Effect of electrolyzed water on wound healing.

Electrolyzed water accelerated the healing of full-thickness cutaneous wounds in rats, but only anode chamber water (acid pH or neutralized) was effective. Hypochlorous acid (HOCl), also produced by electrolysis, was ineffective, suggesting that these types of electrolyzed water enhance wound healing by a mechanism unrelated to the well-known antibacterial action of HOCl. One possibility is that reactive oxygen species, shown to be electron spin resonance spectra present in anode chamber water, might trigger early wound healing through fibroblast migration and proliferation.

Phosphatidic acid signaling mediates lung cytokine expression and lung inflammatory injury after hemorrhage in mice.

Because phosphatidic acid (PA) pathway signaling may mediate many basic reactions involving cytokine-dependent responses, we investigated the effects of CT1501R, a functional inhibitor of the enzyme lysophosphatidic acid acyltransferase (LPAAT) which converts lysophosphatidic acid (Lyso-PA) to PA. We found that CT1501R treatment not only prevented hypoxia-induced PA increases and lyso-PA consumption in human neutrophils, but also prevented neutrophil chemotaxis and adherence in vitro, and lung injury and lung neutrophil accumulation in mice subjected to hemorrhage and resuscitation. In addition, CT1501R treatment prevented increases in mRNA levels and protein production of a variety of proinflammatory cytokines in multiple lung cell populations after blood loss and resuscitation. Our results indicate the fundamental role of PA metabolism in the development of acute inflammatory lung injury after blood loss.

Control of cigarette smoking topography: smoke filtration and draw resistance.

Systematic changes occur in the topography of puff and inhalation behavious as a cigarette is smoked. The role of various physical properties of the cigarette in controlling puff and inhalation behaviors was investigated in two experiments. The first experiment manipulated presmoking cigarette length while the second manipulated smoke filtration and cigarette draw resistance in an independent fashion. The characteristic progressive decrease in puff volume observed with each succeeding puff of a cigarette was not due to smoke satiation, fatigue, or visual cues. Although draw resistance can be a major determinant of puff volume, it did not appear to be a central mechanism accounting for the progressive decrease within normally smoked cigarettes. Rather, this decrease in puff volume appeared to be a response to the increasingly less filtered, more concentrated smoke. Although inhalation and exhalation volumes appeared weakly responsive to smoke satiation and/or fatigue, the subjective qualities of smoke "taste" and "satisfaction" also appeared to control these respiratory parameters. The present study provides some evidence suggesting that inhalation parameters may play a role in determining smoke exposure.

Low-dose caffeine physical dependence in humans.

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

Low-dose caffeine discrimination in humans.

A novel drug discrimination procedure was used to study the discriminability and subjective effects of caffeine in seven human volunteers who abstained from dietary sources of caffeine. Daily sessions involved p.o. ingestion of two capsules sequentially, one of which contained caffeine and the other placebo, under double-blind conditions. Each day subjects attempted to identify and were later informed which capsule contained caffeine and which contained placebo. All subjects acquired rapidly the initial discrimination (100 or 178 mg vs. placebo). Examination of progressively lower caffeine doses showed that accuracy and ratings of confidence in accuracy were increasing functions of dose. There were individual differences in the lowest discriminable dose: three subjects discriminated 56 mg, three discriminated 18 mg and one discriminated 10 mg. Discrimination accuracy was usually higher after the second capsule than after the first capsule. All subjects indicated that they believed that they made the discrimination predominantly on the basis of central effects of caffeine vs. placebo, such as changes in mood and socializing. Compared to placebo, 100 mg of caffeine increased ratings of alertness, well-being, social disposition, motivation for work, concentration, energy and self-confidence and decreased ratings of headache and sleepiness. This dose of caffeine also produced a large increase in a measure of "euphoria." The present study documents biological activity of caffeine at lower doses than heretofore recognized. The general approach to investigating the effects of low drug doses may have broad application in human psychopharmacology research for characterizing other subtle psychotropic effects.

Reinforcing effects of caffeine in humans.

The reinforcing and subjective effects of caffeine were studied under double-blind conditions in 12 normal humans. After 2 forced exposure days on which subjects received color-coded capsules containing either caffeine (100, 200, 400 or 600 mg) or placebo, subjects had a choice day on which they chose which one of the two types of color-coded capsules would be ingested. Subjects were exposed to 10 experimentally independent choices (i.e., involving exposure and choice between novel color-coded capsule conditions) at each of several dose levels. All forced exposure and choice opportunities occurred when subjects were overnight abstinent from their normal dietary caffeine intake (mean, 116 mg/day). Significant caffeine positive reinforcement was demonstrated in 5 of 12 subjects at one or more doses. Percentage of selection of caffeine was inversely related to dose, with four subjects showing significant caffeine avoidance at 400 and/or 600 mg. Choice behavior was correlated positively with feelings of contentedness and was correlated negatively with prestudy trait anxiety scores and with ratings of capsule disliking. Compared to placebo, caffeine produced increases in subjective ratings indicating arousal while producing decreases in headache and "craving" for caffeine-containing foods, even at the lowest dose of 100 mg. At higher doses caffeine produced dysphoric anxiety-like subjective effects. Overall, this study provides the first demonstration in humans of the positive reinforcing effects of caffeine alone (i.e., in capsules) and documents individual differences among normal subjects in both caffeine positive reinforcement and caffeine avoidance.

Reinforcing properties of caffeine: studies in humans and laboratory animals.

Three types of experimental studies are reviewed: (1) intravenous and oral caffeine self-administration by laboratory animals, (2) oral caffeine self-administration by humans, and (3) human subjective effects of caffeine relevant to reinforcing effects. These studies show that, under appropriate conditions, caffeine can serve as a reinforcer and can produce elevations in subjective drug liking and/or euphoria. In this regard, caffeine can be distinguished from a wide range of behaviorally active compounds, such as the amphetamine analog fenfluramine and the major tranquilizer chlorpromazine, which do not produce such effects. Caffeine can also be distinguished from classic drugs of abuse such as cocaine, d-amphetamine or pentobarbital which generally maintain high levels of self-administration (or liking) in contrast to caffeine which tends to maintain lower levels of self-administration (or liking) or maintain self-administration under a more narrow range of parametric conditions. Several human studies and one animal experiment suggest that physical dependence substantially potentiates the reinforcing effects of caffeine. Other human and animal studies indicate that there may be substantial differences between individual subjects in the reinforcing effects of caffeine. An important challenge for future human and animal drug self-administration research will be to delineate more precisely the conditions under which caffeine does and does not serve reliably as a reinforcer.

Effects of smoking on mental performance and vegetative functions in high and low CO absorbing smokers.

The present study investigated effects of smoking on mental performance and concomitant psychophysiological reactions in smokers differing in the strength of their habit. Toward this goal performance in two 30-min rapid information processing (RIP) trials separated by a 10-min smoking period was compared among preselected high and low CO absorbing smokers, nonsmokers, and smokers not allowed to smoke (n = 12 per group). Heart rate, finger pulse amplitude, and respiratory frequency were continuously recorded throughout the experimental sessions in order to assess physiological arousal and to estimate nicotine absorption through smoking. The RIP test consisted in the detection (button pressing) of triads of odd or even digits out of a series of single digits presented in a subject-paced manner on a screen in a pseudorandom sequence. Performance significantly increased from the first to the second trial in all groups, and this increase tended to be greater in both the high and low CO absorbers than in the two control groups. The similar development of RIP in the low and high CO absorbers is contrasted by differential vegetative responses to smoking. Smoking increased heart rate and respiratory frequency and produced peripheral vasoconstriction in the high CO absorbers only, suggesting the absorption of nicotine, whereas no nicotinic effects were noted in the low CO absorbers. The results are discussed in the light of the observed dissociation between psychological and physiological effects of smoking in the two groups of smokers, and the possibly differential role of nicotine for smoking motivation in the two groups.

Caffeine physical dependence: a review of human and laboratory animal studies.

Although caffeine is the most widely used behaviorally active drug in the world, caffeine physical dependence has been poorly characterized in laboratory animals and only moderately well characterized in humans. In humans, a review of 37 clinical reports and experimental studies dating back to 1833 shows that headache and fatigue are the most frequent withdrawal symptoms, with a wide variety of other signs and symptoms occurring at lower frequency (e.g. anxiety, impaired psychomotor performance, nausea/vomiting and craving). When caffeine withdrawal occurs, severity can vary from mild to extreme (i.e. incapacitating). The withdrawal syndrome has an onset at 12-24 h, peak at 20-48 h, and duration of about 1 week. The pharmacological specificity of caffeine withdrawal has been established. The proportion of heavy caffeine users who will experience withdrawal symptoms has been estimated from experimental studies to range from 25% to 100%. Withdrawal symptoms have been documented after relatively short-term exposure to high doses of caffeine (i.e. 6-15 days of greater than or equal to 600 mg/day). Although animal and human studies suggest that physical dependence may potentiate the reinforcing effects of caffeine, human studies also demonstrate that a history of substantial caffeine intake is not a necessary condition for caffeine to function as a reinforcer. The similarities and differences between caffeine and classic drugs of abuse are discussed.

Rapid information processing and concomitant event-related brain potentials in smokers differing in CO absorption.

The present study relates subject-paced rapid information processing to different components of event-related brain potentials in an attempt to gain more information about changes in mental performance in relation to alveolar smoke absorption as assessed by expired air CO measurement. The task consisted in the presentation of pseudorandom sequences of single digits, and the subjects had to respond to each sequence of three odd or three even digits. The triplets evoked a typical late negativity in the event-related potential between the second and third digit as well as a P300 component following the third digit. In 21 smokers, task performance, event-related potentials and tidal air CO concentration were measured before and after smoking a cigarette. The results revealed increases in performance and P300 magnitude from pre- to postsmoking which were unaffected by the amount of CO absorption. A differential trend was seen, however, with the late negativity, which increased from pre- to postsmoking only in subjects with a large amount of CO absorption. The results support the assumption of the distraction arousal model used as an interpretation of these effects on contingent negative variation and suggest that high CO absorbing smokers possibly depend more on neuropharmacological effects of smoking than smokers with a low amount of CO absorption.

Effects of smoking deprivation on smoking behavior and heart rate response in high and low CO absorbing smokers.

Short-term deprivation effects on smoking-induced heart rate response and smoking behavior were compared in consistently high and low CO absorbing smokers, suggested to depend differentially on smoking and/or nicotine. The subjects came to the laboratory for two afternoon sessions and smoked at 1 p.m. and at 5 p.m. both after previous free smoking and following afternoon or overnight-morning deprivation. Overnight-morning deprivation decreased presmoking heart rate in both groups similarly, but it increased heart rate response to smoking more in the high than low CO absorbers. Single cigarette tidal CO boosts concomitantly decreased in the high CO absorbers and remained at the habitually low level among the low CO absorbers. Afternoon deprivation had no effects on presmoking heart rate, presmoking tidal CO concentration and tidal CO boost, but increased the heart rate response to smoking in the high CO absorbers. Smoking need and satisfaction as well as puff volume and duration tended to increase after both deprivations slightly more among the high than low CO absorbers. These results are discussed in terms of a differential development of acute tolerance to nicotine in the two groups of smokers which dissipates during smoking abstinence periods.

Smoking behaviour and personality patterns of smokers with low and high CO absorption.

The present experiment describes an attempt to select differentially nicotine dependent smokers by means of an objective and non-invasive measure of cigarette smoke CO absorption. Toward this goal the differences in expiratory tidal air CO concentration before and after smoking a single cigarette (tidal CO boost) were measured in three experimental sessions. The selection criteria were tidal CO boosts greater than 3.5 p.p.m. and less than 1 p.p.m. According to these criteria 19 out of 171 subjects were consistently found to be high CO absorbers and 20 were found to be low CO absorbers. Puffing behaviour was measured throughout all three test sessions by the flowmeter method and respiratory inhalation by thorax impedance plethysmography. In addition, heart rate was continuously measured during smoking. These data were used to assess for specific differences between the two extremes of inhalation behaviour. High CO absorbers differed from low CO absorbers by more intensive patterns of puffing and respiratory inhalation, by higher daily cigarette and coffee consumption, by lower alcohol consumption, by shorter latencies to the first cigarette in the morning, by greater subjective need for smoking and by lower scores for healthy eating habits. No intergroup differences were observed for smoking induced heart rate acceleration. The high CO absorbers were significantly older than the low CO absorbers; however, no evidence was found that any of the differences in smoking style between the two extremes might be related to their difference in age. No differences were seen in cigarette strengths, in personality or in coronary prone behaviour as assessed by means of standardized questionnaires in all subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Psychophysiological correlates of conflict solving and cigarette smoking.

Twenty-eight subjects participated in three sessions which involved three successive rows of STROOP stimuli presented in a spaced trial technique. The first session was a training session, and in the second and third sessions the subjects had to smoke in balanced sequence a 0.2 mg and a 1.2 mg nicotine cigarette between the second and third rows of STROOP stimuli. For these two smoking sessions these experimental subjects were compared with a yoked-control group which attended the task passively without responding to the stimuli but also had to smoke a 1.2 mg nicotine cigarette. Continuous psychophysiological recording showed: (a) Before smoking the heart rates were lower in the yoked than in the experimental subjects. (b) A gradual but modest habituation of intrasession heart rate and EEG measures developed in all experimental groups. (c) Pronounced skin conductance and vasoconstrictive responses to the STROOP stimuli persisted in the experimental groups without any tendency to habituate and without modification by smoking. (d) Significant smoking-induced tachycardia and cutaneous vasoconstriction were seen in the yoked subjects only. Behaviorally, puffing style of smoking was intensified in the experimental group as opposed to the yoked group, and smoking neither impaired nor improved STROOP performance.

Effect of oxytetracycline administration on antibody response to Brucella abortus vaccination in calves.

In 5- to 7-month-old dairy calves, concurrent oxytetracycline administration and subcutaneous vaccination with 10(9) Brucella abortus strain 19 organisms reduced the percentage of animals with detectable humoral antibodies to Brucella abortus, when compared with untreated vaccinated calves of the same age range. The reduction of antibody reaction in the card test was less than that associated with the injection of 10(9) heat-killed Brucella abortus strain 19 organisms.

Effects of nicotine on the visual evoked response.

The effects of smoking cigarettes differing in nicotine content (0.14 vs 1.34 mg/cigarette) on the peak-to-peak amplitude and peak latency of the human averaged visual evoked response (AVER) were measured in 10 male smokers after a 2-hr smoking deprivation period. The AVER was obtained under five different flash intensities. Eight different peaks were involved in the amplitude and latency measurements. The nicotine dosage and flash intensity factors both had significant effects on peak-to-peak amplitudes while only the flash intensity factor affected peak latencies. The general enhancement of peak-to-peak amplitudes by the 1.34 mg cigarette, relative to the 0.14 mg cigarette, indicates that the effects of cigarette smoking on the AVER are predominantly due to nicotine's psychopharmacologic action, as opposed to other elements in tobacco smoke or as opposed to nonpharmacologic mechanisms involving learning processes. Past research, on an electrophysiological and behavioral level, indicating that nicotine, as administered via cigarette smoking, may have enhancing and/or restorative effects on visual attentional processes in the quiescent smoker was supported.

[Effects of nicotine on visually evoked EEG potentials]. / Nikotinwirkungen auf visuelle evozierte EEG-Potentiale.

The effects of nicotine were measured on the averaged visual evoked response (AVER) through the use of two types of experimental cigarettes which differed only in nicotine content (i.e., 0.14 vs. 1.34 mg/cig.). The results indicate that the restorative and/or enhancing effects of cigarette smoking on peak amplitudes are due predominantly to nicotine's psychopharmacologic effects, and support past research indicating that nicotine may enhance visual attentional processes in the quiescent smoker. This contrasts with other reports indicating nicotine to have a depressant effect on auditory processes.