The effect of physical conditioning on antipyrine clearance

The effects of physical conditioning on antipyrine clearance were studied in two groups of subjects. Healthy men not engaged in the systematic practice of any sport were compared with endurance runners (defined as men running >80 km/week). Studies were carried out at three different periods of the annual plan training at 4-month intervals. Antipyrine was administered orally and pharmacokinetic parameters were obtained from saliva samples by the multiple-sample method. Endurance performance, expressed in terms of the maximal oxygen uptake (V˙O_{2 max}), the ventilatory threshold and the 4-mM · l⁻¹ lactate threshold (OBLA), was higher in trained than in control subjects at each of the three periods. Antipyrine clearance was also significantly elevated and antipyrine half-life reduced in runners during all periods. No significant difference in V˙O_{2 max} or antipyrine clearance was found between the various periods in either trained or control subjects. Both ventilatory threshold and OBLA increased significantly along the training period in conditioned subjects. Significant correlations were found between antipyrine clearance and V˙O_{2 max}, ventilatory threshold and OBLA. In summary, these results indicate an association between aerobic conditioning and increased hepatic oxidative metabolism of low-clearance drugs. Accepted: 15 July 1997     

In vitro activation of cyclo-oxygenase in the rabbit carotid body: effect of its blockade on [3H]catecholamine release.

The release of prostaglandin E2 (PGE2) from rabbit carotid bodies (CBs) incubated in basal conditions (PO2 approximately 132 mmHg; PCO2 approximately 33 mmHg; pH = 7.42) amounts to 94.4 +/- 10.1 pg (mg protein)-1 (10 min)-1 (mean +/- S.E.M.). Incubation of the CB in a hypoxic solution (PO2 approximately 46 mmHg) produced a significant 40% increase (P < 0.05) in the release of PGE2. Indomethacin (2 microM) prevented the hypoxia-induced release of PGE2. Sensory plus sympathetic denervation of the CB 4 days prior to the experiments did not modify either basal or low PO2-induced PGE2 release, indicating that intraglomic nerve endings are not significant sources for the PGE2 released. Incubation of the CB in an acidic-hypercapnic solution (PO2 approximately 132 mmHg; PCO2 approximately 132 mmHg; pH = 6.60) or in a high K(+)-containing solution (35 mM) was also effective in promoting an increase in the outflow of PGE2 from the organs. The release of [3H]catecholamines ([3H]CA) from the CB elicited by incubating the organs in low PO2 solutions (PO2 ranged between 66 and 13 mmHg) was potentiated by two inhibitors of cyclo-oxygenase, acetylsalicylic acid (ASA, 100 microM) and indomethacin (2 microM). The effect persisted after chronic denervation of the organ. The secretory response elicited by acidic stimuli was also augmented by cyclo-oxygenase inhibitors. Thus, [3H]CA release elicited by incubating the CBs in the acidic-hypercapnic solution increased by 300% in the presence of indomethacin (2 microM), and ASA (100 microM) more than doubled the release induced by dinitrophenol (100 microM), a protonophore that mimics an acidic stimulus. Indomethacin, but not ASA, moderately increased the high K(+)-evoked [3H]CA release. The effect of indomethacin on the release of [3H]CA elicited by acidic and hypoxic stimuli was reversed by PGE2 in a dose-dependent manner (0.3-300 nM). These results show that low PO2 and high PCO2-low pH, the natural stimuli to the CB, as well as high extracellular [K+], activate the cyclo-oxygenase pathway in the CB, promoting an increase in the outflow of PGE2. The data also show that the blockade of this pathway activates the stimulus-induced [3H]CA release from the CB, indicating that naturally released prostanoids exert an inhibitory control on chemoreceptor cells. The data lend support to the notion that the hyper-reactivity of the ventilatory response to hypoxia in subjects under anti-inflammatory drug treatment results from CB cycloxygenase inhibition.     

Contraction history affects the in vivo quadriceps torque-velocity relationship in humans

We hypothesized that the history of contraction would affect the in vivo quadriceps torque-velocity relationship. We examined the quadriceps torque-velocity relationship of the human knee extensors at the descending and ascending limb of the torque-position relationship by initiating the knee extension at a knee angle position of 1.39 rad (80°) or 0.87 rad (50°) over a 0.52 rad (30°) range of motion under conditions of constant or linearly increasing velocity. Maximal voluntary isometric knee extension torque (M₀) was measured at 1.87 rad, 0.87 rad, and 0.35 rad, and concentric torque was measured. The subjects carried out ten maximal knee extensions at ten distinct velocities, each velocity ranging between 0.52 rad·s^–1 to 5.24 rad·s^–1 in steps of 0.52 rad·s^–1. Peak concentric torque was measured and mean torque calculated from the respective torque-time curves. Peak or mean torque, computed from the individual torque-time curves, and velocity data were fitted to the Hill equation under the four experimental conditions and the curve parameters computed. The M₀ was similar at 0.87 rad and 1.39 rad, but it was significantly lower at 0.35 rad. In the low-velocity domain of the torque-velocity curve where a plateau normally occurs, peak torque was always lower than M₀. Peak and mean torque were significantly greater under linearly increasing velocity conditions and the 1.39 rad starting knee position. Mean torque but not peak torque data could be well fitted to the Hill equation and the two computations resulted in significantly different Hill curve parameters including the concavity ratio, peak power, and maximal angular velocity. We concluded that the history of contraction significantly modifies the in vivo torque-velocity relationship of the human quadriceps muscle. Muscle mechanics and not neural factors may have accounted for the inconsistencies in the human torque-velocity relationships reported previously. Electronic Publication     

The determinants of attitudinal change among medical students participating in home care training: a multi-center study.

PURPOSE: To report attitudinal changes of medical students from five medical schools rotating through a home care program, and to determine which of the program characteristics influenced attitudes the most. METHOD: A survey instrument covering four home care domains (general attitudes, home-based therapies, home care training, and time and reimbursement) was designed and validated by the five schools involved. Using pre- and post-rotation scores, analyses were done to evaluate for attitudinal changes within and among schools. The programs had similar basic characteristics (home visits, attending physicians' involvement, didactics), but had differing degrees of these components. RESULTS: Significant improvements in attitude scores were found in three domains: general attitudes, homebased therapies, and home care training. For time and reimbursement, only three schools improved significantly between pre- and post-rotation scores. Among the five schools, there were significant differences in the homebased therapies and home care training domains (p <.05), and in the time and reimbursement domain the difference approached significance (p =.06). None of the students' characteristics but all of the programs' characteristics significantly correlated with changes in total scores. In the first multiple regression model, educational level (third year instead of fourth) was the only independent predictor of change in score, (adjusted r(2) =.14). In Model 2, the strongest predictor was "contact with physician-program director," followed by "number of visits" and "physician-precepted visits" (r(2) =.23). CONCLUSION: Educational home care programs of varying intensities can positively affect medical students' attitudes towards home care. At least three program characteristics, (the physician-program director, number of visits, and physician-precepted home visits), are important parts of a successful program.     

Beta-alanine potentiation of [3H]flunitrazepam binding to rat spinal cord homogenates

The effect of beta-alanine, gamma-aminobutyric acid (GABA), and other functionally related amino acids on [3H]flunitrazepam binding to rat spinal cord homogenates was studied. beta-Alanine potentiated [3H]flunitrazepam binding by 40% and GABA by 88%. Taurine increased the binding by 19%. Hypotaurine produced an 11% increase. No significant effect was seen in glycine, alanine, serine, valine or the dipeptide carnosine. The beta-alanine increase in [3H]flunitrazepam binding was completely inhibited by 10 microM strychnine, whereas the GABA increase required 0.1 mM strychnine to be fully suppressed. Results suggest that beta-alanine specifically potentiates binding of [3H]flunitrazepam in rat spinal cord homogenates.     

Enzyme-inductive effect of a hypolipidemic compound N-bis-(p-chlorophenoxy)-acetyl-urea in man and rat

Besides its antilipidaemic effect, the new clofibric acid derivative (N-bis-(p-chlorohenoxy)-acetyl-urea) has an enzyme-inductive effect. The drug was administered (100 mg/kg orally) to male, Wistar rats for three days. The treatment raised the weight of the liver, the content of liver microsomal protein and cytochrome p-450 and shortened the hexobarbital sleeping time. The increase of cytochrome p-450 dependent biotransformation was found by in vitro methods in 9000-g supernatant of liver homogenate. There was a growth in biotransformation of substrates of type I (ethylmorphine, aminopyrine) and an extreme increase in reduction of nitrobenzene. We did not find any change in biotransformation of the type-II substrate aniline. In 16 patients suffering from Gilbert's syndrome, there was a decrease in the level of serum bilirubin, and increase of D-glucuric-acid output in urine and bromsulphophthalein transport maximum following the treatment of this drug given in 150 mg/day orally for three weeks. After this treatment, the level of gamma-glutamyl-transpeptides did not change. The authors highly recommend the serious consideration of metabolic interaction during the clinical application.     

Lack of correlation between impaired Interferon production and natural killer activity of lymphocytes in multiple sclerosis

Summary The ability of lymphocytes from patients with multiple sclerosis (MS) to produce Interferon (IFN-) in response to Newcastle Disease Virus (NDV) was studiedin vitro. The correlation between individual IFN- titers and natural killer (NK) cell activity and the presence of HLA system antigens associated with MS (B-7 and DRW-2) was also investigated.Lymphocytes from MS patients showed a significantly impaired capacity to synthesize IFN-in vitro when compared to lymphocytes from healthy donors (mean titers: 85.9 I.U. and 268.2 I.U., respectively). Marked differences in IFN- titers were observed in the group of MS patients.The production of IFN- by the patients' lymphocytes did not correlate with either the activity of NK cells or with their stimulation by exogenous IFN-. There was also no correlation between IFN- production by lymphocytes from MS patients and the presence or absence of B-7 and DRW-2 antigens.With 3 Figures     

TEMPS-a scale in 'mixed' and 'pure' manic episodes: new data and methodological considerations on the relevance of joint anxious-depressive temperament traits

BACKGROUND: Temperament is an important factor in affective illness. There is some indication that mixed episodes result from an admixture of inverse temperamental factors (e.g. depressive and/or anxious) to a manic syndrome. To test this hypothesis, which has been first formulated by Akiskal [Clin. Neuropharmacol. 15 (Suppl. 1A) (1992) 632-633], we compared the temperament of non-acute bipolar affective patients with and without the history of a previous mixed episode. METHODS: Patients who had been hospitalized for a bipolar disorder were re-assessed at least 6 months after their last in-patient treatment. Those who met the criteria for a partially remitted or full affective or psychotic episode at re-assessment were excluded from the study. Data concerning illness history, current psychopathology (SCID-I interview), depression (BDI), mania (Self-Report Manic Inventory) and temperament (TEMPS-A scale) were obtained. Patients with and without a history of previous mixed episodes were compared. RESULTS: Of 49 eligible former patients, 22 subjects with and 23 subjects without a former mixed episode in bipolar affective disorder fulfilled the inclusion criteria. Subjects suffering from bipolar affective disorder exhibited significantly more depressive and anxious and less hyperthymic temperament, if they had experienced a mixed episode previously. Concerning cyclothymic and irritable temperament, bipolar affective patients with a former mixed episode presented non-significantly higher scores. Patients with a former mixed episode presented with higher depression scores than patients without such a history. No group differences were found concerning current mania scores. LIMITATIONS: (1). This is a preliminary report from an ongoing study. (2). Temperament had not been assessed premorbidly. (3). Although group comparisons revealed significant differences, these did not seem great enough to fully explain the emergence of a mixed episode. CONCLUSION: Our findings support the study's hypothesis that mixed episodes occur more often in subjects with an inverse temperament (e.g. depressive and anxious), although it cannot be ruled out that subsyndromal features of the bipolar illness had an effect on temperament assessment.