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PubMed2005

Ca2+ clearance mechanisms in neurohypophysial terminals of the rat.

The importance of intracellular calcium ([Ca2+]i) in the release of vasopressin (AVP) and oxytocin from the central nervous system neurohypopyhysial nerve terminals has been well-documented. To date, there is no clear understanding of Ca2+ clearance mechanisms and their interplay with transmembrane Ca2+ entry, intracellular [Ca2+]i transients, cytoplasmic Ca2+ stores and hence the release of AVP at the level of a single nerve terminal. Here, we studied the mechanism of Ca2+ clearance in freshly isolated nerve terminals of the rat neurohypophysis using Fura-2 Ca2+ imaging and measured the release of AVP by radioimmuno assay. An increase in the K+ concentration in the perfusion solution from 5 to 50 mM caused a rapid increase in [Ca2+]i and AVP release. Returning K+ concentration to 5 mM led to rapid restoration of both responses to basal level. The K+-evoked [Ca2+]i and AVP increase was concentration-dependent, reliable, and remained of constant amplitude and time course upon successive applications. Extracellular Ca2+ removal completely abolished the K+-evoked responses. The recovery phase was not affected upon replacement of NaCl with sucrose or drugs known to act on intracellular Ca2+ stores such as thapsigargin, cyclopiazonic acid, caffeine or a combination of caffeine and ryanodine did not affect either resting or K+-evoked [Ca2+]i or AVP release. By contrast, the plasma membrane Ca2+ pump inhibitor, La3+, markedly slowed down the recovery phase. The mitochondrial respiration uncoupler, carbonyl cyanide 3-chlorophenylhydrazone (CCCP), slightly but significantly increased the basal [Ca2+]i, and also slowed down the recovery phase of both [Ca2+]i and release responses. In conclusion, we show in nerve terminals that (i) Ca2+ extrusion through the Ca2+ pump in the plasma membrane plays a major role in the Ca2+ clearance mechanisms of (ii) Ca2+ uptake by mitochondria also contributes to the Ca2+ clearance and (iii) neither Na+/Ca2+ exchangers nor Ca2+ stores are involved in the Ca2+ clearance or in the maintenance of basal [Ca2+]i or release of AVP.

Animals↗

PubMed1999

Characteristics of protein and energy metabolism in neonates with necrotizing enterocolitis--a pilot study.

BACKGROUND/PURPOSE: It is assumed that neonates with necrotizing enterocolitis (NEC) are hypermetabolic. However, the dynamics of protein and energy metabolism in neonates with NEC have not been characterized. The purpose of this study was to test the hypothesis that protein turnover and energy expenditure are increased during the acute stage of NEC and later return to normal values. METHODS: A pilot study was performed on six neonates with proven NEC (Bell's stage II or III). Patients were studied in two phases: (1) in the acute stage of their disease and (2) when their clinical condition had stabilized. Whole-body protein turnover was calculated using an intravenous infusion of [1-13C] leucine and by measuring the isotopic enrichment of plasma [13C]alpha-ketoisocaproic acid and 13CO2. Respiratory gas exchange was measured simultaneously by computerized indirect calorimetry. RESULTS: Median gestational age was 36 weeks (range, 28 to 40) with a median postnatal age of 21 days (range, 6 to 47). All patients recovered from the acute episode, although three patients died after recovering from the acute disease from other conditions. The patients studied showed marked variability in protein metabolism kinetics. However, there was no difference in whole-body protein flux between the acute phase (7.6 g/kg/d; range, 5.6 to 18.2) and the recovery phase (7.0 g/kg/d; range, 6.9 to 12.2; P = .89). Furthermore, there was no difference in any of the component parts of wholebody protein turnover. Resting energy expenditure did not change between the acute phase (42.8 kcal/kg/d; range, 34.4 to 52.5) and the recovery phase (51.0 kcal/kg/d; range, 34.9 to 55.3; P = .18). CONCLUSIONS: This pilot study shows that the rates of protein and energy metabolism in neonates with NEC are comparable with reported values in stable neonates. There was no difference in protein or energy dynamics between study phases. The authors speculate that neonates with NEC may divert the products of protein synthesis from growth to tissue repair.

Calorimetry, Indirect↗

PubMed1979

[Psycho-physiological effects of pop music on cardiovascular parameters at rest and during exertion (author's transl)].

The effects of pop music on heart rate, systolic and diastolic blood pressure at rest, during exercise on a bicycle ergometer and in the recovery phase were investigated. The psychological effects of the music were analysed by means of a question sheet and correlated with the physiological effects. The psychological effects of the music points to a reduction of monotony and of fatigue. During exercise, especially during low physical strain, there was a good correlation between the psychological and the physiological parameters. The significant decrease of the cardiovascular parameters in the recovery phase demonstrates, that emotional stimuli are influencing the heart rate not only at rest and work, but also in the recovery phase. The results of the psycho-physiological experiments give rise to the conclusion, that individual attitude to music doesn't primarily influence the effects of music on physiological reactions.

Adult↗

PubMed1994

Non-parenchymal cell responses in paracetamol (acetaminophen)-induced liver injury.

We have analysed Kupffer cell and 'activated' perisinusoidal cell populations in liver biopsies from patients with paracetamol (acetaminophen)-induced hepatic necrosis of varying degrees of severity. Kupffer cells were identified immunohistochemically using the monoclonal antibody KPJ and perisinusoidal cells by identification of alpha-smooth muscle actin expression. Material was available from four groups of individuals: (i) 11 cases with mild (grade I) injury; (ii) six cases with moderate (grade II) injury; (iii) six cases with severe (grade III) injury; and (iv) controls with normal liver histology (n = 23). Biopsies in groups (i)-(iii) were obtained within 5 days of drug ingestion. All patients in this study survived and follow-up biopsies were obtained at 4 months, by which time the histological abnormalities had fully resolved. Kupffer cells and perisinusoidal cell numbers were assessed in immunostained preparations of acute and recovery phase biopsies and in control specimens. In acute phase biopsies from patients with grade II and III injury there was expansion of the Kupffer cell and perisinusoidal cell populations within areas of injury. There was a strong correlation between the size of these two cell populations (r = 0.886). No significant difference in cell numbers was found between those with grade I injury and controls. In recovery phase biopsies from patients with paracetamol-induced injury, perisinusoidal cell numbers did not differ significantly from normal controls. Kupffer cells numbers also decreased in recovery phase biopsies compared with the acute phase, although there was persistent expansion of the Kupffer cells population in those who originally had grade III injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗

PubMed2005

Breastfeeding reduces immune activation in primary respiratory syncytial virus infection.

In epidemiological studies of respiratory syncytial virus (RSV) disease, breast milk has proven to be beneficial. However, a host mechanism that is associated with both disease severity and that is capable of being modulated by breast milk, has not yet been identified. Both the predominance of interleukin-10 (IL-10) over interferon-gamma (IFN-gamma), and high soluble interleukin-2 receptor antagonist (sCD25) concentrations have been associated with RSV severity. We explored if they were modulated by breastfeeding. Previously healthy Chilean infants from Santiago with RSV infection (n = 349) were consecutively enrolled in the study if they were term births, without underlying pathology. Breastfeeding was described as absent or present, and if partial or exclusive. Immune response was expressed through plasma concentrations of IFN-gamma, IL-10 and sCD25, obtained both in the acute and the recovery phase. The acute phase sCD25 concentrations were lower in the breastfed (13.8 ng/mL, n =133), compared with the non-breastfed infants (15.9 ng/mL, n 27, p = 0.015). The difference increased in infants below 3 months of age (p = 0.006) and with exclusive (p = 0.004), compared to partial breastfeeding (p = 0.025). When analyzed together with age, sex, severity and environment, breastfeeding was the only independent predictor of high sCD25 concentrations (above mean + 1SD, OR 4.6, 95% CI 1.8-11.9, p = 0.0015). The recovery phase IFN-gamma/IL-10 ratio was higher in the breastfed infants, but when analyzed with potential confounding factors, only female sex was associated with an increased ratio (OR 2.32, 95% CI 1.02-5.29, p = 0.045). High sCD25 concentrations during the acute phase of infection, previously associated with severe RSV disease, were significantly and independently reduced in association with breastfeeding, whereas the Th1/Th3 balance was only modified in the recovery phase.

Breast Feeding↗

PubMed2002

Effect of an endurance race on muscle amino acids, pro- and macroglycogen and triglycerides.

Glycogenolysis and lipolysis are essential for energy production in muscle during prolonged exercise but less is known about the role of amino acid metabolism. The aim was to study the effect of an endurance race on pro- and macroglycogen, triglycerides and amino acid concentrations in muscle and on selected blood parameters, especially the amino acid response in the blood during the recovery phase. Seven endurance-trained horses completed a race covering 100-120 km. Blood samples were collected one day before the race, after the finish and 1 and 8 days after the race. Needle biopsy specimens from the gluteus medius muscle were taken on completion of the race and 8 days postrace. The pro- and macroglycogen concentrations were lower and most amino acid concentrations were higher in the muscle after the finish of the race, than 8 days postrace, whereas the triglyceride concentrations did not differ. The concentrations of several amino acids in serum were higher during the recovery phase than before the race. The observed changes suggest that an endurance race influences amino acid metabolism and a net protein degradation may occur that persists during the recovery phase. Furthermore, the results suggest that macroglycogen is utilised to a greater extent than proglycogen during an endurance race. Further research is needed concerning amino acid metabolism during an endurance race as it seems to play an important role both for performance and recovery after exercise.

Amino Acids↗

PubMed2005

Modes of heart rate compensations during exercise ECG test.

Heart rate (HR) compensation of electrocardiographic (ECG) parameters is not an unique concept. However, in the detection of coronary artery disease (CAD) ST-segment plotted as a function HR has been studied extensively during the last 20 years. In clinical practice quantitative methods are evolved for the exercise phase of the exercise test and post-exercise recovery phase has not been studied as extensively. Quantitative parameters, as ST/HR hysteresis, which represents the average difference in ST depressions between the exercise and recovery phases at an identical HR up to three minutes of recovery, has been shown to improve the detection of CAD. Furthermore, the ST/HR parameters have been demonstrated to be very competent in a prediction of mortality.

Coronary Disease↗

PubMed1989

Effects of a developmental physical therapy program on oxygen saturation and heart rate in preterm infants.

To evaluate the physiologic responses of 14 preterm infants to physical therapy, pulse oximetry was used to measure the percentage of arterial oxygen saturation (SaO2) and heart rate during baseline, intervention, and recovery phases. Treatment consisted of six one-minute activities that were equally divided between the side-lying and supported-sitting positions. The order of position and activities was randomly varied. A one-way analysis of variance for repeated measures revealed no significant changes in mean SaO2 as a function of the position or duration of intervention. Mean heart rate increased significantly as a result of intervention (p less than .0001), but there was no significant difference between the baseline and recovery phases. Further analysis indicated that the change in heart rate was not a function of duration of intervention. The results indicate that the preterm infants were able to tolerate the intervention without desaturation. The return of heart rate to baseline values during the recovery phase suggested a normal physiologic response to exercise. Despite some technical limitations, pulse oximetry is recommended to monitor preterm infants during physical therapy.

Heart Rate↗

PubMed2001

Role of alpha1-blockade in congenital long QT syndrome: investigation by exercise stress test.

Beta-blockade is widely reported to reduce the incidence of syncope in 75-80% of patients with congenital long QT syndrome (LQTS). However, despite full-dose beta-blockade, 20-25% of patients continue to have syncopal episodes and remain at high risk for sudden cardiac death. In some patients refractory to beta-blockade, the recurrence of arrhythmias is successfully prevented by left stellate ganglionectomy, and also by labetalol, a nonselective beta-blockade with alpha1-blocking action. These observations suggest that not only beta-adrenoceptors, but also alpha1-adrenoceptors, play an important pathogenic role, especially under sympathetic stimulation, in LQTS. The clinical effects of alpha1-blockade in congenital LQTS were investigated in 8 patients with familial or sporadic LQTS. Two measurements of the QT interval were taken, from the QRS onset to the T wave offset (QT) and from the QRS onset to the peak of the T wave (QTp). Using the Bruce protocol, an exercise test was performed after administration of beta-blockade alone and again after administration of alpha1-blockade. The following were compared: (1) Bazzet-corrected QT (QTc) and QTp (QTpc) intervals in the supine and standing position before exercise and in the early recovery phase after exercise; and (2) the slopes (reflecting the dynamic change in the QT interval during exercise) of the QT interval to heart rate were obtained from the linear regression during the exercise test. In the supine position before exercise, there was no change in the QTc before or after the addition of alpha1-blockade (498+/-23 vs 486+/-23 ms [NS]). However, in the upright position before exercise and in the early recovery phase after exercise, QTc was significantly shortened from 523+/-21 to 483+/-22ms (p<0.01), and from 521+/-30 to 490+/-39ms (p<0.01), respectively, by alpha1-blockade. The QTpc was unchanged in any situation. Consequently, QTc-QTpc was significantly shortened by alpha1-blockade in the upright position before exercise and in the early recovery phase after exercise (131+/-36 to 105+/-37ms (p<0.05), and 132+/-29 to 102+/-31 ms (p<0.01), respectively). The slopes of the QT interval-heart rate relation by linear regression became significantly steeper from -2.23+/-0.38 to -2.93+/-0.76 (p<0.01) with the addition of alpha1-blockade. The findings suggest that the addition of alpha1-blockade attenuated the exercise-induced prolongation of the QT interval and that the rate adaptation of the QT interval to heart rate during exercise was improved. This indicates that additional treatment with alpha1-blockade may be beneficial to prevent cardiac events in LQTS patients in whom ventricular arrhythmia is resistant to beta-blockade.

Adolescent↗

PubMed2003

[Standing behavior in horses after inhalation anesthesia with isoflurane (Isoflo) and postanesthetic sedation with romifidine (Sedivet) or xylazine (Rompun)].

Isofluorane is a modern, only slightly depressive inhalation anaesthetic with excellent pharmacologic characteristics in use in equine medicine. In contrast to halothane, isofluorane is hardly broken down in the liver, but is eliminated by the lung. It low solubility in blood permits excellent control of anaesthesia. However, due to its swift elimination from the organism there is heightened risk of premature recovery from isofluorane anaesthesia. In this study the recovery phases of 96 horses were monitored for its duration and the animals' physical coordination. The horses were divided into four groups. Two groups were sedated with xylazine, one of which received postanaesthetic sedation with xylazine, the other saline solution only. The other two groups were sedated with romifidine, either with or without postanaesthetic sedation after general anaesthesia. In this study the horses of Group 4, sedated with 0.02 mg/kg BW romifidine at the moment of extubation, showed the best recovery phase. The number of attempts to arise was reduced and coordination was better. Similar results were obtained by postanaesthetic sedation with 0.2 mg/kg BW xylazine (Group 2). Premedication with 0.08 mg/kg BW romifidine without postanaesthetic sedation (Group 3) could be carried out at mean duration of anaesthesia of 85 minutes with no negative effects observed during the recovery period. Premedication with xylazine without postanaesthetic sedation (Group 1) is not to be recommended, as the number of attemps to stand up was significantly higher and coordination was either weak or significantly poorer than in the other three groups. The results of this study show that post-anaesthetic sedation of horses with an alpha 2-adrenoceptor agonist can improve the recovery phase after inhalant anaesthesia with isofluorane in regard to the number of attempts to arise and the animals' physical coordination.

Adrenergic alpha-Agonists↗

PubMed1992

The use of temperature as a discharge criterion for ambulatory surgery patients.

Evaluating each patient's return to an acceptable state after surgical and anesthetic intervention is the responsibility of the postanesthesia nurse. Postanesthesia nurses use criteria to determine ambulatory surgical patient readiness to be discharged from phase I recovery to phase II recovery and from phase II recovery to home. Temperature is one indicator of postanesthesia recovery. Temperature discharge criteria from phase I postanesthesia recovery have been reported. However, temperature discharge criteria for phase II postanesthesia recovery have been adapted from phase I standards and nursing traditions. This study sought to describe the postoperative temperatures of ambulatory surgical patients from admission to phase II postanesthesia recovery to discharge home. A convenience sample of 101 adult patients undergoing surgery at a hospital-based ambulatory surgical unit (ASU) participated. Tympanic temperature was measured preoperatively on admission to the ASU, postoperatively, at the beginning of phase II postanesthesia recovery, and at the end of phase II postanesthesia recovery immediately before discharge home. All subjects were normothermic during phase II postanesthesia recovery, with temperatures ranging from 36.0 degrees C (96.8 degrees F) to 38.3 degrees C (101 degrees F). Paired Student's t Test showed significant differences (P < .0001) between temperature means. There was a 0.38 degrees C (0.7 degree F) decrease between preoperative admission temperature and temperature on admission to phase II postanesthesia recovery. During phase II postanesthesia recovery the mean temperature increased 0.16 degree C (0.3 degree F) before discharge home. However, the clinical and practical implications of these findings is questionable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1998

Hepatosplenic tuberculosis: a cause of persistent fever during recovery from prolonged neutropenia.

SETTING: Hepatosplenic abscesses in neutropenic patients, especially during the recovery phase, are almost always attributed to fungal infections. We report similar lesions due to Mycobacterium tuberculosis in neutropenic patients in a tertiary care centre in India. OBJECTIVE: To characterize the features of hepatosplenic tuberculosis in neutropenic patients. DESIGN: Retrospective comparison of disease pattern and response to treatment of hepatosplenic tuberculosis in febrile neutropenia patients (four of 30 with severe prolonged neutropenia) and in non neutropenic patients diagnosed during the same 12-month period (n = 4, control group). RESULTS: The disease in the neutropenic patients typically presented during the recovery phase of neutropenia, with ultrasonic abnormalities similar to those seen in hepatosplenic fungal infections. In contrast to the marked organomegaly and typical granulomatous response found in the control group, the disease in the neutropenic patients was characterised by an absence of organomegaly, non-involvement of other sites, poor inflammatory response and a high bacillary load. The initial response to therapy was satisfactory in both groups. CONCLUSION: Tuberculosis needs to be considered in the diagnostic work-up of hepatosplenic abscesses that occur during the recovery phase of neutropenia.

Abscess↗

PubMed1997

Interval training in patients with severe chronic heart failure: analysis and recommendations for exercise procedures.

This study analyzes a new exercise training procedure, which includes interval exercise training on cycle ergometer (IntCT) (30-s work phases/60-s recovery phases) and on treadmill (60-s work and recovery phases each). Training was applied for 3 wk in 18 patients with severe chronic heart failure (CHF) ((mean +/- SEM) age 52 +/- 2 yr, ejection fraction 21 +/- 1%). Peak VO2 was increased from 12.2 +/- 0.7 to 14.6 +/- 0.7 ml-kg-1 min-1 owing to training (P < 0.001). A specific steep ramp test (work rate increments 25 W.10 s-1) was developed to derive exercise intensity for work phases in IntCT, which was 50% of the maximum work rate achieved. Steep ramp test was performed at the start of the study to determine the initial training work rate, then weekly to readjust it. Since the maximum work rate achieved from this test increased weekly (144 +/- 10 W -->172 +/- 10 W-->200 +/- 11 W; P < 0.001), the training work rate also increased (72 +/- 4 W-->86 +/- 6 W-->100 +/- 7 W; P < 0.001). Physical responses to IntCT were measured. There was no significant change in heart rate, blood pressure, and ratings of perceived exertion (RPE) using a Borg Scale between the first and the third week of training (heart rate 88 +/- 3 b.min-1; blood pressure 115 +/- 4/80 +/- 2 mm Hg; leg fatigue 12 +/- 1; dyspnea 10 +/- 1). Mean lactate concentration (1.70 +/- 0.09 mmol-1-1) indicated an overall aerobic range of training intensity. When compared with the commonly used intensity level of 75% peak VO2 from an ordinary ramp test (work rate increments 12.5 W.min-1), the performed training work rate was more than doubled (240%; P < 0.0001) while cardiac stress was lower (86%; P < 0.01). Values of norepinephrine and epinephrine as well as of RPE corresponded to those measured at 75% peak VO2. Interval exercise training is thus recommended for selected patients with CHF as it allows intense exercise stimuli on peripheral muscles with minimal cardiac strain. Using a steep ramp test, training work rate can be determined and readjusted weekly during initial training period.

Bicycling↗

PubMed1998

Necrosis and apoptosis in acute renal failure.

Renal tubular cells that are lethally injured after an acute ischemic or nephrotoxic insult to the kidney can die by necrosis or apoptosis. Necrosis is usually the result of overwhelming and severe cellular ATP depletion. In contrast, there are many potential causes of apoptosis in acute renal failure (ARF). These include cytotoxic events not severe enough to induce necrosis, a relative deficiency of renal growth factors, and loss of cell-matrix or cell-cell adhesive interactions. In some situations, receptor-mediated events induced by tumor necrosis factor-alpha (TNF-alpha) or Fas (CD95) may play a role in apoptosis in ARF. Necrosis and apoptosis are distinct morphologically and biochemically. Necrosis results in an early loss of plasma membrane integrity, the release of injurious substances from the cytosol, and an inflammatory reaction in the surrounding tissue that is readily detected morphologically. In contrast, apoptosis is characterized by progressive cell shrinkage with condensation and fragmentation of nuclear chromatin. Apoptotic cells ultimately break up into plasma membrane-bound vesicles called "apoptotic bodies" that are rapidly phagocytosed by macrophages and neighboring epithelial cells. In experimental models of ARF in vivo, apoptosis of renal tubular cells has been shown to occur in two distinct phases. The first phase of apoptosis occurs early on, between 12 and 48 hours after the acute ischemic or nephrotoxic insult. The second phase of apoptosis occurs many days later, during the recovery phase of ARF. Tubular cell apoptosis occurring shortly after the acute insult probably contributes to tubular cell loss and the tubular dysfunction associated with ARF. In contrast, the apoptosis associated with the recovery phase has been postulated to contribute to the remodeling of injured tubules and to facilitate their return to a normal structural and functional state. Therapeutic interventions that inhibit or promote apoptosis of renal tubular cells have the potential for minimizing renal dysfunction and accelerating recovery after ARF.

Acute Kidney Injury↗

PubMed1988

Silent thyroiditis: a histologic and immunohistochemical study.

Twenty-six specimens obtained from 23 patients with clinically and laboratory-proven silent thyroiditis were examined histologically; 11 specimens were obtained during the thyrotoxic phase, and 15 specimens during the early or late recovery phase. All specimens showed chronic thyroiditis, focal or diffuse type; and lymphoid follicles were present in about half of the specimens. Most specimens showed neither stromal fibrosis nor oxyphilic cell changes. The follicular disruptions, which varied from moderate to severe and involved nearly all the visible follicles, were characteristic and common histologic features of this disorder. Giant cells were present in about two thirds of specimens. Six of the 7 specimens taken during the late recovery phase showed no follicular disruption. In 3 patients who had follow-up biopsies, the histologic involvement in the initial biopsy specimens clearly had disappeared in the second biopsy specimens. These histologic features indicate that silent thyroiditis may be a form of chronic thyroiditis, i.e., "chronic thyroiditis with marked follicular destruction." Thyroid biopsy is recommended as a useful tool in differentiating this disease from other thyroid diseases causing hyperthyroidism. In addition to the histologic analysis, intrathyroidal lymphocyte subsets were examined immunohistochemically and compared to those in chronic thyroiditis (Hashimoto's thyroiditis). In both silent and chronic thyroiditis, a great majority of lymphocytes infiltrating between thyroid follicles showed a T-cell phenotype, and no significant differences in T-cell and B-cell distribution between the diseases were observed.

Antibodies, Monoclonal↗

PubMed2003

Transient kinetics and mechanics of myosin's force-generating rotation in muscle: resolution of millisecond rotational transitions in the spin-labeled myosin light-chain domain.

We have used electron paramagnetic resonance (EPR) of spin-labeled scallop muscle, in conjunction with laser flash photolysis of caged ATP, to resolve millisecond rotational transitions of the myosin light-chain domain (LCD) during transient force generation. We previously used EPR to resolve two distinct orientations of the LCD [Baker, J. E., Brust-Mascher, I., Ramachandran, S., LaConte, L. E., and Thomas, D. D. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 2944-2949], correlated these structural states with biochemical states in the actin-myosin ATPase reaction, and showed that a small shift in the steady-state distribution between these two LCD orientations (i.e., a net lever arm rotation) is associated with force generation in muscle. In the study presented here, we measured millisecond changes in this orientational distribution (i.e., the rates of transition between the two LCD orientations) in muscle following flash photolysis of caged ATP, in both the presence and absence of Ca. The transient acquired in the absence of Ca is dominated by a rapid (1/tau(1) = 37 s(-1)) disordering transition from the single orientation in rigor to the bimodal orientation distribution observed for detached cross-bridges in relaxation (i.e., the reversal of the lever arm rotation), followed by a recovery phase (1/tau(2) = 2.4 s(-1)) of very small amplitude (small fraction of heads participating). In the presence of Ca, the transient exhibited a similar initial disordering phase (1/tau(1) = 38.5 s(-1)), followed by a recovery phase (1/tau(2) = 8.33 s(-1)) of substantial amplitude, corresponding to the forward rotation and ordering of the lever arm. A standard kinetic model was used to fit these data, revealing rate constants consistent with those previously determined by other methods. Surprisingly, a comparison of the EPR transients with force transients reveals that the rate of force development (91 s(-1)) is faster than the rate of the forward lever arm rotation (8 s(-1)). This observed relationship between the kinetics of the lever arm rotation and transient force development in muscle provides new insight into how myosin both generates and responds to muscle force.

Actins↗

PubMed1985

Hormonal effects of gonadotropin-releasing hormone (GnRH) agonist in the human male. III. Effects of long term combined treatment with GnRH agonist and androgen.

Chronic treatment with agonist analogs of GnRH results in reversible oligospermia in man, but leads to impotence and decreased libido due to a concomitant fall in serum testosterone (T) concentrations. We, therefore, assessed the effects of combined treatment with a potent GnRH agonist and T on gonadotropins and spermatogenesis in normal men, anticipating that addition of androgen would prevent agonist-induced changes in libido. Seven normal men were treated with 200 micrograms of the GnRH agonist D-(Nal2)6GnRH (GnRH-A), sc, daily for 16 weeks. In addition, 200 mg T enanthate were administered every 2 weeks for the entire 16-week treatment period. Basal LH, FSH, and T concentrations were measured every week during a 5-week control period, daily on treatment days 0, 1-10, 14, 18, 22, 26, and 28, every week thereafter until day 56, and every 2 weeks thereafter for the remainder of the treatment and recovery phases. Detailed analysis of LH and FSH over the 24-h period was performed by multiple blood sampling on days 0, 1, 10, 28, 56, 84, and 112. Semen analyses were performed every week during the control phase and every 2 weeks during the treatment and recovery phases. The mean sperm count declined by 83%, to a nadir of 16.6 +/- 6.2 (+/- SEM) million/ml. One subject had no significant decrease in sperm count. Azoospermia was not achieved in any subject. Basal serum LH concentrations, after an early phase of stimulation, declined to near baseline by day 14. However, basal, 24-h integrated serum LH concentrations, and 24-h urinary LH excretion were not significantly lowered by combined treatment. Bioassayable serum LH concentrations, however, declined significantly from 20.4 +/- 6.3 to 4.5 +/- 0.5 mIU/ml, and the bioassayable to immunoassayable LH ratio decreased from 2.1 +/- 1.0 to 0.7 +/- 0.1 after 16 weeks of GnRH-A treatment. Basal and 24-h integrated FSH concentrations, after an initial period of stimulation, declined progressively to baseline by days 5-6 and were significantly below baseline by day 112. Serum T concentrations did not fall into the hypogonadal (less than 250 ng/dl) range in any subject at any time during the treatment period. After discontinuation of treatment, LH, FSH, and sperm counts returned to normal in all subjects. Thus, single daily injection of GnRH-A and T failed to predictably induce azoospermia in normal men over the 16-week treatment period.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1984

Dosage requirement of pancuronium in halothane-anesthetized ponies: a comparison of cumulative and single-dose administration.

Cumulative vs single-bolus administration of pancuronium was studied in halothane-anesthetized ponies. Dosage levels were determined by giving small increments (0.01 to 0.04 mg/kg of body weight) until the desired relaxation occurred (0.125 +/- 0.038 mg/kg for 90% to 99% reduction of prerelaxant twitch height), then an additional 0.037 +/- 0.024 mg/kg for obliteration of twitch response. The dosage level defined by cumulative administration was then administered as a single bolus 2 more times, once on each of 2 days. Dosage requirements for the 2 methods correlated well. The difference in duration of paralysis caused by doses of different magnitude was compared, 1 dose to produce discernible surgical relaxation (90% to 99% reduction of twitch height) and a larger dose that obliterated discernible twitch height. The larger dose produced a significantly (P less than 0.05) longer duration of paralysis until a 10% recovery of prerelaxant twitch height was attained. The recovery phase, defined as the duration from 10% to 75% recovery of prerelaxant twitch tension, was not significantly different in ponies given either dose. Seemingly, after relaxant recovery began, the larger dose did not slow recovery. Duration of maximum paralysis until 10% recovery took 41 +/- 16 minutes for the larger dose and 10 +/- 5 minutes for the smaller dose. The recovery phase (10% to 75%) took 12 +/- 3.2 minutes and 11 +/- 4 minutes for the large and smaller doses, respectively.

Anesthesia, General↗