Plasma leptin suppression by arginine vasopressin in normal women and men

Leptin inhibits appetite by activating several neuroendocrine systems, including the hypothalamo-pituitary-adrenal cortical (HPA) axis. In turn, elevated glucocorticoids can increase circulating leptin. We therefore measured plasma leptin in 12 normal women and eight normal men administered low-dose physostigmine (PHYSO) and arginine vasopressin (AVP) to stimulate the HPA axis. The subjects underwent four test sessions 5-7 days apart: PHYSO (8 microg/kg IV), AVP (0.08 U/kg IM), PHYSO + AVP, and saline control. Serial blood samples were taken before and after pharmacologic challenge and analyzed for leptin, adrenocorticotropin (ACTH)1-39, cortisol, and AVP. Estradiol and testosterone also were measured at each test session. PHYSO and AVP produced no side effects in about half the subjects and predominantly mild side effects in the other half, with no significant female-male differences. Correlations between side effects (absent or present) after PHYSO or AVP and the corresponding leptin responses were nonsignificant. Baseline plasma leptin concentrations were significantly higher in the women than in the men (p < 0.003). Leptin concentrations following PHYSO remained unchanged from baseline, indicating that the short-lived ACTH and cortisol increases produced by PHYSO did not affect leptin secretion. In contrast, AVP administration, while also increasing ACTH and cortisol, suppressed leptin, to a significantly greater degree in the women than in the men (p = 0.01). This significant suppression of leptin by AVP has not been previously described; physiologically, it may be part of a negative feedback regulatory system between central leptin and its activation of the HPA axis, by inhibition of leptin production or acceleration of its clearance.     

Effect of REM sleep on retroglossal cross-sectional area and compliance in normal subjects.

It has been proposed that the upper airway compliance should be highest during rapid eye movement (REM) sleep. Evidence suggests that the increased compliance is secondary to an increased retroglossal compliance. To test this hypothesis, we examined the effect of sleep stage on the relationship of retroglossal cross-sectional area (CSA; visualized with a fiber-optic scope) to pharyngeal pressure measured at the level of the oropharynx during eupneic breathing in subjects without significant sleep-disordered breathing. Breaths during REM sleep were divided into phasic (associated with eye movement, PREM) and tonic (not associated with eye movements, TREM). Retroglossal CSA decreased with non-REM (NREM) sleep and decreased further in PREM [wake 156.8 +/- 48.6 mm(2), NREM 104.6 +/- 65.0 mm(2) (P < 0.05 wake vs. NREM), TREM 83.1 +/- 46.4 mm(2) (P = not significant NREM vs. TREM), PREM 73.9 + 39.2 mm(2) (P < 0.05 TREM vs. PREM)]. Retroglossal compliance, defined as the slope of the regression CSA vs. pharyngeal pressure, was the same between all four conditions (wake -0.7 + 2.1 mm(2)/cmH(2)O, NREM 0.6 +/- 3.0 mm(2)/cmH(2)O, TREM -0.2 +/- 3.3 mm(2)/cmH(2)O, PREM -0.6 +/- 5.1 mm(2)/cmH(2)O, P = not significant). We conclude that the intrinsic properties of the airway wall determine retroglossal compliance independent of changes in the neuromuscular activity associated with changes in sleep state.     

Quadriceps cross-sectional area changes in young healthy men with different magnitude of Q angle

Knee pain and dysfunction have been often associated with an ineffective pull of the patella by the vastus medialis (VM) relative to the vastus lateralis (VL), particularly in individuals with knee joint malalignment. Such changes in muscular behavior may be attributed to muscle inhibition and/or atrophy that precedes the onset of symptoms. The aim of this study was to investigate possible effects of knee joint malalignment, indicated by a high quadriceps (Q) angle (HQ angle >15 degrees ), on the anatomic cross-sectional area (aCSA) of the entire quadriceps and its individual parts, in a group of 17 young asymptomatic men compared with a group of 19 asymptomatic individuals with low Q angle (LQ angle <15 degrees ). The aCSA of the entire quadriceps (TQ), VM, VL, vastus intermedius (VI), rectus femoris (RF), and patellar tendon (PT) were measured during static and dynamic magnetic resonance imaging (MRI) with the quadriceps relaxed and under contraction, respectively. A statistically significant lower aCSA was obtained in the HQ angle group, compared with the LQ angle group, for the TQ, VL, and VI in both static (TQ = 9.9%, VL = 12.9%, and VI = 9.1%; P < 0.05) and dynamic imaging (TQ = 10.7%, P < 0.001; VL = 13.4%, P < 0.01; and VI = 9.8%, P < 0.05) and the aCSA of the VM in dynamic MRI (11.9%; P < 0.01). The muscle atrophy obtained in the HQ angle group may be the result of a protective mechanism that inhibits and progressively adapts muscle behavior to reduce abnormal loading and wear of joint structures.     

Muscle cross-sectional area, force production and relaxation characteristics in women at different ages

Thirty women, divided among three different age groups, i.e. 30 years (range 26-35; n = 10), 50 years (range 46-55; n = 10) and 70 years (range 66-75; n = 10) volunteered as subjects for examination of the characteristics of the muscle cross-sectional area (CSA), maximal voluntary isometric force, isometric force-time and relaxation-time of their leg extensor muscles. The CSA of the quadriceps femoris muscle in the youngest age group was slightly larger (NS) than in the middle-aged group and much larger (P less than 0.01) than in the oldest age group whose CSA was markedly smaller (P less than 0.01) than the middle-aged group. Maximal force in the youngest group was slightly greater (NS) than in the middle-aged group and much greater (P less than 0.01) than in the oldest group whose values were markedly smaller (P less than 0.05) than the middle-aged group. The individual values in CSA correlated with maximal force both in the total subject sample (r = 0.82; P less than 0.001) and in the three age groups separately (r = 0.72; P less than 0.01; r = 0.86; P less than 0.01 and r = 0.67; P less than 0.05, respectively). When the force values were related to the CSA of the muscle, the mean values of 45.4 N.cm-2, SD 5.6, 47.6 N.cm-2, SD 5.0 and 46.8 N.cm-2, SD 7.0 for the three groups did not differ significantly from each other.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determinants of fat oxidation during exercise in healthy men and women: a cross-sectional study.

The aim of the present study was to establish fat oxidation rates over a range of exercise intensities in a large group of healthy men and women. It was hypothesised that exercise intensity is of primary importance to the regulation of fat oxidation and that gender, body composition, physical activity level, and training status are secondary and can explain part of the observed interindividual variation. For this purpose, 300 healthy men and women (157 men and 143 women) performed an incremental exercise test to exhaustion on a treadmill [adapted from a previous protocol (Achten J, Venables MC, and Jeukendrup AE. Metabolism 52: 747-752, 2003)]. Substrate oxidation was determined using indirect calorimetry. For each individual, maximal fat oxidation (MFO) and the intensity at which MFO occurred (Fat(max)) were determined. On average, MFO was 7.8 +/- 0.13 mg.kg fat-free mass (FFM)(-1).min(-1) and occurred at 48.3 +/- 0.9% maximal oxygen uptake (Vo(2 max)), equivalent to 61.5 +/- 0.6% maximal heart rate. MFO (7.4 +/- 0.2 vs. 8.3 +/- 0.2 mg.kg.FFM(-1).min(-1); P < 0.01) and Fat(max) (45 +/- 1 vs. 52 +/- 1% Vo(2 max); P < 0.01) were significantly lower in men compared with women. When corrected for FFM, MFO was predicted by physical activity (self-reported physical activity level), Vo(2 max), and gender (R(2) = 0.12) but not with fat mass. Men compared with women had lower rates of fat oxidation and an earlier shift to using carbohydrate as the dominant fuel. Physical activity, Vo(2 max), and gender explained only 12% of the interindividual variation in MFO during exercise, whereas body fatness was not a predictor. The interindividual variation in fat oxidation remains largely unexplained.     

The prolactin response to intravenous dextroamphetamine in normal young men and postmenopausal women

D-amphetamine was administered intravenously in doses of 0.1 mg/kg and 0.15 mg/kg to normal young men and postmenopausal women in both morning and evening. No suppression of PRL secretion after amphetamine was found, and, in the postmenopausal women, no significant change in PRL levels in any dose or time condition occured. However, a significant and relatively consistent PRL release was induced in the young men in the evening by the higher dose. This latter response suggests that, in humans, dextroamphetamine can actually stimulate prolactin perhaps by a mechanism other than alteration in dopaminergic tone.     

A cross-sectional study of muscle strength and mass in 45- to 78-yr-old men and women

The isokinetic strength of the elbow and knee extensors and flexors was measured in 200 healthy 45- to 78-yr-old men and women to examine the relationship between muscle strength, age, and body composition. Peak torque was measured at 60 and 240 degrees/s in the knee and at 60 and 180 degrees/s in the elbow by use of a Cybex II isokinetic dynamometer. Fat-free mass (FFM) was estimated by hydrostatic weighing in all subjects, and muscle mass (MM) was determined in 141 subjects from urinary creatinine excretion. FFM and MM were significantly lower (P less than 0.001) in the oldest group. Strength of all muscle groups at both testing speeds was significantly (P less than 0.006) lower (range 15.5-26.7%) in the 65- to 78- than in the 45- to 54-yr-old men and women. When strength was adjusted for FFM or MM, the age-related differences were not significant in all muscle groups except the knee extensors tested at 240 degrees/s. Absolute strength of the women ranged from 42.2 to 62.8% that of men. When strength was expressed per kilogram of MM, these gender differences were smaller and/or not present. These data suggest that MM is a major determinant of the age- and gender-related differences in skeletal muscle strength. Furthermore, this finding is, to a large extent, independent of muscle location (upper vs. lower extremities) and function (extension vs. flexion).     

In vivo physiological cross-sectional area and specific force are reduced in the gastrocnemius of elderly men.

Sarcopenia and muscle weakness are well-known consequences of aging. The aim of the present study was to ascertain whether a decrease in fascicle force (Ff) could be accounted for entirely by muscle atrophy. In vivo physiological cross-sectional area (PCSA) and specific force (Ff/PCSA) of the lateral head of the gastrocnemius (GL) muscle were assessed in a group of elderly men [EM, aged 73.8 yr (SD 3.5), height 173.4 cm (SD 4.4), weight 78.4 kg (SD 8.3); means (SD)] and for comparison in a group of young men [YM, aged 25.3 yr (SD 4.4), height 176.4 cm (SD 7.7), weight 79.1 kg (SD 11.9)]. GL muscle volume (Vol) and Achilles tendon moment arm length were evaluated using magnetic resonance imaging. Pennation angle and fiber fascicle length (Lf) were measured using B-mode ultrasonography during isometric maximum voluntary contraction of the plantar flexors. PCSA was estimated as Vol/Lf. GL Ff was calculated by dividing Achilles tendon force by the cosine of theta, during the interpolation of a supramaximal doublet, and accounting for antagonist activation level (assessed using EMG), Achilles tendon moment arm length, and the relative PCSA of the GL within the plantar flexor group. Voluntary activation of the plantar flexors was lower in the EM than in the YM (86 vs. 98%, respectively, P < 0.05). Compared with the YM, plantar flexor maximal voluntary contraction torque and Ff of the EM were lower by 47 and 40%, respectively (P < 0.01). Both Vol and PCSA were smaller in the EM by 28% (P < 0.01) and 16% (P < 0.05), respectively. Also, pennation angle was 12% smaller in the EM, whereas there was no significant difference in Lf between the YM and EM. After accounting for differences in agonists and antagonists activation, the Ff/PCSA of the EM was 30% lower than that of the YM (P < 0.01). These findings demonstrate that the loss of muscle strength with aging may be explained not only by a reduction in voluntary drive to the muscle, but mostly by a decrease in intrinsic muscle force. This phenomenon may possibly be due to a reduction in single-fiber specific tension.     

Direct radioimmunoassay of specific urinary estrogen glucosiduronates in normal men and nonpregnant women.

Direct radioimmunoassay are described for the measurement of each of three specific estrogen glucosiduronates: estrone glucosiduronate, 17 beta-estradiol-17-glucosiduronate and estriol-16 alpha-glucosiduronate in urine. Each assay utilizes a specific antiserum prepared by complexing the carboxylic acid group of the appropriate glucosiduronate to the epsilon-amino group of lysine in bovine serum albumin or bovine thyroglobulin. The antisera showed little or no cross reactivity toward other estrogens that might be present in significant amounts in urine. These antisera were used for the direct assay of the conjugates in urine from normal men and nonpregnant women without prior extraction or chromatography. The values were similar to those obtained after extraction, chromatographic purification on DEAE-Sephadex and subsequent immunoassay; The following mean values +/- SE (microgram/g creatinine) were obtained: estrone glucosiduronate, male 10.1 +/- 0.6, follicular phase female 17.3+/- 1.6, luteal phase female 31.8 +/- 2.5; 17 beta-estradiol-17-glucosiduronate, male 1.7 +/- 0.3, follicular phase female 2.4 +/- 0.1, luteal phase female 4.2 +/- 0.4; estriol-16 alpha-glucosiduronate, male 1.8 +/- 0.2, follicular phase female 4.7 +/- 0.9, luteal phase female 10.0 +/- 1.6.     

Respiratory system loop gain in normal men and women measured with proportional-assist ventilation.

We hypothesized that increased chemical control instability (CCI) in men could partially explain the male predominance in obstructive sleep apnea (OSA). CCI was assessed by sequentially increasing respiratory control system loop gain (LG) with proportional-assist ventilation (PAV) in 10 men (age 24-48 yr) and 9 women (age 22-36 yr) until periodic breathing or awakening occurred. Women were studied in both the follicular and luteal phases of the menstrual cycle. The amount by which PAV amplified LG was quantified from the tidal volume amplification factor [(VtAF) assisted tidal volume/unassisted tidal volume]. LG was calculated as the inverse of the VtAF occurring at the assist level immediately preceding the emergence of periodic breathing (when LG x VtAF = 1). Only 1 of 10 men and 2 of 9 women developed periodic breathing with PAV. The rest were resistant to periodic breathing despite moderately high levels of PAV amplification. We conclude that LG is low in the majority of normal men and women and that higher volume amplification factors are needed to determine whether gender differences exist in this low range.     

Total aneuploidy and age-related sex chromosome aneuploidy in cultured lymphocytes of normal men and women

Summary In PHA-cultured lymphocytes, about 8% of metaphases from 32 women were aneuploid compared to 4% of metaphases from 35 men. A significant part of this aneuploidy was characterized by sex chromosome involvement: in women, the loss or gain of X chromosomes; in men, the gain of X chromosomes and the loss or gain of Y chromosomes. The incidence of this aneuploidy was positively age-related for both sexes. Premature division of the X-chromosome centromere was closely associated with X-chromosome aneuploidy in women and men, and appeared to be the mechanism of nondisjunction causing this aneuploidy. Premature centromere division (PCD) indicated a dysfunction of the X-chromosome centromere with aging, and this dysfunction was the basic cause of age-related aneuploidy. A similar mechanism of nondisjunction may operate for the Y chromosome of men, but could not be clearly demonstrated because of the low incidence of Y-chromosome aneuploidy.The balance of the aneuploidy was characterized by chromosome loss and the involvement of all chromosome groups. It was consistent with chromosome loss from metaphase cells damaged during preparation for cytogenetic examination.     

Dependence of media cross-sectional area on circumference of aortic rings from normal and hypertensive rats

The purpose of this study is to determine if cross-sectional area and media thickness depend on circumference in excised vessels. Measurements were obtained from rat aortic rings chemically fixed after excision. Rings were fixed without distention or after mounting on circular rods of different diameters. Media cross-sectional area increased with circumference but thickness decreased. Thickness and area were significantly greater in the SHR than the WKY rat at all circumferences. Results of a theoretical analysis predict that cross-sectional area and thickness will depend on circumference in excised rings. Best-fit curves of the experimental data to the theoretical relationships show that neither thickness nor cross-sectional area of the aorta is consistently better correlated with circumference in SHRs and WKY rats. The following conclusions are made: (i) Media cross-sectional area and thickness depend on circumference in excised-aortic rings, and (ii) for a specific method of preparation, thickness and cross-sectional area are equally accurate when comparing aortic rings from normal and hypertensive rats. If an experimental determination of the relationship between circumference and cross-sectional area (or thickness) cannot be done, we suggest that a reasonable alternative is to compare these measurements at the same circumference.     

Prediction of normal values for lactate threshold estimated by gas exchange in men and women

Lactate threshold (LT) is an index of exercise capacity and can be estimated from the gas exchange consequences of a metabolic acidosis (LT_GE). In recent years, it has emerged as a diagnostic tool in the evaluation of subjects with exercise limitation. The purpose of this study was to develop LT_GE prediction equations on a relatively large sample of adults and to cross-validate each equation. A total of 204 healthy, sedentary, nonsmoking subjects (103 men and 101 women), aged 20–70 years, underwent graded exercise testing on a cycle ergometer. The V-slope technique was used to detect LT_GE as the oxygen uptake (V˙O₂) at the breakpoint of the carbon dioxide output versus V˙O₂ relationship. Multiple linear regression was used to develop 12 equations with combinations of the following predictor variables: age, height, body mass, and fat-free mass. Eight of the equations are gender-specific and four are generalized with gender as a dummy variable. The equations were cross-validated using the predicted residual sum of squares (PRESS) method. The results demonstrate that the equations had relatively high multiple correlations (0.577–0.863) and low standard errors of the estimate (0.123–0.228 1 · min⁻¹). The PRESS method demonstrated that the equations are generalizable, i.e., can be used in future studies without a significant loss of accuracy. Since we tested only healthy, sedentary subjects, our equations can be used to predict the lower limit of normal for a given subject. Using individual data for healthy and diseased subjects from the literature, we found that our gender-specific equations rarely miscategorized subjects unless they were obese and mass was a predictor variable. We conclude that our equations provide accurate predictions of normal values for LT_GE and that they are generalizable to other subject populations. Accepted: 13 February 1997     

Low serum creatinine is associated with type 2 diabetes in morbidly obese women and men: a cross-sectional study

Background

Iodine deficiency is a global problem representing the most common preventable cause of mental retardation. Recently, the impact of subtle deficiencies in iodine intake on children and pregnant women has been questioned. This study was designed to compare hypothyroidism among infants born to US military families in countries of varied iodine nutrition status.

Methods

A cohort design was used to analyze data from the Department of Defense Birth and Infant Health Registry for infants born in 2000-04 (n = 447,691). Hypothyroidism was defined using ICD-9-CM codes from the first year of life (n = 698). The impact of birth location on hypothyroidism was assessed by comparing rates in Germany, Japan, and US territories with the United States, while controlling for infant gender, plurality, gestational age, maternal age, maternal military status, and military parent's race/ethnicity.

Results

Hypothyroidism did not vary by birth location with adjusted odds ratios (OR) as follows: Germany (OR 0.82, [95% CI 0.50, 1.35]), Japan (OR 0.67, [95% CI 0.37, 1.22]), and US territories (OR 1.29, [95% CI 0.57, 2.89]). Hypothyroidism was strongly associated with preterm birth (OR 5.44, [95% CI 4.60, 6.42]). Hypothyroidism was also increased among infants with civilian mothers (OR 1.24, [95% CI 1.00, 1.54]), and older mothers, especially ages 40 years and older (OR 2.09, [95% CI 1.33, 3.30]).

Conclusions

In this study, hypothyroidism in military-dependent infants did not vary by birth location, but was associated with other risk factors, including preterm birth, civilian maternal status, and advanced maternal age.     

Circadian variations of serum sex hormone binding globulin binding capacity in normal adult men and women

Diurnal variations of serum sex hormone binding globulin (SHBG), testosterone (T) and estradiol (E2) in five normal adult men and five normal adult women were investigated. SHBG binding capacity was measured by both polyacrylamide gel electrophoresis and dextran-coated charcoal technique (DCC); T and E2 were assayed by RIA and free T and free E2 were determined by means of equilibrium dialysis. In male subjects the variations of SHBG binding capacity was associated with the changes of total T, free T and T/SHBG index, which had the highest concentrations in the morning and the lowest levels in the evening during the 24 h test period, but percentage free T remained unchanged. Serum protein concentrations did not change significantly during 24 h. No significant diurnal changes of SHBG binding capacity, total E2, free E2, percentage free E2 and percentage free T were found in female subjects in the mid-luteal phase of the menstrual cycle, although significant fluctuations of total T, free T and T/SHBG index were observed throughout the day. The results suggested that SHBG may play a buffer role in the presence of fluctuations of testosterone production during 24 h period, allowing stabilization of a bioactive fraction of the hormone both in normal adult male and female. However, the concentrations of T in normal adult women may be too low to drive any change of SHBG levels while there were no significant variations of E2 throughout a day in the mid-luteal phase of the menstrual cycle.