Search PubMed⌕ Search

Biomedical subjects

A DiMarco

Publications and source records attributed to A DiMarco.

At least 37 records · Page 2Linked to original sources
PubMed1995

Subjective and cardiovascular responses to nicotine combined with alcohol in male and female smokers.

Nicotine and alcohol are often consumed concurrently by smokers. Each drug alone produces significant subjective and cardiovascular responses, but the effects of the two drugs in combination have rarely been examined. Smokers who were moderate alcohol drinkers (n = 18, 9 males and 9 females) participated in four sessions, involving acute administration of nicotine/placebo and alcohol/no alcohol. Subjects abstained overnight from tobacco and alcohol prior to each session. Nicotine (20 micrograms/kg per presentation) or placebo was administered by measured-dose nasal spray every 30 min for 2 h following consumption of diet tonic water with or without alcohol (0.5 g/kg). Subjective (visual analog scales, Profile of Mood States, Addiction Research Center Inventory) and cardiovascular (heart rate, systolic and diastolic blood pressure) responses were assessed after each nicotine/placebo administration. Nicotine increased head rush, dizzy, and most stimulant effects (i.e. jittery, tension, and arousal and decreased fatigue and relaxed), while alcohol increased intoxication, head rush, dizzy, and jittery, with no other stimulant effects. Nicotine and alcohol generally produced additive subjective and cardiovascular effects when consumed together, although nicotine attenuated sedating and intoxicating effects of alcohol alone. Furthermore, there were several interaction effects on subjective measures involving gender. Nicotine plus alcohol tended to attenuate some subjective effects due to one drug or the other alone in men but enhanced the effects of either alone in women. These findings indicate that nicotine and alcohol generally have additive subjective and cardiovascular effects, but that men and women differentially respond on some subjective measures to the combination of alcohol and nicotine.

Adult↗
PubMed1995

N-acetylcysteine administration and loaded breathing.

Recent work has shown that loaded breathing produces alterations in diaphragmatic glutathione metabolism. Moreover, it has been suggested that alterations in glutathione levels may be related to the development of respiratory muscle fatigue and respiratory failure during loading. The purpose of this study was to determine whether it was possible to augment diaphragmatic stores of reduced glutathione (GSH) and thereby delay the development of respiratory failure during loaded breathing by administering N-acetylcysteine (NAC), a glutathione precursor. We compared the effects of massive inspiratory loading on saline- and NAC-treated groups of decerebrate unanesthetized rats with loading continuing until respiratory arrest occurred. As controls, we also studied unloaded saline- and NAC-treated animals. After arrest, diaphragms were excised, measurement was made of diaphragmatic GSH and oxidized glutathione (GSSG) concentrations, and assessment was made of in vitro diaphragmatic contractility (i.e., the force-frequency relationship and in vitro fatigability). We found that loading of saline-treated animals produced reductions in the diaphragmatic force-frequency curve, reductions in GSH, and increases in GSSG levels. NAC administration blunted loading-induced decreases in diaphragmatic GSH levels and reduced the in vitro fatigability of excised diaphragm muscle strips. NAC did not significantly alter the time to respiratory arrest, however, and also failed to alter the effect of loaded breathing on the diaphragmatic force-frequency relationship. These findings suggest that free radical-mediated GSH depletion is not the limiting factor determining the development of respiratory failure in this model of loaded breathing.

Acetylcysteine↗
PubMed1995

Effect of varying inspired oxygen concentration on diaphragm glutathione metabolism during loaded breathing.

Recent studies have suggested that loaded breathing elicits alterations in diaphragmatic glutathione levels that may be mediated by free radicals and may also be linked to the development of diaphragm fatigue. While free-radical generation in a number of pathophysiologic conditions is known to be a function of ambient oxygen concentrations, the effect of varying inspired oxygen concentration on the diaphragmatic response to loaded breathing (i.e., on diaphragm fatigue and glutathione levels) has not been studied. In this study, we compared the effect of loaded breathing, continued until respiratory arrest in decerebrate rats breathing room air (RA), with the effect of the same load on animals breathing 100% oxygen (O2). After arrest, the animals' diaphragms were excised, force generation was assessed in vitro, and diaphragmatic levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) were determined. Similar measurements were made on unloaded control animals. We found both similarities and differences in the response to loading in O2- and RA-breathing animals. O2-breathing loaded animals had a greater load endurance, lower blood pressure at the end of loading, higher carbon dioxide levels, and greater high-frequency fatigue at the conclusion of loaded trials than did RA-breathing animals. The degree of low-frequency fatigue was similar, however, in the O2- and RA-breathing loaded groups (i.e, twitch force averaged 7.9 +/- 0.6, 8.4 +/- 0.5, 3.8 +/- 0.9, and 4.5 +/- 0.8 N/cm2, respectively, in the RA/unloaded, O2/unloaded, RA/loaded, and O2/loaded groups, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

Effect of varying load magnitude on diaphragmatic glutathione metabolism during loaded breathing.

Some studies have suggested that protective mechanisms downregulate diaphragm activity during loaded breathing so as to prevent respiratory-muscle fatigue. Other work has indicated, however, that loading can sometimes elicit significant diaphragmatic fatigue, and that the development of fatigue may be related to alterations in diaphragmatic glutathione concentrations. One potential explanation for these discrepant observations is that the mechanism of respiratory failure may vary as a function of load magnitude, and that some loads evoke little fatigue whereas others produce substantial fatigue and glutathione alterations. The purpose of this study was to examine this issue by determining the diaphragmatic fatigue and alterations in glutathione concentrations produced by a range of inspiratory resistive loads. Experiments were performed on decerebrate rats divided into a control, unloaded group and a group loaded with small, medium, and large inspiratory resistive loads that were applied until respiratory failure occurred. After respiratory arrest, the animals' diaphragms were excised, an in vitro determination was done of diaphragm contractility characteristics, and samples of muscle were assayed for GSH (reduced glutathione) and GSSG (oxidized glutathione). We found that in vitro diaphragm force generation was severely reduced for loaded breathing, and surprisingly, that the magnitude of the low-frequency fatigue present was similar in the three loaded groups. Reductions in diaphragmatic GSH levels and increases in GSSG levels were found in all three loaded groups. Reductions in diaphragmatic GSH levels and increases in GSSG levels were found in all three loaded groups, but again, the magnitude of these changes were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Acute effects of tobacco smoking on hunger and eating in male and female smokers.

Cigarette smoking is associated with reduced body weight, an effect which has often been attributed to acute anorectic actions of nicotine. In this study, male and female smokers (n = 10 each), abstinent overnight from smoking and food, participated in three 2-h sessions, involving intermittent, controlled exposure to their usual cigarette (mean yield = 0.75 mg nicotine), a very low nicotine cigarette (0.1 mg) or an unlit cigarette. Hunger and cigarette craving were assessed throughout each session, which ended with ad libitum consumption of a variety of food items ("lunch"). Plasma nicotine analyses confirmed successful control of nicotine exposure via smoking. Results indicated no differences across cigarette conditions in hunger, in contrast to the sharp differences in cigarette craving. There were no differences in total caloric intake, or in macronutrient or taste selection. There were also no differences in any responses to smoking condition as a function of gender. These findings cast into question the commonly held notion that nicotine or smoking has acute anorectic actions in smokers.

Adult↗
PubMed1994

Subjective and cardiovascular responses to nicotine combined with caffeine during rest and casual activity.

Although nicotine and caffeine have separately been shown to acutely increase subjective arousal, their combined effects are unclear. Furthermore, their effects during casual physical activity, the condition under which individuals usually experience nicotine and caffeine, are unknown. Smokers who were regular coffee drinkers (n = 19, 9 males, 10 females) participated in eight morning sessions, involving nicotine/placebo, caffeine/no caffeine, and rest/physical activity (i.e. 2 x 2 x 2 within-subjects design). Nicotine (15 micrograms/kg) or placebo was given via measured-dose nasal spray intermittently after consumption of decaf coffee with or without added caffeine (5 mg/kg), followed by subjective [Profile of Mood States (POMS), Stress-Arousal Checklist, visual analog scales] and cardiovascular (heart rate, blood pressure) measures. Casual physical activity was standardized by low-intensity bicycle riding while sitting comfortably. Results indicated significant subjective and cardiovascular effects of nicotine and caffeine individually, with the combination of nicotine and caffeine generally producing additive or greater than additive effects for each measure. However, activity mediated some of the subjective effects of nicotine, as nicotine appeared to be "stimulating" during rest but not during activity. There were no differences between males and females. These findings suggest that nicotine per se and caffeine generally have additive subjective and cardiovascular effects, and that nicotine may influence subjective stimulation differentially depending on whether a smoker is resting or engaged in casual activity.

Adult↗
PubMed1994

Nicotine discrimination in male and female smokers.

Discriminative stimulus effects of nicotine were evaluated in humans using formal behavioral drug discrimination procedures. Male and female smokers (n = 9 each) were trained on day 1 to reliably discriminate 0 versus 12 micrograms/kg nicotine administered by measured-dose nasal spray. All subjects were able to reach criterion performance (at least 80% correct). Generalization of responding across nicotine doses of 0, 2, 4, 8, and 12 micrograms/kg (approximately 0-0.8 mg for typical subject) was then examined on day 2. Nicotine-appropriate responding was linearly related to dose, and subjects were able to distinguish the smallest dose (2 micrograms/kg) from placebo. Although there were no differences between males and females in behavioral discrimination, subjective effects were correlated with nicotine discrimination in females but not in males. These findings indicate that humans are able to discriminate among low doses of nicotine per se, that males and females may differ in the stimuli used to discriminate nicotine, and that drug discrimination procedures may be more sensitive than traditional subjective effects measures in distinguishing among low doses of nicotine.

Adult↗
PubMed1994

Acute thermogenic effects of nicotine combined with caffeine during light physical activity in male and female smokers.

The thermogenic effects of nicotine and caffeine during physical activity compared with rest were examined in male and female smokers (n = 10 each). During eight sessions, nicotine (15 micrograms/kg) or placebo was given via measured-dose nasal spray intermittently after consumption of decaffeinated coffee with or without added caffeine (5 mg/kg), followed by assessment of energy expenditure by indirect calorimetry while subjects engaged in standardized, low-intensity cycle ergometer riding (activity) or remained at quiet rest. Results indicated significant thermogenic effects of nicotine and caffeine individually, with the combination of nicotine and caffeine producing additive effects. Expenditure attributable to nicotine, caffeine, or their combination was significantly enhanced during activity compared with rest, but only for males and not females. Plasma nicotine concentrations were influenced by activity and caffeine, but these pharmacokinetic changes did not appear to explain the differences in expenditure. These findings suggest a sex difference in thermogenic effects of nicotine and caffeine during casual physical activity and potentially explain some of the apparent individual variability in expenditure due to tobacco smoking.

Administration, Intranasal↗
PubMed1994

Alterations in diaphragm strength and fatiguability in congestive heart failure.

Recent reports suggested that exercise intolerance associated with congestive heart failure (CHF) may be due to changes in peripheral limb muscle function. Our purpose was to determine whether CHF also elicits alterations in diaphragmatic function. CHF was induced in dogs by rapid ventricular pacing for a period of 4-6 wk. After signs of CHF developed, dogs were anesthetized and an acute study was performed to assess diaphragm function. Diaphragm strips were dissected in situ in the left costal diaphragm, the phrenic artery supplying these strips was cannulated, and strips were perfused with arterial blood at arteriovenous pressure gradient of 90 mmHg. Diaphragm strength and fatiguability were then determined, and phrenic flow response to transient arterial occlusion was assessed. A group of nonpaced normal dogs was similarly studied and served as controls. We found that CHF dogs had a significant reduction in diaphragm strength. For example, tetanic force in response to 100 Hz of stimulation was 25.5 +/- 1.0 N/cm2 in control dogs but only 19.6 +/- 1.9 kg/cm2 in CHF dogs (P < 0.02). In addition, CHF dogs had increased diaphragm fatiguability. Diaphragm force fell to 27 +/- 3% of its baseline value during a 30-min fatigue trial in CHF dogs but only to 44 +/- 4% in control dogs (P < 0.01). CHF dogs also had a altered phrenic arterial hyperemic response to arterial occlusion and a reduction in phrenic arterial blood flow achieved during the fatigue trial. We conclude that development of CHF is associated with significant alterations in diaphragmatic function, causing a marked increase in fatiguability.

Animals↗
PubMed1993

Effect of ischemia-reperfusion on diaphragm strength and fatigability.

Although episodes of prolonged limb skeletal muscle ischemia followed by periods of reperfusion and reoxygenation are known to elicit free radical-mediated injury, the susceptibility of the diaphragm to this form of injury is not known. The purpose of the present study was to determine the effects of a period of severe partial ischemia, followed by reperfusion, on diaphragm contractile function. We also examined the effect of administration of a free radical scavenger, dimethyl sulfoxide (DMSO), on the diaphragmatic response to ischemia-reperfusion. Experiments were performed on three groups of anesthetized dogs in which a vascularly isolated strip of diaphragm was dissected in situ: 1) a control group in which the diaphragm was perfused at the ambient systemic pressure, 2) a group in which the diaphragm was made ischemic for 3 h and reperfused for 1 h, and 3) a group given DMSO before periods of ischemia and reperfusion. In all groups, we measured diaphragm strip strength and fatigability; we also assessed diaphragm blood flow at several levels of contractile activity. Periods of ischemia, followed by reperfusion, were found to produce a downward shift of the diaphragm force-frequency relationship and also to markedly increase diaphragm fatigability. Diaphragm blood flow at rest and at low levels of contractile activity was unaffected by ischemia-reperfusion, but the flow achieved during fatiguing contractions was appreciably lower than that in nonischemic control animals. DMSO administration protected the diaphragm from the effects of ischemia-reperfusion, preventing alterations in fatigability and strength. Diaphragm flow in DMSO-treated animals was similar to that in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effect of free radical scavengers on endotoxin-induced respiratory muscle dysfunction.

Recent studies have suggested that free radicals contribute to the diaphragmatic dysfunction observed in sepsis. However, previous work has not determined which species of free radicals are responsible for producing these effects or whether the intercostal muscles are affected similarly during sepsis. The purpose of this study was to examine these issues using a hamster model of endotoxin-mediated sepsis in which diaphragm and intercostal muscle function was assessed on muscle strips excised from these animals after killing. Several groups of animals were studied, including animals injected with (1) saline, (2) endotoxin, (3) endotoxin plus active PEG-SOD, a superoxide scavenger, (4) endotoxin plus active PEG-catalase, a hydrogen peroxide scavenger, (5) endotoxin plus DMSO, a hydroxyl scavenger, and (6) endotoxin plus denatured PEG-SOD. We found that endotoxin administration elicited significant reductions in diaphragm and intercostal muscle contractility. In each of the three groups of animals to which active free radical scavengers were administered, the effects of endotoxin were attenuated. Denatured PEG-SOD did not protect the respiratory muscles from endotoxin-mediated dysfunction, however. These data indicate that both the diaphragm and intercostal muscles are affected similarly by sepsis; moreover, several free radical species (superoxide ions, hydrogen peroxide, and hydroxyl ions) play a role in mediating this type of injury.

Animals↗
PubMed1990

Effect of N-acetylcysteine on diaphragm fatigue.

It has recently been postulated that diaphragm fatigue may be due, at least in part, to a form of low-grade injury to subcellular organelles. Moreover, several studies have shown that thiol-containing compounds can protect cardiac and striated skeletal muscle organelles from the deleterious effects of a number of physiological stresses. The purpose of the present study was to determine whether pretreatment with N-acetylcysteine (NAC), a thiol-containing compound, would attenuate the rate of development of diaphragmatic fatigue. Studies were performed with the use of an in situ rabbit diaphragm strip preparation that permitted direct and continuous measurement of diaphragm tension development. Diaphragm fatigue was induced by rhythmically stimulating strips to contract at 30/min (20-Hz trains) for 20 min. The diaphragm force-frequency relationship (10-, 20-, 50-, and 100-Hz stimuli) was assessed immediately before and after fatigue trials and then again 20 min into the period of recovery. Half the animals were treated with intravenous NAC before fatigue, whereas the remaining animals were given intravenous saline. The rate of development of fatigue was markedly greater in saline-treated control than in NAC-treated animals, with reductions in tension of 55 +/- 3 and 34 +/- 3%, respectively, in these two groups of animals over 20 min (P less than 0.001). Although rhythmic stimulation resulted in a downward shift in the force-frequency relationship in both NAC- and saline-treated animals, the magnitude of this shift was substantially greater in saline-treated animals (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗
PubMed1988

Reversibility of diaphragm fatigue by mechanical hyperperfusion.

Diaphragm function is thought to depend on the balance between diaphragm blood flow and metabolic demand. If blood flow is inadequate, fatigue should ensue. Likewise, in the presence of fatigue, function should improve when blood flow is increased. To test this hypothesis, we evaluated the effect of increasing blood flow to the fatigued diaphragm. Studies were performed on anesthetized, mechanically ventilated dogs in which strips of costal diaphragm were developed in situ. Strip tension was measured with an isometric tension transducer. The inferior phrenic artery supplying the strip was cannulated and pump perfused at a pressure of 92 +/- 3 mm Hg; phrenic artery flow and pressure were continuously monitored with in-line doppler flow probes and pressure transducers, respectively. Fatigue was produced by electrically stimulating strips to contract 15 times/min (initial tension 80% of maximum, duty cycle 50%). Rhythmic contraction resulted in a downward shift in the diaphragm force-frequency relationship in all strips. In eight strips, stepwise increments in phrenic artery perfusion pressure to 161 +/- 8 and 281 +/- 17 mm Hg were produced by increasing pump speed at 6 and 8 min into rhythmic stimulation; in four strips, phrenic artery perfusion pressure was increased to 152 +/- 20 and 257 +/- 32 mm Hg at 20 and 25 min into rhythmic stimulation, respectively. Each increase in phrenic artery pressure resulted in increases in phrenic artery flow and diaphragm tension and produced an upshift in the diaphragm force-frequency relationship.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1978

The interaction of daunomycin with polydeoxynucleotides.

The ability of daunomycin to bind to various DNA polymers has been sutided by thermal denaturation, spectrophotometric analysis and inhibition of the polymerisation reactions catalysed by Escherichia coli DNA polymerase I and rat liver DNA polymerase alpha. The quantitative binding measurements revealed that the antibiotic binds tightly to all synthetic polydeoxynucleotides studied. The results demonstrated that daunomycin can bind with equal affinity to dG . dC or dA . dT basepaired sequences. However, the number of binding sites per nucleotide for poly(dA) . poly(dT) is significantly lower than that found for poly(dA-dT) . poly(dA-dT), thus indicating an appreciable preference of the drug for the alternating copolymer. The inactivation of the template properties of the synthetic DNA polymers in the DNA polymerase system is consistent with their daunomycin binding ability. However, a lack of correlation was observed between the drug binding ability of different DNA polymers and the binding-induced stabilisation of the double helix to heat denaturation.

Animals↗
PubMed1975

Synthesis and antitumor properties of new glycosides of daunomycinone and adriamycinone.

The synthesis of 4'-epi-daunorubicin and of 4'-epi-adriamycin was performed by condensation of 2,3,6-trideoxy-3-trifluoroacetamido-4-O-trifluoroacetyl-alpha-L-arabino-hexopyranosyl chloride with daunomycinone or the protected adriamycinone derivative 17, respectively. Both the alpha and beta anomers were obtained and characterized. All new compounds are biologically active in cultured cells and the alpha anomers display noticeable activity in experimental tumors in mice. Interestingly, 4'-epi-adriamycin (4) appears nontoxic to cultured heart cells up to a concentration of 5 mug/ml.

Aminoglycosides↗