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Sample records for caffeine suppress cyclin

  1. 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

    Cells respond to DNA damage by activating cell cycle checkpoints to delay proliferation and facilitate DNA repair. Here, to uncover new checkpoint regulators, we perform RNA interference screening targeting genes involved in ubiquitylation processes. We show that the F-box protein cyclin F plays...... 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...... that promotes accumulation of crucial mitosis-promoting proteins. Cyclin F interacts with B-Myb via the cyclin box domain. This interaction is important to suppress cyclin A-mediated phosphorylation of B-Myb, a key step in B-Myb activation. In summary, we uncover a regulatory mechanism linking the F-box protein...

  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. 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 ...

  4. Caffein

    DEFF Research Database (Denmark)

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

    2005-01-01

    /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...

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  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. PAC exhibits potent anti-colon cancer properties through targeting cyclin D1 and suppressing epithelial-to-mesenchymal transition.

    Science.gov (United States)

    Al-Qasem, Abeer; Al-Howail, Huda A; Al-Swailem, Mashael; Al-Mazrou, Amer; Al-Otaibi, Basem; Al-Jammaz, Ibrahim; Al-Khalaf, Huda H; Aboussekhra, Abdelilah

    2016-03-01

    Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality worldwide. Although response rates and overall survival have been improved in recent years, resistance to multiple drug combinations is inevitable. Therefore, the development of more efficient drugs, with fewer side effects is urgently needed. To this end, we have investigated in the present report the effect of PAC, a novel cucumin analogue, on CRC cells both in vitro and in vivo. We have shown that PAC induces apoptosis, mainly via the internal mitochondrial route, and inhibits cell proliferation through delaying the cell cycle at G2/M phase. Interestingly, the pro-apoptotic effect was mediated through STAT3-dependent down-regulation of cyclin D1 and its downstream target survivin. Indeed, change in the expression level of cyclin D1 modulated the expression of survivin and the response of CRC cells to PAC. Furthermore, using the ChIP assay, we have shown PAC-dependent reduction in the binding of STAT3 to the cyclin D1 promoter in vivo. Additionally, PAC suppressed the epithelial-to-mesenchymal process through down-regulating the mesenchymal markers (N-cadherin, vimentin and Twist1) and inhibiting the invasion/migration abilities of the CRC cells via repressing the pro-migration/invasion protein kinases AKT and ERK1/2. In addition, PAC inhibited tumor growth and repressed the JAK2/STAT3, AKT/mTOR and MEK/ERK pathways as well as their common downstream effectors cyclin D1 and survivin in humanized CRC xenografts. Collectively, these results indicate that PAC has potent anti-CRC effects, and therefore could constitute an effective alternative chemotherapeutic agent, which may consolidate the adjuvant treatment of colon cancer.

  13. 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) ...

  14. 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

  15. 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)

  16. 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

  17. 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.

  18. 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

  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.

  20. Standard and Quantitative Analysis of Cyclin E Threshold by Cyclin E/DNA Multiparameter Flow Cytometry

    Institute of Scientific and Technical Information of China (English)

    XIE Daxing; FENG Yongdong; WU Jianhong; LIU Shuangyou; LI Xiaolan; TAO Deding; GONG Jianping

    2005-01-01

    Summary: The threshold of cyclin E expression at G1/S boundary is a characteristic feature of cell cycle progressing. In this study, we tried to develop a quantitative approach to analyze cyclin E threshold by multiparameter flow cytometry. The expression of cyclin E in exponentially growing MOLT-4 cells was detected under different photomultiplier tube (PMT) voltages by cyclin E/DNA multiparameter flow cytometry. Additionally, cyclin E was detected in cells which were treated with caffeine and cycloheximide (CHX) under the same PMT voltage. Moreover, the expression of cyclin E in MOLT-4 cells was compared with that in JURKAT cells. Cyclin E threshold was quantified by formula B2/A×C (A, B, C indicates the minimum, threshold, and maximum of cyclin E fluorescence intensity, respectively). Results showed that in MOLT-4 cells, cyclin E threshold calculated by formula B2/A×C was invariable under different PMT settings. It was decreased in cells treated with caffeine and remained changeless in cells treated with cycloheximide. Cyclin E threshold in JURKAT cells was much lower than that in MOLT-4 cells. It was suggested that Formula B2/A×C we firstly set up could be used to analyze cyclin E expression threshold quantitatively.

  1. Androgen suppresses the proliferation of androgen receptor-positive castration-resistant prostate cancer cells via inhibition of Cdk2, CyclinA, and Skp2.

    Directory of Open Access Journals (Sweden)

    John M Kokontis

    Full Text Available The majority of prostate cancer (PCa patient receiving androgen ablation therapy eventually develop castration-resistant prostate cancer (CRPC. We previously reported that androgen treatment suppresses Skp2 and c-Myc through androgen receptor (AR and induced G1 cell cycle arrest in androgen-independent LNCaP 104-R2 cells, a late stage CRPC cell line model. However, the mechanism of androgenic regulation of Skp2 in CRPC cells was not fully understood. In this study, we investigated the androgenic regulation of Skp2 in two AR-positive CRPC cell line models, the LNCaP 104-R1 and PC-3AR Cells. The former one is an early stage androgen-independent LNCaP cells, while the later one is PC-3 cells re-expressing either wild type AR or mutant LNCaP AR. Proliferation of LNCaP 104-R1 and PC-3AR cells is not dependent on but is suppressed by androgen. We observed in this study that androgen treatment reduced protein expression of Cdk2, Cdk7, Cyclin A, cyclin H, Skp2, c-Myc, and E2F-1; lessened phosphorylation of Thr14, Tyr15, and Thr160 on Cdk2; decreased activity of Cdk2; induced protein level of p27(Kip1; and caused G1 cell cycle arrest in LNCaP 104-R1 cells and PC-3AR cells. Overexpression of Skp2 protein in LNCaP 104-R1 or PC-3AR cells partially blocked accumulation of p27(Kip1 and increased Cdk2 activity under androgen treatment, which partially blocked the androgenic suppressive effects on proliferation and cell cycle. Analyzing on-line gene array data of 214 normal and PCa samples indicated that gene expression of Skp2, Cdk2, and cyclin A positively correlates to each other, while Cdk7 negatively correlates to these genes. These observations suggested that androgen suppresses the proliferation of CRPC cells partially through inhibition of Cyclin A, Cdk2, and Skp2.

  2. Androgen suppresses the proliferation of androgen receptor-positive castration-resistant prostate cancer cells via inhibition of Cdk2, CyclinA, and Skp2.

    Science.gov (United States)

    Kokontis, John M; Lin, Hui-Ping; Jiang, Shih Sheng; Lin, Ching-Yu; Fukuchi, Junichi; Hiipakka, Richard A; Chung, Chi-Jung; Chan, Tzu-Min; Liao, Shutsung; Chang, Chung-Ho; Chuu, Chih-Pin

    2014-01-01

    The majority of prostate cancer (PCa) patient receiving androgen ablation therapy eventually develop castration-resistant prostate cancer (CRPC). We previously reported that androgen treatment suppresses Skp2 and c-Myc through androgen receptor (AR) and induced G1 cell cycle arrest in androgen-independent LNCaP 104-R2 cells, a late stage CRPC cell line model. However, the mechanism of androgenic regulation of Skp2 in CRPC cells was not fully understood. In this study, we investigated the androgenic regulation of Skp2 in two AR-positive CRPC cell line models, the LNCaP 104-R1 and PC-3AR Cells. The former one is an early stage androgen-independent LNCaP cells, while the later one is PC-3 cells re-expressing either wild type AR or mutant LNCaP AR. Proliferation of LNCaP 104-R1 and PC-3AR cells is not dependent on but is suppressed by androgen. We observed in this study that androgen treatment reduced protein expression of Cdk2, Cdk7, Cyclin A, cyclin H, Skp2, c-Myc, and E2F-1; lessened phosphorylation of Thr14, Tyr15, and Thr160 on Cdk2; decreased activity of Cdk2; induced protein level of p27(Kip1); and caused G1 cell cycle arrest in LNCaP 104-R1 cells and PC-3AR cells. Overexpression of Skp2 protein in LNCaP 104-R1 or PC-3AR cells partially blocked accumulation of p27(Kip1) and increased Cdk2 activity under androgen treatment, which partially blocked the androgenic suppressive effects on proliferation and cell cycle. Analyzing on-line gene array data of 214 normal and PCa samples indicated that gene expression of Skp2, Cdk2, and cyclin A positively correlates to each other, while Cdk7 negatively correlates to these genes. These observations suggested that androgen suppresses the proliferation of CRPC cells partially through inhibition of Cyclin A, Cdk2, and Skp2.

  3. 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.

  4. 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...

  5. Long-term stable expression of antisense cDNA of cyclin B1 profoundly inhibits the proliferation of tumor cells and suppresses tumorigenicity in implanted mice

    Institute of Scientific and Technical Information of China (English)

    ZHANG Tao; SU Xiao-mei; ZHANG Ling; LI Ji-cheng; WEI Dong; WEI Yu-quan; ZHANG Ru; CHENG Peng; CHEN Xian-cheng; LIU Huan-yi

    2008-01-01

    Background Cyclin B1 (CLB1) is necessary for mitotic initiation in mammalian cells and plays important roles in cancer development. Therefore, a potential strategy in cancer therapy is to suppress the activity of CLB1 by delivering antisense constructs of CLB1 into tumor cells. In previous CLB1 studies, antisense constructs with a short half life were often used and these constructs might not persistently inhibit CLB1.Methods We successfully created a recombinant plasmid encoding the full-length antisense cDNA of mouse cyclin B1 (AS-mCLB1) and transfected this construct to the murine Lewis lung carcinoma (LL/2) and CT-26 colon carcinoma (CT-26) cells. We isolated clones of LL/2 and CT-26 transfectants with stable expression of AS-mGLB1. Reverse transcriptional polymerase chain reaction (RT-PCR) and Western blot were applied to detect the expression of the mRNA and protein levels of CLB1. To further test the efficacy of this strategy in vivo, AS-mCLBl-expressing LL/2 and CT-26 transfectants were implanted into mice.Results We found the expression of the mRNA and protein levels of CLB1 decrease in these trensfectants. The inhibition of CLB1 caused prominent G1 arrest, abnormal morphology, retarded cell growth and an increase in apoptosis. In AS-mCLB1-expressing LL/2 and CT-26 transfectants implanted mice, tumorigenicity was effectively suppressed compared with the controls. In addition, the expression of AS-mCLB1 also significantly increases the survival duration of implanted animals.Conclusion AS-mCLB1 is likely to be useful in future cancer therapy, which may be associated with its ability to down-regulate the expression of CLB1 and then induce G1 arrest and apoptosis in tumor cells.

  6. 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 ...

  7. Cyclin-dependent kinase suppression by WEE1 kinase protects the genome through control of replication initiation and nucleotide consumption

    DEFF Research Database (Denmark)

    Beck, Halfdan; Nähse-Kumpf, Viola; Larsen, Marie Sofie Yoo;

    2012-01-01

    of replication. This leads to nucleotide shortage and reduces replication fork speed, which is followed by SLX4/MUS81-mediated DNA double-strand breakage. Fork speed is normalized and DNA double-strand break (DSB) formation is suppressed when CDT1, a key factor for replication initiation, is depleted...... that deregulated CDK activity, such as that occurring following inhibition of WEE1 kinase or activation of oncogenes, induces replication stress and loss of genomic integrity through increased firing of replication origins and subsequent nucleotide shortage....

  8. miR-1 suppresses the growth of esophageal squamous cell carcinoma in vivo and in vitro through the downregulation of MET, cyclin D1 and CDK4 expression

    Science.gov (United States)

    JIANG, SEN; ZHAO, CHAO; YANG, XIAODI; LI, XIANGYANG; PAN, QING; HUANG, HAIJIN; WEN, XUYANG; SHAN, HUSHENG; LI, QIANWEN; DU, YUNXIANG; ZHAO, YAPING

    2016-01-01

    Several aberrant microRNAs (miRNAs or miRs) have been implicated in esophageal cancer (EC), which is widely prevalent in China. However, their role in EC tumorigenesis has not yet been fully elucidated. In the present study, we determined that miR-1 was downregulated in esophageal squamous cell carcinoma (ESCC) tissues compared with adjacent non-neoplastic tissues using RT-qPCR, and confirmed this using an ESCC cell line. Using a nude mouse xenograft model, we confirmed that the re-expression of miR-1 significantly inhibited ESCC tumor growth. A tetrazolium assay and a trypan blue exclusion assay revealed that miR-1 suppressed ESCC cell proliferation and increased apoptosis, whereas the silencing of miR-1 promoted cell proliferation and decreased apoptosis, suggesting that miR-1 is a novel tumor suppressor. To elucidate the molecular mechanisms of action of miR-1 in ESCC, we investigated putative targets using bioinformatics tools. MET, cyclin D1 and cyclin-dependent kinase 4 (CDK4), which are involved in the hepatocyte growth factor (HGF)/MET signaling pathway, were found to be targets of miR-1. miR-1 expression inversely correlated with MET, cyclin D1 and CDK4 expression in ESCC cells. miR-1 directly targeted MET, cyclin D1 and CDK4, suppressing ESCC cell growth. The newly identified miR-1/MET/cyclin D1/CDK4 axis provides new insight into the molecular mechanisms of ESCC pathogenesis and indicates a novel strategy for the diagnosis and treatment of ESCC. PMID:27247259

  9. 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

  10. 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.

  11. 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 ...

  12. Bromodichloromethane induces cell proliferation in different tissues of male F344 rats by suppression of E-cadherin expression via hypermethylation or transcriptional activation of c-myc and cyclin D1.

    Science.gov (United States)

    Liao, Jing; Li, Xiao-Feng; Zhou, Shun-Chang; Luo, Yan; Liu, Ai-Lin; Lu, Wen-Qing

    2013-11-25

    The aim of this study was to investigate the mechanism of bromodichloromethane (BDCM) - induced cell proliferation in different tissues of male F344 rats. Rats were administered at doses of 0 and 100mg/kg/day BDCM dissolved in corn oil by gavage for 5 days/week for 1, 4, 8 and 12 weeks. Then the colon, kidney and liver were collected. No histologic lesions were observed in the colon of rats exposed to BDCM, while there were mild nephrotoxicity and marginal hepatotoxicity related to BDCM treatment. Moreover, BDCM enhanced cell proliferation in the colon and kidney but not in the liver. In colons, hypermethylation in E-cadherin promoter might be associated with inhibition of mRNA and protein expression after 12 weeks of BDCM exposure. In kidneys, BDCM decreased E-cadherin mRNA expression, accompanying with transcriptional activation of c-myc and cyclin D1. However, suppression of E-cadherin mRNA and protein expression occurred in the absence of significant changes in DNA methylation. Therefore, suppression of E-cadherin expression via hypermethylation or transcriptional activation of c-myc and cyclin D1 may be involved in BDCM-induced cell proliferation in different tissues of male F344 rats.

  13. Translational control of cyclins

    OpenAIRE

    Lai Ming-Chih; Tarn Woan-Yuh

    2011-01-01

    Abstract Regulation of cyclin levels is important for many cell cycle-related processes and can occur at several different steps of gene expression. Translational regulation of cyclins, which occurs by a variety of regulatory mechanisms, permits a prompt response to signal transduction pathways induced by environmental stimuli. This review will summarize translational control of cyclins and its influence on cell cycle progression.

  14. 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

  15. 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 ( ...

  16. Inhibiting the cyclin-dependent kinase CDK5 blocks pancreatic cancer formation and progression through the suppression of Ras-Ral signaling.

    Science.gov (United States)

    Feldmann, Georg; Mishra, Anjali; Hong, Seung-Mo; Bisht, Savita; Strock, Christopher J; Ball, Douglas W; Goggins, Michael; Maitra, Anirban; Nelkin, Barry D

    2010-06-01

    Cyclin-dependent kinase 5 (CDK5), a neuronal kinase that functions in migration, has been found to be activated in some human cancers in which it has been implicated in promoting metastasis. In this study, we investigated the role of CDK5 in pancreatic cancers in which metastatic disease is most common at diagnosis. CDK5 was widely active in pancreatic cancer cells. Functional ablation significantly inhibited invasion, migration, and anchorage-independent growth in vitro, and orthotopic tumor formation and systemic metastases in vivo. CDK5 blockade resulted in the profound inhibition of Ras signaling through its critical effectors RalA and RalB. Conversely, restoring Ral function rescued the effects of CDK5 inhibition in pancreatic cancer cells. Our findings identify CDK5 as a pharmacologically tractable target to degrade Ras signaling in pancreatic cancer.

  17. Inhibiting the cyclin-dependent kinase CDK5 blocks pancreatic cancer formation and progression via suppression of Ras-Ral signaling

    Science.gov (United States)

    Feldmann, Georg; Mishra, Anjali; Hong, Seung-Mo; Bisht, Savita; Strock, Christopher J.; Ball, Douglas W.; Goggins, Michael; Maitra, Anirban; Nelkin, Barry D.

    2011-01-01

    Cyclin-dependent kinase 5 (CDK5), a neuronal kinase that functions in migration, has been found to be activated in some human cancers where it has been implicated in promoting metastasis. In this study, we investigated the role of CDK5 in pancreatic cancers where metastatic disease is most common at diagnosis. CDK5 was widely active in pancreatic cancer cells. Functional ablation significantly inhibited invasion, migration and anchorage-independent growth in vitro, and orthotopic tumor formation and systemic metastases in vivo. CDK5 blockade resulted in profound inhibition of Ras signaling through its critical effectors RalA and RalB. Conversely, restoring Ral function rescued the effects of CDK5 inhibition in pancreatic cancer cells. Our findings identify CDK5 as a pharmacologically tractable target to degrade Ras signaling in pancreatic cancer. PMID:20484029

  18. Translational control of cyclins

    Directory of Open Access Journals (Sweden)

    Lai Ming-Chih

    2011-02-01

    Full Text Available Abstract Regulation of cyclin levels is important for many cell cycle-related processes and can occur at several different steps of gene expression. Translational regulation of cyclins, which occurs by a variety of regulatory mechanisms, permits a prompt response to signal transduction pathways induced by environmental stimuli. This review will summarize translational control of cyclins and its influence on cell cycle progression.

  19. Caffeine and coffee as therapeutics against Alzheimer's disease.

    Science.gov (United States)

    Arendash, Gary W; Cao, Chuanhai

    2010-01-01

    Epidemiologic studies have increasingly suggested that caffeine/coffee could be an effective therapeutic against Alzheimer's disease (AD). We have utilized a transgenic mouse model for AD in well-controlled studies to determine if caffeine and/or coffee have beneficial actions to protect against or reverse AD-like cognitive impairment and AD pathology. AD mice given caffeine in their drinking water from young adulthood into older age showed protection against memory impairment and lower brain levels of the abnormal protein (amyloid-beta; Abeta) thought to be central to AD pathogenesis. Moreover, "aged" cognitively-impaired AD mice exhibited memory restoration and lower brain Abeta levels following only 1-2 months of caffeine treatment. We believe that the cognitive benefits of chronic caffeine administration in AD mice are due to caffeine itself, and not metabolites of caffeine; this, because our long-term administration of theophylline to AD mice provided no cognitive benefits. In acute studies involving AD mice, one oral caffeine treatment quickly reduced both brain and plasma Abeta levels - similarly rapid alterations in plasma Abeta levels were seen in humans following acute caffeine administration. "Caffeinated" coffee provided to AD mice also quickly decreased plasma Abeta levels, but not "decaffeinated" coffee, suggesting that caffeine is critical to decreasing blood Abeta levels. Caffeine appears to provide its disease-modifying effects through multiple mechanisms, including a direct reduction of Abeta production through suppression of both beta- and gamma-secretase levels. These results indicate a surprising ability of moderate caffeine intake (the human equivalent of 500 mg caffeine or 5 cups of coffee per day) to protect against or treat AD in a mouse model for the disease and a therapeutic potential for caffeine against AD in humans.

  20. 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

  1. 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 ...

  2. 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 ...

  3. 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

  4. 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…

  5. Caffeine: Friend or Foe?

    Science.gov (United States)

    Doepker, Candace; Lieberman, Harris R; Smith, Andrew Paul; Peck, Jennifer D; El-Sohemy, Ahmed; Welsh, Brian T

    2016-01-01

    The debate on the safety of and regulatory approaches for caffeine continues among various stakeholders and regulatory authorities. This decision-making process comes with significant challenges, particularly when considering the complexities of the available scientific data, making the formulation of clear science-based regulatory guidance more difficult. To allow for discussions of a number of key issues, the North American Branch of the International Life Sciences Institute (ILSI) convened a panel of subject matter experts for a caffeine-focused session entitled "Caffeine: Friend or Foe?," which was held during the 2015 ILSI Annual Meeting. The panelists' expertise covered topics ranging from the natural occurrence of caffeine in plants and interindividual metabolism of caffeine in humans to specific behavioral, reproductive, and cardiovascular effects related to caffeine consumption. Each presentation highlighted the potential risks, benefits, and challenges that inform whether caffeine exposure warrants concern. This paper aims to summarize the key topics discussed during the session.

  6. 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 ...

  7. Caffeine intake and fecundability

    DEFF Research Database (Denmark)

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

    1998-01-01

    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...... between caffeine intake and fecundability was analyzed in a logistic regression model with the outcome at each cycle (pregnant or not pregnant) in a Cox discrete model calculating the fecundability odds-ratio (FR). Compared to nonsmoking women with caffeine intake less than 300 mg/d, nonsmoking women who...... caffeine and smoking is biologically plausible, and the lack of effect among smokers may be due to faster metabolism of caffeine. Our findings suggest that especially nonsmoking women who wish to achieve a pregnancy might benefit from a reduced caffeine intake....

  8. Cyclin-dependent kinases.

    Science.gov (United States)

    Malumbres, Marcos

    2014-01-01

    Cyclin-dependent kinases (CDKs) are protein kinases characterized by needing a separate subunit - a cyclin - that provides domains essential for enzymatic activity. CDKs play important roles in the control of cell division and modulate transcription in response to several extra- and intracellular cues. The evolutionary expansion of the CDK family in mammals led to the division of CDKs into three cell-cycle-related subfamilies (Cdk1, Cdk4 and Cdk5) and five transcriptional subfamilies (Cdk7, Cdk8, Cdk9, Cdk11 and Cdk20). Unlike the prototypical Cdc28 kinase of budding yeast, most of these CDKs bind one or a few cyclins, consistent with functional specialization during evolution. This review summarizes how, although CDKs are traditionally separated into cell-cycle or transcriptional CDKs, these activities are frequently combined in many family members. Not surprisingly, deregulation of this family of proteins is a hallmark of several diseases, including cancer, and drug-targeted inhibition of specific members has generated very encouraging results in clinical trials. PMID:25180339

  9. 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 ...

  10. 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.

  11. 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...

  12. Caffeine Positively Modulates Ferritin Heavy Chain Expression in H460 Cells: Effects on Cell Proliferation

    Science.gov (United States)

    Battaglia, Anna Martina; Faniello, Maria Concetta; Cuda, Giovanni; Costanzo, Francesco

    2016-01-01

    Both the methylxanthine caffeine and the heavy subunit of ferritin molecule (FHC) are able to control the proliferation rate of several cancer cell lines. While caffeine acts exclusively as a negative modulator of cell proliferation, FHC might reduce or enhance cell viability depending upon the different cell type. In this work we have demonstrated that physiological concentrations of caffeine reduce the proliferation rate of H460 cells: along with the modulation of p53, pAKT and Cyclin D1, caffeine also determines a significant FHC up-regulation through the activation of its transcriptional efficiency. FHC plays a central role in the molecular pathways modulated by caffeine, ending in a reduced cell growth, since its specific silencing by siRNA almost completely abolishes caffeine effects on H460 cell proliferation. These results allow the inclusion of ferritin heavy subunits among the multiple molecular targets of caffeine and open the way for studying the relationship between caffeine and intracellular iron metabolism. PMID:27657916

  13. 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

  14. 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.

  15. Suberoylanilide hydroxamic acid (SAHA) inhibits EGF-induced cell transformation via reduction of cyclin D1 mRNA stability

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jingjie [State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Rd, Haidian District, Beijing 100191 (China); Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Rd, Tuxedo, NY 10987 (United States); Ouyang, Weiming; Li, Jingxia; Zhang, Dongyun; Yu, Yonghui; Wang, York [Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Rd, Tuxedo, NY 10987 (United States); Li, Xuejun, E-mail: xjli@bjmu.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Rd, Haidian District, Beijing 100191 (China); Huang, Chuanshu, E-mail: chuanshu.huang@nyumc.org [Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Rd, Tuxedo, NY 10987 (United States)

    2012-09-01

    Suberoylanilide hydroxamic acid (SAHA) inhibiting cancer cell growth has been associated with its downregulation of cyclin D1 protein expression at transcription level or translation level. Here, we have demonstrated that SAHA inhibited EGF-induced Cl41 cell transformation via the decrease of cyclin D1 mRNA stability and induction of G0/G1 growth arrest. We found that SAHA treatment resulted in the dramatic inhibition of EGF-induced cell transformation, cyclin D1 protein expression and induction of G0/G1 growth arrest. Further studies showed that SAHA downregulation of cyclin D1 was only observed with endogenous cyclin D1, but not with reconstitutionally expressed cyclin D1 in the same cells, excluding the possibility of SAHA regulating cyclin D1 at level of protein degradation. Moreover, SAHA inhibited EGF-induced cyclin d1 mRNA level, whereas it did not show any inhibitory effect on cyclin D1 promoter-driven luciferase reporter activity under the same experimental conditions, suggesting that SAHA may decrease cyclin D1 mRNA stability. This notion was supported by the results that treatment of cells with SAHA decreased the half-life of cyclin D1 mRNA from 6.95 h to 2.57 h. Consistent with downregulation of cyclin D1 mRNA stability, SAHA treatment also attenuated HuR expression, which has been well-characterized as a positive regulator of cyclin D1 mRNA stability. Thus, our study identifies a novel mechanism responsible for SAHA inhibiting cell transformation via decreasing cyclin D1 mRNA stability and induction of G0/G1 growth arrest in Cl41 cells. -- Highlights: ► SAHA inhibits cell transformation in Cl41 cells. ► SAHA suppresses Cyclin D1 protein expression. ► SAHA decreases cyclin D1 mRNA stability.

  16. 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.

  17. 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

  18. 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

  19. 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…

  20. 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...

  1. Caffeine addiction? Caffeine for youth? Time to act!

    Science.gov (United States)

    Budney, Alan J; Emond, Jennifer A

    2014-11-01

    While data accumulate and discussion evolves on the clinical importance of caffeine addiction and its classification, the growing practices of (i) adding increasing amounts of caffeine to drinks and other consumables, (ii) promoting these as performance enhancers and (iii) targeting youth as the consumer raise concerns that require immediate action.

  2. Role of CyclinD1 and CDK4 in the Carcinogenesis Induced by Silica

    Institute of Scientific and Technical Information of China (English)

    KE-XIA YAN; BING-CI LIU; XIANG-LIN SHI; BAO-RONG YOU; MING XU

    2005-01-01

    Objective To study the role of cyclinD1 and CDK4 in malignant transformation of human fetal lung diploid fibroblast cell line(2BS) induced by silica. Methods Recombination vectors with sense and antisense pXJ41-cyclinD1 and pXJ41-CDK4 were constructed, and then transfected into the malignant transformed cells induced by silica, respectively. At the same time, pXJ41-neo was used as the control. Results During the progress of the malignant transformation of 2BS cells induced by silica, cyclinD1 and CDK4 were overexpressed. Antisense RNA suppressed cyclinD1 and CDK4 gene expression in the antisense pXJ41-cyclinD1 and pXJ41-CDK4 transfected cells. Antisense RNA led to cell cycle arrest, resulting in lengthened G1 phase (the percentages of cells in the G1 phase changed from 45.1% to 52.7% and 58.0% for cyclinD1 and CDK4 transfected cells, respectively), and eventually attenuated the increase of the proliferation of malignant transformed cells induced by silica. Compared with malignant transformed cells induced by silica, cells transfected with antisense pXJ41-cyclinD1 and pXJ41-CDK4 showed obviously reduced growth rates. On the 8th day, the suppression rates were 58.69 and 77.43% (the growth rate of malignant transformed cells induced by silica was 100%), doubling time changed from 21.0 h to 31.4 h and 21.0 h to 42.7 h, respectively, the growth capacities on soft agar of cells transfected by antisense pXJ41-cyclinD1 and pXJ41-CDK4 decreased obviously. Conclusion CyclinD1 and CDK4 play an important role in maintaining transformed phenotype of the cancer cells.

  3. Crude caffeine reduces memory impairment and amyloid β(1-42) levels in an Alzheimer's mouse model.

    Science.gov (United States)

    Chu, Yi-Fang; Chang, Wen-Han; Black, Richard M; Liu, Jia-Ren; Sompol, Pradoldej; Chen, Yumin; Wei, Huilin; Zhao, Qiuyan; Cheng, Irene H

    2012-12-01

    Alzheimer's disease (AD), a chronic neurodegenerative disorder associated with the abnormal accumulations of amyloid β (Aβ) peptide and oxidative stress in the brain, is the most common form of dementia among the elderly. Crude caffeine (CC), a major by-product of the decaffeination of coffee, has potent hydrophilic antioxidant activity and may reduce inflammatory processes. Here, we showed that CC and pure caffeine intake had beneficial effects in a mouse model of AD. Administration of CC or pure caffeine for 2months partially prevented memory impairment in AD mice, with CC having greater effects than pure caffeine. Furthermore, consumption of CC, but not pure caffeine, reduced the Aβ(1-42) levels and the number of amyloid plaques in the hippocampus. Moreover, CC and caffeine protected primary neurons from Aβ-induced cell death and suppressed Aβ-induced caspase-3 activity. Our data indicate that CC may contain prophylactic agents against the cell death and the memory impairment in AD.

  4. 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

  5. Caffeine prevents LPS-induced inflammatory responses in RAW264.7 cells and zebrafish.

    Science.gov (United States)

    Hwang, Ji-Hyun; Kim, Kui-Jin; Ryu, Su-Jung; Lee, Boo-Yong

    2016-03-25

    Caffeine is a white crystalline xanthine alkaloid found in the seeds of coffee plants and leaves of the tea bush. In this study, we evaluated whether caffeine exerts anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation both in vitro and in vivo. RAW264.7 cells were treated with various concentrations of caffeine in the presence or absence of LPS. Caffeine decreased the LPS-induced inflammatory mediator, nitric oxide (NO). Caffeine treatment also reduced the expression of pro-inflammatory genes, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-3, IL-6 and IL-12, and decreased both IL-6 secretion and phosphorylated p38MAPK expression in LPS-treated RAW264.7 cells. Caffeine inhibited nuclear translocation of nuclear factor κB (NF-κB) via IκBα phosphorylation. In addition, caffeine inhibited LPS-induced NO production in zebrafish. These results suggest that caffeine may suppress LPS-induced inflammatory responses in RAW264.7 cells by regulating NF-κB activation and MAPK phosphorylation.

  6. The Effects of Caffeine on Athletic Performance

    Science.gov (United States)

    McDaniel, Larry W.; McIntire, Kyle; Streitz, Carmyn; Jackson, Allen; Gaudet, Laura

    2010-01-01

    Athletes who use caffeine before exercising or competition may be upgrading themselves more than they realize. Caffeine is classified as a stimulant and is the most commonly used drug in the world. Caffeine has the same affects that amphetamines and cocaine have, just to a lesser degree. Caffeine crosses the membranes of all the body's tissues. It…

  7. 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.

  8. 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...

  9. Cyclin B1 Vaccine Delays Spontaneous Tumors

    Science.gov (United States)

    Laura A, Vella; Min, Yu; Amy, Phillips; Olivera J, Finn

    2012-01-01

    We previously identified cyclin B1-specific T cells and antibodies in cancer patients with cyclin B1+ tumors and also in some healthy individuals. We also demonstrated that these responses may be important in cancer immunosurveillance by showing that vaccination against cyclin B1 prevents growth of transplantable cyclin B1+ tumors in mice. Constitutive overexpression of cyclin B1 was determined to correlate with the lack of p53 function. This allowed us to use p53−/− mice as a model that better approximates human disease. p53−/− mice spontaneously develop cyclin B1+ tumors. At 5–6 weeks of age, when the mice were still healthy with no evidence of tumor, they received the cyclin B1 vaccine and were then observed for tumor growth. We demonstrate that cyclin B1 vaccination can delay spontaneous cyclin B1+ tumor growth and increases median survival of tumor bearing p53−/− mice. PMID:19769738

  10. The Cyclin-Dependent Kinase Ortholog pUL97 of Human Cytomegalovirus Interacts with Cyclins

    Directory of Open Access Journals (Sweden)

    Laura Graf

    2013-12-01

    Full Text Available The human cytomegalovirus (HCMV-encoded protein kinase, pUL97, is considered a cyclin-dependent kinase (CDK ortholog, due to shared structural and functional characteristics. The primary mechanism of CDK activation is binding to corresponding cyclins, including cyclin T1, which is the usual regulatory cofactor of CDK9. This study provides evidence of direct interaction between pUL97 and cyclin T1 using yeast two-hybrid and co-immunoprecipitation analyses. Confocal immunofluorescence revealed partial colocalization of pUL97 with cyclin T1 in subnuclear compartments, most pronounced in viral replication centres. The distribution patterns of pUL97 and cyclin T1 were independent of HCMV strain and host cell type. The sequence domain of pUL97 responsible for the interaction with cyclin T1 was between amino acids 231–280. Additional co-immunoprecipitation analyses showed cyclin B1 and cyclin A as further pUL97 interaction partners. Investigation of the pUL97-cyclin T1 interaction in an ATP consumption assay strongly suggested phosphorylation of pUL97 by the CDK9/cyclin T1 complex in a substrate concentration-dependent manner. This is the first demonstration of interaction between a herpesviral CDK ortholog and cellular cyclins.

  11. 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/caffeine....Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/caffeine....Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/caffeine...-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

  12. 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.

  13. Tanshinone I induces cyclin D1 proteasomal degradation in an ERK1/2 dependent way in human colorectal cancer cells.

    Science.gov (United States)

    Kim, Mi Kyoung; Park, Gwang Hun; Eo, Hyun Ji; Song, Hun Min; Lee, Jin Wook; Kwon, Min Ji; Koo, Jin Suk; Jeong, Jin Boo

    2015-03-01

    Tanshinone I (TAN I) as one of the naturally occurring diterpenes from Salvia miltiorrhizae Bunge (Danshen) has been reported to exhibit an anti-cancer activity. However, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to elucidate the biological mechanism by which TAN I may induce the inhibition of cell growth in human colorectal cancer cells. The treatment of TAN I suppressed the cell proliferation in HCT116 and SW480 cells and decreased the level of cyclin D1 protein. However, the mRNA level of cyclin D1 did not changed by TAN I treatment. Inhibition of proteasomal degradation by MG132 blocked TAN I-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with TAN I. In addition, phosphorylation of cyclin D1 at threonine-286 was increased by TAN I and a point mutation of threonine-286 to alanine attenuated TAN I-mediated cyclin D1 downregulation. Inhibition of ERK1/2 suppressed cyclin D1 phosphorylation and subsequent downregulation by TAN I. From these results, we suggest that TAN I-mediated cyclin D1 downregulation may result from proteasomal degradation through its ERK1/2-mediated phosphorylation of threonine-286. In conclusion, the current study provides new mechanistic link between TAN I, cyclin D1 downregulation and cell growth in human colorectal cancer cells. PMID:25615593

  14. MicroRNA-1 and-16 inhibit cardiomyocyte hypertrophy by targeting cyclins/Rb pathway

    Institute of Scientific and Technical Information of China (English)

    SHAN Zhi-xin; ZHU Jie-ning; TANG Chun-mei; ZHU Wen-si; LIN Qiu-xiong; HU Zhi-qin; FU Yong-heng; ZHANG Meng-zhen

    2016-01-01

    AIM:MicroRNAs ( miRNAs) were recognized to play significant roles in cardiac hypertrophy .But, it remains unknown whether cyclin/Rb pathway is modulated by miRNAs during cardiac hypertrophy .This study investigates the potential roles of microRNA-1 (miR-1) and microRNA-16 (miR-16) in modulating cyclin/Rb pathway during cardiomyocyte hypertrophy .METHODS:An animal model of hypertrophy was established in a rat with abdominal aortic constriction (AAC).In addition, a cell model of hypertrophy was also achieved based on PE-promoted neonatal rat ventricular cardiomyocyte .RESULTS:miR-1 and-16 expression were markedly de-creased in hypertrophic myocardium and hypertrophic cardiomyocytes in rats .Overexpression of miR-1 and -16 suppressed rat cardiac hypertrophy and hypertrophic phenotype of cultured cardiomyocytes .Expression of cyclins D1, D2 and E1, CDK6 and phosphorylated pRb was increased in hypertrophic myocardium and hypertrophic cardiomyocytes , but could be reversed by enforced expression of miR-1 and -16.CDK6 was validated to be modulated post-transcriptionally by miR-1, and cyclins D1, D2 and E1 were further validated to be modulated post-transcriptionally by miR-16.CONCLUSION: Attenuations of miR-1 and -16 provoke cardiomyocyte hypertrophy via derepressing the cyclins D1, D2, E1 and CDK6, and activating cyclin/Rb pathway.

  15. Caffeine intake among adolescents in Delhi

    Directory of Open Access Journals (Sweden)

    Mridul Gera

    2016-01-01

    Full Text Available Background: Availability and advertising of caffeinated drinks is on the rise in Indian market. Excess caffeine intake may have deleterious effects on health. Objective: To estimate the daily consumption of caffeine among urban school-going adolescents from Delhi. Materials and Methods: A school-based survey was conducted to determine the amount and pattern of caffeine consumption among students of classes 9-12, using a self-administered questionnaire. Results: Of 300 participants (median age 15 year, 174 boys, 291 (97% were consuming caffeine [mean (SD: 121.0 (98.2 mg/day]. Nineteen (6% students were consuming more than 300 mg of caffeine per day. Tea/coffee contributed to more than 50% of the caffeine intake. The rest was derived from cola beverages, chocolates, and energy drinks. Conclusion: Average caffeine consumption among school-going adolescents from Delhi is high. The findings of this preliminary survey need to be confirmed in larger data sets.

  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 prevents d-galactose-induced cognitive deficits, oxidative stress, neuroinflammation and neurodegeneration in the adult rat brain.

    Science.gov (United States)

    Ullah, Faheem; Ali, Tahir; Ullah, Najeeb; Kim, Myeong Ok

    2015-11-01

    d-galactose has been considered a senescent model for age-related neurodegenerative disease. It induces oxidative stress which triggers memory impairment, neuroinflammation and neurodegeneration. Caffeine act as anti-oxidant and has been used in various model of neurodegenerative disease. Nevertheless, the effect of caffeine against d-galactose aging murine model of age-related neurodegenerative disease elucidated. Here, we investigated the neuroprotective effect of caffeine against d-galactose. We observed that chronic treatment of caffeine (3 mg/kg/day intraperitoneally (i.p) for 60 days) improved memory impairment and synaptic markers (Synaptophysin and PSD95) in the d-galactose treated rats. Chronic caffeine treatment reduced the oxidative stress via the reduction of 8-oxoguanine through immunofluorescence in the d-galactose-treated rats. Consequently caffeine treatment suppressed stress kinases p-JNK. Additionally, caffeine treatment significantly reduced the d-galactose-induced neuroinflammation through alleviation of COX-2, NOS-2, TNFα and IL-1β. Furthermore we also analyzed that caffeine reduced cytochrome C, Bax/Bcl2 ratio, caspase-9, caspase-3 and PARP-1 level. Moreover by evaluating the immunohistochemical results of Nissl and Fluro-Jade B staining showed that caffeine prevented the neurodegeneration in the d-galactose-treated rats. Our results showed that caffeine prevents the d-galactose-induced oxidative stress and consequently alleviated neuroinflammation and neurodegeneration; and synaptic dysfunction and memory impairment. Therefore, we could suggest that caffeine might be a dietary anti-oxidant agent and a good candidate for the age-related neurodegenerative disorders.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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…

  4. 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…

  5. 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.

  6. 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

  7. Caffeine mediates sustained inactivation of breast cancer-associated myofibroblasts via up-regulation of tumor suppressor genes.

    Directory of Open Access Journals (Sweden)

    Mysoon M Al-Ansari

    Full Text Available BACKGROUND: Active cancer-associated fibroblasts (CAFs or myofibroblasts play important roles not only in the development and progression of breast carcinomas, but also in their prognosis and treatment. Therefore, targeting these cells through suppressing their supportive procarcinogenic paracrine effects is mandatory for improving the current therapies that are mainly targeting tumor cells. To this end, we investigated the effect of the natural and pharmacologically safe molecule, caffeine, on CAF cells and their various procarcinogenic effects. METHODOLOGY/PRINCIPAL FINDINGS: We have shown here that caffeine up-regulates the tumor suppressor proteins p16, p21, p53 and Cav-1, and reduces the expression/secretion of various cytokines (IL-6, TGF-β, SDF-1 and MMP-2, and down-regulates α-SMA. Furthermore, caffeine suppressed the migratory/invasiveness abilities of CAF cells through PTEN-dependent Akt/Erk1/2 inactivation. Moreover, caffeine reduced the paracrine pro-invasion/-migration effects of CAF cells on breast cancer cells. These results indicate that caffeine can inactivate breast stromal myofibroblasts. This has been confirmed by showing that caffeine also suppresses the paracrine pro-angiogenic effect of CAF cells through down-regulating HIF-1αand its downstream effector VEGF-A. Interestingly, these effects were sustained in absence of caffeine. CONCLUSION/SIGNIFICANCE: The present findings provide a proof of principle that breast cancer myofibroblasts can be inactivated, and thereby caffeine may provide a safe and effective prevention against breast tumor growth/recurrence through inhibition of the procarcinogenic effects of active stromal fibroblasts.

  8. 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...

  9. 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

  10. 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 ...

  11. The effects of caffeine on wound healing.

    Science.gov (United States)

    Ojeh, Nkemcho; Stojadinovic, Olivera; Pastar, Irena; Sawaya, Andrew; Yin, Natalie; Tomic-Canic, Marjana

    2016-10-01

    The purine alkaloid caffeine is a major component of many beverages such as coffee and tea. Caffeine and its metabolites theobromine and xanthine have been shown to have antioxidant properties. Caffeine can also act as adenosine-receptor antagonist. Although it has been shown that adenosine and antioxidants promote wound healing, the effect of caffeine on wound healing is currently unknown. To investigate the effects of caffeine on processes involved in epithelialisation, we used primary human keratinocytes, HaCaT cell line and ex vivo model of human skin. First, we tested the effects of caffeine on cell proliferation, differentiation, adhesion and migration, processes essential for normal wound epithelialisation and closure. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) proliferation assay to test the effects of seven different caffeine doses ranging from 0·1 to 5 mM. We found that caffeine restricted cell proliferation of keratinocytes in a dose-dependent manner. Furthermore, scratch wound assays performed on keratinocyte monolayers indicated dose-dependent delays in cell migration. Interestingly, adhesion and differentiation remained unaffected in monolayer cultures treated with various doses of caffeine. Using a human ex vivo wound healing model, we tested topical application of caffeine and found that it impedes epithelialisation, confirming in vitro data. We conclude that caffeine, which is known to have antioxidant properties, impedes keratinocyte proliferation and migration, suggesting that it may have an inhibitory effect on wound healing and epithelialisation. Therefore, our findings are more in support of a role for caffeine as adenosine-receptor antagonist that would negate the effect of adenosine in promoting wound healing.

  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. Vitamin C Inhibits Benzo[a]pyrene-lnduced Cell Cycle Changes Partly via Cyclin D1/ E2F Pathway in Human Embryo Lung Fibroblasts

    Institute of Scientific and Technical Information of China (English)

    AI GAO; BING-CI LIU; XIANG-LIN SHI; CHUAN-SHU HUANG; XIAO-WEI JLA; BAO-RONG YOU; MENG YE; FU-HAI SHEN; HONG-JU DU

    2006-01-01

    Objective To study the molecular mechanism of the inhibitory effects of vitamin C on benzo[a]pyrene (B[a]P)-induced changes of cell cycle in human embryo lung fibroblast (HELF) cells. Methods The stable transfectants, HELF transfected with antisense cyclin D1 and antisense CDK4, were established. Cells were cultured and pretreated with vitamin C before stimulation with B[a]P for 24 h. The expression levels of cyclin D1, CDK4, E2F1, and E2F4 were determined by Western blot. Flow cytometric analysis was employed to detect the distributions of cell cycle. Results B[a]P significantly elevated the expression levels of cyclin D1, E2F1, and E2F4 in HELF cells. Vitamin C decreased the expression levels of cyclin D1, E2F1, and E2F4 in B[a]P-stimulated HELF cells. Dose-dependent relationships were not found between the different concentrations of vitamin C (10, 100, 500, 1000, and 5000 μmol/L) and the expression levels of cyclin D1, E2F1, and E2F4 in HELF cells. The expression levels of cyclin D1, E2F1, and E2F4 in B[a]P-treated transfectants were lower than those in B[a]P-treated HELF cells. The expression levels of cyclin D1 and E2F4 treated with vitamin C and antisense cyclin D1 were decreased compared with those treated with antisense cyclin D1 alone. The effects of vitamin C combined with antisense CDK4 on the expression levels of cyclin D1 and E2F1/E2F4 were similar to those of antisense CDK4 alone. B[a]P progressed HELF cells from G1 to S phase. Both vitamin C and antisense cyclin D1 suppressed the changes of cell cycle progressed by B[a]P. However, antisenseCDK4 did not attenuate the above changes. Vitamin C combined with antisense CDK4 markedly suppressed B[a]P-induced changes of cell cycle as compared with antisense CDK4. But the inhibitory effects of vitamin C combined with antisense cyclin D1 on B[a]P-induced changes of cell cycle were similar to those of vitamin C alone or antisense cyclin D1 alone. Conclusions B[a]P progressed HELF cells from G1 to S phase via

  14. 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

  15. 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

  16. 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

    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...

  17. 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.)

  18. 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

  19. 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.

  20. Combined effect of cyclin D3 expression and abrogation of cyclin D1 prevent mouse skin tumor development

    Science.gov (United States)

    Wang, Xian; Sistrunk, Christopher; Miliani de Marval, Paula L; Kim, Yongbaek

    2012-01-01

    We have previously demonstrated that ras-mediated skin tumorigenesis depends on signaling pathways that act preferentially through cyclin D1 and D2. Interestingly, the expression of cyclin D3 inhibits skin tumor development, an observation that conflicts with the oncogenic role of D-type cyclins in the mouse epidermis. Here, we show that simultaneous up and downregulation of particular members of the D-type cyclin family is a valuable approach to reduce skin tumorigenesis. We developed the K5D3/cyclin D1−/− compound mouse, which overexpresses cyclin D3 but lacks expression of cyclin D1 in the skin. Similar to K5D3 transgenic mice, keratinocytes from K5D3/cyclin D1−/− compound mice show a significant reduction of cyclin D2 levels. Therefore, this model allows us to determine the effect of cyclin D3 expression when combined with reduced or absent expression of the remaining two members of the D-type cyclin family in mouse epidermis. Our data show that induced expression of cyclin D3 compensates for the reduced level of cyclin D1 and D2, resulting in normal keratinocyte proliferation. However, simultaneous ablation of cyclin D1 and downregulation of cyclin D2 via cyclin D3 expression resulted in a robust reduction in ras-mediated skin tumorigenesis. We conclude that modulation of the levels of particular members of the D-type cyclin family could be useful to inhibit tumor development and, in particular, ras-mediated tumorigenesis. PMID:22214766

  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 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.

  3. Caffeinated energy drinks--a growing problem.

    Science.gov (United States)

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

    2009-01-01

    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 aggressive marketing of energy drinks, targeted primarily toward young males, for psychoactive, performance-enhancing and stimulant drug effects. There are increasing reports of caffeine intoxication from energy drinks, and it seems likely that problems with caffeine dependence and withdrawal will also increase. In children and adolescents who are not habitual caffeine users, vulnerability to caffeine intoxication may be markedly increased due to an absence of pharmacological tolerance. Genetic factors may also contribute to an individual's vulnerability to caffeine-related disorders including caffeine intoxication, dependence, and withdrawal. The combined use of caffeine and alcohol is increasing sharply, and studies suggest that such combined use may increase the rate of alcohol-related injury. Several studies suggest that energy drinks may serve as a gateway to other forms of drug dependence. Regulatory implications concerning labeling and advertising, and the clinical implications for children and adolescents are discussed. PMID:18809264

  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 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

  6. 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.

  7. 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 ...

  8. p21/Cyclin E pathway modulates anticlastogenic function of Bmi-1 in cancer cells.

    Science.gov (United States)

    Deng, Wen; Zhou, Yuan; Tiwari, Agnes F Y; Su, Hang; Yang, Jie; Zhu, Dandan; Lau, Victoria Ming Yi; Hau, Pok Man; Yip, Yim Ling; Cheung, Annie L M; Guan, Xin-Yuan; Tsao, Sai Wah

    2015-03-15

    Apart from regulating stem cell self-renewal, embryonic development and proliferation, Bmi-1 has been recently reported to be critical in the maintenance of genome integrity. In searching for novel mechanisms underlying the anticlastogenic function of Bmi-1, we observed, for the first time, that Bmi-1 positively regulates p21 expression. We extended the finding that Bmi-1 deficiency induced chromosome breaks in multiple cancer cell models. Interestingly, we further demonstrated that knockdown of cyclin E or ectopic overexpression of p21 rescued Bmi-1 deficiency-induced chromosome breaks. We therefore conclude that p21/cyclin E pathway is crucial in modulating the anticlastogenic function of Bmi-1. As it is well established that the overexpression of cyclin E potently induces genome instability and p21 suppresses the function of cyclin E, the novel and important implication from our findings is that Bmi-1 plays an important role in limiting genomic instability in cylin E-overexpressing cancer cells by positive regulation of p21.

  9. 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.

  10. 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

  11. 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......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...... fluvoxamine and caffeine. The study was carried out as a randomized, in vivo, cross-over study including eight healthy volunteers. In Period A of the study, each subject took 200 mg caffeine orally, and in Period B, the subjects took fluvoxamine 50 mg per day for 4 days and 100 mg per day for 8 days. On day 8...... in Period B, the subjects again ingested 200 mg caffeine. After caffeine intake, blood and urine were sampled at regular intervals. Caffeine and its three primary demethylated metabolites, paraxanthine, theobromine and theophylline in plasma and the same four compounds plus 11 more metabolites in urine were...

  12. 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)

  13. 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...

  14. 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

  15. Caffeine promotes anti-tumor immune response during tumor initiation: Involvement of the adenosine A2A receptor.

    Science.gov (United States)

    Eini, Hadar; Frishman, Valeria; Yulzari, Robert; Kachko, Leonid; Lewis, Eli C; Chaimovitz, Cidio; Douvdevani, Amos

    2015-11-01

    Epidemiologic studies depict a negative correlation between caffeine consumption and incidence of tumors in humans. The main pharmacological effects of caffeine are mediated by antagonism of the adenosine receptor, A2AR. Here, we examine whether the targeting of A2AR by caffeine plays a role in anti-tumor immunity. In particular, the effects of caffeine are studied in wild-type and A2AR knockout (A2AR(-/-)) mice. Tumor induction was achieved using the carcinogen 3-methylcholanthrene (3-MCA). Alternatively, tumor cells, comprised of 3-MCA-induced transformed cells or B16 melanoma cells, were inoculated into animal footpads. Cytokine release was determined in a mixed lymphocyte tumor reaction (MLTR). According to our findings, caffeine-consuming mice (0.1% in water) developed tumors at a lower rate compared to water-consuming mice (14% vs. 53%, respectively, p=0.0286, n=15/group). Within the caffeine-consuming mice, tumor-free mice displayed signs of autoimmune alopecia and pronounced leukocyte recruitment intocarcinogen injection sites. Similarly, A2AR(-/-) mice exhibited reduced rates of 3-MCA-induced tumors. In tumor inoculation studies, caffeine treatment resulted in inhibition of tumor growth and elevation in proinflammatory cytokine release over water-consuming mice, as depicted by MLTR. Addition of the adenosine receptor agonist, NECA, to MLTR resulted in a sharp decrease in IFNγ levels; this was reversed by the highly selective A2AR antagonist, ZM241385. Thus, immune response modulation through either caffeine or genetic deletion of A2AR leads to a Th1 immune profile and suppression of carcinogen-induced tumorigenesis. Taken together, our data suggest that the use of pharmacologic A2AR antagonists may hold therapeutic potential in diminishing the rate of cancer development.

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

    Science.gov (United States)

    Scurachio, R S; Mattiucci, F; Santos, W G; Skibsted, L H; Cardoso, D R

    2016-10-01

    Caffeine metabolites were found to bind riboflavin with dissociation constant in the millimolar region by an exothermic process with positive entropy of reaction, which was found by (1)H NMR and fluorescence spectroscopy to occur predominantly by hydrogen bonding with water being released from riboflavin solvation shell upon caffeine metabolite binding to riboflavin. The caffeine metabolites 1-methyl uric acid and 1,7-dimethyl uric acid were shown by transient absorption laser flash photolysis to be efficient as quenchers of triplet riboflavin with second-order rate constant of 1.4 10(8)Lmol(-1)s(-1) and 1.0 10(8)Lmol(-1)s(-1), respectively, in aqueous solution of pH6.4 at 25°C and more efficient than the other caffeine metabolite 1,7-dimethyl xanthine with second-order rate constant of 4.2 10(7)Lmol(-1)s(-1). Caffeine was in contrast found to be non-reactive towards triplet riboflavin. Caffeine metabolites rather than caffeine seem accordingly important for the observed protective effect against cutaneous melanoma identified for drinkers of regular but not of decaffeinated coffee. The caffeine metabolites, but not caffeine, were by time resolved single photon counting found to quench singlet excited riboflavin through exothermic formation of ground-state precursor complexes indicating importance of hydrogen bounding through keto-enol tautomer's for protection of oxidizable substrates and sensitive structures against riboflavin photosensitization.

  17. Performance effects and metabolic consequences of caffeine and caffeinated energy drink consumption on glucose disposal.

    Science.gov (United States)

    Shearer, Jane; Graham, Terry E

    2014-10-01

    This review documents two opposing effects of caffeine and caffeine-containing energy drinks, i.e., their positive effects on athletic performance and their negative impacts on glucose tolerance in the sedentary state. Analysis of studies examining caffeine administration prior to performance-based exercise showed caffeine improved completion time by 3.6%. Similar analyses following consumption of caffeine-containing energy drinks yielded positive, but more varied, benefits, which were likely due to the diverse nature of the studies performed, the highly variable composition of the beverages consumed, and the range of caffeine doses administered. Conversely, analyses of studies administering caffeine prior to either an oral glucose tolerance test or insulin clamp showed a decline in whole-body glucose disposal of ~30%. The consequences of this resistance are unknown, but there may be implications for the development of a number of chronic diseases. Both caffeine-induced performance enhancement and insulin resistance converge with the primary actions of caffeine on skeletal muscle.

  18. 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

  19. 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...

  20. 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...

  1. AKAP95 promotes cell cycle progression via interactions with cyclin E and low molecular weight cyclin E

    Science.gov (United States)

    Kong, Xiang-Yu; Zhang, Deng-Cheng; Zhuang, Wen-Xin; Hua, Su-Hang; Dai, Yue; Yuan, Yang-Yang; Feng, Li-Li; Huang, Qian; Teng, Bo-Gang; Yu, Xiu-Yi; Liu, Wen-Zhi; Zhang, Yong-Xing

    2016-01-01

    AKAP95 in lung cancer tissues showed higher expression than in paracancerous tissues. AKAP95 can bind with cyclin D and cyclin E during G1/S cell cycle transition, but its molecular mechanisms remain unclear. To identify the mechanism of AKAP95 in cell cycle progression, we performed AKAP95 transfection and silencing in A549 cells, examined AKAP95, cyclin E1 and cyclin E2 expression, and the interactions of AKAP95 with cyclins E1 and E2. Results showed that over-expression of AKAP95 promoted cell growth and AKAP95 bound cyclin E1 and E2, low molecular weight cyclin E1 (LWM-E1) and LWM-E2. Additionally AKAP95 bound cyclin E1 and LMW-E2 in the nucleus during G1/S transition, bound LMW-E1 during G1, S and G2/M, and bound cyclin E2 mainly on the nuclear membrane during interphase. Cyclin E2 and LMW-E2 were also detected. AKAP95 over-expression increased cyclin E1 and LMW-E2 expression but decreased cyclin E2 levels. Unlike cyclin E1 and LMW-E2 that were nuclear located during the G1, S and G1/S phases, cyclin E2 and LMW-E1 were expressed in all cell cycle phases, with cyclin E2 present in the cytoplasm and nuclear membrane, with traces in the nucleus. LMW-E1 was present in both the cytoplasm and nucleus. The 20 kDa form of LMW-E1 showed only cytoplasmic expression, while the 40 kDa form was nuclear expressed. The expression of AKAP95, cyclin E1, LMW-E1 and -E2, might be regulated by cAMP. We conclude that AKAP95 might promote cell cycle progression by interacting with cyclin E1 and LMW-E2. LMW-E2, but not cyclin E2, might be involved in G1/S transition. The binding of AKAP95 and LMW-E1 was found throughout cell cycle. PMID:27158371

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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...

  7. 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

  8. 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.

  9. 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

  10. 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 ...

  11. 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 ...

  12. 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

  13. 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

  14. 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...

  15. Caffeine use among active duty US Army soldiers.

    Science.gov (United States)

    Lieberman, Harris R; Stavinoha, Trisha; McGraw, Susan; White, Alan; Hadden, Louise; Marriott, Bernadette P

    2012-06-01

    Eighty-percent of the US adult population regularly consumes caffeine, but limited information is available on the extent and patterns of use. Caffeine use is a public health issue and its risks and benefits are regularly considered in scientific literature and the lay media. Recently, new caffeine-containing products have been introduced and are widely available on Army bases and are added to rations to maintain cognitive performance. This study surveyed caffeine consumption and demographic characteristics in 990 US Army soldiers. Data were weighted by age, sex, rank, and Special Forces status. Total caffeine intake and intake from specific products were estimated. Logistic regression was used to examine relationships between caffeine use and soldier demographic and lifestyle characteristics. Eighty-two percent of soldiers consumed caffeine at least once a week. Mean daily caffeine consumption was 285 mg/day (347 mg/day among regular caffeine consumers). Male soldiers consumed, on average, 303 mg/day and females 163 mg/day (regular consumers: 365 mg/day for male soldiers, 216 mg/day for female soldiers). Coffee was the main source of caffeine intake. Among young males, energy drinks were the largest source of caffeine intake, but their intake was not greater than older males. Regression analysis indicated an association of higher caffeine intake with male sex, white race, and tobacco use (P<0.01). Most soldiers consume caffeine in levels accepted as safe, but some consume greater quantities than recommended, although definitive information on safe upper limits of caffeine intake is not available. Labels of caffeine-containing products should provide caffeine content so individuals can make informed decisions.

  16. 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

  17. 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.

  18. 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…

  19. Is caffeine consumption a risk factor for osteoporosis?

    Science.gov (United States)

    Cooper, C; Atkinson, E J; Wahner, H W; O'Fallon, W M; Riggs, B L; Judd, H L; Melton, L J

    1992-04-01

    High caffeine consumption has been proposed as a risk factor for osteoporotic fracture, but the evidence associating high caffeine intake with low bone density is inconsistent. We therefore examined the influence of caffeine consumption on bone mineral at six skeletal sites in an age-stratified random sample of white women residing in Rochester, Minnesota. After age adjustment, there was no association between overall caffeine consumption and bone mineral at five of the six sites. In the femoral shaft, however, there was a statistically significant interaction between age and caffeine consumption so that high caffeine intake was associated with slight reductions in bone mineral among elderly subjects but with modestly increased bone mineral at younger ages. When caffeine intake was categorized by source, no consistent influence of coffee, tea, or other caffeinated beverage consumption could be detected on bone mineral. Caffeine intake was, however, positively associated with cigarette smoking and alcohol consumption. After adjusting for age, caffeine consumption was not correlated with biochemical indices of bone turnover, circulating concentrations of estradiol and estrone, or other dietary and musculoskeletal variables. These data suggest that caffeine intake in the range consumed by a representative sample of white women is not an important risk factor for osteoporosis. Among elderly women, however, in whom calcium balance performance is impaired, high caffeine intake may predispose to cortical bone loss from the proximal femur.

  20. 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

  1. CDK-1 and two B-type cyclins promote PAR-6 stabilization during polarization of the early C. elegans embryo.

    Directory of Open Access Journals (Sweden)

    Alexia Rabilotta

    Full Text Available In the C. elegans embryo, formation of an antero-posterior axis of polarity relies on signaling by the conserved PAR proteins, which localize asymmetrically in two mutually exclusive groups at the embryonic cortex. Depletion of any PAR protein causes a loss of polarity and embryonic lethality. A genome-wide RNAi screen previously identified two B-type cyclins, cyb-2.1 and cyb-2.2, as suppressors of par-2(it5ts lethality. We found that the loss of cyb-2.1 or cyb-2.2 suppressed the lethality and polarity defects of par-2(it5ts mutants and that these cyclins act in cell polarity with their cyclin-dependent kinase partner, CDK-1. Interestingly, cyb-2.1; cyb-2.2 double mutants did not show defects in cell cycle progression or timing of polarity establishment, suggesting that they regulate polarity independently of their typical role in cell cycle progression. Loss of both cyclin genes or of cdk-1 resulted in a decrease in PAR-6 levels in the embryo. Furthermore, the activity of the cullin CUL-2 was required to achieve suppression of par-2 lethality when both cyclins were absent. Our results support a model in which CYB-2.1/2/CDK-1 antagonize CUL-2 activity to promote stabilization of PAR-6 levels during polarization of the early C. elegans embryo. They also suggest that CYB-2.1 and CYB-2.2 contribute to the coupling of cell cycle progression and asymmetric segregation of cell fate determinants.

  2. 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

  3. 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.

  4. 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

  5. Coffee Polyphenols Change the Expression of STAT5B and ATF-2 Modifying Cyclin D1 Levels in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Carlota Oleaga

    2012-01-01

    Full Text Available Background. Epidemiological studies suggest that coffee consumption reduces the risk of cancer, but the molecular mechanisms of its chemopreventive effects remain unknown. Objective. To identify differentially expressed genes upon incubation of HT29 colon cancer cells with instant caffeinated coffee (ICC or caffeic acid (CA using whole-genome microarrays. Results. ICC incubation of HT29 cells caused the overexpression of 57 genes and the underexpression of 161, while CA incubation induced the overexpression of 12 genes and the underexpression of 32. Using Venn-Diagrams, we built a list of five overexpressed genes and twelve underexpressed genes in common between the two experimental conditions. This list was used to generate a biological association network in which STAT5B and ATF-2 appeared as highly interconnected nodes. STAT5B overexpression was confirmed at the mRNA and protein levels. For ATF-2, the changes in mRNA levels were confirmed for both ICC and CA, whereas the decrease in protein levels was only observed in CA-treated cells. The levels of cyclin D1, a target gene for both STAT5B and ATF-2, were downregulated by CA in colon cancer cells and by ICC and CA in breast cancer cells. Conclusions. Coffee polyphenols are able to affect cyclin D1 expression in cancer cells through the modulation of STAT5B and ATF-2.

  6. 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

  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. Impact of caffeine and coffee on our health.

    Science.gov (United States)

    Gonzalez de Mejia, Elvira; Ramirez-Mares, Marco Vinicio

    2014-10-01

    Coffee is the most frequently consumed caffeine-containing beverage. The caffeine in coffee is a bioactive compound with stimulatory effects on the central nervous system and a positive effect on long-term memory. Although coffee consumption has been historically linked to adverse health effects, new research indicates that coffee consumption may be beneficial. Here we discuss the impact of coffee and caffeine on health and bring attention to the changing caffeine landscape that includes new caffeine-containing energy drinks and supplements, often targeting children and adolescents.

  9. Reinforcing and subjective effects of caffeine in normal human volunteers.

    Science.gov (United States)

    Stern, K N; Chait, L D; Johanson, C E

    1989-01-01

    The reinforcing and subjective effects of caffeine (100 and 300 mg, PO) were determined in a group of 18 normal, healthy adults. Subjects (eight females, ten males) were light to moderate users of caffeine, and had no history of drug abuse. A discrete-trial choice procedure was used in which subjects were allowed to choose between the self-administration of color-coded capsules containing either placebo or caffeine. The number of times caffeine was chosen over placebo was used as the primary index of reinforcing efficacy. Subjective effects were measured before and several times after capsule ingestion. The low dose of caffeine was chosen on 42.6% of occasions, not significantly different from chance (50%). The high dose of caffeine was chosen on 38.9% of occasions, significantly less than expected by chance, indicating that this dose served as a punisher. Both doses of caffeine produced stimulant-like subjective effects, with aversive effects such as increased anxiety predominating after the high dose. When subjects were divided into groups of caffeine-sensitive choosers and nonchoosers, a consistent relationship emerged between caffeine choice and subjective effects; nonchoosers reported primarily aversive effects after caffeine (increased anxiety and dysphoria), whereas choosers reported stimulant and "positive" mood effects. When compared with previous findings, these results demonstrate that caffeine is less reinforcing than amphetamine and related psychomotor stimulants. PMID:2498963

  10. 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…

  11. The pH dependent Raman spectroscopic study of caffeine

    Science.gov (United States)

    Kang, Jian; Gu, Huaimin; Zhong, Liang; Hu, Yongjun; Liu, Fang

    2011-02-01

    First of all the surface enhanced Raman spectroscopy (SERS) and normal Raman spectra of caffeine aqueous solution were obtained at different pH values. In order to obtain the detailed vibrational assignments of the Raman spectroscopy, the geometry of caffeine molecule was optimized by density functional theory (DFT) calculation. By comparing the SERS of caffeine with its normal spectra at different pH values; it is concluded that pH value can dramatically affect the SERS of caffeine, but barely affect the normal Raman spectrum of caffeine aqueous solution. It can essentially affect the reorientation of caffeine molecule to the Ag colloid surface, but cannot impact the vibration of functional groups and chemical bonds in caffeine molecule.

  12. 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

  13. Caffeine does not modulate inhibitory control

    NARCIS (Netherlands)

    Z. Tieges; J. Snel; A. Kok; K.R. Ridderinkhof

    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, withi

  14. Caffeine effects on perceptual and motor processes

    NARCIS (Netherlands)

    Lorist, MM; Snel, J

    1997-01-01

    The effects of a single dose of caffeine on specific information processing operations were examined by using a visual selective attention task in which subjects were asked to select between a left and right hand response on the basis of two different target letters. The target was presented on a pr

  15. 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…

  16. 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

  17. A Survey of Caffeine Use and Associated Side Effects in a College Population.

    Science.gov (United States)

    Johnson-Greene, Douglas; And Others

    1988-01-01

    Surveyed 270 college students concerning their caffeine consumption. Results suggest there is identifiable group using excessive amounts of caffeine. Identified several deleterious effects possibly related to caffeine use. Approximately 75 percent of caffeine users surveyed rarely sought information on caffeine content of products or avoided…

  18. 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....

  19. Matrine promotes G0/G1 arrest and down-regulates cyclin D1 expression in human rhabdomyosarcoma cells.

    Science.gov (United States)

    Guo, L; Xue, T Y; Xu, W; Gao, J Z

    2013-09-01

    Matrine has a broad-spectrum of anti-cancer effects and is efficient in the inhibition of proliferation of hepatoma cells, leukemia cells and neuroblastoma cell. However, its efficacy and tentative mechanisms in rhabdomyosarcoma have not been addressed before. This study aimed to investigate the effects of Matrine on cell cycle and expression of cyclin D1 in human rhabdomyosarcoma cells (RD cell line). RD cell line was treated with different concentrations (0, 0.5, 1.0, and 1.5 mg/mL) of Matrine, and cell proliferation and cell cycle were evaluated using, respectively, MTT assay and flow cytometry. The effect of Matrine on cyclin D1 mRNA levels was measured by RT-PCR. There was a dose-dependent inhibition of proliferation in the matrine-treated group (inhibition of proliferation rate in control cells 12.70 ± 0.35%; Matrine-treated cells [0.5, 1.0, and 1.5 mg/mL]: 31.16 ± 0.11%, 42.96 ± 0.9%, and 57.26 ± 0.8%). The G0 / G1 ratio in study groups were, respectively, 58.44 ± 3.57%, 64.79 ± 2.03%, 69.97 ± 2.89% and 75.03 ± 1.23%.Cyclin D1 mRNA levels progressively diminished (control group ratio of cyclin D1 / β-actin: 0.59 ± 0.06; Matrine: 0.35 ± 0.05, 0.27 ± 0.02 and 0.04 ± 0.03). All aforementioned changes were significant (PMatrine markedly suppresses cell proliferation in RD cells by decreasing expression of cyclin D1 mRNA and blocking the cell cycle at the G0 / G1 stage.

  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. Caenorhabditis elegans cyclin B3 is required for multiple mitotic processes including alleviation of a spindle checkpoint-dependent block in anaphase chromosome segregation.

    Directory of Open Access Journals (Sweden)

    Gary M R Deyter

    2010-11-01

    Full Text Available The master regulators of the cell cycle are cyclin-dependent kinases (Cdks, which influence the function of a myriad of proteins via phosphorylation. Mitotic Cdk1 is activated by A-type, as well as B1- and B2-type, cyclins. However, the role of a third, conserved cyclin B family member, cyclin B3, is less well defined. Here, we show that Caenorhabditis elegans CYB-3 has essential and distinct functions from cyclin B1 and B2 in the early embryo. CYB-3 is required for the timely execution of a number of cell cycle events including completion of the MII meiotic division of the oocyte nucleus, pronuclear migration, centrosome maturation, mitotic chromosome condensation and congression, and, most strikingly, progression through the metaphase-to-anaphase transition. Our experiments reveal that the extended metaphase delay in CYB-3-depleted embryos is dependent on an intact spindle assembly checkpoint (SAC and results in salient defects in the architecture of holocentric metaphase chromosomes. Furthermore, genetically increasing or decreasing dynein activity results in the respective suppression or enhancement of CYB-3-dependent defects in cell cycle progression. Altogether, these data reveal that CYB-3 plays a unique, essential role in the cell cycle including promoting mitotic dynein functionality and alleviation of a SAC-dependent block in anaphase chromosome segregation.

  2. 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

  3. Caffeine potentiates the enhancement by choline of striatal acetylcholine release

    Science.gov (United States)

    Johnson, D. A.; Ulus, I. H.; Wurtman, R. J.

    1992-01-01

    We investigated the effect of peripherally administered caffeine (50 mg/kg), choline (30, 60, or 120 mg/kg) or combinations of both drugs on the spontaneous release of acetylcholine (ACh) from the corpus striatum of anesthetized rats using in vivo microdialysis. Caffeine alone or choline in the 30 or 60 mg/kg dose failed to increase ACh in microdialysis samples; the 120 mg/kg choline dose significantly enhanced ACh during the 80 min following drug administration. Coadministration of caffeine with choline significantly increased ACh release after each of the choline doses tested. Peak microdialysate levels with the 120 mg/kg dose were increased 112% when caffeine was additionally administered, as compared with 54% without caffeine. These results indicate that choline administration can enhance spontaneous ACh release from neurons, and that caffeine, a drug known to block adenosine receptors on these neurons, can amplify the choline effect.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Caffeine metabolites were found to bind riboflavin with dissociation constant in the millimolar region by an exothermic process with positive entropy of reaction, which was found by 1H NMR and fluorescence spectroscopy to occur predominantly by hydrogen bonding with water being released from...... riboflavin solvation shell upon caffeine metabolite binding to riboflavin. The caffeine metabolites 1-methyl uric acid and 1,7-dimethyl uric acid were shown by transient absorption laser flash photolysis to be efficient as quenchers of triplet riboflavin with second-order rate constant of 1.4 108 L mol− 1 s......− 1 and 1.0 108 L mol− 1 s− 1, respectively, in aqueous solution of pH 6.4 at 25 °C and more efficient than the other caffeine metabolite 1,7-dimethyl xanthine with second-order rate constant of 4.2 107 L mol− 1 s− 1. Caffeine was in contrast found to be non-reactive towards triplet riboflavin...

  5. CyclinE在甲状腺乳头状癌组织中的表达及临床意义%TThe expression and clinical significance of CyclinE in the thyroid gland papilliform tumor organizes

    Institute of Scientific and Technical Information of China (English)

    范晓东; 张鹏霞; 王茉琳; 王伟群

    2014-01-01

    Objective To study the expression and clinical significance of CyclinE in the thyroid gland papilliform tumor .Methods The expression of CyclinE was tested by immunohistochemistry SP law of the thyroid gland papilliform tumor , the thyroid gland adenoma and the lump in the normal thyroid gland .Results The CyclinE expression rate was elevated gradually (P<0.01).CyclinE expression was correlated with stages, peritonsillar tissue infiltration and lymph node shift related of thyroid gland papilliform tumor (P<0.01).Conclusions CyclinE expression level is correlated with the occurrence and development of thyroid gland papilliform tumor .%目的:探讨CyclinE在甲状腺乳头状癌组织中的表达及其与临床病理特征的关系。方法用免疫组化 SP法检测CyclinE在甲状腺乳头状癌、甲状腺腺瘤及瘤旁正常甲状腺组织中的表达情况。结果 CyclinE的阳性表达率在正常甲状腺组织、甲状腺腺瘤、甲状腺乳头状癌组织中逐渐升高(P<0.01)。 CyclinE表达与甲状腺乳头状癌的临床分期、周围组织浸润及淋巴结转移有关(P<0.01)。结论 Cyclin E 的表达水平与甲状腺乳头状癌的发生、发展及预后有关,为甲状腺乳头状癌的治疗提供新的思路。

  6. 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 ...

  7. 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...

  8. 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...

  9. Caffeine reduction in coffee pulp through silage.

    Science.gov (United States)

    Porres, C; Alvarez, D; Calzada, J

    1993-01-01

    Silage tests to study reductions of antiphysiological compounds (caffeine and polyphenols) of fresh coffee pulp during the anaerobic fermentation were done. A concrete silo divided in compartments, with a total capacity of 9 tons of fresh material was utilized. The silage periods ranged between 99-224 days and the following materials were ensiled: 1) coffee pulp, 2) coffee pulp with sugar cane molasses, 3) coffee pulp with a mixture of molasses and ammonia and 4) screw pressed coffee pulp with molasses. Reductions in caffeine, total polyphenols and condensed polyphenols ranged between 13-63%, 28-70% and 51-81% respectively. It was concluded that in the case of coffee pulp, silage presents and ideal method to preserve the material and partially reduce the contents of antiphysiological compounds.

  10. 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.

  11. 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

  12. Regulation of cerebrospinal fluid production by caffeine consumption

    Directory of Open Access Journals (Sweden)

    Yoon Sik

    2009-09-01

    Full Text Available Abstract Background Caffeine is the most commonly consumed psycho-stimulant in the world. The effects of caffeine on the body have been extensively studied; however, its effect on the structure of the brain has not been investigated to date. Results In the present study we found that the long-term consumption of caffeine can induce ventriculomegaly; this was observed in 40% of the study rats. In the caffeine-treated rats with ventriculomegaly, there was increased production of CSF, associated with the increased expression of Na+, K+-ATPase and increased cerebral blood flow (CBF. In contrast to the chronic effects, acute treatment with caffeine decreased the production of CSF, suggesting 'effect inversion' associated with caffeine, which was mediated by increased expression of the A1 adenosine receptor, in the choroid plexus of rats chronically treated with caffeine. The involvement of the A1 adenosine receptor in the effect inversion of caffeine was further supported by the induction of ventriculomegaly and Na+, K+-ATPase, in A1 agonist-treated rats. Conclusion The results of this study show that long-term consumption of caffeine can induce ventriculomegaly, which is mediated in part by increased production of CSF. Moreover, we also showed that adenosine receptor signaling can regulate the production of CSF by controlling the expression of Na+, K+-ATPase and CBF.

  13. 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.

  14. 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

  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 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.

  17. 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...

  18. 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.

  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. Effects of Smoking Cues on Caffeine Urges in Heavy Smokers and Caffeine Consumers with and without Schizophrenia

    Science.gov (United States)

    Adolfo, Amy B.; AhnAllen, Christopher G.; Tidey, Jennifer W.

    2009-01-01

    Cigarette smoking and caffeine use are established and problematic drug-use behaviors in people with schizophrenia. Associative links between drugs of abuse may occur but the relationship between caffeine use and cigarette smoking has received little attention in schizophrenia. In this cross-cue reactivity laboratory study, we examined the effects of neutral and smoking cues on craving for caffeinated beverages in participants with schizophrenia or schizoaffective disorder (SS; n = 15) and non-psychiatric controls (CS; n = 18) all of whom were heavy smokers and daily caffeine users. Participants were tested under non-abstinent and 5-hour abstinent conditions. SS tended to report greater daily levels of caffeine use than CS. Although this difference was not significant, that may be due to the small sample sizes as the size of this effect was large. Daily caffeine intake was significantly correlated with daily smoking rate in SS but not CS. A significant interaction between group and cue type after controlling for caffeine intake indicated that exposure to smoking cues increased urge for caffeinated beverages in SS but not CS. These results indicate support for associative connections between cigarette smoking cues and craving for caffeine in smokers with schizophrenia. PMID:19006656

  1. Increased caffeine consumption is associated with reduced hepatic fibrosis

    Science.gov (United States)

    Modi, Apurva A; Feld, Jordan J; Park, Yoon; Kleiner, David E; Everhart, James E.; Liang, T. Jake; Hoofnagle, Jay H.

    2009-01-01

    Background Although coffee consumption has been associated with reduced frequency of liver disease, it is unclear whether the effect is from coffee or caffeine and whether there is an effect on hepatic fibrosis specifically. Aim To use a food-frequency instrument for dietary caffeine consumption to evaluate the relationship between caffeine intake and liver fibrosis. Methods Patients undergoing liver biopsy completed a detailed caffeine questionnaire on 3 occasions over a 6-month period. Caffeine intake was compared between patients with mild and advanced liver fibrosis (bridging fibrosis/cirrhosis). Logistic regression was used to evaluate the association between caffeine consumption and hepatic fibrosis. Results 177 patients (99 male, 104 Caucasian, 121 with chronic hepatitis C virus [HCV] infection) undergoing liver biopsy completed the caffeine questionnaire on up to three occasions. Results from repeated questionnaires were consistent. Daily caffeine consumption above the 75th percentile for the cohort (308 mg ~2.25 cups of coffee equivalents) was associated with reduced liver fibrosis (OR 0.33, 95% CI: 0.14-0.80, p=0.015) and the protective association persisted after controlling for age, sex, race, liver disease, body mass index and alcohol intake in all patients (OR 0.25, 95% CI: 0.09-0.67, p=0.006), as well as the subset with HCV infection (OR 0.19, 95% CI: 0.05-0.66, p=0.009). Despite a modest trend, consumption of caffeine from sources other than coffee or of decaffeinated coffee was not associated with reduced liver fibrosis. Conclusion A reliable tool for measurement of caffeine consumption demonstrated that caffeine consumption, particularly from regular coffee, above a threshold of approximately 2 coffee-cup equivalents per day, was associated with less severe hepatic fibrosis. PMID:20034049

  2. 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.

  3. 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

  4. 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...

  5. 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.

  6. Caffeine Consumption and Sleep Quality in Australian Adults.

    Science.gov (United States)

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

    2016-08-04

    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 sleep is associated with greater caffeine consumption, and that consumption is greater in adults with reduced sleep quality.

  7. Associations between smoking and caffeine consumption in two European cohorts

    NARCIS (Netherlands)

    Treur, J.L.; Taylor, A.E.; Ware, J.J.; McMahon, G.; Hottenga, J.J.; Baselmans, B.M.L.; Willemsen, G.; Boomsma, D.I.; Munafò, M.R.; Vink, J.M.

    2016-01-01

    Aims To estimate associations between smoking initiation, smoking persistence and smoking heaviness and caffeine consumption, in two population-based samples from the Netherlands and the United Kingdom. Design Observational study employing data on self-reported smoking behaviour and caffeine consump

  8. 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.

  9. 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

  10. Caffeine and the risk of hip fracture: the Framingham Study.

    Science.gov (United States)

    Kiel, D P; Felson, D T; Hannan, M T; Anderson, J J; Wilson, P W

    1990-10-01

    Caffeine increases urinary calcium output and has been implicated as a risk factor for osteoporosis. The authors examined the effect of caffeine on hip fracture risk in 3,170 individuals attending the 12th (1971-1973) Framingham Study examination. Coffee and tea consumption, age, Framingham examination number, weight, smoking, alcohol consumption, and estrogen use were used to evaluate hip fracture risk according to caffeine intake. Hip fractures occurred in 135 subjects during 12 years of follow-up. Fracture risk over each 2-year period increased with increasing caffeine intake (one cup of coffee = one unit of caffeine, one cup of tea = 1/2 unit of caffeine). For intake of 1.5-2.0 units per day, the adjusted relative risk (RR) of fracture was not significantly elevated compared with intake of one or less units per day. Consumption of greater than or equal to 2.5 units per day significantly increased the risk of fracture. Overall, intake of greater than two cups of coffee per day (four cups of tea) increased the risk of fracture. In summary, hip fracture risk was modestly increased with heavy caffeine use, but not for intake equivalent to one cup of coffee per day. Since caffeine use may be associated with other behaviors that are, themselves, risk factors for fracture, the association may be indirect. Further studies should be performed to confirm these findings.

  11. Caffeine Use among Active Duty Navy and Marine Corps Personnel

    Directory of Open Access Journals (Sweden)

    Joseph J. Knapik

    2016-10-01

    Full Text Available Data from the National Health and Nutrition Examination Survey (NHANES indicate 89% of Americans regularly consume caffeine, but these data do not include military personnel. This cross-sectional study examined caffeine use in Navy and Marine Corps personnel, including prevalence, amount of daily consumption, and factors associated with use. A random sample of Navy and Marine Corps personnel was contacted and asked to complete a detailed questionnaire describing their use of caffeine-containing substances, in addition to their demographic, military, and lifestyle characteristics. A total of 1708 service members (SMs completed the questionnaire. Overall, 87% reported using caffeinated beverages ≥1 time/week, with caffeine users consuming a mean ± standard error of 226 ± 5 mg/day (242 ± 7 mg/day for men, 183 ± 8 mg/day for women. The most commonly consumed caffeinated beverages (% users were coffee (65%, colas (54%, teas (40%, and energy drinks (28%. Multivariable logistic regression modeling indicated that characteristics independently associated with caffeine use (≥1 time/week included older age, white race/ethnicity, higher alcohol consumption, and participating in less resistance training. Prevalence of caffeine use in these SMs was similar to that reported in civilian investigations, but daily consumption (mg/day was higher.

  12. 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)…

  13. 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.

  14. The Effects of Caffeine on Memory for Word Lists.

    Science.gov (United States)

    Erikson, George; And Others

    Research has suggested that behavioral differences may account for the effects of caffeine on information processing. To investigate the effects of caffeine on memory for supraspan word lists, 107 college students (47 males, 60 females), divided into 12 groups by high and low impulsivity scores on the Eysenck Personality Inventory, participated in…

  15. 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

  16. Acute caffeine administration affects zebrafish response to a robotic stimulus.

    Science.gov (United States)

    Ladu, Fabrizio; Mwaffo, Violet; Li, Jasmine; Macrì, Simone; Porfiri, Maurizio

    2015-08-01

    Zebrafish has been recently proposed as a valid animal model to investigate the fundamental mechanisms regulating emotional behavior and evaluate the modulatory effects exerted by psychoactive compounds. In this study, we propose a novel methodological framework based on robotics and information theory to investigate the behavioral response of zebrafish exposed to acute caffeine treatment. In a binary preference test, we studied the response of caffeine-treated zebrafish to a replica of a shoal of conspecifics moving in the tank. A purely data-driven information theoretic approach was used to infer the influence of the replica on zebrafish behavior as a function of caffeine concentration. Our results demonstrate that acute caffeine administration modulates both the average speed and the interaction with the replica. Specifically, zebrafish exposed to elevated doses of caffeine show reduced locomotion and increased sensitivity to the motion of the replica. The methodology developed in this study may complement traditional experimental paradigms developed in the field of behavioral pharmacology.

  17. Caffeine challenge test and panic disorder: a systematic literature review.

    Science.gov (United States)

    Vilarim, Marina Machado; Rocha Araujo, Daniele Marano; Nardi, Antonio Egidio

    2011-08-01

    This systematic review aimed to examine the results of studies that have investigated the induction of panic attacks and/or the anxiogenic effect of the caffeine challenge test in patients with panic disorder. The literature search was performed in PubMed, Biblioteca Virtual em Saúde and the ISI Web of Knowledge. The words used for the search were caffeine, caffeine challenge test, panic disorder, panic attacks and anxiety disorder. In total, we selected eight randomized, double-blind studies where caffeine was administered orally, and none of them controlled for confounding factors in the analysis. The percentage of loss during follow-up ranged between 14.3% and 73.1%. The eight studies all showed a positive association between caffeine and anxiogenic effects and/or panic disorder.

  18. Variation in caffeine concentration in single coffee beans.

    Science.gov (United States)

    Fox, Glen P; Wu, Alex; Yiran, Liang; Force, Lesleigh

    2013-11-13

    Twenty-eight coffee samples from around the world were tested for caffeine levels to develop near-infrared reflectance spectroscopy (NIRS) calibrations for whole and ground coffee. Twenty-five individual beans from five of those coffees were used to develop a NIRS calibration for caffeine concentration in single beans. An international standard high-performance liquid chromatography method was used to analyze for caffeine content. Coffee is a legal stimulant and possesses a number of heath properties. However, there is variation in the level of caffeine in brewed coffee and other caffeinated beverages. Being able to sort beans on the basis of caffeine concentration will improve quality control in the level of caffeine in those beverages. The range in caffeine concentration was from 0.01 mg/g (decaffeinated coffee) to 19.9 mg/g (Italian coffee). The majority of coffees were around 10.0-12.0 mg/g. The NIRS results showed r(2) values for bulk unground and ground coffees were >0.90 with standard errors bean calibration the r(2) values were between 0.85 and 0.93 with standard errors of cross validation of 0.8-1.6 mg/g depending upon calibration. The results showed it was possible to develop NIRS calibrations to estimate the caffeine concentration of individual coffee beans. One application of this calibration could be sorting beans on caffeine concentration to provide greater quality control for high-end markets. Furthermore, bean sorting may open new markets for novel coffee products. PMID:24070227

  19. Understanding Adolescent Caffeine Use: Connecting Use Patterns with Expectancies, Reasons, and Sleep

    Science.gov (United States)

    Ludden, Alison Bryant; Wolfson, Amy R.

    2010-01-01

    Little is known about adolescents' caffeine use, yet caffeinated soda, and more recently coffee and energy drinks, are part of youth culture. This study examines adolescents' caffeine use and, using cluster analysis, identifies three groups of caffeine users who differed in their reasons for use, expectancies, and sleep behaviors. In this high…

  20. Caffeine content of Ethiopian Coffea arabica beans

    Directory of Open Access Journals (Sweden)

    Maria Bernadete Silvarolla

    2000-03-01

    Full Text Available The coffee germplasm bank of the Instituto Agronômico de Campinas has many Coffea arabica accessions from Ethiopia, which is considered the primary center of genetic diversity in coffee plants. An evaluation of the caffeine content of beans from 99 progenies revealed intra- and inter-progeny variability. In 68 progenies from the Kaffa region we found caffeine values in the range 0.46-2.82% (mean 1.18%, and in 22 progenies from Illubabor region these values ranged from 0.42 to 2.90% (mean 1.10%. This variability could be exploited in a breeding program aimed at producing beans with low-caffeine content.O banco de germoplasma de café do Instituto Agronômico de Campinas contém grande número de introduções de Coffea arabica provenientes da Etiópia, considerada centro de diversidade genética desta espécie. A avaliação dos teores de cafeína nas sementes de 99 progênies revelou a presença de variabilidade entre e dentro das progênies, de acordo com a região de origem das introduções. Entre as 68 progênies da região de Kaffa encontraram-se valores de cafeína entre 0.46 e 2.82% (média 1.18% e entre as 22 progênies de Illubabor obtiveram-se plantas cujos teores de cafeína variaram de 0.42 a 2.90% (média 1.10%. A variabilidade aqui relatada poderá ser explorada na produção de uma variedade de café com baixos teores de cafeína nas sementes.

  1. 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...

  2. Phospholipase C-delta1 expression is linked to proliferation, DNA synthesis, and cyclin E levels.

    Science.gov (United States)

    Stallings, Jonathan D; Zeng, Yue X; Narvaez, Francisco; Rebecchi, Mario J

    2008-05-16

    We previously reported that phospholipase C-delta1 (PLC-delta1) accumulates in the nucleus at the G1/S transition, which is largely dependent on its binding to phosphatidylinositol 4,5-bisphosphate ( Stallings, J. D., Tall, E. G., Pentyala, S., and Rebecchi, M. J. (2005) J. Biol. Chem. 280, 22060-22069 ). Here, using small interfering RNA (siRNA) that specifically targets rat PLC-delta1, we investigated whether this enzyme plays a role in cell cycle control. Inhibiting expression of PLC-delta1 significantly decreased proliferation of rat C6 glioma cells and altered S phase progression. [3H]Thymidine labeling and fluorescence-activated cell sorting analysis indicated that the rates of G1/S transition and DNA synthesis were enhanced. On the other hand, knockdown cultures released from the G1/S boundary were slower to reach full G2/M DNA content, consistent with a delay in S phase. The levels of cyclin E, a key regulator of the G1/S transition and DNA synthesis, were elevated in asynchronous cultures as well as those blocked at the G1/S boundary. Epifluorescence imaging showed that transient expression of human phospholipase C-delta1, resistant to these siRNA, suppressed expression of cyclin E at the G1/S boundary despite treatment of cultures with rat-specific siRNA. Although whole cell levels of phosphatidylinositol 4,5-bisphosphate were unchanged, suppression of PLC-delta1 led to a significant rise in the nuclear levels of this phospholipid at the G1/S boundary. These results support a role for PLC-delta1 and nuclear phospholipid metabolism in regulating cell cycle progression.

  3. Cyclin D2 Overexpression in Transgenic Mice Induces Thymic and Epidermal Hyperplasia whereas Cyclin D3 Expression Results Only in Epidermal Hyperplasia

    Science.gov (United States)

    Rodriguez-Puebla, Marcelo L.; LaCava, Margaret; Miliani de Marval, Paula L.; Jorcano, Jose L.; Richie, Ellen R.; Conti, Claudio J.

    2000-01-01

    In a previous report, we described the effects of cyclin D1 expression in epithelial tissues of transgenic mice. To study the involvement of D-type cyclins (D1, D2, and D3) in epithelial growth and differentiation and their putative role as oncogenes in skin, transgenic mice were developed which carry cyclin D2 or D3 genes driven by a keratin 5 promoter. As expected, both transgenic lines showed expression of these proteins in most of the squamous tissues analyzed. Epidermal proliferation increased in transgenic animals and basal cell hyperplasia was observed. All of the animals also had a minor thickening of the epidermis. The pattern of expression of keratin 1 and keratin 5 indicated that epidermal differentiation was not affected. Transgenic K5D2 mice developed mild thymic hyperplasia that reversed at 4 months of age. On the other hand, high expression of cyclin D3 in the thymus did not produce hyperplasia. This model provides in vivo evidence of the action of cyclin D2 and cyclin D3 as mediators of proliferation in squamous epithelial cells. A direct comparison among the three D-type cyclin transgenic mice suggests that cyclin D1 and cyclin D2 have similar roles in epithelial thymus cells. However, overexpression of each D-type cyclin produces a distinct phenotype in thymic epithelial cells. PMID:10980142

  4. 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).

  5. 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...

  6. 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...

  7. 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

  8. 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

  9. 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.

  10. Physiology, biochemistry and possible applications of microbial caffeine degradation.

    Science.gov (United States)

    Gummadi, Sathyanarayana N; Bhavya, B; Ashok, Nandhini

    2012-01-01

    Caffeine, a purine alkaloid is a constituent of widely consumed beverages. The scientific evidence which has proved the harm of this alkaloid has paved the way for innumerable research in the area of caffeine degradation. In addition to this, the fact that the by-products of the coffee and tea industry pollute the environment has called for the need of decaffeinating coffee and tea industry's by-products. Though physical and chemical methods for decaffeination are available, the lack of specificity for removal of caffeine in these techniques and their non-eco-friendly nature has opened the area of microbial and enzymatic degradation of caffeine. Another important application of microbial caffeine degradation apart from its advantages like specificity, eco-friendliness and cost-effectiveness is the fact that this process will enable the production of industrially and medically useful components of the caffeine degradation pathway like theobromine and theophylline. This is a comprehensive review which mainly focuses on caffeine degradation, large-scale degradation of the same and its applications in the industrial world.

  11. 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.

  12. Myt1 inhibition of Cyclin A/Cdk1 is essential for fusome integrity and premeiotic centriole engagement in Drosophila spermatocytes.

    Science.gov (United States)

    Varadarajan, Ramya; Ayeni, Joseph; Jin, Zhigang; Homola, Ellen; Campbell, Shelagh D

    2016-07-01

    Regulation of cell cycle arrest in premeiotic G2 phase coordinates germ cell maturation and meiotic cell division with hormonal and developmental signals by mechanisms that control Cyclin B synthesis and inhibitory phosphorylation of the M-phase kinase, Cdk1. In this study, we investigated how inhibitory phosphorylation of Cdk1 by Myt1 kinase regulates premeiotic G2 phase of Drosophila male meiosis. Immature spermatocytes lacking Myt1 activity exhibit two distinct defects: disrupted intercellular bridges (fusomes) and premature centriole disengagement. As a result, the myt1 mutant spermatocytes enter meiosis with multipolar spindles. These myt1 defects can be suppressed by depletion of Cyclin A activity or ectopic expression of Wee1 (a partially redundant Cdk1 inhibitory kinase) and phenocopied by expression of a Cdk1F mutant defective for inhibitory phosphorylation. We therefore conclude that Myt1 inhibition of Cyclin A/Cdk1 is essential for normal fusome behavior and centriole engagement during premeiotic G2 arrest of Drosophila male meiosis. The novel meiotic functions we discovered for Myt1 kinase are spatially and temporally distinct from previously described functions of Myt1 as an inhibitor of Cyclin B/Cdk1 to regulate G2/MI timing. PMID:27170181

  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. Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the anaphase-promoting complex

    DEFF Research Database (Denmark)

    Lukas, C; Sørensen, Claus Storgaard; Kramer, E;

    1999-01-01

    genes beyond the G1/S transition is required for coordinating S-phase progression with cell division, a process driven by cyclin-B-dependent kinase and anaphase-promoting complex (APC)-mediated proteolysis. How E2F-dependent events at G1/S transition are orchestrated with cyclin B and APC activity...... in the timely accumulation of cyclin B1 and the coordination of cell-cycle progression during the post-restriction point period....

  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. 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...

  17. Cyclin D1,Cyclin E,c- Myc在涎腺良恶性多形性腺瘤中的表达研究%Expression of Cyclin D1, Cyclin E, C-myc in Benign and Malignant Pleomorphic Adenoma of Salivary Gland

    Institute of Scientific and Technical Information of China (English)

    冯晓洁; 罗欣; 陈洪伟; 温黎明; 程勇

    2011-01-01

    Objective: To study the expressions of cyclin Dl, cyclin E and c-myc in benign and malignant PA, and to learn their association with clinical features and cell proliferation. Methods: SP immunohistochemical staining was applied to detect the expression levels of cyclin Dl,cyclin E and c - myc in 30 benign pleomorphic adenomas ,30 cellular-type pleomorphic adenomas, 30 malignant pleomorphic adenomas, and compared their expression with 30 normal gland tissues of adjacent carcinoma. Results: Cyclin Dl, cyclin E and c-myc expression were significantly higher in PA than in the normal gland tissues of adjacent carcinoma(P<0. 05). And there was no statistic difference for the expression levels of cyclin Dl, cyclin E, c -myc between benign pleomorphic adenoma and cellular-type pleomorphic adenoma. The expression levels of cyclin Dl, cyclin E and c-myc were uncorrelated with sex, recurrence, location, and tumor size. But in malignant pleomorphic adenoma, the expression level of cyclin Dl was correlated with TNM stage and the expression level of cyclin E was correlated with invasion. Conclusion: Together or alone of cyclin Dl, cyclin E and c-myc might be useful molecular biological markers in predicting the formation, development and carcinogenesis of PA. They might be thought as prognostic markers and chemotherapy targets. They might also contribute to classification of pathology diagnosis.%目的:研究cyclin D1,cyclin E,c- myc在涎腺多形性腺瘤中的表达,与临床生物学特性和细胞增殖的关系以及对于涎腺多形性腺瘤病理学诊断的意义.方法:采用免疫组化方法检测30例良性多形性腺瘤,30例细胞丰富型多形性腺瘤和30例恶性多形性腺瘤中cyclin D1、cyclin E、c- myc蛋白的表达水平,并与30例癌旁正常涎腺组织中的表达对比.结果:cyclin D1、cyclin E和c- myc在恶性多形性腺瘤中的阳性表达率明显高于良性和细胞丰富型多形性腺瘤(P<0.05),而三者在良性多形性腺瘤

  18. 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

  19. 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

  20. [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

  1. Removal of caffeine from industrial wastewater using Trichosporon asahii.

    Science.gov (United States)

    Lakshmi, V; Das, Nilanjana

    2013-07-01

    Caffeine (1,3,7-trimethylxanthine), a natural alkaloid present mainly in tea and coffee products has been suggested as an environmental pollutant. Decaffeination is an important process for the removal of caffeine from coffee industrial wastes. In the present study, caffeine removal (through degradation) by yeast isolate, Trichosporon asahii immobilized on various conventional matrices (sodium alginate, carboxymethyl cellulose, chitosan, agar and agarose) was investigated using the method of entrapment. The biofilm forming ability of T. asahii was monitored by atomic force microscopy and scanning electron microscopy. Exopolysaccharide produced by T asahii biofilm was characterized by FT-IR spectroscopy and HPLC analysis. Caffeine removal from coffee processing industrial effluent was found to be 75 and 80 % by alginate immobilized yeast and yeast biofilm formed on gravels over a period of 48 hr in batch mode. Effectiveness of the process was also tested involving the continuous--flow column studies.

  2. 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....

  3. Protonation of caffeine: A theoretical and experimental study

    Science.gov (United States)

    Bahrami, Hamed; Tabrizchi, Mahmoud; Farrokhpour, Hossein

    2013-03-01

    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.

  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 who had...

  5. 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

  6. 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/ ...

  7. 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...

  8. 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...

  9. 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

  10. The use of caffeine versus prophylactic naps in sustained performance.

    Science.gov (United States)

    Bonnet, M H; Gomez, S; Wirth, O; Arand, D L

    1995-02-01

    Previous studies have shown that performance during sleep loss is improved by prophylactic naps as a function of varying nap length. Based on single-dose caffeine studies, a similar dose-response effect has been hypothesized on performance, alertness and mood during sleep loss. The present study compared the effects of repeated versus single-dose administration of caffeine and varying amounts of sleep taken prior to sleep loss on performance, mood and physiological measures during 2 nights and days of sleep loss. A total of 140 normal, young adult males participated at one of two study sites. Ninety-eight subjects at one site were randomly assigned to one of four nap conditions (0, 2, 4 or 8 hours) and 42 subjects at the second site were assigned to one of four caffeine conditions. After a normal baseline night of sleep and morning baseline tests of performance, mood and nap latency, subjects in the nap groups returned to bed at noon, 1600 hours, 1800 hours or not at all. Bedtimes were varied so that all naps ended at 2000 hours. Subjects in the caffeine groups received either a single 400-mg dose of caffeine at 0130 hours each night or repeated doses of 150 or 300 mg every 6 hours starting at 0130 hours on the 1st night of sleep loss. A placebo control group (no nap and placebo administered every 6 hours on the repeated caffeine schedule) was run at both sites.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. 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.

  12. 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.

  13. Effects of caffeine intake and smoking on neurocognition in schizophrenia.

    Science.gov (United States)

    Núñez, Christian; Stephan-Otto, Christian; Cuevas-Esteban, Jorge; Maria Haro, Josep; Huerta-Ramos, Elena; Ochoa, Susana; Usall, Judith; Brébion, Gildas

    2015-12-30

    Although most studies support the beneficial effects of caffeine on neurocognition, its effects have never been assessed in psychiatric patients. In addition, results from studies in smokers are contradictory. Moreover, there are no data available about the neurocognitive effects of caffeine and tobacco together. We explored the concomitant effects of regular caffeine and tobacco intake on neurocognition in 52 schizophrenic patients and 61 healthy controls. Verbal fluency, processing speed, and working, visual and verbal memory were assessed. For each measurement, two tasks with two levels of complexity were administered. Our results showed that caffeine intake had beneficial effects on male schizophrenic patients only in complex tasks requiring deeper cognitive processing (semantic fluency, cognitive speed, working memory, and visual memory). Female patients and controls were unaffected. In contrast, smoking had a negative effect on male, but not on female, schizophrenic patients in semantic fluency. The effects of smoking in controls were inconsistent. In conclusion, our data showed, for the first time, beneficial effects of caffeine intake on neurocognition in male schizophrenic patients. These data suggest that further research of therapeutics based on caffeine is needed, as this could be beneficial for schizophrenic patients. In contrast, smoking appears to be detrimental.

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Zhang Xiangning

    2012-06-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusions BLU inhibits growth of nasopharyngeal carcinoma cells by regulation of the JNK-cyclin D1 axis to exert tumor suppression.

  16. 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.

  17. Performance pressure and caffeine both affect cognitive performance, but likely through independent mechanisms.

    Science.gov (United States)

    Boere, Julia J; Fellinger, Lizz; Huizinga, Duncan J H; Wong, Sebastiaan F; Bijleveld, Erik

    2016-02-01

    A prevalent combination in daily life, performance pressure and caffeine intake have both been shown to impact people's cognitive performance. Here, we examined the possibility that pressure and caffeine affect cognitive performance via a shared pathway. In an experiment, participants performed a modular arithmetic task. Performance pressure and caffeine intake were orthogonally manipulated. Findings indicated that pressure and caffeine both negatively impacted performance. However, (a) pressure vs. caffeine affected performance on different trial types, and (b) there was no hint of an interactive effect. So, though the evidence is indirect, findings suggest that pressure and caffeine shape performance via distinct mechanisms, rather than a shared one.

  18. The novel agent phospho-glycerol-ibuprofen-amide (MDC-330) inhibits glioblastoma growth in mice: an effect mediated by cyclin D1.

    Science.gov (United States)

    Bartels, Lauren E; Mattheolabakis, George; Vaeth, Brandon M; LaComb, Joseph F; Wang, Ruixue; Zhi, Jizu; Komninou, Despina; Rigas, Basil; Mackenzie, Gerardo G

    2016-04-01

    Given that glioblastoma multiforme (GBM) is associated with poor prognosis, new agents are urgently needed. We developed phospho-glycerol-ibuprofen-amide (PGIA), a novel ibuprofen derivative, and evaluated its safety and efficacy in preclinical models of GBM, and its mechanism of action using human GBM cells and animal tumor models. Furthermore, we explored whether formulating PGIA in polymeric nanoparticles could enhance its levels in the brain. PGIA was 3.7- to 5.1-fold more potent than ibuprofen in suppressing the growth of human GBM cell lines. PGIA 0.75× IC50 inhibited cell proliferation by 91 and 87% in human LN-229 and U87-MG GBM cells, respectively, and induced strong G1/S arrest.In vivo, compared with control, PGIA reduced U118-MG and U87-MG xenograft growth by 77 and 56%, respectively (P2-fold more efficacious than ibuprofen. Normal human astrocytes were resistant to PGIA, indicating selectivity. Mechanistically, PGIA reduced cyclin D1 levels in a time- and concentration-dependent manner in GBM cells and in xenografts. PGIA induced cyclin D1 degradation via the proteasome pathway and induced dephosphorylation of GSK3β, which was required for cyclin D1 turnover. Furthermore, cyclin D1 overexpression rescued GBM cells from the cell growth inhibition by PGIA. Moreover, the formulation of PGIA in poly-(L)-lactic acid poly(ethylene glycol) polymeric nanoparticles improved its pharmacokinetics in mice, delivering PGIA to the brain. PGIA displays strong efficacy against GBM, crosses the blood-brain barrier when properly formulated, reaching the target tissue, and establishes cyclin D1 as an important molecular target. Thus, PGIA merits further evaluation as a potential therapeutic option for GBM.

  19. Targeting cyclin dependent kinase 5 in hepatocellular carcinoma

    OpenAIRE

    Ehrlich, Sandra Monika

    2014-01-01

    For a long time cyclin dependent kinase 5 (Cdk5) was thought to be of exclusive importance in neuronal cells. However, recently increasing evidence suggests a function of Cdk5 in cancer progression. In the present study, we examined the role of Cdk5 in hepatocellular carcinoma (HCC), a highly chemoresistant cancer with poor prognosis. Consequently, development of novel targeted therapies for HCC is of paramount clinical importance. Analysis of human HCC patient samples showed an increased exp...

  20. 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...

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. TSG101 expression in gynecological tumors: relationship to cyclin D1, cyclin E, p53 and p16 proteins.

    Science.gov (United States)

    Bennett, N A; Pattillo, R A; Lin, R S; Hsieh, C Y; Murphy, T; Lyn, D

    2001-11-01

    Recent studies have shown that in vitro steady-state expression of the tumor susceptibility gene TSG101 is important for maintenance of genomic stability and cell cycle regulation. To determine the contribution of TSG101 expression in neoplastic formation, expression of TSG101 protein levels were evaluated in primary ovarian and endometrial adenocarcinoma tumors. Expression of TSG101 was also examined in various tumor cell lines (PA-1, AN3CA, HeLa, HS578T, HCT116). Full-length TSG101 protein was detected in these tumors and cell lines indicating that intragenic deletions were not characteristic of TSG101. In addition, TSG101 protein levels were compared with aberrations of prominent cell cycle regulatory molecules such as cyclin D1, cyclin E, p16 and p53. Reduced TSG101 protein was observed in 36% (8/22) of ovarian and 17% (1/6) of endometrial adenocarcinoma. Aberrant levels of p53, p16, cyclin D or E were comparable to published studies indicating that the clinicopathological distribution of these cases did not favor advanced stage tumors. Altogether, these findings suggest that a down-regulation of TSG101 is associated with tumorigenesis in a subgroup of gynecological tumors. PMID:11838966

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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...

  13. 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...

  14. Alteration of cyclin D1 in gastric carcinoma and its clinicopathologic significance

    Institute of Scientific and Technical Information of China (English)

    Peng Gao; Geng-Yin Zhou; Yuan Liu; Jin-Song Li; Jun-Hui Zhen; Yin-Ping Yuan

    2004-01-01

    AIM: To detect the genetic alteration and abnormal expression of cyclin D1 in gastric carcinoma and investigate its clinicopathologic significance in advanced gastric carcinoma.METHODS: Proteins of cyclin D1 were detected by immunohistochemistry in 42 cases of advanced gastric carcinoma with their follow-up data available, 27 cases of early stage carcinoma, 21 cases of gastric adenoma, 22cases of hyperplastic polyp and 20 cases of normal mucosa adjacent to adenocarcinomas. Genetic alteration of cyclin D1 was detected by Southern blot and expression of cyclin D1 mRNA was detected by PT-PCR in 42 cases of advanced gastric carcinoma.RESULTS: Cyclin D1 protein was not expressed in normal mucosa, hyperplastic polyp and gastric adenoma, while it was only positively expressed in gastric carcinoma. The expression rate of cyclin D1 protein in early stage gastric carcinoma, advanced gastric carcinoma and lymph node metastasis was 48.1%, 47.4% and 50.0%, respectively.The amplification of cyclin D1 gene was detected in 16.6% of advanced gastric carcinomas. The overexpression of cyclin D1 mRNA was detected in 40.5% of the samples.There was no significant correlation between cyclin D1protein expression and age, lymph-node metastasis and histological grading in patients with advanced gastric carcinoma (x2= 0.038,0.059,0.241, P>0.05). Significant correlation was observed between the expression of cyclin D1 protein and the 5-year survival rate (x2 = 3.92, P<0.05).CONCLUSION: Detection of cyclin D1 protein by immunohistochemistry may be useful in the diagnosis of early gastric carcinomas. Patients with positive expression of cyclin D1 protein tend to have a worse prognosis.

  15. Targeting cyclin B1 inhibits proliferation and sensitizes breast cancer cells to taxol

    Directory of Open Access Journals (Sweden)

    Strebhardt Klaus

    2008-12-01

    Full Text Available Abstract Background Cyclin B1, the regulatory subunit of cyclin-dependent kinase 1 (Cdk1, is essential for the transition from G2 phase to mitosis. Cyclin B1 is very often found to be overexpressed in primary breast and cervical cancer cells as well as in cancer cell lines. Its expression is correlated with the malignancy of gynecological cancers. Methods In order to explore cyclin B1 as a potential target for gynecological cancer therapy, we studied the effect of small interfering RNA (siRNA on different gynecological cancer cell lines by monitoring their proliferation rate, cell cycle profile, protein expression and activity, apoptosis induction and colony formation. Tumor formation in vivo was examined using mouse xenograft models. Results Downregulation of cyclin B1 inhibited proliferation of several breast and cervical cancer cell lines including MCF-7, BT-474, SK-BR-3, MDA-MB-231 and HeLa. After combining cyclin B1 siRNA with taxol, we observed an increased apoptotic rate accompanied by an enhanced antiproliferative effect in breast cancer cells. Furthermore, control HeLa cells were progressively growing, whereas the tumor growth of HeLa cells pre-treated with cyclin B1 siRNA was strongly inhibited in nude mice, indicating that cyclin B1 is indispensable for tumor growth in vivo. Conclusion Our data support the notion of cyclin B1 being essential for survival and proliferation of gynecological cancer cells. Concordantly, knockdown of cyclin B1 inhibits proliferation in vitro as well as in vivo. Moreover, targeting cyclin B1 sensitizes breast cancer cells to taxol, suggesting that specific cyclin B1 targeting is an attractive strategy for the combination with conventionally used agents in gynecological cancer therapy.

  16. 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

  17. Determination of caffeine using oscillating chemical reaction in a CSTR.

    Science.gov (United States)

    Gao, Jinzhang; Ren, Jie; Yang, Wu; Liu, XiuHui; Yang, Hua

    2003-07-14

    A new analytical method for the determination of caffeine by the sequential perturbation caused by different amounts of caffeine on the oscillating chemical system involving the manganese(II)-catalyzed reaction between potassium bromate and tyrosine in acidic medium in a CSTR was proposed. The method exposed for the first time in this work. It relies on the relationship between the changes in the oscillation amplitude of the chemical system and the concentration of caffeine. The calibration curve fits a second-order polynomial equation very well when the concentration of caffeine over the range 4.0 x 10(-6) - 1.2 x 10(-4) M (r = 0.9968). The effect of influential variables, such as the concentration of reaction components, injection point, temperature, flow rate and stirring rate were studied. Some aspects of the potential mechanism of action of caffeine on the chemical oscillating system were also discussed. A real sample was determined and the result was satisfactory.

  18. 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

  19. Do energy drinks contain active components other than caffeine?

    Science.gov (United States)

    McLellan, Tom M; Lieberman, Harris R

    2012-12-01

    Energy drinks (EDs) contain caffeine and are a new, popular category of beverage. It has been suggested that EDs enhance physical and cognitive performance; however, it is unclear whether the claimed benefits are attributable to components other than caffeine. A typical 235 mL ED provides between 40 and 250 mg of caffeine, equating to doses that improve cognitive and, at the higher levels, physical performance. EDs often contain taurine, guaraná, ginseng, glucuronolactone, B-vitamins, and other compounds. A literature search using PubMed, Psych Info, and Google Scholar identified 32 articles that examined the effects of ED ingredients alone and/or in combination with caffeine on physical or cognitive performance. A systematic evaluation of the evidence-based findings in these articles was then conducted. With the exception of some weak evidence for glucose and guaraná extract, there is an overwhelming lack of evidence to substantiate claims that components of EDs, other than caffeine, contribute to the enhancement of physical or cognitive performance. Additional well-designed, randomized, placebo-controlled studies replicated across laboratories are needed in order to assess claims made for these products.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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…

  5. 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…

  6. 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

  7. 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.

  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. 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.

  10. 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.

  11. Chromosomal and Extrachromosomal Instability of the cyclin D2 Gene is Induced by Myc Overexpression

    Directory of Open Access Journals (Sweden)

    Sabine Mai

    1999-08-01

    Full Text Available We examined the expression of cyclins D1, D2, D3, and E in mouse B-lymphocytic tumors. Cyclin D2 mRNA was consistently elevated in plasmacytomas, which characteristically contain Myc-activating chromosome translocations and constitutive c-Myc mRNA and protein expression. We examined the nature of cyclin D2 overexpression in plasmacytomas and other tumors. Human and mouse tumor cell lines that exhibited c-Myc dysregulation displayed instability of the cyclin D2 gene, detected by Southern blot, fluorescent in situ hybridization (FISH, and in extrachromosomal preparations (Hirt extracts. Cyclin D2 instability was not seen in cells with low levels of c-Myc protein. To unequivocally demonstrate a role of c-Myc in the instability of the cyclin D2 gene, a Myc-estrogen receptor chimera was activated in two mouse cell lines. After 3 to 4 days of Myc-ERTm activation, instability at the cyclin D2 locus was seen in the form of extrachromosomal elements, determined by FISH of metaphase and interphase nuclei and of purified extrachromosomal elements. At the same time points, Northern and Western blot analyses detected increased cyclin D2 mRNA and protein levels. These data suggest that Myc-induced genomic instability may contribute to neoplasia by increasing the levels of a cell cycle—regulating protein, cyclin D2, via intrachromosomal amplification of its gene or generation of extrachromosomal copies.

  12. D-type cyclins in adult human testis and testicular cancer

    DEFF Research Database (Denmark)

    Bartkova, J; Rajpert-de Meyts, E; Skakkebaek, N E;

    1999-01-01

    on immunohistochemical and immunochemical analysis of human adult testis and 32 testicular tumours to examine the differential expression and abundance of cyclins D1, D2, and D3 in relation to cell type, proliferation, differentiation, and malignancy. In normal testis, the cell type-restricted expression patterns were...... point to potential dual or multiple roles of the D-type cyclins, particularly of cyclin D3. These findings extend current concepts of the biology of the cyclin D subfamily, as well as of the biology and oncopathology of the human adult testis. Apart from practical implications for the assessment...

  13. 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.

  14. 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.

  15. [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

  16. 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).

  17. 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.

  18. 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...

  19. 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

  20. 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...... 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...

  1. 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

  2. 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.

  3. Cip/Kip cyclin-dependent protein kinase inhibitors and the road to polyploidy

    Directory of Open Access Journals (Sweden)

    DePamphilis Melvin L

    2009-06-01

    Full Text Available Abstract Cyclin-dependent kinases (CDKs play a central role in the orderly transition from one phase of the eukaryotic mitotic cell division cycle to the next. In this context, p27Kip1 (one of the CIP/KIP family of CDK specific inhibitors in mammals or its functional analogue in other eukarya prevents a premature transition from G1 to S-phase. Recent studies have revealed that expression of a second member of this family, p57Kip2, is induced as trophoblast stem (TS cells differentiate into trophoblast giant (TG cells. p57 then inhibits CDK1 activity, an enzyme essential for initiating mitosis, thereby triggering genome endoreduplication (multiple S-phases without an intervening mitosis. Expression of p21Cip1, the third member of this family, is also induced in during differentiation of TS cells into TG cells where it appears to play a role in suppressing the DNA damage response pathway. Given the fact that p21 and p57 are unique to mammals, the question arises as to whether one or both of these proteins are responsible for the induction and maintenance of polyploidy during mammalian development.

  4. [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

  5. 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.

  6. Inhibitory effects of caffeine on gustatory plasticity in the nematode Caenorhabditis elegans.

    Science.gov (United States)

    Urushihata, Takuya; Takuwa, Hiroyuki; Higuchi, Yukako; Sakata, Kazumi; Wakabayashi, Tokumitsu; Nishino, Asuka; Matsuura, Tetsuya

    2016-10-01

    The effects of caffeine on salt chemotaxis learning were investigated using the nematode Caenorhabditis elegans. To estimate the degree of salt chemotaxis learning, nematodes were placed in a mixed solution of NaCl and caffeine, and then the chemotaxis index of NaCl was obtained from the nematodes placed on agar medium after pre-exposure to caffeine concentrations of 0.01, 0.1, 0.3, and 1.0%. Locomotor activity and preference behavior for caffeine were also estimated under these caffeine conditions. Nematodes pre-exposed to 0.3% caffeine showed inhibition of salt chemotaxis learning. Additional experiments indicated that nematodes showed a preference response to the middle concentration of caffeine (0.1%), with preference behavior declining in the 0.3% caffeine condition. Stable locomotor activity was observed under 0.01-0.3% caffeine conditions. These results suggest that salt chemotaxis learning with 0.3% caffeine is useful for investigating the effects of caffeine on learning in nematodes.

  7. 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

  8. 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.

  9. 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

    Periodic activity of the anaphase-promoting complex (APC) ubiquitin ligase determines progression through multiple cell cycle transitions by targeting cell cycle regulators for destruction. At the G(1)/S transition, phosphorylation-dependent dissociation of the Cdh1-activating subunit inhibits...... the APC, allowing stabilization of proteins required for subsequent cell cycle progression. Cyclin-dependent kinases (CDKs) that initiate and maintain Cdh1 phosphorylation have been identified. However, the issue of which cyclin-CDK complexes are involved has been a matter of debate, and the mechanism...... of 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...

  10. 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.

  11. Cyclin D1 overexpression and poor clinical outcomes in Taiwanese oral cavity squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Huang Shiang-Fu

    2012-02-01

    Full Text Available Abstract Background Cyclin D1 gene regulates cell cycle and plays an important role in the tumorigenesis of human cancers. The association between cyclin D1, clinicopathologic parameters and prognosis in oral cavity squamous cell carcinoma (OSCC is inconclusive. Methods A total of 264 male OSCCs were examined for cyclin D1 protein expression using immunohistochemistry (IHC. The expression levels of cyclin D1 were defined as overexpression when more than 10% of tumor cells displayed nuclear staining with moderate to strong intensity. Results Overexpression of cyclin D1 was found in 97 (36.7% OSCCs. Cyclin D1 protein overexpression was significantly associated with lymph node metastasis (P = 0.002, tumor cell differentiation (P = 0.031 and tumor stage (P = 0.051, but not associated with age onset, cigarette smoking, alcohol drinking, or areca quid chewing. Overexpression of cyclin D1 was also significantly associated with poor clinical outcomes in terms of disease-free survival (DFS, P = 0.002 and overall survival (OS, P Conclusion Cyclin D1 protein worked as an independent prognostic factor and can be as a biomarker for the aggressiveness of OSCC.

  12. Regulation of the retinoblastoma protein-related p107 by G1 cyclin complexes

    NARCIS (Netherlands)

    Beijersbergen, R.L.; Carlée, L.; Kerkhoven, R.M.; Bernards, R.A.

    1995-01-01

    The orderly progression through the cell cycle is mediated by the sequential activation of several cyclin/cyclin-dependent kinase (cdk) complexes. These kinases phosphorylate a number of cellular substrates, among which is the product of the retinoblastoma gene, pRb. Phosphorylation of pRb in late G

  13. 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.

  14. 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...... analyzed immunohistochemically for cyclin D3 expression. In 43 lymphomas (21.7%), cyclin D3 was overexpressed. T-cell lymphomas more frequently overexpressed cyclin D3 than B-cell lymphomas. Furthermore, cyclin D3-overexpressing indolent lymphomas were associated with higher proliferation rate, higher p21......Waf1 expression, lower p27Kip1 expression, and altered p53. Cyclin D3 overexpression identified a subgroup of patients with indolent B-cell lymphoma with adverse clinical features: patients were older, more frequently had "B" symptoms and extranodal involvement, and were more frequently in the high...

  15. 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

  16. 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.

  17. 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

  18. Cyclin D1 fine-tunes the neurogenic output of embryonic retinal progenitor cells

    Directory of Open Access Journals (Sweden)

    Choi Yoon

    2009-05-01

    Full Text Available Abstract Background Maintaining the correct balance of proliferation versus differentiation in retinal progenitor cells (RPCs is essential for proper development of the retina. The cell cycle regulator cyclin D1 is expressed in RPCs, and mice with a targeted null allele at the cyclin D1 locus (Ccnd1-/- have microphthalmia and hypocellular retinas, the latter phenotype attributed to reduced RPC proliferation and increased photoreceptor cell death during the postnatal period. How cyclin D1 influences RPC behavior, especially during the embryonic period, is unclear. Results In this study, we show that embryonic RPCs lacking cyclin D1 progress through the cell cycle at a slower rate and exit the cell cycle at a faster rate. Consistent with enhanced cell cycle exit, the relative proportions of cell types born in the embryonic period, such as retinal ganglion cells and photoreceptor cells, are increased. Unexpectedly, cyclin D1 deficiency decreases the proportions of other early born retinal neurons, namely horizontal cells and specific amacrine cell types. We also found that the laminar positioning of horizontal cells and other cell types is altered in the absence of cyclin D1. Genetically replacing cyclin D1 with cyclin D2 is not efficient at correcting the phenotypes due to the cyclin D1 deficiency, which suggests the D-cyclins are not fully redundant. Replacement with cyclin E or inactivation of cyclin-dependent kinase inhibitor p27Kip1 restores the balance of RPCs and retinal cell types to more normal distributions, which suggests that regulation of the retinoblastoma pathway is an important function for cyclin D1 during embryonic retinal development. Conclusion Our findings show that cyclin D1 has important roles in RPC cell cycle regulation and retinal histogenesis. The reduction in the RPC population due to a longer cell cycle time and to an enhanced rate of cell cycle exit are likely to be the primary factors driving retinal hypocellularity

  19. Expression of Cyclin E and CDK5 in lung cancer%Cyclin E 、CDK5在肺癌中的表达

    Institute of Scientific and Technical Information of China (English)

    孙延; 唐建武

    2003-01-01

    [目的] 研究Cyclin E、CDK5在不同组织类型肺癌中的表达情况及其与肺癌发生发展的关系.[方法] 采用免疫组织化学法检测91例原发性肺癌及10例正常支气管粘膜组织中的Cyclin E、CDK5表达水平.[结果] Cyclin E、CDK5在肺癌中总的阳性表达率分别为 46.15%、37.36%,而在正常支气管粘膜中几乎无表达. Cyclin E、CDK5表达水平在肺癌各组织类型、分化程度间无显著性差异(P>0.05).Cyclin E与CDK5存在交叉共存现象(91例中有65例表达相同),经相关分析发现两者呈显著正相关(P<0.01). [结论] Cyclin E、CDK5与肺癌发生有关,可作为肺癌的潜在的诊断指标.

  20. 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.

  1. 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

  2. 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...

  3. 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

  4. Caffeine and theobromine levels in selected Nigerian beverages.

    Science.gov (United States)

    Eteng, M U; Eyong, E U; Eka, O U; Umoh, I B; Ebong, P E; Ettarh, R R

    1999-01-01

    Caffeine and theobromine contents (mg/g) were determined in samples of selected Nigerian beverage products. The beverages were cocoa (Milo, Bournvita, Rosevita and Enervita), coffee (Nescafe, Bongo, and Maxwell House decaffeinated) and tea (Lipton). The theobromine contents of samples of Milo, Bournvita, Rosevita, Enervita, Nescafe, Bongo, Maxwell House decaffeinated coffee and Lipton were 62.10+/-5.21, 64.80+/-6.72, 82.80+/-4.43, 80.37+/-6.80, 27.00+/-4.31, 14.67+/-2.90, 23.46+/-3.13 and 12.60+/-1.52, respectively. The corresponding caffeine contents of these samples were 2.78+/-0.43 (Milo), 3.17+/-0.36 (Bournvita), 0.92+/-0.51 (Rosevita), 1.05+/-0.68 (Enervita), 93.66+/-8.91 (Nescafe), 6.47+/-2.42 (Bongo), 37.22+/-5.34 (Lipton), and 0.21+/-0.11 (Maxwell House decaffeinated coffee). Semi-processed cocoa beverages (Rosevita and Enervita) had significantly (p Nescafe contained significantly (p < 0.05) higher levels of caffeine compared to Maxwell House (decaffeinated coffee) and Bongo. Levels of caffeine in Lipton tea were moderate. PMID:10798344

  5. EFFECTS OF CAFFEINE ON EXERCISE PERFORMANCE IN SEDENTARY FEMALES

    Directory of Open Access Journals (Sweden)

    Karen E. Wallman

    2010-06-01

    Full Text Available The purpose of the study was to examine the effect of caffeine ingestion on total work, average power, oxygen consumption (VO2, respiratory exchange ratio (RER, ratings of perceived exertion (RPE, heart rate (HR and energy expenditure (kJ during stationary cycling at a standardised power output, as well as during a set time period where participants were required to cycle as fast as they could. Ten healthy, sedentary, female, non- regular caffeine users completed 15 min of stationary cycling at a standardised power output equating to 65% HRmax (Phase A, followed by 10 min of stationary cycling where they were required to cycled as fast as they could (Phase B after ingesting 6.0 mg·kg-1 of caffeine or placebo 60 min prior to exercise. VO2 and energy expenditure were significantly higher at the end of Phase A (p = 0.008 and p = 0.011, respectively. All other variables examined in Phase A were similar between trials. In Phase B, there were no significant differences found for any variable assessed. While caffeine ingestion resulted in significant increases in VO2 and energy expenditure during steady-state exercise, it did not improve cycling performance during a 10 min trial where participants were required to cycle as fast as they could

  6. 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

  7. Fatigue related impairments in oculomotor control are prevented by caffeine

    Science.gov (United States)

    Connell, Charlotte J. W.; Thompson, Benjamin; Kuhn, Gustav; Claffey, Michael P.; Duncan, Shelley; Gant, Nicholas

    2016-01-01

    Strenuous exercise can result in an inability of the central nervous system to drive skeletal muscle effectively, a phenomenon known as central fatigue. The impact of central fatigue on the oculomotor system is currently unexplored. Fatigue that originates in the central nervous system may be related to perturbations in the synthesis and metabolism of several neurotransmitters. In this study we examine central fatigue in the oculomotor system after prolonged exercise. The involvement of central neurotransmission was explored by administering caffeine during exercise. Within a double-blind, randomized, repeated measures, crossover design, 11 cyclists consumed a placebo or caffeine solution during 180 min of stationary cycling. Saccadic eye movements were measured using infra-red oculography. Exercise decreased saccade velocity by 8% (placebo trial). This effect was reversed by caffeine, whereby velocity was increased by 11% after exercise. A non-oculomotor perceptual task (global motion processing) was unaffected by exercise. The human oculomotor system is impaired by strenuous exercise of the locomotor system. Caffeine exerts a protective effect on oculomotor control, which could be related to up-regulated central neurotransmission. In addition, cortical processes supporting global motion perception appear to be robust to fatigue. PMID:27222342

  8. 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...

  9. Cyclin D1 represses gluconeogenesis via inhibition of the transcriptional coactivator PGC1α.

    Science.gov (United States)

    Bhalla, Kavita; Liu, Wan-Ju; Thompson, Keyata; Anders, Lars; Devarakonda, Srikripa; Dewi, Ruby; Buckley, Stephanie; Hwang, Bor-Jang; Polster, Brian; Dorsey, Susan G; Sun, Yezhou; Sicinski, Piotr; Girnun, Geoffrey D

    2014-10-01

    Hepatic gluconeogenesis is crucial to maintain normal blood glucose during periods of nutrient deprivation. Gluconeogenesis is controlled at multiple levels by a variety of signal transduction and transcriptional pathways. However, dysregulation of these pathways leads to hyperglycemia and type 2 diabetes. While the effects of various signaling pathways on gluconeogenesis are well established, the downstream signaling events repressing gluconeogenic gene expression are not as well understood. The cell-cycle regulator cyclin D1 is expressed in the liver, despite the liver being a quiescent tissue. The most well-studied function of cyclin D1 is activation of cyclin-dependent kinase 4 (CDK4), promoting progression of the cell cycle. We show here a novel role for cyclin D1 as a regulator of gluconeogenic and oxidative phosphorylation (OxPhos) gene expression. In mice, fasting decreases liver cyclin D1 expression, while refeeding induces cyclin D1 expression. Inhibition of CDK4 enhances the gluconeogenic gene expression, whereas cyclin D1-mediated activation of CDK4 represses the gluconeogenic gene-expression program in vitro and in vivo. Importantly, we show that cyclin D1 represses gluconeogenesis and OxPhos in part via inhibition of peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α) activity in a CDK4-dependent manner. Indeed, we demonstrate that PGC1α is novel cyclin D1/CDK4 substrate. These studies reveal a novel role for cyclin D1 on metabolism via PGC1α and reveal a potential link between cell-cycle regulation and metabolic control of glucose homeostasis.

  10. 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

  11. 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

  12. Associations between smoking and caffeine consumption in two European cohorts

    Science.gov (United States)

    Taylor, Amy E.; Ware, Jennifer J.; McMahon, George; Hottenga, Jouke‐Jan; Baselmans, Bart M. L.; Willemsen, Gonneke; Boomsma, Dorret I.; Munafò, Marcus R.; Vink, Jacqueline M.

    2016-01-01

    Abstract Aims To estimate associations between smoking initiation, smoking persistence and smoking heaviness and caffeine consumption in two population‐based samples from the Netherlands and the United Kingdom. Design Observational study employing data on self‐reported smoking behaviour and caffeine consumption. Setting Adults from the general population in the Netherlands and the United Kingdom. Participants Participants from the Netherlands Twin Register [NTR: n = 21 939, mean age 40.8, standard deviation (SD) = 16.9, 62.6% female] and the Avon Longitudinal Study of Parents and Children (ALSPAC: n = 9086, mean age 33.2, SD = 4.7, 100% female). Measurements Smoking initiation (ever versus never smoking), smoking persistence (current versus former smoking), smoking heaviness (number of cigarettes smoked) and caffeine consumption in mg per day through coffee, tea, cola and energy drinks. Findings After correction for age, gender (NTR), education and social class (ALSPAC), smoking initiation was associated with consuming on average 52.8 [95% confidence interval (CI) = 45.6–60.0; NTR] and 59.5 (95% CI = 51.8–67.2; ALSPAC) mg more caffeine per day. Smoking persistence was also associated with consuming more caffeine [+57.9 (95% CI = 45.2–70.5) and +83.2 (95% CI = 70.2–96.3) mg, respectively]. Each additional cigarette smoked per day was associated with 3.7 (95% CI = 1.9–5.5; NTR) and 8.4 (95% CI = 6.9–10.0; ALSPAC) mg higher daily caffeine consumption in current smokers. Smoking was associated positively with coffee consumption and less strongly with cola and energy drinks. For tea, associations were positive in ALSPAC and negative in NTR. Conclusions There appears to be a positive association between smoking and caffeine consumption in the Netherlands and the United Kingdom. PMID:26750569

  13. 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.

  14. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Donna [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore); Zhao Bin [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore); Moochhala, Shabbir [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore)]. E-mail: mshabbir@dso.org.sg; Yang Yiyan [Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, 04-01, The Nanos, Singapore 138669 (Singapore)

    2006-07-25

    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.

  16. Kinetics of growth and caffeine demethylase production of Pseudomonas sp. in bioreactor.

    Science.gov (United States)

    Gummadi, Sathyanarayana N; Santhosh, Devarai

    2010-09-01

    The effect of various initial caffeine concentrations on growth and caffeine demethylase production by Pseudomonas sp. was studied in bioreactor. At initial concentration of 6.5 g l(-1) caffeine, Pseudomonas sp. showed a maximum specific growth rate of 0.2 h(-1), maximum degradation rate of 1.1 g h(-1), and caffeine demethylase activity of 18,762 U g CDW(-1) (CDW: cell dry weight). Caffeine degradation rate was 25 times higher in bioreactor than in shake flask. For the first time, we show highest degradation of 75 g caffeine (initial concentration 20 g l(-1)) in 120 h, suggesting that the tested strain has potential for successful bioprocess for caffeine degradation. Growth kinetics showed substrate inhibition phenomenon. Various substrate inhibition models were fitted to the kinetic data, amongst which the double-exponential (R(2) = 0.94), Luong (R(2) = 0.92), and Yano and Koga 2 (R(2) = 0.94) models were found to be the best. The Luedeking-Piret model showed that caffeine demethylase production kinetics was growth related. This is the first report on production of high levels of caffeine demethylase in batch bioreactor with faster degradation rate and high tolerance to caffeine, hence clearly suggesting that Pseudomonas sp. used in this study is a potential biocatalyst for industrial decaffeination.

  17. 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

  18. 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.

  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. 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

  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. 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.

  5. 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.

  6. 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.

  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. 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.

  9. 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

  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. 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. Phosphorylation of pRb by cyclin D kinase is necessary for development of cardiac hypertrophy

    DEFF Research Database (Denmark)

    Hinrichsen, R.; Hansen, A.H.; Busk, P.K.;

    2008-01-01

    /6-phosphorylated retinoblastoma protein (pRb) during hypertrophy and expression of an unphosphorylatable pRb mutant impaired hypertrophic growth in cardiomyocytes. Transcription factor E2F was activated by hypertrophic elicitors but activation was impaired by pharmacological inhibition of cyclin D-cdk4....../6. Inhibition of cyclin E-cdk2 complex only partly impaired E2F activity and did not prevent hypertrophic growth, but diminished endoreplication during hypertrophy. CONCLUSIONS: These results indicate that cyclin D-cdk4/6-dependent phosphorylation of pRb and activation of E2F is necessary for hypertrophic...

  13. 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...

  14. 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...

  15. 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.

  16. 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

  17. 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)

  18. DETERMINATION OF CAFFEINE CONTENTS OF COFFEE BRANDS IN THE VIETNAMESE MARKET

    Directory of Open Access Journals (Sweden)

    Stanislav Kráčmar

    2012-02-01

    Full Text Available In this study, the caffeine contents in five certain Vietnamese coffee (Dak Tin, Di Linh, Nam Nguyen, Origin and Vinacafe found in the Vietnamese market were determined using UV/vis spectrophotometry. The quantification of caffeine sample was calculated by standard addition method. Our results showed that the caffeine contents in coffee brewing were influenced by temperature of water used to brew, time of brewing, and independent on the volume of water, respectively. In general, higher concentrations of caffeine were found in all samples prepared at temperature 100°C for 5 minutes. The order of caffeine contents in coffee samples was Dak Tin, Di Linh, Nam Nguyen, Origin and Vinacafe, respectively. This study can contribute to a better knowledge of caffeine contents in Vietnamese coffee of Vietnamese consumers.

  19. 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

  20. Therapeutic Opportunities for Caffeine and A2A Receptor Antagonists in Retinal Diseases.

    Science.gov (United States)

    Boia, Raquel; Ambrósio, António Francisco; Santiago, Ana Raquel

    2016-01-01

    Caffeine, the major component of coffee, is the most consumed psychostimulant in the world. Caffeine is an adenosine analog and acts as a nonselective adenosine receptor antagonist. The majority of the effects of caffeine are mainly mediated by the blockade of adenosine receptors, and the proved neuroprotective effects of caffeine in brain disorders have been mimicked by the blockade of adenosine A2A receptor (A2AR). A growing body of evidence demonstrates that microglia-mediated neuroinflammation plays a key role in the pathophysiology of brain and retinal diseases. Moreover, the control of microglia reactivity by blocking A2AR has been proposed to be the mechanism underlying the observed protective effects of caffeine. Hence, it is conceivable that caffeine and A2AR antagonists offer therapeutic value for the treatment of retinal diseases, mainly those involving microglia-mediated neuroinflammation.

  1. [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

  2. Regulation of GATA-binding protein 2 levels via ubiquitin-dependent degradation by Fbw7: involvement of cyclin B-cyclin-dependent kinase 1-mediated phosphorylation of THR176 in GATA-binding protein 2.

    Science.gov (United States)

    Nakajima, Tomomi; Kitagawa, Kyoko; Ohhata, Tatsuya; Sakai, Satoshi; Uchida, Chiharu; Shibata, Kiyoshi; Minegishi, Naoko; Yumimoto, Kanae; Nakayama, Keiichi I; Masumoto, Kazuma; Katou, Fuminori; Niida, Hiroyuki; Kitagawa, Masatoshi

    2015-04-17

    A GATA family transcription factor, GATA-binding protein 2 (GATA2), participates in cell growth and differentiation of various cells, such as hematopoietic stem cells. Although its expression level is controlled by transcriptional induction and proteolytic degradation, the responsible E3 ligase has not been identified. Here, we demonstrate that F-box/WD repeat-containing protein 7 (Fbw7/Fbxw7), a component of Skp1, Cullin 1, F-box-containing complex (SCF)-type E3 ligase, is an E3 ligase for GATA2. GATA2 contains a cell division control protein 4 (Cdc4) phosphodegron (CPD), a consensus motif for ubiquitylation by Fbw7, which includes Thr(176). Ectopic expression of Fbw7 destabilized GATA2 and promoted its proteasomal degradation. Substitution of threonine 176 to alanine in GATA2 inhibited binding with Fbw7, and the ubiquitylation and degradation of GATA2 by Fbw7 was suppressed. The CPD kinase, which mediates the phosphorylation of Thr(176), was cyclin B-cyclin-dependent kinase 1 (CDK1). Moreover, depletion of endogenous Fbw7 stabilized endogenous GATA2 in K562 cells. Conditional Fbw7 depletion in mice increased GATA2 levels in hematopoietic stem cells and myeloid progenitors at the early stage. Increased GATA2 levels in Fbw7-conditional knock-out mice were correlated with a decrease in a c-Kit high expressing population of myeloid progenitor cells. Our results suggest that Fbw7 is a bona fide E3 ubiquitin ligase for GATA2 in vivo.

  3. 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

  4. 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

  5. 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

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

    OpenAIRE

    Dimitrios Moustakas; Michael Mezzio; Branden R Rodriguez; Mic Andre Constable; 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...

  7. 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...

  8. 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.

  9. 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

  10. Histone deacetylase inhibitor, Trichostatin A induces ubiquitin-dependent cyclin D1 degradation in MCF-7 breast cancer cells

    Directory of Open Access Journals (Sweden)

    Charles Coombes R

    2006-02-01

    Full Text Available Abstract Background Cyclin D1 is an important regulator of G1-S phase cell cycle transition and has been shown to be important for breast cancer development. GSK3β phosphorylates cyclin D1 on Thr-286, resulting in enhanced ubiquitylation, nuclear export and degradation of the cyclin in the cytoplasm. Recent findings suggest that the development of small-molecule cyclin D1 ablative agents is of clinical relevance. We have previously shown that the histone deacetylase inhibitor trichostatin A (TSA induces the rapid ubiquitin-dependent degradation of cyclin D1 in MCF-7 breast cancer cells prior to repression of cyclin D1 gene (CCND1 transcription. TSA treatment also resulted in accumulation of polyubiquitylated GFP-cyclin D1 species and reduced levels of the recombinant protein within the nucleus. Results Here we provide further evidence for TSA-induced ubiquitin-dependent degradation of cyclin D1 and demonstrate that GSK3β-mediated nuclear export facilitates this activity. Our observations suggest that TSA treatment results in enhanced cyclin D1 degradation via the GSK3β/CRM1-dependent nuclear export/26S proteasomal degradation pathway in MCF-7 cells. Conclusion We have demonstrated that rapid TSA-induced cyclin D1 degradation in MCF-7 cells requires GSK3β-mediated Thr-286 phosphorylation and the ubiquitin-dependent 26S proteasome pathway. Drug induced cyclin D1 repression contributes to the inhibition of breast cancer cell proliferation and can sensitize cells to CDK and Akt inhibitors. In addition, anti-cyclin D1 therapy may be highly specific for treating human breast cancer. The development of potent and effective cyclin D1 ablative agents is therefore of clinical relevance. Our findings suggest that HDAC inhibitors may have therapeutic potential as small-molecule cyclin D1 ablative agents.

  11. Caffeine improves left hemisphere processing of positive words.

    Directory of Open Access Journals (Sweden)

    Lars Kuchinke

    Full Text Available A positivity advantage is known in emotional word recognition in that positive words are consistently processed faster and with fewer errors compared to emotionally neutral words. A similar advantage is not evident for negative words. Results of divided visual field studies, where stimuli are presented in either the left or right visual field and are initially processed by the contra-lateral brain hemisphere, point to a specificity of the language-dominant left hemisphere. The present study examined this effect by showing that the intake of caffeine further enhanced the recognition performance of positive, but not negative or neutral stimuli compared to a placebo control group. Because this effect was only present in the right visual field/left hemisphere condition, and based on the close link between caffeine intake and dopaminergic transmission, this result points to a dopaminergic explanation of the positivity advantage in emotional word recognition.

  12. Caffeine in coffee: its removal. Why and how?

    Science.gov (United States)

    Ramalakshmi, K; Raghavan, B

    1999-09-01

    The popularity of coffee as a beverage is ever increasing despite the fact that there are reports antagonized to its consumption. Of the several factors cited, the alkaloid caffeine present in coffee can cause addiction and stimulate the central nervous system. It has an effect on the cardiovascular system with a slight increase in blood pressure and heart output. It undergoes biotransformation in the human body to form methylated derivatives of uric acid. In recent times, much effort has gone into the research on the removal of caffeine in coffee, resulting in a specialty product called decaffeinated coffee. Decaffeination methods mainly employ organic solvents or water or supercritical carbon dioxide. These methods with their attendant advantages and disadvantages are reviewed in this article.

  13. Effects of some polymeric additives on the cocrystallization of caffeine

    Science.gov (United States)

    Chung, Jihae; Kim, Il Won

    2011-11-01

    Effects of polymeric additives on the model cocrystallization were examined. The model cocrystal was made from caffeine and oxalic acid, and poly(ethylene glycol) (PEG), poly( L-lactide) (PLLA), poly(ɛ-caprolactone) (PCL), and poly(acrylic acid) (PAA) were the additives. The cocrystals were formed as millimeter-sized crystals without additives, and they became microcrystals with PLLA and PCL, and nanocrystals with PAA. XRD and IR revealed that the cocrystal structure was unchanged despite the strong effects of the additives on the crystal morphology, although some decrease in crystallinity was observed with PAA as confirmed by DSC. The DSC study also showed that the cocrystal melted and recrystallized to form α-caffeine upon heating. The present study verified that the polymeric additives can be utilized to modulate the size and morphology of the cocrystals without interfering the intermolecular interactions essential to the integrity of the cocrystal structures.

  14. Estimating caffeine intake from energy drinks and dietary supplements in the United States.

    Science.gov (United States)

    Bailey, Regan L; Saldanha, Leila G; Gahche, Jaime J; Dwyer, Johanna T

    2014-10-01

    No consistent definition exists for energy products in the United States. These products have been marketed and sold as beverages (conventional foods), energy shots (dietary supplements), and in pill or tablet form. Recently, the number of available products has surged, and formulations have changed to include caffeine. To help characterize the use of caffeine-containing energy products in the United States, three sources of data were analyzed: sales data, data from federal sources, and reports from the Drug Abuse Warning Network. These data indicate that sales of caffeine-containing energy products and emergency room visits involving their consumption appear to be increasing over time. Data from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 indicate that 2.7% [standard error (SE) 0.2%] of the US population ≥1 year of age used a caffeine-containing energy product, providing approximately 150-200 mg/day of caffeine per day in addition to caffeine from traditional sources like coffee, tea, and colas. The highest usage of these products was among males between the ages of 19 and 30 years (7.6%, SE 1.0). Although the prevalence of caffeine-containing energy product use remains low overall in the US population, certain subgroups appear to be using these products in larger amounts. Several challenges remain in determining the level of caffeine exposure from and accurate usage patterns of caffeine-containing energy products.

  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. 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...

  17. 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.

  18. 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.

  19. Does Caffeine Consumption Modify Cerebrospinal Fluid Amyloid-β Levels in Patients with Alzheimer's Disease?

    DEFF Research Database (Denmark)

    Travassos, Maria; Santana, Isabel; Baldeiras, Inês;

    2015-01-01

    Caffeine may be protective against Alzheimer's disease (AD) by modulating amyloid-β (Aβ) metabolic pathways. The present work aimed to study a possible association of caffeine consumption with the cerebrospinal fluid (CSF) biomarkers, particularly Aβ. The study included 88 patients with AD or mild...... cognitive impairment. The consumption of caffeine and theobromine was evaluated using a validated food questionnaire. Quantification of caffeine and main active metabolites was performed with liquid chromatography coupled to tandem mass spectrometry. The levels of A(1-42), total tau, and phosphorylated tau...

  20. 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...

  1. Differential Roles of Two Homologous Cyclin-Dependent Kinase Inhibitor Genes in Regulating Cell Cycle and Innate Immunity in Arabidopsis.

    Science.gov (United States)

    Hamdoun, Safae; Zhang, Chong; Gill, Manroop; Kumar, Narender; Churchman, Michelle; Larkin, John C; Kwon, Ashley; Lu, Hua

    2016-01-01

    Precise cell-cycle control is critical for plant development and responses to pathogen invasion. Two homologous cyclin-dependent kinase inhibitor genes, SIAMESE (SIM) and SIM-RELATED 1 (SMR1), were recently shown to regulate Arabidopsis (Arabidopsis thaliana) defense based on phenotypes conferred by a sim smr1 double mutant. However, whether these two genes play differential roles in cell-cycle and defense control is unknown. In this report, we show that while acting synergistically to promote endoreplication, SIM and SMR1 play different roles in affecting the ploidy of trichome and leaf cells, respectively. In addition, we found that the smr1-1 mutant, but not sim-1, was more susceptible to a virulent Pseudomonas syringae strain, and this susceptibility could be rescued by activating salicylic acid (SA)-mediated defense. Consistent with these results, smr1-1 partially suppressed the dwarfism, high SA levels, and cell death phenotypes in acd6-1, a mutant used to gauge the change of defense levels. Thus, SMR1 functions partly through SA in defense control. The differential roles of SIM and SMR1 are due to differences in temporal and spatial expression of these two genes in Arabidopsis tissues and in response to P. syringae infection. In addition, flow-cytometry analysis of plants with altered SA signaling revealed that SA is necessary, but not sufficient, to change cell-cycle progression. We further found that a mutant with three CYCD3 genes disrupted also compromised disease resistance to P. syringae. Together, this study reveals differential roles of two homologous cyclin-dependent kinase inhibitors in regulating cell-cycle progression and innate immunity in Arabidopsis and provides insights into the importance of cell-cycle control during host-pathogen interactions. PMID:26561564

  2. Cyclin A2:At the crossroads of cell cycle and cell invasion

    Institute of Scientific and Technical Information of China (English)

    Abdelhalim; Loukil; Caroline; T; Cheung; Nawal; Bendris; Bénédicte; Lemmers; Marion; Peter; Jean; Marie; Blanchard

    2015-01-01

    Cyclin A2 is an essential regulator of the cell division cycle through the activation of kinases that participate to the regulation of S phase as well as the mitotic entry. However,whereas its degradation by the proteasome in mid mitosis was thought to be essential for mitosis to proceed,recent observations show that a small fraction of cyclin A2 persists beyond metaphase and is degraded by autophagy. Its implication in the control of cytoskeletal dynamics and cell movement has unveiled its role in the modulation of Rho A activity. Since this GTPase is involved in both cell rounding early in mitosis and later,in the formation of the cleavage furrow,this suggests that cyclin A2 is a novel actor in cytokinesis. Taken together,these data point to this cyclin as a potential mediator of cell-niche interactions whose dysregulation could be taken as a hallmark of metastasis.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. Peptide inhibitors of CDK2-cyclin A that target the cyclin recruitment-site: structural variants of the C-terminal Phe.

    Science.gov (United States)

    Atkinson, Gail E; Cowan, Angela; McInnes, Campbell; Zheleva, Daniella I; Fischer, Peter M; Chan, Weng C

    2002-09-16

    A focused series of octapeptides based on the lead compound H-His-Ala-Lys-Arg-Arg-Leu-Ile-Phe-NH(2) 1, in which the C-terminal phenylalanine residue was replaced by alpha and/or beta-modified variants, was synthesized using solid-phase chemistry. Both the L-threo-beta-hydroxy-phenylalanine (beta-phenylserine, Pse) and (2S)-phenylalaninol derivatives, as competitive binders at the cyclin-recruitment site, displayed potent inhibitory activity towards the CDK2-cyclin A complex. Unexpectedly, the D-threo-Pse derivatives also showed inhibitory activity. PMID:12182847

  8. 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...

  9. Stage-specific requirement for cyclin D1 in glial progenitor cells of the cerebral cortex.

    Science.gov (United States)

    Nobs, Lionel; Baranek, Constanze; Nestel, Sigrun; Kulik, Akos; Kapfhammer, Josef; Nitsch, Cordula; Atanasoski, Suzana

    2014-05-01

    Despite the vast abundance of glial progenitor cells in the mouse brain parenchyma, little is known about the molecular mechanisms driving their proliferation in the adult. Here we unravel a critical role of the G1 cell cycle regulator cyclin D1 in controlling cell division of glial cells in the cortical grey matter. We detect cyclin D1 expression in Olig2-immunopositive (Olig2+) oligodendrocyte progenitor cells, as well as in Iba1+ microglia and S100β+ astrocytes in cortices of 3-month-old mice. Analysis of cyclin D1-deficient mice reveals a cell and stage-specific molecular control of cell cycle progression in the various glial lineages. While proliferation of fast dividing Olig2+ cells at early postnatal stages becomes gradually dependent on cyclin D1, this particular G1 regulator is strictly required for the slow divisions of Olig2+/NG2+ oligodendrocyte progenitors in the adult cerebral cortex. Further, we find that the population of mature oligodendrocytes is markedly reduced in the absence of cyclin D1, leading to a significant decrease in the number of myelinated axons in both the prefrontal cortex and the corpus callosum of 8-month-old mutant mice. In contrast, the pool of Iba1+ cells is diminished already at postnatal day 3 in the absence of cyclin D1, while the number of S100β+ astrocytes remains unchanged in the mutant.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. Improving the controlled delivery formulations of caffeine in alginate hydrogel beads combined with pectin, carrageenan, chitosan and psyllium.

    Science.gov (United States)

    Belščak-Cvitanović, Ana; Komes, Draženka; Karlović, Sven; Djaković, Senka; Spoljarić, Igor; Mršić, Gordan; Ježek, Damir

    2015-01-15

    Alginate-based blends consisting of carrageenan, pectin, chitosan or psyllium husk powder were prepared for assessment of the best formulation aimed at encapsulation of caffeine. Alginate-pectin blend exhibited the lowest viscosity and provided the smallest beads. Alginate-psyllium husk blend was characterised with higher viscosity, yielding the largest bead size and the highest caffeine encapsulation efficiency (83.6%). The release kinetics of caffeine indicated that the porosity of alginate hydrogel was not reduced sufficiently to retard the diffusion of caffeine from the beads. Chitosan coated alginate beads provided the most retarded release of caffeine in water. Morphological characteristics of beads encapsulating caffeine were adversely affected by freeze drying. Bitterness intensity of caffeine-containing beads in water was the lowest for alginate-psyllium beads and chitosan coated alginate beads. Higher sodium alginate concentration (3%) for production of hydrogel beads in combination with psyllium or chitosan coating would present the most favourable carrier systems for immobilization of caffeine.

  20. 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.

  1. 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

  2. Endothelial Nitric Oxide Mediates Caffeine Antagonism of Alcohol-Induced Cerebral Artery Constriction.

    Science.gov (United States)

    Chang, Jennifer; Fedinec, Alexander L; Kuntamallappanavar, Guruprasad; Leffler, Charles W; Bukiya, Anna N; Dopico, Alex M

    2016-01-01

    Despite preventive education, the combined consumption of alcohol and caffeine (particularly from "energy drinks") continues to rise. Physiologic perturbations by separate intake of ethanol and caffeine have been widely documented. However, the biologic actions of the alcohol-caffeine combination and their underlying subcellular mechanisms have been scarcely studied. Using intravital microscopy on a closed-cranial window and isolated, pressurized vessels, we investigated the in vivo and in vitro action of ethanol-caffeine mixtures on cerebral arteries from rats and mice, widely recognized models to address cerebrovascular pathophysiology and pharmacology. Caffeine at concentrations found in human circulation after ingestion of one to two cups of coffee (10 µM) antagonized the endothelium-independent constriction of cerebral arteries evoked by ethanol concentrations found in blood during moderate-heavy alcohol intoxication (40-70 mM). Caffeine antagonism against alcohol was similar whether evaluated in vivo or in vitro, suggesting independence of systemic factors and drug metabolism, but required a functional endothelium. Moreover, caffeine protection against alcohol increased nitric oxide (NO•) levels over those found in the presence of ethanol alone, disappeared upon blocking NO• synthase, and could not be detected in pressurized cerebral arteries from endothelial nitric-oxide synthase knockout (eNOS(-/-)) mice. Finally, incubation of de-endothelialized cerebral arteries with the NO• donor sodium nitroprusside (10 µM) fully restored the protective effect of caffeine. This study demonstrates for the first time that caffeine antagonizes ethanol-induced cerebral artery constriction and identifies endothelial NO• as the critical caffeine effector on smooth muscle targets. Conceivably, situations that perturb endothelial function and/or NO• availability will critically alter caffeine antagonism of alcohol-induced cerebrovascular constriction without

  3. 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...

  4. The effect of caffeine on working memory load-related brain activation in middle-aged males

    NARCIS (Netherlands)

    E.B. Klaassen; R.H.M. de Groot; E.A.T. Evers; J. Snel; E.C.I. Veerman; A.J.M. Ligtenberg; J. Jolles; D.J. Veltman

    2013-01-01

    Caffeine is commonly consumed in an effort to enhance cognitive performance. However, little is known about the usefulness of caffeine with regard to memory enhancement, with previous studies showing inconsistent effects on memory performance. We aimed to determine the effect of caffeine on working

  5. Maternal caffeine intake from coffee and tea, fetal growth, and the risks of adverse birth outcomes: The Generation R Study

    NARCIS (Netherlands)

    R. Bakker (Rachel); R.P.M. Steegers-Theunissen (Régine); A. Obradov (Aleksandra); H. Raat (Hein); A. Hofman (Albert); V.W.V. Jaddoe (Vincent)

    2010-01-01

    textabstractBackground: Caffeine is a widely used and accepted pharmacologically active substance. The effect of caffeine intake during pregnancy on fetal growth and development is still unclear. Objective: We examined the associations of maternal caffeine intake, on the basis of coffee and tea cons

  6. The effect of caffeine on working memory load-related brain activation in middle-aged males

    NARCIS (Netherlands)

    E.B. Klaassen; R.H.M. de Groot; E.A.T. Evers; J. Snel; E.C.I. Veerman; A.J.M. Ligtenberg; J. Jolles; D.J. Veltman

    2012-01-01

    Caffeine is commonly consumed in an effort to enhance cognitive performance. However, little is known about the usefulness of caffeine with regard to memory enhancement, with previous studies showing inconsistent effects on memory performance. We aimed to determine the effect of caffeine on working

  7. 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.

  8. 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

  9. 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.

  10. Illustrating Caffeine's Pharmacological and Expectancy Effects Utilizing a Balanced Placebo Design.

    Science.gov (United States)

    Lotshaw, Sandra C.; And Others

    1996-01-01

    Hypothesizes that pharmacological and expectancy effects may be two principles that govern caffeine consumption in the same way they affect other drug use. Tests this theory through a balanced placebo design on 100 male undergraduate students. Expectancy set and caffeine content appeared equally powerful, and worked additionally, to affect…

  11. Foetal response to maternal coffee intake : role of habitual versus non-habitual caffeine consumption

    NARCIS (Netherlands)

    Mulder, E. J. H.; Tegaldo, L.; Bruschettini, P.; Visser, G. H. A.

    2010-01-01

    Little is known about the effect on the human foetus of long-term and acute exposure to caffeine. We studied the organisation of foetal sleep-wake states in 13 healthy near-term foetuses over a wide range of maternal plasma caffeine concentrations (0-13 mu g/mL) reflecting normal lifestyle condition

  12. The influence of caffeine on spatial-selective attention : an event-related potential study

    NARCIS (Netherlands)

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

    2000-01-01

    Objectives: Following the indications of previous studies that caffeine might have a specific effect on the processing of spatial information compared with other types of information, the present study investigated the influence of caffeine on an often used spatial-selective attention task. Methods:

  13. Performance pressure and caffeine both affect cognitive performance, but likely through independent mechanisms

    NARCIS (Netherlands)

    Boere, J.J.; Fellinger, L.; Huizinga, D.J.H.; Wong, S.F.; Bijleveld, E.H.

    2016-01-01

    A prevalent combination in daily life, performance pressure and caffeine intake have both been shown to impact people's cognitive performance. Here, we examined the possibility that pressure and caffeine affect cognitive performance via a shared pathway. In an experiment, participants performed a mo

  14. Caffeine blocks disruption of blood brain barrier in a rabbit model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Ghribi Othman

    2008-04-01

    Full Text Available Abstract High levels of serum cholesterol and disruptions of the blood brain barrier (BBB have all been implicated as underlying mechanisms in the pathogenesis of Alzheimer's disease. Results from studies conducted in animals and humans suggest that caffeine might be protective against Alzheimer's disease but by poorly understood mechanisms. Using rabbits fed a cholesterol-enriched diet, we tested our hypothesis that chronic ingestion of caffeine protects against high cholesterol diet-induced disruptions of the BBB. New Zealand rabbits were fed a 2% cholesterol-enriched diet, and 3 mg caffeine was administered daily in drinking water for 12 weeks. Total cholesterol and caffeine concentrations from blood were measured. Olfactory bulbs (and for some studies hippocampus and cerebral cortex as well were evaluated for BBB leakage, BBB tight junction protein expression levels, activation of astrocytes, and microglia density using histological, immunostaining and immunoblotting techniques. We found that caffeine blocked high cholesterol diet-induced increases in extravasation of IgG and fibrinogen, increases in leakage of Evan's blue dye, decreases in levels of the tight junction proteins occludin and ZO-1, increases in astrocytes activation and microglia density where IgG extravasation was present. Chronic ingestion of caffeine protects against high cholesterol diet-induced increases in disruptions of the BBB, and caffeine and drugs similar to caffeine might be useful in the treatment of Alzheimer's disease.

  15. Relations Among Caffeine Consumption, Smoking, Smoking Urge, and Subjective Smoking Reinforcement in Daily Life.

    Science.gov (United States)

    Treloar, Hayley R; Piasecki, Thomas M; McCarthy, Danielle E; Baker, Timothy B

    2014-09-01

    Caffeine consumption and cigarette smoking tend to occur within the same individuals and at the same time. One potential explanation for this co-use is that caffeine consumption increases subjective smoking reinforcement. Electronic diaries were used to collect momentary reports of smoking, caffeine consumption, temptation/urge to smoke, and subjective smoking reinforcement in 74 prequit smokers. Momentary reports of caffeine consumption and smoking were associated, replicating previous findings. These results remained significant when contextual factors (time of day, weekday/weekend, presence of others, presence of others smoking, location, and past hour alcohol consumption) were covaried. Caffeine consumption was also associated with positive cigarette appraisals and reports of strong temptation/urge to smoke and urge reduction from the prior cigarette. Under the conditions of caffeine consumption versus at other times, smokers were significantly more likely to report their last cigarette as producing a rush/buzz, being pleasant, relaxing, and tasting good. The effects for temptation/urge to smoke and rush/buzz varied as a function of latency since smoking. Caffeine consumption increased reports of urge to smoke and rush/buzz only when smoking occurred more than 15 minutes prior to the diary entry. Findings suggest that caffeine consumption influences some aspects of smoking motivation or affects memorial processing of smoking reinforcement.

  16. 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

  17. 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.

  18. Use of saliva in therapeutic drug monitoring of caffeine in preterm infants

    NARCIS (Netherlands)

    de Wildt, SN; Kerkvliet, KTM; Wezenberg, MGA; Ottink, S; Hop, WCJ; Vulto, AG; van den Anker, JN

    2001-01-01

    Caffeine is frequently used to treat apnea of prematurity in preterm infants. Because caffeine has a narrow therapeutic window, plasma concentrations are generally monitored weekly. It would be advantageous to monitor this therapy without blood sampling; saliva might offer this possibility. Paired p

  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. 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 (

  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. 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...

  3. 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.

  4. Effects of dilute aqueous NaCl solution on caffeine aggregation

    Science.gov (United States)

    Sharma, Bhanita; Paul, Sandip

    2013-11-01

    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.

  5. BULK AND TEMPLATE-FREE SYNTHESIS OF SILVER NANOWIRES USING CAFFEINE AT ROOM TEMPERATURE

    Science.gov (United States)

    A simple eco-friendly one-pot method is described to synthesize bulk quantities of nanowires of silver (Ag) using caffeine without the need of reducing agent, surfactants, and/or large amounts of insoluble templates. Chemical reduction of silver salts with caffeine dramatically c...

  6. Cell cycle regulation of the cyclin A gene promoter is mediated by a variant E2F site

    DEFF Research Database (Denmark)

    Schulze, A; Zerfass, K; Spitkovsky, D;

    1995-01-01

    Cyclin A is involved in the control of S phase and mitosis in mammalian cells. Expression of the cyclin A gene in nontransformed cells is characterized by repression of its promoter during the G1 phase of the cell cycle and its induction at S-phase entry. We show that this mode of regulation...... is mediated by the transcription factor E2F, which binds to a specific site in the cyclin A promoter. It differs from the prototype E2F site in nucleotide sequence and protein binding; it is bound by E2F complexes containing cyclin E and p107 but not pRB. Ectopic expression of cyclin D1 triggers premature...... activation of the cyclin A promoter by E2F, and this effect is blocked by the tumor suppressor protein p16INK4....

  7. 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

  8. 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.

  9. Cyclin E in centrosome duplication and reduplication in sea urchin zygotes.

    Science.gov (United States)

    Schnackenberg, Bradley J; Marzluff, William F; Sluder, Greenfield

    2008-12-01

    When protein synthesis is completely blocked from before fertilization, the sea urchin zygote arrests in first S phase and the paternal centrosome reduplicates multiple times. However, when protein synthesis is blocked starting in prophase of first mitosis, the zygote divides and the blastomeres arrest in a G1-like state. The centrosome inherited from this mitosis duplicates only once in each blastomere for reasons that are not understood. The late G1 rise in cyclin E/cdk2 kinase activity initiates centrosome duplication in mammalian cells and its activity is needed for centrosome duplication in Xenopus egg extracts. Since the half-time for cyclin E turnover is normally approximately 1 h in sea urchin zygotes, the different behaviors of centrosomes during G1 and S phase arrests could be due to differential losses of cyclin E and its associated kinase activities at these two arrest points. To better understand the mechanisms that limit centrosome duplication, we characterize the levels of cyclin E and its associated kinase activity at the S phase and G1 arrest points. We first demonstrate that cyclin E/cdk2 kinase activity is required for centrosome duplication and reduplication in sea urchin zygotes. Next we find that cyclin E levels and cyclin E/cdk2 kinase activities are both constitutively and equivalently elevated during both the S phase and G1 arrests. This indicates that centrosome duplication during the G1 arrest is limited by a block to reduplication under conditions permissive for duplication. The cytoplasmic conditions of S phase, however, abrogate this block to reduplication.

  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. 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

  12. 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

  13. 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

  14. 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...

  15. Effect of Caffeine-Zn2+ System in Preventing Corrosion of Carbon Steel in Well Water

    Directory of Open Access Journals (Sweden)

    K. Rajam

    2013-01-01

    Full Text Available The inhibition efficiency (IE of caffeine in controlling corrosion of carbon steel in well water in the absence and presence of Zn2+ has been evaluated by mass loss method. The formulation, consisting of 200 ppm of caffeine and 50 ppm Zn2+, offers 82% inhibition efficiency to carbon steel immersed in well water. Addition of malic acid increases inhibition efficiency of the caffeine-Zn2+ system. The inhibition efficiency of caffeine-Zn2+ and caffeine-Zn2+-malic acid system decreases with the increase in immersion period and increases with the increase in pH from 3 to 11. AC impedance spectra, SEM micrographs, and AFM studies reveal the formation of protective film on the metal surface. The film is found to be UV fluorescent.

  16. Caffeine intake and semen quality in a population of 2,554 young Danish men

    DEFF Research Database (Denmark)

    Jensen, Tina Kold; Swan, Shanna H; Skakkebaek, Niels E;

    2010-01-01

    The authors examined the association between semen quality and caffeine intake among 2,554 young Danish men recruited when they were examined to determine their fitness for military service in 2001-2005. The men delivered a semen sample and answered a questionnaire including information about...... caffeine intake from various sources, from which total caffeine intake was calculated. Moderate caffeine and cola intakes (101-800 mg/day and 14 0.5-L bottles....../week) and/or caffeine (>800 mg/day) intake was associated with reduced sperm concentration and total sperm count, although only significant for cola. High-intake cola drinkers had an adjusted sperm concentration and total sperm count of 40 mill/mL (95% confidence interval (CI): 32, 51) and 121 mill (95% CI...

  17. 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.

  18. Caffeine and REM sleep deprivation: Effect on basal levels of signaling molecules in area CA1.

    Science.gov (United States)

    Alkadhi, Karim A; Alhaider, Ibrahim A

    2016-03-01

    We have investigated the neuroprotective effect of chronic caffeine treatment on basal levels of memory-related signaling molecules in area CA1 of sleep-deprived rats. Animals in the caffeine groups were treated with caffeine in drinking water (0.3g/l) for four weeks before they were REM sleep-deprived for 24h in the Modified Multiple Platforms paradigm. Western blot analysis of basal protein levels of plasticity- and memory-related signaling molecules in hippocampal area CA1 showed significant down regulation of the basal levels of phosphorylated- and total-CaMKII, phosphorylated- and total-CREB as well as those of BDNF and CaMKIV in sleep deprived rats. All these changes were completely prevented in rats that chronically consumed caffeine. The present findings suggest an important neuroprotective property of caffeine in sleep deprivation.

  19. 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.

  20. Central nervous system stimulants and drugs that suppress appetite

    DEFF Research Database (Denmark)

    Aagaard, Lise

    2014-01-01

    The Side Effects of Drugs Annuals form a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meyler's Side Effects of Drugs: the International Encyclopedia of Adverse Drug Reactions and Interactions. This revie......, methylxanthines (caffeine and theophylline), drugs that suppress appetite (phentermine, rimonabant, and sibutramine) and drugs used in Alzheimer's disease (donepezil and rivastigmine).......The Side Effects of Drugs Annuals form a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meyler's Side Effects of Drugs: the International Encyclopedia of Adverse Drug Reactions and Interactions. This review...... of the January 2012 to June 2013 publications on central nervous system stimulants and drugs that suppress appetite covers amphetamines (including metamfetamine, paramethoxyamfetamine and paramethoxymetamfetamine), fenfluramine and benfluorex, atomoxetine, methylphenidate, modafinil and armodafinil...

  1. 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

  2. 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

  3. No Enhancement of 24-Hour Visuomotor Skill Retention by Post-Practice Caffeine Administration.

    Directory of Open Access Journals (Sweden)

    Sara J Hussain

    Full Text Available Caffeine is widely consumed throughout the world and appears to indirectly facilitate learning and memory through effects on attention and motivation. Animal work indicates that post-training caffeine administration augments inhibitory avoidance memory, spatial memory, and object memory. In humans, post-training caffeine administration enhances the ability to discern between familiar images and new, similar images. However, the effect of post-training caffeine administration on motor memory has not been examined. Therefore, we tested two groups of low caffeine consumers (average weekly consumption ≤500 mg in a double-blind, placebo-controlled study involving acquisition of a continuous isometric visuomotor tracking skill. On Day 1, subjects completed 5 blocks (150 repetitions of training on the continuous isometric visuomotor skill and subsequently ingested either 200 mg of caffeine or placebo. On day 2, subjects completed an additional 5 blocks of training. Day 1 mean performance and performance variability were both similar between groups, suggesting that both groups acquired the motor skill similarly. For mean performance on Day 2, patterns of re-learning, mean performance learning magnitudes, mean performance learning rates, and mean performance retention magnitudes were all similar between groups. For performance variability on Day 2, there was a small trend towards increased variability in the caffeine group during re-learning, but performance variability learning magnitudes and performance variability retention magnitudes did not differ between groups. Because motor skill acquisition can also be conceptualized as a reduction in performance variability, these results suggest that there may be a small negative effect of post-practice caffeine administration on memory of a newly-learned visuomotor skill. Overall, we found no evidence to suggest that post-training caffeine administration enhances 24-hour retention of a newly

  4. 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 studies there is moderate evidence supporting the use of 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.

  5. Discriminative Stimulus Effects of Binary Drug Mixtures: Studies with Cocaine, MDPV, and Caffeine

    Science.gov (United States)

    Abbott, Megan; Galindo, Kayla; Rush, Elise L.; Rice, Kenner C.; France, Charles P.

    2016-01-01

    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 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

  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. 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

  9. 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...

  10. 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.

  11. 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

  12. 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

  13. c-Fos overexpression increases the proliferation of human hepatocytes by stabilizing nuclear Cyclin D1

    Institute of Scientific and Technical Information of China (English)

    Meryem G(u)ller; Kahina Toualbi-Abed; Agnès Legrand; Laurence Michel; Alain Mauviel; Dominique Bernuau; Fanny Daniel

    2008-01-01

    AIM: To investigate the effect of stable c-Fos over-expression on immortalized human hepatocyte (IHH) proliferation. METHODS: IHHs Stably transfected with c-Fos (IHH-Fos) or an empty "vector (IHH-C) were grown in me-dium supplemented with 1% serum or stimulated with 10% serum. Cell proliferation was assessed by cell counts, 3H-thymidine uptake and flow cytometry analyses. The levels of cell cycle regulatory proteins (Cyclin D1, E, A) cyclin dependent kinases (cdk) cdk2, cdk4, cdk6, and their inhibitors p15, p16, p21, p27, to-tal and phosphorylated GSK-3?and epidermal growth factor receptor (EGF-R) were assayed by Western blot-ting. Analysis of Cyclin D1 mRNA levels was performed by reverse transcription-polymerase chain reaction and real-time polymerase chain reaction (PCR) analysis. Stability of Cyclin D1 was studied by cycloheximide blockade experiments. RESULTS: Stable c-Fos overexpression increased cell proliferation under low serum conditions and resulted in a two-fold increase in [3H]-thymidine incorpora-tion following serum addition. Cell cycle analysis by flow cytometry showed that c-Fos accelerated the cell cycle kinetics. Following serum stimulation, Cyclin D1 was more abundantly expressed in c-Fos overexpress-ing cells. Cyclin D1 accumulation did not result from increased transcriptional activation, but from nuclear stabilization. Overexpression of c-Fos correlated with higher nuclear levels of inactive phosphorylated GSK-3? A kinase involved in Cyclin D1 degradation and higher levels of EGF-R mRNA, and EGF-R protein com-pared to IHH-C both in serum starved, and in serum stimulated cells. Abrogation of EGF-R signalling in IHH-Fos by treatment with AG1478, a specific EGF-R tyro-sine kinase inhibitor, prevented the phosphorylation of GSK-3?induced by serum stimulation and decreased Cyclin D1 stability in the nucleus. CONCLUSION: Our results clearly indicate a positive role for c-Fos in cell cycle regulation in hepatocytes. Importantly, we delineate a new

  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. Fluoride content in caffeinated, decaffeinated and herbal teas.

    Science.gov (United States)

    Chan, J T; Koh, S H

    1996-01-01

    The fluoride contents of infusions prepared from 44 different brands and types of teas were measured. Fluoride concentrations ranged from 0.34 to 3.71 ppm (mean = 1.50 ppm) in caffeinated tea infusions, 0.02-0.14 ppm (mean = 0.05 ppm) in herbal tea infusions, and 1.01-5.20 ppm (mean = 3.19) in decaffeinated tea infusions. This is the first report of the fluoride content of decaffeinated teas. The mean fluoride content of decaffeinated tea infusions is significantly (p decaffeination is the most likely explanation of the above observation.

  16. 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

    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 physiologically...... important. The few studies examining human muscle metabolism directly have also supported the fact that there is no change in fat or carbohydrate metabolism, but these usually have had a small sample size. We combined the data from muscle biopsy analyses of several similar studies to generate a sample size...

  17. Induction of cell cycle arrest via the p21, p27–cyclin E,A/Cdk2 pathway in SMMC-7721 hepatoma cells by clioquinol

    Directory of Open Access Journals (Sweden)

    Huang Zhiwei

    2015-12-01

    Full Text Available Clioquinol has been shown to have anticancer activity in several carcinoma cells. In this study, we preliminarily examined the effect of clioquinol in human SMMC-7721 hepatoma and QSG-7701 normal hepatic cells. Our results indicated that clioquinol did not significantly affect survival of QSG-7701 cells, whereas it reduced cell viability in a concentration- and time-dependent manner in SMMC-7721 cells. Clioquinol did not trigger autophagy and apoptosis, while it induced cell cycle arrest in the S-phase in SMMC- 7721 cells. Additionally, down-regulation of cyclin D1, A2, E1, Cdk2 and up-regulation of p21, p27 were detected after the treatment with clioquinol. The results demonstrated for the first time that clioquinol suppressed cell cycle progression in the S-phase in SMMC-7721 cells via the p21, p27-cyclin E,A/Cdk2 pathway. This suggests that clioquinol may have a therapeutic potential as an anticancer drug for certain malignances.

  18. NFAT1 transcription factor regulates cell cycle progression and cyclin E expression in B lymphocytes.

    Science.gov (United States)

    Teixeira, Leonardo K; Carrossini, Nina; Sécca, Cristiane; Kroll, José E; DaCunha, Déborah C; Faget, Douglas V; Carvalho, Lilian D S; de Souza, Sandro J; Viola, João P B

    2016-09-01

    The NFAT family of transcription factors has been primarily related to T cell development, activation, and differentiation. Further studies have shown that these ubiquitous proteins are observed in many cell types inside and outside the immune system, and are involved in several biological processes, including tumor growth, angiogenesis, and invasiveness. However, the specific role of the NFAT1 family member in naive B cell proliferation remains elusive. Here, we demonstrate that NFAT1 transcription factor controls Cyclin E expression, cell proliferation, and tumor growth in vivo. Specifically, we show that inducible expression of NFAT1 inhibits cell cycle progression, reduces colony formation, and controls tumor growth in nude mice. We also demonstrate that NFAT1-deficient naive B lymphocytes show a hyperproliferative phenotype and high levels of Cyclin E1 and E2 upon BCR stimulation when compared to wild-type B lymphocytes. NFAT1 transcription factor directly regulates Cyclin E expression in B cells, inhibiting the G1/S cell cycle phase transition. Bioinformatics analysis indicates that low levels of NFAT1 correlate with high expression of Cyclin E1 in different human cancers, including Diffuse Large B-cell Lymphomas (DLBCL). Together, our results demonstrate a repressor role for NFAT1 in cell cycle progression and Cyclin E expression in B lymphocytes, and suggest a potential function for NFAT1 protein in B cell malignancies.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. CyclinD1 and Survivin expression in parotid gland tumors%CyclinD1和Survivin在腮腺肿瘤中的表达

    Institute of Scientific and Technical Information of China (English)

    李云杉

    2014-01-01

    ObjectiveTo explore the cell cycle protein (CyclinD1) and apoptosis inhibiting factor (Survivin) expression in parotid gland tumors in the relationship.MethodsSelect from October 19, 2012 to 2012 on July 19 days the hospital for treatment of 54 patients with parotid gland tumor pathological section. ResultsCyclinD1 in the normal group, benign tumor and malignant tumor group, the positive rate of 5.0%, 25.0% and 70.6%, respectively, expression increased obviously, the difference was statistically significant (P<0.05), Survivin in the normal group, benign tumor and malignant tumor group were 0.0%, 30.0% and 67.6%, respectively, to express obviously increased, the difference was statistically significant (P<0.05). ConclusionCyclinD1 and Survivin in parotid gland tumor development played a synergy, can be used as important reference for diagnosis and treatment of parotid gland.%目的:探究细胞周期蛋白(CyclinD1)和凋亡抑制因子(Survivin)在腮腺肿瘤中的表达关系。方法选取自2012年10月19日~2014年7月19日来我院进行治疗的54例腮腺肿瘤患者的病理切片。结果 CyclinD1在常人组、良性肿瘤组和恶性肿瘤组的阳性率分别为5.0%、25.0%和70.6%,表现明显增高,差异有统计学意义(P<0.05),Survivin在常人组、良性肿瘤组和恶性肿瘤组的阳性率分别为0.0%、30.0%和67.6%,表达明显增高,差异有统计学意义(P<0.05)。结论 CyclinD1与Survivin在腮腺肿瘤的发展中起到了协同作用,可作为腮腺诊治的重要参考依据。

  4. Uncovering growth-suppressive MicroRNAs in lung cancer

    DEFF Research Database (Denmark)

    Liu, Xi; Sempere, Lorenzo F; Galimberti, Fabrizio;

    2009-01-01

    transgenic line (designated as ED-1 and ED-2 cells, respectively). Each highlighted miRNA was independently transfected into these cells. Growth-suppressive mechanisms were explored. Expression of a computationally predicted miRNA target was examined. These miRNAs were studied in a paired normal...... tissues. Individual overexpression of miR-34c, miR-145, and miR-142-5p in ED-1 and ED-2 cells markedly repressed cell growth. Anti-miR cotransfections antagonized this inhibition. The miR-34c target, cyclin E, was repressed by miR-34c transfection and provided a mechanism for observed growth suppression...

  5. ASPM regulates symmetric stem cell division by tuning Cyclin E ubiquitination

    Science.gov (United States)

    Capecchi, Mario R.; Pozner, Amir

    2016-01-01

    We generate a mouse model for the human microcephaly syndrome by mutating the ASPM locus, and demonstrate a premature exhaustion of the neuronal progenitor pool due to dysfunctional self-renewal processes. Earlier studies have linked ASPM mutant progenitor excessive cell cycle exit to a mitotic orientation defect. Here, we demonstrate a mitotic orientation-independent effect of ASPM on cell cycle duration. We pinpoint the cell fate-determining factor to the length of time spent in early G1 before traversing the restriction point. Characterization of the molecular mechanism reveals an interaction between ASPM and the Cdk2/Cyclin E complex, regulating the Cyclin activity by modulating its ubiquitination, phosphorylation and localization into the nucleus, before the cell is fated to transverse the restriction point. Thus, we reveal a novel function of ASPM in mediating the tightly coordinated Ubiquitin- Cyclin E- Retinoblastoma- E2F bistable-signalling pathway controlling restriction point progression and stem cell maintenance. PMID:26581405

  6. Cyclin B1和survivin在非小细胞肺癌中的表达和意义%The expression and significance of cyclin B1 and survivin in human non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Guosheng Li; Xuhan Liu; Daorong Zhang; Dong Liu; Zhiyong Li

    2011-01-01

    Objective: We studied the expression of cyclin B1 and survivin in human non-small cell lung cancer (NSCLC), and the relationship between such expression and clinicopathological features of NSCLC. Methods: One hundred cases of tissue specimen including NSCLC, neighboring noncancerous tissue and normal lung tissue were collected at random. These specimens were detected by immunohistochemical methods. Results: The expression of cyclin B1 and survivin showed significant difference (P 0.05) in NSCLC. Statistical significance was marked between different clinical stages of NSCLC and the expression of cyclin B1 and survivin (P < 0.05). Conclusion: The overexpression of cyclin B1 and survivin was found in NSCLC. The expression of cyclin B1 and survivin might be up-regulated during an early step of tumorigenesis and during the development of NSCLC. The progression of cell cycle could be efficiently connected with the control of apoptosis by the interrelations between the overexpression of cyclin B1 and that of survivin in NSCLC during the G2/M phase. The overexpression of cyclin B1 and survivin might be used as marker in showing the dividing and proliferating ability, and the inhibiting apoptosis ability (lengthening cell lifespan) of NSCLC. Moreover, the overexpression of cyclin B1 and survivin was associated with the clinic stages of NSCLC.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Modulatory effects of caffeine on oxidative stress and anxiety-like behavior in ovariectomized rats.

    Science.gov (United States)

    Caravan, Ionut; Sevastre Berghian, Alexandra; Moldovan, Remus; Decea, Nicoleta; Orasan, Remus; Filip, Gabriela Adriana

    2016-09-01

    Menopause is accompanied by enhanced oxidative stress and behavioral changes, effects attenuated by antioxidants. The aim of this study was to evaluate the effects of caffeine on behavior and oxidative stress in an experimental model of menopause. Female rats were divided into the following groups: sham-operated (CON), sham-operated and caffeine-treated (CAF), ovariectomized (OVX), ovariectomized and caffeine-treated (OVX+CAF). Caffeine (6 mg/kg) and vehicle were administered for 21 days (subchronic) and 42 days (chronic), using 2 experimental subsets. Behavioral tests and oxidative stress parameters in the blood, whole brain, and hippocampus were assessed. The subchronic administration of caffeine decreased the lipid peroxidation and improved the antioxidant defense in the blood and brain. The GSH/GGSG ratio in the brain was improved by chronic administration, with reduced activities of antioxidant enzymes and enhanced nitric oxide and malondialdehyde levels. In particular, the lipid peroxidation in the hippocampus decreased in both experiments. The rats became hyperactive after 21 days of treatment, but no effect was observed after chronic administration. In both experimental subsets, caffeine had anxiolytic effects as tested in elevated plus maze. The administration of low doses of caffeine, for a short period of time, may be a new therapeutic approach to modulating the oxidative stress and anxiety in menopause. PMID:27333093

  12. Caffeine Reduces Reaction Time and Improves Performance in Simulated-Contest of Taekwondo

    Directory of Open Access Journals (Sweden)

    Victor G. F. Santos

    2014-02-01

    Full Text Available The aim of this study was to investigate the effects of caffeine on reaction time during a specific taekwondo task and athletic performance during a simulated taekwondo contest. Ten taekwondo athletes ingested either 5 mg·kg−1 body mass caffeine or placebo and performed two combats (spaced apart by 20 min. The reaction-time test (five kicks “Bandal Tchagui” was performed immediately prior to the first combat and immediately after the first and second combats. Caffeine improved reaction time (from 0.42 ± 0.05 to 0.37 ± 0.07 s only prior to the first combat (P = 0.004. During the first combat, break times during the first two rounds were shorter in caffeine ingestion, followed by higher plasma lactate concentrations compared with placebo (P = 0.029 and 0.014, respectively. During the second combat, skipping-time was reduced, and relative attack times and attack/skipping ratio was increased following ingestion of caffeine during the first two rounds (all P < 0.05. Caffeine resulted in no change in combat intensity parameters between the first and second combat (all P > 0.05, but combat intensity was decreased following placebo (all P < 0.05. In conclusion, caffeine reduced reaction time in non-fatigued conditions and delayed fatigue during successive taekwondo combats.

  13. 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.

  14. 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.

  15. In Utero Caffeine Exposure Induces Transgenerational Effects on the Adult Heart

    Science.gov (United States)

    Fang, Xiefan; Poulsen, Ryan R.; Rivkees, Scott A.; Wendler, Christopher C.

    2016-01-01

    Each year millions of pregnant woman are exposed to caffeine, which acts to antagonize adenosine action. The long-term consequences of this exposure on the developing fetus are largely unknown, although in animal models we have found adverse effects on cardiac function. To assess if these effects are transmitted transgenerationally, we exposed pregnant mice to caffeine equivalent to 2–4 cups of coffee at two embryonic stages. Embryos (F1 generation) exposed to caffeine early from embryonic (E) day 6.5–9.5 developed a phenotype similar to dilated cardiomyopathy by 1 year of age. Embryos exposed to caffeine later (E10.5–13.5) were not affected. We next examined the F2 generation and F3 generation of mice exposed to caffeine from E10.5–13.5, as this coincides with germ cell development. These F2 generation adult mice developed a cardiac phenotype similar to hypertrophic cardiomyopathy. The F3 generation exhibited morphological changes in adult hearts, including increased mass. This report shows that in utero caffeine exposure has long-term effects into adulthood and that prenatal caffeine exposure can exert adverse transgenerational effects on adult cardiac function. PMID:27677355

  16. Restoration of cyclin D2 has an inhibitory potential on the proliferation of LNCaP cells

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Takashi [Department of Urology, Kyoto University, Graduate School of Medicine (Japan); Japan Society for the Promotion of Science (JSPS) Research Fellow (Japan); Nakamura, Eijiro; Shimizu, Yosuke; Terada, Naoki; Maeno, Atsushi; Kobori, Go; Kamba, Tomomi; Kamoto, Toshiyuki [Department of Urology, Kyoto University, Graduate School of Medicine (Japan); Ogawa, Osamu, E-mail: ogawao@kuhp.kyoto-u.ac.jp [Department of Urology, Kyoto University, Graduate School of Medicine (Japan); Inoue, Takahiro [Department of Urology, Kyoto University, Graduate School of Medicine (Japan)

    2009-09-11

    Despite well known oncogenic function of G1-S cell-cycle progression, cyclin D2 (CCND2) is often silenced epigenetically in prostate cancers. Here we show that CCND2 has an inhibitory potential on the proliferation of androgen receptor (AR)-dependent prostate cancer LNCaP cells. Forced expression of CCND2 suppressed the proliferative ability and induced cell death in LNCaP cells in a cdk-independent manner. Knocking down CCND2 restored the proliferation of LNCaP subclones with relatively high CCND2 expression and low proliferative profiles. Immunoprecipitation using deletion mutants of CCND2 indicated that a central domain of CCND2 is required for binding to AR. A deletion mutant lacking the central domain failed to hinder LNCaP cells. Collectively, our results indicated that CCND2 inhibits cell proliferation of AR-dependent prostate cancer through the interaction with AR. Our study suggests that restoration of CCND2 expression potentially prevents the carcinogenesis of prostate cancer, which is mostly AR-dependent in the initial settings.

  17. The BMI1 polycomb protein represses cyclin G2-induced autophagy to support proliferation in chronic myeloid leukemia cells.

    Science.gov (United States)

    Mourgues, L; Imbert, V; Nebout, M; Colosetti, P; Neffati, Z; Lagadec, P; Verhoeyen, E; Peng, C; Duprez, E; Legros, L; Rochet, N; Maguer-Satta, V; Nicolini, F-E; Mary, D; Peyron, J-F

    2015-10-01

    The BMI1 polycomb protein regulates self-renewal, proliferation and survival of cancer-initiating cells essentially through epigenetic repression of the CDKN2A tumor suppressor locus. We demonstrate here for the first time that BMI1 also prevents autophagy in chronic myeloid leukemia (CML) cell lines, to support their proliferation and clonogenic activity. Using chromatin immunoprecipitation, we identified CCNG2/cyclin G2 (CCNG2) as a direct BMI1 target. BMI1 downregulation in CD34+ CML cells by PTC-209 pharmacological treatment or shBMI1 transduction triggered CCNG2 expression and decreased clonogenic activity. Also, ectopic expression of CCNG2 in CD34+ CML cells strongly decreased their clonogenicity. CCNG2 was shown to act by disrupting the phosphatase 2A complex, which activates a PKCζ-AMPK-JNK-ERK pathway that engages autophagy. We observed that BMI1 and CCNG2 levels evolved inversely during the progression of CML towards an acute deadly phase, and therefore hypothesized that BMI1 could support acute transformation of CML through the silencing of a CCNG2-mediated tumor-suppressive autophagy response. PMID:25925206

  18. Restoration of cyclin D2 has an inhibitory potential on the proliferation of LNCaP cells

    International Nuclear Information System (INIS)

    Despite well known oncogenic function of G1-S cell-cycle progression, cyclin D2 (CCND2) is often silenced epigenetically in prostate cancers. Here we show that CCND2 has an inhibitory potential on the proliferation of androgen receptor (AR)-dependent prostate cancer LNCaP cells. Forced expression of CCND2 suppressed the proliferative ability and induced cell death in LNCaP cells in a cdk-independent manner. Knocking down CCND2 restored the proliferation of LNCaP subclones with relatively high CCND2 expression and low proliferative profiles. Immunoprecipitation using deletion mutants of CCND2 indicated that a central domain of CCND2 is required for binding to AR. A deletion mutant lacking the central domain failed to hinder LNCaP cells. Collectively, our results indicated that CCND2 inhibits cell proliferation of AR-dependent prostate cancer through the interaction with AR. Our study suggests that restoration of CCND2 expression potentially prevents the carcinogenesis of prostate cancer, which is mostly AR-dependent in the initial settings.

  19. 大鼠海马tau蛋白过度磷酸化时细胞周期蛋白cyclin D1的表达%Expression of mitotic protein cyclin D1 during tau hyperphosphorylation in rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    李妍; 董为人; 王海红; 刘忠英; 晏芳

    2011-01-01

    目的:探讨大鼠海马tau蛋白过度磷酸化时细胞周期蛋白cyclin D1的表达.方法:用cAMP-依赖性蛋白激酶 A (PKA) 的激动剂Forskolin注射大鼠侧脑室,免疫印迹和免疫组织化学技术检测大鼠海马tau蛋白的磷酸化水平,同时采用免疫印迹、免疫组织化学和RT-PCR方法检测海马cyclin D1和cyclin D1 mRNA.结果:侧脑室注射Forskolin 48h,大鼠海马tau蛋白Ser214、Ser396和Ser202/Thr205位点的磷酸化水平升高,同时检测到细胞周期蛋白cyclin D1和cyclin D1 mRNA.结论:侧脑室注射Forskolin诱导大鼠海马 tau蛋白过度磷酸化的同时,大鼠海马出现细胞周期蛋白cyclin D1的表达,提示了tau蛋白过度磷酸化与细胞周期相关蛋白cyclin D1之间可能的内在联系.%Objective: To investigate the expression of mitotic protein cyclin D1 during tau hyperphosphorylation. Methods: Forskolin (80 μmol/L, 40μl) was injected into the lateral ventricle by stereotaxic injection. Tau phosphorylation in the hippocampus of rats was measured by Western blot and immunohistochemistry. The expression of cyclin D1 protein and the level of cyclin D1 mRNA in the hippocampus of rats were detected by Western blot, irnmunohistochemistry and RT-PCR technique. Results: The level of tau phosphorylation at Ser214, Ser396 and Ser202/Thr205 sites was significantly elevated at 48 h after administration of Forskolin. Meanwhile cyclin D1 protein and cyclin D1 mRNA were detected in Forskolin injection group. Conclusion: Mitotic protein cyclin D1 expressed in the hippocampus of rats during tau hyperphosphorylation induced by injection of Forskolin into the lateral ventricle of the rats. Present results suggest a positive correlation between tau hyperphosphorylation and the mitotic protein cyclin D1.

  20. Expression of CDK1(Tyr15, pCDK1(Thr161, Cyclin B1 (total and pCyclin B1(Ser126 in vulvar squamous cell carcinoma and their relations with clinicopatological features and prognosis.

    Directory of Open Access Journals (Sweden)

    Zhihui Wang

    Full Text Available Cyclin B1-CDK1 complex plays an important role in the regulation of cell cycle. Activation of Cyclin B1 and CDK1 and the formation of the complex in G2/M are under multiple regulations involving many regulators such as isoforms of 14-3-3 and CDC25 and Wee1. Abnormal expression of Cyclin B1 and CDK1 has been detected in various tumors. However, to our knowledge no previous study has investigated Cyclin B1 and CDK1 in vulvar cancer. Therefore, we evaluated the statuses of CDK1Tyr15, pCDK1Thr161, Cyclin B1 (total and pCyclin B1Ser126 in 297 cases of vulvar squamous cell carcinomas by immunohistochemistry. Statistical analyses were performed to explore their clinicopathological and prognostic values. In at least 25% of tumor cases high expression of CDK1Tyr15, pCDK1Thr161, Cyclin B1 (total and pCyclin B1Ser126 was observed, compared to the low levels in normal vulvar squamous epithelium. Elevated levels of CDK1Tyr15, pCDK1Thr161, Cyclin B1 (total and pCyclin B1Ser126 were correlated with advanced tumor behaviors and aggressive features. Although CDK1Tyr15, pCDK1Thr161, Cyclin B1 (total and pCyclin B1Ser126 could not be identified as prognostic factors, combinations of (pCDK1Thr161 C+N + 14-3-3σN, (pCDK1Thr161 C+N + 14-3-3ηC, (pCDK1Thr161 C+N + Wee1C and (pCDK1Thr161 C+N + 14-3-3σN + 14-3-3ηC + Wee1C were correlated with disease-specific survival (p = 0.036, p = 0.029, p = 0.042 and p = 0.007, respectively in univariate analysis. The independent prognostic significance of (pCDK1Thr161 C+N + 14-3-3σN + 14-3-3ηC + Wee1C was confirmed by multivariate analysis. In conclusion, CDK1Tyr15, pCDK1Thr161, Cyclin B1 (total and pCyclin B1Ser126 may be involved in progression of vulvar squamous cell carcinoma. The combination of pCDK1Thr161, 14-3-3σ, 14-3-3η and Wee1 was a statistically independent prognostic factor.

  1. 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

  2. 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.

  3. 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

  4. 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

  5. Effects of aripiprazole on caffeine-induced hyperlocomotion and neural activation in the striatum.

    Science.gov (United States)

    Batista, Luara A; Viana, Thércia G; Silveira, Vívian T; Aguiar, Daniele C; Moreira, Fabrício A

    2016-01-01

    Aripiprazole is an antipsychotic that acts as a partial agonist at dopamine D2 receptors. In addition to its antipsychotic activity, this compound blocks the effects of some psychostimulant drugs. It has not been verified, however, if aripiprazole interferes with the effects of caffeine. Hence, this study tested the hypothesis that aripiprazole prevents caffeine-induced hyperlocomotion and investigated the effects of these drugs on neural activity in the striatum. Male Swiss mice received injections of vehicle or antipsychotic drugs followed by vehicle or caffeine. Locomotion was analyzed in a circular arena and c-Fos protein expression was quantified in the dorsolateral, dorsomedial, and ventrolateral striatum, and in the core and shell regions of nucleus accumbens. Aripiprazole (0.1, 1, and 10 mg/kg) prevented caffeine (10 mg/kg)-induced hyperlocomotion at doses that do not change basal locomotion. Haloperidol (0.01, 0.03, and 0.1 mg/kg) also decreased caffeine-induced hyperlocomotion at all doses, although at the two higher doses, this compound reduced basal locomotion. Immunohistochemistry analysis showed that aripiprazole increases c-Fos protein expression in all regions studied, whereas caffeine did not alter c-Fos protein expression. Combined treatment of aripiprazole and caffeine resulted in a decrease in the number of c-Fos positive cells as compared to the group receiving aripiprazole alone. In conclusion, aripiprazole prevents caffeine-induced hyperlocomotion and increases neural activation in the striatum. This latter effect is reduced by subsequent administration of caffeine. These results advance our understanding on the pharmacological profile of aripiprazole.

  6. EFFECTS OF siRNA TARGED CDK2 AND cyclinE ON CELL CYCLE AND APOPTOSIS OF HepG2 CELLS%靶向CDK2、cyclinE的siRNA对HepG2细胞周期及凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    曹银芳; 关泽红; 刘新风

    2009-01-01

    目的:探讨细胞周期蛋白依赖性激酶(cyclin-dependent-kinase 2,CDK2)活性对肝癌细胞株HepG2细胞周期和细胞凋亡的影响.方法:根据基因库中登录的人和鼠CDK2、cyclinE序列,设计并构建CDK2、cyclinE干扰RNA真核表达载体;脂质体法转染肝癌细胞株HepG2细胞,流式细胞术分析CDK2及cyclinE对HepG2细胞增殖的影响;蛋白质印迹法检测CDK2、cyclinE活性的变化caspase-3活性的影响.结果:1.成功构建CDK2及cyclinE干扰RNA真核表达载体psiCDK2、psiCyclinE,用脂质体法导入肝癌细胞株HepG2细胞中,有效表达.2.转染48h后与空载体组相比:psiCDK2、psiCyclinE组G1期细胞增多,G2/M和S期细胞减少;蛋白质印迹法分析表明psiCDK2、psiCyclinE组caspase-3酶原被激活.结论:靶向CDK2、cyclinE的siRNA能抑制HepG2细胞的增殖;靶向CDK2、cyclinE的siRNA能激活caspase-3,诱导肝癌细胞HepG2凋亡.

  7. EXPRESSION OF p16, CYCLIN D1 AND RB PROTEIN IN GASTRIC CARCINOMA AND PREMALIGNANT LESIONS

    Institute of Scientific and Technical Information of China (English)

    缪林; 赵志泉; 季国忠; 范志宁; 金宁; 刘政; 张平; 程铁华

    2003-01-01

    Objective: To investigate the expression of p16, cyclin D1 and Rb protein in gastric carcinoma and premalignant lesions including dysplastic gastric mucosa and intestinal metaplasia gastric mucosa. Methods: Using SP immunohistochemical methods, the expression of pl6, cyclin D1 and Rb proteins was detected in 10 specimens of normal gastric mucosa, 15 specimens of dysplastic gastric mucosa, 15 specimens of intestinal metaplasia gastric mucosa, 30 specimens of gastric carcinoma. The clinical characteristics of the 30 patients with gastric carcinoma were analysed to explore the relationship between the parameter detected and biological action of gastric cancer. Results: Expression of p16 protein was detected in 90% of normal gastric mucosa, 86.67% of dysplastic gastric mucosa, 86.67% of intestinal metaplasia gastric mucosa, 36.67% of gastric carcinoma. The positive rate of p16 protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.01). Expression of cyclin D1 protein was detected in 10% of normal gastric mucosa, 20% of dysplastic gastric mucosa, 20% of intestinal metaplasia gastric mucosa, 53.33% of gastric carcinoma. The positive rate of cyclin D1, protein expression in gastric carcinoma is significantly higher than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.05). Expression of Rb protein was detected in 90% of normal gastric mucosa, 80% of dysplastic gastric mucosa, 80% of intestinal metaplasia gastric mucosa, 50% of gastric carcinoma. The positive rate of Rb protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa (P<0.05). The expression of p16, cyclin D1 gene were associated with the degree of differentiation of gastric carcinoma, lymphnodes metastasis and distant metastasis. Conclusion: p16, Cyclin D1 and Rb gene play important role in gastric carcinoma genesis. The expression of p16, cyclin D1 and Rb gene

  8. Alternative splicing variants of human Fbx4 disturb cyclin D1 proteolysis in human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Xiufeng; Zhang, Ting; Wang, Jie; Li, Meng; Zhang, Xiaolei; Tu, Jing [Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China); Sun, Shiqin [College of Pharmacy, Harbin Medical University-Daqing, Daqing, Heilongjiang 163319 (China); Chen, Xiangmei, E-mail: xm_chen6176@bjmu.edu.cn [Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China); Lu, Fengmin [Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191 (China)

    2014-04-25

    Highlights: • The expression of Fbx4 was significantly lower in HCC tissues. • Novel splicing variants of Fbx4 were identified. • These novel variants are much more abundant in human cancer tissues and cells. • The novel Fbx4 isoforms could promote cell proliferation and migration in vitro. • These isoforms showed less capability for cyclin D1 binding and degradation. - Abstract: 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 168–245nt 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

  9. Unique Cyclin-Dependent Kinase (CDK) Inhibitors at the ATP-site

    Institute of Scientific and Technical Information of China (English)

    LI Lin; LUNDGREN Karen; ESCOBAR Jorge; MINNICK Sharon price; HUBER Andrea; KOUDRIAKOVA Tatiana; ARRUDA Jeannie; SISSON Wes; AUST Robert M.; VERKHIVKER Gennady M.; SCHAFFER Lana; CHONG Wesley K. M.; ROSE Peter w.; LEWIS Cristrina T; DUVADIE Rohit K.; CHU Shao Song; YANG Y. Michelle; NONOMIYA Jim; TUCKER Kadthleen D.; KNIGHTON Daniel R.; FERRE RoseAnn

    2001-01-01

    @@ Control of the cell cycle could be applicable in new approaches for cancer chemotherapy. The cyclin-dependent kinases (CDK's) and their corresponding complexes with cyclins are regulatory enzymes for which we have discovered a novel small molecule series of inhibitors, with potencies in the nanomolar range and good selectivity for the CDK's versus other kinases. We will discuss structure-based drug design efforts with crystal structures of complexes with certain CDK's. Cellular effects and some preliminary examination of in vivo cancer efficacy by these inhibitors will also be discussed.

  10. Specialization of B-Type Cyclins for Mitosis or Meiosis in S. Cerevisiae

    OpenAIRE

    Dahmann, C.; Futcher, B.

    1995-01-01

    The CLB1, CLB2, and CLB3 genes encode B-type cyclins important for mitosis in Saccharomyces cerevisiae, while a fourth B-type cyclin gene, CLB4, has no clear role. The effects of homozygous clb mutations on meiosis were examined. Mutants homozygous for clb1 clb3, or for clb1 clb4, gave high levels of sporulation, but produced mainly two-spored asci instead of four-spored asci. The cells had completed meiosis I but not meiosis II, producing viable diploid ascospores. CLB1 and CLB4 seem to be m...

  11. The elements of human cyclin D1 promoter and regulation involved

    OpenAIRE

    Guo, Zhi-yi; Hao, Xiao-hui; Tan, Fei-Fei; Pei, Xin; Shang, Li-Mei; Jiang, Xue-lian; Yang, Fang

    2011-01-01

    Cyclin D1 is a cell cycle machine, a sensor of extracellular signals and plays an important role in G1-S phase progression. The human cyclin D1 promoter contains multiple transcription factor binding sites such as AP-1, NF-қB, E2F, Oct-1, and so on. The extracellular signals functions through the signal transduction pathways converging at the binding sites to active or inhibit the promoter activity and regulate the cell cycle progression. Different signal transduction pathways regulate the pr...

  12. Prevalence and clinical implications of cyclin D1 expression in diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy

    DEFF Research Database (Denmark)

    Ok, Chi Young; Xu-Monette, Zijun Y; Tzankov, Alexandar;

    2014-01-01

    BACKGROUND: Cyclin D1 expression has been reported in a subset of patients with diffuse large B-cell leukemia (DLBCL), but studies have been few and generally small, and they have demonstrated no obvious clinical implications attributable to cyclin D1 expression. METHODS: The authors reviewed 143...

  13. 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...

  14. 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...

  15. 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...

  16. 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)

  17. Intermolecular Interactions between Eosin Y and Caffeine Using 1H-NMR Spectroscopy

    Directory of Open Access Journals (Sweden)

    Macduff O. Okuom

    2013-01-01

    Full Text Available DETECHIP has been used in testing analytes including caffeine, cocaine, and tetrahydrocannabinol (THC from marijuana, as well as date rape and club drugs such as flunitrazepam, gamma-hydroxybutyric acid (GHB, and methamphetamine. This study investigates the intermolecular interaction between DETECHIP sensor eosin Y (DC1 and the analyte (caffeine that is responsible for the fluorescence and color changes observed in the actual array. Using 1H-NMR, 1H-COSY, and 1H-DOSY NMR methods, a proton exchange from C-8 of caffeine to eosin Y is proposed.

  18. 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...

  19. 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...

  20. 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...... that 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...

  1. 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...

  2. 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

    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 the study period....

  3. Bufalin induces G0/G1 phase arrest through inhibiting the levels of cyclin D, cyclin E, CDK2 and CDK4, and triggers apoptosis via mitochondrial signaling pathway in T24 human bladder cancer cells.

    Science.gov (United States)

    Huang, Wen-Wen; Yang, Jai-Sing; Pai, Shu-Jen; Wu, Ping-Ping; Chang, Shu-Jen; Chueh, Fu-Shin; Fan, Ming-Jen; Chiou, Shang-Ming; Kuo, Hsiu-Maan; Yeh, Chin-Chung; Chen, Po-Yuan; Tsuzuki, Minoru; Chung, Jing-Gung

    2012-04-01

    Most of the chemotherapy treatments for bladder cancer aim to kill the cancer cells, but a high recurrence rate after medical treatments is still occurred. Bufalin from the skin and parotid venom glands of toad has been shown to induce apoptotic cell death in many types of cancer cell lines. However, there is no report addressing that bufalin induced cell death in human bladder cancer cells. The purpose of this study was investigated the mechanisms of bufalin-induced apoptosis in a human bladder cancer cell line (T24). We demonstrated the effects of bufalin on the cell growth and apoptosis in T24 cells by using DAPI/TUNEL double staining, a PI exclusion and flow cytometric analysis. The effects of bufalin on the production of reactive oxygen species (ROS), the level of mitochondrial membrane potential (ΔΨ(m)), and DNA content including sub-G1 (apoptosis) in T24 cells were also determined by flow cytometry. Western blot analysis was used to examine the expression of G(0)/G(1) phase-regulated and apoptosis-associated protein levels in bufalin-treated T24 cells. The results indicated that bufalin significantly decreased the percentage of viability, induced the G(0)/G(1) phase arrest and triggered apoptosis in T24 cells. The down-regulation of the protein levels for cyclin D, CDK4, cyclin E, CDK2, phospho-Rb, phospho-AKT and Bcl-2 with the simultaneous up-regulation of the cytochrome c, Apaf-1, AIF, caspase-3, -7 and -9 and Bax protein expressions and caspase activities were observed in T24 cells after bufalin treatment. Based on our results, bufalin induces apoptotic cell death in T24 cells through suppressing AKT activity and anti-apoptotic Bcl-2 protein as well as inducing pro-apoptotic Bax protein. The levels of caspase-3, -7 and -9 are also mediated apoptosis in bufalin-treated T24 cells. Therefore, bufalin might be used as a therapeutic agent for the treatment of human bladder cancer in the future. PMID:22285700

  4. Bufalin induces G0/G1 phase arrest through inhibiting the levels of cyclin D, cyclin E, CDK2 and CDK4, and triggers apoptosis via mitochondrial signaling pathway in T24 human bladder cancer cells.

    Science.gov (United States)

    Huang, Wen-Wen; Yang, Jai-Sing; Pai, Shu-Jen; Wu, Ping-Ping; Chang, Shu-Jen; Chueh, Fu-Shin; Fan, Ming-Jen; Chiou, Shang-Ming; Kuo, Hsiu-Maan; Yeh, Chin-Chung; Chen, Po-Yuan; Tsuzuki, Minoru; Chung, Jing-Gung

    2012-04-01

    Most of the chemotherapy treatments for bladder cancer aim to kill the cancer cells, but a high recurrence rate after medical treatments is still occurred. Bufalin from the skin and parotid venom glands of toad has been shown to induce apoptotic cell death in many types of cancer cell lines. However, there is no report addressing that bufalin induced cell death in human bladder cancer cells. The purpose of this study was investigated the mechanisms of bufalin-induced apoptosis in a human bladder cancer cell line (T24). We demonstrated the effects of bufalin on the cell growth and apoptosis in T24 cells by using DAPI/TUNEL double staining, a PI exclusion and flow cytometric analysis. The effects of bufalin on the production of reactive oxygen species (ROS), the level of mitochondrial membrane potential (ΔΨ(m)), and DNA content including sub-G1 (apoptosis) in T24 cells were also determined by flow cytometry. Western blot analysis was used to examine the expression of G(0)/G(1) phase-regulated and apoptosis-associated protein levels in bufalin-treated T24 cells. The results indicated that bufalin significantly decreased the percentage of viability, induced the G(0)/G(1) phase arrest and triggered apoptosis in T24 cells. The down-regulation of the protein levels for cyclin D, CDK4, cyclin E, CDK2, phospho-Rb, phospho-AKT and Bcl-2 with the simultaneous up-regulation of the cytochrome c, Apaf-1, AIF, caspase-3, -7 and -9 and Bax protein expressions and caspase activities were observed in T24 cells after bufalin treatment. Based on our results, bufalin induces apoptotic cell death in T24 cells through suppressing AKT activity and anti-apoptotic Bcl-2 protein as well as inducing pro-apoptotic Bax protein. The levels of caspase-3, -7 and -9 are also mediated apoptosis in bufalin-treated T24 cells. Therefore, bufalin might be used as a therapeutic agent for the treatment of human bladder cancer in the future.

  5. Inotodiol inhabits proliferation and induces apoptosis through modulating expression of cyclinE, p27, bcl-2, and bax in human cervical cancer HeLa cells.

    Science.gov (United States)

    Zhao, Li-Wei; Zhong, Xiu-Hong; Yang, Shu-Yan; Zhang, Yi-Zhong; Yang, Ning-Jiang

    2014-01-01

    Inonotus obliquus is a medicinal mushroom that has been used as an effective agent to treat various diseases such as diabetes, tuberculosis and cancer. Inotodiol, an included triterpenoid shows significant anti-tumor effect. However, the mechanisms have not been well documented. In this study, we aimed to explore the effect of inotodiol on proliferation and apoptosis in human cervical cancer HeLa cells and investigated the underlying molecular mechanisms. HeLa cells were treated with different concentrations of inotodiol. The MTT assay was used to evaluate cell proliferating ability, flow cytometry (FCM) was employed for cell cycle analysis and cell apoptosis, while expression of cyclinE, p27, bcl-2 and bax was detected by immunocytochemistry. Proliferation of HeLa cells was inhibited by inotodiolin a dose-dependent manner at 24h (r=0.9999, pInonotus obliquus inhibited the proliferation of HeLa cells and induced apoptosis in vitro. The mechanisms may be related to promoting apoptosis through increasing the expression of bax and cutting bcl-2 and affecting the cell cycle by down-regulation the expression of cyclin E and up-regulation of p27. The results further indicate the potential value of inotodiol for treatment of human cervical cancer. PMID:24815470

  6. Growth hormone suppression test

    Science.gov (United States)

    GH suppression test; Glucose loading test; Acromegaly - blood test; Gigantism - blood test ... during the suppression test, the provider will suspect gigantism or acromegaly. You may need to be retested to confirm ...

  7. Dexamethasone suppression test

    Science.gov (United States)

    DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medication. Afterward, your blood is drawn ...

  8. Acute personalized habitual caffeine doses improve attention and have selective effects when considering the fractionation of executive functions.

    Science.gov (United States)

    Lanini, Juliana; Galduróz, José Carlos Fernandes; Pompéia, Sabine

    2016-01-01

    Caffeine is widely used, often consumed with food, and improves simple and complex/executive attention under fasting conditions. We investigated whether these cognitive effects are observed when personalized habitual doses of caffeine are ingested by caffeine consumers, whether they are influenced by nutriments and if various executive domains are susceptible to improvement. This was a double-blind, placebo-controlled study including 60 young, healthy, rested males randomly assigned to one of four treatments: placebo fasting, caffeine fasting, placebo meal and caffeine meal. Caffeine doses were individualized for each participant based on their self-reported caffeine consumption at the time of testing (morning). The test battery included measures of simple and sustained attention, executive domains (inhibiting, updating, shifting, dual tasking, planning and accessing long-term memory), control measures of subjective alterations, glucose and insulin levels, skin conductance, heart rate and pupil dilation. Regardless of meal intake, acute habitual doses of caffeine decreased fatigue, and improved simple and sustained attention and executive updating. This executive effect was not secondary to the habitual weekly dose consumed, changes in simple and sustained attention, mood, meal ingestion and increases in cognitive effort. We conclude that the morning caffeine "fix" has positive attentional effects and selectively improved executive updating whether or not caffeine is consumed with food.

  9. RELATIONSHIP BETWEEN CYCLIN G1 AND HUMAN PAPILLOMA VIRUS INFECTION IN CERVICAL INTRAEPITHELIAL NEOPLASIA AND CERVICAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To evaluate the overexpression of cyclin G1 in cervical intraepithelial neoplasia (CIN) and cervical carcinoma, and the correlation between cyclin G1 and high-risk human papilloma virus (HPV) infection.Methods All of the specimens were obtained from the Department of Pathology of China-Japan Friendship Hospital from January 2000 to August 2004. We detected the expression of cyclin G1 with immunohistochemistry, HPV16/18infection with in situ hybridization, and high-risk HPV infection with Hybrid capture system Ⅱ (HC-Ⅱ) in normal group (25 cases), CIN Ⅰ (48 cases), CIN Ⅱ (56 cases), CIN Ⅲ (54 cases), and invasive cervical squamous-cell carcinoma (SCC, 31 cases).Results The positive rates of cyclin G1 expression in CIN (77. 85%) and SCC cervical tissues (87.10%) were significantly higher than normal (8.00%,P<0.01), and the intensities of cyclin G1 expression in CIN (40.60%)and SCC cervical tissues (61.51%) were significantly higher than normal (2.72%,P<0.05). The positive rates and intensities of cyclin G1 expression increased gradually with the grade of cervical lesions. High-risk HPV infection rates were higher in CIN and SCC than normal groups (P<0.05). There was a positive correlation between cyclin G1 expression and high-risk HPV infection detected with HC-Ⅱ (Kendall's tau-b =0.316, 0.269, 0.352, and 0. 474 in CIN Ⅰ, CINⅡ, CIN Ⅲ, and SCC, respectively, P<0.05).Conclusions Cyclin G1 is overexpressed in CIN and SCC. Cyclin G1 may be a biomarker for detecting CIN and SCC. Cyclin G1 may play an important role in the oncogenesis of CIN and SCC by high-risk HPV infection.

  10. MicroRNA-16 Modulates HuR Regulation of Cyclin E1 in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xun Guo

    2015-03-01

    Full Text Available RNA binding protein (RBPs and microRNAs (miRNAs or miRs are post-transcriptional regulators of gene expression that are implicated in development of cancers. Although their individual roles have been studied, the crosstalk between RBPs and miRNAs is under intense investigation. Here, we show that in breast cancer cells, cyclin E1 upregulation by the RBP HuR is through specific binding to regions in the cyclin E1 mRNA 3' untranslated region (3'UTR containing U-rich elements. Similarly, miR-16 represses cyclin E1, dependent on its cognate binding sites in the cyclin E1 3'UTR. Evidence in the literature indicates that HuR can regulate miRNA expression and recruit or dissociate RNA-induced silencing complexes (RISC. Despite this, miR-16 and HuR do not affect the other’s expression level or binding to the cyclin E1 3'UTR. While HuR overexpression partially blocks miR-16 repression of a reporter mRNA containing the cyclin E1 3'UTR, it does not block miR-16 repression of endogenous cyclin E1 mRNA. In contrast, miR-16 blocks HuR-mediated upregulation of cyclin E1. Overall our results suggest that miR-16 can override HuR upregulation of cyclin E1 without affecting HuR expression or association with the cyclin E1 mRNA.

  11. Cyclin A degradation by primate cytomegalovirus protein pUL21a counters its innate restriction of virus replication.

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    Nicolas Caffarelli

    Full Text Available Cyclin A is critical for cellular DNA synthesis and S phase progression of the cell cycle. Human cytomegalovirus (HCMV can reduce cyclin A levels and block cellular DNA synthesis, and cyclin A overexpression can repress HCMV replication. This interaction has only been previously observed in HCMV as murine CMV does not downregulate cyclin A, and the responsible viral factor has not been identified. We previously reported that the HCMV protein pUL21a disrupted the anaphase-promoting complex (APC, but a point mutant abrogating this activity did not phenocopy a UL21a-deficient virus, suggesting that pUL21a has an additional function. Here we identified a conserved arginine-x-leucine (RxL cyclin-binding domain within pUL21a, which allowed pUL21a to interact with cyclin A and target it for proteasome degradation. Homologous pUL21a proteins from both chimpanzee and rhesus CMVs also contained the RxL domain and similarly degraded cyclin A, indicating that this function is conserved in primate CMVs. The RxL point mutation disabled the virus' ability to block cellular DNA synthesis and resulted in a growth defect similar to pUL21a-deficient virus. Importantly, knockdown of cyclin A rescued growth of UL21a-deficient virus. Together, these data show that during evolution, the pUL21a family proteins of primate CMVs have acquired a cyclin-binding domain that targets cyclin A for degradation, thus neutralizing its restriction on virus replication. Finally, the combined proteasome-dependent degradation of pUL21a and its cellular targets suggests that pUL21a may act as a novel suicide protein, targeting its protein cargos for destruction.

  12. 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

  13. Molecular Characterization and Expression Profiles of Cyclin B1, B2 and Cdc2 Kinase during Oogenesis and Spermatogenesis in Rainbow Trout (Oncorhynchus mykiss)

    Science.gov (United States)

    The meiotic maturation of oocytes and spermatocytes is controlled by the maturation promotion factor (MPF), a complex of the Cdc2 and cyclin B proteins. To better understand the mechanism of oocyte and spermatocyte maturation in fish, the expression of cyclin B1 (CB1), cyclin B2 (CB2) and Cdc2 kinas...

  14. Cdc20 and Cks direct the spindle checkpoint-independent destruction of cyclin A

    NARCIS (Netherlands)

    Wolthuis, Rob; Clay-Farrace, Lori; van Zon, Wouter; Yekezare, Mona; Koop, Lars; Ogink, Janneke; Medema, Rene; Pines, Jonathon

    2008-01-01

    Successful mitosis requires the right protein be degraded at the right time. Central to this is the spindle checkpoint that prevents the destruction of securin and cyclin 131 when there are improperly attached chromosomes. The principal target of the checkpoint is Cdc20, which activates the anaphase

  15. Acetylation of cyclin-dependent kinase 5 is mediated by GCN5

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Juhyung; Yun, Nuri; Kim, Chiho [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Song, Min-Young; Park, Kang-Sik [Department of Physiology and Biomedical Science Institute, Kyung Hee University School of Medicine, Seoul 130-701 (Korea, Republic of); Oh, Young J., E-mail: yjoh@yonsei.ac.kr [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of)

    2014-04-25

    Highlights: • Cyclin-dependent kinase 5 (CDK5) is present as an acetylated form. • CDK5 is acetylated by GCN5. • CDK5’s acetylation site is mapped at Lys33. • Its acetylation may affect CDK5’s kinase activity. - Abstract: Cyclin-dependent kinase 5 (CDK5), a member of atypical serine/threonine cyclin-dependent kinase family, plays a crucial role in pathophysiology of neurodegenerative disorders. Its kinase activity and substrate specificity are regulated by several independent pathways including binding with its activator, phosphorylation and S-nitrosylation. In the present study, we report that acetylation of CDK5 comprises an additional posttranslational modification within the cells. Among many candidates, we confirmed that its acetylation is enhanced by GCN5, a member of the GCN5-related N-acetyl-transferase family of histone acetyltransferase. Co-immunoprecipitation assay and fluorescent localization study indicated that GCN5 physically interacts with CDK5 and they are co-localized at the specific nuclear foci. Furthermore, liquid chromatography in conjunction with a mass spectrometry indicated that CDK5 is acetylated at Lys33 residue of ATP binding domain. Considering this lysine site is conserved among a wide range of species and other related cyclin-dependent kinases, therefore, we speculate that acetylation may alter the kinase activity of CDK5 via affecting efficacy of ATP coordination.

  16. Cannabinoids Regulate Bcl-2 and Cyclin D2 Expression in Pancreatic β Cells.

    Directory of Open Access Journals (Sweden)

    Jihye Kim

    Full Text Available Recent reports have shown that cannabinoid 1 receptors (CB1Rs are expressed in pancreatic β cells, where they induce cell death and cell cycle arrest by directly inhibiting insulin receptor activation. Here, we report that CB1Rs regulate the expression of the anti-apoptotic protein Bcl-2 and cell cycle regulator cyclin D2 in pancreatic β cells. Treatment of MIN6 and βTC6 cells with a synthetic CB1R agonist, WIN55,212-2, led to a decrease in the expression of Bcl-2 and cyclin D2, in turn inducing cell cycle arrest in G0/G1 phase and caspase-3-dependent apoptosis. Additionally, genetic deletion and pharmacological blockade of CB1Rs after injury in mice led to increased levels of Bcl-2 and cyclin D2 in pancreatic β cells. These findings provide evidence for the involvement of Bcl-2 and cyclin D2 mediated by CB1Rs in the regulation of β-cell survival and growth, and will serve as a basis for developing new therapeutic interventions to enhance β-cell function and growth in diabetes.

  17. THE OVEREXPRESSION AND SIGNIFICANCE OF CYCLIN D1 AND P53 IN CERVICAL SQUAMOUS CELL CARCINOMAS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective:To investigate the significance of overexpresson of eyclin D1 and P53 protein in cervical squamous cell carcinomas.Methods:Fifty cases of invasive cervical squamous cell carcinomas and 10 Cases of normal cervical squamous epithelia were investigated with immunihistochemical technique.Results:The overexpressioin of cyclin D1 and P53 in invasive cervical carcinomas was 70% and 50%,respectively,There was no overexpression of them in the control group.The overexpression of cyclin D1 in grade Ⅱand Ⅲ was much higher than that in grade I(P<0.05),The overexpresson of cyclin D1 in stage Ⅲof cervical carcinoma was significantly higher than that in stage Ⅱ(P<0.05).The overexpression of P53 in grade -Ⅱand gradeⅢ of cervical carcinoma was remarkably higher than that in grade I(P<0.05),Conclusion:The action point of both cyclin D1 and P53 may be at G1/S transtition.The overexpression of them was associated with development and progression of cervical carcinoma probably in different mechanisms and different pathways.

  18. p34Cdc28-Mediated Control of Cln3 Cyclin Degradation

    NARCIS (Netherlands)

    Yaglom, Julia; Linskens, Maarten H.K.; Sadis, Seth; Rubin, David M.; Futcher, Bruce; Finley, Daniel

    1995-01-01

    Cln3 cyclin of the budding yeast Saccharomyces cerevisiae is a key regulator of Start, a cell cycle event in G1 phase at which cells become committed to division. The time of Start is sensitive to Cln3 levels, which in turn depend on the balance between synthesis and rapid degradation. Here we repor

  19. 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.

  20. 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)