s homeostasis will be altered to a new balance, which contributes to the pathologic process. So it is no wonder that almost every heart disease is related to metabolic shift. Furthermore, aging is also found to be related to the reduction in mitochondrial function, insulin resistance, and dysregulated intracellular lipid metabolism. Adenosine monophosphate-activated protein kinase (AMPK) functions as an energy sensor to detect intracellular ATP/AMP ratio and plays a pivotal role in intracellular adaptation to energy stress. During different pathology (like myocardial ischemia and hypertension), the activation of cardiac AMPK appears to be essential for repairing cardiomyocyte’s function by accelerating ATP generation, attenuating ATP depletion, and protecting the myocardium against cardiac dysfunction and apoptosis. In this overview, we will talk about the normal heart’s metabolism, how metabolic shifts during aging and different pathologies, and how AMPK regulates metabolic changes during these conditions. PMID:25880509

  18. Kavalactone metabolism in rat liver microsomes.

    Fu, Shuang; Rowe, Anthony; Ramzan, Iqbal

    2012-07-01

    The specific CYP enzymes involved in kavalactone (KLT) metabolism and their kinetics have not been fully examined. This study used rat liver microsomes (RLM) to determine kavain (KA), methysticin (MTS) and desmethoxyyangonin (DMY) enzyme kinetic parameters, to elucidate the major CYP450 isoforms involved in KLT metabolism and to examine gender differences in KLT metabolism. Formation of the major KLT metabolites was first-order, consistent with classic enzyme kinetics. In both male and female RLM, clotrimazole (CLO) was the most potent inhibitor of KA and MTS metabolism. This suggests CYP3A1/3A23 (females) and CYP3A2 (males) are the main isoenzymes involved in the metabolism of these KLTs in rats, while the roles of CYP1A2, -2 C6, -2 C9, -2E1 and -3A4 are limited. Desmethoxyyangonin metabolism was equally inhibited by cimetidine (CIM) and CLO in females, and CIM and nortriptyline in males. This implies that DMY metabolism involves CYP2C6 and CYP2C11 in males, and CPY2C12 in females. CYP3A1/3A23 may also be involved in females. PMID:22807255

  19. Optimal flux patterns in cellular metabolic networks

    Almaas, E

    2007-01-20

    The availability of whole-cell level metabolic networks of high quality has made it possible to develop a predictive understanding of bacterial metabolism. Using the optimization framework of flux balance analysis, I investigate metabolic response and activity patterns to variations in the availability of nutrient and chemical factors such as oxygen and ammonia by simulating 30,000 random cellular environments. The distribution of reaction fluxes is heavy-tailed for the bacteria H. pylori and E. coli, and the eukaryote S. cerevisiae. While the majority of flux balance investigations have relied on implementations of the simplex method, it is necessary to use interior-point optimization algorithms to adequately characterize the full range of activity patterns on metabolic networks. The interior-point activity pattern is bimodal for E. coli and S. cerevisiae, suggesting that most metabolic reaction are either in frequent use or are rarely active. The trimodal activity pattern of H. pylori indicates that a group of its metabolic reactions (20%) are active in approximately half of the simulated environments. Constructing the high-flux backbone of the network for every environment, there is a clear trend that the more frequently a reaction is active, the more likely it is a part of the backbone. Finally, I briefly discuss the predicted activity patterns of the central-carbon metabolic pathways for the sample of random environments.

  20. Computational model for monitoring cholesterol metabolism.

    Selvakumar, R; Rashith Muhammad, M; Poornima Devi, G

    2014-12-01

    A non-deterministic finite automaton is designed to observe the cholesterol metabolism with the states of acceptance and rejection. The acceptance state of the automaton depicts the normal level of metabolism and production of good cholesterol as an end product. The rejection state of this machine shows the inhibition of enzymatic activity in cholesterol synthesis and removal of free fatty acids. The deficiency in human cholesterol metabolism pathway results in abnormal accumulation of cholesterol in plasma, arterial tissues leading to diseases such as hypercholesterolemia, atherosclerosis respectively and formation of gallstones. The designed machine can be used to monitor the cholesterol metabolism at molecular level through regulation of enzymes involved in the biosynthesis and metabolism of cholesterol for the treatment of diseases incident due to the respective metabolic disorder. In addition, an algorithm for this machine has been developed to compare the programmed string with the given string. This study demonstrates the construction of a machine that is used for the development of molecular targeted therapy for the disorders in cholesterol metabolism. PMID:26396654

  1. Relationship between lung function and metabolic syndrome.

    Wei-Liang Chen

    Full Text Available Although the link between impaired lung function and cardiovascular events and type 2 diabetes mellitus has been recognized, the association between impaired lung function and metabolic syndrome has not been comprehensively assessed in the United States (U.S. population. The aim of our study was to explore the association between impaired lung function and metabolic syndrome in a nationally representative sample of men and women. This cross-sectional population-based study included 8602 participants aged 20-65 years in the Third National Health and Nutrition Examination Survey (NHANES III. We examined the relationship between the different features of metabolic syndrome and lung function, including forced vital capacity (FVC and forced expiratory volume in 1 second (FEV1. After adjusting for potential confounders such as age, body mass index, inflammatory factors, medical condition, and smoking status, participants with more components of metabolic syndrome had lower predicted values of FVC and FEV1 (p for trend <0.001 for both. Impaired pulmonary function was also associated with individual components of metabolic syndrome, such as abdominal obesity, high blood pressure, high triglycerides, and low high density lipoprotein (HDL cholesterol (p<0.05 for all parameters. These results from a nationally representative sample of US adults suggest that a greater number of features of metabolic syndrome is strongly associated with poorer FVC and FEV1. In clinical practice, more comprehensive management strategies to address subjects with metabolic syndrome and impaired lung function need to be developed and investigated.

  2. Molecular interactions between NAFLD and xenobiotic metabolism

    Adviti eNaik

    2013-01-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD, the hepatic manifestation of the metabolic syndrome, is a complex multifactorial disease characterised by metabolic deregulations that include accumulation of lipids in the liver, lipotoxicity and insulin resistance. The progression of NAFLD to NASH and cirrhosis, and ultimately to carcinomas, is governed by interplay of pro-inflammatory pathways, oxidative stress, as well as fibrogenic and apoptotic cues. As the liver is the major organ of biotransformation, deregulations in hepatic signalling pathways have effects on both, xenobiotic and endobiotic metabolism. Several major nuclear receptors involved in the transcription and regulation of phase I and II drug metabolizing enzymes and transporters also have endobiotic ligands including several lipids. Hence, hepatic lipid accumulation in steatosis and NAFLD, which leads to deregulated activation patterns of nuclear receptors, may result in altered drug metabolism capacity in NAFLD patients. On the other hand, genetic and association studies have indicated that a malfunction in drug metabolism can affect the prevalence and severity of NAFLD. This review focuses on the complex interplay between NAFLD pathogenesis and drug metabolism. A better understanding of these relationships is a prerequisite for developing improved drug dosing algorithms for the pharmacotherapy of patients with different stages of NAFLD.

  3. A network perspective on metabolic inconsistency

    Sonnenschein Nikolaus

    2012-05-01

    Full Text Available Abstract Background Integrating gene expression profiles and metabolic pathways under different experimental conditions is essential for understanding the coherence of these two layers of cellular organization. The network character of metabolic systems can be instrumental in developing concepts of agreement between expression data and pathways. A network-driven interpretation of gene expression data has the potential of suggesting novel classifiers for pathological cellular states and of contributing to a general theoretical understanding of gene regulation. Results Here, we analyze the coherence of gene expression patterns and a reconstruction of human metabolism, using consistency scores obtained from network and constraint-based analysis methods. We find a surprisingly strong correlation between the two measures, demonstrating that a substantial part of inconsistencies between metabolic processes and gene expression can be understood from a network perspective alone. Prompted by this finding, we investigate the topological context of the individual biochemical reactions responsible for the observed inconsistencies. On this basis, we are able to separate the differential contributions that bear physiological information about the system, from the unspecific contributions that unravel gaps in the metabolic reconstruction. We demonstrate the biological potential of our network-driven approach by analyzing transcriptome profiles of aldosterone producing adenomas that have been obtained from a cohort of Primary Aldosteronism patients. We unravel systematics in the data that could not have been resolved by conventional microarray data analysis. In particular, we discover two distinct metabolic states in the adenoma expression patterns. Conclusions The methodology presented here can help understand metabolic inconsistencies from a network perspective. It thus serves as a mediator between the topology of metabolic systems and their dynamical

  4. Folate Metabolism and Human Reproduction

    Thaler, C. J.

    2014-01-01

    Folate metabolism affects ovarian function, implantation, embryogenesis and the entire process of pregnancy. In addition to its well-established effect on the incidence of neural tube defects, associations have been found between reduced folic acid levels and increased homocysteine concentrations on the one hand, and recurrent spontaneous abortions and other complications of pregnancy on the other. In infertility patients undergoing IVF/ICSI treatment, a clear correlation was found between plasma folate concentrations and the incidence of dichorionic twin pregnancies. In patients supplemented with 0.4 mg/d folic acid undergoing ovarian hyperstimulation and oocyte pick-up, carriers of the MTHFR 677T mutation were found to have lower serum estradiol concentrations at ovulation and fewer oocytes could be retrieved from them. It appears that these negative effects can be compensated for in full by increasing the daily dose of folic acid to at least 0.8 mg. In carriers of the MTHFR 677TT genotype who receive appropriate supplementation, AMH concentrations were found to be significantly increased, which could indicate a compensatory mechanism. AMH concentrations in homozygous carriers of the MTHFR 677TT genotype could even be overestimated, as almost 20 % fewer oocytes are retrieved from these patients per AMH unit compared to MTHFR 677CC wild-type individuals. PMID:25278626

  5. Melphalan metabolism in cultured cells

    Procedures are presented for the adaptation of reversed-phase-HPLC methods to accomplish separation and isolation of the cancer therapeutic drug melphalan (L-phenylalanine mustard) and its metabolic products from whole cells. Five major degradation products of melphalan were observed following its hydrolysis in phosphate buffer in vitro. The two most polar of these products (or modifications of them) were also found in the cytosol of Chinese hamster CHO cells. The amounts of these two polar products (shown not to be mono- or dihydroxymelphalan) were significantly changed by the pretreatment of cells with ZnC12, one being increased in amount while the other was reduced to an insignificant level. In ZnC12-treated cells, there was also an increased binding of melphalan (or its derivatives) to one protein fraction resolved by gel filtration-HPLC. These observations suggest that changes in polar melphalan products, and perhaps their interaction with a protein, may by involved in the reduction of melphalan cytotoxicity observed in ZnC12-treated cells. While ZnC12 is also known to increase the level of glutathione in cells, no significant amounts of glutathione-melphalan derivatives of the type formed non-enzymatically in vitro could be detected in ZnC12-treated or untreated cells. Formation of derivatives of melphalan with glutathione catabolic products in ZnC12-treated cells has not yet been eliminated, however. 17 refs., 5 figs., 1 tab

  6. Metabolism of technetium in goats

    The yield of 99Tc from nuclear fission is in the order of magnitude of the 90Sr and 137Cs yields. The metabolic pathways of this nuclide with its physical half life of 2.1 x 105 yr have, therefore, to be investigated for radioecological assessments; especially with respect to the wide spread application of sup(99m)Tc in nuclear medical diagnosis. Experiments with goats show that sup(99m)Tc given orally as pertechnetate is readily absorbed from the gastrointestinal tract. Excretion in milk is more than 10 times lower than that of radioiodine. The Tc-content of muscular tissues is also low and seems to be of minor importance for the pathway of this element via meat of grazing animals to man. Finally, urinary excretion of Tc in man is 20-100 times higher than in goats. Therefore, the estimation of radiation burden due to Tc-isotopes from extrapolation of radioiodine data is very conservative. (author)

  7. Purine metabolism in Toxoplasma gondii

    We have studied the incorporation and interconversion of purines into nucleotides by freshly isolated Toxoplasma gondii. They did not synthesize nucleotides from formate, glycine, or serine. The purine bases hypoxanthine, xanthine, guanine, and adenine were incorporated at 9.2, 6.2, 5.1, and 4.3 pmol/10(7) cells/h, respectively. The purine nucleosides adenosine, inosine, guanosine, and xanthosine were incorporated at 110, 9.0, 2.7, and 0.3 pmol/10(7) cells/h, respectively. Guanine, xanthine, and their respective nucleosides labeled only guanine nucleotides. Inosine, hypoxanthine, and adenine labeled both adenine and guanine nucleotide pools at nearly equal ratios. Adenosine kinase was greater than 10-fold more active than the next most active enzyme in vitro. This is consistent with the metabolic data in vivo. No other nucleoside kinase or phosphotransferase activities were found. Phosphorylase activities were detected for guanosine and inosine; no other cleavage activities were detected. Deaminases were found for adenine and guanine. Phosphoribosyltransferase activities were detected for all four purine nucleobases. Interconversion occurs only in the direction of adenine to guanine nucleotides

  8. Plant Specialized Metabolism: the Easy and the Hard

    Shan Lu

    2010-01-01

    @@ Although normally termed" plant secondary metabolism", the phrase" plant specialized metabolism" has become instruments, such as gas chromatography, high performance liquid chromatography, mass spectrometry and nuclear magnetic resonance.

  9. Acyl-CoA metabolism and partitioning

    Grevengoed, Trisha J; Klett, Eric L; Coleman, Rosalind A

    2014-01-01

    expression patterns and subcellular locations. Their acyl-CoA products regulate metabolic enzymes and signaling pathways, become oxidized to provide cellular energy, and are incorporated into acylated proteins and complex lipids such as triacylglycerol, phospholipids, and cholesterol esters. Their differing...... metabolic fates are determined by a network of proteins that channel the acyl-CoAs toward or away from specific metabolic pathways and serve as the basis for partitioning. This review evaluates the evidence for acyl-CoA partitioning by reviewing experimental data on proteins that are believed to contribute...

  10. The role of metabolism in bacterial persistence

    Stephanie M. Amato

    2014-03-01

    Full Text Available Bacterial persisters are phenotypic variants with extraordinary tolerances toward antibiotics. Persister survival has been attributed to inhibition of essential cell functions during antibiotic stress, followed by reversal of the process and resumption of growth upon removal of the antibiotic. Metabolism plays a critical role in this process, since it participates in the entry, maintenance, and exit from the persister phenotype. Here, we review the experimental evidence that demonstrates the importance of metabolism to persistence, highlight the successes and potential for targeting metabolism in the search for anti-persister therapies, and discuss the current methods and challenges to understand persister physiology.

  11. Genome scale metabolic reconstruction of Chlorella variabilis for exploring its metabolic potential for biofuels.

    Juneja, Ankita; Chaplen, Frank W R; Murthy, Ganti S

    2016-08-01

    A compartmentalized genome scale metabolic network was reconstructed for Chlorella variabilis to offer insight into various metabolic potentials from this alga. The model, iAJ526, was reconstructed with 1455 reactions, 1236 metabolites and 526 genes. 21% of the reactions were transport reactions and about 81% of the total reactions were associated with enzymes. Along with gap filling reactions, 2 major sub-pathways were added to the model, chitosan synthesis and rhamnose metabolism. The reconstructed model had reaction participation of 4.3 metabolites per reaction and average lethality fraction of 0.21. The model was effective in capturing the growth of C. variabilis under three light conditions (white, red and red+blue light) with fair agreement. This reconstructed metabolic network will serve an important role in systems biology for further exploration of metabolism for specific target metabolites and enable improved characteristics in the strain through metabolic engineering. PMID:26995318

  12. Metabolic effects of hypergravity on experimental animals

    Oyama, J.

    1982-01-01

    Several experiments concerned with the exposure of animals to acute or chronic centrifugation are described. The effects of hypergravity particularly discussed include the decreased growth rate and body weight, increased metabolic rate, skeletal deformation, and loss of body fat.

  13. Microbial metabolism of organosulfur compounds in petroleum

    The microbial metabolism of a large number of hydrocarbons has been thoroughly studied and described in the literature. In contrast, much less is known about the metabolism of organosulfur compounds found in petroleum. These investigations have been hampered by the commercial unavailability of most of the sulfur compounds of interest. Some of the first studies on the biodegradation of sulfur compounds focused on their fate and removal from oil-contaminated environments. Another major area of study is the microbial process of 'biodesulfurization' which has been suggested as a means of selectively removing sulfur compounds from petroleum prior to refining. Information gathered from these two areas of research provide the basis of the present knowledge of metabolism of organosulfur compounds in petroleum. This information is reviewed with emphasis on the metabolism of dibenzothiophenes and n-alkyl tetrahydrothiophenes (n-alkyl thiolanes)

  14. Topiramate and Metabolic Acidosis in Infants

    J Gordon Millichap

    2002-08-01

    Full Text Available The acid-base metabolism was investigated in 9 infants and toddlers, aged 5 months to 2.3 years (median, 6 months, treated with topiramate (TPM for seizures at Johannes Gutenberg University, Mainz, Germany.

  15. Synthetic redesign of plant lipid metabolism.

    Haslam, Richard P; Sayanova, Olga; Kim, Hae Jin; Cahoon, Edgar B; Napier, Johnathan A

    2016-07-01

    Plant seed lipid metabolism is an area of intensive research, including many examples of transgenic events in which oil composition has been modified. In the selected examples described in this review, progress towards the predictive manipulation of metabolism and the reconstitution of desired traits in a non-native host is considered. The advantages of a particular oilseed crop, Camelina sativa, as a flexible and utilitarian chassis for advanced metabolic engineering and applied synthetic biology are considered, as are the issues that still represent gaps in our ability to predictably alter plant lipid biosynthesis. Opportunities to deliver useful bio-based products via transgenic plants are described, some of which represent the most complex genetic engineering in plants to date. Future prospects are considered, with a focus on the desire to transition to more (computationally) directed manipulations of metabolism. PMID:27483205

  16. Size Dependent Growth in Metabolic Networks

    Dorrian, Henry; borresen, Jon

    2012-01-01

    Accurately determining and classifying the structure of complex networks is the focus of much current research. One class of network of particular interest are metabolic pathways, which have previously been studied from a graph theoretical viewpoint in a number of ways. Metabolic networks describe the chemical reactions within cells and are thus of prime importance from a biological perspective. Here we analyse metabolic networks from a section of microorganisms, using a range of metrics and attempt to address anomalies between the observed metrics and current descriptions of the graphical structure. We propose that the growth of the network may in some way be regulated by network size and attempt to reproduce networks with similar metrics to the metabolic pathways using a generative approach. We provide some hypotheses as to why biological networks may evolve according to these model criteria.

  17. Lipoprotein metabolism indicators improve cardiovascular risk prediction

    Background: Cardiovascular disease risk increases when lipoprotein metabolism is dysfunctional. We have developed a computational model able to derive indicators of lipoprotein production, lipolysis, and uptake processes from a single lipoprotein profile measurement. This is the first study to inves...

  18. Evolutionary algorithm for metabolic pathways synthesis.

    Gerard, Matias F; Stegmayer, Georgina; Milone, Diego H

    2016-06-01

    Metabolic pathway building is an active field of research, necessary to understand and manipulate the metabolism of organisms. There are different approaches, mainly based on classical search methods, to find linear sequences of reactions linking two compounds. However, an important limitation of these methods is the exponential increase of search trees when a large number of compounds and reactions is considered. Besides, such models do not take into account all substrates for each reaction during the search, leading to solutions that lack biological feasibility in many cases. This work proposes a new evolutionary algorithm that allows searching not only linear, but also branched metabolic pathways, formed by feasible reactions that relate multiple compounds simultaneously. Tests performed using several sets of reactions show that this algorithm is able to find feasible linear and branched metabolic pathways. PMID:27080162

  19. Role of metabolism in neurodegenerative disorders.

    Procaccini, Claudio; Santopaolo, Marianna; Faicchia, Deriggio; Colamatteo, Alessandra; Formisano, Luigi; de Candia, Paola; Galgani, Mario; De Rosa, Veronica; Matarese, Giuseppe

    2016-09-01

    Along with the increase in life expectancy over the last century, the prevalence of age-related disorders, such as neurodegenerative diseases continues to rise. This is the case of Alzheimer's, Parkinson's, Huntington's diseases and Multiple sclerosis, which are chronic disorders characterized by neuronal loss in motor, sensory or cognitive systems. Accumulating evidence has suggested the presence of a strong correlation between metabolic changes and neurodegeneration. Indeed epidemiologic studies have shown strong associations between obesity, metabolic dysfunction, and neurodegeneration, while animal models have provided insights into the complex relationships between these conditions. In this context, hormones such as leptin, ghrelin, insulin and IGF-1 seem to play a key role in the regulation of neuronal damage, toxic insults and several other neurodegenerative processes. This review aims to presenting the most recent evidence supporting the crosstalk linking energy metabolism and neurodegeneration, and will focus on metabolic manipulation as a possible therapeutic tool in the prevention and treatment of neurodegenerative diseases. PMID:27506744

  20. Serine and glycine metabolism in cancer☆

    Amelio, Ivano; Cutruzzolá, Francesca; Antonov, Alexey; Agostini, Massimiliano; Melino, Gerry

    2014-01-01

    Serine and glycine are biosynthetically linked, and together provide the essential precursors for the synthesis of proteins, nucleic acids, and lipids that are crucial to cancer cell growth. Moreover, serine/glycine biosynthesis also affects cellular antioxidative capacity, thus supporting tumour homeostasis. A crucial contribution of serine/glycine to cellular metabolism is through the glycine cleavage system, which refuels one-carbon metabolism; a complex cyclic metabolic network based on chemical reactions of folate compounds. The importance of serine/glycine metabolism is further highlighted by genetic and functional evidence indicating that hyperactivation of the serine/glycine biosynthetic pathway drives oncogenesis. Recent developments in our understanding of these pathways provide novel translational opportunities for drug development, dietary intervention, and biomarker identification of human cancers. PMID:24657017

  1. Adaptive diversity: hormones and metabolism in freshwaters.

    Laudet, Vincent

    2010-12-01

    Genes underlying the evolution of morphological traits have recently been identified in a number of model species. In the stickleback, the metabolic adaptations to a freshwater habitat have now been linked to a well-known hormonal system. PMID:21145015

  2. Prolonged platelet preservation by transient metabolic suppression

    Badlou, Bahram Alamdary

    2006-01-01

    Introduction: Different clinical studies have shown that transfusion of stored platelets results in better haemostasis in patients with thrombocytopenia with and without a platelet function defect. Objectives: Current preservation procedures aim to optimally preserve the metabolic status of platel

  3. Regulation of terpene metabolism. Progress report, 1983

    Studies on the metabolism of terpenes by peppermint (Menta piperita) are described. The studies describe the characterization of enzymes involved in the biosynthesis and catabolism of terpenes and the ultrastructure of the oil glands. 10 refs. (DT)

  4. Nitric oxide and mitochondria in metabolic syndrome

    Larisa eLitvinova

    2015-02-01

    Full Text Available Metabolic syndrome (MS is a cluster of metabolic disorders that collectively increase the risk of cardiovascular disease. Nitric oxide (NO plays a crucial role in the pathogeneses of MS components and is involved in different mitochondrial signaling pathways that control respiration and apoptosis. The present review summarizes the recent information regarding the interrelations of mitochondria and NO in MS. Changes in the activities of different NO synthase isoforms lead to the formation of metabolic disorders and therefore are highlighted here. Reduced endothelial NOS activity and NO bioavailability, as the main factors underlying the endothelial dysfunction that occurs in MS, are discussed in this review in relation to mitochondrial dysfunction. We also focus on potential therapeutic strategies involving NO signaling pathways that can be used to treat patients with metabolic disorders associated with mitochondrial dysfunction. The article may help researchers develop new approaches for the diagnosis, prevention and treatment of MS.

  5. Forearm metabolism during infusion of adrenaline

    Simonsen, L; Stefl, B; Bülow, J

    2000-01-01

    Human skeletal muscle metabolism is often investigated by measurements of substrate fluxes across the forearm. To evaluate whether the two forearms give the same metabolic information, nine healthy subjects were studied in the fasted state and during infusion of adrenaline. Both arms were...... catheterized in a cubital vein in the retrograde direction. A femoral artery was catheterized for blood sampling, and a femoral vein for infusion of adrenaline. Forearm blood flow was measured by venous occlusion strain-gauge plethysmography. Forearm subcutaneous adipose tissue blood flow was measured...... by the local 133Xe washout method. Metabolic fluxes were calculated as the product of forearm blood flow and a-v differences of metabolite concentrations. After baseline measurements, adrenaline was infused at a rate of 0.3 nmol kg-1 min-1. No difference in the metabolic information obtained in the fasting...

  6. Carotenoid Metabolism: Biosynthesis, Regulation,and Beyond

    Shan Lu; Li Li

    2008-01-01

    Carotenoids are Indispensable to plants and play a critical role in human nutrition and health. Significant progress has been made in our understanding of carotenoid metabolism in plants. The biosynthetic pathway has been extensively studied.Nearly all the genes encoding the biosynthetic enzymes have been isolated and characterized from various organisms. In recent years, there is an increasing body of work on the signaling pathways and plastid development, which might provide global control of carotenoid biosynthesis and accumulation. Herein, we will highlight recent progress on the biosynthesis,regulation, and metabolic engineering of carotenoids in plants, as well as the future research towards elucidating the regulatory mechanisms and metabolic network that control carotenoid metabolism.

  7. Computational Methods for Modification of Metabolic Networks

    Takeyuki Tamura

    2015-01-01

    Full Text Available In metabolic engineering, modification of metabolic networks is an important biotechnology and a challenging computational task. In the metabolic network modification, we should modify metabolic networks by newly adding enzymes or/and knocking-out genes to maximize the biomass production with minimum side-effect. In this mini-review, we briefly review constraint-based formalizations for Minimum Reaction Cut (MRC problem where the minimum set of reactions is deleted so that the target compound becomes non-producible from the view point of the flux balance analysis (FBA, elementary mode (EM, and Boolean models. Minimum Reaction Insertion (MRI problem where the minimum set of reactions is added so that the target compound newly becomes producible is also explained with a similar formalization approach. The relation between the accuracy of the models and the risk of overfitting is also discussed.

  8. Holter registers and metabolic syndrome

    Muñoz-Diosdado, A.; Ramírez-Hernández, L.; Aguilar-Molina, A. M.; Zamora-Justo, J. A.; Gutiérrez-Calleja, R. A.; Virgilio-González, C. D.

    2014-11-01

    There is a relationship between the state of the cardiovascular system and metabolic syndrome (MS). A way to diagnose the heart state of a person is to monitor the electrical activity of the heart using a 24 hours Holter monitor. Scanned ECG signal can be analyzed beat-by-beat by algorithms that separate normal of abnormal heartbeats. If the percentage of abnormal heartbeats is too high it could be argued that the patient has heart problems. We have algorithms that can not only identify the abnormal heartbeats, but they can also classify them, so we classified and counted abnormal heartbeats in patients with MS and subjects without MS. Most of our patients have large waist circumference, high triglycerides and high levels of LDL (high-density lipoprotein) cholesterol although some of them have high blood pressure. We enrolled adult patients with MS free of diabetes in a four month lifestyle intervention program including diet and physical aerobic exercise, and compared with healthy controls. We made an initial registration with a Holter, and 24 hours ECG signal is analyzed to identify and classify the different types of heartbeats. The patients then begin with diet or exercise (at least half an hour daily). Periodically Holter records were taken up and we describe the evolution in time of the number and type of abnormal heartbeats. Results show that the percentage of abnormal heartbeats decreases over time, in some cases the decline is very significant, and almost a reduction to half or less of abnormal heartbeats after several months since the patients changed their eating or physical activity habits.

  9. Metabolic models for tritium dosimetry

    Tritium (3H or T) is the radioactive isotope of hydrogen, which is produced by both natural, and man made sources. Tritium has a small relative natural abundance compared to hydrogen and deuterium (D). As was assessed by the United Nations scientific committee the contribution of cosmogenic tritium to annual effective dose in human is very small, only about 0.01 μSv (UNSCEAR, 2000). In case of heavy water reactors annual tritium doses for critical groups are also very small but theoretically could reach values of several μSv. In this case professionally exposed personnel could be exposed to tritium doses of some mSv. According to these considerations environmental and dosimetric aspects of this radionuclide are of special concern for health physicists. Tritium dose assessment methodologies have special particularities because hydrogen is a chemical element with an important metabolic role in the human body. Operating experience to date of CANDU reactors has indicated that the major contributor to the internal dose of professionally exposed people is the tritiated heavy water (DTO). DTO, like the tritiated water HTO, is assumed to be uniformly mixed with body water pool and reaching equilibrium immediately after the intake. All the statements in this paper related to HTO dosimetry are also considered valid in case of DTO. The results of the computations performed with different retention functions corresponding to different compartment models are presented. The differences between the models due to OBT (Organically Bound Tritium) contribution are 5.6% for two- compartment model and 13% for three-compartment Dunford - Johnson model, respectively. In practice the contribution of OBT is considered to be about 10%. (authors)

  10. Biorefinery: Toward an industrial metabolism.

    Octave, Stéphane; Thomas, Daniel

    2009-06-01

    Fossil fuel reserves are running out, global warming is becoming a reality, waste recycling is becoming ever more costly and problematic, and unrelenting population growth will require more and more energy and consumer products. There is now an alternative to the 100% oil economy; it is a renewable resource based on agroresources by using the whole plant. Production and development of these new products are based on biorefinery concept. Each constituent of the plant can be extracted and functionalized in order to produce non-food and food fractions, intermediate agro-industrial products and synthons. Three major industrial domains can be concerned: molecules, materials and energy. Molecules can be used as solvent surfactants or chemical intermediates in substitution of petrol derivatives. Fibers can be valorized in materials like composites. Sugars and oils are currently used to produce biofuels like bioethanol or biodiesel, but second-generation biofuels will use lignocellulosic biomass as raw material. Lipids can be used to produce a large diversity of products like solvent, lubricants, pastes or surfactants. Industrial biorefinery will be linked to the creation of new processes based on the twelve principles of green chemistry (clean processes, atom economy, renewable feedstocks...). Biotechnology, especially white biotechnology, will take a major part into these new processes with biotransformations (enzymology, micro-organisms...) and fermentation. The substitution of oil products by biobased products will develop a new bioeconomy and new industrial processes respecting the sustainable development concept. Industrial biorefinery can be developed on the principle that any residues of one can then be exploited as raw material by others in an industrial metabolism. PMID:19332104

  11. Tryptophan Metabolism in Allergic Disorders.

    Gostner, Johanna M; Becker, Katrin; Kofler, Heinz; Strasser, Barbara; Fuchs, Dietmar

    2016-01-01

    Allergic diseases such as asthma and rhinitis, as well the early phase of atopic dermatitis, are characterized by a Th2-skewed immune environment. Th2-type cytokines are upregulated in allergic inflammation, whereas there is downregulation of the Th1-type immune response and related cytokines, such as interferon-x03B3; (IFN-x03B3;). The latter is a strong inducer of indoleamine 2,3-dioxygenase-1 (IDO-1), which degrades the essential amino acid tryptophan, as part of an antiproliferative strategy of immunocompetent cells to halt the growth of infected and malignant cells, and also of T cells - an immunoregulatory intervention to avoid overactivation of the immune system. Raised serum tryptophan concentrations have been reported in patients with pollen allergy compared to healthy blood donors. Moreover, higher baseline tryptophan concentrations have been associated with a poor response to specific immunotherapy. It has been shown that the increase in tryptophan concentrations in patients with pollen allergy only exists outside the pollen season, and not during the season. Interestingly, there is only a minor alteration of the kynurenine to tryptophan ratio (Kyn/Trp, an index of tryptophan breakdown). The reason for the higher tryptophan concentrations in patients with pollen allergy outside the season remains a matter of discussion. To this regard, the specific interaction of nitric oxide (NO∙) with the tryptophan-degrading enzyme IDO-1 could be important, because an enhanced formation of NO∙ has been reported in patients with asthma and allergic rhinitis. Importantly, NO∙ suppresses the activity of the heme enzyme IDO-1, which could explain the higher tryptophan levels. Thus, inhibitors of inducible NO∙ synthase should be reconsidered as candidates for antiallergic therapy out of season that may abrogate the arrest of IDO-1 by decreasing the production of NO∙. Considering its association with the pathophysiology of atopic disease, tryptophan metabolism may

  12. Genetic/metabolic effect of iron metabolism and rare anemias

    Clara Camaschella

    2013-03-01

    Full Text Available Advances in iron metabolism have allowed a novel classification of iron disorders and to identify previously unknown diseases. These disorders include genetic iron overload (hemochromatosis and inherited iron-related anemias, in some cases accompanied by iron overload. Rare inherited anemias may affect the hepcidin pathway, iron absorption, transport, utilization and recycling. Among the genetic iron-related anemias the most common form is likely the iron-refractory iron-deficiency anemia (IRIDA, due to mutations of the hepcidin inhibitor TMPRSS6 encoding the serine protease matriptase-2. IRIDA is characterized by hepcidin up-regulation, decrease iron absorption and macrophage recycling and by microcytic- hypochromic anemia, unresponsive to oral iron. High serum hepcidin levels may suggest the diagnosis, which requires demonstrating the causal TMPRSS6 mutations by gene sequencing. Other rare microcytic hypochromic anemias associated with defects of iron transport-uptake are the rare hypotransferrinemia, and DMT1 and STEAP3 mutations. The degree of anemia is variable and accompanied by secondary iron overload even in the absence of blood transfusions. This is due to the iron-deficient or expanded erythropoiesis that inhibits hepcidin transcription, increases iron absorption, through the erythroid regulator, as in untransfused beta-thalassemia. Sideroblastic anemias are due to decreased mitochondrial iron utilization for heme or sulfur cluster synthesis. Their diagnosis requires demonstrating ringed sideroblasts by Perl’s staining of the bone marrow smears. The commonest X-linked form is due to deltaamino- levulinic-synthase-2-acid (ALAS2 mutations. The recessive, more severe form, affects SLC25A38, which encodes a potential mitochondrial importer of glycine, an amino acid essential for ALA synthesis and thus results in heme deficiency. Two disorders affect iron/sulfur cluster biogenesis: deficiency of the ATP-binding cassette B7 (ABCB7 causes X

  13. Alterations of lipid metabolism in Wilson disease

    Stremmel Wolfgang; Eckert Nicola; Pfeiffenberger Jan; Gotthardt Daniel; Gohdes Annina; Seessle Jessica; Reuner Ulrike; Weiss Karl

    2011-01-01

    Abstract Introduction Wilson disease (WD) is an inherited disorder of human copper metabolism, characterised by accumulation of copper predominantly in the liver and brain, leading to severe hepatic and neurological disease. Interesting findings in animal models of WD (Atp7b-/- and LEC rats) showed altered lipid metabolism with a decrease in the amount of triglycerides and cholesterol in the serum. However, serum lipid profile has not been investigated in large human WD patient cohorts to dat...

  14. Cardiomyocyte autophagy: metabolic profit and loss

    Wang, Zhao V.; Ferdous, Anwarul; Hill, Joseph A.

    2013-01-01

    Cardiovascular disease remains the leading cause of morbidity and mortality worldwide, even despite recent scientific and technological advances and comprehensive preventive strategies. The cardiac myocyte is a voracious consumer of energy, and alterations in metabolic substrate availability and consumption are hallmark features of these disorders. Autophagy, an evolutionarily ancient response to metabolic insufficiency, has been implicated in the pathogenesis of a wide range of heart patholo...

  15. 2-Hydroxy Acids in Plant Metabolism

    Maurino, Veronica G.; Engqvist, Martin K. M.

    2015-01-01

    Glycolate, malate, lactate, and 2-hydroxyglutarate are important 2-hydroxy acids (2HA) in plant metabolism. Most of them can be found as D- and L-stereoisomers. These 2HA play an integral role in plant primary metabolism, where they are involved in fundamental pathways such as photorespiration, tricarboxylic acid cycle, glyoxylate cycle, methylglyoxal pathway, and lysine catabolism. Recent molecular studies in Arabidopsis thaliana have helped elucidate the participation of these 2HA in in pla...

  16. Exploring metabolic dysfunction in chronic kidney disease

    Slee Adrian D

    2012-01-01

    Abstract Impaired kidney function and chronic kidney disease (CKD) leading to kidney failure and end-stage renal disease (ESRD) is a serious medical condition associated with increased morbidity, mortality, and in particular cardiovascular disease (CVD) risk. CKD is associated with multiple physiological and metabolic disturbances, including hypertension, dyslipidemia and the anorexia-cachexia syndrome which are linked to poor outcomes. Specific hormonal, inflammatory, and nutritional-metabol...

  17. Regulation of metabolism in Caenorhabditis elegans longevity

    Gallo, Marco; Riddle, Donald L.

    2010-01-01

    The nematode Caenorhabditis elegans is a favorite model for the study of aging. A wealth of genetic and genomic studies show that metabolic regulation is a hallmark of life-span modulation. A recent study in BMC Biology identifying metabolic signatures for longevity suggests that amino-acid pools may be important in longevity. See research article http://www.biomedcentral.com/1741-7007/8/14.

  18. Skeletal Muscle Autophagy: A New Metabolic Regulator

    Neel, Brian A.; Lin, Yuxi; Pessin, Jeffrey E.

    2013-01-01

    Autophagy classically functions as a physiological process to degrade cytoplasmic components, protein aggregates, and/or organelles, as a mechanism for nutrient breakdown, and as a regulator of cellular architecture. Proper autophagic flux is vital for both functional skeletal muscle, which controls support and movement of the skeleton, and muscle metabolism. The role of autophagy as a metabolic regulator in muscle has been previously studied; however, the underlying molecular mechanisms that...

  19. Equine metabolic syndrome: Etiopathogenesis, diagnostics and therapy

    Trailović Dragiša R.; Trailović Ivana D.; Spasojević-Kosić Ljubica

    2015-01-01

    Equine metabolic syndrome (EMS) is a term adopted in 2002 in aim to define the complex pathology involving obesity, insulin resistance and laminitis in horses and ponies. The EMS was terminologically derived upon similar condition in humans. The metabolic disturbance in equines is developed sequentially to the primary chronic overfeeding, i.e. intake of surplus food to individual needs combined with insufficient activity of animal. The syndrome has been rep...

  20. Origin and evolution of metabolic pathways

    Fani, Renato; Fondi, Marco

    2009-03-01

    The emergence and evolution of metabolic pathways represented a crucial step in molecular and cellular evolution. In fact, the exhaustion of the prebiotic supply of amino acids and other compounds that were likely present in the ancestral environment, imposed an important selective pressure, favoring those primordial heterotrophic cells which became capable of synthesizing those molecules. Thus, the emergence of metabolic pathways allowed primitive organisms to become increasingly less-dependent on exogenous sources of organic compounds. Comparative analyses of genes and genomes from organisms belonging to Archaea, Bacteria and Eukarya revealed that, during evolution, different forces and molecular mechanisms might have driven the shaping of genomes and the arisal of new metabolic abilities. Among these gene elongations, gene and operon duplications undoubtedly played a major role since they can lead to the (immediate) appearance of new genetic material that, in turn, might undergo evolutionary divergence giving rise to new genes coding for new metabolic abilities. Gene duplication has been invoked in the different schemes proposed to explain why and how the extant metabolic pathways have arisen and shaped. Both the analysis of completely sequenced genomes and directed evolution experiments strongly support one of them, i.e. the patchwork hypothesis, according to which metabolic pathways have been assembled through the recruitment of primitive enzymes that could react with a wide range of chemically related substrates. However, the analysis of the structure and organization of genes belonging to ancient metabolic pathways, such as histidine biosynthesis and nitrogen fixation, suggested that other different hypothesis, i.e. the retrograde hypothesis or the semi-enzymatic theory, may account for the arisal of some metabolic routes.

  1. Breakfast Frequency and Development of Metabolic Risk

    Odegaard, Andrew O; Jacobs, David R.; Steffen, Lyn M.; Horn, Linda Van; Ludwig, David S.; Pereira, Mark A

    2013-01-01

    OBJECTIVE The relation of breakfast intake frequency to metabolic health is not well studied. The aim of this study was to examine breakfast intake frequency with incidence of metabolic conditions. RESEARCH DESIGN AND METHODS We performed an analysis of 3,598 participants from the community-based Coronary Artery Risk Development in Young Adults (CARDIA) study who were free of diabetes in the year 7 examination when breakfast and dietary habits were assessed (1992–1993) and participated in at ...

  2. Insulin and metabolic substrates during human sepsis

    Finney, Simon J

    2004-01-01

    Rusavy and colleagues recently endeavoured to dissect out the metabolic effects of insulin in patients with severe sepsis, in the setting of normoglycaemia. Twenty stable patients were studied 3–7 days after admission using a euglycaemic clamp at two supraphysiological insulin levels. Increased doses of exogenous insulin caused preferential use of glucose as a metabolic substrate, while total energy expenditure remained constant. Consequently, hyperinsulinaemia reduced tissue oxygen demand an...

  3. Evidence for Central Regulation of Glucose Metabolism*

    Carey, Michelle; Kehlenbrink, Sylvia; Hawkins, Meredith

    2013-01-01

    Evidence for central regulation of glucose homeostasis is accumulating from both animal and human studies. Central nutrient and hormone sensing in the hypothalamus appears to coordinate regulation of whole body metabolism. Central signals activate ATP-sensitive potassium (KATP) channels, thereby down-regulating glucose production, likely through vagal efferent signals. Recent human studies are consistent with this hypothesis. The contributions of direct and central inputs to metabolic regulat...

  4. METABOLIC INTEGRATION: BEYOND THE BUILDING BLOCKS

    M. D.V. Machado

    2015-08-01

    Full Text Available The theme "metabolic Integration" discussed during Biochemistry classes is considered by many students a complex issue. It could be due to their difficulty in understanding that the metabolic pathways are not isolated reactions, but a completely interdependent system finely regulated. Given this reality, a didactic game was developed. The main objective was to challenge students to understand the metabolism integration, through a playful, interactive and dynamic way. The class was divided into groups and to each group was given a set of parts that represented an important pathway of energetic metabolism. The aim of each group was to complete the metabolic process assigned to them. However, during the assembly, they realized that was always lacking some part of the puzzle and that the game only succeeds if all the groups exchange parts with each other. After that, the pieces came together in order to assemble all the processes in an integrated way. The game was organized into two situations: metabolic reactions that occur in the fasted state and reactions of the fed state. When the groups realized they needed to join themselves to complete the processes, they also had to get into a consensus that the "body" in which the reactions were happening, was in a fasted state or not, because the pieces didn’t match each other if both metabolic states were being assembled at the same time. It is not suitable to the organism performs the reactions of antagonistic states at the same time/or at the same velocity. Along the schema assembly, key points were didactically marked in some pieces with colors and warnings. The proposal was to open a discussion after assembling of the parts.The game was applied to students at the first year of medicine school and had a great acceptance.Key words: metabolism, integration, game.

  5. Novel aspects of carnitine function and metabolism

    Violante, Sara Liliana Nunes, 1983-

    2013-01-01

    Tese de doutoramento, Farmácia (Bioquímica), Universidade de Lisboa, Faculdade de Farmácia, 2013 Normal functioning of fatty acid oxidation and energy metabolism depends on carnitine. Although this compound has been extensively studied over the years, some aspects of carnitine metabolism and function remain unclear. This thesis aimed to: 1) elucidate the reverse action of the carnitine shuttle in the mitochondrial detoxification of intermediates accumulating in mitochondrial fatty acid β-o...

  6. Protein,carbohydrate and lipid metabolism

    1995-01-01

    950255 Effects of TPN and indomethacin on stressresponse and protein metabolism after surgery.QUANZhufu(全竹富),et al.General Hosp,Nanjing Com-mand,Nanjing,210002.Med J Chin PLA 1995;20(1):24-26.The study was planned to evaluate effects of TPNand indomethacin on stress response after trauma,andprotein metabolism in patients who had received totalgastrectomy for cardiac cancer of stomach.19 caseswere divided into control,TPN,and indomethacin

  7. Metabolic model for diversity-generating biosynthesis

    Tianero, Ma. Diarey; Pierce, Elizabeth; Raghuraman, Shrinivasan; Sardar, Debosmita; McIntosh, John A.; Heemstra, John R.; Schonrock, Zachary; Covington, Brett C.; Maschek, J. Alan; Cox, James E.; Bachmann, Brian O.; Olivera, Baldomero M; Ruffner, Duane E.; Schmidt, Eric W.

    2016-01-01

    How is chemical diversity generated by biological systems? Some biosynthetic pathways are constrained to produce one metabolite, but others are relatively relaxed and can produce a set of diverse compounds. Using the example of the tru pathway to cyanobactins, we propose a model of diversity-generating metabolism in which pathway flux and properties are strikingly different from the canonical design of conventional metabolic pathways.

  8. Association between metabolic syndrome and agerelated cataract

    Sangshin; Park; Eun-Hee; Lee

    2015-01-01

    ·AIM: To determine the effect of metabolic syndrome on age-related cataract formation.·METHODS: We analyzed data for 2852 subjects [41.8%men and 58.2% women; mean(±SD) age, 52.9 ±13.9y],taken from the Korea National Health and Nutrition Examination Survey 2008. Metabolic syndrome was diagnosed by criteria proposed by the Joint Interim Societies. Cataract was diagnosed by using the Lens Opacities Classification System III. The association between metabolic syndrome and cataract was determined using age-adjusted and multivariable logistic regression analyses.· RESULTS: In multivariable analyses, men with metabolic syndrome had a 64% increased risk of nuclear cataract [odds ratio(OR), 1.64; 95% confidence interval(CI), 1.12-2.39]. Women with metabolic syndrome had a56% increased risk of cortical cataract(OR, 1.56; 95% CI,1.06-2.30). Men and women with metabolic syndrome had a 46%(OR, 1.46; 95% CI, 1.01-2.12) and 49%(OR,1.49; 95% CI, 1.07-2.08) increased risk of any cataract,respectively. The prevalence of nuclear and any cataract significantly increased with an increasing number of disturbed metabolic components in men, and prevalence of all types of cataracts increased in women. Men using hypoglycemic medication had an increased risk of nuclear(OR, 2.62; 95% CI, 1.41-4.86) and any(OR, 2.27;95% CI, 1.14-4.51) cataract, and women using antidyslipidemia medication had an increased risk of cortical(OR, 2.18; 95% CI, 1.12-4.24) and any(OR, 2.21;95% CI, 1.14-4.26) cataract.·CONCLUSION: Metabolic syndrome and its components,such as abdominal obesity, high blood pressure, andimpaired fasting glucose, are associated with age-related cataract formation in the Korean population.

  9. Energy metabolism of the developing brain

    Cerebral metabolism in utero and in the neonatal period remains incompletely understood. A major investigative technique uses 14C deoxyglucose. Species differences, behavioral states and gestational age all have an impact. Hormonal and sensory stimuli have potential influences. The use of this new investigative technique in the human will allow detailed study of the effects of a variety of pathophysiologic events and possibly of drug therapy on cerebral glucose metabolism

  10. Evaluating Metabolic Syndrome in children and adolescents

    Maria D Rekliti; Ioannis A Kyriazis

    2010-01-01

    Metabolic Syndrome (MS) is consisted by a group of interrelated disorders increasing the risk for cardiovascular diseases and type II diabetes causing diseases and deaths in modern world.Purpose of the current study is to relate the evaluation of the metabolic syndrome parameters in clinical practice.Data sources and methods: The methodology which was used in this study included Greek and international bibliography review with the help of key-words.Results: Bibliography review showed that the...

  11. Linking metabolomics data to underlying metabolic regulation

    Thomas eNägele

    2014-11-01

    Full Text Available The comprehensive experimental analysis of a metabolic constitution plays a central role in approaches of organismal systems biology.Quantifying the impact of a changing environment on the homeostasis of cellular metabolism has been the focus of numerous studies applying various metabolomics techniques. It has been proven that approaches which integrate different analytical techniques, e.g. LC-MS, GC-MS, CE-MS and H-NMR, can provide a comprehensive picture of a certain metabolic homeostasis. Identification of metabolic compounds and quantification of metabolite levels represent the groundwork for the analysis of regulatory strategies in cellular metabolism. This significantly promotes our current understanding of the molecular organization and regulation of cells, tissues and whole organisms.Nevertheless, it is demanding to elicit the pertinent information which is contained in metabolomics data sets.Based on the central dogma of molecular biology, metabolite levels and their fluctuations are the result of a directed flux of information from gene activation over transcription to translation and posttranslational modification.Hence, metabolomics data represent the summed output of a metabolic system comprising various levels of molecular organization.As a consequence, the inverse assignment of metabolomics data to underlying regulatory processes should yield information which-if deciphered correctly-provides comprehensive insight into a metabolic system.Yet, the deduction of regulatory principles is complex not only due to the high number of metabolic compounds, but also because of a high level of cellular compartmentalization and differentiation.Motivated by the question how metabolomics approaches can provide a representative view on regulatory biochemical processes, this article intends to present and discuss current metabolomics applications, strategies of data analysis and their limitations with respect to the interpretability in context of

  12. Nitric oxide and mitochondria in metabolic syndrome

    Litvinova, Larisa; Atochin, Dmitriy N; Fattakhov, Nikolai; Vasilenko, Mariia; Zatolokin, Pavel; Kirienkova, Elena

    2015-01-01

    Metabolic syndrome (MS) is a cluster of metabolic disorders that collectively increase the risk of cardiovascular disease. Nitric oxide (NO) plays a crucial role in the pathogeneses of MS components and is involved in different mitochondrial signaling pathways that control respiration and apoptosis. The present review summarizes the recent information regarding the interrelations of mitochondria and NO in MS. Changes in the activities of different NO synthase isoforms lead to the formation of...

  13. Computational Studies on the Evolution of Metabolism

    Ullrich, Alexander

    2012-01-01

    Living organisms throughout evolution have developed desired properties, such as the ability of maintaining functionality despite changes in the environment or their inner structure, the formation of functional modules, from metabolic pathways to organs, and most essentially the capacity to adapt and evolve in a process called natural selection. It can be observed in the metabolic networks of modern organisms that many key pathways such as the citric acid cycle, glycolysis, or ...

  14. High fat intake and equine lipid metabolism

    Geelen, Suzanne Nicole Jeanne

    2002-01-01

    This thesis deals with the influence of fat feeding on lipid metabolism in horses. Highfat diets have attained considerable interest as a potential tool to improve performance.Many factors affect performance so that large numbers of horses are needed to unequivocally determine the effect of diet on performance. In practice, the execution of trials on diet in relation to performance is not possible. However, based on the reported effects of nutrition on metabolism, it should be possible to pre...

  15. Physical activity in obesity and metabolic syndrome

    Strasser, Barbara

    2012-01-01

    Biological aging is typically associated with a progressive increase in body fat mass and a loss of lean body mass. Owing to the metabolic consequences of reduced muscle mass, it is understood that normal aging and/or decreased physical activity may lead to a higher prevalence of metabolic disorders. Lifestyle modification, specifically changes in diet, physical activity, and exercise, is considered the cornerstone of obesity management. However, for most overweight people it is difficult to ...

  16. Characteristics of metabolic syndrome in women

    Aleksandra Viktorovna Solov'eva; Inessa Ivanovna Dubinina

    2012-01-01

    Aims. To evaluate combination and manifestation sequence of metabolic syndrome (MS) components, as well as cardiovascular risk factors in women. Materials and methods. We examined 100 female subjects with MS. We assessed anthropometric parameters, glycemic control and lipid metabolism. We also conducted cardiac ultrasound in all participants. Results. 44% of patients developed abdominal obesity after pregnancy, 48% - in perimenopausal period and in 8% of studied cases obesity m...

  17. Metabolic flux rewiring in mammalian cell cultures

    Young, Jamey D.

    2013-01-01

    Continuous cell lines (CCLs) engage in “wasteful” glucose and glutamine metabolism that leads to accumulation of inhibitory byproducts, primarily lactate and ammonium. Advances in techniques for mapping intracellular carbon fluxes and profiling global changes in enzyme expression have led to a deeper understanding of the molecular drivers underlying these metabolic alterations. However, recent studies have revealed that CCLs are not necessarily entrenched in a glycolytic or glutaminolytic phe...

  18. Metabolic abnormalities in Williams-Beuren syndrome

    Palacios Verd??, Mar??a Gabriela, 1983-; Segura Puimedon, Maria, 1985-; Borralleras, Cristina; Flores, Raquel; Campo Casanelles, Miguel del, 1966-; Campuzano Uceda, Mar??a Victoria; P??rez Jurado, Luis Alberto

    2015-01-01

    BACKGROUND: Williams-Beuren syndrome (WBS, OMIM-194050) is a neurodevelopmental disorder with multisystemic manifestations caused by a 1.55-1.83???Mb deletion at 7q11.23 including 26-28 genes. Reported endocrine and metabolic abnormalities include transient hypercalcaemia of infancy, subclinical hypothyroidism in ???30% of children and impaired glucose tolerance in ???75% of adult individuals. The purpose of this study was to further study metabolic alterations in patients with WBS, as well a...

  19. Cerebral energy metabolism during induced mitochondrial dysfunction

    Nielsen, T H; Bindslev, TT; Pedersen, S M;

    2013-01-01

    In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes in...... brain tissue oxygen tension (PbtO(2)) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets....

  20. Intrinsic carnosine metabolism in the human kidney

    Peters, Verena; Klessens, Celine Q. F.; Baelde, Hans J.; Singler, Benjamin; Veraar, Kimberley A. M.; Zutinic, Ana; Drozak, Jakub; Zschocke, Johannes; Schmitt, Claus P.; Heer, Emile

    2015-01-01

    Histidine-containing dipeptides like carnosine and anserine have protective functions in both health and disease. Animal studies suggest that carnosine can be metabolized within the kidney. The goal of this study was to obtain evidence of carnosine metabolism in the human kidney and to provide insight with regards to diabetic nephropathy. Expression, distribution, and localization of carnosinase-1 (CNDP1), carnosine synthase (CARNS), and taurine transporters (TauT) were measured in human kidn...