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PubMed2005

Analysis of environmental biomarkers in urine using an electrochemical detector.

Phenols are present in the environment and are prevalent in human populations, as environmental contaminants, dietary components, or their metabolites. Many are potential endocrine-altering agents. Currently available methods analyze single components or single families of chemicals as biomarkers of exposure. In order to assess multiple biologically relevant exposures to such substances, we evaluated the feasibility of determining several phenols simultaneously in urine, using an electrochemical detector (ECD) in combination with high performance liquid chromatography (LC). Based on reported analyses in the literature and the ECD response, we selected four xenobiotic residues, including three phytoestrogens (enterolactone, daidzein, and genistein) and bisphenolA [BPA]. These compounds had detection limits below 1 microg/L in urine using the cleanup procedure (glucuronidase hydrolysis and C18 column) and the urine volume (2 mL) we employed. As a pilot study to demonstrate the method's utility, we determined urinary enterolactone, daidzein, genistein and BPA in samples from nine children and 24 adults.

4-Butyrolactone↗
PubMed2003

Route-specific differences in distribution characteristics of octamethylcyclotetrasiloxane in rats: analysis using PBPK models.

Octamethylcyclotetrasiloxane (D(4)) is used in selected consumer products and has a potential for human exposure from multiple routes. Here we develop a physiologically based pharmacokinetic (PBPK) model to describe the tissue dosimetry, plasma concentration, and clearance in the rat following inhalation and dermal, oral, and iv exposure. An initial multiroute PBPK model, based on a previously published inhalation PBPK model for D(4), provided excellent fits to the observed concentration time course of D(4) metabolites in urine and D(4) exhalation rate following dermal exposures. However, the pharmacokinetics of D(4), following oral and iv exposure, were sensitive to the mode of entry into the blood compartment. A refined model, describing delivery of D(4) from the GI tract to the nonexchangeable/deep blood compartment, provided the best fits to observed plasma D(4), exhaled D(4), and D(4) metabolites excreted in the urine following oral exposure. Pharmacokinetics following iv administration was best described by delivery of D(4) directly into the deep blood compartment, possibly reflecting a kinetically identifiable characteristic of the administration of D(4) as an emulsion for the intravenous route of exposure. This model-based analysis indicates that the pharmacokinetics of D(4) delivered by the inhalation or dermal routes is similar, and is different from the iv or oral delivery routes.

Adjuvants, Immunologic↗
PubMed1984

Stimulation of DNA synthesis in kidney epithelial cells in culture by potassium.

The hypothesis that the K+ concentration of extracellular fluid is a determinant of renal DNA synthesis was examined in quiescent, high-density cultures of monkey kidney epithelial cells of the BSC-1 line. The addition of KCl to the medium increased the number of cells engaged in DNA synthesis in a concentration-dependent manner. The capacity of K+ to stimulate DNA synthesis in a greater number of cells was additive with exogenous NaCl and calf serum and was associated with an increment in the steady-state cell K+ content. Studies with other monovalent cations indicated that the stimulatory effect of K+ on DNA synthesis was not mediated by increments in the chloride concentration or osmotic pressure of the medium. The addition of K+ to confluent cultures was associated with a concentration-dependent increase in cell multiplication. The commitment of cells to increased multiplication required exposure of the culture to added KCl for longer than 3 but not more than 6 h. Addition of KCl to cultures of mouse fibroblasts did not alter DNA synthesis, multiplication, or cell K+ content. These observations indicate that increased availability of K+ in the extracellular fluid can stimulate DNA synthesis in kidney epithelial cells in culture.

Animals↗
PubMed2001

A case of claimed persistent neuropsychological sequelae of chronic formaldehyde exposure: clinical, psychometric, and functional findings.

Many anecdotal cases and some clinical studies have demonstrated that formaldehyde exposure can cause multiple health-related problems and cerebral dysfunction. The U.S. Consumer Product Safety Commission has documented multiple hazards related to formaldehyde exposure. Some of this research has suggested that low levels of exposure can be very hazardous to one's health and can potentially result in heightened chemical sensitivities, seizures, and cognitive decline. Some research suggests that exposure results in long-term immunological changes, cell neurofilament protein changes, and demyelination. Symptomatically, exposure has been associated with respiratory problems, excessive fatigue, headaches, mood changes, and impaired attention, concentration, and memory functioning. This article outlines the case of a biology teacher whose chronic formaldehyde exposure resulted in heightened sensitivity to formaldehyde, three tonic-clonic seizures, and dramatic amnesia as well as other cognitive dysfunction.

Journal Article↗
PubMed1990

Performance evaluation of X-ray computed tomography "TCT-700S".

The performance of the CT scanner "TCT-700S" (Toshiba Medical), including noise, spatial and contrast resolution, and exposure, was evaluated. Noise increased as the slice thickness decreased. No matter what the slice thickness, noise was great when the product of tube current and scan speed (described by mAs in the following sentences) was small. Furthermore, the short scan speed caused considerable large noise. Reduction of the mAs value caused remarkable increase in noise when the slice thickness was 1 mm or 2 mm. At combinations of slice thicknesses of 1 mm or 2 mm and 100 mAs, noise was 1-1.5%. When slice thicknesses were measured as the spatial resolution, in the case of a slice thickness of 1 mm, the measurements were 1.6 to 1.8 mm. When high and low contrast resolutions were measured, maximum diameters for the recognition were large as slice thickness became thinner. Although average exposure promised the improvement in the contrast resolution, great exposure increases failed to contribute to such improvement. These performances depended on the exposure. In the case of multiple scanning, average exposures in the field were uniform. However, at a minimum scan speed of 1.8 sec, a three fold discrepancy occurred in exposures observed reciprocally from the left and right sides. Average exposures were also almost the same with slice thicknesses of 10 mm, 5 mm and 2 mm, but with a slice thickness of 1 mm, average exposure was twice as great. This measurement indicates inadequate collimation in the case of a slice thickness of 1 mm. These average exposures were proportional to the mAs value. The radial-exposure profile depended on the position in the columnar object. Although similar average exposures were observed, high peak values were observed on the upper side, but exposure tended to spread at the bottom in the center. This means that the primary x-ray amounts were great in the peripheral region and scattered x-ray amounts were great at the center.

Evaluation Studies as Topic↗
PubMed1998

On the accommodation of disease rate correlations in aggregate data studies of disease risk factors.

Prentice and Sheppard (1995, Biometrika 82, 113-125) proposed a method for estimating relative risks associated with poorly measured exposures using disease rates from multiple populations and exposure and confounding factor data from sample surveys of persons in each population. The method involved an assumption of independence of disease rates across populations, conditional on exposures and confounding factors. Here, this assumption is relaxed by allowing dependencies among the disease rates within a partition of the populations, perhaps defined on the basis of geographic proximity or cultural similarity. Such dependencies could, for example, derive from unmeasured risk factors that are shared among neighboring populations. Dependencies within an element of the partition are modeled by allowing a common correlation between the disease rates of contiguous populations and by inducing correlations between the rates for noncontiguous populations using a multivariate lognormal assumption. Estimating equations are proposed for relative risk parameter estimation, and robustness and efficiency properties are assessed through simulations. The relaxed estimation procedure is shown to yield useful efficiency gains when moderate or strong disease rate dependencies are present, especially when disease rate variances are large relative to binomial variance.

Aged↗
PubMed2006

Molecular epidemiological studies in 1,3-butadiene exposed Czech workers: female-male comparisons.

Results of a recent molecular epidemiological study of 1,3-butadiene (BD) exposed Czech workers, conducted to compare female to male responses, have confirmed and extended the findings of a previously reported males only study (HEI Research Report 116, 2003). The initial study found that urine concentrations of the metabolites 1,2-dihydroxy-4-(acetyl) butane (M1) and 1-dihydroxy-2-(N-acetylcysteinyl)-3-butene (M2) and blood concentrations of the hemoglobin adducts N-[2-hydroxy-3-butenyl] valine (HB-Val) and N-[2,3,4-trihydroxy-butyl] valine (THB-Val) constitute excellent biomarkers of exposure, both being highly correlated with BD exposure levels, and that GST genotypes modulate at least one metabolic pathway, but that irreversible genotoxic effects such as chromosome aberrations and HPRT gene mutations are neither associated with BD exposure levels nor with worker genotypes (GST [glutathione-S-transferase]-M1, GSTT1, CYP2E1 (5' promoter), CYP2E1 (intron 6), EH [epoxide hydrolase] 113, EH139, ADH [alcohol dehydrogenase]2 and ADH3). The no observed adverse effect level (NOAEL) for chromosome aberrations and HPRT mutations was 1.794 mg/m(3) (0.812 ppm)--the mean exposure level for the highest exposed worker group in this initial study. The second Czech study, reported here, initiated in 2003, included 26 female control workers, 23 female BD exposed workers, 25 male control workers and 30 male BD exposed workers (some repeats from the first study). Multiple external exposure measurements (10 full 8-h shift measures by personal monitoring per worker) over a 4-month period before biological sample collections showed that BD workplace levels were lower than in the first study. Mean 8-h TWA exposure levels were 0.008 mg/m(3) (0.0035 ppm) and 0.397 mg/m(3) (0.180 ppm) for female controls and exposed, respectively, but with individual single 8-h TWA values up to 9.793 mg/m(3) (4.45 ppm) in the exposed group. Mean male 8-h TWA exposure levels were 0.007 mg/m(3) (0.0032 ppm) and 0.808 mg/m(3) (0.370 ppm) for controls and exposed, respectively; however, the individual single 8-h TWA values up to 12.583 mg/m(3) (5.72 ppm) in the exposed group. While the urine metabolite concentrations for both M1 and M2 were elevated in exposed compared to control females, the differences were not significant, possibly due to the relatively low BD exposure levels. For males, with greater BD exposures, the concentrations of both metabolites were significantly elevated in urine from exposed compared to control workers. As in the first study, urine metabolite excretion patterns in both sexes revealed conjugation to be the minor detoxification pathway (yielding the M2 metabolite) but both M1 and M2 concentration values were lower in males in this second study compared to their concentrations in the first, reflecting the lower external exposures of males in this second study compared to the first. Of note, females showed lower concentrations of both M1 and M2 metabolites in the urine per unit of BD exposure than did males while exhibiting the same M1/(M1+M2) ratio, reflecting the same relative utilization of the hydrolytic (producing M1) and the conjugation (producing M2) detoxification pathways as males. Assays for the N,N-(2,3-dihydroxy-1,4-butadyl) valine (pyr-Val) hemoglobin (Hb) adduct, which is specific for the highly genotoxic 1,2,3,4-diepoxybutane (DEB) metabolite of BD, have been conducted on blood samples from all participants in this second Czech study. Any adduct that may have been present was below the limits of quantitation (LOQ) for this assay for all samples, indicating that production of this important BD metabolite in humans is below levels produced in both mice and rats exposed to as little as 1.0 ppm BD by inhalation (J.A. Swenberg, M.G. Bird, R.J. Lewis, Future directions in butadiene risk assessment, Chem. Biol. Int. (2006), this issue). Results of assays for the HB-Val and THB-Val hemoglobin adducts are pending. HPRT mutations, determined by cloning assays, and multiple measures of chromosome level changes (sister-chromatid exchanges [SCE], aberrations determined by conventional methods and FISH) again showed no associations with BD exposures, confirming the findings of the initial study that these irreversible genotoxic changes do not arise in humans occupationally exposed to low levels of BD. Except for lower production of both urine metabolites in females, no female-male differences in response to BD exposures were detected in this study. As in the initial study, there were no significant genotype associations with the irreversible genotoxic endpoints. However, as in the first, differences in the metabolic detoxification of BD as reflected in relative amounts of the M1 and M2 urinary metabolites were associated with genotypes, this time both GST and EH.

Acetylcysteine↗
PubMed1993

Effect of various cytokine combinations on induction of non-MHC-restricted cytotoxicity.

Efforts were directed to achieve an increased lymphokine-activated non-MHC-restricted killing (LAK) activity greater than that induced by rIL-2 alone. Human peripheral blood (PB) and bone marrow (BM)-derived mononuclear cells (MC) were exposed in vitro to multiple cytokine combinations, including rIL-6, rIL-7, rIFN-alpha and rIFN-gamma in the presence of either suboptimal or optimal doses of rIL-2. Our results have shown that BMMC are a potential source for induction of increased LAK activity upon exposure to multiple cytokine combinations, whereas PBMC could not be successfully stimulated under the same conditions. Fifty-five to 62% of BM-derived samples stimulated with high dose rIL-2 + rIL-7 or rIL-2 + rIL-7 + rIL-6 + rIFN-gamma exhibited a higher degree of cytotoxicity than BM samples stimulated with rIL-2 alone. Exposure of PB-derived large granular lymphocytes (LGL) to various cytokine combinations led to increased proliferation after stimulation with suboptimal dose of rIL-2 in the presence of rIL-6 and rIL-7. This increase was not observed in induction of cytotoxicity. We suggest that BMMC activated by multiple cytokine combinations could play an active role in improving antitumor response in vivo by contributing to the control of minimal residual tumor cell growth, particularly post-BM transplantation.

Bone Marrow↗
PubMed2005

Characterization of particulate and gas exposures of sensitive subpopulations living in Baltimore and Boston.

Personal exposures to particulate and gaseous pollutants and corresponding ambient concentrations were measured for 56 subjects living in Baltimore, Maryland, and 43 subjects living in Boston, Massachusetts. The 3 Baltimore cohorts consisted of 20 healthy older adults (seniors), 21 children, and 15 individuals with physician-diagnosed chronic obstructive pulmonary disease (COPD*). The 2 Boston cohorts were 20 healthy seniors and 23 children. All children were 9 to 13 years of age; seniors were 65 years of age or older; and the COPD participants had moderate to severe physician-diagnosed COPD. Personal exposures to particulate matter with aerodynamic diameters less than 2.5 microm (PM2.5), sulfate (SO(4)2-), elemental carbon (EC), ozone (03), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were measured simultaneously for 24 hours/day. All subjects were monitored for 8 to 12 consecutive days. The primary objectives of this study were (1) to characterize the personal particulate and gaseous exposures for individuals sensitive to PM health effects and (2) to assess the appropriateness of exposure assessment strategies for use in PM epidemiologic studies. Personal exposures to multiple pollutants and ambient concentrations were measured for subjects from each cohort from each location. Pollutant data were analyzed using correlation and mixed-model regression analyses. In Baltimore, personal PM2.5 exposures tended to be comparable to (and frequently lower than) corresponding ambient concentrations; in Boston, the personal exposures were frequently higher. Overall, personal exposures to the gaseous pollutants, especially O3 and SO2, were considerably lower than corresponding ambient concentrations because of the lack of indoor sources for these gases and their high removal rate on indoor surfaces. Further, the impact of ambient particles on personal exposure (the infiltration factor) and differences in infiltration factor by city, season, and cohort were investigated. No difference in infiltration factor was found among the cohorts, which suggests that all subjects were exposed to the same fraction of ambient PM2.5 for a given ambient concentration. In addition, the results show significant correlations between ambient PM2.5 concentrations and corresponding personal exposures over time and provide further indication that ambient gaseous pollutant concentrations may be better surrogates for personal PM2.5 exposures, especially personal exposures to PM2.5 of ambient origin, than their respective personal exposures. These results have important implications for PM health effects studies that use regression models including both ambient PM2.5 and gaseous pollutant concentrations as independent variables, because both parameters may be serving as surrogates for PM2.5 exposures.

Adolescent↗
PubMed1993

Double-blind provocation chamber challenges in 20 patients presenting with "multiple chemical sensitivity".

A clinical algorithm was used to discriminate verifiable chemical sensitivity from psychological disorders in patients referred for evaluation of polysomatic symptoms attributed to hypersensitivity to workplace and domestic chemicals. These patients believed that they were reactive or hypersensitive to low-level exposure to multiple chemicals. Some had previously been evaluated and managed by the tenets of "clinical ecology" and diagnosed as having "multiple chemical sensitivity." Double-blind provocation challenges with an olfactory masker were performed in an environmental chamber on each of 20 patients. A variety of chemicals was employed, one or more per subject, dependent on individual clinical history. Clean air challenges with the olfactory masker were used as placebo or sham controls. As a group, probability analyses of patient symptom reports from 145 chemical and clean air challenges failed to show sensitivity (33.3%), specificity (64.7%), or efficiency (52.4%). Individually, none of these patients demonstrated a reliable response pattern across a series of challenges. Implications for future research in assessment methodology incorporating neurophysiologic and neurobehavioral measures are discussed.

Algorithms↗
PubMed1991

Documented male-to-female transmission of HIV-1 after minimal vaginal exposure in the absence of other cofactors for infection.

AIDS cases attributable to heterosexual vaginal intercourse constitute a growing proportion of new AIDS cases in the United States. Major cofactors that possibly increase the efficiency of heterosexual transmission of HIV-1 include genital ulcer disease, multiple sexual exposures, lack of male circumcision, and primary and advanced stages of HIV-1 disease. I report the case of a 33-year-old woman who was recently infected with HIV-1 after one to three nontraumatic episodes of vaginal intercourse with a healthy-appearing, HIV-1-infected, bisexual man. An investigation of her exposure history revealed the precise time frame during which infection occurred. The patient developed a primary HIV-1-infection syndrome and became seropositive for HIV-1 within eight weeks of her last sexual contact with the infected man. An epidemiological and laboratory evaluation of the index patient and her sexual partner identified only one risk factor for enhanced HIV-1 transmission: the patient's use of oral contraceptives. Her partner was immunologically intact, HIV-1 antigen negative, and circumcised. Both of the individuals were from Minnesota, as were their recent sexual partners. This case illustrates that HIV-1 infection by vaginal intercourse can occur in the absence of the major risk factors believed to increase the efficiency of transmission. Even in a low HIV-1 prevalence area like Minnesota, efforts to promote awareness of HIV-1 status, abstinence, non-penetrative sex, or barrier protection need to be expanded and the behaviors adopted by sexually active persons if HIV-1 transmission is to be minimized.

Adult↗
PubMed1975

Electrical injuries to the eye.

The effect of electric current on the eyes of experimental animals was studied. An apparatus was constructed to allow single and multiple shock exposures from 0 to 600 volts at variable exposure times. The current was measured on a Tectronex Storage Oscilloscope. Mature Dutch rabbits were used as experimental animals. When rabbit eyes were subjected to a current of 500 volts for no less than 250 milliseconds and 400 milliamperes or more, a permanent decrease in the amplitude of the b-wave of the Electroretinogram resulted in some animals. No histological or ophthalmological alterations in the retina, optic nerve or vasculature could be observed using conventional techniques. The cataractogenic properties of electric current were also studied. Most previous observations dealing with this subject utilized a multiple shock technique--something which is unlikely to occur in any accidental exposure. This study focussed on the production of lens changes in rabbit eyes following single exposures of measured electric current. The biomicroscopic characteristics of these changes were described. Minimal lens changes were produced by single shock exposures ranging from 6 to 26 watts per second while typical electrical anterior subcapsular cataracts were produced by current of 23 to 80 watts per second. Exposure times were mostly 250 milliseconds or less since the survival rate of animals subjected to longer exposures made such studies unfeasible. Three patients with electrical injuries were presented and some of the pertinent literature was reviewed.

Adult↗
PubMed2003

Biochemical changes in the serum of patients with chronic toxigenic mold exposures: a risk factor for multiple renal dysfunctions.

This paper analyzes and presents the biochemical abnormalities in the sera of patients presenting with chronic mycosis in order to investigate the relationship with the risks of multiple renal disorders. The study population (n = 10) consisted of six females and four males (mean age 36.3 years) exposed by toxic molds in their homes and offices for an average of 2.8 years. The control group comprised ten people, five males and five females (mean age 35.9 years) without any known exposures to toxic molds. Blood samples were obtained from both the patients and the controls and were processed using specific biochemical methods that included enzyme-linked immunoabsorbent assay (ELISA). There were biochemical abnormal concentrations in creatinine, uric acid, phosphorus, alkaline phosphotase, cholesterol, HDH, SGOT/AST, segmented neutrophils, lymphocytes, total T3, IgG and IgA immunoglobulins with significant differences between patients and controls. These abnormalities were consistent with multiple renal disorders. The major complaints of the mycosis patients were headaches, pulmonary symptoms, allergic reactions, memory loss, skin rashes, blurred vision symptoms, fatigue, and runny nose. These findings were depictive of a strong association of chronic mycosis with abnormal renal indicators. It was concluded that, although this research was a pilot investigation, based on the overall results, people exposed to chronic indoor environmental toxic molds were at risk of multiple renal complications.

Adult↗
PubMedDate not supplied

Safety evaluation of chemical mixtures and combinations of chemical and non-chemical stressors.

Recent developments in hazard identification and risk assessment of chemical mixtures are reviewed. Empirical, descriptive approaches to study and characterize the toxicity of mixtures have dominated during the past two decades, but an increasing number of mechanistic approaches have made their entry into mixture toxicology. A series of empirical studies with simple chemical mixtures in rats is described in some detail because of the important lessons from this work. The development of regulatory guidelines for the toxicological evaluation of chemical mixtures is discussed briefly. Current issues in mixture toxicology include the adverse health effects of ambient air pollution; the application of such modern, sophisticated methodologies as genomics, bioinformatics, and physiologically based pharmacokinetic modeling; and databases for mixture toxicity. Finally, the state of the art of our knowledge on the potential adverse health effects of combined exposures to chemicals and non-chemical stressors (noise, heat/cold, microorganisms, immobilization, restraint, or transportation), research initiatives in these fields, and the development of an indicator for the cumulative health impact of multiple environmental exposures are discussed.

Dose-Response Relationship, Drug↗
PubMed1986

A pictorial portrayal of poisoning possibilities: a public awareness approach.

Areas of a high density university housing cooperative were randomly photographed following reports of decreased child supervision and increased potential for childhood poisoning and injury. A slide show was developed using these actual settings which revealed potential exposure to multiple toxic chemicals. This show was presented to the residents and demonstrated the high risk situations. Residents discovered that toxic chemicals were present in their own living environment, that many routes of exposure were possible and the high susceptibility of children during unsupervised play. As a result of this educational program, a poison prevention policy was approved with subsequent visible improvement in the community awareness and environment. This pictorial approach is a useful method for educating residents of a high density housing development about potential poisonings in their home environment and may be applied to other similar settings.

Audiovisual Aids↗
PubMed1987

Characterization of a halothane-induced humoral immune response in rabbits.

An animal model of halothane-induced liver injury has been developed in the rabbit to study the production of humoral immunity towards a biotransformation intermediate of halothane. Rabbits exposed many times to halothane in a 75% O2/25% N2 atmosphere produce an antibody that cross-reacts with the trifluoroacetyl moiety of trifluoroacetylated rabbit serum albumin (TFA-RSA). The generation of this halothane-induced immunogen is dependent upon high oxygen tension as shown by the minimal anti-TFA antibody response seen in rabbits exposed to halothane in a 14% O2/86% N2 atmosphere. In addition, halothane exposure of rabbits specifically immunized with the metabolite-carrier complex, TFA-RSA, induces a secondary antibody response toward the immunogen. In rabbits, either immunized with TFA-RSA or not, multiple halothane exposures induce populations of antibodies with varying specificities. Evidence suggests that predominance of the metabolic intermediate, the ensuing immunogen, and the subsequent antibody response depends upon the oxygen tension during successive exposures to halothane. These successive exposures could potentially generate many different immunogens resulting in varied antibody specificities.

Animals↗
PubMed2002

Effects of caffeine, sleep loss, and stress on cognitive performance and mood during U.S. Navy SEAL training. Sea-Air-Land.

RATIONALE: When humans are acutely exposed to multiple stressors, cognitive performance is substantially degraded. Few practical strategies are available to sustain performance under such conditions. OBJECTIVE: This study examined whether moderate doses of caffeine would reduce adverse effects of sleep deprivation and exposure to severe environmental and operational stress on cognitive performance. METHODS: Volunteers were 68 U.S. Navy Sea-Air-Land (SEAL) trainees, randomly assigned to receive either 100, 200, or 300 mg caffeine or placebo in capsule form after 72 h of sleep deprivation and continuous exposure to other stressors. Cognitive tests administered included scanning visual vigilance, four-choice visual reaction time, a matching-to-sample working memory task and a repeated acquisition test of motor learning and memory. Mood state, marksmanship, and saliva caffeine were also assessed. Testing was conducted 1 and 8 h after treatment. RESULTS: Sleep deprivation and environmental stress adversely affected performance and mood. Caffeine, in a dose-dependent manner, mitigated many adverse effects of exposure to multiple stressors. Caffeine (200 and 300 mg) significantly improved visual vigilance, choice reaction time, repeated acquisition, self-reported fatigue and sleepiness with the greatest effects on tests of vigilance, reaction time, and alertness. Marksmanship, a task that requires fine motor coordination and steadiness, was not affected by caffeine. The greatest effects of caffeine were present 1 h post-administration, but significant effects persisted for 8 h. CONCLUSIONS: Even in the most adverse circumstances, moderate doses of caffeine can improve cognitive function, including vigilance, learning, memory, and mood state. When cognitive performance is critical and must be maintained during exposure to severe stress, administration of caffeine may provide a significant advantage. A dose of 200 mg appears to be optimal under such conditions.

Adult↗