Healthy Adult Male Subjects Research Articles

Sex-dependent alteration in cortisol response to endogenous adrenocorticotropin.

We have investigated ACTH and cortisol secretion patterns in two groups of five healthy adult male and female subjects. Plasma samples were obtained at 10-min intervals for 24 h, and pulsatile hormone release was analyzed by a multiparameter deconvolution technique. ACTH secretion was greater in male than female subjects; the production rate per 24 h was 139 +/- 7 pmol/L distribution volume in males, and 89 +/- 11 pmol/L distribution volume in females (P = 0.007). Cortisol secretion did not differ significantly between sexes; in males, the 24-h secretion rate was 2807 +/- 239 nmol/L distribution volume, and in females, it was 2970 +/- 411 nmol/L distribution volume (P = NS). The number of ACTH secretory pulses per 24 h, as determined by deconvolution analysis, was 16.2 +/- 1.4 in males and 19.6 +/- 2.0 in females (P = NS). There were no sex differences in the number of cortisol pulses or the calculated half-lives of ACTH and cortisol. ACTH and cortisol pulses were significantly concordant at a cortisol lag time of 10 min, as demonstrated by probability analysis and cross-correlation with auto-regressive modeling. Based on a significantly different regression intercept of cortisol pulse height on ACTH pulse height in women than in men (P < 0.001) and a higher ratio of cortisol to ACTH production rates in women than in men (P = 0.013), we suggest that the female adrenal cortex is more responsive to ACTH than its male counterpart in terms of glucocorticoid production. Consequently, equivalent daily cortisol secretion rates are attained in men and women at the expense of greater ACTH release in men.

Computer-based analysis of continuous non-invasive blood pressure and heart rate variability-methodology and normal values during wakefulness and sleep.

Polysomnographic recordings were made in 10 healthy male adult subjects (mean age 25.1 +/- 2.8 years). Parameters were obtained from continuous non-invasive measurement of blood pressure and from heart rate spectra analysed both in the waking state and during sleep (stage 4). The total heart rate variability (mean +/- SE) was not significantly diminished (p < 0.2; paired t-test) during stage 4 sleep (6.2 +/- 0.5%) as compared with the waking state (7.1 +/- 0.5%). The relative heart rate variability coefficient within the frequency band HRV-II ((3-9)/min) was, however, significantly higher (p < 0.001) during slow-wave sleep (0.55 +/- 0.04) than during wakefulness (0.34 +/- 0.04). This fact is in accordance with results concerning an estimated value of the baroreflex sensitivity, which was also significantly higher (p < 0.001) during sleep stage 4 (7.0 +/- 0.8 ms/mmHg vs. 10.4 +/- 1.4 mmHg).

Metabolism of carotenoid analogs in humans

Single oral doses (100 mumol) in peanut oil of 4,4'-dimethoxy-beta-carotene, ethyl beta-apo-8'-carotenoate, and beta-apo-8'-carotenal were administered to healthy adult male subjects (n = 4-6). Blood samples were taken frequently thereafter, and serum carotenoids and retinoids were analyzed by HPLC. The metabolism of the three analogs was very different; 4,4'-dimethoxy-beta-carotene was oxidized at the 4 and 4' positions but apparently not cleaved, whereas ethyl beta-apo-8'-carotenoate was not detectably metabolized, and beta-apo-8'-carotenal was extensively converted to its corresponding acid, alcohol, and fatty acyl ester and detectably converted to retinyl ester and possibly to two shorter beta-apocarotenals. Serum concentrations of endogenous retinoids and carotenoids, except as noted above, were not affected in any case. Kinetically, the maximum serum concentrations, areas under the curve, and mean sojourn times for the three analogs differed by 50-, 270-, and 5-fold, respectively. For any given analog, however, the fractional standard deviations for these parameters were only 0.2-0.5.

23Na-NMR study of cation cotransport in human red blood cells.

Na(+)-K+ cotransport in human erythrocytes from healthy subjects has been studied by means of 23Na-nuclear magnetic resonance (NMR) in the presence of the anionic paramagnetic shift reagent dysprosium (III) tripolyphosphate [Dy(PPP)2(7-)]. The intra- and extracellular 23Na-NMR signals were well separated, giving values of 6 +/- 1 mM for internal sodium concentration. Determination of the furosemide-sensitive Na+ efflux, in the presence of ouabain, was obtained by correlating the chemical shift variation of the external signal with changes in external Na+ concentration. For this purpose, calibration curves were generated. The values of the maximum efflux velocity (Vmax; 0.29-1 mmol.h-1.l cells-1) measured in 10 healthy adult male subjects were found to be within the range of values obtained by other authors. The NMR method proposed for the study of Na(+)-K+ cotransport is relatively simple and allows quick evaluation of cotransport Vmax values for a number of samples, being a good candidate for the study of this transport mechanism in the presence of different pathologies.

Transfer function of sound transmission in subglottal human respiratory system at low frequencies

The amplitude of sound transmission from the mouth to a site overlying the extrathoracic trachea and two sites on the posterior chest wall was measured in eight healthy adult male subjects at resting lung volume over the 100- to 600-Hz frequency range. The ratios of the estimated magnitude spectra of transmission of each of the chest wall sites to the tracheal site were determined, with the resulting spectra representing effective transfer functions of transmission in the subglottal system. For the group, the transfer functions exhibited a single peak, which occurred at 143 +/- 13 Hz (mean +/- SD) with a quality factor (Q) of 2.0 +/- 0.2 for the upper chest wall site and at 129 +/- 6 Hz with a Q of 2.2 +/- 0.4 for the lower site. The trend of decreasing spectral energy with increasing frequency was indicated by roll-offs of -10 +/- 4 and -17 +/- 5 dB/octave from 300 to 600 Hz at the two sites, respectively. The fundamental radial mode of a model thoracic cavity, which is a large rigid cylinder filled with lossless lung tissue, provides a good estimate of the observed low-frequency resonance. This agreement suggests that thoracic cavity resonances may have particularly important effects on sound transmission at frequencies below approximately 250 Hz, where the magnitude of parenchymal attenuation appears to be small.

Hemodynamics of Blood Pressure Responses During Active and Passive Coping

This laboratory study was designed to address a number of interrelated issues regarding cardiovascular reactivity to psychological stress. One objective was to extend the previous research comparing cardiovascular responses during active versus passive coping, by comparing responses to two task conditions designed to be similar in all ways except the opportunity to make a response influencing the task's outcome. A second objective was to compare responses to two different passive film tasks, which differed in outcome uncertainty and the degree of vicarious active coping achieved through identification with the role portrayed by the actors. A third objective was to evaluate whether individuals are predisposed to exhibit a particular hemodynamic pattern underlying their blood pressure adjustments, independently of the task demands imposed. Ninety healthy young adult male subjects were tested in pairs on a series of tasks that included a competitive reaction-time task, an active as well as a passive phase of a team reaction-time task, and passive viewing of two film segments. The tasks demanding active coping responses tended to raise blood pressure due primarily to an increase in cardiac output, while vascular resistance fell. During passive coping demands cardiac output increased to a lesser extent, but vascular resistance also tended to increase, thereby raising blood pressure by their synergistic effects. However, these patterns were not typical of all participating subjects. On the basis of their cardiac output and vascular resistance responses to the competitive reaction-time task, one third of the subjects were categorized as being high myocardial reactors (n = 30) and another third high vascular reactors (n = 31). Post-hoc analyses of responses to the other tasks, based on these categorizations, indicated that the hemodynamic basis of reactivity is an individual characteristic only partially modified by coping demands. The active/passive coping dimension is discussed both conceptually and in relation to the role of stress in the etiology of hypertension.

Effect of mefenamic acid on bowel transit time in healthy adult volunteers

The effect of mefenamic acid on bowel transit time was investigated. Seven healthy adult male subjects of age 39 +/- 2.4 years (mean +/- S.E.M.) received placebo or mefenamic acid (500 mg t.d.s) orally in randomized order for five days, with a 7-day washout between studies. On the third morning after starting the drug they had a meal containing Redi-Brek and baked beans with radio-opaque markers. Small bowel transit time was measured using breath hydrogen, and whole gut transit time was measured using radio-opaque markers. The small bowel transit times were 160 min (median) with placebo and 50 min with mefenamic acid (P less than 0.05). The percentages of appearance of marker in stool within 24 h were 24.9 +/- 11.8 (mean +/- S.E.M.) with placebo and 48.9 +/- 11.7 with mefenamic acid (P less than 0.05). The times of appearance of twenty-fifth marker in stool were 41.0 +/- 4.4 h with placebo and 26.9 +/- 3.2 h with mefenamic acid (P less than 0.05). The total weights of faeces in 72 h were 500.9 +/- 96.2 g with placebo and 657.1 +/- 118.8 g with mefenamic acid (P less than 0.05). Mefenamic acid in therapeutic doses (500 mg t.d.s.) accelerated bowel transit time in healthy subjects.

Urinary excretion of 3-methylhistidine as an index of protein nutrition in total parenteral nutrition.

In 39 healthy adult volunteers and nine patients receiving total parenteral nutrition (TPN), determinations were made of the urinary excretion of 3-methylhistidine (3-Mehis) to estimate the degree to which the urinary output of 3-Mehis reflects the status of protein nutrition. In 19 males and 10 females of the former group, measurements were made of the amount of 3-Mehis and of creatinine (Cr) in 24-hr urine samples. The urinary output of 3-Mehis was also measured in two subgroups of five healthy adult male subjects who were fed one of the two different diets prescribed: meat (M) and meat-free (F) diet. Furthermore, in one of these subgroups which was fed on F diet, the urinary output of 3-Mehis was measured both while the subject was kept at bed rest and while the subject was allowed to live a normal life. From these measurements the standard value was determined for the urine 3-Mehis level and the 3-Mehis/Cr ratio in 24-hr urine in healthy adult human subjects of both sexes. In nine patients maintained on TPN these indices of nutritional status were measured before and at 4 weeks of TPN. The time course of the indices was also investigated. The results obtained suggest that both the urinary output of 3-Mehis and the 3-Mehis/Cr ratio can provide a sensitive index of the status of protein nutrition.

Effects of Exposure to Magnetic Resonance Imaging on Nocturnal Serum Melatonin and Other Hormone Levels in Adult Males: Preliminary Findings

Previous investigations have demonstrated that weak artificial magnetic fields can inhibit nocturnal pineal melatonin synthesis in rats. Nuclear magnetic resonance imaging (MRI) is an increasingly popular procedure used for advanced medical imaging and requires patients to be exposed to a variety of magnetic field conditions which could alter nocturnal melatonin levels. In the present study four healthy adult male subjects were exposed to a typical clinical MRI procedure for 40.5 min during the mid-dark portion of their daily light-dark cycle. Serum levels of melatonin, cortisol, prolactin and growth hormone were measured at hourly intervals for 3 hrs prior to, and for 3 hrs after, exposure to the MRI procedure or a sham exposure condition. Analysis of the results

Glutamine and glutamate kinetics in humans.

To study glutamate and glutamine kinetics, 4-h unprimed intravenous infusions of L-[15N]glutamate, L-[2-15N]glutamine, and L-[5-15N]-glutamine were administered to healthy young adult male subjects in the postabsorptive state. Arterialized-venous blood samples were drawn and analyzed for glutamate and glutamine 15N enrichments. The fractional turnover rates of the tracer-miscible glutamate and glutamine pools were fast, 8.0 and 2.8% min-1, respectively. The glutamate tracer-miscible pool accounted for less than one-tenth the estimated free glutamate pool in the body. The plasma glutamate amino N, glutamine amino N and glutamine amide N rates of appearance were 83 +/- 22 (means +/- SD), 348 +/- 33, and 283 +/- 31 mumol X kg-1 X h-1, respectively. The glutamine amide N appearance rate was 20% slower than the amino N appearance rate, indicating that glutamine transaminase is an active pathway in human glutamine metabolism. From measurement of transfer of tracer 15N, we found that only 5% of the glutamine synthesized in cells and released into plasma was derived from intracellular glutamate that had mixed with plasma. These data demonstrate that intravenously administered tracers of glutamate or glutamine do not mix thoroughly with the intracellular pools, and their measured kinetics reflect transport rates through plasma rather than whole-body fluxes.

Effects of Auricular Transcutaneous Electrical Nerve Stimulation on Experimental Pain Threshold

This study was conducted to examine the effects of high intensity transcutaneous electrical nerve stimulation at auricular acupuncture points on experimental pain threshold. Forty-five healthy adult male and female subjects were assigned randomly to one of two treatment groups or to a control group. Subjects in the two treatment groups received high intensity TENS to either appropriate or inappropriate (placebo) acupuncture points on one ear. Experimental pain threshold at the ipsilateral wrist was determined with a painful electrical stimulus before and after ear stimulation. Only the group receiving stimulation of appropriate ear acupuncture points exhibited a significant increase (p less than .01) in experimental pain threshold after ear stimulation. The comparable placebo and control groups, again, did not exhibit significant pretest-posttest differences in experimental pain threshold. The results suggest that, if applied accurately, auricular TENS can increase pain threshold. Further research is needed to assess the effects of this technique on patient groups.

Effects of Transferrin Genetic Phenotypes on Total Iron-Binding Capacity

Serum transferrin level and total iron-binding capacity (TIBC) were studied in a group of 297 healthy adult male subjects having HbAA and G6PDB+ phenotypes by standard chemical and immunoelectrophoretic techniques to examine the influence of different transferrin variants on these parameters. TIBC (67.1 +/- 13.4 mumol/l) and transferrin concentrations (27.0 +/- 3.95 mumol/l) for the whole group were found to be within reported normal values. Serum transferrin concentrations of the subjects having different electrophoretic variants and TfC subtypes of transferrin were not significantly different from each other. There was no significant difference of TIBC in relation to different electrophoretic variants of Tf. However, the TIBC of the subjects of the 1-1 subtype of TfC (70.4 +/- 13.6 mumol/l) was significantly higher than that of the 2-1 subtype (65.0 +/- 12.8 mumol/l; p less than 0.05) as well as that of the 2-2 subtype (60.4 +/- 11.4 mumol/l; p less than 0.01).

Cellular and humoral modifications during response to HBsAg vaccine in healthy subjects

Summary Eighteen healthy adult male subjects, living in a work environment with hepatitis B surface antigen (HBsAg) carriers, were vaccinated against hepatitis B with French vaccine. Immunological monitoring, performed on days 0, 15, 30, 45, 60, 90 and 120, concerned (1) specific humoral and cell-mediated immunity to HBsAg (cell-mediated immunity was explored in only 13 subjects by the leukocyte migration inhibitory test, or LMIT), (2) autologous mixed lymphocyte reaction (AMLR), (3) OKT3-, T4- and T8-positive lymphocytes, (4) the study of phagocytic respiratory activity, and (5) autoantibodies and circulating immune complexes (CIC). Absolute clinical, hepatic and immunological safety, as documented by the absence of clinical side-effects, no change in serum transaminase levels and the lack of appearance of CIC and/or autoantibodies, was observed. Specific seroconversion, absent on the 15th day, reached 89% in subjects by the 90th day, whereas specific cell-mediated conversion seemed to occur earlier (many subjects already showed LMIT positivity by day 15). For monoclonal antibodies and AMLR, an increase in OKT8+ lymphocytes on day 60, seen only among normal responders, was observed with a subsequent reduction in the OKT4/OKT8 ratio and a reduction of the proliferative response in AMLR on the 45th day (except in the only non-responding subject tested). No significant variations in granulocyte respiratory activity were evident. These results are discussed, focusing on the role of cellular immunity during anti-HBsAg vaccination.

Pulmonary response to threshold levels of sulfur dioxide (1.0 ppm) and ozone (0.3 ppm).

We exposed 22 healthy adult nonsmoking male subjects for 2 h to filtered air, 1.0 ppm sulfur dioxide (SO2), 0.3 ppm ozone (O3), or the combination of 1.0 ppm SO2 + 0.3 ppm O3. We hypothesized that exposure to near-threshold concentrations of these pollutants would allow us to observe any interaction between the two pollutants that might have been masked by the more obvious response to the higher concentrations of O3 used in previous studies. Each subject alternated 30-min treadmill exercise with 10-min rest periods for the 2 h. The average exercise ventilation measured during the last 5 min of exercise was 38 1/min (BTPS). Forced expiratory maneuvers were performed before exposure and 5 min after each of the three exercise periods. Maximum voluntary ventilation, He dilution functional residual capacity, thoracic gas volume, and airway resistance were measured before and after the exposure. After O3 exposure alone, forced expiratory measurements (FVC, FEV1.0, and FEF25-75%) were significantly decreased. The combined exposure to SO2 + O3 produced similar but smaller decreases in these measures. There were small but significant differences between the O3 and the O3 + SO2 exposure for FVC, FEV1.0, FEV2.0, FEV3.0, and FEF25-75% at the end of the 2-h exposure. We conclude that, with these pollutant concentrations, there is no additive or synergistic effect of the two pollutants on pulmonary function.

Orotic acid excretion during starvation and refeeding in normal men

The effects of acute food deprivation and subsequent refeeding on urinary orotic acid excretion were examined in nine healthy adult male subjects. During inpatient metabolic ward conditions, the volunteers were fed a nutritionally complete, pyrimidine- and purine-free diet for three days and subsequently underwent a ten-day fast followed by a ten-day period of refeeding by total parenteral nutrition. Mean daily excretion of 4.33 ± 0.23 mg (2.77 ± 0.12 mg/g creatinine) of orotic acid during the enterally fed state was significantly reduced (mean 46 ± 5%) in all subjects during starvation. This reduction in the excretion of orotic acid during starvation is more likely related to a lowered rate of production and utilization. The starvation adaptation of orotate excretion occurred more rapidly than did the decrease in urinary nitrogen loss. All subjects showed an increase (mean 48 ± 14%) in the excretion of orotic acid during the first day of refeeding which continued throughout the refeeding phase. A significant positive correlation was shown between the daily orotic acid excretion and nitrogen intake ( r = 0.98) or protein balance (r = 0.83). The response to refeeding of acutely malnourished normal male is an increase in orotic acid excretion with a decrease in whole body protein catabolism.

Quantitative Aspects of Glycine and Alanine Nitrogen Metabolism in Postabsorptive Young Men: Effects of Level of Nitrogen and Dispensable Amino Acid Intake

The nutritionally indispensable amino acids (IAA) alone do not maintain body nitrogen (N) balance; a source of “nonspecific” nitrogen from dispensable amino acids (DAA), such as from glycine and alanine or other N compounds, is required. However, the in vivo regulation of the metabolism of these amino acids in humans with varying nutritional states has received little study. Hence, the effects of N intake and the IAA:DAA ratio on kinetic aspects of whole-body alanine and glycine metabolism were examined in eight healthy young adult male subjects. They received an L-amino acid diet supplying N equivalent to about 1.5 g and 0.6 g protein (N × 6.25) per kilogram body weight per day. All were studies at each N level with the IAA:DAA ratio (wt/wt) of 1:1 and 1:0, each for a 7-d diet period. Constant primed, intravenous infusions of L-[l-13C]leucine together with either L-[15N]alanine (four subjects) or [15N]glycine (four subjects) were given to each subject at the end of the diet period, after an overnight fast, to determine rates of de novo whole-body alanine and glycine N synthesis. The rate of alanine synthesis was similar (P > 0.05) for all four diets. Glycine de novo N synthesis declined (P < 0.01) with removal of dietary DAA, especially at the lower intake, where the mean rates [micromoles/(kilogram·hour)] were 59 and 20 for 1:1 and 1:0 ratios, respectively. The possible significance of reduced rates of glycine N synthesis for maintenance of protein nutritional status in the healthy adult is discussed.

Comparative virulence and immunogenicity of the Towne strain and a nonattenuated strain of cytomegalovirus.

The Towne strain cytomegalovirus and a low-passage strain, Toledo-1, were compared for virulence and immunogenicity in healthy adult male subjects to determine the suitability of the Towne strain for vaccination. Five seropositive subjects who received the Toledo-1 strain developed infections ranging in severity from laboratory abnormalities to mild mononucleosis syndromes (mean incubation, 4.7 weeks). None of the four seronegative subjects receiving the Towne strain developed systemic infection, but all developed delayed local reactions at the injection sites. All subjects developed cytotoxic lymphocyte responses specific to cytomegalovirus, usually HLA-restricted, but these were of greater magnitude and duration in the Toledo-1 recipients. The latter also developed natural killer cell and interferon responses, atypical lymphocytosis, inversion of helper/suppressor cell ratios, and depressed responses to T-cell mitogens, none of which occurred in Towne strain recipients. The results further substantiate the avirulence and immunogenicity of the Towne strain cytomegalovirus.

Isokinetic Evaluation of Tibial Rotation: Assessment of a Stabilization Technique

The purpose of this study was to present a wide range of normative data on maximum active tibial rotation utilizing isokinetic resistance and a relatively new stabilization technique. Both legs of 25 healthy adult male subjects were tested at 30, 60, 120, and 180 degrees per second of angular velocity. Data were collected on total range of motion, component internal/external range of motion (via two different methods), joint position at peak torque production, peak torque production, and torque production as a percentage of body weight. The effect of weight and leg length on peak torque production and total range of motion was also determined. In light of recent studies which have shown the need for specific rotational rehabilitation for rotatory knee instabilities, this study serves to present normative data for practical use in either the clinical or research setting. J Orthop Sports Phys Ther 1984;6(1):46-51.

Exposure-effect relationship of selected pulmonary function measurements in subjects exposed to ozone.

Healthy adult male volunteer subjects were exposed to 0.15, 0.3, 0.45 and 0.5 ppm ozone (O3) with and without intermittent light exercise. The results suggest that the subject's level of exercise during exposure is considerably related to the magnitude of changes in lung function and the occurrence rate of respiratory symptoms at any given O3 concentration, and that among healthy subjects there is a considerable range of reactivity to O3 exposure. A level of 0.15 ppm O3 with intermittent light exercise produced a significant decrease of specific airway conductance in most subjects and coughing during deep inspiration in five of 15 subjects, while a level of 0.5 ppm O3 produced fewer effects when the subject did not exercise. The nonsmoker is more reactive to O3 than the smoker. The subject's level of exercise during exposure and his smoking habit are two important factors in evaluating the exposure-effect relationship of O3.

Circadian variation in the urinary excretion of electrolytes and trace elements in men

Three-hour urine specimens were collected over a period of 27 hours from 11 healthy adult male subjects. Each specimen was analyzed for Na, K, Ca, Mg, and Zn using atomic absorption spectrophotometry. Each sample was also dialyzed, pH 7.35, and subsequently analyzed for Na, K, P, Ca, Mg, Zn, Fe, Pb, Al, Ni, Cu, Mo, Hg, Cr, Cd, and Mn using a multielemental argon-plasma emission system. The data were evaluated on conventional time plots (chronograms) and as computer-determined "cosinor" plots. A population circadian rhythm with a statistical significance was detected for total Na, K, Ca, and Mg, and for nondialyzable Na, K, P, Ca, Zn, and Mo. For almost every element studied the increase from lowest to highest 3-hour group mean along the 24-hour time scale was more than 100%. The 24-hour excretion of Na, K, Ca, Mg, and Zn appeared in good agreement with the so-called "normals." The nondialyzable levels of Fe, Pb, Al, Ni, Cu, Mo, Hg, Cr, Cd, and Mn were similar to the total urinary excretions reported in the literature.