Combined Effects Of Caffeine Research Articles

Isolated but not combined ergogenic effects of caffeine and L-arginine during an isokinetic knee extension.

The use of single supplements as ergogenic aids to enhance performance in strength-oriented sports is widespread among athletes (74%). The aim of this study was to increase knowledge about the combined effects of caffeine and L-arginine dietary supplements on performance. In this double-blind, randomized and counterbalanced crossover study, 29 participants (age: 23.2 ± 3.6 yr.; height: 181.0 ± 7.6 cm; weight: 77.0 ± 8.8 kg) each underwent six trials. In each trial performance tests were conducted to examine the effects of the supplement combinations on maximum (NmMax) and averaged torque (NmM), maximum (JMax) and averaged work (JM), the blockwise mean values of torque and work, and rate of perceived exertion (RPE) during an isokinetic leg extension task (90°·s-1) with the right leg for two sets of 40 repetitions and a set rest of 3 min on a dynamometer. The first and second trials were used to familiarize the participants with the movements in the dynamometer and no supplements were taken. After this 2-week pre-test trial, the supplement combinations of placebo/placebo, caffeine/placebo (5 mg·kg-1), L-arginine/placebo (0.15 g·kg-1), and caffeine/L-arginine (5 mg·kg-1 + 0.15 g·kg-1) were ingested. The main finding of this study is the absence of an ergogenic effect of the combined supplements caffeine and L-arginine during voluntary maximal isokinetic leg extensions, although an increase of 3.5% was noted for Nmmax compared to the placebo trial. However, the administration of caffeine was able to increase the NmMax of the quadriceps femoris muscle about 5.1% (p = 0.043). In addition, caffeine (4.2%, p = 0.026) and also L-arginine (4.2%, p = 0.040) significantly increased NmM over a complete set. No single or combined supplement had an effect on muscle fatigue looking at the blockwise mean values of torque and work or RPE (all p > 0.05). The combination of caffeine and L-arginine was not superior to the isolated intake of both supplements in a strength-based exercise and a synergistic effect was absent.

Ergogenic effects of the combination of caffeine and New Zealand blackcurrant supplements on time trial

The use of single supplements to enhance performance is widespread among athletes. The aim of this study was to increase knowledge about the combined effects of caffeine and New Zealand blackcurrant (NZBC) dietary supplements. In this counterbalanced alternating treatment single-case design, two participants each underwent four phases of four sessions in a double-blind, randomized order. After a 3-week pre-test phase, the supplement combinations of placebo/placebo, caffeine/placebo (5 mg/kg), NZBC/placebo (600 mg), and caffeine/NZBC (5 mg/kg + 600 mg) were taken and weekly performance tests were conducted to examine their effects on relative power (W/kg) during a 20-minute time trial on a bicycle. Data were analyzed descriptively and using the Tau-U calculator from Single Case Research. The ergogenic effect of caffeine was confirmed in both participants, with increases of 3.3% and 6.5%, while the positive effect of NZBC on performance was only seen in one participant (13.4%). The combination of caffeine and NZBC again increased performance in both participants (2.2% and 19.2%), but the data only showed a near additive effect of the supplements in one participant. The participants did not show a consistent performance improvement with the combined intake of the supplements caffeine and NZBC. Further studies are required to confirm or refute this evidence of the synergistic effects of these supplements.

A combined effect of fish-originated collagen peptides and caffeine on the cognitive function of sleep-deprived mice.

Refreshing beverages, consumed worldwide, commonly take advantage of caffeine's impacts on attention and motor performance. However, excessive long-term caffeine intake might disturb sleep/wake rhythms and exacerbate daily anxiety. Fish-originated collagen peptides (FCP) are of high nutrient value with stimulating, calming or relaxing effects, which could reduce the excitotoxicity of caffeine. This study aims to investigate two facets: (1) the combined effect of caffeine and FCP (namely C&F) on the cognitive function of sleep-deprived mice by different administration strategies with dose dependence (low and high dose) or time dependence (intervention in a day and prevention for a week); (2) the potential "microbiota-gut-brain" mechanism by which C&F improves sleep deprivation (SD)-induced cognitive impairments. Here, C57BL/6 mice were administered caffeine (10 or 20 mg per kg per bw) combined with FCP (100 or 200 mg per kg per bw) and were then subjected to 48 h SD. The open-field and Morris water maze tests were performed to evaluate the cognitive function and spatial learning capacities of mice. Our results indicated that the cognitive impairments of SD mice were significantly relieved to a different degree by treating C&F in a dose- and time-dependent manner. The pathological observation of the hippocampus indicated both intervention (time of a day) and prevention (time of a week) of the C&F protected brain tissue from SD-induced injuries. The accumulated pro-inflammatory neurometabolites and factors were significantly inhibited by C&F via the hypothalamus-hippocampal circuit. Furthermore, 16S rDNA analysis of colonic contents showed that the level of Lactobacillus murinus was significantly upregulated and that of Clostridia_UCG-014 was suppressed in the C&F group. The receiver operating characteristic (ROC) curve of Lactobacillus murinus indicated a certain diagnostic utility to distinguish C&F intervention (AUC = 0.52) or prevention (AUC = 0.68). Pathways of ko04622 (immune system) and ko00472 (metabolism processes) were significantly regulated by C&F in a time-dependent manner. Based on PICRUSt2 algorithm analysis, C&F might potentially regulate gut microbial functions through several metabolic pathways, including the RIG-I-like receptor signaling pathway and limonene and pinene degradation. In conclusion, C&F plays a key role in brain function and behavior, which could synergistically relieve cognitive impairments via the microbiota-gut-brain axis.

Single and combined effects of caffeine and salicylic acid on mussel Mytilus galloprovincialis: Changes at histomorphological, molecular and biochemical levels

Caffeine (CAF) and salicylic acid (SA) are frequently detected in waterbody, though information on their biological impact is poor. This work assesses the effects of CAF (5 ng/L to 10 µg/L) and SA (0.05 µg/L to 100 µg/L) alone and combined as CAF+SA (5 ng/L+0.05 µg/L to 10 µg/L+100 µg/L) on mussel Mytilus galloprovincialis under 12-days exposure by histomorphology of digestive gland and oxidative stress defense at molecular and biochemical levels. Besides evaluating tissue accumulation, absence of histomorphological damage and haemocyte infiltration highlighted activation of defensive mechanisms. Up-regulation of Cu/Zn-sod, Mn-sod, cat and gst combined with increased catalase and glutathione S-transferase activity were found in CAF-exposed mussels, while SA reduced ROS production and mitochondrial activity. CAF+SA exposure induced differential responses, and the integrated biomarker response (IBR) revealed more pronounced effects of SA than CAF. These results enlarge knowledge on pharmaceuticals impact on non-target organisms, emphasizing the need for proper environmental risk assessment.

Anxiety-like behavior and whole-body cortisol responses to components of energy drinks in zebrafish (Danio rerio).

The current study investigated the independent and combined effects of caffeine and taurine on anxiety-like behavior and neuroendocrine responses in adult zebrafish (Danio rerio). Caffeine (1,3,7-trimethylpurine-2,6-dione), the world’s most commonly used psychoactive drug, acts as an adenosine receptor blocker and a mild central nervous system stimulant. However, excessive use of caffeine is associated with heightened anxiety levels. Taurine (2-aminoethanesulfonic acid), a semi-essential amino acid synthesized within the human brain, has been hypothesized to play a role in regulating anxiolytic behavior. Caffeine and taurine are two common additives in energy drinks and are often found in high concentrations in these beverages. However, few studies have investigated the interaction of these two chemicals with regards to anxiety measures. A suitable vertebrate to examine anxiety-like behavior and physiological stress responses is the zebrafish, which has shown promise due to substantial physiological and genetic homology with humans. Anxiety-like behavior in zebrafish can be determined by analyzing habituation to novelty when fish are placed into a novel tank and scototaxis (light avoidance) behavior in the light-dark test. Stress-related neuroendocrine responses can be measured in zebrafish by analyzing whole-body cortisol levels. The goal of this study was to determine if exposure to caffeine, taurine, or a combination of the two compounds altered anxiety-like behavior and whole-body cortisol levels in zebrafish relative to control. Zebrafish were individually exposed to either caffeine (100 mg/L), taurine (400 mg/L), or both for 15 min. Zebrafish in the control group were handled in the same manner but were only exposed to system tank water. After treatment, fish were transferred to the novel tank test or the light-dark test. Behavior was tracked for the first 6 min in the novel tank and 15 min in the light-tark test. Fifteen min after introduction to the behavioral task, fish were euthanized for the analysis of whole-body cortisol levels. The results demonstrate that caffeine treatment decreased the amount of exploration in the top of the novel tank and increased scototaxis behavior in the light-dark test, which supports the established anxiogenic effect of acute exposure to caffeine. Taurine alone did not alter basal levels of anxiety-like behavioral responses nor ameliorated the anxiogenic effects of caffeine on behavior when the two compounds were administered concurrently. None of the drug treatments altered basal levels of whole-body cortisol. The current results of this study suggest that, at least at this dose and time of exposure, taurine does not mitigate the anxiety-producing effects of caffeine when administered in combination, such as with energy drink consumption.

No individual or combined effects of caffeine and beetroot-juice supplementation during submaximal or maximal running.

Dietary supplements such as caffeine and beetroot juice are used by athletes in an attempt to optimize performance and therefore gain an advantage in competition. The aim of this study was to investigate the individual and combined effects of caffeine and beetroot-juice supplementation during submaximal and maximal treadmill running. Seven males (maximal oxygen uptake: 59.0 ± 2.9 mL·kg-1·min-1) and 2 females (maximal oxygen uptake: 53.1 ± 11.4 mL·kg-1·min-1) performed a preliminary trial followed by 4 experimental test sessions. Each test session consisted of two 5-min submaximal running bouts (at ∼70% and 80% of maximal oxygen uptake) and a maximal 1-km time trial (TT) in a laboratory. Participants ingested 70 mL of concentrated beetroot juice containing either 7.3 mmol of nitrate (BR) or no nitrate (PBR) 2.5 h prior to each test session, then either caffeine (C) at 4.8 ± 0.4 (4.3-5.6) mg/kg of body mass or a caffeine placebo (PC) 45 min before each test session. The 4 test sessions (BR-C, BR-PC, PBR-C, and PBR-PC) were presented in a counterbalanced and double-blind manner. No significant differences were identified between the 4 interventions regarding relative oxygen uptake, running economy, respiratory exchange ratio, heart rate (HR), or rating of perceived exertion (RPE) at the 2 submaximal intensities (P > 0.05). Moreover, there were no significant differences in performance, maximum HR, peak blood lactate concentration, or RPE during the maximal TT when comparing the interventions (P > 0.05). In conclusion, no beneficial effects of supplementing with typical doses of caffeine, beetroot juice, or a combination of the two were observed for physiological, perceptual, or performance responses during submaximal or maximal treadmill running exercise.

Mutations rate in different lines of drosophila melanogaster after the treatment with caffeine and He-Ne laser radiation

The frequency of dominant lethal mutations (DLM) after combined effect of caffeine (1,3,7-trimethylxan- thine) and helium-neon laser radiation in Drosophila has been studied. Caffeine is a natural substance which is presented in many drinks, widely applied in medicine and reveals moderately toxic action and some mutagen- icity/genotoxicity effects; red laser radiation is applied in medicine and can disrupt the processes of DNA and RNA biosynthesis. The aim of this work was to study the characteristics of the mutation process in Drosophila melanogaster under the influence of caffeine and red laser radiation, depending on the genotype. We used wild type Drosophila melanogaster stocks Canton-S (C-S) and Oregon (Or), carrying an ebony mutation, respectively: ebonyC-S and ebonyOr; and mutant stock ebony. Control flies were grown in standard conditions, and in experiments with caffeine it was added in culture medium in concentration 0.5 mg/ml. Vir- gin flies were exposed to a helium-neon laser light (wavelength of 632,8 nm) with a surface power density of 0.03 mW/cm2, the exposure time was 5 minutes. The influence of caffeine causes an increase in the frequency of early DLM on 40 % in mutant line ebony, and on 70.5 % in the line ebonyC-S. Irradiation by light of helium-neon laser either reduces the incidence DLM, or has no effect in all lines used in this work. The simultaneous effect of two external factors induces diverse answers in different genotypes: it increases early DLM in line C-S and early and late DLM in line ebony; but has no effect in lines ebonyOr and ebonyC-S. The two-way analysis ANOVA F-test showed that the DLM frequency dependence impact of external factors is characterized by F= 3.87; of genotype F= 5.14; of the combined effects of genotype and external factors F = 5.69. The power of influence of external factors — 8.1 %; of genotype 6.9 %; and of the combined effects of the genotype and two external factors studied — 31.4 %. Conclusions. Irradiation with laser light had no mutagenic effect on Drosophila, and even revealed anti- mutagenic effect. Caffeine induced the DLM increase, but the combined caffeine and laser light impact increased DLM rate in line ebony and not influenced it in lines: ebonyOr and ebonyC-S.

Placebo effects of caffeine on maximal voluntary concentric force of the knee flexors and extensors.

We examined the placebo effect of caffeine and the combined effect of caffeine and caffeine expectancy on maximal voluntary strength. Fourteen men completed 4 randomized, single-blind experimental trials: (1) told caffeine, given caffeine (5 mg/kg) (CC); (2) told caffeine, given placebo (CP); (3) told placebo, given placebo (PP); and (4) told placebo, given caffeine (PC). Maximal voluntary concentric force and fatigue resistance of the knee flexors and extensors were measured using isokinetic dynamometry. A significant and equal improvement in peak concentric force was found in the CC and PC trials. Despite participants believing caffeine would evoke a performance benefit, there was no effect of CP. Caffeine caused an improvement in some aspects of muscle strength, but there was no additional effect of expectancy. Performance was poorer in participants who believed caffeine would have the greatest benefit, which highlights a link between expected ergogenicity, motivation, and personality characteristics. Muscle Nerve 54: 479-486, 2016.

Separate and Combined Effects of Caffeine and Sodium-Bicarbonate Intake on Judo Performance.

The combined supplementation of caffeine (CAF) and sodium bicarbonate (NaHCO3) may have a potential ergogenic effect during intermittent-exercise tasks such as judo; however, its effect in this sport has not been tested. To investigate the isolated and combined effects of CAF and NaHCO3 on judo performance. Ten judokas performed 4 supplementation protocols-NaHCO3, CAF, NaHCO3 + CAF, and placebo (PLA) (cellulose)-followed by 3 Special Judo Fitness Tests (SJFTs) interspaced with 5 min rest. In the first SJFT, the combined supplement (NaHCO3 + CAF) resulted in a higher number of throws than with PLA (24.4 ± 0.9 and 23.2 ± 1.5 throws, respectively, P = .02). There was no significant difference between conditions for the 2nd SJFT (P = .11). In the 3rd SJFT, NaHCO3 and NaHCO3 + CAF resulted in more throws than with PLA (23.7 ± 1.6, 24.4 ± 1.0, and 22.0 ± 1.6 throws, P = .001 and P = .03, respectively). When the total throws performed in the 3 SJFTs were summed, they were higher than PLA only for NaHCO3 + CAF (68.8 ± 4.4 and 72.7 ± 3.1 throws, respectively, P = .003). Postexercise plasma lactate after each SJFT was higher in all experimental conditions than with PLA (P = .001). There was no significant difference in rating of perceived exertion across the conditions (P = .18). The results of the current study show that the combined supplementation of NaHCO3 + CAF increases judo performance compared with PLA.

Acute effects of consumption of energy drink on intraocular pressure and blood pressure-pilot study

Context: Energy drinks are popular caffeinated beverages believed to improve cognitive function and concentration. They contain two main ingredients taurine and caffeine, which have both been reported to have effects on blood pressure (BP) and intraocular pressure (IOP). Aim: The aim of this study is to investigate the acute effects of consumption of energy drinks on IOP and BP of healthy black young subjects. Materials and Methods: A total of 50 undergraduates from the University of Benin, Nigeria, aged 18-30 years (mean 24.43 ± 1.54) were randomly selected to participate in this study. The subjects were of either gender and were divided into experimental and control groups of 25 subjects each. The subjects were told to abstain from caffeine for 48 h prior to and during the study. Baseline IOP and BP were measured. The experimental group consumed one can of Red Bull (containing 85 mg of caffeine in 250 ml) and measurements were repeated at 30, 60 and 90 min while the control group drank 250 ml of water and were tested over the same period of time. Results: When compared to baseline, a significant decrease in mean IOP was observed at 30, 60 and 90 min ( P P > 0.05). Conclusion: Results suggest that energy drinks produce a significant reduction in IOP, but have no effect on blood pressure. These findings may however reflect the combined effect of caffeine and taurine, as present in Red Bull.

Dopamine D1 Receptor-Mediated Intracellular Responses in the Hypothalamus after Co-Administration of Caffeine with MDMA

Markers of dopamine D(1) receptor activation were determined to elucidate intracellular mechanisms associated with the combined effects of caffeine and 3,4 methylenedioxymethamphetamine (MDMA), reported previously to produce increased toxicity, when compared with either drug alone. Caffeine (10 mg/kg) and MDMA (15 mg/kg) were administered to male Sprague Dawley rats alone and in combination. One hour after drug administration, core body temperature and phosphorylation of the dopamine D(1) -related intracellular markers, cAMP response element binding protein (CREB), the dopamine and c-AMP-regulated phosphoprotein of 32 kDa (DARPP-32) and expression of the immediate early gene and cellular activation marker c-fos were determined in the hypothalamus. Co-administration of caffeine with MDMA increased core body temperature when compared with MDMA or caffeine treatment alone. Pre-treatment with the dopamine D(1) receptor antagonist SCH 23390 (1 mg/kg, i.p.), 30 min. prior to caffeine and MDMA administration, produced a hypothermic response to MDMA that was unaffected by caffeine. Co-administration of caffeine with MDMA increased p-CREB, p-DARPP-32 and c-fos expression when compared with either treatment alone. Pre-treatment with SCH-23390 attenuated the changes in p-CREB, p-DARPP and c-fos. The results show an enhanced intracellular response when caffeine is combined with MDMA but not with either agent alone suggestive of synergistic intracellular actions convergent on a dopamine D(1) receptor signalling pathway. A dopamine-related synergy associated with the combined administration of caffeine and MDMA may have important use and safety implications for recreational drug users.

Study on combined effect of caffeine and analgerics

Study on combined effect of caffeine and analgerics

Advances in Swine In Vitro Embryo Production Technologies

Recent advances in new technologies to produce cloned and genetically modified pigs involve manipulating oocytes and/or embryos in vitro. Although a great deal of progress has been made, the current IVM-IVF systems still result in major problems: a high rate of polyspermy; and a low development rate and low quality of blastocysts for in vitro compared with the in vivo-produced embryos. This study summarizes recent advancements in IVM-IVF-IVC porcine systems. Recent methods to select monospermic embryos are also discussed. Finally, achievements in vitrification and in somatic cell nuclear transfer are discussed.

Separate and combined effects of caffeine and dbcAMP on olive baboon (Papio anubis) sperm

Improvement of baboon sperm capacitation is necessary for achieving high in vitro fertilization (IVF) rates in baboons. In this study, we evaluated separate and combined effects of caffeine and dbcAMP on baboon sperm capacitation. Sixteen male baboons (n = 16) were electroejaculated. Each sperm sample was divided into two aliquots: one for chemical activation and the other untreated control. Group 1: dbcAMP (n = 6); Group 2: caffeine (n = 6) and Group 3: combination of caffeine and dbcAMP (n = 4). In each aliquot, sperm motility after 30 minutes of incubation was evaluated as well as zona pellucida (ZP) binding ability after overnight incubation with 4-5 ZP from unfertilized human oocytes. Sperm motility and ZP binding ability in all chemically activated groups increased significantly as compared to their respective controls (P < 0.05). Combined and separate effects of caffeine and dbcAMP increases baboon sperm motility and ZP binding ability and may improve baboon IVF.

Combined effects of caffeine and malnutrition on the newborn rat’s myocardium

We hypothesized that the pathological effects on the neonatal rat heart could be aggravated by Cu deficiency due to the combined effects of caffeine exposure and malnutrition. Upon birth, pups were mixed and randomly picked; 8 pups were assigned to each dam and then divided into 4 groups. Group 1 dams received a normal diet containing 20% protein. Group 2 dams were fed 20% protein diet supplemented with caffeine (4 mg/100 g BW). Group 3 dams received 6% protein diet as a malnourished group, and group 4 dams received 6% protein diet supplemented with caffeine (4 mg/100 g BW). On postnatal day 10, dams and pups were killed. Group 2 tended to have a decrease in the Cu levels of dams’ plasma and milk and in pups’ plasma and heart tissue compared to those of group 1. This pattern was not observed consistently between groups 3 and 4. Transmission electron microscopy of group 2 pups’ hearts revealed a degree of disruption in the mitochondria compared to normal mitochondria seen in group 1. There was no consistent change in the mitochondria of group 4 compared to group 3. The caffeine level observed in all categories of group 4 (dams’ plasma and milk, pups’ plasma and heart tissue) was lower than those in group 2. Although malnutrition affected body weight and heart weight, combined effects of caffeine and malnutrition on Cu content in the neonatal heart was relatively minor compared to the well nourished group. This well nourished group showed that the effects of caffeine on Cu were more consistent, resulting the changes of mitochondria.

Operator Stress and Display Design

These design guidelines, based on knowledge of how operators perform under time and task pressure, can lead to better decision making in emergencies. IT IS NEAR THE END OF A LONG SHIFT, some hours past midnight, and the combined effects of caffeine, nicotine, and sugared snacks are no longer sufficient to sustain the alertness of tired and weary operators. Circadian rhythms are at their lowest ebb while oppressive, routine operations have so long persisted that chronic boredom reigns supreme. Suddenly a warning sounds, then another, then another — the systems displays are producing a cascade of flashing lights and tone alarms. Operators rush to workstations, where information begins to overflow like a virtual Niagara of bytes. The apprehension in the air is tangible. It is evident to everyone that a coherent response must be made soon if the situation is to be recovered. As a result, time pressure is now added to anxiety and information overload and rapidly shifts the situation from boredom to terror (Hancock, 1997a). The answers to the problem are somewhere in the system, but a massive noise-to-signal problem is building by the minute. Unfortunately, the resolution is spread across a tapestry of displays. Like pieces of a dynamic jigsaw puzzle, the solution resides in separate parts distributed across many minds, but team communication and team cohesion are rapidly failing, overwhelmed by the demands of information overload and the destructive effects of situational stress. If someone doesn't do something soon…

Combined effects of caffeine and alcohol on hemodynamics and coronary artery blood flow in dogs.

Alcohol intake is often followed by coffee drinking because of the universal acceptance of its sobering effect. Such effects were found inconsistent on motor functions. However, it is common belief that caffeine will antagonize the intoxicating effects of alcohol. The independent actions of caffeine and alcohol are well documented, but combined effects of short-term administration are unknown. This experimental work was designed to study the effects due to short-term administration of caffeine and alcohol on the cardiovascular system. In phase I, 30 experiments were performed in our laboratories to study the dose-response curves of both the drugs. In phases II and III, 15 dogs were subjected to 30 experiments. In phase II, caffeine, 5 mg/kg, was given i.v., followed by ethanol, 400 mg/kg i.v., and in phase III, sequence of drug administration was reversed to study the effects on hemodynamics and coronary artery blood flow. Caffeine did not show significant changes in all the cardiovascular parameters, and ethanol administration caused nonsignificant increase in heart rate, mean arterial pressure, left ventricular systolic pressure, and left ventricular (LV) mechanical work and decrease in the maximal rate of first derivative of LV pressure, stroke volume, and systemic vascular resistance. Left ventricular end-diastolic, pulmonary artery mean and right atrial pressures, pulmonary vascular resistance, myocardial oxygen consumption, and as coronary flow reserve increased as compared with controls. Combined caffeine and alcohol had synergistic effects, but when the order of drug administration was reversed (i.e., alcohol was followed by caffeine), the effect was antagonistic.

Combined effects of caffeine and sidnocarb on operative comparation of digital symbols in man

Neurotropic effects of caffeine and sidnocarb were studied on a model of fast operating activity of man involved in operative memorizing: reproduction and comparation of digital symbol flows. Subtherapeutic doses of caffeine (1 mg/kg) and sidnocarb (1 mg) alone were virtually ineffective, while their combination accelerated mental operations in the context of operative mnestic processes.

Combined effects of caffeine and nicotine on cardiovascular hemodynamics in canine model.

The independent effects of caffeine and nicotine on cardiodynamics are well documented, but combined effects of both are not reported. Initially, in phase I, 18 experiments were performed to study the dose-response curve of both the drugs. In phases II and III, 13 mongrel dogs were subjected to 30 experiments. In phase II, caffeine, 5 mg/kg, was given i.v. followed by nicotine, 50 micrograms/kg, and in phase III, the sequence of drug administration was reversed to study the effects on hemodynamics. In phase II, caffeine did not show significant changes in all the cardiovascular parameters, but nicotine administration after caffeine produced marked significant synergistic excitatory effects: the rate of increase of the first derivative of left ventricular pressure (dP/dt) increased from 1,101 +/- 111 to 3,194 +/- 872 (p < 0.003). In phase III, nicotine significantly increased heart rate, mean arterial pressures; left ventricular end-diastolic pressure (LVEDP); and pulmonary artery, pulmonary capillary wedge, and right atrial pressures. Nicotine increased dP/dt (964 +/- 182 to 1,639 +/- 60 mm Hg/s; p < 0.004). The excitatory effects of nicotine were attenuated by administration of caffeine (dP/dt, 918 +/- 140 reduced to 715 +/- 144 mm Hg/s; p < 0.04). Caffeine and nicotine, alone, caused nonsignificant and significant increases in hemodynamics, respectively. In combination, caffeine + nicotine administration produced significant synergistic excitatory effects in dogs. On the other hand, the nicotine + caffeine combination caused attenuation by caffeine of the excitatory effects produced by nicotine.

Combined effects of caffeine and alcohol during pregnancy on bones in newborn rats.

The combined effects of caffeine and alcohol on mineral contents of fetal mandibles and femurs were studied. Pregnant rats were divided into four groups: group 1, control; group 2, caffeine; group 3, alcohol; and group 4, caffeine-plus-alcohol. Alcohol (1.0 g ethanol/kg body weight) was intubated twice daily, beginning at day 9 of gestation. Caffeine (2 mg/100 g body weight) was given as a dietary supplement. Groups 1 and 2 were intubated with isocaloric sucrose solution. At birth, randomly selected pups were killed and the mandible and femur were removed and dried. Ca, P, Mg, Zn and hydroxyproline in these bones were measured. Notwithstanding the dams' intake of caffeine and alcohol administered separately, the present results suggest that the combination of caffeine and alcohol exhibited the most detrimental effects.