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Results for “Recovery phases”

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PubMed1995

Haemostatic effects of supraphysiological levels of testosterone in normal men.

The effects of exogenous testosterone on the haemostatic system were studied in a group of 32 healthy men undergoing a clinical trial of hormonal male contraception. The men received 200 mg testosterone oenanthate (TE) weekly i.m., and plasma samples were taken pretreatment, at defined time points up to 52 weeks of treatment, and 4 and 8 weeks after discontinuing TE. This dose of TE caused a 2-fold increase in trough plasma testosterone levels. TE caused a fall in plasma fibrinogen concentration after 16 weeks of treatment. This was sustained for the duration of TE treatment and recovered to pretreatment levels during the recovery phase. There was also a sustained fall in the level of C4b binding protein which showed a rebound to levels above pretreatment during recovery. Levels of antithrombin III and prothrombin fragment F1.2 rose initially during TE treatment, and levels of protein C, protein S (free) and plasminogen activator inhibitor fell, but the concentrations of these factors all returned to pretreatment levels during continued treatment. There was no change in the plasma concentrations of beta-thromboglobulin, tissue plasminogen activator, protein S (total), or D-dimer. There was a sustained increase in haemoglobin concentration and haematocrit, without any change in platelet count. The observed changes were consistent with mild activation of the haemostatic system during initial treatment with testosterone. After several months the raised activation markers had returned to pretreatment levels indicating that a new equilibrium had been established which did not appear to be prothrombotic.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Excess-substrate inhibition in enzymology and high-dose inhibition in pharmacology: a reinterpretation [corrected].

A kinetic model, called the Recovery Model, which incorporates an obligatory recovery phase of fixed duration (tr) in the operation cycle of a macromolecule (enzyme, receptor) is proposed. Binding of a ligand (substrate, agonist) during tr disturbs the recovery process and causes inhibition (substrate inhibition, agonist autoinhibition). A quantitative stochastic analysis of a minimal version of the Recovery Model reveals that (1) plotting the response versus the logarithm of the ligand concentration never yields a strictly symmetrical bell-shaped dose-response curve, (2) the position and shape of the descent of the dose-response curve can vary greatly in dependence of the kinetic parameters of the system, and (3) a minimal steepness of the descent with a Hill coefficient of 1 exists provided that the response can be totally inhibited by high ligand concentrations. The Recovery Model is equally applicable to macromolecules that can bind single or multiple ligands, and suggests new ways to explain such diverse phenomena as partial agonism, pulse generation, desensitization, memory effects and ultrasensitivity. In addition, substrate inhibition and agonist autoinhibition are regarded as phenomena closely related to other kinds of non-Michaelian behaviour because of a common temporal mechanism, namely the temporal interference of arriving ligand molecules with timing-sensitive phases of the operation cycle.

Enzyme Inhibitors↗

PubMed2001

Determination of skeletal muscle perfusion using arterial spin labeling NMRI: validation by comparison with venous occlusion plethysmography.

T(1)-based determination of perfusion was performed with the high temporal and spatial resolution that monitoring of exercise physiology requires. As no data were available on the validation of this approach in human muscles, T(1)-based NMRI of perfusion was compared to standard strain-gauge venous occlusion plethysmography performed simultaneously within a 4 T magnet. Two different situations were investigated in 21 healthy young volunteers: 1) a 5-min ischemia of the leg, or 2) a 2-3 min ischemic exercise consisting of a plantar flexion on an amagnetic ergometer. Leg perfusion was monitored over 5-15 min of the recovery phase, after the air-cuff arterial occlusion had been released. The interesting features of the sequence were the use of a saturation-recovery module for the introduction of a T(1) modulation and of single-shot spin echo for imaging. Spatial resolution was 1.7 x 2.0 mm and temporal resolution was 2 s. For data analysis, ROIs were traced on different muscles and perfusion was calculated from the differences in muscle signal intensity in successive images. To allow comparison with the global measurement of perfusion by plethysmography, the T(1)-based NMR measurements in exercising muscles were rescaled to the leg cross-section. The perfusion measurements obtained by plethysmography and NMRI were in close agreement with a correlation coefficient between 0.87 and 0.92. This indicates that pulsed arterial techniques provide determination of muscle perfusion not only with superior spatial and temporal resolution but also with exactitude.

Adult↗

PubMed1986

A study of the effects of substrates on intracellular pH in toad ventricular strips.

The ability of different substrates to affect myocardial function is well established but the mechanism for this effect has yet to be determined. To explore this area further, the studies described below were designed to determine the effect of different metabolic substrates, glucose or pyruvate, on myocardial response to hypercapnia. To assess this response, both the mechanical performance and the intracellular pH (pHi) were continuously measured. Intracellular pH was measured using the changes in absorbance of the vital staining dye, neutral red (NR). Although the presence of either substrate did not affect the response to hypercapnia, the addition of pyruvate was accompanied by a significant change in pHi. Specifically, there was a monotonic decrease in pHi comparable to that observed when PCO2 is increased from 5% to 10% (delta OD = -0.018 +/- 0.002 CO2; delta OD = -0.020 +/- 0.002 PYR, respectively). The mechanical response was similar for both; developed tension (tau) decreased initially (97 +/- 6% v. 93 +/- 8%) and then recovered (115 +/- 4% v. 101% +/- 5%). However, the changes in the maximum rate of relaxation, i.e. minimum time derivative: (tau mn) were dependent on the cause of the decrease in pHi. With hypercapnia, tau mn initially decreased and this was followed by a recovery phase which was 147 +/- 8% of the initial value. With pyruvate, tau mn decreased to 81 +/- 5% of control and was followed by no recovery. Because of the difference in the changes in tau mn, the effects of theophylline [3, 5] on these responses were determined. There was no effect on the response to an increase in PCO2. However, with theophylline present, the addition of pyruvate was accompanied by an increase in pHi (delta OD = + 0.005 +/- 0.001). The mechanical response was consistent with this increase and was similar to that seen when PCO2 is decreased from 10% to 5%. Specifically, there was an increase in tau (122 +/- 7%) followed by a small decrease (113 +/- 4%). Tissue assays for lactate showed a significant increase with the introduction of pyruvate. However, this increase was not affected by the presence of theophylline despite the opposite response of pHi. The data suggest that pyruvate affects myocardial function by altering pHi, and this effect is not due to an increase in lactate. In addition, the data are consistent with the model that the heart is capable of accommodating changes in pHi with only transient effects on contractile function.

Animals↗

PubMed1997

Significance of persistent left ventricular dysfunction during recovery after dobutamine stress echocardiography.

OBJECTIVES: This study sought to determine the duration of new or worsening left ventricular regional wall motion abnormalities (RWMAs) after dobutamine stress echocardiography (DSE) and their relation to the extent of coronary artery disease (CAD). BACKGROUND: Despite extensive reports on DSE, little is known about the duration of new or worsening RWMAs during recovery. We hypothesized that the persistence of RWMAs during recovery may be associated with the extent of CAD and therefore ischemia. METHODS: Sixty-five consecutive patients with positive results on DSE and angiographically documented CAD were studied. Each patient underwent 12-lead electrocardiography and two-dimensional echocardiography at rest, during dobutamine infusion and continuously during recovery to assess the recovery time of ischemic myocardial regions. RESULTS: All patients had at least one ischemic region during DSE. Complete resolution of RWMAs occurred within 25 min in patients with multivessel CAD, within 20 min in those with two-vessel disease and within 15 min in those with single-vessel disease (p < 0.001). The greater the wall motion score index at peak stress, the longer the duration of RWMAs into the recovery phase (p < 0.01). RWMAs persisted long after normalization of each patient's symptoms, electrocardiographic (ECG) changes, heart rate and rate-pressure product during recovery. CONCLUSIONS: We demonstrated that normalization of left ventricular RWMAs occurs after resolution of symptoms and ECG changes during recovery. The time to recovery is related to the extent of CAD and myocardial ischemia as well as to the presence or absence of collateral circulation. These findings may represent stunned myocardium after brief period of ischemia.

Adult↗

PubMed1986

Restoration of baroreflex control of heart rate during recovery from anaesthesia.

The effects on baroreflex control of heart rate of halothane or methohexitone used to supplement 67% nitrous oxide in oxygen have been studied in 21 patients. Stable anaesthesia with either agent caused depression of baroreflex sensitivity by more than 50%. The set point of the reflex was also changed by both agents, but in opposite directions. Halothane administration resulted in slower heart rates at lower arterial pressures, whereas the infusion of methohexitone caused faster heart rates at lower arterial pressure. During recovery from anaesthesia, there was a rapid return of baroreflex sensitivity to normal and this was achieved before the patients regained consciousness, with no difference between the two groups. The reflex was reset rapidly and repeatedly during the recovery phase.

Adult↗

PubMed1998

Geographic variation in the molluscan recovery from the end-cretaceous extinction

Biotic recovery patterns after the end-Cretaceous mass extinction differ among the molluscan faunas of the North American Gulf Coast, northern Europe, northern Africa, and Pakistan and northern India. In contrast to the Gulf Coast, the other three regions lack a rapid expansion and decline of "bloom taxa" and have lower proportions of invaders early in the recovery phase. The anomalous Gulf Coast patterns, distinct from extratropical Europe and the tropical regions, provide evidence for the biogeographic and macroevolutionary complexity of biotic recoveries and may have implications for present-day biotas.

Journal Article↗

PubMed1984

Lipoproteins, lipoprotein lipase, and glycogen after prolonged physical activity.

The effect of strenuous exercise on lipoprotein level and composition as well as on lipoprotein lipase activity (LPLA) and glycogen stores in skeletal muscle was studied in 16 healthy young men after military field maneuvers. Body weight was reduced by 1 kg after the maneuvers and was gradually restored during a 5-day recovery phase. Glycogen levels were reduced by 50% and LPLA increased threefold immediately after the exercise, and neither were restored until 3-5 days of recovery. Serum triglycerides were decreased by about 50% after 1 day of recovery and the cholesterol concentration in high-density lipoproteins increased but only immediately after exercise. In contrast, the apolipoproteins A-I and A-II, the main protein constituents, were both decreased and remained so for 3-5 days. The results indicate that significant alterations of plasma lipoprotein level and composition as well as of muscle metabolism occur after prolonged physical exertion and that some changes are still evident after 5 days of recovery.

Adult↗

PubMed1993

Immune reconstitution following peripheral blood stem cell transplantation, autologous bone marrow transplantation and allogeneic bone marrow transplantation.

The rate and pattern of recovery of total lymphocytes, T cell subsets, B cells and NK cells were compared for 12 months following recovery phase peripheral blood stem cell (PBSC) autotransplantation (n = 49), autologous (n = 7) and allogeneic BMT (n = 11). The PBSC group had a significantly faster recovery of total lymphocyte count, total T cells (CD3+ cells), CD8 cells and CD4 cells than the allogeneic BMT group. The pattern of earlier recovery of CD8 cells than CD4 cells was the same for each type of transplant. Reconstitution following autologous BMT was intermediate between PBSC and allogeneic BMT. Multivariate analysis identified type of transplant, number of mononuclear cells transplanted and conditioning regimen as significantly influencing immune recovery.

B-Lymphocyte Subsets↗

PubMed2005

Development and resolution of experimental colitis in mice with targeted deletion of dipeptidyl peptidase IV.

Glucagon-like peptide-2 (GLP-2) is a potent intestinotrophic growth factor that enhances repair of damaged intestinal tissue. However, its bioactivity is limited by dipeptidyl peptidase IV (DPIV)-mediated degradation. We hypothesized that DPIV(-/-) mice would display an increased resistance to, and an enhanced recovery from, dextran sulfate sodium (DSS)-induced colitis compared to DPIV(+/+) mice. DPIV(+/+) and DPIV(-/-) mice consumed 2% DSS for 6 days, followed by a 15 day recovery period. Mice were killed at days 0, 3, 6, 9, 14, and 21 (n = 6-8) and the small intestine and colon removed for histological assessment of villus height, crypt depth, and crypt area. The epithelial cell proliferative labeling index was determined by proliferating cell nuclear antigen (PCNA) immunostaining. Small intestine, colon, and total body weight did not differ between DPIV(+/+) and DPIV(-/-) mice. Distal colon crypt depth did not differ significantly between DPIV(+/+) and DPIV(-/-) mice during the development of DSS-colitis or during the recovery phase. Similarly no significant effects were apparent on distal colon crypt area or PCNA labeling index between DPIV(+/+) and DPIV(-/-) during the development of and recovery from DSS-colitis. However, DPIV(-/-) mice still possessed significant levels of plasma DPIV-like activity. We conclude that loss of DPIV activity does not increase resistance to experimental colitis and hypothesize that other DPIV family members may also be involved in the cleavage of GLP-2.

Animals↗

PubMed1980

Bacterial kill rates of amoxycillin and ampicillin at exponentially diminishing concentrations simulating in vivo conditions.

The responses of bacteria exposed to amoxycillin and ampicillin were studied at continuously decreasing levels with half-life values similar to those which could occur in vivo. For Escherichia coli, the kill-rates were higher with amoxycillin than with ampicillin. The bactericidal response was exponential. With an antibiotic half-life of one hour, the amoxycillin first order inactivation rate was 3.544 h-1 and the viable cell half-life was 0.196 h; the respective values for ampicillin were 2.341 h-1 and 0.296 h. With an antibiotic half-life of five hours, the inactivation rate was 0.704 h-1 corresponding to a viable cell half-life of 0.985 h for amoxycillin compared to 0.358 h-1 and 1.937 h respectively for ampicillin. Comparison of viable counts and photometric monitoring showed that the former is the preferable method for recording the bacterial response to these beta-lactam antibiotics. During the phase of exponential kill, a plateau occurred in the optical density values. This was due in part to an increased biomass per cell. During the recovery phase, the number of viable cells started to increase several hours sooner than did the rise in optical density. For Staphylococcus aureus,the rates of kill were similar with both agents. Amoxycillin had a long bacteriostatic phase which was not seen with ampicillin. This led to a longer lasting antibacterial effect and reduction to a lower total count with amoxycillin. With staphylococci, the viable counts and the photometric responses were parallel.

Amoxicillin↗

PubMed1998

Regulation of telomerase activity in quiescent immortalized human cells.

Telomerase is a key enzyme in carcinogenesis; telomerase activity has been found in more than 90% of human tumors. Understanding the regulation of this enzyme will improve our knowledge of tumor biology and may lead to novel strategies in cancer therapy. We examined effects of growth arrest on telomerase activity in the human immortalized cell lines U 937 (lymphoma) and L 428 (Hodgkin's disease). Cells were starved by serum depletion for 4 days. After readdition of serum, a recovery phase followed. Cell proliferation was monitored with the monoclonal antibody Ki-S5. In the absence of serum, telomerase levels declined fivefold. After serum readdition, recovery to threefold increased level was observed. Furthermore, the prevalence of telomerase-positive cells in normal tissues is an important issue for understanding tumorigenesis. Our TRAP assay is robust against false positives and in mixed cell samples, we found a rather limited sensitivity of the telomere repeat amplification protocol (TRAP) assay. This means that adequate screenings for telomerase-positive somatic cells have to include enrichment steps.

Base Sequence↗

PubMed1994

Hepatitis C virus acute exacerbation during chemotherapy and radiotherapy for oesophageal carcinoma.

AIMS: We report the first case of an hepatitis C virus positive patient presenting with a solid tumor and developing an exacerbation of his hepatitis C after chemotherapy. CASE REPORT: A 56-year-old white male, previously infected with hepatitis C virus and treated for epidermoid carcinoma of the oesophagus, developed hepatitis (alamine aminotransferase 2376 U/l and aspartate aminotransferase 2262 U/l) after chemotherapy with cisplatin and vinblastine. METHODS: Polymerase chain reaction detected hepatitis C virus RNA in the serum during the acute phase, which returned to negative 14 weeks later. DISCUSSION: Viral replication was probably increased during immunosuppression induced by chemotherapy. Enhanced cellular immune response in the recovery phase was the most likely cause of the hepatitis. CONCLUSIONS: More attention should be paid to liver function tests in patients with a previous history of hepatitis C virus infection. Polymerase chain reaction identification of hepatitis C virus RNA can be a very useful tool that permits rapid diagnosis and appropriate management of such cases.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

X-ray phase vortices: theory and experiment.

We review the current work on x-ray phase vortices. We explain the role of an x-ray vortex in phase recovery and speculate on its possible applications in other fields of x-ray optical research. We present our theoretical understanding of the structure of phase vortices and test these predictions against experiment. We present experimental observations of phase vortices with charge greater than 3 and observe that their propagation appears to be consistent with our theoretical models.

Journal Article↗

PubMed1993

[The stress test in adolescents with and without a family history of arterial hypertension: the prognostic role of a systolic arterial pressure index].

A family history of hypertension can influence the behaviour of blood pressure during ergometric stress test (EST) in normotensive subjects, so that it is also used in the assessment of risk of hypertension. To evaluate the relationship between parental history and blood pressure values during exercise, 57 consecutive adolescents (aged 10-16 years) were studied. Out of them, 25 patients have not been considered because of the presence of organic pathologies of various nature that could interfere with the pressure behaviour. All patients underwent EST with a load increase of 25 W every 3 min until the maximal age-related heart rate. The patients were divided in 2 groups based on the presence (PH+ 13 patients, mean age 13 +/- 2 years) or on the absence (PH- 19 patients, mean age 13 +/- 2 years) of parental history of hypertension. No difference in body surface and maximum workload was observed between the 2 groups. Exercise test induced an increase in systolic blood pressure (SBP) both in PH- and PH+ patients, but no significant differences were found in any stage of the exercise in the 2 groups. Maximum heart rate (HR) was not different in the 2 groups and diastolic blood pressure (DBP) was substantially unchanged during exercise. The variation of SBP (delta SBP) between maximum stress and first, third, fifth and tenth min of the recovery phase were considered. Besides, 4 SBP indexes were deduced from the ratio of SBP values at the first, third, fifth and tenth min of the recovery by the SBP value at the acme of stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1998

Sequential expression of mRNA for proinflammatory cytokines and interleukin-10 in the rat peripheral nervous system: comparison between immune-mediated demyelination and Wallerian degeneration.

This study examined the time course of mRNA levels of the proinflammatory cytokines interferon-gamma (IFNgamma), interleukin-1beta (IL1beta), interleukin-12 (IL12; p40 subunit), and the immunosuppressant interleukin-10 (IL10) by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) in rats with actively induced experimental autoimmune neuritis (EAN) and in distal stumps of crushed sciatic nerves undergoing Wallerian degeneration. In EAN IFNgamma- and IL1beta-mRNA peaked at the onset and acute phase of clinical disease. IL12p40-mRNA was upregulated later than IFNgamma-mRNA in the late acute phase from days 15 to 21. IL10-mRNA appeared concomitantly with the proinflammatory cytokines at day 11, but persisted at high levels into the clinical recovery phase. After nerve crush both IL1beta- and IL10-mRNA were rapidly upregulated in the distal stump at day 1 and slowly declined over the next 2 weeks. Significant levels of mRNA for IFNgamma could be found at days 4 and 7, whereas IL12p40-mRNA showed a biphasic induction. We provide evidence for a concomitant induction of pro- and anti-inflammatory cytokines in EAN. Moreover, the rapid upregulation in Wallerian degeneration suggests a more general role of cytokines in the biology of the peripheral nerve.

Animals↗

PubMed1993

Renal immunolocalization of kallikrein in cisplatin nephrotoxicity in rats.

Treatment of rats with cisplatin (4 mg kg-1 body wt i.p. injection) induced variations of urinary kallikrein excretion (UKE). Three phases were observed: a transient increase of UKE one day after injection, followed by a decrease up to 10 days suggesting an altered biosynthesis and a recovery phase with return to normal control values, 21 days after injection. Early morphological lesions were observed in proximal tubule cells on day 1; severe changes and tubular necrosis were observed in the following days. Less marked changes were also present in distal tubules but the vacuolated and desquamated cells appeared in the lumen of the tubules. By immunocytochemical methods, kallikrein was observed in connecting tubule cells, but also in some proximal tubule cells and along the endothelial side of the glomerular basement membrane and urinary space of glomeruli. An intense labelling was present in desquamated epithelial cells in dilated lumen of tubules. This study provides evidence of the presence of immunoreactive kallikrein in the glomerulus, already reported during acute failure, and confirms the use of urinary kallikrein measurements as a useful non-invasive index to assess a possible nephrotoxic effect at the distal level.

Animals↗

PubMed2006

Gonadal steroids in critical illness.

Gonadal steroids are metabolized in target cells and then interact with specific receptors to exert genomic and nongenomic effects. Complex feedback loops that involve the immune-neuroendocrine axis, limbic system, and gonadal steroids play a vital role in the adaptation to critical illness. Preclinical studies demonstrate adverse physiological effects of androgens on the cardiovascular and immune systems despite its purported anabolic effects. Similar models also demonstrate salutary effects of estrogens on these systems. Thus, during the catabolic phases of acute and chronic critical illness, estrogen, and not androgen, therapy may prove to be a valuable intervention. However, during the post-critical illness recovery phase, when anabolism is critical, androgen therapy may still be useful and safe.

Androgens↗