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PubMed1988

Serial evaluation of vasopressin release and thirst in human pregnancy. Role of human chorionic gonadotrophin in the osmoregulatory changes of gestation.

Serial studies were designed to characterized changes in osmoregulation throughout gestation. Eight women underwent a 2-h infusion of hypertonic saline before conception, during gestational weeks 5-8, 10-12, and 28-33, and then 10-12 wk postpartum. Basal plasma osmolality (Posmol) was already significantly decreased by 5-8 wk (P less than 0.001) and remained 10 mosmol.kg-1 below nonpregnant values throughout pregnancy. The apparent threshold for AVP release (defined as the abscissal intercept of the regression line relating plasma AVP [PAVP] to Posmol) was also decreased significantly throughout gestation, as was the osmotic threshold for thirst (derived from analogue scales relating desire to drink to Posmol). The decrement in osmotic thirst threshold appeared to precede that for AVP release, and consistent with this 24-h urine volumes were significantly greater at 5-8 wk gestation (P less than 0.05). The slopes of each regression equation defining PAVP vs. Posmol (whose r values ranged from 0.79 to 0.99), very reproducible before and after pregnancy, were similar at 5-8 and 10-12 wk, but were markedly reduced in the third trimester (P less than 0.001). These volunteers had randomly undergone an additional infusion before conception (both tests in the luteal phase of the menstrual cycle) when 10,000 IU of human chorionic gonadotrophin (hCG) had been given intramuscularly over a 5-d period. Serum hCG values between 0.2 and 3.3 U.ml-1 were lower than usually seen in pregnancy, but the osmotic thresholds for AVP release and thirst decreased by 3 and 4 mosmol.kg-1, respectively (P less than 0.05). Finally we studied a patient with a molar pregnancy in whom thresholds for hormone release and thirst were both decreased to values resembling normal gestation and remained so for approximately 6 wk postevacuation, only normalizing when hCG had virtually disappeared from her serum. In contrast, thresholds increased within the first two puerperal weeks in two women with normal pregnancies. These data demonstrate (a) osmotic thresholds for both AVP release and thirst decrease within the very first gestational weeks; (b) increment in PAVP per unit increase in Posmol is reduced late in gestation; and (c) hCG may be involved in the osmoregulatory changes of pregnancy.

Adolescent↗
PubMed1987

Hydrophobic strip-of-helix algorithm for selection of T cell-presented peptides.

In extension of the hypothesis that an amphipathic alpha helix of Ii (Phe146-Val164) bound to the foreign antigen-presenting site (desetope) of class II MHC molecules through hydrophobic amino acid residues (Phe146, Leu150, Leu153, Met157, Ile160, Val164) which were present in an axial strip along one side of the Ii helix, we developed an algorithm to search for T cell-presented peptides showing a similar hydrophobic strip-of-helix. Such peptides might bind to the class II MHC molecule site which was complementary to the Ii hydrophobic strip-of-helix. The strip-of-helix hydrophobicity index was the mean hydrophobicity (from Kyte-Doolittle values) of sets of amino acids in axial strips down sides of helices for 3-6 turns, at positions, n, n + 4, N + 7, n + 11, n + 14, and n + 18. Peptides correlating well with T cell responsiveness had: (1) 12-19 amino acids (3-5 cycles or 4-6 turns of an alpha helix), (2) a strip with highly hydrophobic residues, (3) adjacent, moderately hydrophilic strips, and (4) no prolines. The degree of hydrophilicity of the remainder of a putative antigenic helix above a threshold value did not count in this index. That is, the magnitude of amphipathicity was not judged to be the principal selecting factor for T cell-presented peptides. This simple algorithm to quantitate strip-of-helix hydrophobicity in a putative amphipathic alpha helix, allowing otherwise generally hydrophilic residues, predicted 10 of 12 T cell-presented peptides in seven well-studied proteins. The derivation and application of this algorithm were analyzed.

Algorithms↗
PubMed1998

Effects of chromosome underreplication on cell division in Escherichia coli.

The key processes of the bacterial cell cycle are controlled and coordinated to match cellular mass growth. We have studied the coordination between replication and cell division by using a temperature-controlled Escherichia coli intR1 strain. In this strain, the initiation time for chromosome replication can be displaced to later (underreplication) or earlier (overreplication) times in the cell cycle. We used underreplication conditions to study the response of cell division to a delayed initiation of replication. The bacteria were grown exponentially at 39 degreesC (normal DNA/mass ratio) and shifted to 38 and 37 degreesC. In the last two cases, new, stable, lower DNA/mass ratios were obtained. The rate of replication elongation was not affected under these conditions. At increasing degrees of underreplication, increasing proportions of the cells became elongated. Cell division took place in the middle in cells of normal size, whereas the longer cells divided at twice that size to produce one daughter cell of normal size and one three times as big. The elongated cells often produced one daughter cell lacking a chromosome; this was always the smallest daughter cells, and it was the size of a normal newborn cell. These results favor a model in which cell division takes place at only distinct cell sizes. Furthermore, the elongated cells had a lower probability of dividing than the cells of normal size, and they often contained more than two nucleoids. This suggests that for cell division to occur, not only must replication and nucleoid partitioning be completed, but also the DNA/mass ratio must be above a certain threshold value. Our data support the ideas that cell division has its own control system and that there is a checkpoint at which cell division may be abolished if previous key cell cycle processes have not run to completion.

Cell Cycle↗
PubMed1997

Lactic threshold vs ventilatory threshold during a ramp test on a cycle ergometer.

OBJECTIVE: The purpose of this investigation was to study the relationship between the lactate (LT) and the ventilatory threshold (VT) during a ramp protocol in cycle ergometry. PARTICIPANTS: Thirty nine trained male subjects were selected as subjects. EXPERIMENTAL DESIGN: All the subjects performed a maximal ergometric test on a cycle ergometer consisting of a ramp protocol (increases of 25 W.min-1). The anaerobic threshold (AT) was determined using both ventilatory gas analysis (VT) and lactate measurement (LT). All the data related to the VT and LT were expressed in work rate (W), VO2 (ml.kg-1.min-1) and heart rate (bpm) and expressed as mean and standard deviation. Lactate threshold (LT) and ventilatory threshold (VT) were compared using the Student's "t"-test for paired data. Correlation coefficients between both variables were also calculated. Statistical significance was accepted at the 5% level. RESULTS: Results showed significant differences (p < 0.05) between mean values of VT and LT when both expressed either as heart rate (bpm), work rate (W), or VO2 (ml.kg-1.min-1). CONCLUSIONS: It was concluded that LT and VT occur at different exercise intensities during ramp protocol exercise on a cycle ergometer.

Adult↗
PubMed1993

Failure of the circulatory system limits exercise performance in patients with systemic sclerosis.

OBJECTIVE: To determine the mechanisms for exercise impairment in symptomatic patients with systemic sclerosis (SSc) using breath-by-breath expired-gas analysis with incremental exercise testing. DESIGN: Prospective, open trial. PATIENTS AND METHODS: Fifteen consecutive patients with SSc seen at the Medical University Hospital (a tertiary referral center) with complaints of exercise intolerance underwent pulmonary function testing (spirometry, helium dilution lung volumes, and diffusing capacity of carbon monoxide) and incremental exercise testing on a cycle ergometer measuring oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (R), oxygen saturation, blood pressure, and heart rate (HR). Values for oxygen uptake at anaerobic threshold (VO2AT) were derived graphically by blinded clinicians experienced in exercise testing, and the results were averaged. Ventilatory reserve and oxygen pulse were calculated from measured values, and all data were subjected to analysis by standard clinical algorithms. MEASUREMENTS AND MAIN RESULTS: Of 15 patients studied, 14 had either restrictive lung disease or normal results of spirometry on pulmonary function testing. One patient with a history of tobacco use had evidence of airways obstruction. Three patients were unable to exercise maximally (as determined by maximum respiratory exchange ratio [Rmax] greater than 1.09 or maximum heart rate [HRmax] greater than 85% predicted), and exercise testing was terminated in one with Mobitz type II atrioventricular block. The following data (mean +/- SEM) were obtained from 11 maximally exercising patients: VO2max 795 +/- 75 mL oxygen (O2)/min, R 1.34 +/- 0.05, VO2AT/VO2max predicted 0.21 +/- 0.02, O2 pulse 5.1 +/- 0.4 mL O2/beat, ventilatory reserve 0.52 +/- 0.06, and tidal volume/forced vital capacity ratio 0.46 +/- 0.02. Of the 11 patients completing breath-by-breath expired-gas analysis, all had circulatory impairment to exercise, as determined by low O2 pulse and low VO2 at anaerobic threshold, and circulatory impairment was limiting in 9 of 11 patients. Of those nine patients, four had evidence of impaired gas exchange compatible with pulmonary vascular disease. Arterial oxygen desaturation occurred in 2 of 11 patients. CONCLUSION: Circulatory impairment to exercise is common in SSc patients with exercise intolerance. Restrictive lung disease, although also common, does not limit exercise tolerance in patients capable of maximal effort.

Adult↗
PubMed2005

Quantitative real-time reverse transcription: polymerase chain reaction of prostate-specific antigen (PSA) for detection of circulating prostatic cells in patients with clinically localized prostate cancer.

OBJECTIVE: To evaluate the clinical utility of using the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify prostate-specific antigen (PSA) mRNA in peripheral blood samples from patients with prostate cancer as a predictor of extraprostatic extension of the disease and to assess any correlations with known predictive markers of this condition. METHODS: Immediately before radical prostatectomy, peripheral blood samples were taken from 42 men with clinically localized prostate cancer and analysed for PSA and 18S ribosomal (endogenous control) genes using real-time RT-PCR (with gene expression assays and the comparative CT-cycle threshold-method for quantifying). A total of 30 healthy male blood donors aged <50 y was taken as a control group. The relationships between PSA mRNA values, pathological and clinical features were analysed. PSA mRNA value, PSA level and biopsy Gleason score were then compared as predictors of extraprostatic extension. RESULTS: PSA gene expression was 3.73 times significantly higher in patients with clinically localized prostate cancer than in healthy men (P<0.05). There was no relationship between PSA real-time RT-PCR values and pathological stage pT2 or pT3 (P=0.5), and no association between PSA mRNA value and serum PSA level (P=0.9) or the Gleason score of the preoperative biopsy (P=0.9). CONCLUSION: There was no significant advantage in using the real-time RT-PCR assay of PSA mRNA before surgery to stage prostate cancer and to discriminate between organ-confined and extraprostatic extension.

Aged↗
PubMed1993

Effects of continuous negative airway pressure-related lung deflation on upper airway collapsibility.

Continuous negative airway pressure (CNAP) causes a decrease in lung volume, which is known to increase upper airway resistance by itself. We studied how this lung volume change could modify upper airway collapsibility with five normal awake subjects. In a first trial, pressure in a nasal mask (Pm) was progressively decreased in 3- to 5-cmH2O steps (CNAP). In a second trial, changes in lung volumes resulting from CNAP were prevented by applying simultaneously an equivalent level of negative extrathoracic pressure into a poncho-type respirator [isovolumetric CNAP (CNAPisovol)]. For each trial, we examined the relationship between the maximal inspiratory airflow of each flow-limited inspiratory cycle and the corresponding Pm by least-squares linear regression analysis and determined the critical pressure. We also determined the Pm threshold corresponding to the first Pm value below which flow limitation occurred. Flow limitation was observed in each subject with CNAP but in only two subjects with CNAPisovol. In these two subjects, the Pm threshold values were -20 and -9 cmH2O with CNAP and -39 and -16 cmH2O with CNAPisovol, respectively. Critical pressures for the same two subjects were -161 and -96 cmH2O with CNAP and -202 and -197 cmH2O with CNAPisovol, respectively. We conclude that CNAP-induced decreases in lung volume increase upper airway collapsibility.

Adult↗
PubMed1994

Lactic acidosis as a facilitator of oxyhemoglobin dissociation during exercise.

The slow rise in O2 uptake (VO2), which has been shown to be linearly correlated with the increase in lactate concentration during heavy constant work rate exercise, led us to investigate the role of H+ from lactic acid in facilitating oxyhemoglobin (O2Hb) dissociation. We measured femoral venous PO2, O2Hb saturation, pH, PCO2, lactate, and standard HCO3- during increasing work rate and two constant work rate cycle ergometer exercise tests [below and above the lactic acidosis threshold (LAT)] in two groups of five healthy subjects. Mean end-exercise femoral vein blood and VO2 values for the below- and above-LAT square waves and the increasing work rate protocol were, respectively, PO2 of 19.8 +/- 2.1 (SD), 18.8 +/- 4.7, and 19.8 +/- 3.3 Torr; O2 saturation of 22.5 +/- 4.1, 13.8 +/- 4.2, and 18.5 +/- 6.3%; pH of 7.26 +/- 0.01, 7.02 +/- 0.11, and 7.09 +/- 0.07; lactate of 1.9 +/- 0.9, 11.0 +/- 3.8, and 8.3 +/- 2.9 mmol/l; and VO2 of 1.77 +/- 0.24, 3.36 +/- 0.4, and 3.91 +/- 0.68 l/min. End-exercise femoral vein PO2 did not differ statistically for the three protocols, whereas O2Hb saturation continued to decrease for work rates above LAT. We conclude that decreasing capillary PO2 accounted for most of the O2Hb dissociation during below-LAT exercise and that acidification of muscle capillary blood due to lactic acidosis accounted for virtually all of the O2Hb dissociation above LAT.

Acidosis, Lactic↗
PubMed1994

Effects of aerobic endurance training on gas exchange kinetics of older men.

The kinetics of gas exchange at the on-transient of exercise are appreciably slowed in older individuals. Eight older men (72 yr) completed 6 months of aerobic cycle training. Ventilation and gas exchange kinetics were determined at the onset of a below threshold (ventilatory threshold, V(E)T) square wave exercise function and compared with control values (N = 4, age 70 yr). Gas exchange data were measured breath-by-breath and signal averaged data were fit with a monoexponential function to determine the time constants (tau). The training group showed significant increases in VO2max (20%) and VO2 at V(E)T (21%). The tau for oxygen uptake kinetics decreased significantly (62.2 +/- 15.5 to 31.9 +/- 7.0 s). The tau VCO2 (70.9 +/- 10.9 to 43.8 +/- 11.4 s) and tau VE (89.2 +/- 18.0 to 50.4 +/- 11.3) also were significantly faster posttraining; however, tau HR (38.1 +/- 20.5 to 28.6 +/- 7.2) was not significantly altered. Thus, with a vigorous training program, the kinetics of gas exchange of older individuals were faster, and approached values reported in fit young subjects.

Aged↗
PubMed2002

Day 5 inhibin B levels in a treatment cycle are predictive of IVF outcome.

BACKGROUND: Day 5 serum inhibin B during IVF treatment has been investigated as a predictor of outcome. METHODS: A total of 54 women (< or = 39 years, normal menses and endocrine profiles) were treated with urinary gonadotrophins or recombinant FSH following pituitary down-regulation. Serum day 3 FSH in a preceding cycle was <8.5 IU/l. Plasma inhibin B, inhibin A and estradiol were determined after 4 days of gonadotrophin administration (day 5). RESULTS: Day 5 inhibin B was the most highly correlated with the number of mature follicles (>14 mm), oocytes retrieved and fertilized. Receiver operating characteristic analysis gave high accuracy for day 5 inhibin B in predicting ovarian response and indicated that a threshold of 400 pg/ml may be helpful in the decision as to whether to continue treatment. Women with <400 pg/ml (n = 16) had lower numbers of follicles, mature follicles, oocytes retrieved, fertilized and cleaved compared with those >400 pg/ml (n = 36) and this threshold gave a positive likelihood ratio of 30, 92.9% sensitivity, 95.0% specificity and 86.7% positive predictive value to detect poor ovarian response. Day 5 inhibin B was the best predictor of pregnancy (no live births and four cycles cancelled, low inhibin group; nine live births and no cancelled cycles, high inhibin group). CONCLUSIONS: Normogonadotrophic, normogonadal women with day 5 inhibin B <400 pg/ml in down-regulated cycles have a poor response to ovarian stimulation and are less likely to conceive compared with women with higher day 5 inhibin B.

Adult↗
PubMed1994

Cavitation threshold ranking and erosion characteristics of bileaflet heart valve prostheses.

In vitro testing was approached using two methods in specially designed cavitation testers. Each method tested production model bileaflet valves with the sewing cuffs removed. First level testing evaluated the visual cavitation thresholds of size 25, 27, and 29 CarboMedics (CPHV), Saint Jude Medical (SJM) and Duromedics (original design prior to 1990 revision) valves using high-speed videographic methods to observe and record the presence of cavitation bubbles generated by each valve upon closure. Visual cavitation thresholds were also determined for size 29 Sorin and Jyros valves. The visual cavitation threshold dP/dt value was 2,500 mmHg/sec for the size 25 SJM and CPHV and 1,600 mmHg/sec for the size 25 Duromedics valve. Second level testing assessed the erosion resistance of size 25 CPHV, SJM, and Duromedics valves cycled at identical drive conditions. Upon visual inspection, damage to the Duromedics valves appeared to be much more severe than on either the CPHV or the SJM valve. Erosion damage observed on the CPHV appeared to be identical to that observed on the SJM valve. All Duromedics valves tested were of the original design (prior to the 1990 revision) and the effects of the sewing cuffs on the cavitation threshold and erosion were not evaluated in this investigation.

Heart Valve Prosthesis↗
PubMed1998

Tension-time index of inspiratory muscles in COPD patients: role of airway obstruction.

Inspiratory muscle function has been shown to be related to general muscle weakness, weight loss, blood gas tensions, airway obstruction and hyperinflation. The aim of this study was to define (1) the factor that is the main determinant of the tension-time index of the inspiratory muscles (TTmus), and which this increases the risk of inspiratory muscle fatigue; and (2) whether a breathing strategy is adopted to avoid inspiratory muscle fatigue. Twenty-seven normal volunteers and 35 stable COPD outpatients (FEV1% predicted, range: 21-89%; and FRC/TLC, range: 49-77%) were studied. The TTmus was determined as follows: TTmus = PI/PImax.TI/Ttot, where Pi is the mean inspiratory pressure calculated from the mouth occlusion pressure (P0.1), PImax is the maximal inspiratory pressure, TI is the inspiratory time, and Ttot is the total time of the breathing cycle. COPD patients showed significantly lower PImax and higher P0.1, PI, PI/PImax, and TTmus than normal subjects. No patient had a TTmus value higher than the inspiratory muscle fatigue threshold of 0.33. The FEV1 was significantly correlated with TTmus and all its components in the patients. The FRC/TLC was also correlated with all components except PI. Body weight was only correlated with PImax. In a forward and backward stepwise regression analysis, FEV1 appeared to be the only significant factor explaining the variance of log (PI/PImax) and log (TTmus), whereas FRC/TLC was the principal determinant of PImax. In COPD patients, a non-linear relationship was found between TI and P0.1. A negative linear relationship was found between TI/Ttot and PI/PImax. In conclusion, although hyperinflation predominantly affected inspiratory muscle strength in a group of stable COPD patients with a wide range of severity, airway obstruction was the principal factor determining the magnitude of TTmus. In addition, in order to remain below the inspiratory muscle fatigue threshold, as the severity of airway obstruction increased, patients adopted a breathing strategy characterized by decreased TI/Ttot as inspiratory pressure demand increased.

Adaptation, Physiological↗
PubMed1999

Threshold dose response for tumor induction by genotoxic carcinogens modeled via cell-cycle delay.

Dose-response relationships for tumor induction in animal bioassays for carcinogenicity are often postulated to include thresholds, particularly for nongenotoxic chemicals that increase the rate of cell proliferation at high doses. In this report, thresholds are postulated also for genotoxic carcinogens. The hypothesis is based on the idea of a delay of the cell cycle induced by low-level DNA damage and an acceleration at cytotoxic dose levels, thus resulting in a J-shaped (or U-shaped) dose response for cell turnover. Calculations were based on the 2-stage clonal expansion model of carcinogenesis. The background values chosen for the model parameters resulted in a 10.5% "spontaneous" 2-year cumulative tumor incidence. Using this as a starting point, a decrease by 3, 10, and 30% in the rates of cell turnover resulted in a decrease in the spontaneous tumor incidence to 9.4, 7.1 and 3.0%, respectively. Dose-responses with J-shaped curves for the rates of cell birth and death were modeled by shifted quadratic functions reaching the minimum at dose 1. Combinations with linearly increasing mutation rates also generated, under certain conditions, J-shaped dose-response curves for tumor incidence. As an example, for a 30% increase in mutation rates and a 10% decrease in cell turnover rates (both at dose 1), the dose-response curve showed an initial decrease of tumor incidence below the spontaneous rate, a reversion to the background value at 0.8 dose units, and an increase thereafter. The 0.8 dose could be considered to represent the "threshold dose." The approach presented might reconcile opposing views on thresholds on a biologically plausible mechanistic basis, and show a way for the quantitative estimation of threshold doses.

Animals↗
PubMed1998

Identifying the integrated electromyographic threshold using different muscles during incremental cycling exercise.

BACKGROUND: The purpose of this study was to identify the IEMG threshold in the vastus lateralis (VL) and rectus femoris (RF) muscles during progressive, incremental exercise and to relate these thresholds to the ventilatory threshold (Tvent). METHODS: Ten men (age: 23.40 +/- 3.13 yrs, mass 76.64 +/- 8.13 kg, % fat: 8.81 +/- 2.32, VO2peak: 66.37 +/- 10.61 ml.kg.min-1) with cycling experience completed a graded exercise test on a cycle ergometer by cycling at 90 rpm using 45 watt increments at two minute intervals. Oxygen uptake was measured continuously and the IEMG activity of the VL and RF was calculated during the last 5 s of each minute. The mean for the IEMG of 6 to 7 complete pedal revolutions was used as the final value. Tvent was visually identified using the VE/VO2 and V-slope methods. The IEMG threshold for VL and RF was visually identified at the inflection point where a non-linear increase in IEMG occurred. Comparisons between Tvent and IEMG thresholds were made using dependent means "t"-tests. RESULTS: Results showed that an IEMG threshold was identified in all 10 subjects for the RF, but in only 5 of 10 subjects for the VL. However, when identified, the IEMG threshold for VL was similar to RF.VO2 at IEMG threshold for RF (3.53 +/- 0.36 L.min-1) was not significantly different from Tvent (3.36 +/- 0.42 L.min-1). CONCLUSIONS: These results show that the IEMG threshold is more consistently detected in the RF compared to VL during incremental cycling exercise. In addition, the IEMG threshold for RF was closely related to Tvent and provides an alternative means to assess the ventilatory threshold.

Adult↗
PubMed1996

Evaluation of a new E-optotype chart for measuring contrast sensitivity.

BACKGROUND: Clinical examinations of the contrast sensitivity (CS) are currently made by one-trial measurements of a restricted number of spatial frequencies around the peak of the CS function (CSF). These methods do not allow calculation of the confidence intervals of the single measurements, thus preventing examiners from evaluating the reliability of their data. We elaborated a new method of CS measurement at the peak of the CSF, aiming at economical clinical applicability together with enhanced reliability. Moreover, we tried to establish lower limits of normal CS that would allow classification of low test results as pathological. METHODS: A chart containing six columns of E optotypes of constant size and decreasing contrast (from about 16% to 0.5%) was used to perform six-fold contrast threshold determination (method of descending limits, forced choice). Optotype dimensions are intended to measure the CS at spatial frequencies corresponding to 3 and 6 cycles per degree (c/deg). The reference values were defined by testing 61 normal subjects: 31 "young" (16-35 years) and 30 "old" (56-81 years). RESULTS: The mean logCS found in the young group was 2.07 +/- 0.086 SD for 3 c/deg and 1.94 +/- 0.154 SD for 6 c/deg, while in the old group the mean logCS was 1.88 +/- 0.095 SD and 1.74 +/- 0.118 SD respectively. CONCLUSION: This simple method of measuring CS can provide a single CS value together with a confidence interval for the individual patient, thus allowing evaluation of measurement reliability.

Adolescent↗
PubMed2004

Antioxidant protection in a new animal model of cisplatin-induced ototoxicity.

Mortality is a major complication in animal models of cisplatin-induced hearing loss due to the systemic toxicity of the drug. Here we report on a novel two-cycle treatment in rats, each cycle consisting of four days of cisplatin injections (1 mg/kg, i.p., twice daily) separated by 10 days of rest. This regimen, similar to clinical courses of cancer chemotherapy, produced significant hearing loss without mortality. Auditory brain stem evoked responses were unchanged after the first cycle but were elevated by 40-50 dB at 16 and 20 kHz after the second. Loss of outer hair cells occurred after the second cycle, predominantly in the base of the cochlea. Total cochlear antioxidants declined progressively during drug treatment and were reduced to 60% of control values after the second cisplatin cycle. Co-administration of salicylate (100 mg/kg, s.c., twice daily) during both cycles or during the second cycle restored antioxidant levels and reduced cisplatin-induced threshold shifts. This model of cisplatin ototoxicity without mortality eliminates potentially confounding factors that may determine the survival of a special cohort of animals. The results also support the notion that reactive oxygen species are involved in cisplatin ototoxicity and show the potential usefulness of antioxidant treatment.

Animals↗
PubMed1992

Effects of captopril chronic intake on the aerobic performance and muscle strength of normotensive trained subjects.

Fifteen normotensive athletes specializing in dynamic sports took part in a randomized double-blind and cross-over study: captopril (50 mg/24 h) vs placebo. Each treatment lasted one month. Maximal exercise tests on cycle ergometer were performed at the end of each period. No significant differences were observed in the maximal values of oxygen uptake, power, heart rate or blood lactate value. The anaerobic threshold, defined as the exercise intensity which corresponded to a 4 mmol.l-1 blood lactate level was unchanged. With captopril, the end-of-exercise systolic and diastolic BP were slightly altered (NS). Lower limb muscle strength, as explored with a Cybex isokinetic system, was not modified by captopril intake. The results indicate that maximal aerobic performance and isokinetic strength of the lower limbs are not altered by captopril chronic administration (50 mg/day) in normotensive trained subjects.

Adult↗
PubMed2006

A novel model-free approach for reconstruction of time-delayed gene regulatory networks.

Reconstruction of genetic networks is one of the key scientific challenges in functional genomics. This paper describes a novel approach for addressing the regulatory dependencies between genes whose activities can be delayed by multiple units of time. The aim of the proposed approach termed TdGRN (time-delayed gene regulatory networking) is to reversely engineer the dynamic mechanisms of gene regulations, which is realized by identifying the time-delayed gene regulations through supervised decision-tree analysis of the newly designed time-delayed gene expression matrix, derived from the original time-series microarray data. A permutation technique is used to determine the statistical classification threshold of a tree, from which a gene regulatory rule(s) is extracted. The proposed TdGRN is a model-free approach that attempts to learn the underlying regulatory rules without relying on any model assumptions. Compared with model-based approaches, it has several significant advantages: it requires neither any arbitrary threshold for discretization of gene transcriptional values nor the definition of the number of regulators (k). We have applied this novel method to the publicly available data for budding yeast cell cycling. The numerical results demonstrate that most of the identified time-delayed gene regulations have current biological knowledge supports.

Algorithms↗