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PubMed2003

A theoretical study of effects of cytosolic Ca2+ oscillations on activation of glycogen phosphorylase.

Taking into account the Ca(2+)-stimulated degradation of inositol 1,4,5-trisphosphate (IP(3)) by a 3-kinase, we have theoretically explored the effects of both simple and complex Ca(2+) oscillations on the regulation of a phosphorylation-dephosphorylation cycle process involved in glycogen degradation by glycogen phosphorylase a-form, respectively. For the case of simple Ca(2+) oscillations, the roles of cytosolic Ca(2+) oscillations in the regulation of active phosphorylase depend upon the maximum rate of IP(3) degradation by the 3-kinase, V(M5). In particular, the smaller the values of V(M5) are, the lower the effective Ca(2+) threshold for the activation of glycogen phosphorylase will be. For the case of complex Ca(2+) oscillations, the average level of fraction of active phosphorylase is nearly independent from the level of stimulation increasing in the bursting oscillatory domain. Both simple and complex Ca(2+) oscillations can contribute to increase the efficiency and specificity of cellular signalling, and some theoretical results of activation of glycogen phosphorylase regulated by Ca(2+) oscillations are close to the experimental results for gene expression in lymphocytes.

Calcium Signaling↗
PubMed1992

[Changes in transitory evoked otoacoustic emissions in chemotherapy with cisplatin and 5FU].

The aim of this study was to detect changes of transient evoked otoacoustic emissions (TEOAE) during chemotherapy with cisplatin and fluorouracil (5FU). A review of the literature reveals that the incidence of cisplatin ototoxicity varies from 9% to 50%; this variation is due to differences in doses, duration of administration, to the criteria for ototoxicity and on audiological methods. Three cycles of chemotherapy (1000 mg/m2 5FU from day 1 to 5 and 100 mg/m2 cisplatin on day 1) were given to 12 patients; the OAE were measured before chemotherapy and after each administration. In 86% of the ears measured we found changes in the TEOAE; the mean values for the amplitude of the TEOAE decreased about 13% after the end of the chemotherapy. Pure tone thresholds were reduced in almost 50% of the measured ears. The decrease of amplitude of TEOAE is an early sign of an ototoxic secondary effect, probably due to damage to the outer hair cells. TEOAE is a sensitive method for detecting ototoxicity in cisplatin-treated patients and more reliable than pure-tone audiometry or evoked acoustic potentials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Sampling arterialised-venous blood from a dorsal-hand vein during exercise without compromising a competitive cycling position.

The arterialisation of dorsal-hand venous blood, using a new hand-heating sleeve that did not disrupt a normal competitive cycling position, was evaluated in 10 male cyclists. Hand-heating was achieved by pumping heated water through a rubberised panel which rested against the dorsal and ventral surfaces of the right hand. Subjects were cannulated near the dorsal venous arch in both hands and blood samples were collected simultaneously at rest under normothermic conditions for 9 subjects, and at rest and after 10, 20 and 30 min of exercise at 50% of the anaerobic threshold for 10 subjects, when only the right hand was heated. No bilateral differences for PO2, PCO2 or pH were observed between normothermic hands at rest (p > 0.05). The heating sleeve increased the hand temperature (p < 0.05) and produced a significant (p < 0.05) arterialisation of blood samples collected from a dorsal-hand vein, compared to values observed in the non-heated hand, at rest and during 30 min of exercise. PO2 and pH were about 10 mm Hg and 0.01 units higher, and PCO2 was about 1.5 mm Hg lower, for samples collected from the heated compared to the non-heated hand. This new method of hand-heating was effective in arterialising venous blood and minimised the need for variation to a normal, competitive cycling position.

Acid-Base Equilibrium↗
PubMed1998

Diagnostic accuracy of computer-assisted sperm motion analysis.

One retrospective and two prospective studies were conducted among 218 couples treated with in-vitro fertilization (IVF) to establish the reproducibility and diagnostic accuracy of computer-assisted sperm analysis (CASA) with swim-up spermatozoa for the prediction of the fertilization rate of oocytes in vitro. Based on the results of a preliminary retrospective analysis in 49 patients, the 'curvilinear velocity' (VCL) was chosen as the most distinctive motion parameter of sperm function and the median was used to represent the entire sperm population. The number of inseminated motile spermatozoa was then adjusted to median VCL during two subsequent prospective studies with clinical IVF. Whereas in the first prospective study (90 couples) the threshold values of VCL with regard to the number of spermatozoa inseminated were based on the results of the preliminary retrospective study (49 couples), in the second prospective study (79 couples) the settings were based on the results of the first prospective study. The reproducibility of CASA was tested by analysing the motion characteristics of spermatozoa at different intervals after termination of swim-up, by repeated analysis of the same video-recording of the incubated spermatozoa by different observers, and by the repeated video-recording of the freshly prepared sperm samples and analysis of both video-recordings by the same observer. Under these conditions the frequency of disagreement between two measurements varied between 2.0 and 8.2%. In both prospective studies the sensitivity of CASA for the prediction of fertilization was high (74.0%), whereas the specificity was low (40.0%). In contrast to successful fertilization, unsuccessful fertilization of oocytes in vitro could not be predicted reliably with CASA. However, the pregnancy rate per cycle among patients with predicted low fertilization rates was significantly lower (5.3%) than in couples with high predicted fertilization rates (24.3%, P < 0.001). Therefore, CASA of washed spermatozoa may still help to identify couples who would benefit more from intracytoplasmic sperm injection (ICSI) than from IVF. A definite threshold level could not be identified for any of the motion parameters to distinguish the motion characteristics of fertilizing and non-fertilizing spermatozoa. Using various algorithms for hyperactivated motility, the percentage of hyperactivated spermatozoa was significantly higher among the successfully fertilizing patients than among the nonfertilizing group. However, the absolute number of hyperactivated spermatozoa added to the oocytes was higher in non-fertilizing couples. Therefore, the lack of fertilization in some patients may be caused by a generalized defect in sperm function rather than by insufficient hyperactivation.

Adult↗
PubMed1998

Differentiated ratings of perceived exertion at ventilatory threshold in children and adults.

The purpose of this study was to examine overall, leg and chest ratings of perceived exertion (RPE) at ventilatory threshold (Thvent) in 16 children (mean age 10.9 years) and 17 adults (mean age 24.3 years). Thvent and maximum oxygen consumption (VO2max) were measured during a graded exercise test on a cycle ergometer. Overall, leg and chest RPE were obtained at the end of each exercise stage. VO2max was 49.9 (8.5) and 47.1 (6.1) ml x kg(-1) x min(-1) [mean (SD)] in the adults and children, respectively (P > 0.05). Relative to VO2max, Thvent was 61.7 (5.3)% in the adults and 64.7 (5.2)% in the children (P > 0.05). Overall, leg, and chest RPE values at Thvent for the adults were 11.5 (2.6), 11.9 (2.5), and 10.5 (2.5), while for the children these values were 13.6 (2.2), 14.1 (2.2), and 12.6 (2.3), respectively. All RPE values were higher for the children (P < 0.05). These results suggest that children are able to discriminate levels of exertion in different parts of their body during graded exercise. Furthermore, children rate an intensity corresponding to Thvent to require a greater overall, leg and chest effort than adults exercising at a similar intensity. This indicates that children experience more pronounced cardiorespiratory and muscular sensations during this type of exercise.

Adult↗
PubMed1999

Levels of serotonin in the hemolymph of Aplysia are modulated by light/dark cycles and sensitization training.

Serotonin (5-hydroxytryptamine, 5-HT) modulates the behavior and physiology of both vertebrate and invertebrate animals. Effects of injections of 5-HT and the morphology of the serotonergic system of Aplysia indicate that 5-HT may have a humoral, in addition to a neurotransmitter, role. To study possible humoral roles of 5-HT, we measured 5-HT in the hemolymph. The concentration of 5-HT in the hemolymph was approximately 18 nM, a value close to previously reported thresholds for eliciting physiological responses. The concentration of 5-HT in the hemolymph expressed a diurnal rhythm. In addition, electrical stimulation that leads to long-term sensitization significantly increased levels of 5-HT in the hemolymph during training, 1.5 hr after training, and 24 hr after training. Moreover, levels of 5-HT in the hemolymph were significantly correlated with the magnitude of sensitization. The half-life of an increase in 5-HT in the hemolymph was approximately 0.5 hr. Therefore, the persistent increase of 5-HT in the hemolymph 24 hr after sensitization training indicates that training caused a long-lasting increase in the release of 5-HT. This long-lasting increase in 5-HT in the hemolymph was blocked by treatment with an inhibitor of protein synthesis during training. Based on the levels of 5-HT in the hemolymph and its regulation by environmental events, we propose that 5-HT has a humoral role in regulation of the behavioral state of Aplysia. In support of this hypothesis, we found that increasing levels of 5-HT in the hemolymph led to significant alterations in feeding behavior. Increasing levels of 5-HT during the daytime when they were normally low increased the latency to assume feeding posture from daytime to nighttime values.

Animals↗
PubMed1993

Correlation between inflection of heart rate/work performance curve and myocardial function in exhausting cycle ergometer exercise.

The heart rate/work performance (fc/W) curve is usually S-shaped but a flattening at the top is not always seen. By means of radionuclide ventricular scintigraphy, the left ventricular ejection fraction (LVEF) of 15 sports students was investigated. The behaviour of the fc/W curve during cycle ergometry with increasing exercise intensities was examined. During exercise, the LVEF showed a distinct initial increase reaching roughly constant values at stress levels below-maximum, and sometimes even falling again. The inflections of the fc/W curve and left ventricular ejection fraction/performance curve (LVEFPC) were calculated from a second degree polynomial fit. From this function, the slopes of the tangents at the points of aerobic threshold and maximum performance were calculated together with the differences of the angles as a measure of the fc/W curve and LVEFPC inflections. It follows that the fc/W curve inflection became less pronounced or was even absent altogether when the decrease in LVEF towards the end of the ergometer exercise became more distinct. A significant negative correlation was found between the existence and extent of the fc/W curve inflection and the stress-dependent myocardial function, expressed as the inflection of the LVEFPC (P < 0.01, r = 0.673). Thus, it would seem that the absence of a fc/W curve inflection was related to a diminished stress-dependent myocardial function.

Adult↗
PubMed2004

Dose-finding study of daily GnRH antagonist for the prevention of premature LH surges in IVF/ICSI patients: optimal changes in LH and progesterone for clinical pregnancy.

BACKGROUND: An optimal range of LH concentrations for achieving pregnancy has not been established. The aim of this study was to investigate the effect of various LH levels induced by different GnRH antagonist doses on IVF outcome. METHODS: This was a prospective, single centre study including 144 IVF patients, stimulated with recombinant FSH from cycle day 2, and co-treated with daily GnRH antagonist (antide/Iturelix) (2 mg/2 ml, 1 mg/ml, 0.5 mg/ml, 0.5 mg/0.5 ml or 0.25 mg/ml) from cycle day 7 onwards. Serum samples were taken three times daily. RESULTS: Clinical pregnancies were only observed within a particular range of change in LH levels. The upper and lower thresholds for the mean LH area under the curve (AUC), adjusted for the baseline LH level before the antagonist was started (LH AUC(-S6); S6=stimulation day 6) were -2.2 and 12.4 (IU/l) respectively (a negative value=below baseline levels). There were no clinical pregnancies outside these threshold values. Similar results were found for progesterone, the threshold levels of progesterone AUC(-S6) were 3.98 and -1.21 ng/ml. Moreover, there were no pregnancies with progesterone levels >0.26 ng/ml/follicle on the day of hCG. CONCLUSIONS: Excessive or insufficient suppression of LH and progesterone levels during GnRH antagonist administration and high progesterone/follicle on hCG day seems to be associated with impaired clinical pregnancy rates.

Adult↗
PubMed2003

An infrared renormalization group limit cycle in QCD.

We use effective field theories to show that small increases in the up and down quark masses would move QCD very close to the critical renormalization group trajectory for an infrared limit cycle in the three-nucleon system. We conjecture that QCD can be tuned to the critical trajectory by adjusting the quark masses independently. At the critical values of the quark masses, the binding energies of the deuteron and its spin-singlet partner would be tuned to zero and the triton would have infinitely many excited states with an accumulation point at the 3-nucleon threshold. The ratio of the binding energies of successive states would approach a universal constant that is close to 515.

Journal Article↗
PubMed1992

The efficacy of aerobic exercise therapy on hypertensive patients with mild cardiac complications.

To investigate the antihypertensive efficacy of aerobic exercise therapy in essential hypertensives, 20 patients underwent eight weeks of cycle ergometer training at anaerobic threshold (AT) point. Cardiopulmonary exercise testings with ramp protocol were performed before and at two/four/eight weeks during the training period in order to determine AT and to evaluate the changes in blood pressure (BP), heart rate (HR), oxygen uptake (VO2; ml/min/kg), and O2 pulse (ml/min/beat) during exercise. 75g glucose tolerance test (OGTT) was measured before and after exercise therapy. The mean values of systolic blood pressure, oxygen uptake, O2 pulse, before and after exercise therapy were as follows: systolic blood pressure at rest = 160 +/- 19 mmHg and 135 +/- 11 mmHg, systolic blood pressure at AT = 195 +/- 13 mmHg and 180 +/- 10 mmHg, oxygen uptake AT = 12.0 +/- 0.9 ml/min/kg and 14.4 +/- 1.0 ml/min/kg, O2 pulse at AT = 6.8 +/- 1.5 ml/min/beat and 7.6 +/- 1.88 ml/min/beat. After exercise therapy, systolic blood pressure decreased (p less than 0.01), while O2 pulse and VO2 increased (p less than 0.01). Hyperresponse of serum insulin to glucose also improved. These results show that aerobic exercise therapy at AT level has beneficial effects on high blood pressure and improves exercise tolerance and hyperresponse of serum insulin to glucose without any complications.

Adult↗
PubMed1981

Inhibition of canine interdigestive proximal gastric motility by cholecystokinin octapeptide.

Feeding abolishes cyclic interdigestive motility and decreases intraluminal pressure in autotransplanted pouches of canine proximal stomach. Our aim was to determine whether cholecystokinin might be the hormonal messenger involved. In four conscious dogs with autotransplanted proximal gastric pouches and chronic duodenal electrodes, intrapouch pressure and duodenal myoelectric activity were measured during fasting, while cholecystokinin octapeptide (CCK-OP) was infused intravenously for 4 h at doses 0, 15, 31, 62, 125, and 250 mg . kg-1 . h-1. Each dose was given five times to each animal. Cholecystokinin octapeptide inhibited the interdigestive cycles in both pouch and duodenum and decreased the pressure in the pouch. The threshold for these effects was 31 ng . kg-1 . h-1, and the ED50 was 62 ng . kg-1 . h-1. The dose of 125 ng . kg-1 . h-1 suppressed the cycles nearly completely and decreased mean +/- SE intrapouch pressure from 15.3 +/- 1.1 to 6.3 +/- 2.8 cmH2O . min (P less than 0.001). After the infusions were stopped, cyclic activity and intrapouch pressure returned promptly to control values. We concluded that CCK-OP at "physiological" doses abolished interdigestive cycles and decreased intraluminal pressure in autotransplanted pouches of canine proximal stomach.

Animals↗
PubMed1976

Kinetic analysis of hormone-induced mitoses in epithelial cells of mouse uterus and vagina.

The intracellular localization of 3H-estradiol-17beta and 3H-progesterone to the different types of cells in the mouse uterus was investigated using autoradiographic techniques. The kinetics of cell proliferation in the surface epithelium of the uterus and in the vaginal epithelium (basal layer) are analysed by means of cumulative labeling method and mitosis chase method using 3H-thymidine autoradiographic procedures. The results are as follows, (1) Epithelial cell population of the uterine lumen and basal cell population of the vaginal epithelium in the ovariectomized mouse are divided into a major subpopulation of GO cells and a minor subpopulation of proliferating cells. (2) Proliferative potencies of uterine surface epithelial cells and vaginal basal cells in the ovariectomized mouse are regulated by a steroid-independent mechanisms through which the proportion of the GO cell-compartment and Tc value of the proliferating cell-compartment are determined according to their age; as the castrated mouse grows older, Tc value becomes longer and the proportion of the Go cell-compartment becomes larger. (3) If the dose levels of estrogen administered exceed the threshold value, estrogen-dependent cell proliferation will be provoked by transferring the cells in the GO cell-compartment to the proliferating cell-compartment in all or none fashion, and by reducing the Tc value of proliferating cell to 1/2-1/3 of that in the castrated mouse. (4) It is suggested that proliferating cells in the uterine surface epithelium and in the vaginal epithelium turn the cell cycle at a constant Tc value during estrous cycle, and that the tissue growth during estrous cycle is dependent on the size of the proliferating cell-compartment but not on the Tc value. (5) The results obtained from autoradiography of tritiated steroids in the mouse uterus gave a supporting clue to the kinetic data.

Animals↗
PubMed1982

Evidence that a critical threshold of DNA polymerase-alpha activity may be required for the initiation of DNA synthesis in mammalian cell heterokaryons.

The specific activity of DNA polymerase (90% alpha) was determined in nine "neoplastoid" cell lines (Martin and Sprague, 1973) and in three different strains of HDF (human diploid fibroblast-like cells), all examined in logarithmic phases of growth. This was compared to the ability of each cell type to "rescue" (reinitiate DNA synthesis in) senescent HDF cells subsequent to polyethylene glycol-mediated cell fusions. A sharp "threshold" value of DNA polymerase activity was observed below which reinitiation of DNA synthesis in heterokaryons with senescent HDF does not occur. This threshold was especially obvious when the specific activity of DNA polymerase (p moles dTTP incorporated per mg protein or per cell) was divided by the percent of S-phase cells present in each culture as determined by flow microfluorometry. Our results indicate that the specific activity of DNA polymerase-alpha (or some other factor tightly coregulated with it) in "recessive" cell types (those unable to rescue senescent cells) is only about two times this theoretical "threshold" value, and that fusion of recessive cell types to senescent HDF cells reduces the specific activity in the heterokaryon to below this minimum, thus preventing the cells from entering S phase.

Cell Cycle↗
PubMed2006

Predictive factors of treatment interruption duration in a cohort of HIV-1 infected patients with CD4 count greater than 350 cells per mm3.

OBJECTIVE: To determine predictive factors of treatment interruption (TI) duration within a cohort of HIV-1 infected patients having stopped their treatment with CD4 above 350 cells per mm(3). DESIGN: Data were collected from computerized medical records. Patients were selected if they were HIV-1 positive, 18 years of age or older, and had stopped their treatment between January 1st, 1999 and July 1st, 2003, with CD4 count above 350 cells per mm(3). The study period was censored on October 1st, 2003. Patients were assessed every 3 months from inclusion to censure. A survival analysis using the Cox proportional hazard model was performed. RESULTS: One hundred eighty-five patients were included. The median duration of TI was 43 weeks. Sixty-three patients remained off-treatment at censure. In the multivariate analysis, TI duration was shorter if CD4 nadir was below 250 cells per mm(3) before TI (relative hazard, 2.10), age superior to 40 (relative hazard, 1.72), viral load higher than 2.3 log.copies per ml (relative hazard, 1.52), and CDC class C (relative hazard, 1.78) at TI. Neither CD4 cell count at TI, numbers of treatments, nor duration of treatment and infection before TI were independent predictive factors of early treatment resumption (TR). CONCLUSION: Some clinical and biological data may be used as predictive factors of early TR. Our results can have implications on future therapeutic strategies, in which the goal of therapy is to maintain CD4 cell count above a predetermined threshold using cycles of therapy followed by prolonged interruption according to CD4 count.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Aerobic parameters of exercise as a function of body size during growth in children.

To examine the relationship between body weight in children and aerobic parameters of exercise, we determined the anaerobic threshold (AT), maximum O2 uptake (VO2max), work efficiency, and response time for O2 uptake (RT-VO2) in 109 healthy children (51 girls and 58 boys, range 6-17 yr old) using a cross-sectional study design. Gas exchange during exercise was measured breath by breath. The protocol consisted of cycle ergometry and a linearly increasing work rate (ramp) to the limit of the subject's tolerance. Both AT and VO2max increased systematically with body weight, whereas work efficiency and RT-VO2 were virtually independent of body size. The ratio of AT to VO2max decreased slightly with age, and its mean value was 60%. AT scaled to body weight to the power of 0.92, not significantly different from the power of 1.01 for VO2max. Thus both the AT and the VO2max increase in a highly ordered manner with increasing size, and as judged by AT/VO2max, the onset of anaerobic metabolism during exercise occurred at a relatively constant proportion of the overall limit of the gas transport system. We conclude that in children cardiorespiratory responses to exercise are regulated at optimized values despite overall change in body size during growth.

Adolescent↗
PubMed1996

Determination of the heart rate deflection point by the Dmax method.

OBJECTIVE: Conconi et al. proposed that the point where heart rate departed from linearity in an incremental exercise test was a good indicator of the anaerobic threshold. However, the heart rate deflection points (HRDPs) can not be determined in many subjects. The aim of this study was to determine the heart rate deflection point by the Dmax method and to compare it with the conventional linear method. SETTING: The study was performed in the Exercise Physiology Laboratory in the Faculty of Medicine, Selçuk University. PARTICIPANTS: Thirty-two untrained males (aged 18-22) performed a maximal exercise test on a cycle ergometer. RESULTS: The deflection from linearity of HR could not be detected in nine subjects (28%) by the linear method. The HRDPs could be detected in all subjects by the Dmax method. It was observed that the HR values in the HRDPs determined by both methods were close to the maximal HR values (approximately 90% of maximum). There were high correlations and no differences (p more than 0.05) between the deflection points expressed as oxygen uptake, HR and work rate determined by two methods (correlation coefficients 0.93, 0.93, 0.97, respectively, p less than 0.001). CONCLUSIONS: The Dmax method is more useful than linear method. The HRDPs of all the people can easily and objectively be found by this method.

Adolescent↗
PubMed2004

Effects of respiratory muscle weakness on daily living function, quality of life, activity levels, and exercise capacity in mild to moderate Parkinson's disease.

OBJECTIVE: To investigate respiratory muscle strength in mild to moderate Parkinson's disease in comparison with prediction equations and age-matched controls. To identify correlations between respiratory muscle strength and daily living function, activity levels, quality of life, and exercise capacity. DESIGN: A total of 66 participants with Parkinson's disease and 32 age-matched, healthy controls participated. Respiratory mouth pressures (representing respiratory muscle strength) were compared with predicted values. A comparison was also made between participants with Parkinson's disease and age-matched controls. Respiratory mouth pressures were correlated with results of the Barthel index (daily living function), a modified Baecke activity questionnaire (activity levels), the Parkinson's disease questionnaire (quality of life in Parkinson's disease), peak heart rate, peak oxygen consumption, blood lactate thresholds, and the number of stages completed during an incremental cycle ergometer test (representing exercise capacity). RESULTS: Respiratory mouth pressures were significantly lower (P < 0.05) in the Parkinson's disease group, but this did not influence the measures of daily living function, activity levels, and quality of life. Respiratory mouth pressures correlated with lactate thresholds (r = 0.308, P < 0.01) and the number of completed stages of the cycle ergometer test (r = 0.490, P < 0.01). CONCLUSIONS: In mild to moderate Parkinson's disease, there is a significant weakness of the respiratory muscles. This can affect the individual during exercise but has no apparent effect on activities that do not require a large effort of the respiratory muscles.

Activities of Daily Living↗
PubMed1994

Effect of supine exercise on platelet aggregation and fibrinolytic activity.

In 12 healthy young men, strenuous cycling exercise in the supine position, caused platelet aggregability to decrease and the ADP threshold to rise from 7.0 microM resting, to 9.5 exercising (P < 0.01). At the same time, fibrinolytic activity increased markedly: euglobulin clot lysis time shortened from 178 to 68 min, PAI-1 fell from 8.91 to 5.16 IU ml-1, and t-PA rose from 0.56 to 3.95 IU ml-1, all three values were significant to P < 0.01. When the erect posture was assumed after lying at ease for 1 h after exercise, it did not increase platelet activity as expected, but caused a modest increase of fibrinolytic activity. These results suggest that supine exercise will not affect the haemostatic system adversely.

Adult↗