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Sample records for caffeine suppress cyclin

  1. The ATM and ATR inhibitors CGK733 and caffeine suppress cyclin D1 levels and inhibit cell proliferation

    International Nuclear Information System (INIS)

    The ataxia telangiectasia mutated (ATM) and the ATM- related (ATR) kinases play a central role in facilitating the resistance of cancer cells to genotoxic treatment regimens. The components of the ATM and ATR regulated signaling pathways thus provide attractive pharmacological targets, since their inhibition enhances cellular sensitivity to chemo- and radiotherapy. Caffeine as well as more specific inhibitors of ATM (KU55933) or ATM and ATR (CGK733) have recently been shown to induce cell death in drug-induced senescent tumor cells. Addition of these agents to cancer cells previously rendered senescent by exposure to genotoxins suppressed the ATM mediated p21 expression required for the survival of these cells. The precise molecular pharmacology of these agents however, is not well characterized. Herein, we report that caffeine, CGK733, and to a lesser extent KU55933, inhibit the proliferation of otherwise untreated human cancer and non-transformed mouse fibroblast cell lines. Exposure of human cancer cell lines to caffeine and CGK733 was associated with a rapid decline in cyclin D1 protein levels and a reduction in the levels of both phosphorylated and total retinoblastoma protein (RB). Our studies suggest that observations based on the effects of these compounds on cell proliferation and survival must be interpreted with caution. The differential effects of caffeine/CGK733 and KU55933 on cyclin D1 protein levels suggest that these agents will exhibit dissimilar molecular pharmacological profiles

  2. Caffeine

    Science.gov (United States)

    ... mood. Caffeine is in tea, coffee, chocolate, many soft drinks, and pain relievers and other over-the-counter ... Teens usually get most of their caffeine from soft drinks and energy drinks. (In addition to caffeine, these ...

  3. Caffein

    DEFF Research Database (Denmark)

    Nørager, Charlotte Buchard; Jensen, Martin Bach; Madsen, Mogens Rørbæk

    2005-01-01

    Summary Caffeine: physiological and pharmacologic aspects Ugeskr Læger 2004;166:2138-2142 Caffeine is the most widely used stimulant in the world. This is due not only to the fact that it is found in a great number of food products and is therefore readily available, but also because caffeine...... intake results in such positive effects as elation, pleasantness and better reactivity and because abstinence from caffeine can result in a withdrawal syndrome including headache, tiredness, restlessness and heart palpitations. Caffeine is also used in sports, as caffeine in moderate doses (3-6 mg....../kg) can increase the endurance of athletes engaged in running, bicycling, swimming and other endurance sports. Caffeine is used both in training and in competitions, and the International Olympic Commitée (IOC) has included caffeine as a drug used for doping. There are several theories about caffeine...

  4. Caffeine

    Science.gov (United States)

    Caffeine is a bitter substance found in coffee, tea, soft drinks, chocolate, kola nuts, and certain medicines. ... of energy. For most people, the amount of caffeine in two to four cups of coffee a ...

  5. Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control

    DEFF Research Database (Denmark)

    Klein, Ditte Kjærsgaard; Hoffmann, Saskia; Ahlskog, Johanna K;

    2015-01-01

    an important role in checkpoint control following ionizing radiation. Cyclin F-depleted cells initiate checkpoint signalling after ionizing radiation, but fail to maintain G2 phase arrest and progress into mitosis prematurely. Importantly, cyclin F suppresses the B-Myb-driven transcriptional programme...

  6. Increased expression of cyclin B1 mRNA coincides with diminished G2-phase arrest in irradiated HeLa cells treated with staurosporine or caffeine

    International Nuclear Information System (INIS)

    The irradiation of cells results in delayed progression through the G2 phase of the cell cycle. Treatment of irradiated HeLa cells with caffeine greatly reduces the G2-phase delay, while caffeine does not alter progression of cells through the cell cycle in unirradiated cells. In this report we demonstrate that treatment of HeLa cells with the kinase inhibitor staurosporine, but not with the inhibitor H7, also results in a reduction of the G2-phase arrest after irradiation. Cell cycle progression in unirradiated cells is unaffected by 4.4 nM (2ng/ml) staurosporine, which releases the radiation-induced G2-phase arrest. In HeLa cells, the G2-phase delay after irradiation in S phase is accompanied by decreased expression of cyclin B1 mRNA. Coincident with the reduction in G2-phase delay, we observed an increase in cyclin B1 mRNA accumulation in irradiated, staurosporine-treated cells compared to cells treated with irradiation alone. Caffeine treatment of irradiated HeLa cells also resulted in an elevation in the levels of cyclin B1 message. These results support the hypothesis that diminished cyclin B1 mRNA levels influence G2-phase arrest to some degree. The findings that both staurosporine and caffeine treatments reverse the depression in cyclin B1 expression suggest that these two compounds may act on a common pathway of cell cycle control in response to radiation injury. 33 refs., 6 figs

  7. miR-340 inhibits glioblastoma cell proliferation by suppressing CDK6, cyclin-D1 and cyclin-D2

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xuesong; Gong, Xuhai [Department of Neurology, Daqing Oilfield General Hospital, Daqing, Heilongjiang 163001 (China); Chen, Jing [Department of Neurology, Daqing Longnan Hospital, Daqing, Heilongjiang, 163001 China (China); Zhang, Jinghui [Department of Cardiology, The Fourth Hospital of Harbin City, Harbin, Heilongjiang 150026 (China); Sun, Jiahang [Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086 (China); Guo, Mian, E-mail: guomian_hyd@163.com [Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086 (China)

    2015-05-08

    Glioblastoma development is often associated with alteration in the activity and expression of cell cycle regulators, such as cyclin-dependent kinases (CKDs) and cyclins, resulting in aberrant cell proliferation. Recent studies have highlighted the pivotal roles of miRNAs in controlling the development and growth of glioblastoma. Here, we provide evidence for a function of miR-340 in the inhibition of glioblastoma cell proliferation. We found that miR-340 is downregulated in human glioblastoma tissue samples and several established glioblastoma cell lines. Proliferation and neurosphere formation assays revealed that miR-340 plays an oncosuppressive role in glioblastoma, and that its ectopic expression causes significant defect in glioblastoma cell growth. Further, using bioinformatics, luciferase assay and western blot, we found that miR-340 specifically targets the 3′UTRs of CDK6, cyclin-D1 and cyclin-D2, leading to the arrest of glioblastoma cells in the G0/G1 cell cycle phase. Confirming these results, we found that re-introducing CDK6, cyclin-D1 or cyclin-D2 expression partially, but significantly, rescues cells from the suppression of cell proliferation and cell cycle arrest mediated by miR-340. Collectively, our results demonstrate that miR-340 plays a tumor-suppressive role in glioblastoma and may be useful as a diagnostic biomarker and/or a therapeutic avenue for glioblastoma. - Highlights: • miR-340 is downregulated in glioblastoma samples and cell lines. • miR-340 inhibits glioblastoma cell proliferation. • miR-340 directly targets CDK6, cyclin-D1, and cyclin-D2. • miR-340 regulates glioblastoma cell proliferation via CDK6, cyclin-D1 and cyclin-D2.

  8. The effect of caffeine and adenine on radiation induced suppression of DNA synthesis, and cell survival

    International Nuclear Information System (INIS)

    Exposure of cultured mammalian cells to ionizing radiation or UV light results in a transient decrease in the rate of DNA synthesis. This depression in synthetic rate may be attenuated or deferred via a post-irradiation treatment with caffeine or adenine. It has been suggested that this attenuation may increase the fixation of damage and, therefore, increase radiation sensitivity. However, it has been previously reported that, for V79 cells treated with caffeine or adenine, no correlation exists between the extent of depression and cell survival. The present investigation expands upon these findings by examining the effect of caffeine or adenine post-irradiation treatment on two cell lines with normal UV sensitivity, mouse 3T3 and CHO AA8 cells, and one UV sensitive cell line, CHO UV5 cells. Both caffeine and adenine have been found to reduce, or delay, the suppression in DNA synthesis in all three cell lines. Surprisingly, caffeine appeared to induced even the UV5 cells to recover DNA synthetic ability. The amount of reduction in suppression of DNA synthesis, however, varies between the different cell lines and no consistent relationship with cell survival has emerged

  9. Berberine inhibits cyclin D1 expression via suppressed binding of AP-1 transcription factors to CCND1 AP-1 motif

    Institute of Scientific and Technical Information of China (English)

    Ye LUO; Yu HAO; Tai-ping SHI; Wei-wei DENG; Na LI

    2008-01-01

    Aim: To verify the suppressive effect of berberine on the proliferation of the human pulmonary giant cell carcinoma cell line PG and to demonstrate the mecha-nisms behind the antitumoral effects of berberine. Methods: The proliferative effects of PG cells were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetry. The cell cycle was examined by flow cytometry. The expression level of cyclin D1 was detected by RT-PCR. The activities of the activating protein-1 (AP-1) and NF-κB signaling pathways related to cyclin D1 were examined by luciferase assay. The cytoplasmic level of c-Jun was detected by Western blot analysis. An electrophoretic mobility shift assay was used to examiae the binding of transcription factors to the cyclin D1 gene (CCNDl) AP-1 motif. Results: The results showed that the proliferation of PG cells treated with different concentrations (10, 20, and 40 μg/mL) of berberine for 24 and 48 h was suppressed significantly compared to the control group. After treatment with berberine, the proportion of PG cells at the G0/G1 phase increased, while cells at the S and G2/M phases decreased. Berberine could inhibit the expression of cyclin D1 in PG cells. Berberine inhibited the activity of the AP-1 signaling pathway, but had no significant effect on the NF-κB signaling pathway. Berberine suppressed the expression of c-Jun and decreased the binding of tran-scription factors to the CCND1 AP-1 motif. Conclusion: Berberine suppresses the activity of the AP-1 signaling pathway and decreases the binding of transcrip-tion factors to the CCND1 AP-1 motif. This is one of the important mechanisms behind the antitumoral effects of berberine as a regulator of cyclin D1.

  10. Abuse of "BRON": a Japanese OTC cough suppressant solution containing methylephedrine, codeine, caffeine and chlorpheniramine.

    Science.gov (United States)

    Ishigooka, J; Yoshida, Y; Murasaki, M

    1991-01-01

    1. The paper describes the mental disturbances of 44 abusive cases of "BRON," an over-the-counter (OTC) cough suppressant solution containing methylephedrine, codeine, caffeine, and chlorpheniramine. 2. Major psychiatric symptoms observed included hallucinatory-paranoid state and affective disorder. There also were groups which exhibited a combination of the two states and abuse only. 3. The hallucinatory-paranoid state group had a relatively small BRON usage amount, short usage term and few withdrawal symptoms. The affective disorder group, in contrast, had large usage amount, longer usage term, and showed significant autonomic nerve disorders during withdrawal. These tendencies were seen more clearly in the mixed state group. 4. The hallucinatory-paranoid state group showed little or no physical dependence, while that of the affective disorder group was thought to be firmly established. Thus, in the former group, methylephedrine was considered the major behavior modifying drug, while in the latter, it was thought to be codeine. PMID:1749828

  11. Caffeine Suppresses Apoptosis of Bladder Cancer RT4 Cells in Response to Ionizing Radiation by Inhibiting Ataxia Telangiectasia Mutated-Chk2-p53 Axis

    Institute of Scientific and Technical Information of China (English)

    Zhe-Wei Zhang; Jing Xiao; Wei Luo; Bo-Han Wang; Ji-Min Chen

    2015-01-01

    Background:Caffeine suppresses ataxia telangiectasia and Rad3 related and ataxia telangiectasia mutated (ATM) activities;ATM is the major kinase for DNA damage detection.This study aimed to investigate the effects of caffeine on DNA damage responses in cells from the bladder cancer cell line RT4 those were exposed to ionizing radiation (IR).Methods:Immunofluorescent staining was performed to investigate changes in the proteins involved in DNA damage responses with or without caffeine.A mouse xenograft model was used to study the effects of caffeine on the DNA damage responses.Western blotting was used to investigate the effects of caffeine pretreatment on the ATM-Chk2-p53-Puma axis,while real-time polymerase chain reaction (RT-PCR) assessed changes in messenger RNA levels of p53 and downstream targets responding to IR.Finally,terminal deoxynucleotidyl transferase-dUTP nick end labeling assay.Western blotting and colony formation assay were used to measure the effects of caffeine on radiation-related apoptosis.All of the data were analyzed with a two-tailed Student's t-test.Results:Immunofluorescent staining showed that caffeine pretreatment profoundly suppressed the formation ofγH2AXand p53-binding protein 1 foci in RT4 cells in response to irradiation.Cellular and animal experiments suggested that this suppression was mediated by suppression of the ATM-Chk2-p53-Puma DNA damage-signaling axis.RT-PCR indicated caffeine also attenuated transactivation of p53 and p53-inducible genes.The colony formation assay revealed that caffeine displayed radioprotective effects on RT4 cells in response to low-dose radiation compared to the radiosensitization effects on T24 cells.Conclusion:Caffeine may inhibit IR-related apoptosis of bladder cancer RT4 cells by suppressing activation of the ATM-Chk2-p53-Puma axis.

  12. A chrysin derivative suppresses skin cancer growth by inhibiting cyclin-dependent kinases.

    Science.gov (United States)

    Liu, Haidan; Liu, Kangdong; Huang, Zunnan; Park, Chan-Mi; Thimmegowda, N R; Jang, Jae-Hyuk; Ryoo, In-Ja; He, Long; Kim, Sun-Ok; Oi, Naomi; Lee, Ki Won; Soung, Nak-Kyun; Bode, Ann M; Yang, Yifeng; Zhou, Xinmin; Erikson, Raymond L; Ahn, Jong-Seog; Hwang, Joonsung; Kim, Kyoon Eon; Dong, Zigang; Kim, Bo-Yeon

    2013-09-01

    Chrysin (5,7-dihydroxyflavone), a natural flavonoid widely distributed in plants, reportedly has chemopreventive properties against various cancers. However, the anticancer activity of chrysin observed in in vivo studies has been disappointing. Here, we report that a chrysin derivative, referred to as compound 69407, more strongly inhibited EGF-induced neoplastic transformation of JB6 P(+) cells compared with chrysin. It attenuated cell cycle progression of EGF-stimulated cells at the G1 phase and inhibited the G1/S transition. It caused loss of retinoblastoma phosphorylation at both Ser-795 and Ser-807/811, the preferred sites phosphorylated by Cdk4/6 and Cdk2, respectively. It also suppressed anchorage-dependent and -independent growth of A431 human epidermoid carcinoma cells. Compound 69407 reduced tumor growth in the A431 mouse xenograft model and retinoblastoma phosphorylation at Ser-795 and Ser-807/811. Immunoprecipitation kinase assay results showed that compound 69407 attenuated endogenous Cdk4 and Cdk2 kinase activities in EGF-stimulated JB6 P(+) cells. Pulldown and in vitro kinase assay results indicated that compound 69407 directly binds with Cdk2 and Cdk4 in an ATP-independent manner and inhibited their kinase activities. A binding model between compound 69407 and a crystal structure of Cdk2 predicted that compound 69407 was located inside the Cdk2 allosteric binding site. The binding was further verified by a point mutation binding assay. Overall results indicated that compound 69407 is an ATP-noncompetitive cyclin-dependent kinase inhibitor with anti-tumor effects, which acts by binding inside the Cdk2 allosteric pocket. This study provides new insights for creating a general pharmacophore model to design and develop novel ATP-noncompetitive agents with chemopreventive or chemotherapeutic potency. PMID:23888052

  13. Caffeine suppresses the progression of human glioblastoma via cathepsin B and MAPK signaling pathway.

    Science.gov (United States)

    Cheng, Yu-Chen; Ding, You-Ming; Hueng, Dueng-Yuan; Chen, Jang-Yi; Chen, Ying

    2016-07-01

    Glioblastoma has aggressive proliferative and invasive properties. We investigated the effect of caffeine on the invasion and the anti-cancer effect in human glioblastomas. Caffeine reduced the invasion in U-87MG, GBM8401 and LN229 cells. Caffeine decreased mRNA, protein expression, and activity of cathepsin B. Besides, mRNA and protein expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) was upregulated by caffeine treatment, whereas matrix metalloproteinase-2 (MMP-2) was downregulated. The expression of Ki67, p-p38, phospforylated extracellular regulated protein kinases (p-ERK), and membranous integrin β1 and β3 was decreased by caffeine. The Rho-associated protein kinase (ROCK) inhibitor, Y27632, blocked the caffeine-mediated reduction of cathepsin B, phosphorylated focal adhesion kinase (p-FAK), and p-ERK, and invasion. Moreover, caffeine decreased the tumor size, cathepsin B and Ki67 expression in animal model. Caffeine reduced the invasion of glioma cells through ROCK-cathepsin B/FAK/ERK signaling pathway and tumor growth in orthotopic xenograft animal model, supporting the anti-cancer potential in glioma therapy. PMID:27260469

  14. Caffeine Confusion

    Science.gov (United States)

    ... Got Homework? Here's Help White House Lunch Recipes Caffeine Confusion KidsHealth > For Kids > Caffeine Confusion Print A ... cup of coffee. So what is caffeine, anyway? Caffeine Is a Common Chemical Caffeine (say: KA-feen) ...

  15. Effect of siRNA-induced CDK2 Expression Suppression on Expression of RB, CyclinE and E2F1 in Hepatic Carcinoma Cells%小分子干扰RNA沉默肝癌细胞CDK2基因对RB、CyclinE、E2F1基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    刘佳维; 于水澜; 宋高臣; 于英君

    2012-01-01

    Objective To investigate the effects of cyclin-dependent kinase 2 ( CDK2 ) expression suppression induced by small interfering RNAs (siRNAs) on mRNA expression of cell cycle related genes RB, CyclinE and E2F1 in hepatic carcinoma cells SMMC7721. Methods The siRNA eukaryotic expression plasmids of CDK2 gene were constructed firstly and then were transfected into SMMC7721 cells with the Lipofectmine TM 2000 liposome. The transfected cells were divided into six groups; recombinant plasmid 190 group, recombinant plasmid 191 group, SMMC7721 group, CDK2-siRNA transfection group, negative control group, and blank vector group. The expression of CDK2 gene was detected with Western blot method. Real-time fluorescent quantitation polymerase chain reaction (PCR) method was utilized to detect the mRNA expression of RB, Cyclin E and E2F1 which were related to CDK2 gene, and then the effective siRNA sequence of CDK2 gene was screened. Results After the siRNA eukaryotic expression plasmids of CDK2 gene was transfected into SMMC7721 cells, mRNA expression of RB was up-regulated and the mRNA expression of CyclinE and E2F1 was down-regulated. Conclusion CDK2 gene expression suppression can up-regulate the mRNA expression of RB in SMMC7721, and down-regulate the mRNA expression of CyclinE and E2F1, indicating that the mRNA expression of RB, Cyclin E and E2F1 genes is correlated with CDK2 gene expression.%[目的]观察小分子干扰RNA (siRNA)沉默细胞周期素依赖性蛋白激酶(CDK2)基因后,细胞周期相关基因RB、CyclinE、E2F1在肝癌细胞SMMC7721中mRNA的表达. [方法]将前期研究中已构建成功并筛选出的最有效干扰抑制CDK2基因的siRNA序列片段,采用Lipofectamine TM2000脂质体转染法转染肝癌细胞株SMMC7721后分6组:重组质粒组190、重组质粒组191、SMMC7721肝癌组、转染试剂组、阴性对照组、空质粒组.采用实时荧光定量PCR法检测RB、CyclinE、E2F1 mRNA水平.[结果]CDK2的siRNA转染SMMC7721细

  16. Dexamethasone suppresses DU145 cell proliferation and cell cycle through inhibition of the extracellular signal-regulated kinase 1/2 pathway and cyclin D1 expression

    Institute of Scientific and Technical Information of China (English)

    Qing-Zhen Gao; Jia-Ju Lu; Zi-Dong Liu; Hui Zhang; Shao-Mei Wang; He Xu

    2008-01-01

    Aim: To determine the mechanisms of glucocorticoids in inhibiting advanced prostate cancer growth. Methods: The cell proliferation and cell cycle of prostate cancer DU145 cells following dexamethasone treatment were determined by proliferation assay and fluorescence-activated cell sorter. Western blot analysis was carried out to evaluate the effects of dexamethasone on phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and expression of cyclin D1 in DU145 cells with or without glucocorticoid receptor (GR) antagonist RU486. Reverse transcription- polymerase chain reaction verified the expression of GR mRNA in DU145 cells. Results: Dexamethasone signifi- cantly inhibited DU145 cell proliferation at the G0/G1 phase. Western blot analysis showed a dramatic reduction of ERK1/2 activity and cyclin D1 expression in dexamethasone-treated cells. The decreased phosphorylation of ERK1/2 in dexamethasone-treated cells was attenuated by GR blockade. Additionally, the effects of dexamethasone in inhibiting cyclin D1 expression were altered by GR blockade. Conclusion: Dexamethasone suppresses DU 145 cell prolifera- tion and cell cycle, and the underlying mechanisms are through the inhibition of phosphorylation of ERK1/2 and cyclin D1 expression. The inhibition of ERK1/2 phosphorylation and cyclin D1 expression is attenuated by GR blockade, suggesting that GR regulates ERK1/2 and cyclin D 1 pathways. These observations suggest that dexamethasone has a potential clinical application in prostate cancer therapy. (Asian JAndrol 2008 Jul; 10: 635-641)

  17. Ionizing Radiation–Inducible miR-27b Suppresses Leukemia Proliferation via Targeting Cyclin A2

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Bo; Li, Dongping; Kovalchuk, Anna; Litvinov, Dmitry; Kovalchuk, Olga, E-mail: olga.kovalchuk@uleth.ca

    2014-09-01

    Purpose: Ionizing radiation is a common carcinogen that is important for the development of leukemia. However, the underlying epigenetic mechanisms remain largely unknown. The goal of the study was to explore microRNAome alterations induced by ionizing radiation (IR) in murine thymus, and to determine the role of IR-inducible microRNA (miRNA/miR) in the development of leukemia. Methods and Materials: We used the well-established C57BL/6 mouse model and miRNA microarray profiling to identify miRNAs that are differentially expressed in murine thymus in response to irradiation. TIB152 human leukemia cell line was used to determine the role of estrogen receptor–α (ERα) in miR-27b transcription. The biological effects of ectopic miR-27b on leukemogenesis were measured by western immunoblotting, cell viability, apoptosis, and cell cycle analyses. Results: Here, we have shown that IR triggers the differential expression of miR-27b in murine thymus tissue in a dose-, time- and sex-dependent manner. miR-27b was significantly down-regulated in leukemia cell lines CCL119 and TIB152. Interestingly, ERα was overexpressed in those 2 cell lines, and it was inversely correlated with miR-27b expression. Therefore, we used TIB152 as a model system to determine the role of ERα in miR-27b expression and the contribution of miR-27b to leukemogenesis. β-Estradiol caused a rapid and transient reduction in miR-27b expression reversed by either ERα-neutralizing antibody or ERK1/2 inhibitor. Ectopic expression of miR-27b remarkably suppressed TIB152 cell proliferation, at least in part, by inducing S-phase arrest. In addition, it attenuated the expression of cyclin A2, although it had no effect on the levels of PCNA, PPARγ, CDK2, p21, p27, p-p53, and cleaved caspase-3. Conclusion: Our data reveal that β-estradiol/ERα signaling may contribute to the down-regulation of miR-27b in acute leukemia cell lines through the ERK1/2 pathway, and that miR-27b may function as a tumor

  18. Antitumor activity of Papua’s Myrmecodia pendans in human oral tongue squamous cell carcinoma cell line through induction of cyclin-dependent kinase inhibitor p27Kip1 and suppression of cyclin E

    Directory of Open Access Journals (Sweden)

    Supriatno DRG

    2014-03-01

    Full Text Available Oral tongue squamous cell carcinoma (OTSCC is one of the most common cancers encountered in Indonesia, due to the prevalent habits of tobacco chewing, alcohol drinking and smoking. Oral tongue cancer is characterized by a high degree of local invasion and a high rate of metastasis to the cervical lymph nodes. Interestingly, treatment options for this cancer are limited. The aim of this study was to examine the antitumor activity of Papua’s Myrmecodia pendans (ant nest plant in a human oral tongue squamous cell carcinoma cell line (B88 and to explore the possible mechanism in it. In the present study, B88 cells were treated with various concentration of ethanol extract of Papua’s M. pendans. The results revealed that B88 cells treated with Papua’s M. pendans were remarkable suppressed in cell growth and cell invasion, and had a significant induction of apoptosis characterized by an increase in activation of caspase-3 and -9. Furthermore, up-regulation of p27Kip1 and down-regulation of cyclin E protein was detected in B88 cells treated with Papua’s M. pendans. These results indicated that Papua’s M. pendans exhibited a high potential antitumor activity in human oral tongue squamous cell carcinoma through induction of p27Kip1 and suppression of cycline E.

  19. The coffee diterpene kahweol suppresses the cell proliferation by inducing cyclin D1 proteasomal degradation via ERK1/2, JNK and GKS3β-dependent threonine-286 phosphorylation in human colorectal cancer cells.

    Science.gov (United States)

    Park, Gwang Hun; Song, Hun Min; Jeong, Jin Boo

    2016-09-01

    Kahweol as a coffee-specific diterpene has been reported to exert anti-cancer properties. However, the mechanism responsible for the anti-cancer effects of kahweol is not fully understood. The main aim of this investigation was to determine the effect of kahweol on cell proliferation and the possible mechanisms in human colorectal cancer cells. Kahweol inhibited markedly the proliferation of human colorectal cancer cell lines such as HCT116, SW480. Kahweol decreased cyclin D1 protein level in HCT116 and SW480 cells. Contrast to protein levels, cyclin D1 mRNA level and promoter activity did not be changed by kahweol treatment. MG132 treatment attenuated kahweol-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in kahweol-treated cells. Kahweol increased phosphorylation of cyclin D1 at threonine-286 and a point mutation of threonine-286 to alanine attenuated cyclin D1 degradation by kahweol. Inhibition of ERK1/2 by PD98059, JNK by SP600125 or GSK3β by LiCl suppressed cyclin D1 phosphorylation and downregulation by kahweol. Furthermore, the inhibition of nuclear export by LMB attenuated cyclin D1 degradation by kahweol. In conclusion, kahweol-mediated cyclin D1 degradation may contribute to the inhibition of the proliferation in human colorectal cancer cells. PMID:27424123

  20. Citrus auraptene suppresses cyclin D1 and significantly delays N-methyl nitrosourea induced mammary carcinogenesis in female Sprague-Dawley rats

    Directory of Open Access Journals (Sweden)

    Grand Robert

    2009-07-01

    Full Text Available Abstract Background Breast cancer is a major problem in the United States leading to tens of thousands of deaths each year. Although citrus auraptene suppresses cancer in numerous rodent models, its role in breast cancer prevention previously has not been reported. Thus, our goal was to determine the anticarcinogenic effects of auraptene against breast cancer. Methods The effects of auraptene on cell proliferation of MCF-7 and MDA-MB-231 human breast carcinoma cells in culture was assessed by measuring metabolism of a substrate to a formazan dye. Dietary effects of auraptene on tumor incidence, multiplicity and latency were studied in the N-methyl nitrosourea (MNU induced mammary carcinogenesis model in female Sprague Dawley rats. The concentration of auraptene in rat tissues was analyzed by reverse phase HPLC. Cyclin D1 expression in MCF-7 cells and rat tumors was measured by western blot. Results Auraptene (500 ppm significantly delayed median time to tumor by 39 days compared to the MNU only group (p Conclusion Overall, these observations suggest that the predominant effect of auraptene was to delay the development of tumors possibly through the suppression of cyclin D1 expression. These results point to the potential chemopreventive effects of auraptene in mammary carcinogenesis.

  1. Inhibition of cyclin-dependent kinase 6 suppresses cell proliferation and enhances radiation sensitivity in medulloblastoma cells

    OpenAIRE

    Whiteway, Susan L.; Harris, Peter S; Venkataraman, Sujatha; Alimova, Irina; Birks, Diane K; Donson, Andrew M; Foreman, Nicholas K.; Vibhakar, Rajeev

    2012-01-01

    Medulloblastoma accounts for 20 % of all primary pediatric intracranial tumors. Current treatment cures 50–80 % of patients but is associated with significant long-term morbidity and thus new therapeutic targets are needed. One such target is cyclin-dependent kinase 6 (CDK6), a serine/threonine kinase that plays a vital role in cell cycle progression and differentiation. CDK6 is overexpressed in medulloblastoma patients and is associated with an adverse prognosis. To investigate the role of C...

  2. Caffeine overdose

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/002579.htm Caffeine overdose To use the sharing features on this page, please enable JavaScript. Caffeine is a substance that exists naturally in certain ...

  3. Caffeine in the diet

    Science.gov (United States)

    Diet - caffeine ... for caffeine. It can be avoided in the diet. Caffeine stimulates, or excites, the brain and nervous ... medications such as pain relievers , over-the-counter diet pills, and cold medicines. Caffeine has no flavor. ...

  4. Caffeine in the diet

    Science.gov (United States)

    Diet - caffeine ... Caffeine is absorbed and passes quickly into the brain. It does not collect in the bloodstream or ... been consumed. There is no nutritional need for caffeine. It can be avoided in the diet. Caffeine ...

  5. Transgenic expression of walleye dermal sarcoma virus rv-cyclin gene in zebrafish and its suppressive effect on liver tumor development after carcinogen treatment.

    Science.gov (United States)

    Zhan, Huiqing; Spitsbergen, Jan M; Qing, Wei; Wu, Yi Lian; Paul, Thomas A; Casey, James W; Her, Guor Muor; Gong, Zhiyuan

    2010-11-01

    A retrovirus homologue gene of cellular cyclin D₁, walleye dermal sarcoma virus rv-cyclin gene (orf A or rv-cyclin), was expressed in the livers of zebrafish under the control of liver fatty acid-binding protein (lfabp) promoter. To prevent possible fatality caused by overexpression of the oncogene, the GAL4/upstream activation sequence (GAL4/UAS) system was used to maintain the transgenic lines. Thus, both GAL4-activator [Tg(lfabp:GAL4)] and UAS-effector [Tg(UAS:rvcyclin)] lines were generated, and the rv-cyclin gene was activated in the liver after crossing these two lines. Since no obvious neoplasia phenotypes were observed in the double-transgenic line, cancer susceptibility of the transgenic fish expressing rv-cyclin was tested by carcinogen treatment. Unexpectedly, transgenic fish expressing rv-cyclin gene (rvcyclin+) were more resistant to the carcinogen than siblings not expressing this gene (rvcyclin-). Lower incidences of multiple and malignant liver tumors were observed in rvcyclin+ than in rvcyclin- fish, and the liver tumors in the rvcyclin+ group appeared later and were less malignant. These results suggest that expression of rv-cyclin protects the fish liver from carcinogen damage and delays onset of malignancy. These findings indicate that transgenic fish models are powerful systems for investigating mechanisms of inhibition and regression of liver tumors. PMID:20052603

  6. Triphala Extract Suppresses Proliferation and Induces Apoptosis in Human Colon Cancer Stem Cells via Suppressing c-Myc/Cyclin D1 and Elevation of Bax/Bcl-2 Ratio

    Directory of Open Access Journals (Sweden)

    Ramakrishna Vadde

    2015-01-01

    Full Text Available Colon cancer is the second leading cause of cancer related deaths in the USA. Cancer stem cells (CSCs have the ability to drive continued expansion of the population of malignant cells. Therefore, strategies that target CSCs could be effective against colon cancer and in reducing the risk of relapse and metastasis. In this study, we evaluated the antiproliferative and proapoptotic effects of triphala, a widely used formulation in Indian traditional medicine, on HCT116 colon cancer cells and human colon cancer stem cells (HCCSCs. The total phenolic content, antioxidant activity, and phytochemical composition (LC-MS-MS of methanol extract of triphala (MET were also measured. We observed that MET contains a variety of phenolics including naringin, quercetin, homoorientin, and isorhamnetin. MET suppressed proliferation independent of p53 status in HCT116 and in HCCSCs. MET also induced p53-independent apoptosis in HCCSCs as indicated by elevated levels of cleaved PARP. Western blotting data suggested that MET suppressed protein levels of c-Myc and cyclin D1, key proteins involved in proliferation, and induced apoptosis through elevation of Bax/Bcl-2 ratio. Furthermore, MET inhibited HCCSCs colony formation, a measure of CSCs self-renewal ability. Anticancer effects of triphala observed in our study warrant future studies to determine its efficacy in vivo.

  7. Caffeine and Your Child

    Science.gov (United States)

    ... a mug of coffee, but might routinely serve soft drinks containing caffeine. Foods and drinks with caffeine are ... consumption: Kids often drink caffeine contained in regular soft drinks. Kids who consume one or more 12-ounce ( ...

  8. Caffeine fostering of mycoparasitic fungi against phytopathogens.

    Science.gov (United States)

    Sugiyama, Akifumi; Sano, Cecile M; Yazaki, Kazufumi; Sano, Hiroshi

    2016-01-01

    Caffeine (1,3,7-trimethixanthine) is a typical purine alkaloid produced in more than 80 plant species. Its biological role is considered to strengthen plant's defense capabilities, directly as a toxicant to biotic attackers (allelopathy) and indirectly as an activator of defense system (priming). Caffeine is actively secreted into rhizosphere through primary root, and possibly affects the structure of microbe community nearby. The fungal community in coffee plant rhizosphere is enriched with particular species, including Trichoderma family, a mycoparasite that attacks and kills phytopathogens by coiling and destroying their hyphae. In the present study, the caffeine response of 8 filamentous fungi, 4 mycoparasitic Trichoderma, and 4 prey phytopathogens, was examined. Results showed that allelopathic effect of caffeine on fungal growth and development was differential, being stronger on pathogens than on Trichoderma species. Upon confronting, the prey immediately ceased the growth, whereas the predator continued to grow, indicating active mycoparasitism to have occurred. Caffeine enhanced mycoparasitism up to 1.7-fold. Caffeine thus functions in a double-track manner against fungal pathogens: first by direct suppression of growth and development, and second by assisting their natural enemy. These observations suggest that caffeine is a powerful weapon in the arms race between plants and pathogens by fostering enemy's enemy, and we propose the idea of "caffeine fostering" as the third role of caffeine. PMID:26529400

  9. EIF3D silencing suppresses renal cell carcinoma tumorigenesis via inducing G2/M arrest through downregulation of Cyclin B1/CDK1 signaling.

    Science.gov (United States)

    Pan, Xiu-Wu; Chen, Lu; Hong, Yi; Xu, Dan-Feng; Liu, Xi; Li, Lin; Huang, Yi; Cui, Li-Ming; Gan, Si-Shun; Yang, Qi-Wei; Huang, Hai; Qu, Fa-Jun; Ye, Jian-Qing; Wang, Lin-Hui; Cui, Xin-Gang

    2016-06-01

    There are no effective therapies for advanced renal cell carcinoma (RCC), except for VEGFR inhibitors with only ~50% response rate. To identify novel targets and biomarkers for RCC is of great importance in treating RCC. In this study, we observed that eukaryotic initiation factor 3d (EIF3D) expression was significantly increased in RCC compared with paracarcinoma tissue using immunohistochemistry staining and western blot analysis. Furthermore, bioinformatics meta-analysis using ONCOMINE microarray datasets showed that EIF3D mRNA expressions in CCRCC tissue specimens were significantly higher than that in normal tissue specimens. In addition, RCC tissue microarray demonstrated that elevated EIF3D expression was positively correlated with TNM stage and tumor size. EIF3D silencing in human 786-O and ACHN CCRCC cell lines by RNA interference demonstrated that EIF3D knockdown obviously inhibited cell proliferation and colony formation, caused G2/M arrest through downregulation of Cyclin B1 and Cdk1 and upregulation of p21, and induced apoptosis shown by sub-G1 accumulation and RARP cleavage. Moreover, correlation analysis using ONCOMINE microarray datasets indicated that increased EIF3D mRNA expression was positively correlated to PCNA, Cyclin B1 and CDK1 mRNA expression in RCC. Collectively, these results provide reasonable evidences that EIF3D may function as a potential proto-oncogene that participates in the occurrence and progression of RCC. PMID:27035563

  10. Caffeine and Migraine

    Science.gov (United States)

    ... on Pinterest Follow us on Instagram DONATE TODAY Caffeine and Migraine Abuse, Maltreatment, and PTSD and Their ... and Headache Alcohol and Migraine Anxiety and Depression Caffeine and Migraine Depression and Migraine Diet Do I ...

  11. Aspirin, Butalbital, and Caffeine

    Science.gov (United States)

    The combination of aspirin, butalbital, and caffeine comes as a capsule and tablet to take by mouth. It usually is taken every 4 ... explain any part you do not understand. Take aspirin, butalbital, and caffeine exactly as directed. Do not ...

  12. Acetaminophen, Butalbital, and Caffeine

    Science.gov (United States)

    The combination of acetaminophen, Butalbital, Caffeine comes as a capsule and tablet to take by mouth. It usually is taken every 4 hours ... explain any part you do not understand. Take acetaminophen, Butalbital, Caffeine exactly as directed. Do not take ...

  13. Caffeine, fatigue, and cognition

    NARCIS (Netherlands)

    Lorist, MM; Tops, M

    2003-01-01

    Effects of caffeine and fatigue are discussed with special attention to adenosine-dopamine interactions. Effects of caffeine on human cognition are diverse. Behavioural measurements indicate a general improvement in the efficiency of information processing after caffeine, while the EEG data support

  14. Caffeine Use and Extroversion.

    Science.gov (United States)

    Landrum, R. Eric; Meliska, Charles J.

    Some research on the stimulant effect of caffeine suggests that the amount of behavioral enhancement produced by caffeine may depend on subjects' prior experience with the task and the drug. A study was undertaken to test whether prior experience with a task while under the influence of caffeine would facilitate performance of that task. Male…

  15. Down-regulation of the PTTG1 proto-oncogene contributes to the melanoma suppressive effects of the cyclin-dependent kinase inhibitor PHA-848125.

    Science.gov (United States)

    Caporali, Simona; Alvino, Ester; Levati, Lauretta; Esposito, Alessia I; Ciomei, Marina; Brasca, Maria G; Del Bufalo, Donatella; Desideri, Marianna; Bonmassar, Enzo; Pfeffer, Ulrich; D'Atri, Stefania

    2012-09-01

    We previously demonstrated that PHA-848125, a cyclin-dependent kinase inhibitor presently under Phase II clinical investigation, impairs melanoma cell growth. In this study, gene expression profiling showed that PHA-848125 significantly modulated the expression of 128 genes, predominantly involved in cell cycle control, in the highly drug-sensitive GL-Mel (p53 wild-type) melanoma cells. Up-regulation of 4 selected genes (PDCD4, SESN2, DDIT4, DEPDC6), and down-regulation of 6 selected genes (PTTG1, CDC25A, AURKA, AURKB, PLK1, BIRC5) was confirmed at protein levels. The same protein analysis performed in PHA-848125-treated M10 melanoma cells - p53 mutated and less sensitive to the drug than GL-Mel cells - revealed no DEPDC6 expression and no changes of PTTG1, PDCD4 and BIRC5 levels. Upon PHA-848125 treatment, a marked PTTG1 down-modulation was also observed in A375 cells (p53 wild-type) but not in CN-Mel cells (p53 mutated). PTTG1 silencing significantly inhibited melanoma cell proliferation and induced senescence, with effects less pronounced in p53 mutated cells. PTTG1 silencing increased PHA-848125 sensitivity of p53 mutated cells but not that of A375 or GL-Mel cells. Accordingly, in M10 but not in A375 cells a higher level of senescence was detected in PHA-848125-treated/PTTG1-silenced cells with respect to PHA-848125-treated controls. In A375 and GL-Mel cells, TP53 silencing attenuated PHA-848125-induced down-modulation of PTTG1 and decreased cell sensitivity to the drug. These findings indicate that PHA-848125-induced down-regulation of PTTG1 depends, at least in part, on p53 function and contributes to the antiproliferative activity of the drug. Our study provides further molecular insight into the antitumor mechanism of PHA-848125. PMID:22704958

  16. Vitamin K2 and cotylenin A synergistically induce monocytic differentiation and growth arrest along with the suppression of c-MYC expression and induction of cyclin G2 expression in human leukemia HL-60 cells.

    Science.gov (United States)

    Maniwa, Yasuhisa; Kasukabe, Takashi; Kumakura, Shunichi

    2015-08-01

    Although all-trans retinoic acid (ATRA) is a standard and effective drug used for differentiation therapy in acute promyelocytic leukemia, ATRA-resistant leukemia cells ultimately emerge during this treatment. Therefore, the development of new drugs or effective combination therapy is urgently needed. We demonstrate that the combined treatment of vitamin K2 and cotylenin A synergistically induced monocytic differentiation in HL-60 cells. This combined treatment also synergistically induced NBT-reducing activity and non-specific esterase-positive cells as well as morphological changes to monocyte/macrophage-like cells. Vitamin K2 and cotylenin A cooperatively inhibited the proliferation of HL-60 cells in short-term and long-term cultures. This treatment also induced growth arrest at the G1 phase. Although 5 µg/ml cotylenin A or 5 µM vitamin K2 alone reduced c-MYC gene expression in HL-60 cells to approximately 45% or 80% that of control cells, respectively, the combined treatment almost completely suppressed c-MYC gene expression. We also demonstrated that the combined treatment of vitamin K2 and cotylenin A synergistically induced the expression of cyclin G2, which had a positive effect on the promotion and maintenance of cell cycle arrest. These results suggest that the combination of vitamin K2 and cotylenin A has therapeutic value in the treatment of acute myeloid leukemia. PMID:26046133

  17. Ergotamine and Caffeine

    Science.gov (United States)

    The combination of ergotamine and caffeine is used to prevent and treat migraine headaches. Ergotamine is in a class of medications called ergot ... The combination of ergotamine and caffeine comes as a tablet to take by mouth and as a suppository to insert rectally. It is ...

  18. Heritability of caffeine metabolism

    DEFF Research Database (Denmark)

    Matthaei, Johannes; Tzvetkov, Mladen V; Strube, Jakob;

    2016-01-01

    Heritability of caffeine pharmacokinetics and CYP1A2 activity is controversial. Here we analyzed the pharmacokinetics of caffeine, an in vivo probe drug for CYP1A2 and arylamine N-acetyltransferase 2 (NAT2) activity, in monozygotic and dizygotic twins. In the entire group, common and unique...... environmental effects explained most variation in caffeine AUC. Apparently, smoking and hormonal contraceptives masked the genetic effects on CYP1A2 activity. However, when excluding smokers and users of hormonal contraceptives, 89% of caffeine AUC variation was due to genetic effects and even in the entire...... group, 8% of caffeine AUC variation could be explained by a CYP1A1/1A2 promotor polymorphism (rs2470893). In contrast, nearly all of the variation (99%) of NAT2 activity was explained by genetic effects. This study illustrates two very different situations in pharmacogenetics, from an almost exclusively...

  19. Caffeine intake and fecundability

    DEFF Research Database (Denmark)

    Jensen, Tina Kold; Henriksen, T B; Hjollund, N H;

    1998-01-01

    Fecundability has been defined as the ability to achieve a recognized pregnancy. Several studies on caffeine and fecundability have been conducted but have been inconclusive. This may be explained partly by lack of stratification by smoking. Furthermore, few researchers have tried to separate the...... effect of caffeine from different sources (coffee, tea, cola, and chocolate). Clearly, the relationship between caffeine and fecundability needs further research, given the high prevalence of caffeine intake among women of childbearing age. We examined the independent and combined effects of smoking and...... caffeine intake from different sources on the probability of conception. From 1992 to 1995, a total of 430 couples were recruited after a nationwide mailing of a personal letter to 52,255 trade union members who were 20 to 35 years old, lived with a partner, and had no previous reproductive experience. At...

  20. Spectrophotometric Analysis of Caffeine

    Directory of Open Access Journals (Sweden)

    Showkat Ahmad Bhawani

    2015-01-01

    Full Text Available The nature of caffeine reveals that it is a bitter white crystalline alkaloid. It is a common ingredient in a variety of drinks (soft and energy drinks and is also used in combination with various medicines. In order to maintain the optimum level of caffeine, various spectrophotometric methods have been developed. The monitoring of caffeine is very important aspect because of its consumption in higher doses that can lead to various physiological disorders. This paper incorporates various spectrophotometric methods used in the analysis of caffeine in various environmental samples such as pharmaceuticals, soft and energy drinks, tea, and coffee. A range of spectrophotometric methodologies including chemometric techniques and derivatization of spectra have been used to analyse the caffeine.

  1. Cyclin E, a redundant cyclin in breast cancer

    OpenAIRE

    Gray-Bablin, Julie; Zalvide, Juan; Fox, M. Pat; Knickerbocker, Chris J.; DeCaprio, James A.; Keyomarsi, Khandan

    1996-01-01

    Cyclin E is an important regulator of cell cycle progression that together with cyclin-dependent kinase (cdk) 2 is crucial for the G1/S transition during the mammalian cell cycle. Previously, we showed that severe overexpression of cyclin E protein in tumor cells and tissues results in the appearance of lower molecular weight isoforms of cyclin E, which together with cdk2 can form a kinase complex active throughout the cell cycle. In this study, we report that one ...

  2. Caffeine as a Gelator

    Directory of Open Access Journals (Sweden)

    Nonappa

    2016-03-01

    Full Text Available Caffeine (a stimulant and ethanol (a depressant may have opposite effects in our body, but under in vitro conditions they can “gel” together. Caffeine, being one of the widely used stimulants, continued to surprise the scientific community with its unprecedented biological, medicinal and physicochemical properties. Here, we disclose the supramolecular self-assembly of anhydrous caffeine in a series of alcoholic and aromatic solvents, rendering a highly entangled microcrystalline network facilitating the encapsulation of the solvents as illustrated using direct imaging, microscopy analysis and NMR studies.

  3. Make caffeine visible: a fluorescent caffeine "traffic light" detector.

    Science.gov (United States)

    Xu, Wang; Kim, Tae-Hyeong; Zhai, Duanting; Er, Jun Cheng; Zhang, Liyun; Kale, Anup Atul; Agrawalla, Bikram Keshari; Cho, Yoon-Kyoung; Chang, Young-Tae

    2013-01-01

    Caffeine has attracted abundant attention due to its extensive existence in beverages and medicines. However, to detect it sensitively and conveniently remains a challenge, especially in resource-limited regions. Here we report a novel aqueous phase fluorescent caffeine sensor named Caffeine Orange which exhibits 250-fold fluorescence enhancement upon caffeine activation and high selectivity. Nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy indicate that π-stacking and hydrogen-bonding contribute to their interactions while dynamic light scattering and transmission electron microscopy experiments demonstrate the change of Caffeine Orange ambient environment induces its fluorescence emission. To utilize this probe in real life, we developed a non-toxic caffeine detection kit and tested it for caffeine quantification in various beverages. Naked-eye sensing of various caffeine concentrations was possible based on color changes upon irradiation with a laser pointer. Lastly, we performed the whole system on a microfluidic device to make caffeine detection quick, sensitive and automated. PMID:23877095

  4. Caffeine withdrawal symptoms and self-administration following caffeine deprivation.

    Science.gov (United States)

    Mitchell, S H; de Wit, H; Zacny, J P

    1995-08-01

    This study examined the effects of complete or partial caffeine deprivation on withdrawal symptomatology and self-administration of coffee in caffeine-dependent coffee drinkers. Nine habitual coffee drinkers abstained from dietary sources of caffeine for 33.5 h. Caffeine deprivation was manipulated by administering capsules containing 0%, 50%, or 100% of each subject's daily caffeine intake (complete, partial, and no deprivation conditions). Caffeine withdrawal symptomatology was measured using self-report questionnaires. Caffeine self-administration was measured using: i) the amount of coffee subjects earned on a series of concurrent random-ratio schedules that yielded coffee and money reinforcers; ii) the amount of earned coffee they consumed. Saliva samples revealed that subjects complied with the caffeine abstinence instructions. Caffeine withdrawal symptoms occurred reliably following complete caffeine deprivation, though not in the partial deprivation condition. Caffeine self-administration was not related to deprivation condition. We conclude that caffeine withdrawal symptomatology is not necessarily associated with increased caffeine consumption. PMID:7675881

  5. Caffeine content of decaffeinated coffee.

    Science.gov (United States)

    McCusker, Rachel R; Fuehrlein, Brian; Goldberger, Bruce A; Gold, Mark S; Cone, Edward J

    2006-10-01

    Caffeine is the most widely consumed drug in the world with coffee representing a major source of intake. Despite widespread availability, various medical conditions necessitate caffeine-restricted diets. Patients on certain prescription medications are advised to discontinue caffeine intake. Such admonition has implications for certain psychiatric patients because of pharmacokinetic interactions between caffeine and certain anti-anxiety drugs. In an effort to abstain from caffeine, patients may substitute decaffeinated for caffeinated coffee. However, decaffeinated beverages are known to contain caffeine in varying amounts. The present study determined the caffeine content in a variety of decaffeinated coffee drinks. In phase 1 of the study, 10 decaffeinated samples were collected from different coffee establishments. In phase 2 of the study, Starbucks espresso decaffeinated (N=6) and Starbucks brewed decaffeinated coffee (N=6) samples were collected from the same outlet to evaluate variability of caffeine content of the same drink. The 10 decaffeinated coffee samples from different outlets contained caffeine in the range of 0-13.9 mg/16-oz serving. The caffeine content for the Starbucks espresso and the Starbucks brewed samples collected from the same outlet were 3.0-15.8 mg/shot and 12.0-13.4 mg/16-oz serving, respectively. Patients vulnerable to caffeine effects should be advised that caffeine may be present in coffees purported to be decaffeinated. Further research is warranted on the potential deleterious effects of consumption of "decaffeinated" coffee that contains caffeine on caffeine-restricted patients. Additionally, further exploration is merited for the possible physical dependence potential of low doses of caffeine such as those concentrations found in decaffeinated coffee. PMID:17132260

  6. Mood, music, and caffeine

    NARCIS (Netherlands)

    Jolij, Jacob; Lorist, Monicque

    2014-01-01

    What we see is affected by how we feel: in positive moods, we are more sensitive to positive stimuli, such as happy faces, but in negative moods we are more sensitive to negative stimuli, such as sad faces. Caffeine is known to affect mood - a cup of coffee results in a more positive mood, but also

  7. Caffeine Reinforces Flavor Preference and Behavior in Moderate Users but Not in Low Caffeine Users

    Science.gov (United States)

    Dack, Charlotte; Reed, Phil

    2009-01-01

    The study examined the role of caffeine consumption in caffeine reinforcement. Previous findings have shown that caffeine reinforced flavor preference in moderate caffeine consumers who are caffeine deprived. However, most of these studies have employed rating procedures only, and have not shown the effectiveness of caffeine to reinforce behaviors…

  8. The aminoglycoside antibiotic kanamycin damages DNA bases in Escherichia coli: caffeine potentiates the DNA-damaging effects of kanamycin while suppressing cell killing by ciprofloxacin in Escherichia coli and Bacillus anthracis.

    Science.gov (United States)

    Kang, Tina Manzhu; Yuan, Jessica; Nguyen, Angelyn; Becket, Elinne; Yang, Hanjing; Miller, Jeffrey H

    2012-06-01

    The distribution of mutants in the Keio collection of Escherichia coli gene knockout mutants that display increased sensitivity to the aminoglycosides kanamycin and neomycin indicates that damaged bases resulting from antibiotic action can lead to cell death. Strains lacking one of a number of glycosylases (e.g., AlkA, YzaB, Ogt, KsgA) or other specific repair proteins (AlkB, PhrB, SmbC) are more sensitive to these antibiotics. Mutants lacking AlkB display the strongest sensitivity among the glycosylase- or direct lesion removal-deficient strains. This perhaps suggests the involvement of ethenoadenine adducts, resulting from reactive oxygen species and lipid peroxidation, since AlkB removes this lesion. Other sensitivities displayed by mutants lacking UvrA, polymerase V (Pol V), or components of double-strand break repair indicate that kanamycin results in damaged base pairs that need to be removed or replicated past in order to avoid double-strand breaks that saturate the cellular repair capacity. Caffeine enhances the sensitivities of these repair-deficient strains to kanamycin and neomycin. The gene knockout mutants that display increased sensitivity to caffeine (dnaQ, holC, holD, and priA knockout mutants) indicate that caffeine blocks DNA replication, ultimately leading to double-strand breaks that require recombinational repair by functions encoded by recA, recB, and recC, among others. Additionally, caffeine partially protects cells of both Escherichia coli and Bacillus anthracis from killing by the widely used fluoroquinolone antibiotic ciprofloxacin. PMID:22391551

  9. Caffeine, Diabetes, Cognition, and Dementia

    NARCIS (Netherlands)

    Biessels, Geert Jan

    2010-01-01

    People with diabetes mellitus are at increased risk of cognitive dysfunction. This review explores the relation between caffeine intake, diabetes, cognition and dementia, focusing on type 2 diabetes (T2DM). Epidemiological studies on caffeine/coffee intake and T2DM risk are reviewed. Next, the impac

  10. Caffeine restriction: effect on mild hypertension.

    OpenAIRE

    MacDonald, T. M.; Sharpe, K; Fowler, G; Lyons, D; FREESTONE, S.; Lovell, H. G.; Webster, J.; Petrie, J C

    1991-01-01

    OBJECTIVE--To determine the effects on blood pressure of modifying dietary caffeine intake in patients with mild and borderline hypertension by monitoring ambulatory and clinic blood pressure. DESIGN--Four way, randomised, crossover trial of four consecutive two week dietary regimens: normal diet, caffeine free diet alone, caffeine free diet with decaffeinated instant coffee, caffeine free diet with caffeinated instant coffee (instant coffee phases conducted double blind). SETTING--Hospital h...

  11. Maternal gestational betaine supplementation-mediated suppression of hepatic cyclin D2 and presenilin1 gene in newborn piglets is associated with epigenetic regulation of the STAT3-dependent pathway.

    Science.gov (United States)

    Cai, Demin; Yuan, Mengjie; Jia, Yimin; Liu, Haoyu; Hu, Yun; Zhao, Ruqian

    2015-12-01

    Betaine, which donates methyl groups through methionine metabolism for DNA and protein methylation, is critical for epigenetic gene regulation, especially during fetal development. Here we fed gestational sows with control or betaine supplemented diets (3 g/kg) throughout the pregnancy to explore the effects of maternal betaine on hepatic cell proliferation in neonatal piglets. Neonatal piglets born to betaine-supplemented sows demonstrated a reduction of cell number and DNA content in the liver, which was associated with significantly down-regulated hepatic expression of cell cycle regulatory genes, cyclin D2 (CCND2) and presenilin1 (PSEN1). Moreover, STAT3 binding to the promoter of CCND2 and PSEN1 was also lower in betaine-exposed piglets, accompanied by strong reduction of STAT3 mRNA and protein expression, along with its phosphorylation at Tyr705 and Ser727 residues. Also, prenatal betaine exposure significantly attenuated upstream kinases of STAT3 signaling pathway (phospho-ERK1/2, phospho-SRC and phospho-JAK2) in the livers of neonates. Furthermore, the repressed STAT3 expression in the liver of betaine-exposed piglets was associated with DNA hypermethylation and more enriched repression histone mark H3K27me3 on its promoter, together with significantly up-regulated expression of H3K27me3 and enhancer of zeste homolog 2 (EZH2) proteins, as well as miR-124a, which targets STAT3. Taken together, our results suggest that maternal dietary betaine supplementation during gestation inhibits hepatic cell proliferation in neonatal piglets, at least partly, through epigenetic regulation of hepatic CCND2 and PSEN1 genes via a STAT3-dependent pathway. These neonatal changes in cell cycle and proliferation regulation may lead to lower liver weight and hepatic DNA content at weaning. PMID:26359029

  12. X-ray-related potentially lethal damage expressed by chromosome condensation and the influence of caffeine

    International Nuclear Information System (INIS)

    Caffeine has been reported to induce premature chromosome condensation (PCC) in S-phase cells in the presence of an inhibitor of DNA synthesis. We found that when S-phase cells are treated with caffeine and hydroxyurea after X irradiation, substantially more potentially lethal damage (PLD) is expressed, but the addition of cycloheximide, which inhibits PCC induction in S-phase cells, in the presence of caffeine and hydroxyurea reduces the expression of PLD to the same level as seen with caffeine alone. This can be interpreted to mean that the expression of PLD seen with caffeine in the absence of an inhibitor of DNA synthesis is not associated with chromosome condensation. Evidence that PCC induction in S-phase cells and the influence of caffeine on PLD expression were suppressed by incubation at 40 degrees C of tsBN75 cells with a ts defect in ubiquitin-activating enzyme indicates the involvement of ubiquitin in these two processes. These observations as well as previous findings on ubiquitin suggest to us that caffeine induces changes in DNA-chromatin conformation, which are caused by induction of PCC or ubiquitination of chromosomal protein. Such changes occurring postirradiation would favor expression of PLD

  13. Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jin Boo [Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742 (United States); Lee, Seong-Ho, E-mail: slee2000@umd.edu [Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742 (United States)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Protocatechualdehyde (PCA) suppressed cell proliferation and induced apoptosis in human colorectal cancer cells. Black-Right-Pointing-Pointer PCA enhanced transcriptional downregulation of cyclin D1 gene. Black-Right-Pointing-Pointer PCA suppressed HDAC2 expression and activity. Black-Right-Pointing-Pointer These findings suggest that anti-cancer activity of PCA may be mediated by reducing HDAC2-derived cyclin D1 expression. -- Abstract: Protocatechualdehyde (PCA) is a naturally occurring polyphenol found in barley, green cavendish bananas, and grapevine leaves. Although a few studies reported growth-inhibitory activity of PCA in breast and leukemia cancer cells, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to investigate if treatment of PCA affects cell proliferation and apoptosis in human colorectal cancer cells and define potential mechanisms by which PCA mediates growth arrest and apoptosis of cancer cells. Exposure of PCA to human colorectal cancer cells (HCT116 and SW480 cells) suppressed cell growth and induced apoptosis in dose-dependent manner. PCA decreased cyclin D1 expression in protein and mRNA level and suppressed luciferase activity of cyclin D1 promoter, indicating transcriptional downregulation of cyclin D1 gene by PCA. We also observed that PCA treatment attenuated enzyme activity of histone deacetylase (HDAC) and reduced expression of HDAC2, but not HDAC1. These findings suggest that cell growth inhibition and apoptosis by PCA may be a result of HDAC2-mediated cyclin D1 suppression.

  14. Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells

    International Nuclear Information System (INIS)

    Highlights: ► Protocatechualdehyde (PCA) suppressed cell proliferation and induced apoptosis in human colorectal cancer cells. ► PCA enhanced transcriptional downregulation of cyclin D1 gene. ► PCA suppressed HDAC2 expression and activity. ► These findings suggest that anti-cancer activity of PCA may be mediated by reducing HDAC2-derived cyclin D1 expression. -- Abstract: Protocatechualdehyde (PCA) is a naturally occurring polyphenol found in barley, green cavendish bananas, and grapevine leaves. Although a few studies reported growth-inhibitory activity of PCA in breast and leukemia cancer cells, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to investigate if treatment of PCA affects cell proliferation and apoptosis in human colorectal cancer cells and define potential mechanisms by which PCA mediates growth arrest and apoptosis of cancer cells. Exposure of PCA to human colorectal cancer cells (HCT116 and SW480 cells) suppressed cell growth and induced apoptosis in dose-dependent manner. PCA decreased cyclin D1 expression in protein and mRNA level and suppressed luciferase activity of cyclin D1 promoter, indicating transcriptional downregulation of cyclin D1 gene by PCA. We also observed that PCA treatment attenuated enzyme activity of histone deacetylase (HDAC) and reduced expression of HDAC2, but not HDAC1. These findings suggest that cell growth inhibition and apoptosis by PCA may be a result of HDAC2-mediated cyclin D1 suppression.

  15. Down-regulation of SOSTDC1 promotes thyroid cancer cell proliferation via regulating cyclin A2 and cyclin E2

    Science.gov (United States)

    He, Xiaoying; Ke, Weijian; Xu, Lijuan; Liu, Liehua; Xiao, Haipeng; Li, Yanbing

    2015-01-01

    Sclerostin domain containing protein 1 (SOSTDC1) is down-regulated and acts as a tumor suppressor in some kinds of cancers. However, the expression pattern and biological significance of SOSTDC1 in thyroid cancer are largely unknown. We demonstrated that SOSTDC1 was significantly down-regulated in thyroid cancer. Ectopic over-expression of SOSTDC1 inhibited proliferation and induced G1/S arrest in thyroid cancer cells. Moreover, SOSTDC1 over-expression suppressed the growth of tumor xenografts in nude mice. We also found that elevated SOSTDC1 led to inhibition of cyclin A2 and cyclin E2. Together, our results demonstrate that SOSTDC1 is down-regulated in thyroid cancer and might be a potential therapeutic target in the treatment of thyroid cancer. PMID:26378658

  16. Caffeine, sleep and quality of life

    NARCIS (Netherlands)

    M.M. Lorist; J. Snel

    2008-01-01

    Caffeine is regarded as a mild stimulant acting on the central nervous system that is responsible for a significant portion of the behavioural and physiological effects of coffee and tea. Motives why people take caffeine are reflected in consumption patterns. Early in the morning caffeine might help

  17. 21 CFR 182.1180 - Caffeine.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Caffeine. 182.1180 Section 182.1180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN....1180 Caffeine. (a) Product. Caffeine. (b) Tolerance. 0.02 percent. (c) Limitations, restrictions,...

  18. Caffeine therapy in preterm infants.

    Science.gov (United States)

    Abdel-Hady, Hesham; Nasef, Nehad; Shabaan, Abd Elazeez; Nour, Islam

    2015-11-01

    Caffeine is the most commonly used medication for treatment of apnea of prematurity. Its effect has been well established in reducing the frequency of apnea, intermittent hypoxemia, and extubation failure in mechanically ventilated preterm infants. Evidence for additional short-term benefits on reducing the incidence of bronchopulmonary dysplasia and patent ductus arteriosus has also been suggested. Controversies exist among various neonatal intensive care units in terms of drug efficacy compared to other methylxanthines, dosage regimen, time of initiation, duration of therapy, drug safety and value of therapeutic drug monitoring. In the current review, we will summarize the available evidence for the best practice in using caffeine therapy in preterm infants. PMID:26566480

  19. Make Caffeine Visible: a Fluorescent Caffeine “Traffic Light” Detector

    Science.gov (United States)

    Xu, Wang; Kim, Tae-Hyeong; Zhai, Duanting; Er, Jun Cheng; Zhang, Liyun; Kale, Anup Atul; Agrawalla, Bikram Keshari; Cho, Yoon-Kyoung; Chang, Young-Tae

    2013-07-01

    Caffeine has attracted abundant attention due to its extensive existence in beverages and medicines. However, to detect it sensitively and conveniently remains a challenge, especially in resource-limited regions. Here we report a novel aqueous phase fluorescent caffeine sensor named Caffeine Orange which exhibits 250-fold fluorescence enhancement upon caffeine activation and high selectivity. Nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy indicate that π-stacking and hydrogen-bonding contribute to their interactions while dynamic light scattering and transmission electron microscopy experiments demonstrate the change of Caffeine Orange ambient environment induces its fluorescence emission. To utilize this probe in real life, we developed a non-toxic caffeine detection kit and tested it for caffeine quantification in various beverages. Naked-eye sensing of various caffeine concentrations was possible based on color changes upon irradiation with a laser pointer. Lastly, we performed the whole system on a microfluidic device to make caffeine detection quick, sensitive and automated.

  20. Dissolution and absorption of caffeine from guarana.

    Science.gov (United States)

    Bempong, D K; Houghton, P J

    1992-09-01

    The rate of release of caffeine from capsules of guarana was compared with that from capsules containing an equivalent amount of caffeine using the British Pharmacopoeia dissolution test apparatus. Determinations were carried out in media of pH 2 and 6.8 and caffeine concentrations in the dissolution fluid were determined by HPLC. No significant differences in release rates were found between the two preparations at either pH. The rate of absorption of caffeine across rat intestine using the everted gut was also compared for a guarana suspension and a solution containing an equivalent amount of caffeine. Experiments were carried out using fluids of pH 4.0 and 7.4. No significant differences in absorption between the two preparations were observed. These results show that the release and uptake of caffeine from guarana is the same as for preparations containing free caffeine. PMID:1360532

  1. [Mechanisms of caffeine-induced diuresis].

    Science.gov (United States)

    Marx, Barbara; Scuvée, Éléonore; Scuvée-Moreau, Jacqueline; Seutin, Vincent; Jouret, François

    2016-05-01

    Caffeine is an alkaloid which belongs to the family of methylxanthines and is present in beverages, food and drugs. Caffeine competitively antagonizes the adenosine receptors (AR), which are G protein-coupled receptors largely distributed throughout the body, including brain, heart, vessels and kidneys. Caffeine consumption has a well-known diuretic effect. The homeostasis of salt and water involves different segments of the nephron, in which adenosine plays complex roles depending on the differential expression of AR. Hence, caffeine increases glomerular filtration rate by opposing the vasoconstriction of renal afferent arteriole mediated by adenosine via type 1 AR during the tubuloglomerular feedback. Caffeine also inhibits Na(+) reabsorption at the level of renal proximal tubules. In addition, caffeine perturbs the hepatorenal reflex via sensory nerves in Mall's intrahepatic spaces. Here, we review the physiology of caffeine-induced natriuresis and diuresis, as well as the putative pathological implications. PMID:27225921

  2. Cyclin D1 expression in prostate carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, R.A.; Ravinal, R.C.; Costa, R.S.; Lima, M.S. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Tucci, S. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Cirurgia e Anatomia, Divisão de Urologia, Ribeirão Preto, SP, Brasil, Divisão de Urologia, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Muglia, V.F. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Medicina Interna (Centro de Ciência da Imagem), Ribeirão Preto, SP, Brasil, Departamento de Medicina Interna (Centro de Ciência da Imagem), Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Reis, R.B. Dos [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Cirurgia e Anatomia, Divisão de Urologia, Ribeirão Preto, SP, Brasil, Divisão de Urologia, Departamento de Cirurgia e Anatomia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Silva, G.E.B. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto, SP, Brasil, Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2014-05-09

    The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in >5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≥7), 86% of patients demonstrated cyclin D1 immunostaining of >5% (P<0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (P<0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness.

  3. Cyclin D1 expression in prostate carcinoma

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in >5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≥7), 86% of patients demonstrated cyclin D1 immunostaining of >5% (P<0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (P<0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness

  4. Caffeine Use Affects Pregnancy Outcome

    Science.gov (United States)

    Diego, Miguel; Field, Tiffany; Hernandez-Reif, Maria; Vera, Yanexy; Gil, Karla; Gonzalez-Garcia, Adolfo

    2008-01-01

    A sample of 750 women were interviewed during pregnancy on their depression and anxiety symptoms, substance use and demographic variables. A subsample was seen again at the neonatal stage (n = 152), and their infants were observed for sleep-wake behavior. Symptoms of depression and anxiety were related to caffeine use. Mothers who consumed more…

  5. Caffeine Modulates Attention Network Function

    Science.gov (United States)

    Brunye, Tad T.; Mahoney, Caroline R.; Lieberman, Harris R.; Taylor, Holly A.

    2010-01-01

    The present work investigated the effects of caffeine (0 mg, 100 mg, 200 mg, 400 mg) on a flanker task designed to test Posner's three visual attention network functions: alerting, orienting, and executive control [Posner, M. I. (2004). "Cognitive neuroscience of attention". New York, NY: Guilford Press]. In a placebo-controlled, double-blind…

  6. p27KIP1 blocks cyclin E-dependent transactivation of cyclin A gene expression

    DEFF Research Database (Denmark)

    Zerfass-Thome, K; Schulze, A; Zwerschke, W;

    1997-01-01

    Cyclin E is necessary and rate limiting for the passage of mammalian cells through the G1 phase of the cell cycle. Control of cell cycle progression by cyclin E involves cdk2 kinase, which requires cyclin E for catalytic activity. Expression of cyclin E/cdk2 leads to an activation of cyclin A gene...... expression, as monitored by reporter gene constructs derived from the human cyclin A promoter. Promoter activation by cyclin E/cdk2 requires an E2F binding site in the cyclin A promoter. We show here that cyclin E/cdk2 kinase can directly bind to E2F/p107 complexes formed on the cyclin A promoter-derived E2F...... binding site, and this association is controlled by p27KIP1, most likely through direct protein-protein interaction. These observation suggest that cyclin E/cdk2 associates with E2F/p107 complexes in late G1 phase, once p27KIP1 has decreased below a critical threshold level. Since a kinase-negative mutant...

  7. Consumption of caffeinated beverages and the awareness of their caffeine content among Dutch students.

    Science.gov (United States)

    Mackus, Marlou; van de Loo, Aurora J A E; Benson, Sarah; Scholey, Andrew; Verster, Joris C

    2016-08-01

    The purpose of the current study was to examine the knowledge of caffeine content of a variety of caffeinated beverages among Dutch university students. A pencil-and-paper survey was conducted among N = 800 Dutch students. Most participants (87.8%) reported consuming caffeinated beverages during the past 24 h. Their mean ± SD past 24-h caffeine intake from beverages was 144.2 ± 169.5 mg (2.2 ± 3.0 mg/kg bw). Most prevalent sources of caffeine were coffee beverages (50.8%) and tea (34.8%), followed by energy drink (9.2%), cola (4.7%), and chocolate milk (0.5%). Participants had poor knowledge on the relative caffeine content of caffeinated beverages. That is, they overestimated the caffeine content of energy drinks and cola, and underestimated the caffeine content of coffee beverages. If caffeine consumption is a concern, it is important to inform consumers about the caffeine content of all caffeine containing beverages, including coffee and tea. The current findings support previous research that the most effective way to reduce caffeine intake is to limit the consumption of coffee beverages and tea. PMID:27142708

  8. Caffeine tolerance: behavioral, electrophysiological and neurochemical evidence

    International Nuclear Information System (INIS)

    The development of tolerance to the stimulatory action of caffeine upon mesencephalic reticular neurons and upon spontaneous locomotor activity was evaluated in rats after two weeks of chronic exposure to low doses of caffeine (5-10 mg/kg/day via their drinking water). These doses are achievable through dietary intake of caffeine-containing beverages in man. Concomitant measurement of [3H]-CHA binding in the mesencephalic reticular formation was also carried out in order to explore the neurochemical basis of the development of tolerance. Caffeine, 2.5 mg/kg i.v., markedly increased the firing rate of reticular neurons in caffeine naive rats but failed to modify the neuronal activity in a group exposed chronically to low doses of caffeine. In addition, in spontaneous locomotor activity studies, the data show a distinct shift to the right of the caffeine dose-response curve in caffeine pretreated rats. These results clearly indicate that tolerance develops to the stimulatory action of caffeine upon the reticular formation at the single neuronal activity level as well as upon spontaneous locomotor activity. Furthermore, in chronically caffeine exposed rats, an increase in the number of binding sites for [3H]-CHA was observed in reticular formation membranes without any change in receptor affinity. 28 references, 4 figures

  9. Make Caffeine Visible: a Fluorescent Caffeine “Traffic Light” Detector

    OpenAIRE

    Wang Xu; Tae-Hyeong Kim; Duanting Zhai; Jun Cheng Er; Liyun Zhang; Anup Atul Kale; Bikram Keshari Agrawalla; Yoon-Kyoung Cho; Young-Tae Chang

    2013-01-01

    Caffeine has attracted abundant attention due to its extensive existence in beverages and medicines. However, to detect it sensitively and conveniently remains a challenge, especially in resource-limited regions. Here we report a novel aqueous phase fluorescent caffeine sensor named Caffeine Orange which exhibits 250-fold fluorescence enhancement upon caffeine activation and high selectivity. Nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy indicate that π-s...

  10. Caffeine reduces myocardial blood flow during exercise.

    Science.gov (United States)

    Higgins, John P; Babu, Kavita M

    2013-08-01

    Caffeine consumption has been receiving increased interest from both the medical and lay press, especially given the increased amounts now available in energy products. Acute ingestion of caffeine usually increases cardiac work; however, caffeine impairs the expected proportional increase in myocardial blood flow to match this increased work of the heart, most notably during exercise. This appears to be mainly due to caffeine's effect on blocking adenosine-induced vasodilatation in the coronary arteries in normal healthy subjects. This review summarizes the available medical literature specifically relating to pure caffeine tablet ingestion and reduced exercise coronary blood flow, and suggests possible mechanisms. Further studies are needed to evaluate this effect for other common caffeine-delivery systems, including coffee, energy beverages, and energy gels, which are often used for exercise performance enhancement, especially in teenagers and young athletes. PMID:23764265

  11. Assessing caffeine exposure in pregnant women.

    OpenAIRE

    Boylan, S. M.; Cade, J E; Kirk, S. F.; Greenwood, D.C.; White, K. L.; Shires, S.; Simpson, N. A.; Wild, C P; Hay, A W

    2008-01-01

    Studies on the effects of caffeine on health, while numerous, have produced inconsistent results. One of the most uncertain and controversial effects is on pregnancy outcome. Studies have produced conflicting results due to a number of methodological variations. The major challenge is the accurate assessment of caffeine intake. The aim of the present study was to explore different methods of assessing caffeine exposure in pregnant women. Twenty-four healthy pregnant women from the UK city of ...

  12. Role of adenosine receptors in caffeine tolerance

    International Nuclear Information System (INIS)

    Caffeine is a competitive antagonist at adenosine receptors. Receptor up-regulation during chronic drug treatment has been proposed to be the mechanism of tolerance to the behavioral stimulant effects of caffeine. This study reassessed the role of adenosine receptors in caffeine tolerance. Separate groups of rats were given scheduled access to drinking bottles containing plain tap water or a 0.1% solution of caffeine. Daily drug intake averaged 60-75 mg/kg and resulted in complete tolerance to caffeine-induced stimulation of locomotor activity, which could not be surmounted by increasing the dose of caffeine. 5'-N-ethylcarboxamidoadenosine (0.001-1.0 mg/kg) dose dependently decreased the locomotor activity of caffeine-tolerant rats and their water-treated controls but was 8-fold more potent in the latter group. Caffeine (1.0-10 mg/kg) injected concurrently with 5-N-ethylcarboxamidoadenosine antagonized the decreases in locomotor activity comparably in both groups. Apparent pA2 values for tolerant and control rats also were comparable: 5.05 and 5.11. Thus, the adenosine-antagonist activity of caffeine was undiminished in tolerant rats. The effects of chronic caffeine administration on parameters of adenosine receptor binding and function were measured in cerebral cortex. There were no differences between brain tissue from control and caffeine-treated rats in number and affinity of adenosine binding sites or in receptor-mediated increases (A2 adenosine receptor) and decreases (A1 adenosine receptor) in cAMP accumulation. These results are consistent with theoretical arguments that changes in receptor density should not affect the potency of a competitive antagonist. Experimental evidence and theoretical considerations indicate that up-regulation of adenosine receptors is not the mechanism of tolerance to caffeine-induced stimulation of locomotor activity

  13. Caffeine synthase and related methyltransferases in plants.

    Science.gov (United States)

    Misako, Kato; Kouichi, Mizuno

    2004-05-01

    Caffeine (1,3,7-trimethylxanthine) is a purine alkaloid present in high concentrations in tea and coffee and it is also found in a number of beverages such as coca cola. It is necessary to elucidate the caffeine biosynthetic pathway and to clone the genes related to the production of caffeine not only to determine the metabolism of the purine alkaloid but also to control the content of caffeine in tea and coffee. The available data support the operation of a xanthosine-->7-methylxanthosine-->7-methylxanthine-->theobromine-->caffeine pathway as the major route to caffeine. Since the caffeine biosynthetic pathway contains three S-adenosyl-L-methionine (SAM) dependent methylation steps, N-methyltransferases play important roles. This review focuses on the enzymes and genes involved in the methylation of purine ring. Caffeine synthase, the SAM-dependent methyltransferase involved in the last two steps of caffeine biosynthesis, was originally purified from young tea leaves (Camellia sinensis). The isolated cDNA, termed TCS1, consists of 1,483 base pairs and encodes a protein of 369 amino acids. Subsequently, the homologous genes that encode caffeine biosynthetic enzymes from coffee (Coffea arabica) were isolated. The recombinant proteins are classified into the three types on the basis of their substrate specificity i.e. 7-methylxanthosine synthase, theobromine synthase and caffeine synthase. The predicted amino acid sequences of caffeine biosynthetic enzymes derived from C. arabica exhibit more than 80% homology with those of the clones and but show only 40% homology with TCS1 derived from C. sinensis. In addition, they share 40% homology with the amino acid sequences of salicylic carboxyl methyltransferase, benzoic acid carboxyl methyltransferase and jasmonic acid carboxyl methyltransferase which belong to a family of motif B' methyltransferases which are novel plant methyltransferases with motif B' instead of motif B as the conserved region. PMID:14977590

  14. Caffeine-induced nuclear translocation of FoxO1 triggers Bim-mediated apoptosis in human glioblastoma cells.

    Science.gov (United States)

    Sun, Fei; Han, Dong-Feng; Cao, Bo-Qiang; Wang, Bo; Dong, Nan; Jiang, De-Hua

    2016-03-01

    Caffeine is one of the most commonly ingested neuroactive compounds and exhibits anticancer effects through induction of apoptosis and suppression of cell proliferation. However, the mechanisms underlying these effects are currently unknown. In this study, we investigated the mechanisms of caffeine-induced apoptosis in U251 cells (human glioma cell line). We analyzed the inhibitory effects of caffeine on cell proliferation by performing WST-8 and colony formation assays; in addition, cell survival was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and flow cytometric analysis. Western blotting was used to investigate the role played by FoxO1 in the proapoptotic effects of caffeine on glioma cells. Results showed that caffeine inhibited proliferation and survival of human glioma cells, induced apoptosis, and increased the expression of FoxO1 and its proapoptotic target Bim. In addition, we found that FoxO1 enhanced the transcription of its proapoptotic target Bim. In summary, our data indicates that FoxO1-Bim mediates caffeine-induced regression of glioma growth by activating cell apoptosis, thereby providing new mechanistic insight into the possible use of caffeine in treating human cancer. PMID:26449824

  15. Resibufogenin Induces G1-Phase Arrest through the Proteasomal Degradation of Cyclin D1 in Human Malignant Tumor Cells.

    Directory of Open Access Journals (Sweden)

    Masami Ichikawa

    Full Text Available Huachansu, a traditional Chinese medicine prepared from the dried toad skin, has been used in clinical studies for various cancers in China. Resibufogenin is a component of huachansu and classified as bufadienolides. Resibufogenin has been shown to exhibit the anti-proliferative effect against cancer cells. However, the molecular mechanism of resibufogenin remains unknown. Here we report that resibufogenin induces G1-phase arrest with hypophosphorylation of retinoblastoma (RB protein and down-regulation of cyclin D1 expression in human colon cancer HT-29 cells. Since the down-regulation of cyclin D1 was completely blocked by a proteasome inhibitor MG132, the suppression of cyclin D1 expression by resibufogenin was considered to be in a proteasome-dependent manner. It is known that glycogen synthase kinase-3β (GSK-3β induces the proteasomal degradation of cyclin D1. The addition of GSK-3β inhibitor SB216763 inhibited the reduction of cyclin D1 caused by resibufogenin. These effects on cyclin D1 by resibufogenin were also observed in human lung cancer A549 cells. These findings suggest that the anti-proliferative effect of resibufogenin may be attributed to the degradation of cyclin D1 caused by the activation of GSK-3β.

  16. MicroRNA-195 inhibits the proliferation of human glioma cells by directly targeting cyclin D1 and cyclin E1.

    Directory of Open Access Journals (Sweden)

    Wang Hui

    Full Text Available Glioma proliferation is a multistep process during which a sequence of genetic and epigenetic alterations randomly occur to affect the genes controlling cell proliferation, cell death and genetic stability. microRNAs are emerging as important epigenetic modulators of multiple target genes, leading to abnormal cellular signaling involving cellular proliferation in cancers.In the present study, we found that expression of miR-195 was markedly downregulated in glioma cell lines and human primary glioma tissues, compared to normal human astrocytes and matched non-tumor associated tissues. Upregulation of miR-195 dramatically reduced the proliferation of glioma cells. Flow cytometry analysis showed that ectopic expression of miR-195 significantly decreased the percentage of S phase cells and increased the percentage of G1/G0 phase cells. Overexpression of miR-195 dramatically reduced the anchorage-independent growth ability of glioma cells. Furthermore, overexpression of miR-195 downregulated the levels of phosphorylated retinoblastoma (pRb and proliferating cell nuclear antigen (PCNA in glioma cells. Conversely, inhibition of miR-195 promoted cell proliferation, increased the percentage of S phase cells, reduced the percentage of G1/G0 phase cells, enhanced anchorage-independent growth ability, upregulated the phosphorylation of pRb and PCNA in glioma cells. Moreover, we show that miR-195 inhibited glioma cell proliferation by downregulating expression of cyclin D1 and cyclin E1, via directly targeting the 3'-untranslated regions (3'-UTR of cyclin D1 and cyclin E1 mRNA. Taken together, our results suggest that miR-195 plays an important role to inhibit the proliferation of glioma cells, and present a novel mechanism for direct miRNA-mediated suppression of cyclin D1 and cyclin E1 in glioma.

  17. Caffeine and exercise: metabolism, endurance and performance.

    Science.gov (United States)

    Graham, T E

    2001-01-01

    Caffeine is a common substance in the diets of most athletes and it is now appearing in many new products, including energy drinks, sport gels, alcoholic beverages and diet aids. It can be a powerful ergogenic aid at levels that are considerably lower than the acceptable limit of the International Olympic Committee and could be beneficial in training and in competition. Caffeine does not improve maximal oxygen capacity directly, but could permit the athlete to train at a greater power output and/or to train longer. It has also been shown to increase speed and/or power output in simulated race conditions. These effects have been found in activities that last as little as 60 seconds or as long as 2 hours. There is less information about the effects of caffeine on strength; however, recent work suggests no effect on maximal ability, but enhanced endurance or resistance to fatigue. There is no evidence that caffeine ingestion before exercise leads to dehydration, ion imbalance, or any other adverse effects. The ingestion of caffeine as coffee appears to be ineffective compared to doping with pure caffeine. Related compounds such as theophylline are also potent ergogenic aids. Caffeine may act synergistically with other drugs including ephedrine and anti-inflammatory agents. It appears that male and female athletes have similar caffeine pharmacokinetics, i.e., for a given dose of caffeine, the time course and absolute plasma concentrations of caffeine and its metabolites are the same. In addition, exercise or dehydration does not affect caffeine pharmacokinetics. The limited information available suggests that caffeine non-users and users respond similarly and that withdrawal from caffeine may not be important. The mechanism(s) by which caffeine elicits its ergogenic effects are unknown, but the popular theory that it enhances fat oxidation and spares muscle glycogen has very little support and is an incomplete explanation at best. Caffeine may work, in part, by

  18. Inhibitor of CDK interacting with cyclin A1 (INCA1) regulates proliferation and is repressed by oncogenic signaling

    DEFF Research Database (Denmark)

    Baumer, Nicole; Tickenbrock, Lara; Tschanter, Petra;

    2011-01-01

    The cell cycle is driven by the kinase activity of cyclin/CDK complexes which is negatively regulated by CDK inhibitor proteins. Recently, we identified INCA1 as interaction partner and substrate of cyclin A1 in complex with CDK2. On a functional level, we identified a novel cyclin binding site in...... the INCA1 protein. INCA1 inhibited CDK2 activity and cell proliferation. The inihibitory effects depended on the cyclin-interacting domain. Mitogenic and oncogenic signals suppressed INCA1 expression, while it was induced by cell cycle arrest. We established a deletional mouse model that showed...... increased CDK2 activity in spleen with altered spleen architecture in Inca1-/- mice. Inca1-/- embryonic fibroblasts showed an increase in the fraction of S-phase cells. Furthermore, blasts from ALL and AML patients expressed significantly reduced INCA1 levels highlighting its relevance for growth control in...

  19. Telomerase activates transcription of cyclin D1 gene through an interaction with NOL1.

    Science.gov (United States)

    Hong, Juyeong; Lee, Ji Hoon; Chung, In Kwon

    2016-04-15

    Telomerase is a ribonucleoprotein enzyme that is required for the maintenance of telomere repeats. Although overexpression of telomerase in normal human somatic cells is sufficient to overcome replicative senescence, the ability of telomerase to promote tumorigenesis requires additional activities that are independent of its role in telomere extension. Here, we identify proliferation-associated nucleolar antigen 120 (NOL1, also known as NOP2) as a telomerase RNA component (TERC)-binding protein that is found in association with catalytically active telomerase. Although NOL1 is highly expressed in the majority of human tumor cells, the molecular mechanism by which NOL1 contributes to tumorigenesis remained unclear. We show that NOL1 binds to the T-cell factor (TCF)-binding element of the cyclin D1 promoter and activates its transcription. Interestingly, telomerase is also recruited to the cyclin D1 promoter in a TERC-dependent manner through the interaction with NOL1, further enhancing transcription of the cyclin D1 gene. Depletion of NOL1 suppresses cyclin D1 promoter activity, thereby leading to induction of growth arrest and altered cell cycle distributions. Collectively, our findings suggest that NOL1 represents a new route by which telomerase activates transcription of cyclin D1 gene, thus maintaining cell proliferation capacity. PMID:26906424

  20. EXPRESSION OF P16 AND CYCLIN D1 IN THE COURSE OF CARCINOGENESIS OF THE STOMACH

    Institute of Scientific and Technical Information of China (English)

    CHEN Yu-long; XU Feng; LI Yan-jie

    1999-01-01

    Objective: To determine p16 and cyclin D1 expression in the specimen of gastric carcinoma, atypic hyperplasia, atrophic gastritis, superficial gastritis and normal gastric mucosa. Methods: Using immunohistochemical method (ABC), the samples of 58 adenocarcinomas, 22 atypic hyperplasias, 28 atrophic gastritis,27 superficial gastritis and 15 gastric epitheliums were analyzed. Results: Positive immunostaining rate for p16 protein was the highest in normal gastric mucosa and decreased with the lesions progressing from superficial gastritis to atrophic gastritis to atypital hyperplasia and to adenocarcinoma (85%, 78.6%, 31.8%,48.3% respectively); Positive immunostaining of cyclin D1 can observed in atrophic gastritis. With the lesions progressing from atrophic gastritis to atypical hyperplasia to adenocarcinoma, its expression rate increased (17.9%, 36.4%, 53.4% respectively), and there was a significant difference between adenocarcinoma and atrophic gastritis group (P<0.05). An interesting observation was that inverse expression between p16and cyclin D1, was shown in most of gastric cancer detected. Conclusion: It is indicated that p16 and cyclin D1 play an important role in the gastric carcinogenesis, the inverse expression between p16 and cyclin D1 suggested that there is a suppression trend in them.

  1. Caffeine withdrawal and high-intensity endurance cycling performance.

    Science.gov (United States)

    Irwin, Christopher; Desbrow, Ben; Ellis, Aleisha; O'Keeffe, Brooke; Grant, Gary; Leveritt, Michael

    2011-03-01

    In this study, we investigated the impact of a controlled 4-day caffeine withdrawal period on the effect of an acute caffeine dose on endurance exercise performance. Twelve well-trained and familiarized male cyclists, who were caffeine consumers (from coffee and a range of other sources), were recruited for the study. A double-blind placebo-controlled cross-over design was employed, involving four experimental trials. Participants abstained from dietary caffeine sources for 4 days before the trials and ingested capsules (one in the morning and one in the afternoon) containing either placebo or caffeine (1.5 mg · kg(-1) body weight · day(-1)). On day 5, capsules containing placebo or caffeine (3 mg · kg(-1) body weight) were ingested 90 min before completing a time trial, equivalent to one hour of cycling at 75% peak sustainable power output. Hence the study was designed to incorporate placebo-placebo, placebo-caffeine, caffeine-placebo, and caffeine-caffeine conditions. Performance time was significantly improved after acute caffeine ingestion by 1:49 ± 1:41 min (3.0%, P = 0.021) following a withdrawal period (placebo-placebo vs. placebo-caffeine), and by 2:07 ± 1:28 min (3.6%, P = 0.002) following the non-withdrawal period (caffeine-placebo vs. caffeine-caffeine). No significant difference was detected between the two acute caffeine trials (placebo-caffeine vs. caffeine-caffeine). Average heart rate throughout exercise was significantly higher following acute caffeine administration compared with placebo. No differences were observed in ratings of perceived exertion between trials. A 3 mg · kg(-1) dose of caffeine significantly improves exercise performance irrespective of whether a 4-day withdrawal period is imposed on habitual caffeine users. PMID:21279864

  2. Effects of caffeine on sleep and cognition

    NARCIS (Netherlands)

    Snel, Jan; Lorist, Monicque M.; van Dongen, H.P.A.; Kerkhof, G.A.

    2011-01-01

    Caffeine can be used effectively to manipulate our mental state. It is beneficial in restoring low levels of wakefulness and in counteracting degraded cognitive task performance due to sleep deprivation. However, caffeine may produce detrimental effects on subsequent sleep, resulting in daytime slee

  3. Extraction of Caffeine--A Modern Experiment

    Science.gov (United States)

    Cohen, Paul Shea; Smith, Eileen Patricia

    1969-01-01

    Describes an organic chemistry experiment suitable for high school students in second year or an advanced chemistry course. The techniques for the extraction and purification of caffeine from various household materials are described. Further experimentation with the extracted caffeine is suggested. (LC)

  4. Creatine and Caffeine: Considerations for Concurrent Supplementation.

    Science.gov (United States)

    Trexler, Eric T; Smith-Ryan, Abbie E

    2015-12-01

    Nutritional supplementation is a common practice among athletes, with creatine and caffeine among the most commonly used ergogenic aids. Hundreds of studies have investigated the ergogenic potential of creatine supplementation, with consistent improvements in strength and power reported for exercise bouts of short duration (≤ 30 s) and high intensity. Caffeine has been shown to improve endurance exercise performance, but results are mixed in the context of strength and sprint performance. Further, there is conflicting evidence from studies comparing the ergogenic effects of coffee and caffeine anhydrous supplementation. Previous research has identified independent mechanisms by which creatine and caffeine may improve strength and sprint performance, leading to the formulation of multi-ingredient supplements containing both ingredients. Although scarce, research has suggested that caffeine ingestion may blunt the ergogenic effect of creatine. While a pharmacokinetic interaction is unlikely, authors have suggested that this effect may be explained by opposing effects on muscle relaxation time or gastrointestinal side effects from simultaneous consumption. The current review aims to evaluate the ergogenic potential of creatine and caffeine in the context of high-intensity exercise. Research directly comparing coffee and caffeine anhydrous is discussed, along with previous studies evaluating the concurrent supplementation of creatine and caffeine. PMID:26219105

  5. Effects of Caffeine on Auditory Brainstem Response

    Directory of Open Access Journals (Sweden)

    Saleheh Soleimanian

    2008-06-01

    Full Text Available Background and Aim: Blocking of the adenosine receptor in central nervous system by caffeine can lead to increasing the level of neurotransmitters like glutamate. As the adenosine receptors are present in almost all brain areas like central auditory pathway, it seems caffeine can change conduction in this way. The purpose of this study was to evaluate the effects of caffeine on latency and amplitude of auditory brainstem response(ABR.Materials and Methods: In this clinical trial study 43 normal 18-25 years old male students were participated. The subjects consumed 0, 2 and 3 mg/kg BW caffeine in three different sessions. Auditory brainstem responses were recorded before and 30 minute after caffeine consumption. The results were analyzed by Friedman and Wilcoxone test to assess the effects of caffeine on auditory brainstem response.Results: Compared to control group the latencies of waves III,V and I-V interpeak interval of the cases decreased significantly after 2 and 3mg/kg BW caffeine consumption. Wave I latency significantly decreased after 3mg/kg BW caffeine consumption(p<0.01. Conclusion: Increasing of the glutamate level resulted from the adenosine receptor blocking brings about changes in conduction in the central auditory pathway.

  6. Consumption of Caffeinated Products and Cardiac Ectopy

    OpenAIRE

    Dixit, Shalini; Stein, Phyllis K.; Dewland, Thomas A.; Dukes, Jonathan W.; Vittinghoff, Eric; Heckbert, Susan R.; Marcus, Gregory M

    2016-01-01

    Background Premature cardiac contractions are associated with increased morbidity and mortality. Though experts associate premature atrial contractions (PACs) and premature ventricular contractions (PVCs) with caffeine, there are no data to support this relationship in the general population. As certain caffeinated products may have cardiovascular benefits, recommendations against them may be detrimental. Methods and Results We studied Cardiovascular Health Study participants with a baseline ...

  7. An optimized and validated SPE-LC-MS/MS method for the determination of caffeine and paraxanthine in hair.

    Science.gov (United States)

    De Kesel, Pieter M M; Lambert, Willy E; Stove, Christophe P

    2015-11-01

    Caffeine is the probe drug of choice to assess the phenotype of the drug metabolizing enzyme CYP1A2. Typically, molar concentration ratios of paraxanthine, caffeine's major metabolite, to its precursor are determined in plasma following administration of a caffeine test dose. The aim of this study was to develop and validate an LC-MS/MS method for the determination of caffeine and paraxanthine in hair. The different steps of a hair extraction procedure were thoroughly optimized. Following a three-step decontamination procedure, caffeine and paraxanthine were extracted from 20 mg of ground hair using a solution of protease type VIII in Tris buffer (pH 7.5). Resulting hair extracts were cleaned up on Strata-X™ SPE cartridges. All samples were analyzed on a Waters Acquity UPLC® system coupled to an AB SCIEX API 4000™ triple quadrupole mass spectrometer. The final method was fully validated based on international guidelines. Linear calibration lines for caffeine and paraxanthine ranged from 20 to 500 pg/mg. Precision (%RSD) and accuracy (%bias) were below 12% and 7%, respectively. The isotopically labeled internal standards compensated for the ion suppression observed for both compounds. Relative matrix effects were below 15%RSD. The recovery of the sample preparation procedure was high (>85%) and reproducible. Caffeine and paraxanthine were stable in hair for at least 644 days. The effect of the hair decontamination procedure was evaluated as well. Finally, the applicability of the developed procedure was demonstrated by determining caffeine and paraxanthine concentrations in hair samples of ten healthy volunteers. The optimized and validated method for determination of caffeine and paraxanthine in hair proved to be reliable and may serve to evaluate the potential of hair analysis for CYP1A2 phenotyping. PMID:26452792

  8. Caffeine reduces dipyridamole-induced myocardial ischemia

    International Nuclear Information System (INIS)

    The mechanism of action of coronary vasodilation after dipyridamole may be based on inhibition of cellular uptake of circulating endogenous adenosine. Since caffeine has been reported to be a competitive antagonist of adenosine we studied the effect of caffeine on the outcome of dipiridamole-201Tl cardiac imaging in one patient. During caffeine abstinence dipyridamole induced myocardial ischemia with down-slope ST depressions on the ECG, and reversible perfusion defects on the scintigrams. When the test was repeated 1 wk later on similar conditions, but now shortly after infusion of caffeine (4 mg/kg), the ECG showed nodepressions, and the scintigrams only slight signs of ischemia. We conclude that when caffeine abstinence is not sufficient, the widespread use of coffee and related products may be responsible for false-negative findings in dipyridamole-201Tl cardiac imaging

  9. Caffeine as a Potential Quorum Sensing Inhibitor

    Directory of Open Access Journals (Sweden)

    Kok-Gan Chan

    2013-04-01

    Full Text Available Quorum sensing enables bacteria to control the gene expression in response to the cell density. It regulates a variety of bacterial physiological functions such as biofilm formation, bioluminescence, virulence factors and swarming which has been shown contribute to bacterial pathogenesis. The use of quorum sensing inhibitor would be of particular interest in treating bacterial pathogenicity and infections. In this work, we have tested caffeine as quorum sensing inhibitor by using Chromobacterium violaceum CV026 as a biosensor. We verified that caffeine did not degrade the N-acyl homoserine lactones tested. In this work, it is shown that caffeine could inhibit N-acyl homoserine lactone production and swarming of a human opportunistic pathogen, namely Pseudomonas aeruginosa PA01. To the best of our knowledge, this is the first documentation providing evidence on the presence of anti-quorum sensing activity in caffeine. Our work will allow caffeine to be explored as anti-infective drugs.

  10. Effect of caffeine on induction of endogenous type C virus in mouse cells in vitro

    International Nuclear Information System (INIS)

    The effect of caffeine on the expression of murine endogenous virus in mouse cells induced by radiation and chemicals was studied. Postirradiation treatment of K-BALB cells with caffeine enhanced cell killing as well as the induction of xenotropic virus after ultraviolet light irradiation. The degree of enhancement for the virus induction was comparable to that for cell killing. On the other hand, colony-forming ability and the expression of xenotropic virus of K-BALB cells after X-irradiation were unaffected by caffeine. These data suggest a linear relationship between the degree of endogenous virus expression and the amount of lethal damages after irradiation. For induction by halogenated pyrimidines, a 24-hr incubation of AKR2B cells with caffeine after 5-iodo-2'-deoxyuridine treatment resulted in marked suppression of the expression of ecotropic virus. On the contrary, in K-BALB cells, caffeine exerted only a small effect on 5-iodo-2'-deoxyuridine-induced expression of ecotropic and xenotropic viruses. These results indicate that, although using the same inducing agent, the pathway of endogenous virus induction may be different for AKR2B cells and for K-BALB cells

  11. Design, formulation and evaluation of caffeine chewing gum

    OpenAIRE

    Abolfazl Aslani; Fatemeh Jalilian

    2013-01-01

    Background: Caffeine which exists in drinks such as coffee as well as in drug dosage forms in the global market is among the materials that increase alertness and decrease fatigue. Compared to other forms of caffeine, caffeine gum can create faster and more prominent effects. In this study, the main goal is to design a new formulation of caffeine gum with desirable taste and assess its physicochemical properties. Materials and Methods: Caffeine gum was prepared by softening of gum bases a...

  12. HIV-1 expression induces cyclin D1 expression and pRb phosphorylation in infected podocytes: cell-cycle mechanisms contributing to the proliferative phenotype in HIV-associated nephropathy

    Directory of Open Access Journals (Sweden)

    Husain Mohammad

    2002-09-01

    Full Text Available Abstract Background The aberrant cell-cycle progression of HIV-1-infected kidney cells plays a major role in the pathogenesis of HIV-associated nephropathy, however the mechanisms whereby HIV-1 induces infected glomerular podocytes or infected tubular epithelium to exit quiescence are largely unknown. Here, we ask whether the expression of HIV-1 genes in infected podocytes induces cyclin D1 and phospho-pRb (Ser780 expression, hallmarks of cyclin D1-mediated G1 → S phase progression. Results We assessed cyclin D1 and phospho-pRb (Ser780 expression in two well-characterized models of HIV-associated nephropathy pathogenesis: HIV-1 infection of cultured podocytes and HIV-1 transgenic mice (Tg26. Compared to controls, cultured podocytes expressing HIV-1 genes, and podocytes and tubular epithelium from hyperplastic nephrons in Tg26 kidneys, had increased levels of phospho-pRb (Ser780, a target of active cyclin D1/cyclin-dependent kinase-4/6 known to promote G1 → S phase progression. HIV-1-infected podocytes showed markedly elevated cyclin D1 mRNA and cyclin D1 protein, the latter of which did not down-regulate during cell-cell contact or differentiation, suggesting post-transcriptional stabilization of cyclin D1 protein levels by HIV-1. The selective suppression of HIV-1 transcription by the cyclin-dependent kinase inhibitor, flavopiridol, abrogated cyclin D1 expression, underlying the requirement for HIV-1 encoded products to induce cyclin D1. Indeed, HIV-1 virus deleted of nef failed to induce cyclin D1 mRNA to the level of other single gene mutant viruses. Conclusions HIV-1 expression induces cyclin D1 and phospho-pRb (Ser780 expression in infected podocytes, suggesting that HIV-1 activates cyclin D1-dependent cell-cycle mechanisms to promote proliferation of infected renal epithelium.

  13. Caffeine and sports activity: a review.

    Science.gov (United States)

    Nehlig, A; Debry, G

    1994-07-01

    Potential ergogenic effects of caffeine at the cellular level are mediated by three main mechanisms of action which are: intracellular mobilization of calcium from sarcoplasmic reticulum and increased sensitivity of myofibrilles to calcium; inhibition of phosphodiesterases leading to an increase in cyclic-3',5'-adenosine monophosphate (cAMP) in various tissues including muscle; and the antagonism at the level of adenosine receptors, mainly in the central nervous system. The main mechanism of action of caffeine at the level usually encountered in vivo after the ingestion of a few cups of coffee is undoubtedly linked to the antagonism of caffeine at adenosine receptors. Caffeine also increases production of plasma catecholamines that allow the body to adapt to the stress created by physical exercise. Catecholamine production increases probably, in turn, the availability of free fatty acids as muscle substrates during work, thus allowing glycogen sparing. Caffeine is able to increase muscle contractility, has no ergogenic effect on intense exercise of brief duration, but can improve the time before exhaustion. Caffeine is also able to improve physical performance and endurance during prolonged activity of submaximal intensity. Glycogen sparing resulting from increased rate of lipolysis could contribute to the prolonged time to exhaustion. Finally, tolerance to the methylxanthine should be taken into account when an athlete wants to draw any benefit from caffeine absorption prior to a sports event. PMID:7960313

  14. Caffeine use and alexithymia in university students.

    Science.gov (United States)

    Lyvers, Michael; Duric, Natalija; Thorberg, Fred Arne

    2014-01-01

    Abstract Alexithymia refers to difficulties with identifying, describing, and regulating one's own emotions. This trait dimension has been linked to risky or harmful use of alcohol and illicit drugs; however, the most widely used psychoactive drug in the world, caffeine, has not been examined previously in relation to alexithymia. The present study assessed 106 male and female university students aged 18-30 years on their caffeine use in relation to several traits, including alexithymia. The 18 participants defined as alexithymic based on their Toronto Alexithymia Scale (TAS-20) scores reported consuming nearly twice as much caffeine per day as did non-alexithymic or borderline alexithymic participants. They also scored significantly higher than controls on indices of frontal lobe dysfunction as well as anxiety symptoms and sensitivity to punishment. In a hierarchical linear regression model, sensitivity to punishment negatively predicted daily caffeine intake, suggesting caffeine avoidance by trait-anxious individuals. Surprisingly, however, TAS-20 alexithymia scores positively predicted caffeine consumption. Possible reasons for the positive relationship between caffeine use and alexithymia are discussed, concluding that this outcome is tentatively consistent with the hypo-arousal model of alexithymia. PMID:25188705

  15. Caffeine Toxicity Due to Supplement Use in Caffeine--Naïve Individual: A Cautionary Tale.

    Science.gov (United States)

    Lystrup, Robert M; Leggit, Jeffery C

    2015-08-01

    Thousands of military members self-medicate with dietary supplements containing unknown quantities of pharmacologically active compounds. These poorly regulated substances can cause real harm to the military population, especially when they contain stimulants such as caffeine. When taken regularly, caffeine has several performance-enhancing benefits. However, when used excessively or in vulnerable populations, caffeine can cause several unwanted side effects such as nervousness, sensory disturbances, insomnia, arrhythmia, excitability, inattentiveness, restlessness, mood changes, gastrointestinal disturbances, and even psychosis. Vulnerable patients include the caffeine-naïve, physiologically stressed, young, and mentally ill patients. One such case describes a caffeine-naïve service member who suffered an adverse reaction after taking an allegedly moderate dose of caffeine from a pill he obtained from a teammate. This case highlights the importance of supplement awareness among service members, increased provider vigilance, third party verification, and enhanced regulation on the approval and marketing of dietary supplements. PMID:26226540

  16. Caffeine Enhances the Calcium-Dependent Cardiac Mitochondrial Permeability Transition: Relevance for Caffeine Toxicity

    OpenAIRE

    Sardão, Vilma A; Oliveira, Paulo J; Moreno, António J. M.

    2002-01-01

    Caffeine (1,3,7-trimethylxanthine), a compound present in beverages such as tea and coffee, is known to be toxic at high concentrations. Some of the observed clinical conditions include cardiovascular disease and reproductive disorders, among others. The possible toxic effects of caffeine on heart mitochondria are still poorly understood. The influence of caffeine on the mitochondrial permeability transition has not been clarified so far. The objective of this study was to investigate whether...

  17. Caffeine induced changes in cerebral circulation

    International Nuclear Information System (INIS)

    While the caffeine induced cerebral vasoconstriction is well documented, the effects of oral ingestion of the drug in a dose range comparable to the quantities in which it is usually consumed and the intensity and duration of the associated reduction in cerebral circulation are unknown. Cerebral blood flow was measured via the 133Xenon inhalation technique before and thirty and ninety minutes after the oral administration of 250 mg of caffeine or a placebo, under double-blind conditions. Caffeine ingestion was found to be associated with significant reductions in cerebral perfusion thirty and ninety minutes later. The placebo group showed no differences between the three sets of cerebral blood flow values

  18. Compound list: caffeine [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available caffeine CAF 00097 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/caf...feine.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/caf...feine.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/caf...-tggates/LATEST/Rat/in_vivo/Liver/Repeat/caffeine.Rat.in_vivo.Liver.Repeat.zip ftp://ftp.biosciencedbc.jp/ar...chive/open-tggates/LATEST/Rat/in_vivo/Kidney/Single/caffeine.Rat.in_vivo.Kidney.Single.zip ftp://ftp.bioscie

  19. Suppressive effects of coffee on the SOS responses induced by UV and chemical mutagens

    International Nuclear Information System (INIS)

    SOS-inducing activity of UV or chemical mutagens was strongly suppressed by instant coffee in Salmonella typhimurium TA1535/pSK1002. As decaffeinated instant coffee showed a similarly strong suppressive effect, it would seem that caffeine, a known inhibitor of SOS responses, is not responsible for the effect observed. The suppression was also shown by freshly brewed coffee extracts. However, the suppression was absent in green coffee-bean extracts. These results suggest that coffee contains some substance(s) which, apart from caffeine, suppresses SOS-inducing activity of UV or chemical mutagens and that the suppressive substance(s) are produced by roasting coffee beans. (Auth.)

  20. Caffeine and caffeinated beverage consumption and fecundability in a preconception cohort.

    Science.gov (United States)

    Wesselink, Amelia K; Wise, Lauren A; Rothman, Kenneth J; Hahn, Kristen A; Mikkelsen, Ellen M; Mahalingaiah, Shruthi; Hatch, Elizabeth E

    2016-07-01

    Caffeine is an adenosine receptor antagonist that may influence fertility by affecting ovulation, menstrual characteristics, or sperm quality. We studied the association between female and male preconception caffeine intake and fecundability in a North American prospective cohort study of 2135 pregnancy planners. Frequency of caffeinated beverage intake was self-reported at baseline. Outcome data were updated every 8 weeks until reported pregnancy; censoring occurred at 12 months. Adjusted fecundability ratios (FR) and 95% confidence intervals (CI) were estimated using proportional probabilities regression. Total caffeine intake among males, but not females, was associated with fecundability (FR for ≥300 vs. energy drink intake were associated with reduced fecundability among males. PMID:27112524

  1. Radio-modification by caffeine alone and in combination with phosphorothioates: in vivo and cell-free studies

    International Nuclear Information System (INIS)

    Caffeine is generally considered to result in radiosensitization by affecting the cell cycle. Data from in vivo studies, however, do not suggest sensitization; caffeine administration did not adversely affect survival of mice irradiated at doses causing hematopoietic injury, or gastrointestinal injury, or when administered in combination with phosphorothioates. For example, caffeine administration (20 mg/kg IP) in combination with the radioprotector WR-151327, S-2-(3-methyl-amino-propyl-amino)propyl-phosphoro-thioic acid. (200 mg/kg IP) resulted in a dose modification factor of 1.54 in comparison to 1.51 for WR-151327 treatment alone. In a cell-free system, the active metabolites of phosphorothiotates, i.e. free thiols and disulfides, appear to mimic polyamines and modulate enzymes involves in DNA structure and synthesis. The free thiol of WR-151327 (WR-151326) actively enhanced topoisomerase I-mediated unwinding of supercoiled plB130 DNA and super-coiling of DNA mediated by DNA gyrase (topoisomerase II). Caffeine, in general, had opposite effects on potoisomerase activities compared to WR-151326. When caffeine was added to the cell-free system together with WR-151326, the stimulatory effects of WR-151326 were suppressed. Further studies are needed in cell-free systems, cells, and animals to elucidate the potential utility of caffeine administration in combination with radiation and other therapeutic agents. (authors)

  2. Caffeinated alcohol beverages: a public health concern.

    Science.gov (United States)

    Attwood, Angela S

    2012-01-01

    Consumption of alcohol mixed with caffeinated energy drinks is becoming popular, and the number of pre-mixed caffeinated alcohol products on the worldwide market is increasing. There is public health concern and even occasional legal restriction relating to these drinks, due to associations with increased intoxication and harms. The precise nature and degree of the pharmacological relationship between caffeine and alcohol is not yet elucidated, but it is proposed that caffeine attenuates the sedative effects of alcohol intoxication while leaving motor and cognitive impairment unaffected. This creates a potentially precarious scenario for users who may underestimate their level of intoxication and impairment. While legislation in some countries has restricted production or marketing of pre-mixed products, many individuals mix their own energy drink-alcohol 'cocktails'. Wider dissemination of the risks might help balance marketing strategies that over-emphasize putative positive effects. PMID:22645036

  3. Caffeine in surface and wastewaters in Barbados, West Indies.

    Science.gov (United States)

    Edwards, Quincy A; Kulikov, Sergei M; Garner-O'Neale, Leah D

    2015-01-01

    Caffeine, a purine alkaloid drug, has been recognized as a contaminant of water bodies in various climatic regions, however, these environmental caffeine concentrations are the first to be reported in the tropical Caribbean. The major objective of this study was to develop an improved method to extract caffeine from surface and wastewaters in the warm Caribbean environment and measure caffeine concentrations in highly populated areas in Barbados. Caffeine was extracted from water via solid phase extraction (SPE); the acidified water samples were loaded onto C-18 cartridges and eluted with pure chloroform. The extracted caffeine was quantified using gas chromatography - mass spectroscopy - multiple reaction monitoring (GC-MS/MS-MRM). Method detection limits of 0.2 ng L(-1) from 1 L water samples were achieved. Caffeine was detected in all environmental water samples investigated. The concentrations of caffeine in surface waters were detected in the range 0.1 - 6.9 μg L(-1). The two wastewater treatment plants, primary and secondary treatment systems, significantly differed in their ability to eliminate caffeine in the raw sewage (38% and 99% caffeine removal efficiencies respectively). Thus, it may be essential to employ secondary treatment to effectively remove caffeine from wastewater systems in Barbados. Caffeine in water bodies are principally attributed to anthropogenic sources as caffeine-producing plants are not commonly grown on the island of Barbados. The study also shows the recalcitrance of caffeine to hydrolytic degradation. PMID:25729634

  4. Caffeinated drinks, alcohol consumption and hangover severity

    OpenAIRE

    Penning, R.; de Haan, L.; Verster, J.C.

    2011-01-01

    This study examined the relationship between consumption of caffeinated beverages and alcohol, and effects on next day hangover severity. In 2010, a survey funded by Utrecht University was conducted among N=549 Dutch students. Beverages consumed on their latest drinking session that produced a hangover were recorded. Hangover severity was scored using the Acute Hangover Scale. No significant correlation between caffeine use and hangover severity was found. Subjects who mixed alcohol with cola...

  5. Topical and transdermal delivery of caffeine.

    OpenAIRE

    Luo, L.; Lane, M. E.

    2015-01-01

    Caffeine is administered topically and transdermally for a variety of pharmaceutical and cosmetic applications and it is also used as a model hydrophilic compound in dermal risk assessment studies. This review considers the physicochemical and permeation properties of caffeine with reference to its delivery to and through the skin. Since it has been used as a model compound the findings have implications for the delivery of many hydrophilic compounds having similar properties. Various passive...

  6. PARK2 orchestrates cyclins to avoid cancer

    Czech Academy of Sciences Publication Activity Database

    Bartek, Jiří; Hodný, Zdeněk

    2014-01-01

    Roč. 46, č. 6 (2014), s. 527-528. ISSN 1061-4036 Institutional support: RVO:68378050 Keywords : PARK2 * G1/S-phase cyclin * cancer Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 29.352, year: 2014

  7. Prenatal Caffeine Exposure Impairs Pregnancy in Rats

    Directory of Open Access Journals (Sweden)

    Maryam Yadegari

    2016-12-01

    Full Text Available Background: In recent years, concerns have been raised about human reproductive disorders. Caffeine consumption is increasing by the world’s population and there is a relationship between caffeine intake and adverse reproductive outcomes. The aim of this study was to evaluate the effects of caffeine on implantation sites, number of live births, birth weight, crown-rump length (CRL and abnormality in pregnant rats. Materials and Methods: In this experimental study, 40 female albino rats (170-190 g were randomly divided into two experimental and two control groups (n=10/each group. In both experimental groups, animals received caffeine intraperitoneally (IP: 150 mg/kg/day on days 1-5 of pregnancy. In experimental group 1, treated animals were euthanized on day 7of pregnancy and the number of implantation sites was counted. In experimental group 2, treated animals maintained pregnant and after delivery, the number of live births, birth weight, CRL and abnormality of neonates were investigated. In control group, animals received IP injections of distilled water. Data were analyzed by independent t test. Results: Results showed that administration of caffeine significantly decreased the number of implantation sites, number of live births and CRL as compared with control group (P<0.05. There were no significant differences regarding birth weight and abnormality of neonate rats between experimental and control groups. Conclusion: These results suggest that caffeine caused anti-fertility effect and significantly decreased CRL in neonate rats.

  8. Cyclin B synthesis and rapamycin-sensitive regulation of protein synthesis during starfish oocyte meiotic divisions.

    Science.gov (United States)

    Lapasset, Laure; Pradet-Balade, Bérengère; Vergé, Valérie; Lozano, Jean-Claude; Oulhen, Nathalie; Cormier, Patrick; Peaucellier, Gérard

    2008-11-01

    Translation of cyclin mRNAs represents an important event for proper meiotic maturation and post-fertilization mitoses in many species. Translational control of cyclin B mRNA has been described to be achieved through two separate but related mechanisms: translational repression and polyadenylation. In this paper, we evaluated the contribution of global translational regulation by the cap-dependent translation repressor 4E-BP (eukaryotic initiation factor 4E-binding protein) on the cyclin B protein synthesis during meiotic maturation of the starfish oocytes. We used the immunosupressant drug rapamycin, a strong inhibitor of cap-dependent translation, to check for the involvement of this protein synthesis during this physiological process. Rapamycin was found to prevent dissociation of 4E-BP from the initiation factor eIF4E and to suppress correlatively a burst of global protein synthesis occurring at the G2/M transition. The drug had no effect on first meiotic division but defects in meiotic spindle formation prevented second polar body emission, demonstrating that a rapamycin-sensitive pathway is involved in this mechanism. While rapamycin affected the global protein synthesis, the drug altered neither the specific translation of cyclin B mRNA nor the expression of the Mos protein. The expression of these two proteins was correlated with the phosphorylation and the dissociation of the cytoplasmic polyadenylation element-binding protein from eIF4E. PMID:18361417

  9. Degradation of exogenous caffeine by Populus alba and its effects on endogenous caffeine metabolism.

    Science.gov (United States)

    Pierattini, Erika C; Francini, Alessandra; Raffaelli, Andrea; Sebastiani, Luca

    2016-04-01

    This is the first study reporting the presence of endogenous caffeine, theobromine, and theophylline in all organs of poplar plants. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was used in order to evaluate the uptake, translocation, and metabolism of caffeine-(trimethyl-(13)C) in Populus alba L. Villafranca clone grown in hydroponic conditions. We investigated the remediation of caffeine since it is one of the most widely consumed drugs and it is frequently detected in wastewater treatment plant effluents, surface water, and groundwater worldwide. Our results demonstrated that poplar can absorb and degrade exogenous caffeine without negative effects on plant health. Data showed that concentrations of all endogenous compounds varied depending on caffeine-(trimethyl-(13)C) treatments. In particular, in control conditions, endogenous caffeine, theobromine, and theophylline were mainly distributed in roots. On the other hand, once caffeine-(trimethyl-(13)C) was provided, this compound and its dimethy-(13)C metabolites are mainly localized at leaf level. In conclusion, our results support the possible use of Villafranca clone in association with other water treatment systems in order to complete the process of caffeine remediation. PMID:26681326

  10. Caffeine intake by patients with autosomal dominant polycystic kidney disease

    Energy Technology Data Exchange (ETDEWEB)

    Vendramini, L.C.; Nishiura, J.L.; Baxmann, A.C.; Heilberg, I.P. [Disciplina de Nefrologia, Departamento de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2012-07-20

    Because caffeine may induce cyst and kidney enlargement in autosomal dominant polycystic kidney disease (ADPKD), we evaluated caffeine intake and renal volume using renal ultrasound in ADPKD patients. Caffeine intake was estimated by the average of 24-h dietary recalls obtained on 3 nonconsecutive days in 102 ADPKD patients (68 females, 34 males; 39 ± 12 years) and compared to that of 102 healthy volunteers (74 females, 28 males; 38 ± 14 years). The awareness of the need for caffeine restriction was assessed. Clinical and laboratory data were obtained from the medical records of the patients. Mean caffeine intake was significantly lower in ADPKD patients versus controls (86 vs 134 mg/day), and 63% of the ADPKD patients had been previously aware of caffeine restriction. Caffeine intake did not correlate with renal volume in ADPKD patients. There were no significant differences between the renal volumes of patients in the highest and lowest tertiles of caffeine consumption. Finally, age-adjusted multiple linear regression revealed that renal volume was associated with hypertension, chronic kidney disease stage 3 and the time since diagnosis, but not with caffeine intake. The present small cross-sectional study indicated a low level of caffeine consumption by ADPKD patients when compared to healthy volunteers, which was most likely due to prior awareness of the need for caffeine restriction. Within the range of caffeine intake observed by ADPKD patients in this study (0-471 mg/day), the renal volume was not directly associated with caffeine intake.

  11. Caffeine intake by patients with autosomal dominant polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    L.C. Vendramini

    2012-09-01

    Full Text Available Because caffeine may induce cyst and kidney enlargement in autosomal dominant polycystic kidney disease (ADPKD, we evaluated caffeine intake and renal volume using renal ultrasound in ADPKD patients. Caffeine intake was estimated by the average of 24-h dietary recalls obtained on 3 nonconsecutive days in 102 ADPKD patients (68 females, 34 males; 39 ± 12 years and compared to that of 102 healthy volunteers (74 females, 28 males; 38 ± 14 years. The awareness of the need for caffeine restriction was assessed. Clinical and laboratory data were obtained from the medical records of the patients. Mean caffeine intake was significantly lower in ADPKD patients versus controls (86 vs 134 mg/day, and 63% of the ADPKD patients had been previously aware of caffeine restriction. Caffeine intake did not correlate with renal volume in ADPKD patients. There were no significant differences between the renal volumes of patients in the highest and lowest tertiles of caffeine consumption. Finally, age-adjusted multiple linear regression revealed that renal volume was associated with hypertension, chronic kidney disease stage 3 and the time since diagnosis, but not with caffeine intake. The present small cross-sectional study indicated a low level of caffeine consumption by ADPKD patients when compared to healthy volunteers, which was most likely due to prior awareness of the need for caffeine restriction. Within the range of caffeine intake observed by ADPKD patients in this study (0-471 mg/day, the renal volume was not directly associated with caffeine intake.

  12. Molecular evolution of cyclin proteins in animals and fungi

    Directory of Open Access Journals (Sweden)

    Afonnikov Dmitry A

    2011-07-01

    Full Text Available Abstract Background The passage through the cell cycle is controlled by complexes of cyclins, the regulatory units, with cyclin-dependent kinases, the catalytic units. It is also known that cyclins form several families, which differ considerably in primary structure from one eukaryotic organism to another. Despite these lines of evidence, the relationship between the evolution of cyclins and their function is an open issue. Here we present the results of our study on the molecular evolution of A-, B-, D-, E-type cyclin proteins in animals and fungi. Results We constructed phylogenetic trees for these proteins, their ancestral sequences and analyzed patterns of amino acid replacements. The analysis of infrequently fixed atypical amino acid replacements in cyclins evidenced that accelerated evolution proceeded predominantly during paralog duplication or after it in animals and fungi and that it was related to aromorphic changes in animals. It was shown also that evolutionary flexibility of cyclin function may be provided by consequential reorganization of regions on protein surface remote from CDK binding sites in animal and fungal cyclins and by functional differentiation of paralogous cyclins formed in animal evolution. Conclusions The results suggested that changes in the number and/or nature of cyclin-binding proteins may underlie the evolutionary role of the alterations in the molecular structure of cyclins and their involvement in diverse molecular-genetic events.

  13. Neurobehavioral hazard identification and characterization for caffeine.

    Science.gov (United States)

    Turnbull, Duncan; Rodricks, Joseph V; Mariano, Gregory F

    2016-02-01

    This report evaluates the scientific literature on caffeine with respect to potential central nervous system (CNS) effects, specifically effects on sleep, anxiety, and aggression/risk-taking. Caffeine has been the subject of more scientific safety studies than any other food ingredient. It is important, therefore, to evaluate new studies in the context of this large existing body of knowledge. The safety of caffeine can best be described in a narrative form, and is not usefully expressed in terms of a "bright line" numerical value like an "acceptable daily intake" (ADI). Caffeine intake has been associated with a range of reversible physiological effects, in a few studies at levels of less than 100 mg in sensitive individuals. It is also clear that many people can tolerate much greater levels - perhaps up to 600-800 mg/day or more - without experiencing such effects. The reasons for this type of variability in response are described in this report. Based on all the available evidence, there is no reason to believe that experiencing such effects from caffeine intake has any significant or lasting effect on health. The point at which caffeine intake may cause harm to the CNS is not readily identifiable, in part because data on the effects of daily intakes greater than 600 mg is limited. Effects of caffeine on risk-taking and aggressive behavior in young people have received considerable publicity, yet are the most difficult to study because of ethical concerns and limitations in the ability to design appropriate studies. At present, the weight of available evidence does not support these concerns, yet this should not preclude ongoing careful monitoring of the scientific literature. PMID:26702789

  14. Caffeine's Jolt Can Sometimes Be Short-Lived

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159413.html Caffeine's Jolt Can Sometimes Be Short-Lived Stimulant effect ... 17, 2016 THURSDAY, June 16, 2016 (HealthDay News) -- Caffeine no longer improves alertness or mental performance after ...

  15. Serious Concerns Over Alcoholic Beverages with Added Caffeine

    Science.gov (United States)

    ... Espanol Serious Concerns Over Alcoholic Beverages with Added Caffeine Please share copies of this printer-friendly PDF ( ... beverages, or CABs, are alcoholic beverages that contain caffeine as an additive and are packaged in combined ...

  16. Caffeine prevents protection in two human models of ischemic preconditioning.

    NARCIS (Netherlands)

    Riksen, N.P.; Zhou, Z.; Oyen, W.J.G.; Jaspers, R.A.; Ramakers, B.P.; Brouwer, R.M.H.J.; Boerman, O.C.; Steinmetz, N.; Smits, P.; Rongen, G.A.

    2006-01-01

    OBJECTIVES: We studied whether caffeine impairs protection by ischemic preconditioning (IP) in humans. BACKGROUND: Ischemic preconditioning is critically dependent on adenosine receptor stimulation. We hypothesize that the adenosine receptor antagonist caffeine blocks the protective effect of IP. ME

  17. Determination of CaffeineIn Beverages: A Review

    OpenAIRE

    Igelige Gerald; David Ebuka Arthur; Adebiyi Adedayo

    2014-01-01

    Caffeine is a well-known stimulant which is added as an ingredient to various carbonated soft drinks. Caffeine has drawn more attention due to its physiological effects beyond that of its stimulatory effect. Consumers are interested in knowing the exact amounts of caffeine existing in beverages. However, limited data exist, especially for store brand beverages. Therefore, it is pertinent to review the various methods that will effectively determine the caffeine contents in different carbonate...

  18. Reinforcing effects of caffeine in coffee and capsules.

    OpenAIRE

    Griffiths, R R; Bigelow, G E; Liebson, I A

    1989-01-01

    In a residential research ward the reinforcing and subjective effects of caffeine were studied under double-blind conditions in volunteer subjects with histories of heavy coffee drinking. In Experiment 1, 6 subjects had 13 opportunities each day to self-administer either a caffeine (100 mg) or a placebo capsule for periods of 14 to 61 days. All subjects developed a clear preference for caffeine, with intake of caffeine becoming relatively stable after preference had been attained. Preference ...

  19. Caffeine Taste Signaling in Drosophila Larvae.

    Science.gov (United States)

    Apostolopoulou, Anthi A; Köhn, Saskia; Stehle, Bernhard; Lutz, Michael; Wüst, Alexander; Mazija, Lorena; Rist, Anna; Galizia, C Giovanni; Lüdke, Alja; Thum, Andreas S

    2016-01-01

    The Drosophila larva has a simple peripheral nervous system with a comparably small number of sensory neurons located externally at the head or internally along the pharynx to assess its chemical environment. It is assumed that larval taste coding occurs mainly via external organs (the dorsal, terminal, and ventral organ). However, the contribution of the internal pharyngeal sensory organs has not been explored. Here we find that larvae require a single pharyngeal gustatory receptor neuron pair called D1, which is located in the dorsal pharyngeal sensilla, in order to avoid caffeine and to associate an odor with caffeine punishment. In contrast, caffeine-driven reduction in feeding in non-choice situations does not require D1. Hence, this work provides data on taste coding via different receptor neurons, depending on the behavioral context. Furthermore, we show that the larval pharyngeal system is involved in bitter tasting. Using ectopic expressions, we show that the caffeine receptor in neuron D1 requires the function of at least four receptor genes: the putative co-receptors Gr33a, Gr66a, the putative caffeine-specific receptor Gr93a, and yet unknown additional molecular component(s). This suggests that larval taste perception is more complex than previously assumed already at the sensory level. Taste information from different sensory organs located outside at the head or inside along the pharynx of the larva is assembled to trigger taste guided behaviors. PMID:27555807

  20. EVALUATION OF ANTIBACTERIAL ACTIVITY OF CAFFEINE

    Directory of Open Access Journals (Sweden)

    Pawar Pruthviraj

    2011-04-01

    Full Text Available The present study was carried out with water soluble portion and pure solvent of the acetone, ethanol, methanol, acetonitrile, water extracts of leaves and leaf buds of Camellia sinensis (green tea, and beans of Coffea arabica (coffee. Caffeine (3,7-dihydro-1, 3,7-trimethyl-1H-purine-2,6-dione was isolated from both plants using a liquid-liquid extraction method, detected on thin layer chromatography (TLC plates in comparison with standard caffeine, which served as a positive control. After performing the gross behavioral study, the Antibacterial activity was evaluated against Gram-negative bacteria included; Escherichia coli, Proteus mirabilis, Klebsiella pneumonia and Pseudomonas aeruginosa Both compounds at a concentration of 2 mg/ml showed similar antibacterial activities against all tested bacteria, except for P. mirabilis, and the highest inhibitory effect was observed against P. aeruginosa using a modified agar diffusion method. The minimal inhibitory concentration (MIC of caffeine was determined using a broth microdilution method in 96 multi-well microtitre plates. MIC values ranged from 65.5 to 250.0 µg/ml for the caffeine isolated from coffee and 65.5 to 500.0 µg/ml for green tea caffeine. Combination results showed additive effects against most pathogenic bacteria especially for P. aeruginosa, using both antibacterial assays.

  1. Luminescence characteristics of caffeine and theophylline1

    Science.gov (United States)

    Andino, M. M.; De Lima, C. G.; Winefordner, J. D.

    The luminescence properties of solutions of caffeine and theophylline in methanol are observed. The effects of the solvent pH, the presence of a heavy atom and the matrix or substrate on the fluorescence and phosphorescence properties of the compounds are evaluated. Caffeine and theophylline fluorescence can be observed at room temperature from dilute methanolic solutions and strong phosphorescence is observed at low temperature when the matrix is in a polycrystalline state. Acidic and basic media cause spectral changes and reduce the intensity of the low temperature phosphorescence. Iodide is a good heavy-atom enhancer of both the low temperature and room temperature phosphorescence of caffeine and theophylline. The intensity of the phosphorescence at room temperature and when spotted on filter paper depends on the type of filter paper and the pH of the spotting solution and/or the pH of the wet surface at the moment of spotting. Theophylline is more sensitive than caffeine to the microenvironment. Under the appropriate experimental conditions, both low temperature and room temperature phosphorescence could be used as analytical tools for the determination of caffeine and theophylline.

  2. Caffeine Consumption Patterns and Beliefs of College Freshmen

    Science.gov (United States)

    McIlvain, Gary E.; Noland, Melody P.; Bickel, Robert

    2011-01-01

    Background: Caffeine consumption by young people has increased dramatically over the last decade through increased coffee consumption and "energy drinks." In higher amounts, caffeine causes many adverse effects that are cause for concern. Purpose: Purposes of this study were to determine: (1) the amount of caffeine consumed by a sample of college…

  3. Associations of ambulatory blood pressure with urinary caffeine and caffeine metabolite excretions.

    Science.gov (United States)

    Guessous, Idris; Pruijm, Menno; Ponte, Belén; Ackermann, Daniel; Ehret, Georg; Ansermot, Nicolas; Vuistiner, Philippe; Staessen, Jan; Gu, Yumei; Paccaud, Fred; Mohaupt, Markus; Vogt, Bruno; Pechère-Bertschi, Antoinette; Pechère-Berstchi, Antoinette; Martin, Pierre-Yves; Burnier, Michel; Eap, Chin B; Bochud, Murielle

    2015-03-01

    Intake of caffeinated beverages might be associated with reduced cardiovascular mortality possibly via the lowering of blood pressure. We estimated the association of ambulatory blood pressure with urinary caffeine and caffeine metabolites in a population-based sample. Families were randomly selected from the general population of Swiss cities. Ambulatory blood pressure monitoring was conducted using validated devices. Urinary caffeine, paraxanthine, theophylline, and theobromine excretions were measured in 24 hours urine using ultrahigh performance liquid chromatography tandem mass spectrometry. We used mixed models to explore the associations of urinary excretions with blood pressure although adjusting for major confounders. The 836 participants (48.9% men) included in this analysis had mean age of 47.8 and mean 24-hour systolic and diastolic blood pressure of 120.1 and 78.0 mm Hg. For each doubling of caffeine excretion, 24-hour and night-time systolic blood pressure decreased by 0.642 and 1.107 mm Hg (both P values <0.040). Similar inverse associations were observed for paraxanthine and theophylline. Adjusted night-time systolic blood pressure in the first (lowest), second, third, and fourth (highest) quartile of paraxanthine urinary excretions were 110.3, 107.3, 107.3, and 105.1 mm Hg, respectively (P trend <0.05). No associations of urinary excretions with diastolic blood pressure were generally found, and theobromine excretion was not associated with blood pressure. Anti-hypertensive therapy, diabetes mellitus, and alcohol consumption modify the association of caffeine urinary excretion with systolic blood pressure. Ambulatory systolic blood pressure was inversely associated with urinary excretions of caffeine and other caffeine metabolites. Our results are compatible with a potential protective effect of caffeine on blood pressure. PMID:25489060

  4. Caffeine Inhibits Acetylcholinesterase, But Not Butyrylcholinesterase

    Directory of Open Access Journals (Sweden)

    Petr Dobes

    2013-05-01

    Full Text Available Caffeine is an alkaloid with a stimulant effect in the body. It can interfere in transmissions based on acetylcholine, epinephrine, norepinephrine, serotonin, dopamine and glutamate. Clinical studies indicate that it can be involved in the slowing of Alzheimer disease pathology and some other effects. The effects are not well understood. In the present work, we focused on the question whether caffeine can inhibit acetylcholinesterase (AChE and/or, butyrylcholinesterase (BChE, the two enzymes participating in cholinergic neurotransmission. A standard Ellman test with human AChE and BChE was done for altering concentrations of caffeine. The test was supported by an in silico examination as well. Donepezil and tacrine were used as standards. In compliance with Dixon’s plot, caffeine was proved to be a non-competitive inhibitor of AChE and BChE. However, inhibition of BChE was quite weak, as the inhibition constant, Ki, was 13.9 ± 7.4 mol/L. Inhibition of AChE was more relevant, as Ki was found to be 175 ± 9 µmol/L. The predicted free energy of binding was −6.7 kcal/mol. The proposed binding orientation of caffeine can interact with Trp86, and it can be stabilize by Tyr337 in comparison to the smaller Ala328 in the case of human BChE; thus, it can explain the lower binding affinity of caffeine for BChE with reference to AChE. The biological relevance of the findings is discussed.

  5. Potentiation of morphine analgesia by caffeine.

    Science.gov (United States)

    Misra, A L; Pontani, R B; Vadlamani, N L

    1985-04-01

    Significant potentiation of morphine (5 mg kg-1 s.c. or 1 mg kg-1 i.v.) analgesia (tail-withdrawal reflex at 55 degrees C) was observed in caffeine-treated (100 mg kg-1 i.p.) rats as compared to the control group and lower doses of caffeine (2mg kg-1 i.p.) did not show this effect. Potentiated analgesia was reversed by naloxone. Pharmacokinetic or dispositional factors appear to be involved in part in this potentiation. PMID:4005485

  6. Potentiation of morphine analgesia by caffeine.

    OpenAIRE

    Misra, A. L.; Pontani, R. B.; Vadlamani, N. L.

    1985-01-01

    Significant potentiation of morphine (5 mg kg-1 s.c. or 1 mg kg-1 i.v.) analgesia (tail-withdrawal reflex at 55 degrees C) was observed in caffeine-treated (100 mg kg-1 i.p.) rats as compared to the control group and lower doses of caffeine (2mg kg-1 i.p.) did not show this effect. Potentiated analgesia was reversed by naloxone. Pharmacokinetic or dispositional factors appear to be involved in part in this potentiation.

  7. EVALUATION OF ANTIBACTERIAL ACTIVITY OF CAFFEINE

    OpenAIRE

    Pawar Pruthviraj; Bikkad Suchita; Kurhade Shital; Kadbane Shilpa

    2011-01-01

    The present study was carried out with water soluble portion and pure solvent of the acetone, ethanol, methanol, acetonitrile, water) extracts of leaves and leaf buds of Camellia sinensis (green tea), and beans of Coffea arabica (coffee). Caffeine (3,7-dihydro-1, 3,7-trimethyl-1H-purine-2,6-dione) was isolated from both plants using a liquid-liquid extraction method, detected on thin layer chromatography (TLC) plates in comparison with standard caffeine, which served as a positive control. Af...

  8. Caffeine Expectancy Questionnaire (CaffEQ): Construction, Psychometric Properties, and Associations with Caffeine Use, Caffeine Dependence, and Other Related Variables

    Science.gov (United States)

    Huntley, Edward D.; Juliano, Laura M.

    2012-01-01

    Expectancies for drug effects predict drug initiation, use, cessation, and relapse, and may play a causal role in drug effects (i.e., placebo effects). Surprisingly little is known about expectancies for caffeine even though it is the most widely used psychoactive drug in the world. In a series of independent studies, the nature and scope of…

  9. Energy drinks and the neurophysiological impacts of caffeine

    Directory of Open Access Journals (Sweden)

    Leeana Bagwath Persad

    2011-10-01

    Full Text Available Caffeine is the most widely used psychoactive stimulant with prevalent use across all age groups. It is a naturally occurring substance found in the coffee bean, tea leaf, the kola nut, cocoa bean. Recently there has been an increase in energy drink consumption leading to caffeine abuse, with aggressive marketing and poor awareness on the consequences of high caffeine use. With caffeine consumption being so common, it is vital to know the impact caffeine has on the body, as its effects can influence cardio-respiratory, endocrine and perhaps most importantly neurological systems. Detrimental effects have being described especially since an over consumption of caffeine has being noted. This review focuses on the neurophysiological impact of caffeine and its biochemical pathways in the human body.

  10. Human Cyclin a Is Required for Mitosis until Mid Prophase

    OpenAIRE

    Furuno, Nobuaki; den Elzen, Nicole; Pines, Jonathon

    1999-01-01

    We have used microinjection and time-lapse video microscopy to study the role of cyclin A in mitosis. We have injected purified, active cyclin A/cyclin-dependent kinase 2 (CDK2) into synchronized cells at specific points in the cell cycle and assayed its effect on cell division. We find that cyclin A/CDK2 will drive G2 phase cells into mitosis within 30 min of microinjection, up to 4 h before control cells enter mitosis. Often this premature mitosis is abnormal; the chromosomes do not complet...

  11. Hypophagic and hypolocomotive effects of metachloro phenyl piperazine in rats treated with theophylline and caffeine.

    Science.gov (United States)

    Alam, Nausheen; Haleem, Darakshan Jabeen; Najam, Rahila; Haider, Syeda; Ahmed, Shahida Perveen

    2011-07-01

    Long term intake of coffee is known to produce anxiety and suppression of appetite. 5- hydroxytryptamine (5-HT) acting via 5-HT-2C receptors elicits anorexia and anxiety. The present study is design to monitor metachloro phenyl piperazine (m-CPP) at a dose of 3mg/ml/kg, induces hypophagia and hypolocomotion in rats taking a solution of caffeine (a component of coffee and tea) or theophylline (a component of tea) as a sole source of water. We found that hypophagic and hypolocomotive effects of m-CPP were attenuated in theophylline but not in caffeine treated animals suggesting that long term intake of theophylline may attenuate anorexiogenic and anxiogenic effects of 5-HT. A possible role of 5-HT-2C receptors in the modulation of anxiety and appetite in people drinking coffee or tea discussed. PMID:21715256

  12. Reinforcing effects of caffeine in coffee and capsules.

    Science.gov (United States)

    Griffiths, R R; Bigelow, G E; Liebson, I A

    1989-09-01

    In a residential research ward the reinforcing and subjective effects of caffeine were studied under double-blind conditions in volunteer subjects with histories of heavy coffee drinking. In Experiment 1, 6 subjects had 13 opportunities each day to self-administer either a caffeine (100 mg) or a placebo capsule for periods of 14 to 61 days. All subjects developed a clear preference for caffeine, with intake of caffeine becoming relatively stable after preference had been attained. Preference for caffeine was demonstrated whether or not preference testing was preceded by a period of 10 to 37 days of caffeine abstinence, suggesting that a recent history of heavy caffeine intake (tolerance/dependence) was not a necessary condition for caffeine to function as a reinforcer. In Experiment 2, 6 subjects had 10 opportunities each day to self-administer a cup of coffee or (on different days) a capsule, dependent upon completing a work requirement that progressively increased and then decreased over days. Each day, one of four conditions was studied: caffeinated coffee (100 mg/cup), decaffeinated coffee, caffeine capsules (100 mg/capsule), or placebo capsules. Caffeinated coffee maintained the most self-administration, significantly higher than decaffeinated coffee and placebo capsules but not different from caffeine capsules. Both decaffeinated coffee and caffeine capsules were significantly higher than placebo capsules but not different from each other. In both experiments, subject ratings of "linking" of coffee or capsules covaried with the self-administration measures. These experiments provide the clearest demonstrations to date of the reinforcing effects of caffeine in capsules and in coffee. PMID:2794839

  13. Caffeinated drinks, alcohol consumption and hangover severity

    NARCIS (Netherlands)

    Penning, R.; de Haan, L.; Verster, J.C.

    2011-01-01

    This study examined the relationship between consumption of caffeinated beverages and alcohol, and effects on next day hangover severity. In 2010, a survey funded by Utrecht University was conducted among N=549 Dutch students. Beverages consumed on their latest drinking session that produced a hango

  14. Caffeine Does Not Modulate Inhibitory Control

    Science.gov (United States)

    Tieges, Zoe; Snel, Jan; Kok, Albert; Ridderinkhof, K. Richard

    2009-01-01

    The effects of a 3 mg/kg body weight (BW) dose of caffeine were assessed on behavioral indices of response inhibition. To meet these aims, we selected a modified AX version of the Continuous Performance Test (CPT), the stop task, and the flanker task. In three double-blind, placebo-controlled, within-subjects experiments, these tasks were…

  15. Soxhlet Extraction of Caffeine from Beverage Plants

    Science.gov (United States)

    Adam, D. J.; Mainwaring, J.; Quigley, Michael N.

    1996-12-01

    A simple procedure is described for the extraction of caffeine from coffee beans or granules, tea leaves, mat leaves, etc. Since dichloromethane and several other hazardous substances are used, the procedure is best performed in a fume hood. Following extraction, melting point determination of the crystalline precipitate establishes its positive identity. Includes 33 references.

  16. A fluvoxamine-caffeine interaction study

    DEFF Research Database (Denmark)

    Jeppesen, U; Loft, S; Poulsen, H E;

    1996-01-01

    The selective serotonin reuptake inhibitor fluvoxamine is a very potent inhibitor of the liver enzyme CYP1A2, which is the major P450 catalysing the biotransformation of caffeine. Thus, a pharmacokinetic study was undertaken with the purpose of documenting a drug-drug interaction between fluvoxam...

  17. Action of caffeine on x-irradiated HeLa cells. I. Delayed inhibition of DNA synthesis

    International Nuclear Information System (INIS)

    Treatment of HeLa S3 cells with 1 mM caffeine delays progression through G1 by 1.5 hours but causes no other detectable inhibition of cell progression; it sometimes results in a large stimulation of thymidine incorporation. When this concentration is applied to cells that have been irradiated with 1-krad doses of 220-kV x rays, there is a marked suppression of both the inhibition of DNA synthesis and G2 arrest induced by the radiation. Larger doses require higher concentrations of caffeine to suppress the inhibition of DNA synthesis. Delaying addition until the rate of synthesis is at its minimum (1.5 hours after irradiation with 1 krad) results in a slightly accelerated recovery of the rate. Treatment before or during irradiation is without effect on the inhibition. Removal of the caffeine as late as 6 hours after its addition at the time of irradiation results in a prompt inhibition in DNA synthesis that mimics that observed immediately after irradiation in the absence of caffeine. These findings raise the possibility that the depression in rate of DNA systhesis might not result from radiation damage introduced into the replicon initiation system, but rather may be an indirect consequence of damage residing elsewhere in the irradiated cell

  18. Tumor suppressor BLU inhibits proliferation of nasopharyngeal carcinoma cells by regulation of cell cycle, c-Jun N-terminal kinase and the cyclin D1 promoter

    International Nuclear Information System (INIS)

    Tumor suppressor genes function to regulate and block tumor cell proliferation. To explore the mechanisms underlying the tumor suppression of BLU/ZMYND10 gene on a frequently lost human chromosomal region, an adenoviral vector with BLU cDNA insert was constructed. BLU was re-expressed in nasopharyngeal carcinoma cells by transfection or viral infection. Clonogenic growth was assayed; cell cycle was analyzed by flow cytometry-based DNA content detection; c-Jun N-terminal kinase (JNK) and cyclin D1 promoter activities were measured by reporter gene assay, and phosphorylation was measured by immunoblotting. The data for each pair of groups were compared with Student t tests. BLU inhibits clonogenic growth of nasopharyngeal carcinoma cells, arrests cell cycle at G1 phase, downregulates JNK and cyclin D1 promoter activities, and inhibits phosphorylation of c-Jun. BLU inhibits growth of nasopharyngeal carcinoma cells by regulation of the JNK-cyclin D1 axis to exert tumor suppression

  19. Spectrophotometric determination of caffeine using polyaniline films

    International Nuclear Information System (INIS)

    Polyaniline (PANI) films were fabricated by chemical oxidative polymerization of aniline monomers using ammonium persulfate (APS). The effects of varying oxidant concentration, oxidant solvent and washing solution in the PANI film deposition were first evaluated. 0.250 M APS in 0.200 M HCl and 0.200 M aniline in 0.200 M HCl were used to produce the emeraldine PANI (green) films which were deposited onto commercially available acctate films. The fabricated PANI film acts as an optical sensor baed on its redox-dependent switching of polyaniline from emeraldine (green) to pernigranilline (blue) form. The change in absorbance of blue PANI films immerse in caffeine-containing solution vs green fabricated PANI films were utilized in analysis of caffeine at 829 nm using a UV-VIS spectrophotometer. Repeatable results were obtained in intra-branch and inter-branch repeatability studies, with coefficient of variation (CV) values ranging rom 9.8-13.9% and 5.1-14.5%, respectively. Linear response was obtained over the concentration of 10.0-50.0 μg/mL. The limit of detection (LOD) and limit of quantitation (LOQ) were determined to be 2.5 and 8.5μg/mL, respectively. The obtained % recovery values of caffeine spiked in aqueous solution ranged from 84.9-107%. Three pharmaceutical formulations containing 20.0 or 25.0 μg/Ml caffeine where analyzed using PANI films by external calibration method. The obtained average caffeine values were 25.2 mg/tablet, 22.4 mg/tablet and 15.4 mg/capsule for Fevadol®, Fevergan® and Alaxan®FR, respectively. These values were 77.0% to 101% of the label claims. Human urine samples spiked with caffeine were also analyzed, after sample pre-treatment. Obtained percent recovery values ranged from 79.1 to 105%. This method demonstrated the potential of laboratory-fabricated PANI films as a low-cost rapid, reliable, simple and accurate method for caffeine quantification in pharmaceutical and clinical specimens. (author)

  20. Regulation of cyclin E stability in Xenopus laevis embryos

    Science.gov (United States)

    Brandt-(Webb), Yekaterina

    Cyclin-Cdk complexes positively regulate cell cycle progression. Cyclins are regulatory subunits that bind to and activate cyclin-dependent kinases or Cdks. Cyclin E associates with Cdk2 to mediate G1/S phase transition of the cell cycle. Cyclin E is overexpressed in breast, lung, skin, gastrointestinal, cervical, and ovarian cancers. Its overexpression correlates with poor patient prognosis and is involved in the etiology of breast cancer. We have been studying how this protein is downregulated during development in order to determine if these mechanisms are disrupted during tumorigenesis, leading to its overexpression. Using Xenopus laevis embryos as a model, we have shown previously that during the first 12 embryonic cell cycles Cyclin E levels remain constant yet Cdk2 activity oscillates twice per cell cycle. Cyclin E is abruptly destabilized by an undefined mechanism after the 12th cell cycle, which corresponds to the midblastula transition (MBT). Based on work our work and work by others, we have hypothesized that differential phosphorylation and a change in localization result in Cyclin E degradation by the 26S proteasome at the MBT. To test this, we generated a series of point mutations in conserved threonine/serine residues implicated in degradation of human Cyclin E. Using Western blot analysis, we show that similarly to human Cyclin E, mutation of these residues to unphosphorylatable alanine stabilizes Cyclin E past the MBT when they are expressed in vivo. Cyclin E localization was studied by immunofluorescence analysis of endogenous and exogenous protein in pre-MBT, MBT, and post-MBT embryos. In addition, we developed a novel method of conjugating recombinant His6-tagged Cyclin E to fluorescent (CdSe)ZnS nanoparticles (quantum dots) capped with dihydrolipoic acid. Confocal microscopy was used to visualize His6Cyclin E-quantum dot complexes inside embryo cells in real time. We found that re-localization at the MBT from the cytoplasm to the nucleus

  1. Cyclin Dl expression in B-cell non Hodgkin lymphoma.

    Science.gov (United States)

    Aref, Salah; Mossad, Y; El-Khodary, T; Awad, M; El-Shahat, E

    2006-10-01

    Disorders of the cell cycle regulatory machinery play a key role in the pathogenesis of cancer. Over-expression of cyclin D1 protein has been reported in several solid tumors and certain lymphoid malignancies, but little is known about the effect of its expression on clinical behavior and outcome in B-cell Non-Hodgkin lymphoma (NHL). In this study, we investigated the expression of cyclin Dl in group of patients with NHL and correlated the results with the clinical and laboratory data. The degree of expression of cyclin Dl protein was evaluated by flow cytometry in a group of NHL patients (n = 46) and in normal control group (n = 10). Cyclin Dl over expression was detected in 10 out of 46 (21.7%) patients; they were 5/5-mantle cell lymphoma (MCL) (100%) and 5/28 large B-cell lymphoma (17.8%). All other NHL subtypes showed normal cyclin D1 expression. The clinical signs (hepatomegaly, splenomegaly and B-symptoms, clinical staging) and laboratory data (hemoglobin, white cell count (WBCs), platelet count, and bone marrow infiltration) were not significantly different between NHL subgroup with cyclin Dl over expression and that with normal cyclin Dl expression. Serum lactic dehydrogenase (LDH) levels and lymphadenopathy were significantly higher in NHL group with cyclin D1 over expression as compared to those without. Also, cyclin D1 over expression is associated with poor outcome of NHL patients. Cyclin Dl over expression was evident among all cases of MCL and few cases of large B-cell lymphoma. Cyclin Dl over expression might be used as adjuvant tool for diagnosis of MCL; has role in NHL biology and is bad prognostic index in NHL. PMID:17607588

  2. Caffeine increases food intake while reducing anxiety-related behaviors.

    Science.gov (United States)

    Sweeney, Patrick; Levack, Russell; Watters, Jared; Xu, Zhenping; Yang, Yunlei

    2016-06-01

    The objective of this study was to determine the effects of different doses of caffeine on appetite and anxiety-related behavior. Additionally, we sought to determine if withdrawal from chronic caffeine administration promotes anxiety. In this study, we utilized rodent open field testing and feeding behavior assays to determine the effects of caffeine on feeding and anxiety-related behavior (n = 8 mice; 4-8 weeks old). We also measured 2 h and 24 h food intake and body-weight during daily administration of caffeine (n = 12 mice; 4-8 weeks old). To test for caffeine withdrawal induced anxiety, anxiety-related behavior in rodents was quantified following withdrawal from four consecutive days of caffeine administration (n = 12 mice; 4-8 weeks old). We find that acute caffeine administration increases food intake in a dose-dependent manner with lower doses of caffeine more significantly increasing food intake than higher doses. Acute caffeine administration also reduced anxiety-related behaviors in mice without significantly altering locomotor activity. However, we did not observe any differences in 24 h food intake or body weight following chronic caffeine administration and there were no observable differences in anxiety-related behaviors during caffeine withdrawal. In conclusion, we find that caffeine can both increase appetite and decrease anxiety-related behaviors in a dose dependent fashion. Given the complex relationship between appetite and anxiety, the present study provides additional insights into potential caffeine-based pharmacological mechanisms governing appetite and anxiety disorders, such as bulimia nervosa. PMID:26972351

  3. Paradoxical roles of cyclin D1 in DNA stability.

    Science.gov (United States)

    Jirawatnotai, Siwanon; Sittithumcharee, Gunya

    2016-06-01

    Maintenance of DNA integrity is vital for all of the living organisms. Consequence of DNA damaging ranges from, introducing harmless synonymous mutations, to causing disease-associated mutations, genome instability, and cell death. A cell cycle protein cyclin D1 is an established cancer-driving protein. However, contribution of cyclin D1 to cancer formation and cancer survival is not entirely known. In cancer tissues, overexpression of cyclin D1 is associated with both cancer genome instability, and resistance to DNA-damaging cancer drugs. Emerging evidence indicated that cyclin D1 may play novel direct roles in regulating DNA repair. Here we provide an insight how cyclin D1 expression may contribute to DNA repair and chromosome instability, and how these functions may facilitate cancer formation, and drug resistance. PMID:27155130

  4. Quantitative Analysis by Isotopic Dilution Using Mass Spectroscopy: The Determination of Caffeine by GC-MS.

    Science.gov (United States)

    Hill, Devon W.; And Others

    1988-01-01

    Describes a laboratory technique for quantitative analysis of caffeine by an isotopic dilution method for coupled gas chromatography-mass spectroscopy. Discusses caffeine analysis and experimental methodology. Lists sample caffeine concentrations found in common products. (MVL)

  5. Effect of caffeine on cocaine locomotor stimulant activity in rats.

    Science.gov (United States)

    Misra, A L; Vadlamani, N L; Pontani, R B

    1986-03-01

    The effect of caffeine on the locomotor stimulant activity induced by intravenous cocaine in rats was investigated. Low doses of caffeine (20 mg/kg IP) potentiated the locomotor activity induced by 1, 2.5 mg/kg intravenous doses of cocaine and higher doses of caffeine (50, 100 mg/kg IP) had no significant effect. The locomotor stimulant effect of 20 mg/kg IP dose of caffeine per se in vehicle was significantly higher and that with 100 mg/kg dose significantly lower than that of the vehicle control. Thus caffeine produced dose-dependent effects on cocaine-induced locomotor stimulant activity, with low dose potentiating and higher doses having no significant effect on such activity. Pharmacokinetic or dispositional factors did not appear to play a role in potentiation of cocaine locomotor stimulant activity by caffeine. PMID:3703910

  6. Caffeine content of energy drinks, carbonated sodas, and other beverages.

    Science.gov (United States)

    McCusker, Rachel R; Goldberger, Bruce A; Cone, Edward J

    2006-03-01

    The caffeine content of 10 energy drinks, 19 carbonated sodas, and 7 other beverages was determined. In addition, the variability of the caffeine content of Coca-Cola fountain soda was evaluated. Caffeine was isolated from the samples by liquid-liquid extraction and analyzed by gas chromatography with nitrogen-phosphorus detection. The caffeine concentration of the caffeinated energy drinks ranged from none detected to 141.1 mg/serving. The caffeine content of the carbonated sodas ranged from none detected to 48.2 mg/serving, and the content of the other beverages ranged from Coca-Cola fountain samples were 44.5, 2.95, and 6.64 mg/serving, respectively. PMID:16620542

  7. Plant cyclins: a unified nomenclature for plant A-, B- and D-type cyclins based on sequence organization.

    Science.gov (United States)

    Renaudin, J P; Doonan, J H; Freeman, D; Hashimoto, J; Hirt, H; Inzé, D; Jacobs, T; Kouchi, H; Rouzé, P; Sauter, M; Savouré, A; Sorrell, D A; Sundaresan, V; Murray, J A

    1996-12-01

    The comparative analysis of a large number of plant cyclins of the A/B family has recently revealed that plants possess two distinct B-type groups and three distinct A-type groups of cyclins. Despite earlier uncertainties, this large-scale comparative analysis has allowed an unequivocal definition of plant cyclins into either A or B classes. We present here the most important results obtained in this study, and extend them to the case of plant D-type cyclins, in which three groups are identified. For each of the plant cyclin groups, consensus sequences have been established and a new, rational, plant-wide naming system is proposed in accordance with the guidelines of the Commission on Plant Gene Nomenclature. This nomenclature is based on the animal system indicating cyclin classes by an upper-case roman letter, and distinct groups within these classes by an arabic numeral suffix. The naming of plant cyclin classes is chosen to indicate homology to their closest animal class. The revised nomenclature of all described plant cyclins is presented, with their classification into groups CycA1, CycA2, CycA3, CycB1, CycB2, CycD1, CycD2 and CycD3. PMID:9002599

  8. International society of sports nutrition position stand: caffeine and performance

    OpenAIRE

    Wildman Robert; Graves B Sue; Stout Jeff; Willoughby Darryn; Taylor Lem; Wilborn Colin; Campbell Bill; Kreider Richard; Kalman Doug; Ziegenfuss Tim; Goldstein Erica R; Ivy John L; Spano Marie; Smith Abbie E; Antonio Jose

    2010-01-01

    Abstract Position Statement: The position of The Society regarding caffeine supplementation and sport performance is summarized by the following seven points: 1.) Caffeine is effective for enhancing sport performance in trained athletes when consumed in low-to-moderate dosages (~3-6 mg/kg) and overall does not result in further enhancement in performance when consumed in higher dosages (≥ 9 mg/kg). 2.) Caffeine exerts a greater ergogenic effect when consumed in an anhydrous state as compared ...

  9. Ultrastructural changes in the developing chicken cornea following caffeine administration.

    OpenAIRE

    Bartel Hieronim; Tosik Dariusz; Kujawa-Hadryś Monika

    2010-01-01

    Caffeine is one of the most frequently consumed psychoactive substances. It has been known for many years that caffeine at high concentrations exerts harmful effects on both women's and laboratory animals' fertility, moreover it may impair normal development of many organs in the prenatal period. So far there have been few studies performed that demonstrate teratogenic effects of caffeine on structures of the developing eye, particularly the cornea. The aim of the study was to show ultrastruc...

  10. Caffeine Accelerates Absorption and Enhances the Analgesic Effect of Acetaminophen

    OpenAIRE

    Renner, Bertold; Clarke, Geoff; Grattan, Tim; Beisel, Angelika; Mueller, Christian; Werner, Ulrike; Kobal, Gerd; Brune, Kay

    2013-01-01

    The aim of this study was to determine the analgesic effect of acetaminophen compared to a combination of both caffeine and acetaminophen or caffeine alone using tonic and phasic pain stimulation. Twenty-four subjects were treated orally with 1000 mg acetaminophen, 130 mg caffeine, and a combination of both in a 4-way crossover, double-blind, placebo-controlled study. Pharmacokinetics and analgesic effects were assessed by means of an experimental pain model based on pain-related cortical pot...

  11. Antioxidant Activity of Aqueous Extracts of Different Caffeine Products

    OpenAIRE

    Abd El-Moneim M.R. AFIFY; Emad A. SHALABY; Hossam Saad EL-BELTAGI

    2011-01-01

    The antioxidant activity of water extracts (cold and hot) of six caffeine products were carried out. The extracts were screened for total polyphenol contents and antioxidant activity using DPPH, ABTS methods and reducing power method at 50 and 100 μg/ml after 15 min and 30 min using DPPH, ABTS BHA and Caffeine as standard compounds. The results indicated that, the hot water extracts for different caffeine products showed higher antioxidant activity than those of cold extracts and this activit...

  12. Alcohol, nicotine, caffeine, and mental disorders

    OpenAIRE

    Crocq, Marc-Antoine

    2003-01-01

    Alcohol, nicotine, and caffeine are the most widely consumed psychotropic drugs worldwide. They are largely consumed by normal individuals, but their use is even more frequent in psychiatric patients, Thus, patients with schizophrenia tend to abuse all three substances. The interrelationships between depression and alcohol are complex. These drugs can all create dependence, as understood in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Alcohol abuse is cl...

  13. The Role of Cyclins and Cyclins Inhibitors in the Multistep Process of HPV-Associated Cervical Carcinoma

    International Nuclear Information System (INIS)

    Background: Human papillomavirus (HPV) types 16 and 18 are associated with cervical carcinogenesis. This is possibly achieved through an interaction between HPV oncogenic proteins and some cell cycle regulatory genes. However, the exact pathogenetic mechanisms are not well defined yet. Methods: We investigated 110 subjects (43 invasive squamous cell carcinoma [ISCC], 38 CIN Ill, II CIN II, 18 CIN I) confirmed to be positive for HPV 16 and/or 18 as well as 20 normal cervical tissue (NCT) samples for abnormal expression of cyclin DJ, cyclin E, CDK4, cyclin inhibitors (p2Jwa/; p27, pI6/NK4A) and Ki-67 using immunohistochemistry and differential PCR techniques. Results: There was a significant increase in the expression of Ki-67, cyclin E, CDK4, pJ6/NK4A (p=0003, 0.001,0.001) and a significant decrease in p27K1P/ from NCT to ISCC (p=0.003). There was a significant correlation between altered expression of p27K1P I and p 161NK4A (pKIpl (ρ=0.011) in all studied groups In ISCC, there was significant relationship between standard clinico-pathological prognostic factors and high Ki-67 index, increased cyclin D J and cyclin E, reduced p2 7Kip / and p21 waf Conclusion: I) Aberrations involving p27K/P 1, cyclin E, CDK4 and pJ6/NK4A are considered early events in HPV 16 and IS-associated cervical carcinogenesis (CINI and lI), whereas cyclin DI aberrations are late events (CINIII and ISCC). 2) immunohistochemical tests for pJ61NK4A and cyclin E could help in early diagnosis of cervical carcinoma. 3) Only FIGO stage, cyclin DI, p27K1P1 and Ki-67 are independent prognostic factors that might help in predicting outcome of cervical cancer palients

  14. Determination of CaffeineIn Beverages: A Review

    Directory of Open Access Journals (Sweden)

    Igelige Gerald

    2014-08-01

    Full Text Available Caffeine is a well-known stimulant which is added as an ingredient to various carbonated soft drinks. Caffeine has drawn more attention due to its physiological effects beyond that of its stimulatory effect. Consumers are interested in knowing the exact amounts of caffeine existing in beverages. However, limited data exist, especially for store brand beverages. Therefore, it is pertinent to review the various methods that will effectively determine the caffeine contents in different carbonated drinks. HPLC, UV-Visible Spectrometry and Gas Chromatography are among the popular used methods.

  15. Antibacterial activity of caffeine against plant pathogenic bacteria.

    Science.gov (United States)

    Sledz, Wojciech; Los, Emilia; Paczek, Agnieszka; Rischka, Jacek; Motyka, Agata; Zoledowska, Sabina; Piosik, Jacek; Lojkowska, Ewa

    2015-01-01

    The objective of the present study was to evaluate the antibacterial properties of a plant secondary metabolite - caffeine. Caffeine is present in over 100 plant species. Antibacterial activity of caffeine was examined against the following plant-pathogenic bacteria: Ralstonia solanacearum (Rsol), Clavibacter michiganesis subsp. sepedonicus (Cms), Dickeya solani (Dsol), Pectobacterium atrosepticum (Pba), Pectobacterium carotovorum subsp. carotovorum (Pcc), Pseudomonas syringae pv. tomato (Pst), and Xanthomonas campestris subsp. campestris (Xcc). MIC and MBC values ranged from 5 to 20 mM and from 43 to 100 mM, respectively. Caffeine increased the bacterial generation time of all tested species and caused changes in cell morphology. The influence of caffeine on the synthesis of DNA, RNA and proteins was investigated in cultures of plant pathogenic bacteria with labelled precursors: [(3)H]thymidine, [(3)H]uridine or (14)C leucine, respectively. RNA biosynthesis was more affected than DNA or protein biosynthesis in bacterial cells treated with caffeine. Treatment of Pba with caffeine for 336 h did not induce resistance to this compound. Caffeine application reduced disease symptoms caused by Dsol on chicory leaves, potato slices, and whole potato tubers. The data presented indicate caffeine as a potential tool for the control of diseases caused by plant-pathogenic bacteria, especially under storage conditions. PMID:26307771

  16. Caffeine Content in Popular Energy Drinks and Energy Shots.

    Science.gov (United States)

    Attipoe, Selasi; Leggit, Jeffrey; Deuster, Patricia A

    2016-09-01

    The use of energy beverages is high among the general population and military personnel. Previous studies have reported discrepancies between the actual amount of caffeine in products and the amount of caffeine on stated labels. Thus, the purpose of this study was to examine the content of caffeine listed on the labels of various energy drinks and energy shots. Top-selling energy drinks (n = 9) and energy shots (n = 5) were purchased from retail stores. Three of each of the 14 products were purchased and analyzed for caffeine content by an independent laboratory. Of the 14 products tested, 5 did not provide caffeine amounts on their facts panel-of those, 3 listed caffeine as an ingredient and 2 listed caffeine as part of a proprietary blend. The remaining 9 (of 14) products stated the amounts of caffeine on their labels, all of which were within 15% of the amount indicated on the label. In this study, although the energy beverages that indicated the amount of caffeine it contained had values within ±15% of the amount listed on the label, a potentially acceptable range, this finding is not acceptable with regard to current labeling regulations, which require added ingredients to total 100%. PMID:27612347

  17. Caffeine Consumption and Sleep Quality in Australian Adults.

    Science.gov (United States)

    Watson, Emily J; Coates, Alison M; Kohler, Mark; Banks, Siobhan

    2016-01-01

    Caffeine is commonly consumed to help offset fatigue, however, it can have several negative effects on sleep quality and quantity. The aim of this study was to determine the relationship between caffeine consumption and sleep quality in adults using a newly validated caffeine food frequency questionnaire (C-FFQ). In this cross sectional study, 80 adults (M ± SD: 38.9 ± 19.3 years) attended the University of South Australia to complete a C-FFQ and the Pittsburgh Sleep Quality Index (PSQI). Caffeine consumption remained stable across age groups while the source of caffeine varied. Higher total caffeine consumption was associated with decreased time in bed, as an estimate of sleep time (r = -0.229, p = 0.041), but other PSQI variables were not. Participants who reported poor sleep (PSQI global score ≥ 5) consumed 192.1 ± 122.5 mg (M ± SD) of caffeine which was significantly more than those who reported good sleep quality (PSQI global score caffeine consumption data. The data suggests that shorter sleep is associated with greater caffeine consumption, and that consumption is greater in adults with reduced sleep quality. PMID:27527212

  18. Caffeine Intake May Modulate Inflammation Markers in Trained Rats

    Directory of Open Access Journals (Sweden)

    Rômulo Pillon Barcelos

    2014-04-01

    Full Text Available Caffeine is presented in many commercial products and has been proven to induce ergogenic effects in exercise, mainly related to redox status homeostasis, inflammation and oxidative stress-related adaptation mechanisms. However, most studies have mainly focused on muscle adaptations, and the role of caffeine in different tissues during exercise training has not been fully described. The aim of this study was therefore, to analyze the effects of chronic caffeine intake and exercise training on liver mitochondria functioning and plasma inflammation markers. Rats were divided into control, control/caffeine, exercise, and exercise/caffeine groups. Exercise groups underwent four weeks of swimming training and caffeine groups were supplemented with 6 mg/kg/day. Liver mitochondrial swelling and complex I activity, and plasma myeloperoxidase (MPO and acetylcholinesterase (AChE activities were measured. An anti-inflammatory effect of exercise was evidenced by reduced plasma MPO activity. Additionally, caffeine intake alone and combined with exercise decreased the plasma AChE and MPO activities. The per se anti-inflammatory effect of caffeine intake should be highlighted considering its widespread use as an ergogenic aid. Therefore, caffeine seems to interfere on exercise-induced adaptations and could also be used in different exercise-related health treatments.

  19. Thermochemical parameters of caffeine, theophylline, and xanthine

    Energy Technology Data Exchange (ETDEWEB)

    Ngo Tuan Cuong; Truong Ba Tai [Department of Chemistry, and Mathematical Modeling and Computational Science Center (LMCC), Katholieke Universiteit Leuven, B-3001 Leuven (Belgium); Vu Thi Thu Ha [Institute of Chemistry, Vietnam Academy of Science and Technology, Hanoi (Viet Nam); Minh Tho Nguyen, E-mail: minh.nguyen@chem.kuleuven.b [Department of Chemistry, and Mathematical Modeling and Computational Science Center (LMCC), Katholieke Universiteit Leuven, B-3001 Leuven (Belgium)

    2010-04-15

    Thermochemical parameters of caffeine 1, theophylline 2, xanthine 3, uracil, and imidazole derivatives are determined by quantum chemical calculations. Using the composite G3B3 method, the standard heat of formation of caffeine in the gaseous phase amounts to DELTA{sub f}H{sub g}{sup 0}(1)=-243+-8kJ.mol{sup -1}, which lends a support for the recent experimental value of -237.0 +- 2.5 kcal . mol{sup -1}. We also obtain DELTA{sub f}H{sub g}{sup 0}(2)=-232+-8kJ.mol{sup -1}andDELTA{sub f}H{sub g}{sup 0}(3)=-209+-8kJ.mol{sup -1}. The adiabatic ionization energies are IE{sub a}(1) = 7.9 eV, IE{sub a}(2) = 8.1 eV, and IE{sub a}(3) = 8.5 eV using B3LYP calculations. The enhanced ability of caffeine to eject electron, as compared to the parent compounds and cyclic components, is of interest with regard to its potential use as a corrosion inhibitor.

  20. Thermochemical parameters of caffeine, theophylline, and xanthine

    International Nuclear Information System (INIS)

    Thermochemical parameters of caffeine 1, theophylline 2, xanthine 3, uracil, and imidazole derivatives are determined by quantum chemical calculations. Using the composite G3B3 method, the standard heat of formation of caffeine in the gaseous phase amounts to ΔfHg0(1)=-243±8kJ.mol-1, which lends a support for the recent experimental value of -237.0 ± 2.5 kcal . mol-1. We also obtain ΔfHg0(2)=-232±8kJ.mol-1andΔfHg0(3)=-209±8kJ.mol-1. The adiabatic ionization energies are IEa(1) = 7.9 eV, IEa(2) = 8.1 eV, and IEa(3) = 8.5 eV using B3LYP calculations. The enhanced ability of caffeine to eject electron, as compared to the parent compounds and cyclic components, is of interest with regard to its potential use as a corrosion inhibitor.

  1. Association of the anxiogenic and alerting effects of caffeine with ADORA2A and ADORA1 polymorphisms and habitual level of caffeine consumption

    OpenAIRE

    Rogers, Peter John; Hohoff, Christa; Heatherley, Susan; Mullings, Emma; Maxfield, Peter; Evershed, Richard,; Deckert, Jürgen; Nutt, David

    2010-01-01

    Caffeine, a widely consumed adenosine A1 and A2A receptor antagonist, is valued as a psychostimulant, but it is also anxiogenic. An association between a variant within the ADORA2A gene (rs5751876) and caffeine-induced anxiety has been reported for individuals who habitually consume little caffeine. This study investigated whether this single nucleotide polymorphism (SNP) might also affect habitual caffeine intake, and whether habitual intake might moderate the anxiogenic effect of caffeine. ...

  2. Caffeine Abolishes the Ultraviolet-Induced REV3 Translesion Replication Pathway in Mouse Cells

    Directory of Open Access Journals (Sweden)

    Kouichi Yamada

    2011-11-01

    Full Text Available When a replicative DNA polymerase stalls upon encountering a photoproduct on the template strand, it is relieved by other low-processivity polymerase(s, which insert nucleotide(s opposite the lesion. Using an alkaline sucrose density gradient sedimentation technique, we previously classified this process termed UV-induced translesion replication (UV-TLS into two types. In human cancer cells or xeroderma pigmentosum variant (XP-V cells, UV-TLS was inhibited by caffeine or proteasome inhibitors. However, in normal human cells, the process was insensitive to these reagents. Reportedly, in yeast or mammalian cells, REV3 protein (a catalytic subunit of DNA polymerase ζ is predominantly involved in the former type of TLS. Here, we studied UV-TLS in fibroblasts derived from the Rev3-knockout mouse embryo (Rev3KO-MEF. In the wild-type MEF, UV-TLS was slow (similar to that of human cancer cells or XP-V cells, and was abolished by caffeine or MG-262. In 2 cell lines of Rev3KO-MEF (Rev3−/− p53−/−, UV-TLS was not observed. In p53KO-MEF, which is a strict control for Rev3KO-MEF, the UV-TLS response was similar to that of the wild-type. Introduction of the Rev3 expression plasmid into Rev3KO-MEF restored the UV-TLS response in selected stable transformants. In some transformants, viability to UV was the same as that in the wild-type, and the death rate was increased by caffeine. Our findings indicate that REV3 is predominantly involved in UV-TLS in mouse cells, and that the REV3 translesion pathway is suppressed by caffeine or proteasome inhibitors.

  3. Rising cyclin-CDK levels order cell cycle events.

    Directory of Open Access Journals (Sweden)

    Catherine Oikonomou

    Full Text Available BACKGROUND: Diverse mitotic events can be triggered in the correct order and time by a single cyclin-CDK. A single regulator could confer order and timing on multiple events if later events require higher cyclin-CDK than earlier events, so that gradually rising cyclin-CDK levels can sequentially trigger responsive events: the "quantitative model" of ordering. METHODOLOGY/PRINCIPAL FINDINGS: This 'quantitative model' makes predictions for the effect of locking cyclin at fixed levels for a protracted period: at low cyclin levels, early events should occur rapidly, while late events should be slow, defective, or highly variable (depending on threshold mechanism. We titrated the budding yeast mitotic cyclin Clb2 within its endogenous expression range to a stable, fixed level and measured time to occurrence of three mitotic events: growth depolarization, spindle formation, and spindle elongation, as a function of fixed Clb2 level. These events require increasingly more Clb2 according to their normal order of occurrence. Events occur efficiently and with low variability at fixed Clb2 levels similar to those observed when the events normally occur. A second prediction of the model is that increasing the rate of cyclin accumulation should globally advance timing of all events. Moderate (<2-fold overexpression of Clb2 accelerates all events of mitosis, resulting in consistently rapid sequential cell cycles. However, this moderate overexpression also causes a significant frequency of premature mitoses leading to inviability, suggesting that Clb2 expression level is optimized to balance the fitness costs of variability and catastrophe. CONCLUSIONS/SIGNIFICANCE: We conclude that mitotic events are regulated by discrete cyclin-CDK thresholds. These thresholds are sequentially triggered as cyclin increases, yielding reliable order and timing. In many biological processes a graded input must be translated into discrete outputs. In such systems, expression of

  4. Effects of remifentanil on intracellular Ca2+ and its transients induced by electrical stimulation and caffeine in rat ventricular myocytes

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ye; Michael G. Irwin; LI Rui; CHEN Zhiwu; Tak-Ming Wong

    2009-01-01

    Background Preconditioning with remifentanil confers cardioprotection. Since Ca2+ overload is a precipitating factor of injury, we determined the effects of remefentanil on intracellular Ca2+ ([Ca2+]I) and its transients induced by electrical stimulation and caffeine, which reflects Ca2+ handling by Ca2+ handling proteins, in rat ventricular myocytes. Methods Freshly isolated adult male Sprague-Dawley rat myocytes were loaded with Fura-2/AM and [Ca]I was determined by spectrofluorometry. Remifentanil at 0.1-1000 μg/L was administered. Ten minutes after administration, either 0.2 Hz electrical stimulation was applied or 10 mmol/L caffeine was added. The [Ca2+]I, and the amplitude, time resting and 50% decay (t50) of both transients induced by electrical stimulation (E[Ca2+]I) and caffeine (C[Ca2+]I) were determined.Results Remifentanil (0.1-1000.0 μg/L) decreased the [Ca2+]I in a dose-dependent manner. It also decreased the amplitude of both transients dose-dependently. Furthermore, it increased the time to peak and t50 of both transients dose-dependently.Conclusion Remifentanil reduced the [Ca2+]I and suppressed the transients induced by electrical stimulation and caffeine in rat ventricular myocytes.

  5. Energy drink consumption and impact on caffeine risk.

    Science.gov (United States)

    Thomson, Barbara M; Campbell, Donald M; Cressey, Peter; Egan, Ursula; Horn, Beverley

    2014-01-01

    The impact of caffeine from energy drinks occurs against a background exposure from naturally occurring caffeine (coffee, tea, cocoa and foods containing these ingredients) and caffeinated beverages (kola-type soft drinks). Background caffeine exposure, excluding energy drinks, was assessed for six New Zealand population groups aged 15 years and over (n = 4503) by combining concentration data for 53 caffeine-containing foods with consumption information from the 2008/09 New Zealand Adult Nutrition Survey (ANS). Caffeine exposure for those who consumed energy drinks (n = 138) was similarly assessed, with inclusion of energy drinks. Forty-seven energy drink products were identified on the New Zealand market in 2010. Product volumes ranged from 30 to 600 ml per unit, resulting in exposures of 10-300 mg caffeine per retail unit consumed. A small percentage, 3.1%, of New Zealanders reported consuming energy drinks, with most energy drink consumers (110/138) drinking one serving per 24 h. The maximum number of energy drinks consumed per 24 h was 14 (total caffeine of 390 mg). A high degree of brand loyalty was evident. Since only a minor proportion of New Zealanders reported consuming energy drinks, a greater number of New Zealanders exceeded a potentially adverse effect level (AEL) of 3 mg kg(-1) bw day(-1) for caffeine from caffeine-containing foods than from energy drinks. Energy drink consumption is not a risk at a population level because of the low prevalence of consumption. At an individual level, however, teenagers, adults (20-64 years) and females (16-44 years) were more likely to exceed the AEL by consuming energy drinks in combination with caffeine-containing foods. PMID:25010189

  6. Cytochrome P450-dependent metabolism of caffeine in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Alexandra Coelho

    Full Text Available Caffeine (1, 3, 7-trimethylxanthine, an alkaloid produced by plants, has antioxidant and insecticide properties that can affect metabolism and cognition. In vertebrates, the metabolites derived from caffeine have been identified, and their functions have been characterized. However, the metabolites of caffeine in insects remain unknown. Thus, using radiolabelled caffeine, we have identified some of the primary caffeine metabolites produced in the body of Drosophila melanogaster males, including theobromine, paraxanthine and theophylline. In contrast to mammals, theobromine was the predominant metabolite (paraxanthine in humans; theophylline in monkeys; 1, 3, 7-trimethyluric acid in rodents. A transcriptomic screen of Drosophila flies exposed to caffeine revealed the coordinated variation of a large set of genes that encode xenobiotic-metabolizing proteins, including several cytochromes P450s (CYPs that were highly overexpressed. Flies treated with metyrapone--an inhibitor of CYP enzymes--showed dramatically decreased caffeine metabolism, indicating that CYPs are involved in this process. Using interference RNA genetic silencing, we measured the metabolic and transcriptomic effect of three candidate CYPs. Silencing of CYP6d5 completely abolished theobromine synthesis, whereas CYP6a8 and CYP12d1 silencing induced different consequences on metabolism and gene expression. Therefore, we characterized several metabolic products and some enzymes potentially involved in the degradation of caffeine. In conclusion, this pioneer approach to caffeine metabolism in insects opens novel perspectives for the investigation of the physiological effects of caffeine metabolites. It also indicates that caffeine could be used as a biomarker to evaluate CYP phenotypes in Drosophila and other insects.

  7. Caffeine triggers behavioral and neurochemical alterations in adolescent rats.

    Science.gov (United States)

    Ardais, A P; Borges, M F; Rocha, A S; Sallaberry, C; Cunha, R A; Porciúncula, L O

    2014-06-13

    Caffeine is the psychostimulant most consumed worldwide but concerns arise about the growing intake of caffeine-containing drinks by adolescents since the effects of caffeine on cognitive functions and neurochemical aspects of late brain maturation during adolescence are poorly known. We now studied the behavioral impact in adolescent male rats of regular caffeine intake at low (0.1mg/mL), moderate (0.3mg/mL) and moderate/high (1.0mg/mL) doses only during their active period (from 7:00 P.M. to 7:00 A.M.). All tested doses of caffeine were devoid of effects on locomotor activity, but triggered anxiogenic effects. Caffeine (0.3 and 1mg/mL) improved the performance in the object recognition task, but the higher dose of caffeine (1.0mg/mL) decreased the habituation to an open-field arena, suggesting impaired non-associative memory. All tested doses of caffeine decreased the density of glial fibrillary acidic protein and synaptosomal-associated protein-25, but failed to modify neuron-specific nuclear protein immunoreactivity in the hippocampus and cerebral cortex. Caffeine (0.3-1mg/mL) increased the density of brain-derived neurotrophic factor (BDNF) and proBDNF density as well as adenosine A1 receptor density in the hippocampus, whereas the higher dose of caffeine (1mg/mL) increased the density of proBDNF and BDNF and decreased A1 receptor density in the cerebral cortex. These findings document an impact of caffeine consumption in adolescent rats with a dual impact on anxiety and recognition memory, associated with changes in BDNF levels and decreases of astrocytic and nerve terminal markers without overt neuronal damage in hippocampal and cortical regions. PMID:24726984

  8. Optimization of luminescent assay for screening of cyclin-dependent kinase 2 inhibitors

    Directory of Open Access Journals (Sweden)

    Suthar M

    2010-01-01

    Full Text Available Cyclin-dependent kinases are most extensively studied targets for cancer chemotherapy since the tumor cells exhibit false checkpoints and can proliferate even if the genome is compromised. Cyclin-dependent kinases ensure the tight regulation of the cell cycle execution by mediating phosphorylation of cellular proteins. Deregulation of the cyclin-dependent kinase 2 activity by cellular and external factors leads to many diseases like cancers. Different methods like radiolabeled, fluorescence and luminescence are available for screening of library of compounds against kinases. However, bioluminescent methods offer several advantages like low background and no effect of fluorescent compound interference. Present study is focused on development, optimization and validation of cyclin-dependent kinase 2 assay which is suitable for identification potent and selective, ATP competitive and non-competitive inhibitors of cyclin-dependent kinase 2. The aim of present investigation was to optimize the assay for cyclin-dependent kinase 2/cylin A and cyclin-dependent kinase 2/cyclin E with use of bioluminescence based biochemical reaction. Both cyclin-dependent kinase 2 which are cyclin-dependent kinase 2/cyclin A and cyclin-dependent kinase 2/cyclin E complexes, have different affinity for ATP. Therefore, both isoform analogs of cyclin-dependent kinase 2 were optimized separately. Optimum cyclin-dependent kinase 2/cyclin A and cyclin-dependent kinase 2/cyclin E concentration were found to be 250 ng/well and 200 ng/well, respectively. Optimum substrate (histone H1 concentration was found to be 2.5 mg/ml for both cyclin-dependent kinase 2 analogs. Optimum reaction time was found to be 20 min for both cyclin-dependent kinase 2/cyclin complexes.

  9. The effect of caffeine on p53-dependent radioresponses in undifferentiated mouse embryonal carcinoma cells after X-ray and UV-irradiations

    International Nuclear Information System (INIS)

    The effect of caffeine was studied on the radioresponses of undifferentiated mouse embryonal carcinoma cells (EC cells) with or without the functional p53. The radioresponses studied included radiosensitivity, the activation of p53, apoptosis with characteristic DNA ladder formation and cell cycle progression. An undifferentiated mouse EC cell line, ECA2, and a newly established p53-deficient EC cell line, p53δ, were used in the present study. The status of the p53 gene did not significantly affect the colony survivals of undifferentiated EC cells to X-rays and UV. Although a post-irradiation treatment with caffeine sensitized both lines to X-rays marginally, the sensitization was prominent for UV regardless of the p53 status of the cells. The activation of a p53 responsible lacZ reporter construct was observed in stably transfected ECA2 cells after X-ray and UV irradiations. Caffeine suppressed the X-ray induced activation of the lacZ reporter, while it drastically enhanced the activation after UV irradiation. X-rays and UV readily triggered the apoptosis of ECA2 cells with the characteristic DNA ladder. Although UV-induced DNA ladder formation was enhanced by caffeine, that induced by X-rays was unaffected. Therefore, the effects of caffeine on the p53-dependent radioresponses were found to be agent specific: suppression for the X-ray induced and augmentation for the UV induced. In contrast to p53-proficient ECA2 cells, smear-like DNA degradation was observed for irradiated p53δ cells, suggesting the presence of a mode of cell death without DNA ladder formation. UV induction of the smear-like DNA degradation was enhanced in the presence of caffeine. Regardless of the state of the p53 gene, G1/S arrest was not observed in X-ray and UV irradiated EC cells. X-rays induced G2/M arrest in both lines, which was abrogated by caffeine, while G2/M arrest after UV was unaffected by a caffeine treatment. These results indicate that the radioresponses of undifferentiated

  10. Caffeine and human DNA metabolism: the magic and the mystery

    International Nuclear Information System (INIS)

    The ability of caffeine to reverse cell cycle checkpoint function and enhance genotoxicity after DNA damage was examined in telomerase-expressing human fibroblasts. Caffeine reversed the ATM-dependent S and G2 checkpoint responses to DNA damage induced by ionizing radiation (IR), as well as the ATR- and Chk1-dependent S checkpoint response to ultraviolet radiation (UVC). Remarkably, under conditions in which IR-induced G2 delay was reversed by caffeine, IR-induced G1 arrest was not. Incubation in caffeine did not increase the percentage of cells entering the S phase 6-8 h after irradiation; ATM-dependent phosphorylation of p53 and transactivation of p21Cip1/Waf1 post-IR were resistant to caffeine. Caffeine alone induced a concentration- and time-dependent inhibition of DNA synthesis. It inhibited the entry of human fibroblasts into S phase by 70-80% regardless of the presence or absence of wildtype ATM or p53. Caffeine also enhanced the inhibition of cell proliferation induced by UVC in XP variant fibroblasts. This effect was reversed by expression of DNA polymerase η, indicating that translesion synthesis of UVC-induced pyrimidine dimers by DNA pol η protects human fibroblasts against UVC genotoxic effects even when other DNA repair functions are compromised by caffeine

  11. Fast inhibition of glutamate-activated currents by caffeine.

    Directory of Open Access Journals (Sweden)

    Nicholas P Vyleta

    Full Text Available BACKGROUND: Caffeine stimulates calcium-induced calcium release (CICR in many cell types. In neurons, caffeine stimulates CICR presynaptically and thus modulates neurotransmitter release. METHODOLOGY/PRINCIPAL FINDINGS: Using the whole-cell patch-clamp technique we found that caffeine (20 mM reversibly increased the frequency and decreased the amplitude of miniature excitatory postsynaptic currents (mEPSCs in neocortical neurons. The increase in mEPSC frequency is consistent with a presynaptic mechanism. Caffeine also reduced exogenously applied glutamate-activated currents, confirming a separate postsynaptic action. This inhibition developed in tens of milliseconds, consistent with block of channel currents. Caffeine (20 mM did not reduce currents activated by exogenous NMDA, indicating that caffeine block is specific to non-NMDA type glutamate receptors. CONCLUSIONS/SIGNIFICANCE: Caffeine-induced inhibition of mEPSC amplitude occurs through postsynaptic block of non-NMDA type ionotropic glutamate receptors. Caffeine thus has both pre and postsynaptic sites of action at excitatory synapses.

  12. Design, formulation and evaluation of caffeine chewing gum

    Directory of Open Access Journals (Sweden)

    Abolfazl Aslani

    2013-01-01

    Conclusion: In this study, 20 and 50 mg caffeine gums with suitable and desirable properties (i.e., good taste and satisfactory release were formulated. The best flavor for caffeine gum was cinnamon. Both kinds of 20 and 50 mg gums succeeded in content uniformity test.

  13. Caffeine. Courseware Evaluation for Vocational and Technical Education.

    Science.gov (United States)

    Ohio State Univ., Columbus. National Center for Research in Vocational Education.

    This courseware evaluation rates the "Caffeine" program developed by Lane Community College and sold by the Oregon Department of Education. (The program--not included in this document--is part of a computer-assisted instruction project with nursing applications.) Part A describes "Caffeine" in terms of topics (food and nutrition, allied health)…

  14. International society of sports nutrition position stand: caffeine and performance.

    Science.gov (United States)

    Goldstein, Erica R; Ziegenfuss, Tim; Kalman, Doug; Kreider, Richard; Campbell, Bill; Wilborn, Colin; Taylor, Lem; Willoughby, Darryn; Stout, Jeff; Graves, B Sue; Wildman, Robert; Ivy, John L; Spano, Marie; Smith, Abbie E; Antonio, Jose

    2010-01-01

    Position Statement: The position of The Society regarding caffeine supplementation and sport performance is summarized by the following seven points: 1.) Caffeine is effective for enhancing sport performance in trained athletes when consumed in low-to-moderate dosages (~3-6 mg/kg) and overall does not result in further enhancement in performance when consumed in higher dosages (>/= 9 mg/kg). 2.) Caffeine exerts a greater ergogenic effect when consumed in an anhydrous state as compared to coffee. 3.) It has been shown that caffeine can enhance vigilance during bouts of extended exhaustive exercise, as well as periods of sustained sleep deprivation. 4.) Caffeine is ergogenic for sustained maximal endurance exercise, and has been shown to be highly effective for time-trial performance. 5.) Caffeine supplementation is beneficial for high-intensity exercise, including team sports such as soccer and rugby, both of which are categorized by intermittent activity within a period of prolonged duration. 6.) The literature is equivocal when considering the effects of caffeine supplementation on strength-power performance, and additional research in this area is warranted. 7.) The scientific literature does not support caffeine-induced diuresis during exercise, or any harmful change in fluid balance that would negatively affect performance. PMID:20205813

  15. International society of sports nutrition position stand: caffeine and performance

    Directory of Open Access Journals (Sweden)

    Wildman Robert

    2010-01-01

    Full Text Available Abstract Position Statement: The position of The Society regarding caffeine supplementation and sport performance is summarized by the following seven points: 1. Caffeine is effective for enhancing sport performance in trained athletes when consumed in low-to-moderate dosages (~3-6 mg/kg and overall does not result in further enhancement in performance when consumed in higher dosages (≥ 9 mg/kg. 2. Caffeine exerts a greater ergogenic effect when consumed in an anhydrous state as compared to coffee. 3. It has been shown that caffeine can enhance vigilance during bouts of extended exhaustive exercise, as well as periods of sustained sleep deprivation. 4. Caffeine is ergogenic for sustained maximal endurance exercise, and has been shown to be highly effective for time-trial performance. 5. Caffeine supplementation is beneficial for high-intensity exercise, including team sports such as soccer and rugby, both of which are categorized by intermittent activity within a period of prolonged duration. 6. The literature is equivocal when considering the effects of caffeine supplementation on strength-power performance, and additional research in this area is warranted. 7. The scientific literature does not support caffeine-induced diuresis during exercise, or any harmful change in fluid balance that would negatively affect performance.

  16. Structural features of DNA interaction with caffeine and theophylline

    Science.gov (United States)

    Nafisi, Shohreh; Manouchehri, Firouzeh; Tajmir-Riahi, Heidar-Ali; Varavipour, Maryam

    2008-03-01

    Caffeine and theophylline are strong antioxidants that prevent DNA damage. The anticancer and antiviral activities of these natural products are implicated in their mechanism of actions. However, there has been no information on the interactions of these xanthine derivatives with individual DNA at molecular level. The aim of this study was to examine the stability and structural features of calf-thymus DNA complexes with caffeine and theophylline in aqueous solution, using constant DNA concentration (6.25 mM) and various caffeine or theophylline/DNA(P) ratios of 1/80, 1/40, 1/20, 1/10, 1/5, 1/2 and 1/1. FTIR, UV-visible spectroscopic methods were used to determine the ligand external binding modes, the binding constant and the stability of caffeine, theophylline-DNA complexes in aqueous solution. Spectroscopic evidence showed that the complexation of caffeine and theophylline with DNA occurred via G-C and A-T and PO 2 group with overall binding constants of K(caffeine-DNA) = 9.7 × 10 3 M -1 and K(theophylline-DNA) = 1.7 × 10 4 M -1. The affinity of ligand-DNA binding is in the order of theophylline > caffeine. A partial B to A-DNA transition occurs upon caffeine and theophylline complexation.

  17. Low-dose caffeine physical dependence in humans.

    Science.gov (United States)

    Griffiths, R R; Evans, S M; Heishman, S J; Preston, K L; Sannerud, C A; Wolf, B; Woodson, P P

    1990-12-01

    This study investigated the effects of terminating low dose levels of caffeine (100 mg/day) in 7 normal humans. Substitution of placebo capsules for caffeine capsules occurred under double-blind conditions while subjects rated various dimensions of their mood and behavior. In the first phase of the study, substitution of placebo for 12 consecutive days resulted in an orderly withdrawal syndrome in 4 subjects which peaked on days 1 or 2 and progressively decreased toward prewithdrawal levels over about 1 week. Data from the remaining three subjects provided no evidence of withdrawal. In the second phase of the study, the generality of the withdrawal effect was examined by repeatedly substituting placebo for 100 mg/day of caffeine for 1-day periods separated by an average of 9 days. Despite differences within and across subjects with respect to the presence, nature and magnitude of symptoms, each of the seven subjects demonstrated a statistically significant withdrawal effect. Although the phenomenon of caffeine withdrawal has been described previously, the present report documents that the incidence of caffeine withdrawal is higher (100% of subjects), the daily dose level at which withdrawal occurs is lower (roughly equivalent to the amount of caffeine in a single cup of strong brewed coffee or 3 cans of caffeinated soft drink) and the range of symptoms experienced is broader (including headache, fatigue and other dysphoric mood changes, muscle pain/stiffness, flu-like feelings, nausea/vomiting and craving for caffeine) than heretofore recognized. PMID:2262896

  18. Influence of caffeine and caffeine withdrawal on headache and cerebral blood flow velocities

    NARCIS (Netherlands)

    Couturier, EGM; Laman, DM; vanDuijn, MAJ; vanDuijn, H

    1997-01-01

    Caffeine consumption may cause headache, particularly migraine. Its withdrawal also produces headaches and may be related to weekend migraine attacks. Transcranial Doppler sonography (TCD) has shown changes in cerebral blood flow velocities (BFV) during and between attacks of migraine. In order to e

  19. Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization

    DEFF Research Database (Denmark)

    Petersen, B O; Lukas, J; Sørensen, Claus Storgaard;

    1999-01-01

    CDKs. CDC6 interacts specifically with the active Cyclin A/CDK2 complex in vitro and in vivo, but not with Cyclin E or Cyclin B kinase complexes. The cyclin binding domain of CDC6 was mapped to an N-terminal Cy-motif that is similar to the cyclin binding regions in p21(WAF1/SDI1) and E2F-1. The in vivo...... relocalizes to the cytoplasm when Cyclin A/CDK2 is activated. In agreement with CDC6 phosphorylation being specifically mediated by Cyclin A/CDK2, we show that ectopic expression of Cyclin A, but not of Cyclin E, leads to rapid relocalization of CDC6 from the nucleus to the cytoplasm. Based on our data we...... suggest that the phosphorylation of CDC6 by Cyclin A/CDK2 is a negative regulatory event that could be implicated in preventing re-replication during S phase and G2....

  20. Xenopus oocyte maturation does not require new cyclin synthesis

    OpenAIRE

    1991-01-01

    Progesterone induces fully grown, stage VI, Xenopus oocytes to pass through meiosis I and arrest in metaphase of meiosis II. Protein synthesis is required twice in this process: in order to activate maturation promoting factor (MPF) which induces meiosis I, and then again after the completion of meiosis I to reactivate MPF in order to induce meiosis II. We have used antisense oligonucleotides to destroy maternal stores of cyclin mRNAs, and demonstrate that new cyclin synthesis is not required...

  1. Cyclin-dependent kinase Inhibitors Inspired by Roscovitine: Purine Bioisosteres

    Czech Academy of Sciences Publication Activity Database

    Jorda, Radek; Paruch, K.; Kryštof, Vladimír

    2012-01-01

    Roč. 18, č. 20 (2012), s. 2974-2980. ISSN 1381-6128 R&D Projects: GA ČR GAP305/12/0783 Institutional research plan: CEZ:AV0Z50380511 Keywords : Cancer * cyclin-dependent kinase * inhibitor Subject RIV: ED - Physiology Impact factor: 3.311, year: 2012 http://www.benthamdirect.org/pages/article/1/3177382/cyclin-dependent-kinase-inhibitors-inspired-by-roscovitine-purine-bioisosteres.html

  2. Beverages of Daily Life: Impact of Caffeine on Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Dr. Anna Vittoria Mattioli

    2014-08-01

    Full Text Available In recent years, clinical and observational studies reported that caffeine consumption was associated with cardiac arrhythmias, affected heart rate variability, and subsequently increased cardiovascular risk. The analysis of these paper shows that data are controversial and strongly depends on methodology. Moderate intake of caffeine seems to have protective effects on arrhythmias, on contrary high intake of caffeine seems to be associated with increased risk of atrial fibrillation. There is a deep difference when we analysed intake of caffeine from coffee compared to other sources. In very recent time an increase in caffeinated beverages, namely energy drinks, has been reported in young people and several arrhythmic complications has been observed. A review of literature is presented

  3. Effects of caffeine or maternal repair systems in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Drosophila melanogaster females were treated with 1% caffeine, mated with X-rayed males and the frequencies of induced sex-chromosome loss, translocations between the major autosomes and between the Y-chromosome and the major autosomes determined. In a reversal of the results obtained previously with 0.2% caffeine by Mendelson and Sobels, treatment of females with 1% caffeine led to a decrease in sex-chromosome loss, confirming preliminary data of Zimmering and Osgood and in increase in autosome-autosome translocations. It is suggested that the higher concentration of caffeine inhibits replication permitting more time available for chromosome-type restitutions by means of caffeine-insensitive repair mechanisms. In contrast with results for autosome-autosome translocation, the fequency of Y-autosome translocations was depressed below controls suggesting an isolation (by any one of several means) of Y-chromosome breaks from those in the autosomes. (Auth.)

  4. [Study on interaction of caffeine with myoglobin by fluorescence spectroscopy].

    Science.gov (United States)

    Huang, He-Yong; Gu, Xiao-Tian; Ding, Yan; Zhou, Jia-Hong; Feng, Yu-Ying

    2009-10-01

    The interaction of caffein and myoglobin was investigated by fluorescence spectroscopy and synchronous fluorescence spectroscopy. The intrinsic fluorescence of myoglobin was significantly quenched by caffein under the physiological condition (pH 7.4). The results indicated that caffeine was capable of binding with myoglobin to form a 1:1 complex and the quenching mechanism of myoglobin affected by caffeine was shown to be a static quenching procedure by calculating quenching constant, binding sites and binding constant. According to the thermodynamic parameters, the main binding force of the interaction is electrostatic force and hydrophobic force. The change in the micro-circumstance of aminos of myoglobin was analyzed by synchronous fluorescence spectrometry. The result indicated that caffeine can change the conformation of the protein, leading to the change in the micro-environment of tryptophane and tyrosine residues from hydrophobic environment to hydrophilic environment to different extent. PMID:20038063

  5. Caffeinated Energy Drinks -- A Growing Problem

    OpenAIRE

    Reissig, Chad J.; Strain, Eric C.; Griffiths, Roland R.

    2008-01-01

    Since the introduction of Red Bull in Austria in 1987 and in the United States in 1997, the energy drink market has grown exponentially. Hundreds of different brands are now marketed, with caffeine content ranging from a modest 50 mg to an alarming 505 mg per can or bottle. Regulation of energy drinks, including content labeling and health warnings differs across countries, with some of the most lax regulatory requirements in the U.S. The absence of regulatory oversight has resulted in aggres...

  6. Genome-Wide Analysis of the Cyclin Gene Family in Tomato

    Directory of Open Access Journals (Sweden)

    Tingyan Zhang

    2013-12-01

    Full Text Available Cyclins play important roles in cell division and cell expansion. They also interact with cyclin-dependent kinases to control cell cycle progression in plants. Our genome-wide analysis identified 52 expressed cyclin genes in tomato. Phylogenetic analysis of the deduced amino sequences of tomato and Arabidopsis cyclin genes divided them into 10 types, A-, B-, C-, D-, H-, L-, T-, U-, SDS- and J18. Pfam analysis indicated that most tomato cyclins contain a cyclin-N domain. C-, H- and J18 types only contain a cyclin-C domain, and U-type cyclins contain another potential cyclin domain. All of the cyclin genes are distributed throughout the tomato genome except for chromosome 8, and 30 of them were found to be segmentally duplicated; they are found on the duplicate segments of chromosome 1, 2, 3, 4, 5, 6, 10, 11 and 12, suggesting that tomato cyclin genes experienced a mass of segmental duplication. Quantitative real-time polymerase chain reaction analysis indicates that the expression patterns of tomato cyclin genes were significantly different in vegetative and reproductive stages. Transcription of most cyclin genes can be enhanced or repressed by exogenous application of gibberellin, which implies that gibberellin maybe a direct regulator of cyclin genes. The study presented here may be useful as a guide for further functional research on tomato cyclins.

  7. Modifying effect of caffeine on lethality and mutability of Chlamydomonas reinhardii cells following UV irradiation

    International Nuclear Information System (INIS)

    The modifying effect of caffeine was studied using two standard and two UV-sensitive strains of Chlamydomonas reinhardii Dang. Cell survival and mutation frequency was microscopically evaluated on media without caffeine and on media with 1.5 mM of caffeine. The obtained results were indicative of the stimulating effect of caffeine upon survival in all strains. (author)

  8. Replicative bypass repair of ultraviolet damage to DNA of mammalian cells: caffeine sensitive and caffeine resistant mechanism

    International Nuclear Information System (INIS)

    Replicative bypass repair of UV damage to DNA was studied in a wide variaty of human, mouse and hamster cells in culture. Survival curve analysis revealed that in established cell lines (mouse L, Chinese hamster V79, HeLa S3 and SV40-transformed xeroderma pigmentosum (XP), post-UV caffeine treatment potentiated cell killing by reducing the extrapolation number and mean lethal UV fluence (Do). In the Do reduction as the result of random inactivation by caffeine of sensitive repair there were marked clonal differences among such cell lines, V79 being most sensitive to caffeine potentiation. However, other diploid cell lines (normal human, excision-defective XP and Syrian hamster) exhibited no obvious reduction in Do by caffeine. In parallel, alkaline sucrose sedimentation results showed that the conversion of initially smaller segments of DNA synthesized after irradiation with 10 J/m2 to high-molecular-weight DNA was inhibited by caffeine in transformed XP cells, but not in the diploid human cell lines. Exceptionally, diploid XP variants had a retarded ability of bypass repair which was drastically prevented by caffeine, so that caffeine enhanced the lethal effect of UV. Neutral CsCl study on the bypass repair mechanism by use of bromodeoxyuridine for DNA synthesis on damaged template suggests that the pyrimodine dimer acts as a block to replication and subsequently it is circumvented presumably by a new process involving replicative bypassing following strand displacement, rather than by gap-filling de novo. This mechanism worked similarly in normal and XP cells, whether or not caffeine was present, indicating that excision of dimer is not always necessary. However, replicative bypassing became defective in XP variant and transformed XP cells when caffeine was present. It appears, therefore, that the replicative bypass repair process is either caffeine resistant or sensitive, depending on the cell type used, but not necessarily on the excision repair capability

  9. Caffeine Content Labeling: A Missed Opportunity for Promoting Personal and Public Health

    OpenAIRE

    Kole, Jon; Barnhill, Anne

    2013-01-01

    Current regulation of caffeine-containing products is incoherent, fails to protect consumers' interests, and should be modified in multiple ways. We make the case for one of the regulatory reforms that are needed: all consumable products containing added caffeine should be required by the Food and Drug Administration (FDA) to include caffeine quantity on their labels. Currently, no foods or beverages that contain caffeine are required to include caffeine content on their labels. Strengthening...

  10. The Relationship of Caffeine Intake with Depression, Anxiety, Stress, and Sleep in Korean Adolescents

    OpenAIRE

    Jin, Mi-Joo; Yoon, Chang-Ho; Ko, Hae-Jin; Kim, Hyo-Min; Kim, A-Sol; Moon, Ha-Na; Jung, Seung-Pi

    2016-01-01

    Background In various studies in adults, caffeine may increase wakefulness and relieve pain, but caffeine overdose can cause many adverse serious effects on health. Caffeine intake has recently been increasing in adolescents. In spite of importance of caffeine effects on Korean adolescents, there are lack of scientific and systematic studies. The purpose of our study was to identify the relationship between caffeine consumption and effects on adolescents. Methods We performed study on 234 mid...

  11. Influence of drug concentration on the diffusion parameters of caffeine

    Directory of Open Access Journals (Sweden)

    R Ben Mustapha

    2011-01-01

    Full Text Available Background and Objectives : In the fields of the pharmaceutical and cosmetic industries and in toxicology, the study of the skin penetration of molecules is very interesting. Various studies have considered the impact of different physicochemical drug characteristics, skin thickness, and formulations, on the transition from the surface of the skin to the underlying tissues or to the systemic circulation; however, the influence of drug concentration on the permeation flux of molecules has rarely been raised. Our study aims to discover the influence of caffeine concentration in a formulation on the percutaneous penetration from gels, as a result of different dose applications to polysulfate membrane and human skin. Materials and Methods : For this purpose, three identical base gels were used at 1, 3, and 5% of caffeine, to evaluate the effect of the concentration of caffeine on in vitro release through the synthetic membrane and ex vivo permeation through the human skin, using diffusion Franz TM cells. Results : The diffusion through the epidermal tissue was significantly slower than through the synthetic membrane, which recorded an increase of flux with an increase in the concentration of caffeine. The skin permeation study showed that diffusion depended not only on the concentration, but also on the deposited amount of gel. Nevertheless, for the same amount of caffeine applied, the flux was more significant from the less concentrated gel. Conclusion : Among all the different concentrations of caffeine examined, 1% gel of caffeine applied at 5 mg / cm 2 showed the highest absorption characteristics across human skin.

  12. Radioprotective and antioxidant action of caffeine: mechanistic considerations

    International Nuclear Information System (INIS)

    Caffeine, a major constituent of coffee and other beverages has significant abilities to scavenge highly reactive free radicals and excited states of oxygen and to protect crucial biological molecules against these species. This is one of the possible reasons why caffeine acts as a radioprotector against oxygen-dependent (oxic) pathway of radiation damage and as an anti mutagen/anti carcinogen under certain conditions. The possible physicochemical and molecular mechanisms of caffeine action are briefly reviewed in the light of the recent finding. (author). 69 refs., 1 fig

  13. Evaluation of the central effects of alcohol and caffeine interaction.

    OpenAIRE

    Azcona, O; Barbanoj, M. J.; Torrent, J.; Jané, F

    1995-01-01

    1. The dynamic and kinetic interactions of alcohol and caffeine were studied in a double-blind, placebo controlled, cross-over trial. Treatments were administered to eight healthy subjects in four experimental sessions, leaving a 1 week wash-out period between each, as follows: 1) placebo, 2) alcohol (0.8 g kg-1), 3) caffeine (400 mg) and 4) alcohol (0.8 g kg-1) + caffeine (400 mg). 2. Evaluations were performed by means of: 1) objective measures: a) psychomotor performance (critical flicker ...

  14. Inhibitor of Cyclin-dependent Kinase (CDK) Interacting with Cyclin A1 (INCA1) Regulates Proliferation and Is Repressed by Oncogenic Signaling*

    OpenAIRE

    Bäumer, Nicole; Tickenbrock, Lara; Tschanter, Petra; Lohmeyer, Lisa; Diederichs, Sven; Bäumer, Sebastian; Skryabin, Boris V.; Zhang, Feng; Agrawal-Singh, Shuchi; Köhler, Gabriele; Berdel, Wolfgang E.; Serve, Hubert; Koschmieder, Steffen; Müller-Tidow, Carsten

    2011-01-01

    The cell cycle is driven by the kinase activity of cyclin·cyclin-dependent kinase (CDK) complexes, which is negatively regulated by CDK inhibitor proteins. Recently, we identified INCA1 as an interaction partner and a substrate of cyclin A1 in complex with CDK2. On a functional level, we identified a novel cyclin-binding site in the INCA1 protein. INCA1 inhibited CDK2 activity and cell proliferation. The inhibitory effects depended on the cyclin-interacting domain. Mitogenic and oncogenic sig...

  15. Cyclin D1, Id1 and EMT in breast cancer

    Directory of Open Access Journals (Sweden)

    Lehn Sophie

    2011-09-01

    Full Text Available Abstract Background Cyclin D1 is a well-characterised cell cycle regulator with established oncogenic capabilities. Despite these properties, studies report contrasting links to tumour aggressiveness. It has previously been shown that silencing cyclin D1 increases the migratory capacity of MDA-MB-231 breast cancer cells with concomitant increase in 'inhibitor of differentiation 1' (ID1 gene expression. Id1 is known to be associated with more invasive features of cancer and with the epithelial-mesenchymal transition (EMT. Here, we sought to determine if the increase in cell motility following cyclin D1 silencing was mediated by Id1 and enhanced EMT-features. To further substantiate these findings we aimed to delineate the link between CCND1, ID1 and EMT, as well as clinical properties in primary breast cancer. Methods Protein and gene expression of ID1, CCND1 and EMT markers were determined in MDA-MB-231 and ZR75 cells by western blot and qPCR. Cell migration and promoter occupancy were monitored by transwell and ChIP assays, respectively. Gene expression was analysed from publicly available datasets. Results The increase in cell migration following cyclin D1 silencing in MDA-MB-231 cells was abolished by Id1 siRNA treatment and we observed cyclin D1 occupancy of the Id1 promoter region. Moreover, ID1 and SNAI2 gene expression was increased following cyclin D1 knock-down, an effect reversed with Id1 siRNA treatment. Similar migratory and SNAI2 increases were noted for the ER-positive ZR75-1 cell line, but in an Id1-independent manner. In a meta-analysis of 1107 breast cancer samples, CCND1low/ID1high tumours displayed increased expression of EMT markers and were associated with reduced recurrence free survival. Finally, a greater percentage of CCND1low/ID1high tumours were found in the EMT-like 'claudin-low' subtype of breast cancer than in other subtypes. Conclusions These results indicate that increased migration of MDA-MB-231 cells following

  16. Cdh1-APC/C, cyclin B-Cdc2, and Alzheimer's disease pathology

    International Nuclear Information System (INIS)

    The anaphase-promoting complex/cyclosome (APC/C) is a key E3 ubiquitin ligase complex that functions in regulating cell cycle transitions in proliferating cells and has, as revealed recently, novel roles in postmitotic neurons. Regulated by its activator Cdh1 (or Hct1), whose level is high in postmitotic neurons, APC/C seems to have multiple functions at different cellular locations, modulating diverse processes such as synaptic development and axonal growth. These processes do not, however, appear to be directly connected to cell cycle regulation. It is now shown that Cdh1-APC/C activity may also have a basic role in suppressing cyclin B levels, thus preventing terminally differentiated neurons from aberrantly re-entering the cell cycle. The result of an aberrant cyclin B-induced S-phase entry, at least for some of these neurons, would be death via apoptosis. Cdh1 thus play an active role in maintaining the terminally differentiated, non-cycling state of postmitotic neurons-a function that could become impaired in Alzheimer's and other neurodegenerative diseases

  17. Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrial function

    OpenAIRE

    Wang, Chenguang; Li, Zhiping; Lu, Yinan; Du, Runlei; Katiyar, Sanjay; Yang, Jianguo; Fu, Maofu; Leader, Jennifer E.; Quong, Andrew; Novikoff, Phyllis M.; Pestell, Richard G

    2006-01-01

    Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. Herein, cyclin D1 deficiency increased mitochondrial size and activity that was rescued by cyclin D1 in a Cdk-dependent manner. Nuclear respiratory factor 1 (NRF-1), which induces nuclear-encoded mitochondrial genes, was repressed in expression and activity by cyclin D1. Cyclin D1-dependent kinase phosphorylates NRF-1 at S47. Cyclin D1 abundance thus coordinates nuclear DNA synthesis...

  18. Cyclin E Is Stabilized in Response to Replication Fork Barriers Leading to Prolonged S Phase Arrest*

    OpenAIRE

    Lu, Xiaoyan; Jia LIU; Legerski, Randy J.

    2009-01-01

    Cyclin E is a regulator of cyclin-dependent protein kinases (Cdks) and is involved in mediating the cell cycle transition from G1 to S phase. Here, we describe a novel function for cyclin E in the long term maintenance of checkpoint arrest in response to replication barriers. Exposure of cells to mitomycin C or UV irradiation, but not ionizing radiation, induces stabilization of cyclin E. Stabilization of cyclin E reduces the activity of Cdk2-cyclin A, resulting in a slowing of S phase progre...

  19. Cyclin D2 Protein Stability Is Regulated in Pancreatic β-Cells

    OpenAIRE

    He, Lu Mei; Sartori, Daniel J.; Teta, Monica; Opare-Addo, Lynn M.; Rankin, Matthew M.; Long, Simon Y.; Diehl, J. Alan; Kushner, Jake A.

    2009-01-01

    The molecular determinants of β-cell mass expansion remain poorly understood. Cyclin D2 is the major D-type cyclin expressed in β-cells, essential for adult β-cell growth. We hypothesized that cyclin D2 could be actively regulated in β-cells, which could allow mitogenic stimuli to influence β-cell expansion. Cyclin D2 protein was sharply increased after partial pancreatectomy, but cyclin D2 mRNA was unchanged, suggesting posttranscriptional regulatory mechanisms influence cyclin D2 expression...

  20. A conserved cyclin-binding domain determines functional interplay between anaphase-promoting complex-Cdh1 and cyclin A-Cdk2 during cell cycle progression

    DEFF Research Database (Denmark)

    Lukas, C; Kramer, E R; Peters, J M;

    2001-01-01

    how cyclin-CDKs interact with APC subunits remains unresolved. Here we substantiate the evidence that mammalian cyclin A-Cdk2 prevents unscheduled APC reactivation during S phase by demonstrating its periodic interaction with Cdh1 at the level of endogenous proteins. Moreover, we identified a...... conserved cyclin-binding motif within the Cdh1 WD-40 domain and show that its disruption abolished the Cdh1-cyclin A-Cdk2 interaction, eliminated Cdh1-associated histone H1 kinase activity, and impaired Cdh1 phosphorylation by cyclin A-Cdk2 in vitro and in vivo. Overexpression of cyclin binding......, these data provide a mechanistic explanation for the mutual functional interplay between cyclin A-Cdk2 and APC-Cdh1 and the first evidence that Cdh1 may activate the APC by binding specific substrates....

  1. Cigarette, alcohol, and caffeine consumption: risk factors for spontaneous abortion

    DEFF Research Database (Denmark)

    Rasch, Vibeke

    2003-01-01

    , and caffeine consumption was studied using logistic regression analyzes while controlling for confounding variables. In addition stratified analyzes of the association between caffeine consumption and spontaneous abortion on the basis of cigarette and alcohol consumption were performed. RESULTS: Women...... 375 mg or more caffeine per day were 4.84 (2.87-8.16) and 2.21 (1.53-3.18), respectively. Women who smoked 10-19 cigarettes and 20 or more cigarettes per day did not have significantly increased ORs for having spontaneous abortions, after adjusting for other risk factors. CONCLUSION: Consumption of 5...... or more units alcohol per week and 375 mg or more caffeine per day during pregnancy may increase the risk of spontaneous abortion....

  2. [Evaluation of liberation of caffeine from dermal semisolids drugs].

    Science.gov (United States)

    Kodadová, Alexandra; Vitková, Zuzana; Herdová, Petra

    2013-10-01

    The paper deals with formulation of caffeine into dermal semisolid dosage forms - hydrogels. Caffeine was chosen as a model drug because its properties can be successfully used just in hydrogels. Protective and tranquilization effects can be used in the preparations for sunbathing, and its lipolytic and regenerative effect can be used for the treatment of androgenic alopecia or cellular bioprotection. The aim of the study was to investigate the influence of different concentrations of chitosan and caffeine on the liberation of gels. Besides, stability of the prepared samples was evaluated by means of the evaluation of their rheological parameters. Based on the obtained results, there was determined the optimal drug concentration - caffeine 0.2% (w/w) and also the gel forming substance - chitosan 2.3% (w/w). PMID:24237472

  3. On the interaction of caffeine with nucleic acids. 4

    International Nuclear Information System (INIS)

    The DNA-caffeine interaction at high concentration of caffeine (Cf) leads to an arrangement of Cf molecules outside of the DNA double helix with an orientation parallel to the bases both in the A and B form as demonstrated by infrared linear dichroism. Addition of DNA broadens the 1H NMR lines of Cf in aqueous solution indicating a specific binding. Intercalation is not the predominant mechanism, the deuterium relaxation time T1 = (38 +- 7) ms and the estimated reorientation correlation time tausub(cb) = 0.17 ns of caffeine-8-[2H] in the Cf-DNA complex suggest an outside stacking of the ligand. According to the results a model on the DNA-Cf complex at high Cf concentration (binding process II) is suggested including the caffeine-induced reorientation of the hydration shell of DNA. (Auth.)

  4. Cigarette, alcohol, and caffeine consumption: risk factors for spontaneous abortion

    DEFF Research Database (Denmark)

    Rasch, Vibeke

    2003-01-01

    OBJECTIVE: To study the association between cigarette, alcohol, and caffeine consumption and the occurrence of spontaneous abortion. METHODS: The study population consisted of 330 women with spontaneous abortion and 1168 pregnant women receiving antenatal care. A case-control design was utilized......; cases were defined as women with a spontaneous abortion in gestational week 6-16 and controls as women with a live fetus in gestational week 6-16. The variables studied comprise age, parity, occupational situation, cigarette, alcohol, and caffeine consumption. The association between cigarette, alcohol......, and caffeine consumption was studied using logistic regression analyzes while controlling for confounding variables. In addition stratified analyzes of the association between caffeine consumption and spontaneous abortion on the basis of cigarette and alcohol consumption were performed. RESULTS: Women...

  5. Does caffeine alter muscle carbohydrate and fat metabolism during exercise?

    DEFF Research Database (Denmark)

    Graham, Terry E; Battram, Danielle S; Dela, Flemming;

    2008-01-01

    Caffeine, an adenosine receptor antagonist, has been studied for decades as a putative ergogenic aid. In the past 2 decades, the information has overwhelmingly demonstrated that it indeed is a powerful ergogenic aid, and frequently theories have been proposed that this is due to alterations in fat...... and carbohydrate metabolism. While caffeine certainly mobilizes fatty acids from adipose tissue, rarely have measures of the respiratory exchange ratio indicated an increase in fat oxidation. However, this is a difficult measure to perform accurately during exercise, and small changes could be.......05) glycogen and increased (p < 0.05) citrate, acetyl-CoA, and glucose-6-phosphate. The only effects of caffeine were to increase (p < 0.05) citrate in resting muscle and cAMP in exercise. There is very little evidence to support the hypothesis that caffeine has ergogenic effects as a result of enhanced fat...

  6. Assessing Caffeine as an Emerging Environmental Concern Using Conventional Approaches

    Science.gov (United States)

    Organic wastewater contaminants, including pharmaceuticals, caffeine, and nicotine, have received increased scrutiny because of their detection in water bodies receiving wastewater discharge. Despite recent measurement in US streams, caffeine’s effect on freshwater organisms is not well documented....

  7. Caffeine and cardiovascular diseases: critical review of current research.

    Science.gov (United States)

    Zulli, Anthony; Smith, Renee M; Kubatka, Peter; Novak, Jan; Uehara, Yoshio; Loftus, Hayley; Qaradakhi, Tawar; Pohanka, Miroslav; Kobyliak, Nazarii; Zagatina, Angela; Klimas, Jan; Hayes, Alan; La Rocca, Giampiero; Soucek, Miroslav; Kruzliak, Peter

    2016-06-01

    Caffeine is a most widely consumed physiological stimulant worldwide, which is consumed via natural sources, such as coffee and tea, and now marketed sources such as energy drinks and other dietary supplements. This wide use has led to concerns regarding the safety of caffeine and its proposed beneficial role in alertness, performance and energy expenditure and side effects in the cardiovascular system. The question remains "Which dose is safe?", as the population does not appear to adhere to the strict guidelines listed on caffeine consumption. Studies in humans and animal models yield controversial results, which can be explained by population, type and dose of caffeine and low statistical power. This review will focus on comprehensive and critical review of the current literature and provide an avenue for further study. PMID:26932503

  8. Couples' Pre-Pregnancy Caffeine Consumption Linked to Miscarriage Risk

    Science.gov (United States)

    ... couples or cumulative exposure to substances in the environment, which could be expected to increase as people age. Both male and female consumption of more than two caffeinated beverages a day ...

  9. The effect of caffeine on cerebral asymmetry in rats.

    Science.gov (United States)

    Voiculescu, M; Segarceanu, A; Negutu, M; Ghita, I; Fulga, I; Coman, O A

    2015-01-01

    EEG recordings reflect the gross electrical activity emanating from synaptic currents of individual neurons across large cortical areas. During periods of cortical activation, waking, and higher EEG frequencies, neurons display increased excitability and exhibit more asynchronous discharge. The activity of a number of subcortical neurotransmitter systems from several brain regions outside the thalamus can directly affect cortical activity patterns. These neurotransmitter systems are generally targets of pharmacological intervention or participate in neurological disease states. The EEG trace comprises 4 primary rhythms: alfa (α), beta (β), theta (θ) and delta (δ), which differ in frequency and amplitude. Caffeine effect on brain asymmetry will be studied in this work. The study was realized by means of Fourier spectral frequency analysis (Fast Fourier Transformation) of the EEG signal on anesthetized rats. All 3 doses of caffeine increased the global wave power of brain activity compared to the control group. All 3 doses of caffeine reduced the number of peaks for the 0.5-4 Hz frequency band, with the intermediate dose of caffeine having such an effect in the 4-7 Hz frequency band and the high dose of caffeine for the 23-33 Hz frequency band. The group that received high doses of caffeine showed an increase of the percentage of delta waves, with a concurrent decrease of the percentage of alpha1, alpha2, beta and theta 2 compared to the control group. Low-dose caffeine produced positive values of left-right difference in brain electrical activity (left predominance) for the 0.5-5 Hz and 7.8-10.3 Hz frequency intervals. The group that received high-dose caffeine exhibited a left hemisphere dominance for the 0.5-1.5 Hz; 13.9-14.1 Hz and 19-20 Hz frequency ranges while right dominance was present in the 1.7-13.9 Hz, 15-19 Hz and 21-25 Hz frequency ranges. In conclusion, all doses of caffeine modified the global power of the brain as well as the number of peaks on

  10. Influence of nicotine and caffeine on rat embryonic development

    OpenAIRE

    Nash, J. E.; Persaud, T.V.N.

    1988-01-01

    The influence on embryonic development of nicotine and caffeine at dose levels approximating human consumption was investigated in Sprague- Dawley rats. One group of animals received nicotine administered subcutaneously by an Alzet mini-osmotic pump from gestational day 6 through 12 (25 mg over 7 days; rate 149 pg/hr). Control animals received physiological saline in a similar manner. A second group received a single intravenous injection of caffeine (25 mg/ ...

  11. Skin delivery of caffeine contained in biofunctional textiles

    OpenAIRE

    Valldeperas Morell, José; Rubio, Laia; Alonso, Cristina; Coderch, Luisa; Parra, José Luis; Martí, Meritxell; Cebrián, Juan; Navarro Viciana, Juan Antonio; Lis Arias, Manuel José

    2010-01-01

    Biofunctional textiles are materials with new properties and added value. In this work, emphasis was placed on the release capacity of the active principle (caffeine) from the formulation or from the biofunctional textile. In addition, a new in vitro methodology of percutaneous absorption was designed to demonstrate the delivery of encapsulated caffeine from the biofunctional textile to the different skin layers. In the first step, permeation studies through a nylon membrane were performed an...

  12. Does acute caffeine ingestion alter brain metabolism in young adults?

    Science.gov (United States)

    Xu, Feng; Liu, Peiying; Pekar, James J; Lu, Hanzhang

    2015-04-15

    Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (pextraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain's response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine's effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors. PMID:25644657

  13. Severe acute caffeine poisoning due to intradermal injections: Mesotherapy hazard

    OpenAIRE

    Perković-Vukčević Nataša; Babić Gordana; Šegrt Zoran; Vuković-Ercegović Gordana; Janković Snežana; Aćimović Ljubomir

    2012-01-01

    Introduction. Caffeine is indicated in the treatment of migraine headaches, as well as neonatal apnea and bradycardia syndrome. In mild poisoning, the most prevalent symptoms are nausea, vomiting, diarrhea, tremor, anxiety and headache. In more severe cases, symptoms consist of heart rythym abnormalities, myocardial infarction and seizures. Due to its common lipolytic effect, caffeine is used in mesotherapy, usually in combination with drugs of similar effect. We presented a patient wit...

  14. Human coffee drinking: manipulation of concentration and caffeine dose.

    OpenAIRE

    Griffiths, R R; Bigelow, G E; Liebson, I A; O'Keeffe, M; O'Leary, D.; Russ, N

    1986-01-01

    In a residential research ward coffee drinking was studied in 9 volunteer human subjects with histories of heavy coffee drinking. A series of five experiments was undertaken to characterize adlibitum coffee consumption and to investigate the effects of manipulating coffee concentration, caffeine dose per cup, and caffeine preloads prior to coffee drinking. Manipulations were double-blind and scheduled in randomized sequences across days. When cups of coffee were freely available, coffee drink...

  15. Caffeine causes pulmonary hypertension syndrome (ascites) in broilers.

    Science.gov (United States)

    Kamely, M; Torshizi, M A Karimi; Rahimi, S; Wideman, R F

    2016-04-01

    Pulmonary hypertension syndrome (PHS), or ascites, is characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance accompanied by right ventricular hypertrophy (RVH) and fluid accumulation in the abdominal cavity. Experimental models are required for triggering PHS to study the pathogenesis of this syndrome and to select resistant genetic lines. Caffeine increases vascular resistance and promotes systemic hypertension in mammals, but a similar effect of caffeine on the pulmonary circulation had not previously been demonstrated. Two experiments were conducted to evaluate the impact of caffeine alone (Exp. 1) or in combination with cold temperature (Exp. 2) on parameters associated with PHS in young broiler chicks. In Exp. 1, 288 chicks were distributed among 24 pens and brooded at standard environmental temperatures, and on d 3 through 42 caffeine was added to the water at doses of 0 (control), 6.25, 12.5, 25, 50, and 100 mg/(kg BW·d). In Exp. 2, 192 chicks were distributed among 16 pens and brooded at cool environmental temperatures, and on d 3 through 42 caffeine was added to the water at doses of 0 (control), 15, 30, and 45 mg/(kg BW·d). In Exp. 1 caffeine administered at or above 12.5 mg/(kg BW·d) induced severe PHS and resulted in acute mortality and RVH ( broilers exposed to cold temperatures remarkably exhibited PHS incidences and developed RVH with right ventricular to total ventricular weight ratios of 30% or greater. Moreover, hematocrit significantly increased because of caffeine supplementation in cool ambient temperature ( = 0.002). Our data demonstrate that caffeine induces high incidences of PHS in broilers, which is exacerbated by exposure to low temperatures. PMID:27136008

  16. Multiple gustatory receptors required for the caffeine response in Drosophila

    OpenAIRE

    Lee, Youngseok; Moon, Seok Jun; Montell, Craig

    2009-01-01

    The ability of insects to detect and avoid ingesting naturally occurring repellents and insecticides is essential for their survival. Nevertheless, the gustatory receptors enabling them to sense toxic botanical compounds are largely unknown. The only insect gustatory receptor shown to be required for avoiding noxious compounds is the Drosophila caffeine receptor, Gr66a. However, this receptor is not sufficient for the caffeine response, suggesting that Gr66a may be a subunit of a larger recep...

  17. Influence of caffeine on blood pressure and platelet aggregation

    OpenAIRE

    2000-01-01

    OBJECTIVE: Studies have demonstrated that methylxanthines, such as caffeine, are A1 and A2 adenosine receptor antagonists found in the brain, heart, lungs, peripheral vessels, and platelets. Considering the high consumption of products with caffeine in their composition, in Brazil and throughout the rest of the world, the authors proposed to observe the effects of this substance on blood pressure and platelet aggregation. METHODS: Thirteen young adults, ranging from 21 to 27 years of age, par...

  18. Cloning of four cycling from maize indicates that higher plants have three structurally distinct groups of mitotic cyclins

    OpenAIRE

    Renaudin, J P; Colasanti, J; RIME, Hélène; Z. Yuan; Sundaresan, V.

    1994-01-01

    While a large number of cyclins have been described in animals and yeasts, very limited information is available regarding cyclins in plants. We describe here the isolation of cDNA clones encoding four putative mitotic cyclins from maize. All four cyclins were able to induce maturation of Xenopus oocytes, demonstrating that they can act as mitotic cyclins in this system. Northern analysis showed that all four cyclins were expressed only in actively dividing tissues and organs, with a stronger...

  19. Effect of caffeine on the vocal folds: a pilot study.

    Science.gov (United States)

    Akhtar, S; Wood, G; Rubin, J S; O'Flynn, P E; Ratcliffe, P

    1999-04-01

    Caffeine is considered to be a dehydrating agent with detrimental effects on the quality of voice of persons ingesting it. This has led medical personnel dealing with voice disorders, especially in the case of professional voice users, to give advice against the use of caffeine. Yet this is an anecdotal truth as an extensive Medline literature search did not reveal any scientific evidence of caffeine being proven to have adverse effects on the vocal folds. We, therefore, initiated this pilot study to ascertain the connection between caffeine and voice quality on a laboratory basis. Two hundred and fifty mg of caffeine were provided to eight volunteers in tablet form, and blood levels along with laryngograph readings were recorded to document the changes produced. Analysing the irregularities of frequencies in a) free speech b) a reading passage and c) singing 'Happy Birthday', substantial changes were seen to authenticate the fact that caffeine does produce alterations in voice quality but these alterations have considerable intra-subject variability. A full study with wider parameters is to be performed on this subject as we consider it to be of importance in the management of voice disorders. PMID:10474669

  20. Effect of caffeine on information processing: Evidence from stroop task

    Directory of Open Access Journals (Sweden)

    Abhinav Dixit

    2012-01-01

    Full Text Available Background: Caffeine is a pyschostimulant present in various beverages and known to alter alertness and performance by acting on the central nervous system. Its effects on central nervous system have been studied using EEG, evoked potentials, fMRI, and neuropsychological tests. The Stroop task is a widely used tool in psychophysiology to understand the attention processes and is based on the principle that processing of two different kinds of information (like the word or colour is parallel and at different speeds with a common response channel. Aim: To study the effect of caffeine on classical color word Stroop task. Materials and Methods: This study was conducted on 30 male undergraduate students by performing a test before and 40 minutes after consuming 3 mg/Kg caffeine and evaluating the effect of caffeine on Stroop interference and facilitation. Results: The results revealed that practice has no effect on the performance in a Stroop task. However, there was reduction in Stroop interference and increase in facilitation after consumption of caffeine as was evident by changes in the reaction times in response to neutral, incongruent, and congruent stimuli. Conclusion: We hypothesize that caffeine led to faster processing of relevant information.

  1. Protonation of caffeine: A theoretical and experimental study

    International Nuclear Information System (INIS)

    Highlights: ► Protonation of caffeine was examined by ion mobility spectrometry equipped with two ionization sources. ► Experimental and theoretical evidence was collected to assign the observed peaks to caffeine related ionic species. ► A new concept of “internal proton affinity”, the protonation tendency for each atom in a molecule, was defined. - Abstract: Protonation of caffeine was examined by ion mobility spectrometry equipped with two ionization sources, corona discharge (CD) and UV photoionization. Three peaks were observed in ion mobility spectrum by simultaneously running the two ionization sources. Experimental and theoretical evidence was collected to link the observed peaks to caffeine related ionic species. One peak was attributed to the M+ ion while the other two were assigned to different protonated isomers of caffeine. In the case of CD ionization source, it was observed that different sites of caffeine compete for protonation and their relative intensities, depends on the sample concentration as well as the nature of the reactant ions. The new concept of “internal proton affinity” (IPA) was defined to express the tendency of holding the added proton for each atom in a molecule

  2. Influence of caffeine on fractionated irradiation in wheat and barley

    International Nuclear Information System (INIS)

    Fractionated irradiation is one of the important methods studying repair of radiation damage. Some authors reported that caffeine, a repair inhibitor, had no effects on fractionated irradiation in human cell, animal cell and Vicia faba. And they concluded that caffeine inhibited the repair of potentially lethal damage (PLD), but did not inhibit the repair of sub-lethal damage (SLD). In this study, the effect of caffeine on the repair of PLD and SLD were reexamined in wheat and barley systems. The germinating seeds of wheat of barley were pre-irradiation treated 3 h with 5 x 10-3 mol/L caffeine, then they were irradiated by single or fractionated X-ray doses. The results showed that after caffeine treatment the effect of fractionated irradiation was disappeared. In this case, caffeine not only inhibited the repair of PLD but also inhibited the repair SLD. In previous fracttionated radiation experiments, the repairs during interval were discussed in detail, but the repairs after whole irradiation were neglected. According to the resuls of this experiment and some early reported about fractionated irradiation, the repair efficiency during interval and the repair function after whole irradiation were discussed

  3. Protonation of caffeine: A theoretical and experimental study

    Energy Technology Data Exchange (ETDEWEB)

    Bahrami, Hamed [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Tabrizchi, Mahmoud, E-mail: m-tabriz@cc.iut.ac.ir [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Farrokhpour, Hossein [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of)

    2013-03-29

    Highlights: ► Protonation of caffeine was examined by ion mobility spectrometry equipped with two ionization sources. ► Experimental and theoretical evidence was collected to assign the observed peaks to caffeine related ionic species. ► A new concept of “internal proton affinity”, the protonation tendency for each atom in a molecule, was defined. - Abstract: Protonation of caffeine was examined by ion mobility spectrometry equipped with two ionization sources, corona discharge (CD) and UV photoionization. Three peaks were observed in ion mobility spectrum by simultaneously running the two ionization sources. Experimental and theoretical evidence was collected to link the observed peaks to caffeine related ionic species. One peak was attributed to the M{sup +} ion while the other two were assigned to different protonated isomers of caffeine. In the case of CD ionization source, it was observed that different sites of caffeine compete for protonation and their relative intensities, depends on the sample concentration as well as the nature of the reactant ions. The new concept of “internal proton affinity” (IPA) was defined to express the tendency of holding the added proton for each atom in a molecule.

  4. Caffeine treatment aggravates secondary degeneration after spinal cord injury.

    Science.gov (United States)

    Yang, Cheng-Chang; Jou, I-Ming

    2016-03-01

    Spinal cord injury (SCI) often results in some form of paralysis. Recently, SCI therapy has been focused on preventing secondary injury to reduce both neuroinflammation and lesion size so that functional outcome after an SCI may be improved. Previous studies have shown that adenosine receptors (AR) are a major regulator of inflammation after an SCI. The current study was performed to examine the effect of caffeine, a pan-AR blocker, on spontaneous functional recovery after an SCI. Animals were assigned into 3 groups randomly, including sham, PBS and caffeine groups. The rat SCI was generated by an NYU impactor with a 10 g rod dropped from a 25 mm height at thoracic 9 spinal cord level. Caffeine and PBS were injected daily during the experiment period. Hind limb motor function was evaluated by the Basso, Beattie, Bresnahan (BBB) locomotor rating scale at 1 week and 4 weeks after the SCI. Spinal cord segments were collected after final behavior evaluation for morphological analysis. The tissue sparing was evaluated by luxol fast blue staining. Immunofluorescence stain was employed to assess astrocyte activation and neurofilament positioning, while microglia activation was examined by immunohistochemistry stain.The results showed that spontaneous functional recovery was blocked after the animals were subjected caffeine daily. Moreover, caffeine administration increased the demyelination area, promoted astrocyte and microglia activation and decreased the quantity of neurofilaments. These findings suggest that the neurotoxicity effect of caffeine may be associated with the inhibition of neural repair and the promotion of neuroinflammation. PMID:26746340

  5. Ultrastructural changes in the developing chicken cornea following caffeine administration.

    Directory of Open Access Journals (Sweden)

    Bartel Hieronim

    2010-11-01

    Full Text Available Caffeine is one of the most frequently consumed psychoactive substances. It has been known for many years that caffeine at high concentrations exerts harmful effects on both women's and laboratory animals' fertility, moreover it may impair normal development of many organs in the prenatal period. So far there have been few studies performed that demonstrate teratogenic effects of caffeine on structures of the developing eye, particularly the cornea. The aim of the study was to show ultrastructural changes in the developing cornea, as the effect of caffeine administration to chicken embryos. The experimental materials were 26 chicken embryos from incubated breeding eggs. Eggs were divided into two groups: control (n=30 in which Ringer liquid was administrated, and experimental (n=30 in which teratogenic dose of caffeine 3.5mg/egg was given. In 36th hour of incubation solutions were given with cannula through hole in an egg shell directly onto amniotic membrane. After closing the hole with a glass plate and paraffine, eggs were put back to incubator. In 10th and 19th day of incubation corneas were taken for morphological analysis with a use of electron microscopy. Administration of caffeine during chicken development causes changes of collagen fibers of Bowman's membrane patterns and of the corneal stroma but it also changes proportion of amount of collagen fibers and of the stromal cells.

  6. Binding of the potential antitumour agent indirubin-5-sulphonate at the inhibitor site of rabbit muscle glycogen phosphorylase b. Comparison with ligand binding to pCDK2-cyclin A complex.

    Science.gov (United States)

    Kosmopoulou, Magda N; Leonidas, Demetres D; Chrysina, Evangelia D; Bischler, Nicolas; Eisenbrand, Gerhard; Sakarellos, Constantinos E; Pauptit, Richard; Oikonomakos, Nikos G

    2004-06-01

    The binding of indirubin-5-sulphonate (E226), a potential anti-tumour agent and a potent inhibitor (IC(50) = 35 nm) of cyclin-dependent kinase 2 (CDK2) and glycogen phosphorylase (GP) has been studied by kinetic and crystallographic methods. Kinetic analysis revealed that E226 is a moderate inhibitor of GPb (K(i) = 13.8 +/- 0.2 micro m) and GPa (K(i) = 57.8 +/- 7.1 micro m) and acts synergistically with glucose. To explore the molecular basis of E226 binding we have determined the crystal structure of the GPb/E226 complex at 2.3 A resolution. Structure analysis shows clearly that E226 binds at the purine inhibitor site, where caffeine and flavopiridol also bind [Oikonomakos, N.G., Schnier, J.B., Zographos, S.E., Skamnaki, V.T., Tsitsanou, K.E. & Johnson, L.N. (2000) J. Biol. Chem.275, 34566-34573], by intercalating between the two aromatic rings of Phe285 and Tyr613. The mode of binding of E226 to GPb is similar, but not identical, to that of caffeine and flavopiridol. Comparative structural analyses of the GPb-E226, GPb-caffeine and GPb-flavopiridol complex structures reveal the structural basis of the differences in the potencies of the three inhibitors and indicate binding residues in the inhibitor site that can be exploited to obtain more potent inhibitors. Structural comparison of the GPb-E226 complex structure with the active pCDK2-cyclin A-E226 complex structure clearly shows the different binding modes of the ligand to GPb and CDK2; the more extensive interactions of E226 with the active site of CDK2 may explain its higher affinity towards the latter enzyme. PMID:15153119

  7. Caffeine and human cerebral blood flow: A positron emission tomography study

    International Nuclear Information System (INIS)

    Positron emission tomography (PET) was used to quantify the effect of caffeine on whole brain and regional cerebral blood flow (CBF) in humans. A mean dose of 250 mg of caffeine produced approximately a 30% decrease in whole brain CBF; regional differences in caffeine effect were not observed. Pre-caffeine CBF strongly influenced the magnitude of the caffeine-induced decrease. Caffeine decreased paCO2 and increased systolic blood pressure significantly; the change in paCO2 did not account for the change in CBF. Smaller increases in diastolic blood pressure, heart rate, plasma epinephrine and norepinephrine, and subjectively reported anxiety were also observed

  8. Caffeine and cognitive decline in elderly women at high vascular risk. : Caffeine and cognition in high-risk women

    OpenAIRE

    Vercambre, Marie-Noël; BERR, Claudine; Ritchie, Karen; Kang, Jae,

    2013-01-01

    International audience BACKGROUND: Persons with vascular disorders are at higher risk of cognitive decline. OBJECTIVE: To determine whether caffeine may be associated with cognitive decline reduction in elderly at high vascular risk. METHODS: We included 2,475 women aged 65+ years in the Women's Antioxidant Cardiovascular Study, a randomized trial of antioxidants and B vitamins for cardiovascular disease secondary prevention. We ascertained regular caffeine intake at baseline (1995-1996) u...

  9. Expression of δ-cyclins of Brassica rapa L. embryos by clinorotation

    Science.gov (United States)

    Artemenko, O. A.

    Cyclins is one of the important regulators of cell cycle. There are several types of cyclins exists. They are responding for different phases of cycle and have high homology in plant's and mammalian's cells. δ -cyclins are specific for plants and controlling the presynthetic phase events. These cyclins likes to mammalian D-cyclins and have similar functions. This class consist three types of cyclins -- δ 1, δ 2 and δ 3. Cyclin δ 1 is responding for events in cell, which take place before exiting from stage of quiet (G0). Cyclin δ 1 is responding for entering and outputting from G0, and cyclin δ 3 -- for events, which happen in cell after stage of quiet, by entering to S-phase (phase of DNA's synthesis). In present research was used δ 1- and δ 3-cyclins. For determination of δ -cyclins gene's expression level was excreted RNA from embryos: 3-days (spherical stage), 6-days (heart-shaped stage) and 9-days (generated stage) seedlings of Brassica rapa L. in control and under clinorotation. For definition the cyclins gene's expression level applied Northern Blot Analysis. Obtained data testify about difference in level of gene's expression of cyclin δ 1 between control and clinorotation variants. After three days by pollination the expression of this gene in embryos was observed in control only. By clinorotation the gene's expression was detected on 6 days later, but it level was lower than in control variant. On 9 days it was gently expressed by clinorotation, where as by control it was not detected absolutely. Cyclin δ 3 gene's expression was observed during all time of the experiment. These data also confirm known one about expression δ 1- cyclin, which expressed on beginning of cell cycle only. And δ 3 --cyclin that express during whole presinthetic phase of cell cycle (Sony et al., 1995, Murray, 1994, Inze et al, 1999, Umeda, 2000).

  10. Cyclin B2 and p53 control proper timing of centrosome separation

    NARCIS (Netherlands)

    Nam, H.J.; Deursen, J.M.A. van

    2014-01-01

    Cyclins B1 and B2 are frequently elevated in human cancers and are associated with tumour aggressiveness and poor clinical outcome; however, whether and how B-type cyclins drive tumorigenesis is unknown. Here we show that cyclin B1 and B2 transgenic mice are highly prone to tumours, including tumour

  11. Caffeine exposure during rat brain development causes memory impairment in a sex selective manner that is offset by caffeine consumption throughout life.

    Science.gov (United States)

    Ardais, Ana Paula; Rocha, Andréia S; Borges, Maurício Felisberto; Fioreze, Gabriela T; Sallaberry, Cássia; Mioranzza, Sabrina; Nunes, Fernanda; Pagnussat, Natália; Botton, Paulo Henrique S; Cunha, Rodrigo A; Porciúncula, Lisiane de Oliveira

    2016-04-15

    Caffeine is the psychostimulant most consumed worldwide. In moderate doses, it affords a beneficial effect in adults and upon aging, but has a deleterious effect during brain development. We now tested if caffeine consumption by rats (0.1, 0.3, 1.0 g/L in the drinking water, only during active cycle and weekdays) during adulthood could revert the potentially negative effects of caffeine during early life. Thus, we compared caffeine intake starting 15 days before mating and lasting either up to weaning (development) or up to adulthood, on behavior and synaptic proteins in male and female rats. Recognition memory was impaired only in female rats receiving caffeine (0.3 and 1.0 g/L) during development, coincident with increased proBDNF and unchanged BDNF levels in the hippocampus. Caffeine in both treatment regimens caused hyperlocomotion only in male rats, whereas anxiety-related behavior was attenuated in both sexes by caffeine (1.0 g/L) throughout life. Both caffeine treatment regimens decreased GFAP (as an astrocyte marker) and SNAP-25 (as a nerve terminals marker) in the hippocampus from male rats. TrkB receptor was decreased in the hippocampus from both sexes and treatment regimens. These findings revealed that caffeine intake during a specific time window of brain development promotes sex-dependent behavioral outcomes related to modification in BDNF signaling. Furthermore, caffeine throughout life can overcome the deleterious effects of caffeine on recognition memory during brain development in female rats. PMID:26774980

  12. miR-206 is down-regulated in breast cancer and inhibits cell proliferation through the up-regulation of cyclinD2

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jing, E-mail: zhougjing9888@163.com [Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu (China); Tian, Ye, E-mail: tianye2010077@163.com [Department of Hepatobiliary Surgery, Affiliated Yijishan Hospital of Wannan Medical College, Wuhu, Anhui (China); Li, Juan, E-mail: 402310848@163.com [Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu (China); Lu, Binbin, E-mail: lubin1976@163.com [Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu (China); Sun, Ming, E-mail: 422825636@qq.com [Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu (China); Zou, Yanfen, E-mail: 569111165@qq.com [Department of Obstetrics and Gynaecology, Jiangsu Province Hospital, Nanjing, Jiangsu (China); Kong, Rong, E-mail: 31815857@qq.com [Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu (China); Luo, Yanhong, E-mail: 252376737@qq.com [School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu (China); Shi, Yongguo, E-mail: 12071018@qq.com [Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu (China); Wang, Keming, E-mail: Tianyr1@163.com [Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu (China); Ji, Guozhong, E-mail: 252376737@qq.com [Department of Oncology, Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu (China)

    2013-04-05

    Highlights: ► miR-206 was downexpressed in tumor samples compared with matched normal samples. ► Enhanced expression of miR-206 could inhibit breast cancer growth in vitro. ► Luciferase confirmed miR-206 functions as an anti-oncogene by targeting cyclinD2. ► A reverse correlation between miR-206 and cyclinD2 in breast cancer was found. -- Abstract: MicroRNAs act as important gene regulators in human genomes, and their aberrant expression is linked to many malignancies. Aberrant expression of miR-206 has been frequently reported in cancer studies; however, the role and mechanism of its function in breast cancer remains unclear. Quantitative real-time PCR was performed to detect the relative expression levels of miR-206 in breast cancer and normal breast tissues. Lower expression of miR-206 in breast cancer tissues was associated with larger tumour size and a more advanced clinical stage. Further in vitro observations showed that the enforced expression of miR-206 in MCF-7 breast cancer cells inhibited cell growth by blocking the G1/S transition and suppressed cell proliferation and colony formation, implying that miR-206 functions as a tumour suppressor in the progression of breast cancer. Interestingly, Luciferase assays first revealed that miR-206 inhibited cyclinD2 expression by targeting two binding sites in the 3′-untranslated region of cyclinD2 mRNA. qRT-PCR and Western blot assays verified that miR-206 reduced cyclinD2 expression at both the mRNA and protein levels. A reverse correlation between miR-206 and cyclinD2 expression was noted in breast cancer tissues. Altogether, our results identify a crucial tumour suppressive role of miR-206 in the progression of breast cancer, at least partly via up-regulation of the expression of cyclinD2, and suggest that miR-206 might be a candidate prognostic predictor or an anticancer therapeutic target for breast cancer patients.

  13. Control of cyclin C levels during development of Dictyostelium.

    Directory of Open Access Journals (Sweden)

    David M Greene

    Full Text Available BACKGROUND: Cdk8 and its partner cyclin C form part of the mediator complex which links the basal transcription machinery to regulatory proteins. The pair are required for correct regulation of a subset of genes and have been implicated in control of development in a number of organisms including the social amoeba Dictyostelium discoideum. When feeding, Dictyostelium amoebae are unicellular but upon starvation they aggregate to form a multicellular structure which develops into a fruiting body containing spores. Cells in which the gene encoding Cdk8 has been deleted fail to enter aggregates due to a failure of early gene expression. PRINCIPAL FINDINGS: We have monitored the expression levels of cyclin C protein during development and find levels decrease after the multicellular mound is formed. This decrease is triggered by extracellular cAMP that, in turn, is working in part through an increase in intracellular cAMP. The loss of cyclin C is coincident with a reduction in the association of Cdk8 with a high molecular weight complex in the nucleus. Overexpression of cyclin C and Cdk8 lead to an increased rate of early development, consistent with the levels being rate limiting. CONCLUSIONS: Overall these results show that both cyclin C and Cdk8 are regulated during development in response to extracellular signals and the levels of these proteins are important in controlling the timing of developmental processes. These findings have important implications for the role of these proteins in controlling development, suggesting that they are targets for developmental signals to regulate gene expression.

  14. Small Beneficial Effect of Caffeinated Energy Drink Ingestion on Strength.

    Science.gov (United States)

    Collier, Nora B; Hardy, Michelle A; Millard-Stafford, Mindy L; Warren, Gordon L

    2016-07-01

    Collier, NB, Hardy, MA, Millard-Stafford, ML, and Warren, GL. Small beneficial effect of caffeinated energy drink ingestion on strength. J Strength Cond Res 30(7): 1862-1870, 2016-Because caffeine ingestion has been found to increase muscle strength, our aim was to determine whether caffeine when combined with other potential ergogenic ingredients, such as those in commercial energy drinks, would have a similar effect. Fifteen young healthy subjects were used in a double-blind, repeated-measures experimental design. Each subject performed 3 trials, ingesting either a caffeinated energy drink, an uncaffeinated version of the drink, or a placebo drink. The interpolated twitch procedure was used to assess maximum voluntary isometric contraction (MVIC) strength, electrically evoked strength, and percent muscle activation during MVIC of the knee extensors both before and after drink ingestion, and after a fatiguing bout of contractions; electromyographic (EMG) amplitude of the knee extensors during MVIC was also assessed. The mean (±SE) change in MVIC strength from before to after drink ingestion was significantly greater for the caffeinated energy drink compared with placebo [+5.0 (±1.7) vs. -0.5 (±1.5)%] and the difference between the drinks remained after fatigue (p = 0.015); the strength changes for the uncaffeinated energy drink were not significantly different from those of the other 2 drinks at any time. There was no significant effect of drink type on the changes in electrically evoked strength, percent muscle activation, and EMG from before to after drink ingestion. This study indicates that a caffeinated energy drink can increase MVIC strength but the effect is modest and the strength increase cannot be attributed to increased muscle activation. Whether the efficacy of energy drinks can be attributed solely to caffeine remains unclear. PMID:26670991

  15. Expression of cell cycle regulator p57kip2, cyclinE protein and proliferating cell nuclear antigen in human pancreatic cancer: An immunohistochemical study

    Institute of Scientific and Technical Information of China (English)

    Hui Yue; Hui-Yong Jiang

    2005-01-01

    AIM: To investigate the effects of p57kip2, cyclinE protein and proliferating cell nuclear antigen (PCNA) on occurrence and progression of human pancreatic cancer.METHODS: The expression of p57kip2, cyclinE protein and PCNA in tumor tissues and adjacent tissues from 32patients with pancreatic cancer was detected by SP immunohistochemical technique.RESULTS: The positive expression rate of p57kip2 protein in tumor tissues was 46.9%, which was lower than that in adjacent pancreatic tissues (x2 = 5.317, P<0.05). P57kip2protein positive expression remarkably correlated with tumor cell differentiation (P<0.05), but not with lymph node metastasis (P>0.05). The positive expression rate of cyclinE protein in tumor tissues was 68.8%, which was higher than that in adjacent pancreatic tissues (x2 = 4.063,P<0.05). CyclinE protein positive expression significantly correlated with tumor cell differentiation and lymph node metastasis (P<0.05). The positive expression rate of PCNA in the tumor tissues was 71.9%, which was higher than that in adjacent pancreatic tissues (x2 = 5.189, P<0.05).PCNA positive expression remarkably correlated with tumor cell differentiation and lymph node metastasis (P<0.05).CONCLUSION: The decreased expression of p57kip2 and/or overexpression of cyclinE protein and PCNA may contribute to the occurrence and progression of pancreatic cancer.p57kip2, cyclinE protein, and PCNA play an important role in occurrence and progression of pancreatic cancer.

  16. Caffeine toxicity in forensic practice: possible effects and under-appreciated sources.

    Science.gov (United States)

    Musgrave, Ian F; Farrington, Rachael L; Hoban, Claire; Byard, Roger W

    2016-09-01

    Caffeine is considered a very safe stimulant and is widely consumed in a variety of forms, from pure caffeine to beverages and foods. Typically, death is only seen when gram quantities of caffeine are consumed, usually in suicide attempts. Even in this scenario, death is rare. However, there are special populations that need to be considered in forensic presentations, who may be at greater risk. These include poor metabolizers, people with liver disease, and people with cardiac conditions, who can die as a result of caffeine intake at levels well below what is ordinarily considered toxic. Also, caffeine intake may be hidden. For example, herbal medicines with substantial caffeine content may not disclose these concentrations on their product label. The role of caffeine in medicolegal deaths is yet to be defined, however, herbal medicines and herbal weight loss supplements may represent an underappreciated source of caffeine in this context. PMID:27344159

  17. Caffeine, Is it effective for prevention of postdural puncture headache in young adult patients?

    Directory of Open Access Journals (Sweden)

    Ashraf Ragab

    2014-04-01

    Conclusion: It seems that the incidence of postdural puncture headache decreases in those patients who received caffeine sodium benzoate. The article can potentially help clinicians to use caffeine as an effective drug for prevention of PDPH.

  18. Physiological and cognitive responses to caffeine during repeated, high-intensity exercise.

    Science.gov (United States)

    Crowe, Melissa J; Leicht, Anthony S; Spinks, Warwick L

    2006-10-01

    This study investigated the effects of caffeine on repeated, anaerobic exercise using a double-blind, randomized, crossover design. Seventeen subjects (five female) underwent cognitive (reaction time, number recall) and blood (glucose, potassium, catecholamines, lactate) testing before and after consuming caffeine (6 mg/kg), placebo, or nothing (control). An exercise test (two 60 s maximal cycling bouts) was conducted 90 min after caffeine/placebo consumption. Plasma caffeine concentrations significantly increased after caffeine ingestion, however, there were no positive effects on cognitive or blood parameters except a significant decrease in plasma potassium concentrations at rest. Potentially negative effects of caffeine included significantly higher blood lactate compared to control and significantly slower time to peak power in exercise bout 2 compared to control and placebo. Caffeine had no significant effect on peak power, work output, RPE, or peak heart rate. In conclusion, caffeine had no ergogenic effect on repeated, maximal cycling bouts and may be detrimental to anaerobic performance. PMID:17240784

  19. Foci of cyclin A2 interact with actin and RhoA in mitosis

    OpenAIRE

    Abdelhalim Loukil; Fanny Izard; Mariya Georgieva; Shaereh Mashayekhan; Jean-Marie Blanchard; Andrea Parmeggiani; Marion Peter

    2016-01-01

    Cyclin A2 is a key player in the regulation of the cell cycle. Its degradation in mid-mitosis depends primarily on the ubiquitin-proteasome system (UPS), while autophagy also contributes. However, a fraction of cyclin A2 persists beyond metaphase. In this work, we focus on cyclin A2-rich foci detected in mitosis by high resolution imaging and analyse their movements. We demonstrate that cyclin A2 interacts with actin and RhoA during mitosis, and that cyclin A2 depletion induces a dramatic dec...

  20. Synergistic action of Drosophila cyclins A and B during the G2-M transition.

    OpenAIRE

    Knoblich, J A; Lehner, C F

    1993-01-01

    A variety of different cyclin proteins have been identified in higher eukaryotes. In the case of cyclin B, functional analyses have clearly demonstrated an important role in the control of entry into mitosis. The function of cyclin A is more complex. It appears to function in the control of both S- and M-phase. The results of our genetic analyses in Drosophila demonstrate that cyclin A has a mitotic function and that it acts synergistically with cyclin B during the G2-M transition. In double ...

  1. Conditioned Reinforcement and Locomotor Activating Effects of Caffeine and Ethanol Combinations in Mice

    OpenAIRE

    Megan L.T. Hilbert; May, Christina E.; Griffin, William C.

    2013-01-01

    A growing trend among ethanol drinkers, especially young adults, is to combine caffeinated energy drinks with ethanol during a drinking episode. The primary active ingredient of these mixers is caffeine, which may significantly interact with ethanol. We tested the two hypotheses that caffeine would enhance ethanol-conditioned place preference and also enhance ethanol-stimulated locomotor activity. The interactive pharmacology of ethanol and caffeine was examined in C57BL/6J (B6) mice in a con...

  2. Storm in a coffee cup: caffeine modifies brain activation to social signals of threat

    OpenAIRE

    Smith, Jessica E.; Lawrence, Andrew D; Diukova, Ana; Wise, Richard G; Rogers, Peter J.

    2011-01-01

    Caffeine, an adenosine A1 and A2A receptor antagonist, is the most popular psychostimulant drug in the world, but it is also anxiogenic. The neural correlates of caffeine-induced anxiety are currently unknown. This study investigated the effects of caffeine on brain regions implicated in social threat processing and anxiety. Participants were 14 healthy male non/infrequent caffeine consumers. In a double-blind placebo-controlled crossover design, they underwent blood oxygenation level-depende...

  3. The Metabolic and Performance Effects of Caffeine Compared to Coffee during Endurance Exercise

    OpenAIRE

    Hodgson, Adrian B.; Randell, Rebecca K.; Jeukendrup, Asker E.

    2013-01-01

    There is consistent evidence supporting the ergogenic effects of caffeine for endurance based exercise. However, whether caffeine ingested through coffee has the same effects is still subject to debate. The primary aim of the study was to investigate the performance enhancing effects of caffeine and coffee using a time trial performance test, while also investigating the metabolic effects of caffeine and coffee. In a single-blind, crossover, randomised counter-balanced study design, eight tra...

  4. Concomitant Effects of Caffeine and Gamma Irradiation in Female Rats

    International Nuclear Information System (INIS)

    The present study was undertaken to evaluate the protective potential of caffeine as an antioxidant (80 mg/kg b.w.) i.p. injected 1 hr before exposure to a dose of (7 Gy) gamma irradiation in female rats. Alterations in serum lipids, cholesterol, triacylglycerol and fatty acids as well as total proteins, urea and uric acid have been investigated 1, 3 and 7 days post irradiation and /or caffeine treatment. Histological and histochemical changes of the dorsal aorta have been studied 7 days post treatment. Results revealed elevated total lipids, cholesterol, triacylglycerol, beside distortion in fatty acids throughout the whole experimentation period by caffeine pre injection, irradiation application and by dual treatment. Protein and urea were elevated by caffeine or irradiation, while both treatments dropped their levels, whereas uric was decreased by all treatments. Histopathological changes and deposition of sudanophilic material in the dorsal aorta wall were detected by either one or both treatments, which point out a limitation in the protective potential of caffeine

  5. Graphene platforms for the detection of caffeine in real samples

    Energy Technology Data Exchange (ETDEWEB)

    Khoo, Weslie Yu Heng; Pumera, Martin; Bonanni, Alessandra, E-mail: a.bonanni@ntu.edu.sg

    2013-12-04

    Graphical abstract: -- Highlights: •Commercial caffeine was detected on different chemically modified graphenes. •Electrochemically reduced graphene (ERGO) provided the best performance. •ERGO was then employed for the detection of caffeine in real samples. -- Abstract: The analysis of food components is of high importance due to food safety and security. Here the electrochemical detection of caffeine was performed on different chemically modified graphene (CMG) surfaces carrying diverse amount of defects and oxygen functionalities. The analytical performances of graphite oxide (GPO), graphene oxide (GO), and electrochemically reduced graphene oxide (ERGO) were compared for the first time for the detection of caffeine. It was found that ERGO showed the most favourable analytical parameters, such as lower oxidation potential, sensitivity, linearity and reproducibility of the response. ERGO was then used for the analysis of real samples. Caffeine levels of soluble coffee, teas and energetic drinks were measured without the need of any sample pre-treatment. Our findings are very important to gain more insight into the applicability of different graphene materials to real samples for sense-and-act analysis.

  6. Potential Role of Caffeine in the Treatment of Parkinson's Disease.

    Science.gov (United States)

    Roshan, Mohsin H K; Tambo, Amos; Pace, Nikolai P

    2016-01-01

    Parkinson's disease [PD] is the second most common neurodegenerative disorder after Alzheimer's disease, affecting 1% of the population over the age of 55. The underlying neuropathology seen in PD is characterised by progressive loss of dopaminergic neurons in the substantia nigra pars compacta with the presence of Lewy bodies. The Lewy bodies are composed of aggregates of α-synuclein. The motor manifestations of PD include a resting tremor, bradykinesia, and muscle rigidity. Currently there is no cure for PD and motor symptoms are treated with a number of drugs including levodopa [L-dopa]. These drugs do not delay progression of the disease and often provide only temporary relief. Their use is often accompanied by severe adverse effects. Emerging evidence from both in vivo and in vitro studies suggests that caffeine may reduce parkinsonian motor symptoms by antagonising the adenosine A2A receptor, which is predominately expressed in the basal ganglia. It is hypothesised that caffeine may increase the excitatory activity in local areas by inhibiting the astrocytic inflammatory processes but evidence remains inconclusive. In addition, the co-administration of caffeine with currently available PD drugs helps to reduce drug tolerance, suggesting that caffeine may be used as an adjuvant in treating PD. In conclusion, caffeine may have a wide range of therapeutic effects which are yet to be explored, and therefore warrants further investigation in randomized clinical trials. PMID:27563362

  7. Pharmacokinetic Interaction of Chrysin with Caffeine in Rats.

    Science.gov (United States)

    Noh, Keumhan; Oh, Do Gyeong; Nepal, Mahesh Raj; Jeong, Ki Sun; Choi, Yongjoo; Kang, Mi Jeong; Kang, Wonku; Jeong, Hye Gwang; Jeong, Tae Cheon

    2016-07-01

    Pharmacokinetic interaction of chrysin, a flavone present in honey, propolis and herbs, with caffeine was investigated in male Sprague-Dawley rats. Because chrysin inhibited CYP1A-selective ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase activities in enriched rat liver microsomes, the pharmacokinetics of caffeine, a CYP 1A substrate, was studied following an intragastric administration with 100 mg/kg chrysin. In addition to the oral bioavailability of chrysin, its phase 2 metabolites, chrysin sulfate and chrysin glucuronide, were determined in rat plasma. As results, the pharmacokinetic parameters for caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) were not changed following chrysin treatment in vivo, despite of its inhibitory effect on CYP 1A in vitro. The bioavailability of chrysin was found to be almost zero, because chrysin was rapidly metabolized to its sulfate and glucuronide conjugates in rats. Taken together, it was concluded that the little interaction of chrysin with caffeine might be resulted from the rapid metabolism of chrysin to its phase 2 metabolites which would not have inhibitory effects on CYP enzymes responsible for caffeine metabolism. PMID:27098862

  8. Influence of caffeine on blood pressure and platelet aggregation

    Directory of Open Access Journals (Sweden)

    José Wilson S. Cavalcante

    2000-08-01

    Full Text Available OBJECTIVE: Studies have demonstrated that methylxanthines, such as caffeine, are A1 and A2 adenosine receptor antagonists found in the brain, heart, lungs, peripheral vessels, and platelets. Considering the high consumption of products with caffeine in their composition, in Brazil and throughout the rest of the world, the authors proposed to observe the effects of this substance on blood pressure and platelet aggregation. METHODS: Thirteen young adults, ranging from 21 to 27 years of age, participated in this study. Each individual took 750mg/day of caffeine (250mg tid, over a period of seven days. The effects on blood pressure were analyzed through the pressor test with handgrip, and platelet aggregation was analyzed using adenosine diphosphate, collagen, and adrenaline. RESULTS: Diastolic pressure showed a significant increase 24 hours after the first intake (p<0.05. This effect, however, disappeared in the subsequent days. The platelet aggregation tests did not reveal statistically significant alterations, at any time during the study. CONCLUSION: The data suggest that caffeine increases diastolic blood pressure at the beginning of caffeine intake. This hypertensive effect disappears with chronic use. The absence of alterations in platelet aggregation indicates the need for larger randomized studies.

  9. Assessing dietary exposure to caffeine from beverages in the U.S. population using brand-specific versus category-specific caffeine values.

    Science.gov (United States)

    Mitchell, Diane C; Hockenberry, Jon; Teplansky, Robyn; Hartman, Terryl J

    2015-06-01

    Recent reports on caffeine intakes in the United States have highlighted the importance of obtaining accurate and valid measures of caffeine exposure. The objective of this study is to compare two methods of assigning caffeine values to beverages: brand-specific values versus an aggregate single value representing a broader range of products within a beverage category (i.e., category-specific). The two methods yielded some small, but statistically significant differences in the estimation of caffeine intake from coffee, tea, and carbonated soft drinks (CSDs) for all ages combined and within several of the adult age groups (i.e., 35-49, 50-64, and ≥65 years). These differences, while small, suggest that detailed brand-specific data, particularly for CSDs, commercially pre-packaged or bottled teas, coffee, and specialty coffee drinks, provide more accurate estimates of caffeine exposure for some age groups. Despite these differences, these data provide some assurance that studies using a single aggregate caffeine value provide reasonable measures of caffeine exposure, particularly for studies conducted over a decade ago when there were fewer caffeinated products and brand-specific data available. As the caffeinated beverage marketplace continues to evolve, the use of more detailed, brand-specific data will likely strengthen the assessment of caffeine exposure in the United States. PMID:25818465

  10. Lack of specific association between panicogenic properties of caffeine and HPA-axis activation. A placebo-controlled study of caffeine challenge in patients with panic disorder.

    Science.gov (United States)

    Masdrakis, Vasilios G; Markianos, Manolis; Oulis, Panagiotis

    2015-09-30

    A subgroup of patients with Panic Disorder (PD) exhibits increased sensitivity to caffeine administration. However, the association between caffeine-induced panic attacks and post-caffeine hypothalamic-pituitary-adrenal (HPA)-axis activation in PD patients remains unclear. In a randomized, double-blind, cross-over experiment, 19 PD patients underwent a 400-mg caffeine-challenge and a placebo-challenge, both administered in the form of instant coffee. Plasma levels of adrenocorticotropic hormone (ACTH), cortisol and dehydroepiandrosterone sulfate (DHEAS) were assessed at both baseline and post-challenge. No patient panicked after placebo-challenge, while nine patients (47.3%) panicked after caffeine-challenge. Placebo administration did not result in any significant change in hormones' plasma levels. Overall, sample's patients demonstrated significant increases in ACTH, cortisol, and DHEAS plasma levels after caffeine administration. However, post-caffeine panickers and non-panickers did not differ with respect to the magnitude of the increases. Our results indicate that in PD patients, caffeine-induced panic attacks are not specifically associated with HPA-axis activation, as this is reflected in post-caffeine increases in ACTH, cortisol and DHEAS plasma levels, suggesting that caffeine-induced panic attacks in PD patients are not specifically mediated by the biological processes underlying fear or stress. More generally, our results add to the evidence that HPA-axis activation is not a specific characteristic of panic. PMID:26243374

  11. Adolescent Caffeine Consumption and Self-Reported Violence and Conduct Disorder

    Science.gov (United States)

    Kristjansson, Alfgeir L.; Sigfusdottir, Inga Dora; Frost, Stephanie S.; James, Jack E.

    2013-01-01

    Caffeine is the most widely used psychoactive substance in the world and currently the only one legally available to children and adolescents. The sale and use of caffeinated beverages has increased markedly among adolescents during the last decade. However, research on caffeine use and behaviors among adolescents is scarce. We investigate the…

  12. Acute Caffeine Consumption Enhances the Executive Control of Visual Attention in Habitual Consumers

    Science.gov (United States)

    Brunye, Tad T.; Mahoney, Caroline R.; Lieberman, Harris R.; Giles, Grace E.; Taylor, Holly A.

    2010-01-01

    Recent work suggests that a dose of 200-400mg caffeine can enhance both vigilance and the executive control of visual attention in individuals with low caffeine consumption profiles. The present study seeks to determine whether individuals with relatively high caffeine consumption profiles would show similar advantages. To this end, we examined…

  13. The buzz on caffeine in invertebrates: effects on behavior and molecular mechanisms.

    Science.gov (United States)

    Mustard, Julie A

    2014-04-01

    A number of recent studies from as diverse fields as plant-pollinator interactions, analyses of caffeine as an environmental pollutant, and the ability of caffeine to provide protection against neurodegenerative diseases have generated interest in understanding the actions of caffeine in invertebrates. This review summarizes what is currently known about the effects of caffeine on behavior and its molecular mechanisms in invertebrates. Caffeine appears to have similar effects on locomotion and sleep in both invertebrates and mammals. Furthermore, as in mammals, caffeine appears to have complex effects on learning and memory. However, the underlying mechanisms for these effects may differ between invertebrates and vertebrates. While caffeine's ability to cause release of intracellular calcium stores via ryanodine receptors and its actions as a phosphodiesterase inhibitor have been clearly established in invertebrates, its ability to interact with invertebrate adenosine receptors remains an important open question. Initial studies in insects and mollusks suggest an interaction between caffeine and the dopamine signaling pathway; more work needs to be done to understand the mechanisms by which caffeine influences signaling via biogenic amines. As of yet, little is known about whether other actions of caffeine in vertebrates, such as its effects on GABAA and glycine receptors, are conserved. Furthermore, the pharmacokinetics of caffeine remains to be elucidated. Overall behavioral responses to caffeine appear to be conserved amongst organisms; however, we are just beginning to understand the mechanisms underlying its effects across animal phyla. PMID:24162934

  14. [Self-rated Caffeine Sensitivity: Implications for Personalized Sleep Medicine?].

    Science.gov (United States)

    Landolt, Hans Peter

    2016-05-11

    The prevalence of the insomnia syndrome and the effects of caffeine on sleep are in part genetically determined. Pharmacogenetic studies in humans demonstrate that functional polymorphisms of the genes encoding adenosine A2A receptors and dopamine transporters contribute to individual differences in impaired sleep quality by caffeine. The A2A receptor and dopamine transporter are preferentially expressed in the striatum. Together, these observations suggest that the striatum plays an important role in sleep-wake regulation. Individual caffeine sensitivity and A2A receptor genotype should be taken into account in the development of possible novel adenosine-based pharmacotherapies of sleep-wake disorders and neurodegenerative disorders such as Parkinson's disease. This may permit the prediction of individual drug effects and improve the reliability of clinical trials. PMID:27167478

  15. Caffeine Markedly Enhanced Radiation-Induced Bystander Effects

    Institute of Scientific and Technical Information of China (English)

    JIANG Erkang; WU Lijun

    2009-01-01

    A bstract In this paper it is shown that incubation with 2 mM caffeine enhanced significantly the MN (micronucleus) formation in both the 1 cGy a-particle irradiated and non-irradiated by- stander regions. Moreover, caffeine treatment made the non-irradiated bystander cells more sensi- tive to damage signals. Treated by c-PTIO(2-(4-carboxy-phenyl)-4,4,5,5-tetramethyl-imidazoline- 1-oxyl-3-oxide), a nitric oxide (NO) scavenger, the MN frequencies were effectively inhibited, showing that nitric oxide might be very important in mediating the enhanced damage. These results indicated that caffeine enhanced the low dose a-particle radiation-induced damage in ir- radiated and non-irradiated bystander regions, and therefore it is important to investigate the relationship between the radiosensitizer and radiation-induced bystander effects (RIBE).

  16. Spontaneous Abortion and a Diet Drug Containing Caffeine and Ephedrine

    DEFF Research Database (Denmark)

    Howards, Penelope P; Hertz-Picciotto, Irva; Bech, Bodil H;

    2012-01-01

    BACKGROUND: Medications may be consumed periconceptionally before a woman knows she is pregnant. In this study, the authors evaluate the association of a prescription diet drug (Letigen) containing ephedrine (20 mg) and caffeine (200 mg) with spontaneous abortion (SAB) in the Danish National Birth...... pregnancy Letigen use on SAB. PRINCIPAL FINDINGS: The estimated maternal age-adjusted hazard ratio for SAB was 1.1 (95% confidence interval 0.8-1.6) for any periconceptional Letigen use compared to no periconceptional use. CONCLUSIONS: Although Letigen has high levels of caffeine (the recommended 3 pills....../day are approximately equivalent to caffeine from 6 cups of coffee), periconceptional use does not appear to be associated with an appreciably increased hazard of clinically recognized SAB....

  17. Suppressive effects of 3-bromopyruvate on the proliferation and the motility of hepatocellular carcinoma cells.

    Science.gov (United States)

    Tomizawa, Minoru; Shinozaki, Fuminobu; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

    2016-01-01

    The compound 3-bromopyruvate (3BP) is an analogue of pyruvate, which is the final product of glycolysis that enters the citric acid cycle. The present study aimed to investigate the suppressive effects of 3BP on the proliferation and motility of hepatocellular carcinoma (HCC) cells. HLF and PLC/PRF/5 cells were cultured with 3BP and subjected to an MTS assay. Apoptosis was analyzed by hematoxylin and eosin staining. Cell motility was analyzed using a scratch assay. Real-time quantitative polymerase chain reaction (PCR) was performed to determine the expression levels of cyclin D1 and matrix metalloproteinase (MMP)9. Proliferation of both cell lines was significantly suppressed by 3BP at 100 µM (P<0.05). The expression level of cyclin D1 was decreased after 3BP treatment at 100 µM in both cell lines (P<0.05). Pyknotic nuclei were observed in the cells cultured with 3BP at 100 µM. These results revealed that 3BP suppressed cell proliferation, decreased the expression of cyclin D1, and induced apoptosis in HCC cells. 3BP significantly suppressed motility in both cell lines (P<0.05). The expression level of MMP9 was significantly decreased (P<0.05). 3BP suppressed the proliferation and motility of HCC cells by decreasing the expression of cyclin D1 and MMP9. PMID:26530887

  18. Cyclin Y Is Involved in the Regulation of Adipogenesis and Lipid Production.

    Directory of Open Access Journals (Sweden)

    Weiwei An

    Full Text Available A new member of the cyclin family cyclin Y (CCNY is involved in the regulation of various physiological processes. In this study, the role of CCNY in energy metabolism was characterized. We found that compared with wild-type (WT mice, Ccny knockout (KO mice had both lower body weight and lower fat content. The Ccny KO mice also had a higher metabolic rate, resisted the stress of a high-fat diet, and were sensitive to calorie restriction. The expression levels of UCP1 and PGC1α were significantly higher in the brown adipose tissue (BAT of the Ccny KO mice than that of the WT littermate controls, whereas there was no significant difference in BAT weight between the WT and the Ccny KO mice. In addition, the down-regulation of Ccny resulted in suppression of white adipocyte differentiation both in vivo and in vitro, while the expression of Ccny was up-regulated by C/EBPα. Furthermore, both hepatocytes and HepG2 cells that were depleted of Ccny were insensitive to insulin stimulation, consistent with the significant inhibition of insulin sensitivity in the liver of the Ccny KO mice, but no significant changes in WAT and muscle, indicating that CCNY is involved in regulating the hepatic insulin signaling pathway. The hepatic insulin resistance generated by Ccny depletion resulted in down-regulation of the sterol-regulatory element-binding protein (SREBP1 and fatty acid synthase (FASN. Together, these results provide a new link between CCNY and lipid metabolism in mice, and suggest that inhibition of CCNY may offer a therapeutic approach to obesity and diabetes.

  19. Absorption of caffeine in fermented Pu-er tea is inhibited in mice.

    Science.gov (United States)

    Huang, Ye-wei; Xu, Huan-huan; Wang, Su-min; Zhao, Yi; Huang, Yu-min; Li, Run-bo; Wang, Xuan-jun; Hao, Shu-mei; Sheng, Jun

    2014-07-25

    Caffeine is present in a number of dietary sources consumed worldwide. Although its pharmacokinetics has been intensively explored, little is known about complexed caffeine (C-CAF) in aqueous extraction of fermented Pu-er tea. The major components of C-CAF are oxidative tea polyphenols (OTP) and caffeine. Furthermore, the C-CAF can be precipitated in low pH solution. After administering the same amount of total caffeine and comparing the peak level of plasma caffeine with the coffee (contains 0.11 ± 0.01% C-CAF) group, the results showed that the caffeine/OTP (contains 66.67 ± 0.02% C-CAF) group and the instant Pu-er tea (contains 23.18 ± 0.02% C-CAF) group were 33.39% and 25.86% lower, respectively. The concentration of the metabolites of caffeine supports the idea that the absorption of the C-CAF was inhibited in mice. Congruent with this result, the amount of caffeine detected in mice excrement showed that more caffeine was eliminated in the caffeine/OTP group and the Pu-er tea group. The locomotor activity tests of mice demonstrated that the stimulating effect of caffeine in caffeine/OTP and Pu-er tea was weaker than in coffee. Our findings demonstrate that caffeine can be combined with OTP and the absorption of C-CAF is inhibited in mice, thus decreasing the irritation effect of caffeine. This may also be developed as a slow release formulation of caffeine. PMID:24836454

  20. Novel arylazopyrazole inhibitors of cyclin-dependent kinases

    Czech Academy of Sciences Publication Activity Database

    Jorda, Radek; Schütznerová, E.; Cankař, P.; Brychtová, Veronika; Navrátilová, Jana; Kryštof, Vladimír

    2015-01-01

    Roč. 23, č. 9 (2015), s. 1975-1981. ISSN 0968-0896 R&D Projects: GA ČR GAP305/12/0783; GA ČR GA14-19590S; GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Cyclin-dependent kinases * Inhibitor * Cell cycle Subject RIV: CE - Biochemistry Impact factor: 2.793, year: 2014

  1. Online Activity Levels Are Related to Caffeine Dependency.

    Science.gov (United States)

    Phillips, James G; Landhuis, C Erik; Shepherd, Daniel; Ogeil, Rowan P

    2016-05-01

    Online activity could serve in the future as behavioral markers of emotional states for computer systems (i.e., affective computing). Hence, this study considered relationships between self-reported stimulant use and online study patterns. Sixty-two undergraduate psychology students estimated their daily caffeine use, and this was related to study patterns as tracked by their use of a Learning Management System (Blackboard). Caffeine dependency was associated with less time spent online, lower rates of file access, and fewer online activities completed. Reduced breadth or depth of processing during work/study could be used as a behavioral marker of stimulant use. PMID:27096737

  2. Caffeine, cyclic AMP and postreplication repair of mammalian DNA

    International Nuclear Information System (INIS)

    The methylxanthines, caffeine and theophylline, inhibit postreplication repair of DNA in mammalian cells. Because they also inhibit cyclic AMP phosphodiesterase, it was thought that there might be some connection between concentrations of cyclic AMP and postreplication repair. This possibility was tested by performing DNA sedimentation experiments with a cyclic AMP-resistant mouse lymphoma cell mutant and its wild-type counterpart. The results show that there is no connection between cellular cyclic AMP concentrations and the rate of postreplication repair. Therefore, it is more likely that caffeine and theophylline inhibit postreplication repair by some other means, such as by binding to DNA

  3. Effect of coffee (caffeine) against human cataract blindness

    Science.gov (United States)

    Varma, Shambhu D

    2016-01-01

    Previous biochemical and morphological studies with animal experiments have demonstrated that caffeine given topically or orally to certain experimental animal models has significant inhibitory effect on cataract formation. The present studies were undertaken to examine if there is a correlation between coffee drinking and incidence of cataract blindness in human beings. That has been found to be the case. Incidence of cataract blindness was found to be significantly lower in groups consuming higher amounts of coffee in comparison to the groups with lower coffee intake. Mechanistically, the caffeine effect could be multifactorial, involving its antioxidant as well as its bioenergetic effects on the lens. PMID:26869755

  4. The effects of catechin rich teas and caffeine on energy expenditure and fat oxidation: a meta-analysis

    Science.gov (United States)

    Different outcomes of the effect of catechin-caffeine mixtures and caffeine-only supplementation on energy expenditure and fat oxidation have been reported in short-term studies. Therefore, a meta-analysis was conducted to elucidate whether catechin-caffeine mixtures and caffeine-only supplementatio...

  5. Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Ya-Hsin, E-mail: yhcheng@mail.cmu.edu.tw [Department of Physiology, School of Medicine, China Medical University, Taichung 40402, Taiwan, ROC (China); Li, Lih-Ann; Lin, Pinpin; Cheng, Li-Chuan [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan, ROC (China); Hung, Chein-Hui [Graduate Institute of Clinical Medicine Sciences, Chang Gung University, Puizi City, Chiayi 613, Taiwan, ROC (China); Chang, Nai Wen [Department of Biochemistry, School of Medicine, China Medical University, Taichung, Taiwan, ROC (China); Lin, Chingju [Department of Physiology, School of Medicine, China Medical University, Taichung 40402, Taiwan, ROC (China)

    2012-09-15

    Baicalein is a flavonoid, known to have anti-inflammatory and anti-cancer effects. As an aryl hydrocarbon receptor (AhR) ligand, baicalein at high concentrations blocks AhR-mediated dioxin toxicity. Because AhR had been reported to play a role in regulating the cell cycle, we suspected that the anti-cancer effect of baicalein is associated with AhR. This study investigated the molecular mechanism involved in the anti-cancer effect of baicalein in oral cancer cells HSC-3, including whether such effect would be AhR-mediated. Results revealed that baicalein inhibited cell proliferation and increased AhR activity in a dose-dependent manner. Cell cycle was arrested at the G1 phase and the expression of CDK4, cyclin D1, and phosphorylated retinoblastoma (pRb) was decreased. When the AhR was suppressed by siRNA, the reduction of pRb was partially reversed, accompanied by a decrease of cell population at G1 phase and an increase at S phase, while the reduction of cyclin D1 and CDK4 did not change. This finding suggests that the baicalein activation of AhR is indeed associated with the reduction of pRb, but is independent of the reduction of cyclin D1 and CDK4. When cells were pre-treated with LiCl, the inhibitor of GSK-3β, the decrease of cyclin D1 was blocked and the reduction of pRb was recovered. The data indicates that in HSC-3 the reduction of pRb is both mediated by baicalein through activation of AhR and facilitation of cyclin D1 degradation, which causes cell cycle arrest at the G1 phase, and results in the inhibition of cell proliferation. -- Highlights: ► Baicalein causes the G1 phase arrest by decreasing Rb phosphorylation. ► Baicalein modulates AhR-mediated cell proliferation. ► Both AhR activation and cyclin D1 degradation results in hypophosphorylation of Rb. ► Baicalein facilitates cyclin D1 degradation by signalling the GSK-3β pathway.

  6. Baicalein induces G1 arrest in oral cancer cells by enhancing the degradation of cyclin D1 and activating AhR to decrease Rb phosphorylation

    International Nuclear Information System (INIS)

    Baicalein is a flavonoid, known to have anti-inflammatory and anti-cancer effects. As an aryl hydrocarbon receptor (AhR) ligand, baicalein at high concentrations blocks AhR-mediated dioxin toxicity. Because AhR had been reported to play a role in regulating the cell cycle, we suspected that the anti-cancer effect of baicalein is associated with AhR. This study investigated the molecular mechanism involved in the anti-cancer effect of baicalein in oral cancer cells HSC-3, including whether such effect would be AhR-mediated. Results revealed that baicalein inhibited cell proliferation and increased AhR activity in a dose-dependent manner. Cell cycle was arrested at the G1 phase and the expression of CDK4, cyclin D1, and phosphorylated retinoblastoma (pRb) was decreased. When the AhR was suppressed by siRNA, the reduction of pRb was partially reversed, accompanied by a decrease of cell population at G1 phase and an increase at S phase, while the reduction of cyclin D1 and CDK4 did not change. This finding suggests that the baicalein activation of AhR is indeed associated with the reduction of pRb, but is independent of the reduction of cyclin D1 and CDK4. When cells were pre-treated with LiCl, the inhibitor of GSK-3β, the decrease of cyclin D1 was blocked and the reduction of pRb was recovered. The data indicates that in HSC-3 the reduction of pRb is both mediated by baicalein through activation of AhR and facilitation of cyclin D1 degradation, which causes cell cycle arrest at the G1 phase, and results in the inhibition of cell proliferation. -- Highlights: ► Baicalein causes the G1 phase arrest by decreasing Rb phosphorylation. ► Baicalein modulates AhR-mediated cell proliferation. ► Both AhR activation and cyclin D1 degradation results in hypophosphorylation of Rb. ► Baicalein facilitates cyclin D1 degradation by signalling the GSK-3β pathway.

  7. D-type cyclins and G1 progression during liver development in the rat

    International Nuclear Information System (INIS)

    Initiation and progression through G1 requires the activity of signaling complexes containing cyclins (D- or E-type) and cyclin-dependent kinases (CDK4/6 and CDK2, respectively). We set out to identify the G1-phase cyclins and CDKs that are operative during late gestation liver development in the rat. This is a period during which hepatocytes show a high rate of proliferation that is, at least in part, independent of the mitogenic signaling pathways that are functional in mature hepatocytes. RNase protection assay and Western immunoblotting indicated that cyclin D1 is expressed at similar levels in fetal and adult liver. When cyclin D1 was induced after partial hepatectomy, its predominant CDK-binding partner was CDK4. In contrast, cyclins D2 and D3 predominated in fetal liver and were complexed with both CDK4 and CDK6. Little CDK6 protein was expressed in quiescent or regenerating adult liver. Cyclins E1 and E2 were both transcriptionally up-regulated in fetal liver. Activity of complexes containing cyclins E1 and E2 was higher in fetal liver, as was content of the cell cycle regulator, Rb. In fetal liver, Rb was highly phosphorylated at both cyclin D- and cyclin E-dependent sites. In conclusion, liver development is associated with a switch from cyclin D2/D3-containing complexes to cyclin D1:CDK4 complexes. We speculate that the switch in D-type cyclins may be associated with the dependence on mitogenic signaling that develops as hepatocytes mature

  8. Action of Caffeine as an Amyloid Inhibitor in the Aggregation of Aβ16-22 Peptides.

    Science.gov (United States)

    Sharma, Bhanita; Paul, Sandip

    2016-09-01

    Alzheimer's disease (AD) is a neurodegenerative disease caused due to aggregation of Aβ peptides in the brain tissues. Recently, several studies on AD transgenic mice have shown the effect of caffeine in significantly reducing the Aβ amyloid level in their brains. However, the mechanism and mode of caffeine action on amyloid aggregation are not known. Therefore, in this study, we have carried out molecular dynamics simulations of five amyloid-forming Aβ16-22 peptides in pure water and in a regime of caffeine solutions, with different caffeine/peptide stoichiometric ratios. The secondary structure analyses of peptides in pure water show the formation of β-sheet conformations, whereas on addition of caffeine, these ordered conformations become negligible. The radial distribution function, contact map, nonbonding interaction energy, hydrogen bonding, potential of mean force, and hydration analyses show that there is less interpeptide interaction in the presence of caffeine, and the effect is greater with an increasing caffeine ratio. The interaction of aromatic phenylalanine residues of peptides with caffeine restricts the interpeptide interaction tendency. Upon increasing the number of caffeine molecules, interaction of caffeine with other hydrophobic residues also increases. Thus, the hydrophobic core-recognition motif of amyloid formation of peptides is physically blocked by caffeine, thereby abolishing the self-assembly formation. PMID:27487451

  9. Oxidation of caffeine by phosphate radical anion in aqueous solution under anoxic conditions

    Indian Academy of Sciences (India)

    Maram Ravi Kumar; Mundra Adinarayana

    2000-10-01

    The photooxidation of caffeine in presence of peroxydiphosphate (PDP) in aqueous solution at natural H (∼7 5) has been carried out in a quantum yield reactor using a high-pressure mercury lamp. The reactions were followed spectrophotometrically by measuring the absorbance of caffeine at max (272 nm). The rates of reaction were calculated under different experimental conditions. The quantum yields were calculated from the rates of oxidation of caffeine and the intensity of light at 254 nm which was measured by using peroxydisulphate solution as a standard chemical actinometer. The reaction rates of oxidation of caffeine by PDP increase with increase in [PDP] as well as with increase in light intensity, while they are independent of [caffeine]. The quantum yields of oxidation of caffeine by PDP are independent of [PDP] as well as light intensity. However, quantum yields of oxidation of caffeine by PDP increase with increase in caffeine concentration. On the basis of these experimental results and product analysis, a probable mechanism has been suggested in which PDP is activated to phosphate radical anions (PO$_{4}^{\\bullet 2-}$) by direct photolysis of PDP and also by the sensitizing effect of caffeine. The phosphate radical anions thus produced react with caffeine by electron transfer reaction, resulting in the formation of caffeine radical cation, which deprotonates in a fast step to produce C8OH adduct radicals. These radicals might react with PDP to give final product 1,3,7-trimethyluric acid and PO$_{4}^{\\bullet 2-}$ radicals, the latter propagates the chain reaction.

  10. Relationship of chromosomal damage induced by caffeine to growth temperature and ATP level in proliferating cells.

    Science.gov (United States)

    Hernández, P; Mingo, R; González-Fernández, A; López-Sáez, J F

    1986-10-01

    Caffeine is known to induce chromosomal aberrations in proliferating cells when they are incubated during G2 and mitotic prophase. In the present paper, this caffeine effect has been analyzed in Allium cepa root meristems growing at different culture temperatures under steady-state kinetics. Caffeine (1-10 mM) induces chromosomal aberrations in a dose-dependent manner, and the treatment efficiency correlates linearly with the square of caffeine concentration. The efficiency of caffeine incubations, within the range 5-25 degrees C during equivalent cycle time periods has also been studied. It has been found that the lower the culture temperature, the higher the level of chromosomal aberrations. Moreover, at different temperatures, the level of chromosomal aberrations is a simple function of caffeine concentration and the ATP level. Therefore, the efficiency of caffeine treatment appears to be determined by some interaction between caffeine concentration and cellular ATP level. Our present results demonstrate that the influence of growth temperature on the chromosome-breaking effect of caffeine can be, at least partially, explained by the ATP levels during the incubation periods. In short, under different kinetics of plant cell proliferation, the ATP level, and/or something correlating with it, could explain the efficiency of caffeine in inducing chromosomal aberrations: the lower the ATP level, the higher the caffeine efficiency. PMID:3773927

  11. Role of state-dependent learning in the cognitive effects of caffeine in mice.

    Science.gov (United States)

    Sanday, Leandro; Zanin, Karina A; Patti, Camilla L; Fernandes-Santos, Luciano; Oliveira, Larissa C; Longo, Beatriz M; Andersen, Monica L; Tufik, Sergio; Frussa-Filho, Roberto

    2013-08-01

    Caffeine is the most widely used psychoactive substance in the world and it is generally believed that it promotes beneficial effects on cognitive performance. However, there is also evidence suggesting that caffeine has inhibitory effects on learning and memory. Considering that caffeine may have anxiogenic effects, thus changing the emotional state of the subjects, state-dependent learning may play a role in caffeine-induced cognitive alterations. Mice were administered 20 mg/kg caffeine before training and/or before testing both in the plus-maze discriminative avoidance task (an animal model that concomitantly evaluates learning, memory, anxiety-like behaviour and general activity) and in the inhibitory avoidance task, a classic paradigm for evaluating memory in rodents. Pre-training caffeine administration did not modify learning, but produced an anxiogenic effect and impaired memory retention. While pre-test administration of caffeine did not modify retrieval on its own, the pre-test administration counteracted the memory deficit induced by the pre-training caffeine injection in both the plus-maze discriminative and inhibitory avoidance tasks. Our data demonstrate that caffeine-induced memory deficits are critically related to state-dependent learning, reinforcing the importance of considering the participation of state-dependency on the interpretation of the cognitive effects of caffeine. The possible participation of caffeine-induced anxiety alterations in state-dependent memory deficits is discussed. PMID:23363704

  12. Effects of caffeine on DNA repair of UV-irradiated Dictyostelium discoideum

    International Nuclear Information System (INIS)

    Caffeine enhances the UV-killing of amoeboid cells of NC-4, but UV-irradiated γs-13 is insensitive to caffeine. UV-irradiated NC-4 becomes insensitive to the effect of caffeine during a postirradiation incubation in buffer for about 90 min, but γs-13 remains unchanged in the sensitivity to caffeine throughout the incubation for 180 min. Amoeboid cells of γs-13 can remove pyrimidine dimers as well as NC-4 even in the presence of caffeine. Caffeine inhibits rejoining of strand-breaks of DNA in UV-irradiated NC-4, but the rejoining in γs-13 is insensitive to caffeine. (author)

  13. Caffeine as a repair inhibitor and its action on the normal cell cycle in protozoa

    International Nuclear Information System (INIS)

    Caffeine has been demonstrated to inhibit repair of ionizing radiation damage, UV, and chemical DNA damage. The mechanism of caffeine action is not completely established at the present time but it has been clearly demonstrated that excision repair is inhibited in prokaryotes. The levels of caffeine which inhibit DNA repair are well tolerated by unirradiated organisms but radiation might impose an extra stress which would cause the irradiated organism to die from the normal caffeine sensitive function. The authors have tested synchronized protozoans at various times in the growth cycle for caffeine sensitivity. They infer sensitivity by the measured disruption of the normal growth cycle induced by a pulse treatment with lethal levels of caffeine. Some parts (G1) of the cell cycle show little sensitivity while late cycle (late S) may be quite sensitive. The relationship of cyclic caffeine sensitivity to repair inhibition is not obvious

  14. Study of Caffein - Catechin Association in Lyophilized Fresh Seeds and in Stabilized Extract of Cola nitida.

    Science.gov (United States)

    Maillard, C; Babadjamian, A; Balansard, G; Ollivier, B; Bamba, D

    1985-12-01

    Caffein-catechin association has been demonstrated in lyophilized fresh seeds and in stabilized extract of COLA NITIDA (Vent.) A. Chev. by using various analytical techniques which have made it possible to determine specifically the concentrations of free caffein versus associated caffein. Associated caffein varies from 0% in dried seeds to 91% in lyophilized fresh seeds and in stabilized extract of COLA. It was possible to simulate these quantitative variations of associated caffein by using an experimental model with a saturated aqueous solution of caffein and various amounts of catechin. Infrared spectrophotometric studies have shown the hydrogen bond type of the association. The differences of pharmacological effects of fresh and dried seeds may be due to the varying concentrations of associated and free caffein. PMID:17345274

  15. Modulation of cell cycle regulatory protein expression and suppression of tumor growth by mimosine in nude mice.

    Science.gov (United States)

    Chang, H C; Weng, C F; Yen, M H; Chuang, L Y; Hung, W C

    2000-10-01

    Our previous results demonstrated that the plant amino acid mimosine blocked cell cycle progression and suppressed proliferation of human lung cancer cells in vitro by multiple mechanisms. Inhibition of cyclin D1 expression or induction of cyclin-dependent kinase inhibitor p21WAF1 expression was found in mimosine-treated lung cancer cells. However, whether mimosine may modulate the expression of these cell cycle regulatory proteins and suppress tumor growth in vivo is unknown. In this study, we examined the anti-cancer effect of mimosine on human H226 lung cancer cells grown in nude mice. Our results demonstrated that mimosine inhibits cyclin D1 and induces p21WAF1 expression in vivo. Furthermore, results of TUNEL analysis indicated that mimosine may induce apoptosis to suppress tumor growth in nude mice. Collectively, these results suggest that mimosine exerts anti-cancer effect in vivo and might be useful in the therapy of lung cancer. PMID:10995875

  16. Relationship between cyclin D1 expression and poor radioresponse of murine carcinomas

    International Nuclear Information System (INIS)

    Purpose: We recently reported that overexpression of epidermal growth factor receptor (EGFR) positively correlated with radioresistance of murine carcinomas. Because cyclin D1 is a downstream sensor of EGFR activation, the present study investigated whether a relationship exists between the extent of cyclin D1 expression and in vivo radiocurability of murine tumors. We further investigated the influence of radiation on cyclin D1 expression and the expression of p27, an inhibitor of the cyclin D1 downstream pathway, as well as the relationship of these molecular determinants to cell proliferation and induced apoptosis in tumors exposed to radiation. Methods and Materials: Cyclin D1 expression was assayed in nine carcinomas syngeneic to C3Hf/Kam mice using Western blot analysis. These tumors greatly differed in their radioresponse as assessed by TCD50. The expression of cyclin D1 and p27 proteins was determined by Western blotting. Cell proliferative activity in tumors was determined by proliferating cell nuclear antigen (PCNA) immunochemistry. The effect of irradiation on the expression of cyclin D1 or p27 proteins and on PCNA positivity was determined in the radiosensitive OCa-I and in the radioresistant SCC-VII tumors. Results: Cyclin D1 expression varied among tumors by 40-fold, and its magnitude positively correlated with poorer tumor radioresponse (higher TCD50 values). The level of cyclin D1 expression paralleled that of EGFR. A 15-Gy dose reduced constitutive expression of cyclin D1 in the radiosensitive OCa-I tumors, but had no influence on expression of cyclin D1 in the radioresistant SCC-VII tumors. In contrast, 15 Gy increased the expression of p27 in radiosensitive tumors and reduced it in radioresistant tumors. Radiation induced no significant apoptosis or change in the percentage of PCNA-positive (proliferating) cells in SCC-VII tumors with high cyclin D1 levels, but it induced significant apoptosis and a decrease in the percentage of proliferating

  17. Structural and functional analysis of cyclin D1 reveals p27 and substrate inhibitor binding requirements

    Science.gov (United States)

    Liu, Shu; Bolger, Joshua K.; Kirkland, Lindsay O.; Premnath, Padmavathy N.; McInnes, Campbell

    2012-01-01

    An alternative strategy for inhibition of the cyclin dependent kinases in anti-tumor drug discovery is afforded through the substrate recruitment site on the cyclin positive regulatory subunit. Critical CDK substrates such as the Rb and E2F families must undergo cyclin groove binding before phosphorylation and hence inhibitors of this interaction also block substrate specific kinase activity. This approach offers the potential of generating highly selective and cell cycle specific CDK inhibitors and to reduce the inhibition of transcription mediated through CDK7 and 9, commonly observed with ATP competitive compounds. While highly potent peptide and small molecule inhibitors of CDK2/cyclin A, E substrate recruitment have been reported, little information has been generated on the determinants of inhibitor binding to the cyclin groove of the CDK4/cyclin D1 complex. CDK4/cyclin D is a validated anti-cancer drug target and continues to be widely pursued in the development of new therapeutics based on cell cycle blockade. We have therefore investigated the structural basis for peptide binding to its cyclin groove and have examined the features contributing to potency and selectivity of inhibitors. Peptidic inhibitors of CDK4/cyclin D of pRb phosphorylation have been synthesized, and their complexes with CDK4/cyclin D1 crystal structures have been generated. Based on available structural information, comparisons of the cyclin grooves of cyclin A2 and D1 are presented and provide insights into the determinants for peptide binding and the basis for differential binding and inhibition. In addition, a complex structure has been generated in order to model the interactions of the CDKI, p27KIP1, with cyclin D1. This information has been used shed light onto the endogenous inhibition of CDK4 and also to identify unique aspects of cyclin D1 and which can be exploited in the design of cyclin groove based CDK inhibitors. Peptidic and non-peptidic compounds have been synthesized

  18. The influence of caffeine on sustained attention : An ERP study

    NARCIS (Netherlands)

    Lorist, MM; Snel, J; De Ruiter, MB; Ruijter, J

    2000-01-01

    The present study investigated the effects of caffeine on sustained attention by measuring concentration and fatigue. Event-related potentials (ERPs) and behavioral measures were recorded from 12 participants who worked continuously for approximately 10 min in a self-paced reaction task under condit

  19. The Determination of Caffeine in Coffee: Sense or Nonsense?

    Science.gov (United States)

    Beckers, Jozef L.

    2004-01-01

    The presence of caffeine in coffee is determined by the use of separation devices and UV-vis spectrophotometry. The results indicate that the use of various analytical tools helps to perceive the higher concentration values obtained through UV-vis spectrophotometry than with separation methods.

  20. Effect of caffeine on target detection and rifle marksmanship.

    Science.gov (United States)

    Gillingham, R; Keefe, A A; Keillor, J; Tikuisis, P

    2003-12-15

    Thirteen healthy and rifle-trained male military reservists performed shooting sessions on two separate occasions 1 h following the ingestion of placebo or 300 mg of caffeine. Shooting included both friend-foe (FF) and vigilance (VIG) tasks, and were performed in the following order: two FF sequences (4 min each), four VIG sequences (30 min each), and two additional FF sequences. The shooting sessions lasted approximately 2.5 h under outdoor conditions (air temperature range from - 3 to 14 degrees C) and were held 48 h apart in a counter-balanced order. Performance measures during the shooting session included engagement time, friend-foe discrimination, and marksmanship accuracy and precision. Assessments of thermal comfort, tiredness, and debilitating symptoms preceded and followed the shooting session, while a self-assessment on performance was administered post-shooting only. Blood was sampled immediately prior to the beginning of the shooting session and was used to determine plasma caffeine, cortisol, and testosterone levels. Engagement times were faster and certain measures of accuracy and precision were impaired during the later FF and VIG sequences. However, caffeine ingestion had no affect upon any of the marksmanship measures, although it did alleviate cold stress and tiredness. That caffeine ingestion did not affect target detection and rifle marksmanship is a finding that differs from other studies, and is explained by a beneficial arousal caused by the mild level of cold stress experienced by the participants. PMID:14668172

  1. Cyclin D1 and mammary carcinoma: new insights from transgenic mouse models

    International Nuclear Information System (INIS)

    Cyclin D1 is one of the most commonly overexpressed oncogenes in breast cancer, with 45–50% of primary ductal carcinomas overexpressing this oncoprotein. Targeted deletion of the gene encoding cyclin D1 demonstrates an essential role in normal mammary gland development while transgenic studies provide evidence that cyclin D1 is a weak oncogene in mammary epithelium. In a recent exciting development, Yu et al. demonstrate that cyclin D1-deficient mice are resistant to mammary carcinomas induced by c-neu and v-Ha-ras, but not those induced by c-myc or Wnt-1. These findings define a pivotal role for cyclin D1 in a subset of mammary cancers in mice and imply a functional role for cyclin D1 overexpression in human breast cancer

  2. Cyclin Y和Cyclin X在肺癌细胞株A549中的细胞定位和功能%The Function Study and Cell Localization of Cyclin Y and Cyclin X in Lung Cancer Cell Line A549

    Institute of Scientific and Technical Information of China (English)

    周世杰; 江姝; 赵晓婷; 岳文涛

    2013-01-01

    [Purpose] To construct pEGFP-N1/CCNY vector and pEGFP-N1/CCNX eukaryotic expression vector,and to explore the location and function of CyclinY/CyclinX in lung caner A549 cell.[Methods] CCNY and CCNX genes were amplified from human lung adenocarcinoma cell line H1299 by PCR.The recombinant plasmids pEGFP-N1/CCNY and pEGFP-N1/CCNX were constructed and transfected into A549 cells.The cellular localization and expression of CyclinY and Cyclin X were detected by fluorescence microscopy and Western Blot.[Results] The recombinant plasmid pEGFP-N1/CCNY and pEGFP-N1/CCNX were constructed successfully.Green fluorescence on the surface of transfected cells was found by fluorescence microscope.Western Blot confirmed Cyclin Y,Cyclin X expression.Cyclin Y and Cyclin X located at cellular membrane and nucleus in recombinant plasmid cell respectively.After transfection,A549-CCNY pEGFPN1 cell viability was 1.36±0.02,A549-CCNX pEGFPN cell viability was 11.45 ±0.05,which was higher than that in A549-pEGFPN1 (1.31±0.03) (P all<0.01).[Conclusion] In A549 cell,Cyclin Y and Cyclin X are differently distributed,Cyclin X plays more important role in promoting proliferation than Cyclin Y.%[目的]构建CCNY和CCNX基因的真核表达载体并观察其在人肺癌细胞株A549中的表达及定位,为进一步探讨Cyclin Y、Cyclin X在肺癌中的细胞定位和功能奠定了基础.[方法]以人肺腺癌细胞株H1299 cDNA为模板扩增CCNY和CCNX基因,并构建CCNY和CCNX过表达真核表达载体.应用荧光显微照相及Western Blot方法鉴定该细胞株中Cyclin Y、Cyclin X的定位及表达.[结果]成功构建pEGFP-N1/CCNY和pEGFP-N1/CCNX真核表达载体.荧光显微照相显示绿色荧光,Western Blot检测证实转染重组质粒细胞表达Cyclin Y、Cyclin X蛋白,Cyclin Y和Cyclin X分别定位于胞膜与胞核.A549-pEGFPN1细胞活性为1.31±0.03,而转染后的A549-CCNY pEGFPN1细胞活性为1.36±0.02,A549-CCNX pEGFPN1细胞活性为1.45±0.05(P<0

  3. Severe acute caffeine poisoning due to intradermal injections: Mesotherapy hazard

    Directory of Open Access Journals (Sweden)

    Perković-Vukčević Nataša

    2012-01-01

    Full Text Available Introduction. Caffeine is indicated in the treatment of migraine headaches, as well as neonatal apnea and bradycardia syndrome. In mild poisoning, the most prevalent symptoms are nausea, vomiting, diarrhea, tremor, anxiety and headache. In more severe cases, symptoms consist of heart rythym abnormalities, myocardial infarction and seizures. Due to its common lipolytic effect, caffeine is used in mesotherapy, usually in combination with drugs of similar effect. We presented a patient with acute iatrogenic caffeine poisoning. Case report. A 51-year-old woman, with preexisting hypertension and hypertensive cardiomyopathy was subjected to cosmetic treatment in order to remove fat by intradermal caffeine injections. During the treatment the patient felt sickness, an urge to vomit, and a pronounced deterioration of general condition. Upon examination, the patient exhibited somnolence, hypotension and nonsustained ventricular tachycardia, which was sufficient enough evidence for further hospitalization. On admission to the intensive care unit the patient was anxious with increased heart rate, normotensive, with cold, damp skin, and visible traces of injection sites with surrounding hematomas on the anterior abdominal wall. Paroxysmal supraventricular tachycardia (PSVT on electrocardiographic monitoring was found. The laboratory analysis determined a lowered potassium level of 2.1 mmol/L (normal range 3,5 - 5.2 mmol/L, and a toxicological analysis (liquid chromatography with ultraviolet detection proved a toxic concentration of caffeine in plasma - 85.03 mg/L (toxic concentration over 25 mg/L. On application of intensive therapy, antiarrhythmics, and substitution of potassium, as well as both symptomatic and supportive therapy, there was a significant recovery. The patient was discharged without any sequele within four days. Conclusion. A presented rare iatrogenic acute caffeine poisoning occured due to massive absorption of caffeine from the

  4. Differential requirement of cyclin-dependent kinase 2 for oligodendrocyte progenitor cell proliferation and differentiation

    OpenAIRE

    Caillava Céline; Baron-Van Evercooren Anne

    2012-01-01

    Abstract Cyclin-dependent kinases (Cdks) and their cyclin regulatory subunits control cell growth and division. Cdk2-cyclin E complexes, phosphorylating the retinoblastoma protein, drive cells through the G1/S transition into the S phase of the cell cycle. Despite its fundamental role, Cdk2 was found to be indispensable only in specific cell types due to molecular redundancies in its function. Converging studies highlight involvement of Cdk2 and associated cell cycle regulatory proteins in ol...

  5. Iterative Conversion of Cyclin Binding Groove Peptides into Druglike CDK Inhibitors with Antitumor Activity

    OpenAIRE

    Premnath, Padmavathy Nandha; Craig, Sandra N.; Liu, Shu; Anderson, Erin L.; Grigoroudis, Asterios I.; Kontopidis, George; Perkins, Tracy L.; Wyatt, Michael D.; Pittman, Douglas L.; McInnes, Campbell

    2014-01-01

    The cyclin groove is an important recognition site for substrates of the cell cycle cyclin dependent kinases and provides an opportunity for highly selective inhibition of kinase activity through a non-ATP competitive mechanism. The key peptide residues of the cyclin binding motif have been studied in order to precisely define the structure–activity relationship for CDK kinase inhibition. Through this information, new insights into the interactions of peptide CDK inhibitors with key subsites ...

  6. Cyclin D1 Governs Adhesion and Motility of MacrophagesV⃞

    OpenAIRE

    Neumeister, Peter; Pixley, Fiona J.; Xiong, Ying; Xie, Huafeng; Wu, Kongming; Ashton, Anthony; Cammer, Michael; Chan, Amanda; Symons, Marc; Stanley, E. Richard; Pestell, Richard G.

    2003-01-01

    The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates the retinoblastoma protein, thereby promoting cell-cycle progression. Cyclin D1 is overexpressed in hematopoetic and epithelial malignancies correlating with poor prognosis and metastasis in several cancer types. Because tumor-associated macrophages have been shown to enhance malignant progression and metastasis, and cyclin D1-deficient mice are resistant to oncogene-induced malignancie...

  7. Schizophrenia susceptibility gene product dysbindin-1 regulates the homeostasis of cyclin D1.

    Science.gov (United States)

    Ito, Hidenori; Morishita, Rika; Nagata, Koh-Ichi

    2016-08-01

    Dysbindin-1 (dystrobrevin binding protein-1, DTNBP1) is now widely accepted as a potential schizophrenia susceptibility gene and accumulating evidence indicates its functions in the neural development. In this study, we tried to identify new binding partners for dysbindin-1 to clarify the novel function of this molecule. When consulted with BioGRID protein interaction database, cyclin D3 was found to be a possible binding partner for dysbindin-1. We then examined the interaction between various dysbindin-1 isoforms (dysbindin-1A, -1B and -1C) and all three D-type cyclins (cyclin D1, D2, and D3) by immunoprecipitation with the COS7 cell expression system, and found that dysbindin-1A preferentially interacts with cyclin D1. The mode of interaction between these molecules was considered as direct binding since recombinant dysbindin-1A and cyclin D1 formed a complex in vitro. Mapping analyses revealed that the C-terminal region of dysbindin-1A binds to the C-terminal of cyclin D1. Consistent with the results of the biochemical analyses, endogenous dysbindin-1was partially colocalized with cyclin D1 in NIH3T3 fibroblast cells and in neuronal stem and/or progenitor cells in embryonic mouse brain. While co-expression of dysbindin-1A with cyclin D1 changed the localization of the latter from the nucleus to cytosol, cyclin D1-binding partner CDK4 inhibited the dysbindin-cyclin D1 interaction. Meanwhile, depletion of endogenous dysbindin-1A increased cyclin D1 expression. These results indicate that dysbindin-1A may control the cyclin D1 function spatiotemporally and might contribute to better understanding of the pathophysiology of dysbindin-1-associated disorders. PMID:27130439

  8. [Clinical study of BRON-L syrup (cough suppressant) abuse].

    Science.gov (United States)

    Miyatake, Ryosuke; Doi, Tomoko; Date, Kenji; Naitoh, Tomomichi; Suwaki, Hiroshi

    2002-02-01

    In 1980s, abuse and dependence of BRON-W syrup (cough suppressant), which contains methylephedrine, dihydrocodeine, chlorpheniramine and caffeine, were prevalent in Japan. Pharmacological and clinical studies suggest that methylephedrine and dihydrocodeine cause dependence. Although BRON-L syrup, newly modified cough suppressant contains only chlorpheniramine and caffeine, there still are abuse and dependence of this drug. In this report, three cases of BRON-L syrup abuse are demonstrated. All cases started using BRON-L syrup in the late teens in their peer groups, and dropped out from school. Case 1 misused only BRON-L syrup, but case 2 and 3 were multi-drug abusers (case 2: amphetamine, cocaine, and marijuana, case 3: solvent, alcohol, bromovalerylurea), and had kept in tough with the peer groups. Case 2 and 3 hospitalized more than 2 times. Withdrawal symptoms, such as headache, insomnia, and irritability were mild and improved in a few weeks after drug use was stopped. These findings suggest that 1) psychosocial backgrounds of these cases are in common with those of BRON-W syrup abusers, but 2) the clinical course and prognosis of multi-drug abusers are different from the BRON single abuser, 3) chlorpheniramine and caffeine possibly cause dependence, 4) abusers are likely to choose BRON brand although two main dependence-producing constituents are removed from it now. Therefore, prevention and care of BRON-L abusers requires both psychosocial and pharmacological aspects. PMID:11915306

  9. Effects of caffeine ingestion on metabolism and exercise performance.

    Science.gov (United States)

    Costill, D L; Dalsky, G P; Fink, W J

    1978-01-01

    In an effort to assess the effects of caffeine ingestion on metabolism and performance during prolonged exercise, nine competitive cyclists (two females and seven males) exercised until exhaustion on a bicycle ergometer at 80% of Vo2 max. One trial was performed an hour after ingesting decaffeinated coffee (Trial D), while a second trial (C) required that each subject consume coffee containing 330 mg of caffeine 60 min before the exercise. Following the ingestion of caffeine (Trial C), the subjects were able to perform an average of 90.2 (SE +/- 7.2) min of cycling as compared to an average of 75.5 (SE +/- 5.1) min in the D Trial. Measurements of plasma free fatty acids, glycerol and respiratory exchange ratios evidenced a greater rate of lipid metabolism during the caffeine trial as compared to the decaffeinated exercise treatment. Calculations of carbohydrate (CHO) metabolism from respiratory exchange data revealed that the subjects oxidized roughly 240 g of CHO in both trials. Fat oxidation, however, was significantly higher (P less than 0.05) during the C Trial (118 g or 1.31 g/min) than in the D Trial (57 g or 0.75 g/min). On the average the participants rated (Perceived Exertion Scale) their effort during the C Trial to be significantly (P less than 0.05) easier than the demands of the D treatment. Thus, the enhanced endurance performance observed in the C Trial was likely the combined effects of caffeine on lipolysis and its positive influence on nerve impulse transmission. PMID:723503

  10. Potential gene regulatory role for cyclin D3 in muscle cells

    Indian Academy of Sciences (India)

    Fathima Athar; Veena K Parnaik

    2015-09-01

    Cyclin D3 is important for muscle development and regeneration, and is involved in post-mitotic arrest of muscle cells. Cyclin D3 also has cell-cycle-independent functions such as regulation of specific genes in other tissues. Ectopic expression of cyclin D3 in myoblasts, where it is normally undetectable, promotes muscle gene expression and faster differentiation kinetics upon serum depletion. In the present study, we investigated the mechanistic role of cyclin D3 in muscle gene regulation. We initially showed by mutational analysis that a stable and functional cyclin D3 was required for promoting muscle differentiation. Using chromatin immunoprecipitation assays, we demonstrated that expression of cyclin D3 in undifferentiated myoblasts altered histone epigenetic marks at promoters of muscle-specific genes like MyoD, Pax7, myogenin and muscle creatine kinase but not non-muscle genes. Cyclin D3 expression also reduced the mRNA levels of certain epigenetic modifier genes. Our data suggest that epigenetic modulation of muscle-specific genes in cyclin-D3-expressing myoblasts may be responsible for faster differentiation kinetics upon serum depletion. Our results have implications for a regulatory role for cyclin D3 in muscle-specific gene activation.

  11. Promoter de-methylation of cyclin D2 by sulforaphane in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Hsu Anna

    2011-10-01

    Full Text Available Abstract Sulforaphane (SFN, an isothiocyanate derived from cruciferous vegetables, induces potent anti-proliferative effects in prostate cancer cells. One mechanism that may contribute to the anti-proliferative effects of SFN is the modulation of epigenetic marks, such as inhibition of histone deacetylase (HDAC enzymes. However, the effects of SFN on other common epigenetic marks such as DNA methylation are understudied. Promoter hyper-methylation of cyclin D2, a major regulator of cell cycle, is correlated with prostate cancer progression, and restoration of cyclin D2 expression exerts anti-proliferative effects on LnCap prostate cancer cells. Our study aimed to investigate the effects of SFN on DNA methylation status of cyclin D2 promoter, and how alteration in promoter methylation impacts cyclin D2 gene expression in LnCap cells. We found that SFN significantly decreased the expression of DNA methyltransferases (DNMTs, especially DNMT1 and DNMT3b. Furthermore, SFN significantly decreased methylation in cyclin D2 promoter regions containing c-Myc and multiple Sp1 binding sites. Reduced methlyation of cyclin D2 promoter corresponded to an increase in cyclin D2 transcript levels, suggesting that SFN may de-repress methylation-silenced cyclin D2 by impacting epigenetic pathways. Our results demonstrated the ability of SFN to epigenetically modulate cyclin D2 expression, and provide novel insights into the mechanisms by which SFN may regulate gene expression as a prostate cancer chemopreventive agent.

  12. Cyclin E Is Stabilized in Response to Replication Fork Barriers Leading to Prolonged S Phase Arrest*

    Science.gov (United States)

    Lu, Xiaoyan; Liu, Jia; Legerski, Randy J.

    2009-01-01

    Cyclin E is a regulator of cyclin-dependent protein kinases (Cdks) and is involved in mediating the cell cycle transition from G1 to S phase. Here, we describe a novel function for cyclin E in the long term maintenance of checkpoint arrest in response to replication barriers. Exposure of cells to mitomycin C or UV irradiation, but not ionizing radiation, induces stabilization of cyclin E. Stabilization of cyclin E reduces the activity of Cdk2-cyclin A, resulting in a slowing of S phase progression and arrest. In addition, cyclin E is shown to be required for stabilization of Cdc6, which is required for activation of Chk1 and the replication checkpoint pathway. Furthermore, the stabilization of cyclin E in response to replication fork barriers depends on ATR, but not Nbs1 or Chk1. These results indicate that in addition to its well studied role in promoting cell cycle progression, cyclin E also has a role in regulating cell cycle arrest in response to DNA damage. PMID:19812034

  13. Adolescent caffeine consumption increases adulthood anxiety-related behavior and modifies neuroendocrine signaling.

    Science.gov (United States)

    O'Neill, Casey E; Newsom, Ryan J; Stafford, Jacob; Scott, Talia; Archuleta, Solana; Levis, Sophia C; Spencer, Robert L; Campeau, Serge; Bachtell, Ryan K

    2016-05-01

    Caffeine is a commonly used psychoactive substance and consumption by children and adolescents continues to rise. Here, we examine the lasting effects of adolescent caffeine consumption on anxiety-related behaviors and several neuroendocrine measures in adulthood. Adolescent male Sprague-Dawley rats consumed caffeine (0.3g/L) for 28 consecutive days from postnatal day 28 (P28) to P55. Age-matched control rats consumed water. Behavioral testing for anxiety-related behavior began in adulthood (P62) 7 days after removal of caffeine. Adolescent caffeine consumption enhanced anxiety-related behavior in an open field, social interaction test, and elevated plus maze. Similar caffeine consumption in adult rats did not alter anxiety-related behavior after caffeine removal. Characterization of neuroendocrine measures was next assessed to determine whether the changes in anxiety were associated with modifications in the HPA axis. Blood plasma levels of corticosterone (CORT) were assessed throughout the caffeine consumption procedure in adolescent rats. Adolescent caffeine consumption elevated plasma CORT 24h after initiation of caffeine consumption that normalized over the course of the 28-day consumption procedure. CORT levels were also elevated 24h after caffeine removal and remained elevated for 7 days. Despite elevated basal CORT in adult rats that consumed caffeine during adolescence, the adrenocorticotropic hormone (ACTH) and CORT response to placement on an elevated pedestal (a mild stressor) was significantly blunted. Lastly, we assessed changes in basal and stress-induced c-fos and corticotropin-releasing factor (Crf) mRNA expression in brain tissue collected at 7 days withdrawal from adolescent caffeine. Adolescent caffeine consumption increased basal c-fos mRNA in the paraventricular nucleus of the hypothalamus. Adolescent caffeine consumption had no other effects on the basal or stress-induced c-fos mRNA changes. Caffeine consumption during adolescence increased

  14. No effect of caffeine on exercise performance in high ambient temperature.

    Science.gov (United States)

    Roelands, Bart; Buyse, Luk; Pauwels, Frank; Delbeke, Frans; Deventer, Koen; Meeusen, Romain

    2011-12-01

    Caffeine, an adenosine receptor antagonist, has shown to improve performance in normal ambient temperature, presumably via an effect on dopaminergic neurotransmission through the antagonism of adenosine receptors. However, there is very limited evidence from studies that administered caffeine and examined its effects on exercise in the heat. Therefore, we wanted to study the effects of caffeine on performance and thermoregulation in high ambient temperature. Eight healthy trained male cyclists completed two experimental trials (in 30°C) in a double-blind-randomized crossover design. Subjects ingested either placebo (6 mg/kg) or caffeine (6 mg/kg) 1 h prior to exercise. Subjects cycled for 60 min at 55% W (max), immediately followed by a time trial to measure performance. The significance level was set at p endorphin plasma concentrations at the end of the time trial (p = 0.032). The present study showed no ergogenic effect of caffeine when administered 1 h before exercise in 30°C. This confirms results from a previous study that examined the effects of caffeine administration on a short (15 min) time trial in 40°C. However, caffeine increased core temperature during exercise. Presumably, the rate of increase in core temperature may have counteracted the ergogenic effects of caffeine. However, other factors such as interindividual differences in response to caffeine and changes in neurotransmitter concentrations might also be responsible for the lack of performance improvement of caffeine in high ambient temperature. PMID:21461761

  15. Caffeine intake antagonizes salt sensitive hypertension through improvement of renal sodium handling.

    Science.gov (United States)

    Yu, Hao; Yang, Tao; Gao, Peng; Wei, Xing; Zhang, Hexuan; Xiong, Shiqiang; Lu, Zongshi; Li, Li; Wei, Xiao; Chen, Jing; Zhao, Yu; Arendshorst, William J; Shang, Qianhui; Liu, Daoyan; Zhu, Zhiming

    2016-01-01

    High salt intake is a major risk factor for hypertension. Although acute caffeine intake produces moderate diuresis and natriuresis, caffeine increases the blood pressure (BP) through activating sympathetic activity. However, the long-term effects of caffeine on urinary sodium excretion and blood pressure are rarely investigated. Here, we investigated whether chronic caffeine administration antagonizes salt sensitive hypertension by promoting urinary sodium excretion. Dahl salt-sensitive (Dahl-S) rats were fed with high salt diet with or without 0.1% caffeine in drinking water for 15 days. The BP, heart rate and locomotor activity of rats was analyzed and urinary sodium excretion was determined. The renal epithelial Na(+) channel (ENaC) expression and function were measured by in vivo and in vitro experiments. Chronic consumption of caffeine attenuates hypertension induced by high salt without affecting sympathetic nerve activity in Dahl-S rats. The renal α-ENaC expression and ENaC activity of rats decreased after chronic caffeine administration. Caffeine increased phosphorylation of AMPK and decrease α-ENaC expression in cortical collecting duct cells. Inhibiting AMPK abolished the effect of caffeine on α-ENaC. Chronic caffeine intake prevented the development of salt-sensitive hypertension through promoting urinary sodium excretion, which was associated with activation of renal AMPK and inhibition of renal tubular ENaC. PMID:27173481

  16. Caffeine Consuming Children and Adolescents Show Altered Sleep Behavior and Deep Sleep

    Directory of Open Access Journals (Sweden)

    Andrina Aepli

    2015-10-01

    Full Text Available Caffeine is the most commonly ingested psychoactive drug worldwide with increasing consumption rates among young individuals. While caffeine leads to decreased sleep quality in adults, studies investigating how caffeine consumption affects children’s and adolescents’ sleep remain scarce. We explored the effects of regular caffeine consumption on sleep behavior and the sleep electroencephalogram (EEG in children and adolescents (10–16 years. While later habitual bedtimes (Caffeine 23:14 ± 11.4, Controls 22:17 ± 15.4 and less time in bed were found in caffeine consumers compared to the control group (Caffeine 08:10 ± 13.3, Controls 09:03 ± 16.1, morning tiredness was unaffected. Furthermore, caffeine consumers exhibited reduced sleep EEG slow-wave activity (SWA, 1–4.5 Hz at the beginning of the night compared to controls (20% ± 9% average reduction across all electrodes and subjects. Comparable reductions were found for alpha activity (8.25–9.75 Hz. These effects, however, disappeared in the morning hours. Our findings suggest that caffeine consumption in adolescents may lead to later bedtimes and reduced SWA, a well-established marker of sleep depth. Because deep sleep is involved in recovery processes during sleep, further research is needed to understand whether a caffeine-induced loss of sleep depth interacts with neuronal network refinement processes that occur during the sensitive period of adolescent development.

  17. Maternal caffeine exposure alters neuromotor development and hippocampus acetylcholinesterase activity in rat offspring.

    Science.gov (United States)

    Souza, Ana Claudia; Souza, Andressa; Medeiros, Liciane Fernandes; De Oliveira, Carla; Scarabelot, Vanessa Leal; Da Silva, Rosane Souza; Bogo, Mauricio Reis; Capiotti, Katiucia Marques; Kist, Luiza Wilges; Bonan, Carla D; Caumo, Wolnei; Torres, Iraci L S

    2015-01-21

    The objective of this study was to evaluate the effects of maternal caffeine intake on the neuromotor development of rat offspring and on acetylcholine degradation and acetylcholinesterase (AChE) expression in the hippocampus of 14-day-old infant rats. Rat dams were treated with caffeine (0.3g/L) throughout gestation and lactation until the pups were 14 days old. The pups were divided into three groups: (1) control, (2) caffeine, and (3) washout caffeine. The washout group received a caffeine solution until the seventh postnatal day (P7). Righting reflex (RR) and negative geotaxis (NG) were assessed to evaluate postural parameters as an index of neuromotor reflexes. An open-field (OF) test was conducted to assess locomotor and exploratory activities as well as anxiety-like behaviors. Caffeine treatment increased both RR and NG latency times. In the OF test, the caffeine group had fewer outer crossings and reduced locomotion compared to control, while the washout group showed increased inner crossings in relation to the other groups and fewer rearings only in comparison to the control group. We found decreased AChE activity in the caffeine group compared to the other groups, with no alteration in AChE transcriptional regulation. Chronic maternal exposure to caffeine promotes important alterations in neuromotor development. These results highlight the ability of maternal caffeine intake to interfere with cholinergic neurotransmission during brain development. PMID:25451122

  18. Complex interactions of caffeine and its structural analogs with ultraviolet light in cell killing

    International Nuclear Information System (INIS)

    We measured the clonogenic survival response of cultured mouse 10 Tsup(1/2) cells exposed to UV light and caffeine post-treatment. When 0.5 and 1 mM caffeine were present for 24 h immediately following UV, the D0 values of the biphasic survival curves suggest that one subpopulation was sensitized and one subpopulation was protected from killing by UV light. A cloned survivor from the radioprotected subpopulation responded to UV plus caffeine in identical manner as the parent cells. When the caffeine exposure was prolonged to 48 h, only the radiosensitizing effect was observed. Two demethylated analogs of caffeine were also tested. The response of 10 Tsup(1/2) cells to 1 mM theophylline present for 24 h after UV irradiation was approximately the same as that for the same treatment with 1 mM caffeine. However, prolonging the theophylline exposure to 48 h failed to produce the same kind of potentiation of cell killing as that observed for caffeine. Xanthine by itself was a toxic to 10 Tsup(1/2) cells as caffeine, but had no synergistic effect as caffeine when given to UV-irradiated cells for 24 or 48 h. It is therefore unlikely that all the effects of caffeine on UV-irradiated cells are mediated by its demethylated metabolites. (orig.)

  19. Sustained-release of caffeine from a polymeric tablet matrix: An in vitro and pharmacokinetic study

    International Nuclear Information System (INIS)

    Caffeine is utilized as a stimulant to impart a desired level of alertness during certain working hours. Usually, a single dose of caffeine induces 2-3 h of alertness coupled with side effects whereas a longer effect of 8-12 h is very useful for both daily life and military action. Thus, there is a need to deliver the stimulant continuously to an individual at one time to impart an increased level of alertness for the period stated after administration. This study aimed to design a polymeric microparticle system for sustained delivery of caffeine using a polymeric matrix. Poly(ethylene oxide) (PEO) was used as the erodible matrix material and the caffeine polymeric tablets were fabricated by compression using a Graseby Specac hydraulic press. In vitro release profiles as well as the pharmacokinetics studies data were obtained. Caffeine tablets fabricated using various polymers showed a high initial burst release type profile as compared to the caffeine-PEO-tablet. The PK studies showed sustained delivery of caffeine resulted in two expected phenomena: a reduction in the initial high rate of caffeine release (burst release) as well as a reduction in the change in caffeine concentration in the systemic circulation. A simple two-component system for sustained-release caffeine formulation therefore has been achieved

  20. The synergistic effects of radiation and caffeine on embryonic development in mice

    International Nuclear Information System (INIS)

    The combined action of radiation with caffeine has been studied in mouse embryos. Radiation and/or caffeine were administered to ICR mice on day 7 of gestation, at which time the embryos were in the early stage of organogenesis. Intrauterine death, gross malformation, body weight and sex ratio were selected as indicators of effects. Doses of gamma irradiation were 0.5, 1.0 and 2.0 Gy and those of caffeine were 0.10 and 0.25 mg/g of body weight. Intrauterine mortality increased with increasing radiation dose and this trend was more remarkable in combination with caffeine. The malformation such as parietal hernia, exencephalia, hydrocephalia and cleft palate appeared frequently in the fetuses treated with both radiation and caffeine compared to the fetuses treated with each agent separately. Fetal body weight was a sensitive indicator of the effects on growth retardation of radiation and/or caffeine. The sex ratio of live fetuses did not change by means of treatment with radiation and/or caffeine. Intrauterine mortality and frequency of malformations in mice treated with both radiation and caffeine were higher than the sum of those induced by radiation and those by caffeine separately. The results demonstrated that the combined effects of radiation and caffeine were synergistic. (author)

  1. By using tissue chip technique to study the expression of p27 and cyclinE in breast carcinoma%采用组织芯片技术研究乳腺癌中p27和cyclinE的表达

    Institute of Scientific and Technical Information of China (English)

    戴艳枝; 刘勇; 袁晟; 邓宇

    2003-01-01

    To study the expressions of p27 ,cyclinE and analysis its meaning in breast carcinoma. Methods By using tissue chip technique creating 80 cases breast carcinoma tissue chip. at the same time using the S-P immunohis-tochemical methods, the expressions of p27 and cyclinE in breast carcinoma tissue chip was studied.Results The positive rates of p27 and cyclinE were 38.8% and 52.5% in 80 eases breast carcinoma respectively. A significant correlation was found between the lowexpression of p27, overexpression of cyclinE and metastasis of lymph node in breast carcinoma. A simaificant correlation was found be-tween the lowexpression of p27 and overexpression of cyclinE in breast carcinoma. Conclusion The expression of p27 and cyclinE might be considered to be a reference indicator for prognosis of breast carcinoma. The lowexpression of p27 has an ability to effect the overexpression of cyclinE in breast carcinoma. It is feasible to utilize tissue chip for a rapid, economic and accurate screening of clinical tissue specimens on a large scale.

  2. Trends and patterns of caffeine consumption among US teenagers and young adults, NHANES 2003-2012.

    Science.gov (United States)

    Tran, N L; Barraj, L M; Bi, X; Jack, M M

    2016-08-01

    Caffeine consumption among US teenagers (13-17y), young adults (18-24y) and adults (25-29y) for a 10 year period was examined using NHANES 2003-12. Of the 85% who consume caffeine 84% consume caffeinated beverages. This percentage remained constant despite new caffeine sources. Less than 7.1% of the population consume energy drinks. While mean caffeine intake among teenage caffeine consumers decreased from 62 to 55 mg/day (p-value = 0.018) over the 10-year period, no discernable trend was observed for other age groups. Caffeine intake from energy drinks increased, and was only statistically significant for age 18-24y accounting for <9% of total caffeine intake. Mean caffeine intake per consumption occasion was equivalent between coffee and energy drinks for teenagers and young adults. During a 30-min period mean caffeine consumption was similar when an energy drink was the only consumption event or when it occurred with other caffeinated beverage products suggestive of a substitution effect. Linear regression models of caffeine intake from energy drinks against caffeine from coffee, tea and soda among energy drink consumers in the upper 50th percentile shows a statistically significant inverse relationship (R2 = 28%, coffee: β = -0.35, p < 0.001; tea: β = -0.44, p < 0.001; soda: β = -0.22, p = 0.036) and further supports the substitution concept. PMID:27288929

  3. Effects of caffeine on X-irradiated synchronous, asynchronous and plateau phase mouse ascites cells: the importance of progression through the cell cycle for caffeine enhancement of killing

    International Nuclear Information System (INIS)

    Caffeine potentiated the killing effect of X-rays on exponentially growing cells giving rise to exponential curves (D0=(0.8+-0.05)Gy) at 4mM and 14 hours treatment. Irradiated plateau phase cells were less sensitive. Exponentially growing cells also became less sensitive to the effects of caffeine when they were incubated in the conditioned medium of plateau phase cells(C-medium) in which cell growth was considerably inhibited. Low caffeine concentrations(2mM) enhanced X-ray induced killing of cells irradiated in G1-,G1/S- or S-phase, but more effectively G2-phase cells. High caffeine concentrations (6mM) enhanced killing of cells in all phases of the cell cycle. Incubation of synchronized populations in C-medium during treatment with caffeine (2mM and 6mM) resulted in less potentiation than in cells treated in fresh medium. The expression of X-ray induced potentially lethal damage caused by 6mM caffeine in cells irradiated in various phases resulted in an exponential survival curve with a mean lethal dose of (0.8+-0.05)Gy, but the time of caffeine treatment necessary to reach this curve was different for cells irradiated in different phases. PLD repair, measured as loss of sensitivity to 6mM caffeine (4 hours treatment) was of 1-2 hours duration. (author)

  4. Molecular dynamic behavior and binding affinity of flavonoid analogues to the cyclin dependent kinase 6/cyclin D complex.

    Science.gov (United States)

    Khuntawee, Wasinee; Rungrotmongkol, Thanyada; Hannongbua, Supot

    2012-01-23

    The cyclin dependent kinases (CDKs), each with their respective regulatory partner cyclin that are involved in the regulation of the cell cycle, apoptosis, and transcription, are potentially interesting targets for cancer therapy. The CDK6 complex with cyclin D (CDK6/cycD) drives cellular proliferation by phosphorylation of specific key target proteins. To understand the flavonoids that inhibit the CDK6/cycD functions, molecular dynamics simulations (MDSs) were performed on three inhibitors, fisetin (FST), apigenin (AGN), and chrysin (CHS), complexed with CDK6/cycD, including the two different binding orientations of CHS: FST-like (CHS_A) and deschloro-flavopiridol-like (CHS_B). For all three inhibitors, including both CHS orientations, the conserved interaction between the 4-keto group of the flavonoid and the backbone V101 nitrogen of CDK6 was strongly detected. The 3'- and 4'-OH groups on the flavonoid phenyl ring and the 3-OH group on the benzopyranone ring of inhibitor were found to significantly increase the binding and inhibitory efficiency. Besides the electrostatic interactions, especially through hydrogen bond formation, the van der Waals (vdW) interactions with the I19, V27, F98, H100, and L152 residues of CDK6 are also important factors in the binding efficiency of flavonoids against the CDK6/cycD complex. On the basis of the docking calculation and MM-PBSA method, the order of the predicted inhibitory affinities of these three inhibitors toward the CDK6/cycD was FST > AGN > CHS, which is in good agreement with the experimental data. In addition, CHS preferentially binds to the active CDK6 in a different orientation to FST and AGN but similar to its related analog, deschloro-flavopiridol. The obtained results are useful as the basic information for the further design of potent anticancer drugs specifically targeting the CDK6 enzyme. PMID:22172011

  5. Effect of the caffeine on treated and non-treated plasmid DNA with stannic chloride

    International Nuclear Information System (INIS)

    Caffeine, a methilxantine drug is a component of coffee, tea, stimulants and other drinks. Caffeine inhibits phosphodiesterase leading to intracellular accumulation of cyclic AMP, blocks adenosine receptors, and increases the release of Ca2+. We have studied the possible effect of caffeine in DNA plasmid treated or not with stannous chloride (SnCl2). Previous evaluations of the effect of caffeine on the labeling of red blood cells and plasma proteins with technetium-99m have showed a decrease of % ATI in the insoluble fraction of plasma proteins. Samples of DNA were treated with SnCl2 (0 and 200μg/ml) in 0.8% agarose. SnCl2 has induced break on DNA and caffeine has not showed effect on the DNA. This indicates that caffeine does not eliminate the oxidant action of SnCl2 and does not promote break in isolated DNA plasmid. (author)

  6. Effect of caffeine on the ultraviolet light induction of SV40 virus from transformed hamster cells

    International Nuclear Information System (INIS)

    The effect of caffeine on the uv light induction of SV40 virus from two transformed hamster cell lines heterogeneous for the induction of infectious virus was studied. The amount of virus induced was significantly increased in both cell lines when exposure to uv light was followed by treatment with caffeine. Caffeine in the absence of uv irradiation did not stimulate virus induction, nor did it stimulate SV40 replication in a lytic infection. There was an apparent difference in the concentrations of caffeine which maximally stimulated SV40 virus induction in the two cell lines. This effect could not be explained by differences in cell survival after exposure to uv light and caffeine. Since caffeine is known to cause the accumulation of gaps formed in DNA during postreplication repair of uv-irradiated rodent cells, our results support the hypothesis that the formation of gaps or breaks in DNA is an important early step in virus induction

  7. Effect of caffeine on radiation-induced mitotic delay: delayed expression of G2 arrest

    International Nuclear Information System (INIS)

    In the presence of 5 mM caffeine, irradiated (1.5 Gy) S and G2 cells progressed to mitosis in register and without arrest in G2. Caffeine (5 mM) markedly reduced mitotic delay even after radiation doses up to 20 Gy. When caffeine was removed from irradiated (1.5 Gy) and caffeine-treated cells, a period of G2 arrest followed, similar in length to that produced by radiation alone. The arrest expressed was independent of the duration of the caffeine treatment for exposures up to 3 hr. The similarity of the response to the cited effects of caffeine on S-phase delay suggests a common basis for delay induction in S and G2 phases

  8. Caffeine elevates blood pressure response to exercise in mild hypertensive men.

    Science.gov (United States)

    Sung, B H; Lovallo, W R; Whitsett, T; Wilson, M F

    1995-12-01

    The present study examined the effects of caffeine on blood pressure (BP) regulation in hypertensive men during exercise. Twenty unmedicated, mild hypertensives (HT, BP = 140/90 to 160/105 mm Hg) and 12 age-matched, normotensives (NT, BP pressure products were significantly higher on caffeine days in HT at postdrug and during exercise. On caffeine day, 7 (39%) HT and 1 (8%) NT showed an excessive BP response (> 230 for systolic or > 120 for diastolic) during exercise. In conclusion, caffeine has significant hemodynamic effects on mild hypertensives at rest and during exercise. The increased rate-pressure products following caffeine during exercise place a greater workload on the heart, and abstinence from caffeine, especially before exercise, may be beneficial for persons with hypertension. PMID:8998252

  9. Caffeine and human cerebral blood flow: A positron emission tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Cameron, O.G.; Modell, J.G.; Hariharan, M. (Univ. of Michigan Medical Center, Ann Arbor (USA))

    1990-01-01

    Positron emission tomography (PET) was used to quantify the effect of caffeine on whole brain and regional cerebral blood flow (CBF) in humans. A mean dose of 250 mg of caffeine produced approximately a 30% decrease in whole brain CBF; regional differences in caffeine effect were not observed. Pre-caffeine CBF strongly influenced the magnitude of the caffeine-induced decrease. Caffeine decreased p{sub a}CO{sub 2} and increased systolic blood pressure significantly; the change in p{sub a}CO{sub 2} did not account for the change in CBF. Smaller increases in diastolic blood pressure, heart rate, plasma epinephrine and norepinephrine, and subjectively reported anxiety were also observed.

  10. Acute caffeine treatment increases extracellular nucleotide hydrolysis from rat striatal and hippocampal synaptosomes.

    Science.gov (United States)

    da Silva, Rosane Souza; Bruno, Alessandra Nejar; Battastini, Ana Maria Oliveira; Sarkis, João José Freitas; Lara, Diogo Rizzato; Bonan, Carla Denise

    2003-08-01

    The psychostimulant caffeine promotes behavioral effects such as hyperlocomotion, anxiety, and disruption of sleep by blockade of adenosine receptors. The availability of extracellular adenosine depends on its release by transporters or by the extracellular ATP catabolism performed by the ecto-nucleotidase pathway. This study verified the effect of caffeine on NTPDase 1 (ATP diphosphohydrolase) and 5'-nucleotidase of synaptosomes from hippocampus and striatum of rats. Caffeine and theophylline tested in vitro were unable to modify nucleotide hydrolysis. Caffeine chronically administered in the drinking water at 0.3 g/L or 1 g/L for 14 days failed to affect nucleotide hydrolysis. However, acute administration of caffeine (30 mg/kg, i.p.) produced an enhancement of ATP (50%) and ADP (32%) hydrolysis in synaptosomes of hippocampus and striatum, respectively. This activation of ATP and ADP hydrolysis after acute treatment suggests a compensatory effect to increase adenosine levels and counteract the antagonist action of caffeine. PMID:12834266

  11. Effects of caffeine co-treatment with radiation on breast cancer susceptibility gene BRCA1

    International Nuclear Information System (INIS)

    The sensitizing effect of caffeine to carbon ion radiation was investigated and the change of BRCA1 expression was observed. The MCF-7 breast carcinoma cells were exposed to carbon ion beams with or without caffeine. The cell survival was automatically monitored by RT-CES system. Cell cycle distribution was assessed by flow cytometry. The levels of BRCA1 mRNA were analyzed by real-time RT-PCR.The expression of BRCA1 protein and its phosphorylation were examined by Western blot. The results show that caffeine increases the sensitivity of MCF-7 cells to carbon ion radiation, and abrogates the radiation-induced G2 arrest. Caffeine inhibits radiation-induced BRCA1 expression both at mRNA and protein level. At the same time, caffeine specifically abolishes BRCA1 phosphorylation of Ser-1524. The data implicate that caffeine inhibits the expression of BRCA1 protein and its phosphorylation. (authors)

  12. Tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces cell proliferation in normal human bronchial epithelial cells through NFκB activation and cyclin D1 up-regulation

    International Nuclear Information System (INIS)

    Cigarette smoke contains several carcinogens known to initiate and promote tumorigenesis as well as metastasis. Nicotine is one of the major components of the cigarette smoke and the 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific carcinogen. Here, we demonstrated that NNK stimulated cell proliferation in normal human bronchial epithelial cells (NHBE) and small airway epithelial cells (SAEC). Cells exposed to NNK resulted in an increase in the level of cyclin D1 protein (as early as 3-6 h). Increased phosphorylation of the Rb Ser795 was detected at 6-15 h after NNK treatment and thereby promoted cells entering into the S phase (at 15-21 h). The increased cyclin D1 protein level was induced through activation of the transcription factor, nuclear factor kB (NFκB), in the NHBE cells. Treatment of the NHBE cells with PD98059, an ERK1/2 (extracellular signal-regulated protein kinase)-specific inhibitor, specifically suppressed the NNK-induced IκBα phosphorylation at position 32 of the serine residue, suggesting that the ERK1/2 kinase was involved in the IκBα phosphorylation induced by NFκB activation. To determine whether the NNK-induced NFκB activation and cyclin D1 induction were also observed in vivo, A/J mice were treated with NNK (9.1 mg) for 20 weeks and the results showed a significant induction of cyclin D1 and NFκB translocation determined by immunoblotting analyses. We further demonstrated that the nicotine acetylcholine receptor (nAchR), which contains the α3-subunit, was the major target mediating NNK-induced cyclin D1 expression in the NHBE cells. In summary, our findings demonstrate for the first time that NNK could stimulate normal human bronchial cell proliferation through activation of the NFκB, which in turn up-regulated the cyclin D1 expression

  13. Activation of Cyclin-Dependent Kinase 5 Is a Consequence of Cell Death

    Directory of Open Access Journals (Sweden)

    Yixia Ye

    2009-01-01

    Full Text Available Cyclin-dependent kinase 5 (Cdk5 is similar to other Cdks but is activated during cell differentiation and cell death rather than cell division. Since activation of Cdk5 has been reported in many situations leading to cell death, we attempted to determine if it was required for any form of cell death. We found that Cdk5 is activated during apoptotic deaths and that the activation can be detected even when the cells continue to secondary necrosis. This activation can occur in the absence of Bim, calpain, or neutral cathepsins. The kinase is typically activated by p25, derived from p35 by calpain-mediated cleavage, but inhibition of calpain does not affect cell death or the activation of Cdk5. Likewise, RNAi-forced suppression of the synthesis of Cdk5 does not affect the incidence or kinetics of cell death. We conclude that Cdk5 is activated as a consequence of metabolic changes that are common to many forms of cell death. Thus its activation suggests processes during cell death that will be interesting or important to understand, but activation of Cdk5 is not necessary for cells to die.

  14. [Expression of cyclin-dependent kinase 2-associated protein 1 in chicken embryos of different sexes].

    Science.gov (United States)

    Yang, Yu; Feng, Yan-Ping; Gong, Ping; Huang, Pan; Li, Shi-Jun; Peng, Xiu-Li; Gong, Yan-Zhang

    2009-09-01

    To investigate the expression and functions of cyclin-dependent kinase 2-associated protein 1 (cdk2ap1) screened by suppression subtractive hybridization in chicken embryo development, a pair of primers was designed to amplify the cdk2ap1 fragment by RT-PCR and subsequently the fragment obtained was cloned into the plasmid pGEM-T. Sense and antisense probes labeled with digoxigenin were generated using SP6 and T7 RNA polymerases, respectively, and used to examine cdk2ap1 expression in chicken embryos of both sexes by whole-mount in situ hybridization. In both sexes, cdk2ap1 was expressed in the head mesenchyme, rhombencephalon, optic vesicles, spinal neural tube, and forelimb of 4.0-day-old embryos and the expression in males was significantly higher than that in females. In addition, in the genital ridge and hindlimb of the 4.0-day-old chicken embryo, cdk2ap1 was obviously expressed in the males but not in females. It is supposed that cdk2ap1 may play a role in the sexual differentiation and development of gonad of chicken embryo. PMID:19819846

  15. Quarkonium suppression

    Indian Academy of Sciences (India)

    P Petreczky

    2003-04-01

    I discuss quarkonium suppression in equilibrated strongly interacting matter. After a brief review of basic features of quarkonium production I discuss the application of recent lattice data on the heavy quark potential to the problem of quarkonium dissociation as well as the problem of direct lattice determination of quarkonium properties in finite temperature lattice QCD.

  16. [Clinical research on improvement of glucose metabolic marker level by coffee drinking-validity of saliva caffeine concentration measurement].

    Science.gov (United States)

    Okada, Tomoko; Kobayashi, Daisuke; Kono, Suminori; Shimazoe, Takao

    2010-05-01

    We measured both serum and saliva caffeine concentration using HPLC and assessed the correlation between them in volunteers with mild obesity. Significant correlation was shown between saliva and serum caffeine concentration. It may be necessary to measure caffeine metabolite concentration because its metabolites may also have an improving effect of glucose metabolism. In summary, we found that saliva caffeine concentration measurement was useful to assess caffeine intake level. Moreover, it will be helpful to know whether caffeine has an improving effect of glucose metabolism. PMID:20460869

  17. Guarana Provides Additional Stimulation over Caffeine Alone in the Planarian Model

    OpenAIRE

    Moustakas, Dimitrios; Mezzio, Michael; Rodriguez, Branden R.; Constable, Mic Andre; Mulligan, Margaret E.; Voura, Evelyn B.

    2015-01-01

    The stimulant effect of energy drinks is primarily attributed to the caffeine they contain. Many energy drinks also contain other ingredients that might enhance the tonic effects of these caffeinated beverages. One of these additives is guarana. Guarana is a climbing plant native to the Amazon whose seeds contain approximately four times the amount of caffeine found in coffee beans. The mix of other natural chemicals contained in guarana seeds is thought to heighten the stimulant effects of g...

  18. Chronic caffeine exposure attenuates blast-induced memory deficit in mice

    Institute of Scientific and Technical Information of China (English)

    Ya-Lei Ning; Nan Yang; Xing Chen; Zi-Ai Zhao; Xiu-Zhu Zhang; Xing-Yun Chen; Ping Li

    2015-01-01

    Objective:To investigate the effects of three different ways of chronic caffeine administration on blastinduced memory dysfunction and to explore the underlying mechanisms.Methods:Adult male C57BL/6 mice were used and randomly divided into five groups:control:without blast exposure,con-water:administrated with water continuously before and after blast-induced traumatic brain injury (bTBI),con-caffeine:administrated with caffeine continuously for 1 month before and after bTBI,pre-caffeine:chronically administrated with caffeine for 1 month before bTBI and withdrawal after bTBI,post-caffeine:chronically administrated with caffeine after bTBI.After being subjected to moderate intensity of blast injury,mice were recorded for learning and memory performance using Morris water maze (MWM) paradigms at 1,4,and 8 weeks post-blast injury.Neurological deficit scoring,glutamate concentration,proinflammatory cytokines production,and neuropathological changes at 24 h,1,4,and 8 weeks post-bTBI were examined to evaluate the brain injury in early and prolonged stages.Adenosine A1 receptor expression was detected using qPCR.Results:All of the three ways of chronic caffeine exposure ameliorated blast-induced memory deficit,which is correlated with the neuroprotective effects against excitotoxicity,inflammation,astrogliosis and neuronal loss at different stages of injury.Continuous caffeine treatment played positive roles in both early and prolonged stages of bTBI;pre-bTBl and post-bTBl treatment of caffeine tended to exert neuroprotective effects at early and prolonged stages of bTBI respectively.Up-regulation of adenosine A1 receptor expression might contribute to the favorable effects of chronic caffeine consumption.Conclusion:Since caffeinated beverages are widely consumed in both civilian and military personnel and are convenient to get,the results may provide a promising prophylactic strategy for blast-induced neurotrauma and the consequent cognitive impairment.

  19. Consumption of dietary caffeine and coffee in physically active populations: physiological interactions.

    Science.gov (United States)

    Tunnicliffe, Jasmine M; Erdman, Kelly Anne; Reimer, Raylene A; Lun, Victor; Shearer, Jane

    2008-12-01

    Caffeine is a proven ergogenic aid, increasing athletic performance, endurance, and mental chronometry at doses as low as 1-3 mg.kg-1. As coffee is a readily available and commonly ingested form of caffeine, the two are often equated. However, coffee also contains hundreds of other biologically active compounds, many of which are metabolically distinct from caffeine. The purpose of this review was to examine the prevalence of coffee and (or) caffeine consumption among elite Canadian athletes, and to delineate the effects of coffee and caffeine on physical activity, weight maintenance, performance, and metabolism. A total of 270 self-reported 3-day food records were examined for caffeine intake from athletes registered with Canadian Sport Centres in 2005 and 2006. Athletes ranged in age from 16-45 years, and competed in 38 different sports. Results showed that 30% of athletes ingested >1 mg.kg-1.day-1 from a variety of sources. Average daily intake was 0.85 +/- 13 mg.kg-1. Caffeine intake was not correlated with any 1 sport; the 10 highest caffeine users were athletes from 9 different sports, including skill, endurance, and power sports. No differences were noted for average caffeine ingestion between summer and winter sports. High caffeine intakes corresponded to coffee ingestion, with the 25 highest individual intakes (193-895 mg.day-1) from coffee drinkers. In summary, it can be concluded that the majority of high-level Canadian athletes consume dietary caffeine primarily in the form of coffee. However, levels consumed are insufficient to elicit performance enhancement. Potential detrimental effects of caffeine consumption on exercise performance include gastric upset, withdrawal, sleep disturbance, and interactions with other dietary supplements. PMID:19088792

  20. Awareness and use of caffeine by athletes competing at the 2005 Ironman Triathlon World Championships.

    Science.gov (United States)

    Desbrow, Ben; Leveritt, Michael

    2006-10-01

    This study assessed the knowledge, prevalence, and quantity of caffeine use by athletes competing at the 2005 Ironman Triathlon World Championships. Caffeine-related questionnaires were self-administered to 140 (105 male and 35 female, 40.3 +/- 10.7 y) athletes representing 16 countries. Fifty of these athletes further consented to immediate post-race blood samples for analysis of plasma caffeine and paraxanthine using high-performance liquid chromatography (HPLC). Seventy-two percent of 70 athletes correctly identified caffeine as being an unrestricted substance in triathlon. The majority of athletes [125 (89%)] were planning on using a caffeinated substance immediately prior to or throughout the race. Cola drinks (78%), caffeinated gels (42%), coffee (usually pre-race) (37%), energy drinks (13%), and NoDoz tablets (9%) were the most popular caffeinated choices. Mean +/- standard deviation (and range) post race plasma caffeine and paraxanthine levels were 22.3 +/- 20 micromol/L (1.7 to 98.4) and 9.4 +/- 6 micromol/L (1.8 to 28.9), respectively. Seven athletes (14%) finished with plasma caffeine levels > or = 40 micromol/L. Plasma values from elite athletes did not differ from age group competitors. Despite the prevalence of its consumption and the training experience of this athletic group, over one quarter of athletes remained either confused or uninformed about caffeine's legality. Levels of plasma caffeine taken immediately post race indicated that athletes typically finish with quantities of caffeine that have been shown to improve endurance performance (i.e., approximately 20 micromol/L or a dose of > or = 3 mg/kg body weight). PMID:17240785

  1. The Extraction of Caffeine from Tea: An Old Undergraduate Experiment Revisited

    Science.gov (United States)

    Murray, Scott D.; Hansen, Peter J.

    1995-09-01

    The extraction of caffeine from tea leaves is a common organic chemistry experiment. A water/1-propanol/sodium chloride ternary system was found to be a suitable replacement for the more traditional water/organochlorine solvent systems. Approximately 80% of the caffeine in the tea leaves can be recovered as crude caffeine. The ternary system employs chemicals which are not only less expensive, but also less toxic.

  2. Caffeine consumption and self-assessed stress, anxiety, and depression in secondary school children

    OpenAIRE

    Richards, Gareth; Smith, Andrew

    2015-01-01

    Previous research suggests that effects of caffeine on behaviour are positive unless one is investigating sensitive groups or ingestion of large amounts. Children are a potentially sensitive subgroup, and especially so considering the high levels of caffeine currently found in energy drinks. The present study used data from the Cornish Academies Project to investigate associations between caffeine (both its total consumption, and that derived separately from energy drinks, cola, tea, and coff...

  3. A benefit-risk assessment of caffeine as an analgesic adjuvant.

    Science.gov (United States)

    Zhang, W Y

    2001-01-01

    Caffeine has been an additive in analgesics for many years. However, the analgesic adjuvant effects of caffeine have not been seriously investigated since a pooled analysis conducted in 1984 showed that caffeine reduces the amount of paracetamol (acetaminophen) necessary for the same effect by approximately 40%. In vitro and in vivo pharmacological research has provided some evidence that caffeine can have anti-nociceptive actions through blockade of adenosine receptors, inhibition of cyclo-oxygenase-2 enzyme synthesis, or by changes in emotion state. Nevertheless, these actions are only considered in some cases. It is suggested that the actual doses of analgesics and caffeine used can influence the analgesic adjuvant effects of caffeine, and doses that are either too low or too high lead to no analgesic enhancement. Clinical trials suggest that caffeine in doses of more than 65 mg may be useful for enhancement of analgesia. However, except for in headache pain, the benefits are equivocal. While adding caffeine to analgesics increases the number of patients who become free from headache [rate ratio = 1.36, 95% confidence interval (CI) 1.17 to 1.58], it also leads to more patients with nervousness and dizziness (relative risk = 1.60, 95% CI 1.26 to 2.03). It is suggested that long-term use or overuse of analgesic medications is associated with rebound headache. However, there is no robust evidence that headache after use or withdrawal of caffeine-containing analgesics is more frequent than after other analgesics. Case-control studies have shown that caffeine-containing analgesics are associated with analgesic nephropathy (odds ratio = 4.9, 95% CI 2.3 to 10.3). However, no specific contribution of caffeine to analgesic nephropathy can be identified from these studies. Whether caffeine produces nephrotoxicity on its own, or increases nephrotoxicity due to analgesics, is yet to be established. PMID:11772146

  4. High-dose adenosine overcomes the attenuation of myocardial perfusion reserve caused by caffeine.

    OpenAIRE

    Reyes, E.; Loong, C Y; Harbinson, Mark; Donovan, J; Anagnostopoulos, C.; Underwood, S. R.

    2008-01-01

    Objectives:We studied whether an increase in adenosine dose overcomes caffeine antagonism on adenosine-mediated coronary vasodilation.Background:Caffeine is a competitive antagonist at the adenosine receptors, but it is unclear whether caffeine in coffee alters the actions of exogenous adenosine, and whether the antagonism can be surmounted by increasing the adenosine dose.Methods:Myocardial perfusion scintigraphy (MPS) was used to assess adenosine-induced hyperemia in 30 patients before (bas...

  5. Cyclin D1 Gene Expression in Oral Mucosa of Tobacco Chewers”–An Immunohistochemical Study

    OpenAIRE

    Basnaker, Maharudrappa; SP, Srikala; BNVS, Satish

    2014-01-01

    Objective: The objective of the present study was to evaluate the expression of cyclin D1 in normal oral mucosa of both non tobacco habituated and tobacco habituated individuals histologically and also compare and correlate cyclin D1 expression with histopathologically confirmed cases of oral squamous cell carcinomas.

  6. Cyclin A-Cdk2 Phosphorylates BH3 only Protein Bad in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    HE Kan; CHEN Yue; LI Jing-hua; ZHAN Zhuo; WU Yong-ge; KONG Wei; JIN Ying-hua

    2007-01-01

    Increasing evidence suggests that Cyclin A-Cdk2 activity is required in the apoptosis process induced by various stimuli. To determine a specific substrate of Cyclin A-Cdk2 for apoptosis, in this study, we carried out anin vitro kinase assay using immunoprecipitated complex Cyclin A-Cdk2 as an enzyme source, and recombinant protein GST-Bad as a substrate. Our study showed that Bad was clearly phosphorylated by Cyclin A-Cdk2 in vitro. To examine whether protein Bad can also be phosphorylated by Cyclin A-Cdk2 kinase in vivo, we transiently overexpressed protein Bad with Cyclin A or Cdk2-dn, a dominant negative version of Cdk2, in Hela cells and determined the phosphorylation status of protein Bad. The test showed that protein Bad was clearly phosphorylated in Cyclin A overexpressed cells,but not in Cdk2-dn or mock transfectent. Moreover, etoposide also caused the phosphorylation of endogenetic Bad. In conclusion, here we provide first time evidence that protein Bad can be a substrate of Cyclin A-Cdk2 apoptosis for in vitro and in vivo.

  7. Caffeine–N-phthaloyl-β-alanine (1/1)

    OpenAIRE

    Bhatti, Moazzam H.; Uzma Yunus; Syed Raza Shah; Ulrich Flörke

    2012-01-01

    The title co-crystal [systematic name: 3-(1,3-dioxoisoindolin-2-yl)propanoic acid–1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione (1/1)], C8H10N4O2·C11H9NO4, is the combination of 1:1 adduct of N-phthaloyl-β-alanine with caffeine. The phthalimide and purine rings in the N-phthaloyl-β-alanine and caffeine molecules are essentially planar, with r.m.s. deviations of the fitted atoms of 0.0078 and 0.0118 Å, respectively. In the crystal, the two m...

  8. Molecular mechanisms of DNA repair inhibition by caffeine

    International Nuclear Information System (INIS)

    Caffeine potentiates the mutagenic and lethal effects of genotoxic agents. It is thought that this is due, at least in some organisms, to inhibition of DNA repair. However, direct evidence for inhibition of repair enzymes has been lacking. Using purified Escherichia coli DNA photolyase and (A)BC excinuclease, we show that the drug inhibits photoreactivation and nucleotide excision repair by two different mechanisms. Caffeine inhibits photoreactivation by interfering with the specific binding of photolyase to damaged DNA, and it inhibits nucleotide excision repair by promoting nonspecific binding of the damage-recognition subunit, UvrA, of (A)BC excinuclease. A number of other intercalators, including acriflavin and ethidium bromide, appear to inhibit the excinuclease by a similar mechanism--that is, by trapping the UvrA subunit in nonproductive complexes on undamaged DNA

  9. Caffeine for the prevention of postoperative nausea and vomiting

    Directory of Open Access Journals (Sweden)

    Richard A Steinbrook

    2013-01-01

    Statistical analysis: Statistical comparisons were tested using bivariable linear and logistic regression for each outcome and then adjusted for high/low risk. Results: Nausea in the postanesthesia care unit (PACU was more common in the caffeine (16 of 62 patients than the placebo group (seven of 69; P = 0.02. There were no significant differences in the use of rescue antiemetics in the PACU, in the incidence of nausea or vomiting over 24 h postoperatively, nor in other outcomes (headache, fatigue, or overall satisfaction either in the PACU or at 24 h; time-to-discharge was similar for both groups. Conclusion: Caffeine was not effective in the prevention of PONV or headache, and did not improve time-to-discharge or patient satisfaction.

  10. Methotrexate and its therapeutic antagonists caffeine and theophylline, target a motogenic T-cell mechanism driven by thrombospondin-1 (TSP-1).

    Science.gov (United States)

    Talme, Toomas; Bergdahl, Eva; Sundqvist, Karl-Gösta

    2016-05-01

    Methotrexate (MTX) is a widely used treatment for inflammatory diseases such as rheumatoid arthritis and psoriasis, based on the concept that it is immunosuppressive. Its mechanism of action, however, remains unclear, although it is thought to depend on adenosine. Caffeine and theophylline, which have several targets including adenosine receptors, have been shown to suppress the beneficial clinical effects of MTX. Here we show that MTX and caffeine and theophylline differentially affect a motogenic T-cell mechanism driven by endogenous thrombospondin-1 (TSP-1) and its receptor, low density lipoprotein receptor-related protein 1 (LRP1). MTX stimulated TSP-1 expression and the motogenic TSP-1/TSP-1 receptor mechanism in primary human T cells, hence mimicking IL-2 and CXCL12, which similar to MTX, dampen inflammatory disease. SiRNA-mediated gene silencing of TSP-1 and LRP1 inhibited this stimulatory effect. Caffeine and theophylline inhibited the TSP-1/TSP-1 receptor mechanism by inhibiting LRP1 expression. These results indicate that the effect of MTX on T cells is immunoregulatory rather than immunosuppressive, and suggest a pathway dependent on TSP-1/TSP-1 receptor interactions for the regulation of immune responses. PMID:26909742

  11. The cloning of cyclin B3 and its gene expression during hormonally induced spermatogenesis in the teleost, Anguilla japonica

    International Nuclear Information System (INIS)

    We cloned cyclin B1, B2, and B3 cDNAs from the eel testis. Northern blot analysis indicated that these cyclin B mRNAs were expressed and increased from day 3 onward after the hormonal induction of spermatogenesis, and that cyclin B3 was most dominantly expressed during spermatogenesis. In situ hybridization showed that cyclin B1 and B2 were present from the spermatogonium stage to the spermatocyte stage. On the other hand, cyclin B3 mRNA was present only in spermatogonia. Although mouse cyclin B3 is expressed specifically in the early meiotic prophase, these results indicate that eel cyclin B3 expression is limited during spermatogenesis to spermatogonia, but is not present in spermatocytes. These facts together suggest that eel cyclin B3 is specifically involved in spermatogonial proliferation (mitosis), but not in meiosis

  12. Overexpression of miR-155 promotes the proliferation and invasion of oral squamous carcinoma cells by regulating BCL6/cyclin D2

    Science.gov (United States)

    ZENG, QI; TAO, XIAOAN; HUANG, FANG; WU, TONG; WANG, JUAN; JIANG, XIAO; KUANG, ZIRONG; CHENG, BIN

    2016-01-01

    Although microRNA-155 (miR-155) is known to play an important role in many cancers, its expression and function in oral squamous cell carcinoma (OSCC) was not fully understood. Thus, in the present study, we investigated the expression of miR-155 and also the role this miR plays in OSCC. We used the OSCC cell line (CAL27) and paired tumor and non-tumor tissue samples from patients with OSCC in order to detect the expression of miR-155. Cell proliferation, migration and invasion assays were then undertaken in order to determine the effect of miR-155 on the biological behavior of CAL27 cells following transient transfection with miR-155 mimic and antagomir. The regulatory effect of miR-155 on its target gene B-cell CLL/lymphoma 6 (BCL6) and downstream gene cyclin D2 (CCND2) was also analyzed. We found that miR-155 expression in OSCC cell and tumor tissues was significantly higher than that of the controls. We noted that the miR-155 mimic enhanced CAL27 cell proliferation, migration and invasion ability, downregulated BCL6 levels, and increased cyclin D2 expression. However, we noted that abrogating miR-155 with the miR-155 antagomir suppressed CAL27 cell proliferation, migration and invasion, upregulated BCL6 and reduced cyclin D2 expression. These results indicate that miR-155 plays a tumor-promoting role in OSCC by regulating the BCL6/cyclin D2 axis. PMID:26986233

  13. Disrupted G1 to S phase clearance via cyclin signaling impairs liver tissue repair in thioacetamide-treated type 1 diabetic rats

    International Nuclear Information System (INIS)

    Previously we reported that a nonlethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats because of irreversible acute liver injury owing to inhibited hepatic tissue repair, primarily due to blockage of G0 to S phase progression of cell division cycle. On the other hand, DB rats receiving 30 mg TA/kg exhibited equal initial liver injury and delayed tissue repair compared to nondiabetic (NDB) rats receiving 300 mg TA/kg, resulting in a delay in recovery from liver injury and survival. The objective of the present study was to test the hypothesis that impaired cyclin-regulated progression of G1 to S phase of the cell cycle may explain inhibited liver tissue repair, hepatic failure, and death, contrasted with delayed liver tissue repair but survival observed in the DB rats receiving 300 in contrast to 30 mg TA/kg. In the TA-treated NDB rats sustained MAPKs and cyclin expression resulted in higher phosphorylation of retinoblastoma (pRb), explaining prompt tissue repair and survival. In contrast, DB rats receiving the same dose of TA (300 mg/kg) exhibited suppressed MAPKs and cyclin expression that led to inhibition of pRb, inhibited tissue repair, and death. On the other hand, DB rats receiving 30 mg TA/kg exhibited delayed up regulation of MAPK signaling that delayed the expression of CD1 and pRb, explaining delayed stimulation of tissue repair observed in this group. In conclusion, the hepatotoxicant TA has a dose-dependent adverse effect on cyclin-regulated pRb signaling: the lower dose causes a recoverable delay, whereas the higher dose inhibits it with corresponding effect on the ultimate outcomes on hepatic tissue repair; this dose-dependent adverse effect is substantially shifted to the left of the dose response curve in diabetes

  14. Effects of Cyclooxygenase Inhibitors in Combination with Taxol on Expression of Cyclin D1 and Ki-67 in a Xenograft Model of Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Liang Wan

    2012-08-01

    Full Text Available The present study was designed to investigate the effects of cyclooxygenase (COX inhibitors in combination with taxol on the expression of cyclin D1 and Ki-67 in human ovarian SKOV-3 carcinoma cells xenograft-bearing mice. The animals were treated with 100 mg/kg celecoxib (a COX-2 selective inhibitor alone, 3 mg/kg SC-560 (a COX-1 selective inhibitor alone by gavage twice a day, 20 mg/kg taxol alone by intraperitoneally (i.p. once a week, or celecoxib/taxol, SC-560/celecoxib, SC-560/taxol or SC-560/celecoxib/taxol, for three weeks. To test the mechanism of the combination treatment, the index of cell proliferation and expression of cyclin D1 in tumor tissues were determined by immunohistochemistry. The mean tumor volume in the treated groups was significantly lower than control (p < 0.05, and in the three-drug combination group, tumor volume was reduced by 58.27% (p < 0.01; downregulated cell proliferation and cyclin D1 expression were statistically significant compared with those of the control group (both p < 0.01. This study suggests that the effects of COX selective inhibitors on the growth of tumors and decreased cell proliferation in a SKOV-3 cells mouse xenograft model were similar to taxol. The three-drug combination showing a better decreasing tendency in growth-inhibitory effect during the experiment may have been caused by suppressing cyclin D1 expression.

  15. The effect of caffeine on repair in chlamydomonas reinhardtii. Pt. 1

    International Nuclear Information System (INIS)

    The effect of caffeine on repair was studied in the green alga Chlamydomonas reinhardtii. Treatment of UV-irradiated wild-type (UVS+) cells with a sublethal level of caffeine caused a significant increase in survival compared to untreated UV-irradiated cells. Caffeine did not affect survival in the repair-deficient strain UVSE1, which is deficient in repair of UV-induced damage carried out by enzymes associated with recombination during meiosis. A significant increase in survival in the presence of caffeine was observed in the repair-deficient strain UVSE4 in which recombination during meiosis is not affected. Treatment of zygotes homozygous for UVS+, UVSE1, or UVSE4 with sublethal levels of caffeine caused marked increases in recombination frequency in UVS+ and UVSE4 zygotes and no increase in recombination in UVSE1 zygotes. These results indicate that caffeine increases recombination in normal strains. Increased opportunity for recombination caused by caffeine would not result in increased recombination frequency in the UVSE1 strain, assuming limited-recombination enzyme activity in this strain. The observed increase in survival following UV-irradiation in the presence of caffeine in strains having normal recombination would therefore be associated with a caffeine-induced increase in opportunities for recombination repair. (orig.)

  16. Influence of caffeine on sparing effect of dose fractionation in housefly larvae

    International Nuclear Information System (INIS)

    Caffeine, given during interfraction interval, abolishes the sparing effect of dose fractionation observed for delay of pupariation in Musca domestica larvae. When given as postirradiation treatment after single exposure, caffeine increases the delay in a synergistic manner. Pretreatment of the larvae with ascorbic acid for 3 h protects from radiation-induced delay whereas pretreatment with caffeine does not have any effect. Combination of ascorbic acid and caffeine pretreatment protects the larvae only at low concentration (0.05%) and not at high concentration (0.1%). (orig.)

  17. Influence of caffeine on chromosome lesions induced by chemical mutagens and radiation. 2

    International Nuclear Information System (INIS)

    The modifying influence of caffeine on γ-ray induced chromosome lesions was studied by chromosome aberration anaysis. Caffeine was applied as a pre- and post-treatment agent following seed (G1) and root meristem (G2 and S) irradiation of C.capillaris. The frequency of chromosome aberrations induced in G1 was changed neither by post- nor by pre-treatment with caffeine. This fact proves the lack of caffeine modifying effect. Applied as a post-treatment agent caffeine enhances considerably the frequency of chromosome aberrations induced in root meristem cells. This is especially valid for G2 irradiated cells, while in S cells no synergistic effect was established between induced chromosome lesions and caffeine. The enhancement of chromosome aberration frequency produced in G2 shows a clearly manifested dependence on the time (moment) of caffeine application post irradiation. Most considerable enhancement was obtained following post-treatment with caffeine immediately after irradiation. In the following intervals - 15 and 30 min - it decreases progressively, while after 60, 180 and 300 min no enhancing effect is observed. The probable causes for the manifestation and the lack of synergistic effect between chromosome lesions induced in the various mitotic cycle phases and caffeine are discussed. (author)

  18. BRCA1 and its phosphorylation involved in caffeine-inhibitable event upstream of G2 checkpoint

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Caffeine,which specifically inhibits ATM/ATR kinases,efficiently abrogates the ionizing radiation(IR)-induced G2 arrest and increases the sensitivity of various tumor cells to IR.Mechanisms for the effect of caffeine remain to be elucidated.As a target of ATM/ATR kinases,BRCA1 becomes activated and phosphorylated in response to IR.Thus,in this work,we investigated the possible role of BRCA1 in the effect of caffeine on G2 checkpoint and observed how BRCA1 phosphorylation was regulated in this process.For these purposes,the BRCA1 protein level and the phosphorylation states were analyzed by Western blotting by using an antibody against BRCA1 and phospho-specific antibodies against Ser-1423 and Ser-1524 residues in cells exposed to a combination of IR and caffeine.The results showed that caffeine down-regulated IR-induced BRCA1 expression and specifically abolished BRCA1 phosphorylation of Ser-1524,which was followed by an override of G2 arrest by caffeine.In addition,the ability of BRCA1 to transactivate p21 may be required for MCF-7 but not necessary for Hela response to caffeine.These data suggest that BRCA1 may be a potential target of caffeine.BRCA1 and its phosphorylation are most likely to be involved in the caffeine-inhibitable event upstream of G2 arrest.

  19. ASSOCIATION OF CAFFEINE INTAKE AND LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C

    Directory of Open Access Journals (Sweden)

    Kalinca da Silva OLIVEIRA

    2015-03-01

    Full Text Available Background Caffeine consumption has been associated to decreased levels of liver enzymes and lower risk of fibrosis in patients with hepatitis C virus. Objectives This study aimed to evaluate the association between caffeine consumption and inflammatory activity or degree of liver fibrosis in patients with hepatitis C virus infection. Methods A cross-sectional study of patients with chronic hepatitis C virus infection treated in an outpatient Gastroenterology Unit of Santa Casa Hospital (Porto Alegre - Brasil. Patients were interviewed regarding the consumption of caffeine and anthropometric assessment was performed. Liver biopsy was performed in a maximum period of 36 months before inclusion in the study Results There were 113 patients, 67 (59.3% females, 48 (42.5% were aged between 52 and 62 years, and 101 (89.4% were white. The average caffeine consumption was 251.41 ± 232.32 mg/day, and 70 (62% patients consumed up to 250 mg/day of caffeine. There was no association between caffeine consumption and inflammatory activity on liver biopsy. On the other hand, when evaluating the caffeine consumption liver fibrosis an inverse association was observed. Conclusions The greater consumption of caffeine was associated with lower liver fibrosis. There was no association between caffeine consumption and inflammatory activity.

  20. Caffeine and 3-km cycling performance: Effects of mouth rinsing, genotype, and time of day.

    Science.gov (United States)

    Pataky, M W; Womack, C J; Saunders, M J; Goffe, J L; D'Lugos, A C; El-Sohemy, A; Luden, N D

    2016-06-01

    We assessed the efficacy of caffeine mouth rinsing on 3-km cycling performance and determined whether caffeine mouth rinsing affects performance gains influenced by the CYP1A2 polymorphism. Thirty-eight recreational cyclists completed four simulated 3-km time trials (TT). Subjects ingested either 6 mg/kg BW of caffeine or placebo 1 h prior to each TT. Additionally, 25 mL of 1.14% caffeine or placebo solution were mouth rinsed before each TT. The treatments were Placebo, caffeine Ingestion, caffeine Rinse and Ingestion+Rinse. Subjects were genotyped and classified as AA homozygotes or AC heterozygotes for the rs762551 polymorphism of the CYP1A2 gene involved in caffeine metabolism. Magnitude-based inferences were used to evaluate treatment differences in mean power output based on a predetermined meaningful treatment effect of 1.0%. AC heterozygotes (4.1%) and AA homozygotes (3.4%) benefited from Ingestion+Rinse, but only AC performed better with Ingestion (6.0%). Additionally, Rinse and Ingestion+Rinse elicited better performance relative to Placebo among subjects that performed prior to 10:00 h (Early) compared with after 10:00 h (Late). The present study provides additional evidence of genotype and time of day factors that affect the ergogenic value of caffeine intake that may allow for more personalized caffeine intake strategies to maximize performance. PMID:26062916

  1. Enhancement of nootropic effect of duloxetine and bupropion by caffeine in mice

    OpenAIRE

    Pravin Popatrao Kale; Veeranjaneyulu Addepalli

    2015-01-01

    Objective: The existing evidence suggests an association between depression and memory impairment. The objective of present study was to assess the effect of low dose caffeine with duloxetine and bupropion on memory. Materials and Methods: Mice were divided randomly into seven groups. Intra-peritoneal treatment of normal saline (10 ml/kg), caffeine (10 mg/kg), duloxetine (10 mg/kg), bupropion alone (10 mg/kg), caffeine + duloxetine (5 mg/kg, each), caffeine + bupropion (5 mg/kg, each), an...

  2. BRCA1 and its phosphorylation involved in caffeine-inhibitable event upstream of G2 checkpoint

    Science.gov (United States)

    Li, Ning; Zhang, Hong; Wang, Yanling; Hao, Jifang

    2010-07-01

    Caffeine, which specifically inhibits ATM/ATR kinases, efficiently abrogates the ionizing radiation (IR)-induced G2 arrest and increases the sensitivity of various tumor cells to IR. Mechanisms for the effect of caffeine remain to be elucidated. As a target of ATM/ATR kinases, BRCA1 becomes activated and phosphorylated in response to IR. Thus, in this work, we investigated the possible role of BRCA1 in the effect of caffeine on G2 checkpoint and observed how BRCA1 phosphorylation was regulated in this process. For these purposes, the BRCA1 protein level and the phosphorylation states were analyzed by Western blotting by using an antibody against BRCA1 and phospho-specific antibodies against Ser-1423 and Ser-1524 residues in cells exposed to a combination of IR and caffeine. The results showed that caffeine down-regulated IR-induced BRCA1 expression and specifically abolished BRCA1 phosphorylation of Ser-1524, which was followed by an override of G2 arrest by caffeine. In addition, the ability of BRCA1 to transactivate p21 may be required for MCF-7 but not necessary for Hela response to caffeine. These data suggest that BRCA1 may be a potential target of caffeine. BRCA1 and its phosphorylation are most likely to be involved in the caffeine-inhibitable event upstream of G2 arrest.

  3. The mode of action of caffeine on catecholamine release from perfused adrenal glands of cat.

    OpenAIRE

    Yamada, Y.; Nakazato, Y; Ohga, A.

    1989-01-01

    1 Adrenaline and noradrenaline secretion induced by caffeine was investigated in the perfused cat adrenal glands. 2 Caffeine (10-80 mM) caused a dose-dependent increase in both adrenaline and noradrenaline secretion when applied for 1 min and 10 min after replacing Ca2+ with 10(-5)M EGTA in the perfusion solution. The ratio of adrenaline to noradrenaline was about 1:1. Mg2+ and/or Ca2+ inhibited the response to caffeine. 3 When caffeine (40 mM) was repeatedly applied in the absence of extrace...

  4. The effect of gamma radiation and caffeine during the embrionic development of Biomphalaria glabrata

    International Nuclear Information System (INIS)

    Some experiments have been carried out, dealing with the interations of caffeine and gamma radiation in the embryonic development of Biomphalaria glabrata. Gamma radiation was used in a dosis of 1000r (exposure time of 1/2 hour) and caffeine concentration was 0.1% (Exposure time of 24 hours). Experiment I. The embryos were irradiated before treatment with caffeine. In this experiment we have observed a synergistic effect between caffeine and gamma radiation. Experiment II. The embryos in the caffeine solution were irradiated 8 hours after the beginning of the experiment. The synergistic effect observed in this experiment was reduced when compared with the first one. Experiment III. In this experiment we made the pre-treatment with caffeine. We have not observed any synergistic effect between the drug and gamma radiation. Experiment IV. Embryos were irradiated, and after 24 hours treated with caffeine during another 24 hours. As in the previous experiment, we have not observed any synergism between the radiation and the drug. According to the above results, we conclude that the synergistic effect between caffeine and gamma radiation in the embryos was more effective when the embryos have been treated with caffeine after irradiation. (Author)

  5. Galectin-3 and cyclin D1 expression in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Gołecki Marcin

    2011-10-01

    Full Text Available Abstract Introduction Lung cancer is a major cause of mortality and morbidity worldwide. Galectin-3 is multifunctional protein, which is involved in regulation of cell growth, cell adhesion, cell proliferation, angiogenesis and apoptosis. Cyclin D1 together with other cyclin plays an important role in cell cycle control. Cyclin D1 regulates the G1-to-S phase transition. The aim of this study was the evaluation of correlations between clinicopathological findings and cyclin D1 and galectin-3 expression in non-small cell lung cancer (NSCLC. We wanted also to analyze the prognostic value of cyclin D1 and galectin-3 expression. Moreover we tried to evaluate the correlations between galectin-3 and cyclin D1 expression in tumor tissue. Materials and methods We used the immunochemistry method to investigate the expression of galectin-3 and cyclin D1 in the paraffin-embedded tumor tissue of 47 patients (32 men and 15 women; mean age 59.34 ± 8.90. years. We used monoclonal antibodies to cyclin D1 (NCL-L-cyclin D1-GM clone P2D11F11 NOVO CASTRA and to galectin-3 (mouse monoclonal antibody NCL-GAL3 NOVO CASTRA. Results Galectin-3 expression was positive in 18 cases (38.29% and cyclin D1 in 39 (82.97%. We showed only weak trend, that galectin-3 expression was lower in patients without lymph node involvement (p = 0.07 and cyclin D1 expression was higher in this group (p = 0.080. We didn't reveal differences in cyclin D1 and galectin-3 expression in SCC and adenocarcinoma patients. We didn't demonstrated also differences in galectin-3 and cyclin D1 expression depending on disease stage. Moreover we analyzed the prognostic value of cyclin D1 expression and galectin-3 in all examinated patients and separately in SCC and in adenocarcinoma and in all stages, but we didn't find any statistical differences. We demonstrated that in galectin-3 positive tumors cyclin D1 expression was higher (96.55% vs 61.11%, Chi2 Yatesa 7.53, p = 0.0061 and we revealed negative

  6. Low-molecular-weight cyclin E: the missing link between biology and clinical outcome

    International Nuclear Information System (INIS)

    Cyclin E, a key mediator of transition during the G1/S cellular division phase, is deregulated in a wide variety of human cancers. Our group recently reported that overexpression and generation of low-molecular-weight (LMW) isoforms of cyclin E were associated with poor clinical outcome among breast cancer patients. However, the link between LMW cyclin E biology in mediating a tumorigenic phenotype and clinical outcome is unknown. To address this gap in knowledge, we assessed the role of LMW isoforms in breast cancer cells; we found that these forms of cyclin E induced genomic instability and resistance to p21, p27, and antiestrogens in breast cancer. These findings suggest that high levels of LMW isoforms of cyclin E not only can predict failure to endocrine therapy but also are true prognostic indicators because of their influence on cell proliferation and genetic instability

  7. The Expression and Clinic Significance of Cdk2 and CyclinE in Cholangiocarcinoma%Cdk2蛋白和CyclinE在胆管细胞癌中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    胡逸林; 张端莲; 曹廷加; 高友兵

    2010-01-01

    目的:探讨细胞周期蛋白依赖性激酶2(Cdk2)和细胞周期蛋白E(CyclinE)在胆管细胞癌中的表达及临床意义.方法:收集武汉大学人民医院病理科2002-2008年胆管细胞癌存档蜡块40例,其中男性20例,女性20例.另取胆管细胞癌周围正常组织5例作对照.采用免疫组织化学方法检测各组中Cdk2蛋白和CyclinE的表达,利用HPIAS-2000图像分析系统测定各组中Cdk2蛋白和CyclinE表达的平均光密度和平均阳性面积率.结果:胆管细胞癌中Cdk2蛋白和CyclinE呈高表达,对照组中Cdk2蛋白和CyclinE呈低表达,胆管细胞癌组与对照组之间Cdk2蛋白和CyclinE表达的平均光密度及阳性面积率有显著性差异(P<0.05).结论:Cdk2与CyclinE在胆管细胞癌的发生发展中发挥正性调节因子的作用.

  8. Lipid Peroxidation and Electrolytes in Irradiated Rats Treated with Caffeine

    International Nuclear Information System (INIS)

    This Study was conducted to elarify the potential role of caffeine (1,3,7-trimethyl xanthine), a major component of coffee, against damages induced by gamma rays. Thirty adult female albino rats (130+10) were divided into three groups, each of ten animals. The first group acted as control animals. The second was sujected to a single dose of (7) Gy whole body gamma irradiation. The third group was injected intraperitoneally with a single dose (80mg/kg body weight) of caffeine one-hour prior irradiation. Blood samples were collected five time intervals 1,3,7,15 and 30 days post-irradiation. The content of serum lipid peroxides was measured as thiobarbituric acid reactive substance (TBARS). Electrolytes as calcium (Ca2+), sodium (Na+) and potassium (K+) and levels were estimated and Na+/K+ ratio was calculated. Also serum enzymes as alkaline phosphatase (ALP) and aminotransaminases (AST and ALT) activity levels were measured. The data revealed significant increase in TBARS, AST and ALT levels in serum due to irradiation exposure. While, radiation induced significant decrease in serum level of ALP, level of electrolytes Ca2+, Ma+, and Na+/K+ ratio. On the other hand, group injected intraperitoneally with caffeine pre-irradiation exhibited reduction in the changes produced by gamma-radiation with variable degree. The data showed that this antioxidant confers protection damage inflicted by radiation when given prior to irradiation exposure on the examined parameters

  9. Chronic caffeine produces sexually dimorphic effects on amphetamine-induced behavior, anxiety and depressive-like behavior in adolescent rats.

    Science.gov (United States)

    Turgeon, Sarah M; Townsend, Shannon E; Dixon, Rushell S; Hickman, Emma T; Lee, Sabrina M

    2016-04-01

    Caffeine consumption has been increasing rapidly in adolescents; however, most research on the behavioral effects of caffeine has been conducted in adults. Two experiments were conducted in which adolescent male and female rats were treated with a moderate dose of caffeine (0.25g/l) in their drinking water beginning on P26-28. In the first experiment, animals were maintained on caffeinated drinking water or normal tap water for 14days and were then tested for behavioral and striatal c-Fos response to amphetamine (1.5mg/kg). In the second experiment, rats were maintained on caffeinated drinking water or normal tap water beginning on P28 and were tested for novel object recognition, anxiety in the light/dark test (L/D) and elevated plus maze (EPM), and depressive like behavior in the forced swim test (FST) beginning on the 14th day of caffeine exposure. Caffeine decreased amphetamine-induced rearing in males, but had no effect in females; however, this behavioral effect was not accompanied by changes in striatal c-Fos, which was increased by amphetamine but not altered by caffeine. No effects of caffeine were observed on novel object recognition or elevated plus maze behavior. However, in the L/D test, there was a sex by caffeine interaction on time spent in the light driven by a caffeine-induced increase in light time in the males but not the females. On the pretest day of the FST, sex by caffeine interactions were observed for swimming and struggling; caffeine decreased struggling behavior and increased swimming behavior in males and caffeine-treated females demonstrated significantly more struggling and significantly less swimming than caffeine-treated males. A similar pattern was observed on the test day in which caffeine decreased immobility overall and increased swimming. These data reveal sex dependent effects of caffeine on behavior in adolescent rats. PMID:26850920

  10. The proteolysis of mitotic cyclins in mammalian cells persists from the end of mitosis until the onset of S phase.

    OpenAIRE

    Brandeis, M.; Hunt, T

    1996-01-01

    We have studied how the cell cycle-specific oscillations of mitotic B-type cyclins are generated in mouse fibroblasts. A reporter enzyme comprising the N-terminus of a B-type cyclin fused to bacterial chloramphenicol acetyl transferase (CAT) was degraded at the end of mitosis like endogenous cyclins. Point mutations in the destruction box of this construct completely abolished its mitotic instability. When the destructible reporter was driven by the cyclin B2 promoter, CAT activity mimicked t...

  11. The dual role of cyclin C connects stress regulated gene expression to mitochondrial dynamics

    Directory of Open Access Journals (Sweden)

    Randy Strich

    2014-09-01

    Full Text Available Following exposure to cytotoxic agents, cellular damage is first recognized by a variety of sensor mechanisms. Thenceforth, the damage signal is transduced to the nucleus to install the correct gene expression program including the induction of genes whose products either detoxify destructive compounds or repair the damage they cause. Next, the stress signal is disseminated throughout the cell to effect the appropriate changes at organelles including the mitochondria. The mitochondria represent an important signaling platform for the stress response. An initial stress response of the mitochondria is extensive fragmentation. If the damage is prodigious, the mitochondria fragment (fission and lose their outer membrane integrity leading to the release of pro-apoptotic factors necessary for programmed cell death (PCD execution. As this complex biological process contains many moving parts, it must be exquisitely coordinated as the ultimate decision is life or death. The conserved C-type cyclin plays an important role in executing this molecular Rubicon by coupling changes in gene expression to mitochondrial fission and PCD. Cyclin C, along with its cyclin dependent kinase partner Cdk8, associates with the RNA polymerase holoenzyme to regulate transcription. In particular, cyclin C-Cdk8 repress many stress responsive genes. To relieve this repression, cyclin C is destroyed in cells exposed to pro-oxidants and other stressors. However, prior to its destruction, cyclin C, but not Cdk8, is released from its nuclear anchor (Med13, translocates from the nucleus to the cytoplasm where it interacts with the fission machinery and is both necessary and sufficient to induce extensive mitochondria fragmentation. Furthermore, cytoplasmic cyclin C promotes PCD indicating that it mediates both mitochondrial fission and cell death pathways. This review will summarize the role cyclin C plays in regulating stress-responsive transcription. In addition, we will detail

  12. Rictor regulates FBXW7-dependent c-Myc and cyclin E degradation in colorectal cancer cells

    International Nuclear Information System (INIS)

    Highlights: ► Rictor associates with FBXW7 to form an E3 complex. ► Knockdown of rictor decreases ubiquitination of c-Myc and cylin E. ► Knockdown of rictor increases protein levels of c-Myc and cylin E. ► Overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. ► Rictor regulation of c-Myc and cyclin E requires FBXW7. -- Abstract: Rictor (Rapamycin-insensitive companion of mTOR) forms a complex with mTOR and phosphorylates and activates Akt. Activation of Akt induces expression of c-Myc and cyclin E, which are overexpressed in colorectal cancer and play an important role in colorectal cancer cell proliferation. Here, we show that rictor associates with FBXW7 to form an E3 complex participating in the regulation of c-Myc and cyclin E degradation. The Rictor–FBXW7 complex is biochemically distinct from the previously reported mTORC2 and can be immunoprecipitated independently of mTORC2. Moreover, knocking down of rictor in serum-deprived colorectal cancer cells results in the decreased ubiquitination and increased protein levels of c-Myc and cyclin E while overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. Genetic knockout of FBXW7 blunts the effects of rictor, suggesting that rictor regulation of c-Myc and cyclin E requires FBXW7. Our findings identify rictor as an important component of FBXW7 E3 ligase complex participating in the regulation of c-Myc and cyclin E protein ubiquitination and degradation. Importantly, our results suggest that elevated growth factor signaling may contribute to decrease rictor/FBXW7-mediated ubiquitination of c-Myc and cyclin E, thus leading to accumulation of cyclin E and c-Myc in colorectal cancer cells.

  13. Caffeinated and non-caffeinated alcohol use and indirect aggression: The impact of self-regulation.

    Science.gov (United States)

    Sheehan, Brynn E; Linden-Carmichael, Ashley N; Lau-Barraco, Cathy

    2016-07-01

    Research shows that heavier alcohol use is associated with physical aggression. Scant research has examined the way in which alcohol relates to other forms of aggression, such as indirect aggression (e.g., malicious humor, social exclusion). Given the possible negative consequences of indirect aggression and the limited evidence suggesting alcohol use can elicit indirectly aggressive responses, research is needed to further investigate the association between drinking behavior and indirect aggression. Additionally, specific alcoholic beverages, such as caffeinated alcoholic beverages (CABs; e.g., Red Bull and vodka), may potentiate aggression above the influence of typical use, and thus warrant examination with regard to indirect aggression. One factor that may impact the strength of the alcohol-indirect aggression and CAB-indirect aggression relationships is one's level of self-regulation. Consequently, our study examined the relationships between (1) alcohol use and indirect aggression, (2) CAB use and indirect aggression, and (3) self-regulation as a moderator. Participants were 733 (67.6% female) undergraduate students who reported their CAB and alcohol use, self-regulation, and aggressive behaviors. Results revealed that heavier alcohol use was associated with more frequent indirect aggression after controlling for dispositional aggression. Heavier CAB use was related to more frequent indirect aggression after accounting for typical use and dispositional aggression. Self-regulation moderated these associations such that for those with lower self-regulation, greater alcohol and CAB consumption was associated with greater indirect aggression. Our findings suggest that heavier alcohol and CAB consumption may be risk factors for engaging in indirect aggression and this risk is impacted by one's regulatory control. PMID:26905765

  14. Enhancement of SV40 transformation by treatment of C3H2K cells with uv light and caffeine. I. Combined effect of uv light and caffeine

    International Nuclear Information System (INIS)

    Treatment of cultured mouse cells, C3H2K, with uv light and/or caffeine enhanced the frequency of SV40-induced transformation. This enhancement depends upon the doses of uv and caffeine and the mode of combination of these agents. Irradiation of cells with increasing doses of uv just before infection resulted in approximately 2-fold enhancement of the transformation frequency up to a dose of 90 ergs/mm2 and 3.3-fold at 150 ergs/mm2. Addition of 1 mM caffeine to the medium for 4 days subsequent to infection brought about a 2-fold enhancement. When cells were irradiated and treated with 1 mM caffeine, the enhancement was approximately 4-fold up to a uv dose of 90 ergs/mm2 and 5.9-fold at 150 ergs/mm2. When 0.1 to 4 mM caffeine was added for 4 days postinfection, the absolute number of transformations increased, and an enhancement ratio of 1.3 to 6.8 resulted. After the addition of the same increasing doses of caffeine to uv-irradiated cells (75 ergs/mm2), the enhancement of transformation frequency was even higher ranging 2.0 to 13.3. The transformation frequencies thus obtained by the double treatment were always higher than those predicted if uv and caffeine acted additively. The transformation frequency was little affected by the addition of dibutyrylcyclic AMP and theophylline

  15. Cyclin B1 is localized to unattached kinetochores and contributes to efficient microtubule attachment and proper chromosome alignment during mitosis

    Institute of Scientific and Technical Information of China (English)

    Qiang Chen; Xiaoyan Zhang; Qing Jiang; Paul R Clarke; Chuanmao Zhang

    2008-01-01

    Cyclin Bl is a key regulatory protein controlling cell cycle progression in vertebrates. Cyclin Bl binds CDK1, a cyclin-dependent kinase catalytic subunit, forming a complex that orchestrates mitosis through phosphorylation of key proteins. Cyclin Bl regulates both the activation of CDK1 and its subcellular localization, which may be critical for substrate selection. Here, we demonstrate that cyclin Bl is concentrated on the outer plate of the kinetochore during prometaphase. This localization requires the cyclin box region of the protein. Cyclin Bl is displaced from individual kinetochores to the spindle poles by microtubule attachment to the kinetochores, and this displacement is dependent on the dynein/dynactin complex. Depletion of cyclin Bl by vector-based siRNA causes inefficient attachment between kinetochores and microtubules, and chromosome alignment defects, and delays the onset of anaphase. We conclude that cyclin Bl accumulates at kinetochores during prometaphase, where it contributes to the correct attachment of microtubules to kinetochores and efficient alignment of the chromosomes, most likely through localized phosphorylation of specific substrates by cyclin B1-CDK1. Cyclin Bl is then transported from each kinetochore as microtubule attachment is completed, and this relocalization may redirect the activity of cyclin B1-CDK1 and contribute to inactivation of the spindle assembly checkpoint.

  16. Cyclin D3 expression in non-Hodgkin lymphoma. Correlation with other cell cycle regulators and clinical features

    DEFF Research Database (Denmark)

    Møller, Michael Boe; Nielsen, O; Pedersen, Niels Tinggaard

    2001-01-01

    Cyclin D3 is the most widely expressed D-type cyclin and can be rate limiting for G1/S transition. To study the expression of cyclin D3 in non-Hodgkin lymphoma, samples from 198 previously untreated patients with lymphoma from a prospectively collected, population-based lymphoma registry were ana...

  17. THE TESTING OF CAFFEIN “IN VITRO” REACTION ON CYMBIDIUM HYBRIDUM PROTOCORMS SUBCULTURED ON ESPECIALLY BRIDGE OF FILTERED PAPER

    Directory of Open Access Journals (Sweden)

    C.F. Blidar

    2005-08-01

    biomass of these, was registered at the variants of culture medium with caffeine in a 0,001% concentration. On the lowest or highest concentration of 0,001% caffeine, we find out a progressive decrease of the protocorms vitality.

  18. Radiation genetic studies in garden pea. Part 2. Caffeine potentiation and chromosome damage

    International Nuclear Information System (INIS)

    The effect of 1.5x10-2 M caffeine post-treatments over the chromosome damage induced by 4kR X-ray 1.5x10-2 M Maleic hydrazide (MH) and N-Nitroso-N-urethane (NMU) treatments in the root top cells of a normal and trigenic leaf mutant of Pisum sativum was studied. While MH and NMU produced S-dependent effects, X-rays induced non-delayed S-independent effects. These effects got potentiated by caffeine treatments. With MH, the potentiation occurred when the cells got exposed to caffeine during S-phase and with X-rays, it occurred when the irradiated cells are treated in G2 or prophase stage. The caffeine potentiation of chromosome damage produced by MH was similar in the roots exposed to caffeine at 16 and 31degC but with NMU, the potentiation was lower at 31 than at 16degC. If the inhibitory effect of caffeine on gap filling process of the damaged DNA is the molecular mechanism responsible for caffeine potentiation of reproductive death it may be the mechanism responsible for the observed chromosome damage in MH treated cells exposed to caffeine during G1 and S phase. But the X-irradiated cells are insensitive to caffeine at such phases. In these cells caffeine probably acts as an inhibitor of the photoreactivating enzymes for binding sites or with the substrate in the irradiated cells post-treated during G2 and prophase. However, temperature independence of caffeine potentiation is not compatible with eithr of the above two views. Compared to the normal genotype, the trigenic mutant exhibited an increased chromosomal damage, but not the potentiation. Probably mutant genes reduce the resistance of a genome against mutagenic action, consequently enhance the suseptibility to chromosome damage. (author)

  19. Caffeine alters the behavioural and body temperature responses to mephedrone without causing long-term neurotoxicity in rats

    OpenAIRE

    Shortall, Sinead E.; Green, A. Richard; Fone, Kevin C.F.; King, Madeleine V.

    2016-01-01

    Administration of caffeine with 3,4-methylenedioxymethamphetamine (MDMA) alters the pharmacological properties of MDMA in rats. The current study examined whether caffeine alters the behavioural and neurochemical effects of mephedrone, which has similar psychoactive effects to MDMA. Rats received either i.p. saline, mephedrone (10mg/kg), caffeine (10mg/kg) or combined caffeine and mephedrone twice weekly on consecutive days for three weeks. Locomotor activity (days 1 and 16), novel object dis...

  20. Structural basis for CDK6 activation by a virus-encoded cyclin

    Energy Technology Data Exchange (ETDEWEB)

    Schulze-Gahmen, Ursula; Kim, Sung-Hou

    2002-01-17

    Cyclin from herpesvirus saimiri (Vcyclin) preferentially forms complexes with cyclin-dependent kinase 6 (CDK6) from primate host cells. These complexes show higher kinase activity than host cell CDK complexes with cellular cyclins and are resistant to cyclin-dependent inhibitory proteins (CDKIs). The crystal structure of human CDK6-Vcyclin in an active state was determined to 3.1 Angstrom resolution to get a better understanding of the structural basis of CDK6 activation by viral cyclins. The unphosphorylated CDK6 complexed to Vcyclin has many features characteristic of cyclinA-activated, phosphorylated CDK2. There are, however, differences in the conformation at the tip of the T-loop and its interactions with Vcyclin. Residues in the N-terminal extension of Vcyclin wrap around the tip of the CDK6 T-loop and form a short b-sheet with the T-loop backbone. These interactions lead to a 20 percent larger buried surface in the CDK6-Vcyclin interface than in the CDK2-cyclinA complex and are probably largely responsible for Vcyclin specificity for CDK6 and resistance of the complex to inhibition by INK-typeCDKIs.

  1. Plasmodium P-Type Cyclin CYC3 Modulates Endomitotic Growth during Oocyst Development in Mosquitoes

    KAUST Repository

    Roques, Magali

    2015-11-13

    Cell-cycle progression and cell division in eukaryotes are governed in part by the cyclin family and their regulation of cyclin-dependent kinases (CDKs). Cyclins are very well characterised in model systems such as yeast and human cells, but surprisingly little is known about their number and role in Plasmodium, the unicellular protozoan parasite that causes malaria. Malaria parasite cell division and proliferation differs from that of many eukaryotes. During its life cycle it undergoes two types of mitosis: endomitosis in asexual stages and an extremely rapid mitotic process during male gametogenesis. Both schizogony (producing merozoites) in host liver and red blood cells, and sporogony (producing sporozoites) in the mosquito vector, are endomitotic with repeated nuclear replication, without chromosome condensation, before cell division. The role of specific cyclins during Plasmodium cell proliferation was unknown. We show here that the Plasmodium genome contains only three cyclin genes, representing an unusual repertoire of cyclin classes. Expression and reverse genetic analyses of the single Plant (P)-type cyclin, CYC3, in the rodent malaria parasite, Plasmodium berghei, revealed a cytoplasmic and nuclear location of the GFP-tagged protein throughout the lifecycle. Deletion of cyc3 resulted in defects in size, number and growth of oocysts, with abnormalities in budding and sporozoite formation. Furthermore, global transcript analysis of the cyc3-deleted and wild type parasites at gametocyte and ookinete stages identified differentially expressed genes required for signalling, invasion and oocyst development. Collectively these data suggest that cyc3 modulates oocyst endomitotic development in Plasmodium berghei.

  2. Amygdalin Blocks Bladder Cancer Cell Growth In Vitro by Diminishing Cyclin A and cdk2

    Science.gov (United States)

    Makarević, Jasmina; Rutz, Jochen; Juengel, Eva; Kaulfuss, Silke; Reiter, Michael; Tsaur, Igor; Bartsch, Georg; Haferkamp, Axel; Blaheta, Roman A.

    2014-01-01

    Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25–10 mg/ml) on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP). Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR) related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug. PMID:25136960

  3. Amygdalin blocks bladder cancer cell growth in vitro by diminishing cyclin A and cdk2.

    Directory of Open Access Journals (Sweden)

    Jasmina Makarević

    Full Text Available Amygdalin, a natural compound, has been used by many cancer patients as an alternative approach to treat their illness. However, whether or not this substance truly exerts an anti-tumor effect has never been settled. An in vitro study was initiated to investigate the influence of amygdalin (1.25-10 mg/ml on the growth of a panel of bladder cancer cell lines (UMUC-3, RT112 and TCCSUP. Tumor growth, proliferation, clonal growth and cell cycle progression were investigated. The cell cycle regulating proteins cdk1, cdk2, cdk4, cyclin A, cyclin B, cyclin D1, p19, p27 as well as the mammalian target of rapamycin (mTOR related signals phosphoAkt, phosphoRaptor and phosphoRictor were examined. Amygdalin dose-dependently reduced growth and proliferation in all three bladder cancer cell lines, reflected in a significant delay in cell cycle progression and G0/G1 arrest. Molecular evaluation revealed diminished phosphoAkt, phosphoRictor and loss of Cdk and cyclin components. Since the most outstanding effects of amygdalin were observed on the cdk2-cyclin A axis, siRNA knock down studies were carried out, revealing a positive correlation between cdk2/cyclin A expression level and tumor growth. Amygdalin, therefore, may block tumor growth by down-modulating cdk2 and cyclin A. In vivo investigation must follow to assess amygdalin's practical value as an anti-tumor drug.

  4. COMBINED DETECTION OF CYCLIN D1, P27 AND DNA CONTENT IN ESOPHAGEAL CANCER

    Institute of Scientific and Technical Information of China (English)

    MA Ping; YIN Yuan-qin; WANG Xiao-hua

    2006-01-01

    Objective: To investigate the expressions of cyclin D1 and p27 and DNA content in esophageal cancer and adjacent normal tissues, and to discuss the relationship between them. Methods: The cyclinD1 and p27 were detected by immunohistochemical staining; DNA content was measured by flow cytometry. Results: The positive expression rates of cyclinD1 and p27 in cancer were 45.8% and 33.3% respectively, the DNA content in the positive group of cyclinD1 was higher than that in the negative group of cyclinD1(1.54(0.21 versus 1.08(0.43, P<0.05), while the DNA content and SPF (S-phase fraction) in the positive group of p27 were lower than those in the negative group (1.10(0.19 and 5.56%(5.18% versus 1.66(0.28 and 19.78%(6.12%, P<0.05). Conclusion: The data show that the expression of cyclinD1 and p27 are related to the ontogenesis and progression of esophageal cancer. The combined detection of cyclinD1, p27 and DNA content may be indicators of diagnosis and assessment of esophageal cancer.

  5. The loss of PIN1 deregulates cyclin E and sensitizes mouse embryo fibroblasts to genomic instability.

    Science.gov (United States)

    Yeh, Elizabeth S; Lew, Brian O; Means, Anthony R

    2006-01-01

    During the G0/G1-S phase transition, the timely synthesis and degradation of key regulatory proteins is required for normal cell cycle progression. Two of these proteins, c-Myc and cyclin E, are recognized by the Cdc4 E3 ligase of the Skp1/Cul1/Rbx1 (SCF) complex. SCF(Cdc4) binds to a similar phosphodegron sequence in c-Myc and cyclin E proteins resulting in ubiquitylation and degradation of both proteins via the 26 S proteosome. Since the prolyl isomerase Pin1 binds the c-Myc phosphodegron and participates in regulation of c-Myc turnover, we hypothesized that Pin1 would bind to and regulate cyclin E turnover in a similar manner. Here we show that Pin1 regulates the turnover of cyclin E in mouse embryo fibroblasts. Pin1 binds to the cyclin E-Cdk2 complex in a manner that depends on Ser384 of cyclin E, which is phosphorylated by Cdk2. The absence of Pin1 results in an increased steady-state level of cyclin E and stalling of the cells in the G1/S phase of the cell cycle. The cellular changes that result from the loss of Pin1 predispose Pin1 null mouse embryo fibroblasts to undergo more rapid genomic instability when immortalized by conditional inactivation of p53 and sensitizes these cells to more aggressive Ras-dependent transformation and tumorigenesis. PMID:16223725

  6. Altered expression of cyclin A 1 in muscle of patients with facioscapulohumeral muscle dystrophy (FSHD-1.

    Directory of Open Access Journals (Sweden)

    Anna Pakula

    Full Text Available OBJECTIVES: Cyclin A1 regulates cell cycle activity and proliferation in somatic and germ-line cells. Its expression increases in G1/S phase and reaches a maximum in G2 and M phases. Altered cyclin A1 expression might contribute to clinical symptoms in facioscapulohumeral muscular dystrophy (FSHD. METHODS: Muscle biopsies were taken from the Vastus lateralis muscle for cDNA microarray, RT-PCR, immunohistochemistry and Western blot analyses to assess RNA and protein expression of cyclin A1 in human muscle cell lines and muscle tissue. Muscle fibers diameter was calculated on cryosections to test for hypertrophy. RESULTS: cDNA microarray data showed specifically elevated cyclin A1 levels in FSHD vs. other muscular disorders such as caveolinopathy, dysferlinopathy, four and a half LIM domains protein 1 deficiency and healthy controls. Data could be confirmed with RT-PCR and Western blot analysis showing up-regulated cyclin A1 levels also at protein level. We found also clear signs of hypertrophy within the Vastus lateralis muscle in FSHD-1 patients. CONCLUSIONS: In most somatic human cell lines, cyclin A1 levels are low. Overexpression of cyclin A1 in FSHD indicates cell cycle dysregulation in FSHD and might contribute to clinical symptoms of this disease.

  7. Cyclin A2 promotes DNA repair in the brain during both development and aging.

    Science.gov (United States)

    Gygli, Patrick E; Chang, Joshua C; Gokozan, Hamza N; Catacutan, Fay P; Schmidt, Theresa A; Kaya, Behiye; Goksel, Mustafa; Baig, Faisal S; Chen, Shannon; Griveau, Amelie; Michowski, Wojciech; Wong, Michael; Palanichamy, Kamalakannan; Sicinski, Piotr; Nelson, Randy J; Czeisler, Catherine; Otero, José J

    2016-07-01

    Various stem cell niches of the brain have differential requirements for Cyclin A2. Cyclin A2 loss results in marked cerebellar dysmorphia, whereas forebrain growth is retarded during early embryonic development yet achieves normal size at birth. To understand the differential requirements of distinct brain regions for Cyclin A2, we utilized neuroanatomical, transgenic mouse, and mathematical modeling techniques to generate testable hypotheses that provide insight into how Cyclin A2 loss results in compensatory forebrain growth during late embryonic development. Using unbiased measurements of the forebrain stem cell niche, we parameterized a mathematical model whereby logistic growth instructs progenitor cells as to the cell-types of their progeny. Our data was consistent with prior findings that progenitors proliferate along an auto-inhibitory growth curve. The growth retardation inCCNA2-null brains corresponded to cell cycle lengthening, imposing a developmental delay. We hypothesized that Cyclin A2 regulates DNA repair and that CCNA2-null progenitors thus experienced lengthened cell cycle. We demonstrate that CCNA2-null progenitors suffer abnormal DNA repair, and implicate Cyclin A2 in double-strand break repair. Cyclin A2's DNA repair functions are conserved among cell lines, neural progenitors, and hippocampal neurons. We further demonstrate that neuronal CCNA2 ablation results in learning and memory deficits in aged mice. PMID:27425845

  8. Cyclin D3 interacts with vitamin D receptor and regulates its transcription activity

    International Nuclear Information System (INIS)

    D-type cyclins are essential for the progression through the G1 phase of the cell cycle. Besides serving as cell cycle regulators, D-type cyclins were recently reported to have transcription regulation functions. Here, we report that cyclin D3 is a new interacting partner of vitamin D receptor (VDR), a member of the superfamily of nuclear receptors for steroid hormones, thyroid hormone, and the fat-soluble vitamins A and D. The interaction was confirmed with methods of yeast two-hybrid system, in vitro binding analysis and in vivo co-immunoprecipitation. Cyclin D3 interacted with VDR in a ligand-independent manner, but treatment of the ligand, 1,25-dihydroxyvitamin D3, strengthened the interaction. Confocal microscopy analysis showed that ligand-activated VDR led to an accumulation of cyclin D3 in the nuclear region. Cyclin D3 up-regulated transcriptional activity of VDR and this effect was counteracted by overexpression of CDK4 and CDK6. These findings provide us a new clue to understand the transcription regulation functions of D-type cyclins

  9. Systematic validation of predicted microRNAs for cyclin D1

    Directory of Open Access Journals (Sweden)

    Feng Ming-Guang

    2009-06-01

    Full Text Available Abstract Background MicroRNAs are the endogenous small non-coding RNA molecules capable of silencing protein coding genes at the posttranscriptional level. Based on computer-aided predictions, a single microRNA could have over a hundred of targets. On the other hand, a single protein-coding gene could be targeted by many potential microRNAs. However, only a relatively small number of these predicted microRNA/mRNA interactions are experimentally validated, and no systematic validation has been carried out using a reporter system. Methods In this study, we used luciferease reporter assays to validate microRNAs that can silence cyclin D1 (CCND1 because CCND1 is a well known proto-oncogene implicated in a variety of types of cancers. We chose miRanda http://www.microRNA.org as a primary prediction method. We then cloned 51 of 58 predicted microRNA precursors into pCDH-CMV-MCS-EF1-copGFP and tested for their effect on the luciferase reporter carrying the 3'-untranslated region (UTR of CCND1 gene. Results Real-time PCR revealed the 45 of 51 cloned microRNA precursors expressed a relatively high level of the exogenous microRNAs which were used in our validation experiments. By an arbitrary cutoff of 35% reduction, we identified 7 microRNAs that were able to suppress Luc-CCND1-UTR activity. Among them, 4 of them were previously validated targets and the rest 3 microRNAs were validated to be positive in this study. Of interest, we found that miR-503 not only suppressed the luciferase activity, but also suppressed the endogenous CCND1 both at protein and mRNA levels. Furthermore, we showed that miR-503 was able to reduce S phase cell populations and caused cell growth inhibition, suggesting that miR-503 may be a putative tumor suppressor. Conclusion This study provides a more comprehensive picture of microRNA/CCND1 interactions and it further demonstrates the importance of experimental target validation.

  10. Dysregulation of CDK8 and Cyclin C in tumorigenesis %Dysregulation of CDK8 and Cyclin C in tumorigenesis

    Institute of Scientific and Technical Information of China (English)

    Wu Xu; Jun-Yuan Ji

    2011-01-01

    Appropriately controlled gene expression is fundamental for normal growth and survival of all living organisms.In eukaryotes,the transcription of protein-coding mRNAs is dependent on RNA polymerase Ⅱ (Pol Ⅱ).The multi-subunit transcription cofactor Mediator complex is proposed to regulate most,if not all,of the Pol Ⅱ-dependent transcription.Here we focus our discussion on two subunits of the Mediator complex,cyclin-dependent kinase 8 (CDK8) and its regulatory partner Cyclin C (CycC),because they are either mutated or amplified in a variety of human cancers.CDK8 functions as an oncoprotein in melanoma and colorectal cancers,thus there are considerable interests in developing drugs specifically targeting the CDK8 kinase activity.However,to evaluate the feasibility of targeting CDK8 for cancer therapy and to understand how their dysregulation contributes to tumorigenesis,it is essential to elucidate the in vivo function and regulation of CDK8-CycC,which are still poorly understood in multi-cellular organisms.We summarize the evidence linking their dysregulation to various cancers and present our bioinformatics and computational analyses on the structure and evolution of CDK8.We also discuss the implications of these observations in tumorigenesis.Because most of the Mediator subunits,including CDK8 and CycC,are highly conserved during eukaryotic evolution,we expect that investigations using model organisms such as Drosophila will provide important insights into the function and regulation of CDK8 and CycC in different cellular and developmental contexts.

  11. Differential contributions of theobromine and caffeine on mood, psychomotor performance and blood pressure.

    Science.gov (United States)

    Mitchell, E S; Slettenaar, M; vd Meer, N; Transler, C; Jans, L; Quadt, F; Berry, M

    2011-10-24

    The combination of theobromine and caffeine, methylxanthines found in chocolate, has previously been shown to improve mood and cognition. However, it is unknown whether these molecules act synergistically. This study tested the hypothesis that a combination of caffeine and theobromine has synergistic effects on cognition, mood and blood pressure in 24 healthy female subjects. The effects of theobromine (700 mg), caffeine (120 mg) or the combination of both, or placebo were tested on mood (the Bond-Lader visual analog scale), psychomotor performance (the Digit Symbol Substitution Test (DSST)) and blood pressure before and at 1, 2 and 3 h after administration. Theobromine alone decreased self-reported calmness 3h after ingestion and lowered blood pressure relative to placebo 1 h after ingestion. Caffeine increased self-reported alertness 1, 2 and 3h after ingestion and contentedness 1 and 2 h after ingestion, and increased blood pressure relative to placebo (at 1 h). The combination of caffeine+theobromine had similar effects as caffeine alone on mood, but with no effect on blood pressure. There was no treatment effect on DSST performance. Together these results suggest that theobromine and caffeine could have differential effects on mood and blood pressure. It was tentatively concluded that caffeine may have more CNS-mediated effects on alertness, while theobromine may be acting primarily via peripheral physiological changes. PMID:21839757

  12. CHROMATOGRAPHIC DETERMINATION OF CAFFEINE CONTENTS IN SOFT AND ENERGY DRINKS AVAILABLE ON THE ROMANIAN MARKET

    Directory of Open Access Journals (Sweden)

    Mira Elena Ionică

    2010-10-01

    Full Text Available Caffeine is a stimulant that is commonly found in many foods and drinks that we consume. Concerns exist about the potential adverse health effects of high consumption of dietary caffeine, especially in children and pregnant women. Recommended caffeine intakes corresponding to no adverse health effects have been suggested recently for healthy adults (400 – 450 mg/day, for women contemplating pregnancy (300 mg/day, and for young children age 4 – 6 years (45 mg/day. Different brands of soft and energy carbonated beverages available on the Romanian market were analysed for caffeine by HPLC with a diode array UV-VIS detector at 217 nm. The column was a reverse phase C18 and the mobile phase consisted of potassium dihydrogen orthophosphate buffer (0.02 mol/L, pH 4.3 and acetonitrile (88:12, v/v. The caffeine contents in energy drink samples ranged from 16.82 mg/100 mL to 39.48 mg/100 mL while the carbonated soft drink group showed caffeine content in the range of 9.79 – 14.38 mg/100 mL. In addition, the concentrations of caffeine have been converted into the daily intake doses based on beverages consumption. The mean values of caffeine daily intakes were 124 mg and 49 mg through the ingestion of energy drinks and soft drinks, respectively.

  13. The influence of a CYP1A2 polymorphism on the ergogenic effects of caffeine

    Directory of Open Access Journals (Sweden)

    Womack Christopher J

    2012-03-01

    Full Text Available Abstract Background Although caffeine supplementation improves performance, the ergogenic effect is variable. The cause(s of this variability are unknown. A (C/A single nucleotide polymorphism at intron 1 of the cytochrome P450 (CYP1A2 gene influences caffeine metabolism and clinical outcomes from caffeine ingestion. The purpose of this study was to determine if this polymorphism influences the ergogenic effect of caffeine supplementation. Methods Thirty-five trained male cyclists (age = 25.0 ± 7.3 yrs, height = 178.2 ± 8.8 cm, weight = 74.3 ± 8.8 kg, VO2max = 59.35 ± 9.72 ml·kg-1·min-1 participated in two computer-simulated 40-kilometer time trials on a cycle ergometer. Each test was performed one hour following ingestion of 6 mg·kg-1 of anhydrous caffeine or a placebo administered in double-blind fashion. DNA was obtained from whole blood samples and genotyped using restriction fragment length polymorphism-polymerase chain reaction. Participants were classified as AA homozygotes (N = 16 or C allele carriers (N = 19. The effects of treatment (caffeine, placebo and the treatment × genotype interaction were assessed using Repeated Measures Analysis of Variance. Results Caffeine supplementation reduced 40 kilometer time by a greater (p Conclusions Results suggest that individuals homozygous for the A allele of this polymorphism may have a larger ergogenic effect following caffeine ingestion.

  14. Modulation of Radiation Induced Toxicity by Caffeine Pre injection in Female Rats

    International Nuclear Information System (INIS)

    The present work aims to evaluate the antioxidative role of caffeine (80 mg/kg b.w.). injected 1hour before exposure of female rats to a dose of (7 Gy) gamma irradiation. Haematological parameters, lipid peroxides, glutathione, AST and ALT were investigated 1, 3 and 7 days post irradiation and/or caffeine treatment. Exposure to ionizing radiation resulted in haematological disorders, elevated lipid peroxides, dropped glutathione levels and disturbed AST and ALT levels. Caffeine preinjection led to noticeable limitation of the drop in RBCs, Hb and Ht, improved MCV, MCHC, elevated glutathione, depressed lipid peroxide levels and moderated ALT level. Caffeine is an alkaloid (purine derivative) that contains flavonoids, which increases the antioxidative capacity of blood plasma (Hempel et al., 1999). It is an antioxidant that may help to protect against chemically-induced or radiation induced cancer in mice (Abraham, 1991 and Haung et al., 1997). Caffeine competes with oxygen for electrons and also scavenges hydroxyl radicals and reactive oxygen (Devasagayam and Kesavan, 1996). Contrary to previous investigations, conducted since 1960 reporting that caffeine potentiates DNA damage (Kihlman, 1977 and George et al., 1999) administered caffeine i.p. at a dose of 80 mg/kg body weight 1hour before irradiation of mice at 7.5 Gy. They described remarkable protection by caffeine resulting in the survival of 70% of mice at the end of 25 days and the number remained the same till 90 days

  15. Combined effects of radiation and caffeine on embryonic development in mice

    International Nuclear Information System (INIS)

    The combined effect of radiation and caffeine has been studied in mouse embryos. Radiation and/or caffeine were administered to ICR mice on Day 11 of gestation. Intrauterine death, gross malformation, and fetal body weight were selected as indicators of effects. Doses of whole-body gamma irradiation were 0.5 to 2.5 Gy and those of caffeine were 100 and 250 mg/kg maternal body wt. Intrauterine mortality increased with increasing radiation dose; this trend was more remarkable in combination with caffeine. Gross malformations such as cleft palate and defects of forelegs and hindlegs appeared frequently in the fetuses treated with both radiation and caffeine. Decreased fetal weight was observed even in mice treated with 0.5 Gy of radiation or 100 mg/kg caffeine. There was a linear relationship between dose and reduction of fetal weight. The fetal weight was a sensitive, precise, and easy-to-handle indicator for the effects of growth retardation. Intrauterine mortality and frequencies of cleft palate and defects of forelegs and hindlegs were higher than the sum of those induced by radiation and by caffeine separately. The results indicated that the combined action of radiation and caffeine on intrauterine death and malformations was synergistic

  16. Introversion/extroversion, time stress, and caffeine: effect on verbal performance.

    Science.gov (United States)

    Revelle, W; Amaral, P; Turriff, S

    1976-04-01

    Time pressure and caffeine differentially affected the performance of introverts on verbal ability tests similar to the Graduate Record Examination. With time pressure and 200 milligrams of caffeine, the performance of introverts fell by 0.63 standard deviation, but extroverts by 0.44 standard deviation. PMID:1257762

  17. Effects of dilute aqueous NaCl solution on caffeine aggregation

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Bhanita; Paul, Sandip, E-mail: sandipp@iitg.ernet.in [Department of Chemistry, Indian Institute of Technology, Guwahati 781039, Assam (India)

    2013-11-21

    The effect of salt concentration on association properties of caffeine molecule was investigated by employing molecular dynamics simulations in isothermal-isobaric ensemble of eight caffeine molecules in pure water and three different salt (NaCl) concentrations, at 300 K temperature and 1 atm pressure. The concentration of caffeine was taken almost at the solubility limit. With increasing salt concentration, we observe enhancement of first peak height and appearance of a second peak in the caffeine-caffeine distribution function. Furthermore, our calculated solvent accessible area values and cluster structure analyses suggest formation of higher order caffeine cluster on addition of salt. The calculated hydrogen bond properties reveal that there is a modest decrease in the average number of water-caffeine hydrogen bonds on addition of NaCl salt. Also observed are: (i) decrease in probability of salt contact ion pair as well as decrease in the solvent separated ion pair formation with increasing salt concentration, (ii) a modest second shell collapse in the water structure, and (iii) dehydration of hydrophobic atomic sites of caffeine on addition of NaCl.

  18. Influence of caffeine on information processing stages in well rested and fatigued subjects.

    NARCIS (Netherlands)

    L.M. Lorist; J. Snel; A. Kok

    1994-01-01

    Examined the effects of caffeine on different information processing stages using choice reaction time (RT) tasks. A 200-mg dose at the beginning and a maintenance dose of 50 mg caffeine or lactose half-way through the session were administered to 15 well-rested and 15 fatigued university students (

  19. INFLUENCE OF CAFFEINE ON SELECTIVE ATTENTION IN WELL-RESTED AND FATIGUED SUBJECTS

    NARCIS (Netherlands)

    LORIST, MM; SNEL, J; KOK, A; MULDER, G

    1994-01-01

    Effects of caffeine were studied in a visual focused selective search task in well-rested and fatigued subjects. A dose of 200 + 50 mg caffeine or placebo, dissolved in decaffeinated coffee, was administered in a double-blind and deceptive fashion. The task was to detect a target letter on one diago

  20. CAFFEINE SPECIFICITY OF VARIOUS NON-IMPRINTED POLYMERS IN AQUEOUS MEDIA

    Science.gov (United States)

    Limitations exist in applying the conventional microbial methods to the detection of human fecal contamination in water. Certain organic compounds such as caffeine, have been reported by the U.S. Geological Survey as a more suitable tracer. The employment of caffeine has been h...

  1. Caffeine Enhances Real-World Language Processing: Evidence from a Proofreading Task

    Science.gov (United States)

    Brunye, Tad T.; Mahoney, Caroline R.; Rapp, David N.; Ditman, Tali; Taylor, Holly A.

    2012-01-01

    Caffeine has become the most prevalently consumed psychostimulant in the world, but its influences on daily real-world functioning are relatively unknown. The present work investigated the effects of caffeine (0 mg, 100 mg, 200 mg, 400 mg) on a commonplace language task that required readers to identify and correct 4 error types in extended…

  2. ACUTE LETHAL CONCENTRATIONS OF CAFFEINE ON NON-TARGET FRESHWATER ORGANISMS

    Science.gov (United States)

    Despite the recent detection of caffeine in US streams, studies investigating caffeine's toxic effects on non-target freshwater organisms lack acute data for several standard surrogate species and chronic data for any freshwater species. The present study describes the mortality rate at different c...

  3. Investigations of the presence of caffeine in the Rudawa River, Kraków, Poland.

    Science.gov (United States)

    Jagoda, Agnieszka; Żukowski, Witold; Dąbrowska, Barbara

    2015-09-01

    Caffeine concentration in surface water (Rudawa River, Kraków, Poland) has been being investigated since 2011. The method applied for investigations was developed in 2011, and the first series of measurements of caffeine concentration in surface water began in 2011. Caffeine concentration was determined by the gas chromatography-mass spectrometry (GC-MS) method. Solid phase extraction (SPE) was used to enrich the concentration of caffeine in water samples. As an internal standard, the caffeine isotope (13)C3 in methanol (Sigma Aldrich) was used. The values of four additional parameters (concentration of nitrates, biochemical oxygen demand after 7 days, number of Escherichia coli and number of Enterococcus faecalis) were determined for the water sample analyzed. Caffeine was detected in all studied samples. The control series of measurements during 2011-2014 confirmed that caffeine is present in Rudawa River water and that the concentration of this substance in Rudawa River ranges from 14.0 to 852.0 ng/dm(3). There is no correlation between the concentration of caffeine and the concentration of other anthropogenic contaminants determined in water. PMID:26264791

  4. The protective effect of caffeine on DNA photosensitive damage: a gel electrophoresis

    International Nuclear Information System (INIS)

    Agarose gel electrophoresis was performed to study interaction effect of caffeine on photosensitive injury of DNA caused by anthraquinone-2-sulphonic acid disodium (AQS), a model compound of strong photosensitizer, under 254 nm or 365nm UV irradiation Photosensitive injury of DNA induced by AQS under deoxidized condition was used as control. The results show that caffeine may resist effectively the injury effect of photosensitive damage and strong UV irradiation on DNA. The effects depend on the caffeine and AQS concentration, and irradiation time. Caffeine in concentration of 0.01-3.0 μg/μL, may prevent DNA from damage induced by UV light, but caffeine in concentration of >5.0 μg/μL accelerates the DNA damage. In particular, in the aqueous solution system of DNA, caffeine and AQS, at pH 6.25-7.35, the caffeine in concentration of 2.5-4.50 μg/μL may resist the photosensitive injury of DNA caused by AQS under the deoxidized condition and exposure by 254 nm UV for 10 min. And caffeine in concentration of 5 μg/μL would present a synergetic effect on the photosensitive injury of DNA. Possible molecular mechanism also is discussed. (authors)

  5. 1-Methylxanthine derived from caffeine as a pharmacodynamic probe of oxypurinol effect

    OpenAIRE

    Birkett, D J; Miners, J O; Valente, L. (Luísa); Lillywhite, K J; Day, R. O.

    1997-01-01

    Aims In the present study we have investigated the use of caffeine, administered in the form of instant coffee, as a prodrug for 1MX to validate the use of the 1MU:1MX ratio following caffeine administration as a pharmacodynamic measure of oxypurinol effect on xanthine oxidase.

  6. Effects of caffeinated chewing gum on muscle pain during submaximal isometric exercise in individuals with fibromyalgia.

    Science.gov (United States)

    Umeda, Masataka; Kempka, Laura; Weatherby, Amy; Greenlee, Brennan; Mansion, Kimberly

    2016-04-01

    Physical activity is important to manage symptom of fibromyalgia (FM); however, individuals with FM typically experience augmented muscle pain during exercise. This study examined the effects of caffeinated chewing gum on exercise-induced muscle pain in individuals with FM. This study was conducted with a double-blind, placebo-controlled, cross-over design. Twenty-three patients with FM completed a caffeine condition where they consumed a caffeinated chewing gum that contains 100mg of caffeine, and a placebo condition where they consumed a non-caffeinated chewing gum. They completed isometric handgrip exercise at 25% of their maximal strength for 3min, and muscle pain rating (MPR) was recorded every 30s during exercise. Clinical pain severity was assessed in each condition using a pain questionnaire. The order of the two conditions was randomly determined. MPR increased during exercise, but caffeinated chewing gum did not attenuate the increase in MPR compared to placebo gum. Clinical pain severity was generally associated with the average MPR and the caffeine effects on MPR, calculated as difference in the average MPR between the two conditions. The results suggest that more symptomatic individuals with FM may experience greater exercise-induced muscle pain, but benefit more from caffeinated chewing gum to reduce exercise-induced muscle pain. PMID:26855267

  7. The effect of caffeine ingestion on skill maintenance and fatigue in epee fencers.

    Science.gov (United States)

    Bottoms, Lindsay; Greenhalgh, Andrew; Gregory, Kim

    2013-01-01

    The ergogenic effect of caffeine on sports performance focuses predominantly on endurance sports (Doherty & Smith, 2004 ) with little research on intermittent high intensity sports. This study aimed to explore the effect of caffeine ingestion on skill maintenance following fencing simulated exercise. Eleven competitive fencers participated (four female; seven male; age 33 ± 6.5 years). Following a maximal test to exhaustion, fencers completed two trials assessing accuracy and reaction times (Stroop test) before and after a fatiguing protocol designed to simulate the demands of a fencing competition. Skill testing involved 30 lunges to hit a target. 500 ml placebo or 3 mg · kg(-1) caffeine supplemented drink was administered after the initial reaction and skill tests in a single-blind crossover design. The fatiguing protocol involved simulating six fights with 6-minute rests between each. Fencers rated their perceived exertion (arm, legs, overall) using the Borg scale. There was no overall effect of caffeine on total skill score (P = 0.40), however there was a tendency for fewer misses with caffeine (P = 0.10). Caffeine had no effect on the Stroop Test. Caffeine produced significantly lower perceived fatigue for overall (P < 0.01). These results provide some support for caffeine producing maintenance of skill and reducing perceived fatigue during fencing. PMID:23383959

  8. Irish coffee: Effects of alcohol and caffeine on object discrimination in zebrafish.

    Science.gov (United States)

    Santos, Luana C; Ruiz-Oliveira, Julia; Oliveira, Jéssica J; Silva, Priscila F; Luchiari, Ana C

    2016-04-01

    Many studies regarding the effects of drugs investigate the acute and chronic use of alcohol, but only a few address the effects of caffeine and alcohol combined to the performance of the zebrafish in cognitive tasks. The zebrafish is an important model for studying the effects of drugs on learning, because it has large genetic similarities to humans and the non-invasive administration of the substances favors translational bias of research. In this study, we observed the effects of alcohol and caffeine on zebrafish cognition through an object discrimination test. We noticed that animals subjected to acute alcohol dose and those under alcohol or caffeine withdrawal did not show discrimination. When fish were treated with associated alcohol and caffeine, those chronically treated with alcohol and subjected to moderate acute dose of caffeine showed learning of the task. Our results reinforce the harmful effects of the alcohol use on cognitive tasks, and suggest that continued use of high doses of caffeine cause cognitive impairment during withdrawal of the substance. However, the acute use of caffeine appears to reverse the harmful effects of alcohol withdrawal, allowing discriminative performance equivalent to control fish. Finally, we reiterate the use of zebrafish as a model for drug effects screening and search for active compounds that modulate the alcohol and caffeine effects. PMID:26850919

  9. All in the mind? Pain, placebo effect, and ergogenic effect of caffeine in sports performance

    Directory of Open Access Journals (Sweden)

    Christopher J Beedie

    2010-07-01

    Full Text Available Christopher J BeedieDepartment of Sports Science, Tourism and Leisure, Canterbury Christ Church, University, Canterbury, UKAbstract: The ergogenic effects of caffeine on performance are well documented. These effects are more evident in endurance and short-duration, sustained-effort events than in interactive or stop-go sports. Experimentally-induced placebo effects of caffeine on sports performance have also been observed in a number of recent studies. In the present paper it is argued that, given the nature of the sports in which caffeine effects are observed, the well documented hypoalgesic effects of caffeine, and the fact that pain is highly placebo-responsive, a reduction in perceived pain might be the common factor in both the biologic and placebo ergogenic effects of caffeine on sports performance. This idea is supported by evidence from medicine that suggests placebo effects are often associated with mechanisms similar or identical to those of the substance the subject believes they have ingested. Research findings from both biomedicine and sports medicine that attest to the interaction of biologic and psychologic factors in caffeine and pain responses are briefly reviewed. In conclusion, it is recommended that researchers investigate the pain hypothesis. Furthermore, researchers should consider psychosocial factors that might modulate the pain response as variables of interest in future caffeine and performance research.Keywords: caffeine hypoalgesia, nocebo effects, research methods

  10. Effects of dilute aqueous NaCl solution on caffeine aggregation

    International Nuclear Information System (INIS)

    The effect of salt concentration on association properties of caffeine molecule was investigated by employing molecular dynamics simulations in isothermal-isobaric ensemble of eight caffeine molecules in pure water and three different salt (NaCl) concentrations, at 300 K temperature and 1 atm pressure. The concentration of caffeine was taken almost at the solubility limit. With increasing salt concentration, we observe enhancement of first peak height and appearance of a second peak in the caffeine-caffeine distribution function. Furthermore, our calculated solvent accessible area values and cluster structure analyses suggest formation of higher order caffeine cluster on addition of salt. The calculated hydrogen bond properties reveal that there is a modest decrease in the average number of water-caffeine hydrogen bonds on addition of NaCl salt. Also observed are: (i) decrease in probability of salt contact ion pair as well as decrease in the solvent separated ion pair formation with increasing salt concentration, (ii) a modest second shell collapse in the water structure, and (iii) dehydration of hydrophobic atomic sites of caffeine on addition of NaCl

  11. Sensory mother cell division is specifically affected in a Cyclin-A mutant of Drosophila melanogaster.

    OpenAIRE

    Ueda, R; Togashi, S; Takahisa, M; Tsurumura, S; Mikuni, M; Kondo, K.(Yamagata University, Yamagata, 992-8510, Japan); Miyake, T

    1992-01-01

    Cyclin proteins are one of the important components of the mechanism regulating mitosis in eukaryotic cells. We isolated a Drosophila Cyclin-A mutant in which the progenitor cells of the peripheral nervous system (the sensory mother cells) do not divide properly, causing the loss and other abnormalities of mechanosensory organs in the adult fly. Sequence analysis of the mutant genome reveals that a P element is inserted into the first intron of the Cyclin-A gene. A 13 kb wild-type genomic DNA...

  12. Limited prognostic value of tissue protein expression levels of cyclin E in Danish ovarian cancer patients

    DEFF Research Database (Denmark)

    Heeran, Mel C; Høgdall, Claus K; Kjaer, Susanne K;

    2012-01-01

    tissue arrays (TA), we analysed the cyclin E expression levels in tissues from 168 women with borderline ovarian tumours (BOT) (147 stage I, 4 stage II, 17 stage III) and 493 Ovarian cancer (OC) patients (127 stage I, 45 stage II, 276 stage III, 45 stage IV). Using a 10% cut-off level for cyclin E...... overexpression, 20% of the BOTs were positive with a higher proportion of serous than mucinous tumours. Sixty-two per cent of the OCs were positive for cyclin E expression with the highest percentage found in clear cell carcinomas. Results based on univariate and multivariate survival analyses with a 10% cut-off...

  13. Complexes of D-type cyclins with CDKs during maize germination

    OpenAIRE

    Godínez-Palma, Silvia K.; García, Elpidio; Sánchez, María de la Paz; Rosas, Fernando; Vázquez-Ramos, Jorge M

    2013-01-01

    The importance of cell proliferation in plant growth and development has been well documented. The majority of studies on basic cell cycle mechanisms in plants have been at the level of gene expression and much less knowledge has accumulated in terms of protein interactions and activation. Two key proteins, cyclins and cyclin-dependent kinases (CDKs) are fundamental for cell cycle regulation and advancement. Our aim has been to understand the role of D-type cyclins and type A and B CDKs in th...

  14. Implications of caspase-dependent proteolytic cleavage of cyclin A1 in DNA damage-induced cell death

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Sang Hyeok; Seo, Sung-Keum [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); An, Sungkwan; Choe, Tae-Boo [Department of Microbiological Engineering, Kon-Kuk University, Gwangjin-gu, Seoul (Korea, Republic of); Hong, Seok-Il [Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Lee, Yun-Han, E-mail: yhlee87@yuhs.ac [Department of Radiation Oncology, College of Medicine, Yonsei University, 250 Seongsan-no, Seodaemun-gu, Seoul (Korea, Republic of); Park, In-Chul, E-mail: parkic@kcch.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of)

    2014-10-24

    Highlights: • Caspase-1 mediates doxorubicin-induced downregulation of cyclin A1. • Active caspase-1 effectively cleaved cyclin A1 at D165. • Cyclin A1 expression is involved in DNA damage-induced cell death. - Abstract: Cyclin A1 is an A-type cyclin that directly binds to CDK2 to regulate cell-cycle progression. In the present study, we found that doxorubicin decreased the expression of cyclin A1 at the protein level in A549 lung cancer cells, while markedly downregulating its mRNA levels. Interestingly, doxorubicin upregulated caspase-1 in a concentration-dependent manner, and z-YAVD-fmk, a specific inhibitor of caspase-1, reversed the doxorubicin-induced decrease in cyclin A1 in A549 lung cancer and MCF7 breast cancer cells. Active caspase-1 effectively cleaved cyclin A1 at D165 into two fragments, which in vitro cleavage assays showed were further cleaved by caspase-3. Finally, we found that overexpression of cyclin A1 significantly reduced the cytotoxicity of doxorubicin, and knockdown of cyclin A1 by RNA interference enhanced the sensitivity of cells to ionizing radiation. Our data suggest a new mechanism for the downregulation of cyclin A1 by DNA-damaging stimuli that could be intimately involved in the cell death induced by DNA damage-inducing stimuli, including doxorubicin and ionizing radiation.

  15. Implications of caspase-dependent proteolytic cleavage of cyclin A1 in DNA damage-induced cell death

    International Nuclear Information System (INIS)

    Highlights: • Caspase-1 mediates doxorubicin-induced downregulation of cyclin A1. • Active caspase-1 effectively cleaved cyclin A1 at D165. • Cyclin A1 expression is involved in DNA damage-induced cell death. - Abstract: Cyclin A1 is an A-type cyclin that directly binds to CDK2 to regulate cell-cycle progression. In the present study, we found that doxorubicin decreased the expression of cyclin A1 at the protein level in A549 lung cancer cells, while markedly downregulating its mRNA levels. Interestingly, doxorubicin upregulated caspase-1 in a concentration-dependent manner, and z-YAVD-fmk, a specific inhibitor of caspase-1, reversed the doxorubicin-induced decrease in cyclin A1 in A549 lung cancer and MCF7 breast cancer cells. Active caspase-1 effectively cleaved cyclin A1 at D165 into two fragments, which in vitro cleavage assays showed were further cleaved by caspase-3. Finally, we found that overexpression of cyclin A1 significantly reduced the cytotoxicity of doxorubicin, and knockdown of cyclin A1 by RNA interference enhanced the sensitivity of cells to ionizing radiation. Our data suggest a new mechanism for the downregulation of cyclin A1 by DNA-damaging stimuli that could be intimately involved in the cell death induced by DNA damage-inducing stimuli, including doxorubicin and ionizing radiation

  16. Sensitization of rad mutants of Dictyostelium discoideum to ultraviolet light by postirradiation treatment with caffeine

    International Nuclear Information System (INIS)

    The extent of caffeine sensitization following ultraviolet light irradiation for various UV-sensitive strains and the parental resistant strain are compared. Several features of these results are to be noted. (i) With the exception of the M28 strain, the more sensitive the strain is to UV, the lesser the effect of post-irradiation treatment with caffeine. For example, the D10 with caffeine for the wt parental strain is 0.13 of that with no caffeine, whereas for the three most sensitive strains, γs-13 (radB), HPS73 (rad AradB), and HPS82 (rad AradC), this ratio is about 1.0. The slight desensitizing effect of caffeine with γs-13 is reproducible and was observed previously. (orig./AJ)

  17. Voltammetric sensor for caffeine based on a glassy carbon electrode modified with Nafion and graphene oxide

    International Nuclear Information System (INIS)

    We report on a voltammetric sensor for caffeine that is based on a glassy carbon electrode modified with Nafion and graphene oxide (GO). It exhibits a good affinity for caffeine (resulting from the presence of Nafion), and excellent electrochemical response (resulting from the pressence of GO) for the oxidation of caffeine. The electrode enables the determination of caffeine in the range from 4.0 x 10-7 to 8.0 x 10-5 mol L-1, with a detection limit of 2.0 x 10-7 mol L-1. The sensor displays good stability, reproducibility, and high sensitivity. It was successfully applied to the quantitative determination of caffeine in beverages. (author)

  18. DNA repair in gamma-and UV-irradiated Escherichia coli treated with caffeine and acriflavine

    International Nuclear Information System (INIS)

    A study is made of the postradiation effect of caffeine and acriflavine on the survival rate and DNA repair in E. coli exposed to γ- and UV-radiation. When added to postradiation growth medium caffeine and acriflavine lower the survival rate of γ-irradiated radioresistant strains, B/r and Bsub(s-1)γR, and UV-irradiated UV-resistant strain B/r, and do not appreciably influence the survival of strains that are sensitive to γ- and UV-radiation. The survival rate of UV-irradiated mutant BsUb(s-1) somewhat increases in the presence of caffeine. Caffeine and acriflavine inhibit repair of single-stranded DNA breaks induced in strain B/r by γ-radiation (slow repair) and UV light. Acriflavine arrests a recombination branch of postreplication repair of DNA in E. coli Bsub(s-1)γR Whereas caffeine does not influence this process

  19. Comparative study of the binding of trypsin to caffeine and theophylline by spectrofluorimetry

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ruiyong, E-mail: wangry@zzu.edu.cn [Department of Chemistry, Zhengzhou University, Zhengzhou 450001 (China); Kang, Xiaohui [Department of Chemistry, Zhengzhou University, Zhengzhou 450001 (China); Wang, Ruiqiang [The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052 (China); Wang, Rui; Dou, Huanjing; Wu, Jing; Song, Chuanjun [Department of Chemistry, Zhengzhou University, Zhengzhou 450001 (China); Chang, Junbiao, E-mail: changjunbiao@zzu.edu.cn [Department of Chemistry, Zhengzhou University, Zhengzhou 450001 (China)

    2013-06-15

    The interactions between trypsin and caffeine/theophylline were investigated by fluorescence spectroscopy, UV–visible absorption spectroscopy, resonance light scattering and synchronous fluorescence spectroscopy under mimic physiological conditions. The results revealed that the fluorescence quenching of trypsin by caffeine and theophylline was the result of the formed complex of caffeine–trypsin and theophylline–trypsin. The binding constants and thermodynamic parameters at three different temperatures were obtained. The hydrophobic interaction was the predominant intermolecular forces to stabilize the complex. Results showed that caffeine was the stronger quencher and bound to trypsin with higher affinity than theophylline. -- Highlights: ► The fluorescence of trypsin can be quenched by caffeine or theophylline via hydrophobic contacts. ► Caffeine binds to trypsin with higher affinity than theophylline. ► The influence of molecular structure on the binding aspects is reported.

  20. The effect of caffeine on glucose kinetics in humans - influence of adrenaline

    DEFF Research Database (Denmark)

    Battram, Danielle S.; Graham, Terry E.; Richter, Erik A.;

    2005-01-01

    While caffeine impedes insulin-mediated glucose disposal in humans, its effect on endo-genous glucose production (EGP) remains unknown. In addition, the mechanism involved in these effects is unclear, but may be due to the accompanying increase in adrenaline concentration. We studied the effect of...... caffeine on EGP and glucose infusion rates (GIR), and whether or not adrenaline can account for all of caffeine's effects. Subjects completed three isoglycaemic-hyperinsulinaemic clamps (with 3-[3H]glucose infusion) 30 min after ingesting: (1) placebo capsules (n= 12); (2) caffeine capsules (5 mg kg-1) (n......= 12); and either (3) placebo plus a high-dose adrenaline infusion (HAdr; adrenaline concentration, 1.2 nM; n= 8) or (4) placebo plus a low-dose adrenaline infusion (LAdr; adrenaline concentration, 0.75 nM; n= 6). With caffeine, adrenaline increased to 0.6 nM but no effect on EGP was observed. While...

  1. Pregnancy-induced changes in the pharmacokinetics of caffeine and its metabolites.

    Science.gov (United States)

    Yu, Tian; Campbell, Sarah C; Stockmann, Chris; Tak, Casey; Schoen, Katherine; Clark, Erin A S; Varner, Michael W; Spigarelli, Michael G; Sherwin, Catherine M T

    2016-05-01

    This study sought to assess the pharmacokinetic (PK) changes of caffeine and its CYP1A2 metabolites across the 3 trimesters of pregnancy. A prospective, multicenter PK study was conducted among 59 pregnant women (93.2% white) who were studied once during a trimester. One beverage with 30-95 mg caffeine was consumed, and a blood/urine sample was collected within 1 hour postingestion. Concentrations of caffeine and its primary metabolites were quantified from serum and urine by LC-MS/MS. There was a significant increase in dose-normalized caffeine serum and urine concentrations between the first and third trimesters (P theophylline concentrations also increased significantly in the third trimester in serum (P theophylline concentrations during pregnancy, especially in the third trimester, revealing evidence of the large role that pregnancy plays in influencing caffeine metabolism. PMID:26358647

  2. Comparative study of the binding of trypsin to caffeine and theophylline by spectrofluorimetry

    International Nuclear Information System (INIS)

    The interactions between trypsin and caffeine/theophylline were investigated by fluorescence spectroscopy, UV–visible absorption spectroscopy, resonance light scattering and synchronous fluorescence spectroscopy under mimic physiological conditions. The results revealed that the fluorescence quenching of trypsin by caffeine and theophylline was the result of the formed complex of caffeine–trypsin and theophylline–trypsin. The binding constants and thermodynamic parameters at three different temperatures were obtained. The hydrophobic interaction was the predominant intermolecular forces to stabilize the complex. Results showed that caffeine was the stronger quencher and bound to trypsin with higher affinity than theophylline. -- Highlights: ► The fluorescence of trypsin can be quenched by caffeine or theophylline via hydrophobic contacts. ► Caffeine binds to trypsin with higher affinity than theophylline. ► The influence of molecular structure on the binding aspects is reported

  3. Gut microbiota mediate caffeine detoxification in the primary insect pest of coffee.

    Science.gov (United States)

    Ceja-Navarro, Javier A; Vega, Fernando E; Karaoz, Ulas; Hao, Zhao; Jenkins, Stefan; Lim, Hsiao Chien; Kosina, Petr; Infante, Francisco; Northen, Trent R; Brodie, Eoin L

    2015-01-01

    The coffee berry borer (Hypothenemus hampei) is the most devastating insect pest of coffee worldwide with its infestations decreasing crop yield by up to 80%. Caffeine is an alkaloid that can be toxic to insects and is hypothesized to act as a defence mechanism to inhibit herbivory. Here we show that caffeine is degraded in the gut of H. hampei, and that experimental inactivation of the gut microbiota eliminates this activity. We demonstrate that gut microbiota in H. hampei specimens from seven major coffee-producing countries and laboratory-reared colonies share a core of microorganisms. Globally ubiquitous members of the gut microbiota, including prominent Pseudomonas species, subsist on caffeine as a sole source of carbon and nitrogen. Pseudomonas caffeine demethylase genes are expressed in vivo in the gut of H. hampei, and re-inoculation of antibiotic-treated insects with an isolated Pseudomonas strain reinstates caffeine-degradation ability confirming their key role. PMID:26173063

  4. Expression of cyclin E2 and cyclin dependent kinase 2 in acute leukemia patients and prognosis%白血病患者cyclin E2、CDK2的表达与复发的关系

    Institute of Scientific and Technical Information of China (English)

    徐丽粉; 郭晓楠; 刘英芳

    2012-01-01

    目的 探讨急性白血病患者细胞周期蛋白E2 (cyclin E2)和细胞周期蛋白依赖性激酶2(CDK2)的表达情况及预后意义.方法 急性白血病(AL)患者70例,包括新近诊断急性白血病患者41例、复发患者10例和完全缓解期患者19例.14例健康人为正常对照.应用半定量反转录-聚合酶链反应(RT-PCR)方法检测骨髓或外周血单个核细胞cyclin E2和CDK2 mRNA表达水平.结果 Cyclin E2和CDK2 mRNA在初治的AL患者阳性表达明显高于正常对照组(70.7% vs 0%,P<0.05),cyclin E2在完全缓解组中阳性率低于初治组(47.4% vs 70.7%,P<0.05),初治组CDK2阳性率高于正常对照组(78.0% vs 28.6%,P<0.05).cyclin E2 mRNA阳性表达患者完全缓解率低于阴性表达者(48.3% vs 91.7%,x2 =5.016,P<0.05).结论 Cyclin E2和CDK2可望成为急性白血病早期预后指标和复发判断指标.%Objective To study the expression and clinical prognostic significance of cyclin E2 and cyclin dependent kinase 2(CDK2) Mrna in acute leukemia patients. Methods This study included 70 patients with acute leukemia (including 41 cases of newly diagnosed acute leukemia, 10 patients with recurrent leukemia and 19 cases of complete remission) ,and 14 healthy controls. Cyclin E2 and CDK2 Mrna expression were detected in acute leukemia patients and normal controls with RT-PCR. Results Cyclin E2 and CDK2 Mrna expression of newly diagnosed acute leukemia were significantly higher than those of normal controls(70. 7% vs 0%, P <0. 05),and the expressions of two items in complete remission were significantly lower than those in newly diagnosed acute leukemia(47. 4% vs 70. 7%, P <0. 05),newly diagnosed group CDK2 positive rate were higher than normal control group(78. 0% vs 28. 6% , P < 0. 05). The complete remission rate was significantly lower in the positive expression of cyclin E2 Mrna patients than that in the negative patients(48. 3% vs 91. 7% ,χ2 =5. 016, P <0. 05). Conclusion Cyclin E

  5. Discriminative Stimulus Effects of Binary Drug Mixtures: Studies with Cocaine, MDPV, and Caffeine.

    Science.gov (United States)

    Collins, Gregory T; Abbott, Megan; Galindo, Kayla; Rush, Elise L; Rice, Kenner C; France, Charles P

    2016-10-01

    Illicit drug preparations often include more than one pharmacologically active compound. For example, cocaine and synthetic cathinones [e.g., 3,4-methylenedioxypyrovalerone (MDPV)] are often mixed with caffeine before sale. Caffeine is likely added to these preparations because it is inexpensive and legal; however, caffeine might also mimic or enhance some of the effects of cocaine or MDPV. In these studies, male Sprague-Dawley rats were trained to discriminate 10 mg/kg cocaine from saline, and the discriminative stimulus effects of cocaine, caffeine, and MDPV were evaluated alone and as binary mixtures (cocaine and caffeine, MDPV and caffeine, and cocaine and MDPV) at fixed-dose ratios of 3:1, 1:1, and 1:3 relative to the dose of each drug that produced 50% cocaine-appropriate responding. Dose-addition analyses were used to determine the nature of the drug-drug interactions for each mixture (e.g., additive, supra-additive, or subadditive). Although additive interactions were observed for most mixtures, supra-additive interactions were observed at the 50% effect level for the 1:1 mixture of cocaine and caffeine and at the 80% effect level for all three mixtures of cocaine and caffeine, as well as for the 3:1 and 1:3 mixtures of cocaine and MDPV. These results demonstrate that with respect to cocaine-like discriminative stimulus effects, caffeine can function as a substitute in drug preparations containing either cocaine or MDPV, with enhancements of cocaine-like effects possible under certain conditions. Further research is needed to determine whether similar interactions exist for other abuse-related or toxic effects of drug preparations, including cocaine, synthetic cathinones, and caffeine. PMID:27493274

  6. The Effects of Preexercise Caffeinated Coffee Ingestion on Endurance Performance: An Evidence-Based Review.

    Science.gov (United States)

    Higgins, Simon; Straight, Chad R; Lewis, Richard D

    2016-06-01

    Endurance athletes commonly ingest caffeine as a means to enhance training intensity and competitive performance. A widely-used source of caffeine is coffee, however conflicting evidence exists regarding the efficacy of coffee in improving endurance performance. In this context, the aims of this evidence-based review were threefold: 1) to evaluate the effects of preexercise coffee on endurance performance, 2) to evaluate the effects of coffee on perceived exertion during endurance performance, and 3) to translate the research into usable information for athletes to make an informed decision regarding the intake of caffeine via coffee as a potential ergogenic aid. Searches of three major databases were performed using terms caffeine and coffee, or coffee-caffeine, and endurance, or aerobic. Included studies (n = 9) evaluated the effects of caffeinated coffee on human subjects, provided the caffeine dose administered, administered caffeine ≥ 45 min before testing, and included a measure of endurance performance (e.g., time trial). Significant improvements in endurance performance were observed in five of nine studies, which were on average 24.2% over controls for time to exhaustion trials, and 3.1% for time to completion trials. Three of six studies found that coffee reduced perceived exertion during performance measures significantly more than control conditions (p coffee as an ergogenic aid to improve performance in endurance cycling and running. Coffee providing 3-8.1 mg/kg (1.36-3.68 mg/lb) of caffeine may be used as a safe alternative to anhydrous caffeine to improve endurance performance. PMID:26568580

  7. Molecular and biochemical characterization of caffeine synthase and purine alkaloid concentration in guarana fruit.

    Science.gov (United States)

    Schimpl, Flávia Camila; Kiyota, Eduardo; Mayer, Juliana Lischka Sampaio; Gonçalves, José Francisco de Carvalho; da Silva, José Ferreira; Mazzafera, Paulo

    2014-09-01

    Guarana seeds have the highest caffeine concentration among plants accumulating purine alkaloids, but in contrast with coffee and tea, practically nothing is known about caffeine metabolism in this Amazonian plant. In this study, the levels of purine alkaloids in tissues of five guarana cultivars were determined. Theobromine was the main alkaloid that accumulated in leaves, stems, inflorescences and pericarps of fruit, while caffeine accumulated in the seeds and reached levels from 3.3% to 5.8%. In all tissues analysed, the alkaloid concentration, whether theobromine or caffeine, was higher in young/immature tissues, then decreasing with plant development/maturation. Caffeine synthase activity was highest in seeds of immature fruit. A nucleotide sequence (PcCS) was assembled with sequences retrieved from the EST database REALGENE using sequences of caffeine synthase from coffee and tea, whose expression was also highest in seeds from immature fruit. The PcCS has 1083bp and the protein sequence has greater similarity and identity with the caffeine synthase from cocoa (BTS1) and tea (TCS1). A recombinant PcCS allowed functional characterization of the enzyme as a bifunctional CS, able to catalyse the methylation of 7-methylxanthine to theobromine (3,7-dimethylxanthine), and theobromine to caffeine (1,3,7-trimethylxanthine), respectively. Among several substrates tested, PcCS showed higher affinity for theobromine, differing from all other caffeine synthases described so far, which have higher affinity for paraxanthine. When compared to previous knowledge on the protein structure of coffee caffeine synthase, the unique substrate affinity of PcCS is probably explained by the amino acid residues found in the active site of the predicted protein. PMID:24856135

  8. Action of caffeine on x-irradiated HeLa cells. VII. Evidence that caffeine enhances expression of potentially lethal radiation damage

    International Nuclear Information System (INIS)

    HeLa cells irradiated with 2 Gy of 220-kV X rays suffer a 60-70% loss of colony-forming ability which is increased to 90% by postirradiation treatment with 10 mM caffeine for 6 hr. The detailed postirradiation patterns of cell death and sister-cell fusion in such cultures and in cultures in which the colony-forming ability was brought to about the same level by treatment with a larger (4 Gy) X-ray dose alone or by longer (48 hr) treatment with 10 mM caffeine alone were recorded by time-lapse cinemicrography. Because the patterns of cell death and fusion differ radically in irradiated and in caffeine-treated cultures, the response of the additional cells killed by the combined treatment can be identified as X-ray induced rather than caffeine induced. The appearance of cultures after several days of incubation confirms the similarity of the post-treatment patterns of proliferation in cultures suffering enhanced killing to those occurring in cultures treated with larger doses of X rays alone. It is concluded that x rays do not sensitize cells to caffeine, but rather that caffeine enhanced the expression of potentially lethal radiation-induced damage

  9. Caffeine potentiates or protects against radiation-induced DNA and chromosomal damage in human lymphocytes depending on temperature and concentration

    International Nuclear Information System (INIS)

    The effect of caffeine on radiation-induced chromosomal aberrations and DNA strand breaks in unstimulated human lymphocytes was investigated. When present prior to and during the radiation exposure, caffeine treatment was found to cause either potentiation or protection against induction of chromosomal aberrations depending on the concentration and temperature. When the nucleoid sedimentation technique was applied, enhancement or reduction of radiation-induced DNA strand breaks by caffeine was also found to be dependent on temperature and caffeine concentration. It is proposed that caffeine, in addition to its suspected ability to influence DNA repair, can also influence the induction of DNA damage, leading to alterations in the yield of chromosomal aberrations

  10. The δ-cyclin expression at early stages of embryogenesis of Brassica rapa L. under clinorotation

    Science.gov (United States)

    Artemenko, O. A.; Popova, A. F.

    We present some results of comparison studying of Brassica embryo development and the δ-cyclin genes expression under slow horizontal clinorotation and in the laboratory control. Some backlog of the δ1-cyclin genes expression at early stages of embryogenesis under clinorotation was revealed in comparison with the laboratory control. The similar level of the δ3-cyclin expression at all stages of embryo formation (from one to nine days) in both variants is shown. Some delays in the rate of Brassica rapa embryo development under clinorotation in comparison with the laboratory control can be a result of decrease of a level and some backlog of the δ1-cyclin expression at early stages of embryogenesis.

  11. Cyclin-dependent kinases and cell-cycle transitions: does one fit all?

    Science.gov (United States)

    Hochegger, Helfrid; Takeda, Shunichi; Hunt, Tim

    2008-11-01

    Cell-cycle transitions in higher eukaryotes are regulated by different cyclin-dependent kinases (CDKs) and their activating cyclin subunits. Based on pioneering findings that a dominant-negative mutation of CDK1 blocks the cell cycle at G2-M phase, whereas dominant-negative CDK2 inhibits the transition into S phase, a model of cell-cycle control has emerged in which each transition is regulated by a specific subset of CDKs and cyclins. Recent work with gene-targeted mice has led to a revision of this model. We discuss cell-cycle control in light of overlapping and essential functions of the different CDKs and cyclins. PMID:18813291

  12. Opposing action of estrogen receptors alpha and beta on cyclin D1 gene expression.

    Science.gov (United States)

    Liu, Meng-Min; Albanese, Chris; Anderson, Carol M; Hilty, Kristin; Webb, Paul; Uht, Rosalie M; Price, Richard H; Pestell, Richard G; Kushner, Peter J

    2002-07-01

    Induction of cyclin D1 gene transcription by estrogen receptor alpha (ERalpha) plays an important role in estrogen-mediated proliferation. There is no classical estrogen response element in the cyclin D1 promoter, and induction by ERalpha has been mapped to an alternative response element, a cyclic AMP-response element at -57, with possible participation of an activating protein-1 site at -954. The action of ERbeta at the cyclin D1 promoter is unknown, although evidence suggests that ERbeta may inhibit the proliferative action of ERalpha. We examined the response of cyclin D1 promoter constructs by luciferase assay and the response of the endogenous protein by Western blot in HeLa cells transiently expressing ERalpha, ERalphaK206A (a derivative that is superactive at alternative response elements), or ERbeta. In each case, ER activation at the cyclin D1 promoter is mediated by both the cyclic AMP-response element and the activating protein-1 site, which play partly redundant roles. The activation by ERbeta occurs only with antiestrogens. Estrogens, which activate cyclin D1 gene expression with ERalpha, inhibit expression with ERbeta. Strikingly, the presence of ERbeta completely inhibits cyclin D1 gene activation by estrogen and ERalpha or even by estrogen and the superactive ERalphaK206A. The observation of the opposing action and dominance of ERbeta over ERalpha in activation of cyclin D1 gene expression has implications for the postulated role of ERbeta as a modulator of the proliferative effects of estrogen. PMID:11986316

  13. Dexamethasone Induces Cardiomyocyte Terminal Differentiation via Epigenetic Repression of Cyclin D2 Gene.

    Science.gov (United States)

    Gay, Maresha S; Dasgupta, Chiranjib; Li, Yong; Kanna, Angela; Zhang, Lubo

    2016-08-01

    Dexamethasone treatment of newborn rats inhibited cardiomyocyte proliferation and stimulated premature terminal differentiation of cardiomyocytes in the developing heart. Yet mechanisms remain undetermined. The present study tested the hypothesis that the direct effect of glucocorticoid receptor-mediated epigenetic repression of cyclin D2 gene in the cardiomyocyte plays a key role in the dexamethasone-mediated effects in the developing heart. Cardiomyocytes were isolated from 2-day-old rats. Cells were stained with a cardiomyocyte marker α-actinin and a proliferation marker Ki67. Cyclin D2 expression was evaluated by Western blot and quantitative real-time polymerase chain reaction. Promoter methylation of CcnD2 was determined by methylated DNA immunoprecipitation (MeDIP). Overexpression of Cyclin D2 was conducted by transfection of FlexiCcnD2 (+CcnD2) construct. Treatment of cardiomyocytes isolated from newborn rats with dexamethasone for 48 hours significantly inhibited cardiomyocyte proliferation with increased binucleation and decreased cyclin D2 protein abundance. These effects were blocked with Ru486 (mifepristone). In addition, the dexamethasone treatment significantly increased cyclin D2 gene promoter methylation in newborn rat cardiomyocytes. 5-Aza-2'-deoxycytidine inhibited dexamethasone-mediated promoter methylation, recovered dexamethasone-induced cyclin D2 gene repression, and blocked the dexamethasone-elicited effects on cardiomyocyte proliferation and binucleation. In addition, the overexpression of cyclin D2 restored the dexamethasone-mediated inhibition of proliferation and increase in binucleation in newborn rat cardiomyocytes. The results demonstrate that dexamethasone acting on glucocorticoid receptors has a direct effect and inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via epigenetic repression of cyclin D2 gene. PMID:27302109

  14. Complexes of D-type cyclins with CDKs during maize germination.

    Science.gov (United States)

    Godínez-Palma, Silvia K; García, Elpidio; Sánchez, María de la Paz; Rosas, Fernando; Vázquez-Ramos, Jorge M

    2013-12-01

    The importance of cell proliferation in plant growth and development has been well documented. The majority of studies on basic cell cycle mechanisms in plants have been at the level of gene expression and much less knowledge has accumulated in terms of protein interactions and activation. Two key proteins, cyclins and cyclin-dependent kinases (CDKs) are fundamental for cell cycle regulation and advancement. Our aim has been to understand the role of D-type cyclins and type A and B CDKs in the cell cycle taking place during a developmental process such as maize seed germination. Results indicate that three maize D-type cyclins-D2;2, D4;2, and D5;3-(G1-S cyclins by definition) bind and activate two different types of CDK-A and B1;1-in a differential way during germination. Whereas CDKA-D-type cyclin complexes are more active at early germination times than at later times, it was surprising to observe that CDKB1;1, a supposedly G2-M kinase, bound in a differential way to all D-type cyclins tested during germination. Binding to cyclin D2;2 was detectable at all germination times, forming a complex with kinase activity, whereas binding to D4;2 and D5;3 was more variable; in particular, D5;3 was only detected at late germination times. Results are discussed in terms of cell cycle advancement and its importance for seed germination. PMID:24127516

  15. Involvement of cyclin K posttranscriptional regulation in the formation of Artemia diapause cysts.

    Directory of Open Access Journals (Sweden)

    Yang Zhao

    Full Text Available BACKGROUND: Artemia eggs tend to develop ovoviviparously to yield nauplius larvae in good rearing conditions; while under adverse situations, they tend to develop oviparously and encysted diapause embryos are formed instead. However, the intrinsic mechanisms regulating this process are not well understood. PRINCIPAL FINDING: This study has characterized the function of cyclin K, a regulatory subunit of the positive transcription elongation factor b (P-TEFb in the two different developmental pathways of Artemia. In the diapause-destined embryo, Western blots showed that the cyclin K protein was down-regulated as the embryo entered dormancy and reverted to relatively high levels of expression once development resumed, consistent with the fluctuations in phosphorylation of position 2 serines (Ser2 in the C-terminal domain (CTD of the largest subunit (Rpb1 of RNA polymerase II (RNAP II. Interestingly, the cyclin K transcript levels remained constant during this process. In vitro translation data indicated that the template activity of cyclin K mRNA stored in the postdiapause cyst was repressed. In addition, in vivo knockdown of cyclin K in developing embryos by RNA interference eliminated phosphorylation of the CTD Ser2 of RNAP II and induced apoptosis by inhibiting the extracellular signal-regulated kinase (ERK survival signaling pathway. CONCLUSIONS/SIGNIFICANCE: Taken together, these findings reveal a role for cyclin K in regulating RNAP II activity during diapause embryo development, which involves the post-transcriptional regulation of cyclin K. In addition, a further role was identified for cyclin K in regulating the control of cell survival during embryogenesis through ERK signaling pathways.

  16. Cyclin H binding to the RARα activation function (AF)-2 domain directs phosphorylation of the AF-1 domain by cyclin-dependent kinase 7

    OpenAIRE

    Bour, Gaétan; Gaillard, Emilie; Bruck, Nathalie; Lalevée, Sébastien; Plassat, Jean-Luc; Busso, Didier; Samama, Jean-Pierre; Rochette-Egly, Cécile

    2005-01-01

    The transcriptional activity of nuclear retinoic acid receptors (RARs), which act as RAR/retinoid X receptor (RXR) heterodimers, depends on two activation functions, AF-1 and AF-2, which are targets for phosphorylations and synergize for the activation of retinoic acid target genes. The N-terminal AF-1 domain of RARα is phosphorylated at S77 by the cyclin-dependent kinase (cdk)-activating kinase (CAK) subcomplex (cdk7/cyclin H/MAT1) of the general transcription factor TFIIH. Here, we show tha...

  17. Efficacy of acute caffeine ingestion for short-term high-intensity exercise performance: a systematic review.

    Science.gov (United States)

    Astorino, Todd A; Roberson, Daniel W

    2010-01-01

    Caffeine is the most widely used drug in the world, commonly ingested in coffee, tea, soda, and energy drinks. Its ability to enhance muscular work has been apparent since the early 1900s. Caffeine typically increases endurance performance; however, efficacy of caffeine ingestion for short-term high-intensity exercise is equivocal, which may be explained by discrepancies in exercise protocols, dosing, and subjects' training status and habitual caffeine intake found across studies. The primary aim of this review is to critically examine studies that have tested caffeine's ability to augment performance during exercise dependent on nonoxidative metabolism such as sprinting, team sports, and resistance training. A review of the literature revealed 29 studies that measured alterations in short-term performance after caffeine ingestion. Each study was critically analyzed using the Physiotherapy Evidence Database (PEDro) scale. The mean PEDro score was 7.76 +/- 0.87. Eleven of 17 studies revealed significant improvements in team sports exercise and power-based sports with caffeine ingestion, yet these effects were more common in elite athletes who do not regularly ingest caffeine. Six of 11 studies revealed significant benefits of caffeine for resistance training. Some studies show decreased performance with caffeine ingestion when repeated bouts are completed. The exact mechanism explaining the ergogenic effect of caffeine for short-term exercise is unknown. PMID:19924012

  18. A PRELIMINARY STUDY AND FIRST REPORT ON CAFFEINE DEGRADING BACTERIA ISOLATED FROM THE SOILS OF CHITTOOR AND VELLORE

    Directory of Open Access Journals (Sweden)

    Sharan Siddharth

    2012-03-01

    Full Text Available An attempt on basic study of the caffeine degrading organism and screening of potential ‘caffeinase’ producing bacteria has been studied and reported. Caffeine is present in soft drinks, coffee plants, tea leaves, and kola nuts and is used extensively in human consumption. Various health and environmental demerits makes it significant to reduce the levels of caffeine into a much less harmful compound, which can be done biologically using specific microorganisms. The enzyme responsible for caffeine degradation plays a major role and hence needs to be studied for caffeinase isolation and improvement of available caffeine products. Isolation of such microorganisms and their study of extent of caffeine degradation would prove to be helpful in generating an economic and safer method of caffeine removal in food products and coffee left over which could be less harmful to human health and the environment.

  19. Investigation of pharmaceutical drugs and caffeine-containing foods using Fourier and terahertz time-domain spectroscopy

    Science.gov (United States)

    KaraliÅ«nas, Mindaugas; Venckevičius, Rimvydas; Kašalynas, Irmantas; Puc, Uroš; Abina, Andreja; Jeglič, Anton; Zidanšek, Aleksander; Valušis, Gintaras

    2015-08-01

    Several pharmaceutical drugs, such as alprazolam, ibuprofen, acetaminophen, activated carbon and others, and caffeine-containing foods were tested using terahertz (THz) time domain spectroscopy in the range from 0.3 to 2 THz. The dry powder of pharmaceutical drugs was mixed with HDPE and pressed into the pellets using hydraulic press. The coffee grounds were also pressed into the pellets after ball-milling and mixing with HDPE. The caffeine containing liquid foods were dried out on the paper strips of various stacking. Experiments allow one to determine characteristic spectral signatures of the investigated substances within THz range caused by active pharmaceutical ingredients, like in the case of caffeine, as well as supporting pharmaceutical ingredients. Spectroscopic THz imaging approach is considered as a possible option to identify packaged pharmaceutical drugs. The caffeine spectral features in the tested caffeine containing foods are difficult to observed due to the low caffeine concentration and complex caffeine chemical surrounding.

  20. Cyclin D1 Expression and Its Correlation with Histopathological Differentiation in Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Swati Saawarn

    2012-01-01

    Full Text Available Background. Cyclin D1 regulates the G1 to S transition of cell cycle. Its deregulation or overexpression may lead to disturbance in the normal cell cycle control and tumour formation. Overexpression of cyclin D1 has been reported in various tumors of diverse histogenesis. This case control retrospective study was carried out to study the immunohistochemical reactivity and expression of cyclin D1 and its association with site, clinical staging, and histopathological differentiation of oral squamous cell carcinoma (OSCC. Methods. Forty formalin-fixed paraffin-embedded tissue blocks of biopsy specimens of oral squamous cell carcinoma were immunohistochemically evaluated for expression of cyclin D1. Results. Cyclin D1 expression was seen in 45% cases of OSCC. It did not correlate with site and clinical staging. Highest expression was seen in well-differentiated, followed by moderately differentiated, and poorly differentiated squamous cell carcinomas, with a statistically significant correlation. Conclusion. Cyclin D1 expression significantly increases with increase in differentiation.

  1. Temperature dependent expression of cdc2 and cyclin B1 in spermatogenic cells during spermatogenesis

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    p34cdc2 and Cyclin Bi are key components of cell cycle controlling machine and are believed to play a fundamental role in gametogenesis. It is also well known that, in scrotal mammals, spermatogenesis depends greatly on the maintenance of comparatively low temperature in the scrotum. To investigate whether the expression of cdc2 and cyclin B1 in spermatogenic cells during spermatogenesis is actually a temperature dependent event, in situ hybridization, Western blotting and immunohistochemistry analysis were used to study the expression of cdc2 and cyclin B1 in normal and cryptorchid testis. Results showed that the abdominal temperature had no significant influence on the transcription of cdc2 and cyclin B1 in the spermatogonia and pachytene/diplotene primary spermatocytes, but it blocked the translation of them. Due to the deficiency of p34cdc2 and Cyclin B1, the spermatogonia and pachytene/diplotene primary spermatocytes were unable to form MPF, hence, they couldn't undergo karyokinesis. The development of primary spermato cytes was arrested at the G2 to M phase transition. We also found that testosterone could regulate the Cyclin B1 expression in spermatogenic cells. Muscular injection of testosterone could recover spermatogenesis in the unilateral scrotal testis which was influenced by the contralateral cryptorchid testis, but it could not salvage the spermatogenesis block in the cryptorchid testis.

  2. Expression and significance of cyclin D1, p27kipl protein in bronchioloalveolar carcinoma

    Institute of Scientific and Technical Information of China (English)

    袁键群; 许敬尧; 张静; 何启才; 祝佳; 盛彩霞

    2004-01-01

    Purpose: To investigate the relationship between expression of cell cycle-related protein cyclin D1, p27kipl and the pathogenesis of bronchioloalveolar carcinoma (BAC) and the value of prediction of prognosis. Methods: Cyclin D1 and p27kipl protein were detected by immunohistochemical En Vision method in 43 BACs. Results: The positivity of cyclin D1 in BAC was 65.1% (28/43), which was significantly higher than that in normal pulmonary tissue (0/13), P0.05), while cyclin D1 expression was found to be negatively correlated with tumor size (P0.05), but was negatively correlated with stromal fibrosis, lymph node metastasis and clinical stage (P<0.05); and positively associated with postoperative survival period (P<0.01). The survival rate of p27kipl positive group was significantly higher than that of p27kipl negative group (P<0.01). No statistically significant correlation was found between cyclin D1 and p27kipl expression. Conclusions: Increased cyclin D1 expression and decreased p27kipl expression are related to the pathogenesis of BAC; decreased p27kipl expression is associated with metastasis progression; immunodetection ofp27kipl is useful for assessment of prognosis.

  3. Coexpression of cyclin D1 and alpha-internexin in oligodendroglial tumors.

    Science.gov (United States)

    Matsumura, Nozomi; Nobusawa, Sumihito; Ikota, Hayato; Hirato, Junko; Hirose, Takanori; Yokoo, Hideaki; Nakazato, Yoichi

    2015-10-01

    Oligodendroglial tumors with neuronal differentiation cases have been reported in recent studies. Oligodendrocyte precursor cells (OPCs) give rise to both oligodendrocytes and neurons; however, little is known about the association between OPCs and oligodendroglial tumors with neuronal differentiation. Previously, we observed the coexpression of cyclin D1, one of the OPC markers, and alpha-internexin (INA) in oligodendroglial tumor cells. INA is a neuronal marker, and has been indicated as an immunohistochemical surrogate of chromosome 1p/19q co-deletion in oligodendroglial tumors. In this study, we investigated the expression status in 83 gliomas immunohistochemically, and found that cyclin D1-positive cells were commonly detected in gliomas. There was no correlation between the cyclin D1 and Ki-67 labeling indices, suggesting an unrecognized role of cyclin D1 other than a cell cycle regulator in gliomas. Cyclin D1/INA double-positive cells were consistently observed in oligodendroglial tumors regardless of histological grade. In 2 cases of oligodendroglioma with neuronal differentiation, the tumor cells of neuronal morphology showed higher expression of INA, suggesting INA expression may be associated with a bona fide neuronal phenotype. The prevalence of cyclin D1/INA double-positive cells is a distinct feature of oligodendroglial tumors. This new characteristic finding may have practical utility in glioma classification. PMID:26233522

  4. Effect of berberine on Cdk9 and cyclin T1 expressions in myocardium of diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Zhou Jiyin; Zhou Shiwen; Tang Jianlin; Xu Ying; Ying Yi

    2008-01-01

    Objective: To investigate the effect of berberine, one of the main alkaloids of Rhizoma coptidis, on myocardial orphology and the expressions of cyclin-dependent kinase 9 (Cdk9) and cyclin T1 protein in the myocardium of type diabetic rats. Methods: Type 2 diabetes mellitus rats were induced by an injection of 35 mg/kg streptozotocin (STZ) nd a high-carbohydrate/high-fat diet for 16 weeks. Diabetic rats were given low-, middle-, high-dose berberine (75,150, 300 mg/kg), fenofibrate (100 mg/kg) and rosiglitazone (4 mg/kg) for another 16 weeks, respectively. The myocardium structure was observed with hematoxylin & eosin (H&E) staining and Cdk9 and cyclin T1 protein expressions were detected by immunohistochemistry. Results: Middle-dose, high-dose berberine improved myocardial hypertrophy and interstitial fibrosis of diabetic rats. Cdk9 and cyclin T1 protein were significantly lower in diabetic myocardium than in control one (P<0.01), and middle-dose, high-dose berberine and fenofibrate obviously increased oth Cdk9 and cyclin T1 expression to near control level (P<0.01). Conclusion: Berberine modulates Cdk9 and cyclin I protein expression in diabetic myocardium which may contribute to ameliorate myocardium damage.

  5. FSH和17β-雌二醇联合作用对Cyclin D1 mRNA和Cyclin E1 mRNA表达的影响%Effect of Combination of FSH and 17β-estradiol on the mRNA Expression of Cyclin D1 and Cyclin E1 in the Cultured Immature Boar Sertoli Cell

    Institute of Scientific and Technical Information of China (English)

    王怡; 张姣姣; 汪勇; 张会琼; 孙思; 王鲜忠; 张家骅

    2013-01-01

    The objective of the study was to identify whether the combination of FSH and 17-betaestradiol regulated the mRNA expression of Cyclin D1 and Cyclin E1 in the cultured immature boar Sertoli cells.Cultured immature boar Sertoli cells were treated with the combination of 17-beta-estradiol (10-9 mol · L-1) and FSH (50 ng · mL-1) and added a variety of different signaling pathway inhibitors.And Real-time PCR was applied to detect the mRNA expression of Cyclin D1 and Cyclin E1.Compared to FSH (50 ng · mL-1) or 17-beta-estradio1 (10-9 mol · L-1)alone,the combination of FSH and 17-beta-estradiol had no significant effect on the mRNA expression of Cyclin D1 mRNA and Cyclin E1 (P>0.05).In addition,Rp-cAMP (cAMP inhibitor),Verapamil (L-type Ca2+ ionic channel inhibitor) or U0126 (ERK1/2 inhibitor) alone had no significant effect on the mRNA expression of Cyclin D1 and Cyclin E1 in comparison to the control group (no FSH or17-beta-estradiol) (P>0.05).However,three inhibitors could reduce the mRNA expression of Cyclin D1 and Cyclin E1 in a dose-dependent way (P<0.05,for all) when compared to the combined FSH (50 ng · mL-1) and 17-beta-estradiol (10-9 mol · L-1).cAMP,Ca2+ and ERK1/2 were involved in the effect of the combination of FSH and 17-beta-estradiol regulating the mRNA expression of Cyclin D1 and Cyclin E1.%为了确定FSH和雌激素联合作用对培养条件下未成熟仔猪睾丸支持细胞中Cyclin D1 mRNA和Cyclin E1 mRNA表达的影响.以培养的仔猪睾丸支持细胞为研究材料,通过添加各种信号通路的抑制剂,应用实时荧光定量PCR检测Cyclin D1 mRNA和Cyclin E1 mRNA的相对表达量.FSH(50ng·mL-1)和17β雌二醇(10-9mol·L-1)联合作用时对Cyclin D1 mRNA和Cyclin E1 mRNA表达的影响与FSH或17β-雌二醇(10-9 mol·L-1)单独作用相比无显著影响(P>0.05);环磷酸腺苷抑制剂(Rp-cAMP)、L-Ca2+离子通道抑制剂(Verapamil)和ERK1/2抑制剂(U0126)单独作用时对Cyclin D1 mRNA和Cyclin E1 mRNA表

  6. Cyclin G2 Promotes Hypoxia- Driven Local Invasion of Glioblastoma by Orchestrating Cytoskeletal Dynamics

    Directory of Open Access Journals (Sweden)

    Atsushi Fujimura

    2013-11-01

    Full Text Available Microenvironmental conditions such as hypoxia potentiate the local invasion of malignant tumors including glioblastomas by modulating signal transduction and protein modification, yet the mechanism by which hypoxia controls cytoskeletal dynamics to promote the local invasion is not well defined. Here, we show that cyclin G2 plays pivotal roles in the cytoskeletal dynamics in hypoxia-driven invasion by glioblastoma cells. Cyclin G2 is a hypoxia-induced and cytoskeleton-associated protein and is required for glioblastoma expansion. Mechanistically, cyclin G2 recruits cortactin to the juxtamembrane through its SH3 domain-binding motif and consequently promotes the restricted tyrosine phosphorylation of cortactin in concert with src. Moreover, cyclin G2 interacts with filamentous actin to facilitate the formation of membrane ruffles. In primary glioblastoma, cyclin G2 is abundantly expressed in severely hypoxic regions such as pseudopalisades, which consist of actively migrating glioma cells. Furthermore, we show the effectiveness of dasatinib against hypoxia-driven, cyclin G2-involved invasion in vitro and in vivo. Our findings elucidate the mechanism of cytoskeletal regulation by which severe hypoxia promotes the local invasion and may provide a therapeutic target in glioblastoma.

  7. Expressions of cyclin D1 and p27kip1 in carcinogenesis of stomach mucosa

    Institute of Scientific and Technical Information of China (English)

    Qunqing Liu; Guiying Zhang

    2008-01-01

    Objective: To evaluate the relationship between the expressions of cyclin D1 and p27kipl in the canceration course of the stomach.Methods: The immunohistochemical staining technique (SP method) was used to detect the expressions of cyclin D1, p27kip1 in chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM), dysplasia (DYS), gastric carcinoma (GCA) biopsy specimens.Results: The positive cyclin D1 expression rates increased with the progressing from CAG→IM→DYS→GCA respectively, and those in IM, DYS and GCA were different from those in CSG, P<0.05, while DYS group was indifferent from GCA group, P>0.05.The positive p27k'pl expression rates decreased with the mucosa progressing from CAG→IM→DYS→GCA.There was a negative correlation between the expression cyclin D1 and p27kip1 (y=-0.53, P=0.000).Conclusion: Expression rates of cyclin D1 in the canceration course of the stomach mucosa trend were increased and those of p27kip1 were decreased; the abnormal expressions of them were found in the early term of the canceration course of the stomach mucosa, and the inverse expression suggests there may be a negative feedback regulatory loop between cyclin D1 and p27kip1.

  8. A critical role for FBXW8 and MAPK in cyclin D1 degradation and cancer cell proliferation.

    Directory of Open Access Journals (Sweden)

    Hiroshi Okabe

    Full Text Available Cyclin D1 regulates G1 progression. Its transcriptional regulation is well understood. However, the mechanism underlying cyclin D1 ubiquitination and its subsequent degradation is not yet clear. We report that cyclin D1 undergoes increased degradation in the cytoplasm during S phase in a variety of cancer cells. This is mediated by phosphorylation at Thr286 through the activity of the Ras/Raf/MEK/ERK cascade and the F-box protein FBXW8, which is an E3 ligase. The majority of FBXW8 is expressed in the cytoplasm during G1 and S phase. In contrast, cyclin D1 accumulates in the nucleus during G1 phase and exits into the cytoplasm in S phase. Increased cyclin D1 degradation is linked to association with FBXW8 in the cytoplasm, and enhanced phosphorylation of cyclin D1 through sustained ERK1/2 signaling. Depletion of FBXW8 caused a significant accumulation of cyclin D1, as well as sequestration of CDK1 in the cytoplasm. This resulted in a severe reduction of cell proliferation. These effects could be rescued by constitutive nuclear expression of cyclin D1-T286A. Thus, FBXW8 plays an essential role in cancer cell proliferation through proteolysis of cyclin D1. It may present new opportunities to develop therapies targeting destruction of cyclin D1 or its regulator E3 ligase selectively.

  9. The multiple roles of cyclin E1 in controlling cell cycle progression and cellular morphology of Trypanosoma brucei.

    Science.gov (United States)

    Gourguechon, Stéphane; Savich, Jason M; Wang, Ching C

    2007-05-11

    Regulation of eukaryotic cell cycle progression requires sequential activation and inactivation of cyclin-dependent kinases. Previous RNA interference (RNAi) experiments in Trypanosoma brucei indicated that cyclin E1, cdc2-related kinase (CRK)1 and CRK2 are involved in regulating G1/S transition, whereas cyclin B2 and CRK3 play a pivotal role in controlling the G2/M checkpoint. To search for potential interactions between the other cyclins and CRKs that may not have been revealed by the RNAi assays, we used the yeast two-hybrid system and an in vitro glutathione-S-transferase pulldown assay and observed interactions between cyclin E1 and CRK1, CRK2 and CRK3. Cyclins E1-E4 are homologues of yeast Pho80 cyclin. But yeast complementation assays indicated that none of them possesses a Pho80-like function. Analysis of cyclin E1+CRK1 and cyclin E1+CRK2 double knockdowns in the procyclic form of T. brucei indicated that the cells were arrested more extensively in the G1 phase beyond the cumulative effect of individual knockdowns. But BrdU incorporation was impaired significantly only in cyclin E1+CRK1-depleted cells, whereas a higher percentage of cyclin E1+CRK2 knockdown cells assumed a grossly elongated posterior end morphology. A double knockdown of cyclin E1 and CRK3 arrested cells in G2/M much more efficiently than if only CRK3 was depleted. Taken together, these data suggest multiple functions of cyclin E1: it forms a complex with CRK1 in promoting G1/S phase transition; it forms a complex with CRK2 in controlling the posterior morphogenesis during G1/S transition; and it forms a complex with CRK3 in promoting passage across the G2/M checkpoint in the trypanosome. PMID:17376478

  10. Repair in schizosaccharomyces pombe as measured by recovery from caffeine enhancement of radiation-induced lethality

    International Nuclear Information System (INIS)

    Inhibition of DNA repair by caffeine is manifested in Schizosaccharomyces pombe wild-type cells as an enhancement of UV- or γ-irradiation-induced lethality. The progress of DNA repair processes involving one or more caffeine-sensitive steps may be conveniently followed by measuring the concomitant decrease of this lethal enhancement effect. By measuring, during post-irradiation incubation, the ability of cells to overcome susceptibility to repair inhibition by caffeine, we have determined the time course and requirements for repair in S. pombe. Recovery began immediately and took 150-200 min after γ-irradiation and more than 500 min after UV-irradiation, for exposures which gave about 10% survival in the absence of caffeine. An incubation medium capable of supporting growth was required for caffeine-sensitive repair; no recovery occurred under liquid holding conditions. Survival curves after various recovery times indicated that a logarithmic phase cell population was homogeneous with respect to caffeine-sensitive repair of both UV- and γ-ray-induced damage. Recovery from caffeine inhibition was compared for cells of different physiological states (logarithmic and stationary phase); although the importance of the physiological state was not the same for the two types of radiation, recovery was found to occur more rapidly in the more radiation-resistant state, in each case. (orig.)

  11. False-negative dipyridamole-thallium-201 myocardial imaging after caffeine infusion

    International Nuclear Information System (INIS)

    The vasodilator effect of intravenously administered dipyridamole may be caused by an increase in endogenous plasma adenosine levels. The authors evaluated the effect of caffeine, an adenosine receptor antagonist, on the diagnostic results of dipyridamole-201Tl myocardial imaging in eight patients with coronary artery disease. Caffeine infusion significantly attenuated the dipyridamole-induced fall in blood pressure and the accompanied increase in heart rate. The infusion of dipyridamole alone resulted in chest pain and ST-segment depressions on the electrocardiogram in four patients, whereas none of these problems occurred when the tests were repeated after caffeine. In six of eight patients, caffeine was responsible for false-negative dipyridamole-201Tl tests. Semiquantitive scores of the dipyridamole-induced 201Tl perfusion defects were decreased by caffeine from 9.0 ± 0.9 to 2.0 ± 1.1 points (p less than 0.05). Computerized analysis revealed a caffeine-mediated reduction in the percent reversibility of the images from 46% ± 16% to 6% ± 10% (p less than 0.05). They conclude that the use of caffeinated products prior to dipyridamole-201Tl testing may be responsible for false-negative findings

  12. Protein synthetic requirements for caffeine amelioration of radiation-induced G/sub 2/-arrest

    International Nuclear Information System (INIS)

    Irradiated cells are arrested in G/sub 2/ (transition point [TP] = 32 min before cell selection in mitosis). Irradiated cells do not recover from G/sub 2/ arrest in the presence of cycloheximide (CHM) indicating dependence of recovery on protein synthesis. Irradiated cells in the presence of caffeine progress to mitosis without arrest. The authors investigate whether irradiated cells in the presence of caffeine require protein synthesis to progress to mitosis. Mitotic cell selection was used to monitor the progression of irradiated CHO cells (150 rad) during exposure to 5 mM caffeine and/or 50 μg/ml CHM. Protein synthesis inhibition was confirmed using /sup 3/H-leucine incorporation. Cells exposed to CHM alone are arrested in G/sub 2/ (TP=49 min), thus cells beyond this point have synthesized all proteins necessary for entry into mitosis. In the presence of caffeine, unirradiated cells exposed to CHM are not arrested at all in G/sub 2/, instead arrest occurs near the S/G/sub 2/ boundary (TP=95 min) indicating that caffeine alleviates the dependence of G/sub 2/ cell progression on protein synthesis. However, irradiated cells exposed to both caffeine and CHM are only able to progress to mitosis if beyond the CHM-TP. Irradiated cells in the presence of caffeine thus behave as untreated cells and require protein synthesis for progression to mitosis when prior to the CHM-TP

  13. What can isolated skeletal muscle experiments tell us about the effects of caffeine on exercise performance?

    Science.gov (United States)

    Tallis, Jason; Duncan, Michael J; James, Rob S

    2015-08-01

    Caffeine is an increasingly popular nutritional supplement due to the legal, significant improvements in sporting performance that it has been documented to elicit, with minimal side effects. Therefore, the effects of caffeine on human performance continue to be a popular area of research as we strive to improve our understanding of this drug and make more precise recommendations for its use in sport. Although variations in exercise intensity seems to affect its ergogenic benefits, it is largely thought that caffeine can induce significant improvements in endurance, power and strength-based activities. There are a number of limitations to testing caffeine-induced effects on human performance that can be better controlled when investigating its effects on isolated muscles under in vitro conditions. The hydrophobic nature of caffeine results in a post-digestion distribution to all tissues of the body making it difficult to accurately quantify its key mechanism of action. This review considers the contribution of evidence from isolated muscle studies to our understating of the direct effects of caffeine on muscle during human performance. The body of in vitro evidence presented suggests that caffeine can directly potentiate skeletal muscle force, work and power, which may be important contributors to the performance-enhancing effects seen in humans. PMID:25988508

  14. Non specific drug distribution in an autopsy case report of fatal caffeine intoxication.

    Science.gov (United States)

    Ishikawa, Takaki; Yuasa, Isao; Endoh, Minoru

    2015-11-01

    Caffeine has long been recognized as an addictive substance that causes autonomic nerve effect, and is known to increase catecholamine secretion from the adrenal glands. In recent years, the risk of ingesting toxic levels of caffeine has increased because of the easy availability of analgesics, CNS (Central Nervous System) stimulant medicine and dietary supplements at shops, health stores and through online purchases. We report the death of a young female resulting from the ingestion for suicide of an online purchased sleepiness-preventing medicine containing caffeine. The autopsy findings included pulmonary edema and congestion plus cutaneous emphysema. The stomach contents included a dark-brown viscous fluid without tablet or food residue. Toxicological examination revealed the presence of caffeine in the right heart blood (154.2 μg/mL) and stomach contents (197.5 μg/mL) (lethal blood level, >80 μg/mL). The highest caffeine content was in the bile (852.3 μg/mL). Biochemical findings showed that catecholamine concentration in the peripheral blood in the iliac vein was elevated. Immunostaining of catecholamine was weak in the adrenal medulla. We recommend highlighting the toxicity risk of ingesting substances with a high caffeine concentration, and we propose that caffeine concentrations should be included in the comprehensive routine forensic toxicological tests for all cases. PMID:26594005

  15. Variations in caffeine and chlorogenic acid contents of coffees: what are we drinking?

    Science.gov (United States)

    Ludwig, Iziar A; Mena, Pedro; Calani, Luca; Cid, Concepción; Del Rio, Daniele; Lean, Michael E J; Crozier, Alan

    2014-08-01

    The effect of roasting of coffee beans and the extraction of ground coffee with different volumes of hot pressurised water on the caffeine and the total caffeoylquinic acids (CQAs) content of the resultant beverages was investigated. While caffeine was stable higher roasting temperatures resulted in a loss of CQAs so that the caffeine/CQA ratio was a good marker of the degree of roasting. The caffeine and CQA content and volume was determined for 104 espresso coffees obtained from coffee shops in Scotland, Italy and Spain, limited numbers of cappuccino coffees from commercial outlets and several instant coffees. The caffeine content ranged from 48-317 mg per serving and CQAs from 6-188 mg. It is evident that the ingestion of 200 mg of caffeine per day can be readily and unwittingly exceeded by regular coffee drinkers. This is the upper limit of caffeine intake from all sources recommended by US and UK health agencies for pregnant women. In view of the variable volume of serving sizes, it is also clear that the term "one cup of coffee" is not a reproducible measurement for consumption, yet it is the prevailing unit used in epidemiology to assess coffee consumption and to link the potential effects of the beverage and its components on the outcome of diseases. More accurate measurement of the intake of coffee and its potentially bioactive components are required if epidemiological studies are to produce more reliable information. PMID:25014672

  16. Effects of caffeine on the electrophysiological, cognitive and motor responses of the central nervous system

    Directory of Open Access Journals (Sweden)

    Deslandes A.C.

    2005-01-01

    Full Text Available Caffeine is the most consumed psychoactive substance in the world. The effects of caffeine have been studied using cognitive and motor measures, quantitative electroencephalography (qEEG and event-related potentials. However, these methods are not usually employed in combination, a fact that impairs the interpretation of the results. The objective of the present study was to analyze changes in electrophysiological, cognitive and motor variables with the ingestion of caffeine, and to relate central to peripheral responses. For this purpose we recorded event-related potentials and eyes-closed, resting EEG, applied the Stroop test, and measured reaction time. Fifteen volunteers took caffeine (400 mg or placebo in a randomized, crossover, double-blind design. A significant reduction of alpha absolute power over the entire scalp and of P300 latency at the Fz electrode were observed after caffeine ingestion. These results are consistent with a stimulatory effect of caffeine, although there was no change in the attention (Stroop test or in reaction time. The qEEG seems to be the most sensitive index of the changes produced by caffeine in the central nervous system since it proved to be capable of detecting changes that were not evident in the tests of cognitive or motor performance.

  17. Computational study of the binding modes of caffeine to the adenosine A2A receptor.

    Science.gov (United States)

    Liu, Yuli; Burger, Steven K; Ayers, Paul W; Vöhringer-Martinez, Esteban

    2011-12-01

    Using the recently solved crystal structure of the human adenosine A(2A) receptor, we applied MM/PBSA to compare the binding modes of caffeine with those of the high-affinity selective antagonist ZM241385. MD simulations were performed in the environment of the lipid membrane bilayer. Four low-energy binding modes of caffeine-A(2A) were found, all of which had similar energies. Assuming an equal contribution of each binding mode of caffeine, the computed binding free energy difference between caffeine and ZM241385 is -2.4 kcal/mol, which compares favorably with the experimental value, -3.6 kcal/mol. The configurational entropy contribution of -0.9 kcal/mol from multiple binding modes of caffeine helps explain how a small molecule like caffeine can compete with a significantly larger molecule, ZM241385, which can form many more interactions with the receptor. We also performed residue-wise energy decomposition and found that Phe168, Leu249, and Ile274 contribute most significantly to the binding modes of caffeine and ZM241385. PMID:21970461

  18. Effects of coffee/caffeine on brain health and disease: What should I tell my patients?

    Science.gov (United States)

    Nehlig, Astrid

    2016-04-01

    Over the last decade, Food Regulation Authorities have concluded that coffee/caffeine consumption is not harmful if consumed at levels of 200 mg in one sitting (around 2½ cups of coffee) or 400 mg daily (around 5 cups of coffee). In addition, caffeine has many positive actions on the brain. It can increase alertness and well-being, help concentration, improve mood and limit depression. Caffeine may disturb sleep, but only in sensitive individuals. It may raise anxiety in a small subset of particularly sensitive people. Caffeine does not seem to lead to dependence, although a minority of people experience withdrawal symptoms. Caffeine can potentiate the effect of regular analgesic drugs in headache and migraine. Lifelong coffee/caffeine consumption has been associated with prevention of cognitive decline, and reduced risk of developing stroke, Parkinson's disease and Alzheimer's disease. Its consumption does not seem to influence seizure occurrence. Thus, daily coffee and caffeine intake can be part of a healthy balanced diet; its consumption does not need to be stopped in elderly people. PMID:26677204

  19. Caffeine consumption and self-assessed stress, anxiety, and depression in secondary school children.

    Science.gov (United States)

    Richards, Gareth; Smith, Andrew

    2015-12-01

    Previous research suggests that effects of caffeine on behaviour are positive unless one is investigating sensitive groups or ingestion of large amounts. Children are a potentially sensitive subgroup, and especially so considering the high levels of caffeine currently found in energy drinks. The present study used data from the Cornish Academies Project to investigate associations between caffeine (both its total consumption, and that derived separately from energy drinks, cola, tea, and coffee) and single-item measures of stress, anxiety, and depression, in a large cohort of secondary school children from the South West of England. After adjusting for additional dietary, demographic, and lifestyle covariates, positive associations between total weekly caffeine intake and anxiety and depression remained significant, and the effects differed between males and females. Initially, effects were also observed in relation to caffeine consumed specifically from coffee. However, coffee was found to be the major contributor to high overall caffeine intake, providing explanation as to why effects relating to this source were also apparent. Findings from the current study increase our knowledge regarding associations between caffeine intake and stress, anxiety, and depression in secondary school children, though the cross-sectional nature of the research made it impossible to infer causality. PMID:26508718

  20. Effects of coffee and caffeine on bladder dysfunction in streptozotocin-induced diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Chao-ran YI; Zhong-qing WEI; Xiang-lei DENG; Ze-yu SUN; Xing-rang LI; Cheng-gong TIAN

    2006-01-01

    Aim: To explore the effects and mechanisms of caffeine and coffee on bladder dysfunction in streptozotocin-induced diabetic rats. Methods: Sprague-Dawley male rats were divided randomly into 4 groups: control, diabetes mellitus (DM), DM with coffee treatment, and DM with caffeine treatment. The diabetic rat was induced by intraperitoneal injection of streptozotocin (60 mg/kg). After 7 weeks of treatment with coffee and caffeine, cystometrogram, contractile responses to electrical field stimulation (EFS) and acetylcholine (ACh), and cyclic AMP (cAMP) concentration of the bladder body and base were measured. Results: The bladder weight, volume threshold for micturition and post-void residual volume (PVR) in the diabetic rats were significantly higher compared to those in the control animals. Coffee or caffeine treatment significantly reduced the bladder weight, bladder capacity and PVR in the diabetic rats. DM caused significant decreases in cAMP concentration of the bladder and coffee and caffeine caused upregulation of cAMP content in the diabetic bladder. In addition, coffee and caffeine tended to normalize the altered detrusor contractile responses to EFS and ACh in the diabetic rats. Conclusion: These results indicate that caffeine and coffee may have beneficial effects on bladder dysfunction in the early stage of diabetes by increasing cAMP content in the lower urinary tract, recovering the micturition reflex and improving the detrusor contractility.

  1. Caffeine inheritance in interspecific hybrids of Coffea arabica x Coffea canephora (Gentianales, Rubiaceae

    Directory of Open Access Journals (Sweden)

    Regina H.G. Priolli

    2008-01-01

    Full Text Available Caffeine inheritance was investigated in F2 and BC1F1 generations between Coffea arabica var. Bourbon Vermelho (BV and Coffea canephora var. Robusta 4x (R4x. The caffeine content of seeds and leaves was determined during 2004 and 2005. Microsatellite loci-markers were used to deduce the meiotic pattern of chromosome pairing of tetraploid interspecific hybrids. Genetic analysis indicated that caffeine content in seeds was quantitatively inherited and controlled by genes with additive effects. The estimates of broad-sense heritability of caffeine content in seeds were high for both generations. In coffee leaves, the caffeine content (BSH from the same populations showed transgressive segregants with enhanced levels and high BSH. Segregation of loci-markers in BC1F1 populations showed that the ratios of the gametes genotype did not differ significantly from those expected assuming random associations and tetrasomic inheritance. The results confirm the existence of distinct mechanisms controlling the caffeine content in seeds and leaves, the gene exchange between the C. arabica BV and C. canephora R4x genomes and favorable conditions for improving caffeine content in this coffee population.

  2. Nuclear suppression

    International Nuclear Information System (INIS)

    This article draws attention to a number of cases where it seems that scientists and technologists have been penalized in various ways for having views opposed to those of the nuclear industry. Attempts to encourage the general public to understand nuclear issues have also been discouraged, nuclear knowledge being kept as the preserve of the experts and policy makers, especially in the military applications of nuclear power. It may be that publications are suppressed or careers are destroyed. One example highlighted in the article is of Dhirendra Shama, a critic of India's nuclear policy, who was suddenly transferred from the Centre of Studies in Science Policy at his University to the School of Languages. Other examples are given from other countries - Australia, Britain, Canada, Federal Republic of Germany, India, Japan, New Zealand, Soviet Union, Sweden and the United States of America. The main 'crime' of those victimised is not in having critical views, but in alerting the general public to those critical view and ideas. (UK)

  3. Caffeine content of prepackaged national-brand and private-label carbonated beverages.

    Science.gov (United States)

    Chou, K-H; Bell, L N

    2007-08-01

    Caffeine is a well-known stimulant that is added as an ingredient to various carbonated soft drinks. Due to its stimulatory and other physiological effects, individuals desire to know the exact amount of caffeine consumed from these beverages. This study analyzed the caffeine contents of 56 national-brand and 75 private-label store-brand carbonated beverages using high-performance liquid chromatography. Caffeine contents ranged from 4.9 mg/12 oz (IGA Cola) to 74 mg/12 oz (Vault Zero). Some of the more common national-brand carbonated beverages analyzed in this study with their caffeine contents were Coca-Cola (33.9 mg/12 oz), Diet Coke (46.3 mg/12 oz), Pepsi (38.9 mg/12 oz), Diet Pepsi (36.7 mg/12 oz), Dr Pepper (42.6 mg/12 oz), Diet Dr Pepper (44.1 mg/12 oz), Mountain Dew (54.8 mg/12 oz), and Diet Mountain Dew (55.2 mg/12 oz). The Wal-Mart store-brand beverages with their caffeine contents were Sam's Cola (12.7 mg/12 oz), Sam's Diet Cola (13.3 mg/12 oz), Dr Thunder (30.6 mg/12 oz), Diet Dr Thunder (29.9 mg/12 oz), and Mountain Lightning (46.5 mg/12 oz). Beverages from 14 other stores were also analyzed. Most store-brand carbonated beverages were found to contain less caffeine than their national-brand counterparts. The wide range of caffeine contents in carbonated beverages indicates that consumers would benefit from the placement of caffeine values on food labels. PMID:17995675

  4. Effects of caffeine on locomotor activity of horses: determination of the no-effect threshold.

    Science.gov (United States)

    Queiroz-Neto, A; Zamur, G; Carregaro, A B; Mataqueiro, M I; Salvadori, M C; Azevedo, C P; Harkins, J D; Tobin, T

    2001-01-01

    Caffeine is the legal stimulant consumed most extensively by the human world population and may be found eventually in the urine and/or blood of race horses. The fact that caffeine is in foods led us to determine the highest no-effect dose (HNED) of caffeine on the spontaneous locomotor activity of horses and then to quantify this substance in urine until it disappeared. We built two behavioural stalls equipped with juxtaposed photoelectric sensors that emit infrared beams that divide the stall into nine sectors in a 'tic-tac-toe' fashion. Each time a beam was interrupted by a leg of the horse, a pulse was generated; the pulses were counted at 5-min intervals and stored by a microcomputer. Environmental effects were minimized by installing exhaust fans producing white noise that obscured outside sounds. One-way observation windows prevented the animals from seeing outside. The sensors were turned on 45 min before drug administration (saline control or caffeine). The animals were observed for up to 8 h after i.v. administration of 2.0, 2.5, 3.0 or 5.0 mg caffeine kg(-1). The HNED of caffeine for stimulation of the spontaneous locomotor activity of horses was 2.0 mg kg(-1). The quantification of caffeine in urine and plasma samples was done by gradient HPLC with UV detection. The no-effect threshold should not be greater than 2.0 microg caffeine ml(-1) plasma or 5.0 microg caffeine ml(-1) urine. PMID:11404835

  5. Clastogenic interactions of #betta# radiation and caffeine in human peripheral blood cultures

    International Nuclear Information System (INIS)

    In order to determine whether the micronucleus test could be used as a rapid assay for mutagenic interactions, we studied the effect of 50-800 R of #betta# radiation in combination with 10-6-10-3 M caffeine in cultured human lymphocytes, with two treatment protocols. In one protocol (T0), whole blood was irradiated with 50-800 R of #betta# radiation, then stimulated with PHA and cultured for 72, 96 or 120 h in the presence or absence of caffeine. Under these conditions, #betta# radiation produced micronuclei in proportion to dose but post-treatment with 1 mM caffein significantly decreased the number of micronuclei observed. The effect of caffeine was greater with the higher radiation doses and at earlier fixation times. Caffeine also decreased the mitotic index which, in turn, decreased the number of micronuclei observed; but caffeine post-treatment still had a significant effect even after mitotic activity was taken into account. In a second protocol (T48), PHA-stimulated (actively cycling) cultures were irradiated 48 h after innoculation, then treated with caffeine, and fixed at 72 h post-innoculation (PI). With this protocol #betta# radiation produced more micronuclei than at T0; this suggests that many of the cells damaged at T0 are either lost or repaired. At T48 1 mM caffeine significantly increased the number of micronuclei observed after #betta# radiation at all doses except 50 and 200 R. The mitotic index increased after 400-600 R, but only in the absence of caffeine. (orig./AJ)

  6. The Effects of Caffeine on Vertical Jump Height and Execution in Collegiate Athletes.

    Science.gov (United States)

    Bloms, Lucas P; Fitzgerald, John S; Short, Martin W; Whitehead, James R

    2016-07-01

    Bloms, LP, Fitzgerald, JS, Short, MW, and Whitehead, JR. The effects of caffeine on vertical jump height and execution in collegiate athletes. J Strength Cond Res 30(7): 1855-1861, 2016-Caffeine ingestion elicits a variety of physiological effects that may be beneficial to maximal-intensity exercise performance, although its effectiveness and physical mechanism of action enhancing ballistic task performance are unclear. The purpose of this study was to examine the effects of caffeine ingestion on vertical jump height and jump execution in Division I collegiate athletes. The study used a single-blind, randomized, crossover design. Athletes (n = 25) consumed either caffeine (5 mg·kg) or placebo. After a 60-minute waiting period, athletes performed 3 squat jumps (SJ) and 3 countermovement jumps (CMJ) while standing on a force platform. Jump height and execution variables were calculated from mechanography data. In comparison with placebo, caffeine increased SJ height (32.8 ± 6.2 vs. 34.5 ± 6.7 cm; p = 0.001) and CMJ height (36.4 ± 6.9 vs. 37.9 ± 7.4 cm; p = 0.001). Peak force (p = 0.032) and average rate of force development (p = 0.037) were increased during the CMJ in the caffeine trail compared with the control. Time to half peak force was the only execution variable improved with caffeine (p = 0.019) during the SJ. It seems that caffeine affects both height and execution of jumping. Our data indicate that the physical mechanism of jump enhancement is increased peak force production or rate of force development during jumping depending on technique. The physical mechanism of jump enhancement suggests that the ergogenic effects of caffeine may transfer to other ballistic tasks involving the lower-body musculature in collegiate athletes. PMID:26626028

  7. Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

    International Nuclear Information System (INIS)

    Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine

  8. Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Hanwen [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Deng, Zixin; Liu, Lian; Shen, Lang; Kou, Hao; He, Zheng [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, Jie; Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Ma, Lu [Department of Epidemiology and Health Statistics, Public Health School of Wuhan University, Wuhan 430071 (China); Chen, Liaobin, E-mail: lbchen@whu.edu.cn [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2014-02-01

    Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine

  9. Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial.

    Science.gov (United States)

    MacKenzie, Todd; Comi, Richard; Sluss, Patrick; Keisari, Ronit; Manwar, Simone; Kim, Janice; Larson, Robin; Baron, John A

    2007-12-01

    In short-term studies, caffeine has been shown to increase insulin levels, reduce insulin sensitivity, and increase cortisol levels. However, epidemiological studies have indicated that long-term consumption of beverages containing caffeine such as coffee and green tea is associated with a reduced risk of type 2 diabetes mellitus. There is a paucity of randomized studies addressing the metabolic and hormonal effects of consuming caffeine over periods of more than 1 day. We evaluated the effect of oral intake of 200 mg of caffeine taken twice a day for 7 days on glucose metabolism, as well as on serum cortisol, dehydroepiandrosterone (DHEA), and androstenedione, and on nighttime salivary melatonin. A double-blind, randomized, placebo-controlled crossover study with periods of 7 days and washouts of 5 days comparing caffeine with placebo capsules was conducted. Participants were 16 healthy adults aged 18 to 22 years with a history of caffeine consumption. Blood samples from each subject were assayed for glucose, insulin, serum cortisol, DHEA, and androstenedione on the eighth day of each period after an overnight fast. Nighttime salivary melatonin was also measured. Insulin levels were significantly higher (by 1.80 microU/mL; 95% confidence interval, 0.33-3.28) after caffeine intake than after placebo. The homeostasis model assessment index of insulin sensitivity was reduced by 35% (95% confidence interval, 7%-62%) by caffeine. There were no differences in glucose, DHEA, androstenedione, and melatonin between treatment periods. This study provides evidence that daily caffeine intake reduces insulin sensitivity; the effect persists for at least a week and is evident up to 12 hours after administration. PMID:17998023

  10. Serum caffeine levels after 24 hours of caffeine abstention: observations on clinical patients undergoing myocardial perfusion imaging with dipyridamole or adenosine

    International Nuclear Information System (INIS)

    Although caffeine attenuates the vasodilatation produced by dipyridamole and adenosine, and is therefore contraindicated when these agents are used for myocardial perfusion scintigraphy, caffeine levels in clinical patients undergoing standard imaging protocols have not been studied. Eighty-six patients undergoing clinically indicated intravenous dipyridamole (n=75) or adenosine (n=11) thallium-201 myocardial perfusion scintigraphy, all of whom reported abstention from products containing caffeine for 24 h, were studied prospectively. Blood samples were drawn prior to initiation of the pharmacologic infusion, and serum caffeine levels were determined using an enzyme immunoassay technique. Results of these determinations were correlated with maximum pulse and blood pressure changes measured during and immediately after the stressor infusion, and thallium imaging findings. Detectable caffeine levels were found in 34 patients (40%), ranging from 0.1 to 5.0 mg/l. There was no significant difference in mean systolic blood pressure decrease or mean pulse increase between patients with caffeine levels > 1.0 mg/l (20.4 ± 18.2 mmHg, 11.0 ± 8.9 BPM; n=5) and those with lower (0.1 to 0.9 mg/l) (15.4 ± 9.5 mmHg, 14.4 ± 8.2 BPM; n=29) or no detectable caffeine levels (18.0 ± 11.5 mmHg, 16.6 ± 10.1 BPM; n=52). Redistribution on thallium imaging was also identified with a similar frequency in these three groups (2/5, 40%; 8/29, 28%; 22/52, 42% respectively). (orig.)

  11. Ultra-violet Spectrophotometric Determination of Caffeine in Soft and Energy Drinks Available in Yenagoa, Nigeria

    OpenAIRE

    Amos-Tautua; W. Bamidele Martin; E.R.E. Diepreye

    2014-01-01

    This study was carried out to determine the pH and levels of caffeine in eight brands of carbonated and energy drinks available in local market in Yenagoa, Nigeria. Quantitative analysis of caffeine was performed by a simple and fast standard UV spectrophotometric method, using carbon tetrachloride as the extracting solvent. Results showed that the pH of the beverages were slightly acidic ranging from 5.92-6.44. The minimum caffeine level was observed in the carbonated soft drink Coca Cola (4...

  12. CHROMATOGRAPHIC DETERMINATION OF CAFFEINE CONTENTS IN SOFT AND ENERGY DRINKS AVAILABLE ON THE ROMANIAN MARKET

    OpenAIRE

    Mira Elena Ionică; Ion Trandafir; Violeta Nour

    2010-01-01

    Caffeine is a stimulant that is commonly found in many foods and drinks that we consume. Concerns exist about the potential adverse health effects of high consumption of dietary caffeine, especially in children and pregnant women. Recommended caffeine intakes corresponding to no adverse health effects have been suggested recently for healthy adults (400 – 450 mg/day), for women contemplating pregnancy (300 mg/day), and for young children age 4 – 6 years (45 mg/day). Different brands of soft a...

  13. Likely Additive Ergogenic Effects of Combined Preexercise Dietary Nitrate and Caffeine Ingestion in Trained Cyclists

    OpenAIRE

    Handzlik, Michal K.; Gleeson, Michael

    2013-01-01

    Aims. To evaluate the possible additive effects of beetroot juice plus caffeine on exercise performance. Methods. In a randomized, double-blinded study design, fourteen healthy well-trained men aged 22 ± 3 years performed four trials on different occasions following preexercise ingestion of placebo (PLA), PLA plus 5 mg/kg caffeine (PLA+C), beetroot juice providing 8 mmol of nitrate (BR), and beetroot juice plus caffeine (BR+C). Participants cycled at 60% maximal oxygen uptake ( V ˙ O 2 max) f...

  14. Placental passage of benzoic acid, caffeine, and glyphosate in an ex vivo human perfusion system

    DEFF Research Database (Denmark)

    Mose, Tina; Kjaerstad, Mia Birkhoej; Mathiesen, Line;

    2008-01-01

    given group of compounds. Benzoic acid, caffeine, and glyphosate were chosen as model compounds because they are small molecules with large differences in physiochemical properties. Caffeine crossed the placenta by passive diffusion. The initial transfer rate of benzoic acid was more limited in the...... first part of the perfusion compared to caffeine, but reached the same steady-state level by the end of perfusion. The transfer of glyphosate was restricted throughout perfusion, with a lower permeation rate, and only around 15% glyphosate in maternal circulation crossed to the fetal circulation during...

  15. Electrospun polyvinyl-alcohol nanofibers as oral fast-dissolving delivery system of caffeine and riboflavin

    DEFF Research Database (Denmark)

    Li, Xiaoqiang; Kanjwal, Muzafar Ahmed; Lin, Lin;

    2013-01-01

    Fast-dissolving drug delivery systems were prepared by electrospinning using polyvinyl alcohol (PVA) as the filament-forming polymer and drug carrier. Caffeine and riboflavin were used as the model drugs. Scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) and X-ray diffraction...... PVA/caffeine and PVA/riboflavin nanofibrous mats had almost the same dissolution time (about 1.5 s) and wetting time (about 4.5 s). The release measurements indicated that drugs can be released in a burst manner (caffeine to an extent of 100% and riboflavin to an extent of 40% within 60 s) from the...

  16. Caffeine intake improves intense intermittent exercise performance and reduces muscle interstitial potassium accumulation

    DEFF Research Database (Denmark)

    Mohr, Magni; Nielsen, Jens Jung; Bangsbo, Jens

    2011-01-01

    The effect of oral caffeine ingestion on intense intermittent exercise performance and muscle interstitial ion concentrations was examined. The study consists of two studies (S1 and S2). In S1 twelve subjects completed the Yo-Yo intermittent recovery level 2 (Yo-Yo IR2) test with prior caffeine (6...... mg/kg b.w.; CAF) or placebo (PLA) intake. In S2 six subjects performed one low intense (20 W) and three intense (50 W) 3-min (separated by 5 min) one-legged knee-extension exercise bouts with (CAF) and without (CON) prior caffeine supplementation for determination of muscle interstitial K(+) and Na...

  17. HPLC determination of caffeine and theophylline in Paullinia cupana Kunth (guarana) and Cola spp. samples.

    Science.gov (United States)

    Belliardo, F; Martelli, A; Valle, M G

    1985-05-01

    A reversed-phase high-performance liquid-chromatographic method for the determination of caffeine and theophylline in commercial guarana samples (drug obtained from the seeds of Paulinia cupana Kunth, Sapindaceae of the Amazon Region) and in Cola spp. samples is described and discussed. The methodology developed is simple and rapid with a minimum of samples preparation required. A comparison of five different techniques for the extraction of caffeine and theophylline is discussed. Furthermore the quantitative determination of caffeine and theophylline in five samples of Brasilian guarana, in two samples of dietetic products containing guarana, in two samples of Cola extract and in three of Cola seed powder are reported. PMID:4013524

  18. Caffeine potentiates the lethality of tumour necrosis factor in cancer cells.

    OpenAIRE

    Belizario, J. E.; Tilly, J L; Sherwood, S W

    1993-01-01

    In this study we have investigated the interaction of caffeine, a prototypic methylxanthine, and TNF on the induction of cell death in mouse and human cell lines during progression from G1 to successive phases of the cell cycle. Exposure of cells to TNF (0.1-100 ng ml-1) as single agent for 48 h caused low or no lethality. The rates of cell death increased significantly when cells cultured with TNF for 24 h were exposed to caffeine (2.5-20 mM). The magnitude of the enhancement by caffeine was...

  19. Analysis of caffeine and heavy metal contents in branded and unbranded tea available in Pakistan

    International Nuclear Information System (INIS)

    In the investigation of caffeine and heavy metal contents in four branded and six unbranded tea samples collected from local markets of Lahore, Faisalabad and Peshawar, the amount of caffeine and heavy metals in all the branded tea samples were in agreement with the international standards. In unbranded tea samples, though the amount of caffeine was within standard limits but two of the samples collected from Peshawar had high concentrations of lead being, 13.69 and 15.78 mg/kg, consumption of which can lead to serious problems. (author)

  20. Novel, Highly Specific N-Demethylases Enable Bacteria To Live on Caffeine and Related Purine Alkaloids

    OpenAIRE

    Summers, Ryan M.; Louie, Tai Man; Yu, Chi-Li; Gakhar, Lokesh; Louie, Kailin C.; Subramanian, Mani

    2012-01-01

    The molecular basis for the ability of bacteria to live on caffeine as a sole carbon and nitrogen source is unknown. Pseudomonas putida CBB5, which grows on several purine alkaloids, metabolizes caffeine and related methylxanthines via sequential N-demethylation to xanthine. Metabolism of caffeine by CBB5 was previously attributed to one broad-specificity methylxanthine N-demethylase composed of two subunits, NdmA and NdmB. Here, we report that NdmA and NdmB are actually two independent Riesk...

  1. Low doses of caffeine reduce heart rate during submaximal cycle ergometry

    OpenAIRE

    Wetter Thomas J; McClaran Steven R

    2007-01-01

    Abstract Background The purpose of this study was to examine the cardiovascular effects of two low-levels of caffeine ingestion in non habitual caffeine users at various submaximal and maximal exercise intensities. Methods Nine male subjects (19–25 yr; 83.3 ± 3.1 kg; 184 ± 2 cm), underwent three testing sessions administered in a randomized and double-blind fashion. During each session, subjects were provided 4 oz of water and a gelatin capsule containing a placebo, 1.5 mg/kg caffeine, or 3.0...

  2. Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry

    DEFF Research Database (Denmark)

    Hein, Jamin B; Nilsson, Jakob

    2016-01-01

    window of the cell cycle, if any, is unknown. Here we show that cyclin A2-Cdk2 binds and phosphorylates Cdc20 in interphase and this inhibits APC/C-Cdc20 activity. Preventing Cdc20 phosphorylation results in pre-mature activation of the APC/C-Cdc20 and several substrates, including cyclin B1 and A2, are...... destabilized which lengthens G2 and slows mitotic entry. Expressing non-degradable cyclin A2 but not cyclin B1 restores mitotic entry in these cells. We have thus uncovered a novel positive feedback loop centred on cyclin A2-Cdk2 inhibition of interphase APC/C-Cdc20 to allow further cyclin A2 accumulation and...

  3. Cyc17, a meiosis-specific cyclin, is essential for anaphase initiation and chromosome segregation in Tetrahymena thermophila.

    Science.gov (United States)

    Yan, Guan-Xiong; Dang, Huai; Tian, Miao; Zhang, Jing; Shodhan, Anura; Ning, Ying-Zhi; Xiong, Jie; Miao, Wei

    2016-07-17

    Although the role of cyclins in controlling nuclear division is well established, their function in ciliate meiosis remains unknown. In ciliates, the cyclin family has undergone massive expansion which suggests that diverse cell cycle systems exist, and this warrants further investigation. A screen for cyclins in the model ciliate Tetrahymena thermophila showed that there are 34 cyclins in this organism. Only 1 cyclin, Cyc17, contains the complete cyclin core and is specifically expressed during meiosis. Deletion of CYC17 led to meiotic arrest at the diakinesis-like metaphase I stage. Expression of genes involved in DNA metabolism and chromosome organization (chromatin remodeling and basic chromosomal structure) was repressed in cyc17 knockout matings. Further investigation suggested that Cyc17 is involved in regulating spindle pole attachment, and is thus essential for chromosome segregation at meiosis. These findings suggest a simple model in which chromosome segregation is influenced by Cyc17. PMID:27192402

  4. Characteristics of Cyclin B and its potential role in regulating oogenesis in the red claw crayfish (Cherax quadricarinatus).

    Science.gov (United States)

    Wang, L M; Lv, W W; Zuo, D; Dong, Z J; Zhao, Y L

    2015-01-01

    Cyclin B is a regulatory subunit of maturation-promoting factor (MPF), which has a key role in the induction of meiotic maturation of oocytes. MPF has been studied in a wide variety of animal species; however, its expression in crustaceans is poorly characterized. In this study, the complete cDNA sequence of Cyclin B was cloned from the red claw crayfish, Cherax quadricarinatus, and its spatiotemporal expression profiles were analyzed. Cyclin B cDNA (1779 bp) encoded a 401 amino acid protein with a calculated molecular weight of 45.1 kDa. Quantitative real-time PCR demonstrated that Cyclin B mRNA was expressed mainly in the ovarian tissue and that the expression decreased as the ovaries developed. Immunofluorescence analysis revealed that the Cyclin B protein relocated from the cytoplasm to the nucleus during oogenesis. These findings suggest that Cyclin B plays an important role in gametogenesis and gonad development in C. quadricarinatus. PMID:26400307

  5. THE EXPRESSION AND CLINICAL SIGNIFICANCE OF P21 (WAF1/CIP1)AND CYCLIN D1 PROTEIN IN COLORECTAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To study the effect of P21 (WAF1/CIP1) and cyclin D1 and their relationship in colorec- tal carcinoma. Methods The expression of P21 and cyclin D1 was studied in 40 colorectal carcinoma and 10 normal tissues using S-P immunohistochemical technique. Results Decreased expression of P12 and overexpression of cyclin D1 were revealed in colorectal carcinoma. Decreased expression of P21 was related to lymph node metastasis. No cor- relation was found between cyclin D1 and clinicopathological parameters. Conclusion Decreased expression of P21 and overexpression of cyclin D1 may be involved in colorectal tumorigenesis,and were associated with poor prognosis. No correlation was found between P21 and cyclin D1 in colorectai carcinoma.

  6. The human HECA interacts with cyclins and CDKs to antagonize Wnt-mediated proliferation and chemoresistance of head and neck cancer cells

    International Nuclear Information System (INIS)

    There is a growing evidence that the human homologue of the Drosophila headcase (HECA) plays an important role in human carcinogenesis. So far specific protein interaction partners and affected signaling pathways of HECA are still elusive. In a recent study we showed that HECA overexpression in oral squamous-cell carcinoma (OSCC) keratinocytes has tumor suppressive effects resulting in a recuperation of cell cycle control concerning the entry and progression of S-phase, G2- and M-phase. Currently, quantitative RT-PCR and immunohistochemical analysis of primary tumor tissue from OSCC patients demonstrate that HECA expression is markedly decreased compared to normal control patients with abundant HECA expression. Additionally, there is nearly no HECA expression in OSCC metastases. Here, we show that HECA expression is negatively controlled by the Wnt-pathway and TCF4, a Wnt related transcription factor, binds to the HECA promoter. Furthermore, immunocytochemistry reveals colocalization of HECA with the cyclin dependent kinase CDK9. Immunoprecipitation experiments and proximity ligation assays further reveal an interaction of HECA with CDK2, CDK9, Cyclin A and Cyclin K, a direct transcriptional target of the p53 tumor suppressor. Silencing HECA in OSCC cell lines leads to a significant increase of cell division and a markedly increased resistance against the chemotherapeutic cisplatin. On the contrary, HECA overexpressing OSCC cell lines show decreased resistance of OSCC cells against cisplatin. Therefore, HECA could be considered as future therapeutic agent against Wnt-dependent tumor progression. -- Highlights: ► HECA is a new cell cycle regulator with anti-tumor features in head and neck cancer. ► During tumor progression HECA mRNA and protein expression decrease. ► The HECA promotor is a direct target of the Wnt/beta-catenin/TCF-pathway. ► The HECA protein antagonizes Wnt-mediated cell proliferation through interaction with major cell cycle factors.

  7. Metronomic Ceramide Analogs Inhibit Angiogenesis in Pancreatic Cancer through Up-regulation of Caveolin-1 and Thrombospondin-1 and Down-regulation of Cyclin D1

    Directory of Open Access Journals (Sweden)

    Guido Bocci

    2012-09-01

    Full Text Available AIMS: To evaluate the antitumor and antiangiogenic activity of metronomic ceramide analogs and their relevant molecular mechanisms. METHODS: Human endothelial cells [human dermal microvascular endothelial cells and human umbilical vascular endothelial cell (HUVEC] and pancreatic cancer cells (Capan-1 and MIA PaCa-2 were treated with the ceramide analogs (C2, AL6, C6, and C8, at low concentrations for 144 hours to evaluate any antiproliferative and proapoptotic effects and inhibition of migration and to measure the expression of caveolin-1 (CAV-1 and thrombospondin-1 (TSP-1 mRNAs by real-time reverse transcription-polymerase chain reaction. Assessment of extracellular signal-regulated kinases 1 and 2 (ERK1/2 and Akt phosphorylation and of CAV-1 and cyclin D1 protein expression was performed by ELISA. Maximum tolerated dose (MTD gemcitabine was compared against metronomic doses of the ceramide analogs by evaluating the inhibition of MIA PaCa-2 subcutaneous tumor growth in nude mice. RESULTS: Metronomic ceramide analogs preferentially inhibited cell proliferation and enhanced apoptosis in endothelial cells. Low concentrations of AL6 and C2 caused a significant inhibition of HUVEC migration. ERK1/2 and Akt phosphorylation were significantly decreased after metronomic ceramide analog treatment. Such treatment caused the overexpression of CAV-1 and TSP-1 mRNAs and proteins in endothelial cells, whereas cyclin D1 protein levels were reduced. The antiangiogenic and antitumor impact in vivo of metronomic C2 and AL6 regimens was similar to that caused by MTD gemcitabine. CONCLUSIONS: Metronomic C2 and AL6 analogs have antitumor and antiangiogenic activity, determining the up-regulation of CAV-1 and TSP-1 and the suppression of cyclin D1.

  8. Cyclin-dependent kinase 5 regulates degranulation in human eosinophils.

    Science.gov (United States)

    Odemuyiwa, Solomon O; Ilarraza, Ramses; Davoine, Francis; Logan, Michael R; Shayeganpour, Anooshirvan; Wu, Yingqi; Majaesic, Carina; Adamko, Darryl J; Moqbel, Redwan; Lacy, Paige

    2015-04-01

    Degranulation from eosinophils in response to secretagogue stimulation is a regulated process that involves exocytosis of granule proteins through specific signalling pathways. One potential pathway is dependent on cyclin-dependent kinase 5 (Cdk5) and its effector molecules, p35 and p39, which play a central role in neuronal cell exocytosis by phosphorylating Munc18, a regulator of SNARE binding. Emerging evidence suggests a role for Cdk5 in exocytosis in immune cells, although its role in eosinophils is not known. We sought to examine the expression of Cdk5 and its activators in human eosinophils, and to assess the role of Cdk5 in eosinophil degranulation. We used freshly isolated human eosinophils and analysed the expression of Cdk5, p35, p39 and Munc18c by Western blot, RT-PCR, flow cytometry and immunoprecipitation. Cdk5 kinase activity was determined following eosinophil activation. Cdk5 inhibitors were used (roscovitine, AT7519 and small interfering RNA) to determine its role in eosinophil peroxidase (EPX) secretion. Cdk5 was expressed in association with Munc18c, p35 and p39, and phosphorylated following human eosinophil activation with eotaxin/CCL11, platelet-activating factor, and secretory IgA-Sepharose. Cdk5 inhibitors (roscovitine, AT7519) reduced EPX release when cells were stimulated by PMA or secretory IgA. In assays using small interfering RNA knock-down of Cdk5 expression in human eosinophils, we observed inhibition of EPX release. Our findings suggest that in activated eosinophils, Cdk5 is phosphorylated and binds to Munc18c, resulting in Munc18c release from syntaxin-4, allowing SNARE binding and vesicle fusion, with subsequent eosinophil degranulation. Our work identifies a novel role for Cdk5 in eosinophil mediator release by agonist-induced degranulation. PMID:25346443

  9. Characterization of TcCYC6 from Trypanosoma cruzi, a gene with homology to mitotic cyclins.

    Science.gov (United States)

    Di Renzo, María Agostina; Laverrière, Marc; Schenkman, Sergio; Wehrendt, Diana Patricia; Tellez-Iñón, María Teresa; Potenza, Mariana

    2016-06-01

    Trypanosoma cruzi, the etiologic agent of Chagas disease, is a protozoan parasite with a life cycle that alternates between replicative and non-replicative forms, but the components and mechanisms that regulate its cell cycle are poorly described. In higher eukaryotes, cyclins are proteins that activate cyclin-dependent kinases (CDKs), by associating with them along the different stages of the cell cycle. These cyclin-CDK complexes exert their role as major modulators of the cell cycle by phosphorylating specific substrates. For the correct progression of the cell cycle, the mechanisms that regulate the activity of cyclins and their associated CDKs are diverse and must be controlled precisely. Different types of cyclins are involved in specific phases of the eukaryotic cell cycle, preferentially activating certain CDKs. In this work, we characterized TcCYC6, a putative coding sequence of T. cruzi which encodes a protein with homology to mitotic cyclins. The overexpression of this sequence, fused to a tag of nine amino acids from influenza virus hemagglutinin (TcCYC6-HA), showed to be detrimental for the proliferation of epimastigotes in axenic culture and affected the cell cycle progression. In silico analysis revealed an N-terminal segment similar to the consensus sequence of the destruction box, a hallmark for the degradation of several mitotic cyclins. We experimentally determined that the TcCYC6-HA turnover decreased in the presence of proteasome inhibitors, suggesting that TcCYC6 degradation occurs via ubiquitin-proteasome pathway. The results obtained in this study provide first evidence that TcCYC6 expression and degradation are finely regulated in T. cruzi. PMID:26709077

  10. Expression and significance of cyclin D1, p27kip1 protein in bronchioloalveolar carcinoma

    Institute of Scientific and Technical Information of China (English)

    袁键群; 许敬尧; 张静; 何启才; 祝佳; 盛彩霞

    2004-01-01

    Purpose: To investigate the relationship between expression of cell cycle-related protein cyclin D1, p27kipl and the pathogenesis of bronchioloalveolar carcinoma (BAC) and the value of prediction of prognosis. Methods: Cyclin D 1 and p27kip 1 protein were detected by immunohistochemical En Vision method in 43 BACs. Results: The positivity of cyclin D 1 in BAC was 65.1% (28/43), which was significantly higher than that in normal pulmonary tissue (0/13), P<0.01. No statistically significant association was found between cyclin D1 expression data and sex, age, tobacco-use history, histologic subtype (mucinous vs nonmucinous), stromal fibrosis, lymph node metastasis, clinical stage or postoperative survival period (P>0.05), while cyclin D1 expression was found to be negatively correlated with tumor size (P<0.05). The positivity of p27kipl in BACs was 51.2% (22/43), significantly lower than that in normal pulmonary tissue (12/13), P<0.01. p27kipl expression level was not associated with sex, age, tobacco-use history, tumor size or histologic subtype (P>0.05), but was negatively correlated with stromal fibrosis, lymph node metastasis and clinical stage (P<0.05); and positively associated with postoperative survival period (P<0.01). The survival rate of p27kipl positive group was significantly higher than that of p27kipl negative group (P<0.01). No statistically significant correlation was found between cyclin D 1 and p27kipl expression. Conclusions: Increased cyclin D1 expression and decreased p27kip 1 expression are related to the pathogenesis of BAC;decreased p27kipl expression is associated with metastasis progression; immunodetection ofp27kip 1 is useful for assessment of prognosis.

  11. Detection of cyclin D1 in B cell lymphoproliferative disorders by flow cytometry

    Science.gov (United States)

    Jain, P; Giustolisi, G M; Atkinson, S; Elnenaei, M O; Morilla, R; Owusu-Ankomah, K; Rafiq-Mohammed, F; Matutes, E; Wotherspoon, A; Catovsky, D

    2002-01-01

    Aims: To describe and revise a flow cytometric assay for evaluating cyclin D1 overexpression in B cell lymphoproliferative disorders (B-LPDs). Methods: Cyclin D1 expression was evaluated in 11 healthy controls and 51 patients with B-LPD by flow cytometry using the 5D4 monoclonal antibody. In 25 cases, experiments were repeated up to four times with mononuclear cells (MNC) fixed in ethanol for 1–120 days to evaluate the consistency of cyclin D1 expression. Flow cytometry results were compared with fluorescence in situ hybridisation (FISH) for the t(11;14) translocation in 19 patients and with immunohistochemistry (IHC) using the DCS-6 monoclonal antibody in nine patients. Results: A mean fluorescence intensity ratio (MFIR) of 4.8 was defined as the cut off point for positivity based on cyclin D1 expression in healthy controls (mean + 3 SD). Ten patients overexpressed cyclin D1 by flow cytometry. These included five of eight patients with mantle cell lymphoma, four of 19 with chronic lymphocytic leukaemia, and one with follicular lymphoma. MFIR in the repeat experiments differed less than 25% in 20 of 25 patients and in no cases did it cross the cut off point. There was a good correlation between cyclin D1 expression by flow cytometry and FISH for t(11;14) in 15 of 19 patients and six of nine had concordant results with flow cytometry, FISH, and IHC. Conclusion: Cyclin D1 expression remains fairly stable once MNC are fixed in ethanol and the flow cytometric assay can be used for the routine screening of B-LPD. Further comparisons between flow cytometry, IHC, and FISH may be needed to ascertain the diagnostic value of the flow cytometric assay. PMID:12461064

  12. Alternative splicing variants of human Fbx4 disturb cyclin D1 proteolysis in human cancer.

    Science.gov (United States)

    Chu, Xiufeng; Zhang, Ting; Wang, Jie; Li, Meng; Zhang, Xiaolei; Tu, Jing; Sun, Shiqin; Chen, Xiangmei; Lu, Fengmin

    2014-04-25

    Fbx4 is a specific substrate recognition component of SCF ubiquitin ligases that catalyzes the ubiquitination and subsequent degradation of cyclin D1 and Trx1. Two isoforms of human Fbx4 protein, the full length Fbx4α and the C-terminal truncated Fbx4β have been identified, but their functions remain elusive. In this study, we demonstrated that the mRNA level of Fbx4 was significantly lower in hepatocellular carcinoma tissues than that in the corresponding non-tumor tissues. More importantly, we identified three novel splicing variants of Fbx4: Fbx4γ (missing 168-245 nt of exon1), Fbx4δ (missing exon6) and a N-terminal reading frame shift variant (missing exon2). Using cloning sequencing and RT-PCR, we demonstrated these novel splice variants are much more abundant in human cancer tissues and cell lines than that in normal tissues. When expressed in Sk-Hep1 and NIH3T3 cell lines, Fbx4β, Fbx4γ and Fbx4δ could promote cell proliferation and migration in vitro. Concordantly, these isoforms could disrupt cyclin D1 degradation and therefore increase cyclin D1 expression. Moreover, unlike the full-length isoform Fbx4α that mainly exists in cytoplasm, Fbx4β, Fbx4γ, and Fbx4δ locate in both cytoplasm and nucleus. Since cyclin D1 degradation takes place in cytoplasm, the nuclear distribution of these Fbx4 isoforms may not be involved in the down-regulation of cytoplasmic cyclin D1. These results define the impact of alternative splicing on Fbx4 function, and suggest that the attenuated cyclin D1 degradation by these novel Fbx4 isoforms provides a new insight for aberrant cyclin D1 expression in human cancers. PMID:24704453

  13. Plasmodium P-Type Cyclin CYC3 Modulates Endomitotic Growth during Oocyst Development in Mosquitoes.

    Science.gov (United States)

    Roques, Magali; Wall, Richard J; Douglass, Alexander P; Ramaprasad, Abhinay; Ferguson, David J P; Kaindama, Mbinda L; Brusini, Lorenzo; Joshi, Nimitray; Rchiad, Zineb; Brady, Declan; Guttery, David S; Wheatley, Sally P; Yamano, Hiroyuki; Holder, Anthony A; Pain, Arnab; Wickstead, Bill; Tewari, Rita

    2015-11-01

    Cell-cycle progression and cell division in eukaryotes are governed in part by the cyclin family and their regulation of cyclin-dependent kinases (CDKs). Cyclins are very well characterised in model systems such as yeast and human cells, but surprisingly little is known about their number and role in Plasmodium, the unicellular protozoan parasite that causes malaria. Malaria parasite cell division and proliferation differs from that of many eukaryotes. During its life cycle it undergoes two types of mitosis: endomitosis in asexual stages and an extremely rapid mitotic process during male gametogenesis. Both schizogony (producing merozoites) in host liver and red blood cells, and sporogony (producing sporozoites) in the mosquito vector, are endomitotic with repeated nuclear replication, without chromosome condensation, before cell division. The role of specific cyclins during Plasmodium cell proliferation was unknown. We show here that the Plasmodium genome contains only three cyclin genes, representing an unusual repertoire of cyclin classes. Expression and reverse genetic analyses of the single Plant (P)-type cyclin, CYC3, in the rodent malaria parasite, Plasmodium berghei, revealed a cytoplasmic and nuclear location of the GFP-tagged protein throughout the lifecycle. Deletion of cyc3 resulted in defects in size, number and growth of oocysts, with abnormalities in budding and sporozoite formation. Furthermore, global transcript analysis of the cyc3-deleted and wild type parasites at gametocyte and ookinete stages identified differentially expressed genes required for signalling, invasion and oocyst development. Collectively these data suggest that cyc3 modulates oocyst endomitotic development in Plasmodium berghei. PMID:26565797

  14. BRCA1-IRIS regulates cyclin D1 expression in breast cancer cells

    International Nuclear Information System (INIS)

    The regulator of cell cycle progression, cyclin D1, is up-regulated in breast cancer cells; its expression is, in part, dependent on ERα signaling. However, many ERα-negative tumors and tumor cell lines (e.g., SKBR3) also show over-expression of cyclin D1. This suggests that, in addition to ERα signaling, cyclin D1 expression is under the control of other signaling pathways; these pathways may even be over-expressed in the ERα-negative cells. We previously noticed that both ERα-positive and -negative cell lines over-express BRCA1-IRIS mRNA and protein. Furthermore, the level of over-expression of BRCA1-IRIS in ERα-negative cell lines even exceeded its over-expression level in ERα-positive cell lines. In this study, we show that: (1) BRCA1-IRIS forms complex with two of the nuclear receptor co-activators, namely, SRC1 and SRC3 (AIB1) in an ERα-independent manner. (2) BRCA1-IRIS alone, or in connection with co-activators, is recruited to the cyclin D1 promoter through its binding to c-Jun/AP1 complex; this binding activates the cyclin D1 expression. (3) Over-expression of BRCA1-IRIS in breast cells over-activates JNK/c-Jun; this leads to the induction of cyclin D1 expression and cellular proliferation. (4) BRCA1-IRIS activation of JNK/c-Jun/AP1 appears to account for this, because in cells that were depleted from BRCA1-IRIS, JNK remained inactive. However, depletion of SRC1 or SRC3 instead reduced c-Jun expression. Our data suggest that this novel signaling pathway links BRCA1-IRIS to cellular proliferation through c-Jun/AP1 nuclear pathway; finally, this culminates in the increased expression of the cyclin D1 gene

  15. The expression of MIF and Cyclin D1 in hepatocellular carcinoma%MIF和Cyclin D1在肝细胞癌中的表达

    Institute of Scientific and Technical Information of China (English)

    夏金堂; 伍兆锋; 李雯; 赖越元; 赵杰; 徐晨; 王花; 滕元; 李瑜元

    2009-01-01

    Objective To investigate the expression of macrophage migration inhibition factor (MIF) and cell cycle regulating factor Cyclin D1 in hepatocellular carcinoma tissue and the interaction between MIF and Cyclin D1 in hepatocellular carcinoma cell cycle controlling. Methods Using quantitative real-time PCR and Western blotting to detect mRNA and protein expression of MIF and Cyelin DI in HCC tissues and tumor adjacent tissues. Specific small interfering RNA(siRNA) targeting MIF gene was transfccted at doses of 50 nmol/L and 100 nmoL/L into HCC cell lines of PLC and HepG2 with lipofeetamine 2000 methods to knockdown the expression of M1F gene and to investigare the the interaction between M1F and Cyclin D1. Results MIF and Cyclin D1 protein and mRNA were overexpressed in HCC tumor tissues. The relative expression of MIF,Cyclin D1 protein and mRNA were 0.825±0.13,0.843± 0.104 and 7.31±1.85 folds、4.27±1.05 folds, compared with the tumor adjacent tissues (FMIF= 15.5, P<0.01;FCyclin D1=87.5,P <0.01). In MIF siRNA treated PLC and HepG2 cells, MIF mRNA down regulation 71.2%±7.2%, 87.4%±2.9% ,74.3%±8.9% and 88.4%±4.6% respectively (FPLC = 315.5 ,P < 0.01 ; FHepG2= 201.2 P < 0.01). While MIF protein expression were significandy reduced to 0.33±0.03,0.11±0.02, 0.81±0.08 and 0.36±0.02 in a dose-dependent manner (FPLC= 43.9, P <0.01 ;FHepG2 = 133.4 P <0.01). Cyclin D1 mRNA was significantly down-regnlated in MIF siRNA treated PLC and HepG2 cell lines when compared with control group(P <0.01). In 50 nmol/L and 100 nmol/L groups, Cyclin DI mRNA levels were respectively decreased by 68.2%±3% and 78.1%±1.4% in PLC cell, 65.8%±4.7% and 77.3%±2.6% in HepG2 cell (FPLC= 1569, P < 0.01 ; FHepG2= 480.4, P <0.01). Compared with control groups, Cyclin D1 protein levels significantly reduced to 0.28±0.06、0.15±0.03 and 0.44 ±0.04、0.13±0.02 in the PLC and HepG2 after M IF siRNA treatment(FPLC= 35.5, P < 0.01 ; FHepG2 = 114.7, P < 0.01). Conclusions MIF and Cyclin D1 m

  16. Expression of cyclins A and E in melanocytic skin lesions and its correlation with some clinicopathologic features

    Directory of Open Access Journals (Sweden)

    Ana Alekseenko

    2012-07-01

    Full Text Available Cyclins play a fundamental role in the cell cycle. Recent studies have focused on their role in the development of various malignancies. The objective of this study was to evaluate and compare the expression of cyclins A and E in common nevi, dysplastic nevi and malignant melanomas, and to investigate the relationship between cyclin expression and some pathological parameters such as tumor thickness, ulceration, regression, and mitotic rate, as well as several clinical and phenotypic parameters such as skin phototype, hair and eye color, number of nevi, personal or family melanoma history, and personal history of nonmelanoma skin cancer (NMSC. A total of 102 melanocytic skin lesions, including 30 common nevi, 38 dysplastic nevi and 34 melanomas, were examined. Expression of cyclins was detected by immunohistochemistry and quantified as a percentage of immunostained cell nuclei in each sample. Significant differences in expression of both cyclins were found between all lesion types: the median percentage of cyclin A-positive nuclei was 8.2% in melanomas, 3.4% in dysplastic nevi, and 0.95% in common nevi (p < 0.001. The corresponding percentages for cyclin E were 9.5%, 4.25% and 1.44% (p < 0.001. Expression of both cyclins was significantly higher among patients with a personal history of NMSC. Cyclin A was also significantly overexpressed in patients with a high total nevus count (TNC compared to moderate and low TNC. Expression of cyclins did not significantly correlate with the other clinicopathologic features investigated. These findings indicate the possible involvement of cyclins A and E in the pathogenesis of malignant melanoma. Our results also show a potential diagnostic significance of these cyclins as markers allowing discrimination between dysplastic nevi and melanoma.

  17. Cyclin B1 overexpression in conventional oral squamous cell carcinoma and verrucous carcinoma-A correlation with clinicopathological features

    OpenAIRE

    Patil, Gururaj B.; Hallikeri, Kaveri S.; Balappanavar, Aswini Y.; Hongal, Sudheer G.; Sanjaya, PR; Sagari, Sheetalkumar G.

    2013-01-01

    Background: Nuclear localization of cyclin B1 is an indicator for cells undergoing mitotic division, and the overexpression has shown promising results as a good prognostic predictor for patients of squamous cell carcinoma (SCC). Cyclin B1 overexpression among histological grades of conventional oral squamous cell carcinoma (COSCC), as well as comparison with verrucous carcinoma (VC) has been less investigated. Study Design: Immunohistochemical expression of cyclin B1 was compared with variou...

  18. Action of caffeine on x-irradiated HeLa cells. IV. Progression delays and enhanced cell killing at high caffeine concentrations

    International Nuclear Information System (INIS)

    The response of x-irradiated and unirradiated HeLa S3 cells to treatment with caffeine at concentrations between 1 and 10 nM has been examined with respect to both delay in progression through the cell generation cycle and enhancement of the expression of potentially lethal x-ray damage. Progression is delayed in a concentration-dependent fashion: the generation time is doubled at about 4 mM. The duration of G1 is lengthened, and the rate of DNA synthesis is reduced, although the kinetics are different in the two phases; the rate of DNA synthesis is usually unaffected at 1 or 2 mM, while there is no concentration threshold for the slowing of progression through G1. Progression through G2 appears to be unaffected by concentrations up to at least 10 mM. Killing of irradiated cells in G2 is somewhat greater after treatment with the higher caffeine concentrations than reported previously for 1 mM. Moreover, an additional mode of killing is observed in irradiated G1 cells which had been found previously to be only slightly affected by 1 mM caffeine; they suffer extensive killing at concentrations above 5 mM. The time-survival curves for irradiated, caffeine-treated G1 and G2 cells have characteristically different shapes. The dose-survival curves for cells treated with the higher caffeine concentrations display steeper terminal slopes and narrower shoulders

  19. Antioxidant properties of thio-caffeine derivatives: Identification of the newly synthesized 8-[(pyrrolidin-1-ylcarbonothioyl)sulfanyl]caffeine as antioxidant and highly potent cytoprotective agent.

    Science.gov (United States)

    Jasiewicz, Beata; Sierakowska, Arleta; Wandyszewska, Natalia; Warżajtis, Beata; Rychlewska, Urszula; Wawrzyniak, Rafał; Mrówczyńska, Lucyna

    2016-08-15

    A series of nine thio-caffeine analogues were synthesized and characterised by NMR, FT-IR and MS spectroscopic methods. Molecular structures of four of them were determined using single crystal X-ray diffraction methods. The antioxidant properties of all compounds, at concentration ranges from 0.025 to 0.1mg/mL, were evaluated by various chemical- and cell-based antioxidant assays. Human erythrocytes were used to examine in vitro haemolytic activity of all compounds and their protective effect against oxidative haemolysis induced by AAPH, one of the commonly used free radical generator. All compounds studied showed no effect on the human erythrocytes membrane structure and permeability with the exception of 8-(phenylsulfanyl)caffeine. Among the nine caffeine thio-analogues tested, the newly synthesized 8-[(pyrrolidin-1-ylcarbonothioyl)sulfanyl]caffeine possessed exceptionally high antioxidant properties. Moreover, it protects human erythrocytes against AAPH-induced oxidative damage as efficiently as the standard antioxidant Trolox. Therefore, 8-[(pyrrolidin-1-ylcarbonothioyl)sulfanyl]caffeine may have a significant cytoprotective potential caused by its antioxidant activity. PMID:27400888

  20. Caffeine provokes adverse interactions with 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and related psychostimulants: mechanisms and mediators.

    Science.gov (United States)

    Vanattou-Saïfoudine, N; McNamara, R; Harkin, A

    2012-11-01

    Concomitant consumption of caffeine with recreational psychostimulant drugs of abuse can provoke severe acute adverse reactions in addition to longer term consequences. The mechanisms by which caffeine increases the toxicity of psychostimulants include changes in body temperature regulation, cardiotoxicity and lowering of the seizure threshold. Caffeine also influences the stimulatory, discriminative and reinforcing effects of psychostimulant drugs. In this review, we consider our current understanding of such caffeine-related drug interactions, placing a particular emphasis on an adverse interaction between caffeine and the substituted amphetamine, 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'), which has been most recently described and characterized. Co-administration of caffeine profoundly enhances the acute toxicity of MDMA in rats, as manifested by high core body temperature, tachycardia and increased mortality. In addition, co-administration of caffeine enhances the long-term serotonergic neurotoxicity induced by MDMA. Observations to date support an interactive model of drug-induced toxicity comprising MDMA-related enhancement of dopamine release coupled to a caffeine-mediated antagonism of adenosine receptors in addition to inhibition of PDE. These experiments are reviewed together with reports of caffeine-related drug interactions with cocaine, d-amphetamine and ephedrine where similar mechanisms are implicated. Understanding the underlying mechanisms will guide appropriate intervention strategies for the management of severe reactions and potential for increased drug-related toxicity, resulting from concomitant caffeine consumption. PMID:22671762

  1. The proteolysis of mitotic cyclins in mammalian cells persists from the end of mitosis until the onset of S phase.

    Science.gov (United States)

    Brandeis, M; Hunt, T

    1996-10-01

    We have studied how the cell cycle-specific oscillations of mitotic B-type cyclins are generated in mouse fibroblasts. A reporter enzyme comprising the N-terminus of a B-type cyclin fused to bacterial chloramphenicol acetyl transferase (CAT) was degraded at the end of mitosis like endogenous cyclins. Point mutations in the destruction box of this construct completely abolished its mitotic instability. When the destructible reporter was driven by the cyclin B2 promoter, CAT activity mimicked the oscillations in the level of the endogenous cyclin B2. These oscillations were largely conserved when the reporter was transcribed constitutively from the SV40 promoter. Pulse-chase experiments or addition of the proteasome inhibitors lactacystin and ALLN showed that cyclin synthesis continued after the end of mitosis. The destruction box-specific degradation of cyclins normally ceases at the onset of S phase, and is active in fibroblasts arrested in G0 and in differentiated C2 myoblasts. We were able to reproduce this proteolysis in vitro in extracts of synchronized cells. Extracts of G1 cells degraded cyclin B1 whereas p27Kip1 was stable, in contrast, cyclin B1 remained stable and p27Kip1 was degraded in extracts of S phase cells. PMID:8895573

  2. The cyclin D1 proto-oncogene is sequestered in the cytoplasm of mammalian cancer cell lines

    Directory of Open Access Journals (Sweden)

    Coombes R Charles

    2006-02-01

    Full Text Available Abstract Background The cyclin D1 proto-oncogene is an important regulator of G1 to S-phase transition and an important cofactor for several transcription factors in numerous cell types. Studies on neonatal cardiomyocytes and postmitotic neurons indicate that the activity of cyclin D1 may be regulated through its cytoplasmic sequestration. We have demonstrated previously, that TSA induces the ubiquitin-dependent degradation of cyclin D1 in MCF-7 breast cancer cells. Additional studies were initiated in order to further investigate the effect of TSA on cyclin D1 regulation using sub-cellular fractionation techniques. Results Our studies revealed cyclin D1 to be localized predominantly within the cytoplasmic fraction of all cell lines tested. These observations were confirmed by confocal microscopy. GSK3β was found to be localized within both the nucleus and cytoplasm throughout the cell cycle. Inhibition of GSK3β or CRM1-dependent nuclear export resulted in only modest nuclear accumulation, suggesting that the cytoplasmic localization of cyclin D1 results from the inhibition of its nuclear import. Conclusion We have shown by several different experimental approaches, that cyclin D1 is in fact a predominantly cytoplasmic protein in mammalian cancer cell lines. Recent studies have shown that the cytoplasmic sequestration of cyclin D1 prevents apoptosis in neuronal cells. Our results suggest that cytoplasmic sequestration may additionally serve to regulate cyclin D1 activity in mammalian cancer cells.

  3. Requirement of the SCFPop1/Pop2 Ubiquitin Ligase for Degradation of the Fission Yeast S Phase Cyclin Cig2

    OpenAIRE

    Yamano, H; Kominami, K; Harrison, C; Kitamura, K.; Katayama, S; Dhut, S.; Hunt, T; Toda, T.

    2004-01-01

    Two multiprotein E3 (ubiquitin-protein ligase) ubiquitin ligases, the SCF (Skp1-Cullin-1-F-box) and the APC/C (anaphase promoting complex/cyclosome), are vital in ensuring the temporal order of the cell cycle. Particularly, timely destruction of cyclins via these two E3s is essential for down-regulation of cyclin-dependent kinase. In general, G(1) and S phase cyclins are ubiquitylated by the SCF, whereas ubiquitylation of mitotic cyclins is catalyzed by the APC/C. Here we show that fission ye...

  4. Cyclin-Dependent Kinase Inhibitor P27Kip1 Is Required for Mouse Mammary Gland Morphogenesis and Function

    OpenAIRE

    Muraoka, Rebecca S.; Lenferink, Anne E.G.; Simpson, Jean; Brantley, Dana M.; Roebuck, L. Renee; Yakes, F. Michael; Arteaga, Carlos L

    2001-01-01

    We have studied the role of the cyclin-dependent kinase (Cdk) inhibitor p27Kip1 in postnatal mammary gland morphogenesis. Based on its ability to negatively regulate cyclin/Cdk function, loss of p27 may result in unrestrained cellular proliferation. However, recent evidence about the stabilizing effect of p27 on cyclin D1–Cdk4 complexes suggests that p27 deficiency might recapitulate the hypoplastic mammary phenotype of cyclin D1–deficient animals. These hypotheses were investigated in postna...

  5. Differential expression of cyclin Dl in human pituitary tumors: relation to MIB-1 and p27/Kipl labeling indices

    International Nuclear Information System (INIS)

    Pituitary tumors are a common form of endocrine neoplasia. However few studies assessed the expression of the principal cyclin regulating checkpoint exit, cyclin Dl. Cyclin Dl expression in pituitary tumors and its possible relation to MIB-1 and p27/K.ipl labeling indices (Us) was explored. Design: We studied a total of 199 pituitaries, including normal pituitaries (n = 7), pituitary adenomas (n = 187), and pituitary carcinoma (n = 5). All tissues were tested as cores of archived tissue microarrays that were immuno stained for cyclin Dl, MIB-1 and p27 using a standard technique. Tissue cores were subjected to automated analysis to evaluate the staining LIs, Results: No cyclin Dl positive cells in the normal anterior pituitary gland was found. Sparse nuclear staining was noted in pituitary tumors. Higher expression of cyclin Dl was noted in pituitary carcinomas compared to adenomas (p < 0.001), in non-functioning adenomas compared to functioning ones (p < 0.001) in macroadenomas versus micro adenomas (p — 0.017) and in recurrent non recurrent adenomas (p < 0.001). Cyclin Dl LI and MIB-1 LI were related among adenomas (p < 0.001) and carcinomas (p = 0.041). p27 LI was neither related to pituitary adenoma recurrence nor invasion. Conclusions: Expression of cyclin Dl in pituitary tumors is related to cell proliferation, recurrence, and metastatic potential. Nuclear cyclin Dl expression is a good marker of aggressive behavior in pituitary tumors

  6. A detailed analysis of cyclin A accumulation at the G(1)/S border in normal and transformed cells.

    Science.gov (United States)

    Erlandsson, F; Linnman, C; Ekholm, S; Bengtsson, E; Zetterberg, A

    2000-08-25

    The temporal relationship between cyclin A accumulation and the onset of DNA replication was analyzed in detail. Five untransformed and nine transformed asynchronously growing cell cultures were investigated using a triple immunofluorescence staining protocol combined with computerized evaluation of staining intensities in individual cells. The simultaneous staining of BrdU, cyclin A, and cyclin E made it possible to determine the cell cycle position of each cell investigated. Cells at the G(1)/S border were identified on the basis of cyclin E content and were further analyzed with respect to cyclin A and BrdU content. A method was developed to calculate objective thresholds defining the highest staining intensity found in the negative cells in the population. Using the thresholds we could distinguish cells with minute amounts of cyclin A and BrdU from truly negative cells. We show that the onset of cyclin A accumulation and the start of DNA replication occurs at the same time, or deviating by a few minutes at the most. We also show that cyclin A accumulates continuously during S. This study clearly demonstrates that nuclear cyclin A can be used as a reliable marker for the S and G(2) phases in both normal and transformed interphase cells. PMID:10942581

  7. THE MULTIPLE ROLES OF CYCLIN E1 IN CONTROLLING CELL CYCLE PROGRESSION AND CELLULAR MORPHOLOGY OF TRYPANOSOMA BRUCEI

    OpenAIRE

    Gourguechon, Stéphane; Savich, Jason M.; Ching C Wang

    2007-01-01

    Regulation of eukaryotic cell cycle progression requires sequential activation and inactivation of cyclin-dependent kinases. Previous RNA interference (RNAi) experiments in Trypanosoma brucei indicated that cyclin E1, cdc2-related kinase (CRK)1 and CRK2 are involved in regulating G1/S transition, whereas cyclin B2 and CRK3 play a pivotal role in controlling the G2/M checkpoint. To search for potential interactions between the other cyclins and CRKs that may not have been revealed by the RNAi ...

  8. Modification of the radiosensitivity of barley seed by post-treatment with caffeine

    International Nuclear Information System (INIS)

    Barley seeds of a hull-less variety (IB 65) were γ-irradiated (40 and 45 krad, 100 rad/sec) at 250C, and the seeds were post-hydrated for 12 hours at approximately 30C in oxygenated and oxygen-free water or caffeine solutions (3.8 x 10-4 to 3.8 x 10-2M). Measurements of 8-day seedling growth showed that the different caffeine concentrations applied during oxygenated or oxygen-free hydrations produced no observable effects on the growth of unirradiated seeds. All caffeine concentrations afforded protection for the irradiated seeds under oxygenated conditions, and potentiated the damage under oxygen-free conditions. A maximum radio-protection occurred at a caffeine concentration of 3.8 x 10-3M, whereas radiosensitization under oxygen-free conditions was concentration-dependent. Possible mechanisms are discussed. (U.K.)

  9. Modification of the radiosensitivity of barley seed by post-treatment with caffeine

    International Nuclear Information System (INIS)

    In dry barley seeds (3.1 per cent moisture content), the maximal level of oxic damage (class III damage) was reached within the first 40 min a post-hydration in oxygenated water at 5 +- 10C. The decay of the gamma-ray-induced oxygensensitive sites required however, about 120 min. The mechanism leading to partial protection against the class III damage were initiated when caffeine was present during the dirst 30 min of oxygenated post-hydration. If added after 30 min of oxygenated hydration, caffeine had no protective action. For the potentiation of an oxygen-independent component of damage, caffeine had to be present during the first 240 min of oxygen-free hydration. These observations involving a physiologically inert system raised questions regarding physico-chemical vis-a-vis biochemical mechanisms of caffeine effect on irradiated systems and these have been briefly discussed. (author)

  10. Effects of caffeine on purine metabolism and ultraviolet light-induced lethality in cultured mammalian cells

    International Nuclear Information System (INIS)

    Caffeine, at doses which enhance the killing action of ultraviolet light, inhibits both de novo synthesis and the utilization of exogenous purines in cultured CHO-K1, a Chinese hamster ovary cell line. The effect is dose dependent, with a caffeine concentration of 7.5 mM producing a 90% reduction in 15 min. Interference with utilization of exogenous purines was seen as a substantial decrease in the conversion of [14C]hypoxanthine, [14C]adenine, or [14C]guanine into their respective di- and triphosphates in the presence of caffeine. Thus, one of the ways by which antimetabolites and caffeine act to enhance ultraviolet light killing may be by interference with the supply of purine nucleotides needed for repair

  11. Determination of Aspartame, Caffeine, Saccharin, and Benzoic Acid in Beverages by High Performance Liquid Chromatography.

    Science.gov (United States)

    Delaney, Michael F.; And Others

    1985-01-01

    Describes a simple and reliable new quantitative analysis experiment using liquid chromatography for the determinaiton of caffeine, saccharin, and sodium benzoate in beverages. Background information, procedures used, and typical results obtained are provided. (JN)

  12. Caffeine degradation in water by gamma irradiation, ozonation and ozonation/gamma irradiation

    Directory of Open Access Journals (Sweden)

    Torun Murat

    2014-03-01

    Full Text Available Aqueous solutions of caffeine were treated with ozone and gamma irradiation. The amounts of remaining caffeine were determined after solid phase extraction as a function of absorbed dose and ozonation time. In addition to this, some important parameters such as inorganic ions, chemical oxygen demand (COD dissolved oxygen and total acidity changes were followed. Caffeine (50 ppm is found to be completely decomposed at 3.0 kGy and 1.2 kGy doses in the absence of H2O2 and in 1.20 mM H2O2 solutions, respectively. In the case of gamma irradiation after ozonation, 50 ppm caffeine was removed at 0.2 kGy when the solution was ozonized for 100 s at a rate of 10 g O3 h-1 in 400 mL 50 ppm paracetamol solution.

  13. Cyclin-dependent protein kinase inhibitors including palbociclib as anticancer drugs.

    Science.gov (United States)

    Roskoski, Robert

    2016-05-01

    Cyclins and cyclin-dependent protein kinases (CDKs) are important regulatory components that are required for cell cycle progression. The levels of the cell cycle CDKs are generally constant and their activities are controlled by cyclins, proteins whose levels oscillate during each cell cycle. Additional CDK family members were subsequently discovered that play significant roles in a wide range of activities including the control of gene transcription, metabolism, and neuronal function. In response to mitogenic stimuli, cells in the G1 phase of the cell cycle produce cyclins of the D type that activate CDK4/6. These activated enzymes catalyze the monophosphorylation of the retinoblastoma protein. Then CDK2-cyclin E catalyzes the hyperphosphorylation of Rb that promotes the release and activation of the E2F transcription factors, which in turn lead to the generation of several proteins required for cell cycle progression. As a result, cells pass through the G1-restriction point and are committed to complete cell division. CDK2-cyclin A, CDK1-cyclin A, and CDK1-cyclin B are required for S, G2, and M-phase progression. Increased cyclin or CDK expression or decreased levels of endogenous CDK inhibitors such as INK4 or CIP/KIP have been observed in various cancers. In contrast to the mutational activation of EGFR, Kit, or B-Raf in the pathogenesis of malignancies, mutations in the CDKs that cause cancers are rare. Owing to their role in cell proliferation, CDKs represent natural targets for anticancer therapies. Abemaciclib (LY2835219), ribociclib (Lee011), and palbociclib (Ibrance(®) or PD0332991) target CDK4/6 with IC50 values in the low nanomolar range. Palbociclib and other CDK inhibitors bind in the cleft between the small and large lobes of the CDKs and inhibit the binding of ATP. Like ATP, palbociclib forms hydrogen bonds with residues in the hinge segment of the cleft. Like the adenine base of ATP, palbociclib interacts with catalytic spine residues CS6 and CS7

  14. THE EXPRESSION OF p16 AND CYCLIN D1 IN PROLIFERATIVE ENDOMETRIUM AND ENDOMETRIAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To studythe role of p16 and cyclin in the genesis and development of endometrial car-cinoma. Methods 12 cases of normal endometrium, 22 cases of proliferative endometrium and 41 cases of endome- trial carcinoma were detected for the expression of p16 and cyclin D1 by means of immunohistochemical S-P. Results In normal endometrium p16 was expressed while cyclm D1was almost negative in the proliferative phase, but both of them were negative in the secretory phase. Among the groups of the simple and compound hyperplasia, the atypical hyperplasia and the endometrial carcinoma,the expression of p16 showed a descending tendency, while the expression of cyclin showed an ascending tendency. In endometrial carcinomas the expression of p16 was significantly lower than that of normal endometrium and proliferative endometrium (P<0. 01 ,P<0.05). However, the expression of cy- clin in proliferate endometrium and endometrial carcinoma was significantly higher than that in normal endometri- un (P<0. 05,P<0. 01). The overexpression of cyclin D1 in the atypical hyperplasia group was obviously different from that in the simple and compound hyperplasia group (P<0.01). In endometrial carcinoma,the expression of p16 was decreasing with the descending of cell differentiate degree, on the opposite, the expression of cyclin was in-creased and there existed a negative correlation between them. It was also observed that the overexpression of cyclin was significant different between and ( P <0. 01 ). Conclusion p1 6 is a negative regulating factor of cell cycle in endometrial carcinoma, while cyclin is a positive one. Both of them are important in the genesis and devel-opment of endometrial carcinoma. The Iow expression of p1 6 and the overexpression of cyclin are related with the malicious biological behaviors of endometrial carcinoma and maybe play an important role in the judgement of prog- nosis. Overexpression of cyclin may be an earlier molecular event in the genesis of

  15. Identification and characterization of 2 testicular germ cell markers, Glut3 and CyclinA2.

    Science.gov (United States)

    Howitt, Brooke E; Brooks, James D; Jones, Sunita; Higgins, John P T

    2013-10-01

    Testicular germ cell tumors (TGCT) are the most common type of testicular tumor and encompass different histologic types that greatly influence treatment and prognosis. Immunohistochemical studies may be required for accurate classification, particularly when these tumors present at extragonadal sites, and to aid in distinguishing histologic types. Traditional markers for identifying and distinguishing TGCT include PLAP, CD117, AFP, and CD30. More recently, the addition of OCT3/4 and SALL4 has increased sensitivity for immunohistochemical detection of germ cell tumors. We examined gene expression data from a previously published microarray study that compared normal testis mRNA expression to various TGCT. We also performed a search of the literature to identify less well-characterized markers. Glut3 and cyclinA2 showed promise as TGCT markers. Therefore, we evaluated expression of glut3 and cyclinA2 by immunohistochemistry using tissue microarrays (TMAs). Of 66 seminomas included in the TMA, 64 (97%) showed positive nuclear staining for cyclinA2 and 58 (88%) were strongly positive. Strong positive staining for cyclinA2 was also seen in the spermatocytic seminoma. All 20 of the embryonal carcinomas stained positively with cyclinA2, and 19 (95%) displayed strong nuclear staining for cyclinA2. Twenty of the 20 embryonal carcinomas stained for glut3 in a strong membranous pattern. Of 8 yolk sac tumors, 100% stained with glut3. We also evaluated glut3 and cyclinA2 staining on a general TMA containing 486 samples representing 156 different tumors. CyclinA2 stained a number of other tumor types, but the majority of these were weak or focal staining. Glut3 was rarely positive in other tumors; interestingly, most of these were of ovarian origin. We conclude that glut3 is a sensitive (96%) and specific (92%) marker for embryonal carcinomas and yolk sac tumors. Although cyclinA2 is a sensitive marker of seminomas and embryonal carcinomas (98%), its specificity is lower if

  16. Intake of Caffeinated Soft Drinks before and during Pregnancy, but Not Total Caffeine Intake, Is Associated with Increased Cerebral Palsy Risk in the Norwegian Mother and Child Cohort Study

    DEFF Research Database (Denmark)

    Tollånes, Mette C; Strandberg-Larsen, Katrine; Eichelberger, Kacey Y;

    2016-01-01

    caffeine intake before and during pregnancy was not associated with CP risk. High consumption (≥6 servings/d) of caffeinated soft drinks before pregnancy was associated with an increased CP risk (HR: 1.9; 95% CI: 1.2, 3.1), and children of women consuming 3-5 daily servings of caffeinated soft drinks...... during pregnancy weeks 13-30 also had an increased CP risk (HR: 1.7; 95% CI: 1.1, 2.8). A mean daily consumption of 51-100 mg caffeine from soft drinks during the first half of pregnancy was associated with a 1.9-fold increased risk of CP in children (HR: 1.9; 95% CI: 1.1, 3.6). CONCLUSIONS: Maternal...... total daily caffeine consumption before and during pregnancy was not associated with CP risk in children. The observed increased risk with caffeinated soft drinks warrants further investigation....

  17. Analysis of the mitotic exit control system using locked levels of stable mitotic cyclin.

    Science.gov (United States)

    Drapkin, Benjamin J; Lu, Ying; Procko, Andrea L; Timney, Benjamin L; Cross, Frederick R

    2009-01-01

    Cyclin-dependent kinase (Cdk) both promotes mitotic entry (spindle assembly and anaphase) and inhibits mitotic exit (spindle disassembly and cytokinesis), leading to an elegant quantitative hypothesis that a single cyclin oscillation can function as a ratchet to order these events. This ratchet is at the core of a published ODE model for the yeast cell cycle. However, the ratchet model requires appropriate cyclin dose-response thresholds. Here, we test the inhibition of mitotic exit in budding yeast using graded levels of stable mitotic cyclin (Clb2). In opposition to the ratchet model, stable levels of Clb2 introduced dose-dependent delays, rather than hard thresholds, that varied by mitotic exit event. The ensuing cell cycle was highly abnormal, suggesting a novel reason for cyclin degradation. Cdc14 phosphatase antagonizes Clb2-Cdk, and Cdc14 is released from inhibitory nucleolar sequestration independently of stable Clb2. Thus, Cdc14/Clb2 balance may be the appropriate variable for mitotic regulation. Although our results are inconsistent with the aforementioned ODE model, revision of the model to allow Cdc14/Clb2 balance to control mitotic exit corrects these discrepancies, providing theoretical support for our conclusions. PMID:19920813

  18. Caffeine Intake, Smoking, and Risk of Parkinson Disease in Men and Women

    OpenAIRE

    Liu, Rui; Guo, Xuguang; Park, Yikyung; Huang, Xuemei; Sinha, Rashmi; Freedman, Neal D; Hollenbeck, Albert R.; Blair, Aaron; Chen, Honglei

    2012-01-01

    The authors prospectively examined whether caffeine intake was associated with lower risk of Parkinson disease (PD) in both men and women among 304,980 participants in the National Institutes of Health-AARP Diet and Health Study and whether smoking affected this relation. Multivariate odds ratios and 95% confidence intervals were derived from logistic regression models. Higher caffeine intake as assessed in 1995–1996 was monotonically associated with lower PD risk (diagnosed in 2000–2006) in ...

  19. Calcium and caffeine interaction in increased calcium balance in ovariectomized rats

    OpenAIRE

    Sandra Tavares da Silva; Neuza Maria Brunoro Costa; Frederico Souzalima Caldoncelli Franco; Antônio José Natali

    2013-01-01

    OBJECTIVE: This study investigated the effects of caffeine intake associated with inadequate or adequate calcium intake in laparotomized or ovariectomized rats by means of the calcium balance. Forty adults Wistar rats were ovariectomized or laparotomized. METHODS: The animals (n=40) were randomly placed in eight groups receiving the AIN-93 diet with 100% or 50% of the recommended calcium intake with or without added caffeine (6mg/kg/day). The animals were kept in individuals metabolic cages a...

  20. Driver’s Attitudes about the Impact of Caffeine and Energy Drinks on Road Traffic Safety

    OpenAIRE

    Pešić, Dalibor; Antić, Boris; Brčić, Davor; Davidović, Jelica

    2015-01-01

    Large amounts of energy drinks and caffeine, which is the main ingredient of energy drinks, produce a negative effect on the drivers, and therefore affect traffic safety.In order to determine the attitudes of drivers toward the impact of energy drinks and caffeine, a research was conducted using a questionnaire form and the targeted group of the survey were drivers. The research was conducted in the City of Belgrade in December 2012. There were 420 survey papers distributed to drivers of diff...