Naloxone decreases the inhibitory effect of ethanol on the release of arginine-vasopressin induced by physical exercise in man.

To establish whether ethanol and/or endogenous opioids play a role in the control of arginine-vasopressin (AVP) response to physical exercise, six healthy men underwent six bicycle-ergometer tests until exhaustion [exercise control test; exercise plus ethanol (50 of 110 ml proof whiskey orally), exercise plus naloxone (2 mg injected plus 5 mg infused or 4 mg injected plus 10 mg infused intravenously] or exercise plus ethanol plus naloxone). Plasma AVP levels, physiological and biochemical variables were measured during tests. Physiological and biochemical variables were similar in all tests. During the control test, exercise significantly increased plasma AVP levels, with a peak value five times higher than baseline. The AVP response to exercise was similar in the presence of naloxone, whereas it was abolished by ethanol. When ethanol tests were repeated in the presence of naloxone, at both lower and higher dose, ethanol inhibition on AVP secretion was only partial, with mean peak responses 2.5 times higher than basal values. Results indicate an ethanol involvement in regulation of the AVP response to physical exercise. Furthermore, naloxone-sensitive endogenous opioids appear to play a role in the mechanism underlying ethanol inhibitory action, but not in mediation of the AVP response to physical exercise.

Effect of naloxone on somatostatin inhibition of arginine vasopressin response to physical exercise in normal men.

To establish whether somatostatin (SRIH) and/or endogenous opioids play a role in the control of arginine-vasopressin (AVP) response to physical exercise, eight healthy men underwent four bicycle-ergometer tests until exhaustion: exercise control test; exercise plus SRIH, naloxone or SRIH plus naloxone. Serum AVP levels, physiological and biochemical variables were measured during tests. Physiological and biochemical variables were similar in all tests. During control test exercise significantly increased serum AVP levels, with a peak value 4.1 times higher than baseline. The AVP response to exercise was similar in the presence of naloxone, whereas it was significantly reduced by SRIH (AVP peak was only 2.8 times higher than baseline). When SRIH and naloxone were given together, the exercise-induced AVP rise was comparable to that observed in the control test. Results indicate a somatostatinergic involvement in the regulation of the AVP response to physical exercise. Furthermore, naloxone-sensitive endogenous opioids appear to play a role in the mechanism underlying SRIH inhibitory action, but not in mediation of the AVP response to physical exercise.

Free fatty acids inhibit adrenocorticotropin and cortisol secretion stimulated by physical exercise in normal men.

BACKGROUND: The basal circulating levels of ACTH and cortisol, but not the ACTH/cortisol response to hCRH, are significantly reduced by free fatty acid (FFA) infusion. OBJECTIVE: To verify whether FFA infusion modifies the ACTH/cortisol response to physical exercise, a well-known activator of the HPA axis at suprapituitary level. DESIGN: Exercise tests on a bicycle ergometer during infusion of a lipid-heparin emulsion (LHE) (experimental test) or normal saline (NaCl 0.9%) (control test). SETTING: Department of Cardiology at the University-Hospital. SUBJECTS: Seven healthy male subjects aged 25-33 years. INTERVENTIONS: On two mornings, at weekly intervals, LHE or saline were infused for 60 min; infusion started 10 min before exercise test on a bicycle ergometer, which lasted about 15 min. MAIN OUTCOME MEASURES: Circulating ACTH/cortisol levels and physiological variables during physical exercise. RESULTS: FFA levels (0.4 +/- 0.1 mEq/l) remained constant during control test, whereas they progressively rose (peak at 60 min, 2.7 +/- 1.0 mEq/l) during LHE infusion. Neither basal nor exercise-induced changes in physiological variables were modified by LHE infusion. Both ACTH and cortisol increased during exercise, with peak levels at 20 min and 30 min (control test: 103% and 42%, P < 0.001; experimental test: 28.5% and 18.6%, P < 0.05 higher than baseline, respectively). Both ACTH and cortisol responses were significantly lower in the experimental than in the control test (at 20 min P < 0.002 and at 30 min P < 0.05 for ACTH; at 20 min P < 0.05 and at 30 min, 40 min and 50 min P < 0.001 for cortisol). CONCLUSIONS: These data represent the first demonstration of an inhibitory action of increased circulating FFA levels on the HPA axis under stimulatory conditions (i.e. physical exercise, a challenge acting at suprapituitary level). In contrast, previous studies did not show FFA effects on the CRH-induced ACTH/cortisol response. Therefore, our data suggest negative effects of FFAs on the HPA axis at hypothalamic or higher centres in the central nervous system.

Correlates of HIV, HBV, and HCV infections in a prison inmate population: results from a multicentre study in Italy.

A cross-sectional study was undertaken on the correlates of infection for the human immunodeficiency virus (HIV) and hepatitis viruses B and C (HBV and HCV) in a sample of inmates from eight Italian prisons. A total of 973 inmates were enrolled [87.0% males, median age of 36 years, 30.4% intravenous drug users (IDUs), 0.6% men who have sex with men (MSWM)]. In this sample, high seroprevalence rates were found (HIV: 7.5%; HCV: 38.0%; anti-HBc: 52.7%; HBsAg: 6.7%). HIV and HCV seropositivity were associated strongly with intravenous drug use (OR: 5.9 for HIV; 10.5 for HCV); after excluding IDUs and male homosexuals, the HIV prevalence remained nonetheless relatively high (2.6%). HIV prevalence was higher for persons from Northern Italy and Sardinia. The age effect was U-shaped for HIV and HCV infections; HBV prevalence increased with age. Tattoos were associated with HCV positivity (OR: 2.9). The number of imprisonments was associated with HIV infection, whereas the duration of imprisonment was only associated with anti-HBc. The probability of being HIV-seropositive was higher for HCV-seropositive individuals, especially if IDUs. In conclusion, a high prevalence of HIV, HCV, and HBV infections among inmates was observed: these high rates are in part attributable to the high proportion of IDUs. Frequency of imprisonment and tattoos were associated, respectively, with HIV and HCV positivity. Although it is possible that the study population is not representative of Italy's prison inmate population, the results stress the need to improve infection control measures users was prisons.

Difference between diabetic and nondiabetic smokers in the pituitary response to physical exercise.

The growth hormone (GH), cortisol, and arginine vasopressin (AVP) responses to bicycle ergometry (with increasing workload until exhaustion) were measured in 20 patients affected by insulin-dependent diabetes mellitus (IDDM) (10 habitual smokers and 10 nonsmokers) and 20 nondiabetic subjects (normal controls) (10 habitual smokers and 10 nonsmokers). Cardiorespiratory parameters such as heart rate, blood pressure, ventilation, frequency of breathing, tidal volume, oxygen consumption (Vo(2)), carbondioxide production (Vco(2)), and respiratory exchange ratio (R) were monitored before and during exercise tests. No significant differences between groups were observed; furthermore, there were no differences in circulating somatomedin-C (SM-C) and free fatty acids (FFA) levels between groups. Blood glucose levels were similar before exercise and followed a similar pattern during tests in diabetic smokers and nonsmokers. Basal GH, cortisol, and AVP levels were similar in diabetic smokers, diabetic nonsmokers, normal smokers, and normal nonsmokers. In all groups, exercise induced a significant increase in the serum concentrations of all examined hormones. Increments were significantly higher in diabetic than in nondiabetic groups. No significant differences were observed between diabetic smokers and nonsmokers for all examined hormones. AVP responses during tests were similar in normal smokers and nonsmokers. In contrast, exercise-induced GH and cortisol increments were significantly lower in normal smokers than in normal nonsmokers. These data support the hypothesis that in normal subjects habitual nicotine consumption may attenuate both GH and cortisol responses to a releasing stimulation, such as physical exercise. This phenomenon may represent an expression of adaptation of nicotinic neurotransmission to chronic stimulation. Furthermore, the data show that the effect induced by habitual smoking is absent in diabetics, probably because of diabetes-induced neuroendocrine alterations in the central nervous system.

A population study of integrate-and-fire-or-burst neurons.

Any realistic model of the neuronal pathway from the retina to the visual cortex (V1) must account for the bursting behavior of neurons in the lateral geniculate nucleus (LGN). A robust but minimal model, the integrate-and-fire-or-burst (IFB) model, has recently been proposed for individual LGN neurons. Based on this, we derive a dynamic population model and study a population of such LGN cells. This population model, the first simulation of its kind evolving in a two-dimensional phase space, is used to study the behavior of bursting populations in response to diverse stimulus conditions.

Shortage of circulating naive CD8(+) T cells provides new insights on immunodeficiency in aging.

Clinical observations indicate that elderly people are prone to severe, often lethal infectious diseases induced by novel pathogens. Since the ability to mount primary immune responses relies on the availability of naive T cells, the circulating naive T-cell reservoir was evaluated throughout the human life span. Naive T cells were identified as CD95(-) T lymphocytes for their phenotypic and functional features. Indeed, the lack of CD95 marker is sufficient to identify a population of naive T cells, as defined by coincidence with previously characterized CD45RA(+) CD62L(+) T cells. Naive CD95(-) T cells, as expected, require a costimulatory signal, such as CD28, to optimally proliferate after anti-CD3 stimulation. Cytofluorimetric analysis of circulating T lymphocytes from 120 healthy subjects ranging in age from 18 to 105 years revealed that naive T cells decreased sharply with age. The younger subjects had a naive T-lymphocyte count of 825 +/- 48 cells/microL, and the centenarians had a naive T-lymphocyte count of 177 +/- 28 cells/microL. Surprisingly, the naive T-cell count was lower in CD8(+) than in CD4(+) subsets at any age, and the oldest individuals were almost completely depleted of circulating naive CD8(+) T cells (13 +/- 4 cells/microL). Concomitantly, a progressive expansion of CD28(-) T cells occurs with age, which can be interpreted as a compensatory mechanism. These data provide new insights into age-related T-cell-mediated immunodeficiency and reveal some analogies of T-cell dynamics between advanced aging and human immunodeficiency virus (HIV) infection. In conclusion, the exhaustion of the naive CD8(+) T-cell reservoir, which has never been reported before, suggests that this T-cell pool is a major target of the aging process and may define a parameter possibly related to the life span of humans. (Blood. 2000;95:2860-2868)

Negative energy modes and gravitational instability of interpenetrating fluids.

We study the longitudinal instabilities of two interpenetrating fluids interacting only through gravity. When one of the constituents is of relatively low density, it is possible to have a band of unstable wavenumbers well separated from those involved in the usual Jeans instability. If the initial streaming is large enough, and there is no linear instability, the indefinite sign of the free energy has the possible consequence of explosive interactions between positive and negative energy modes in the nonlinear regime. The effect of dissipation on the negative energy modes is also examined.

Acute and chronic hyperbaric oxygen exposure in humans: effects on blood polyamines, adrenocorticotropin and beta-endorphin.

Plasma beta-endorphin, adrenocorticotropin (ACTH) and blood polyamine (spermidine and spermine) concentrations were evaluated in healthy adult male athletes undergoing hyperbaric oxygen exposure for 10 days (2.8 atm, 100% O2, 60 min daily). In the "acute phase", corresponding to the first day of treatment, and in the "acute in the chronic phase", corresponding to the values obtained on the 5th and 10th days after 60 min of hyperbaric O2, both ACTH and beta-endorphin levels increased significantly, whereas no variations were observed for polyamine concentrations. In the "chronic phase", corresponding to the basal values of the 5th and 10th days of treatment, we found a different pattern. In fact, the concentration of polyamines showed a remarkable enhancement, while ACTH and beta-endorphin levels remained unchanged. No significant variations were observed during hyperbarism with air. These results demonstrate different modifications of polyamines and beta-endorphin and ACTH in subjects submitted to hyperbaric oxygen exposure.

Tissue polyamine concentrations in the European sea bass (Dicentrarchus labrax L.): change with age and season of the year.

Independently of the age of the European sea bass, putrescine and spermidine are much higher in liver and brain than in muscles, while spermine concentrations are more similar to one another. The polyamine concentrations are higher in 2 years old sea bass than in 1 year old fish except for heart spermidine and liver spermine. Lowering in water temperature causes a decrease in the concentration of spermidine and spermine in all tissues examined. Putrescine, however, increases in heart, caudal muscle, liver and brain and it is unchanged in red and dorsal muscles.

Effect of GnRH administration on blood polyamines and LH levels in normal and obese children.

Blood polyamines (spermidine and spermine) and LH levels have been studied after acute GnRH injection both in obese and normal weight children. In both groups LH values significantly increased after stimulation but reached higher peaks in normal children than in obese ones (P less than 0.05). On the contrary, polyamine levels increased significantly only in the normal weight children. LH peaked at 30 min and polyamines at 60 min after GnRH injection. On the basis of the proposed role of polyamines in hormone action and of our results, we suggest that polyamines may play a pivotal role in hormone responsiveness of hypothalamic-hypophyseal axis.

Changes of polyamine concentrations in infants during the first six months of life.

Polyamines were detected in the blood of infants during the first six months of life. The highest spermidine levels were found at the 2nd and the 4th month after birth. Spermine, on the contrary, does not show significant differences. Different types of diet produced no changes in the polyamine pattern.

Polyamine distribution and activity of their biosynthetic enzymes in the European sea bass (Dicentrarchus labrax L.) compared to the rat.

1. In the liver, heart and brain of the European sea bass, putrescine concentrations are much higher than in the equivalent rat tissues; spermidine and spermine levels are smaller. 2. Ornithine decarboxylase in the bass liver is more active, but less stable than that in the rat; stability is acquired upon partial purification. Bass liver adenosylmethionine decarboxylase activity is less than that found in the rat. Both are activated and stabilized by putrescine. 4. The activating effect of putrescine decreases as the assay temperature is decreased. This may explain the high level of putrescine but low levels of spermidine and spermine in the bass liver.

Ornithine decarboxylase in perfused rat heart.

In the isolated perfused rat hearts, the activity of tissue ornithine decarboxylase gradually decreases over 90 min. In contrast, the activity of S-adenosylmethionine decarboxylase, lactate dehydrogenase, and glutamate-oxalacetate transaminase stays unchanged after a small decrease during the first 10 min. Ornithine decarboxylase is released from the perfused heart under conditions in which neither the lower molecular weight S-adenosylmethionine decarboxylase nor polyamines leak out. Ten minutes of ischaemia did not change the rate of release of ornithine decarboxylase. Ischaemia followed by reperfusion (20 min) increased release of ornithine decarboxylase.

Intracellular location of polyamines associated to red blood cells.

The polyamines associated to human erythrocytes from healthy donors are mainly localized intracellularly. In fact chromatography of the erythrocytes on a resin which has a high affinity and capacity for polyamines does not affect the amount of polyamines associated to the erythrocytes. The low ability of spermine to adsorb to the external surface of erythrocytes at physiological ionic strength is suggested also by studies conducted with sealed ghosts. Also erythrocytes from patients with hematological and dermatological diseases which contain increased levels of polyamines show an intracellular location of these amines.

Pattern of human blood spermidine and spermine in prematurity.

Blood polyamines have been determined in preterm newborns (24-37 gestation weeks) during the first hours of life and until 20 days after birth. The most elevated polyamine concentrations were found in preterm newborns from the 24th-33rd gestational week. In all preterms, however, polyamine concentrations are higher than in full term newborns. In preterm infants two different patterns of blood polyamines appear in relation to the gestational age: in infants born at 24-34 wk, spermidine reaches the peak at 12 h and spermine shows high concentrations between 12 and 48 h. In infants born at 35-37 wk maximal concentrations of polyamines were reached at 12 h. Successively, in both groups the polyamines progressively decrease up to the 20th day, with some individual variations. Our results may provide a further support to the suggestion of a fetal genesis of polyamines and their involvement in fetal growth.

Pattern of blood polyamines in healthy subjects from infancy to the adult age.

Blood polyamine levels have been determined in 161 healthy subjects from newborn to adult age. During the growth period spermidine concentrations are always higher than in adulthood. In the first days of life a typical pattern for spermidine and spermine appeared with an early increase in the first hours after birth and a maximum at 24 h; afterwards the levels of both amines gradually and progressively decreased. The levels reached by 10 days of life were maintained until adulthood, at which time a further decrease was evident. The high levels of polyamines during the period of body growth may suggest that also in humans these substances play a role in the process of cellular proliferation.