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Sample records for reduced caffeine radiosensitization

  1. Modification of the radiosensitizing effect of metronidazole by 5-fluorouracil and caffeine

    International Nuclear Information System (INIS)

    Esel'baeva, G.O.; Ermekova, S.A.

    1986-01-01

    A study was made of the combined effect of 5-fluorouracil, metronidazole, caffeine and radiation on radiosensitivity of Pliss lymphosarcoma and protein synthesis rate during the first few hours following irradiation. A complete regression of the tumor was noted in 100% of animals after a 3-fold exposure. Effective postirradiation inhibition of protein synthesis was achieved by injection of metronidazole and caffeine together with 5-fluorouracil

  2. Modification of the radiosensitivity of barley seed by post-treatment with caffeine

    International Nuclear Information System (INIS)

    Kesavan, P.C.; Ahmad, A.

    1976-01-01

    Barley seeds of a hull-less variety (IB 65) were γ-irradiated (40 and 45 krad, 100 rad/sec) at 25 0 C, and the seeds were post-hydrated for 12 hours at approximately 3 0 C in oxygenated and oxygen-free water or caffeine solutions (3.8 x 10 -4 to 3.8 x 10 -2 M). Measurements of 8-day seedling growth showed that the different caffeine concentrations applied during oxygenated or oxygen-free hydrations produced no observable effects on the growth of unirradiated seeds. All caffeine concentrations afforded protection for the irradiated seeds under oxygenated conditions, and potentiated the damage under oxygen-free conditions. A maximum radio-protection occurred at a caffeine concentration of 3.8 x 10 -3 M, whereas radiosensitization under oxygen-free conditions was concentration-dependent. Possible mechanisms are discussed. (U.K.)

  3. ATM-induced radiosensitization in vitro and in vivo

    International Nuclear Information System (INIS)

    Choi, E. K.; Ahn, S. D.; Rhee, Y. H.; Chung, H. S.; Ha, S. W; Song, C. W.; Griffin, R. J.; Park, H. J.

    2003-01-01

    It has been known that ATM plays a central role in response of cells to ionizing radiation by enhancing DNA repair. We have investigated the feasibility of increasing radiosensitivity of tumor cells with the use of ATM inhibitors such as caffeine, pentoxifylline and wortmannin. Human colorectal cancer RKO.C cells and RKO-ATM cells (RKO cells overexpressing ATM) were used in the present study. The clonogenic cell survival in vitro indicated that RKO-ATM cells were markedly radioresistant than RKO.C cells. Treatment with 3 mM of caffeine significantly increased the radiosensitivity of cells, particulary the RKO-ATM cells, so that the radiosensitivity of RKO.C cells and RKO-ATM cells were almost similar. The radiation induced G2/M arrest in RKO-ATM cells was noticeably longer than that in RKO.C cells and caffeine treatment significantly reduced the length of the radiation induced G2/M arrest in both RKO.C and RKO-ATM cells. Pentoxifylline and wortmannin were also less effective than caffeine to radiosensitize RKO.C or RKO-ATM cells. However, wortmannin was more effective than caffeine against human lung adenocarcinoma A549 cells indicating the efficacy of ATM inhibitor to increase radiosensitivity is cell line dependent. For in vivo study, RKO.C cells were injected s.c. into the hind-leg of BALB/c-nuslc nude mice, and allowed to grow to 130mm3 tumor. The mice were i.p. injected with caffeine solution or saline and the tumors irradiated with 10 Gy of X-rays. The radiation induced growth delay was markedly increased by 1-2 mg/g of caffeine. It was concluded that caffeine increases radiosensitivity of tumor cells by inhibiting ATM kinase function, thereby inhibiting DNA repair, that occurs during the G2/M arrest after radiation

  4. Caffeine inhibits homology-directed repair of I-SceI-induced DNA double-strand breaks.

    Science.gov (United States)

    Wang, Huichen; Boecker, Wilfried; Wang, Hongyan; Wang, Xiang; Guan, Jun; Thompson, Larry H; Nickoloff, Jac A; Iliakis, George

    2004-01-22

    We recently reported that two Chinese hamster mutants deficient in the RAD51 paralogs XRCC2 and XRCC3 show reduced radiosensitization after treatment with caffeine, thus implicating homology-directed repair (HDR) of DNA double-strand breaks (DSBs) in the mechanism of caffeine radiosensitization. Here, we investigate directly the effect of caffeine on HDR initiated by DSBs induced by a rare cutting endonuclease (I-SceI) into one of two direct DNA repeats. The results demonstrate a strong inhibition by caffeine of HDR in wild-type cells, and a substantial reduction of this effect in HDR-deficient XRCC3 mutant cells. Inhibition of HDR and cell radiosensitization to killing shows similar dependence on caffeine concentration suggesting a cause-effect relationship between these effects. UCN-01, a kinase inhibitor that effectively abrogates checkpoint activation in irradiated cells, has only a small effect on HDR, indicating that similar to radiosensitization, inhibition of checkpoint signaling is not sufficient for HDR inhibition. Recombination events occurring during treatment with caffeine are characterized by rearrangements reminiscent to those previously reported for the XRCC3 mutant, and immunofluorescence microscopy demonstrates significantly reduced formation of IR-specific RAD51 foci after caffeine treatment. In summary, our results identify inhibition of HDR as a significant contributor to caffeine radiosensitization.

  5. Modification of the radiosensitivity of barley seed by post-treatment with caffeine

    International Nuclear Information System (INIS)

    Kesavan, P.C.; Nadkarni, S.

    1977-01-01

    The oxygen-dependent damage which developed in barley seeds with approximately 7.8 per cent moisture content disappeared after post-irradiation storage in vacuo for 48 hours at 40 0 C and for 24 hours at 50 0 C. When the duration of storage at 40 0 C was extended to 384 hours, oxygen-independent damage became potentiated. There was oxygen-dependent damage in seeds of approximately 13.3 per cent moisture content and after the seeds had been stored in vacuo at 50 0 C, the oxygen-independent damage began to increase by 168 hours, and it was significantly potentiated by 192 hours. Under these circumstances, caffeine acted as a radioprotector only as long as the precursors of oxic damage were present in the seeds. Once these sites were lost, caffeine acted only as a radiosensitizer. The oxygen-independent damage which increased with storage at high temperature was further potentiated by caffeine. (author)

  6. Evaluation of a MTT assay in measurement of radiosensitizing effect

    International Nuclear Information System (INIS)

    Higuchi, Keiko; Mitsuhashi, Norio; Saitoh, Jun-ichi; Maebayashi, Katsuya; Sakurai, Hideyuki; Akimoto, Tetsuo; Niibe, Hideo

    1999-01-01

    The usefulness of a MTT assay by measuring the radiosensitizing effect of caffeine on rat yolk sac tumor cell line with a mutant-type p53 in vitro was evaluated. A rat yolk sac tumor cell line with a mutant-type p53, NMT-1R, was used in this study. The radiosensitivity of NMT-1R with or without caffeine was measured with a MTT assay. The results were compared with those by a clonogenic assay. Caffeine at a concentration of 2.0 mM which released radiation-induced G 2 block demonstrated a radiosensitizing effect, but caffeine at a concentration of 0.5 mM did not. The radiosensitizing effect of caffeine measured by a MTT assay correlated with that measured by a clonogenic assay. A MTT assay was useful to measure radiosensitivity and/or a radiosensitizing effect in vitro. (author)

  7. Differential sensitivity of p53+ and p53- cells to caffeine-induced radiosensitization and override of G2 delay

    International Nuclear Information System (INIS)

    Powell, S.N.; DeFrank, J.S.; Connell, P.; Eogan, M.; Preffer, F.; Dombkowski, D.; Tang, W.; Friend, S.H.

    1995-01-01

    Purpose: Most drug discovery efforts have focused on finding new DNA damaging agents to kill tumor cells preferentially. An alternative approach is to find ways to increase tumor specific killing by modifying tumor specific responses to that damage. We asked whether cells lacking the G1/S arrest in response to X-rays are more sensitive to X-ray damage when treated with agents that override G2/M arrest. Materials and Methods: Mouse embryonic fibroblasts genetically matched to be (+/+) or (-/-) p53 and rat embryonic fibroblasts (REF) made (+) or (-) for wild-type p53 function by transfection were irradiated with and without caffeine, a known checkpoint inhibitor. Caffeine treatment was maintained for 24 hours from 1 hour prior to irradiation. Cell survival following ionizing radiation was measured by clonogenic assay. For cell-cycle analysis, cells were in exponential asynchronous growth at the time of irradiation. The proportion of cells in G1, S and G2/M phases of the cell cycle were recorded immediately before and following irradiation and subsequently at 3,6,9,12,24 and 48 hours following irradiation. Results: Caffeine was found to cause radiosensitzation at low dose (0.5mM) in (-/-) cells but not in (+/+) cells. The sensitization enhancement ratio (SER) was 1.45 at 0.1 survival and 1.56 at 0.01 survival. At this dose of caffeine, this SER reflected therapeutic gain as there was no detectable effect on (+/+) cells. At 1mM caffeine, sensitization of (-/-) cells was 1.77, but (+/+) cells now also showed sensitization (SER=1.25). In (-/-) cells at 0.1mM caffeine the SER was 1.5 at 0.01 survival. The transfected REF cells (functionally null for p53) also exhibited caffeine-induced radiosensitization at both 0.5 and 2mM caffeine with a SER 1.45 for 2mM at 0.1 survival. No significant sensitization could be demonstrated for REF cells at the same doses of caffeine. The REF cells, with wild-type p53, transfected with pCMVneo alone showed no change in radiosensitivity or

  8. Effect of varying concentrations of caffeine and ascorbic acid on the radiosensitivity of barley seed irradiated in oxygenated or oxygen-free hydration medium at 25 and 3700C

    International Nuclear Information System (INIS)

    Afzal, S.M.J.; Kesavan, P.C.

    1977-01-01

    The modification of radiosensitivity of barley seed with 1.75 x 10 -3 M and 3.8 x 10 -3 M concentrations of caffeine and ascorbic acid during irradiation in oxygenated and oxygen-free hydration medium was studied at 25 and 37 0 C, respectively. Both concentrations of caffeine and ascorbic acid afforded protection against oxic radiation damage which was maximal at 25 0 C. Caffeine effectively potentiated the anoxic component of damage but ascorbic acid had no influence at all. At 25 0 C there was no concentration-dependent effect of caffeine or ascorbic acid. At 37 0 C, there was no effect, whatsoever, of either concentration of ascorbic acid, whereas caffeine dramatically potentiated the radiation damage under both oxygenated and oxygen-free conditions, and the magnitude of potentiation was concentration-dependent. The possible reactivity of caffeine and ascorbic acid towards the precursors of oxygen-dependent and -independent components of damage in determining the mode and magnitudes of modification is discussed briefly. (author)

  9. Variation in sensitizing effect of caffeine in human tumour cell lines after γ-irradiation

    International Nuclear Information System (INIS)

    Valenzuela, M.T.; Almodovar, M.R. de; Mateos, S.; McMillan, T.J.

    2000-01-01

    We have investigated whether the protective role of the G2 checkpoint has increasing importance when the p53-dependent G1 checkpoint is inactivated. We have studied the differential effect of caffeine by clonogenic assays and flow cytometry in three human tumour cell lines with different functionality of p53 protein. The radiosensitizing effect of caffeine (2 mM) expressed itself as a significant decrease in surviving fraction at 2 Gy and a significant increase in α-values in RT112 and TE671, both with non-functional p53. However, no radiosensitizing effect was seen in cells with a normal p53 function (MCF-7 BUS). Two millimoles of caffeine also caused important changes in the cell cycle progression after irradiation. MCF-7 BUS showed a G1 arrest after irradiation and an early G2 arrest but those cells that reached the second G2 did not arrest significantly. In contrast, TE671 exhibited radiosensitization by caffeine, no G1 arrest, a G2 arrest in those cells irradiated in G2, no significant accumulation in the second G2 but an overall delay in release from the first cell cycle, which could be abrogated by caffeine. RT112 was similar to TE671 except that the emphasis in a G2 arrest was shifted from the block in cells irradiated in G2 to those irradiated at other cell cycle phases. The data presented confirm that p53 status can be a significant determinant of the efficacy of caffeine as radiosensitizer in these tumour cell lines, and document the importance of the G2 checkpoint in this effect. (author)

  10. Reduction of radiation-induced cell cycle blocks by caffeine does not necessarily lead to increased cell killing

    Energy Technology Data Exchange (ETDEWEB)

    Musk, S.R. (Institute of Cancer Research, Sutton, Surrey (England))

    1991-03-01

    The effect of caffeine upon the radiosensitivities of three human tumor lines was examined and correlated with its action upon the radiation-induced S-phase and G2-phase blocks. Caffeine was found to reduce at least partially the S-phase and G2-phase blocks in all the cell lines examined but potentiated cytotoxicity in only one of the three tumor lines. That reductions have been demonstrated to occur in the absence of increased cell killing provides supporting evidence for the hypothesis that reductions may not be causal in those cases when potentiation of radiation-induced cytotoxicity is observed in the presence of caffeine.

  11. Radiobiology of Bacillus megaterium spores: physicochemical events involving oxygen and caffeine

    International Nuclear Information System (INIS)

    Raghu, B.; Kesavan, P.C.

    1986-01-01

    Caffeine which is now known to react with the radiolytically produced electrons and hydroxyl radicals, is a radioprotector against the oxic, but a radiosensitizer of the anoxic component of the gamma-ray-induced damage to B. megaterium spores. A specific scavenger of hydroxyl radicals, t-butanol, also affords partial protection to spores irradiated in O 2 , thus revealing an 'OH-component' within the oxygen-dependent damage. Based on the data on inactivation constant (k) and H 2 O 2 yields of spores irradiated in O 2 or N 2 with a mixture of caffeine and t-butanol, it is suggested that radioprotection against oxic damage accrues from the competition of the former with oxygen for electrons. The simplest interpretation of radioprotection, therefore, is the substantial reduction in the formation of oxygen-electron adducts (HO 2 , O 2 , RO 2 ). The hypothesis of 'electron sequestration' satisfactorily accounts for the anoxic radiosensitization by caffeine. (author)

  12. Coculture with astrocytes reduces the radiosensitivity of glioblastoma stem-like cells and identifies additional targets for radiosensitization

    International Nuclear Information System (INIS)

    Rath, Barbara H; Wahba, Amy; Camphausen, Kevin; Tofilon, Philip J

    2015-01-01

    Toward developing a model system for investigating the role of the microenvironment in the radioresistance of glioblastoma (GBM), human glioblastoma stem-like cells (GSCs) were grown in coculture with human astrocytes. Using a trans-well assay, survival analyses showed that astrocytes significantly decreased the radiosensitivity of GSCs compared to standard culture conditions. In addition, when irradiated in coculture, the initial level of radiation-induced γH2AX foci in GSCs was reduced and foci dispersal was enhanced suggesting that the presence of astrocytes influenced the induction and repair of DNA double-strand breaks. These data indicate that astrocytes can decrease the radiosensitivity of GSCs in vitro via a paracrine-based mechanism and further support a role for the microenvironment as a determinant of GBM radioresponse. Chemokine profiling of coculture media identified a number of bioactive molecules not present under standard culture conditions. The gene expression profiles of GSCs grown in coculture were significantly different as compared to GSCs grown alone. These analyses were consistent with an astrocyte-mediated modification in GSC phenotype and, moreover, suggested a number of potential targets for GSC radiosensitization that were unique to coculture conditions. Along these lines, STAT3 was activated in GSCs grown with astrocytes; the JAK/STAT3 inhibitor WP1066 enhanced the radiosensitivity of GSCs under coculture conditions and when grown as orthotopic xenografts. Further, this coculture system may also provide an approach for identifying additional targets for GBM radiosensitization

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

    Science.gov (United States)

    Santos, Victor G. F.; Santos, Vander R. F.; Felippe, Leandro J. C.; Almeida, Jose W.; Bertuzzi, Rômulo; Kiss, Maria A. P. D. M.; Lima-Silva, Adriano E.

    2014-01-01

    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 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 caffeine reduced reaction time in non-fatigued conditions and delayed fatigue during successive taekwondo combats. PMID:24518826

  14. Caffeine Markedly Enhanced Radiation-Induced Bystander Effects

    International Nuclear Information System (INIS)

    Jiang Erkang; Wu Lijun

    2009-01-01

    In this paper it is shown that incubation with 2 mM caffeine enhanced significantly the MN (micronucleus) formation in both the 1 cGy α-particle irradiated and non-irradiated bystander regions. Moreover, caffeine treatment made the non-irradiated bystander cells more sensitive 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 α-particle radiation-induced damage in irradiated and non-irradiated bystander regions, and therefore it is important to investigate the relationship between the radiosensitizer and radiation-induced bystander effects (RIBE). (ion beam bioengineering)

  15. Caffeine reduces dipyridamole-induced myocardial ischemia

    International Nuclear Information System (INIS)

    Smits, P.; Aengevaeren, W.R.; Corstens, F.H.; Thien, T.

    1989-01-01

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

  16. Caffeine reduces dipyridamole-induced myocardial ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Smits, P.; Aengevaeren, W.R.; Corstens, F.H.; Thien, T. (Univ. of Nijmegen (Netherlands))

    1989-10-01

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

  17. Radiomodifying effect of caffeine on mammalian cellular system using gamma radiation and proton beam radiation

    International Nuclear Information System (INIS)

    Samanth, Sneha P.; Yadav, Usha; Shirsath, K.B.; Desai, Utkarsha N.; Chaurasia, Rajesh K.; Bhat, Nagesh N.; Anjaria, K.B.; Sapra, B.K.

    2016-01-01

    Caffeine is a commonly consumed neurostimulant in the world. Reports suggest the radiomodifying effects of caffeine against low Linear Energy Transfer (LET) radiation when administered pre and post irradiation by releasing checkpoint arrest. In the present report, the radioprotective and radiosensitizing ability of caffeine (10μM - 2mM) were studied on Chinese Hamster Ovary (CRO) cell line against low as well as high LET radiation when administered pre, post and continuously during radiation. Effect of caffeine treatment on the genotoxicity induced by gamma and proton beam radiation was assessed by micronucleus assay. Effect of caffeine treatment on clonogenic survival of irradiated cells was also assessed

  18. Modification of the radiosensitivity of barley seed by post-treatment with caffeine

    International Nuclear Information System (INIS)

    Nadkarni, S.; Kesavan, P.C.

    1975-01-01

    In dry barley seeds (3.1 per cent moisture content), the maximal level of oxic damage (class III damage) was reached within the first 40 min a post-hydration in oxygenated water at 5 +- 1 0 C. The decay of the gamma-ray-induced oxygensensitive sites required however, about 120 min. The mechanism leading to partial protection against the class III damage were initiated when caffeine was present during the dirst 30 min of oxygenated post-hydration. If added after 30 min of oxygenated hydration, caffeine had no protective action. For the potentiation of an oxygen-independent component of damage, caffeine had to be present during the first 240 min of oxygen-free hydration. These observations involving a physiologically inert system raised questions regarding physico-chemical vis-a-vis biochemical mechanisms of caffeine effect on irradiated systems and these have been briefly discussed. (author)

  19. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Acute high-caffeine exposure increases autophagic flux and reduces protein synthesis in C2C12 skeletal myotubes.

    Science.gov (United States)

    Hughes, M A; Downs, R M; Webb, G W; Crocker, C L; Kinsey, S T; Baumgarner, Bradley L

    2017-04-01

    Caffeine is a highly catabolic dietary stimulant. High caffeine concentrations (1-10 mM) have previously been shown to inhibit protein synthesis and increase protein degradation in various mammalian cell lines. The purpose of this study was to examine the effect of short-term caffeine exposure on cell signaling pathways that regulate protein metabolism in mammalian skeletal muscle cells. Fully differentiated C2C12 skeletal myotubes either received vehicle (DMSO) or 5 mM caffeine for 6 h. Our analysis revealed that caffeine promoted a 40% increase in autolysosome formation and a 25% increase in autophagic flux. In contrast, caffeine treatment did not significantly increase the expression of the skeletal muscle specific ubiquitin ligases MAFbx and MuRF1 or 20S proteasome activity. Caffeine treatment significantly reduced mTORC1 signaling, total protein synthesis and myotube diameter in a CaMKKβ/AMPK-dependent manner. Further, caffeine promoted a CaMKII-dependent increase in myostatin mRNA expression that did not significantly contribute to the caffeine-dependent reduction in protein synthesis. Our results indicate that short-term caffeine exposure significantly reduced skeletal myotube diameter by increasing autophagic flux and promoting a CaMKKβ/AMPK-dependent reduction in protein synthesis.

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

    International Nuclear Information System (INIS)

    Chan, G.L.; Little, J.B.

    1981-01-01

    We measured the clonogenic survival response of cultured mouse 10 Tsup(1/2) cells exposed to UV light and caffeine post-treatment. When 0.5 and 1 mM caffeine were present for 24 h immediately following UV, the D 0 values of the biphasic survival curves suggest that one subpopulation was sensitized and one subpopulation was protected from killing by UV light. A cloned survivor from the radioprotected subpopulation responded to UV plus caffeine in identical manner as the parent cells. When the caffeine exposure was prolonged to 48 h, only the radiosensitizing effect was observed. Two demethylated analogs of caffeine were also tested. The response of 10 Tsup(1/2) cells to 1 mM theophylline present for 24 h after UV irradiation was approximately the same as that for the same treatment with 1 mM caffeine. However, prolonging the theophylline exposure to 48 h failed to produce the same kind of potentiation of cell killing as that observed for caffeine. Xanthine by itself was a toxic to 10 Tsup(1/2) cells as caffeine, but had no synergistic effect as caffeine when given to UV-irradiated cells for 24 or 48 h. It is therefore unlikely that all the effects of caffeine on UV-irradiated cells are mediated by its demethylated metabolites. (orig.)

  2. Consumption of an acute dose of caffeine reduces acquisition but not memory in the honey bee.

    Science.gov (United States)

    Mustard, Julie A; Dews, Lauren; Brugato, Arlana; Dey, Kevin; Wright, Geraldine A

    2012-06-15

    Caffeine affects several molecules that are also involved in the processes underlying learning and memory such as cAMP and calcium. However, studies of caffeine's influence on learning and memory in mammals are often contradictory. Invertebrate model systems have provided valuable insight into the actions of many neuroactive compounds including ethanol and cocaine. We use the honey bee (Apis mellifera) to investigate how the ingestion of acute doses of caffeine before, during, and after conditioning influences performance in an appetitive olfactory learning and memory task. Consumption of caffeine doses of 0.01 M or greater during or prior to conditioning causes a significant reduction in response levels during acquisition. Although bees find the taste of caffeine to be aversive at high concentrations, the bitter taste does not explain the reduction in acquisition observed for bees fed caffeine before conditioning. While high doses of caffeine reduced performance during acquisition, the response levels of bees given caffeine were the same as those of the sucrose only control group in a recall test 24h after conditioning. In addition, caffeine administered after conditioning had no affect on recall. These results suggest that caffeine specifically affects performance during acquisition and not the processes involved in the formation of early long term memory. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Caffeine for asthma

    OpenAIRE

    Welsh, EJ; Bara, A; Barley, E; Cates, CJ

    2010-01-01

    Background\\ud \\ud Caffeine has a variety of pharmacological effects; it is a weak bronchodilator and it also reduces respiratory muscle fatigue. It is chemically related to the drug theophylline which is used to treat asthma. It has been suggested that caffeine may reduce asthma symptoms and interest has been expressed in its potential role as an asthma treatment. A number of studies have explored the effects of caffeine in asthma, this is the first review to systematically examine and summar...

  4. Caffeine and exercise.

    Science.gov (United States)

    Paluska, Scott A

    2003-08-01

    Caffeine is the most commonly consumed drug in the world, and athletes frequently use it as an ergogenic aid. It improves performance and endurance during prolonged, exhaustive exercise. To a lesser degree it also enhances short-term, high-intensity athletic performance. Caffeine improves concentration, reduces fatigue, and enhances alertness. Habitual intake does not diminish caffeine's ergogenic properties. Several mechanisms have been proposed to explain the physiologic effects of caffeine, but adenosine receptor antagonism most likely accounts for the primary mode of action. It is relatively safe and has no known negative performance effects, nor does it cause significant dehydration or electrolyte imbalance during exercise. Routine caffeine consumption may cause tolerance or dependence, and abrupt discontinuation produces irritability, mood shifts, headache, drowsiness, or fatigue. Major sport governing bodies ban excessive use of caffeine, but current monitoring techniques are inadequate, and ethical dilemmas persist regarding caffeine intake by athletes.

  5. Reduced Stress and Improved Sleep Quality Caused by Green Tea Are Associated with a Reduced Caffeine Content

    Directory of Open Access Journals (Sweden)

    Keiko Unno

    2017-07-01

    Full Text Available Caffeine, one of the main components in green tea, can interfere with sleep and block the effect of theanine. Since theanine, the main amino acid in tea leaves, has significant anti-stress effects in animals and humans, we examined the effects of green tea with lowered caffeine content, i.e., low-caffeine green tea (LCGT, on stress and quality of sleep of middle–aged individuals (n = 20, mean age 51.3 ± 6.7 years in a double-blind crossover design. Standard green tea (SGT was used as the control. These teas (≥300 mL/day, which were eluted with room temperature water, were consumed over a period of seven days after a single washout term. The level of salivary α-amylase activity (sAA, a stress marker, was significantly lower in participants that consumed LCGT (64.7 U/mL than in those that consumed SGT (73.9 U/mL. Sleep quality was higher in participants that consumed a larger quantity of LCGT. In addition, a self-diagnostic check for accumulated fatigue was significantly lower in those participants that consumed LCGT than SGT. These results indicate that LCGT intake can reduce stress in middle-aged individuals and improve their quality of sleep. The reduction in caffeine is suggested to be a valid reason for enhancing the anti-stress effect of green tea.

  6. Reduced Stress and Improved Sleep Quality Caused by Green Tea Are Associated with a Reduced Caffeine Content.

    Science.gov (United States)

    Unno, Keiko; Noda, Shigenori; Kawasaki, Yohei; Yamada, Hiroshi; Morita, Akio; Iguchi, Kazuaki; Nakamura, Yoriyuki

    2017-07-19

    Caffeine, one of the main components in green tea, can interfere with sleep and block the effect of theanine. Since theanine, the main amino acid in tea leaves, has significant anti-stress effects in animals and humans, we examined the effects of green tea with lowered caffeine content, i.e., low-caffeine green tea (LCGT), on stress and quality of sleep of middle-aged individuals ( n = 20, mean age 51.3 ± 6.7 years) in a double-blind crossover design. Standard green tea (SGT) was used as the control. These teas (≥300 mL/day), which were eluted with room temperature water, were consumed over a period of seven days after a single washout term. The level of salivary α-amylase activity (sAA), a stress marker, was significantly lower in participants that consumed LCGT (64.7 U/mL) than in those that consumed SGT (73.9 U/mL). Sleep quality was higher in participants that consumed a larger quantity of LCGT. In addition, a self-diagnostic check for accumulated fatigue was significantly lower in those participants that consumed LCGT than SGT. These results indicate that LCGT intake can reduce stress in middle-aged individuals and improve their quality of sleep. The reduction in caffeine is suggested to be a valid reason for enhancing the anti-stress effect of green tea.

  7. Differential repair of radiation-induced DNA damage in cells of human squamous cell carcinoma and the effect of caffeine and cysteamine on induction and repair of DNA double-strand breaks

    Energy Technology Data Exchange (ETDEWEB)

    Smeets, M.F.M.A.; Mooren, E.H.M.; Abdel-Wahab, A.H.A.; Begg, A.C. [Netherlands Cancer Institute, Amsterdam (Netherlands)

    1994-11-01

    The goal of these experiments was to investigate further the relationship between DNA double-strand breaks and cell killing in human tumor cells, first by comparing different cell lines, and second by radiomodification studies. Field-inversion gel electrophoresis was used to quantify double-strand breaks. Two subclones of the radioresistant human squamous cell carcinoma line SQ20B (SQD9 and SQG6) were compared. These subclones differed in DNA index by a factor of 1.7 but showed the same resistance to radiation as cells of the parental cell line. It was found that, although induction of DSBs was not significantly different in the two cell lines, the t{sub 1/2} of the fast component of repair was significantly shorter for SQD9 cells, leading to greater overall repair which was not reflected in increased survival. Caffeine and cysteamine were tested as modifiers of radiosensitivity, using the radioresistant SQ20B line and the radiosensitive SCC61 cell line. No effect of caffeine was seen when the drug was present only during irradiation. Postirradiation incubations with caffeine, however, resulted in a dose reduction factor greater than 2.0 in cell survival for both cell lines. In contrast, induction of DSBs was reduced by caffeine, and no effect on DSB repair was observed. Cysteamine led to a dose protection factor greater than 1.8 in cell survival in both cell lines. A reduction in induced DSBs was found at high doses corresponding approximately with the increase in cell survival. Over the same (low) dose range, however, the correlation between DSB induction and cell killing was poor. These data indicate that DSB induction does not correlate well with cell killing either for different cell lines, for radiochemical modification (cysteamine) or for some other types of modification (caffeine). 31 refs., 8 figs.

  8. Caffeine ingestion after rapid weight loss in judo athletes reduces perceived effort and increases plasma lactate concentration without improving performance.

    Science.gov (United States)

    Lopes-Silva, Joao P; Felippe, Leandro J C; Silva-Cavalcante, Marcos D; Bertuzzi, Romulo; Lima-Silva, Adriano E

    2014-07-22

    The objective of this study was to examine the effect of caffeine on judo performance, perceived exertion, and plasma lactate response when ingested during recovery from a 5-day weight loss period. Six judokas performed two cycles of a 5-day rapid weight loss procedure to reduce their body weight by ~5%. After weigh-in, subjects re-fed and rehydrated over a 4-h recovery period. In the third hour of this "loading period", subjects ingested a capsule containing either caffeine (6 mg·kg-1) or placebo. One hour later, participants performed three bouts of a judo fitness test with 5-min recovery periods. Perceived exertion and plasma lactate were measured before and immediately after each test bout. Body weight was reduced in both caffeine and placebo conditions after the weight loss period (-3.9% ± 1.6% and -4.0% ± 2.3% from control, respectively, p caffeine or placebo groups. However, plasma lactate was systemically higher and perceived exertion lower in the subjects who ingested caffeine compared to either the control or placebo subjects (p caffeine did not improve performance during the judo fitness test after a 5-day weight loss period, but reduced perceived exertion and increased plasma lactate.

  9. The effect of caffeine on x-ray repair of radioresistant HeLa cells

    International Nuclear Information System (INIS)

    Kubo, Kihei; Koiwai, Soichiro; Morita, Kazuo

    1985-01-01

    The contribution of caffeine-modifiable repair process to the radiosensitivity of a radioresistant HeLa strain (RC-355) has been investigated in comparison with control HeLa strain (CC-24). Both the final slope and the shoulder of X-ray survival curve for log-phase cells were affected by caffeine posttreatment. When the treatment with 10 mM caffeine delayed, an increase in survival was observed with increasing interval between irradiation and the treatment. During first several hours of the repair interval, the steepness of the final slope of survival curve decreased rapidly, and rate of the decrease was found to be higher in RC-355 than in CC-24 cells. Longer time (24 hours or more) before the initiation of caffeine treatment was required for the complete recovery of the shoulder. When the cells were incubated in plateau-phase after irradiation, an appreciable increase in survival was observed in comparison with when plated immediately following X-ray. The increase was found to be greater for RC-355 than for CC-24. The results suggest that the radioresistant RC-355 cells repaired more X-ray-induced PLD than CC-24 cells did. (author)

  10. Caffeine alters emotion and emotional responses in low habitual caffeine consumers.

    Science.gov (United States)

    Giles, Grace E; Spring, Alexander M; Urry, Heather L; Moran, Joseph M; Mahoney, Caroline R; Kanarek, Robin B

    2018-02-01

    Caffeine reliably increases emotional arousal, but it is unclear whether and how it influences other dimensions of emotion such as emotional valence. These experiments documented whether caffeine influences emotion and emotion regulation choice and success. Low to abstinent caffeine consumers (maximum 100 mg/day) completed measures of state anxiety, positive and negative emotion, and salivary cortisol before, 45 min after, and 75 min after consuming 400 mg caffeine or placebo. Participants also completed an emotion regulation choice task, in which they chose to employ cognitive reappraisal or distraction in response to high and low intensity negative pictures (Experiment 1), or a cognitive reappraisal task, in which they employed cognitive reappraisal or no emotion regulation strategy in response to negative and neutral pictures (Experiment 2). State anxiety, negative emotion, and salivary cortisol were heightened both 45 and 75 min after caffeine intake relative to placebo. In Experiment 1, caffeine did not influence the frequency with which participants chose reappraisal or distraction, but reduced negativity of the picture ratings. In Experiment 2, caffeine did not influence cognitive reappraisal success. Thus, caffeine mitigated emotional responses to negative situations, but not how participants chose to regulate such responses or the success with which they did so.

  11. Influence of radiation dose and dose-rate on modification of barley seed radiosensitivity by post-treatment with caffeine

    International Nuclear Information System (INIS)

    Sharma, G.J.

    1987-01-01

    Influence of radiation doses (100, 150 and 200 Gy) and dose-rates (1.27-0.023 Gy/Sec) on the modification of oxic and anoxic radiation damage by caffeine at different concentrations has been investigated using metabolizing barley seeds as test system. As the radiation dose increases from 100 to 200 Gy, the magnitude of oxic and anoxic damages increase at all the dose-rates. Caffeine is able to afford partial radioprotection against the oxic damage, at the same time potentiating the anoxic damage. However, caffeine effect against the oxic and anoxic components of damage depend largely upon the dose of radiation applied and also on the dose-rate used. The possible mechanism of action of caffeine in bringing about the differential modification of oxic and anoxic damages has been discussed. 19 refs., 2 tables. (author)

  12. Stattic Enhances Radiosensitivity and Reduces Radio-Induced Migration and Invasion in HCC Cell Lines through an Apoptosis Pathway

    Directory of Open Access Journals (Sweden)

    Gang Xu

    2017-01-01

    Full Text Available Purpose. Signal transducer and activator of transcription factor 3 (STAT3 is involved in tumorigenesis, development, and radioresistance of many solid tumors. The aim of this study is to investigate the effects of stattic (an inhibitor of STAT3 on the radiosensitivity and radio-induced migration and invasion ability in hepatocellular carcinoma (HCC cell lines. Methods. HCC cells were treated with stattic, and cell survival rate was analyzed through CCK-8 assay. Radiosensitivity was evaluated using cloning formation analysis; STAT3, p-STAT3, and apoptosis related proteins were detected by western blot. Radio-induced migration and invasion ability in HCC cells were analyzed by wound-healing assay and transwell test. Results. Stattic inhibits the expression of p-STAT3 and reduces cell survival in a dose-dependent manner in HCC cell lines, and the IC50 values for Hep G2, Bel-7402, and SMMC-7721 are 2.94 μM, 2.5 μM, and 5.1 μM, respectively. Cloning formation analysis shows that stattic enhances the radiosensitivity of HCC cells. Wound-healing assay and transwell test show that stattic inhibits radio-induced migration and invasion. Further study indicates that stattic promotes radio-induce apoptosis through regulating the expression of apoptosis related proteins in HCC cells. Conclusion. Stattic enhances radiosensitivity and reduces radio-induced migration and invasion ability in HCC cells probably through apoptosis pathway.

  13. Modifying effect of caffeine on cell radiosensitivity in stationary and logarithmic phases of growth

    International Nuclear Information System (INIS)

    Plotnikova, E.D.; Kostenko, G.A.

    1978-01-01

    Studied was reproductive killing of cultivated fibroblasts of a Chinese hamster in stationary and exponential growth phases after gamma irradiation. After cell irradiation in a stationary phase at 1200 rad dose rate and postirradiation incubation in conditioned medium before resowing for 5 hrs the survival rate increased almost 5 times due to the reparation of potential-lethal injuries. Under sodium caffein-benzoate (4 mg/ml) effect on cells in a stationary growth phase for 5 hrs before irradiation the survival rate increased; protection level was almost the same as in case of reduction in a conditioned media. Modification factor of dose curve incline was 1.3. Caffein protective effect may be conjectured to relate to the inhibition of potentially-lethal injury fraction realization

  14. 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 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. © 2014 American Heart Association, Inc.

  15. Caffeine Ingestion after Rapid Weight Loss in Judo Athletes Reduces Perceived Effort and Increases Plasma Lactate Concentration without Improving Performance

    Directory of Open Access Journals (Sweden)

    Joao P. Lopes-Silva

    2014-07-01

    Full Text Available The objective of this study was to examine the effect of caffeine on judo performance, perceived exertion, and plasma lactate response when ingested during recovery from a 5-day weight loss period. Six judokas performed two cycles of a 5-day rapid weight loss procedure to reduce their body weight by ~5%. After weigh-in, subjects re-fed and rehydrated over a 4-h recovery period. In the third hour of this “loading period”, subjects ingested a capsule containing either caffeine (6 mg·kg−1 or placebo. One hour later, participants performed three bouts of a judo fitness test with 5-min recovery periods. Perceived exertion and plasma lactate were measured before and immediately after each test bout. Body weight was reduced in both caffeine and placebo conditions after the weight loss period (−3.9% ± 1.6% and −4.0% ± 2.3% from control, respectively, p < 0.05. At three hours after weigh-in, body weight had increased with both treatments but remained below the control (−3.0% ± 1.3% and −2.7% ± 2.2%. There were no significant differences in the number of throws between the control, caffeine or placebo groups. However, plasma lactate was systemically higher and perceived exertion lower in the subjects who ingested caffeine compared to either the control or placebo subjects (p < 0.05. In conclusion, caffeine did not improve performance during the judo fitness test after a 5-day weight loss period, but reduced perceived exertion and increased plasma lactate.

  16. ATM-induced radiosensitization in vitro and in vivo

    International Nuclear Information System (INIS)

    Song, C. W.; Griffin, R. J.; Park, H. J.; Chung, H. S.; Choi, E. K.; Ahn, S. D.; Rhee, Y. H.; Ha, S. W.

    2002-01-01

    It has been known that ATM plays a central role in response of cells to ionizing radiation by enhancing DNA repair. Based in large part on studies of the homologous proteins in yeast, it is predicted that ATM function as proximal signal transducers in G1, S, and G2 checkpoint pathways. With the exception of p53, the downstream components of these pathways remain largely undefined. We have investigated the feasibility of increasing radiosensitivity of tumor cells with the use of ATM inhibitors such as caffeine, pentoxifylline, and wortmannin. Also in an effort to examine and understand the molecular mechanism by which ATM might exert its cellular effects, we have expressed the full length wild type ATM in RKO cells

  17. Nutrition Influences Caffeine-Mediated Sleep Loss in Drosophila.

    Science.gov (United States)

    Keebaugh, Erin S; Park, Jin Hong; Su, Chenchen; Yamada, Ryuichi; Ja, William W

    2017-11-01

    Plant-derived caffeine is regarded as a defensive compound produced to prevent herbivory. Caffeine is generally repellent to insects and often used to study the neurological basis for aversive responses in the model insect, Drosophila melanogaster. Caffeine is also studied for its stimulatory properties where sleep or drowsiness is suppressed across a range of species. Since limiting access to food also inhibits fly sleep-an effect known as starvation-induced sleep suppression-we tested whether aversion to caffeinated food results in reduced nutrient intake and assessed how this might influence fly studies on the stimulatory effects of caffeine. We measured sleep and total consumption during the first 24 hours of exposure to caffeinated diets containing a range of sucrose concentrations to determine the relative influence of caffeine and nutrient ingestion on sleep. Experiments were replicated using three fly strains. Caffeine reduced total consumption and nighttime sleep, but only at intermediate sucrose concentrations. Although sleep can be modeled by an exponential dose response to nutrient intake, caffeine-mediated sleep loss cannot be explained by absolute caffeine or sucrose ingestion alone. Instead, reduced sleep strongly correlates with changes in total consumption due to caffeine. Other bitter compounds phenocopy the effect of caffeine on sleep and food intake. Our results suggest that a major effect of dietary caffeine is on fly feeding behavior. Changes in feeding behavior may drive caffeine-mediated sleep loss. Future studies using psychoactive compounds should consider the potential impact of nutrition when investigating effects on sleep. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  18. Low doses of caffeine reduce heart rate during submaximal cycle ergometry

    Directory of Open Access Journals (Sweden)

    Wetter Thomas J

    2007-10-01

    Full Text Available 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 mg/kg caffeine. After thirty minutes of rest, a warm-up (30 Watts for 2 min the pedal rate of 60 rpm was maintained at a steady-state output of 60 watts for five minutes; increased to 120 watts for five minutes and to 180 watts for five minutes. After a 2 min rest the workload was 180 watts for one minute and increased by 30 watts every minute until exhaustion. Heart rate (HR was measured during the last 15-seconds of each minute of submaximal exercise. Systolic blood pressure (BP was measured at rest and during each of the three sub-maximal steady state power outputs. Minute ventilation (VE, Tidal volume (VT, Breathing frequency (Bf, Rating of perceived exertion (RPE, Respiratory exchange ratio (RER, and Oxygen consumption (VO2 were measured at rest and during each minute of exercise. Results Caffeine at 1.5 and 3.0 mg/kg body weight significantly lowered (p E, VT, VO2, RPE, maximal power output or time to exhaustion. Conclusion In non habitual caffeine users it appears that consuming a caffeine pill (1.5 & 3.0 mg/kg at a dose comparable to 1–3 cups of coffee lowers heart rate during submaximal exercise but not at near maximal and maximal exercise. In addition, this caffeine dose also only appears to affect systolic blood pressure at rest but not during cycling exercise.

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

    International Nuclear Information System (INIS)

    Swenberg, C.E.; Landauer, M.R.; Weiss, J.F.

    1997-01-01

    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)

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

    Energy Technology Data Exchange (ETDEWEB)

    Swenberg, C.E.; Landauer, M.R. [Armed Forces Radiobiology Research Institute, Bethesda (United States); Weiss, J.F. [Office of International Health Programs, Department of Energy, Germantown (United States)

    1997-03-01

    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)

  1. Is caffeine a cognitive enhancer?

    Science.gov (United States)

    Nehlig, Astrid

    2010-01-01

    The effects of caffeine on cognition were reviewed based on the large body of literature available on the topic. Caffeine does not usually affect performance in learning and memory tasks, although caffeine may occasionally have facilitatory or inhibitory effects on memory and learning. Caffeine facilitates learning in tasks in which information is presented passively; in tasks in which material is learned intentionally, caffeine has no effect. Caffeine facilitates performance in tasks involving working memory to a limited extent, but hinders performance in tasks that heavily depend on working memory, and caffeine appears to rather improve memory performance under suboptimal alertness conditions. Most studies, however, found improvements in reaction time. The ingestion of caffeine does not seem to affect long-term memory. At low doses, caffeine improves hedonic tone and reduces anxiety, while at high doses, there is an increase in tense arousal, including anxiety, nervousness, jitteriness. The larger improvement of performance in fatigued subjects confirms that caffeine is a mild stimulant. Caffeine has also been reported to prevent cognitive decline in healthy subjects but the results of the studies are heterogeneous, some finding no age-related effect while others reported effects only in one sex and mainly in the oldest population. In conclusion, it appears that caffeine cannot be considered a ;pure' cognitive enhancer. Its indirect action on arousal, mood and concentration contributes in large part to its cognitive enhancing properties.

  2. Radiosensitivity of mouse germ cells

    International Nuclear Information System (INIS)

    Matsuda, Yoichi; Takeuchi, Toyoko; Maemori, Mamiko; Seki, Naohiko; Tobari, Izuo

    1991-01-01

    To estimate radiosensitivity of mouse germ cells the analysis of chromosome aberrations was performed at diakinesis-metaphase I of spermatocytes and first-cleavage metaphase of one-cell embryos after exposure to radiations at various stages of primary spermatocytes and spermatids. The result provided evidence that there are two major types of DNA damage in X-irradiated sperm : (1) short-lived DNA lesions ; the lesions are subject to repair inhibition by agents added in G 1 , and are converted into chromosome-type aberrations during G 1 , and (2) long-lived DNA lesions ; the lesions persist until S phase and repair of the lesions is inhibited by caffeine, hydroxyurea and arabinofuranosyl cytosine in G 2 . The characteristic of X-ray damage induced in spermiogenic stage and repair mechanism for the damage in the fertilized egg were discussed comparing with the results with two chemicals, methyl methanesulfonate (MMS) and mitomycin C (MMC). (J.P.N.)

  3. X-ray induced degradation of DNA in radiosensitive mutants of Anacystis nidulans

    Energy Technology Data Exchange (ETDEWEB)

    Zhukas, K I; Vorontsova, G V; Groshev, V V; Shestakov, S V [Moskovskij Gosudarstvennyj Univ. (USSR). Biologo-Pochvennyj Fakul' tet

    1975-01-01

    In irradiated Cyanophyceae (Anacystis nidulans) cells there occurs a process of DNA degeneration to acid-soluble products which is linked with protein synthesis and stimulated by caffeine and acriflavine. The degree of DNA degeneration increases with x-ray dose, is not very dependent on the composition of the incubation medium and is weakly linked with photosynthesis. In the cells of a radiation-resistant mutant the degree of DNA degeneration is slighter, and in the cells of radiosensitive mutants larger, than in ordinary cells. The role of DNA degradation in the radiation detruction of cells is discussed.

  4. Caffeine dependence in combination with a family history of alcoholism as a predictor of continued use of caffeine during pregnancy.

    Science.gov (United States)

    Svikis, Dace S; Berger, Nathan; Haug, Nancy A; Griffiths, Roland R

    2005-12-01

    The purpose of the study was to examine whether caffeine dependence and a family history of alcoholism are associated with continued use of caffeine during pregnancy. Forty-four women seeking obstetrical care in an office-based practice completed questionnaires and provided saliva samples at three prenatal visits occurring 2-3, 3-4, and 7 months postconception. On visit 1, the patients received the physician's instructions to stop using caffeine. Structured interviews were used to assign a diagnosis of caffeine dependence (lifetime) and to identify family history of alcoholism. Outcome measures included self-reported levels of caffeine use and saliva caffeine levels at the three prenatal visits. Although most women eliminated or substantially reduced their caffeine consumption between pregnancy awareness and prenatal visit 1, those with a lifetime diagnosis of caffeine dependence and a family history of alcoholism had higher levels of caffeine use and lower rates of abstinence throughout pregnancy. Saliva caffeine levels confirmed these effects. Withdrawal symptoms, functional impairment, and craving were cited as reasons they failed to eliminate or cut back on caffeine use. Fifty percent of the women with both a lifetime diagnosis of caffeine dependence and a family history of alcoholism continued to use caffeine in amounts (>300 mg/day) greater than those considered safe during pregnancy, compared to none of the women without caffeine dependence and a family history of alcoholism. Women with a lifetime diagnosis of caffeine dependence and a family history of alcoholism also reported higher rates of past cigarette smoking and problematic alcohol use. Caffeine-dependent women with a family history of alcoholism were not able to follow their physician's advice to reduce or eliminate caffeine consumption during pregnancy, despite their wanting to do so. This subgroup may require more intensive intervention to ensure caffeine abstinence and may be at greater risk for

  5. 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.

  6. Effects of caffeine and caffeine withdrawal on mood and cognitive performance degraded by sleep restriction.

    Science.gov (United States)

    Rogers, Peter J; Heatherley, Susan V; Hayward, Robert C; Seers, Helen E; Hill, Joanne; Kane, Marian

    2005-06-01

    It has been suggested that caffeine is most likely to benefit mood and performance when alertness is low. To measure the effects of caffeine on psychomotor and cognitive performance, mood, blood pressure and heart rate in sleep-restricted participants. To do this in a group of participants who had also been previously deprived of caffeine for 3 weeks, thereby potentially removing the confounding effects of acute caffeine withdrawal. Participants were moderate to moderate-high caffeine consumers who were provided with either decaffeinated tea and/or coffee for 3 weeks (LTW) or regular tea and/or coffee for 3 weeks (overnight caffeine-withdrawn participants, ONW). Then, following overnight caffeine abstinence, they were tested on a battery of tasks assessing mood, cognitive performance, etc. before and after receiving caffeine (1.2 mg/kg) or on another day after receiving placebo. Final analyses were based on 17 long-term caffeine-withdrawn participants (LTW) and 17 ONW participants whose salivary caffeine levels on each test day confirmed probable compliance with the instructions concerning restrictions on consumption of caffeine-containing drinks. Acute caffeine withdrawal (ONW) had a number of negative effects, including impairment of cognitive performance, increased headache, and reduced alertness and clear-headedness. Caffeine (versus placebo) did not significantly improve cognitive performance in LTW participants, although it prevented further deterioration of performance in ONW participants. Caffeine increased tapping speed (but tended to impair hand steadiness), increased blood pressure, and had some effects on mood in both groups. The findings provide strong support for the withdrawal reversal hypothesis. In particular, cognitive performance was found to be affected adversely by acute caffeine withdrawal and, even in the context of alertness lowered by sleep restriction, cognitive performance was not improved by caffeine in the absence of these withdrawal

  7. Caffeine reduces resting-state BOLD functional connectivity in the motor cortex.

    Science.gov (United States)

    Rack-Gomer, Anna Leigh; Liau, Joy; Liu, Thomas T

    2009-05-15

    In resting-state functional magnetic resonance imaging (fMRI), correlations between spontaneous low-frequency fluctuations in the blood oxygenation level dependent (BOLD) signal are used to assess functional connectivity between different brain regions. Changes in resting-state BOLD connectivity measures are typically interpreted as changes in coherent neural activity across spatially distinct brain regions. However, this interpretation can be complicated by the complex dependence of the BOLD signal on both neural and vascular factors. For example, prior studies have shown that vasoactive agents that alter baseline cerebral blood flow, such as caffeine and carbon dioxide, can significantly alter the amplitude and dynamics of the task-related BOLD response. In this study, we examined the effect of caffeine (200 mg dose) on resting-state BOLD connectivity in the motor cortex across a sample of healthy young subjects (N=9). We found that caffeine significantly (pcaffeine. These results suggest that caffeine usage should be carefully considered in the design and interpretation of resting-state BOLD fMRI studies.

  8. ADPRT inhibitors and hyperthermia as radiosensitizers

    International Nuclear Information System (INIS)

    Jonsson, G.G.

    1985-01-01

    Hyperthermia given in combination with gamma radiation has given considerable improvement in the therapeutic results for treatment of malignant tumors. The mechanism behind the hyperthermia effect is probably operative at the tissue level as well as at the molecular level. The metabolism of NAD + in relation to the activity of the chromosomal enzyme ADP-ribosyl transferase (ADPRT) has been studied as a possible molecular mechanism for this effect. The ADPRT activity was measured after radiosensitization with both hyperthermia and nicotinamide, which is a potent inhibitor of ADPRT. The results indicate that hyperthermia can improve the effect of radiotherapy by reducing the supply of NAD + , which is a co-substrate for ADPRT, while nicotinamide functions as a radiosensitizing agent by direct inhibition of the enzyme. The hypothesis is discussed in the thesis where inhibition of ADPRT might increase the radiosensitivity because the radiation-induced DNA damage can not be repaired with normal efficiency. The function of nicotinamide as a radiosensitizer was verified by studies on C3H mice with transplanted spontaneous mammary tumors. Because nicotinamide is not toxic, it seems quite attractive to test this vitamin as a radiosensitizing agent against human tumors. (251 refs.) (author)

  9. Radiosensitivity of higher plants

    International Nuclear Information System (INIS)

    Feng Zhijie

    1992-11-01

    The general views on radiosensitivity of higher plants have been introduced from published references. The radiosensitivity varies with species, varieties and organs or tissues. The main factors of determining the radiosensitivity in different species are nucleus volume, chromosome volume, DNA content and endogenous compounds. The self-repair ability of DNA damage and chemical group of biological molecules, such as -SH thiohydroxy of proteins, are main factors to determine the radiosensitivity in different varieties. The moisture, oxygen, temperature radiosensitizer and protector are important external factors for radiosensitivity. Both the multiple target model and Chadwick-Leenhouts model are ideal mathematical models for describing the radiosensitivity of higher plants and the latter has more clear significance in biology

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

    Science.gov (United States)

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

    1995-08-01

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

  11. Caffeine as a model drug of dependence: recent developments in understanding caffeine withdrawal, the caffeine dependence syndrome, and caffeine negative reinforcement.

    Science.gov (United States)

    Griffiths, R R; Chausmer, A L

    2000-11-01

    Caffeine is an excellent model compound for understanding drugs of abuse/dependence. The results of self-administration and choice studies in humans clearly demonstrate the reinforcing effects of low and moderate doses of caffeine. Caffeine reinforcement has been demonstrated in about 45% of normal subjects with histories of moderate and heavy caffeine use. Recent studies provide compelling evidence that caffeine physical dependence potentiates the reinforcing effects of caffeine through the mechanism of withdrawal symptom avoidance. Tolerance to the subjective and sleep-disrupting effects of caffeine in humans has been demonstrated. Physical dependence as reflected in a withdrawal syndrome in humans has been repeatedly demonstrated in adults and recently demonstrated in children. Withdrawal severity is an increasing function of caffeine maintenance dose, with withdrawal occurring at doses as low as 100 mg per day. Increased cerebral blood flow may be the physiological mechanism for caffeine withdrawal headache. Case studies in adults and adolescents clearly demonstrate that some individuals meet DSM-IV diagnostic criteria for a substance dependence syndrome on caffeine, including feeling compelled to continue caffeine use despite desires and recommendations to the contrary. Survey data suggest that 9% to 30% percent of caffeine consumers may be caffeine dependent according to DSM-IV criteria.

  12. X-ray induced degradation of DNA in radiosensitive mutants of Anacystis nidulans x-rays

    International Nuclear Information System (INIS)

    Zhukas, K.I.; Vorontsova, G.V.; Groshev, V.V.; Shestakov, S.V.

    1975-01-01

    In irradiated Cyanophyceae (Anacystis nidulans) cells there occurs a process of DNA degeneration to acid-soluble products which is linked with protein synthesis and stimulated by caffeine and acriflavine. The degree of DNA degeneration increases with X-ray dose, is not very dependent on the composition of the incubation medium and is weakly linked with photosynthesis. In the cells of a radiation-resistant mutant the degree of DNA degeneration is slighter, and in the cells of radiosensitive mutants larger, than in ordinary cells. The role of DNA degradation in the radiation detruction of cells is discussed. (author)

  13. Inhibiting c-Jun N-terminal kinase partially attenuates caffeine-dependent cell death without alleviating the caffeine-induced reduction in mitochondrial respiration in C2C12 skeletal myotubes

    International Nuclear Information System (INIS)

    Downs, R.M.; Hughes, M.A.; Kinsey, S.T.; Johnson, M.C.; Baumgarner, B.L.

    2016-01-01

    Caffeine is a widely consumed stimulant that has previously been shown to promote cytotoxic stress and even cell death in numerous mammalian cell lines. Thus far there is little information available regarding the toxicity of caffeine in skeletal muscle cells. Our preliminary data revealed that treating C2C12 myotubes with 5 mM caffeine for 6 h increased nuclear fragmentation and reduced basal and maximal oxygen consumption rate (OCR) in skeletal myotubes. The purpose of this study was to further elucidate the pathways by which caffeine increased cell death and reduced mitochondrial respiration. We specifically examined the role of c-Jun N-terminal kinase (JNK), which has previously been shown to simultaneously increase caspase-dependent cell death and reduce mitochondrial respiration in other mammalian cell lines. We found that caffeine promoted a dose-dependent increase in cell death in multinucleated myotubes but did not in mononucleated myoblasts. The addition of 10 μM Z-DEVD-FMK, a specific inhibitor of executioner caspases, completely inhibited caffeine-dependent cell death. Further, the addition of 400 μM dantrolene, a specific ryanodine receptor (RYR) inhibitor, prevented the caffeine-dependent increase in cell death and the reduction in basal and maximal OCR. We also discovered that caffeine treatment significantly increased the phosphorylation of JNK and that the addition of 30 μM SP600125 (JNKi), a specific JNK inhibitor, partially attenuated caffeine-induced cell death without preventing the caffeine-dependent reduction in basal and maximal OCR. Our results suggest that JNK partially mediates the increase in caspase-dependent cell death but does not contribute to reduced mitochondrial respiration in caffeine-treated skeletal muscle cells. We conclude that caffeine increased cell death and reduced mitochondrial respiration in a calcium-dependent manner by activating the RYR and promoting reticular calcium release. - Highlights: • Caffeine

  14. Differential cognitive effects of energy drink ingredients: caffeine, taurine, and glucose.

    Science.gov (United States)

    Giles, Grace E; Mahoney, Caroline R; Brunyé, Tad T; Gardony, Aaron L; Taylor, Holly A; Kanarek, Robin B

    2012-10-01

    Energy drinks containing caffeine, taurine, and glucose may improve mood and cognitive performance. However, there are no studies assessing the individual and interactive effects of these ingredients. We evaluated the effects of caffeine, taurine, and glucose alone and in combination on cognitive performance and mood in 24-hour caffeine-abstained habitual caffeine consumers. Using a randomized, double-blind, mixed design, 48 habitual caffeine consumers (18 male, 30 female) who were 24-hour caffeine deprived received one of four treatments (200 mg caffeine/0 mg taurine, 0 mg caffeine/2000 mg taurine, 200 mg caffeine/2000 mg taurine, 0 mg caffeine/0 mg taurine), on each of four separate days, separated by a 3-day wash-out period. Between-participants treatment was a glucose drink (50 g glucose, placebo). Salivary cortisol, mood and heart rate were measured. An attention task was administered 30-minutes post-treatment, followed by a working memory and reaction time task 60-minutes post-treatment. Caffeine enhanced executive control and working memory, and reduced simple and choice reaction time. Taurine increased choice reaction time but reduced reaction time in the working memory tasks. Glucose alone slowed choice reaction time. Glucose in combination with caffeine, enhanced object working memory and in combination with taurine, enhanced orienting attention. Limited glucose effects may reflect low task difficulty relative to subjects' cognitive ability. Caffeine reduced feelings of fatigue and increased tension and vigor. Taurine reversed the effects of caffeine on vigor and caffeine-withdrawal symptoms. No effects were found for salivary cortisol or heart rate. Caffeine, not taurine or glucose, is likely responsible for reported changes in cognitive performance following consumption of energy drinks, especially in caffeine-withdrawn habitual caffeine consumers. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Caffeine promotes wakefulness via dopamine signaling in Drosophila

    Science.gov (United States)

    Nall, Aleksandra H.; Shakhmantsir, Iryna; Cichewicz, Karol; Birman, Serge; Hirsh, Jay; Sehgal, Amita

    2016-01-01

    Caffeine is the most widely-consumed psychoactive drug in the world, but our understanding of how caffeine affects our brains is relatively incomplete. Most studies focus on effects of caffeine on adenosine receptors, but there is evidence for other, more complex mechanisms. In the fruit fly Drosophila melanogaster, which shows a robust diurnal pattern of sleep/wake activity, caffeine reduces nighttime sleep behavior independently of the one known adenosine receptor. Here, we show that dopamine is required for the wake-promoting effect of caffeine in the fly, and that caffeine likely acts presynaptically to increase dopamine signaling. We identify a cluster of neurons, the paired anterior medial (PAM) cluster of dopaminergic neurons, as the ones relevant for the caffeine response. PAM neurons show increased activity following caffeine administration, and promote wake when activated. Also, inhibition of these neurons abrogates sleep suppression by caffeine. While previous studies have focused on adenosine-receptor mediated mechanisms for caffeine action, we have identified a role for dopaminergic neurons in the arousal-promoting effect of caffeine. PMID:26868675

  16. Normal cellular radiosensitivity in an adult Fanconi anaemia patient with marked clinical radiosensitivity

    International Nuclear Information System (INIS)

    Marcou, Yiola; D'Andrea, Andrew; Jeggo, Penelope A.; Plowman, Piers N.

    2001-01-01

    Background: Fanconi anaemia is a rare disease associated with cellular sensitivity to chemicals (e.g. mitomycin C and diepoxybutane); variable but mild cellular radiosensitivity has also been reported. Materials and methods: A 32-year-old patient with Fanconi anaemia and tonsillar carcinoma, treated by radiotherapy, was found to exhibit profound clinical radiosensitivity. Confluent, ulcerating oropharyngeal mucositis developed after a conventionally fractionated dose of 34 Gy and healing was incomplete by 2 months after cessation of therapy. Results: Cellular radiosensitivity assays and RPLD studies from this patient did not suggest any major detectable radiosensitivity. Conclusion: There is a discrepancy between the observed clinical radiosensitivity and the usual 'predictive' radiosensitivity assays in this patient with Fanconi anaemia

  17. Association of the Anxiogenic and Alerting Effects of Caffeine with ADORA2A and ADORA1 Polymorphisms and Habitual Level of Caffeine Consumption

    Science.gov (United States)

    Rogers, Peter J; Hohoff, Christa; Heatherley, Susan V; Mullings, Emma L; Maxfield, Peter J; Evershed, Richard P; Deckert, Jürgen; Nutt, David J

    2010-01-01

    Caffeine, a widely consumed adenosine A1 and A2A receptor antagonist, is valued as a psychostimulant, but it is also anxiogenic. An association between a variant within the ADORA2A gene (rs5751876) and caffeine-induced anxiety has been reported for individuals who habitually consume little caffeine. This study investigated whether this single nucleotide polymorphism (SNP) might also affect habitual caffeine intake, and whether habitual intake might moderate the anxiogenic effect of caffeine. Participants were 162 non-/low (NL) and 217 medium/high (MH) caffeine consumers. In a randomized, double-blind, parallel groups design they rated anxiety, alertness, and headache before and after 100 mg caffeine and again after another 150 mg caffeine given 90 min later, or after placebo on both occasions. Caffeine intake was prohibited for 16 h before the first dose of caffeine/placebo. Results showed greater susceptibility to caffeine-induced anxiety, but not lower habitual caffeine intake (indeed coffee intake was higher), in the rs5751876 TT genotype group, and a reduced anxiety response in MH vs NL participants irrespective of genotype. Apart from the almost completely linked ADORA2A SNP rs3761422, no other of eight ADORA2A and seven ADORA1 SNPs studied were found to be clearly associated with effects of caffeine on anxiety, alertness, or headache. Placebo administration in MH participants decreased alertness and increased headache. Caffeine did not increase alertness in NL participants. With frequent consumption, substantial tolerance develops to the anxiogenic effect of caffeine, even in genetically susceptible individuals, but no net benefit for alertness is gained, as caffeine abstinence reduces alertness and consumption merely returns it to baseline. PMID:20520601

  18. Differential responsiveness to caffeine and perceived effects of caffeine in moderate and high regular caffeine consumers.

    Science.gov (United States)

    Attwood, A S; Higgs, S; Terry, P

    2007-03-01

    Individual differences in responsiveness to caffeine occur even within a caffeine-consuming population, but the factors that mediate differential responsiveness remain unclear. To compare caffeine's effects on performance and mood in a group of high vs moderate consumers of caffeine and to examine the potential role of subjective awareness of the effects of caffeine in mediating any differential responsiveness. Two groups of regular caffeine consumers (200 mg/day) attended two sessions at which mood and cognitive functions were measured before and 30 min after consumption of 400-mg caffeine or placebo in a capsule. Cognitive tests included visual information processing, match-to-sample visual search (MTS) and simple and choice reaction times. Post-session questionnaires asked participants to describe any perceived effect of capsule consumption. High consumers, but not moderate consumers, demonstrated significantly faster simple and choice reaction times after caffeine relative to placebo. These effects were not attributable to obvious group differences in withdrawal or tolerance because there were no group differences in baseline mood or in reports of negative affect after caffeine. Instead, the high consumers were more likely to report experiencing positive effects of caffeine, whereas the moderate consumers were more likely to report no effect. The sensitivity of caffeine consumers to the mood- and performance-enhancing effects of caffeine is related to their levels of habitual intake. High caffeine consumers are more likely than moderate consumers to perceive broadly positive effects of caffeine, and this may contribute to their levels of use.

  19. Separating neural and vascular effects of caffeine using simultaneous EEG–FMRI: Differential effects of caffeine on cognitive and sensorimotor brain responses

    Science.gov (United States)

    Diukova, Ana; Ware, Jennifer; Smith, Jessica E.; Evans, C. John; Murphy, Kevin; Rogers, Peter J.; Wise, Richard G.

    2012-01-01

    The effects of caffeine are mediated through its non-selective antagonistic effects on adenosine A1 and A2A adenosine receptors resulting in increased neuronal activity but also vasoconstriction in the brain. Caffeine, therefore, can modify BOLD FMRI signal responses through both its neural and its vascular effects depending on receptor distributions in different brain regions. In this study we aim to distinguish neural and vascular influences of a single dose of caffeine in measurements of task-related brain activity using simultaneous EEG–FMRI. We chose to compare low-level visual and motor (paced finger tapping) tasks with a cognitive (auditory oddball) task, with the expectation that caffeine would differentially affect brain responses in relation to these tasks. To avoid the influence of chronic caffeine intake, we examined the effect of 250 mg of oral caffeine on 14 non and infrequent caffeine consumers in a double-blind placebo-controlled cross-over study. Our results show that the task-related BOLD signal change in visual and primary motor cortex was significantly reduced by caffeine, while the amplitude and latency of visual evoked potentials over occipital cortex remained unaltered. However, during the auditory oddball task (target versus non-target stimuli) caffeine significantly increased the BOLD signal in frontal cortex. Correspondingly, there was also a significant effect of caffeine in reducing the target evoked response potential (P300) latency in the oddball task and this was associated with a positive potential over frontal cortex. Behavioural data showed that caffeine also improved performance in the oddball task with a significantly reduced number of missed responses. Our results are consistent with earlier studies demonstrating altered flow-metabolism coupling after caffeine administration in the context of our observation of a generalised caffeine-induced reduction in cerebral blood flow demonstrated by arterial spin labelling (19

  20. Caffeine

    Science.gov (United States)

    What is caffeine? Caffeine is a bitter substance that occurs naturally in more than 60 plants including Coffee beans Tea leaves Kola nuts, ... chocolate products There is also synthetic (man-made) caffeine, which is added to some medicines, foods, and ...

  1. Caffeine deprivation affects vigilance performance and mood.

    Science.gov (United States)

    Lane, J D; Phillips-Bute, B G

    1998-08-01

    The effects of brief caffeine deprivation on vigilance performance, mood, and symptoms of caffeine withdrawal were studied in habitual coffee drinkers. Thirty male and female coffee drinkers were tested twice at midday (1130 to 1330 hours) after mornings in which they either consumed caffeinated beverages ad lib or abstained. Vigilance performance was tested with a 30-min computerized visual monitoring task. Mood and withdrawal symptom reports were collected by questionnaires. Caffeine deprivation was associated with impaired vigilance performance characterized by a reduction in the percentage of targets detected and an increase in response time, and by subjective reports of decreased vigor and increased fatigue and symptoms characterized by sleepiness, headache, and reduced ability to work. Even short periods of caffeine deprivation, equivalent in length to skipping regular morning coffee, can produce deficits in sustained attention and noticeable unpleasant caffeine-withdrawal symptoms in habitual coffee drinkers. Such symptoms may be a common side-effect of habitual caffeine consumption that contributes to the maintenance of this behavior.

  2. Inhibitory effects of caffeine on hippocampal neurogenesis and function.

    Science.gov (United States)

    Han, Myoung-Eun; Park, Kyu-Hyun; Baek, Sun-Yong; Kim, Bong-Seon; Kim, Jae-Bong; Kim, Hak-Jin; Oh, Sae-Ock

    2007-05-18

    Caffeine is one of the most extensively consumed psychostimulants in the world. However, compared to short-term effects of caffeine, the long-term effects of caffeine consumption on learning and memory are poorly characterized. The present study found that long-term consumption of low dose caffeine (0.3 g/L) slowed hippocampus-dependent learning and impaired long-term memory. Caffeine consumption for 4 weeks also significantly reduced hippocampal neurogenesis compared to controls. From these results, we concluded that long-term consumption of caffeine could inhibit hippocampus-dependent learning and memory partially through inhibition of hippocampal neurogenesis.

  3. Caffeine and cognitive performance: persistent methodological challenges in caffeine research.

    Science.gov (United States)

    James, Jack E

    2014-09-01

    Human cognitive performance is widely perceived to be enhanced by caffeine at usual dietary doses. However, the evidence for and against this belief continues to be vigorously contested. Controversy has centred on caffeine withdrawal and withdrawal reversal as potential sources of experimental confounding. In response, some researchers have enlisted "caffeine-naïve" experimental participants (persons alleged to consume little or no caffeine) assuming that they are not subject to withdrawal. This mini-review examines relevant research to illustrate general methodological challenges that have been the cause of enduring confusion in caffeine research. At issue are the processes of caffeine withdrawal and withdrawal reversal, the definition of caffeine-naïve, the population representativeness of participants deemed to be caffeine-naïve, and confounding due to caffeine tolerance. Attention to these processes is necessary if premature conclusions are to be avoided, and if caffeine's complex effects and the mechanisms responsible for those effects are to be illuminated. Strategies are described for future caffeine research aimed at minimising confounding from withdrawal and withdrawal reversal. Copyright © 2014 Elsevier Inc. All rights reserved.

  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. Integrating nanohybrid membranes of reduced graphene oxide: chitosan: silica sol gel with fiber optic SPR for caffeine detection

    Science.gov (United States)

    Kant, Ravi; Tabassum, Rana; Gupta, Banshi D.

    2017-05-01

    Caffeine is the most popular psychoactive drug consumed in the world for improving alertness and enhancing wakefulness. However, caffeine consumption beyond limits can result in lot of physiological complications in human beings. In this work, we report a novel detection scheme for caffeine integrating nanohybrid membranes of reduced graphene oxide (rGO) in chitosan modified silica sol gel (rGO: chitosan: silica sol gel) with fiber optic surface plasmon resonance. The chemically synthesized nanohybrid membrane forming the sensing route has been dip coated over silver coated unclad central portion of an optical fiber. The sensor works on the mechanism of modification of dielectric function of sensing layer on exposure to analyte solution which is manifested in terms of red shift in resonance wavelength. The concentration of rGO in polymer network of chitosan and silica sol gel and dipping time of the silver coated probe in the solution of nanohybrid membrane have been optimized to extricate the supreme performance of the sensor. The optimized sensing probe possesses a reasonably good sensitivity and follows an exponentially declining trend within the entire investigating range of caffeine concentration. The sensor boasts of an unparalleled limit of detection value of 1.994 nM and works well in concentration range of 0-500 nM with a response time of 16 s. The impeccable sensor methodology adopted in this work combining fiber optic SPR with nanotechnology furnishes a novel perspective for caffeine determination in commercial foodstuffs and biological fluids.

  6. Predisposition to cancer and radiosensitivity

    International Nuclear Information System (INIS)

    Pichierri, P.; Franchitto, A.; Palitti, F.

    2000-01-01

    Many cancer-prone diseases have been shown to be radiosensitive. The radiosensitivity has been attributed to pitfalls in the mechanisms of repair of induced DNA lesions or to an impaired cell cycle checkpoint response. Although discrepancies exist in the results obtained by various authors on the radiosensitivity of individuals affected by the same disease, these can be attributed to the large variability observed already in the response to radiation of normal individuals. To date three test are commonly used to assess radiosensitivity in human cells: survival, micronucleus and G 2 chromosomal assay. The three tests may be performed using either fibroblasts or peripheral blood lymphocytes and all the three tests share large interindividual variability. In this regard a new approach to the G 2 chromosomal assay which takes into account the eventual differences in cell cycle progression among individuals has been developed. This new approach is based on the analysis of G 2 homogeneous cell populations. Cells irradiated are immediately challenged with medium containing bromodeoxyuridine (BrdU rd). Then cells are sampled at different post-irradiation times and BrdU rd incorporation detected on metaphases spread and the scoring is done only at time points showing similar incidence of labelled cells among the different donors. Using this approach it has been possible to reduce the interindividual variability of the G 2 chromosomal assay. (author)

  7. Caffeine Use Disorder: A Comprehensive Review and Research Agenda

    OpenAIRE

    Meredith, Steven E.; Juliano, Laura M.; Hughes, John R.; Griffiths, Roland R.

    2013-01-01

    Caffeine is the most commonly used drug in the world. Although consumption of low to moderate doses of caffeine is generally safe, an increasing number of clinical studies are showing that some caffeine users become dependent on the drug and are unable to reduce consumption despite knowledge of recurrent health problems associated with continued use. Thus, the World Health Organization and some health care professionals recognize caffeine dependence as a clinical disorder. In this comprehensi...

  8. Characterization of individuals seeking treatment for caffeine dependence.

    Science.gov (United States)

    Juliano, Laura M; Evatt, Daniel P; Richards, Brian D; Griffiths, Roland R

    2012-12-01

    Previous investigations have identified individuals who meet criteria for Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR; American Psychiatric Association, 2000) substance dependence as applied to caffeine, but there is little research on treatments for caffeine dependence. This study aimed to thoroughly characterize individuals who are seeking treatment for problematic caffeine use. Ninety-four individuals who identified as being psychologically or physically dependent on caffeine, or who had tried unsuccessfully to modify caffeine consumption participated in a face-to-face diagnostic clinical interview. They also completed measures concerning caffeine use and quitting history, reasons for seeking treatment, and standardized self-report measures of psychological functioning. Caffeine treatment seekers (mean age 41 years, 55% women) consumed an average of 548 mg caffeine per day. The primary source of caffeine was coffee for 50% of the sample and soft drinks for 37%. Eighty-eight percent reported prior serious attempts to modify caffeine use (mean 2.7 prior attempts), and 43% reported being advised by a medical professional to reduce or eliminate caffeine. Ninety-three percent met criteria for caffeine dependence when generic DSM-IV-TR substance dependence criteria were applied to caffeine use. The most commonly endorsed criteria were withdrawal (96%), persistent desire or unsuccessful efforts to control use (89%), and use despite knowledge of physical or psychological problems caused by caffeine (87%). The most common reasons for wanting to modify caffeine use were health-related (59%) and not wanting to be dependent on caffeine (35%). This investigation reveals that there are individuals with problematic caffeine use who are seeking treatment and suggests that there is a need for effective caffeine dependence treatments. 2013 APA, all rights reserved

  9. [Caffeine dependence].

    Science.gov (United States)

    Ogawa, Naoshi; Ueki, Hirofumi

    2010-08-01

    Caffeine is the most widely consumed psychoactive substance in the world and is a legal stimulant that is readily available to children. The potential for dependence on caffeine has been debated. Presently, due to a paucity of clinical evidence on caffeine dependence, no such diagnosis is included in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR). Although in recent studies, a subset of the general population was found to demonstrate caffeine dependence. It is valuable for psychiatrists and primary care physicians to recognize caffeine dependence as a clinical syndrome, since some people are distressed by their caffeine use and feel they can not control or stop their problematic use.

  10. The Combined Effects of Alcohol, Caffeine and Expectancies on Subjective Experience, Impulsivity and Risk-Taking

    Science.gov (United States)

    Heinz, Adrienne J.; de Wit, Harriet; Lilje, Todd C.; Kassel, Jon D.

    2013-01-01

    Caffeinated alcoholic beverage (CAB) consumption is a rapidly growing phenomenon among young adults and is associated with a variety of health-risk behaviors. The current study examined whether either caffeinated alcohol or the expectation of receiving caffeinated alcohol altered affective, cognitive and behavioral outcomes hypothesized to contribute to risk behavior. Young adult social drinkers (N=146) participated in a single session where they received alcohol (peak Breath Alcohol Content = .088 g/dL, SD = .019; equivalent to about 4 standard drinks) and were randomly assigned to one of four further conditions 1) no caffeine, no caffeine expectancy, 2) caffeine and caffeine expectancy, 3) no caffeine but caffeine expectancy, 4) caffeine but no caffeine expectancy. Participants’ habitual CAB consumption was positively correlated with measures of impulsivity and risky behavior, independently of study drugs. Administration of caffeine (mean dose = 220 mg, SD = 38; equivalent to about 2.75 Red Bulls) in the study reduced subjective ratings of intoxication and reversed the decrease in desire to continue drinking, regardless of expectancy. Caffeine also reduced the effect of alcohol on inhibitory reaction time (faster incorrect responses). Participants not expecting caffeine were less attentive after alcohol, whereas participants expecting caffeine were not, regardless of caffeine administration. Alcohol decreased response accuracy in all participants except those who both expected and received caffeine. Findings suggest that CABs may elevate risk for continued drinking by reducing perceived intoxication, and by maintaining the desire to continue drinking. Simply expecting to consume caffeine may reduce the effects of alcohol on inattention, and either expecting or consuming caffeine may protect against other alcohol-related performance decrements. Caffeine, when combined with alcohol, has both beneficial and detrimental effects on mechanisms known to contribute to

  11. 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.

  12. Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay

    Energy Technology Data Exchange (ETDEWEB)

    Sebastià, N., E-mail: natividad.sebastia@uv.es [Radiation Protection Service, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Montoro, A. [Radiation Protection Service, Universitary and Politechnic Hospital La Fe, Valencia (Spain); Grupo de Investigación Biomédica en Imagen GIBI230, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Unidad Mixta de Investigación en Endocrinología, Nutrición y Dietética Clínica, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Hervás, D. [Biostatistics Unit, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Pantelias, G.; Hatzi, V.I. [Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety, National Centre for Scientific Research “Demokritos”, Aghia Paraskevi, Athens (Greece); Soriano, J.M. [Grupo de Investigación Biomédica en Imagen GIBI230, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Unidad Mixta de Investigación en Endocrinología, Nutrición y Dietética Clínica, IIS La Fe, Health Research Institute La Fe, Valencia (Spain); Department of Preventive Medicine and Public Health, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia (Spain); Villaescusa, J.I. [Radiation Protection Service, Universitary and Politechnic Hospital La Fe, Valencia (Spain); and others

    2014-08-15

    Highlights: • Curcumin and trans-resveratrol can exert radioprotective or radiosensitizing effects. • The mechanisms underlying such dual action were elucidated using the PCC and G2-assay. • Radioprotection occurs in non-cycling cells exposed to curcumin and resveratrol. • Radiosensitization occurs in cycling cells exposed to the chemicals. • G2-checkpoint abrogation by the chemicals underlies the radiosensitizing mechanism. - Abstract: Curcumin and trans-resveratrol are well-known antioxidant polyphenols with radiomodulatory properties, radioprotecting non-cancerous cells while radiosensitizing tumor cells. This dual action may be the result of their radical scavenging properties and their effects on cell-cycle checkpoints that are activated in response to radiation-induced chromosomal damage. It could be also caused by their effect on regulatory pathways with impact on detoxification enzymes, the up-regulation of endogenous protective systems, and cell-cycle-dependent processes of DNA damage. This work aims to elucidate the mechanisms underlying the dual action of these polyphenols and investigates under which conditions they exhibit radioprotecting or radiosensitizing properties. The peripheral blood lymphocyte test system was used, applying concentrations ranging from 1.4 to 140 μM curcumin and 2.2 to 220 μM trans-resveratrol. The experimental design focuses first on their radioprotective effects in non-cycling lymphocytes, as uniquely visualized using cell fusion-mediated premature chromosome condensation, excluding, thus, cell-cycle interference to repair processes and activation of checkpoints. Second, the radiosensitizing potential of these chemicals on the induction of chromatid breaks in cultured lymphocytes following G2-phase irradiation was evaluated by a standardized G2-chromosomal radiosensitivity predictive assay. This assay uses caffeine for G2-checkpoint abrogation and it was applied to obtain an internal control for radiosensitivity

  13. Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay

    International Nuclear Information System (INIS)

    Sebastià, N.; Montoro, A.; Hervás, D.; Pantelias, G.; Hatzi, V.I.; Soriano, J.M.; Villaescusa, J.I.

    2014-01-01

    Highlights: • Curcumin and trans-resveratrol can exert radioprotective or radiosensitizing effects. • The mechanisms underlying such dual action were elucidated using the PCC and G2-assay. • Radioprotection occurs in non-cycling cells exposed to curcumin and resveratrol. • Radiosensitization occurs in cycling cells exposed to the chemicals. • G2-checkpoint abrogation by the chemicals underlies the radiosensitizing mechanism. - Abstract: Curcumin and trans-resveratrol are well-known antioxidant polyphenols with radiomodulatory properties, radioprotecting non-cancerous cells while radiosensitizing tumor cells. This dual action may be the result of their radical scavenging properties and their effects on cell-cycle checkpoints that are activated in response to radiation-induced chromosomal damage. It could be also caused by their effect on regulatory pathways with impact on detoxification enzymes, the up-regulation of endogenous protective systems, and cell-cycle-dependent processes of DNA damage. This work aims to elucidate the mechanisms underlying the dual action of these polyphenols and investigates under which conditions they exhibit radioprotecting or radiosensitizing properties. The peripheral blood lymphocyte test system was used, applying concentrations ranging from 1.4 to 140 μM curcumin and 2.2 to 220 μM trans-resveratrol. The experimental design focuses first on their radioprotective effects in non-cycling lymphocytes, as uniquely visualized using cell fusion-mediated premature chromosome condensation, excluding, thus, cell-cycle interference to repair processes and activation of checkpoints. Second, the radiosensitizing potential of these chemicals on the induction of chromatid breaks in cultured lymphocytes following G2-phase irradiation was evaluated by a standardized G2-chromosomal radiosensitivity predictive assay. This assay uses caffeine for G2-checkpoint abrogation and it was applied to obtain an internal control for radiosensitivity

  14. Interaction of caffeine with the SOS response pathway in Escherichia coli.

    Science.gov (United States)

    Whitney, Alyssa K; Weir, Tiffany L

    2015-01-01

    Previous studies have highlighted the antimicrobial activity of caffeine, both individually and in combination with other compounds. A proposed mechanism for caffeine's antimicrobial effects is inhibition of bacterial DNA repair pathways. The current study examines the influence of sub-lethal caffeine levels on the growth and morphology of SOS response pathway mutants of Escherichia coli. Growth inhibition after treatment with caffeine and methyl methane sulfonate (MMS), a mutagenic agent, was determined for E. coli mutants lacking key genes in the SOS response pathway. The persistence of caffeine's effects was explored by examining growth and morphology of caffeine and MMS-treated bacterial isolates in the absence of selective pressure. Caffeine significantly reduced growth of E. coli recA- and uvrA-mutants treated with MMS. However, there was no significant difference in growth between umuC-isolates treated with MMS alone and MMS in combination with caffeine after 48 h of incubation. When recA-isolates from each treatment group were grown in untreated medium, bacterial isolates that had been exposed to MMS or MMS with caffeine showed increased growth relative to controls and caffeine-treated isolates. Morphologically, recA-isolates that had been treated with caffeine and both caffeine and MMS together had begun to display filamentous growth. Caffeine treatment further reduced growth of recA- and uvrA-mutants treated with MMS, despite a non-functional SOS response pathway. However, addition of caffeine had very little effect on MMS inhibition of umuC-mutants. Thus, growth inhibition of E. coli with caffeine treatment may be driven by caffeine interaction with UmuC, but also appears to induce damage by additional mechanisms as evidenced by the additive effects of caffeine in recA- and uvrA-mutants.

  15. 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...

  16. Caffeine intake and its sources: A review of national representative studies.

    Science.gov (United States)

    Verster, Joris C; Koenig, Juergen

    2018-05-24

    Aim of this review is to summarize current daily caffeine intake of children, adolescents, and adults, and trends in caffeine intake over the past decade. A literature search was conducted (1997-2015) which yielded 18 reports on nationally representative studies, describing caffeine consumption of over 275,000 children, adolescents and adults. The data revealed that mean total daily caffeine intake in children, adolescents, and adults is below caffeine intake recommendations such as those stated by Health Canada (2.5 mg/kg bw/day for children and adolescents, and 400 mg/day for adults) and the European Food Safety Authority, EFSA (3 mg/kg bw/day for children and adolescents, and 400 mg/day for adults). Total daily caffeine intake has remained stable in the last 10-15 years, and coffee, tea and soft drinks are the most important caffeine sources. Across all age groups, energy drinks contribute little to total caffeine intake. The highest potential for reducing daily caffeine intake is by limiting coffee consumption, and in some countries and age groups, by reducing tea and soft drink consumption.

  17. Effect of electroporation on radiosensitization with cisplatin in two cell lines with different chemo- and radiosensitivity

    International Nuclear Information System (INIS)

    Kranjc, S.; Cemazar, M.; Grosel, A.; Pipan, Z.; Sersa, G.

    2003-01-01

    Aim. Radiosensitization with cisplatin can be enhanced by electroporation of cells and tumours. The aim of this study was to extend our previous studies on two carcinoma tumour models with different chemo- and radiosensitivity in order to evaluate whether this treatment is effective also on less chemo- and radiosensitive tumour cells. Materials and methods. This in vitro study was performed on carcinoma SCK and EAT-E cells. The cytotoxicity of three-modality treatment consisting of cisplatin, electroporation and irradiation was determined by the clonogenic assay. Results. The radiosensitizing effect of cisplatin on the two cell lines was greatly enhanced by electroporation. By this combined treatment, less chemo and radiosensitive EAT-E cells were rendered as sensitive as more chemo and radiosensitive SCK cells. Conclusion. The enhancement of cisplatin-induced radiosensitization of cells by electroporation could be beneficially used in the treatment of intrinsically less chemo- and radiosensitive tumours. (author)

  18. Reaction between nitracrine and glutathione: implications for hypoxic cell radiosensitization and cytotoxicity

    International Nuclear Information System (INIS)

    Wilson, W.R.; Anderson, R.F.

    1989-01-01

    Nitracrine (NC) is an electron affinic DNA intercalating agent and a potent hypoxia-selective cytotoxin and radiosensitizer in cell culture. Although NC is too cytotoxic and too rapidly metabolized to provide hypoxic cell radiosensitization in tumors, it is of mechanistic interest as an example of a DNA affinic radiosensitizer. We have observed a rapid chemical reaction between NC and reduced glutathione (GSH), which suggests that the observed potent in vitro cytotoxicity and radiosensitization might be dependent on thiol depletion by the large extracellular reservoir of drug. However, no GSH depletion was observed under conditions providing radiosensitization or rapid cell killing, and prior depletion of GSH by buthionine sulphoximine had no effect on cytotoxicity or formation of macromolecular adducts. Further, the intracellular reaction of NC with GSH is slower than predicted on the basis of the measured second order rate constant and the total intracellular concentrations of both species. The results are consistent with a role for DNA binding in protecting NC from reaction with GSH, and in improving the efficiency with which reduced electrophilic metabolites react with DNA in preference to GSH

  19. Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption.

    Science.gov (United States)

    Nehlig, Astrid

    2018-04-01

    Most individuals adjust their caffeine intake according to the objective and subjective effects induced by the methylxanthine. However, to reach the desired effects, the quantity of caffeine consumed varies largely among individuals. It has been known for decades that the metabolism, clearance, and pharmacokinetics of caffeine is affected by many factors such as age, sex and hormones, liver disease, obesity, smoking, and diet. Caffeine also interacts with many medications. All these factors will be reviewed in the present document and discussed in light of the most recent data concerning the genetic variability affecting caffeine levels and effects at the pharmacokinetic and pharmacodynamic levels that both critically drive the level of caffeine consumption. The pharmacokinetics of caffeine are highly variable among individuals due to a polymorphism at the level of the CYP1A2 isoform of cytochrome P450, which metabolizes 95% of the caffeine ingested. Moreover there is a polymorphism at the level of another critical enzyme, N -acetyltransferase 2. At the pharmacodynamic level, there are several polymorphisms at the main brain target of caffeine, the adenosine A2A receptor or ADORA2. Genetic studies, including genome-wide association studies, identified several loci critically involved in caffeine consumption and its consequences on sleep, anxiety, and potentially in neurodegenerative and psychiatric diseases. We start reaching a better picture on how a multiplicity of biologic mechanisms seems to drive the levels of caffeine consumption, although much more knowledge is still required to understand caffeine consumption and effects on body functions. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  20. Caffeine, exercise and the brain.

    Science.gov (United States)

    Meeusen, Romain; Roelands, Bart; Spriet, Lawrence L

    2013-01-01

    Caffeine can improve exercise performance when it is ingested at moderate doses (3-6 mg/kg body mass). Caffeine also has an effect on the central nervous system (CNS), and it is now recognized that most of the performance-enhancing effect of caffeine is accomplished through the antagonism of the adenosine receptors, influencing the dopaminergic and other neurotransmitter systems. Adenosine and dopamine interact in the brain, and this might be one mechanism to explain how the important components of motivation (i.e. vigor, persistence and work output) and higher-order brain processes are involved in motor control. Caffeine maintains a higher dopamine concentration especially in those brain areas linked with 'attention'. Through this neurochemical interaction, caffeine improves sustained attention, vigilance, and reduces symptoms of fatigue. Other aspects that are localized in the CNS are a reduction in skeletal muscle pain and force sensation, leading to a reduction in perception of effort during exercise and therefore influencing the motivational factors to sustain effort during exercise. Because not all CNS aspects have been examined in detail, one should consider that a placebo effect may also be present. Overall, it appears that the performance-enhancing effects of caffeine reside in the brain, although more research is necessary to reveal the exact mechanisms through which the CNS effect is established. Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.

  1. Radiosensitivity of Bombyx mori embryos and its modification by thermal shock

    International Nuclear Information System (INIS)

    Agaev, F.A.; Zakrzhevskaya, D.T.; Yusifov, N.I.; Gaziev, A.I.; AN Azerbajdzhanskoj SSR, Baku

    1991-01-01

    Radiosensitivity of Bombyx mori embryos on days 3-4 of their development is more than 10 times higher than that of 7-9 day embryos. The rate of DNA synthesis in the embryos correlates with their radiosensitivity. Heat treatment (40 deg C, 60 min) of embryos just before γ-irradiation increases their radioresistance (DMF=+1.6), whereas such a treatment immediately after irradiation reduces the survival rate of embryos as compared to the controls irradiated without heat treatment (DMA=-1.5). The radiomodifying effect of the thermal shock on the Bombyx mori embryos is the same with exposure at both the radioresistant and the radiosensitive stage of their development. However, it is more pronounced at the radiosensitive stage

  2. Radiosensitizers and protectors

    International Nuclear Information System (INIS)

    Nori, D.; Kim, J.H.; Hilaris, B.; Chu, F.C.

    1987-01-01

    Over the past decades, various physical, biological, and clinical strategies have been investigated to improve the therapeutic effectiveness of radiation. One of these efforts has been to develop chemical radiosensitizers and protectors. In the broadest sense, a radiation sensitizer is any agent that enhances the cytolethal effects of radiation. Drugs that selectively protect tissues from radiation injury are under active study. This chapter briefly reviews the present status of chemical radiosensitizers and protectors. The discussion of sensitizers will be limited to the oxic cell and hypoxic cell radiosensitizers and their clinical applications

  3. Caffeine, cognitive failures and health in a non-working community sample.

    Science.gov (United States)

    Smith, Andrew P

    2009-01-01

    Most studies of the effects of caffeine on performance have been conducted in the laboratory and further information is required on the real-life effects of caffeine consumption on cognition. In addition, possible effects of caffeine consumption on a range of health outcomes should also be assessed in these studies to enable cost-benefit analyses to be conducted. Secondary analyses of a large epidemiological database (N = 3223 non-working participants, 57% female, with a mean age of 49.6 years, range 17-92 years) were conducted to examine associations between caffeine consumption (mean caffeine consumption was 140 mg/day, range 0-1800 mg) and cognitive failures (errors of memory, attention and action) in a non-working sample. Associations between caffeine consumption and physical and mental health problems were also examined. The study involved secondary analyses of a database formed by combining the Bristol Stress and Health at Work and Cardiff Health and Safety at Work studies. Associations between caffeine consumption and frequency of cognitive failures and health outcomes were examined in a sample of non-workers. After controlling for possible confounding factors significant associations between caffeine consumption and fewer cognitive failures were observed. Initial analyses suggested that many health variables were associated with regular level of caffeine consumption. However, most of the significant effects of caffeine disappeared when demographic and lifestyle factors were controlled for. Consumption of caffeine was, however, associated with a reduced risk of depression. These effects were also observed in separate analyses examining the source of the caffeine (coffee and tea). Overall, the results show that caffeine consumption may benefit cognitive functioning in a non-working population. This confirms earlier findings from working samples. This beneficial effect of caffeine was not associated with negative health consequences. Indeed, consumption of

  4. Clonal cell populations unresponsive to radiosensitization induced by telomerase inhibition

    International Nuclear Information System (INIS)

    Ju, Yeun-Jin; Shin, Hyun-Jin; Park, Jeong-Eun; Juhn, Kyoung-Mi; Woo, Seon Rang; Kim, Hee-Young; Han, Young-Hoon; Hwang, Sang-Gu; Hong, Sung-Hee; Kang, Chang-Mo; Yoo, Young-Do; Park, Won-Bong; Cho, Myung-Haing; Park, Gil Hong; Lee, Kee-Ho

    2010-01-01

    Research highlights: → In our present manuscript, we have clearly showed an interesting but problematic obstacle of a radiosensitization strategy based on telomerase inhibition by showing that: Clonal population unresponsive to this radiosensitization occasionally arise. → The telomere length of unsensitized clones was reduced, as was that of most sensitized clones. → The unsensitized clones did not show chromosome end fusion which was noted in all sensitized clones. → P53 status is not associated with the occurrence of unsensitized clone. → Telomere end capping in unsensitized clone is operative even under telomerase deficiency. -- Abstract: A combination of a radiotherapeutic regimen with telomerase inhibition is valuable when tumor cells are to be sensitized to radiation. Here, we describe cell clones unresponsive to radiosensitization after telomere shortening. After extensive division of individual transformed clones of mTERC -/- cells, about 22% of clones were unresponsive to radiosensitization even though telomerase action was inhibited. The telomere lengths of unsensitized mTERC -/- clones were reduced, as were those of most sensitized clones. However, the unsensitized clones did not exhibit chromosomal end-to-end fusion to the extent noted in all sensitized clones. Thus, a defense mechanism preventing telomere erosion is operative even when telomeres become shorter under conditions of telomerase deficiency, and results in unresponsiveness to the radiosensitization generally mediated by telomere shortening.

  5. 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.

  6. Effects of caffeine on performance and mood depend on the level of caffeine abstinence.

    Science.gov (United States)

    Yeomans, Martin R; Ripley, Tamzin; Davies, Laura H; Rusted, Jennifer M; Rogers, Peter J

    2002-11-01

    Most studies of the effects of caffeine on performance have used regular caffeine consumers who are deprived at test. Thus the reported effects of caffeine could be explained through reversal of caffeine withdrawal. To test how preloading deprived caffeine consumers with 0, 1 or 2 mg/kg caffeine altered the subsequent ability of caffeine to modify mood and performance. Thirty moderate caffeine consumers were given a drink containing 0, 1 or 2 mg/kg caffeine at breakfast followed 60 min later by a second drink containing either 0 or 1 mg/kg caffeine. Performance on a measure of sustained attention and mood were measured before and after each drink. Administration of both 1 and 2 mg/kg caffeine at breakfast decreased reaction time and 1 mg/kg caffeine also increased performance accuracy on the sustained attention (RVIP) task relative to placebo. Both breakfast doses of caffeine also improved rated mental alertness. Similarly, 1 mg/kg caffeine administered 60 min after breakfast decreased reaction time and increased rated mental alertness in the group who had not been given caffeine at breakfast. However, this second dose of caffeine had no effect on subsequent performance or mood in the two groups who had received caffeine at breakfast. Caffeine reliably improved performance on a sustained attention task, and increased rated mental alertness, in moderate caffeine consumers who were tested when caffeine-deprived. However, caffeine had no such effects when consumers were no longer caffeine deprived. These data are consistent with the view that reversal of caffeine withdrawal is a major component of the effects of caffeine on mood and performance.

  7. Caffeine Use Disorder: A Comprehensive Review and Research Agenda.

    Science.gov (United States)

    Meredith, Steven E; Juliano, Laura M; Hughes, John R; Griffiths, Roland R

    2013-09-01

    Caffeine is the most commonly used drug in the world. Although consumption of low to moderate doses of caffeine is generally safe, an increasing number of clinical studies are showing that some caffeine users become dependent on the drug and are unable to reduce consumption despite knowledge of recurrent health problems associated with continued use. Thus, the World Health Organization and some health care professionals recognize caffeine dependence as a clinical disorder. In this comprehensive literature review, we summarize published research on the biological evidence for caffeine dependence; we provide a systematic review of the prevalence of caffeine dependence and rates of endorsement of clinically meaningful indicators of distress and functional impairment among habitual caffeine users; we discuss the diagnostic criteria for Caffeine Use Disorder-a condition for further study included in the Diagnostic and Statistical Manual of Mental Disorders ( 5 th ed .); and we outline a research agenda to help guide future clinical, epidemiological, and genetic investigations of caffeine dependence. Numerous controlled laboratory investigations reviewed in this article show that caffeine produces behavioral and physiological effects similar to other drugs of dependence. Moreover, several recent clinical studies indicate that caffeine dependence is a clinically meaningful disorder that affects a nontrivial proportion of caffeine users. Nevertheless, more research is needed to determine the reliability, validity, and prevalence of this clinically important health problem.

  8. Potential clinical impact of normal-tissue intrinsic radiosensitivity testing

    International Nuclear Information System (INIS)

    Bentzen, Soeren M.

    1997-01-01

    A critical appraisal is given of the possible benefit from a reliable pre-treatment knowledge of individual normal-tissue sensitivity to radiotherapy. The considerations are in part, but not exclusively, based on the recent experience with in vitro colony-forming assays of the surviving fraction at 2 Gy, the SF 2 . Three strategies are reviewed: (1) to screen for rare cases with extreme radiosensitivity, so-called over-reactors, and treat these with reduced total dose, (2) to identify the sensitive tail of the distribution of 'normal' radiosensitivities, refer these patients to other treatment, and to escalate the dose to the remaining patients, or (3) to individualize dose prescriptions based on individual radiosensitivity, i.e. treating to isoeffect rather than to a specific dose-fractionation schedule. It is shown that these strategies will have a small, if any, impact on routine radiotherapy. Screening for over-reactors is hampered by the low prevalence of these among otherwise un-selected patients that leads to a low positive predictive value of in vitro radiosensitivity assays. It is argued, that this problem may persist even if the noise on current assays could be reduced to (the unrealistic value of) zero, simply because of the large biological variation in SF 2 . Removing the sensitive tail of the patient population, will only have a minor effect on the dose that could be delivered to the remaining patients, because of the sigmoid shape of empirical dose-response relationships. Finally, individualizing dose prescriptions based exclusively on information from a normal-tissue radiosensitivity assay, leads to a nearly symmetrical distribution of dose-changes that would produce a very small gain, or even a loss, of tumor control probability if implemented in the clinic. From a theoretical point of view, other strategies could be devised and some of these are considered in this review. Right now the most promising clinical use of in vitro radiosensitivity

  9. A comparison of the effects of caffeine following abstinence and normal caffeine use.

    Science.gov (United States)

    Addicott, Merideth A; Laurienti, Paul J

    2009-12-01

    Caffeine typically produces positive effects on mood and performance. However, tolerance may develop following habitual use, and abrupt cessation can result in withdrawal symptoms, such as fatigue. This study investigated whether caffeine has a greater stimulant effect in a withdrawn state compared to a normal caffeinated state, among moderate daily caffeine consumers. Using a within-subjects design, 17 caffeine consumers (mean +/- sd = 375 +/- 101 mg/day) ingested placebo or caffeine (250 mg) following 30-h of caffeine abstention or normal dietary caffeine use on four separate days. Self-reported mood and performance on choice reaction time, selective attention, and memory tasks were measured. Caffeine had a greater effect on mood and choice reaction time in the abstained state than in the normal caffeinated state, but caffeine improved selective attention and memory in both states. Although improvements in mood and reaction time may best explained as relief from withdrawal symptoms, other performance measures showed no evidence of withdrawal and were equally sensitive to an acute dose of caffeine in the normal caffeinated state.

  10. Radiosensitivity in plants

    International Nuclear Information System (INIS)

    Nauman, A.F.

    1979-01-01

    The report presents a compilation of available data on the sensitivity of plants to ionizing radiation, and provides basic information on methods of determining such sensitivities, or of estimating radiosensitivities by calcuation of the nuclear factors upon which they depend. The scope of the data presented here is necessarily limited to the most generally useful radiobiological end points and to the most commonly-used types of radiation. Many of the factors which influence radiosensitivity, particularly nuclear factors, will be discussed. Emphasis will be upon whole-plant studies done at Brookhaven National Laboratory by A.H. Sparrow and his associates, since these studies are the source of most of the available radiosensitivity data and of all the sensitivity predictions listed here. Data presented here include summaries of experimentally-determined radiosensitivities at various end points for both herbaceous and woody higher plants, and for a few species of ferns and lower plants. The algae and fungi have not been considered here due to space limitations

  11. Radiosensitivity in plants

    Energy Technology Data Exchange (ETDEWEB)

    Nauman, A F

    1979-01-01

    The report presents a compilation of available data on the sensitivity of plants to ionizing radiation, and provides basic information on methods of determining such sensitivities, or of estimating radiosensitivities by calcuation of the nuclear factors upon which they depend. The scope of the data presented here is necessarily limited to the most generally useful radiobiological end points and to the most commonly-used types of radiation. Many of the factors which influence radiosensitivity, particularly nuclear factors, will be discussed. Emphasis will be upon whole-plant studies done at Brookhaven National Laboratory by A.H. Sparrow and his associates, since these studies are the source of most of the available radiosensitivity data and of all the sensitivity predictions listed here. Data presented here include summaries of experimentally-determined radiosensitivities at various end points for both herbaceous and woody higher plants, and for a few species of ferns and lower plants. The algae and fungi have not been considered here due to space limitations.

  12. Biodegradation of Caffeine by Trichosporon asahii Isolated from Caffeine Contaminated Soil

    OpenAIRE

    LAKSHMI V.; NILANJANA DAS

    2011-01-01

    Studies were carried out on caffeine degradation using Trichosporon asahii, a yeast species isolated from caffeine contaminated soil. There was 100 % degradation of caffeine at 54 h by the yeast cells acclimated to the medium containing caffeine and sucrose both. Experiments with T. asahii growing on caffeine in the presenceof 1 mM 1-aminobenzotriazole (ABT), an inhibitor of the cytochrome P-450 enzyme system, resulted inhibition of biomass production relative to positive control implicating ...

  13. Caffeine dependence in teenagers.

    Science.gov (United States)

    Bernstein, Gail A; Carroll, Marilyn E; Thuras, Paul D; Cosgrove, Kelly P; Roth, Megan E

    2002-03-01

    This study identifies and characterizes symptoms of caffeine dependence in adolescents. Thirty-six adolescents who consumed caffeine daily and had some features of caffeine dependence on telephone screen were scheduled for outpatient evaluation. Evaluation included the Diagnostic Interview Schedule for Children-IV-Youth Version (DISC-IV) and modified DISC-IV questions that assessed caffeine dependence based on DSM-IV substance dependence criteria. Of 36 subjects, 41.7% (n=15) reported tolerance to caffeine, 77.8% (n=28) described withdrawal symptoms after cessation or reduction of caffeine intake, 38.9% (n=14) reported desire or unsuccessful attempts to control use, and 16.7% (n=6) endorsed use despite knowledge of physical or psychological problems associated with caffeine. There was no significant difference in the amount of caffeine consumed daily by caffeine dependent versus non-dependent teenagers. These findings are important due to the vast number of adolescents who drink caffeinated beverages.

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

    International Nuclear Information System (INIS)

    Fujiwara, Y.; Tatsumi, M.

    1976-01-01

    Replicative bypass repair of UV damage to DNA was studied in a wide variaty of human, mouse and hamster cells in culture. Survival curve analysis revealed that in established cell lines (mouse L, Chinese hamster V79, HeLa S3 and SV40-transformed xeroderma pigmentosum (XP), post-UV caffeine treatment potentiated cell killing by reducing the extrapolation number and mean lethal UV fluence (Do). In the Do reduction as the result of random inactivation by caffeine of sensitive repair there were marked clonal differences among such cell lines, V79 being most sensitive to caffeine potentiation. However, other diploid cell lines (normal human, excision-defective XP and Syrian hamster) exhibited no obvious reduction in Do by caffeine. In parallel, alkaline sucrose sedimentation results showed that the conversion of initially smaller segments of DNA synthesized after irradiation with 10 J/m 2 to high-molecular-weight DNA was inhibited by caffeine in transformed XP cells, but not in the diploid human cell lines. Exceptionally, diploid XP variants had a retarded ability of bypass repair which was drastically prevented by caffeine, so that caffeine enhanced the lethal effect of UV. Neutral CsCl study on the bypass repair mechanism by use of bromodeoxyuridine for DNA synthesis on damaged template suggests that the pyrimodine dimer acts as a block to replication and subsequently it is circumvented presumably by a new process involving replicative bypassing following strand displacement, rather than by gap-filling de novo. This mechanism worked similarly in normal and XP cells, whether or not caffeine was present, indicating that excision of dimer is not always necessary. However, replicative bypassing became defective in XP variant and transformed XP cells when caffeine was present. It appears, therefore, that the replicative bypass repair process is either caffeine resistant or sensitive, depending on the cell type used, but not necessarily on the excision repair capability

  15. Caffeine controversies.

    Science.gov (United States)

    Gentle, Samuel J; Travers, Colm P; Carlo, Waldemar A

    2018-04-01

    Caffeine use in preterm infants has endured several paradigms: from standard of care to possible neurotoxin to one of the few medications for which there is evidence of bronchopulmonary dysplasia (BPD) risk reduction. The purpose of the review is to analyze this dynamic trajectory and discuss controversies that still remain after decades of caffeine use. Following concerns for caffeine safety in preterm infants, a large randomized controlled trial demonstrated a reduction in BPD and treatment for patent ductus arteriosus. The lower rate of death or neurodevelopmental impairment noted at 18-21 months was not statistically different at later timepoints; however, infants in the caffeine group had lower rates of motor impairment at 11-year follow-up. The time of caffeine therapy initiation is now substantially earlier, and doses used are sometimes higher that previously used, but there are limited data to support these practices. Caffeine therapy for apnea of prematurity (AOP) remains one of the pillars of neonatal care, although more evidence to support dosing and timing of initiation and discontinuation are needed.

  16. Prenatal caffeine exposure induced a lower level of fetal blood leptin mainly via placental mechanism

    International Nuclear Information System (INIS)

    Wu, Yi-meng; Luo, Han-wen; Kou, Hao; Wen, Yin-xian; Shen, Lang; Pei, Ling-guo; Zhou, Jin; Zhang, Yuan-zhen; Wang, Hui

    2015-01-01

    It's known that blood leptin level is reduced in intrauterine growth retardation (IUGR) fetus, and placental leptin is the major source of fetal blood leptin. This study aimed to investigate the decreased fetal blood leptin level by prenatal caffeine exposure (PCE) and its underlying placental mechanisms. Pregnant Wistar rats were intragastrically administered caffeine (30–120 mg/kg day) from gestational day 9 to 20. The level of fetal serum leptin and the expression of placental leptin-related genes were analyzed. Furthermore, we investigated the molecular mechanism of the reduced placental leptin's expression by treatment with caffeine (0.8–20 μM) in the BeWo cells. In vivo, PCE significantly decreased fetal serum leptin level in caffeine dose-dependent manner. Meanwhile, placental mRNA expression of adenosine A2a receptor (Adora2a), cAMP-response element binding protein (CREB), a short-type leptin receptor (Ob-Ra) and leptin was reduced in the PCE groups. In vitro, caffeine significantly decreased the mRNA expression of leptin, CREB and ADORA2A in concentration and time-dependent manners. The addition of ADORA2A agonist or adenylyl cyclase (AC) agonist reversed the inhibition of leptin expression induced by caffeine. PCE induced a lower level of fetal blood leptin, which the primary mechanism is that caffeine inhibited antagonized Adora2a and AC activities to decreased cAMP synthesis, thus inhibited the expression of the transcription factor CREB and target gene leptin in the placenta. Meantime, the reduced transportation of maternal leptin by placental Ob-Ra also contributed to the reduced fetal blood leptin. Together, PCE decreased fetal blood leptin mainly via reducing the expression and transportation of leptin in the placenta. - Highlights: • Caffeine reduced fetal blood leptin level. • Caffeine inhibited placental leptin production and transport. • Caffeine down-regulated placental leptin expression via antagonizing ADORA2.

  17. Prenatal caffeine exposure induced a lower level of fetal blood leptin mainly via placental mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Yi-meng [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Luo, Han-wen [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Kou, Hao [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Wen, Yin-xian [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Shen, Lang; Pei, Ling-guo; Zhou, Jin [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Zhang, Yuan-zhen [Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China)

    2015-11-15

    It's known that blood leptin level is reduced in intrauterine growth retardation (IUGR) fetus, and placental leptin is the major source of fetal blood leptin. This study aimed to investigate the decreased fetal blood leptin level by prenatal caffeine exposure (PCE) and its underlying placental mechanisms. Pregnant Wistar rats were intragastrically administered caffeine (30–120 mg/kg day) from gestational day 9 to 20. The level of fetal serum leptin and the expression of placental leptin-related genes were analyzed. Furthermore, we investigated the molecular mechanism of the reduced placental leptin's expression by treatment with caffeine (0.8–20 μM) in the BeWo cells. In vivo, PCE significantly decreased fetal serum leptin level in caffeine dose-dependent manner. Meanwhile, placental mRNA expression of adenosine A2a receptor (Adora2a), cAMP-response element binding protein (CREB), a short-type leptin receptor (Ob-Ra) and leptin was reduced in the PCE groups. In vitro, caffeine significantly decreased the mRNA expression of leptin, CREB and ADORA2A in concentration and time-dependent manners. The addition of ADORA2A agonist or adenylyl cyclase (AC) agonist reversed the inhibition of leptin expression induced by caffeine. PCE induced a lower level of fetal blood leptin, which the primary mechanism is that caffeine inhibited antagonized Adora2a and AC activities to decreased cAMP synthesis, thus inhibited the expression of the transcription factor CREB and target gene leptin in the placenta. Meantime, the reduced transportation of maternal leptin by placental Ob-Ra also contributed to the reduced fetal blood leptin. Together, PCE decreased fetal blood leptin mainly via reducing the expression and transportation of leptin in the placenta. - Highlights: • Caffeine reduced fetal blood leptin level. • Caffeine inhibited placental leptin production and transport. • Caffeine down-regulated placental leptin expression via antagonizing ADORA2.

  18. Caffeine Citrate Dosing Adjustments to Assure Stable Caffeine Concentrations in Preterm Neonates.

    Science.gov (United States)

    Koch, Gilbert; Datta, Alexandre N; Jost, Kerstin; Schulzke, Sven M; van den Anker, John; Pfister, Marc

    2017-12-01

    To identify dosing strategies that will assure stable caffeine concentrations in preterm neonates despite changing caffeine clearance during the first 8 weeks of life. A 3-step simulation approach was used to compute caffeine doses that would achieve stable caffeine concentrations in the first 8 weeks after birth: (1) a mathematical weight change model was developed based on published weight distribution data; (2) a pharmacokinetic model was developed based on published models that accounts for individual body weight, postnatal, and gestational age on caffeine clearance and volume of distribution; and (3) caffeine concentrations were simulated for different dosing regimens. A standard dosing regimen of caffeine citrate (using a 20 mg/kg loading dose and 5 mg/kg/day maintenance dose) is associated with a maximal trough caffeine concentration of 15 mg/L after 1 week of treatment. However, trough concentrations subsequently exhibit a clinically relevant decrease because of increasing clearance. Model-based simulations indicate that an adjusted maintenance dose of 6 mg/kg/day in the second week, 7 mg/kg/day in the third to fourth week and 8 mg/kg/day in the fifth to eighth week assures stable caffeine concentrations with a target trough concentration of 15 mg/L. To assure stable caffeine concentrations during the first 8 weeks of life, the caffeine citrate maintenance dose needs to be increased by 1 mg/kg every 1-2 weeks. These simple adjustments are expected to maintain exposure to stable caffeine concentrations throughout this important developmental period and might enhance both the short- and long-term beneficial effects of caffeine treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Neuroprotection by Caffeine in Hyperoxia-Induced Neonatal Brain Injury

    Directory of Open Access Journals (Sweden)

    Stefanie Endesfelder

    2017-01-01

    Full Text Available Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term “oxygen radical disease of prematurity”. Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats. The brain of a rat pups at postnatal Day 6 (P6 corresponds to that of a human fetal brain at 28–32 weeks gestation and the neonatal rat is an ideal model in which to investigate effects of oxidative stress and neuroprotection of caffeine on the developing brain. Six-day-old Wistar rats were pre-treated with caffeine and exposed to 80% oxygen for 24 and 48 h. Caffeine reduced oxidative stress marker (heme oxygenase-1, lipid peroxidation, hydrogen peroxide, and glutamate-cysteine ligase catalytic subunit (GCLC, promoted anti-oxidative response (superoxide dismutase, peroxiredoxin 1, and sulfiredoxin 1, down-regulated pro-inflammatory cytokines, modulated redox-sensitive transcription factor expression (Nrf2/Keap1, and NFκB, reduced pro-apoptotic effectors (poly (ADP-ribose polymerase-1 (PARP-1, apoptosis inducing factor (AIF, and caspase-3, and diminished extracellular matrix degeneration (matrix metalloproteinases (MMP 2, and inhibitor of metalloproteinase (TIMP 1/2. Our study affirms that caffeine is a pleiotropic neuroprotective drug in the developing brain due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.

  20. The paradox of caffeine-zolpidem interaction: a network analysis.

    Science.gov (United States)

    Myslobodsky, Michael

    2009-10-01

    A widely prescribed and potent short-acting hypnotic, zolpidem has become the mainstay for the treatment of middle-of-the-night sleeplessness. It is expected to be antagonized by caffeine. Paradoxically, in some cases caffeine appears to slightly enhance zolpidem sedation. The pharmacokinetic and pharmacodynamic nature of this odd effect remains unexplored. The purpose of this study is to reproduce a hypothetical molecular network recruited by caffeine when co-administered with zolpidem using Ingenuity Pathway Analysis. Thus generated, network drew attention to several possible contributors to caffeine sedation, such as tachykinin precursor 1, cannabinoid, and GABA receptors. The present overview is centered on the possibility that caffeine potentiation of zolpidem sedation does not involve a centralized interaction of specific neurotransmitters, but rather is contributed by its antioxidant capacity. It is proposed that by modifying the cellular redox state, caffeine ultimately reduces the pool of reactive oxygen species, thereby increasing the bioavailability of endogenous melatonin for interaction with zolpidem. This side effect of caffeine encourages further studies of multiple antioxidants as an attractive way to potentially increasing somnolence.

  1. Metabolic and hormonal effects of caffeine: randomized, double-blind, placebo-controlled crossover trial.

    Science.gov (United States)

    MacKenzie, Todd; Comi, Richard; Sluss, Patrick; Keisari, Ronit; Manwar, Simone; Kim, Janice; Larson, Robin; Baron, John A

    2007-12-01

    In short-term studies, caffeine has been shown to increase insulin levels, reduce insulin sensitivity, and increase cortisol levels. However, epidemiological studies have indicated that long-term consumption of beverages containing caffeine such as coffee and green tea is associated with a reduced risk of type 2 diabetes mellitus. There is a paucity of randomized studies addressing the metabolic and hormonal effects of consuming caffeine over periods of more than 1 day. We evaluated the effect of oral intake of 200 mg of caffeine taken twice a day for 7 days on glucose metabolism, as well as on serum cortisol, dehydroepiandrosterone (DHEA), and androstenedione, and on nighttime salivary melatonin. A double-blind, randomized, placebo-controlled crossover study with periods of 7 days and washouts of 5 days comparing caffeine with placebo capsules was conducted. Participants were 16 healthy adults aged 18 to 22 years with a history of caffeine consumption. Blood samples from each subject were assayed for glucose, insulin, serum cortisol, DHEA, and androstenedione on the eighth day of each period after an overnight fast. Nighttime salivary melatonin was also measured. Insulin levels were significantly higher (by 1.80 microU/mL; 95% confidence interval, 0.33-3.28) after caffeine intake than after placebo. The homeostasis model assessment index of insulin sensitivity was reduced by 35% (95% confidence interval, 7%-62%) by caffeine. There were no differences in glucose, DHEA, androstenedione, and melatonin between treatment periods. This study provides evidence that daily caffeine intake reduces insulin sensitivity; the effect persists for at least a week and is evident up to 12 hours after administration.

  2. 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...... of menstrual cycle. No dose-response relationship was found among smokers. Among males, the same decline in point estimates of the FR was present. Smoking women whose only source of caffeine was coffee (>300 mg/d) had a reduced fecundability odds-ratio (FR = 0.34; 95% CI 0.12-0.98). An interaction between...

  3. Anaphylaxis due to caffeine

    OpenAIRE

    Sugiyama, Kumiya; Cho, Tatsurai; Tatewaki, Masamitsu; Onishi, Shogo; Yokoyama, Tatsuya; Yoshida, Naruo; Fujimatsu, Takayoshi; Hirata, Hirokuni; Fukuda, Takeshi; Fukushima, Yasutsugu

    2015-01-01

    We report a rare case of anaphylaxis due to caffeine intake. A 27-year-old woman suffered her first episode of anaphylaxis and a positive skin prick test suggested that the anaphylaxis was due to an IgE-mediated hypersensitivity reaction to caffeine. She was diagnosed with caffeine allergy and has not had an allergic reaction after avoiding foods and drinks containing caffeine. Although caffeine is known to have antiallergic effects, this case shows that caffeine can be an allergen and cause ...

  4. Chromosomal aberrations induced by caffeine, 3H-thymidine and by X-rays in two L5178Y sublines of different radiosensitivity. Part 1. Chromosomal aberrations in cells treated with 2mM caffeine and tritiated thymidine

    International Nuclear Information System (INIS)

    Bocian, E.; Bouzyk, E.; Rosiek, O.; Ziemba-Zoltowska, B.

    1982-01-01

    Chromosomal aberrations were studied in two sublines of L5178Y cells with different sensitivity to X-rays. Cells were treated with 2 mM caffeine for 12 h. Then they were examined at various time intervals from 5 to 24 h. Caffeine caused over three times more aberrations, mainly chromatid breaks and gaps, in radiation-sensitive L5178Y-S than in radiation-resistant L5178Y-R cells. The maximum frequency of chromatid breaks in both sublines was found at 8 h and that of chromatid exchanges and isochromatid breaks at 12 h after treatment. A dramatic decrease of the frequency of all types of aberrations at 24 h was observed. In the pulse labelled experiments caffeine enhanced the frequency of aberrations that were induced by 3 H-thymidine at a concentration of 1 μCi/ml. This effect of caffeine was greater in L5178Y-R than in L5178Y-S cells. (author)

  5. Attentional bias for caffeine-related stimuli in high but not moderate or non-caffeine consumers.

    Science.gov (United States)

    Yeomans, Martin R; Javaherian, Shabnam; Tovey, Heather M; Stafford, Lorenzo D

    2005-09-01

    Attentional bias for drug-related cues has been reported with a wide range of drugs, but to date the extent to which caffeine consumers show similar biases for caffeine-related stimuli has not been tested. The present study therefore examined this issue in terms of differences in attentional bias for caffeine-related words in High, Moderate and Non-caffeine consumers using a dot-probe word task following overnight caffeine abstinence. This study was conducted to test whether caffeine consumers show an attentional bias for caffeine-related words, and whether such biases relate to habitual levels of caffeine use. Sixteen High, Moderate and Non-consumers of caffeine were asked to complete a modified dot-probe task in order to measure attentional bias for caffeine-related relative to neutral control word groups. The task was completed following overnight caffeine abstinence, and participants also completed mood and caffeine-craving measures. The High consumer group showed a significant attentional bias for the caffeine-related words, but no such bias was seen in Moderate or Non-consumer groups. As expected, craving for caffeine was strongest in the High consumers and weakest in the Non-consumers. Attentional bias in the High group correlated with self-reported caffeine consumption and with craving for caffeine, but neither effect was significant in the Moderate group. These data confirm that High caffeine consumers show attentional bias for caffeine-related stimuli, consistent with current theories of drug addiction.

  6. 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 ...

  7. Acute effects of theanine, caffeine and theanine-caffeine combination on attention.

    Science.gov (United States)

    Kahathuduwa, Chanaka N; Dassanayake, Tharaka L; Amarakoon, A M Tissa; Weerasinghe, Vajira S

    2017-07-01

    l-theanine is a constituent of tea which is claimed to enhance cognitive functions. We aimed to determine whether theanine and theanine-caffeine combination have acute positive effects on cognitive and neurophysiological measures of attention, compared to caffeine (a positive control) and a placebo in healthy individuals. In a placebo-controlled, five-way crossover trial in 20 healthy male volunteers, we compared the effects of l-theanine (200 mg), caffeine (160 mg), their combination, black tea (one cup) and a placebo (distilled water) on cognitive (simple [SVRT] and recognition visual reaction time [RVRT]) and neurophysiological (event-related potentials [ERPs]) measures of attention. We also recorded visual (VEPs) and motor evoked potentials (MEPs) to examine any effects of treatments on peripheral visual and motor conduction, respectively. Mean RVRT was significantly improved by theanine (P = 0.019), caffeine (P = 0.043), and theanine-caffeine combination (P = 0.001), but not by tea (P = 0.429) or placebo (P = 0.822). VEP or MEP latencies or SVRT did not show significant inter-treatment differences. Theanine (P = 0.001) and caffeine (P = 0.001) elicited significantly larger mean peak-to-peak N2-P300 ERP amplitudes than the placebo, whereas theanine-caffeine combination elicited a significantly larger mean N2-P300 amplitude than placebo (P caffeine (P = 0.005). No significant theanine × caffeine interaction was observed for RVRT or N2-P300 amplitude. A dose of theanine equivalent of eight cups of back tea improves cognitive and neurophysiological measures of selective attention, to a degree that is comparable with that of caffeine. Theanine and caffeine seem to have additive effects on attention in high doses.

  8. Electrophysiological studies in healthy subjects involving caffeine.

    Science.gov (United States)

    de Carvalho, Mamede; Marcelino, Erica; de Mendonça, Alexandre

    2010-01-01

    We review the electrophysiological studies concerning the effects of caffeine on muscle, lower and upper motor neuron excitability and cognition. Several different methods have been used, such as electromyography, recruitment analysis, H-reflex, transcranial magnetic stimulation (TMS), electroencephalography and event-related potentials. The positive effect of caffeine on vigilance, attention, speed of reaction, information processing and arousal is supported by a number of electrophysiological studies. The evidence in favor of an increased muscle fiber resistance is not definitive, but higher or lower motor neuron excitability can occur as a consequence of a greater excitation of the descending input from the brainstem and upper motor neurons. TMS can address the influence of caffeine on the upper motor neuron. Previous studies showed that cortico-motor threshold and intracortical excitatory and inhibitory pathways are not influenced by caffeine. Nonetheless, our results indicate that cortical silent period (CSP) is reduced in resting muscles after caffeine consumption, when stimulating the motor cortex with intensities slightly above threshold. We present new data demonstrating that this effect is also observed in fatigued muscle. We conclude that CSP can be considered a surrogate marker of the effect of caffeine in the brain, in particular of its central ergogenic effect.

  9. Estimation of caffeine intake from analysis of caffeine metabolites in wastewater

    DEFF Research Database (Denmark)

    Gracia-Lor, Emma; Rousis, Nikolaos I.; Zuccato, Ettore

    2017-01-01

    with the human urinary excretion profile. A good match was found for 1,7-dimethyluric acid, an exclusive caffeine metabolite, suggesting that might be a suitable biomarker in wastewater for assessing population-level caffeine consumption. A correction factor was developed considering the percentage of excretion......Caffeine metabolites in wastewater were investigated as potential biomarkers for assessing caffeine intake in a population. The main human urinary metabolites of caffeine were measured in the urban wastewater of ten European cities and the metabolic profiles in wastewater were compared...... of this metabolite in humans, according to published pharmacokinetic studies. Daily caffeine intake estimated from wastewater analysis was compared with the average daily intake calculated from the average amount of coffee consumed by country per capita. Good agreement was found in some cities but further...

  10. Genetic components for radiosensitivity. Gene expression in radiosensitive monocygotic twins. Final report

    International Nuclear Information System (INIS)

    Dikomey, Ekkehard

    2012-01-01

    The underlying hypothesis of this project was that the variation of individual radiosensitivity is determined by the different expression of single gens. This concept was tested using 60 monozygotic twin pairs, followed by an evaluation with 80 prostate cancer patients. Radiosensitivity was assessed for both G0- as well as G2-phase using chromosomal assays. G0- radiosensitivity is determined by lethal chromosomal aberrations and reflects the individual amount of cell killing, while G2-sensitivity is determined by chromatid breaks and is taken as an indicator of individual cancer risk. For both populations, G0- and G2-radiosensitivity are characterized by substantial variation with a CV of 11 and 14% or 27 and 21%, respectively. While the mean G0-sensitivity is the same for both populations, there is a slight difference for G2. The slightly higher value of G2-sensitivity found for prostate cancer patients might result from the higher age of this group. For both populations gene expression profiles were determined using the Affymetrix chip HG-U133+2.0. Overall gene expression was characterized by a huge variation covering more than four decades. However, for single genes, expression showed little variation with CV generally ranging only between 2 and 8%. Analysis of data using several different methods revealed that variation of both G0- as well as G2-radiosensitivity cannot be ascribed to the different expression of single genes. For twins, random forests can be used to identify 8 to 10 genes than are relevant either for G0- or G2-radiosensitivity. However, these genes cannot be confirmed by an evaluation with 80 prostate cancer patients. This finding clearly demonstrates that the hypothesis, due to which variation of individual radiosensitivity is caused by different expression of single genes, has to be rejected. It appears more likely that this parameter is determined by complex interactions of several genes in functional networks. (orig.)

  11. Survival curves of irradiated glutathione-deficient human fibroblasts: indication of a reduced enhancement of radiosensitivity by oxygen and misonidazole

    International Nuclear Information System (INIS)

    Midander, J.; Deschavanne, P.J.; Malaise, E.P.; Revesz, L.

    1982-01-01

    Fibroblasts derived from a patient with 5-oxoprolinuria are genetically deficient in glutathione synthetase. This deficiency causes a dramatic decrease in intracellular glutathione (GSH) level. The radiosensitivity of GSH deficient cells (GSH) was studied in vitro using colony forming ability as an endpoint. Cells with normal GSH level, obtained from the healthy brother of the patient, were used as controls. When irradiated in 95% air-5% CO 2 , GSH - cells are slightly but significantly more radiosensitive than GSH + controls (dose modifying factor (DMF) of 1.2). When irradiated in argon, the survival curve of GSH - cells indicates an oxygen enhancement ratio (OER) of 1.5 when compared to the curve obtained in oxic conditions. The OER of control cells in the same conditions is 2.9. In comparison to results obtained in air, 100% oxygen moderately increases the radiosensitivity of GSH + cells (DMF 1,23), while it has a very low effect on GSH - cells (DMF 1.06). These results suggest that intracellular GSH plays an essential protective role in hypoxia, its effect is reduced in air and practically disappears in 100% oxygen. When cells are incubated with 8 mM misonidazole 2 hours before irradiation, the drug has a much greater sensitizing effect on GSH + cells (DMF 2.33) than on GSH - cells (DMF 1.55). The results demonstrate that intracellular GSH level plays a major role in the response of hypoxic cells, irradiated either alone or in the presence of misonidazole

  12. 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.

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

    International Nuclear Information System (INIS)

    Khoo, Weslie Yu Heng; Pumera, Martin; Bonanni, Alessandra

    2013-01-01

    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

  14. Caffeine and Your Child

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Caffeine KidsHealth / For Parents / Caffeine What's in this article? ... español La cafeína y su hijo What Is Caffeine? Caffeine is a natural stimulant found in coffee, ...

  15. Caffeine, postmenopausal estrogen, and risk of Parkinson's disease.

    Science.gov (United States)

    Ascherio, A; Chen, H; Schwarzschild, M A; Zhang, S M; Colditz, G A; Speizer, F E

    2003-03-11

    Men who regularly consume caffeinated drinks have a lower risk of PD than do nondrinkers, but this relation has not been found in women. Because this sex difference could be due to hormonal effects, the authors examined prospectively the risk of PD according to use of postmenopausal hormones and caffeine intake among participants in the Nurses' Health Study. The study population comprised 77,713 women free of PD, stroke, or cancer at baseline, who were postmenopausal at baseline or reached menopause before the end of the study. During 18 years of follow-up the authors documented 154 cases of PD. Overall, the risk of PD was similar in women using hormones and women who never used hormones (relative risk 1.02, 95% CI 0.69 to 1.52). Use of hormones, however, was associated with a reduced risk of PD among women with low caffeine consumption (RR 0.39, 95% CI 0.13 to 1.17), and with increased risk among women with high caffeine consumption (RR 2.44, 95% CI 0.75 to 7.86; p for interaction = 0.01). Among hormone users, women consuming six or more cups of coffee per day had a fourfold higher risk of PD (RR 3.92, 95% CI 1.49 to 10.34; p = 0.006) than did women who never drink coffee. These results suggest that caffeine reduces the risk of PD among women who do not use postmenopausal hormones, but increases risk among hormone users. Clinical trials of caffeine or estrogens in women should avoid the combined use of these agents.

  16. Caffeine promotes global spatial processing in habitual and non-habitual caffeine consumers

    Directory of Open Access Journals (Sweden)

    Grace E. Giles

    2013-10-01

    Full Text Available Information processing is generally biased toward global cues, often at the expense of local information. Equivocal extant data suggests that arousal states may accentuate either a local or global processing bias, at least partially dependent on the nature of the manipulation, task and stimuli. To further differentiate the conditions responsible for such equivocal results we varied caffeine doses to alter physiological arousal states and measured their effect on tasks requiring the retrieval of local versus global spatial knowledge. In a double-blind, repeated-measures design, non-habitual (Exp. 1; N=36, M=42.5±29 mg/day caffeine and habitual (Exp. 2; N=34, M=579.5±311.5 mg/day caffeine caffeine consumers completed four test sessions corresponding to each of four caffeine doses (0 mg, 100 mg, 200 mg, 400 mg. During each test session, participants consumed a capsule containing one of the three doses of caffeine or placebo, waited sixty minutes, and then completed two spatial tasks, one involving memorizing maps and one spatial descriptions. A spatial statement verification task tested local versus global spatial knowledge by differentially probing memory for proximal versus distal landmark relationships. On the map learning task, results indicated that caffeine enhanced memory for distal (i.e. global compared to proximal (i.e. local comparisons at 100 (marginal, 200, and 400 mg caffeine in non-habitual consumers, and marginally beginning at 200 mg caffeine in habitual consumers. On the spatial descriptions task, caffeine enhanced memory for distal compared to proximal comparisons beginning at 100 mg in non-habitual but not habitual consumers. We thus provide evidence that caffeine-induced physiological arousal amplifies global spatial processing biases, and these effects are at least partially driven by habitual caffeine consumption.

  17. 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…

  18. Barley seed radiosensitivity following post-hydration in oxygen-, nitrogen- and nitrous oxide-saturated water, 1; Influence of caffeine and t-butyl alcohol

    Energy Technology Data Exchange (ETDEWEB)

    Singh, S.P.; Kesavan, P.C. (Jawaharlal Nehru Univ., New Delhi (India). School of Life Sciences)

    1990-06-01

    Dry ({approx}3.5 and 4.0 per cent moisture content) barley seeds were exposed to 350 Gy of {sup 60}Co-{gamma}-rays in vacuo and post-hydrated at 4degC for 8 h in O{sub 2}-, N{sub 2}-, or N{sub 2}O-saturated water. The effect of caffeine and t-butyl alcohol (t-BuOH) dissolved in the post-hydration medium on the magnitude of damage developing under these three different gaseous circumstances was studied. The post-irradiation damage and its modification by caffeine and t-BuOH was assessed in terms of 8-day-old seedling injury, peroxidase activity and total peroxides in the 8-day-old seedlings. Post-irradiation O{sub 2}-saturated hydration caused maximal 8-day-old seedling injury, and increased peroxidase activity with concomitant reduction in total peroxides. Both caffeine and t-BuOH afforded significant radioprotection against post-irradiation O{sub 2}-dependent damage. Post-irradiation N{sub 2}O-saturated hydration was even more significantly radioprotective than the N{sub 2}-saturated post-hydration. Under these circumstances, t-BuOH exerted no effect whatsoever on the N{sub 2}- and N{sub 2}O-mediated post-irradiation damage. Caffeine, on the other hand, significantly potentiated these two components of damage. A brief consideration of the physicochemical events which possibly account for the observed effects is presented. (author).

  19. Chromosomal aberrations induced by caffeine, 3H-thymidine and by X-rays in two L5178Y sublines of different radiosensitivity. Part 2. Effect of 2 mM caffeine on the frequency of chromosomal aberrations induced by X-radiation

    International Nuclear Information System (INIS)

    Bocian, E.; Bouzyk, E.; Rosiek, O.; Ziemba-Zoltowska, B.

    1982-01-01

    The effect of 2 mM caffeine on the frequency of X-ray induced chromatid aberrations in two sublines of L5178Y cells with different sensitivity to X-rays was examined. Cells were irradiated with 1 Gy of X-rays and treated with caffeine for 12 h after irradiation. The frequency of aberrations was estimated at time intervals from 5 to 48 h after irradiation. Caffeine increased the frequency of cells with numerous aberrations produced by X radiation in both sublines. Its potentiating effect was greater in the radiation-resistant subline L5178Y-R than in the radiation-sensitive one L5178Y-S. In caffeine-treated L5178Y-S cells chromosomal aberrations were revealed earlier than in the untreated cells. (author)

  20. Faster but not smarter:effects of caffeine and caffeine withdrawal on alertness and performance

    OpenAIRE

    Rogers, Peter J; Heatherley, Susan V; Mullings, Emma L; Smith, Jessica E

    2013-01-01

    Despite 100 years of psychopharmacological research, the extent to which caffeine consumption benefits human functioning remains unclear.To measure the effects of overnight caffeine abstinence and caffeine administration as a function of level of habitual caffeine consumption.Medium-high (n = 212) and non-low (n = 157) caffeine consumers completed self-report measures and computer-based tasks before (starting at 10:30 AM) and after double-blind treatment with either caffeine (100 mg, then 150...

  1. Effect of caffeine on prospective and retrospective duration judgements.

    Science.gov (United States)

    Gruber, Ronald P; Block, Richard A

    2003-07-01

    The effects of caffeine on prospective and retrospective duration judgements were evaluated in a double-blind placebo-controlled experiment. After taking either 200 mg caffeine or a placebo, participants touched a 17-sided polygon for 15 s. Then they verbally estimated the number of angles and the duration. Participants in the prospective group were told in advance they would be making a duration estimate, whereas those in the retrospective group were not told. Caffeine reduced duration estimates in the prospective condition but not in the retrospective condition. The effect of caffeine on very long duration comparisons (the past year compared with a year at one-half and one-quarter of one's age) was also evaluated, but none was found. The findings do not support the hypothesis that caffeine affects duration experience by increasing the internal clock rate as a result of its dopamine D(2) agonist properties. The hypothesis that caffeine produces its effect by enhancing memory was considered and rejected. The most parsimonious explanation is that caffeine increased arousal level, which led to a narrowing of the focus of attention to the most salient task. Copyright 2003 John Wiley & Sons, Ltd.

  2. Radiosensitizers: rationale and potential

    International Nuclear Information System (INIS)

    Brown, J.M.

    1981-01-01

    This paper briefly reviews agents that are capable of sensitizing hypoxic cells to radiation and chemotherapeutic agents. The first part is a synopsis of the development of hypoxic radiosensitizers, which concludes that misonidazole can be effective against human tumors. Unfortunately, neurotoxicity limits its effectiveness in humans because the dose that can be given in conjunction with daily fractionated radiation is five to ten times lower than is required for full radiosensitization of the hypoxic cells. The second part covers our recent efforts to develop a drug that does not produce such limiting neurotoxicity. The primary rationale of our program was to synthesize a drug with a short plasma half-life that was too hydrophilic to cross the blood-brain barrier but was able to penetrate tumors and radiosensitize hypoxic cells. From this program, a new drug, SR-2508, has been found that is as efficient as misonidazole in its radiosensitizing ability, but is four to ten times less toxic. Finally, the potential of radiosensitizers not only as agents that can sensitize tumor cells to radiation, but also as agents that can specifically sensitize tumors to chemotherapeutic agents, is discussed. In addition, these drugs may be potential cytotoxic agents that produce toxicity only in solid tumors

  3. Caffeine May Reduce Perceived Sweet Taste in Humans, Supporting Evidence That Adenosine Receptors Modulate Taste.

    Science.gov (United States)

    Choo, Ezen; Picket, Benjamin; Dando, Robin

    2017-09-01

    Multiple recent reports have detailed the presence of adenosine receptors in sweet sensitive taste cells of mice. These receptors are activated by endogenous adenosine in the plasma to enhance sweet signals within the taste bud, before reporting to the primary afferent. As we commonly consume caffeine, a powerful antagonist for such receptors, in our daily lives, an intriguing question we sought to answer was whether the caffeine we habitually consume in coffee can inhibit the perception of sweet taste in humans. 107 panelists were randomly assigned to 2 groups, sampling decaffeinated coffee supplemented with either 200 mg of caffeine, about the level found in a strong cup of coffee, or an equally bitter concentration of quinine. Participants subsequently performed sensory testing, with the session repeated in the alternative condition in a second session on a separate day. Panelists rated both the sweetened coffee itself and subsequent sucrose solutions as less sweet in the caffeine condition, despite the treatment having no effect on bitter, sour, salty, or umami perception. Panelists were also unable to discern whether they had consumed the caffeinated or noncaffeinated coffee, with ratings of alertness increased equally, but no significant improvement in reaction times, highlighting coffee's powerful placebo effect. This work validates earlier observations in rodents in a human population. © 2017 Institute of Food Technologists®.

  4. Development of novel radiosensitizers for cancer therapy

    CERN Document Server

    Akamatsu, K

    2002-01-01

    The novel radiosensitizers for cancer therapy, which have some atoms with large X-ray absorption cross sections, were synthesized. The chemical and radiation (X-rays, W target, 100kVp) toxicities and the radiosensitivities to LS-180 human colon adenocarcinoma cells were also evaluated. 2,3,4,5,6-pentabromobenzylalcohol (PBBA) derivatives were not radiosensitive even around the maximum concentration. On the other hand, the hydrophilic sodium 2,4,6-triiodobenzoate (STIB) indicated meaningful radiosensitivity to the cells. Moreover, the membrane-specific radiosensitizers, cetyl fluorescein isthiocyanate (cetyl FITC), cetyl eosin isothiocyanate (cetyl br-FITC), cetyl erythrosin isothiocyanate (cetyl I-FITC), which aim for the membrane damage by X-ray photoabsorption on the target atoms, were localized in the plasma membrane. As the results of the colony formation assay, it was found that both cetyl FITC are similarly radiosensitive. In this report, we demonstrate the synthetic methods of the radiosensitizers, the...

  5. Estimation of caffeine intake from analysis of caffeine metabolites in wastewater

    NARCIS (Netherlands)

    Gracia-Lor, E.; Rousis, N.I.; Zuccato, E.; Bade, R.; Baz-Lomba, J.A.; Castrignanò, E.; Causanilles Llanes, A.; Hernández, F.; Kasprzyk-Hordern, B.; Kinyua, J.; McCall, A.-K.; van Nuijs, A.L.N.; Plósz, B.G.; Ramin, P.; Ryu, Y.; Santos, M.M.; Thomas, K.; de Voogt, P.; Yang, Z.; Castiglioni, S.

    2017-01-01

    Caffeine metabolites in wastewater were investigated as potential biomarkers for assessing caffeine intake in a population. The main human urinary metabolites of caffeine were measured in the urban wastewater of ten European cities and the metabolic profiles in wastewater were compared with the

  6. Quantitative HPLC Analysis of an Analgesic/Caffeine Formulation: Determination of Caffeine

    Science.gov (United States)

    Ferguson, Glenda K.

    1998-04-01

    A modern high performance liquid chromatography (HPLC) laboratory experiment which entails the separation of acetaminophen, aspirin, and caffeine and the quantitative assay of caffeine in commercial mixtures of these compounds has been developed. Our HPLC protocol resolves these compounds in only three minutes with a straightforward chromatographic apparatus which consists of a C-18 column, an isocratic mobile phase, UV detection at 254 nm, and an integrator; an expensive, sophisticated system is not required. The separation is both repeatable and rapid. Moreover, the experiment can be completed in a single three-hour period. The experiment is appropriate for any chemistry student who has completed a minimum of one year of general chemistry and is ideal for an analytical or instrumental analysis course. The experiment detailed herein involves the determination of caffeine in Goody's Extra Strength Headache Powders, a commercially available medication which contains acetaminophen, aspirin, and caffeine as active ingredients. However, the separation scheme is not limited to this brand of medication nor is it limited to caffeine as the analyte. With only minor procedural modifications, students can simultaneously quantitate all of these compounds in a commercial mixture. In our procedure, students prepare a series of four caffeine standard solutions as well as a solution from a pharmaceutical analgesic/caffeine mixture, chromatographically analyze each solution in quadruplicate, and plot relative average caffeine standard peak area versus concentration. From the mathematical relationship that results, the concentration of caffeine in the commercial formulation is obtained. Finally, the absolute standard deviation of the mean concentration is calculated.

  7. 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.

  8. 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 ...

  9. Subjective, behavioral, and physiological effects of acute caffeine in light, nondependent caffeine users.

    Science.gov (United States)

    Childs, Emma; de Wit, Harriet

    2006-05-01

    Caffeine produces mild psychostimulant effects that are thought to underlie its widespread use. However, the direct effects of caffeine are difficult to evaluate in regular users of caffeine because of tolerance and withdrawal. Indeed, some researchers hypothesize that the psychostimulant effects of caffeine are due largely to the reversal of withdrawal and question whether there are direct effects of caffeine consumption upon mood, alertness, or mental performance in nondependent individuals. This study investigated the physiological, subjective, and behavioral effects of 0, 50, 150, and 450 mg caffeine in 102 light, nondependent caffeine users. Using a within-subjects design, subjects participated in four experimental sessions, in which they received each of the four drug conditions in random order under double blind conditions. Participants completed subjective effects questionnaires and vital signs were measured before and at repeated time points after drug administration. Forty minutes after the capsules were ingested, subjects completed behavioral tasks that included tests of sustained attention, short-term memory, psychomotor performance, and behavioral inhibition. Caffeine significantly increased blood pressure, and produced feelings of arousal, positive mood, and high. Caffeine increased the number of hits and decreased reaction times in a vigilance task, but impaired performance on a memory task. We confirm that acute doses of caffeine, at levels typically found in a cup of coffee, produce stimulant-like subjective effects and enhance performance in light, nondependent caffeine users. These findings support the idea that the drug has psychoactive effects even in the absence of withdrawal.

  10. Caffeine's implications for women's health and survey of obstetrician-gynecologists' caffeine knowledge and assessment practices.

    Science.gov (United States)

    Anderson, Britta L; Juliano, Laura M; Schulkin, Jay

    2009-09-01

    Caffeine has relevance for women's health and pregnancy, including significant associations with spontaneous abortion and low birth weight. According to scientific data, pregnant women and women of reproductive age should be advised to limit their caffeine consumption. This article reviews the implications of caffeine for women's psychological and physical health, and presents data on obstetrician-gynecologists' (ob-gyns) knowledge and practices pertaining to caffeine. Ob-gyns (N = 386) who are members of the American College of Obstetricians and Gynecologists' Collaborative Ambulatory Research Network responded to a 21-item survey about caffeine. Although most knew that caffeine is passed through breast milk, only 24.8% were aware that caffeine metabolism significantly slows as pregnancy progresses. Many respondents were not aware of the caffeine content of commonly used products, such as espresso and Diet Coke, with 14.3% and 57.8% indicating amounts within an accurate range, respectively. Furthermore, ob-gyns did not take into account large differences in caffeine content across different caffeinated beverages with most recommending one to two servings of coffee or tea or soft drinks per day. There was substantial inconsistency in what was considered to be "high levels" of maternal caffeine consumption, with only 31.6% providing a response. When asked to indicate the risk that high levels of caffeine have on various pregnancy outcomes, responses were not consistent with scientific data. For example, respondents overestimated the relative risk of stillbirths and underestimated the relative risk of spontaneous abortion. There was great variability in assessment and advice practices pertaining to caffeine. More than half advise their pregnant patients to consume caffeine under certain circumstances, most commonly to alleviate headache and caffeine withdrawal. The data suggest that ob-gyns could benefit from information about caffeine and its relevance to their

  11. Caffeine, fatigue, and cognition.

    Science.gov (United States)

    Lorist, Monicque M; Tops, Mattie

    2003-10-01

    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 the general belief that caffeine acts as a stimulant. Studies using ERP measures indicate that caffeine has an effect on attention, which is independent of specific stimulus characteristics. Behavioural effects on response related processes turned out to be mainly related to more peripheral motor processes. Recent insights in adenosine and dopamine physiology and functionality and their relationships with fatigue point to a possible modulation by caffeine of mechanisms involved in the regulation of behavioural energy expenditure.

  12. Caffeine Inhibits Fluid Secretion by Interlobular Ducts From Guinea Pig Pancreas.

    Science.gov (United States)

    Mochimaru, Yuka; Yamamoto, Akiko; Nakakuki, Miyuki; Yamaguchi, Makoto; Taniguchi, Ituka; Ishiguro, Hiroshi

    2017-04-01

    Caffeine is contained in coffee, tea, and numerous beverages and foods. We examined the direct effects of caffeine on the physiological function of pancreatic duct cells by using interlobular duct segments isolated from guinea pig pancreas. The rate of fluid secretion was continuously measured by monitoring the luminal volume of isolated duct segments. Changes in intracellular Ca concentration ([Ca]i) were estimated by microfluorometry in ducts loaded with Fura-2. Both secretin-stimulated and acetylcholine (ACh)-stimulated fluid secretions were substantially and reversibly inhibited by relatively low concentrations of caffeine as low as 0.03 mM relevant to blood levels after ingestion of caffeine-containing beverages. Caffeine inhibited ACh-induced elevation of [Ca]i and secretin-induced fluctuation of [Ca]i. Caffeine abolished thapsigargin-induced intracellular Ca release but did not affect the entry of extracellular Ca. Caffeine (0.05 mM) abolished ethanol (1 mM)-induced fluid hypersecretion in secretin-stimulated pancreatic duct. Low concentrations of caffeine directly inhibit pancreatic ductal fluid secretion stimulated by secretin or ACh and also ethanol-induced fluid hypersecretion. The inhibition by caffeine seems to be mediated by the blockade of intracellular Ca mobilization. Daily intake of caffeine may reduce the volume of pancreatic juice secretion.

  13. Caffeine inhibits STAT1 signaling and downregulates inflammatory pathways involved in autoimmunity.

    Science.gov (United States)

    Iris, Merve; Tsou, Pei-Suen; Sawalha, Amr H

    2018-04-18

    Caffeine is a widely consumed pharmacologically active product. We focused on characterizing immunomodulatory effects of caffeine on peripheral blood mononuclear cells. Caffeine at high doses showed a robust downregulatory effect on cytokine activity and genes related to several autoimmune diseases including lupus and rheumatoid arthritis. Dose-dependent validation experiments showed downregulation at the mRNA levels of key inflammation-related genes including STAT1, TNF, IFNG, and PPARG. TNF and PPARG were suppressed even with the lowest caffeine dose tested, which corresponds to the serum concentration of caffeine after administration of one cup of coffee. Cytokine levels of IL-8, MIP-1β, IL-6, IFN-γ, GM-CSF, TNF, IL-2, IL-4, MCP-1, and IL-10 were decreased significantly with caffeine treatment. Upstream regulator analysis suggests that caffeine inhibits STAT1 signaling, which was confirmed by showing reduced phosphorylated STAT1 after caffeine treatment. Further studies exploring disease-modulating potential of caffeine in autoimmune diseases and further exploring the mechanisms involved are warranted. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Effects of Oral Maternal Administration of Caffeine on Reproductive ...

    African Journals Online (AJOL)

    Offspring of GD 8-14 and GD 15-21 dams treated with 3.42 and 5.70 mg/kg body weight of caffeine respectively, showed significantly reduced serum testosterone level. There was a significant decrease in the weight of testes of offspring from dams treated with caffeine during GD 8-14. Histological sections of testes of ...

  15. The Cumulative Neurobehavioral and Physiological Effects of Chronic Caffeine Intake: Individual Differences and Implications for the Use of Caffeinated Energy Products

    Science.gov (United States)

    Spaeth, Andrea M; Goel, Namni; Dinges, David F

    2014-01-01

    The use of caffeine-containing energy products (CCEP) has increased worldwide in recent years and research shows that CCEP can improve cognitive and physical performance. All of the top-selling energy drinks contain caffeine, which is likely to be the primary psychoactive ingredient in CCEP. Presumably, individuals consume CCEP to counteract feelings of ‘low-energy’ in situations causing tiredness, fatigue, and/or reduced alertness. This review discusses the scientific evidence for sleep loss, circadian phase, sleep inertia and the time-on-task effect as causes of ‘low energy’ and summarizes research assessing the efficacy of caffeine to counteract decreased alertness and increased fatigue in such situations. The results of a placebo-controlled experiment on healthy adults undergoing three nights of total sleep deprivation (with or without 2 hour naps every 12 hours) are presented to illustrate the physiological and neurobehavioral effects of sustained low-dose caffeine. Individual differences, including genetic factors, in the response to caffeine and to sleep loss are discussed. We conclude with future directions for research on this important and evolving topic. PMID:25293542

  16. 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.

  17. The Effects of Caffeine Use on Driving Safety Among Truck Drivers Who Are Habitual Caffeine Users.

    Science.gov (United States)

    Heaton, Karen; Griffin, Russell

    2015-08-01

    The purpose of this study was to describe caffeine use among a group of habitual caffeine users, truck drivers, and to explore the associations between caffeine use and critical safety events by age in the naturalistic work setting. A secondary analysis of existing data from the Naturalistic Truck Driving Study was conducted. Analyses focused on the association between sleep and caffeine consumption by duty status, comparisons of sleep and caffeine use by age, and the associations between caffeine use and safety-critical events (SCEs). Findings indicated differences in caffeine use by duty status. However, no difference in sleep time by duty status, or between sleep time and caffeine use was found regardless of when the caffeine was consumed during the 5 hours prior to sleep. Sleep time did not vary significantly by age, although increasing age was associated with decreased caffeine use. Overall, a 6% reduction in the rate of SCEs per eight ounces of caffeinated beverage consumed was found. This study makes a unique scientific contribution because it uses real-time observations of truckers in the naturalistic work setting. It also does not involve caffeine withdrawal but rather an investigation of the effects of the naturalistic consumption of caffeine on sleep and driving performance. Findings suggest that caffeine use among habitual users offers a protective effect for safety-critical driving events. Occupational health nurses may use this information to counsel workers in the use of caffeine to enhance driving safety. © 2015 The Author(s).

  18. Radiosensitivity of grapevines. Empirical modelling of the radiosensitivity of some clones to x-ray irradiation. Pt. 1

    International Nuclear Information System (INIS)

    Koeroesi, F.; Jezierska-Szabo, E.

    1999-01-01

    Empirical and formal (Poisson) models were utilized, applying experimental growth data to characterize the radiosensitivity of six grapevine clones to X-ray irradiation. According to the radiosensitivity constants (k), target numbers (n) and volumes, GR 37 doses and energy deposition, the following radiosensitivity order has been found for various vine brands: Chardonnay clone type < Harslevelue K. 9 < Koevidinka K. 8 < Muscat Ottonel clone type < Irsai Oliver K. 11 < Cabernet Sauvignon E. 153. The model can be expanded to describe the radiosensitivity of other plant species and varieties, and also the efficiency of various radioprotecting agents and conditions. (author)

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

    International Nuclear Information System (INIS)

    Taga, Masataka; Shiraishi, Kazunori; Shimura, Tsutomu; Uematsu, Norio; Kato, Tomohisa; Niwa, Ohtsura; Nishimune, Yoshitake; Aizawa, Shinichi; Oshimura, Mitsuo

    2000-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Taga, Masataka; Shiraishi, Kazunori; Shimura, Tsutomu; Uematsu, Norio; Kato, Tomohisa; Niwa, Ohtsura [Kyoto Univ. (Japan). Radiation Biology Center; Nishimune, Yoshitake; Aizawa, Shinichi; Oshimura, Mitsuo

    2000-09-01

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

  1. 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. © 2014 International Life Sciences Institute.

  2. Faster but not smarter: effects of caffeine and caffeine withdrawal on alertness and performance.

    Science.gov (United States)

    Rogers, Peter J; Heatherley, Susan V; Mullings, Emma L; Smith, Jessica E

    2013-03-01

    Despite 100 years of psychopharmacological research, the extent to which caffeine consumption benefits human functioning remains unclear. To measure the effects of overnight caffeine abstinence and caffeine administration as a function of level of habitual caffeine consumption. Medium-high (n = 212) and non-low (n = 157) caffeine consumers completed self-report measures and computer-based tasks before (starting at 10:30 AM) and after double-blind treatment with either caffeine (100 mg, then 150 mg) or placebo. The first treatment was given at 11:15 AM and the second at 12:45 PM, with post-treatment measures repeated twice between 1:45 PM and 3:30 PM. Caffeine withdrawal was associated with some detrimental effects at 10:30 AM, and more severe effects, including greater sleepiness, lower mental alertness, and poorer performance on simple reaction time, choice reaction time and recognition memory tasks, later in the afternoon. Caffeine improved these measures in medium-high consumers but, apart from decreasing sleepiness, had little effect on them in non-low consumers. The failure of caffeine to increase mental alertness and improve mental performance in non-low consumers was related to a substantial caffeine-induced increase in anxiety/jitteriness that offset the benefit of decreased sleepiness. Caffeine enhanced physical performance (faster tapping speed and faster simple and choice reaction times) in both medium-high and non-low consumers. While caffeine benefits motor performance and tolerance develops to its tendency to increase anxiety/jitteriness, tolerance to its effects on sleepiness means that frequent consumption fails to enhance mental alertness and mental performance.

  3. The inherited basis of human radiosensitivity

    International Nuclear Information System (INIS)

    Gatti, R.A.

    2001-01-01

    Certain individuals cannot tolerate 'conventional' doses of radiation therapy. This is known to be true of patients with ataxia-telangiectasia and ligase IV deficiency. Although in vitro testing may not correlate completely with clinical radiosensitivity, fibroblasts and lymphoblasts from patients with both of these disorders have been clearly shown to be radiosensitive. Using a colony survival assay (CSA) to test lymphoblastoid cells after irradiation with 1 Gy, a variety of other genetic disorders have been identified as strong candidates for clinical radiosensitivity, such as Nijmegen breakage syndrome, Mre11 deficiency, and Fanconi's anemia. These data are presented and considered as a starting-point for the inherited basis of human radiosensitivity

  4. Dispelling the myth that habitual caffeine consumption influences the performance response to acute caffeine supplementation.

    Science.gov (United States)

    Gonçalves, Lívia de Souza; Painelli, Vitor de Salles; Yamaguchi, Guilherme; Oliveira, Luana Farias de; Saunders, Bryan; da Silva, Rafael Pires; Maciel, Erika; Artioli, Guilherme Giannini; Roschel, Hamilton; Gualano, Bruno

    2017-07-01

    This study investigates the influence of habitual caffeine intake on aerobic exercise-performance responses to acute caffeine supplementation. A double-blind, crossover, counterbalanced study was performed. Forty male endurance-trained cyclists were allocated into tertiles, according to their daily caffeine intake: low (58 ± 29 mg/d), moderate (143 ± 25 mg/d), and high (351 ± 139 mg/d) consumers. Participants completed three trials in which they performed simulated cycling time trials (TTs) in the fastest time possible following ingestion of the following: caffeine (CAF: 6 mg/kg body mass), placebo (PLA), and no supplement (CON). A mixed-model analysis revealed that TT performance was significantly improved in CAF compared with PLA and CON (29.92 ± 2.18 vs. 30.81 ± 2.67 and 31.14 ± 2.71 min, respectively; P = 0.0002). Analysis of covariance revealed no influence of habitual caffeine intake as a covariate on exercise performance ( P = 0.47). TT performance was not significantly different among tertiles ( P = 0.75). No correlation was observed between habitual caffeine intake and absolute changes (CAF - CON) in TT performance with caffeine ( P = 0.524). Individual analysis showed that eight, seven, and five individuals improved above the variation of the test in CAF in the low, moderate, and high tertiles, respectively. A Fisher's exact test did not show any significant differences in the number of individuals who improved in CAF among the tertiles ( P > 0.05). Blood lactate and ratings of perceived exertion were not different between trials and tertiles ( P > 0.05). Performance effects of acute caffeine supplementation during an ~30-min cycling TT performance were not influenced by the level of habitual caffeine consumption. NEW & NOTEWORTHY There has been a long-standing paradigm that habitual caffeine intake may influence the ergogenicity of caffeine supplementation. Low, moderate, and high caffeine consumers showed similar absolute and

  5. Neoplasms radiosensitivity: how to increase the efficiency of radiotherapy

    International Nuclear Information System (INIS)

    Calais, G.

    1991-01-01

    The hypoxia in the neoplasms is a radioresistance factor. This article is about the methods able to reduce the hypoxia in tumors: use of hyperbaric oxygen, radiosensitizers (as metronidazole), hyperthermia and modification of oxygen release in the tissues in modifying the blood flow and in reducing the hemoglobin affinity for oxygen [fr

  6. Caffeine, extraversion and working memory.

    Science.gov (United States)

    Smith, Andrew P

    2013-01-01

    Research has shown that extraverts performing a working memory task benefit more from caffeine than do introverts. The present study aimed to replicate this and extend our knowledge by using a lower dose of caffeine (65 mg) and a range of tasks related to different components of working memory. In addition, tasks assessing psychomotor speed and the encoding of new information were included to determine whether caffeine-extraversion interactions were restricted to working memory tasks. A double-blind design was used, with 128 participants being randomly assigned to caffeinated or de-caffeinated coffee conditions. The results showed that caffeine interacted with extraversion in the predicted direction for serial recall and running memory tasks. Caffeine improved simple reaction time and the speed of encoding of new information, effects which were not modified by extraversion. These results suggest possible biological mechanisms underlying effects of caffeine on cognitive performance.

  7. Caffeine exposure alters cardiac gene expression in embryonic cardiomyocytes

    Science.gov (United States)

    Fang, Xiefan; Mei, Wenbin; Barbazuk, William B.; Rivkees, Scott A.

    2014-01-01

    Previous studies demonstrated that in utero caffeine treatment at embryonic day (E) 8.5 alters DNA methylation patterns, gene expression, and cardiac function in adult mice. To provide insight into the mechanisms, we examined cardiac gene and microRNA (miRNA) expression in cardiomyocytes shortly after exposure to physiologically relevant doses of caffeine. In HL-1 and primary embryonic cardiomyocytes, caffeine treatment for 48 h significantly altered the expression of cardiac structural genes (Myh6, Myh7, Myh7b, Tnni3), hormonal genes (Anp and BnP), cardiac transcription factors (Gata4, Mef2c, Mef2d, Nfatc1), and microRNAs (miRNAs; miR208a, miR208b, miR499). In addition, expressions of these genes were significantly altered in embryonic hearts exposed to in utero caffeine. For in utero experiments, pregnant CD-1 dams were treated with 20–60 mg/kg of caffeine, which resulted in maternal circulation levels of 37.3–65.3 μM 2 h after treatment. RNA sequencing was performed on embryonic ventricles treated with vehicle or 20 mg/kg of caffeine daily from E6.5-9.5. Differential expression (DE) analysis revealed that 124 genes and 849 transcripts were significantly altered, and differential exon usage (DEU) analysis identified 597 exons that were changed in response to prenatal caffeine exposure. Among the DE genes identified by RNA sequencing were several cardiac structural genes and genes that control DNA methylation and histone modification. Pathway analysis revealed that pathways related to cardiovascular development and diseases were significantly affected by caffeine. In addition, global cardiac DNA methylation was reduced in caffeine-treated cardiomyocytes. Collectively, these data demonstrate that caffeine exposure alters gene expression and DNA methylation in embryonic cardiomyocytes. PMID:25354728

  8. Caffeine, fatigue, and cognition

    NARCIS (Netherlands)

    Lorist, M.M.; 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

  9. The inherited basis of human radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Gatti, R.A. [Univ. of California, School of Medicine, Los Angeles, CA (United States). Experimental Pathology

    2001-11-01

    Certain individuals cannot tolerate 'conventional' doses of radiation therapy. This is known to be true of patients with ataxia-telangiectasia and ligase IV deficiency. Although in vitro testing may not correlate completely with clinical radiosensitivity, fibroblasts and lymphoblasts from patients with both of these disorders have been clearly shown to be radiosensitive. Using a colony survival assay (CSA) to test lymphoblastoid cells after irradiation with 1 Gy, a variety of other genetic disorders have been identified as strong candidates for clinical radiosensitivity, such as Nijmegen breakage syndrome, Mre11 deficiency, and Fanconi's anemia. These data are presented and considered as a starting-point for the inherited basis of human radiosensitivity.

  10. A Randomized, Two-Way Crossover Study to Evaluate the Pharmacokinetics of Caffeine Delivered Using Caffeinated Chewing Gum Versus a Marketed Caffeinated Beverage in Healthy Adult Volunteers.

    Science.gov (United States)

    Sadek, Paul; Pan, Xiao; Shepherd, Phil; Malandain, Elise; Carney, John; Coleman, Hugh

    2017-12-01

    Background: This study was conducted to compare the pharmacokinetics of caffeine delivered using caffeinated chewing gum to that delivered using a marketed caffeinated beverage (instant coffee) in 16 healthy adult volunteers. Materials and Methods: This was a controlled open-label, randomized, two-period crossover study. Caffeinated chewing gum and a serving of instant coffee, each containing ∼50 mg caffeine, were administered with blood samples collected before and up to 24 hours after administration starts. Plasma caffeine levels were analyzed using validated liquid chromatography coupled with tandem mass spectrometry methodology. Results: There were no statistical differences between the two caffeine products in t max ( p  = 0.3308) and k a ( p  = 0.3894). Although formulated at ∼50 mg caffeine each, mean dose released from chewing gum was ∼18% less than beverage. Dose-normalized area under the concentration-time curve (AUC) 0-t , AUC 0-∞ , and C max was similar between products. Although the criteria were not set a priori and the study was not powered for concluding bioequivalence, the 90% confidence intervals fell within the bioequivalence limit of 80% to 125%. Conclusions: Existing scientific literature on caffeine, based mostly on data from caffeinated beverages, can be leveraged to support the safety of caffeine delivered by chewing gum and current maximum safe caffeine dose advice should be applicable irrespective of delivery method.

  11. Beneficial effects of caffeine in a transgenic model of Alzheimer's disease-like tau pathology.

    Science.gov (United States)

    Laurent, Cyril; Eddarkaoui, Sabiha; Derisbourg, Maxime; Leboucher, Antoine; Demeyer, Dominique; Carrier, Sébastien; Schneider, Marion; Hamdane, Malika; Müller, Christa E; Buée, Luc; Blum, David

    2014-09-01

    Tau pathology found in Alzheimer's disease (AD) is crucial in cognitive decline. Epidemiologic evidences support that habitual caffeine intake prevents memory decline during aging and reduces the risk to develop Alzheimer's disease. So far, experimental studies addressed the impact of caffeine in models mimicking the amyloid pathology of AD. However, in vivo effects of caffeine in a model of AD-like tauopathy remain unknown. Here, we evaluated effects of chronic caffeine intake (0.3 g/L through drinking water), given at an early pathologic stage, in the THY-Tau22 transgenic mouse model of progressive AD-like tau pathology. We found that chronic caffeine intake prevents from the development of spatial memory deficits in tau mice. Improved memory was associated with reduced hippocampal tau phosphorylation and proteolytic fragments. Moreover, caffeine treatment mitigated several proinflammatory and oxidative stress markers found upregulated in the hippocampus of THY-Tau22 animals. Together, our data support that moderate caffeine intake is beneficial in a model of AD-like tau pathology, paving the way for future clinical evaluation in AD patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Modeling caffeine concentrations with the Stanford Caffeine Questionnaire: preliminary evidence for an interaction of chronotype with the effects of caffeine on sleep.

    Science.gov (United States)

    Nova, Philip; Hernandez, Beatriz; Ptolemy, Adam S; Zeitzer, Jamie M

    2012-04-01

    To examine the validity of a novel caffeine intake questionnaire and to examine the effects of caffeine on sleep in college students. One-week, ad libitum behavior of 50 university students (28 female, 22 male; aged 20.9 ± 1.78 years) was examined with sleep logs, wrist actigraphy, and a novel daily questionnaire assessing caffeine intake at different times of day. Saliva samples were collected for caffeine assessment (questionnaire validation) and DNA extraction, and for analysis of a single nucleotide polymorphism in the adenosine receptor 2A (ADORA2A) gene. The caffeine questionnaire was able to accurately predict salivary concentrations of caffeine (R(2) = 0.41, Psleep were correlated with wake after sleep onset (WASO) most strongly in morning-type individuals (R(2) = 0.49; Psleep and genotype and chronotype. Published by Elsevier B.V.

  13. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Cognitive and psychomotor performance, mood, and pressor effects of caffeine after 4, 6 and 8 h caffeine abstinence.

    Science.gov (United States)

    Heatherley, Susan V; Hayward, Robert C; Seers, Helen E; Rogers, Peter J

    2005-04-01

    Many studies have found that caffeine consumed after overnight caffeine abstinence improves cognitive performance and mood. Much less is known, however, about the effects of caffeine after shorter periods of caffeine abstinence. The aim of this study was to measure the effects on psychomotor and cognitive performance, mood, hand steadiness, blood pressure and heart rate of caffeine administration after periods of 4, 6, and 8 h of caffeine abstinence. Participants (n = 49, 27 female) were moderate to moderate-high caffeine consumers (mean daily intake 370 mg/day). Following overnight caffeine abstinence, a 'pre-dose' of caffeine (1.2 mg/kg) was administered at 9 A.M, 11 A.M or 1 P.M. The participants started a baseline battery of measurements at 4 P.M.: before receiving caffeine (1.2 mg/kg) or placebo at 5 P.M.: They then performed the battery of tests again, starting at 5:30 P.M. This was a double-blind, placebo-controlled, randomised study. Performance and mood measurements confirmed a psychostimulant action of caffeine (versus placebo), but only after 8 h of caffeine abstinence. Caffeine also increased blood pressure after 8-h abstinence, whereas hand steadiness was decreased and perception of task demand was increased by caffeine after 4 h, but not after 6- and 8-h abstinence. A second cup-of-coffee equivalent dose of caffeine only reliably affected cognitive performance and mood after an 8-h interval between doses, but not after shorter intervals (when caffeine had some adverse effects). These results show that, apart from caffeine consumption soon after waking, the daily pattern of caffeine intake of many typical caffeine consumers is not well explained by the short-term psychostimulant effects of caffeine.

  15. Effects of low doses of caffeine on cognitive performance, mood and thirst in low and higher caffeine consumers.

    Science.gov (United States)

    Smit, H J; Rogers, P J

    2000-10-01

    Caffeine is present in many widely consumed drinks and some foods. In the fairly extensive literature on the psychostimulant effects of caffeine, there are few dose-response studies and even fewer studies of the effects of doses of caffeine lower than 50 mg (the range of the amounts of caffeine contained in, for example, a typical serving of tea or cola). This study measured the effects of 0, 12.5, 25, 50 and 100 mg caffeine on cognitive performance, mood and thirst in adults with low and moderate to high habitual caffeine intakes. This was a double-blind, within-subjects study. Following overnight caffeine abstinence, participants (n=23) completed a test battery once before and three times after placebo or caffeine administration. The test battery consisted of two performance tests, a long duration simple reaction time task and a rapid visual information processing task, and a mood questionnaire (including also an item on thirst). Effects on performance and mood confirmed a psychostimulant action of caffeine. All doses of caffeine significantly affected cognitive performance, and the dose-response relationships for these effects were rather flat. The effects on performance were more marked in individuals with a higher level of habitual caffeine intake, whereas caffeine increased thirst only in low caffeine consumers. After overnight caffeine abstinence, caffeine can significantly affect cognitive performance, mood and thirst at doses within and even lower than the range of amounts of caffeine contained in a single serving of popular caffeine-containing drinks. Regular caffeine consumers appear to show substantial tolerance to the thirst-increasing but not to the performance and mood effects of caffeine.

  16. Chromosomal fragility syndrome and family history of radiosensitivity as indicators for radiotherapy dose modification

    International Nuclear Information System (INIS)

    Alsbeih, Ghazi; Story, Michael D.; Maor, Moshe H.; Geara, Fady B.; Brock, William A.

    2003-01-01

    Beside a few known radiosensitive syndromes, a patient's reaction to radiotherapy is difficult to predict. In this report we describe the management of a pediatric cancer patient presented with a family history of radiosensitivity and cancer proneness. Laboratory investigations revealed a chromosomal fragility syndrome and an increased cellular radiosensitivity in vitro. AT gene sequencing revealed no mutations. The patient was treated with reduced radiation doses to avoid the presumed increased risks of toxicity to normal tissues. The patient tolerated well the treatment with no significant acute or late radiation sequelae. Five years later, the patient remains both disease and complications free. While an accurate laboratory test for radiosensitivity is still lacking, assessments of chromosomal fragility, cell survival and clinical medicine will continue to be useful for a small number of patients

  17. Caffeine Confusion

    Science.gov (United States)

    ... 20 mg* Milk chocolate 1 ounce 6 mg* Cocoa beverage 5 ounces 4 mg* Chocolate milk beverage 8 ounces 5 mg* Cold relief medication 1 tablet 30 mg* *This is an average amount of caffeine. That means some of these products may contain a little more caffeine; some may ...

  18. Caffeine in the milk prevents respiratory disorders caused by in utero caffeine exposure in rats.

    Science.gov (United States)

    Bodineau, Laurence; Saadani-Makki, Fadoua; Jullien, Hugues; Frugière, Alain

    2006-01-25

    Consequences of postnatal caffeine exposure by the milk on ponto-medullary respiratory disturbances observed following an in utero caffeine exposure were analysed. Ponto-medullary-spinal cord preparations from newborn rats exposed to caffeine during gestation but not after the birth display an increase in respiratory frequency and an exaggeration of the hypoxic respiratory depression compared to not treated preparations. These data suggest that tachypneic and apneic episodes encountered in human newborns whose mother consumed caffeine during pregnancy are due in large part to central effect of caffeine at the ponto-medullary level. Both baseline respiratory frequency increase and emphasis of hypoxic respiratory depression are not encountered if rat dams consumed caffeine during nursing. Our hypothesis is that newborn rats exposed to caffeine during gestation but not after the birth would be in withdrawal situation whereas, when caffeine is present in drinking fluid of lactating dams, it goes down the milk and is able to prevent ponto-medullary respiratory disturbances.

  19. Association of caffeine intake and histological features of chronic hepatitis C.

    Science.gov (United States)

    Costentin, Charlotte E; Roudot-Thoraval, Françoise; Zafrani, Elie-Serge; Medkour, Fatiha; Pawlotsky, Jean-Michel; Mallat, Ariane; Hézode, Christophe

    2011-06-01

    The severity of chronic hepatitis C (CHC) is modulated by host and environmental factors. Several reports suggest that caffeine intake exerts hepatoprotective effects in patients with chronic liver disease. The aim of this study was to evaluate the impact of caffeine consumption on activity grade and fibrosis stage in patients with CHC. A total of 238 treatment-naïve patients with histologically-proven CHC were included in the study. Demographic, epidemiological, environmental, virological, and metabolic data were collected, including daily consumption of alcohol, cannabis, tobacco, and caffeine during the six months preceding liver biopsy. Daily caffeine consumption was estimated as the sum of mean intakes of caffeinated coffee, tea, and caffeine-containing sodas. Histological activity grade and fibrosis stage were scored according to Metavir. Patients (154 men, 84 women, mean age: 45±11 years) were categorized according to caffeine consumption quartiles: group 1 (678 mg/day, n=60). There was a significant inverse relationship between activity grade and daily caffeine consumption: activity grade>A2 was present in 78%, 61%, 52%, and 48% of patients in group 1, 2, 3, and 4, respectively (pA2 (OR=0.32 (0.12-0.85). Caffeine intake showed no relation with fibrosis stage. Caffeine consumption greater than 408 mg/day (3 cups or more) is associated with reduced histological activity in patients with CHC. These findings support potential hepatoprotective properties of caffeine in chronic liver diseases. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  20. Blood biochemistry, thyroid hormones, and performance in broilers with ascites caused by caffeine.

    Science.gov (United States)

    Kamely, Mohammad; Karimi Torshizi, Mohammad Amir; Rahimi, Shaban

    2016-11-01

    Previously, we demonstrated that caffeine, a natural alkaloid, stimulates increased incidences of pulmonary hypertension syndrome (ascites) in broilers. The present study was designed to evaluate the ergogenic effects of caffeine on broiler performance and blood parameters. One-hundred-and-ninety-two Ross 308 male broiler chicks were randomly assigned at one d of age to 16 pens with 4 treatment groups. On d 3, the drinking water was supplemented with caffeine at levels of zero, 12.5, 25, and 50 mg/kg BW/day. Caffeine supplementation linearly improved (P caffeine (P > 0.05). On d 28, increasing caffeine supplementation caused linear reductions in plasma albumin, total protein, globulin, and triglyceride concentrations, and caffeine supplementation increased plasma uric acid concentrations (P caffeine did not consistently affect plasma albumin, globulin, triglyceride, total protein, uric acid, or urea concentrations (P > 0.05), whereas plasma glucose concentrations increased linearly with increasing caffeine levels (P caffeine (P > 0.05), but plasma T 3 concentrations were reduced by caffeine supplementation on d 28 and 42 (P caffeine supplementation on d 42. Skin temperature was not influenced by caffeine supplementation (P > 0.05). There was a negative correlation between thyroid hormone concentrations and BW on d 42 (P caffeine supplementation at the levels of 12.5 to 25 mg/kg BW/day increased BWG, decreased FCR and T 3 , and significantly altered blood biochemistry parameters. © 2016 Poultry Science Association Inc.

  1. Targeting Mcl-1 for Radiosensitization of Pancreatic Cancers

    Directory of Open Access Journals (Sweden)

    Dongping Wei

    2015-02-01

    Full Text Available In order to identify targets whose inhibition may enhance the efficacy of chemoradiation in pancreatic cancer, we previously conducted an RNAi library screen of 8,800 genes. We identified Mcl-1 (myeloid cell leukemia-1, an anti-apoptotic member of the Bcl-2 family, as a target for sensitizing pancreatic cancer cells to chemoradiation. In the present study we investigated Mcl-1 inhibition by either genetic or pharmacological approaches as a radiosensitizing strategy in pancreatic cancer cells. Mcl-1 depletion by siRNA produced significant radiosensitization in BxPC-3 and Panc-1 cells in association with Caspase-3 activation and PARP cleavage, but only minimal radiosensitization in MiaPaCa-2 cells. We next tested the ability of the recently identified, selective, small molecule inhibitor of Mcl-1, UMI77, to radiosensitize in pancreatic cancer cells. UMI77 caused dissociation of Mcl-1 from the pro-apoptotic protein Bak and produced significant radiosensitization in BxPC-3 and Panc-1 cells, but minimal radiosensitization in MiaPaCa-2 cells. Radiosensitization by UMI77 was associated with Caspase-3 activation and PARP cleavage. Importantly, UMI77 did not radiosensitize normal small intestinal cells. In contrast, ABT-737, an established inhibitor of Bcl-2, Bcl-XL, and Bcl-w, failed to radiosensitize pancreatic cancer cells suggesting the unique importance of Mcl-1 relative to other Bcl-2 family members to radiation survival in pancreatic cancer cells. Taken together, these results validate Mcl-1 as a target for radiosensitization of pancreatic cancer cells and demonstrate the ability of small molecules which bind the canonical BH3 groove of Mcl-1, causing displacement of Mcl-1 from Bak, to selectively radiosensitize pancreatic cancer cells.

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

    International Nuclear Information System (INIS)

    Rowley, R.; Zorch, M.; Leeper, D.B.

    1984-01-01

    In the presence of 5 mM caffeine, irradiated (1.5 Gy) S and G 2 cells progressed to mitosis in register and without arrest in G 2 . Caffeine (5 mM) markedly reduced mitotic delay even after radiation doses up to 20 Gy. When caffeine was removed from irradiated (1.5 Gy) and caffeine-treated cells, a period of G 2 arrest followed, similar in length to that produced by radiation alone. The arrest expressed was independent of the duration of the caffeine treatment for exposures up to 3 hr. The similarity of the response to the cited effects of caffeine on S-phase delay suggests a common basis for delay induction in S and G 2 phases

  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.

  4. Evaluating Dependence Criteria for Caffeine.

    Science.gov (United States)

    Striley, Catherine L W; Griffiths, Roland R; Cottler, Linda B

    2011-12-01

    Background: Although caffeine is the most widely used mood-altering drug in the world, few studies have operationalized and characterized Diagnostic and Statistical Manual IV (DSM-IV) substance dependence criteria applied to caffeine. Methods: As a part of a nosological study of substance use disorders funded by the National Institute on Drug Abuse, we assessed caffeine use and dependence symptoms among high school and college students, drug treatment patients, and pain clinic patients who reported caffeine use in the last 7 days and also reported use of alcohol, nicotine, or illicit drugs within the past year ( n =167). Results: Thirty-five percent met the criteria for dependence when all seven of the adopted DSM dependence criteria were used. Rates of endorsement of several of the most applicable diagnostic criteria were as follows: 26% withdrawal, 23% desire to cut down or control use, and 44% continued use despite harm. In addition, 34% endorsed craving, 26% said they needed caffeine to function, and 10% indicated that they talked to a physician or counselor about problems experienced with caffeine. There was a trend towards increased caffeine dependence among those dependent on nicotine or alcohol. Within a subgroup that had used caffeine, alcohol, and nicotine in the past year, 28% fulfilled criteria for caffeine dependence compared to 50% for alcohol and 80% for nicotine. Conclusion: The present study adds to a growing literature suggesting the reliability, validity, and clinical utility of the caffeine dependence diagnosis. Recognition of caffeine dependence in the DSM-V may be clinically useful.

  5. Comparative radiosensitivity in the class insecta

    International Nuclear Information System (INIS)

    Willard, W.K.; Cherry, D.S.

    1975-01-01

    A 'radiosensitivity index' (LT 50 /mean longevity) was correlated with the mean longevity and dry weight of 37 insect species (both sexes of 12 species) representing eight orders. Curvilinear regression analysis relating radiosensitivity to mean longevity and mean dry weight indicated that 46.3% of the observed variation could be attributed to longevity and 32.6% to the dry weight of the species. In general, large long-lived adults were more radiosensitive than small short-lived adults. Correlation of the phylogeny of insect orders and order groupings with the radio-sensitivity index was found to be poor. However, when the index was related to longevity, there was a tendency for species comprising the major orders investigated to occur in groups along the predicted curve. (author)

  6. Administration of Caffeine in Alternate Forms.

    Science.gov (United States)

    Wickham, Kate A; Spriet, Lawrence L

    2018-03-01

    There has been recent interest in the ergogenic effects of caffeine delivered in low doses (~ 200 mg or ~ 3 mg/kg body mass) and administered in forms other than capsules, coffee and sports drinks, including chewing gum, bars, gels, mouth rinses, energy drinks and aerosols. Caffeinated chewing gum is absorbed quicker through the buccal mucosa compared with capsule delivery and absorption in the gut, although total caffeine absorption over time is not different. Rapid absorption may be important in many sporting situations. Caffeinated chewing gum improved endurance cycling performance, and there is limited evidence that repeated sprint cycling and power production may also be improved. Mouth rinsing with caffeine may stimulate nerves with direct links to the brain, in addition to caffeine absorption in the mouth. However, caffeine mouth rinsing has not been shown to have significant effects on cognitive performance. Delivering caffeine with mouth rinsing improved short-duration, high-intensity, repeated sprinting in normal and depleted glycogen states, while the majority of the literature indicates no ergogenic effect on aerobic exercise performance, and resistance exercise has not been adequately studied. Studies with caffeinated energy drinks have generally not examined the individual effects of caffeine on performance, making conclusions about this form of caffeine delivery impossible. Caffeinated aerosol mouth and nasal sprays may stimulate nerves with direct brain connections and enter the blood via mucosal and pulmonary absorption, although little support exists for caffeine delivered in this manner. Overall, more research is needed examining alternate forms of caffeine delivery including direct measures of brain activation and entry of caffeine into the blood, as well as more studies examining trained athletes and female subjects.

  7. 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.

  8. Sequential updating of a new dynamic pharmacokinetic model for caffeine in premature neonates.

    Science.gov (United States)

    Micallef, Sandrine; Amzal, Billy; Bach, Véronique; Chardon, Karen; Tourneux, Pierre; Bois, Frédéric Y

    2007-01-01

    Caffeine treatment is widely used in nursing care to reduce the risk of apnoea in premature neonates. To check the therapeutic efficacy of the treatment against apnoea, caffeine concentration in blood is an important indicator. The present study was aimed at building a pharmacokinetic model as a basis for a medical decision support tool. In the proposed model, time dependence of physiological parameters is introduced to describe rapid growth of neonates. To take into account the large variability in the population, the pharmacokinetic model is embedded in a population structure. The whole model is inferred within a Bayesian framework. To update caffeine concentration predictions as data of an incoming patient are collected, we propose a fast method that can be used in a medical context. This involves the sequential updating of model parameters (at individual and population levels) via a stochastic particle algorithm. Our model provides better predictions than the ones obtained with models previously published. We show, through an example, that sequential updating improves predictions of caffeine concentration in blood (reduce bias and length of credibility intervals). The update of the pharmacokinetic model using body mass and caffeine concentration data is studied. It shows how informative caffeine concentration data are in contrast to body mass data. This study provides the methodological basis to predict caffeine concentration in blood, after a given treatment if data are collected on the treated neonate.

  9. Caffeine in an Urbanized Estuary: Past and Present Influence ...

    Science.gov (United States)

    Caffeine has been identified by previous research as a potential tracer of sanitary wastewater. To further assess the utility of caffeine as a tracer of wastewater sources, samples from 25 sites throughout Boston Harbor were collected and analyzed for caffeine by LC-MS/MS. Caffeine concentrations in Boston Harbor ranged from 15 ng/L in the outer harbor to a high of 185 ng/L in the inner harbor; mean concentrations and median concentrations were 51 ng/L were 33 ng/L respectively. These data were visualized by a simple inverse distance weighting model to improve the understanding of transport and fate dynamics of wastewater derived contaminants. Elevated concentrations of caffeine in the inner harbor during the sampling period were determined to be the result of a combined sewage overflow (CSO) event as well as illicit discharge of sanitary sewage into municipal storm drains. A comparison of contemporary results to data from 1998 to 1999 shows significant reductions in caffeine levels within the harbor. For instance, concentrations were reduced by a factor of approximately 20 at the site of the former wastewater effluent discharge outfall in Boston Harbor. Lower present-day concentrations throughout the harbor were attributed to the relocation of effluent discharge from within the harbor to Massachusetts Bay, and a reduction in the number and discharge volume of CSOs. Spatial distributions of caffeine identified CSOs as the major contemporary source of con

  10. Radiosensitivity of amphibia

    Energy Technology Data Exchange (ETDEWEB)

    Muramatsu, S [National Inst. of Radiological Sciences, Chiba (Japan)

    1975-04-01

    Radiosensitivity (semi-lethal dose) and the damages of radiation in the amphibia were studied by /sup 3/H-TdR from the standpoint of cellular kinetics. The cell mitosis cycle of the amphibia required a long time. The functional cell regeneration and the physiological function of the cell were slower than in mice. The reason for the low radiosensitivity of the amphibia was discussed relative to the environmental factor of temperature. Because the amphibia change body temperature according to environmental temperature, the danger of radiation damage, the actual lethal dose and the period of survival were influenced by the environmental temperature. Acute radiation danger to amphibia was essentially the same as the danger to mammalia, both young and old. LD/sub 50/ irradiation effects varied among the species. The cell regeneration, turn over, and the mitosis in the amphibia, were affected by environmental temperature, however, the courses proceeded slower than those of the mammalia. Therefore, the question remains, whether the comparison of the radiosensitivities of amphibia with other classes of animal by LDsub(50/30) irradiation was appropriate.

  11. The radio-sensitizing effects and mechanisms of artemisinin and its derivates

    Energy Technology Data Exchange (ETDEWEB)

    Jing, Zeng; Jianping, Cao; Saijun, Fan [School of Radiation Medicine and Public Health, Suzhou Univ., Suzhou (China)

    2008-10-15

    It has been proved that the antimalarial agent, Artemisinin and its derivates (such as artemether, arteether, artesunate, dihydroartemisinine, etc) boast powerful antitumor effects. Recently, researches have found that Artemisinin and its derivates can also enhance the radio-sensitivity of tumors through regulating cell cycle, creating cytotoxic effects induced by ROS, suppressing GSH activity and inhibiting the reparation of DNA damage etc. Moreover, they can reduce cell survival in a dose-dependent manner. This paper is paying more attention on the radio-sensitizing effects, characteristics and mechanisms of artemisinin and its derivates. (authors)

  12. The radio-sensitizing effects and mechanisms of artemisinin and its derivates

    International Nuclear Information System (INIS)

    Zeng Jing; Cao Jianping; Fan Saijun

    2008-01-01

    It has been proved that the antimalarial agent, Artemisinin and its derivates (such as artemether, arteether, artesunate, dihydroartemisinine, etc) boast powerful antitumor effects. Recently, researches have found that Artemisinin and its derivates can also enhance the radio-sensitivity of tumors through regulating cell cycle, creating cytotoxic effects induced by ROS, suppressing GSH activity and inhibiting the reparation of DNA damage etc. Moreover, they can reduce cell survival in a dose-dependent manner. This paper is paying more attention on the radio-sensitizing effects, characteristics and mechanisms of artemisinin and its derivates. (authors)

  13. Caffeine in Pregnancy

    Science.gov (United States)

    ... Global Map Premature Birth Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal ... Nutrition, weight & fitness > Caffeine in pregnancy Caffeine in pregnancy E-mail to a friend Please fill in ...

  14. Caffeine Use and Extroversion.

    Science.gov (United States)

    Landrum, R. Eric; Meliska, Charles J.

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

  15. Caffeine: sleep and daytime sleepiness.

    Science.gov (United States)

    Roehrs, Timothy; Roth, Thomas

    2008-04-01

    Caffeine is one of the most widely consumed psychoactive substances and it has profound effects on sleep and wake function. Laboratory studies have documented its sleep-disruptive effects. It clearly enhances alertness and performance in studies with explicit sleep deprivation, restriction, or circadian sleep schedule reversals. But, under conditions of habitual sleep the evidence indicates that caffeine, rather then enhancing performance, is merely restoring performance degraded by sleepiness. The sleepiness and degraded function may be due to basal sleep insufficiency, circadian sleep schedule reversals, rebound sleepiness, and/or a withdrawal syndrome after the acute, over-night, caffeine discontinuation typical of most studies. Studies have shown that caffeine dependence develops at relatively low daily doses and after short periods of regular daily use. Large sample and population-based studies indicate that regular daily dietary caffeine intake is associated with disturbed sleep and associated daytime sleepiness. Further, children and adolescents, while reporting lower daily, weight-corrected caffeine intake, similarly experience sleep disturbance and daytime sleepiness associated with their caffeine use. The risks to sleep and alertness of regular caffeine use are greatly underestimated by both the general population and physicians.

  16. The Janus face of caffeine.

    Science.gov (United States)

    Porciúncula, Lisiane O; Sallaberry, Cássia; Mioranzza, Sabrina; Botton, Paulo Henrique S; Rosemberg, Denis B

    2013-11-01

    Caffeine is certainly the psychostimulant substance most consumed worldwide. Over the past years, chronic consumption of caffeine has been associated with prevention of cognitive decline associated to aging and mnemonic deficits of brain disorders. While its preventive effects have been reported extensively, the cognitive enhancer properties of caffeine are relatively under debate. Surprisingly, there are scarce detailed ontogenetic studies focusing on neurochemical parameters related to the effects of caffeine during prenatal and earlier postnatal periods. Furthermore, despite the large number of epidemiological studies, it remains unclear how safe is caffeine consumption during pregnancy and brain development. Thus, the purpose of this article is to review what is currently known about the actions of caffeine intake on neurobehavioral and adenosinergic system during brain development. We also reviewed other neurochemical systems affected by caffeine, but not only during brain development. Besides, some recent epidemiological studies were also outlined with the control of "pregnancy signal" as confounding variable. The idea is to tease out how studies on the impact of caffeine consumption during brain development deserve more attention and further investigation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Caffeine levels in beverages from Argentina's market: application to caffeine dietary intake assessment.

    Science.gov (United States)

    Olmos, V; Bardoni, N; Ridolfi, A S; Villaamil Lepori, E C

    2009-03-01

    The caffeine content of different beverages from Argentina's market was measured. Several brands of coffees, teas, mates, chocolate milks, soft and energy drinks were analysed by high-performance liquid chromatography (HPLC) with ultraviolet detection. The highest concentration level was found in short coffee (1.38 mg ml(-1)) and the highest amount per serving was found in instant coffee (95 mg per serving). A consumption study was also carried out among 471 people from 2 to 93 years of age to evaluate caffeine total dietary intake by age and to identify the sources of caffeine intake. The mean caffeine intake among adults was 288 mg day(-1) and mate was the main contributor to that intake. The mean caffeine intake among children of 10 years of age and under was 35 mg day(-1) and soft drinks were the major contributors to that intake. Children between 11 and 15 years old and teenagers (between 16 and 20 years) had caffeine mean intakes of 120 and 240 mg day(-1), respectively, and mate was the major contributor to those intakes. Drinking mate is a deep-rooted habit among Argentine people and it might be the reason for their elevated caffeine mean daily intake.

  18. High Doses of Caffeine during the Peripubertal Period in the Rat Impair the Growth and Function of the Testis

    Directory of Open Access Journals (Sweden)

    Minji Park

    2015-01-01

    Full Text Available Prenatal caffeine exposure adversely affects the development of the reproductive organs of male rat offspring. Thus, it is conceivable that peripubertal caffeine exposure would also influence physiologic gonadal changes and function during this critical period for sexual maturation. This study investigated the impact of high doses of caffeine on the testes of prepubertal male rats. A total of 45 immature male rats were divided randomly into three groups: a control group and 2 groups fed 120 and 180 mg/kg/day of caffeine, respectively, via the stomach for 4 weeks. Caffeine caused a significant decrease in body weight gain, accompanied by proportional decreases in lean body mass and body fat. The caffeine-fed animals had smaller and lighter testes than those of the control that were accompanied by negative influences on the histologic parameters of the testes. In addition, stimulated-testosterone ex vivo production was reduced in Leydig cells retrieved from the caffeine-fed animals. Our results demonstrate that peripubertal caffeine consumption can interfere with the maturation and function of the testis, possibly by interrupting endogenous testosterone secretion and reducing the sensitivity of Leydig cells to gonadotrophic stimulation. In addition, we confirmed that pubertal administration of caffeine reduced testis growth and altered testis histomorphology.

  19. Clinical importance of caffeine dependence and abuse.

    Science.gov (United States)

    Ogawa, Naoshi; Ueki, Hirofumi

    2007-06-01

    Caffeine is the most widely consumed psychoactive substance and is a legal stimulant that is readily available to children. Caffeine has occasionally been considered a drug of abuse and the potential for dependence on caffeine has been debated. Presently, due to a paucity of clinical evidence on caffeine dependence or abuse, no such diagnosis is included in the Diagnostic and Statistical Manual of Mental Disorder-fourth edition. The authors present two cases of abuse or dependence on the caffeine contained in 'eutrophic' (energy/nutritional) beverages or caffeine preparations, followed by a review of clinical studies demonstrating evidence that some people can manifest a clinical syndrome of caffeine dependence or abuse. The cases suggest that caffeine can produce a clinical dependence syndrome similar to those produced by other psychoactive substances and has a potential for abuse. In a recent study using a structured interview and the Diagnostic and Statistical Manual of Mental Disorder-fourth edition criteria for substance dependence and abuse, a subset of the general population was found to demonstrate caffeine dependence or caffeine abuse. Therefore, the authors propose that companies or businesses manufacturing or marketing caffeine or products containing caffeine must meet the following guidelines: (i) clearly indicate the caffeine content of products containing comparatively higher quantities of caffeine; (ii) warn that such products should be avoided by infants and children wherever possible, and inform adult consumers about the precise quantity of caffeine that is considered safe for consumption; and (iii) clearly state that consuming large quantities of caffeine and the long-term use of caffeine carry health risks.

  20. Radiogenomics: predicting clinical normal tissue radiosensitivity

    DEFF Research Database (Denmark)

    Alsner, Jan

    2006-01-01

    Studies on the genetic basis of normal tissue radiosensitivity, or  'radiogenomics', aims at predicting clinical radiosensitivity and optimize treatment from individual genetic profiles. Several studies have now reported links between variations in certain genes related to the biological response...... to radiation injury and risk of normal tissue morbidity in cancer patients treated with radiotherapy. However, after these initial association studies including few genes, we are still far from being able to predict clinical radiosensitivity on an individual level. Recent data from our own studies on risk...

  1. Prospective study evaluating the radiosensitizing effect of reduced doses of temozolomide in the treatment of Egyptian patients with glioblastoma multiforme

    Directory of Open Access Journals (Sweden)

    Gaber M

    2013-10-01

    Full Text Available May Gaber, Hanan Selim, Tamer El-NahasDepartment of Clinical Oncology, Cairo University, Cairo, EgyptPurpose: In view of the documented toxicity of continuous daily radiosensitizer doses of temozolomide concomitant with radiation in the treatment of glioblastoma multiforme, we aimed to compare it with a different schedule of abbreviated radiosensitizer dosing.Patients and methods: This was a randomized prospective study comparing toxicity and survival in 60 Egyptian patients with glioblastoma multiforme. Patients in arm I received temozolomide at a dose of 75 mg/m2 daily with radiotherapy for 42 days, starting 4 weeks after surgery and reaching to a total radiation dose of 60 Gy/30 Fractions/6 weeks, while patients in arm II received temozolomide at a dose of 75 mg/m2 concomitantly with the same radiotherapy schedule daily in the first and last weeks of the same radiotherapy program.Results: Common grade 1–2 adverse events were malaise in 28 patients (46.7%, followed by alopecia (40% and nausea (26.7%. Grade 3–4 convulsion and decreased level of consciousness was seen in only four patients who were all from arm I. The median progression-free survival (PFS for the entire study population was 10.6 months (95% confidence interval [CI] 7.3–14, and PFS at 12 months was 32%. The median PFS in arm I was 8.8 months (95% CI 5.9–11.7 and in arm II 11.5 months (95% CI 8.9–14.2, and PFS at 12 months for both arms was 32% and 30% respectively (P=0.571. The median overall survival (OS of the whole group of patients was 14.2 months (95% CI 13–15.5, and OS was 70% at 12 months and 25% at 18 months. The median OS for patients in arm I was 12.3 months (95% CI 7.7–16.9, whereas in arm II it was 14.3 months (95% CI 14–14.7 (P=0.83.Conclusion: Reduced radiosensitizer dosing of temozolomide concomitant with radiotherapy in glioblastoma multiforme exhibited comparable efficacy with a classic continuous daily schedule, though with better tolerability

  2. 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

  3. Glyoxylic compounds as radiosensitizers of hypoxic cells

    International Nuclear Information System (INIS)

    Cornago, M.P.; Lopez Zumel, M.C.; Alvarez, M.V.; Izquierdo, M.C.

    1990-01-01

    The radiosensitizing effect of five glyoxal derivatives on the survival of TC-SV40 cells has been measured, under aerobic and hypoxic conditions. A toxicity study was previously performed in order to use nontoxic concentrations. The OER for the TC-SV40 cells was 2.74. None of the glyoxylic compounds showed radiosensitizing activity under aerobic conditions while in hypoxia their radiosensitizing factors decreased in the order phenylglyoxylic acid (1.68 at 8 x 10(-3) mole dm-3) greater than phenylglyoxal (1.55 at 5 x 10(-6) mole dm-3) greater than 2-2' furil (1.48 at 5 x 10(-5) mole dm-3) greater than glyoxylic acid (1.39 at 1 x 10(-3) mole dm-3) greater than glyoxal (1.30 at 5 x 10(-5) mole dm-3). The dose-modifying factors were also determined at two equimolar concentrations 5 x 10(-5) and 5 x 10(-6) mole dm-3. A concentration effect was noticed for all the compounds although their relative radiosensitizing activity kept, independently of the concentration, the same order noted above. Glyoxals with aromatic or heterocyclic rings exert a greater radiosensitization than the others. The acidic compounds have less radiosensitizing activity than their aldehydic counterparts. Interaction of these glyoxals with NPSH cellular groups was tested and the low degree of inhibition shows that this mechanism would contribute very little, if any, to the radiosensitization effect

  4. Caffeine-containing beverages, total fluid consumption, and premenstrual syndrome.

    Science.gov (United States)

    Rossignol, A M; Bonnlander, H

    1990-09-01

    The main objective of this study was to evaluate whether daily consumption of caffeine-containing beverages is related to the prevalence and severity of premenstrual syndrome apart from any effects of daily total fluid consumption. A secondary objective was to determine whether daily total fluid consumption itself is related to premenstrual syndrome. The study is based on 841 responses to a questionnaire probing menstrual and premenstrual health, and daily fluid consumption, which was mailed to female university students in Oregon. Analysis of the data revealed that consumption of caffeine-containing beverages was strongly related to the prevalence of premenstrual syndrome. Among women with more severe symptoms, the relation between consumption of caffeine-containing beverages and premenstrual syndrome was dose-dependent, with prevalence odds ratios equal to 1.3 for consumers of one cup of a caffeine-containing beverage per day and increasing steadily to 7.0 for consumers of eight to 10 cups per day. The effects were apparent among both caffeine-containing tea/coffee consumers and caffeine-containing soda consumers. The observed effects were only slightly reduced when daily total fluid consumption was controlled. Daily total fluid consumption also was related to the prevalence of premenstrual symptoms although the effects were large only for consumers of 13-19 cups of fluid per day (the largest amount studied).

  5. Effects of caffeine on alcohol reinforcement: Beverage choice, self-administration, and subjective ratings

    Science.gov (United States)

    Sweeney, Mary M.; Meredith, Steven E.; Evatt, Daniel P.; Griffiths, Roland R.

    2017-01-01

    Rationale Combining alcohol and caffeine is associated with increased alcohol consumption, but no prospective experimental studies have examined whether added caffeine increases alcohol consumption. Objectives This study examined how caffeine alters alcohol self-administration and subjective reinforcing effects in healthy adults. Methods Thirty-one participants completed six double-blind alcohol self-administration sessions: three sessions with alcohol only (e.g., Beverage A) and three sessions with alcohol and caffeine (e.g., Beverage B). Participants chose which beverage to consume on a subsequent session (e.g., Beverage A or B). Effects of caffeine on overall beverage choice, number of self-administered drinks, subjective ratings (e.g., Biphasic Alcohol Effects Scale), and psychomotor performance were examined. Results A majority of participants (65%) chose to drink the alcohol beverage containing caffeine on their final self-administration session. Caffeine did not increase the number of self-administered drinks. Caffeine significantly increased stimulant effects, decreased sedative effects, and attenuated decreases in psychomotor performance attributable to alcohol. Relative to nonchoosers, caffeine choosers reported overall lower stimulant ratings, and reported greater drinking behavior prior to the study. Conclusions Although caffeine did not increase the number of self-administered drinks, most participants chose the alcohol beverage containing caffeine. Given the differences in subjective ratings and pre-existing differences in self-reported alcohol consumption for caffeine choosers and nonchoosers, these data suggest decreased stimulant effects of alcohol and heavier self-reported drinking may predict subsequent choice of combined caffeine and alcohol beverages. These predictors may identify individuals who would benefit from efforts to reduce risk behaviors associated with combining alcohol and caffeine. PMID:28108773

  6. Altered expression of the caffeine synthase gene in a naturally caffeine-free mutant of Coffea arabica

    Directory of Open Access Journals (Sweden)

    Mirian Perez Maluf

    2009-01-01

    Full Text Available In this work, we studied the biosynthesis of caffeine by examining the expression of genes involved in this biosynthetic pathway in coffee fruits containing normal or low levels of this substance. The amplification of gene-specific transcripts during fruit development revealed that low-caffeine fruits had a lower expression of the theobromine synthase and caffeine synthase genes and also contained an extra transcript of the caffeine synthase gene. This extra transcript contained only part of exon 1 and all of exon 3. The sequence of the mutant caffeine synthase gene revealed the substitution of isoleucine for valine in the enzyme active site that probably interfered with enzymatic activity. These findings indicate that the absence of caffeine in these mutants probably resulted from a combination of transcriptional regulation and the presence of mutations in the caffeine synthase amino acid sequence.

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

    NARCIS (Netherlands)

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

    2016-01-01

    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

  8. Caffeine Content of Tea and Coffee

    African Journals Online (AJOL)

    1974-03-13

    Mar 13, 1974 ... The xanthines (caffeine, theophylline, and theobromine) occur in plants widely distributed throughout the world. Best known for the preparation of beverages are coffee beans which contain caffeine, tea leaves which contain caffeine and theophylline, and cocoa seeds which contain caffeine and ...

  9. 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...

  10. 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...

  11. Gamma radiosensitivity of a common bean cultivar

    International Nuclear Information System (INIS)

    Colaco, W.; Martinez, C.R.

    1995-01-01

    A preliminary experiment was conducted to evaluate the radiosensitivity of common bean (Phaseolous vulgaris L.), cultivar to gamma rays from a 60 Co source. Sets of seeds (60 seed/sample) irradiated with 50, 100, 150, 200, and 250 Gy, were compared to a control without irradiation (0 Gy), under greenhouse conditions. The radiosensitivity was evaluated through seedling height reduction, determined at 15 days after emergence (DAE), and also through seedling survival, root length, and dry matter production of leaves, shoots and roots. Seedling height was significantly reduced for the treatments with 150 and 250 Gy, in relation to the control. The dose causing reduction of 50% seedling height was between 150 and 200 Gy. Survival rates corresponding to these doses, were, respectively, 85% and 60%. Root length and dry matter of leaves, shoots and roots, were inversely related to the doses. (author). 15 refs, 3 figs, 1 tab

  12. CORRELATION BETWEEN CAFFEINE CONTENTS OF GREEN ...

    African Journals Online (AJOL)

    KEY WORDS: Green coffee beans, Caffeine, Correlation between caffeine content and altitude of coffee plant,. UV-Vis .... The extraction of caffeine from green coffee bean samples in to water was carried out by the reported method ..... caffeine in proposed green tea standard reference materials by liquid chromatography.

  13. Intake of Caffeinated Soft Drinks before and during Pregnancy, but Not Total Caffeine Intake, Is Associated with Increased Cerebral Palsy Risk in the Norwegian Mother and Child Cohort Study

    DEFF Research Database (Denmark)

    Tollånes, Mette C.; Strandberg-Larsen, Katrine; Eichelberger, Kacey Y.

    2016-01-01

    BACKGROUND: Postnatal administration of caffeine may reduce the risk of cerebral palsy (CP) in vulnerable low-birth-weight neonates. The effect of antenatal caffeine exposure remains unknown. OBJECTIVE: We investigated the association of intake of caffeine by pregnant women and risk of CP...... in their children. METHODS: The study was based on The Norwegian Mother and Child Cohort Study, comprising >100,000 live-born children, of whom 222 were subsequently diagnosed with CP. Mothers reported their caffeine consumption in questionnaires completed around pregnancy week 17 (102,986 mother-child pairs), week...... 22 (87,987 mother-child pairs), and week 30 (94,372 mother-child pairs). At week 17, participants were asked about present and prepregnancy consumption. We used Cox regression models to estimate associations between exposure [daily servings (1 serving = 125 mL) of caffeinated coffee, tea, and soft...

  14. 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.

  15. Effects of caffeine on alcohol-related changes in behavioural control and perceived intoxication in light caffeine consumers.

    Science.gov (United States)

    Attwood, Angela S; Rogers, Peter J; Ataya, Alia F; Adams, Sally; Munafò, Marcus R

    2012-06-01

    Caffeinated alcoholic beverages have been associated with increased risk of alcohol-related harms. However, few studies have examined these combined effects on behavioural control, which is believed to underlie many of the negative effects of alcohol consumption. In addition, studies have often omitted subjective measures, and none have directly assessed the role of caffeine consumer history. To examine the combined effects of alcohol and caffeine on measures of behavioural control and perceived intoxication in abstinent, light caffeine consumers. Participants (n = 28; 50% male) attended four sessions at which they consumed one of the following beverages in a randomised order: placebo, alcohol alone (0.6 g/kg), caffeine alone (2.0 mg/kg), and alcohol/caffeine. They completed measures of mood, intoxication, anxiety and alcohol craving before and after a task battery comprising measures of behavioural control and reaction time performance. Caffeine attenuated alcohol-related performance deficits on stop-signal accuracy, had no effect on go-no-go performance deficits, and worsened accuracy on the Stroop task. Caffeine did not influence absolute changes in perceived intoxication but there was suggestion that caffeine may have changed the nature of intoxication with increases in stimulation. Caffeine appears to have mixed effects on alcohol intoxication that are task-dependent. We found increased stimulation in the alcohol/caffeine condition, supporting the contention that caffeinated alcoholic beverages enable an individual to drink for longer. Future research should model real world drinking behaviour by examining how these effects change across multiple drink administrations.

  16. Effects of acute caffeine supplementation on reducing exercise-associated hypoglycaemia in individuals with Type 1 diabetes mellitus.

    Science.gov (United States)

    Zaharieva, D P; Miadovnik, L A; Rowan, C P; Gumieniak, R J; Jamnik, V K; Riddell, M C

    2016-04-01

    To determine the effects of acute caffeine ingestion on glycaemia during moderate to vigorous intensity aerobic exercise and in recovery in individuals with Type 1 diabetes. A total of 13 patients with Type 1 diabetes [eight women, five men: mean ± sd age 25.9 ± 8.8 years, BMI 71.9 ± 11.0 kg, maximal oxygen consumption 46.6 ± 12.7 ml/kg/min, body fat 19.9 ± 7.2%, duration of diabetes 14.4 ± 10.1 years and HbA1c 55 ± 8 mmol/mol (7.4 ± 0.8%)] were recruited. Participants ingested capsules that contained gelatin or pure caffeine (6.0 mg/kg body mass) and performed afternoon exercise for 45 min at 60% maximal oxygen consumption on two separate visits with only circulating basal insulin levels. The main finding was that a single caffeine dose attenuates the drop in glycaemia by 1.8 ± 2.8 mmol/l compared with placebo intake during exercise (P=0.056). Continuous glucose monitoring data, however, showed that caffeine was associated with elevated glycaemia at bedtime after exercise, compared with placebo, but lower glucose concentrations in the early morning the next day. Caffeine intake should be considered as another strategy that may modestly attenuate hypoglycaemia in individuals with Type 1 diabetes during exercise, but should be taken with precautionary measures as it may increase the risk of late-onset hypoglycaemia. © 2015 Diabetes UK.

  17. Radiosensitivity and genes

    Energy Technology Data Exchange (ETDEWEB)

    Qiyue, Hu; Mingyue, Lun [Suzhou Medical Coll., JS (China)

    1995-07-01

    Reported effects of some oncogenes, tumour suppressor genes and DNA repair genes on sensitivity of cells to ionizing radiation are reviewed. The role of oncogenes in cellular response to irradiation is discussed, especially the extensively studied oncogenes such as the ras gene family. For tumour suppressor genes, mainly the p53, which is increasingly implicated as a gene affecting radiosensitivity, is reviewed. It is considered that there is a cell cycle checkpoint determinant which is postulated to be able to arrest the irradiated cells in G{sub 1} phase to allow them to repair damage before they undergo DNA synthesis. So far there are six DNA repair genes which have been cloned in mammalian cells, but only one, XRCC1, appears to be involved in repair of human X-ray damage. XRCC1 can correct high sisterchromatid exchange levels when transferred into EM{sub 9} cells, but its expression seems to have no correlation with radiosensitivity of human neck and head tumour cells. Radiosensitivity is an intricate issue which may involve many factors. A scheme of cellular reactions after exposure to irradiation is proposed to indicate a possible sequence of events initiated by ionizing radiation.

  18. Radiosensitivity and genes

    International Nuclear Information System (INIS)

    Hu Qiyue; Lun Mingyue

    1995-07-01

    Reported effects of some oncogenes, tumour suppressor genes and DNA repair genes on sensitivity of cells to ionizing radiation are reviewed. The role of oncogenes in cellular response to irradiation is discussed, especially the extensively studied oncogenes such as the ras gene family. For tumour suppressor genes, mainly the p53, which is increasingly implicated as a gene affecting radiosensitivity, is reviewed. It is considered that there is a cell cycle checkpoint determinant which is postulated to be able to arrest the irradiated cells in G 1 phase to allow them to repair damage before they undergo DNA synthesis. So far there are six DNA repair genes which have been cloned in mammalian cells, but only one, XRCC1, appears to be involved in repair of human X-ray damage. XRCC1 can correct high sisterchromatid exchange levels when transferred into EM 9 cells, but its expression seems to have no correlation with radiosensitivity of human neck and head tumour cells. Radiosensitivity is an intricate issue which may involve many factors. A scheme of cellular reactions after exposure to irradiation is proposed to indicate a possible sequence of events initiated by ionizing radiation

  19. Caffeine reduces apnea frequency and enhances ventilatory long-term facilitation in rat pups raised in chronic intermittent hypoxia.

    Science.gov (United States)

    Julien, Cécile A; Joseph, Vincent; Bairam, Aida

    2010-08-01

    The mechanisms underlying the therapeutic function of caffeine on apneas in preterm neonates are not well determined. To better understand these effects, we exposed rat pups from postnatal d 3-12 to chronic intermittent hypoxia (5% O2/100 s every 10 min; 6 cycles/h followed by 1 h at 21% O2, 24 h/d), a model mimicking hypoxemic exposure in apneic neonates. Then, using whole-body plethysmography, we evaluated minute ventilation, apnea frequency, and duration after i.p injection of caffeine citrate (20 mg/kg) or saline under normoxia and in response to either sustained (FiO2 12%, 20 min) or brief (FiO2 5%, 60 s, total 10 episodes of 8 min each) hypoxia. These tests were used to assess peripheral and central components of hypoxic response. The latter also assessed the ventilatory long-term facilitation during recovery (2 h). Caffeine injection increased minute ventilation under baseline and during recovery. This effect was correlated with a decrease in apnea frequency (not duration). On the contrary, caffeine did not change the ventilatory response to sustained or brief hypoxic exposure. These results suggest that the effects of caffeine on apnea depend on increased central normoxic respiratory drive and enhancement of ventilatory long-term facilitation rather than on higher hypoxic ventilatory response.

  20. Caffeine administration alters the behaviour and development of Galleria mellonella larvae.

    Science.gov (United States)

    Maguire, Ronan; Kunc, Martin; Hyrsl, Pavel; Kavanagh, Kevin

    2017-11-01

    The effect of feeding caffeine on the behaviour and neural proteome of Galleria mellonella larvae was assessed. Caffeine was administered to larvae by force feeding and the metabolites theobromine and theophylline were subsequently detected by RP-HPLC analysis. Administration of caffeine to larvae resulted in reduced movement and a reduction in the formation of pupae. The production of the muscle relaxant theophylline may contribute to the reduction in larval movement. Analysis of the changes in proteome of the brain and surrounding tissues of caffeine fed larvae revealed an increase in the abundance of immune related proteins such as immune-related Hdd1 (6.28 fold increase) and hemolin (1.68 fold increase), ATPase associated proteins such as H+ transporting ATP synthase O subunit isoform 1 (1.87 fold increase) and H+ transporting ATP synthase delta subunit (1.53 fold increase) and proteins indicative of brain trauma such as troponin T transcript variant B, partial (1.55 fold increase). Proteins involved in development and protein degradation such as SUMO-activating enzyme subunit 1 (3.08 fold decrease) and chitin deacetylase, partial (3.67 fold decrease) were decreased in abundance. The results presented here indicate that caffeine is metabolised in a similar way in G. mellonella larvae to that in mammals and results in a variety of behavioural and developmental alterations. Utilisation of insects for studying the effects of caffeine and other neuroactive compounds may offer new insights into their mode of action and reduce the need to use mammals for this type of analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

  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.

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

    International Nuclear Information System (INIS)

    Kawano, T.

    1982-01-01

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

  3. Sensing radiosensitivity of human epidermal stem cells

    International Nuclear Information System (INIS)

    Rachidi, Walid; Harfourche, Ghida; Lemaitre, Gilles; Amiot, Franck; Vaigot, Pierre; Martin, Michele T.

    2007-01-01

    Purpose: Radiosensitivity of stem cells is a matter of debate. For mouse somatic stem cells, both radiosensitive and radioresistant stem cells have been described. By contrast, the response of human stem cells to radiation has been poorly studied. As epidermis is a radiosensitive tissue, we evaluated in the present work the radiosensitivity of cell populations enriched for epithelial stem cells of human epidermis. Methods and materials: The total keratinocyte population was enzymatically isolated from normal human skin. We used flow cytometry and antibodies against cell surface markers to isolate basal cell populations from human foreskin. Cell survival was measured after a dose of 2 Gy with the XTT assay at 72 h after exposure and with a clonogenic assay at 2 weeks. Transcriptome analysis using oligonucleotide microarrays was performed to assess the genomic cell responses to radiation. Results: Cell sorting based on two membrane proteins, α6 integrin and the transferrin receptor CD71, allowed isolation of keratinocyte populations enriched for the two types of cells found in the basal layer of epidermis: stem cells and progenitors. Both the XTT assay and the clonogenic assay showed that the stem cells were radioresistant whereas the progenitors were radiosensitive. We made the hypothesis that upstream DNA damage signalling might be different in the stem cells and used microarray technology to test this hypothesis. The stem cells exhibited a much more reduced gene response to a dose of 2 Gy than the progenitors, as we found that 6% of the spotted genes were regulated in the stem cells and 20% in the progenitors. Using Ingenuity Pathway Analysis software, we found that radiation exposure induced very specific pathways in the stem cells. The most striking responses were the repression of a network of genes involved in apoptosis and the induction of a network of cytokines and growth factors. Conclusion: These results show for the first time that keratinocyte

  4. Increased chromosome radiosensitivity during pregnancy

    International Nuclear Information System (INIS)

    Ricoul, Michelle; Sabatier, Laure; Dutrillaux, Bernard

    1997-01-01

    It was necessary to consider the risks of exposure of pregnant women, not only in relation to the child, but also in relation to their own hypersensitivity. We have demonstrated that pregnancy increases radiosensitivity of chromosome in the mouse at the end of gestation. This is of importance since it may have implications on radioprotection of pregnant women and give experimental guidelines to the problems of hypersensitivity to drugs and cancer aggravation during pregnancy. Blood obtained from women at various times of pregnancy was exposed to ionizing radiations. By comparison to non-pregnant women, an increase in chromosome breakage was observed in metaphases from lymphocytes, after short-term culture in the presence of the serum of the same donor. Immediately after delivery, this increase in radiosensitivity disappeared. In a prospective study, serial analyses showed a very strong correlation between the amount of pregnancy hormones, progesterone in particular, and the increase in radiosensitivity. Pregnant women may have an increased sensitivity to ionizing radiation during the second half of their pregnancy. This study provides the first evidence in human that radiosensitivity may vary in relation to physiological conditions

  5. 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

    2009-02-01

    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.

  6. Radiosensitization: enhancing the radiation inactivation of foodborne bacteria

    Science.gov (United States)

    Borsa, J.; Lacroix, M.; Ouattara, B.; Chiasson, F.

    2004-09-01

    Irradiation of meat products to kill pathogens can be limited by radiation-induced detriment of sensory quality. Since such detriment is directly related to dose, one approach to reduce it is by devising means to lower the dose of radiation required for processing. Increasing the radiation sensitivity of the target microorganisms would lower the dose required for a given level of microbial kill. In this work, the radiation sensitivities of inoculated Escherichia coli and Salmonella typhi in ground beef were examined under a variety of conditions. Results showed that specific manipulations of treatment conditions significantly increased the radiation sensitivity of the test organisms, ranging from a few percent to several-fold reduction in D10. In particular, radiation sensitization could be effected by certain additives, including carvacrol, thymol and trans-cinnamaldehyde, and also by certain compositions of modified atmosphere in the package headspace. A combination of additives and modified atmosphere effected a greater radiosensitization effect than could be achieved by either factor applied alone. Radiosensitization could be demonstrated with irradiation of either fresh or frozen ground meat. The radiosensitization phenomenon may be of practical utility in enhancing the technical effectiveness and feasibility of irradiation of a variety of meat and other food products.

  7. Radiosensitization: enhancing the radiation inactivation of foodborne bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Borsa, J. E-mail: jborsa@mds.nordion.com; Lacroix, M.; Ouattara, B.; Chiasson, F

    2004-10-01

    Irradiation of meat products to kill pathogens can be limited by radiation-induced detriment of sensory quality. Since such detriment is directly related to dose, one approach to reduce it is by devising means to lower the dose of radiation required for processing. Increasing the radiation sensitivity of the target microorganisms would lower the dose required for a given level of microbial kill. In this work, the radiation sensitivities of inoculated Escherichia coli and Salmonella typhi in ground beef were examined under a variety of conditions. Results showed that specific manipulations of treatment conditions significantly increased the radiation sensitivity of the test organisms, ranging from a few percent to several-fold reduction in D{sub 10}. In particular, radiation sensitization could be effected by certain additives, including carvacrol, thymol and trans-cinnamaldehyde, and also by certain compositions of modified atmosphere in the package headspace. A combination of additives and modified atmosphere effected a greater radiosensitization effect than could be achieved by either factor applied alone. Radiosensitization could be demonstrated with irradiation of either fresh or frozen ground meat. The radiosensitization phenomenon may be of practical utility in enhancing the technical effectiveness and feasibility of irradiation of a variety of meat and other food products.

  8. Effect of cisplatin on the clinically relevant radiosensitivity of human cervical carcinoma cell lines

    International Nuclear Information System (INIS)

    Britten, Richard A.; Evans, Andrew J.; Allalunis-Turner, M. Joan; Pearcey, Robert G.

    1996-01-01

    Purpose: To evaluate the effect of clinically relevant levels of cisplatin on the radiosensitivity of human cervical tumor cells, and to estimate what changes in local control rates might be expected to accrue from the concomitant use of cisplatin during fractionated radiotherapy. Methods and Materials: The effects of concomitant cisplatin (1 μg/ml, a typical intratumor concentration) on the clinically relevant radiosensitivity, i.e., surviving fraction after 2 G (SF 2 ) values, was determined in 19 cloned human cervical tumor cell lines. These early passage cell lines had SF 2 values ranging from 0.26 to 0.87. Results: The concomitant administration of cisplatin reduced the clinically relevant radiosensitivity in the majority (11 out of 19) of the human tumor cell lines investigated. In only 4 out of 19 was any radiosensitization observed, and in 4 out of 19 cell lines there was no significant change in radiosensitivity. However, the sum of the independent cell killing by radiation and cisplatin, was approximately twofold higher than after radiation alone. There was no apparent dependence of the cisplatin-induced changes in SF 2 values upon the level of cell killing by cisplatin. However, there is a suggestion that concomitant cisplatin administration may have a differential effect in inherently radiosensitive and resistant human tumor cell lines. Conclusions: Our data suggest that concomitant cisplatin/radiotherapy regimens may result in a higher level of local tumor control, but primarily through additive toxicity and not through radiosensitization. Future improvements in local tumor control may, thus, be derived by increasing the total dose of cisplatin

  9. Caffeine synergizes with another coffee component to increase plasma GCSF: linkage to cognitive benefits in Alzheimer's mice.

    Science.gov (United States)

    Cao, Chuanhai; Wang, Li; Lin, Xiaoyang; Mamcarz, Malgorzata; Zhang, Chi; Bai, Ge; Nong, Jasson; Sussman, Sam; Arendash, Gary

    2011-01-01

    Retrospective and prospective epidemiologic studies suggest that enhanced coffee/caffeine intake during aging reduces risk of Alzheimer's disease (AD). Underscoring this premise, our studies in AD transgenic mice show that long-term caffeine administration protects against cognitive impairment and reduces brain amyloid-β levels/deposition through suppression of both β- and γ-secretase. Because coffee contains many constituents in addition to caffeine that may provide cognitive benefits against AD, we examined effects of caffeinated and decaffeinated coffee on plasma cytokines, comparing their effects to caffeine alone. In both AβPPsw+PS1 transgenic mice and non-transgenic littermates, acute i.p. treatment with caffeinated coffee greatly and specifically increased plasma levels of granulocyte-colony stimulating factor (GCSF), IL-10, and IL-6. Neither caffeine solution alone (which provided high plasma caffeine levels) or decaffeinated coffee provided this effect, indicating that caffeine synergized with some as yet unidentified component of coffee to selectively elevate these three plasma cytokines. The increase in GCSF is particularly important because long-term treatment with coffee (but not decaffeinated coffee) enhanced working memory in a fashion that was associated only with increased plasma GCSF levels among all cytokines. Since we have previously reported that long-term GCSF treatment enhances cognitive performance in AD mice through three possible mechanisms (e.g., recruitment of microglia from bone marrow, synaptogenesis, and neurogenesis), the same mechanisms could be complimentary to caffeine's established ability to suppress Aβ production. We conclude that coffee may be the best source of caffeine to protect against AD because of a component in coffee that synergizes with caffeine to enhance plasma GCSF levels, resulting in multiple therapeutic actions against AD.

  10. Coffee, caffeine, and sleep: A systematic review of epidemiological studies and randomized controlled trials.

    Science.gov (United States)

    Clark, Ian; Landolt, Hans Peter

    2017-02-01

    Caffeine is the most widely consumed psychoactive substance in the world. It is readily available in coffee and other foods and beverages, and is used to mitigate sleepiness, enhance performance, and treat apnea in premature infants. This review systematically explores evidence from epidemiological studies and randomized controlled trials as to whether coffee and caffeine have deleterious effects on sleep. Caffeine typically prolonged sleep latency, reduced total sleep time and sleep efficiency, and worsened perceived sleep quality. Slow-wave sleep and electroencephalographic (EEG) slow-wave activity were typically reduced, whereas stage-1, wakefulness, and arousals were increased. Dose- and timing-response relationships were established. The sleep of older adults may be more sensitive to caffeine compared to younger adults. Pronounced individual differences are also present in young people, and genetic studies isolated functional polymorphisms of genes implicated in adenosine neurotransmission and metabolism contributing to individual sensitivity to sleep disruption by caffeine. Most studies were conducted in male adults of Western countries, which limits the generalizability of the findings. Given the importance of good sleep for general health and functioning, longitudinal investigations aimed at establishing possible causal relationships among coffee- and caffeine-induced changes in sleep quality and health development are warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. 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, or...

  12. Does Caffeine Enhance Athletic Performance?

    Directory of Open Access Journals (Sweden)

    Marcou Juliana

    2016-04-01

    Conclusion: Caffeine consumption may enhance athletic endurance, based on strong evidence, but further research needs to be conducted. High caffeine doses than the optimal, 3-6 mg/kg, before exercise does not confer any additional improvement in athletic performance. Additional, higher caffeine doses may cause side effects in athletes.

  13. Acute Caffeine Ingestion on Performance in Young Judo Athletes.

    Science.gov (United States)

    Astley, Camilla; Souza, Diego; Polito, Marcos

    2017-08-01

    To compare the acute effect of caffeine ingestion on performance in young judo athletes. In a randomized double-blind design, eighteen judo athletes (16.1 ± 1.4 yrs.) were evaluated on three nonconsecutive days. On the first day, the special judo fitness test (SJFT) was used as a control session. On the second day, the sample was randomly divided into two equal groups. One group received 4 mg.kg -1 of caffeine (capsule) and the other group received a placebo. After resting for 60 min, the sample performed the SJFT. On the final day of testing, the same procedure was performed but the substance ingested was exchanged between the groups. Heart rate (HR) and rating of perceived exertion (RPE) were recorded throughout the applications of the SJFTs. Caffeine ingestion did not induce changes in HR, but reduced the RPE compared with the placebo session (7.0 ± 1.1 vs 8.2 ± 2.0; p performance on SJFT in young judo athletes and reduced the RPE.

  14. Action of caffeine on x-irradiated HeLa cells. IV. Progression delays and enhanced cell killing at high caffeine concentrations

    International Nuclear Information System (INIS)

    Tolmach, L.J.; Busse, P.M.

    1980-01-01

    The response of x-irradiated and unirradiated HeLa S3 cells to treatment with caffeine at concentrations between 1 and 10 nM has been examined with respect to both delay in progression through the cell generation cycle and enhancement of the expression of potentially lethal x-ray damage. Progression is delayed in a concentration-dependent fashion: the generation time is doubled at about 4 mM. The duration of G 1 is lengthened, and the rate of DNA synthesis is reduced, although the kinetics are different in the two phases; the rate of DNA synthesis is usually unaffected at 1 or 2 mM, while there is no concentration threshold for the slowing of progression through G 1 . Progression through G 2 appears to be unaffected by concentrations up to at least 10 mM. Killing of irradiated cells in G 2 is somewhat greater after treatment with the higher caffeine concentrations than reported previously for 1 mM. Moreover, an additional mode of killing is observed in irradiated G 1 cells which had been found previously to be only slightly affected by 1 mM caffeine; they suffer extensive killing at concentrations above 5 mM. The time-survival curves for irradiated, caffeine-treated G 1 and G 2 cells have characteristically different shapes. The dose-survival curves for cells treated with the higher caffeine concentrations display steeper terminal slopes and narrower shoulders

  15. Hormonal status can modify radiosensitivity

    International Nuclear Information System (INIS)

    Ricoul, M.; Sabatier, L.; Dutrillaux, B.

    1997-01-01

    In preliminary experiments, we have demonstrated that pregnancy increases chromosome radiosensitivity in the mouse at the end of gestation. Blood obtained from women at various times of pregnancy was then exposed to ionizing radiations in vitro. By comparison to non pregnant women, an increase in chromosome breakages was observed in metaphases from lymphocytes. Immediately after delivery, this increase of radiosensitivity disappeared. In a prospective study, serial analyses showed a very strong correlation between the amount of pregnancy hormones, progesterone in particular, and the increase of radiosensitivity. Thus, pregnant women may have an increased sensitivity to ionizing radiation during the second half of their pregnancy and the risks of radiation exposure of pregnant women have to be considered not only n relation to the child, but also to their own hypersensitivity. (authors)

  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. Caffeine impairs resection during DNA break repair by reducing the levels of nucleases Sae2 and Dna2

    Science.gov (United States)

    Tsabar, Michael; Eapen, Vinay V.; Mason, Jennifer M.; Memisoglu, Gonen; Waterman, David P.; Long, Marcus J.; Bishop, Douglas K.; Haber, James E.

    2015-01-01

    In response to chromosomal double-strand breaks (DSBs), eukaryotic cells activate the DNA damage checkpoint, which is orchestrated by the PI3 kinase-like protein kinases ATR and ATM (Mec1 and Tel1 in budding yeast). Following DSB formation, Mec1 and Tel1 phosphorylate histone H2A on serine 129 (known as γ-H2AX). We used caffeine to inhibit the checkpoint kinases after DSB induction. We show that prolonged phosphorylation of H2A-S129 does not require continuous Mec1 and Tel1 activity. Unexpectedly, caffeine treatment impaired homologous recombination by inhibiting 5′ to 3′ end resection, independent of Mec1 and Tel1 inhibition. Caffeine treatment led to the rapid loss, by proteasomal degradation, of both Sae2, a nuclease that plays a role in early steps of resection, and Dna2, a nuclease that facilitates one of two extensive resection pathways. Sae2's instability is evident in the absence of DNA damage. A similar loss is seen when protein synthesis is inhibited by cycloheximide. Caffeine treatment had similar effects on irradiated HeLa cells, blocking the formation of RPA and Rad51 foci that depend on 5′ to 3′ resection of broken chromosome ends. Our findings provide insight toward the use of caffeine as a DNA damage-sensitizing agent in cancer cells. PMID:26019182

  18. Caffeine, mental health, and psychiatric disorders.

    Science.gov (United States)

    Lara, Diogo R

    2010-01-01

    Caffeine intake is so common that its pharmacological effects on the mind are undervalued. Since it is so readily available, individuals can adjust their own dose, time of administration and dose intervals of caffeine, according to the perceived benefits and side effects of each dose. This review focuses on human studies of caffeine in subjects with and without psychiatric disorders. Besides the possibility of mild drug dependence, caffeine may bring benefits that contribute to its widespread use. These benefits seem to be related to adaptation of mental energy to the context by increasing alertness, attention, and cognitive function (more evident in longer or more difficult tasks or situations of low arousal) and by elevating mood. Accordingly, moderate caffeine intake (caffeine can induce psychotic and manic symptoms, and more commonly, anxiety. Patients with panic disorder and performance social anxiety disorder seem to be particularly sensitive to the anxiogenic effects of caffeine, whereas preliminary data suggests that it may be effective for some patients with obsessive compulsive disorder (OCD). The threshold for the anxiogenic effect of caffeine is influenced by a polymorphism of the A2A receptor. In summary, caffeine can be regarded as a pharmacological tool to increase energy and effortful behavior in daily activities. More populational (cross-sectional and prospective) and experimental studies are necessary to establish the role of caffeine intake in psychiatric disorders, especially its putative efficacy on depressive mood and cognitive/attentional disorders.

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

    Science.gov (United States)

    Lystrup, Robert M; Leggit, Jeffery C

    2015-08-01

    Thousands of military members self-medicate with dietary supplements containing unknown quantities of pharmacologically active compounds. These poorly regulated substances can cause real harm to the military population, especially when they contain stimulants such as caffeine. When taken regularly, caffeine has several performance-enhancing benefits. However, when used excessively or in vulnerable populations, caffeine can cause several unwanted side effects such as nervousness, sensory disturbances, insomnia, arrhythmia, excitability, inattentiveness, restlessness, mood changes, gastrointestinal disturbances, and even psychosis. Vulnerable patients include the caffeine-naïve, physiologically stressed, young, and mentally ill patients. One such case describes a caffeine-naïve service member who suffered an adverse reaction after taking an allegedly moderate dose of caffeine from a pill he obtained from a teammate. This case highlights the importance of supplement awareness among service members, increased provider vigilance, third party verification, and enhanced regulation on the approval and marketing of dietary supplements. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

  20. Studies on Drosophila radiosensitive strains

    International Nuclear Information System (INIS)

    Varentsova, E.P.; Zakharov, I.A.

    1976-01-01

    45 of radiosensitive strains of Drosophila melanogaster were isolated by Curly/Lobe technique after EMS treatment of Livadia population males. The lethality of non-Curly late larvae after gamma-irradiation (4000r) characterized radiosensitivity strains. Most of them exhibited higher frequency of the spontaneous dominant lethals (up to 69%). The males of 6 strains were semi-sterile. 5 of these strains exhibited higher frequency of X-chromosome non-disjunction

  1. The effects of L-theanine, caffeine and their combination on cognition and mood.

    Science.gov (United States)

    Haskell, Crystal F; Kennedy, David O; Milne, Anthea L; Wesnes, Keith A; Scholey, Andrew B

    2008-02-01

    L-Theanine is an amino acid found naturally in tea. Despite the common consumption of L-theanine, predominantly in combination with caffeine in the form of tea, only one study to date has examined the cognitive effects of this substance alone, and none have examined its effects when combined with caffeine. The present randomised, placebo-controlled, double-blind, balanced crossover study investigated the acute cognitive and mood effects of L-theanine (250 mg), and caffeine (150 mg), in isolation and in combination. Salivary caffeine levels were co-monitored. L-Theanine increased 'headache' ratings and decreased correct serial seven subtractions. Caffeine led to faster digit vigilance reaction time, improved Rapid Visual Information Processing (RVIP) accuracy and attenuated increases in self-reported 'mental fatigue'. In addition to improving RVIP accuracy and 'mental fatigue' ratings, the combination also led to faster simple reaction time, faster numeric working memory reaction time and improved sentence verification accuracy. 'Headache' and 'tired' ratings were reduced and 'alert' ratings increased. There was also a significant positive caffeine x L-theanine interaction on delayed word recognition reaction time. These results suggest that beverages containing L-theanine and caffeine may have a different pharmacological profile to those containing caffeine alone.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  3. Systematic review of randomised controlled trials of the effects of caffeine or caffeinated drinks on blood glucose concentrations and insulin sensitivity in people with diabetes mellitus.

    Science.gov (United States)

    Whitehead, N; White, H

    2013-04-01

    Compounds other than macronutrients have been shown to influence blood glucose concentrations and insulin sensitivity in people with diabetes, with caffeine being one such substance. The present study systematically reviewed the evidence of the effects of caffeine on blood glucose concentrations and/or insulin sensitivity in people with diabetes. Four databases, including MEDLINE and EMBASE, were searched up to 1 February 2012. Randomised controlled trials (RCTs) investigating the effects of caffeine on blood glucose and/or insulin sensitivity in humans, diagnosed with type I, type II or gestational diabetes mellitus (GDM), were included. Quality assessment and data extraction were conducted and agreed by both authors. Of 253 articles retrieved, nine trials (134 participants) were identified. Trials in people with type II diabetes demonstrated that the ingestion of caffeine (approximately 200-500 mg) significantly increased blood glucose concentrations by 16-28% of the area under the curve (AUC) and insulin concentrations by 19-48% of the AUC when taken prior to a glucose load, at the same time as decreasing insulin sensitivity by 14-37%. In type I diabetes, trials indicated enhanced recognition and a reduced duration of hypoglycaemic episodes following ingestion of 400-500 mg caffeine, without altering glycated haemoglobin. In GDM, a single trial demonstrated that approximately 200 mg of caffeine induced a decrease in insulin sensitivity by 18% and a subsequent increase in blood glucose concentrations by 19% of the AUC. Evidence indicates a negative effect of caffeine intake on blood glucose control in individuals with type II diabetes, as replicated in a single trial in GDM. Larger-scale RCTs of longer duration are needed to determine the effects of timing and dose. Early indications of a reduced duration and an improved awareness of hypoglycaemia in type I diabetes require further confirmation. © 2013 The Authors Journal of Human Nutrition and Dietetics

  4. Caffeine and cardiovascular health.

    Science.gov (United States)

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

    2017-10-01

    This report evaluates the scientific literature on caffeine with respect to potential cardiovascular outcomes, specifically relative risks of total cardiovascular disease (CVD), coronary heart disease (CHD) and acute myocardial infarction (AMI), effects on arrhythmia, heart failure, sudden cardiac arrest, stroke, blood pressure, hypertension, and other biomarkers of effect, including heart rate, cerebral blood flow, cardiac output, plasma homocysteine levels, serum cholesterol levels, electrocardiogram (EKG) parameters, heart rate variability, endothelial/platelet function and plasma/urine catecholamine levels. Caffeine intake has been associated with a range of reversible and transient physiological effects broadly and cardiovascular effects specifically. This report attempts to understand where the delineations exist in caffeine intake and corresponding cardiovascular effects among various subpopulations. The available literature suggests that cardiovascular effects experienced by caffeine consumers at levels up to 600 mg/day are in most cases mild, transient, and reversible, with no lasting adverse effect. The point at which caffeine intake may cause harm to the cardiovascular system is not readily identifiable in part because data on the effects of daily intakes greater than 600 mg is limited. However, the evidence considered within this review suggests that typical moderate caffeine intake is not associated with increased risks of total cardiovascular disease; arrhythmia; heart failure; blood pressure changes among regular coffee drinkers; or hypertension in baseline populations. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Chronic ingestion of a low dose of caffeine induces tolerance to the performance benefits of caffeine.

    Science.gov (United States)

    Beaumont, Ross; Cordery, Philip; Funnell, Mark; Mears, Stephen; James, Lewis; Watson, Phillip

    2017-10-01

    This study examined effects of 4 weeks of caffeine supplementation on endurance performance. Eighteen low-habitual caffeine consumers (caffeine (1.5-3.0 mg · kg -1 day -1 ; titrated) or placebo for 28 days. Groups were matched for age, body mass, V̇O 2peak and W max (P > 0.05). Before supplementation, all participants completed one V̇O 2peak test, one practice trial and 2 experimental trials (acute 3 mg · kg -1 caffeine [precaf] and placebo [testpla]). During the supplementation period a second V̇O 2peak test was completed on day 21 before a final, acute 3 mg · kg -1 caffeine trial (postcaf) on day 29. Trials consisted of 60 min cycle exercise at 60% V̇O 2peak followed by a 30 min performance task. All participants produced more external work during the precaf trial than testpla, with increases in the caffeine (383.3 ± 75 kJ vs. 344.9 ± 80.3 kJ; Cohen's d effect size [ES] = 0.49; P = 0.001) and placebo (354.5 ± 55.2 kJ vs. 333.1 ± 56.4 kJ; ES = 0.38; P = 0.004) supplementation group, respectively. This performance benefit was no longer apparent after 4 weeks of caffeine supplementation (precaf: 383.3 ± 75.0 kJ vs. postcaf: 358.0 ± 89.8 kJ; ES = 0.31; P = 0.025), but was retained in the placebo group (precaf: 354.5 ± 55.2 kJ vs. postcaf: 351.8 ± 49.4 kJ; ES = 0.05; P > 0.05). Circulating caffeine, hormonal concentrations and substrate oxidation did not differ between groups (all P > 0.05). Chronic ingestion of a low dose of caffeine develops tolerance in low-caffeine consumers. Therefore, individuals with low-habitual intakes should refrain from chronic caffeine supplementation to maximise performance benefits from acute caffeine ingestion.

  6. 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.

  7. Catecholamines of the body tissues and radiosensitivity of rodents

    International Nuclear Information System (INIS)

    Grayevskaya, V.M.; Zolotariova, N.N.

    1975-01-01

    Various species of rodents are distinguished by their radiosensitivity (increasing): bank vole 57 Br mouse < golden hamster < BALB mouse < guinea pig. There is a positive correlation between radiosensitivity of these species and catecholamines content in the adrenals, urea and blood; and negative correlation between radiosensitivity and adrenaline and noradrenaline concentrations in liver and spleen cells. Presumable causes of this correlation, and the possibility of application of the index under study for predicting the organism radiosensitivity and forecasting the outcome of radiation damage are discussed

  8. Sex-specific respiratory effects of acute and chronic caffeine administration in newborn rats.

    Science.gov (United States)

    Kouchi, Hayet; Uppari, NagaPraveena; Joseph, Vincent; Bairam, Aida

    2017-06-01

    Caffeine is widely used for the treatment of apnea of prematurity (AoP) but whether this effect varies with sex is unknown. To shed some light on this question, we present a summary of data obtained on the effects of caffeine on the respiratory chemoreflexes and apnea frequency in 1- and 12-days old male and female rats. Caffeine was either administered as a single acute injection (10mg/kg, i.p.) or for 10 consecutive days (7.5mg/kg/day between 3 and 12days of life by gavage, simulating its clinical use). Acute caffeine had little effects on breathing in 1-day old male and female rats. In 12-days old female rats caffeine reduced the response to hypercapnia (not hypoxia) compared to males. During the steady state of hypoxia females had a lower frequency of apneas than males, and acute injection of caffeine decreased the frequency of apnea, suppressing the differences between males and females. In 12-days old rats chronic administration of caffeine stimulated basal breathing and decreased the frequency of apnea similarly in males and females. In response to hypoxia, chronic caffeine administration also masked the difference in respiratory frequency between males and females observed in control rats. Female rats had lower frequency of apnea than males with or without caffeine treatment. These observations indicate that sex influences the respiratory responses to caffeine and this effect seems to depend on the modality of administration (acute vs chronic) and environmental oxygen (normoxia vs hypoxia). Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Effects of glutathione depletion by buthionine sulfoximine on radiosensitization by oxygen and misonidazole in vitro

    International Nuclear Information System (INIS)

    Shrieve, D.C.; Denekamp, J.; Minchinton, A.I.

    1985-01-01

    Buthionine sulfoximine (BSO) has been used to deplete glutathione (GSH) in V79-379A cells in vitro, and the effect on the efficiency of oxygen and misonidazole (MISO) as radiosensitizers has been determined. Treatment with 50 or 500 μM BSO caused a rapid decline in GSH content to less than 5% of control values after 10 hr of exposure. Removal of BSO resulted in a rapid regeneration of GSH after 50 μM BSO, but little regeneration was observed over the subsequent 10-hr period after 500 μM. Cells irradiated in monolayer on glass had an oxygen enhancement ratio (OER) of 3.1. After 10-14 hr pretreatment with 50 μM BSO, washed cells were radiosensitized by GSH depletion at all oxygen tensions tested. The OER was reduced to 2.6, due to greater radiosensitization of hypoxic cells than aerated ones by GSH depletion. In similar experiments performed with MISO, an enhancement ratio of 2.0 could be achieved with 0.2 mM MISO in anoxic BSO-pretreated cells, compared to 2.7 mM MISO in non-BSO-treated cells. These apparent increases in radiosensitizer efficiency in GSH-depleted cells could be explained on the basis of radiosensitization of hypoxic cells by GSH depletion alone. These results are consistent with hypoxic cell radiosensitization by GSH depletion and by MISO or oxygen acting by separate mechanisms

  10. Caffeine and diphenyl diselenide improve long-term memory impaired in middle-aged rats.

    Science.gov (United States)

    Leite, Marlon R; Marcondes Sari, Marcel Henrique; de Freitas, Mayara L; Oliveira, Lia P; Dalmolin, Laíza; Brandão, Ricardo; Zeni, Gilson

    2014-05-01

    The aim of the present study was to evaluate the effects of diphenyl diselenide (PhSe)2 supplemented diet (10ppm) associated to the administration of caffeine (15mg/kg; i.g.) for 30days on the novel object recognition memory in middle-aged rats. The present findings showed that (PhSe)2-supplemented diet enhanced short-term memory, but not long-term memory, of middle-aged rats in the novel object recognition task. The (PhSe)2 supplemented diet associated with caffeine administration improved long-term memory, but did not alter short-term memory, impaired in middle-aged rats. Daily caffeine administration to middle-aged rats had no effect on the memory tasks. Diet supplemented with (PhSe)2 plus caffeine administration increased the number of crossings and rearings reduced in middle-aged rats. Caffeine administration plus (PhSe)2 diets were effective in increasing the number of rearings and crossings, respectively, in middle-aged rats, [(3)H] glutamate uptake was reduced in hippocampal slices of rats from (PhSe)2 and caffeine plus (PhSe)2 groups. In addition, animals supplemented with (PhSe)2 showed an increase in the pCREB/CREB ratio whereas pAkt/Akt ratio was not modified. These results suggest that the effects of (PhSe)2 on the short-term memory may be related to its ability to decrease the uptake of glutamate, influencing the increase of CREB phosphorylation. (PhSe)2-supplemented diet associated to the administration of caffeine improved long-term memory impaired in middle-aged rats, an effect independent of CREB and Akt phosphorylation. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Caffeine tolerance: behavioral, electrophysiological and neurochemical evidence

    International Nuclear Information System (INIS)

    Chou, D.T.; Khan, S.; Forde, J.; Hirsh, K.R.

    1985-01-01

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

  12. Radiosensitivity of cells

    International Nuclear Information System (INIS)

    Alexander, P.

    1960-01-01

    The mechanism by which radiation kills cells must be investigated with the goal to make possible to devise means to alter the radiosensitivity of cells. The object of our investigation, supported by IAEA, is to try and find the reasons for the variation in sensitivity between different cells. Once we know the reason for the differences in radiosensitivity of different micro-organisms we can begin to look rationally for ways of enhancing the radiation response of the more sensitive organisms. An investigation of this type has implications far beyond food sterilization, as it cannot fail to provide fundamental facts about radiation injury to cells in general. Cancer researchers have looked for many years for means of sensitizing cancer cells to radiation

  13. Radiosensitivity of cells

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, P [Radiation Biology Section, Chester Beatty Research Institute, Royal Cancer Hospital, London (United Kingdom)

    1960-07-15

    The mechanism by which radiation kills cells must be investigated with the goal to make possible to devise means to alter the radiosensitivity of cells. The object of our investigation, supported by IAEA, is to try and find the reasons for the variation in sensitivity between different cells. Once we know the reason for the differences in radiosensitivity of different micro-organisms we can begin to look rationally for ways of enhancing the radiation response of the more sensitive organisms. An investigation of this type has implications far beyond food sterilization, as it cannot fail to provide fundamental facts about radiation injury to cells in general. Cancer researchers have looked for many years for means of sensitizing cancer cells to radiation

  14. Caffeine Consumption Among Naval Aviation Candidates.

    Science.gov (United States)

    Sather, Thomas E; Williams, Ronald D; Delorey, Donald R; Woolsey, Conrad L

    2017-04-01

    Education frequently dictates students need to study for prolonged periods of time to adequately prepare for examinations. This is especially true with aviation preflight indoctrination (API) candidates who have to assimilate large volumes of information in a limited amount of time during API training. The purpose of this study was to assess caffeine consumption patterns (frequency, type, and volume) among naval aviation candidates attending API to determine the most frequently consumed caffeinated beverage and to examine if the consumption of a nonenergy drink caffeinated beverage was related to energy drink consumption. Data were collected by means of an anonymous 44-item survey administered and completed by 302 students enrolled in API at Naval Air Station Pensacola, FL. Results indicated the most frequently consumed caffeinated beverage consumed by API students was coffee (86.4%), with daily coffee consumption being approximately 28% and the most frequent pattern of consumption being 2 cups per day (85%). The least frequently consumed caffeinated beverages reported were energy drinks (52%) and energy shots (29.1%). The present study also found that the consumption patterns (weekly and daily) of caffeinated beverages (coffee and cola) were positively correlated to energy drink consumption patterns. Naval aviation candidates' consumption of caffeinated beverages is comparable to other college and high school cohorts. This study found that coffee and colas were the beverages of choice, with energy drinks and energy shots being the least frequently reported caffeinated beverages used. Additionally, a relationship between the consumption of caffeinated beverages and energy drinks was identified.Sather TE, Williams RD, Delorey DR, Woolsey CL. Caffeine consumption among naval aviation candidates. Aerosp Med Hum Perform. 2017; 88(4):399-405.

  15. Caffeine and risk of Parkinson disease in a large cohort of men and women

    Science.gov (United States)

    Palacios, Natalia; Gao, Xiang; McCullough, Marjorie L.; Schwarzschild, Michael A.; Shah, Roma; Gapstur, Susan; Ascherio, Alberto

    2012-01-01

    Background Caffeine consumption has been associated with a reduced risk of Parkinson disease. The association is strong and consistent in men, but uncertain in women, possibly because of an interaction with hormone replacement therapy. We sought to confirm these findings using data on Parkinson disease incidence in the CPS II Nutrition Cohort, a large prospective study of men and women. Methods We conducted a prospective study of caffeine intake and risk of PD within the Cancer Prevention Study II Nutrition Cohort. Intakes of coffee and other sources of caffeine were assessed at baseline. Incident cases of PD (n = 317; 197 men and 120 women) were confirmed by treating physicians and medical record review. Relative risks (RR) were estimated using proportional hazards models, adjusting for age, smoking and alcohol consumption. Results After adjustment for age, smoking and alcohol intake, high caffeine consumption was associated with a reduced risk of PD. The relative risk comparing the 5th to the 1st quintile of caffeine intake was 0.43 (CI: 0.26, 0.71, p-trend = coffee was not associated with PD risk. Conclusion Findings from this large prospective study of men and women are consistent with a protective effect of caffeine intake on PD incidence, with an attenuating influence of hormone replacement therapy in women. PMID:22927157

  16. Caffeine and risk of Parkinson's disease in a large cohort of men and women.

    Science.gov (United States)

    Palacios, Natalia; Gao, Xiang; McCullough, Marjorie L; Schwarzschild, Michael A; Shah, Roma; Gapstur, Susan; Ascherio, Alberto

    2012-09-01

    Caffeine consumption has been associated with a reduced risk of Parkinson's disease (PD). The association is strong and consistent in men, but uncertain in women, possibly because of an interaction with hormone replacement therapy (HRT). We sought to confirm these findings using data on PD incidence in the Cancer Prevention Study II Nutrition Cohort (CPS II-Nutrition), a large, prospective study of men and women. We conducted a prospective study of caffeine intake and risk of PD within the CPS II Nutrition Cohort. Intakes of coffee and other sources of caffeine were assessed at baseline. Incident cases of PD (n = 317; 197 men and 120 women) were confirmed by treating physicians and medical record review. Relative risks (RRs) were estimated using proportional hazards models, adjusting for age, smoking, and alcohol consumption. After adjustment for age, smoking, and alcohol intake, high caffeine consumption was associated with a reduced risk of PD. The RR comparing the 5th to the 1st quintile of caffeine intake was 0.43 (95% confidence interval [CI]: 0.26, 0.71; P trend = coffee was not associated with PD risk. Findings from this large, prospective study of men and women are consistent with a protective effect of caffeine intake on PD incidence, with an attenuating influence of HRT in women. © 2012 Movement Disorder Society. Copyright © 2012 Movement Disorder Society.

  17. Peripubertal Caffeine Exposure Impairs Longitudinal Bone Growth in Immature Male Rats in a Dose- and Time-Dependent Manner.

    Science.gov (United States)

    Choi, Yun-Young; Choi, Yuri; Kim, Jisook; Choi, Hyeonhae; Shin, Jiwon; Roh, Jaesook

    2016-01-01

    This study investigated the dose- and time-dependent effects of caffeine consumption throughout puberty in peripubertal rats. A total of 85 male SD rats were randomly divided into four groups: control and caffeine-fed groups with 20, 60, or 120 mg/kg/day through oral gavage for 10, 20, 30, or 40 days. Caffeine decreased body weight gain and food consumption in a dose- and time-dependent manner, accompanied by a reduction in muscle and body fat. In addition, it caused a shortening and lightening of leg bones and spinal column. The total height of the growth plate decreased sharply at 40 days in the controls, but not in the caffeine-fed groups, and the height of hypertrophic zone in the caffeine-fed groups was lower than in the control. Caffeine increased the height of the secondary spongiosa, whereas parameters related to bone formation, such as bone area ratio, thickness and number of trabeculae, and bone perimeter, were significantly reduced. Furthermore, serum levels of IGF-1, estradiol, and testosterone were also reduced by the dose of caffeine exposure. Our results demonstrate that caffeine consumption can dose- and time-dependently inhibit longitudinal bone growth in immature male rats, possibly by blocking the physiologic changes in body composition and hormones relevant to bone growth.

  18. Clinical studies on radiosensitization of cervical cancer by cisplatinum

    International Nuclear Information System (INIS)

    Yu Shiying; Chen Yuan; Xu Zhiqiang

    1993-01-01

    A prospective randomized clinical trial on the radiosensitizing effect of cisplatinum was carried out in 60 patients with cervical cancer, of whom 30 were given cisplatinum in combination with radiotherapy (radiosensitizing group) and the remaining 30 radiotherapy alone (control group). The results showed that the length of time of immediate CR and PR was shorter in the radiosensitizing group than in the control group. The sensitive enhancement ratio was 1.846. No toxicity was observed in the radiosensitizing group, and the treatment was well tolerated by the patients

  19. Catecholamines of the body tissues and radiosensitivity of rodents

    Energy Technology Data Exchange (ETDEWEB)

    Grayevskaya, V M; Zolotariova, N N [AN SSSR, Moscow. Inst. Morfologii Zhivotnykh

    1975-01-01

    Various species of rodents are distinguished by their radiosensitivity (increasing): bank vole < Wistar rat < wild mouse < CC/sub 57/Br mouse < golden hamster < BALB mouse < guinea pig. There is a positive correlation between radiosensitivity of these species and catecholamines content in the adrenals, urea and blood; and negative correlation between radiosensitivity and adrenaline and noradrenaline concentrations in liver and spleen cells. Presumable causes of this correlation, and the possibility of application of the index under study for predicting the organism radiosensitivity and forecasting the outcome of radiation damage are discussed.

  20. 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.

  1. Molecular imprinting of caffeine on cellulose/silica composite and its characterization

    Science.gov (United States)

    Gill, Rajinder Singh

    This dissertation presents a study to prepare molecularly imprinted inorganic/organic hybrid composite which not only confirm the higher binding capabilities for the target molecule (template) but also discriminate its structural analogs. Molecularly imprinted Cellulose/Silica composite (MIP) was prepared by using caffeine as the template. Silica derived from TEOS by using sol-gel techniques was deposited on cheap, abundant organic matrix such as cellulose, which can provide a filtering medium while coffee brewing. Removal of the template from the precursor was verified by Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS). Remarkably reduced intensity of -NH2 scissor like mode of caffeine and the presence of traces of "N" by elemental analysis, confirmed the complete removal of caffeine on washing with ethanol. Cellulose to TEOS mass ratio of 2:1 was found to be close to optimal during our analysis. Energy dispersive spectroscopy results leads to an important fact that the deposition of silica was stable even at 373 K. Focus was on the adsorption affinities of caffeine by MIP and was tested by performing relative adsorption of caffeine by MIP and blank (standard) using demountable path length cell in IR. It was observed that MIP showed almost 3-folds higher adsorption capabilities as compared to blank. The initial rate of adsorption of caffeine by MIP is much higher than blank which is one of the desirable feature according the its intended use. The higher adsorption of caffeine by MIP not only depends on the amount of silica deposited but also the available binding sites present on its surface. Selectivity of MIP was also verified by the competitive adsorption of caffeine and its structure analogs such as theophylline. Clearly, MIP showed greater and more rapid binding capabilities for caffeine than theophylline. At short contact times, the binding capability for caffeine is almost 1.8 times greater than the binding capabilities for theophylline.

  2. The Safety of Ingested Caffeine: A Comprehensive Review

    Directory of Open Access Journals (Sweden)

    Jennifer L. Temple

    2017-05-01

    Full Text Available Caffeine is the most widely consumed psychoactive drug in the world. Natural sources of caffeine include coffee, tea, and chocolate. Synthetic caffeine is also added to products to promote arousal, alertness, energy, and elevated mood. Over the past decade, the introduction of new caffeine-containing food products, as well as changes in consumption patterns of the more traditional sources of caffeine, has increased scrutiny by health authorities and regulatory bodies about the overall consumption of caffeine and its potential cumulative effects on behavior and physiology. Of particular concern is the rate of caffeine intake among populations potentially vulnerable to the negative effects of caffeine consumption: pregnant and lactating women, children and adolescents, young adults, and people with underlying heart or other health conditions, such as mental illness. Here, we review the research into the safety and safe doses of ingested caffeine in healthy and in vulnerable populations. We report that, for healthy adults, caffeine consumption is relatively safe, but that for some vulnerable populations, caffeine consumption could be harmful, including impairments in cardiovascular function, sleep, and substance use. We also identified several gaps in the literature on which we based recommendations for the future of caffeine research.

  3. Effects of heat-shock treatment and genotype on radiosensitivity of maize seeds

    International Nuclear Information System (INIS)

    Yamagata, Hirotada; Tanisaka, Takatoshi; Harima, Kunio

    1975-01-01

    In order to clarify the internal and external factors responsible for radiosensitivity of seed, and to induce mutations more effectively, two experiments were conducted using maize. (1) Seeds of an inbred line were irradiated with γ rays at an extremely low temperature (-70 0 C) and then dipped in hot water (60 0 C, 30 sec.). Through such heat-shock treatment the radiosensitivity of maize seeds was remarkably reduced: LD 50 and RD 50 for growth rose as high as about three times and about twice, respectively. (2) Seeds of seven strains including four inbred lines, two single-cross hybrids and one double-cross hybrid were exposed to γ rays by the ordinary procedure. Hybrids, regardless of whether they were single cross or double cross, were clearly proved to surpass their parental strains in radiation tolerance, both in survival rate and in culm length. These descents of radiosensitivity were considered to be due mainly to the increased heterozygosity. (auth.)

  4. 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 ...

  5. Reinforcing effects of caffeine in coffee and capsules.

    Science.gov (United States)

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

    1989-09-01

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

  6. Caffeine inhibits nonselective cationic currents in interstitial cells of Cajal from the murine jejunum.

    Science.gov (United States)

    Jin, Nan Ge; Koh, Sang Don; Sanders, Kenton M

    2009-10-01

    Interstitial cells of Cajal (ICC) discharge unitary potentials in gastrointestinal muscles that constitute the basis for pacemaker activity. Caffeine has been used to block unitary potentials, but the ionic conductance responsible for unitary potentials is controversial. We investigated currents in cultured ICC from murine jejunum that may underlie unitary potentials and studied the effects of caffeine. Networks of ICC generated slow wave events under current clamp, and these events were blocked by caffeine in a concentration-dependent manner. Single ICC generated spontaneous transient inward currents (STICs) under voltage clamp at -60 mV and noisy voltage fluctuations in current clamp. STICs were unaffected when the equilibrium potential for Cl- (ECl) was set to -60 mV (excluding Cl- currents) and reversed at 0 mV, demonstrating that a nonselective cationic conductance, and not a Cl- conductance, is responsible for STICs in ICC. Caffeine inhibited STICs in a concentration-dependent manner. Reduced intracellular Ca2+ and calmidazolium (CMZ; 1 microM) activated persistent inward, nonselective cation currents in ICC. Currents activated by CMZ and by dialysis of cells with 10 mM BAPTA were also inhibited by caffeine. Excised inside-out patches contained channels that exhibited spontaneous openings, and resulting currents reversed at 0 mV. Channel openings were increased by reducing Ca2+ concentration from 10(-6) M to 10(-8) M. CMZ (1 microM) also increased openings of nonselective cation channels. Spontaneous currents and channels activated by CMZ were inhibited by caffeine (5 mM). The findings demonstrate that the Ca2+-inhibited nonselective cation channels that generate STICs in ICC are blocked directly by caffeine. STICs are responsible for unitary potentials in intact muscles, and the block of these events by caffeine is consistent with the idea that a nonselective cation conductance underlies unitary potentials in ICC.

  7. Effects of caffeine on behavioural and cognitive deficits in rats.

    Science.gov (United States)

    Assis, Melissa S; Soares, Aluízio C; de Sousa, Dircilei N; Eudes-Filho, João; Faro, Lilian Rosana F; Carneiro, Fabiana P; da Silva, Mônica V; Motoyama, Andrea B; de Souza, Greice Maria R; Marchiori, Stéphanie; de Lima, Nadyelle T; Boëchat-Barros, Raphael; Ferreira, Vania M

    2018-05-07

    There are many studies that have sought to find drug therapies to prevent harm arising from sepsis. Such studies have represented a progress in the support to septic patients and also in the development of new pharmacological alternatives. Our interest was to investigate the caffeine effect on sepsis behavioural and memory impairments. Male rats were anaesthetized and the surgery was made to allow exposure of the cecum, which was then squeezed to extrude a small amount of faeces from the perforation site, which was later placed back into the peritoneal cavity. This procedure, which served to generate experimental sepsis, is herein referred to as ceccum ligation and perforation (CLP). The caffeine (10 mg/kg) was administered by gavage route, once daily, during 7 or 14 consecutive days to investigate the effects of acute or subchronic caffeine treatment on long-term behavioural and cognitive deficits induced by CLP. On the last day, one hour after caffeine administration, the animals were submitted to open-field, elevated plus-maze (EPM), forced swimming, and step-down inhibitory avoidance tests. The results showed that caffeine increased the percentage of open arm entries and open arm time in the EPM test, and reduced the immobility time when compared to the sham-operated group. The caffeine also increased the latency in the inhibitory avoidance test platform. Our results demonstrated that the caffeine improved behavioural changes and improved the neurocognitive deficits of sepsis-surviving animals. It is possible that blockage of the adenosine receptors may be responsible for the results here observed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  8. [Combined effect of cisplatin and caffeine on murine B16-BL6 melanoma cells].

    Science.gov (United States)

    Yasutake, H; Tsuchiya, H; Sugihara, M; Tomita, K; Ueda, Y; Tanaka, M; Sasaki, T

    1989-05-01

    Combined effect of cisplatin and caffeine on murine B16-BL6 melanoma cells was studied. Synergistic inhibition of the cell growth was observed when caffeine (2 mM) was added continuously after one hour exposure of cisplatin. On the other hand, when caffeine was added before one hour exposure of cisplatin or one hour simultaneous exposure with cisplatin, synergistic effect was not shown. In the analysis of DNA histogram obtained from flow cytometry, S and G2/M accumulation was observed by the treatment of cisplatin and that accumulation was reduced by the combination of cisplatin and caffeine. From this findings, it was suggested that caffeine would inhibit DNA repair process. Furthermore, according to morphological studies with hematoxylin-eosin stain and Fontana-Masson stain, the addition of caffeine alone resulted in mild swelling of melanoma cells and the decrease of nuclear-cytoplasmic ratio. The combination of cisplatin and caffeine caused marked swelling of melanoma cells and remarkable increase of dendrite-like processes. Melanogenesis was also enhanced by the addition of these two drugs. Many matured melanosomes, increases of mitochondria, Golgi's apparatus and endoplasmic reticula were observed by the use of electron microscope. These findings implied that the combination of cisplatin and caffeine induced a differentiation of murine melanoma cells.

  9. Application of bio-marker to study on tumor radiosensitivity

    International Nuclear Information System (INIS)

    Guo Wanfeng; Ding Guirong; Han Liangfu

    2001-01-01

    To definite tumor radiosensitivity is important for applying the schedules of individualization of patient radiotherapy. Many laboratories were carrying on the research which predict the tumor radiosensitivity with one bio-marker or/and multi-bio-marker in various levels. At present has not witnessed the specific bio-marker, but it provides an excellent model for predicting tumor radiosensitivity

  10. Caffeine Increases Hippocampal Sharp Waves in Vitro.

    Science.gov (United States)

    Watanabe, Yusuke; Ikegaya, Yuji

    2017-01-01

    Caffeine promotes memory consolidation. Memory consolidation is thought to depend at least in part on hippocampal sharp waves (SWs). In the present study, we investigated the effect of bath-application of caffeine in spontaneously occurring SWs in mouse acute hippocampal slices. Caffeine induced an about 100% increase in the event frequency of SWs at concentrations of 60 and 200 µM. The effect of caffeine was reversible after washout of caffeine and was mimicked by an adenosine A 1 receptor antagonist, but not by an A 2A receptor antagonist. Caffeine increased SWs even in dentate-CA3 mini-slices without the CA2 regions, in which adenosine A 1 receptors are abundantly expressed in the hippocampus. Thus, caffeine facilitates SWs by inhibiting adenosine A 1 receptors in the hippocampal CA3 region or the dentate gyrus.

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

    International Nuclear Information System (INIS)

    Kaul, M.L.H.

    1979-01-01

    The effect of 1.5x10 -2 M caffeine post-treatments over the chromosome damage induced by 4kR X-ray 1.5x10 -2 M Maleic hydrazide (MH) and N-Nitroso-N-urethane (NMU) treatments in the root top cells of a normal and trigenic leaf mutant of Pisum sativum was studied. While MH and NMU produced S-dependent effects, X-rays induced non-delayed S-independent effects. These effects got potentiated by caffeine treatments. With MH, the potentiation occurred when the cells got exposed to caffeine during S-phase and with X-rays, it occurred when the irradiated cells are treated in G 2 or prophase stage. The caffeine potentiation of chromosome damage produced by MH was similar in the roots exposed to caffeine at 16 and 31degC but with NMU, the potentiation was lower at 31 than at 16degC. If the inhibitory effect of caffeine on gap filling process of the damaged DNA is the molecular mechanism responsible for caffeine potentiation of reproductive death it may be the mechanism responsible for the observed chromosome damage in MH treated cells exposed to caffeine during G 1 and S phase. But the X-irradiated cells are insensitive to caffeine at such phases. In these cells caffeine probably acts as an inhibitor of the photoreactivating enzymes for binding sites or with the substrate in the irradiated cells post-treated during G 2 and prophase. However, temperature independence of caffeine potentiation is not compatible with eithr of the above two views. Compared to the normal genotype, the trigenic mutant exhibited an increased chromosomal damage, but not the potentiation. Probably mutant genes reduce the resistance of a genome against mutagenic action, consequently enhance the suseptibility to chromosome damage. (author)

  12. The effect of caffeine on X-ray-induced mitotic delay in normal human and ataxia-telangiectasia fibroblasts

    International Nuclear Information System (INIS)

    Zampetti-Bosseler, F.; Scott, D.

    1985-01-01

    The authors previously showed that radiation-sensitive fibroblasts from ataxia-telangiectasia (A-T) patients sustain less G 2 delay after X-irradiation than normal fibroblasts. Caffeine is known to reduce the amount of X-ray-induced delay in various mammalian cell types. It is proposed that A-T cells have an altered chromatin structure, similar to that of caffeine-treated normal cells and that this results in a failure of A-T cells to delay their progression through the cell cycle to allow time for DNA repair. The authors now show that caffeine treatment after X-irradiation reduces G 2 delay in both A-T and normal cells. The authors confirm the results previously obtained on lymphocytes that caffeine potentiates the chromosome-damaging effects of X-rays in both A-T and normal fibroblasts. These and other data suggest that the radiation responses of A-T cells and of caffeine-treated normal cells are caused by different mechanisms. (Auth.)

  13. 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

  14. Determination of caffeine and identification of undeclared substances in dietary supplements and caffeine dietary exposure assessment.

    Science.gov (United States)

    Neves, Diana Brito da Justa; Caldas, Eloisa Dutra

    2017-07-01

    Caffeine is one of the most consumed stimulants in the world, and is a frequent ingredient of dietary supplements. The aims of this work were to validate a GC-MS method for the quantitation of caffeine and identification of other substances in supplements, mainly weight loss products, and to estimate the caffeine intake by consumers. Sample preparation included extraction with chloroform:water in ultrasonic bath, centrifugation and analysis of the organic layer for caffeine quantitation, and extraction with methanol for identification of other substances. A total of 213 samples of 52 supplement products not registered in Brazil and seized by the Brazilian Federal Police were analyzed. From the 109 samples that declared the amount of caffeine present, 26.6% contained more than 120% of the specified content. Considering the maximum recommended dose stated on the product labels, the consumption of 47.9% of the samples would lead to a daily intake of caffeine above the safe limit of 400 mg. Undeclared drugs, including sibutramine, phenolphthalein, amphepramone and femproporex were found in 28 samples. These results show that consumers of dietary supplements should be aware that these products might contain caffeine at levels that could represent potential health risks, in addition to undeclared pharmaceutical drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Caffeine reversal of ethanol effects on the multiple sleep latency test, memory, and psychomotor performance.

    Science.gov (United States)

    Drake, Christopher L; Roehrs, Timothy; Turner, Lauren; Scofield, Holly M; Roth, Thomas

    2003-02-01

    Caffeine has been shown to reverse some of the performance-impairing effects of ethanol. However, it is not known whether this antagonistic effect of caffeine is mediated by a reduction in sleepiness. The present study assessed physiological alertness/sleepiness, memory, and psychomotor performance following the administration of placebo, ethanol, and caffeine+ethanol combinations. A total of 13 healthy individuals (21-35 years old) underwent four conditions presented in a Latin Square Design: placebo-placebo, ethanol (0.5 g/kg)-placebo, ethanol (0.5 g/kg)-caffeine 150 mg, and ethanol (0.5 g/kg)-caffeine 300-mg. The Multiple Sleep Latency Test (MSLT), psychomotor performance battery, memory test, and mood/sleepiness questionnaires were administered following each condition. The peak breadth ethanol concentration (BrEC) was 0.043+/-0.0197% and did not differ among the three caffeine treatments. As expected, ethanol reduced mean latency on the MSLT. The lowest caffeine dose reversed this effect and the highest dose increased mean latency (greater alertness) significantly beyond placebo levels. Ethanol also impaired psychomotor performance and memory. The 300-mg caffeine dose restored performance and memory measures to placebo levels. Although visual analog ratings of dizziness were increased by ethanol, they were not diminished by either caffeine dose. In conclusion, Low-dose caffeine prevented the sleepiness and performance impairment associated with a moderate dose of ethanol. Thus, caffeine, similar to other stimulants, can reverse the physiologically sedating effects of ethanol, although other negative effects remain.

  16. Role of adenosine receptors in caffeine tolerance

    International Nuclear Information System (INIS)

    Holtzman, S.G.; Mante, S.; Minneman, K.P.

    1991-01-01

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

  17. Role of adenosine receptors in caffeine tolerance

    Energy Technology Data Exchange (ETDEWEB)

    Holtzman, S.G.; Mante, S.; Minneman, K.P. (Emory Univ. School of Medicine, Atlanta, GA (USA))

    1991-01-01

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

  18. Increased catalase activity by all-trans retinoic acid and its effect on radiosensitivity in rat glioma cells

    International Nuclear Information System (INIS)

    Jin, Hua; Jeon, Ha Yeun; Park, Woo Yoon; Kim, Won Dong; Ahn, Hee Yul; Yu, Jae Ran

    2005-01-01

    It has been reported that all-trans retinoic acid (ATRA) can inhibit glioma growing in vitro. However, clinical trials with ATRA alone in gliomas revealed modest results. ATRA has been shown to increase radiosensitivity in other tumor types, so combining radiation and ATRA would be one of alternatives to increase therapeutic efficacy in malignant gliomas. Thus, we intended to know the role of catalase, which is induced by ATRA, for radiosensitivity. If radiation-reduced reactive oxygen species (ROS) is removed by catalase, the effect of radiation will be reduced. A rat glioma cell line (36B10) was used for this study. The change of catalase activity and radiosensitivity by ATRA, with or without 3-amino-1, 2, 4-triazole (ATZ), a chemical inhibitor of catalase were measured. Catalase activity was measured by the decomposition of H 2 O 2 spectrophotometrically. Radiosensitivity was measured with clonogenic assay. Also ROS was measured using a 2, 7-dichlorofluores-cein diacetate spectrophotometrically. When 36B10 cells were exposed to 10, 25 and 50 μ M of ATRA for 48 h, the expression of catalase activity were increased with increasing concentration and incubation time of ATRA. Catalase activity was decreased with increasing the concentration of AT (1, 10 mM) dose-dependently. ROS was increased with ATRA and it was augmented with the combination of ATRA and radiation. ATZ decreased ROS production and increased cell survival in combination of ATRA and radiation despite the reduction of catalase. The increase of ROS is one of the reasons for the increased radiosensitivity in combination with ATRA. The catalase that is induced by ATRA doesn't decrease ROS production and radiosensitivity

  19. Caffeine, sleep and quality of life

    NARCIS (Netherlands)

    Lorist, M.M.; Snel, J.; Verster, J.C.; Pandi-Perumal, S.R.; Streiner, D.L.

    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

  20. Acute Ingestion of Caffeinated Chewing Gum Improves Repeated Sprint Performance of Team Sport Athletes With Low Habitual Caffeine Consumption.

    Science.gov (United States)

    Evans, Mark; Tierney, Peter; Gray, Nicola; Hawe, Greg; Macken, Maria; Egan, Brendan

    2018-04-23

    The effects of acute ingestion of caffeine on short-duration high-intensity performance are equivocal, while studies of novel modes of delivery and the efficacy of low doses of caffeine are warranted. The aims of the present study were to investigate the effect of acute ingestion of caffeinated chewing gum on repeated sprint performance (RSP) in team sport athletes, and whether habitual caffeine consumption alters the ergogenic effect, if any, on RSP. A total of 18 male team sport athletes undertook four RSP trials using a 40-m maximum shuttle run test, which incorporates 10 × 40-m sprints with 30 s between the start of each sprint. Each participant completed two familiarization sessions, followed by caffeine (CAF; caffeinated chewing gum; 200 mg caffeine) and placebo (PLA; noncaffeinated chewing gum) trials in a randomized, double-blind manner. RSP, assessed by sprint performance decrement (%), did not differ (p = .209; effect size = 0.16; N = 18) between CAF (5.00 ± 2.84%) and PLA (5.43 ± 2.68%). Secondary analysis revealed that low habitual caffeine consumers (130 mg/day, n = 6; 3.98 ± 2.57% vs. 3.80 ± 1.79%, respectively; p = .684; effect size = 0.08). The data suggest that a low dose of caffeine in the form of caffeinated chewing gum attenuates the sprint performance decrement during RSP by team sport athletes with low, but not moderate-to-high, habitual consumption of caffeine.

  1. Development of Radiosensitizer using farnesyltransferase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jong Seok; Choe, Yong Kyung; Han, Mi Young; Kim, Kwang Dong [Korea Research Institute of Bioscience and Biotechnology, Taejon (Korea)

    1999-03-01

    We selected some compounds that were reported to have an activity of farneyltransferase inhibitor and tested the hypothesis that they might be used to radiosensitize cells transformed by ras oncogenes. The inhibition of ras processing using some, but not all, inhibitors resulted in higher levels of cell death after {gamma}-irradiation and increased radiosensitivity in H-ras-transformed NIH3T3 cells and MCF-10A human tumor cells. They did not induce additional cell death in control cells that doe not have ras mutation. Furthermore, the treatment of inhibitors alone induced a weak G0/G1 block, whereas inhibitors in combination with {gamma}-irradiation induced an additional enrichment in the G2/M phase of the cell cycle that typically represents irradiation-induced growth arrest. At present, the underling mechanism by which the farnesylltransferase inhibitors exert radiosensitizing effect is not known. In summary, our results suggest and lead to the possibility that some of farnesylation inhibitors may prove clinically useful not only as antitumor agents, but also radiosensitizers of tumors whose growth is dependent on ras function. (author). 15 refs., 10 figs., 4 tabs.

  2. Photosensitizers and radiosensitizers in dermatology and oncology

    International Nuclear Information System (INIS)

    Bruckner, V.

    1979-01-01

    Two therapeutic modalities are currently of great interest, namely photo- and radiosensitization. Whereas photosensitizers only function in combination with ultraviolet (UV) light, radiosensitizers act only in combination with ionizing radiation. Because of the small UV penetration, up to a maximum of 0,5 mm, photosensitization can take place only at the surface of the body, i.e. the skin. Photosensitizers are applied in dermatology in order to optimize and improve the UV therapy of certain diseases (mainly psoriasis, mycosis fungoides and vitiligo). Radiosensitizers lead to an increase in sensitivity of the hypoxic and therefore radioresistant parts of tumours against X- and gamma-radiation. With sufficient concentration within the tumour, they can act where the radiation can reach, even in the deeper parts of the body. They represent a modern and useful aid to radiation oncology. Because of neurotoxic effects, however, their practical use is limited. A short review of the history, mechanisms of action, application and side-effects of these photo- and radiosensitizers is presented

  3. Photosensitizers and radiosensitizers in dermatology and oncology

    Energy Technology Data Exchange (ETDEWEB)

    Bruckner, V [Stellenbosch University, Parowvallei (South Africa). Departments of Medical Physics and Radiology

    1979-09-22

    Two therapeutic modalities are currently of great interest, namely photo- and radiosensitization. Whereas photosensitizers only function in combination with ultraviolet (UV) light, radiosensitizers act only in combination with ionizing radiation. Because of the small UV penetration, up to a maximum of 0,5 mm, photosensitization can take place only at the surface of the body, i.e. the skin. Photosensitizers are applied in dermatology in order to optimize and improve the UV therapy of certain diseases (mainly psoriasis, mycosis fungoides and vitiligo). Radiosensitizers lead to an increase in sensitivity of the hypoxic and therefore radioresistant parts of tumours against X- and gamma-radiation. With sufficient concentration within the tumour, they can act where the radiation can reach, even in the deeper parts of the body. They represent a modern and useful aid to radiation oncology. Because of neurotoxic effects, however, their practical use is limited. A short review of the history, mechanisms of action, application and side-effects of these photo- and radiosensitizers is presented.

  4. Phytochemicals radiosensitize cancer cells by inhibiting DNA repair

    International Nuclear Information System (INIS)

    Singh, Rana P.

    2017-01-01

    Solid tumors are mostly treated with radiotherapy. Radiotherapy is toxic to normal tissues and also promote the invasiveness and radioresistance in cancer cells. The resistance against radiotherapy and adverse effects to normal cells reduce the overall therapeutic effects of the treatment. Radiosensitizing agents usually show limited success during clinical trials. Therefore, the search and development of new radiosensitizers showing selective response to only cancer cells is desirable. We analyzed the radiosensitizing effects including cell death effect of silibinin, a phytochemical on prostate cancer cells. Silibinin enhanced gamma radiation (2.5-10 Gy) induced inhibition in colony formation selectively in prostate cancer cells. In cell cycle progression, G2/M phase is the most sensitive phase for radiation-induced damage which was delayed by the compound treatment in radiation exposed cells. The lower concentrations of silibinin substantially enhanced radiation-induced apoptosis. A prolonged reactive oxygen species production was also observed in these treatments EGFR signaling pathway can contribute to radiation-induced pro-survival mechanisms and to the therapeutic resistance. Agent treatment reduced the IR-induced EGFR phosphorylation and consequently reversed the resistance mediating mechanisms within the cancer cell. Thus, inhibiting DNA repair in cancer cells would enhance therapeutic response of radiation in cancer cells. Silibinin affected the localization of EGFR and DNA-dependent protein kinase, the DNA-PK is known to be an important mediator of DSB repair in human cells, and showed increased number of pH2AX (ser139) foci, and thus indicating lower DNA repair in these cancer cells. This was also confirmed in the tumor xenograft study. Our findings suggest that a combination of silibinin with radiation could be an effective treatment of radioresistant human prostate cancer and warrants further investigation. (author)

  5. Hereditary syndromes with enhanced radiosensitivity

    International Nuclear Information System (INIS)

    Lohmann, D.

    2000-01-01

    Sensitivity to ionizing radiation is modified by heritable genetic factors. This is exemplified by heritable disorders that are characterized by predisposition to the development of neoplasms. Cells derived from patients with ataxia telangiectasia, Nijmegen breakage syndrome and ataxia telangiektasia-like disorder show a markedly changed reaction to exposure to ionizing radiation. Correspondingly, at least in patients with ataxia telangiectasia, an enhanced radiosensitivity that is of clinical importance has been observed. In addition to these recessive disorders, some autosomal dominant cancer predisposition syndromes are associated with increased radiosensitivity. As cells from these patients still have a normal allele (that is dominant over the mutant allele), the cellular phenotype is most often normal. Specifically, there is no overtly altered reaction in response to ionizing radiation. Nevertheless, two dominant cancer predisposition syndromes, namely hereditary retinoblastoma and naevoid basal cell carcinoma syndrome, are associated with a enhanced radiosensitivity as indicated by increased development of tumors following radiation therapy. (orig.) [de

  6. MiR-122 Induces Radiosensitization in Non-Small Cell Lung Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Debin Ma

    2015-09-01

    Full Text Available MiR-122 is a novel tumor suppresser and its expression induces cell cycle arrest, or apoptosis, and inhibits cell proliferation in multiple cancer cells, including non-small cell lung cancer (NSCLC cells. Radioresistance of cancer cell leads to the major drawback of radiotherapy for NSCLC and the induction of radiosensitization could be a useful strategy to fix this problem. The present work investigates the function of miR-122 in inducing radiosensitization in A549 cell, a type of NSCLC cells. MiR-122 induces the radiosensitization of A549 cells. MiR-122 also boosts the inhibitory activity of ionizing radiation (IR on cancer cell anchor-independent growth and invasion. Moreover, miR-122 reduced the expression of its targeted genes related to tumor-survival or cellular stress response. These results indicate that miR-122 would be a novel strategy for NSCLC radiation-therapy.

  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. Caffeine and the olfactory bulb.

    Science.gov (United States)

    Hadfield, M G

    1997-08-01

    Caffeine, a popular CNS stimulant, is the most widely used neuroactive drug. Present in coffee, tea, chocolate, and soft drinks as well as over-the-counter and prescription medications, it influences millions of users. This agent has achieved recent notoriety because its dependency consequences and addictive potential have been re-examined and emphasized. Caffeine's central actions are thought to be mediated through adenosine (A) receptors and monoamine neurotransmitters. The present article suggests that the olfactory bulb (OB) may be an important site in the brain that is responsible for caffeine's central actions in several species. This conclusion is based on the extraordinarily robust and selective effects of caffeine on norepinephrine (NE), dopamine (DA), and particularly serotonin (5HT) utilization in the OB of mice. We believe that these phenomena should be given appropriate consideration as a basis for caffeine's central actions, even in primates. Concurrently, we review a rich rodent literature concerned with A, 5HT, NE, and DA receptors in the OB and related structures along with other monoamine parameters. We also review a more limited literature concerned with the primate OB. Finally, we cite the literature that treats the dependency and addictive effects of caffeine in humans, and relate the findings to possible olfactory mechanisms.

  9. Design, formulation and evaluation of caffeine chewing gum.

    Science.gov (United States)

    Aslani, Abolfazl; Jalilian, Fatemeh

    2013-01-01

    Caffeine which exists in drinks such as coffee as well as in drug dosage forms in the global market is among the materials that increase alertness and decrease fatigue. Compared to other forms of caffeine, caffeine gum can create faster and more prominent effects. In this study, the main goal is to design a new formulation of caffeine gum with desirable taste and assess its physicochemical properties. Caffeine gum was prepared by softening of gum bases and then mixing with other formulation ingredients. To decrease the bitterness of caffeine, sugar, aspartame, liquid glucose, sorbitol, manitol, xylitol, and various flavors were used. Caffeine release from gum base was investigated by mechanical chewing set. Content uniformity test was also performed on the gums. The gums were evaluated in terms of organoleptic properties by the Latin-Square design at different stages. After making 22 formulations of caffeine gums, F11 from 20 mg caffeine gums and F22 from 50 mg caffeine gums were chosen as the best formulation in organoleptic properties. Both types of gum released about 90% of their own drug content after 30 min. Drug content of 20 and 50 mg caffeine gum was about 18.2-21.3 mg and 45.7-53.6 mg respectively. 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.

  10. Caffeinated beverage intake and reproductive hormones among premenopausal women in the BioCycle Study.

    Science.gov (United States)

    Schliep, Karen C; Schisterman, Enrique F; Mumford, Sunni L; Pollack, Anna Z; Zhang, Cuilin; Ye, Aijun; Stanford, Joseph B; Hammoud, Ahmad O; Porucznik, Christina A; Wactawski-Wende, Jean

    2012-02-01

    Caffeinated beverages are widely consumed among women of reproductive age, but their association with reproductive hormones, and whether race modifies any such associations, is not well understood. We assessed the relation between caffeine and caffeinated beverage intake and reproductive hormones in healthy premenopausal women and evaluated the potential effect modification by race. Participants (n = 259) were followed for up to 2 menstrual cycles and provided fasting blood specimens for hormonal assessment at up to 8 visits per cycle and four 24-h dietary recalls per cycle. Weighted linear mixed models and nonlinear mixed models with harmonic terms were used to estimate associations between caffeine and hormone concentrations, adjusted for age, adiposity, physical activity, energy and alcohol intakes, and perceived stress. On the basis of a priori assumptions, an interaction between race and caffeine was tested, and stratified results are presented. Caffeine intake ≥200 mg/d was inversely associated with free estradiol concentrations among white women (β = -0.15; 95% CI: -0.26, -0.05) and positively associated among Asian women (β = 0.61; 95% CI: 0.31, 0.92). Caffeinated soda intake and green tea intake ≥1 cup/d (1 cup = 240 mL) were positively associated with free estradiol concentrations among all races: β = 0.14 (95% CI: 0.06, 0.22) and β = 0.26 (95% CI: 0.07, 0.45), respectively. Moderate consumption of caffeine was associated with reduced estradiol concentrations among white women, whereas caffeinated soda and green tea intakes were associated with increased estradiol concentrations among all races. Further research is warranted on the association between caffeine and caffeinated beverages and reproductive hormones and whether these relations differ by race.

  11. Protective effect of low dose caffeine on psychological stress and cognitive function.

    Science.gov (United States)

    Çakır, Özgür Kasımay; Ellek, Nurfitnat; Salehin, Nabila; Hamamcı, Rabia; Keleş, Hülya; Kayalı, Damla Gökçeoğlu; Akakın, Dilek; Yüksel, Meral; Özbeyli, Dilek

    2017-01-01

    Caffeine is an adrenergic antagonist that enhances neuronal activity. Psychological stress depresses cognitive function. To investigate the effects of acute and chronic low dose caffeine on anxiety-like behavior and cognitive functions of acute or chronic psychological stressed rats. Acute or chronic caffeine (3mg/kg) was administered to male Sprague Dawley rats (200-250g, n=42) before acute (cat odor) and chronic variable psychological stress (restraint overcrowding stress, elevated plus maze, cat odor, forced swimming) induction. Anxiety and cognitive functions were evaluated by hole-board and object recognition tests. The brain glutathione and malondialdehyde assays, myeloperoxidase, nitric oxide (NO), superoxide dismutase (SOD), luminol and lucigenin activity and histological examination were done. ANOVA and Student's t-test were used for statistical analysis. The depressed cognitive function with chronic stress exposure and the increased anxiety-like behavior with both stress inductions were improved via both caffeine applications (pcaffeine pretreatments in chronic stressed rats, and chronic caffeine in acute stressed ones reduced the elevated myeloperoxidase activities (pcaffeine (pcaffeine (pcaffeine decreased SOD activity (pcaffeine. The increased anxiety-like behavior and depleted cognitive functions under stress conditions were improved with both acute and predominantly chronic caffeine pretreatments by decreasing oxidative damage parameters. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. QSAR Study on Caffeine Derivatives Docked on Poly(ARNA Polymerase Protein Cid1

    Directory of Open Access Journals (Sweden)

    Teodora E. Harsa

    2016-06-01

    Full Text Available Caffeine is the most commonly ingested alkylxantine and is recognized as a psycho-stimulant. It improves some aspects of cognitive performance, however it reduces the cerebral blood flow both in animals and humans. In this paper a QSAR study on caffeine derivatives, docked on the Poly(ARNA polymerase protein cid1, is reported. A set of forty caffeine derivatives, downloaded from PubChem, was modeled, within the hypermolecule strategy; the predicted activity was LD50 and prediction was done on similarity clusters with the leaders chosen as the best docked ligands on the Poly(ARNA polymerase protein cid1. It was concluded that LD50 of the studied caffeines is not influenced by their binding to the target protein. This work is licensed under a Creative Commons Attribution 4.0 International License.

  13. Evaluating Dependence Criteria for Caffeine

    OpenAIRE

    Striley, Catherine L.W.; Griffiths, Roland R.; Cottler, Linda B.

    2011-01-01

    Background: Although caffeine is the most widely used mood-altering drug in the world, few studies have operationalized and characterized Diagnostic and Statistical Manual IV (DSM-IV) substance dependence criteria applied to caffeine. Methods: As a part of a nosological study of substance use disorders funded by the National Institute on Drug Abuse, we assessed caffeine use and dependence symptoms among high school and college students, drug treatment patients, and pain clinic patients who re...

  14. Caffeine as a cause of urticaria-angioedema

    Directory of Open Access Journals (Sweden)

    Linda Tognetti

    2014-01-01

    Full Text Available We report the case of a young woman presenting with recurrent urticaria. The episodes occurred both in and out of the workplace. On three occasions it presented as urticaria-angioedema, requiring emergency care on one occassion. A thorough clinical history along with serological and allergological tests allowed a diagnosis of caffeine-induced urticaria-angioedema. We advised the patient to follow a caffeine-free diet and to avoid all caffeine or methylxanthine-containing drugs. After two years of caffeine abstinence, she had not experienced any further episodes of urticaria-angioedema. Only a few cases of caffeine-induced urticaria and/or anaphylaxis have been reported till date, with varying outcomes in allergologic investigations. Moreover, several cases are probably undiagnosed or misdiagnosed as idiopathic urticaria or as occupational allergy. We speculate that hypersensitivity to caffeine rather than autoimmine reaction may be the probable cause of urticaria. Caffeine should considered as a potential urticaria-inducing agent and should be included in the allergological test series.

  15. Stimulation of Intestinal Cl- Secretion Through CFTR by Caffeine Intake in Salt-Sensitive Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Xiao Wei

    2018-03-01

    Full Text Available Background/Aims: High salt consumption is a major risk factor for hypertension, and sodium homeostasis is regulated by both intestinal sodium absorption and urinary sodium excretion. Chronic caffeine intake has been reported to attenuate salt-sensitive hypertension by promoting urinary sodium excretion; however, its exact role in intestinal sodium absorption remains unknown. Here, we investigated whether and how chronic caffeine consumption antagonizes salt-sensitive hypertension by inhibiting intestinal sodium absorption. Methods: Dahl salt-sensitive rats were fed 8% NaCl chow and 0.1% caffeine in their drinking water for 15 days. The blood pressure and fecal sodium content were measured. The effect of caffeine on the movement of Cl- in enterocyte cells was determined with the Ussing chamber assay. Results: Rats that were treated with caffeine displayed significantly lower mean blood pressure and higher fecal sodium content than the controls. Consistent with these findings, caffeine intake decreased fluid absorption by the intestine in the fluid perfusion experiment. Further, the results from the Ussing chamber assay indicated that caffeine promoted Cl- secretion through enterocyte apical cystic fibrosis transmembrane conductance regulator (CFTR, and thus inhibited sodium absorption. Moreover, depletion of cAMP or inhibition of CFTR completely abolished the effect of caffeine on Cl- secretion. Conclusion: The results indicate that chronic caffeine consumption reduces sodium absorption by promoting CFTR-mediated Cl- secretion in the intestine, which contributes to the anti-hypertensive effect of caffeine in salt-sensitive rats.

  16. High Blood Caffeine Levels in MCI Linked to Lack of Progression to Dementia

    Science.gov (United States)

    Cao, Chuanhai; Loewenstein, David A.; Lin, Xiaoyang; Zhang, Chi; Wang, Li; Duara, Ranjan; Wu, Yougui; Giannini, Alessandra; Bai, Ge; Cai, Jianfeng; Greig, Maria; Schofield, Elizabeth; Ashok, Raj; Small, Brent; Potter, Huntington; Arendash, Gary W.

    2017-01-01

    Although both human epidemiologic and animal model studies have suggested that caffeine/coffee protects against Alzheimer’s disease, direct human evidence for this premise has been lacking. In the present case-control study, two separate cohorts consisting of 124 total individuals (65–88 years old) were cognitively assessed and a blood sample taken for caffeine/biomarker analysis. Subjects were then monitored for cognitive status over the ensuing 2–4 year period to determine the extent to which initial plasma caffeine/biomarkers levels would be predictive of changes in cognitive status. Plasma caffeine levels at study onset were substantially lower (−51%) in mild cognitive impairment (MCI) subjects who later progressed to dementia (MCI→DEM) compared to levels in stable MCI subjects (MCI→MCI). Moreover, none of the MCI→DEM subjects had initial blood caffeine levels that were above a critical level of 1200 ng/ml, while half of stable MCI→MCI subjects had blood caffeine levels higher than that critical level. Thus, plasma caffeine levels greater than 1200 ng/ml (≈6 µM) in MCI subjects were associated with no conversion to dementia during the ensuing 2–4 year follow-up period. Among the 11 cytokines measured in plasma, three of them (GCSF, IL-10, and IL-6) were decreased in MCI→DEM subjects, but not in stable MCI→MCI subjects with high plasma caffeine levels. Coffee would appear to be the major or perhaps only source of caffeine for such stable MCI patients. This case-control study provides the first direct evidence that caffeine/coffee intake is associated with a reduced risk of dementia or delayed onset, particularly for those who already have MCI. PMID:22430531

  17. Artificial sweeteners, caffeine, and alcohol intoxication in bar patrons.

    Science.gov (United States)

    Rossheim, Matthew E; Thombs, Dennis L

    2011-10-01

    Previous laboratory research on alcohol absorption has found that substitution of artificially sweetened alcohol mixers for sucrose-based mixers has a marked effect on the rate of gastric emptying, resulting in elevated blood alcohol concentrations. Studies conducted in natural drinking settings, such as bars, have indicated that caffeine ingestion while drinking is associated with higher levels of intoxication. To our knowledge, research has not examined the effects of alcohol mixers that contain both an artificial sweetener and caffeine, that is, diet cola. Therefore, we assessed the event-specific association between diet cola consumption and alcohol intoxication in bar patrons. We sought to determine whether putative increases in blood alcohol, produced by accelerated gastric emptying following diet cola consumption, as identified in the laboratory, also appear in a natural setting associated with impaired driving. We conducted a secondary analysis of data from 2 nighttime field studies that collected anonymous information from 413 randomly selected bar patrons in 2008 and 2010. Data sets were merged and recoded to distinguish between energy drink, regular cola, diet cola, and noncaffeinated alcohol mixers. Caffeinated alcohol mixers were consumed by 33.9% of the patrons. Cola-caffeinated mixed drinks were much more popular than those mixed with energy drinks. A large majority of regular cola-caffeinated mixed drink consumers were men (75%), whereas diet cola-caffeinated mixed drink consumers were more likely to be women (57%). After adjusting for the number of drinks consumed and other potential confounders, number of diet cola mixed drinks had a significant association with patron intoxication (β = 0.233, p 0.05). Caffeine's effect on intoxication may be most pronounced when mixers are artificially sweetened, that is, lack sucrose which slows the rate of gastric emptying of alcohol. Risks associated with on-premise drinking may be reduced by greater

  18. Characterization of Individuals Seeking Treatment for Caffeine Dependence

    OpenAIRE

    Juliano, Laura M.; Evatt, Daniel P.; Richards, Brian D.; Griffiths, Roland R.

    2012-01-01

    Previous investigations have identified individuals who meet criteria for DSM-IV-TR substance dependence as applied to caffeine, but there is little research on treatments for caffeine dependence. This study aimed to thoroughly characterize individuals who are seeking treatment for problematic caffeine use. Ninety-four individuals who identified as being psychologically or physically dependent on caffeine, or who had tried unsuccessfully to modify caffeine consumption participated in a face-t...

  19. 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...... fluvoxamine treatment may lead to caffeine intoxication. Finally, our study provides additional evidence that fluvoxamine can be used to probe CYP1A2 in drug metabolism....

  20. Radiosensitization of human endothelial cells by IL-24

    International Nuclear Information System (INIS)

    Meyn, R.E.

    2003-01-01

    Radiation therapy remains an important cancer treatment modality but despite improvements in dose delivery many patients still fail at their primary tumor site. Therefore, new strategies designed to improve local control are needed. Protocols combining radiation with anti-angiogenic agents might be of particular advantage based on their documented low toxicity. In this regard, we have been conducting preclinical investigations of a novel cytokine, mda7/IL-24. Our collaborators have shown that mda7/IL-24 protein targets the endothelial cells of the tumor microvascular system and has potent anti-angiogenic properties in both in vitro and in vivo assays. Recently, we have demonstrated that recombinant mda7/IL-24 protein radiosensitizes human endothelial cells in vitro. Specifically, 10 ng/ml of recombinant human IL-24 protein for 12 hrs reduced the survival at 2 Gy for human umbilical vein endothelial cells (HUVECs) from 0.33 to 0.12. We are also working on understanding the molecular basis for this radiosensitizing effect. Preliminary data suggest a model whereby mda7/IL-24 engages a specific receptor on the surface of endothelial cells and initiates a signal transduction pathway that modulates the cell's propensity for radiation-induced apoptosis and capacity for repairing radiation-induced DNA double strand breaks. Mechanistic insight gained from these studies may have implications for the actions of other anti-angiogenic agents and may generally explain the regulation of radiosensitivity imparted by growth factors and cytokines

  1. Energy drinks and the neurophysiological impact of caffeine.

    Science.gov (United States)

    Persad, Leeana Aarthi Bagwath

    2011-01-01

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

  2. Energy drinks and the neurophysiological impacts of caffeine

    Directory of Open Access Journals (Sweden)

    Leeana eBagwath Persad

    2011-10-01

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

  3. Caffeine and cognition in functional magnetic resonance imaging.

    Science.gov (United States)

    Koppelstaetter, Florian; Poeppel, Thorsten D; Siedentopf, Christian M; Ischebeck, Anja; Kolbitsch, Christian; Mottaghy, Felix M; Felber, Stephan R; Jaschke, Werner R; Krause, Bernd J

    2010-01-01

    Caffeine has been consumed since ancient times due to its beneficial effects on attention, psychomotor function, and memory. Caffeine exerts its action mainly through an antagonism of cerebral adenosine receptors, although there are important secondary effects on other neurotransmitter systems. Recently, functional MRI (fMRI) entered the field of neuropharmacology to explore the intracerebral sites and mechanisms of action of pharmacological agents. However, as caffeine possesses vasoconstrictive properties it may interfere with the mechanisms underlying the functional contrast in fMRI. Yet, only a limited number of studies dealt with the effect of caffeine on measures in fMRI. Even fewer neuroimaging studies examined the effects that caffeine exerts on cognition: Portas and colleagues used fMRI in an attentional task under different levels of arousal (sleep deprivation or caffeine administration), concluding that the thalamus is involved in mediating the interaction of attention and arousal. Bendlin and colleagues found caffeine to stabilize the extent of neuronal activation in repetitive word stem completion, counteracting the general task practice effect. Recently, Koppelstaetter and colleagues assessed the effect of caffeine on verbal working memory demonstrating a modulatory effect of caffeine on brain regions (medial frontopolar and anterior cingulate cortex) that have been associated with attentional and executive functions. This review surveys and discusses neuroimaging findings on 1) how caffeine affects the contrast underlying fMRI techniques, particularly the blood oxygen level dependent contrast (BOLD fMRI), and 2) how caffeine operates on neuronal activity underlying cognition, to understand the effect of caffeine on behavior and its neurobiological underpinnings.

  4. Effects of Cola-Flavored Beverages and Caffeine on Streptococcus mutans Biofilm Formation and Metabolic Activity.

    Science.gov (United States)

    Dotsey, Roger P; Moser, Elizabeth A S; Eckert, George J; Gregory, Richard L

    To examine the effects of cola-flavored beverages and caffeine on growth and metabolism of Streptococcus mutans biofilm. This study was designed to determine if carbonated beverages or caffeine can increase S. mutans growth and biofilm formation and metabolic activity in vitro, potentially leading to increased S. mutans-associated cariogenicity in children that consume them. Six different cola-flavored products, plus pure caffeine, and pure high fructose corn syrup (HFCS), at different concentrations similar to those in the beverages were tested. A 16-hour culture of S. mutans was treated with different dilutions in bacteriological media. To test for the effect on biofilm formation, the biofilm was stained with crystal violet. The absorbance was determined to evaluate biofilm growth. Biofilm metabolic activity was measured based on biofilm having the ability to reduce XTT to a water-soluble orange compound. The inclusion of HFCS in the beverages, as well as pure HFCS, significantly enhanced bacterial biofilm formation and metabolic activity. Pure caffeine and the presence of caffeine in beverages did not significantly increase biofilm formation, but pure caffeine significantly increased metabolism, and Diet Coke had significantly greater metabolic activity than Caffeine-Free Diet Coke. HFCS increases both the biofilm formation and metabolism of S. mutans, and caffeine in some cases increases metabolism of S. mutans.

  5. Radiosensitivity of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hennequin, C.; Quero, L.; Rivera, S.

    2011-01-01

    The frequency of hepatocellular carcinoma (HCC) is increasing in the western world and the role of radiotherapy is more and more discussed. Classically, hepatocellular carcinoma was considered as a radioresistant tumour: in fact, modern radio-biologic studies, performed on cell lines directly established from patients, showed that hepatocellular carcinoma has the same radiosensitivity than the other epithelial tumours. From clinical studies, its α/β ratio has been estimated to be around 15 Gy. Radiosensitivity of normal hepatic parenchyma is now well evaluated and some accurate NTCP models are available to guide hepatic irradiation. The biology of hepatocellular carcinoma is also better described: the combination of radiotherapy and targeted therapies will be a promising approach in the near future. (authors)

  6. Associations of Urinary Caffeine and Caffeine Metabolites With Arterial Stiffness in a Large Population-Based Study.

    Science.gov (United States)

    Ponte, Belen; Pruijm, Menno; Ackermann, Daniel; Ehret, Georg; Ansermot, Nicolas; Staessen, Jan A; Vogt, Bruno; Pechère-Bertschi, Antoinette; Burnier, Michel; Martin, Pierre-Yves; Eap, Chin B; Bochud, Murielle; Guessous, Idris

    2018-05-01

    To assess the influence of caffeine on arterial stiffness by exploring the association of urinary excretion of caffeine and its related metabolites with pulse pressure (PP) and pulse wave velocity (PWV). Families were randomly selected from the general population of 3 Swiss cities from November 25, 2009, through April 4, 2013. Pulse pressure was defined as the difference between the systolic and diastolic blood pressures obtained by 24-hour ambulatory monitoring. Carotid-femoral PWV was determined by applanation tonometry. Urinary caffeine, paraxanthine, theophylline, and theobromine excretions were measured in 24-hour urine collections. Multivariate linear and logistic mixed models were used to explore the associations of quartiles of urinary caffeine and metabolite excretions with PP, high PP, and PWV. We included 863 participants with a mean ± SD age of 47.1±17.6 years, 24-hour PP of 41.9±9.2 mm Hg, and PWV of 8.0±2.3 m/s. Mean (SE) brachial PP decreased from 43.5 (0.5) to 40.5 (0.6) mm Hg from the lowest to the highest quartiles of 24-hour urinary caffeine excretion (P<.001). The odds ratio (95% CI) of high PP decreased linearly from 1.0 to 0.52 (0.31-0.89), 0.38 (0.22-0.65), and 0.31 (0.18-0.55) from the lowest to the highest quartile of 24-hour urinary caffeine excretion (P<.001). Mean (SE) PWV in the highest caffeine excretion quartile was significantly lower than in the lowest quartile (7.8 [0.1] vs 8.1 [0.1] m/s; P=.03). Similar associations were found for paraxanthine and theophylline, whereas no associations were found with theobromine. Urinary caffeine, paraxanthine, and theophylline excretions were associated with decreased parameters of arterial stiffness, suggesting a protective effect of caffeine intake beyond its blood pressure-lowering effect. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  7. Radiosensitivity of human lymphocytes and thymocytes

    International Nuclear Information System (INIS)

    Kwan, D.K.; Norman, A.

    1977-01-01

    The in vitro survival of human peripheral blood lymphocytes and thymocytes was measured 4 days following graded doses of γ radiation. Results indicate considerable heterogeneity among lymphocyte subpopulations with respect to radiosensitivity. Total T lymphocytes were characterized by rosette formation with neuraminidase-treated sheep red blood cells (nSRBC); early T (T/sub E/) cells, by early rosettes; and B cells, by their inability to form nSRBC rosettes. Late T (T/sub L/) cells were defined as T -- T/sub E/. Survival curves of T, T/sub E/, and B cells are biphasic. The radiosensitive and radioresistant components of T, T/sub E/, and B cells all have a D 0 of about 50 and 550 rad, respectively. B cells appeared to be slightly more radiosensitive than T cells. T/sub L/ cells and thymocytes, however, appeared to be homogeneous with respect to radiosensitivity, both having D 0 values of about 135 rad. The survival of T cells in mixed T and B cell cultures resembled that of separated T cells, suggesting that ionizing radiation has no significant effect on rosette formation. It also indicates that interactions of T and B cells do not significantly affect their radiation responses

  8. 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.

  9. Caffeine intake and fecundability: a follow-up study among 430 Danish couples planning their first pregnancy.

    Science.gov (United States)

    Jensen, T K; Henriksen, T B; Hjollund, N H; Scheike, T; Kolstad, H; Giwercman, A; Ernst, E; Bonde, J P; Skakkebaek, N E; Olsen, J

    1998-01-01

    only source of caffeine was coffee (>300 mg/d) had a reduced fecundability odds-ratio (FR = 0.34; 95% CI 0.12-0.98). An interaction between 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.

  10. Antioxidant and cytotoxic activity of new di- and polyamine caffeine analogues.

    Science.gov (United States)

    Jasiewicz, Beata; Sierakowska, Arleta; Jankowski, Wojciech; Hoffmann, Marcin; Piorońska, Weronika; Górnicka, Agnieszka; Bielawska, Anna; Bielawski, Krzysztof; Mrówczyńska, Lucyna

    2018-04-18

    A series of new di- and polyamine-caffeine analogues were synthesized and characterized by NMR, FT-IR and MS spectroscopic methods. To access stability of the investigated caffeine analogues Molecular Dynamic simulations were performed in NAMD 2.9 assuming CHARMM36 force field. To evaluate the antioxidant capacity of new compounds, three different antioxidant assays were used, namely 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH • ) scavenging activity, ferrous ions (Fe 2+ ) chelating activity and Fe 3+ →Fe 2+ reducing ability. In vitro, the ability of new derivatives to protect human erythrocytes against oxidative haemolysis induced by free radical from 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH) was estimated. The cytotoxic activity was tested using MCF-7 breast cancer cells and human erythrocytes. All compounds showed the antioxidant capacity depending mostly on their ferrous ions chelating activity. In the presence of AAPH, some derivatives were able to effectively inhibit the oxidative haemolysis. Two derivatives, namely 8-(methyl(2-(methylamino)ethyl)-amino)caffeine and 8-(methyl(3-(methylamino)propyl)amino)caffeine, showed cytotoxic activity against MCF-7 breast cancer cells but not against human erythrocytes. Therefore, it is concluded that the selected di- and polyamine caffeine analogues, depending on their chemical structure, were able to minimize the oxidative stress and to inhibit the tumour cell grow. The confirmed antioxidant and cytotoxic properties of some caffeine derivatives make them attractive for potential applications in food or pharmaceutical industries.

  11. Review of our histological criteria for the radiosensitivity of uterine cervical cancer

    International Nuclear Information System (INIS)

    Tsukahara, Yoshiharu; Shiozawa, Kyuyo; Tsukamoto, Takashi; Sonehara, Morio; Noguchi, Hiroshi

    1975-01-01

    The determination of radiosensitiveness based on 111 operated specimens after test irradiation of 1000R was compared with that based on 64 specimens which had received biopsies seven days after irradiation. It was concluded that the determination of radiosensitiveness by local biopsy could be applied to practical use. The results of this study are listed as follows: (1) Radiosensitivity exists within tumor cells themselves before irradiation, while radiosensitiveness is a complicated change in which some reaction on the host side added to degenerated tumor cells. (2) In the determination of radio-sensitiveness, there was a good accordance of 85% between biopsies and removed specimens. (3) The followings are findings of favorable radiosensitiveness based on the removed specimens; (a) neutrocyte infiltration within cancer nests, (b) lysis of cancer nests, (c) destruction of fundus of cancer nests, (d) damages of advanced sites of cancer infiltration, (e) damages of chromatin. As unfavorable findings, (f) mitosis, (g) abundant viable cells. (4) Various histological findings within cancer nests and variation of radiosensitiveness according to various regions of the tumor often cause a discord with biopsies. (5) Many specimens which show the intermediate histological type in maturation before irradiation indicate favorable radiosensitiveness. Even if they belong to the intermediate type, the specimens in which the issued histological findings are mixed show mostly unfavorable radiosensitiveness. (6) Removed specimens can be expressed in indices of radiosensitiveness. (Ichikawa, K.)

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

    International Nuclear Information System (INIS)

    Sasaki, H.; Nishimoto, T.

    1989-01-01

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

  13. Chronic Caffeine Treatment Protects Against α-Synucleinopathy by Reestablishing Autophagy Activity in the Mouse Striatum.

    Science.gov (United States)

    Luan, Yanan; Ren, Xiangpeng; Zheng, Wu; Zeng, Zhenhai; Guo, Yingzi; Hou, Zhidong; Guo, Wei; Chen, Xingjun; Li, Fei; Chen, Jiang-Fan

    2018-01-01

    Despite converging epidemiological evidence for the inverse relationship of regular caffeine consumption and risk of developing Parkinson's disease (PD) with animal studies demonstrating protective effect of caffeine in various neurotoxin models of PD, whether caffeine can protect against mutant α-synuclein (α-Syn) A53T-induced neurotoxicity in intact animals has not been examined. Here, we determined the effect of chronic caffeine treatment using the α-Syn fibril model of PD by intra-striatal injection of preformed A53T α-Syn fibrils. We demonstrated that chronic caffeine treatment blunted a cascade of pathological events leading to α-synucleinopathy, including pSer129α-Syn-rich aggregates, apoptotic neuronal cell death, microglia, and astroglia reactivation. Importantly, chronic caffeine treatment did not affect autophagy processes in the normal striatum, but selectively reversed α-Syn-induced defects in macroautophagy (by enhancing microtubule-associated protein 1 light chain 3, and reducing the receptor protein sequestosome 1, SQSTM1/p62) and chaperone-mediated autophagy (CMA, by enhancing LAMP2A). These findings support that caffeine-a strongly protective environment factor as suggested by epidemiological evidence-may represent a novel pharmacological therapy for PD by targeting autophagy pathway.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, H.; Nishimoto, T. (Kyushu Univ., Fukuoka (Japan))

    1989-10-01

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

  15. Hyperthermic radiosensitization : mode of action and clinical relevance

    NARCIS (Netherlands)

    Kampinga, HH; Dikomey, E

    Purpose: To provide an update on the recent knowledge about the molecular mechanisms of thermal radiosensitization and its possible relevance to thermoradiotherapy. Summary: Hyperthermia is probably the most potent cellular radiosensitizer known to date. Heat interacts with radiation and potentiates

  16. HPLC determination of caffeine in coffee beverage

    Science.gov (United States)

    Fajara, B. E. P.; Susanti, H.

    2017-11-01

    Coffee is the second largest beverage which is consumed by people in the world, besides the water. One of the compounds which contained in coffee is caffeine. Caffeine has the pharmacological effect such as stimulating the central nervous system. The purpose of this study is to determine the level of caffeine in coffee beverages with HPLC method. Three branded coffee beverages which include in 3 of Top Brand Index 2016 Phase 2 were used as samples. Qualitative analysis was performed by Parry method, Dragendorff reagent, and comparing the retention time between sample and caffeine standard. Quantitative analysis was done by HPLC method with methanol-water (95:5v/v) as mobile phase and ODS as stationary phasewith flow rate 1 mL/min and UV 272 nm as the detector. The level of caffeine data was statistically analyzed using Anova at 95% confidence level. The Qualitative analysis showed that the three samples contained caffeine. The average of caffeine level in coffee bottles of X, Y, and Z were 138.048 mg/bottle, 109.699 mg/bottle, and 147.669 mg/bottle, respectively. The caffeine content of the three coffee beverage samples are statistically different (pcoffee beverage samples were not meet the requirements set by the Indonesian Standard Agency of 50 mg/serving.

  17. 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.

  18. 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.

  19. Caffeine-enhanced survival of radiation-sensitive, repair-deficient Chinese hamster cells

    International Nuclear Information System (INIS)

    Utsumi, H.; Elkind, M.M.

    1983-01-01

    A clone of V79 Chinese hamster cells (V79-AL162/S-10) with unique properties has been isolated after a challenge of parental cells (V79-AL162) with 1 mM ouabain. Compared with parental cells, or with other clones isolated after the ouabain challenge, these cells form smaller colonies, are more sensitive to both x rays and fission-spectrum neutrons, and respond atypically to a postirradiation treatment with caffeine. Their enhanced response to x rays results mainly from a large reduction in the shoulder of their survival curve, probably because in late S phase, the most resistant phase in the cell cycle, the survival curve of these cells has a reduced shoulder width. Caffeine, and to a lesser extent theophylline, added to the colony-forming medium immediately after exposure appreciably increases the width of the shoulder of these sensitive cells, whereas caffeine has the opposite effect on the response of normal V79 cells. Thus the unique response of the V79-AL162/S-10 cells to a radiation posttreatment with caffeine (increased survival) results from a net increase in their ability to repair damage that is otherwise lethal; caffeine treatment ordinarly prevents normal V79 cells from repairing damage that is only potentially lethal

  20. Caffeine protects mice against whole-body lethal dose of {gamma}-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    George, K.C.; Hebbar, S.A.; Kale, S.P.; Kesavan, P.C. [Biosciences Group, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)

    1999-06-01

    Administration of caffeine (1,3,7-trimethylxanthine), a major component of coffee, to Swiss mice at doses of 80 or 100 mg/kg body weight 60 min prior to whole-body lethal dose of {gamma}-irradiation (7.5 Gy) resulted in the survival of 70 and 63% of animals, respectively, at the above doses in contrast to absolutely no survivors (LD-100/25 days) in the group exposed to radiation alone. Pre-treatment with a lower concentration of caffeine (50 mg/kg) did not confer any radioprotection. The protection exerted by caffeine (80 mg/kg), however, was reduced from 70 to 50% if administered 30 min prior to irradiation. The trend statistics reveal that a dose of 80 mg/kg administered 60 min before whole-body exposure to 7.5 Gy is optimal for maximal radioprotection. However, caffeine (80 mg/kg) administered within 3 min after irradiation offered no protection. While there is documentation in the literature that caffeine is an antioxidant and radioprotector against the toxic pathway of radiation damage in a wide range of cells and organisms, this is the first report demonstrating unequivocally its potent radioprotective action in terms of survival of lethally whole-body irradiated mice. (author)

  1. Having a Coffee Break: The Impact of Caffeine Consumption on Microglia-Mediated Inflammation in Neurodegenerative Diseases.

    Science.gov (United States)

    Madeira, Maria H; Boia, Raquel; Ambrósio, António F; Santiago, Ana R

    2017-01-01

    Caffeine is the major component of coffee and the most consumed psychostimulant in the world and at nontoxic doses acts as a nonselective adenosine receptor antagonist. Epidemiological evidence suggests that caffeine consumption reduces the risk of several neurological and neurodegenerative diseases. However, despite the beneficial effects of caffeine consumption in human health and behaviour, the mechanisms by which it impacts the pathophysiology of neurodegenerative diseases still remain to be clarified. A promising hypothesis is that caffeine controls microglia-mediated neuroinflammatory response associated with the majority of neurodegenerative conditions. Accordingly, it has been already described that the modulation of adenosine receptors, namely, the A 2A receptor, affords neuroprotection through the control of microglia reactivity and neuroinflammation. In this review, we will summarize the main effects of caffeine in the modulation of neuroinflammation in neurodegenerative diseases.

  2. 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...

  3. Studies on Drosophila radiosensitivity strains

    International Nuclear Information System (INIS)

    Varentsova, E.R.; Sharygin, V.I.; Khromykh, Yu.U.

    1985-01-01

    Fertility of radiosensitive mutant drosophila female strain rad (2) 201 61 after irradiation and frequency of dominant lethal mutations (DLM), induced by γ-radiation for 0-5 h and 5-7 days, are investigated. It is shown, that oocytes of the mutant strain are more radiosensitive as compared with cells of mongrel flies as to criterion of DLM appearance over the period of maturing. Early oocytes of stages 2-7 are the most sensitive, i.e. at the stages, corresponding to the manifestation of previously established recombination-defective properties of mutations rad (2) 201 61 . It is also sown, that doses of γ-rays, exceeding 10 Gy produce a strong sterilizing effect on mutant females due to destruction and resorption of egg chambers, irradiated at the stages of previtellogenetic growth of oocytes. In females, carrying mutation of radiosensitivity there is no direct correlation betwen sensitivity of oocytes proper to DLM induction and sensitivity of egg folleicles to resorbing effect of γ-rays. The ways of possible involvement of mutant locus studied into genetic processes in various specialized cells of drosophila

  4. 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 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.

  5. Radiosensitivity of primary cultured fish cells with different ploidy

    International Nuclear Information System (INIS)

    Mitani, Hiroshi; Egami, Nobuo; Kobayashi, Hiromu.

    1986-01-01

    The radiosensitivity of primary cultured goldfish cells (Carassius auratus) was investigated by colony formation assay. The radiosensitivity of cells from two varieties of goldfish, which show different sensitivity to lethal effect of ionizing radiation in vivo, was almost identical. Primary cultured cells from diploid, triploid and tetraploid fish retained their DNA content as measured by microfluorometry, and the nuclear size increases as ploidy increases. However, radiosensitivity was not related to ploidy. (author)

  6. Caffeine products consumption habits of vilnius university students

    OpenAIRE

    Acus, Edgaras

    2017-01-01

    A small amount of caffeine in caffeine-containing products helps with stimulating labor activity, but an overdose of caffeine can cause a health hazard, so it is important to pay close attention to the use of caffeine-containing products. The use of psychoactive drugs is very important public health problem, because students attitude to addictive substances can influence their behavior in their family, the labor market and in society in general. Although caffeine is a natural product, but the...

  7. Effects of catechins and caffeine on the development of atherosclerosis in mice.

    Science.gov (United States)

    Liu, Litong; Nagai, Izumi; Gao, Ying; Matsushima, Yoshibumi; Kawai, Yoshichika; Sayama, Kazutoshi

    2017-10-01

    Atherosclerosis is one of the diseases related to metabolic syndrome which is caused by obesity. Previous reports have shown that green tea and its components have anti-obesity effect. We examined whether catechins and caffeine can prevent the development of atherosclerosis by oral administration, singly or in combination to the atherosclerosis model mice. Results demonstrated that the number of atherosclerotic regions in the aorta was significantly reduced by the combined treatment, and the atherosclerotic area was also improved. Serum HDL-C increased by caffeine single treatment, but no effect on the TG and TC by any treatments. Moreover, ECG illuviated to atheromatous lesions in aorta and the illuviation was enhanced by caffeine. The mRNA expression levels of LOX-1 and TNF-α showed a tendency to suppress by the combined treatment. These results indicated that the combined administration of catechins and caffeine has the inhibitory effect on the development of atherosclerosis in mice.

  8. Study of radiosensitization of chloroquine on esophageal cancer cell line

    International Nuclear Information System (INIS)

    Yuan Xiaoli; Li Tao; Huang Jianming; Zha Xiao; Deng Bifang; Lang Jinyi

    2014-01-01

    Objective: To investigate the possibility of chloroquine radiosensitization of esophageal cancer cell line TE-1 and its further mechanism. Methods: Effect of chloroquine on cell viability of TE-1 cells was determined by MTT method. Expression of LC3, Beclin-1 and formation of acidic vesicular organelles (AVOs) were determined by Western blot, and fluorescence staining with Lyso-Tracker Red DND-99, respectively. Clonogenic survival of TE-1 cells was examined by clonogenic forming assay. Results: Chloroquine showed dose-dependent inhibition of TE-1 cell growth, and its values of IC_5_0 and IC_1_0 were (72.33±5.28) and (15.42±3.33) μmol/L, respectively. The expression of Beclin-1 and LC3-II/I markedly increased in irradiated TE-1 cells. The addition of chloroquine with IC_1_0 concentration significantly reduced the fluorescence and intensity of AVOs accumulation in the cytoplasm of TE-1 cells. Clonogenic survival fraction decreased obviously in TE-1 cells with addition of chloroquine after radiation and the value of SERD0 was 1.439. Conclusions: Chloroquine could radiosensitize esophageal cancer cells by blocking autophagy-lysosomal pathway and be used as a potential radiosensitizing strategy. (authors)

  9. Mutagenic and epigenetic influence of caffeine on the frequencies of UV-induced ouabain-resistant Chinese hamster cells

    International Nuclear Information System (INIS)

    Chang, Chia-Cheng; Philipps, C.; Trosko, J.E.; Hart, R.W.

    1977-01-01

    Caffeine, given as a post-treatment to UV-irradiated Chinese hamster cells in vitro, modified the frequency of induced mutations at the ouabain resistance locus. Mutation frequencies were increased when caffeine was added only for the DNA repair and mutation fixation period. When caffeine was added after the DNA repair and mutation fixation period, or immediately after DNA damage and for the entire repair and selection period, mutation frequencies were reduced. A hypothesis, given to explain both results, is that caffeine, by blocking a constitutive 'error-free' postreplication repair process, allows an 'error-prone' DNA repair process to produce many mutations. Moreover, caffeine, possibly by modifying C-AMP metabolism, causes a repression of induced mutations which, in effect, explains its anti-mutagenic and anti-carcinogenic properties

  10. Lethality of radiation-induced chromosome aberrations in human tumour cell lines with different radiosensitivities.

    Science.gov (United States)

    Coco-Martin, J M; Ottenheim, C P; Bartelink, H; Begg, A C

    1996-03-01

    In order to find an explanation for the eventual disappearance of all chromosome aberrations in two radiosensitive human tumour cell lines, the type and stability of different aberration types was investigated in more detail. To classify the aberrations into unstable and stable types, three-colour fluorescence in situ hybridization was performed, including a whole-chromosome probe, a pancentromere probe, and a stain for total DNA. This technique enables the appropriate classification of the aberrations principally by the presence (stable) or not (unstable) of a single centromere per chromosome. Unstable-type aberrations were found to disappear within 7 days (several divisions) in the two radiosensitive and the two radioresistant tumour lines investigated. Stable-type aberrations were found to remain at an approximately constant level over the duration of the experiment (14 days; 8-10 divisions) in the two radioresistant lines. In contrast, the majority of these stable-type aberrations had disappeared by 14 days in the two radiosensitive lines. The previous findings of disappearance of total aberrations in radiosensitive cells was therefore not due to a reduced induction of stable-type aberrations, but the complete disappearance of cells with this aberration type. These results could not be explained by differences in apoptosis or G1 blocks. Two possible explanations for these unexpected findings involve non-random induction of unstable-type aberrations, or lethality of stable-type aberrations. The results suggest caution in the use of stable-type aberration numbers as a predictor for radiosensitivity.

  11. Energy Drinks and the Neurophysiological Impact of Caffeine

    OpenAIRE

    Persad, Leeana Aarthi Bagwath

    2011-01-01

    Caffeine is the most widely used psychoactive stimulant with prevalent use across all age groups. It is a naturally occurring substance found in the coffee bean, tea leaf, the kola nut, cocoa bean. Recently there has been an increase in energy drink consumption leading to caffeine abuse, with aggressive marketing and poor awareness on the consequences of high caffeine use. With caffeine consumption being so common, it is vital to know the impact caffeine has on the body, as its effects can in...

  12. Energy drinks and the neurophysiological impacts of caffeine

    OpenAIRE

    Leeana eBagwath Persad

    2011-01-01

    Caffeine is the most widely used psychoactive stimulant with prevalent use across all age groups. It is a naturally occurring substance found in the coffee bean, tea leaf, the kola nut, cocoa bean. Recently there has been an increase in energy drink consumption leading to caffeine abuse, with aggressive marketing and poor awareness on the consequences of high caffeine use. With caffeine consumption being so common, it is vital to know the impact caffeine has on the body, as its effects can in...

  13. Caffeine effects on mood and memory.

    Science.gov (United States)

    Herz, R S

    1999-09-01

    The purpose of the present research was to assess whether a psychoactive dose of caffeine would have differential affects on the mood dimensions of arousal versus feelings of pleasantness and whether these mood alterations would influence memory either by (1) the experience of arousal at learning and/or (2) altered and congruent mood states at learning and recall. To address these questions, the administration of 5 mg/kg caffeine or placebo at learning and retrieval sessions was manipulated and subjects' mood was evaluated by several different self-report measures. Sixteen words were incidentally studied during the learning session and memory was evaluated by the number of words correctly recalled at the retrieval session two days later. Results revealed that caffeine reliably increased arousal, but did not affect any emotion dimensions related to feelings of pleasure. Subjects who received caffeine at learning and retrieval were also in equivalent mood states at both sessions. Moreover, caffeine did not produce any effects on memory; thus, neither hypothesis concerning the influence of arousal on memory was supported. These data show that caffeine is a useful method for manipulating arousal in the laboratory without influencing feelings of pleasantness or learning and memory performance.

  14. Differential radiosensitivity among B cell subpopulations

    International Nuclear Information System (INIS)

    Riggs, J.E.

    1988-01-01

    The selective radiosensitivity of sIgM >> sIgD marginal zone B cells is associated with the selective loss of B cell function. The simultaneous restoration of impaired function and recovery of these cells with time supports this premise. B cell recovery, delayed one week after irradiation, is in progress at two weeks, and virtually complete by three weeks. XID mice reveal similar recovery kinetics although there are fewer recovering cells and these bear reduced levels of Ia. This observation represents additional evidence that xid B cells are distinct from those of normal mice. The simultaneous loss, and concurrent recovery, of sIgM >> sIgD B cells and TI-2 responsiveness in irradiated mice suggests the existence of a unique B cell subpopulation possessing both phenotypes. Additional support for this hypothesis is provided by demonstrating that splenocytes, depleted of IgD + cells adoptively reconstitute this response in XID mice. The peritoneal B cell pool, which, compared to the spleen, consist of increased numbers of sIgM >> sIgD B cells, is shown to be a source of radiosensitive B cells that are TI-2 responsive. These observations represent additional evidence for an association between sIgM >> sIgD B cells and TI-2 responsiveness

  15. Temporal patterns of caffeine intake in the United States.

    Science.gov (United States)

    Martyn, Danika; Lau, Annette; Richardson, Philip; Roberts, Ashley

    2018-01-01

    To investigate whether caffeine intake among adolescents and adults in the U.S. varies across the week or throughout the day, data from a 7-day online beverage consumption survey (2010-2011) were analyzed. Mean (206.8-213.0 mg/day) and 90th percentile (437.4-452.6 mg/day) daily caffeine intakes among consumers 13 years and older were relatively constant across the week with no marked difference among weekdays versus weekend days. Percent consumers of caffeinated beverages likewise remained stable across the week. Mean daily caffeine intake for coffee and energy drink consumers 13 years and older was higher than contributions for tea and carbonated soft drink consumers. Caffeinated beverage consumers (13 + yrs) consumed most of their caffeine in the morning (61% versus 21% and 18% in the afternoon and evening) which was driven by coffee. Caffeinated beverage consumption patterns among adolescents (13-17 yrs) - who typically consume less daily caffeine - were more evenly distributed throughout the day. These findings provide insight into U.S. temporal caffeine consumption patterns among specific caffeinated beverage consumers and different age brackets. These data suggest that while caffeine intakes do not vary from day-to-day, mornings generally drive the daily caffeine intake of adults and is predominantly attributed to coffee. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Metabolic effects of physiological levels of caffeine in myotubes.

    Science.gov (United States)

    Schnuck, Jamie K; Gould, Lacey M; Parry, Hailey A; Johnson, Michele A; Gannon, Nicholas P; Sunderland, Kyle L; Vaughan, Roger A

    2018-02-01

    Caffeine has been shown to stimulate multiple major regulators of cell energetics including AMP-activated protein kinase (AMPK) and Ca 2+ /calmodulin-dependent protein kinase II (CaMKII). Additionally, caffeine induces peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial biogenesis. While caffeine enhances oxidative metabolism, experimental concentrations often exceed physiologically attainable concentrations through diet. This work measured the effects of low-level caffeine on cellular metabolism and gene expression in myotubes, as well as the dependence of caffeine's effects on the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPARβ/δ). C2C12 myotubes were treated with various doses of caffeine for up to 24 h. Gene and protein expression were measured via qRT-PCR and Western blot, respectively. Cellular metabolism was determined via oxygen consumption and extracellular acidification rate. Caffeine significantly induced regulators of mitochondrial biogenesis and oxidative metabolism. Mitochondrial staining was suppressed in PPARβ/δ-inhibited cells which was rescued by concurrent caffeine treatment. Caffeine-treated cells also displayed elevated peak oxidative metabolism which was partially abolished following PPARβ/δ inhibition. Similar to past observations, glucose uptake and GLUT4 content were elevated in caffeine-treated cells, however, glycolytic metabolism was unaltered following caffeine treatment. Physiological levels of caffeine appear to enhance cell metabolism through mechanisms partially dependent on PPARβ/δ.

  17. Caffeine addiction: Need for awareness and research and regulatory measures.

    Science.gov (United States)

    Jain, Shobhit; Srivastava, Adya Shanker; Verma, Raghunath Prasad; Maggu, Gaurav

    2017-02-04

    Caffeine consumption has been constantly growing in India especially among children and youngsters. Addictive potential of caffeine has long been reported, still there is lack of awareness about caffeine abuse in India. There is an intense need for appropriate public health regulatory measures and awareness about addictive potential & harms related to caffeine. To the best of our knowledge this is first case from India highlighting several important issues with progressive caffeine abuse resulting in dependence leading to physical, psychological, academic and social consequences; psychotic symptoms during intoxication; predisposing factors as impulsivity and novelty seeking traits in pre-morbid personality; psychosis in family; poor awareness of health hazards even among medical professionals. Widely variable caffeine containing products are available but caffeine content or its safety limit is not mentioned on caffeine products in India. Due to harmful consequences, legal availability to children, growing consumption of caffeine products, it is utmost essential to recognize caffeine as addictive substance and impose regulatory measures on sale, advertisement, maximum caffeine content, health consequences and safety limits of caffeine containing products. Further school teachers, parents and medical practitioners need to be made aware of health hazards of caffeine. Caffeine use shall always be enquired from patients presenting with psychiatric complaints. Further research and survey are required on caffeine use and related problems. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Tumour-specific radiosensitizers for radiation therapy

    International Nuclear Information System (INIS)

    Denekamp, J.

    1977-01-01

    Recently Adams and coworkers at the Gray Laboratory have developed a new class of radiosensitizers which act specifically on hypoxic cells by abolishing the protection afforded by low oxygen concentrations. Since most experimental tumours contain a high proportion of oxygen-deprived cells, and most normal tissues are well oxygenated, these drugs are tumour specific radiosensitizers. Based on the hypothesis that sensitization increases with increasing electron affinity, the two nitroimidazoles, metronidazole (Flagyl) and Ro-07/0582 were identified as potent radiosensitizers with low toxicity. These drugs are effective only in the absence of oxygen, and only if the drug is present at the time of irradiation. The degree of sensitization increases with drug concentration rapidly over the range 0.1 to 1.0mg/g body weight for Ro-07-0582, and more gradually for Flagyl. Tumour studies have been performed on at least 12 different experimental tumours, using a variety of end points. Significant sensitization has been observed in every tumour studied, often corresponding to a dose reduction factor of 2.0 for high but non-toxic drug doses. Fractionated studies have also been performed on a few tumour lines. In most cases a useful therapeutic advantage was observed, although the sensitization was smaller. Ro-07-0582 used with X-rays gives a therapeutic gain comparable with that from cyclotron-produced fast neutrons. Neutrons used together with Ro-07-0582 are even more effective. In addition to the radiosensitization there is a specific cytotoxicity to hypoxic cells after prolonged exposure to Ro-07-0582. This cytotoxicity can be greatly enhanced in vitro by moderate hyperthermia. Flagyl and Ro-07-0582 have been used clinically as radiosensitizers, with promising early results. The clinical application is limited to certain dose fractionation patterns because of neurotoxicity. (author)

  19. Radiosensitivity of lymphocytes among Filipinos: final report

    International Nuclear Information System (INIS)

    Medina, F.I.S.; Gregorio, J.S.; Aguilar, C.P.; Poblete, E.E.

    1996-01-01

    This report is about the studies on the radiosensitivity of Filipino lymphocytes to radiation that can elucidate on the potential of blood chromosomes as biological dosimeters. The objective of this study is to determine the radiosensitivity of lymphocytes among Filipinos and to establish the radiation-induced chromosome anomaly standard curve in lymphocytes for radiological dosimetry. 47 refs., 9 figs., 1 tab

  20. Caffeine use and dependence in adolescents: one-year follow-up.

    Science.gov (United States)

    Oberstar, Joel V; Bernstein, Gail A; Thuras, Paul D

    2002-01-01

    The objectives were to conduct a 1-year follow-up of daily caffeine-using adolescents to further describe caffeine dependence symptoms and to determine whether caffeine dependence is associated with other substance dependence disorders. Twenty-one of 36 (58.3%) adolescents who participated in a study of caffeine dependence returned for follow-up. The previous study was a case series of adolescents who consumed caffeine daily and met some Diagnostic and Statistical Manual of Mental Disorders (fourth edition) substance dependence criteria as applied to caffeine. At follow-up, caffeine consumption from beverages was 179.9 +/- 151.8 mg/day. Of the 21 teenagers, 23.8% (n = 5) met criteria for caffeine dependence. Four of these participants developed caffeine dependence during the follow-up period. Other substance dependence disorders were not overrepresented in the caffeine dependent group compared to the caffeine nondependent group. The most commonly reported withdrawal symptoms in dependent teenagers (at baseline and follow-up combined) were feeling drowsy/tired, fatigued, or sluggish/slowed down (83.3% each) and headache (75.0%). Caffeine dependence occurs in some adolescents who drink caffeine daily and is marked by symptoms similar to those found in adults.

  1. Cellular radiosensitivity in human severe-combined-immunodeficiency (SCID) syndromes

    International Nuclear Information System (INIS)

    Sproston, Anthony R.M.; West, Catharine M.L.; Hendry, Jolyon H.

    1997-01-01

    Purpose: The aim of the work was to establish to what extent a variety of human severe-combined-immunodeficiency (SCID) disorders are associated with in vitro cellular hypersensitivity to ionizing radiation. Materials and methods: A study was made of fibroblast strains established from individuals with adenosine deaminase deficiency, T(-)B(-) SCID, Omenn's syndrome and a SCID heterozygote. For comparison, an assessment was also made of the radiosensitivity of a series of fibroblast strains derived from: normal donors, a patient with ataxia-telangiectasia (A-T) and an A-T heterozygote. Radiosensitivity was determined using a clonogenic assay following both high (HDR) and low (LDR) dose-rate irradiation. Results: Following HDR irradiation, the fibroblast strains derived from the different human SCID disorders displayed a wide range of radiosensitivity: the adenosine deaminase deficiency cells were similar in radiosensitivity to normal fibroblasts, T(-)B(-) cells were as hypersensitive to radiation as A-T cells and the Omenn's syndrome cells showed intermediate radiosensitivity. However, whereas all four normal cell strains studied showed significant LDR sparing, none of the SCID fibroblasts did. Conclusions: These data indicate that human SCID is variable in terms of radiosensitivity depending on the particular defect. In addition, the lack of LDR sparing of radiation-induced damage suggests the involvement of some form(s) of DNA repair defect in all the human SCID syndromes

  2. Having a Coffee Break: The Impact of Caffeine Consumption on Microglia-Mediated Inflammation in Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Maria H. Madeira

    2017-01-01

    Full Text Available Caffeine is the major component of coffee and the most consumed psychostimulant in the world and at nontoxic doses acts as a nonselective adenosine receptor antagonist. Epidemiological evidence suggests that caffeine consumption reduces the risk of several neurological and neurodegenerative diseases. However, despite the beneficial effects of caffeine consumption in human health and behaviour, the mechanisms by which it impacts the pathophysiology of neurodegenerative diseases still remain to be clarified. A promising hypothesis is that caffeine controls microglia-mediated neuroinflammatory response associated with the majority of neurodegenerative conditions. Accordingly, it has been already described that the modulation of adenosine receptors, namely, the A2A receptor, affords neuroprotection through the control of microglia reactivity and neuroinflammation. In this review, we will summarize the main effects of caffeine in the modulation of neuroinflammation in neurodegenerative diseases.

  3. The reduction of radiation-induced mitotic delay by caffeine: a test of the cyclic AMP hypothesis

    International Nuclear Information System (INIS)

    Oleinick, N.L.; Brewer, E.N.; Rustad, R.C.

    1978-01-01

    A study has been made of the reduction in γ-radiation-induced mitotic delay by caffeine in the naturally-synchronous plasmodial slime mould. Physarum polycephalum during late G 2 and early prophase, and the results compared with those obtained with other compounds of similar structure and/or physiological function. The reduction of radiation-induced mitotic delay was related to increasing concentrations of caffeine over at least two orders of magnitude. Pre-irradiation treatment with caffeine had no detectable effect. Caffeine had to be present for most, if not all, of the post-irradiation pre-mitotic period. Other chemicals which are reported to inhibit cyclic AMP phosphodiesterase either reduce or increase radiation-induced mitotic delay. The results therefore indicate that the reduction of mitotic delay by caffeine is not a result of altered cyclic AMP levels. (UK)

  4. Sucrose or sucrose and caffeine differentially impact memory and anxiety-like behaviours, and alter hippocampal parvalbumin and doublecortin.

    Science.gov (United States)

    Xu, Tanya J; Reichelt, Amy C

    2018-04-11

    Caffeinated sugar-sweetened "energy" drinks are a subset of soft drinks that are popular among young people worldwide. High sucrose diets impair cognition and alter aspects of emotional behaviour in rats, however, little is known about sucrose combined with caffeine. Rats were allocated to 2 h/day 10% sucrose (Suc), 10% sucrose plus 0.04% caffeine (CafSuc) or control (water) conditions. The addition of caffeine to sucrose appeared to increase the rewarding aspect of sucrose, as the CafSuc group consumed more solution than the Suc group. After 14 days of intermittent Suc or CafSuc access, anxiety was assessed in the elevated plus maze (EPM) prior to their daily solution access, whereby CafSuc and Suc rats spent more time in the closed arms, indicative of increased anxiety. Following daily solution access, CafSuc, but not Suc, rats showed reduced anxiety-like behaviour in the open-field. Control and CafSuc rats displayed intact place and long-term object memory, while Suc showed impaired memory performance. Sucrose reduced parvalbumin immunoreactivity in the hippocampus, but no differences were observed between Control and CafSuc conditions. Parvalbumin reactivity in the basolateral amygdala did not differ between conditions. Reduced doublecortin immunoreactivity in the dentate gyrus relative to controls was seen in the CafSuc, but not Suc, treatment conditions. These findings indicate that the addition of caffeine to sucrose attenuated cognitive deficits. However, the addition of caffeine to sucrose evoked anxiety-like responses under certain testing conditions, suggesting that frequent consumption of caffeinated energy drinks may promote emotional alterations and brain changes compared to standard soft drinks. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Caffeine, coffee, and appetite control: a review.

    Science.gov (United States)

    Schubert, Matthew M; Irwin, Christopher; Seay, Rebekah F; Clarke, Holly E; Allegro, Deanne; Desbrow, Ben

    2017-12-01

    Coffee and caffeine consumption has global popularity. However, evidence for the potential of these dietary constituents to influence energy intake, gut physiology, and appetite perceptions remains unclear. The purpose of this review was to examine the evidence regarding coffee and caffeine's influence on energy intake and appetite control. The literature was examined for studies that assessed the effects of caffeine and coffee on energy intake, gastric emptying, appetite-related hormones, and perceptual measures of appetite. The literature review indicated that coffee administered 3-4.5 h before a meal had minimal influence on food and macronutrient intake, while caffeine ingested 0.5-4 h before a meal may suppress acute energy intake. Evidence regarding the influence of caffeine and coffee on gastric emptying, appetite hormones, and appetite perceptions was equivocal. The influence of covariates such as genetics of caffeine metabolism and bitter taste phenotype remain unknown; longer controlled studies are needed.

  6. Energy drink consumption and impact on caffeine risk.

    Science.gov (United States)

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

    2014-01-01

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

  7. Radiosensitizing effect of RHOB protein in melanoma cells

    International Nuclear Information System (INIS)

    Notcovich, C.; Grissi, C.; Sánchez Crespo, R.; Delgado, D.C.; Molinari, B.; Ibañez, I.L.; Durán, H.

    2015-01-01

    Melanoma cells are highly resistant to chemo or radiotherapy. DNA damage agents such as ionizing radiation induce apoptosis involving RhoB protein. In a great variety of tumors the levels of this protein decrease along tumor progression. RhoB is considered a tumor suppressor gene due to its antiproliferative and proapoptotic effect. Considering the aforementioned, the aim of this study was to characterize the radiobiological response of different human melanoma cell lines, and to evaluate the possible correlation between RhoB expression and radiosensitivity. The human melanoma cell lines A375, MELJ and SB2 were gamma-irradiated ( 137 Cs). Survival curves were obtained by clonogenic assay and fitted to the Linear-Quadratic (LQ) model. Radiosensitivity was evaluated by surviving fraction at 2 Gy (SF2). Results showed that MELJ was significantly more radioresistant (SF2=0.71) than A375 and SB2 (0.29 and 0.21 respectively. Expression levels of RhoB, evaluated by western blot, increased in all lines vs. non-irradiated control. SB2, the most radiosensitive cells, showed a greater induction (p<0.05) of RhoB. Finally, to study whether RhoB has a radiosensitizing effect, these cell lines were stably transfected with a wild type RhoB construction, a constitutively active RhoB mutant V14, or with the empty plasmid as control. For all cell lines higher expression level of this protein was found in RhoB or V14 transfected cells (p<0.05). Sensitization was evaluated by SF2. Significant radiosensitization was demonstrated in clones derived from A375 and SB2 ((p<0.05), while for MELJ cells, radio-sensitization was only found in clones overexpressing V14. In conclusion, the increase of RhoB in melanoma cell lines, either by radiation or transfection has a radiosensitizing effect. Thus, we propose RhoB modulation as a potential therapeutic tool to improve the radiation response of radioresistant melanoma. (authors)

  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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Action of caffeine on the survival of x-irradiated cells

    International Nuclear Information System (INIS)

    Busse, P.M.

    1978-01-01

    Post-irradiation treatment of HeLa S3 cells with 1 mM caffeine results in a marked diminution of the surviving fraction as scored by colony formation. The decrease is dose-dependent; the effect of a 24-h post-irradiation treatment of a non-synchronous population with caffeine is to change the terminal slope of the survival curve and its intercept. Do is reduced from 130 to 60 rad; the extrapolation number is increased about twofold. The amount of post-irradiation killing is maximal if cells are exposed to caffeine at a concentration of at least 1 mM for 8 hours; less than 10% of unirradiated cells are killed under these conditions. Dose-response curves were also obtained for synchronous cells at various phases of the cell cycle. Similar results were obtained at all cell ages, but the magnitude of the effect is age-dependent. This age dependence was further explored in experiments in which mitotically collected cells were exposed to 300 or 500 rad doses at 2-hour intervals throughout the cell cycle. Treatment with caffeine for 24 hours after irradiation enhances the killing of cells late in the cycle more than in G 1 . The sensitivities of two other cell lines, CHO and EMT6, also were examined; both are substantially less sensitive to caffeine. The smaller cell-cycle dependence of CHO cells is qualitatively the same as that of HeLa cells

  10. Expectation of having consumed caffeine can improve performance and mood.

    Science.gov (United States)

    Dawkins, Lynne; Shahzad, Fatima-Zahra; Ahmed, Suada S; Edmonds, Caroline J

    2011-12-01

    We explored whether caffeine, and expectation of having consumed caffeine, affects attention, reward responsivity and mood using double-blinded methodology. 88 participants were randomly allocated to 'drink-type' (caffeinated/decaffeinated coffee) and 'expectancy' (told caffeinated/told decaffeinated coffee) manipulations. Both caffeine and expectation of having consumed caffeine improved attention and psychomotor speed. Expectation enhanced self-reported vigour and reward responsivity. Self-reported depression increased at post-drink for all participants, but less in those receiving or expecting caffeine. These results suggest caffeine expectation can affect mood and performance but do not support a synergistic effect. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Caffeine promotes hyperthermia and serotonergic loss following co-administration of the substituted amphetamines, MDMA ("Ecstasy") and MDA ("Love").

    Science.gov (United States)

    McNamara, Ruth; Kerans, Aoife; O'Neill, Barry; Harkin, Andrew

    2006-01-01

    The present study determined the effect of caffeine co-administration on the core body temperature response and long-term serotonin (5-HT) loss induced by methylenedioxymethamphetamine (MDMA; "Ecstasy") and its metabolite methylenedioxyamphetamine (MDA; "Love") to rats. In group-housed animals, caffeine (10 mg/kg) enhanced the acute toxicity of MDMA (15 mg/kg) and MDA (7.5 mg/kg), resulting in an exaggerated hyperthermic response (+2 degrees C for 5 h following MDMA and +1.5 degrees C for 3 h following MDA) when compared to MDMA (+1 degree C for 3 h) and MDA (+1 degree C for 1 h) alone. Co-administration of caffeine with MDMA or MDA was also associated with increased lethality. To reduce the risk of lethality, doses of MDMA and MDA were reduced in further experiments and the animals were housed individually. To examine the effects of repeated administration, animals received MDMA (10 mg/kg) or MDA (5 mg/kg) with or without caffeine (10 mg/kg) twice daily for 4 consecutive days. MDMA and MDA alone induced hypothermia (fall of 1 to 2 degrees C) over the 4 treatment days. Co-administration of caffeine with MDMA or MDA resulted in hyperthermia (increase of up to 2.5 degrees C) following acute administration compared to animals treated with caffeine or MDMA/MDA alone. This hyperthermic response to caffeine and MDMA was not observed with repeated administration, unlike caffeine + MDA, where hyperthermia was obtained over the 4 day treatment period. In addition, 4 weeks after the last treatment, co-administration of caffeine with MDA (but not MDMA) induced a reduction in 5-HT and 5-hydroxyindole acetic acid (5-HIAA) concentrations in frontal cortex (to 61% and 58% of control, respectively), hippocampus (48% and 60%), striatum (79% and 64%) and amygdala (63% and 37%). However, when caffeine (10 mg/kg) and MDMA (2.5 mg/kg) were co-administered four times daily for 2 days to group-housed animals, both hyperthermia and hippocampal 5-HT loss were observed (reduced to 68% of

  12. Caffeinated beverage intake and reproductive hormones among premenopausal women in the BioCycle Study123

    Science.gov (United States)

    Schisterman, Enrique F; Mumford, Sunni L; Pollack, Anna Z; Zhang, Cuilin; Ye, Aijun; Stanford, Joseph B; Hammoud, Ahmad O; Porucznik, Christina A; Wactawski-Wende, Jean

    2012-01-01

    Background: Caffeinated beverages are widely consumed among women of reproductive age, but their association with reproductive hormones, and whether race modifies any such associations, is not well understood. Objective: We assessed the relation between caffeine and caffeinated beverage intake and reproductive hormones in healthy premenopausal women and evaluated the potential effect modification by race. Design: Participants (n = 259) were followed for up to 2 menstrual cycles and provided fasting blood specimens for hormonal assessment at up to 8 visits per cycle and four 24-h dietary recalls per cycle. Weighted linear mixed models and nonlinear mixed models with harmonic terms were used to estimate associations between caffeine and hormone concentrations, adjusted for age, adiposity, physical activity, energy and alcohol intakes, and perceived stress. On the basis of a priori assumptions, an interaction between race and caffeine was tested, and stratified results are presented. Results: Caffeine intake ≥200 mg/d was inversely associated with free estradiol concentrations among white women (β = −0.15; 95% CI: −0.26, −0.05) and positively associated among Asian women (β = 0.61; 95% CI: 0.31, 0.92). Caffeinated soda intake and green tea intake ≥1 cup/d (1 cup = 240 mL) were positively associated with free estradiol concentrations among all races: β = 0.14 (95% CI: 0.06, 0.22) and β = 0.26 (95% CI: 0.07, 0.45), respectively. Conclusions: Moderate consumption of caffeine was associated with reduced estradiol concentrations among white women, whereas caffeinated soda and green tea intakes were associated with increased estradiol concentrations among all races. Further research is warranted on the association between caffeine and caffeinated beverages and reproductive hormones and whether these relations differ by race. PMID:22237060

  13. 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.

  14. Effects of coffee/caffeine on brain health and disease: What should I tell my patients?

    Science.gov (United States)

    Nehlig, Astrid

    2016-04-01

    Over the last decade, Food Regulation Authorities have concluded that coffee/caffeine consumption is not harmful if consumed at levels of 200 mg in one sitting (around 2½ cups of coffee) or 400 mg daily (around 5 cups of coffee). In addition, caffeine has many positive actions on the brain. It can increase alertness and well-being, help concentration, improve mood and limit depression. Caffeine may disturb sleep, but only in sensitive individuals. It may raise anxiety in a small subset of particularly sensitive people. Caffeine does not seem to lead to dependence, although a minority of people experience withdrawal symptoms. Caffeine can potentiate the effect of regular analgesic drugs in headache and migraine. Lifelong coffee/caffeine consumption has been associated with prevention of cognitive decline, and reduced risk of developing stroke, Parkinson's disease and Alzheimer's disease. Its consumption does not seem to influence seizure occurrence. Thus, daily coffee and caffeine intake can be part of a healthy balanced diet; its consumption does not need to be stopped in elderly people. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  15. Cigarette, alcohol, and caffeine consumption

    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;...... units alcohol per week and 375 mg or more caffeine per day during pregnancy may increase the risk of spontaneous abortion.......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...

  16. Expectation of having consumed caffeine can improve performance and mood

    OpenAIRE

    Dawkins, Lynne; Shahzad, Fatima-Zahra; Ahmed, Suada S.; Edmonds, Caroline J.

    2011-01-01

    We explored whether caffeine, and expectation of having consumed caffeine, affects attention, reward responsivity and mood using double-blinded methodology. 88 participants were randomly allocated to ‘drink-type’ (caffeinated/decaffeinated coffee) and ‘expectancy’ (told caffeinated/told decaffeinated coffee) manipulations. Both caffeine and expectation of having consumed caffeine improved attention and psychomotor speed. Expectation enhanced self-reported vigour and reward responsivity. Self-...

  17. Inhibiting DNA-PKCS radiosensitizes human osteosarcoma cells

    International Nuclear Information System (INIS)

    Mamo, Tewodros; Mladek, Ann C.; Shogren, Kris L.; Gustafson, Carl; Gupta, Shiv K.; Riester, Scott M.; Maran, Avudaiappan; Galindo, Mario; Wijnen, Andre J. van; Sarkaria, Jann N.; Yaszemski, Michael J.

    2017-01-01

    Osteosarcoma survival rate has not improved over the past three decades, and the debilitating side effects of the surgical treatment suggest the need for alternative local control approaches. Radiotherapy is largely ineffective in osteosarcoma, indicating a potential role for radiosensitizers. Blocking DNA repair, particularly by inhibiting the catalytic subunit of DNA-dependent protein kinase (DNA-PK CS ), is an attractive option for the radiosensitization of osteosarcoma. In this study, the expression of DNA-PK CS in osteosarcoma tissue specimens and cell lines was examined. Moreover, the small molecule DNA-PK CS inhibitor, KU60648, was investigated as a radiosensitizing strategy for osteosarcoma cells in vitro. DNA-PK CS was consistently expressed in the osteosarcoma tissue specimens and cell lines studied. Additionally, KU60648 effectively sensitized two of those osteosarcoma cell lines (143B cells by 1.5-fold and U2OS cells by 2.5-fold). KU60648 co-treatment also altered cell cycle distribution and enhanced DNA damage. Cell accumulation at the G2/M transition point increased by 55% and 45%, while the percentage of cells with >20 γH2AX foci were enhanced by 59% and 107% for 143B and U2OS cells, respectively. These results indicate that the DNA-PK CS inhibitor, KU60648, is a promising radiosensitizing agent for osteosarcoma. - Highlights: • DNA-PKcs is consistently expressed in human osteosarcoma tissue and cell lines. • The DNA-PKcs inhibitor, KU60648, effectively radiosensitizes osteosarcoma cells. • Combining KU60648 with radiation increases G2/M accumulation and DNA damage.

  18. Low-dose caffeine physical dependence in humans.

    Science.gov (United States)

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

    1990-12-01

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

  19. Age-dependent radiosensitivity of mouse oocytes

    International Nuclear Information System (INIS)

    Koehler, C.

    1976-01-01

    It has been shown that there are three distinct phases of radiosensitivity in oocytes of prepubertal mice: a period of rapidly increasing sensitivity between 0 and 4 days of age; a period of consistent, high sensitivity between 5 and 18 days of age; and a period of decreasing sensitivity from 19 to at least 21 days of age. Two distinct phases have been demonstrated for the rate of population decline of the oocytes of primary follicles: an initial period of rapid loss from 0 to 4 days of age; and a period of much slower loss from 5 through 23 days of age. Correlations have been drawn between the first two phases of radiosensitivity and morphological changes in the oocyte, and between the third phase of radiosensitivity and endocrinological changes in the maturing animal. The reaction of oocytes to radiation has been separated into two categories: immediate death (within 24 hours); and delayed death (over the entire lifespan of the animal)

  20. The effects of caffeine ingestion on cortical areas: functional imaging study.

    Science.gov (United States)

    Park, Chan-A; Kang, Chang-Ki; Son, Young-Don; Choi, Eun-Jung; Kim, Sang-Hoon; Oh, Seung-Taek; Kim, Young-Bo; Park, Chan-Woong; Cho, Zang-Hee

    2014-05-01

    The effect of caffeine as a cognitive enhancer is well known; however, caffeine-induced changes in the cortical regions are still not very clear. Therefore, in this study, we conducted an investigation of the activation and deactivation with blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) and of metabolic activity change with positron emission tomography (PET) in the human brain. Fourteen healthy subjects performed a visuomotor task inducing attention with 3T MRI, and PET imaging was also carried out in seven subjects to determine the cerebral glucose metabolic changes of caffeine at rest. The result by fMRI showed increased BOLD activation in the left cerebellum, putamen, insula, thalamus and the right primary motor cortex, and decreased BOLD deactivation in the posterior medial and the left posterior lateral cortex. Also, the resting state PET data showed reduced metabolic activity in the putamen, caudate nucleus, insula, pallidum and posterior medial cortex. The common cortical regions between fMRI and PET, such as putamen, insula and posterior medial cortex, where significant changes occurred after caffeine ingestion, are well known to play an important role in cognitive function like attention. This result suggests that the effect of caffeine as a cognitive enhancer is derived by modulating the attentional areas. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. 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.

  2. Radiosensitivity in ataxia-telangiectasia

    International Nuclear Information System (INIS)

    Lavin, M.F.; Khanna, K.K.; Watters, D.

    1998-01-01

    Full text: Radiosensitivity is a major hallmark of the human genetic disorder ataxia-telangiectasia. This hypersensitivity to ionizing radiation has been demonstrated in vitro after exposure of patients to therapeutic thought to be the major factor contculture. Clearly an understanding of the nature of the molecular defect in ataxia-telangiectasia will be of considerable assistance in delineating additional pathways that determine cellular radiosensitivity/radioresistance. Furthermore, since patients with this syndrome are also predisposed to developing a number of leukaemias and lymphomas the possible connection between radiosensitivity and cancer predisposition is of interest. Now that the gene (ATM) responsible for this genetic disease has been cloned and identified, progress is being made in determining the role of the ATM protein in mediating the effects of cellular exposure to ionizing radiation and other forms of redox stress. Proteins such as the product of the tumour suppressor gene p53 and the proto-oncogene c-Abl (a protein tyrosine kinase) have been shown to interact with ATM. Since several intermediate steps in both the p53 and c-Abl pathways, activated by ionizing radiation, are known it will be possible to map the position of ATM in these pathways and describe its mechanism of action. What are the clinical implications of understanding the molecular basis of the defect in ataxia-telangiectasia? As outlined above since radiosensitivity is a universal characteristic of A-T understanding the mechanism of action of ATM will provide additional information or radiation signalling in human cells. With this information it may be possible to sensitize tumour cells to radiation and thus increase the therapeutic benefit of radiotherapy. This might involve the use of small molecules that would interfere with the normal ATM controlled pathways and thus sensitize cells to radiation or alternatively it might involve the efficient introduction of ATM anti-sense c

  3. Radiosensitivity in ataxia-telangiectasia

    Energy Technology Data Exchange (ETDEWEB)

    Lavin, M.F. [Royal Brisbane Hospital, QLD (Australia). Queensland Institute of Medical Research and The Department of Surgery; Khanna, K.K.; Watters, D. [Royal Brisbane Hospital, QLD (Australia). Queensland Institute of Medical Research

    1998-12-31

    Full text: Radiosensitivity is a major hallmark of the human genetic disorder ataxia-telangiectasia. This hypersensitivity to ionizing radiation has been demonstrated in vitro after exposure of patients to therapeutic thought to be the major factor contculture. Clearly an understanding of the nature of the molecular defect in ataxia-telangiectasia will be of considerable assistance in delineating additional pathways that determine cellular radiosensitivity/radioresistance. Furthermore, since patients with this syndrome are also predisposed to developing a number of leukaemias and lymphomas the possible connection between radiosensitivity and cancer predisposition is of interest. Now that the gene (ATM) responsible for this genetic disease has been cloned and identified, progress is being made in determining the role of the ATM protein in mediating the effects of cellular exposure to ionizing radiation and other forms of redox stress. Proteins such as the product of the tumour suppressor gene p53 and the proto-oncogene c-Abl (a protein tyrosine kinase) have been shown to interact with ATM. Since several intermediate steps in both the p53 and c-Abl pathways, activated by ionizing radiation, are known it will be possible to map the position of ATM in these pathways and describe its mechanism of action. What are the clinical implications of understanding the molecular basis of the defect in ataxia-telangiectasia? As outlined above since radiosensitivity is a universal characteristic of A-T understanding the mechanism of action of ATM will provide additional information or radiation signalling in human cells. With this information it may be possible to sensitize tumour cells to radiation and thus increase the therapeutic benefit of radiotherapy. This might involve the use of small molecules that would interfere with the normal ATM controlled pathways and thus sensitize cells to radiation or alternatively it might involve the efficient introduction of ATM anti-sense c

  4. Contributions concerning radiosensitivity proffered by the basic sciences to clinical radiation therapy

    International Nuclear Information System (INIS)

    Caputo, A.

    1974-01-01

    Basic concepts of radiosensitivity are reviewed. Some topics discussed are: probability of lethal injury as a dose dependent function; mutations resulting from radiation damage to DNA; relation of cell radiosensitivity to chromosome volume; relation of molecular structure of DNA to relative radiosensitivity of the organism; repair replication of DNA following uv and x irradiation of Escherichia coli and mammalian cells; and relation of the cell cycle to radiosensitivity. (U.S.)

  5. Early Caffeine and Weaning from Mechanical Ventilation in Preterm Infants: A Randomized, Placebo-Controlled Trial.

    Science.gov (United States)

    Amaro, Cynthia M; Bello, Jose A; Jain, Deepak; Ramnath, Alexandra; D'Ugard, Carmen; Vanbuskirk, Silvia; Bancalari, Eduardo; Claure, Nelson

    2018-05-01

    To evaluate in a randomized, double-blind, placebo-controlled trial the effect of early caffeine on the age of first successful extubation in preterm infants. Preterm infants born at 23-30 weeks of gestation requiring mechanical ventilation in the first 5 postnatal days were randomized to receive a 20 mg/kg loading dose followed by 5 mg/kg/day of caffeine or placebo until considered ready for extubation. The placebo group received a blinded loading dose of caffeine before extubation. Infants were randomized to receive caffeine (n = 41) or placebo (n = 42). Age at first successful extubation did not differ between early caffeine (median, 24 days; IQR, 10-41 days) and control groups (median, 20 days; IQR, 9-43 days; P = .7). An interim analysis at 75% enrollment showed a trend toward higher mortality in 1 of the groups and the data safety and monitoring board recommended stopping the trial. Unblinded analysis revealed mortality did not differ significantly between the early caffeine (9 [22%]) and control groups (5 [12%]; P = .22). Early initiation of caffeine in this group of premature infants did not reduce the age of first successful extubation. A nonsignificant trend toward higher mortality in the early caffeine group led to a cautious decision to stop the trial. These findings suggest caution with early use of caffeine in mechanically ventilated preterm infants until more efficacy and safety data become available. ClinicalTrials.gov: NCT01751724. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Radiosensitivity of fingermillet genotypes

    Energy Technology Data Exchange (ETDEWEB)

    Raveendran, T S; Nagarajan, C; Appadurai, R; Prasad, M N; Sundaresan, N [Tamil Nadu Agricultural Univ., Coimbatore (India)

    1984-07-01

    Varietal differences in radiosensitivity were observed in a study involving 4 genotypes of fingermillet (Eleusine coracana (Linn.) Gaertn.) subjected to gamma-irradiation. Harder seeds were found to tolerate a higher dose of the mutagen.

  7. Modern concepts for basic radiobiological factors characterizing tumor tissue radiosensitivity

    International Nuclear Information System (INIS)

    Gocheva, L.; Sergieva, K.

    2002-01-01

    Traditionally radiotherapy is prescribed at doses consistent with the expected therapeutic response and tolerance of tumor and normal tissues without consideration to individual differences in radiosensitivity. However, the basic radiobiological knowledge and clinical experience along this line point to significant variations in the observed therapeutic results. It has been established that cells and tissues under experimental and clinical conditions manifest a wide spectrum of individual radiosensitivity. The aim of this survey is to outline the current concepts for the basic radiobiological factors influencing tumor radiosensitivity. A thorough discussion is done of the essence, mechanisms of action, methods of determination and measurement, and effect on the prognosis in patients with malignant diseases of a number of radiobiological factors, such as: tumor-cell proliferation, apoptosis, tumor hypoxia and neovascularization. Although the knowledge of the mechanisms of radiosensitivity is constantly expanding, its clinical implementation is still rather limited. The true role of radiosensitivity in predicting the therapeutic response should be more accurately defined. (authors)

  8. Determination of the caffeine contents of various food items within the Austrian market and validation of a caffeine assessment tool (CAT).

    Science.gov (United States)

    Rudolph, E; Färbinger, A; König, J

    2012-01-01

    The caffeine content of 124 products, including coffee, coffee-based beverages, energy drinks, tea, colas, yoghurt and chocolate, were determined using RP-HPLC with UV detection after solid-phase extraction. Highest concentrations of caffeine were found for coffee prepared from pads (755 mg l⁻¹) and regular filtered coffee (659 mg l⁻¹). The total caffeine content of coffee and chocolate-based beverages was between 15 mg l⁻¹ in chocolate milk and 448 mg l⁻¹ in canned ice coffee. For energy drinks the caffeine content varied in a range from 266 to 340 mg l⁻¹. Caffeine concentrations in tea and ice teas were between 13 and 183 mg l⁻¹. Coffee-flavoured yoghurts ranged from 33 to 48 mg kg⁻¹. The caffeine concentration in chocolate and chocolate bars was between 17 mg kg⁻¹ in whole milk chocolate and 551 mg kg⁻¹ in a chocolate with coffee filling. A caffeine assessment tool was developed and validated by a 3-day dietary record (r²= 0.817, p < 0.01) using these analytical data and caffeine saliva concentrations (r²= 0.427, p < 0.01).

  9. Caffeine and sports performance.

    Science.gov (United States)

    Burke, Louise M

    2008-12-01

    Athletes are among the groups of people who are interested in the effects of caffeine on endurance and exercise capacity. Although many studies have investigated the effect of caffeine ingestion on exercise, not all are suited to draw conclusions regarding caffeine and sports performance. Characteristics of studies that can better explore the issues of athletes include the use of well-trained subjects, conditions that reflect actual practices in sport, and exercise protocols that simulate real-life events. There is a scarcity of field-based studies and investigations involving elite performers. Researchers are encouraged to use statistical analyses that consider the magnitude of changes, and to establish whether these are meaningful to the outcome of sport. The available literature that follows such guidelines suggests that performance benefits can be seen with moderate amounts (~3 mg.kg-1 body mass) of caffeine. Furthermore, these benefits are likely to occur across a range of sports, including endurance events, stop-and-go events (e.g., team and racquet sports), and sports involving sustained high-intensity activity lasting from 1-60 min (e.g., swimming, rowing, and middle and distance running races). The direct effects on single events involving strength and power, such as lifts, throws, and sprints, are unclear. Further studies are needed to better elucidate the range of protocols (timing and amount of doses) that produce benefits and the range of sports to which these may apply. Individual responses, the politics of sport, and the effects of caffeine on other goals, such as sleep, hydration, and refuelling, also need to be considered.

  10. A review of human cell radiosensitivity in vitro

    International Nuclear Information System (INIS)

    Deschavanne, Patrick J.; Fertil, Bernard

    1996-01-01

    The survival curves of 694 human cell lines irradiated in exponentially growing phase in vitro were collected from the literature. Among them, 271 were derived from tumors, 423 were nontransformed fibroblasts and other normal cell strains from healthy people or people with some genetic disorders. Seventy-six different cell types are identified, and a specific radiosensitivity could be associated with each, using D-bar and surviving fraction at 2 Gy. Technical factors such as culture medium, feeder cells, and scoring method were found to affect intrinsic radiosensitivity. In particular, the cell type is not a discriminating factor when cells are studied in agar. Results obtained with cells irradiated in agar must be used cautiously, depending on how the cells were prepared for the experiments. The use of feeder cells narrows the range of radiosensitivity of human cells. For cells irradiated as monolayer, it was possible to build a scale of radiosensitivity according to cell type, ranging, in terms of D-bar from 0.6 Gy for the most sensitive cell lines to more than 4 Gy for the most resistant. Considering that, in most cases, we could estimate the variation of radiosensitivity within each cell type, our classification among cell types can be used by researchers to place their results in the context of the literature

  11. Effect of caffeine on γ-ray induced G2 delay in ataxia telangiectasia

    International Nuclear Information System (INIS)

    Bates, P.R.; Lavin, M.F.

    1985-01-01

    Exposure of normal control and ataxia-telangiectasia (A-T) lymphoblastoid cell lines to ionizing radiation gives rise to an increase in the proportion of G2 phase cells. The size and extent of the G2 phase block is greater in A-T cells than in normal cells. Caffeine has a similar overall effect in control and A-T cell lines in reducing the G2 arrest observed after ionizing radiation. While the proportion of cells accumulated in G2 in A-T cells is considerably greater than in controls, addition of caffeine at the time of maximal G2 block brings about a return of G2 phase cell numbers to unirradiated values in 3 hours in both cell types. In normal control cells the caffeine-mediated decrease in G2 cells is reflected by an increase in mitotic cells. These mitotic cells have a higher frequency of chromosome aberrations compared to cells harvested in the absence of caffeine. Similarly in A-T cells addition of caffeine to irradiated cultures, delayed in G2 phase, increased the number of mitotic cells and the frequency of chromosome aberrations. (author)

  12. Chronic coffee and caffeine ingestion effects on the cognitive function and antioxidant system of rat brains.

    Science.gov (United States)

    Abreu, Renata Viana; Silva-Oliveira, Eliane Moretto; Moraes, Márcio Flávio Dutra; Pereira, Grace Schenatto; Moraes-Santos, Tasso

    2011-10-01

    Coffee is a popular beverage consumed worldwide and its effect on health protection has been well studied throughout literature. This study investigates the effect of chronic coffee and caffeine ingestion on cognitive behavior and the antioxidant system of rat brains. The paradigms of open field and object recognition were used to assess locomotor and exploratory activities, as well as learning and memory. The antioxidant system was evaluated by determining the activities of glutathione reductase (GR), glutathione peroxidase (GPx) and superoxide dismutase (SOD), as well as the lipid peroxidation and reduced glutathione content. Five groups of male rats were fed for approximately 80 days with different diets: control diet (CD), fed a control diet; 3% coffee diet (3%Co) and 6% coffee diet (6%Co), both fed a diet containing brewed coffee; 0.04% caffeine diet (0.04%Ca) and 0.08% caffeine diet (0.08%Ca), both fed a control diet supplemented with caffeine. The estimated caffeine intake was approximately 20 and 40 mg/kg per day, for the 3%Co-0.04%Ca and 6%Co-0.08%Ca treatments, respectively. At 90 days of life, the animals were subjected to the behavioral tasks and then sacrificed. The results indicated that the intake of coffee, similar to caffeine, improved long-term memory when tested with object recognition; however, this was not accompanied by an increase in locomotor and exploratory activities. In addition, chronic coffee and caffeine ingestion reduced the lipid peroxidation of brain membranes and increased the concentration of reduced-glutathione. The activities of the GR and SOD were similarly increased, but no change in GPx activity could be observed. Thus, besides improving cognitive function, our data show that chronic coffee consumption modulates the endogenous antioxidant system in the brain. Therefore, chronic coffee ingestion, through the protection of the antioxidant system, may play an important role in preventing age-associated decline in the cognitive

  13. Radiosensitization of mouse skin by oxygen and depletion of glutathione

    International Nuclear Information System (INIS)

    Stevens, Graham; Joiner, Michael; Joiner, Barbara; Johns, Helen; Denekamp, Juliana

    1995-01-01

    Purpose: To determine the oxygen enhancement ratio (OER) and shape of the oxygen sensitization curve of mouse foot skin, the extent to which glutathione (GSH) depletion radiosensitized skin, and the dependence of such sensitization on the ambient oxygen tension. Methods and Materials: The feet of WHT mice were irradiated with single doses of 240 kVp x-rays while mice were exposed to carbogen or gases with oxygen/nitrogen mixtures containing 8-100% O 2 . The anoxic response was obtained by occluding the blood supply to the leg of anesthetized mice with a tourniquet, surrounding the foot with nitrogen, and allowing the mice to breathe 10% O 2 . Further experiments were performed to assess the efficacy of this method to obtain an anoxic response. Radiosensitivity of skin was assessed using the acute skin-reaction assay. Glutathione levels were modified using two schedules of dl-buthionine sulphoximine (BSO) and diethylmaleate (DEM), which were considered to produce extensive and intermediate levels of GSH depletion in the skin of the foot during irradiation. Results: Carbogen caused the greatest radiosensitization of skin, with a reproducible enhancement of 2.2 relative to the anoxic response. The OER of 2.2 is lower than other reports for mouse skin. This may indicate that the extremes of oxygenation were not produced, although there was no direct evidence for this. When skin radiosensitivity was plotted against the logarithm of the oxygen tension in the ambient gas, a sigmoid curve with a K value of 17-21% O 2 in the ambient gas was obtained. Depletion of GSH caused minimal radiosensitization when skin was irradiated under anoxic or well-oxygenated conditions. Radiosensitization by GSH depletion was maximal at intermediate oxygen tensions of 10-21% O 2 in the ambient gas. Increasing the extent of GSH depletion led to increasing radiosensitization, with sensitization enhancement ratios of 1.2 and 1.1, respectively, for extensive and intermediate levels of GSH

  14. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Targeted radiosensitization of cells expressing truncated DNA polymerase {beta}.

    NARCIS (Netherlands)

    Neijenhuis, S.; Verwijs-Janssen, M.; Broek, Bart van den; Begg, A.C.; Vens, C.

    2010-01-01

    Ionizing radiation (IR) is an effective anticancer treatment, although failures still occur. To improve radiotherapy, tumor-targeted strategies are needed to increase radiosensitivity of tumor cells, without influencing normal tissue radiosensitivity. Base excision repair (BER) and single-strand

  16. 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

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

    OpenAIRE

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

    2008-01-01

    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 no...

  18. HLA‐G modulates the radiosensitivity of human neoplastic cells

    International Nuclear Information System (INIS)

    Michelin, Severino; Gallegos, Cristina; Baffa Trasci, Sofía; Dubner, Diana; Favier, B.; Carosella, E.D.

    2011-01-01

    Tumor cells show a very broad range of radiosensitivities. The differential radiosensitivity may depend on many factors, being the efficiency to recognize and/or repair the DNA lesion, and the cell cycle control mechanisms, the most important (Jeggo and Lavin, 2009; Kumala et al., 2003). Human leukocyte antigen‐G (HLA‐G) is a non‐classical HLA class I molecule involved in fetus protection form the maternal immune system, transplant tolerance, and viral and tumoral immune escape (Carosella et al., 2008). It has been determined that gamma radiation modulates HLA‐G expression at the plasma membrane of human melanoma cells. However, its role in tumoral radiosensitivity has not been demonstrated yet. The objective of this work was to determine if the radiosensitivity of human neoplastic cell lines cultured in vitro was mediated by HLA‐G expression. (authors)

  19. Naturalistic Effects of Five Days of Bedtime Caffeine Use on Sleep, Next-Day Cognitive Performance, and Mood

    Science.gov (United States)

    Tiplady, Brian; Priestley, Caroline M.; Rogers, Peter J.

    2014-01-01

    Background: Disruptive effects of caffeine on sleep have previously been reported, although measures of next-day mood and performance have rarely been included. The present study aims to evaluate the effects of caffeine on sleep and associated next-day effects in a naturalistic field setting. Methods: Nineteen participants (daily caffeine intake 0–141 mg), assessed as good sleepers, took part in a randomized, placebo-controlled, double-blind, 2-week crossover study to assess the effects of bedtime caffeine use (250 mg) on sleep and next-day cognitive performance and mood, which were assessed on a mobile phone in the morning and afternoon. Sleep was assessed objectively (actiwatch) and subjectively (sleep diary). Results: Caffeine's effects on sleep were largely restricted to the first day of administration, with actigraphically measured reduced sleep efficiency, increased activity score and fragmentation index, decreased self-rated sleep quality, and an increased occurrence of participants waking early; only decreased sleep efficiency remained over the week. Effects on next-day performance and mood were evident over the whole week, although despite disrupting sleep, accuracy on a working memory task was higher after caffeine than placebo administration. Conclusions: Caffeine disrupted sleep, although when assessing next-day performance, which may have been affected by the presence of residual caffeine, performance appeared better after caffeine compared to placebo, although this was most likely due to prevention of the effects of overnight withdrawal from caffeine rather than representing a net benefit. Furthermore, partial tolerance developed to the effects of caffeine on sleep. PMID:24868491

  20. Decision-making style, nicotine and caffeine use and dependence.

    Science.gov (United States)

    Phillips, James G; Ogeil, Rowan P

    2015-11-01

    As therapeutic interventions are being developed utilising telehealth and mobile phones, it is important to understand how substance-dependent individuals will respond to offers of online assistance. The present paper considered the following: (1) how decision-making style is associated with use and dependence upon commonly used stimulants and (2) how it influences behavioural responses to electronic offers of further information about these drugs. An online survey examined patterns of nicotine and caffeine use, administered Severity of Dependence Scales for caffeine and nicotine and assessed decision-making style using the Melbourne Decision Making Questionnaire and mood using the Kessler Distress Scale. Upon completing these scales, the 181 participants with a mean age of 28.14 years were offered further information online. Stimulant dependence was associated with psychological distress. Caffeine dependence was linked to hypervigilance (panic). Decisional self-esteem varied with stimulant dependence and Kessler Distress Scale score. Participants with high decisional self-esteem declined electronic offers of further information. Confidence rather than defensive avoidance was a factor in reducing information-seeking behaviours on the Internet. Copyright © 2015 John Wiley & Sons, Ltd.

  1. Caffeine markedly sensitizes human mesothelioma cell lines to pemetrexed

    Science.gov (United States)

    Min, Sang Hee; Goldman, I. David; Zhao, Rongbao

    2013-01-01

    Pemetrexed is a new generation antifolate approved for the treatment of mesothelioma and non-small cell lung cancer. Caffeine is known to augment radiation or chemotherapeutic drug-induced cell killing. The current study addresses the impact of caffeine on the activity of pemetrexed in mesothelioma cell lines. Caffeine enhanced pemetrexed activity in all four mesothelioma cell lines tested (H2052, H2373, H28 and MSTO-211H). Caffeine sensitized H2052 cells in a dose- and schedule-dependent manner, and was associated with a markedly decreased clonogenic survival. Caffeine sensitization occurred only in cells subjected to pulse, but not continuous, exposure to pemetrexed. Similar pemetrexed sensitization was also observed with the clinically better tolerated caffeine analog, theobromine. Pemetrexed sensitization by caffeine was associated with an increase in pemetrexed-induced phosphorylation of ataxia-telangiectasia-mutated (ATM) and Chk1. These data indicate that caffeine and its analog, theobromine, may be a useful approach to enhance pemetrexed-based chemotherapy. PMID:17594092

  2. Chromosomal radiosensitivity in patients with multiple sclerosis

    International Nuclear Information System (INIS)

    Milenkova, Maria; Milanov, Ivan; Kmetska, Ksenia; Deleva, Sofia; Popova, Ljubomira; Hadjidekova, Valeria; Groudeva, Violeta; Hadjidekova, Savina; Domínguez, Inmaculada

    2013-01-01

    Highlights: • We studied radiosensitivity to in vitro γ-irradiated lymphocytes from MS patients. • Immunotherapy in RRMS patients reduced the yield of radiation induced MN. • The group of treated RRMS accounts for the low radiosensitivity in MS patients. • Spontaneous yield of MN was similar in treated and untreated RRMS patients. - Abstract: Multiple sclerosis is a clinically heterogeneous autoimmune disease leading to severe neurological disability. Although during the last years many disease-modifying agents as treatment options for multiple sclerosis have been made available, their mechanisms of action are still not fully determined. In the present study radiosensitivity in lymphocytes of patients with relapsing–remitting multiple sclerosis, secondary progressive multiple sclerosis and healthy controls was investigated. Whole blood cultures from multiple sclerosis patients and healthy controls were used to analyze the spontaneous and radiation-induced micronuclei in binucleated lymphocytes. A subgroup of patients with relapsing–remitting multiple sclerosis was treated with immunomodulatory agents, interferon β or glatiramer acetate. The secondary progressive multiple sclerosis patients group was not receiving any treatment. Our results reveal that the basal DNA damage was not different between relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls. No differences between gamma-irradiation induced micronuclei frequencies in binucleated cells from relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls were found either. Nevertheless, when we compared the radiation induced DNA damage in binucleated cells from healthy individuals with the whole group of patients, a reduction in the frequency of micronuclei was obtained in the patients group. Induced micronuclei yield was significantly lower in the irradiated samples from treated relapsing–remitting multiple

  3. Chromosomal radiosensitivity in patients with multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Milenkova, Maria; Milanov, Ivan; Kmetska, Ksenia [III Neurological Clinic, University Hospital Saint Naum, Sofia (Bulgaria); Deleva, Sofia; Popova, Ljubomira; Hadjidekova, Valeria [Laboratory of Radiation Genetics, NCRRP, Sofia (Bulgaria); Groudeva, Violeta [Department of Diagnostic Imaging, University Hospital St. Ekaterina, Sofia (Bulgaria); Hadjidekova, Savina [Department of Medical Genetics, Medical University, Sofia (Bulgaria); Domínguez, Inmaculada, E-mail: idomin@us.es [Department of Cell Biology, Faculty of Biology, University of Seville, Avda. Reina Mercedes 6, 41012 (Spain)

    2013-09-15

    Highlights: • We studied radiosensitivity to in vitro γ-irradiated lymphocytes from MS patients. • Immunotherapy in RRMS patients reduced the yield of radiation induced MN. • The group of treated RRMS accounts for the low radiosensitivity in MS patients. • Spontaneous yield of MN was similar in treated and untreated RRMS patients. - Abstract: Multiple sclerosis is a clinically heterogeneous autoimmune disease leading to severe neurological disability. Although during the last years many disease-modifying agents as treatment options for multiple sclerosis have been made available, their mechanisms of action are still not fully determined. In the present study radiosensitivity in lymphocytes of patients with relapsing–remitting multiple sclerosis, secondary progressive multiple sclerosis and healthy controls was investigated. Whole blood cultures from multiple sclerosis patients and healthy controls were used to analyze the spontaneous and radiation-induced micronuclei in binucleated lymphocytes. A subgroup of patients with relapsing–remitting multiple sclerosis was treated with immunomodulatory agents, interferon β or glatiramer acetate. The secondary progressive multiple sclerosis patients group was not receiving any treatment. Our results reveal that the basal DNA damage was not different between relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls. No differences between gamma-irradiation induced micronuclei frequencies in binucleated cells from relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls were found either. Nevertheless, when we compared the radiation induced DNA damage in binucleated cells from healthy individuals with the whole group of patients, a reduction in the frequency of micronuclei was obtained in the patients group. Induced micronuclei yield was significantly lower in the irradiated samples from treated relapsing–remitting multiple

  4. Does caffeine reduce postoperative bowel paralysis after elective laparoscopic colectomy? (CaCo trial): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Kruse, Christina; Müller, Sascha A; Warschkow, René; Lüthi, Cornelia; Brunner, Walter; Marti, Lukas; Sulz, Michael Christian; Schmied, Bruno M; Tarantino, Ignazio; Beutner, Ulrich

    2016-04-04

    Postoperative bowel paralysis is common after abdominal operations, including colectomy. As a result, hospitalization may be prolonged, thereby leading to increased cost. A recent randomized controlled trial showed that the consumption of regular black coffee after colectomy is associated with a significantly faster resumption of intestinal motility. The mechanism by which coffee stimulates intestinal motility is unknown, but caffeine seems to be the most likely stimulating agent. Thus, the effect of caffeine on postoperative bowel activity after colon surgery will be analyzed in this trial, herein referred to as CaCo. Patients scheduled for elective laparoscopic colectomy or upper rectum resection are eligible to participate in this double-blinded, placebo-controlled, randomized trial. Patients fulfilling all inclusion criteria will be allocated after the surgical procedure to one of three treatment arms: 100 mg caffeine, 200 mg caffeine, or placebo (corn starch). Patients will take the capsules containing the study medication three times daily with a meal. The primary endpoint of the study is the time to a solid bowel movement. The study treatment will be stopped after the patient produces a solid bowel movement or has taken ten capsules, whichever occurs first. To determine the colonic passage time, patients will take a capsule with radiopaque markers at breakfast for the first 3 days after surgery. On the fourth day, the location of the markers will be determined with an abdominal X-ray scan. Further secondary objectives are the postoperative morbidity and mortality, well-being, sleeping behavior, and length of hospital stay. The study size was calculated to be 180 patients with an interim analysis occurring after 60 patients. From a previous study investigating coffee, evidence exists that caffeine might have a positive influence on the postoperative bowel activity. This double-blinded, placebo-controlled, randomized trial tries to show that caffeine will

  5. Effect of Gamma Radiation on Amino Acid Based Vesicle Carrying Radiosensitizer

    International Nuclear Information System (INIS)

    Nur Ratasha Alia Mohd Rosli; Faizal Mohamed; Muhammad Amir Syafiq Mohd Sah; Irman Abdul Rahman

    2014-01-01

    Vesicles has been developed and studied to be used as a medium to transport radiosensitizer in treating cancer cells by increasing its sensitivity effectively towards the radiation given during radiotherapy. This study was conducted to investigate the effect of gamma radiation on amino acid-based vesicle carrying radiosensitizer. Amino acid based vesicles carrying radiosensitizer were synthesized using sonication method with sodium N-lauroylsarcosinate hydrate and decanol being the primary surfactant, while hydrogen peroxide and sodium hyaluronate as the encapsulated radiosensitizer. The synthesized vesicle was then irradiated at radiation doses equivalent to those given during radiotherapy. Irradiated vesicle carrying radiosensitizer were then characterized using Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR) and Polarized Light Microscope. Results obtained shows that there were no significant changes in morphology and molecular conformation of the synthesized vesicle after irradiation. Even at higher radiation dose of 100 Gray and 200 Gray, the results remained unchanged. This indicates that the synthesized vesicle carrying radiosensitizer is morphologically and spectroscopically stable even at high radiation doses. (author)

  6. The HSP90 Inhibitor Ganetespib Radiosensitizes Human Lung Adenocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Roberto Gomez-Casal

    2015-05-01

    Full Text Available The molecular chaperone HSP90 is involved in stabilization and function of multiple client proteins, many of which represent important oncogenic drivers in NSCLC. Utilization of HSP90 inhibitors as radiosensitizing agents is a promising approach. The antitumor activity of ganetespib, HSP90 inhibitor, was evaluated in human lung adenocarcinoma (AC cells for its ability to potentiate the effects of IR treatment in both in vitro and in vivo. The cytotoxic effects of ganetespib included; G2/M cell cycle arrest, inhibition of DNA repair, apoptosis induction, and promotion of senescence. All of these antitumor effects were both concentration- and time-dependent. Both pretreatment and post-radiation treatment with ganetespib at low nanomolar concentrations induced radiosensitization in lung AC cells in vitro. Ganetespib may impart radiosensitization through multiple mechanisms: such as down regulation of the PI3K/Akt pathway; diminished DNA repair capacity and promotion of cellular senescence. In vivo, ganetespib reduced growth of T2821 tumor xenografts in mice and sensitized tumors to IR. Tumor irradiation led to dramatic upregulation of β-catenin expression in tumor tissues, an effect that was mitigated in T2821 xenografts when ganetespib was combined with IR treatments. These data highlight the promise of combining ganetespib with IR therapies in the treatment of AC lung tumors.

  7. Enhanced Radiosensitivity of Tumor Cells Treated with Vanadate in Vitro

    International Nuclear Information System (INIS)

    Lee, Myung Za; Lee, Won Young

    1994-01-01

    Intracellular ions which have a major role in cellular function have been reported to affect repair of radiation damage. Recently it has been reported that ouabain sensitizes A549 tumor cells hut not CCL-120 normal cells to radiation. Ouabain inhibits the Na+-K+-pump rapidly thus it increases intracellular Na concentration. Vanadate which is distributed extensively in almost all living organisms in known to be a Na+-K+-ATPase inhibitors. This study was performed to see any change in radiosensitivity of tumor cell by vanadate and any role of Na+-K+-ATPase in radiosensitization. Experiments have been carried out by pretreatment with vanadate in human cell line(A549, JMG) and mouse cell line(L1210, spleen). For the cell survival MTT assay was performed for A549 and JMG cell and trypan blue dye exclusion test for L120, and spleen cells. Measurements of Na+-K+-ATPase activity in control, vanadate treated cell, radiation treated cell (9 Gy for A549 and JMG, 2 Gy for L1201, spleen), and combined 10-6 M vanadate and radiation treated cells were done. The results were summarized as follows. 1. L1210 cell was most radiosensitive, and spleen cell and JMG cell were intermediate, and A549 cell was least radiosensitive. 2. Minimum or cytotoxicity was seen with vanadate below concentration of 10-6 M. 3. In A549 cells there was a little change in radiosensitivity with treatment of vanadate. However radiation sensitization was shown in low dose level of radiation i. E. 2-Gy. In JMG cells no change in radiosensitivity was noted. Both L1210 and spleen cell had radiosensitization but change was greater in tumor cell. 4. Na+-K+-ATPase activity was inhibited significantly in tumor cell by treatment of vanadate. 5. Radiation itself inhibited Na+-K+-ATPase activity of tumor cell with high Na+- K+-ATPase concention. Increase in radiosensitivity by vanadate was closely associated with original Na+-K+-ATPase contents. From the above results vanadate had little cytotoxicity and it sensitized

  8. Effect of caffeine on radiation-induced apoptosis in TK6 cells

    International Nuclear Information System (INIS)

    Zhen, W.; Vaughan, A.T.M.

    1995-01-01

    Apoptosis has been measured in cells of the human TK6 lymphoblastoid cell line by recording the release of endonuclease-digested DNA from affected cells using flow cytometry. In asynchronously dividing cells, DNA degradation characteristic of apoptosis was first seen 12 h after irradiation as a defined DNA fluorescent peak of sub-G 1 -phase content, reaching a maximum of 30-50% of the population by 24-72 h. Treating cells with 2 mM caffeine either before or up to 3 h after irradiation eliminated the degradation of DNA entirely. In addition, the percentage of cells in which apoptosis could be detected microscopically decreased from 62.4 ± 0.95% to 16.7 ± 1.5% 72 h after caffeine treatment. Delaying caffeine treatment for 12 h after irradiation reduced DNA degradation by approximately 50% compared to cells receiving radiation alone. DNA degradation induced by serum deprivation was unaffected by caffeine treatment. These data support the contention that irradiation of TK6 cells produces a long-lived cellular signal which triggers apoptosis. Apoptosis produced by serum deprivation does not operate through the same pathway. 36 refs., 5 figs

  9. Effect of caffeine on radiation-induced apoptosis in TK6 cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhen, W.; Vaughan, A.T.M. [Loyola Univ. Chicago, Maywood, IL (United States)

    1995-02-01

    Apoptosis has been measured in cells of the human TK6 lymphoblastoid cell line by recording the release of endonuclease-digested DNA from affected cells using flow cytometry. In asynchronously dividing cells, DNA degradation characteristic of apoptosis was first seen 12 h after irradiation as a defined DNA fluorescent peak of sub-G{sub 1}-phase content, reaching a maximum of 30-50% of the population by 24-72 h. Treating cells with 2 mM caffeine either before or up to 3 h after irradiation eliminated the degradation of DNA entirely. In addition, the percentage of cells in which apoptosis could be detected microscopically decreased from 62.4 {+-} 0.95% to 16.7 {+-} 1.5% 72 h after caffeine treatment. Delaying caffeine treatment for 12 h after irradiation reduced DNA degradation by approximately 50% compared to cells receiving radiation alone. DNA degradation induced by serum deprivation was unaffected by caffeine treatment. These data support the contention that irradiation of TK6 cells produces a long-lived cellular signal which triggers apoptosis. Apoptosis produced by serum deprivation does not operate through the same pathway. 36 refs., 5 figs.

  10. Validation of a radiosensitivity molecular signature in breast cancer

    NARCIS (Netherlands)

    S.A. Eschrich (Steven); C. Fulp (Carl); Y. Pawitan (Yudi); J.A. Foekens (John); M. Smid (Marcel); J.W.M. Martens (John); M. Echevarria (Michelle); P.S. Kamath (Patrick); J.-H. Lee (Ji-Hyun); E.E. Harris (Eleanor); J. Bergh (Jonas); J.F. Torres-Roca (Javier)

    2012-01-01

    textabstractPurpose: Previously, we developed a radiosensitivity molecular signature [radiosensitivity index (RSI)] that was clinically validated in 3 independent datasets (rectal, esophageal, and head and neck) in 118 patients. Here, we test RSI in radiotherapy (RT)-treated breast cancer patients.

  11. Effects of caffeinated chewing gum on muscle pain during submaximal isometric exercise in individuals with fibromyalgia.

    Science.gov (United States)

    Umeda, Masataka; Kempka, Laura; Weatherby, Amy; Greenlee, Brennan; Mansion, Kimberly

    2016-04-01

    Physical activity is important to manage symptom of fibromyalgia (FM); however, individuals with FM typically experience augmented muscle pain during exercise. This study examined the effects of caffeinated chewing gum on exercise-induced muscle pain in individuals with FM. This study was conducted with a double-blind, placebo-controlled, cross-over design. Twenty-three patients with FM completed a caffeine condition where they consumed a caffeinated chewing gum that contains 100mg of caffeine, and a placebo condition where they consumed a non-caffeinated chewing gum. They completed isometric handgrip exercise at 25% of their maximal strength for 3 min, and muscle pain rating (MPR) was recorded every 30s during exercise. Clinical pain severity was assessed in each condition using a pain questionnaire. The order of the two conditions was randomly determined. MPR increased during exercise, but caffeinated chewing gum did not attenuate the increase in MPR compared to placebo gum. Clinical pain severity was generally associated with the average MPR and the caffeine effects on MPR, calculated as difference in the average MPR between the two conditions. The results suggest that more symptomatic individuals with FM may experience greater exercise-induced muscle pain, but benefit more from caffeinated chewing gum to reduce exercise-induced muscle pain. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Exercise and sport performance with low doses of caffeine.

    Science.gov (United States)

    Spriet, Lawrence L

    2014-11-01

    Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. The majority of research has examined the effects of moderate to high caffeine doses (5-13 mg/kg body mass) on exercise and sport. These caffeine doses have profound effects on the responses to exercise at the whole-body level and are associated with variable results and some undesirable side effects. Low doses of caffeine (caffeine doses (1) do not alter the peripheral whole-body responses to exercise; (2) improve vigilance, alertness, and mood and cognitive processes during and after exercise; and (3) are associated with few, if any, side effects. Therefore, the ergogenic effect of low caffeine doses appears to result from alterations in the central nervous system. However, several aspects of consuming low doses of caffeine remain unresolved and suffer from a paucity of research, including the potential effects on high-intensity sprint and burst activities. The responses to low doses of caffeine are also variable and athletes need to determine whether the ingestion of ~200 mg of caffeine before and/or during training and competitions is ergogenic on an individual basis.

  13. Higher Caffeinated Coffee Intake Is Associated with Reduced Malignant Melanoma Risk: A Meta-Analysis Study.

    Directory of Open Access Journals (Sweden)

    Jibin Liu

    Full Text Available Several epidemiological studies have determined the associations between coffee intake level and skin cancer risk; however, the results were not yet conclusive. Herein, we conducted a systematic review and meta-analysis of the cohort and case-control studies for the association between coffee intake level and malignant melanoma (MM risk.Studies were identified through searching the PubMed and MEDLINE databases (to November, 2015. Study-specific risk estimates were pooled under the random-effects model.Two case-control studies (846 MM patients and 843 controls and five cohort studies (including 844,246 participants and 5,737 MM cases were identified. For caffeinated coffee, the pooled relative risk (RR of MM was 0.81 [95% confidential interval (95% CI = 0.68-0.97; P-value for Q-test = 0.003; I2 = 63.5%] for those with highest versus lowest quantity of intake. In the dose-response analysis, the RR of MM was 0.955 (95% CI = 0.912-0.999 for per 1 cup/day increment of caffeinated coffee consumption and linearity dose-response association was found (P-value for nonlinearity = 0.326. Strikingly, no significant association was found between the decaffeinated coffee intake level and MM risk (pooled RR = 0.92, 95% CI = 0.81-1.05; P-value for Q-test = 0.967; I2 = 0%; highest versus lowest quantity of intake.This meta-analysis suggested that caffeinated coffee might have chemo-preventive effects against MM but not decaffeinated coffee. However, larger prospective studies and the intervention studies are warranted to confirm these findings.

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

    International Nuclear Information System (INIS)

    Vendramini, L.C.; Nishiura, J.L.; Baxmann, A.C.; Heilberg, I.P.

    2012-01-01

    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

  15. 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.

  16. Caffeine cravings impair memory and metacognition.

    Science.gov (United States)

    Palmer, Matthew A; Sauer, James D; Ling, Angus; Riza, Joshua

    2017-10-01

    Cravings for food and other substances can impair cognition. We extended previous research by testing the effects of caffeine cravings on cued-recall and recognition memory tasks, and on the accuracy of judgements of learning (JOLs; predicted future recall) and feeling-of-knowing (FOK; predicted future recognition for items that cannot be recalled). Participants (N = 55) studied word pairs (POND-BOOK) and completed a cued-recall test and a recognition test. Participants made JOLs prior to the cued-recall test and FOK judgements prior to the recognition test. Participants were randomly allocated to a craving or control condition; we manipulated caffeine cravings via a combination of abstinence, cue exposure, and imagery. Cravings impaired memory performance on the cued-recall and recognition tasks. Cravings also impaired resolution (the ability to distinguish items that would be remembered from those that would not) for FOK judgements but not JOLs, and reduced calibration (correspondence between predicted and actual accuracy) for JOLs but not FOK judgements. Additional analysis of the cued-recall data suggested that cravings also reduced participants' ability to monitor the likely accuracy of answers during the cued-recall test. These findings add to prior research demonstrating that memory strength manipulations have systematically different effects on different types of metacognitive judgements.

  17. [birthweight And Caffeine Consumption].

    OpenAIRE

    Bicalho, Gladys Gripp; Barros Filho, Antônio de Azevedo

    2015-01-01

    To assess the association between maternal caffeine consumption during pregnancy and low birth weight, prematurity and intrauterine growth retardation. A case-control was carried out and 354 newborns of single labor with birthweight 3,000 g (controls) were analyzed. Caffeine consumption was calculated based on daily consumption of coffee, soft drinks and tea. Results were adjusted using multiple logistic regression for the following confounders: mother's age, schooling, income, marital status...

  18. D-ribose--an additive with caffeine.

    Science.gov (United States)

    Herrick, Jim; Shecterle, L M; St Cyr, J A

    2009-05-01

    Caffeine acts as a stimulant, in which approximately 90% of people in the United States consume daily. Besides its beneficial effects, many individuals have experienced unpleasant reactions following the consumption of caffeine: such as insomnia, an increase in heart rate, feelings of nervousness, headaches, occasional lightheadedness, a state of "jitters," and a potential "crash" state following its metabolism. Researchers have proposed mechanisms responsible for caffeine's interactions, which include its blocking capacity of adenosine receptors, its role with the pituitary gland, increasing levels of dopamine, and its role with the intracellular release of calcium from the sarcoplasmic reticulum, which is dependent on intracellular adenosine triphosphate levels. Specific substrates have been investigated to lessen the undesirable effects of caffeine and still preserve its stimulatory benefits. The results of these investigations have produced no positive consensus. However, D-ribose, an important pentose carbohydrate in the energy molecule of adenosine triphosphate, as well as our genetic code and other cellular processes, could offer such a solution to this problem. D-ribose could potentially aid in maintaining or potentially lowering extra-cellular adenosine concentrations, aid in the flux of intracellular calcium, aid in intracellular energy production, and potentially lessen the perceived "crash" state felt by many. Every cell requires adequate levels of energy to maintain its integrity and function. Caffeine has the potential to task this energy equilibrium. D-ribose with caffeine may be the substrate to aid in the potential intracellular energy demand, aid in lessening the perceived unpleasant side effects of caffeine, and still preserving the desired benefits of this stimulant consumed by all of us daily.

  19. Caffeine effects on resting-state arousal.

    Science.gov (United States)

    Barry, Robert J; Rushby, Jacqueline A; Wallace, Mark J; Clarke, Adam R; Johnstone, Stuart J; Zlojutro, Ilinka

    2005-11-01

    This study examined the use of caffeine to manipulate arousal level without the confounds associated with task-related activation. From previous work in our laboratory, an increase in skin conductance level (SCL) and EEG alpha frequency, together with a global decrease in alpha power, were used as markers of arousal increase, and we sought to identify these effects with caffeine ingestion. We examined the effect of a single oral dose of caffeine (250 mg) in a randomised double-blind placebo-controlled repeated-measures cross-over study. Eighteen healthy university students (mean age 21 years; 13/18 females) participated in two sessions 1 week apart. EEG and autonomic data (SCL, heart rate, systolic and diastolic blood pressure, and respiration rate) from a 2 min eyes-closed epoch, commencing approximately 30 min after ingestion of caffeine or placebo, were examined. Caffeine was associated with increased SCL, a global reduction in EEG power in the alpha band, and a global increase in alpha frequency. There were no cardiovascular effects. The positive results are consistent with recent electrodermal and EEG studies of arousal and suggest that caffeine may be utilised as a task-free means of manipulating arousal in future investigations. Further work is necessary to clarify the absence of cardiovascular effects, and to integrate those data with emerging conceptualisations of arousal and activation. The present data support the use of caffeine as a simple tool to explore the role of arousal in both normal and atypical functioning, and this may be useful in determining the validity and importance of supposed hyper- or hypo-arousal in such syndromes as attention-deficit/hyperactivity disorder (AD/HD).

  20. Administration of Caffeine in Alternate Forms

    OpenAIRE

    Wickham, Kate A.; Spriet, Lawrence L.

    2018-01-01

    There has been recent interest in the ergogenic effects of caffeine delivered in low doses (~ 200 mg or ~ 3 mg/kg body mass) and administered in forms other than capsules, coffee and sports drinks, including chewing gum, bars, gels, mouth rinses, energy drinks and aerosols. Caffeinated chewing gum is absorbed quicker through the buccal mucosa compared with capsule delivery and absorption in the gut, although total caffeine absorption over time is not different. Rapid absorption may be importa...

  1. High versus standard dose caffeine for apnoea: a systematic review

    NARCIS (Netherlands)

    Vliegenthart, Roos; Miedema, Martijn; Hutten, Gerard J.; van Kaam, Anton H.; Onland, Wes

    2018-01-01

    Placebo-controlled trials have shown that caffeine is highly effective in treating apnoea of prematurity and reduces the risk of bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment (NDI). To identify, appraise and summarise studies investigating the modulating effect of different

  2. Chromosomal radiosensitivity of prostate cancer patients

    International Nuclear Information System (INIS)

    McRobbie, M.L.; Riches, A.; Baxby, K.

    2003-01-01

    Full text: Radiosensitivity of peripheral blood lymphocytes from prostate cancer patients is being investigated using the G2 assay and the Cytokinesis Block Micronucleus(CBMN)assay. The G2 assay evaluates chromosomal damage caused by irradiating cells in the G2 phase of the cell cycle. The CBMN assay quantifies the post mitotic micronuclei, which are the expression of damage incurred during G0. An association between hypersensitivity to the chromosome damaging effects of ionising radiation and cancer predispostion has been demonstrated in a number of heritable conditions by using the aforementioned techniques. Recently, increased chromosomal radiosensitivity has been demonstrated in a significant proportion of patients with no obvious family history of malignancy. The aim of this study is to establish whether a group of prostatic carcinoma patients exists and if so whether there are any correlations between their G2 and G0 sensitivities. The study has shown there is no correlation between G2 and G0 sensitivity, confirming the general trend that individuals exhibiting chromosomal radiosensitivity are defective in only one mechanism and G2 and G0 sensitivity are largely independent. Current data indicates that there is an identifiable group of men within the prostate cancer population with increased chromosomal radiosensitivity. Using the G2 assay and the 90th percentile of the controls as a cut off point for sensitivity, no significant difference between the controls and the patient population has been found. However, using the CBMN assay and again the 90th percentile, approximately 11% of the control group are sensitive compared with approximately 40% of the carcinoma cases. The implications of this increased radiosensitivity are as yet unclear, but it is indicative of increased chromosomal fragility and therefore, possibly associated with malignant transformation. Hence, it may prove a useful tool in identifying individuals at increased risk of developing

  3. Predictive radiosensitivity tests in human lymphocytes

    International Nuclear Information System (INIS)

    Di Giorgio, Marina; Vallerga, Maria B.; Taja, Maria R.; Sardi, M.; Busto, E.; Mairal, L.; Roth, B.; Menendez, P.; Bonomi, M.

    2004-01-01

    Individual radiosensitivity is an inherent characteristic, associated with an abnormally increased reaction to ionising radiation of both the whole body and cells derived from body tissues. Human population is not uniform in its radiation sensitivity. Radiosensitive sub-groups exist, which would suffer an increased incidence of both deterministic and stochastic effects. Clinical studies have suggested that a large part of the spectrum of normal tissue reaction may be due to differences in individual radiosensitivity. The identification of such sub-groups should be relevant for radiation therapy and radiation protection purposes. It is suggested that DNA repair mechanisms are involved. Consequently, the characterization of DNA repair in lymphocytes through cytokinesis blocked micronucleus (MN) and alkaline single-cell microgel electrophoresis (comet) assays could be a suitable approache to evaluate individual radiosensitivity in vitro. The aims of this study were: 1) To assess the in vitro radiosensitivity of peripheral blood lymphocytes from two groups of cancer patients (prospectively and retrospectively studied), using MN and comet assays, in comparison with the clinical radiation reaction and 2) To test the predictive potential of both techniques for the identification of radiosensitivity sub-groups. 38 cancer patients receiving radiation therapy were enrolled in this study. 19 patients were evaluated prior, mid-way and on completion of treatment (prospective group) and 19 patients were evaluated about 6-18 month after radiotherapy (retrospective group). Cytogenetic data from the prospective group were analysed using a mathematical model to evaluate the attenuation of the cytogenetic effect as a function of the time between a single exposure and blood sampling, estimating a cytogenetic recovery factor k. In the retrospective group, blood samples were irradiated in vitro with 0 (control) or 2 Gy and evaluated using MN test. Cytogenetic data were analysed

  4. Fewer but heavier caffeine consumers in schizophrenia: a case-control study.

    Science.gov (United States)

    Gurpegui, Manuel; Aguilar, M Carmen; Martínez-Ortega, José M; Jurado, Dolores; Diaz, Francisco J; Quintana, Hernando M; de Leon, Jose

    2006-09-01

    According to the literature, there is an association between schizophrenia and caffeine consumption, but it is not clear whether schizophrenia is associated with either higher prevalence of daily caffeine intake or the amount consumed. In this study we compared our previously published schizophrenia patients (n=250) with a control sample (n=290) after controlling for demographic variables and tobacco and alcohol consumption. Current caffeine intake was less frequent in schizophrenia patients (59%, 147/250) than in controls (70%, 204/290). In the multivariate analyses, caffeine intake was less frequent at an older age and in schizophrenia patients, and more frequent in smokers and alcohol users. Among caffeine consumers, heavy caffeine intake (> or =200 mg/day) was significantly associated with schizophrenia (64%, 94/147 in schizophrenia versus 36%, 73/204 in controls), as well as older age and smoking. Daily amount of caffeine intake and smoked cigarettes correlated significantly in the schizophrenia group but not in the control group; the correlation of caffeine intake with nicotine dependence was low and non-significant in both groups. The association between current smoking and heavy caffeine intake may be partly explained by a pharmacokinetic effect: tobacco smoke compounds induce caffeine metabolism by the cytochrome P450 1A2. Although schizophrenia by itself may be associated with heavy caffeine intake in caffeine users, part of this association was explained by the association between schizophrenia and smoking. The relationship between caffeine and alcohol intake appeared to be more complex; alcohol and caffeine use were significantly associated, but within caffeine users alcohol was associated with less frequent heavy caffeine consumption among smokers. In future studies, the measurement of plasma caffeine levels will help both to better define heavy caffeine intake and to control for smoking pharmacokinetic effects.

  5. Reinforcing effects of caffeine in coffee and capsules.

    OpenAIRE

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

    1989-01-01

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

  6. The inhibition of PARP but not EGFR results in the radiosensitization of HPV/p16-positive HNSCC cell lines

    International Nuclear Information System (INIS)

    Güster, Julian David; Weissleder, Stephanie Valerie; Busch, Chia-Jung; Kriegs, Malte; Petersen, Cordula; Knecht, Rainald; Dikomey, Ekkehard; Rieckmann, Thorsten

    2014-01-01

    Background and purpose: HPV-negative and HPV-positive HNSCC comprise distinct tumor entities with different biological characteristics. Specific regimens for the comparably well curable HPV-positive entity that reduce side effects without compromising outcome have yet to be established. Therefore, we tested here whether the inhibition of EGFR or PARP may be used to specifically enhance the radiosensitivity of HPV-positive HNSCC cells. Materials and methods: Experiments were performed with five HPV/p16-positive HNSCC cell lines. Inhibitors used were cetuximab, olaparib and PF-00477736. The respective inhibition of EGFR, PARP and Chk1 was evaluated by Western blot, immunofluorescence analysis and assessment of cell cycle distribution. Cell survival was assessed by colony formation assay. Results: Inhibition of EGFR by cetuximab failed to radiosensitize any of the HPV-positive HNSCC cell lines tested. In contrast, PARP-inhibition resulted in a substantial radiosensitization of all strains, with the sensitization being further enhanced by the additional inhibition of Chk1. Conclusions: PARP-inhibition effectively radiosensitizes HPV-positive HNSCC cells and may therefore represent a viable alternative to chemotherapy possibly even allowing for a reduction in radiation dose. For the latter, PARP-inhibition may be combined with the inhibition of Chk1. In contrast, the inhibition of EGFR cannot be expected to radiosensitize HPV-positive HNSCC through the modulation of cellular radiosensitivity

  7. Caffeine Withdrawal and Dependence: A Convenience Survey Among Addiction Professionals.

    Science.gov (United States)

    Budney, Alan J; Brown, Pamela C; Griffiths, Roland R; Hughes, John R; Juliano, Laura M

    2013-06-01

    Caffeine withdrawal was included in the research appendix of the DSM-IV to encourage additional research to assist with determining its status for the next version of the manual. Caffeine dependence was not included because of a lack of empirical research at the time of publication. This study assessed the beliefs of addiction professionals about the clinical importance of caffeine withdrawal and dependence. A 6-item survey was developed and delivered electronically to the members of six professional organizations that focus on addiction. Open-ended comments were also solicited. Five hundred members responded. The majority (95%) thought that cessation of caffeine could produce a withdrawal syndrome, and that caffeine withdrawal can have clinical importance (73%); however, only half (48%) thought that caffeine withdrawal should be included in the Diagnostic and Statistical Manual of Mental Disorders (DSM). A majority (58%) believed that some people develop caffeine dependence; however, only 44% indicated that it should be in the DSM. Comments suggested that trepidation about inclusion of caffeine diagnoses was due to the concerns about the field of psychiatry being criticized for including common disorders with a relatively low clinical severity. Others, however, expressed an urgent need to take caffeine-related problems more seriously. The majority of addiction professionals believe that caffeine withdrawal and dependence disorders exist and are clinically important; however, these professionals are divided in whether caffeine withdrawal and dependence should be included in DSM. Wider dissemination of the extant literature on caffeine withdrawal and additional research on caffeine dependence will be needed to provide additional guidance to policymakers and healthcare workers.

  8. Caffeine antagonism of alcohol-induced driving impairment.

    Science.gov (United States)

    Liguori, A; Robinson, J H

    2001-07-01

    The extent to which caffeine antagonizes alcohol-induced impairment of simulated automobile driving at the current lowest legal American limit (0.08% BrAC) was the focus of this study. Fifteen adults swallowed a capsule (0, 200, or 400 mg caffeine) then drank a beverage (0.0 or 0.6 g/kg ethanol) in a within-subject, double-blind, randomized procedure. Forty-five minutes later, participants completed a test battery of subjective effects scales, dynamic posturography, critical flicker fusion (CFF), choice reaction time (CRT), divided attention (Stroop test), and simulated driving. Alcohol alone increased ratings of 'dizzy', 'drug effect', and 'high', slowed CRT and brake latency, and increased body sway. Caffeine alone increased ratings of 'alert' and 'jittery', but did not significantly affect body sway or psychomotor performance. Both caffeine doses comparably counteracted alcohol impairment of brake latency but not CRT or body sway. Brake latency with either alcohol-caffeine combination remained significantly longer than that with placebo. Stroop and CFF performance were unaffected by any drug condition. The results suggest that caffeine may increase alertness and improve reaction time after alcohol use but will not completely counteract alcohol impairment in a driver.

  9. Efficacy of a cosmetic phyto-caffeine shampoo in female androgenetic alopecia.

    Science.gov (United States)

    Bussoletti, Carolina; Tolaini, Maria V; Celleno, Leonardo

    2018-03-06

    Androgenetic alopecia (AGA) is the most common type of hair loss in both males as well as females, occurring in up to 57% of women by the age of 80 years. Androgenetic alopecia is associated with a high psychological burden and often results in substantially reduced quality of life, poor body image and low self-esteem, particularly in women. Caffeine-based products have shown promise, both in vitro and in vivo, as potential treatments for AGA. This study was performed to determine the efficacy of a phyto-caffeine- containing shampoo used over a 6-month period in female subjects with AGA. This was a single-centre, double-blind parallel trial in which female subjects with AGA were randomized to either a phyto-caffeine-containing shampoo or a control shampoo. The primary endpoint was the change from baseline in the number of hairs pulled in a hair pull test at 6 months. Hair loss intensity, hair strength, subject satisfaction and tolerability were also assessed. Subjects using the phyto-caffeine-containing shampoo had significantly fewer hairs pulled in a hair pull test at 6 months, compared with subjects using the control shampoo (-3.1 vs -0.5 hairs; pshampoo, compared with controls. Both products were very well tolerated. Compared with a control shampoo, a phyto-caffeine-containing shampoo was more efficacious, with respect to the number of hairs being pulled out at 6 months, hair loss intensity and hair strength in subjects with AGA.

  10. 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%. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

  11. Enhancement of P53-Mutant Human Colorectal Cancer Cells Radiosensitivity by Flavonoid Fisetin

    International Nuclear Information System (INIS)

    Chen Wenshu; Lee Yijang; Yu Yichu; Hsaio Chinghui

    2010-01-01

    Purpose: The aim of this study was to investigate whether fisetin is a potential radiosensitizer for human colorectal cancer cells, which are relatively resistant to radiotherapy. Methods and Materials: Cell survival was examined by clonogenic survival assay, and DNA fragmentation was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. The effects of treatments on cell cycle distribution and apoptosis were examined by flow cytometry. Western blot analysis was performed to ascertain the protein levels of γ-H2AX, phospho-Chk2, active caspase-3, PARP cleavage, phospho-p38, phospho-AKT, and phospho-ERK1/2. Results: Fisetin pretreatment enhanced the radiosensitivity of p53-mutant HT-29 human colorectal cancer cells but not human keratocyte HaCaT cells; it also prolonged radiation-induced G 2 /M arrest, enhanced radiation-induced cell growth arrest in HT-29 cells, and suppressed radiation-induced phospho-H2AX (Ser-139) and phospho-Chk2 (Thr-68) in p53-mutant HT-29 cells. Pretreatment with fisetin enhanced radiation-induced caspase-dependent apoptosis in HT-29 cells. Fisetin pretreatment augmented radiation-induced phosphorylation of p38 mitogen-activated protein kinase, which is involved in caspase-mediated apoptosis, and SB202190 significantly reduced apoptosis and radiosensitivity in fisetin-pretreated HT-29 cells. By contrast, both phospho-AKT and phospho-ERK1/2, which are involved in cell proliferation and antiapoptotic pathways, were suppressed after irradiation combined with fisetin pretreatment. Conclusions: To our knowledge, this study is the first to provide evidence that fisetin exerts a radiosensitizing effect in p53-mutant HT-29 cells. Fisetin could potentially be developed as a novel radiosensitizer against radioresistant human cancer cells.

  12. The influence of CYP1A2 genotype in the blood pressure response to caffeine ingestion is affected by physical activity status and caffeine consumption level.

    Science.gov (United States)

    Soares, Rogerio Nogueira; Schneider, Augusto; Valle, Sandra Costa; Schenkel, Paulo Cavalheiro

    2018-03-06

    This study aimed to investigate whether the influence of CYP1A2 genotype in the blood pressure (BP) response to caffeine ingestion was affected by physical activity status and habitual caffeine consumption. Thirty-seven participants (19-50 years old) took place in the study and were categorized according to i) genotype: CYP1A2 (AA) "fast metabolizer", and CYP1A2 (AC) "slow metabolizer"; ii) physical activity level: sedentary (S) and physically active (A); and iii) caffeine consumption level: non-habitual caffeine consumer (NC) and habitual heavy caffeine consumer (C). All groups had BP assessed before (basal) and 1 hourh after (post) caffeine ingestion (6 mg·kg -1 ). It was observed that AC genotype individuals had increased basal-DBP and post-caffeine SBP when compared to AA individuals. Additionally, acute caffeine ingestion increased SBP only in the AC group. It was also found that physical activity only modulated the BP responses to acute caffeine ingestion in AC individuals. Furthermore, the results indicated that the habitual heavy caffeine consumers AC individuals had increased basal-DBP when compared to the AA ones. Our results suggest that the influence of CYP1A2 genotype in the basal and post-caffeine BP response to caffeine ingestion is modified by physical activity status and caffeine consumption level. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Teratogenic effects of caffeine and clomipramine on rat fetus

    Directory of Open Access Journals (Sweden)

    Takzare N

    2012-09-01

    Full Text Available Background: Obsessive-compulsive disorders and depression have a high prevalence during pregnancy therefore, pregnant women may take clomipramine and also take other drugs or consume foods that contain caffeine. As investigations about the teratogenic effects of clomipramine and its concurrent administration with caffeine during organogenesis period are scarce, we aimed to study the teratogenicity of simultaneous administration of clomipramine and caffeine in rat fetus.Methods: After dividing 42 pregnant rats to several case and control groups, we injected different doses of caffeine and clomipramine to the animals. All the injections were performed on the eighth until the 15th day of pregnancy. We removed the fetuses on the 17th day of pregnancy and studied the morphological features and apparent anomalies of the fetuses macroscopically. Results: We found a significant rate of mortality, apparent anomalies, abnormal torsion, shrinkage of skin and subcutaneous bleeding in fetuses of rats receiving high doses of caffeine or a combination of caffeine and clomipramine. Statistical analysis of the data revealed a significant increase (P?0.001 in teratogenicity of high doses of caffeine and its combination with clomipramine. Conclusion: This study implies simultaneous intake of high amounts of caffeine and clomipramine lead to teratogenicity. We recommend pregnant women to avoid uncontrolled consumption of foods that contain caffeine or drugs that contain high amounts of this substance. They should not also take clomipramine with caffeine in the first trimester of pregnancy.

  14. Effects of caffeine on protein phosphorylation and cell cycle progression in X-irradiated two-cell mouse embryos

    International Nuclear Information System (INIS)

    Jung, Th.; Streffer, C.

    1992-01-01

    To understand the mechanism of the caffeine-induced uncoupling of mitosis and the cellular reactions to DNA-damaging agents, the authors studied the effects of caffeine treatment on cell cycle progression and protein phosphorylation in two-cell mouse embryos after X-irradiation. Caffeine alone had no effect on timing of and changes in phosphorylation associated with the embryonic cell cycle. In combination with X-rays, caffeine was able to override the radiation induced G 2 block and restored normal timing of these phosphorylation changes after X-irradiation. New additional changes in protein phosphorylation appeared after the combined treatment. Isobutyl-methylxanthine (IBMX), a substance chemically related to caffeine but a more specific inhibitor of the phosphodiesterase that breaks down cyclic AMP, reduced radiation induced G 2 block from 4 to 5 h to about 1 h and restored the cell cycle associated changes in protein phosphorylation. (author)

  15. Effects of caffeine on protein phosphorylation and cell cycle progression in X-irradiated two-cell mouse embryos

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Th. (AFRC Institute of Animal Physiology and Genetics Research, Babraham (United Kingdom)); Streffer, C. (Essen Univ (Germany). Inst. fuer Medizinische Strahlenbiolgie)

    1992-08-01

    To understand the mechanism of the caffeine-induced uncoupling of mitosis and the cellular reactions to DNA-damaging agents, the authors studied the effects of caffeine treatment on cell cycle progression and protein phosphorylation in two-cell mouse embryos after X-irradiation. Caffeine alone had no effect on timing of and changes in phosphorylation associated with the embryonic cell cycle. In combination with X-rays, caffeine was able to override the radiation induced G[sub 2] block and restored normal timing of these phosphorylation changes after X-irradiation. New additional changes in protein phosphorylation appeared after the combined treatment. Isobutyl-methylxanthine (IBMX), a substance chemically related to caffeine but a more specific inhibitor of the phosphodiesterase that breaks down cyclic AMP, reduced radiation induced G[sub 2] block from 4 to 5 h to about 1 h and restored the cell cycle associated changes in protein phosphorylation. (author).

  16. Effect of Carbohydrate, Caffeine, and Carbohydrate + Caffeine Mouth Rinsing on Intermittent Running Performance in Collegiate Male Lacrosse Athletes.

    Science.gov (United States)

    Dolan, Patrick; Witherbee, Kyle E; Peterson, Kimi M; Kerksick, Chad M

    2017-09-01

    Dolan, P, Witherbee, KE, Peterson, KM, and Kerksick, CM. Effect of carbohydrate, caffeine, and carbohydrate + caffeine mouth rinsing on intermittent running performance in collegiate male lacrosse athletes. J Strength Cond Res 31(9): 2473-2479, 2017-Recently, an interest has developed in the potential to rinse the oral cavity with key nutrients to impact various types of exercise and presumably sporting performance. Although multiple studies examining carbohydrate mouth rinsing have been completed, conflicting evidence surrounding caffeine mouth rinsing persists, and no research has explored its ability to impact high-intensity, intermittent running performance. This study investigated the independent and synergistic ability of carbohydrate and caffeine mouth rinsing to improve intermittent running performance. The Yo-Yo Intermittent Recovery Test-Level 1 (Yo-Yo Level 1) was completed in 10 collegiate (National Collegiate Athletic Association [NCAA] Division II) male lacrosse players after a 10-second mouth rinse with a solution of either carbohydrate (CHO), caffeine (CAF), carbohydrate + caffeine (CHO + CAF), placebo (H2O), or a no rinse control (CON). No significant improvements in Yo-Yo IRT-1 performance were found (p > 0.05). Perceptual indications of effort (i.e., rating of their perceived exertion [RPE]) were significantly lower (p ≤ 0.05) in CHO and CHO + CAF when compared with CON after speed level 11. Interestingly, RPE levels were nonsignificantly lower in all but one level of the Yo-Yo Level 1 for CHO in comparison with other groups. Carbohydrate and caffeine mouth rinsing seems to exert no impact on running performance before maximal intermittent running in a group of male collegiate lacrosse players.

  17. [Caffeine as a preventive drug for Parkinson's disease: epidemiologic evidence and experimental support].

    Science.gov (United States)

    Góngora-Alfaro, José Luis

    Prospective epidemiologic studies performed in large cohorts of men (total: 374,003 subjects) agree in which the risk of suffering Parkinson's disease diminishes progressively as the consumption of coffee and other caffeinated beverages increases. In the case of women (total: 345,184 subjects) the protective effect of caffeine is only observed in menopausal women which do not receive estrogen replacement therapy. Studies with models of acute parkinsonism in rodents have shown that caffeine reduces the loss of nigrostriatal dopaminergic neurons induced with the neurotoxins 6-hidroxidopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, effect that seems to be mediated through blockade of A(2A) adenosine receptors. Recently, it was shown that male rats treated with moderate doses of caffeine (5 mg/kg/day) during six months, followed by a withdrawal period of at least two weeks, developed a greater resistance to the catalepsy induced with the dopaminergic antagonist haloperidol, which was possibly mediated by an increase of dopaminergic transmission in the corpus striatum. More studies are needed to demonstrate unequivocally that caffeine prevents the degeneration of dopaminergic neurons in animal models of moderate, chronic, and progressive parkinsonism, since it could lead to the discovery of more effective drugs for the prevention of aging-related degenerative diseases of the central nervous system.

  18. The role of propranolol as a radiosensitizer in gastric cancer treatment

    Directory of Open Access Journals (Sweden)

    Liao XH

    2018-03-01

    Full Text Available Xinhua Liao, Prakash Chaudhary, Guanglin Qiu, Xiangming Che, Lin Fan General Surgery Department, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China Purpose: The National Comprehensive Cancer Network guidelines indicate that radiotherapy in gastric cancer shows limited effectiveness at reducing the growth of gastric cancer. Therefore, enhancing the sensitivity and effect of radiotherapy with propranolol, a β-adrenoceptor antagonist, could reduce tumor growth. The role of propranolol as a radiosensitizer has not been adequately studied; therefore, the purpose of the present study is to evaluate the effect of propranolol as a radiosensitizer against gastric cancer in vivo. Methods: Sixty-four male nude mice bearing tumor xenografts were randomly divided into four groups. Cell culture was performed using the human gastric adenocarcinoma cell line SGC-7901. Mice with tumor xenografts were treated with propranolol, isoproterenol, and radiation. The data for tumor weight and volume were obtained for statistical analyses. Furthermore, the expression levels of COX-2, NF-κB, VEGF, and EGFR were examined using immunohistochemical techniques and Western blotting.Results: The growth in the volume and weight of the tumor was lower in mouse models treated with propranolol and radiation therapy compared to the other groups. Decreased expression of NF-κB was also observed in treatment groups where both propranolol and radiation were used, leading to the reduction of COX-2, EGFR, and VEGF expression compared to that in the other groups.Conclusion: The present study indicated that propranolol potentiates the antitumor effects of radiotherapy in gastric cancer by inhibiting NF-κB expression and its downstream genes: VEGF, EGFR, and COX-2. Keywords: propranolol, radiosensitizer, gastric cancer, radiation therapy 

  19. Early-life exposure to caffeine affects the construction and activity of cortical networks in mice.

    Science.gov (United States)

    Fazeli, Walid; Zappettini, Stefania; Marguet, Stephan Lawrence; Grendel, Jasper; Esclapez, Monique; Bernard, Christophe; Isbrandt, Dirk

    2017-09-01

    The consumption of psychoactive drugs during pregnancy can have deleterious effects on newborns. It remains unclear whether early-life exposure to caffeine, the most widely consumed psychoactive substance, alters brain development. We hypothesized that maternal caffeine ingestion during pregnancy and the early postnatal period in mice affects the construction and activity of cortical networks in offspring. To test this hypothesis, we focused on primary visual cortex (V1) as a model neocortical region. In a study design mimicking the daily consumption of approximately three cups of coffee during pregnancy in humans, caffeine was added to the drinking water of female mice and their offspring were compared to control offspring. Caffeine altered the construction of GABAergic neuronal networks in V1, as reflected by a reduced number of somatostatin-containing GABA neurons at postnatal days 6-7, with the remaining ones showing poorly developed dendritic arbors. These findings were accompanied by increased synaptic activity in vitro and elevated network activity in vivo in V1. Similarly, in vivo hippocampal network activity was altered from the neonatal period until adulthood. Finally, caffeine-exposed offspring showed increased seizure susceptibility in a hyperthermia-induced seizure model. In summary, our results indicate detrimental effects of developmental caffeine exposure on mouse brain development. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. ATM induction insufficiency in a radiosensitive breast-cancer patient

    International Nuclear Information System (INIS)

    Clarke, R.A.; Fang, Z.H.; Marr, P.J.; Kearsley, J.H.; Papadatos, G.; Lee, C.S.; University of Sydney, Camperdown, NSW

    2002-01-01

    ATM induction insufficiency in a radiosensitive breast-cancer patient The ataxia telangiectasia (A-T) gene (ATM) is a dominant breast cancer gene with tumour suppressor activity. ATM also regulates cellular sensitivity to ionising radiation (IR) presumably through its role as a facilitator of DNA repair. In normal cells and tissues the ATM protein is rapidly induced by IR to threshold/maximum levels. The kinase function of the ATM protein is also rapidly activated in response to IR. The fact that women carriers of ATM mutations can have an increased risk of developing breast cancer and that many sporadic breast tumours have reduced levels of the ATM protein broadens the scope of ATM's tumour suppressor within the breast. This report describes the downregulation of ATM protein levels in a radiosensitive breast cancer patient. Postinduction ATM levels were up to tenfold lower in the patient's fresh tissues compared to normal controls. These results might indicate a much broader role for ATM anomalies in breast cancer aetiology. Copyright (2002) Blackwell Science Pty Ltd

  1. Evaluation of Timing and Dosing of Caffeine Citrate in Preterm Neonates for the Prevention of Bronchopulmonary Dysplasia.

    Science.gov (United States)

    Shenk, Eleni E; Bondi, Deborah S; Pellerite, Matthew M; Sriram, Sudhir

    2018-01-01

    The aim of this study was to evaluate the timing and dosing of caffeine therapy in relation to the development of bronchopulmonary dysplasia (BPD). This was a single-center, retrospective cohort study comparing early (days of life 0-2) to late (day of life 3 or greater) caffeine initiation in extremely low birth weight neonates, with a secondary analysis of large (10 mg/kg/day) to small dose (5 mg/kg/day) caffeine. There were 138 patients in the primary timing analysis. The early caffeine group had a lower incidence and reduced odds of the composite outcome of BPD or all-cause mortality, compared with the late caffeine group (64% vs. 88%, respectively; adjusted p < 0.05; adjusted OR 0.36 [95% CI 0.13-0.98]). No statistically significant difference was found between dosing groups (p = 0.29) in the primary outcome; however, there was a lower rate of patent ductus arteriosus requiring treatment (p = 0.05) and decreased likelihood of discharging home on oxygen (p = 0.02) in the large-dose group compared with the small-dose group. Early caffeine initiation significantly decreased the incidence of BPD or all-cause mortality in extremely low birth weight neonates. Patients receiving large-dose caffeine had improved secondary outcomes, although no difference in BPD was noted. Further studies are needed to determine the optimal dosing of caffeine.

  2. Effect of caffeine on peroxidase activity and gamma-ray-induced oxic and anoxic damage in Hordeum vulgare

    International Nuclear Information System (INIS)

    Balachandran, R.; Kesavan, P.C.

    1978-01-01

    The influence of caffeine during and after gamma radiation of barley seeds was studied using seedling injury and peroxidase activity as parameters. The radiation-induced stimulation of peroxidase activity is evident in eight-day only seedlings but not in embryos (i.e. immediately after irradiation). Caffeine present during irradiation of seeds soaked in oxygenated water diminishes seedling injury and also reduces the peroxidase activity to the level observed in eight-day old seedlings of unirradiated seeds. Caffeine, however, produces just the opposite effect (i.e. enhances the seedling injury and peroxidase activity of eight-day old seedlings) when applied during irradiation of seeds soaked in oxygen-free water. There is no evidence that caffeine effects enzyme activity under in vitro conditions. (author)

  3. Relation between number of hemopoietic stem cells in newborn mice and their radiosensitivity

    International Nuclear Information System (INIS)

    Sutter, T.; Maes, J.; Gerber, G.B.; Leonard, A.

    1985-01-01

    Fractionation of a radiation exposure causes greater damage in newborn mice than a single application since it induces radioresistant foetal hemopoietic stem cells to differentiate prematurely to more radiosensitive adult ones. In the present investigation, it was studied whether other agents that give rise to extensive stem cell destruction also lead to such a change in radiosensitivity. Indeed, treatment with cytostatic drugs which reduces the number of spleen colony forming units (CFU-s) and total cells also diminished the D 0 value of the surviving cells 3 days later. Adriamycin was most effective in causing damage to hemopoietic stem cells and in inducing micronuclei in bone marrow; it also had the most marked action on the D 0 of the surviving stem cells. (orig.)

  4. Caffeine delays autonomic recovery following acute exercise.

    Science.gov (United States)

    Bunsawat, Kanokwan; White, Daniel W; Kappus, Rebecca M; Baynard, Tracy

    2015-11-01

    Impaired autonomic recovery of heart rate (HR) following exercise is associated with an increased risk of sudden death. Caffeine, a potent stimulator of catecholamine release, has been shown to augment blood pressure (BP) and sympathetic nerve activity; however, whether caffeine alters autonomic function after a bout of exercise bout remains unclear. In a randomized, crossover study, 18 healthy individuals (26 ± 1 years; 23.9 ± 0.8 kg·m(-2)) ingested caffeine (400 mg) or placebo pills, followed by a maximal treadmill test to exhaustion. Autonomic function and ventricular depolarization/repolarization were determined using heart rate variability (HRV) and corrected QT interval (QTc), respectively, at baseline, 5, 15, and 30 minutes post-exercise. Maximal HR (HRmax) was greater with caffeine (192 ± 2 vs. 190 ± 2 beat·min(-1), p < 0.05). During recovery, HR, mean arterial pressure (MAP), and diastolic blood pressure (DBP) remained elevated with caffeine (p < 0.05). Natural log transformation of low-to-high frequency ratio (LnLF/LnHF) of HRV was increased compared with baseline at all time points in both trials (p < 0.05), with less of an increase during 5 and 15 minutes post-exercise in the caffeine trial (p < 0.05). QTc increased from baseline at all time points in both trials, with greater increases in the caffeine trial (p < 0.05). Caffeine ingestion disrupts post-exercise autonomic recovery because of increased sympathetic nerve activity. The prolonged sympathetic recovery time could subsequently hinder baroreflex function during recovery and disrupt the stability of autonomic function, potentiating a pro-arrhythmogenic state in young adults. © The European Society of Cardiology 2014.

  5. The Interaction of Sorbitol with Caffeine in Aqueous Solution.

    Science.gov (United States)

    Tavagnacco, Letizia; Brady, John W; Cesàro, Attilio

    2013-09-01

    Molecular dynamics simulations were carried out on a system of caffeine interacting with the sugar alcohol sorbitol. The system examined had a caffeine concentration 0.083 m and a sugar concentration 1.08 m. The trajectories of all molecules in the system were collected over a period of 80 ns and analyzed to determine whether there is any tendency for sorbitol to bind to caffeine, and if so, by what mechanism. The results show that the sorbitol molecules have an affinity for the caffeine molecules and that the binding occurred by the interaction of the aliphatic hydrophobic protons of the sugar with the caffeine face. This intermolecular association via face-to-face stacking, as suggested by simulation studies, is similar to that found for sucrose and for D-glucose, which overwhelmingly exists in the pyranose ring chair form in aqueous solution, as well as for caffeine-caffeine association. The sorbitol molecules, however, exist as relatively extended chains and are, therefore, topologically quite different from the sugars sucrose and glucose. The comparison of the average conformation of sorbitol molecules bound to caffeine with that of molecules in the free state shows a substantial similarity.

  6. Endorsement of DSM-IV dependence criteria among caffeine users.

    Science.gov (United States)

    Hughes, J R; Oliveto, A H; Liguori, A; Carpenter, J; Howard, T

    1998-10-01

    The purpose of this article is to determine whether some caffeine users endorse clinical indicators of dependence and abuse. We asked 162 randomly-selected caffeine users generic DSM-IV criteria for dependence, abuse, intoxication and withdrawal pertaining to their caffeine use in the last year via a structured telephone interview. The prevalence of endorsement of dependence items was 56% for strong desire or unsuccessful attempt to stop use, 50% for spending a great deal of time with the drug, 28% for using more than intended, 18% for withdrawal, 14% for using despite knowledge of harm, 8% for tolerance and 1% for foregoing activities to use. Seven percent of users met DSM-IV criteria for caffeine intoxication and, among those who had tried to stop caffeine permanently, 24% met DSM-IV research criteria for caffeine withdrawal. Test-retest interviews for dependency agreed in 29/30 cases (97%). Eight expert substance abuse clinicians agreed with self-endorsed caffeine dependence 91% of the time. Our results replicate earlier work and suggest that a substantial proportion of caffeine users exhibit dependence-like behaviors. Further studies are needed to determine whether such users exhibit a clinically significant syndrome of drug dependence.

  7. Re-evaluation of in vitro radiosensitivity of human fibroblasts of different genetic origins

    Energy Technology Data Exchange (ETDEWEB)

    Deschavanne, P.J.; Debieu, D.; Malaise, E.P.; Fertil, B.

    1986-08-01

    Statistical analysis of the radiosensitivity of 204 survival curves of non-transformed human fibroblast cell strains of different genetic origins was made using the multi-target one-hit model (characterized by parameters eta and D/sub 0/), the surviving fraction for a 2 Gy dose (S/sub 2/) and the mean inactivation dose (D-bar). D-bar is found to be the parameter for characterization of anomalous radiosensitivity linked to a genetic disorder and discrimination between groups of cell strains of differing radiosensitivity. It allows the description of a range of 'normal' radiosensitivity for control fibroblasts and classification of genetic disorders as a function of their mean radiosensitivity expressed in terms of D-bar. Nine groups of cell strains appear to exhibit radiosensitivity differing significantly from the controls: seven groups are hypersensitive (ataxia-telengiectasia homozygotes and heterozygotes, Cockayne's syndrome, Gardner's syndrome, 5-oxoprolinuria homozygotes and heterozygotes, Fanconi's anaemia) and two groups are more radioresistant (fibroblasts from retinoblastoma patients and individuals with chromosome 13 anomalies). Since the coupled parameter eta and D/sub 0/ failed to discriminate between the radiosensitivity of the different genetic groups, the use of D-bar to make an intercomparison of intrinsic radiosensitivity of non-transformed human fibroblasts is recommended. (U.K.).

  8. Re-evaluation of in vitro radiosensitivity of human fibroblasts of different genetic origins

    International Nuclear Information System (INIS)

    Deschavanne, P.J.; Debieu, D.; Malaise, E.P.; Fertil, B.

    1986-01-01

    Statistical analysis of the radiosensitivity of 204 survival curves of non-transformed human fibroblast cell strains of different genetic origins was made using the multi-target one-hit model (characterized by parameters eta and D 0 ), the surviving fraction for a 2 Gy dose (S 2 ) and the mean inactivation dose (D-bar). D-bar is found to be the parameter for characterization of anomalous radiosensitivity linked to a genetic disorder and discrimination between groups of cell strains of differing radiosensitivity. It allows the description of a range of 'normal' radiosensitivity for control fibroblasts and classification of genetic disorders as a function of their mean radiosensitivity expressed in terms of D-bar. Nine groups of cell strains appear to exhibit radiosensitivity differing significantly from the controls: seven groups are hypersensitive (ataxia-telengiectasia homozygotes and heterozygotes, Cockayne's syndrome, Gardner's syndrome, 5-oxoprolinuria homozygotes and heterozygotes, Fanconi's anaemia) and two groups are more radioresistant (fibroblasts from retinoblastoma patients and individuals with chromosome 13 anomalies). Since the coupled parameter eta and D 0 failed to discriminate between the radiosensitivity of the different genetic groups, the use of D-bar to make an intercomparison of intrinsic radiosensitivity of non-transformed human fibroblasts is recommended. (U.K.)

  9. Excess caffeine exposure impairs eye development during chick embryogenesis

    Science.gov (United States)

    Ma, Zheng-lai; Wang, Guang; Cheng, Xin; Chuai, Manli; Kurihara, Hiroshi; Lee, Kenneth Ka Ho; Yang, Xuesong

    2014-01-01

    Caffeine has been an integral component of our diet and medicines for centuries. It is now known that over consumption of caffeine has detrimental effects on our health, and also disrupts normal foetal development in pregnant mothers. In this study, we investigated the potential teratogenic effect of caffeine over-exposure on eye development in the early chick embryo. Firstly, we demonstrated that caffeine exposure caused chick embryos to develop asymmetrical microphthalmia and induced the orbital bone to develop abnormally. Secondly, caffeine exposure perturbed Pax6 expression in the retina of the developing eye. In addition, it perturbed the migration of HNK-1+ cranial neural crest cells. Pax6 is an important gene that regulates eye development, so altering the expression of this gene might be the cause for the abnormal eye development. Thirdly, we found that reactive oxygen species (ROS) production was significantly increased in eye tissues following caffeine treatment, and that the addition of anti-oxidant vitamin C could rescue the eyes from developing abnormally in the presence of caffeine. This suggests that excess ROS induced by caffeine is one of the mechanisms involved in the teratogenic alterations observed in the eye during embryogenesis. In sum, our experiments in the chick embryo demonstrated that caffeine is a potential teratogen. It causes asymmetrical microphthalmia to develop by increasing ROS production and perturbs Pax6 expression. PMID:24636305

  10. Enhanced intrinsic radiosensitivity after treatment with stereotactic radiosurgery for an acoustic neuroma

    International Nuclear Information System (INIS)

    Adams, Gerard; Martin, Olga A.; Roos, Daniel E.; Lobachevsky, Pavel N.; Potter, Andrew E.; Zacest, Andrew C.; Bezak, Eva; Bonner, William M.; Martin, Roger F.; Leong, Trevor

    2012-01-01

    Enhanced radiosensitivity is an uncommon phenomenon attributable to deficient DNA repair after radiotherapy which can be assessed with the γ-H2AX assay. Reports of radiosensitivity after stereotactic radiosurgery (SRS) are uncommon. We describe a case where the clinical, radiological and laboratory findings suggest enhanced radiosensitivity after SRS for an acoustic neuroma.

  11. Genotoxicity of antiobesity drug orlistat and effect of caffeine intervention: an in vitro study.

    Science.gov (United States)

    Chakrabarti, Manoswini; Ghosh, Ilika; Jana, Aditi; Ghosh, Manosij; Mukherjee, Anita

    2017-07-01

    Obesity is a major global health problem associated with various adverse effects. Pharmacological interventions are often necessary for the management of obesity. Orlistat is an FDA-approved antiobesity drug which is a potent inhibitor of intestinal lipases. In the current study, orlistat was evaluated for its genotoxic potential in human lymphocyte cells in vitro and was compared with that of another antiobesity drug sibutramine, presently withdrawn from market due its undesirable health effects. Caffeine intake may be an additional burden in people using anorectic drugs, therefore, further work is needed to be carried out to evaluate the possible effects of caffeine on orlistat-induced DNA damage. Human lymphocytes were exposed to orlistat (250, 500 and 1000 μg/ml), sibutramine (250, 500 and 1000 μg/ml) and caffeine (25, 50, 75, 100, 125 and 150 μg/ml) to assess their genotoxicity by comet assay in vitro. In addition, lymphocytes were co-incubated with caffeine (50, 75 and 100 μg/ml) and a single concentration of orlistat (250 μg/ml). Orlistat and sibutramine were genotoxic at all concentrations tested, sibutramine being more genotoxic. Caffeine was found to be genotoxic at concentrations 125 μg/ml and above. Co-treatment of orlistat with non-genotoxic concentrations (50, 75 and 100 μg/ml) of caffeine lead to a decrease in DNA damage. Orlistat can induce DNA damage in human lymphocytes in vitro and caffeine was found to reduce orlistat-induced genotoxicity.

  12. Effects of upper respiratory tract illnesses, ibuprofen and caffeine on reaction time and alertness.

    Science.gov (United States)

    Smith, Andrew P; Nutt, David J

    2014-05-01

    Compared with healthy individuals, those with upper respiratory tract illnesses (URTIs) report reduced alertness and have slower reaction times. It is important to evaluate medication that can remove this behavioural malaise. The aim of this study was to compare the effects of a combination of ibuprofen plus caffeine with ibuprofen and caffeine alone, and placebo on malaise associated with URTIs, as measured by psychomotor performance and mood testing. Volunteers were randomly assigned to one of four medication conditions as follows: 200 mg ibuprofen and 100 mg caffeine; 200 mg ibuprofen; 100 mg caffeine; placebo. A single oral dose was given and testing followed for 3 h. Efficacy variables were based on the volunteers' performance, measured by psychomotor performance and mood. The pre-drug results confirmed that those with an URTI had a more negative mood and impaired performance. Results from the simple reaction time task, at both 55- and 110-min post-dosing, showed that a single-dose of caffeinated products (I200/C100 and CAF100) led to significantly faster reaction times than IBU200 and placebo. These effects were generally confirmed with the other performance tasks. Subjective measures showed that the combination of ibuprofen and caffeine was superior to the other conditions. There were no serious adverse events reported, and study medication was well tolerated. The results from the post-drug assessments suggest that a combination of ibuprofen and caffeine was the optimum treatment for malaise associated with URTIs in that it had significant effects on objective performance and subjective measures.

  13. Caffeine Use Disorder: A Review of the Evidence and Future Implications.

    Science.gov (United States)

    Addicott, Merideth A

    2014-09-01

    The latest edition of the Diagnostic and Statistical Manual (DSM-5) has introduced new provisions for caffeine-related disorders. Caffeine Withdrawal is now an officially recognized diagnosis, and criteria for caffeine use disorder have been proposed for additional study. caffeine use disorder is intended to be characterized by cognitive, behavioral, and physiological symptoms indicative of caffeine use despite significant caffeine-related problems, similar to other Substance Use Disorders. However, since nonproblematic caffeine use is so common and widespread, it may be difficult for some health professionals to accept that caffeine use can result in the same types of pathological behaviors caused by alcohol, cocaine, opiates, or other drugs of abuse. Yet there is evidence that some individuals are psychologically and physiologically dependent on caffeine, although the prevalence and severity of these problems is unknown. This article reviews the recent changes to the DSM, the concerns regarding these changes, and some potential impacts these changes could have on caffeine consumers.

  14. 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…

  15. Caffeine in the management of patients with headache.

    Science.gov (United States)

    Lipton, Richard B; Diener, Hans-Christoph; Robbins, Matthew S; Garas, Sandy Yacoub; Patel, Ketu

    2017-10-24

    Caffeinated headache medications, either alone or in combination with other treatments, are widely used by patients with headache. Clinicians should be familiar with their use as well as the chemistry, pharmacology, dietary and medical sources, clinical benefits, and potential safety issues of caffeine. In this review, we consider the role of caffeine in the over-the-counter treatment of headache. The MEDLINE and Cochrane databases were searched by combining "caffeine" with the terms "headache," "migraine," and "tension-type." Studies that were not placebo-controlled or that involved medications available only with a prescription, as well as those not assessing patients with migraine and/or tension-type headache (TTH), were excluded. Compared with analgesic medication alone, combinations of caffeine with analgesic medications, including acetaminophen, acetylsalicylic acid, and ibuprofen, showed significantly improved efficacy in the treatment of patients with TTH or migraine, with favorable tolerability in the vast majority of patients. The most common adverse events were nervousness (6.5%), nausea (4.3%), abdominal pain/discomfort (4.1%), and dizziness (3.2%). This review provides evidence for the role of caffeine as an analgesic adjuvant in the acute treatment of primary headache with over-the-counter drugs, caffeine doses of 130 mg enhance the efficacy of analgesics in TTH and doses of ≥100 mg enhance benefits in migraine. Additional studies are needed to assess the relationship between caffeine dosing and clinical benefits in patients with TTH and migraine.

  16. Radiosensitizing efficiency of sodium glycididazole on V79 cells in vitro

    International Nuclear Information System (INIS)

    Zheng Xiulong; Gao Jianguo; Zhang Hong; Zhu Qin; Meng Xiangshun; Zhao Fang

    1995-01-01

    Radiosensitizing effect of sodium glycididazole (SGDD) on the hypoxic V 79 cells by standard in vitro colon formation method has been further studied. The results showed its toxicity was low. Its ID 50 in cells under hypoxic and aerobic condition were 23.5 and 35.7 mmol/L respectively. These indicated that SGDD showed more toxicity under hypoxic than under aerobic condition (p 1.6 was 0.48 mmol/L. Its maximum SER was 2.3 at 1.38 mmol/L. Comparisons of radiosensitizing effect of SGDD versus MISO and its mother compound (metronidazole) under the same experimental condition, SER for SGDD, MISO and metronidazole were 1.75, 1.53 and 1.07 at 0.3 mmol/L respectively. SGDD showed more radiosensitizing efficiency than MISO and much greater than metronidazole. This study further confirms our previous results i.e. SGDD is a hypoxic radiosensitizer with low toxic, high efficiency and selectively enhances the radiosensitivity of hypoxic cells for tumor radiotherapy

  17. Evaluation of 2-amino-5-nitrothiazole as a hypoxic cell radiosensitizer

    International Nuclear Information System (INIS)

    Rockwell, S.; Mroczkowski, Z.; Rupp, W.D.

    1982-01-01

    The nitroheterocyclic compound 2-amino-5-nitrothiazole (ANT) was evaluated as a hypoxic radiosensitizer. Experiments with bacteria showed that this agent was similar to misonidozole in radiosensitizing activity, but was less cytotoxic and less mutagenic than misonidazole. Experiments with EMT6 tumor cells in culture showed ANT to be an effective hypoxic radiosensitizer, although slightly less active than misonidazole, and to be less cytotoxic than misonidazole. ANT was more toxic to mice than misonidazole and produced a spectrum of symptoms, including hyperactivity and agitation, different from those of misonidazole. The toxicities of ANT and misonidazole were additive. The maximum levels of ANT achieveable in the tumors after ip injection of nontoxic doses of drug were low ( -4 M) and the radiosensitization obtainable with the drug in vivo was inferior to that obtainable with misonidazole. These findings suggest that nitrothiazoles might be an interesting class of nitroheterocyclic radiosensitizers, but that molecules with increased solubility and improved pharmacokinetics would be necessary for efficacy in vivo

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

    Science.gov (United States)

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

    2014-06-13

    Caffeine is the psychostimulant most consumed worldwide but concerns arise about the growing intake of caffeine-containing drinks by adolescents since the effects of caffeine on cognitive functions and neurochemical aspects of late brain maturation during adolescence are poorly known. We now studied the behavioral impact in adolescent male rats of regular caffeine intake at low (0.1mg/mL), moderate (0.3mg/mL) and moderate/high (1.0mg/mL) doses only during their active period (from 7:00 P.M. to 7:00 A.M.). All tested doses of caffeine were devoid of effects on locomotor activity, but triggered anxiogenic effects. Caffeine (0.3 and 1mg/mL) improved the performance in the object recognition task, but the higher dose of caffeine (1.0mg/mL) decreased the habituation to an open-field arena, suggesting impaired non-associative memory. All tested doses of caffeine decreased the density of glial fibrillary acidic protein and synaptosomal-associated protein-25, but failed to modify neuron-specific nuclear protein immunoreactivity in the hippocampus and cerebral cortex. Caffeine (0.3-1mg/mL) increased the density of brain-derived neurotrophic factor (BDNF) and proBDNF density as well as adenosine A1 receptor density in the hippocampus, whereas the higher dose of caffeine (1mg/mL) increased the density of proBDNF and BDNF and decreased A1 receptor density in the cerebral cortex. These findings document an impact of caffeine consumption in adolescent rats with a dual impact on anxiety and recognition memory, associated with changes in BDNF levels and decreases of astrocytic and nerve terminal markers without overt neuronal damage in hippocampal and cortical regions. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Determining and predictive factors for the tumor radiosensitivity

    International Nuclear Information System (INIS)

    Hennequin, Ch.; Quero, L.; Hennequin, Ch.; Quero, L.; Favaudon, V.

    2008-01-01

    Many predictive factors of tumor radiosensitivity have been described. Number of clonogenic cells, proliferation rate, hypoxia and intrinsic radiosensitivity are usually considered as the main parameters of tumor control. Intrinsic radiosensitivity is correlated in a first approach to the ability of the cell to detect and repair DNA damages, and so integrity of the different pathways involved in this function: P.A.R.P.-1, X.R.C.C.1, A.T.M., p 53, M.R.N. complex or B.R.C.A.1. Genetic polymorphisms of some of these genes, found in normal lymphocytes, have been correlated to late toxicity of normal tissues. But, in tumors, because of the difficulty to obtain samplings and heterogeneity, accurate molecular analysis is not possible in many cases, and no valuable test of radiosensitivity exist at this moment. For example, T.P. 53 gene has been evaluated in many studies and results regarding its potential as a predictive factor of tumor sensitivity are conflicting. Surviving fraction at 2 Gy (S.F.2) allowed a global evaluation of sensitivity, but the obtention of this parameter often takes a long time and failed in 20 to 40%. Evaluation of double-strand break repair capacity by immuno chemistry quantification of phosphorylated forms of A.T.M., H.2 A.X. or M.R.E.11 is an interesting topic. However, discovery of tumor stem cells in a number of epithelial tumors could revolutionize the understanding of radiosensitivity. Combination of genomic and functional techniques are probably essential to better predict this parameter. (authors)

  20. Effects of binding metronidazole to a copper-acetate compound on radiosensitizer properties

    International Nuclear Information System (INIS)

    Negron, Ana C. Valderrama; Silva, Denise de Oliveira; Cruz, Aurea S.

    2009-01-01

    Copper compounds exhibit interesting biological properties. Nitroimidazoles show radiosensitizer properties for radiotherapy tumor treatment. In the present work, the effect of binding metronidazole (1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole = MTZ) to copper-acetate on the radiosensitizer properties has been investigated. A compound of copper-acetate-MTZ was prepared and characterized. The experiments were carried out by gamma-irradiation of Hep2 (human larynx cancer) cells under hypoxic conditions. The radiation doses for 50% cell survival in the presence of radiosensitizer were about 8.2 Gy for CuAcMTZ or free MTZ. The effect of binding metronidazole to copper acetate on radiosensitizer properties is mainly related to the radiosensitizer process which involves two events for CuAcMTZ in contrast to one event observed for the MTZ free drug. (author)

  1. On the Path to Seeking Novel Radiosensitizers

    International Nuclear Information System (INIS)

    Katz, David; Ito, Emma; Liu Feifei

    2009-01-01

    Radiation therapy is a highly effective cancer treatment modality, and extensive investigations have been undertaken over the years to augment its efficacy in the clinic. This review summarizes the current understanding of the biologic bases underpinning many of the clinically used radiosensitizers. In addition, this review illustrates how the advent of innovative, high-throughput technologies with integration of different disciplines could be harnessed for an expeditious discovery process for novel radiosensitizers, providing an exciting future for such pursuits in radiation biology and oncology

  2. Biosynthesis of caffeine by tea-leaf extracts. Enzymic formation of theobromine from 7-methylxanthine and of caffeine from theobromine.

    Science.gov (United States)

    Suzuki, T; Takahashi, E

    1975-01-01

    1. Extracts prepared from tea leaves with Polyclar AT (insoluble polyvinylpyrrolidine) contained two methyltransferase activities catalysing the transfer of methyl groups from S-adenosylmethionine to 7-methylxanthine, producing theobromine, and to theobromine, producing caffeine. 2. The methyltransferases exhibited the same pH optimum (8.4) and a similar pattern of effects by metal ions, thiol inhibitors and metal-chelating reagents, both for theobromine and caffeine synthesis. Mg2+, Mn2+ and Ca2+ slightly stimulated enzyme activity but they were not essential. Paraxanthine was shown to be most active among methylxanthines, as the methyl acceptor. However, the formation of paraxanthine from 1-methylxanthine was very low and that from 7-methylxanthine was nil, suggesting that the synthesis of caffeine from paraxanthine is of little importance in intact plants. Xanthine, xanthosine, XMP and hypoxanthine were all inactive as methyl acceptors, whereas [2(-14)C]xanthine and [8(-14)C]hypoxanthine were catabolized to allantoin and urea by tea-leaf extracts. The apparent Km values are as follows: 7-methylxanthine, 1.0 times 10(-14)M; theobromine, 1.0 times 10(-3)M; paraxanthine, 0.2 times 10(-3)M; S-adenosylmethionine, 0.25 times 10(-4)M (with each of the three substrates). 3. The results suggest that the pathway for caffeine biosynthesis is as follows: 7-methylxanthine leads to theobromine leads to caffeine. In contrast, it is suggested that theophylline is synthesized from 1-methylxanthine. The methyl groups of the purine ring of caffeine are all derived directly from the methyl group of S-adenosylmethionine. Little is known about the pathways leading to the formation of 7-methylxanthine. 4. A good correlation between caffeine synthesis and shoot formation or growth of tea seedlings was shown, suggesting that the methylating systems in caffeine synthesis are closely associated with purine nucleotide and nucleic acid metabolism in tea plants. PMID:238504

  3. Withdrawal syndrome after the double-blind cessation of caffeine consumption.

    Science.gov (United States)

    Silverman, K; Evans, S M; Strain, E C; Griffiths, R R

    1992-10-15

    People who stop consuming caffeine may have symptoms, but the incidence and severity of caffeine withdrawal are not known. This study was performed to determine the effects in the general population of ending one's dietary intake of caffeine. We studied 62 normal adults whose intake of caffeine was low to moderate (mean amount, 235 mg--the equivalent of 2.5 cups of coffee--per day). They completed questionnaires about symptoms and tests of their mood and performance when consuming their normal diets (base-line period) and at the end of each of two two-day periods during which they consumed caffeine-free diets and under double-blind conditions received capsules containing placebo (placebo period) or caffeine (caffeine period) in amounts equal to their daily caffeine consumption. More subjects had abnormally high Beck Depression Inventory scores (11 percent), high scores on the trait scale of the State-Trait Anxiety Inventory (8 percent), low vigor scores (11 percent) and high fatigue scores (8 percent) on the Profile of Mood States, and moderate or severe headache (52 percent) during the placebo period than during either the base-line period (2, 0, 0, 0, and 2 percent, respectively; P less than 0.05) or the caffeine period (3, 2, 2, 0, and 6 percent; P less than 0.05). More subjects reported unauthorized use of medications during the placebo period (13 percent) than during the caffeine period (2 percent, P = 0.017). Performance of a tapping task was slower during the placebo period than during the base-line and caffeine periods (P less than 0.01). Persons who consume low or moderate amounts of caffeine may have a withdrawal syndrome after their daily consumption of caffeine ceases.

  4. Preliminary screening of the radiosensitivity-associated genes on colorectal cancer

    International Nuclear Information System (INIS)

    Xing Chungen; Yang Xiaodong; Zhou Liying; Wu Yongyou; Jiang Yinfen; Dai Hong; Lv Xiaodong; Gong Wei

    2007-01-01

    The screening of radiosensitive genes of human colorectal cancer was made by gene chip. Two human colorectal cancer cell lines LOVO and SW480 were cultivated and the total RNA was extracted from at least lxl0 7 cells. Then the gene expression profiling was performed by HG-U133 Plus 2.0 Array and the difference of gene expression has been analyzed. The results shows that there are 16882 genes expressed in LOVO cell and 17114 genes expressed in SW480 cell through gene expression profiling. It has been found that the genes with 2-fold expressed differentially include 908 genes up-regulated and 1312 genes down-regulated. The same genes, such as Fas and NFkB which is up-regulated, Caspas6, and RAD21 which is down-regulated, have been proved to be related to radiosensitivity. The genes with high expression level including CEACAM5, THBS1, SERPINE2, ARL7, HPGD in LOVO cell may also be related to the radiosensitivity. And the genes with high expression level including SCD, NQ01, LYZ, KRT20, ATP1B1 in SW480 cell may be related to the radioresistance of human colorectal cancer. It could be concluded that the radiosensitivity of colorectal cancer can be reflected from gene and protein expression level. And gene expression profiling is a fast and sensitive tool to predict the radiosensitivity and screen radiosensitive genes of colorectal cancer. (authors)

  5. Effects of caffeine on neuromuscular fatigue and performance during high-intensity cycling exercise in moderate hypoxia.

    Science.gov (United States)

    Smirmaul, Bruno P C; de Moraes, Antonio Carlos; Angius, Luca; Marcora, Samuele M

    2017-01-01

    To investigate the effects of caffeine on performance, neuromuscular fatigue and perception of effort during high-intensity cycling exercise in moderate hypoxia. Seven adult male participants firstly underwent an incremental exercise test on a cycle ergometer in conditions of acute normobaric hypoxia (fraction inspired oxygen = 0.15) to establish peak power output (PPO). In the following two visits, they performed a time to exhaustion test (78 ± 3% PPO) in the same hypoxic conditions after caffeine ingestion (4 mg kg -1 ) and one after placebo ingestion in a double-blind, randomized, counterbalanced cross-over design. Caffeine significantly improved time to exhaustion by 12%. A significant decrease in subjective fatigue was found after caffeine consumption. Perception of effort and surface electromyographic signal amplitude of the vastus lateralis were lower and heart rate was higher in the caffeine condition when compared to placebo. However, caffeine did not reduce the peripheral and central fatigue induced by high-intensity cycling exercise in moderate hypoxia. The caffeine-induced improvement in time to exhaustion during high-intensity cycling exercise in moderate hypoxia seems to be mediated by a reduction in perception of effort, which occurs despite no reduction in neuromuscular fatigue.

  6. Radiosensitizers in cervical cancer. Cisplatin and beyond

    International Nuclear Information System (INIS)

    Candelaria, Myrna; Garcia-Arias, Alicia; Cetina, Lucely; Dueñas-Gonzalez, Alfonso

    2006-01-01

    Cervical cancer continues to be a significant health burden worldwide. Globally, the majority of cancers are locally advanced at diagnosis; hence, radiation remains the most frequently used therapeutical modality. Currently, the value of adding cisplatin or cisplatin-based chemotherapy to radiation for treatment of locally advanced cervical cancer is strongly supported by randomized studies and meta-analyses. Nevertheless, despite these significant achievements, therapeutic results are far from optimal; thus, novel therapies need to be assayed. A strategy currently being investigated is the use of newer radiosensitizers alone or in combination with platinum compounds. In the present work, we present preclinical information on known and newer cytotoxic agents as radiosensitizers on cervical cancer models, as well as the clinical information emanating from early phase trials that incorporate them to the cervical cancer management. In addition, we present the perspectives on the combined approach of radiation therapy and molecular target-based drugs with proven radiosensitizing capacity

  7. 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.

  8. Clinical and Functional Assays of Radiosensitivity and Radiation-Induced Second Cancer

    Directory of Open Access Journals (Sweden)

    Mohammad Habash

    2017-10-01

    Full Text Available Whilst the near instantaneous physical interaction of radiation energy with living cells leaves little opportunity for inter-individual variation in the initial yield of DNA damage, all the downstream processes in how damage is recognized, repaired or resolved and therefore the ultimate fate of cells can vary across the population. In the clinic, this variability is observed most readily as rare extreme sensitivity to radiotherapy with acute and late tissue toxic reactions. Though some radiosensitivity can be anticipated in individuals with known genetic predispositions manifest through recognizable phenotypes and clinical presentations, others exhibit unexpected radiosensitivity which nevertheless has an underlying genetic cause. Currently, functional assays for cellular radiosensitivity represent a strategy to identify patients with potential radiosensitivity before radiotherapy begins, without needing to discover or evaluate the impact of the precise genetic determinants. Yet, some of the genes responsible for extreme radiosensitivity would also be expected to confer susceptibility to radiation-induced cancer, which can be considered another late adverse event associated with radiotherapy. Here, the utility of functional assays of radiosensitivity for identifying individuals susceptible to radiotherapy-induced second cancer is discussed, considering both the common mechanisms and important differences between stochastic radiation carcinogenesis and the range of deterministic acute and late toxic effects of radiotherapy.

  9. Parkinson's disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake.

    Science.gov (United States)

    Checkoway, Harvey; Powers, Karen; Smith-Weller, Terri; Franklin, Gary M; Longstreth, W T; Swanson, Phillip D

    2002-04-15

    A reduced risk for Parkinson's disease (PD) among cigarette smokers has been observed consistently during the past 30 years. Recent evidence suggests that caffeine may also be protective. Findings are presented regarding associations of PD with smoking, caffeine intake, and alcohol consumption from a case-control study conducted in western Washington State in 1992-2000. Incident PD cases (n = 210) and controls (n = 347), frequency matched on gender and age were identified from enrollees of the Group Health Cooperative health maintenance organization. Exposure data were obtained by in-person questionnaires. Ever having smoked cigarettes was associated with a reduced risk of PD (odds ratio (OR) = 0.5, 95% confidence interval (CI): 0.4, 0.8). A stronger relation was found among current smokers (OR = 0.3, 95% CI: 0.1, 0.7) than among ex-smokers (OR = 0.6, 95% CI: 0.4, 0.9), and there was an inverse gradient with pack-years smoked (trend p coffee consumption or total caffeine intake or for alcohol consumption. However, reduced risks were observed for consumption of 2 cups/day or more of tea (OR = 0.4, 95% CI: 0.2, 0.9) and two or more cola drinks/day (OR = 0.6, 95% CI: 0.3, 1.4). The associations for tea and cola drinks were not confounded by smoking or coffee consumption.

  10. Influence of caffeine on the protective activity of gabapentin and topiramate in a mouse model of generalized tonic-clonic seizures.

    Science.gov (United States)

    Jargiełło-Baszak, Małgorzata; Chrościńska-Krawczyk, Magdalena; Andres-Mach, Marta; Łuszczki, Jarogniew J; Czuczwar, Stanisław J

    2016-08-01

    Caffeine may interact with classical antiepileptic drugs (AEDs), reducing their anticonvulsant effects in basic seizure models. The aim of the present study was to ascertain whether intraperitoneal caffeine (acute or chronic for 15 days) could attenuate the anticonvulsant effect of some newer AEDs: gabapentin (GBP) and topiramate (TPM) against electroconvulsions in mice. Maximal electroshock (MES)-induced mouse seizure model was used for the estimation of the anticonvulsant activity of TPM whilst the protective activity of GBP was evaluated in the threshold test for maximal (tonic) convulsions. Adverse effects were evaluated by measurement of long-term memory (the step-through passive avoidance task) and motor coordination (chimney test). Plasma AED concentrations were also measured to determinate any pharmacokinetic contribution to the observed effects. Caffeine (both acute and chronic at 23.1 and 46.2mg/kg) significantly reduced the protective effects of TPM against MES. As regards GBP, caffeine (acutely at 46.2mg/kg and chronically at 23.1 or 46.2mg/kg) significantly diminished the GBP-induced increases in the electroconvulsive threshold. In addition, caffeine did not affect the free plasma concentrations of TPM or GBP. Acute and chronic caffeine (23.1 and 46.2mg/kg) enhanced the impairment of motor coordination in mice pretreated with GBP whilst an opposite effect was observed in TPM injected mice and pretreated with chronic caffeine at 46.2mg/kg. The results indicate that newer AEDs, GBP or TPM behave in the exactly same way as classical antiepileptics in mice challenged with caffeine. This hazardous effect of caffeine is not subject to tolerance. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  11. Association Between Early Caffeine Citrate Administration and Risk of Acute Kidney Injury in Preterm Neonates: Results From the AWAKEN Study.

    Science.gov (United States)

    Harer, Matthew W; Askenazi, David J; Boohaker, Louis J; Carmody, J Bryan; Griffin, Russell L; Guillet, Ronnie; Selewski, David T; Swanson, Jonathan R; Charlton, Jennifer R

    2018-04-02

    Acute kidney injury (AKI) occurs commonly in preterm neonates and is associated with increased morbidity and mortality. To examine the association between caffeine citrate administration and AKI in preterm neonates in the first 7 days after birth and to test the hypothesis that caffeine administration would be associated with reduced incidence and severity of AKI. This study was a secondary analysis of the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study, a retrospective observational cohort that enrolled neonates born from January 1 to March 31, 2014. The dates of analysis were October 2016 to December 2017. The setting was an international, multicenter cohort study of neonates admitted to 24 participating level III or IV neonatal intensive care units. Participants met the original inclusion and exclusion criteria of the AWAKEN study. Additional exclusion criteria for this study included participants greater than or equal to 33 weeks' gestation at birth, admission after age 7 days, use of theophylline in the neonatal intensive care unit, or lack of data to define AKI. There were 675 preterm neonates available for analysis. Administration of caffeine in the first 7 days after birth. The primary outcome was the incidence of AKI (based on the modified neonatal Kidney Disease: Improving Global Outcomes [KDIGO] definition) in the first 7 days after birth. The hypothesis that caffeine administration would be associated with reduced AKI incidence was formulated before data analysis. The study cohort (n = 675) was 55.4% (n = 374) male, with a mean (SD) gestational age of 28.9 (2.8) weeks and a mean (SD) birth weight of 1285 (477) g. Acute kidney injury occurred in 122 neonates (18.1%) in the first 7 days after birth. Acute kidney injury occurred less frequently among neonates who received caffeine than among those who did not (50 of 447 [11.2%] vs 72 of 228 [31.6%], P < .01). After multivariable adjustment, administration of

  12. Studies of action of heavy metals on caffeine degradation by ...

    African Journals Online (AJOL)

    Caffeine is an important naturally occurring compound that can be degraded by bacteria. Excessive caffeine consumption is known to have some adverse problems. Previously, Leifsonia sp. strain SIU capable of degrading caffeine was isolated from agricultural soil. The bacterium was tested for its ability to degrade caffeine ...

  13. Effects of taurolidine on radiosensitivity of murine melanoma cells and its mechanism

    International Nuclear Information System (INIS)

    Sun Baosheng; Liu Shixin; Wang Tiejun; Liu Linlin; Huang Guomin; Gong Shouliang

    2008-01-01

    Objective: To observe the effects of taurolidine on radiosensitivity of B16-F10 cells of murine melanoma via the enhancement of Bax and Bad proteins and induction of Bcl-2 protein. Methods: The apoptosis of B16-F10 cells was assessed after treated with 0, 10, 25, 50, 100 and 150 μmol·L -1 taurolidine, clone survival assay was used to detect the radiosensitivity of B16-F10 cells, and protein expressions were determined by Western blotting. Results: The apoptosis of 5% cells was induced in a dose-and time-dependent manner after B16-F10 cells were treated with 50 μmol·L -1 taurolidine. The survival rate decreased after treated with tautolidine in combination with 2 Gy X-irradiation with the increase of taurolidine concentration and doses of irradiation (P 0 and SER D q ) also increased with the increase of its concentration, there was significant difference between 50 μmol·L -1 taurolidine group and 10 μmol·L -1 taurolidine group (P<0.05); meantime, the level of proapototic protein Bax and Bad increased and the level of antiapoptotic protein Bcl-2 reduced. Conclusion: Taurolidine in combination with irradiation can enhance the radiosensitivity by the mediation of Bcl-2 family protein. (authors)

  14. Caffeine enhances working memory for extraverts.

    Science.gov (United States)

    Smillie, Luke D; Gökçen, Elif

    2010-12-01

    Using a randomized double-blind placebo-controlled design we examined the effects of caffeine on working memory (WM) as a function of extraverted personality. Participants (N=59) received 200mg of caffeine and placebo in counterbalanced-order over two sessions prior to completing a 'N-Back' WM paradigm. Findings revealed that caffeine administration relative to the placebo condition resulted in heightened WM performance, but only for extraverted participants. We suggest based on previous theory and research that dopamine function (DA) may be the most plausible mechanism underlying this finding. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

  15. [Caffeine: a nutrient, a drug or a drug of abuse].

    Science.gov (United States)

    Pardo Lozano, Ricardo; Alvarez García, Yolanda; Barral Tafalla, Diego; Farré Albaladejo, Magí

    2007-01-01

    Coffee, tea, chocolate and caffeinated drinks are the main sources of caffeine, which is consumed in almost all ages and socioeconomic levels. Caffeine acts as a non-selective adenosine receptor antagonist in the central nervous system. Its main effects are as psychostimulant, acting in addition on the respiratory, muscular and cardiovascular systems. Basically, caffeine is metabolized by the hepatic cytochrome P-450 1A2 enzymes (CYP1A2). Several drugs can interact with its metabolism. The observed interindividual differences of its effects can be explained by variations in its metabolism. The main therapeutic use of caffeine is bronchodilator in respiratory diseases. Other possible uses are under investigation. Acute or chronic consumption of caffeine can induce several adverse effects, including intoxication that can be lethal. Finally, caffeine can be considered a drug of abuse. It has positive reinforcing actions, produces tolerance, and a withdrawal syndrome after stopping its consumption. Caffeine can cause different mental disorders such as dependence, which is not included in the DSM-IV-R, withdrawal syndrome and intoxication. Depending on its use, caffeine can be considered a nutrient, a drug or a drug of abuse.

  16. Therapeutic Effect of Caffeine Treatment Immediately Following Neonatal Hypoxic-Ischemic Injury on Spatial Memory in Male Rats

    Directory of Open Access Journals (Sweden)

    R. Holly Fitch

    2013-03-01

    Full Text Available Hypoxia Ischemia (HI refers to the disruption of blood and/or oxygen delivery to the brain. Term infants suffering perinatal complications that result in decreased blood flow and/or oxygen delivery to the brain are at risk for HI. Among a variety of developmental delays in this population, HI injured infants demonstrate subsequent memory deficits. The Rice-Vannucci rodent HI model can be used to explore behavioral deficits following early HI events, as well as possible therapeutic agents to help reduce deleterious outcomes. Caffeine is an adenosine receptor antagonist that has recently shown promising results as a therapeutic agent following HI injury. The current study sought to investigate the therapeutic benefit of caffeine following early HI injury in male rats. On post-natal day (P 7, HI injury was induced (cauterization of the right common carotid artery, followed by two hours of 8% oxygen. Male sham animals received only a midline incision with no manipulation of the artery followed by room air exposure for two hours. Subsets of HI and sham animals then received either an intraperitoneal (i.p. injection of caffeine (10 mg/kg, or vehicle (sterile saline immediately following hypoxia. All animals later underwent testing on the Morris Water Maze (MWM from P90 to P95. Results show that HI injured animals (with no caffeine treatment displayed significant deficits on the MWM task relative to shams. These deficits were attenuated by caffeine treatment when given immediately following the induction of HI. We also found a reduction in right cortical volume (ipsilateral to injury in HI saline animals as compared to shams, while right cortical volume in the HI caffeine treated animals was intermediate. These findings suggest that caffeine is a potential therapeutic agent that could be used in HI injured infants to reduce brain injury and preserve subsequent cognitive function.

  17. Caffeine, creatine, GRIN2A and Parkinson's disease progression.

    Science.gov (United States)

    Simon, David K; Wu, Cai; Tilley, Barbara C; Lohmann, Katja; Klein, Christine; Payami, Haydeh; Wills, Anne-Marie; Aminoff, Michael J; Bainbridge, Jacquelyn; Dewey, Richard; Hauser, Robert A; Schaake, Susen; Schneider, Jay S; Sharma, Saloni; Singer, Carlos; Tanner, Caroline M; Truong, Daniel; Wei, Peng; Wong, Pei Shieen; Yang, Tianzhong

    2017-04-15

    Caffeine is neuroprotective in animal models of Parkinson's disease (PD) and caffeine intake is inversely associated with the risk of PD. This association may be influenced by the genotype of GRIN2A, which encodes an NMDA-glutamate-receptor subunit. In two placebo-controlled studies, we detected no association of caffeine intake with the rate of clinical progression of PD, except among subjects taking creatine, for whom higher caffeine intake was associated with more rapid progression. We now have analyzed data from 420 subjects for whom DNA samples and caffeine intake data were available from a placebo-controlled study of creatine in PD. The GRIN2A genotype was not associated with the rate of clinical progression of PD in the placebo group. However, there was a 4-way interaction between GRIN2A genotype, caffeine, creatine and the time since baseline. Among subjects in the creatine group with high levels of caffeine intake, but not among those with low caffeine intake, the GRIN2A T allele was associated with more rapid progression (p=0.03). These data indicate that the deleterious interaction between caffeine and creatine with respect to rate of progression of PD is influenced by GRIN2A genotype. This example of a genetic factor interacting with environmental factors illustrates the complexity of gene-environment interactions in the progression of PD. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Action of caffeine on x-irradiated HeLa cells. VII. Evidence that caffeine enhances expression of potentially lethal radiation damage

    International Nuclear Information System (INIS)

    Beetham, K.L.; Tolmach, L.J.

    1984-01-01

    HeLa cells irradiated with 2 Gy of 220-kV X rays suffer a 60-70% loss of colony-forming ability which is increased to 90% by postirradiation treatment with 10 mM caffeine for 6 hr. The detailed postirradiation patterns of cell death and sister-cell fusion in such cultures and in cultures in which the colony-forming ability was brought to about the same level by treatment with a larger (4 Gy) X-ray dose alone or by longer (48 hr) treatment with 10 mM caffeine alone were recorded by time-lapse cinemicrography. Because the patterns of cell death and fusion differ radically in irradiated and in caffeine-treated cultures, the response of the additional cells killed by the combined treatment can be identified as X-ray induced rather than caffeine induced. The appearance of cultures after several days of incubation confirms the similarity of the post-treatment patterns of proliferation in cultures suffering enhanced killing to those occurring in cultures treated with larger doses of X rays alone. It is concluded that x rays do not sensitize cells to caffeine, but rather that caffeine enhanced the expression of potentially lethal radiation-induced damage

  19. Effects of caffeine on endurance capacity and psychological state in young females and males exercising in the heat.

    Science.gov (United States)

    Suvi, Silva; Timpmann, Saima; Tamm, Maria; Aedma, Martin; Kreegipuu, Kairi; Ööpik, Vahur

    2017-01-01

    Acute caffeine ingestion is considered effective in improving endurance capacity and psychological state. However, current knowledge is based on the findings of studies that have been conducted on male subjects mainly in temperate environmental conditions, but some physiological and psychological effects of caffeine differ between the sexes. The purpose of this study was to compare the physical performance and psychological effects of caffeine in young women and men exercising in the heat. Thirteen male and 10 female students completed 2 constant-load walks (60% of thermoneutral peak oxygen consumption on a treadmill until volitional exhaustion) in a hot-dry environment (air temperature, 42 °C; relative humidity, 20%) after caffeine (6 mg·kg -1 ) and placebo (wheat flour) ingestion in a double-blind, randomly assigned, crossover manner. Caffeine, compared with placebo, induced greater increases (p exercise in the heat, but it has no impact on thermoregulation or endurance capacity in either gender. Under exercise-heat stress, caffeine reduces ratings of perceived exertion and fatigue in males but not in females.

  20. Nearly half of the adolescents in an Italian school-based study exceeded the recommended upper limits for daily caffeine consumption.

    Science.gov (United States)

    Santangelo, Barbara; Lapolla, Rosa; Rutigliano, Irene; Pettoello Mantovani, Massimo; Campanozzi, Angelo

    2018-06-01

    No data are available on caffeine consumption among Italian adolescents. We investigated caffeine intake from coffee, soft drinks and energy drinks in a sample of Italian adolescents and determined if they exceeded the recommended limits. The study comprised 1213 adolescents with a mean age of 15.1 years (range 12-19) from four schools in Foggia, southern Italy. Caffeine intake was assessed using an anonymous self-reported questionnaire during the 2013/2014 school year. We calculated the percentage of daily caffeine consumers, their mean intake of caffeine from beverages and the contribution of each beverage category to the total caffeine intake. Approximately 76% of the sample consumed caffeine every day, amounting to 125.5 ± 69.2 mg/day and 2.1 ± 1.2 mg/kg/day. When we applied the reference values from the Academy of Pediatrics, we found that 46% of the adolescents exceeded the recommended upper limits. Coffee was the most frequently consumed caffeinated drink and the main contributor to daily caffeine intake. More than three quarters (76%) of the Italian adolescents in our study drank coffee on a daily basis and nearly half (46%) exceeded the recommended upper limits. Strategies are needed to reduce caffeine consumption by adolescents. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  1. [Caffeine--common ingredient in a diet and its influence on human health].

    Science.gov (United States)

    Wierzejska, Regina

    2012-01-01

    Caffeine is widely consumed by people of all ages. In the last period a market of caffeine-containing products, particularly energy drinks and food supplements increased. Caffeine for years is under discussion, whether has positive whether adverse impact on health. Children are a group of special anxieties. Caffeine is a stimulant of central nervous system and therefore is probably the most commonly used psychoactive substance in the world. The physiological effect of caffeine and the lack of nutrition value causes a great interest its impact on health, especially with reference to the risk of cardiovascular diseases. Results of scientific research are not clear. The influence of caffeine on the human body is conditioned with the individual metabolism of caffeine which also depends on many endogenic and environmental factors. According to the current knowledge moderate caffeine intake by healthy adults at a dose level of 400 mg a day is not associated with adverse effects, but it also depends on other health determinants of a lifestyle. Excessive caffeine consumption can cause negative health consequences such as psychomotor agitation, insomnia, headache, gastrointestinal complaints. Adverse effect of caffeine intoxication is classified in World Health Organization's International Classification of Diseases (ICD-10). Metabolism of caffeine by pregnant woman is slowed down. Caffeine and its metabolites pass freely across the placenta into a fetus. For this reason pregnant women should limit caffeine intake. Children and adolescents should also limit daily caffeine consumption. It results from the influence of caffeine on the central nervous system in the period of rapid growth and the final stage of brain development, calcium balance and sleep duration. Average daily caffeine consumption in European countries ranging from 280-490 mg. The highest caffeine intake is in Scandinavian countries what results from the great consumption of the coffee. As far as caffeine

  2. Caffeine Extraction from Raw and Roasted Coffee Beans.

    Science.gov (United States)

    Chiang, Donyau; Lin, Chih-Yang; Hu, Chen-Ti; Lee, Sanboh

    2018-04-01

    Coffee is a stimulant, psychoactive, popular daily beverage, and its caffeine affects human physiological health and behavior. These important issues prompted us to study caffeine extraction from both the raw and roasted coffee beans of 3 types at different temperatures. A hemispheric model is developed to simulate the extraction process of the caffeine from the coffee beans of hemisphere is proposed. The experimental data are in good agreement with the predicted model. The effective diffusivities of caffeine in both the raw and roasted beans increase with temperature in all 3 types. An incubation period, decreasing with increasing temperature, is observed in all samples studied. Caffeine extraction in roasted beans is more rapid than that for the raw beans and the time difference is significant at low temperatures. In both the raw and roasted samples, caffeine diffusion in the raw beans and the incubation behavior are thermally activated processes. Single activation energies are obtained for diffusion within the extraction temperature range for all beans tested with the exception of one type of the coffee beans, Mandheling, which exhibits 2 activation energies in raw samples. The surface energies of the epidermis of the raw beans and roasted beans obtained from the contact angle measurements are used to interpret the difference of incubation periods. This study has a potential application to the decaffeinated coffee industry.Caffeine affects human physiological health and behavior so that caffeine extraction from coffee beans of different types at different temperatures is important for product refining and customers. © 2018 Institute of Food Technologists®.

  3. Post-study caffeine administration enhances memory consolidation in humans.

    Science.gov (United States)

    Borota, Daniel; Murray, Elizabeth; Keceli, Gizem; Chang, Allen; Watabe, Joseph M; Ly, Maria; Toscano, John P; Yassa, Michael A

    2014-02-01

    It is currently not known whether caffeine has an enhancing effect on long-term memory in humans. We used post-study caffeine administration to test its effect on memory consolidation using a behavioral discrimination task. Caffeine enhanced performance 24 h after administration according to an inverted U-shaped dose-response curve; this effect was specific to consolidation and not retrieval. We conclude that caffeine enhanced consolidation of long-term memories in humans.

  4. Exercise and Sport Performance with Low Doses of Caffeine

    OpenAIRE

    Spriet, Lawrence L.

    2014-01-01

    Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. The majority of research has examined the effects of moderate to high caffeine doses (5–13 mg/kg body mass) on exercise and sport. These caffeine doses have profound effects on the responses to exercise at the whole-body level and are associated with variable results and some undesirable side effects. Low doses of caffeine (

  5. Caffeine: How Much Is Too Much?

    Science.gov (United States)

    Healthy Lifestyle Nutrition and healthy eating Caffeine has its perks, but it can pose problems too. Find out how much is too much and if you need to curb ... By Mayo Clinic Staff If you rely on caffeine to wake you up and keep you going, ...

  6. HAP1 gene expression is associated with radiosensitivity in breast cancer cells

    International Nuclear Information System (INIS)

    Wu, Jing; Zhang, Jun-ying; Yin, Li; Wu, Jian-zhong; Guo, Wen-jie; Wu, Jian-feng; Chen, Meng; Xia, You-you; Tang, Jin-hai; Ma, Yong-chao; He, Xia

    2015-01-01

    Highlights: • Overexpression of HAP1 gene promotes apoptosis in MCF-7 cells after irradiation. • HAP1 reduces tumor volume in nude mice xenograft models after irradiation. • HAP1 increases radiosensitivity of breast cancer cells in vitro and vivo. - Abstract: Objectives: The purpose of this study was to investigate the relationship between huntingtin-associated protein1 (HAP1) gene and radiation therapy of breast cancer cells. Methods: HAP1 gene was transfected into breast cancer MCF-7 cells, which was confirmed by quantitative reverse transcription-polymerase chain reaction analysis (qRT-PCR) and Western blot in vitro. The changes of cell radiosensitivity were assessed by colony formation assay. Apoptosis were examined by flow cytometry. The expressions of two radiation-induced genes were evaluated by Western blot. Tumor growth was investigated in nude mice xenograft models in vivo. Results: Our data showed that HAP1 gene expression was significantly increased in HAP1-transfected MCF-7 cells in comparison with the parental cells or negative control cells. The survival rate in MCF-7/HAP1 cells was significantly decreased after irradiation (0, 2, 4, 6, 8 Gy), compared to cells in MCF-7 and MCF-7/Pb groups in vitro. HAP1 gene increased apoptosis in MCF-7 cells after irradiation. Additionally, the tumor volume and weight in MCF-7/HAP1 + RT group were observably lower than in MCF-7/HAP1 group and MCF-7/Pb + RT group. Conclusion: The present study indicated that HAP1 gene expression was related to the radiosensitivity of breast cancer cells and may play an important role in the regulation of cellular radiosensitivity

  7. Molecular Dynamics Simulation Studies of Caffeine Aggregation in Aqueous Solution

    OpenAIRE

    Tavagnacco, Letizia; Schnupf, Udo; Mason, Philip E.; Saboungi, Marie-Louise; Cesàro, Attilio; Brady, John W.

    2011-01-01

    Molecular dynamics simulations were carried out on a system of eight independent caffeine molecules in a periodic box of water at 300 K, representing a solution near the solubility limit for caffeine at room temperature, using a newly-developed CHARMM-type force field for caffeine in water. Simulations were also conducted for single caffeine molecules in water using two different water models (TIP3P and TIP4P). Water was found to structure in a complex fashion around the planar caffeine molec...

  8. A caffeine-maltodextrin mouth rinse counters mental fatigue.

    Science.gov (United States)

    Van Cutsem, Jeroen; De Pauw, Kevin; Marcora, Samuele; Meeusen, Romain; Roelands, Bart

    2018-04-01

    Mental fatigue is a psychobiological state caused by prolonged periods of demanding cognitive activity that has negative implications on many aspects in daily life. Caffeine and carbohydrate ingestion have been shown to be able to reduce these negative effects of mental fatigue. Intake of these substances might however be less desirable in some situations (e.g., restricted caloric intake, Ramadan). Rinsing caffeine or glucose within the mouth has already been shown to improve exercise performance. Therefore, we sought to evaluate the effect of frequent caffeine-maltodextrin (CAF-MALT) mouth rinsing on mental fatigue induced by a prolonged cognitive task. Ten males (age 23 ± 2 years, physical activity 7.3 ± 4.3 h/week, low CAF users) performed two trials. Participants first completed a Flanker task (3 min), then performed a 90-min mentally fatiguing task (Stroop task), followed by another Flanker task. Before the start and after each 12.5% of the Stroop task (eight blocks), subjects received a CAF-MALT mouth rinse (MR: 0.3 g/25 ml CAF: 1.6g/25 ml MALT) or placebo (PLAC: 25 ml artificial saliva). Self-reported mental fatigue was lower in MR (p = 0.017) compared to PLAC. Normalized accuracy (accuracy first block = 100%) was higher in the last block of the Stroop in MR (p = 0.032) compared to PLAC. P2 amplitude in the dorsolateral prefrontal cortex (DLPFC) decreased over time only in PLAC (p = 0.017). Frequent mouth rinsing during a prolonged and demanding cognitive task reduces mental fatigue compared to mouth rinsing with artificial saliva.

  9. Caffeine and blood pressure response: sex, age, and hormonal status.

    Science.gov (United States)

    Farag, Noha H; Whitsett, Thomas L; McKey, Barbara S; Wilson, Michael F; Vincent, Andrea S; Everson-Rose, Susan A; Lovallo, William R

    2010-06-01

    The pressor effect of caffeine has been established in young men and premenopausal women. The effect of caffeine on blood pressure (BP) remains unknown in postmenopausal women and in relation to hormone replacement therapy (HRT) use. In a randomized, 2-week cross-over design, we studied 165 healthy men and women in 6 groups: men and premenopausal women (35-49 yrs) vs. men and postmenopausal women (50-64 yrs), with postmenopausal women divided into those taking no hormone replacements (HR), estrogen alone, or estrogen and progesterone. Testing during one week of the study involved 6 days of caffeine maintenance at home (80 mg, 3x/day) followed by testing of responses to a challenge dose of caffeine (250 mg) in the laboratory. The other week involved ingesting placebos on maintenance and lab days. Resting BP responses to caffeine were measured at baseline and at 45 to 60 min following caffeine vs placebo ingestion, using automated monitors. Ingestion of caffeine resulted in a significant increase in systolic BP in all 6 groups (4 +/- .6, p < 0.01). Diastolic BP significantly increased in response to caffeine in all (3 +/- .4, p < 0.04) but the group of older men (2 +/- 1.0, p = 0.1). The observed pressor responses to caffeine did not vary by age. Caffeine resulted in an increase in BP in healthy, normotensive, young and older men and women. This finding warrants the consideration of caffeine in the lifestyle interventions recommended for BP control across the age span.

  10. Cytochrome P450-Dependent Metabolism of Caffeine in Drosophila melanogaster

    Science.gov (United States)

    Coelho, Alexandra; Fraichard, Stephane; Le Goff, Gaëlle; Faure, Philippe; Artur, Yves; Ferveur, Jean-François; Heydel, Jean-Marie

    2015-01-01

    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. PMID:25671424

  11. 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.

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

    International Nuclear Information System (INIS)

    Ohnishi, T.; Okaichi, K.; Ohashi, Y.; Nozu, K.

    1981-01-01

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

  13. Nicotine and caffeine modulate haloperidol-induced changes in postsynaptic density transcripts expression: Translational insights in psychosis therapy and treatment resistance.

    Science.gov (United States)

    de Bartolomeis, Andrea; Iasevoli, Felice; Marmo, Federica; Buonaguro, Elisabetta Filomena; Avvisati, Livia; Latte, Gianmarco; Tomasetti, Carmine

    2018-04-01

    Caffeine and nicotine are widely used by schizophrenia patients and may worsen psychosis and affect antipsychotic therapies. However, they have also been accounted as augmentation strategies in treatment-resistant schizophrenia. Despite both substances are known to modulate dopamine and glutamate transmission, little is known about the molecular changes induced by these compounds in association to antipsychotics, mostly at the level of the postsynaptic density (PSD), a site of dopamine-glutamate interplay. Here we investigated whether caffeine and nicotine, alone or combined with haloperidol, elicited significant changes in the levels of both transcripts and proteins of the PSD members Homer1 and Arc, which have been implicated in synaptic plasticity, schizophrenia pathophysiology, and antipsychotics molecular action. Homer1a mRNA expression was significantly reduced by caffeine and nicotine, alone or combined with haloperidol, compared to haloperidol. Haloperidol induced significantly higher Arc mRNA levels than both caffeine and caffeine plus haloperidol in the striatum. Arc mRNA expression was significantly higher by nicotine plus haloperidol vs. haloperidol in the cortex, while in striatum gene expression by nicotine was significantly lower than that by both haloperidol and nicotine plus haloperidol. Both Homer1a and Arc protein levels were significantly increased by caffeine, nicotine, and nicotine plus haloperidol. Homer1b mRNA expression was significantly increased by nicotine and nicotine plus haloperidol, while protein levels were unaffected. Locomotor activity was not significantly affected by caffeine, while it was reduced by nicotine. These data indicate that both caffeine and nicotine trigger relevant molecular changes in PSD sites when given in association with haloperidol. Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.

  14. Contribution of a caffeine-sensitive recombinational repair pathway to survival and mutagenesis in UV-irradiated Schizosaccharomyces pombe

    International Nuclear Information System (INIS)

    Gentner, N.E.; Werner, M.M.; Hannan, M.A.; Nasim, A.

    1978-01-01

    Cells of wild-type Schizosacharomyces pombe exposed to UV radiation in either G1 or G2 phase show enhanced inactivation of colony-forming ability if plated in the presence of caffeine. This UV-sensitization by caffeine is abolished in both G1 an G2 phase cells by the radlmutation; since both caffeine and the radl mutation markedly reduce recombinational events, this suggests that a recombinational repair process is active in cells irradiated either in G1 or G2 phase. Caffeine-sensitive repair begins immediately and is completed before resumption of DNA synthesis. Caffeine-sensitive repair of UV-damage in G1 cells displays a considerable lag and then occurs concomitantly with DNA synthesis. UV-induced mutagenesis was examined in wild-type and rad mutants using a forward mutation system. Rad mutants which show higher UV-induced mutation rates than wild-type retain the recombinational mechanism. In contrast, rad strains which are relatively UV-immutable compared to wild-type do not possess the caffeine-sensitive UV-repair process. The recombinational process therefore may be the major pathway responsible for UV-induced mutation. (orig./AJ) [de

  15. Radiosensitivities of cultured barley of different type (Hordeum vulgare)

    International Nuclear Information System (INIS)

    Wang Cailian; Shen Mei; Xu Gang; Zhao Kongnan

    1990-01-01

    The dormant seeds (with 13% moisture) of 47 barley varieties were irradiated with various doses (0-40 krad) of 137 Cs γ-rays. The radiosensitivities of naked barley was significantly higher than that of hulled barley. The sensitive coefficients of seedling height were 0.04945 and 0.03667 for naked barley and hulled barley, respectively. The radiosensitivity of four-row naked barley was significantly higher than that of two-row hulled barley and six-row hulled barley. 47 varieties studied could be divided into five types with different radiosensitivities, i.e. extreme resistant, resistant, intermediate, sensitive and extreme sensitive. It was also found that the dose-effect curves of cell nucleus volume had a peal at 30 krad

  16. Action of caffeine on x-irradiated HeLa cells. II. Synergistic lethality

    International Nuclear Information System (INIS)

    Busse, P.M.; Bose, S.K.; Jones, R.W.; Tolmach, L.J.

    1977-01-01

    Postirradiation treatment of HeLa S3 cells with 1 mM caffeine results in a marked diminution of the surviving fraction as scored by colony formation. The decrease is dose dependent; the effect of a 24-hour postirradiation treatment of a nonsynchronous population with caffeine is to change the terminal slope of the survival curve and its intercept. D 0 is reduced from 130 to 60 rad; the extrapolation number is increased about twofold. The amount of postirradiation killing is maximal if cells are exposed to caffeine at a concentration of at least 1 mM for 8 hours; less than 10% of unirradiated cells are killed under these conditions. Dose-response curves were also obtained for synchronous cells at various phases of the cell cycle. Similar results were obtained at all cell ages, but the magnitude of the effect is age dependent. This age dependence was further explored in experiments in which mitotically collected cells were exposed to 300 or 500 rad doses at 2-hour intervals throughout the cell cycle. Treatment with caffeine for 24 hours after irradiation enchances the killing of cells late in the cycle more than cells in G1. The sensitivities of two other cell lines, CHO and EMT6, also were examined; both are substantially less sensitive to caffeine. The smaller cell-cycle dependence of CHO cells is qualitatively the same as that of HeLa cells

  17. The molecular basis of radiosensitivity

    International Nuclear Information System (INIS)

    McMillan, T.J.

    1989-01-01

    This paper considers how DNA damage induced by ionising radiation is processed within the cell. The current view of radiobiology is discussed. The author explains the molecular processes that underlie the differences in radiosensitivity

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

    Science.gov (United States)

    Ning, Ya-Lei; Yang, Nan; Chen, Xing; Zhao, Zi-Ai; Zhang, Xiu-Zhu; Chen, Xing-Yun; Li, Ping; Zhao, Yan; Zhou, Yuan-Guo

    2015-01-01

    To investigate the effects of three different ways of chronic caffeine administration on blast- induced memory dysfunction and to explore the underlying mechanisms. 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. 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-bTBI and post-bTBI 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. Since caffeinated beverages are widely consumed in both civilian and military personnel and are convenient to get, the results may provide a promising prophylactic strategy for blast-induced neurotrauma and the consequent cognitive impairment.

  19. The effects of caffeine and expectancy on attention and memory.

    Science.gov (United States)

    Oei, Adam; Hartley, Laurence R

    2005-04-01

    The present study contrasted caffeine's effects on individuals who expect caffeine to stimulate them and those who do not. Secondly, whether a message that caffeine rather than placebo was administered would also affect these two groups of subjects differently was investigated. The study was conducted single-blind in a 2x2x2 mixed design. The between subjects factor was whether they expected caffeine to stimulate them (E+) or not (E-) according to their self reports obtained before the experiment began. The within subjects factors were message (told caffeine vs told placebo) and beverage type (given caffeine vs placebo). Sixteen subjects in each group (n=32) performed on signal detection, memory scanning and delayed free recall tasks following ingestion of either caffeinated or decaffeinated coffee on two sessions each, a total of four experimental sessions. On each session, subjects were given a message regarding their drink (told caffeine vs told placebo). However, on two sessions there was a mismatch between the message and drink given. For signal detection, performance under caffeine was better than placebo in the E+ but not the E- group. However, subjects in the E+ group did not benefit more than the E- group in either message condition. On memory scanning, detections and false alarms did not differ for either beverage, nor was there a differential finding in the E+ and E- groups. However, reaction time under caffeine condition was shorter. No effects of message were found. Caffeine and message also did not have any effect on performance on the delayed free recall task. The hypothesis that caffeine and message would affect E+ and E- subjects differentially was partly supported. Copyright (c) 2005 John Wiley & Sons, Ltd.

  20. Caffeine and acetaminophen association: Effects on mitochondrial bioenergetics.

    Science.gov (United States)

    Gonçalves, Débora F; de Carvalho, Nelson R; Leite, Martim B; Courtes, Aline A; Hartmann, Diane D; Stefanello, Sílvio T; da Silva, Ingrid K; Franco, Jéferson L; Soares, Félix A A; Dalla Corte, Cristiane L

    2018-01-15

    Many studies have been demonstrating the role of mitochondrial function in acetaminophen (APAP) hepatotoxicity. Since APAP is commonly consumed with caffeine, this work evaluated the effects of the combination of APAP and caffeine on hepatic mitochondrial bioenergetic function in mice. Mice were treated with caffeine (20mg/kg, intraperitoneal (i.p.)) or its vehicle and, after 30minutes, APAP (250mg/kg, i.p.) or its vehicle. Four hours later, livers were removed, and the parameters associated with mitochondrial function and oxidative stress were evaluated. Hepatic cellular oxygen consumption was evaluated by high-resolution respirometry (HRR). APAP treatment decreased cellular oxygen consumption and mitochondrial complex activities in the livers of mice. Additionally, treatment with APAP increased swelling of isolated mitochondria from mice livers. On the other hand, caffeine administered with APAP was able to improve hepatic mitochondrial bioenergetic function. Treatment with APAP increased lipid peroxidation and reactive oxygen species (ROS) production and decreased glutathione levels in the livers of mice. Caffeine administered with APAP was able to prevent lipid peroxidation and the ROS production in mice livers, which may be associated with the improvement of mitochondrial function caused by caffeine treatment. We suggest that the antioxidant effects of caffeine and/or its interactions with mitochondrial bioenergetics may be involved in its beneficial effects against APAP hepatotoxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. 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.

  2. Effects of dilute aqueous NaCl solution on caffeine aggregation

    International Nuclear Information System (INIS)

    Sharma, Bhanita; Paul, Sandip

    2013-01-01

    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

  3. Caffeine accelerates recovery from general anesthesia via multiple pathways.

    Science.gov (United States)

    Fong, Robert; Khokhar, Suhail; Chowdhury, Atif N; Xie, Kelvin G; Wong, Josiah Hiu-Yuen; Fox, Aaron P; Xie, Zheng

    2017-09-01

    Various studies have explored different ways to speed emergence from anesthesia. Previously, we have shown that three drugs that elevate intracellular cAMP (forskolin, theophylline, and caffeine) accelerate emergence from anesthesia in rats. However, our earlier studies left two main questions unanswered. First, were cAMP-elevating drugs effective at all anesthetic concentrations? Second, given that caffeine was the most effective of the drugs tested, why was caffeine more effective than forskolin since both drugs elevate cAMP? In our current study, emergence time from anesthesia was measured in adult rats exposed to 3% isoflurane for 60 min. Caffeine dramatically accelerated emergence from anesthesia, even at the high level of anesthetic employed. Caffeine has multiple actions including blockade of adenosine receptors. We show that the selective A 2a adenosine receptor antagonist preladenant or the intracellular cAMP ([cAMP] i )-elevating drug forskolin, accelerated recovery from anesthesia. When preladenant and forskolin were tested together, the effect on anesthesia recovery time was additive indicating that these drugs operate via different pathways. Furthermore, the combination of preladenant and forskolin was about as effective as caffeine suggesting that both A 2A receptor blockade and [cAMP] i elevation play a role in caffeine's ability to accelerate emergence from anesthesia. Because anesthesia in rodents is thought to be similar to that in humans, these results suggest that caffeine might allow for rapid and uniform emergence from general anesthesia in humans at all anesthetic concentrations and that both the elevation of [cAMP] i and adenosine receptor blockade play a role in this response. NEW & NOTEWORTHY Currently, there is no method to accelerate emergence from anesthesia. Patients "wake" when they clear the anesthetic from their systems. Previously, we have shown that caffeine can accelerate emergence from anesthesia. In this study, we show that

  4. Chronic caffeine prevents changes in inhibitory avoidance memory and hippocampal BDNF immunocontent in middle-aged rats.

    Science.gov (United States)

    Sallaberry, Cássia; Nunes, Fernanda; Costa, Marcelo S; Fioreze, Gabriela T; Ardais, Ana Paula; Botton, Paulo Henrique S; Klaudat, Bruno; Forte, Thomás; Souza, Diogo O; Elisabetsky, Elaine; Porciúncula, Lisiane O

    2013-01-01

    Beneficial effects of caffeine on memory processes have been observed in animal models relevant to neurodegenerative diseases and aging, although the underlying mechanisms remain unknown. Because brain-derived neurotrophic factor (BDNF) is associated with memory formation and BDNF's actions are modulated by adenosine receptors, the molecular targets for the psychostimulant actions of caffeine, we here compare the effects of chronic caffeine (1 mg/mL drinking solution for 30 days) on short- and long term memory and on levels of hippocampal proBDNF, mature BDNF, TrkB and CREB in young (3 month old) and middle-aged (12 month old) rats. Caffeine treatment substantially reduced i) age-related impairments in the two types of memory in an inhibitory avoidance paradigm, and ii) parallel increases in hippocampal BDNF levels. In addition, chronic caffeine increased proBDNF and CREB concentrations, and decreased TrkB levels, in hippocampus regardless of age. These data provide new evidence in favor of the hypothesis that modifications in BDNF and related proteins in the hippocampus contribute to the pro-cognitive effects of caffeine on age-associated losses in memory encoding. This article is part of a Special Issue entitled 'Cognitive Enhancers'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Hemodynamic mechanisms underlying the incomplete tolerance to caffeine's pressor effects.

    Science.gov (United States)

    Farag, Noha H; Vincent, Andrea S; McKey, Barbara S; Whitsett, Thomas L; Lovallo, William R

    2005-06-01

    Blood pressure (BP) and cardiovascular hemodynamics were assessed at baseline and after caffeine administration in a 4-week, placebo-controlled, double-blind, randomized, crossover trial of caffeine tolerance formation. Half of the subjects developed tolerance to the pressor effect of caffeine, whereas the other half continued to show increases in BP after caffeine ingestion (F = 16.7, p <0.0001). In the subjects who did not develop tolerance, peripheral resistance increased incrementally as the daily dose of caffeine increased (F = 2.8, p = 0.05).

  6. Randomized double-blind placebo-controlled crossover study of caffeine in patients with intermittent claudication.

    Science.gov (United States)

    Momsen, A H; Jensen, M B; Norager, C B; Madsen, M R; Vestersgaard-Andersen, T; Lindholt, J S

    2010-10-01

    Intermittent claudication is a disabling symptom of peripheral arterial disease for which few medical treatments are available. This study investigated the effect of caffeine on physical capacity in patients with intermittent claudication. This randomized double-blind placebo-controlled crossover study included 88 patients recruited by surgeons from outpatient clinics. The participants abstained from caffeine for 48 h before each test and then received either a placebo or oral caffeine (6 mg/kg). After 75 min, pain-free and maximal walking distance on a treadmill, perceived pain, reaction times, postural stability, maximal isometric knee extension strength, submaximal knee extension endurance and cognitive function were measured. The analysis was by intention to treat. Caffeine increased the pain-free walking distance by 20.0 (95 per cent confidence interval 3.7 to 38.8) per cent (P = 0.014), maximal walking distance by 26.6 (12.1 to 43.0) per cent (P postural stability was reduced significantly, by 22.1 (11.7 to 33.4) per cent with eyes open (P < 0.001) and by 21.8 (7.6 to 37.8) per cent with eyes closed (P = 0.002). Neither reaction time nor cognition was affected. In patients with moderate intermittent claudication, caffeine increased walking distance, maximal strength and endurance, but affected balance adversely.

  7. Correlation of RAD51 and radiosensitization of methotrexate

    International Nuclear Information System (INIS)

    Du Liqing; Bai Jianqiang; Liu Qiang; Wang Yan; Zhao Peng; Chen Fenghua; Wang Hong; Fan Feiyue

    2012-01-01

    Objective: To evaluate the correlation between homologous recombination repair protein RAD51 and methotrexate-enhanced radiosensitivity. Methods: Western blot and RT-PCR assays were used to detect RAD51 expression in HOS osteosarcoma cells exposed to γ-ray irradiation alone and in combination with methotrexate. Colony formation assay was used to test the survival fraction of HOS cells exposed to γ-rays and methotrexate. Results: Methotrexate inhibited both protein and RNA expressions of RAD51, and the combination of radiation and methotrexate enhanced the inhibition of RAD51 expression. Moreover, transfection of cells with RAD51 gene decreased cellular sensitivity to methotrexate and γ-rays. The sensitizer enhancement ratios after irradiation in combination with methotrexate were 1.51 and 0.99, respectively. Methotrexate was a preferred radiosensitizer to HOS cell. Conclusions: RAD51 might be involved in the methotrexate-enhanced radiosensitivity. (authors)

  8. Formation of radical anions of radiosensitizers and related model compounds via electrospray ionization

    DEFF Research Database (Denmark)

    Feketeová, Linda; Albright, Abigail L; Sørensen, Brita Singers

    2014-01-01

    Radiosensitizers are used in radiotherapy to enhance tumour control of radioresistant hypoxic tumours. While the detailed mechanism of radiosensitization is still unknown, the formation of radical anions is believed to be a key step. Thus understanding the ionization reactions of radiosensitizers......, misonidazole and related compounds using a hybrid linear ion trap – Fourier Transform Ion Cyclotron Resonance mass spectrometer (Finnigan-LTQ-FT). A key finding is that negative electrospray ionization of these radiosensitizers leads to the formation of radical anions, allowing their fragmentation reactions...

  9. Radioprotection by caffeine pre-treatment and post-treatment in the bone marrow chromosomes of mice given whole-body γ-irradiation

    International Nuclear Information System (INIS)

    Farooqi, Z.; Kesavan, P.C.

    1992-01-01

    The effect of caffeine given as pre- and post-treatment in mice exposed to whole-body γ-irradiation (1.5 Gy 60 Co γ-rays) was studied. The pre-treatment was either acute or chronic. The acute dose (5 mg/kg and 15 mg/kg body weight) was in the form of an injection given intraperitoneally, 30 min before irradiation. The chronic administration was in the form of caffeine solution (4.208x10 -3 M and 7.72x10 -4 M) contained in drinking water for 5 weeks prior to radiation exposure. The acute pre-treatment with caffeine reduced the radiation-induced frequency of chromosomal aberrations discernibly, whereas chronic pre-treatment afforded a much more significant degree of radioprotection. The caffeine post-treatment (5 mg/kg and 15 mg/kg body weight) was given in the form of an intraperitoneal injection to the mice immediately following whole-body γ-irradiation. It is noted that both post-treatment concentrations of caffeine also significantly reduced the frequency of chromosomal aberrations induced by γ-rays. These data are briefly discussed in terms of possible mechanistic considerations. (author). 33 refs.; 3 tabs

  10. Radioprotection by caffeine pre-treatment and post-treatment in the bone marrow chromosomes of mice given whole-body [gamma]-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Farooqi, Z.; Kesavan, P.C. (Jawaharlal Nehru Univ., New Delhi (India). School of Life Sciences)

    1992-10-01

    The effect of caffeine given as pre- and post-treatment in mice exposed to whole-body [gamma]-irradiation (1.5 Gy [sup 60]Co [gamma]-rays) was studied. The pre-treatment was either acute or chronic. The acute dose (5 mg/kg and 15 mg/kg body weight) was in the form of an injection given intraperitoneally, 30 min before irradiation. The chronic administration was in the form of caffeine solution (4.208x10[sup -3] M and 7.72x10[sup -4] M) contained in drinking water for 5 weeks prior to radiation exposure. The acute pre-treatment with caffeine reduced the radiation-induced frequency of chromosomal aberrations discernibly, whereas chronic pre-treatment afforded a much more significant degree of radioprotection. The caffeine post-treatment (5 mg/kg and 15 mg/kg body weight) was given in the form of an intraperitoneal injection to the mice immediately following whole-body [gamma]-irradiation. It is noted that both post-treatment concentrations of caffeine also significantly reduced the frequency of chromosomal aberrations induced by [gamma]-rays. These data are briefly discussed in terms of possible mechanistic considerations. (author). 33 refs.; 3 tabs.

  11. The development of genes associated with radiosensitivity of cervical cancer

    International Nuclear Information System (INIS)

    Li Hongyan; Chen Zhihua; He Guifang

    2007-01-01

    It has a good application prospect to predict effects of radiotherapy by examining radiosensitivity of patients with cervical cancers before their radiotherapy. Prediction of tumor cell radiosensitivity according to their level of gene expression and gene therapy to reverse radio-resistance prior to radiation on cervical cancers are heated researches on tumor therapy. The expression of some proliferation-related genes, apoptosis-related genes and hypoxia-related genes can inerease the radiosensitivity of cervical cancer. Microarray technology may have more direct applications to the study of biological pathway contributing to radiation resistance and may lead to development of alternative treatment modalities. (authors)

  12. Caffeine ingestion enhances Wingate performance: a meta-analysis.

    Science.gov (United States)

    Grgic, Jozo

    2018-03-01

    The positive effects of caffeine ingestion on aerobic performance are well-established; however, recent findings are suggesting that caffeine ingestion might also enhance components of anaerobic performance. A commonly used test of anaerobic performance and power output is the 30-second Wingate test. Several studies explored the effects of caffeine ingestion on Wingate performance, with equivocal findings. To elucidate this topic, this paper aims to determine the effects of caffeine ingestion on Wingate performance using meta-analytic statistical techniques. Following a search through PubMed/MEDLINE, Scopus, and SportDiscus ® , 16 studies were found meeting the inclusion criteria (pooled number of participants = 246). Random-effects meta-analysis of standardized mean differences (SMD) for peak power output and mean power output was performed. Study quality was assessed using the modified version of the PEDro checklist. Results of the meta-analysis indicated a significant difference (p = .005) between the placebo and caffeine trials on mean power output with SMD values of small magnitude (0.18; 95% confidence interval: 0.05, 0.31; +3%). The meta-analysis performed for peak power output indicated a significant difference (p = .006) between the placebo and caffeine trials (SMD = 0.27; 95% confidence interval: 0.08, 0.47 [moderate magnitude]; +4%). The results from the PEDro checklist indicated that, in general, studies are of good and excellent methodological quality. This meta-analysis adds on to the current body of evidence showing that caffeine ingestion can also enhance components of anaerobic performance. The results presented herein may be helpful for developing more efficient evidence-based recommendations regarding caffeine supplementation.

  13. CORRELATION BETWEEN CAFFEINE CONTENTS OF GREEN ...

    African Journals Online (AJOL)

    AND ALTITUDES OF THE COFFEE PLANTS GROWN IN SOUTHWEST ETHIOPIA .... sublimation temperature of caffeine, during it only a small percentage of .... the tube and extracted for a second time with 5.00 mL of boiling water. ..... Sridevi, V.; Giridhar, P. Changes in caffeine content during fruit development in Coffea.

  14. THE EFFECT OF CAFFEINE ON TEAR FORMATION

    African Journals Online (AJOL)

    improvement in physical performance and other. Caffeine is of ... function is also influenced by other factors like age, menopause ... influence of such drugs on the lacrimal gland function .... Pharmacokinetic profile on caffeine in premature ...

  15. Beliefs, Behaviors, and Contexts of Adolescent Caffeine Use: A Focus Group Study.

    Science.gov (United States)

    Ludden, Alison B; O'Brien, Elizabeth M; Pasch, Keryn E

    2017-07-29

    Caffeinated products are widely available to adolescents, and consumption of caffeine products-energy drinks and coffee in particular-is on the rise in this age group (Branum, Rossen, & Schoendorf, 2014). Yet, little is known about the psychosocial context of caffeine use. Previous studies on adolescent caffeine use have focused on caffeine's acute physiological effects, rather than the psychosocial contexts and beliefs regarding different types of caffeinated beverages (e.g., coffee, energy drinks, soda). The current research examines the contexts and beliefs associated with adolescents' use of caffeinated beverages (e.g., coffee, energy drinks, soda) using a focus group approach. Eleven focus group interviews (49 total participants) addressed adolescents' motivations for and patterns of caffeine use; they were transcribed and axial coding was used to identify common themes. Coffee and energy drinks were perceived to be the most popular caffeinated beverages. Reasons for consuming caffeine included the effect of caffeine as a stimulant, the pleasant feelings experienced when drinking it, and the fact that caffeine was available. As for contexts, coffee was consumed in more diverse social contexts than other caffeinated beverages. Friends and sports were the most popular contexts for energy drink use. The present findings inform adolescent health promotion efforts and provide researchers and practitioners alike detailed information in adolescents' own words about how and why they use caffeine. Adolescents' beliefs about caffeinated products are not uniform; the reasons adolescents articulate regarding their use of coffee, soda, and energy drinks are different across contexts and beverage type.

  16. 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.

  17. Protonation of caffeine: A theoretical and experimental study

    International Nuclear Information System (INIS)

    Bahrami, Hamed; Tabrizchi, Mahmoud; Farrokhpour, Hossein

    2013-01-01

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

  18. Modification of radiation-induced division delay by caffeine analogues and dibutyryl cyclic AMP

    Energy Technology Data Exchange (ETDEWEB)

    Kimler, B.F.; Leeper, D.B.; Snyder, M.H.; Rowley, R.; Schneiderman, M.H. (Thomas Jefferson Univ., Philadelphia, PA (USA). Hospital)

    1982-01-01

    The mitotic selection procedure for cell cycle analysis was utilized to investigate the concentration-dependent modification of x-radiation-induced division delay in Chinese hamster ovary (CHO) cells by methyl xanthines (caffeine, theophylline, and theobromine) and by dibutyryl cyclic AMP. The methyl xanthines (concentrations from 0.5 to 1000 ..mu..g/ml) all reduced radiation-induced division delay with the effect being linear between approximately 100 and 1000 ..mu..g/ml. After doses of 100-300 rad, delay was reduced by 75, 94 or 83 per cent at 1000 ..mu..g/ml for each drug, respectively. However, the addition of dibutyryl cyclic AMP had an opposite effect: radiation-induced delay was increased by the concentration range of 0.3 to 300 ..mu..g/ml. These results indicate that in mammalian cells the control of cell cycle progression and the modification of radiation-induced division delay are not simply related to intracellular levels of cyclic AMP. Rather, there appear to be at least two competing mechanisms which are differentially affected by caffeine analogues or by direct addition of dibutyryl cyclic AMP. The direct effect of caffeine and the methyl xanthines on membrane calcium permeability is considered.

  19. Modification of radiation-induced division delay by caffeine analogues and dibutyryl cyclic AMP

    International Nuclear Information System (INIS)

    Kimler, B.F.; Leeper, D.B.; Snyder, M.H.; Rowley, R.; SChneiderman, M.H.

    1982-01-01

    The mitotic selection procedure for cell cycle analysis was utilized to investigate the concentration-dependent modification of x-radiation-induced division delay in Chinese hamster ovary (CHO) cells by methyl xanthines (caffeine, theophylline, and theobromine) and by dibutyryl cyclic AMP. The methyl xanthines (concentrations from 0.5 to 1000 μg/ml) all reduced radiation-induced division delay with the effect being linear between approximately 100 and 1000 μg/ml. After doses of 100-300 rad, delay was reduced by 75, 94 or 83 per cent at 1000 μg/ml for each drug, respectively. However, the addition of dibutyryl cyclic AMP had an opposite effect: radiation-induced delay was increased by the concentration range of 0.3 to 300 μg/ml. These results indicate that in mammalian cells the control of cell cycle progression and the modification of radiation-induced division delay are not simply related to intracellular levels of cyclic AMP. Rather, there appear to be at least two competing mechanisms which are differentially affected by caffeine analogues or by direct addition of dibutyryl cyclic AMP. The direct effect of caffeine and the methyl xanthines on membrane calcium permeability is considered. (author)

  20. Energy drink ingredients. Contribution of caffeine and taurine to performance outcomes.

    Science.gov (United States)

    Peacock, Amy; Martin, Frances Heritage; Carr, Andrea

    2013-05-01

    While the performance-enhancing effects of energy drinks are commonly attributed to caffeine, recent research has shown greater facilitation of performance post-consumption than typically expected from caffeine content alone. Consequently, the aim of the present study was to investigate the independent and combined effect of taurine and caffeine on behavioural performance, specifically reaction time. Using a double-blind, placebo-controlled, crossover, within-subjects design, female undergraduates (N=19) completed a visual oddball task and a stimulus degradation task 45min post-ingestion of capsules containing: (i) 80mg caffeine, (ii) 1000mg taurine, (iii) caffeine and taurine combined, and (iv) matched placebo. Participants completed each treatment condition, with sessions separated by a minimum 2-day washout period. Whereas no significant treatment effects were recorded for reaction time in the visual oddball task, facilitative caffeine effects were evident in the stimulus degradation task, with significantly faster reaction time in active relative to placebo caffeine conditions. Furthermore, there was a trend towards faster mean reaction time in the caffeine condition relative to the taurine condition and combined caffeine and taurine condition. Thus, treatment effects were task-dependent, in that independent caffeine administration exerted a positive effect on performance, and co-administration with taurine tended to attenuate the facilitative effects of caffeine in the stimulus degradation task only. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Metabolism and radiosensitization of 4,5-dimethylmisonidazole, a ring-substituted analog of misonidazole

    International Nuclear Information System (INIS)

    Born, J.L.; Smith, B.R.; Harper, N.; Koch, C.J.

    1992-01-01

    In the present study, methyl groups were added to the imidazole ring of misonidazole in order to hinder adduct formation with cellular molecules after reductive-activation of the compound. It was anticipated that this would substantially decrease the hypoxic-cell toxicity of the parent drug. The presence of the two methyl groups reduced the half-wave reduction potential of dimethyl misonidazole (DMM) by about 70 mV, so we expected that its radiosensitizing ability would also decrease. In direct comparison with misonidazole, DMM, at equimolar concentrations, showed dramatically reduced binding to cellular macromolecules under bioreductive conditions, both in vivo, using a liver perfusion system, and in vitro, using tissue culture cells incubated under extreme hypoxia. However, DMM was only moderately less toxic than the parent compound, and showed greatly diminished radiation sensitization capacity. Since the decrease in toxicity was much less than expected, and the decrease in radiosensitization was much more than expected, this compound may be an important drug for continuing studies on the mechanisms of radiation sensitization, binding and cytotoxicity caused by electron affinic drugs. (Author)

  2. The reversible N-oxidation of the nitroimidazole radiosensitizer Ro 03-8799

    International Nuclear Information System (INIS)

    Walton, M.I.; Bleehen, N.M.; Workman, P.; Cambridge Univ.

    1985-01-01

    The nitroimidazole radiosensitizer Ro 03-8799 and the N-oxide Ro 31-0313 were dissolved in buffered solution and given i.v. to inbred male mice. Drug concentrations in whole blood, blood plasma and urine were determined by MPLC. Ro 03 8799 is rapidly cleared and extensively metabolised. Ro 31-0313 is reduced back to Ro 03-8799 by whole blood. The pharmacological and toxicological consequences of this are unknown. (UK)

  3. Caffeine dependence in rats: effects of exposure duration and concentration.

    Science.gov (United States)

    Dingle, Rachel N; Dreumont-Boudreau, Sarah E; Lolordo, Vincent M

    2008-09-03

    Groups of rats were chronically exposed to a 1.0-g/L caffeine solution for 5, 10, 15 or 20 days. Upon removal of caffeine, rats were given brief exposure to a novel flavour CS (withdrawal CS) followed by 12 days of plain water and then brief exposure to a second flavour CS (neutral CS). Only rats exposed to 20 days of caffeine strongly preferred the neutral CS to the withdrawal CS in a 2-bottle test. In Experiment 2, groups of rats were chronically exposed to caffeine at one of four concentrations (1.0, 0.5, 0.25, or 0.125 g/L) for 21 days, after which withdrawal and neutral CSs were established. Only rats that drank the highest caffeine concentration, 1.0 g/L, preferred the neutral CS to the withdrawal CS. This suggests that long exposure to a strong caffeine solution is required in order to induce dependence in rats such that a CS associated with the withdrawal of caffeine becomes avoided.

  4. Effect of Coffee and Caffeine Ingestion on Resistance Exercise Performance.

    Science.gov (United States)

    Richardson, Darren L; Clarke, Neil D

    2016-10-01

    Richardson, DL and Clarke, ND. Effect of coffee and caffeine ingestion on resistance exercise performance. J Strength Cond Res 30(10): 2892-2900, 2016-The aim of the present study was to determine the effect of ingesting caffeine dose-matched anhydrous caffeine, coffee, or decaffeinated coffee plus anhydrous caffeine during resistance exercise on performance. Nine resistance-trained men (mean ± SD: age, 24 ± 2 years; weight, 84 ± 8 kg; height, 180 ± 8 cm) completed a squat and bench press exercise protocol at 60% 1 repetition maximum until failure on 5 occasions consuming 0.15 g·kg caffeinated coffee (COF), 0.15 g·kg decaffeinated coffee (DEC), 0.15 g·kg decaffeinated coffee plus 5 mg·kg anhydrous caffeine (D + C), 5 mg·kg anhydrous caffeine (CAF), or a placebo (PLA). Felt arousal and rating of perceived exertion (RPE) were used to assess perceptual variables and heart rate (HR) to assess physiological responses between trials. There were significant differences in total weight lifted for the squat between conditions (p caffeine have the ability to improve performance during a resistance exercise protocol, although possibly not over multiple bouts.

  5. Caffeine attenuates scopolamine-induced memory impairment in humans.

    Science.gov (United States)

    Riedel, W; Hogervorst, E; Leboux, R; Verhey, F; van Praag, H; Jolles, J

    1995-11-01

    Caffeine consumption can be beneficial for cognitive functioning. Although caffeine is widely recognized as a mild CNS stimulant drug, the most important consequence of its adenosine antagonism is cholinergic stimulation, which might lead to improvement of higher cognitive functions, particularly memory. In this study, the scopolamine model of amnesia was used to test the cholinergic effects of caffeine, administered as three cups of coffee. Subjects were 16 healthy volunteers who received 250 mg caffeine and 2 mg nicotine separately, in a placebo-controlled double-blind cross-over design. Compared to placebo, nicotine attenuated the scopolamine-induced impairment of storage in short-term memory and attenuated the scopolamine-induced slowing of speed of short-term memory scanning. Nicotine also attenuated the scopolamine-induced slowing of reaction time in a response competition task. Caffeine attenuated the scopolamine-induced impairment of free recall from short- and long-term memory, quality and speed of retrieval from long-term memory in a word learning task, and other cognitive and non-cognitive measures, such as perceptual sensitivity in visual search, reading speed, and rate of finger-tapping. On the basis of these results it was concluded that caffeine possesses cholinergic cognition enhancing properties. Caffeine could be used as a control drug in studies using the scopolamine paradigm and possibly also in other experimental studies of cognitive enhancers, as the effects of a newly developed cognition enhancing drug should at least be superior to the effects of three cups of coffee.

  6. Correlation between radiosensitivity of transplanted solid tumor and nutritive condition of host animal

    Energy Technology Data Exchange (ETDEWEB)

    Ando, K [Showa Univ., Tokyo (Japan). School of Medicine

    1975-04-01

    Studies on radiosensitivity of the transplanted tumor were carried out and the following results were obtained: 1. Radiosensitivity of the tumor ran parallel to the growth rate. 2. Malnutrition of the host after irradiation made the tumor radiosensitive, probably because the sublethally damaged tumor cell did not recover. 3. Mitotic index correlated well with radiosensitivity, and the low mitotic index caused by starvation made the tumor cell recover poorly. 4. The DNA synthetic rate measured by means of iodine labeled IUdR did not successfully correlate with the mitotic rate, presumably because of the role of thymidine pool size in this experiment. 5. The serum protein level possibly with the tumor growth, which modified the radiosensitivity. 6. Serum oxygen was difficult to interpret, however, it might be compensated by erythrocytosis in a starved condition.

  7. Synergism between two helper cell subpopulations characterized by different radiosensitivity and nylon adherence

    International Nuclear Information System (INIS)

    Agarossi, G.; Mancini, C.; Doria, G.

    1981-01-01

    The present work extends our previous results on the radiosensitivity of the helper cell function. Two helper cell subpopulations, 1 radiosensitive and the other radioresistant, have been demonstrated in the spleen of mice at different times after priming with HRBC. The radiosensitive subpopulation increases with the increasing time interval between carrier-priming and irradiation. The 2 cell subpopulations have been further characterized by different nylon adherence properties: radioresistant helper cells adhere to nylon wool, whereas radiosensitive cells pass through. The 2 cell subpopulations were separated by x-irradiation and nylon wool filtration, and their helper activity was assessed separately or after recombination. The results favor the notion that 2 functionally independent helper T cells, as characterized by different radiosensitivity and nylon adherence, participate synergistically in the helper activity of primed spleen cells

  8. The Interaction of Sorbitol with Caffeine in Aqueous Solution

    OpenAIRE

    Tavagnacco, Letizia; Brady, John W.; Cesàro, Attilio

    2013-01-01

    Molecular dynamics simulations were carried out on a system of caffeine interacting with the sugar alcohol sorbitol. The system examined had a caffeine concentration 0.083 m and a sugar concentration 1.08 m. The trajectories of all molecules in the system were collected over a period of 80 ns and analyzed to determine whether there is any tendency for sorbitol to bind to caffeine, and if so, by what mechanism. The results show that the sorbitol molecules have an affinity for the caffeine mole...

  9. 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.

  10. Evaluation of the Reproductive and Developmental Risks of Caffeine

    Science.gov (United States)

    Brent, Robert L; Christian, Mildred S; Diener, Robert M

    2011-01-01

    A risk analysis of in utero caffeine exposure is presented utilizing epidemiological studies and animal studies dealing with congenital malformation, pregnancy loss, and weight reduction. These effects are of interest to teratologists, because animal studies are useful in their evaluation. Many of the epidemiology studies did not evaluate the impact of the “pregnancy signal,” which identifies healthy pregnancies and permits investigators to identify subjects with low pregnancy risks. The spontaneous abortion epidemiology studies were inconsistent and the majority did not consider the confounding introduced by not considering the pregnancy signal. The animal studies do not support the concept that caffeine is an abortafacient for the wide range of human caffeine exposures. Almost all the congenital malformation epidemiology studies were negative. Animal pharmacokinetic studies indicate that the teratogenic plasma level of caffeine has to reach or exceed 60 µg/ml, which is not attainable from ingesting large amounts of caffeine in foods and beverages. No epidemiological study described the “caffeine teratogenic syndrome.” Six of the 17 recent epidemiology studies dealing with the risk of caffeine and fetal weight reduction were negative. Seven of the positive studies had growth reductions that were clinically insignificant and none of the studies cited the animal literature. Analysis of caffeine's reproductive toxicity considers reproducibility and plausibility of clinical, epidemiological, and animal data. Moderate or even high amounts of beverages and foods containing caffeine do not increase the risks of congenital malformations, miscarriage or growth retardation. Pharmacokinetic studies markedly improve the ability to perform the risk analyses. Birth Defects Res (Part B) 92:152–187, 2011. © 2011 Wiley-Liss, Inc. PMID:21370398

  11. Synergistic effects of radiation and caffeine on embryonic development in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kusama, Tomoko; Yoshizawa, Yasuo (Tokyo Univ. (Japan). Faculty of Medicine)

    1984-09-01

    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.

  12. Caffeine use in sports. A pharmacological review.

    Science.gov (United States)

    Sinclair, C J; Geiger, J D

    2000-03-01

    Caffeine is the most widely ingested psychoactive drug in the world. As many know, chronic use of caffeine leads to dependence, tolerance, drug craving, and upon abrupt cessation unpleasant withdrawal symptoms. Thus, caffeine fulfills pharmacological criteria by which agents are classified as drugs of abuse. Nevertheless, its use is legal and only at high, but readily attainable, levels is it banned from sport. Its use is widespread by athletes as young as 11 years of age who are seeking athletic advantage over fellow competitors. It is likely that its use will not decline any time soon because it is inexpensive, readily available, medically quite safe, socially acceptable, and by most measures legal. However, at levels allowed in sport, caffeine through its wide-ranging physiological and psychological effects increases endurance in well-trained athletes. If the goal of drug-testing and education programs in sport is to protect the health of athletes, prevent unfair advantage (cheating) and encourage ethical behavior then it seems obvious that the allowable levels of caffeine ingestion should be decreased. The alternative is to continue with policies designed largely to punish only those that get caught.

  13. Bacterial radiosensitivity to gamma and ultraviolet. Compositional dependence and repair mechanisms

    International Nuclear Information System (INIS)

    Saez Angulo, R. M.; Davila, C. A.

    1974-01-01

    The gamma and ultraviolet radiosensitivity of several species of bacteria has been determined its dependence on DNAs composition and repair processes has been studied. Base composition are evaluated by chromatography, DNA melting temperature and isopycnic sedimentation on CsCl gradient. Repair capacity of gamma -and UV- lesions has been studied in two bacterial strains with same DMA base composition. It is concluded that the postulated correlation between radiosensitivity and base composition can not be generalized, the enzymatic repair mechanisms being of determining on radiosensitivity. (Author) 248 refs

  14. 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.

  15. Caffeine's influence on gambling behavior and other types of impulsivity.

    Science.gov (United States)

    Grant, Jon E; Chamberlain, Samuel R

    2018-01-01

    Young adulthood is a developmental period frequently associated with occurrence of impulsive behaviors including gambling. It is estimated that 73% of children and 87% of adults in the United States regularly use caffeine. Questions remain, however, concerning the role of caffeine in the development and maintenance of impulsive behaviors such as gambling. Sixty-one young adults with at least some degree of disordered gambling were recruited from two Mid-Western university communities in the United States using media advertisements. Caffeine intake over the preceding month was quantified using the Caffeine Use Questionnaire. Clinician rating scales, questionnaires, and cognitive tests germane to impulsivity were completed. Relationships between caffeine intake and demographic, gambling symptom, and neurocognitive measures were evaluated using the statistical technique of partial least squares (PLS). Average weekly caffeine intake in the gamblers was 1218.5mg (a figure higher than previously reported in the general population). PLS yielded an optimal model with one latent factor, which explained 14.8% of variation in demographic/clinical/cognitive measures and 32.3% of variation in caffeine intake. In this model, higher caffeine intake was significantly associated with earlier age at first gambling, higher personality-related impulsiveness, more nicotine consumption, older age, and more impulsive decision-making. These data suggest a particularly strong relationship between caffeine intake, earlier age of first gambling, and certain types of impulsivity in gamblers. Providing education about healthy caffeine use may be especially valuable in gamblers. Future work should explore whether the relationship between caffeine use and gambling is due to a common predisposing factor (impulsive tendencies) or, rather, constitutes a form of self-medication in gamblers (or a means of sustaining gambling habits for longer). Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Caffeine for the prevention of injuries and errors in shift workers.

    Science.gov (United States)

    Ker, Katharine; Edwards, Philip James; Felix, Lambert M; Blackhall, Karen; Roberts, Ian

    2010-05-12

    Sleepiness leads to a deterioration in performance and attention, and is associated with an increased risk of injury. Jet lag and shift work disorder are circadian rhythm sleep disorders which result in sleepiness and can elevate injury risk. They create a need for individuals to operate at times which are different to those dictated by their circadian rhythms. Consequently there is also a need for interventions to help ensure that these persons can do so safely. Caffeine has a potential role in promoting alertness during times of desired wakefulness in persons with jet lag or shift work disorder, however its effects on injury and error are unclear. To assess the effects of caffeine for preventing injuries caused by impaired alertness in persons with jet lag or shift work disorder. We searched the Cochrane Injuries Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE, PsycINFO, CINAHL, TRANSPORT (to July 2008); and PubMed databases (to April 2010). We also searched the Internet and checked reference lists of relevant papers. Randomised controlled trials investigating the effects of caffeine on injury, error or cognitive performance in people with jet lag or shift work disorder. Two authors independently screened search results and assessed full texts for inclusion. Data were extracted and risk of bias was assessed. Estimates of treatment effect (odds ratio and standardised mean difference (SMD)) and 95% confidence intervals (CI) were calculated and pooled using the fixed-effect model. Thirteen trials were included. None measured an injury outcome. Two trials measured error, and the remaining trials used neuropsychological tests to assess cognitive performance. The trials assessing the impact on errors found that caffeine significantly reduced the number of errors compared to placebo. The pooled effect estimates on performance by cognitive domain suggest that, when compared to placebo, caffeine improved concept formation and reasoning (SMD -0

  17. Growth inhibition and differentiation of murine melanoma B16-BL6 cells caused by the combination of cisplatin and caffeine.

    Science.gov (United States)

    Tsuchiya, H; Tomita, K; Yasutake, H; Ueda, Y; Tanaka, M; Sasaki, T

    1989-12-01

    We preliminarily investigated the combined effects of cisplatin and caffeine on murine melanoma B16-BL6 cells in vitro. When caffeine was added before or simultaneously with cisplatin, there was little growth inhibition. The addition of 2.0 mM caffeine after 1 h of exposure to cisplatin inhibited growth and induced cell differentiation. This treatment resulted in fewer cells, and the numbers of melanosomes and mitochondria and the amount of Golgi's complex and endoplasmic reticulum were increased. DNA histograms obtained by flow cytometry showed that cells treated with cisplatin alone accumulated in the G2/M phase, with a partial G2 block. The addition of 2.0 mM caffeine after 1 h of treatment with cisplatin reduced this block. Caffeine caused murine melanoma B16-BL6 cells treated with cisplatin to differentiate, and this inhibited growth.

  18. Membrane specific drugs as radiosensitizers

    Energy Technology Data Exchange (ETDEWEB)

    George, K.C.; Mishra, K.P.; Shenoy, M.A.; Singh, B.B.; Srinivasan, V.T.; Verma, N.C.

    1981-01-01

    Procaine, paracetamol, and chlorpromazine showed inhibition of post irradiation repair. The chlorpromazie effect could be further augmented by treatment of cells with procaine. Chlorpromazine was also found to be preferentially toxic to hypoxid bacterial cells, and the survivors showed extreme radiosensitivity to gamma rays. Chlorpromazine was found to inhibit tumour growth in swiss mice when given intraperitoneally as well as when injected directly into the tumour. When combined with single x-ray doses, significant radiosensitization was observed in two in vivo tumours sarcoma 180A and fibrosarcoma. These results indicated that chlorpromazine may prove a good drug for combined chemo-radiotherapy of solid tumours. Investigations continued studying various aspects such as effectiveness in other tumour lines, distribution in healthy and tumour bearing animals, hyperthermia and drug combination effects, and encapsulation of the drug in artificial liposomes and blood cells. (ERB)

  19. Silencing of osteopontin promotes the radiosensitivity of breast cancer cells by reducing the expression of hypoxia inducible factor 1 and vascular endothelial growth factor

    Institute of Scientific and Technical Information of China (English)

    YANG Li; ZHAO Wei; ZUO Wen-shu; WEI Ling; SONG Xian-rang; WANG Xing-wu; ZHENG Gang; ZHENG Mei-zhu

    2012-01-01

    Background Osteopontin (OPN) is a secreted phosphoglycoprotein (SSP) that is overexpressed in a variety of tumors and was regarded as a molecular marker of tumors.In this study,we intended to demonstrate the role of OPN in human breast cancer cell line MDA-MB-231.Methods Recombinant plasmid expressing small interfering RNA (siRNA) specific to OPN mRNA was transfected into MDA-MB-231 cells to generate the stable transfected cell line MDA-MB-343,and the empty plasmid tansfected cells (MDA-MB-neg) or wildtype MDA-MB-231 cells were used as control cells respectively.Expression of OPN,hypoxia inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) proteins was analyzed by Western blotting analysis.The radiosensitivity of cells was determined by detecting cell apoptosis,cell proliferation and cell senescence.Results HIF-1 and VEGF proteins in MDA-MB-343 cells were significantly downregulated upon the efficient knockdown of OPN expression under either hypoxia or normoxia environment.Moreover,expression of OPN protein was upregualted upon hypoxic culture.Stable OPN-silencing also decreased cell invasion,increased cell apoptosis and cell senescence,as well as reduced clonogenic survival,resulting in increase radiation tolerance.Conclusions Suppression of OPN gene expression can enhance radiosensitivity and affect cell apoptosis in breast cancer cells.OPN seems to be an attractive target for the improvement of radiotherapy.

  20. Mechanisms of caffeine-induced inhibition of UVB carcinogenesis

    Directory of Open Access Journals (Sweden)

    Allan H Conney

    2013-06-01

    Full Text Available Sunlight-induced nonmelanoma skin cancer is the most prevalent cancer in the United States with more than 2 million cases per year. Several studies have shown an inhibitory effect of caffeine administration on UVB-induced skin cancer in mice, and these studies are paralleled by epidemiology studies that indicate an inhibitory effect of coffee drinking on nonmelanoma skin cancer in humans. Strikingly, decaffeinated coffee consumption had no such inhibitory effect.Mechanism studies indicate that caffeine has a sunscreen effect that inhibits UVB-induced formation of thymine dimers and sunburn lesions in the epidermis of mice. In addition, caffeine administration has a biological effect that enhances UVB-induced apoptosis thereby enhancing the elimination of damaged precancerous cells, and caffeine administration also enhances apoptosis in tumors. Caffeine administration enhances UVB-induced apoptosis by p53-dependent and p53-independent mechanisms. Exploration of the p53-independent effect indicated that caffeine administration enhanced UVB-induced apoptosis by inhibiting the UVB-induced increase in ATR-mediated formation of phospho-Chk1 (Ser345 and abolishing the UVB-induced decrease in cyclin B1 which resulted in caffeine-induced premature and lethal mitosis in mouse skin. In studies with cultured primary human keratinocytes, inhibition of ATR with siRNA against ATR inhibited Chk1 phosphorylation and enhanced UVB-induced apoptosis. Transgenic mice with decreased epidermal ATR function that were irradiated chronically with UVB had 69% fewer tumors at the end of the study compared with irradiated littermate controls with normal ATR function. These results, which indicate that genetic inhibition of ATR (like pharmacologic inhibition of ATR via caffeine inhibits UVB-induced carcinogenesis and supports the concept that ATR-mediated phosphorylation of Chk1 is an important target for caffeine’s inhibitory effect on UVB-induced carcinogenesis.