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Young Male Subjects (young + male_subject)
Selected AbstractsPharmacokinetics of dipeptidylpeptidase-4 inhibitorsDIABETES OBESITY & METABOLISM, Issue 8 2010A. J. Scheen Type 2 diabetes (T2DM) is a complex disease combining defects in insulin secretion and insulin action. New compounds have been developed for improving glucose-induced insulin secretion and glucose control, without inducing hypoglycaemia or weight gain. Dipeptidylpeptidase-4 (DPP-4) inhibitors are new oral glucose-lowering agents, so-called incretin enhancers, which may be used as monotherapy or in combination with other antidiabetic compounds. Sitagliptin, vildaglipin and saxagliptin are already on the market in many countries, either as single agents or in fixed-dose combined formulations with metformin. Other DPP-4 inhibitors, such as alogliptin and linagliptin, are currently in late phase of development. The present paper summarizes and compares the main pharmacokinetics (PK) properties, that is, absorption, distribution, metabolism and elimination, of these five DPP-4 inhibitors. Available data were obtained in clinical trials performed in healthy young male subjects, patients with T2DM, and patients with either renal insufficiency or hepatic impairment. PK characteristics were generally similar in young healthy subjects and in middle-aged overweight patients with diabetes. All together gliptins have a good oral bioavailability which is not significantly influenced by food intake. PK/pharmacodynamics characteristics, that is, sufficiently prolonged half-life and sustained DPP-4 enzyme inactivation, generally allow one single oral administration per day for the management of T2DM; the only exception is vildagliptin for which a twice-daily administration is recommended because of a shorter half-life. DPP-4 inhibitors are in general not substrates for cytochrome P450 (except saxagliptin that is metabolized via CYP 3A4/A5) and do not act as inducers or inhibitors of this system. Several metabolites have been documented but most of them are inactive; however, the main metabolite of saxagliptin also exerts a significant DPP-4 inhibition and is half as potent as the parent compound. Renal excretion is the most important elimination pathway, except for linagliptin whose metabolism in the liver appears to be predominant. PK properties of gliptins, combined with their good safety profile, explain why no dose adjustment is necessary in elderly patients or in patients with mild to moderate hepatic impairment. As far as patients with renal impairment are concerned, significant increases in drug exposure for sitagliptin and saxagliptin have been reported so that appropriate reductions in daily dosages are recommended according to estimated glomerular filtration rate. The PK characteristics of DPP-4 inhibitors suggest that these compounds are not exposed to a high risk of drug,drug interactions. However, the daily dose of saxagliptin should be reduced when coadministered with potent CYP 3A4 inhibitors. In conclusion, besides their pharmacodynamic properties leading to effective glucose-lowering effect without inducing hypoglycaemia or weight gain, DPP-4 inhibitors show favourable PK properties, which contribute to a good efficacy/safety ratio for the management of T2DM in clinical practice. [source] Variability of the masticatory process during chewing of elastic model foodsEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 6 2000Claire Lassauzay Many studies show a consistent individual chewing pattern; chewing being governed by a pattern generator and regulated by sensory feedback. The aim of this study was to determine the variation in chewing between sessions, replicates and subjects using elastic model foods. Fifteen young male subjects were selected to chew four food products differing in hardness. Four sessions were performed at 1-wk intervals for each subject and, within each session, the four model foods were presented 3 times each. Jaw movement was recorded simultaneously with masseter and anterior temporalis electromyographic activities. Several chewing characteristics increased progressively from one session to the next; the largest increase occurred from the 1st to the 2nd session, with little difference between the last two sessions. No differences were observed between the samples of the same food product within a session. As mastication progressed, the amplitude and speed of the cycles and the muscular work decreased progressively. The first cycle appeared to be very different from the subsequent for all parameters except for occlusal duration. Thus, under our experimental conditions, the origin and amount of variation in chewing patterns were identified and provide information to improve the accuracy and comparability of results in studies of mastication. [source] Proton and sodium MRI assessment of fluid level in calf tissueJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 1 2006Chun S. Zuo PhD Abstract Purpose To investigate the feasibility of using 1H and 23Na MRI to detect fluid levels in the lower leg muscle. Materials and Methods Proton and sodium MRI was applied to detect body fluid levels in the lower leg muscles of 18 healthy young male subjects at 3T and 4T. The paradigms under investigation were a postural change from sitting upright to lying supine, and saline infusion. Results We found that the average proton MR signal in gastrocnemius and soleus muscles were reduced following the postural change by 3.5% ± 1.4% (P < 0.05) and rose following saline infusion by 3.7% ± 0.9% (P < 0.01). More dramatically, the sodium MR signal decreased by 7.1% ± 1.2% (P < 0.01) following the postural change and increased following saline infusion by 12% ± 3.8% (P < 0.05). The ratio of intra- to extracellular fluid levels was 1.6 ± 0.5 for the subjects based on the acquired proton and sodium data. Conclusion Our results indicate that proton and sodium MRI can be used to assess fluid levels in the lower extremities, and this technique may be applied to evaluate fluid retention. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc. [source] Daytime sleepiness during Ramadan intermittent fasting: polysomnographic and quantitative waking EEG studyJOURNAL OF SLEEP RESEARCH, Issue 2 2003Rachida Roky Summary During the lunar month of Ramadan, Muslims abstain from eating, drinking and smoking from sunrise to sunset. We reported previously that Ramadan provokes a shortening in nocturnal total sleep time by 40 min, an increase in sleep latency, and a decrease in slow-wave sleep (SWS) and rapid eye movement (REM) sleep duration during Ramadan. During the same study, the effects of Ramadan intermittent fasting on daytime sleepiness were also investigated in eight healthy young male subjects using a quantitative waking electroencephalograph (EEG) analysis following the multiple sleep latency test (MSLT) procedure. This procedure was combined with subjective alertness and mood ratings and was conducted during four successive experimental sessions: (1) baseline (BL) 15 days before Ramadan, (2) beginning of Ramadan (R11) on the 11th day of Ramadan, (3) end of Ramadan (R25) on the 25th day of Ramadan, (4) recovery 2 weeks after Ramadan (AR). During each session, four 20-min nap opportunities (MSLTs) were given at 10:00, 12:00, 14:00 and 16:00 h and were preceded by rectal temperature readings. Nocturnal sleep was recorded before each daytime session. Subjective daytime alertness did not change in R25 but decreased in R11 at 12:00 h, and subjective mood decreased at 16:00 h, both in R11 and R25. During the MSLT, mean sleep latency decreased by an average of 2 min in R11 (especially at 10:00 and 16:00 h) and 6 min in R25 (especially at 10:00 and 12:00 h) compared with BL. There was an increase in the daily mean of waking EEG absolute power in the theta (5.5,8.5 Hz) frequency band. Significant correlations were found between sleep latency during the MSLT and the waking EEG absolute power of the fast alpha (10.5,12.5 Hz), sigma (11.5,15.5 Hz) and beta (12.5,30 Hz) frequency bands. Sleep latency was also related to rectal temperature. In conclusion, Ramadan diurnal fasting induced an increase in subjective and objective daytime sleepiness associated with changes in diurnal rectal temperature. [source] Olivocochlear Activity and Temporary Threshold Shift-Susceptibility in HumansTHE LARYNGOSCOPE, Issue 11 2005W Wagner MD Abstract Study Objectives: Animal studies (guinea pig, cat, chinchilla) have shown that activity of the medial olivocochlear efferents can exert noise-protective effects on the cochlea. It is not yet known whether such effects are also existent in humans. Olivocochlear activity can be estimated indirectly by contralateral suppression (CS) of otoacoustic emissions (OAE). Material and Methods: We measured Input/Output functions of distortion products of OAE (DPOAE), with and without contralateral acoustic stimulation by white noise, in 94 normal hearing young male subjects. Seven stimuli with L2 between 20 and 60 dB SPL and L1 = 39 dB + 0.4 L2 ("scissor paradigm") were used at f2 = 2, 3, 4, 5, and 6 kHz. The measurement was repeated 2 weeks later. In 83 subjects of the same group, pure tone audiometry was registered before and 6 minutes after shooting exercises to evaluate individual susceptibility to develop a temporary threshold shift (TTS). Results: Test-retest repeatability of CS was generally good. CS averaged 0.98 dB SPL (SD 1.19 dB, median 0.56 dB). As expected, CS was greatest at low stimulus levels (median 1.06 dB at L2 = 20 dB, as compared with 0.33 dB at L2 = 60 dB). The smallest average CS was found at 4 kHz, and the greatest CS appeared at 2 kHz. A TTS occurred in 7 of 83 (8.5%) subjects. Statistical analysis did not reveal any correlation between the amount of CS and individual TTS susceptibility. Conclusions and Outlook: 1) Measurement of CS of DPOAE using an extensive measurement paradigm revealed good test-retest repeatability, confirming the reliability of this audiologic tool. 2) CS of DPOAE does not predict individual susceptibility to mild TTS induced by impulse noise in humans. Possible explanations for the missing association are discussed. Future perspectives include longitudinal studies to further elucidate the association between medial olivocochlear bundle-activity and permanent threshold shift in humans. The goal is to develop a diagnostic tool for the prediction of individual noise vulnerability in humans, thereby preventing noise-induced hearing loss. [source] | ||||||||||