Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.Central Nervous System Stimulants: A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here.Theobromine: 3,7-Dimethylxanthine. The principle alkaloid in Theobroma cacao (the cacao bean) and other plants. A xanthine alkaloid that is used as a bronchodilator and as a vasodilator. It has a weaker diuretic activity than THEOPHYLLINE and is also a less powerful stimulant of smooth muscle. It has practically no stimulant effect on the central nervous system. It was formerly used as a diuretic and in the treatment of angina pectoris and hypertension. (From Martindale, The Extra Pharmacopoeia, 30th ed, pp1318-9)Coffee: A beverage made from ground COFFEA beans (SEEDS) infused in hot water. It generally contains CAFFEINE and THEOPHYLLINE unless it is decaffeinated.Ryanodine: A methylpyrrole-carboxylate from RYANIA that disrupts the RYANODINE RECEPTOR CALCIUM RELEASE CHANNEL to modify CALCIUM release from SARCOPLASMIC RETICULUM resulting in alteration of MUSCLE CONTRACTION. It was previously used in INSECTICIDES. It is used experimentally in conjunction with THAPSIGARGIN and other inhibitors of CALCIUM ATPASE uptake of calcium into SARCOPLASMIC RETICULUM.Cytochrome P-450 CYP1A2: A cytochrome P450 enzyme subtype that has specificity for relatively planar heteroaromatic small molecules, such as CAFFEINE and ACETAMINOPHEN.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016).Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.Sarcoplasmic Reticulum: A network of tubules and sacs in the cytoplasm of SKELETAL MUSCLE FIBERS that assist with muscle contraction and relaxation by releasing and storing calcium ions.Ryanodine Receptor Calcium Release Channel: A tetrameric calcium release channel in the SARCOPLASMIC RETICULUM membrane of SMOOTH MUSCLE CELLS, acting oppositely to SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES. It is important in skeletal and cardiac excitation-contraction coupling and studied by using RYANODINE. Abnormalities are implicated in CARDIAC ARRHYTHMIAS and MUSCULAR DISEASES.Receptor, Adenosine A2A: A subclass of adenosine A2 receptors found in LEUKOCYTES, the SPLEEN, the THYMUS and a variety of other tissues. It is generally considered to be a receptor for ADENOSINE that couples to the GS, STIMULATORY G-PROTEIN.Beverages: Liquids that are suitable for drinking. (From Merriam Webster Collegiate Dictionary, 10th ed)Adenosine A2 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.Receptor, Adenosine A1: A subtype of ADENOSINE RECEPTOR that is found expressed in a variety of tissues including the BRAIN and DORSAL HORN NEURONS. The receptor is generally considered to be coupled to the GI, INHIBITORY G-PROTEIN which causes down regulation of CYCLIC AMP.Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.Ephedrine: A phenethylamine found in EPHEDRA SINICA. PSEUDOEPHEDRINE is an isomer. It is an alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used for asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists.Paullinia: A plant genus of the family SAPINDACEAE. The seed of P. cupana is the source of guarana powder which contains 4% CAFFEINE.Malignant Hyperthermia: Rapid and excessive rise of temperature accompanied by muscular rigidity following general anesthesia.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Drinking Behavior: Behaviors associated with the ingesting of water and other liquids; includes rhythmic patterns of drinking (time intervals - onset and duration), frequency and satiety.Purinergic P1 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.Adenosine A1 Receptor Antagonists: Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.Receptors, Adenosine A2: A subclass of ADENOSINE RECEPTORS that are generally considered to be coupled to the GS, STIMULATORY G-PROTEIN which causes up regulation of CYCLIC AMP.Tetracaine: A potent local anesthetic of the ester type used for surface and spinal anesthesia.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.

*  Effects of Caffeine on Intermittent Hypoxia in Infants Born Preterm - Full Text View - ClinicalTrials.gov

Caffeine citrate 6 mg/kg/day. Drug: Caffeine citrate 6 mg/kg/day Comparison of caffeine citrate 6 mg/kg/day versus no caffeine ... No Intervention: Active Comparator: no caffeine Compare extended use of caffeine citrate 6 mg/kg/day to no caffeine (usual care ... The group randomized to start caffeine will receive an oral loading dose of caffeine citrate of 20 mg/kg on Day #1, followed by ... Caffeine. Caffeine citrate. Anticoagulants. Calcium Chelating Agents. Chelating Agents. Sequestering Agents. Molecular ...
https://clinicaltrials.gov/ct2/show/NCT01875159?term=SIDS&rank=19

*  Which soda has the most caffeine? | Reference.com

Some other sodas with high amounts of caffeine include Kick Citrus with... ... Pepsi One has 55.5 milligrams of caffeine in 12 ounces, edging out Mountain Dew, which has 55 milligrams in a 12-ounce serving ... Some other sodas with high amounts of caffeine include Kick Citrus with 54 milligrams of caffeine, Mellow Yellow with 52.8 ... Pepsi One has 55.5 milligrams of caffeine in 12 ounces, edging out Mountain Dew, which has 55 milligrams in a 12-ounce serving. ...
https://reference.com/food/soda-caffeine-a2d1869b00c36241

*  Hidupkukan Damaikan Hatimu Lyrics - Caffeine

Lyrics to Hidupkukan Damaikan Hatimu by Caffeine: berjalan di tepi pantai / tertiup angin berhembus / sejukkan hati damaikan ...
lyricsfreak.com/c/caffeine/hidupkukan damaikan hatimu_20599027.html

*  Submit a Revision

Data on caffeine intake were also collected, and the association between caffeine intake before and during pregnancy and ... Regarding caffeine consumption, women were asked about the intake of beverages containing caffeine such as coffee, tea, and ... Quartiles for the distribution of caffeine consumption ( 321mg/day) were used as cutoffs for caffeine intake, and the category ... An extensive accounting of all different sources of caffeine exposure would have allowed the authors to study 'caffeine ...
biology-online.org/kb/revision.php?p_id=1295&a_id=419

*  caffeine

Four Loko drops caffeine from its beverages amid an expected FDA ban. By Jaclyn Giovis. November 17, 2010 ... How much caffeine is in that Starbucks cup?. By Lizzie O'Leary. August 08, 2013 ... Wrigley plans to start selling "Alert" gum next month -- that is, gum with caffeine. Gum sales overall are down, and "energy" ... Journalist Murray Carpenter goes inside the big business of caffeine in his new book, 'Caffeinated: How our daily habit helps, ...
https://marketplace.org/tags/caffeine

*  Plants trick honeybees with caffeine | Science Articles | Naked Scientists

Plants lace their nectar with caffeine to encourage bees to keep returning and pollinate them in the process.Caffeine is ... "The presence of caffeine in the nectar can cause the honeybees to behave as if the nectar is of much better quality than it ... Caffeine is abundant in plants, mostly in the leaves, seeds and stems. It is very bitter, which helps to deter most animals ... The bees that had foraged on the caffeine substance persistently came back to check the empty feeder much more than the other ...
https://thenakedscientists.com/articles/science-news/plants-trick-honeybees-caffeine

*  Caffeine | POPSUGAR Fitness

On POPSUGAR Fitness you will find everything you need on fitness, health and Caffeine. ... The latest tips and news on Caffeine are on POPSUGAR Fitness. ... I Gave Up Caffeine 18 Months Ago, and This Is How It Changed ... Exactly What to Order at Starbucks If You Want the Most Caffeine ... 6 Ways to Break Your Caffeine Addiction (and Why You Should) by ... Parents Share Heartbreaking Warning After Their Child Died From Too Much Caffeine ...
https://popsugar.com/latest/Caffeine

*  Caffeine and bacteria

... Colin Davidson c.davidson at biotech.cam.ac.uk Wed Sep 20 07:25:05 EST 2000 *Previous message: Caffeine ... I would like to know if anyone knows , anything about caffeine and it's effects on bacterial , chromosomes that might help me. ... I'm doing a research project on Caffeine as a , DNA targeting antibioitc for Antibiotic Resistant , bacteria. ...
bio.net/bionet/mm/microbio/2000-September/018858.html

*  Caffeine - Wikipedia

EN) Caffeine, su Metacritic, CBS Interactive Inc. (EN) Caffeine, in TV.com, CBS Interactive Inc. (EN) Caffeine, in AFI Catalog ... EN) Caffeine, su Internet Movie Database, IMDb.com. (EN) Caffeine, su AllMovie, All Media Network. (EN) Caffeine, in Rotten ... Caffeine è un film del 2006 diretto da John Cosgrove. Durante una pausa pranzo in un'insolita caffetteria di Londra, le ...
https://it.wikipedia.org/wiki/Caffeine

*  Drugs - apap/asa/caffeine - usage, dosage, interactions, images - AARP

ACETAMINOPHEN; ASPIRIN; CAFFEINE (a set a MEE noe fen; AS pir in; KAF een) is a pain reliever. It is used to treat mild aches ... Generic Name: apap/asa/caffeine. It is used to treat mild aches and pains ... an unusual or allergic reaction to acetaminophen, aspirin, caffeine, other medicines, foods, dyes or preservatives ...
healthtools.aarp.org/goldcontent/acetaminophen-aspirin-caffeine?brand=Excedrin

*  Efficacy of Caffeine Injection as an Adjuvant to Opioid Therapy in Cancer Pain - Full Text View - ClinicalTrials.gov

Drug: Caffeine Intravenous injection of caffeine 200mg with 100ml of normal saline over 1 hour, once a day, for two days. ... Experimental: Caffeine Intravenous injections of 200mg of caffeine with 100ml of normal saline over 1 hour ... Caffeine. Sodium Benzoate. Caffeine, sodium benzoate drug combination. Central Nervous System Stimulants. Physiological Effects ... Caffeine is a well known psychostimulant,and it is widely used as an analgesics. Thus, the investigators aimed to prove the ...
https://clinicaltrials.gov/ct2/show/NCT00879775

*  Time Release Caffeine Capsules | ThinkGeek

Why? Because inside you, 200mg of caffeine will be released in small doses throughout the day - keeping you alert and awake and ...
https://thinkgeek.com/product/bed8/images/3909/

*  04 March 2013 - Higher caffeine intake may prolong pregnancy, study finds - Features - My Sinchew

Another study published last year in the Journal of Caffeine Research likewise found that mothers who drink caffeine and ... Consumption of caffeine from all sources was also found to lengthen pregnancy terms by a rate of five hours per 100 mg of ... According to new research published in BioMed Central's open access journal BMC Medicine, for every 100 mg of caffeine consumed ... Meanwhile, the World Health Organization's daily recommended caffeine intake for pregnant women is 300 mg a day. The average ...
mysinchew.com/node/83179?tid=163

*  Is the key to disease the stomach? | Debate.org

Eating better and abstaining from alcohol and caffeine can do our health a world of good. ...
debate.org/opinions/is-the-key-to-disease-the-stomach

*  Nutrend Carnitin Activity Drink + Caffeine 750 ml | SportObchod.cz

NUTREND CARNITINE ACTIVITY DRINK with caffeine je osv uj c hotov n poj bez cukru s obsahem L-karnitinu (1000 mg) a s p davkem ... Sportobchod.cz Sportovn v iva Hubnut Nutrend Carnitin Activity Drink + Caffeine 750 ml Zp t do kategorie Hubnut ... CARNITINE ACTIVITY DRINK with caffeine efektivn pom h s d le itou hydratac organismu b hem z t e. D ky lehk a osv uj c chuti v ... Nutrend Carnitin Activity Drink + Caffeine 750 mlPopis. d Pr m rn hodnocen 100.00 % 100% ...
https://sportobchod.cz/nutrend-carnitin-activity-drink-caffeine-750-ml.htm

*  Caffeine and your body;

The U.S. Food and Drug Administration is investigating deaths linked to popular caffeine drinks. These highly caffeinated ... The U.S. Food and Drug Administration is investigating deaths linked to popular caffeine drinks. These highly caffeinated ... beverages are the fastest-growing type of soft drink in the U.S. What follows is a look at how caffeine gives your body an ... beverages are the fastest-growing type of soft drink in the U.S. What follows is a look at how caffeine gives your body an ...
bendbulletin.com/csp/mediapool/sites/BendBulletin/News/story.csp?cid=1561845&fid=151

*  Pregnancy Safety and Risk Factors - Age, Caffeine, Drugs, and Alcohol

Risk factors such as age, caffeine consumption, and the use of drugs and alcohol during pregnancy and while breastfeeding. ...
https://everydayfamily.com/pregnancy-safety-and-risk-factors/

*  Is caffeine good for you? | Reference.com

For adults in good health, up to 400 milligrams of caffeine per day is... ... A moderate amount of caffeine may help a person feel more alert and awake, but excessive consumption does present health risks ... Caffeine consumption in excess of 400 milligrams per day can lead to several undesirable side effects, warns Mayo Clinic, ... Caffeine is not recommended for kids, and adolescents should limit consumption to a maximum of 100 milligrams a day. ...
https://reference.com/health/caffeine-good-d536db7ef309cfc8

*  Caffeine

But how much do you know about caffeine and its side effects? ... Caffeine has probably helped you through long nights of ...
kidshealth.org/Renown/en/teens/caffeine.html?view=rr

*  Caffeine Confusion

Should kids have caffeine? And what is it exactly? Find out in this article for kids. ... So what is caffeine, anyway?. Caffeine Is a Common Chemical. Caffeine (say: KA-feen) is a natural chemical found in tea leaves ... You also may notice that caffeine makes you feel hyper. Caffeine can boost a person's energy temporarily, but a lot of caffeine ... Do You Need Caffeine?. Caffeine isn't a nutrient, like calcium, so you don't need a certain amount to be healthy. The United ...
kidshealth.org/en/kids/caffeine.html?WT.ac=k-ra

*  Caffeine Confusion

Should kids have caffeine? And what is it exactly? Find out in this article for kids. ... Caffeine Confusion. Resources. Please Note: By clicking a link to any resource listed on this page, you will be leaving this ...
kidshealth.org/Renown/en/kids/caffeine.html?view=rr

*  caffeine : NPR

Caffeine Gives Athletes An Edge, But Don't Overdo It. August 1, 2014 Studies show the caffeine in just a few cups of coffee ... Why Caffeine In Coffee Is A Miracle Drug For The Tired. April 26, 2013 Historians tell us that caffeine in coffee helped ... Wrigley says its new Alert Energy Caffeine Gum gives consumers the power to control how much caffeine they get. Wrigley ... But when it comes to caffeine intake, teenagers seem to be getting far more caffeine from coffee drinks. Overall, about three- ...
npr.org/tags/137113336/caffeine/archive?start=placeholder

*  Caffeine addiction

... * 1. Caffeine Addiction By: Brianna Capone * 2. What is Caffeine?  Caffeine is a bitter substance which ... 3. Is Caffeine Addictive?  Caffeine is a stimulant of the central nervous system  Regular use/consumption does cause mild ... 5. Negative Effects of CaffeineCaffeine effects individuals differently and can sometimes cause problems such as ... Conclusions  Overall, caffeine can lead to a mild form of physical dependence but when consumed in moderation it tends to ...
https://slideshare.net/bcapone522/caffeine-addiction

*  Sprayable Caffeine : NPR

Sprayable Caffeine
npr.org/tags/221367255/sprayable-caffeine/archive?date=8-31-2004

CaffeineBeta-Phenylmethamphetamine: β-Phenylmethamphetamine (N,α-dimethyl-β-phenyl-phenethylamine) is a potent and long lasting stimulant drug.Pharmazie 1973;28(10):677.TheobromineWhite coffee: White coffee can refer to any of a number of different kinds of coffees or coffee substitutes worldwide.Calcium signaling: Calcium ions are important for cellular signalling, as once they enter the cytosol of the cytoplasm they exert allosteric regulatory effects on many enzymes and proteins. Calcium can act in signal transduction resulting from activation of ion channels or as a second messenger caused by indirect signal transduction pathways such as G protein-coupled receptors.ProcainePhosphodiesterase inhibitor: A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), thereby preventing the inactivation of the intracellular second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) by the respective PDE subtype(s).Sarcalumenin: Sarcalumenin is a protein that in humans is encoded by the SAR gene.Ryanodine receptor: Ryanodine receptors (RyRs) form a class of intracellular calcium channels in various forms of excitable animal tissue like muscles and neurons. There are three major isoforms of the ryanodine receptor, which are found in different tissues and participate in different signaling pathways involving calcium release from intracellular organelles.Sports drink: Sports drinks are beverages whose stated purpose is to help athletes replace water, electrolytes, and energy after training or competition, though their efficacy for that purpose has been questioned, particularly after exercise which is only moderate.PreladenantMuscle contraction: Muscle contraction is the activation of tension-generating sites within muscle fibers. In physiology, muscle contraction does not mean muscle shortening because muscle tension can be produced without changes in muscle length such as holding a heavy book or a dumbbell at the same position.EphedrineMalignant hyperthermiaConcentration effect: In the study of inhaled anesthetics, the concentration effect is the increase in the rate that the Fa(alveolar concentration)/Fi(inspired concentration) ratio rises as the alveolar concentration of that gas is increased. In simple terms, the higher the concentration of gas administered, the faster the alveolar concentration of that gas approaches the inspired concentration.Drug interaction: A drug interaction is a situation in which a substance (usually another drug) affects the activity of a drug when both are administered together. This action can be synergistic (when the drug's effect is increased) or antagonistic (when the drug's effect is decreased) or a new effect can be produced that neither produces on its own.

(1/3667) Ca-releasing action of beta, gamma-methylene adenosine triphosphate on fragmented sarcoplasmic reticulum.

beta,gamma-Methylene adenosine triphosphate (AMPOPCP) has two effects on fragmented sarcoplasmic reticulum (FSR), i.e., inhibition of the rate of Ca uptake and the induction of Ca release from FSR filled with Ca. The Ca release brought about by AMPOPCP has many features in common with the mechanism of Ca-induced Ca release: i) it is inhibited by 10 mM procaine; ii) the amount of Ca release increases with increase in the extent of saturation of FSR with Ca; iii) increase of the Ca concentration in the extent of saturation of FSR with Ca; iii) increase of the Ca concentration in the medium facilitates the release of Ca. However, no facilitation of Ca release upon decrease of Mg concentration in the medium is observable. AMPOPCP and caffeine potentiate each other remarkably in their Ca-releasing action, irrespective of the kind of substrate. From the mode of action of AMPOPCP on the rate of Ca uptake, the amount of phosphorylated intermediate (EP), and the effect on Sr release, it is suggested that the state of the FSR-ATP complex is crucial for Ca-induced Ca release.  (+info)

(2/3667) Drug-protein binding and blood-brain barrier permeability.

The permeability surface area (PS) product, an index of permeability of the blood-brain barrier (BBB), was measured by using the in situ perfusion method. In the cerebral circulation, the fraction of drug that permeates into the brain through the BBB is not only the unbound fraction but also the fraction dissociated from the protein in the perfusate. The sum of these two fractions, the apparent exchangeable fraction, was estimated by fitting the parameters of the BBB permeability under the condition of varying BSA concentrations in the perfusate. The unbound fraction of drugs in a buffer containing 0.5 mM BSA was measured by using the ultrafiltration method in vitro, and the apparent exchangeable fraction was measured in vivo by using the intracarotid artery injection method. The apparent exchange fraction was 100% for S-8510, 96.5% for diazepam, 90.9% for caffeine, 38.3% for S-312-d, 33.1% for propranolol, and 6.68% for (+)-S-145 Na, and each of these was higher than the corresponding unbound fraction in vitro in all drugs. The apparent exchangeable fractions, for example, were 8 times higher for diazepam and 38 times for S-312-d than the unbound fractions in vitro. The apparent exchangeable fraction of drugs was also estimated from the parameters obtained with the perfusion method. Because drugs can be infused for an arbitrary length of time in the perfusion method, substances with low permeability can be measured. The apparent exchangeable fractions obtained with this method were almost the same as those obtained with the intracarotid artery injection method.  (+info)

(3/3667) Acquisition of nicotine discrimination and discriminative stimulus effects of nicotine in rats chronically exposed to caffeine.

Caffeine and nicotine are the main psychoactive ingredients of coffee and tobacco, with a high frequency of concurrent use in humans. This study examined the effects of chronic caffeine exposure on 1) rates of acquisition of a nicotine discrimination (0.1 or 0.4 mg/kg, s.c., training doses) and 2) the pharmacological characteristics of the established nicotine discrimination in male Sprague-Dawley rats. Once rats learned to lever-press reliably under a fixed ratio of 10 schedule for food pellets, they were randomly divided into two groups; 12 animals were maintained continuously on caffeine added to the drinking water (3 mg/ml) and another 12 control rats continued to drink tap water. In each group of water- and caffeine-drinking rats, there were six rats trained to discriminate 0.1 mg/kg of nicotine from saline and six rats trained to discriminate 0.4 mg/kg of nicotine from saline. Regardless of the training dose of nicotine, both water- and caffeine-drinking groups required a comparable number of training sessions to attain reliable stimulus control, although there was a trend for a slower acquisition in the caffeine-drinking group trained with 0.1 mg/kg of nicotine. Tests for generalization to different doses of nicotine revealed no significant differences in potency of nicotine between water- and caffeine-drinking groups. The nicotinic-receptor antagonist mecamylamine blocked the discriminative effects of 0.1 and 0.4 mg/kg nicotine with comparable potency and efficacy in water- and caffeine-drinking groups. There was a dose-related generalization to both the 0.1 and 0.4 mg/kg nicotine cue (maximum average of 51-83%) in water-drinking rats after i.p. treatment with d-amphetamine, cocaine, the selective dopamine uptake inhibitor GBR-12909, apomorphine, and the selective dopamine D1 receptor agonist SKF-82958, but not in caffeine-drinking rats (0-22%). There was no generalization to the nicotine cues after i.p. treatment with caffeine or the selective D2 (NPA) and D3 (PD 128,907) dopamine-receptor agonists in water- and caffeine-drinking rats. The dopamine-release inhibitor CGS 10746B reduced the discriminative effects of 0.4 mg/kg nicotine in water-drinking rats, but not in caffeine-drinking rats. There was no evidence of development of tolerance or sensitization to nicotine's effects throughout the study. In conclusion, chronic caffeine exposure (average, 135 mg/kg/day) did not affect the rate of acquisition of the nicotine discrimination, but it did reduce the dopaminergic component of the nicotine-discriminative cue. The reduction of the dopaminergic component of the nicotine cue was permanent, as this effect was still evident after the caffeine solution was replaced with water in caffeine-drinking rats. That nicotine could reliably serve as a discriminative stimulus in the absence of the dopaminergic component of its discriminative cue may differentiate nicotine from "classical dopaminergic" drugs of abuse such as cocaine and amphetamine.  (+info)

(4/3667) Caffeine can override the S-M checkpoint in fission yeast.

The replication checkpoint (or 'S-M checkpoint') control prevents progression into mitosis when DNA replication is incomplete. Caffeine has been known for some time to have the capacity to override the S-M checkpoint in animal cells. We show here that caffeine also disrupts the S-M checkpoint in the fission yeast Schizosaccharomyces pombe. By contrast, no comparable effects of caffeine on the S. pombe DNA damage checkpoint were seen. S. pombe cells arrested in early S phase and then exposed to caffeine lost viability rapidly as they attempted to enter mitosis, which was accompanied by tyrosine dephosphorylation of Cdc2. Despite this, the caffeine-induced loss of viability was not blocked in a temperature-sensitive cdc2 mutant incubated at the restrictive temperature, although catastrophic mitosis was prevented under these conditions. This suggests that, in addition to S-M checkpoint control, a caffeine-sensitive function may be important for maintenance of cell viability during S phase arrest. The lethality of a combination of caffeine with the DNA replication inhibitor hydroxyurea was suppressed by overexpression of Cds1 or Chk1, protein kinases previously implicated in S-M checkpoint control and recovery from S phase arrest. In addition, the same combination of drugs was specifically tolerated in cells overexpressing either of two novel S. pombe genes isolated in a cDNA library screen. These findings should allow further molecular investigation of the regulation of S phase arrest, and may provide a useful system with which to identify novel drugs that specifically abrogate the checkpoint control.  (+info)

(5/3667) Mutation screening of the RYR1 gene and identification of two novel mutations in Italian malignant hyperthermia families.

Point mutations in the ryanodine receptor (RYR1) gene are associated with malignant hyperthermia, an autosomal dominant disorder triggered in susceptible people (MHS) by volatile anaesthetics and depolarising skeletal muscle relaxants. To date, 17 missense point mutations have been identified in the human RYR1 gene by screening of the cDNA obtained from muscle biopsies. Here we report single strand conformation polymorphism (SSCP) screening for nine of the most frequent RYR1 mutations using genomic DNA isolated from MHS patients. In addition, the Argl63Cys mutation was analysed by restriction enzyme digestion. We analysed 57 unrelated patients and detected seven of the known RYR1 point mutations. Furthermore, we found a new mutation, Arg2454His, segregating with the MHS phenotype in a large pedigree and a novel amino acid substitution at position 2436 in another patient, indicating a 15.8% frequency of these mutations in Italian patients. A new polymorphic site in intron 16 that causes the substitution of a G at position -7 with a C residue was identified.  (+info)

(6/3667) Infrared dichroism of the DNA-caffeine complex. A new method for determination of the ligand orientation.

Infrared linear dichroism (LD) measurements on films of the DNA-caffeine complex in terms of the relative humidity (r.h.) show two main effects. Firstly, there is an insertion of caffeine molecules into the DNA double helix (B form), as evidenced by a very strong parallel LD behaviour of the 745 cm-1 band due to the C-H out-of-plane deformation vibration of caffeine. Furthermore, a high r.h. values a modified B form occurs in the complex similar to the B form recently reported by BRAHMS and coworkers for DNA-polypeptide complexes. The reversible B-A transition of the DNA in dependence of the r.h. is not affected in general in the presence of caffeine.  (+info)

(7/3667) The sarcoplasmic reticulum and the Na+/Ca2+ exchanger both contribute to the Ca2+ transient of failing human ventricular myocytes.

Our objective was to determine the respective roles of the sarcoplasmic reticulum (SR) and the Na+/Ca2+ exchanger in the small, slowly decaying Ca2+ transients of failing human ventricular myocytes. Left ventricular myocytes were isolated from explanted hearts of patients with severe heart failure (n=18). Cytosolic Ca2+, contraction, and action potentials were measured by using indo-1, edge detection, and patch pipettes, respectively. Selective inhibitors of SR Ca2+ transport (thapsigargin) and reverse-mode Na+/Ca2+ exchange activity (No. 7943, Kanebo Ltd) were used to define the respective contribution of these processes to the Ca2+ transient. Ca2+ transients and contractions induced by action potentials (AP transients) at 0.5 Hz exhibited phasic and tonic components. The duration of the tonic component was determined by the action potential duration. Ca2+ transients induced by caffeine (Caf transients) exhibited only a phasic component with a rapid rate of decay that was dependent on extracellular Na+. The SR Ca2+-ATPase inhibitor thapsigargin abolished the phasic component of the AP Ca2+ transient and of the Caf transient but had no significant effect on the tonic component of the AP transient. The Na+/Ca2+ exchange inhibitor No. 7943 eliminated the tonic component of the AP transient and reduced the magnitude of the phasic component. In failing human myocytes, Ca2+ transients and contractions exhibit an SR-related, phasic component and a slow, reverse-mode Na+/Ca2+ exchange-related tonic component. These findings suggest that Ca2+ influx via reverse-mode Na+/Ca2+ exchange during the action potential may contribute to the slow decay of the Ca2+ transient in failing human myocytes.  (+info)

(8/3667) Effects of impaired Ca2+ homeostasis on contraction in postinfarction myocytes.

The significance of altered Ca2+ influx and efflux pathways on contractile abnormalities of myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) was investigated by varying extracellular Ca2+ concentration ([Ca2+]o, 0.6-5.0 mM) and pacing frequency (0.1-5.0 Hz). Myocytes isolated from 3-wk MI hearts were significantly longer than those from sham-treated (Sham) hearts (125 +/- 1 vs. 114 +/- 1 micrometer, P < 0.0001). At high [Ca2+]o and low pacing frequency, conditions that preferentially favored Ca2+ influx over efflux, Sham myocytes shortened to a greater extent than 3-wk MI myocytes. Conversely, under conditions that favored Ca2+ efflux (low [Ca2+]o and high pacing frequency), MI myocytes shortened more than Sham myocytes. At intermediate [Ca2+]o and pacing frequencies, differences in steady-state contraction amplitudes between Sham and MI myocytes were no longer significant. Collectively, the interpretation of these data was that Ca2+ influx and efflux pathways were subnormal in MI myocytes and that they contributed to abnormal cellular contractile behavior. Because Na+/Ca2+ exchange activity, but not whole cell Ca2+ current, was depressed in 3-wk MI rat myocytes, our results on steady-state contraction are consistent with, but not proof of, the hypothesis that depressed Na+/Ca2+ exchange accounted for abnormal contractility in MI myocytes. The effects of depressed Na+/Ca2+ exchange on MI myocyte mechanical activity were further evaluated in relaxation from caffeine-induced contractures. Because Ca2+ uptake by sarcoplasmic reticulum was inhibited by caffeine and with the assumption that intracellular Na+ and membrane potential were similar between Sham and MI myocytes, myocyte relaxation from caffeine-induced contracture can be taken as an estimate of Ca2+ extrusion by Na+/Ca2+ exchange. In MI myocytes, in which Na+/Ca2+ exchange activity was depressed, the half time of relaxation (1.54 +/- 0.14 s) was significantly (P < 0.02) prolonged compared with that measured in Sham myocytes (1.10 +/- 0.10 s).  (+info)



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  • But these kinds of studies are great to have on hand, so that when DNA is well understood and cheaply examined we can find the factors that make caffeine good and bad for a person. (slashdot.org)