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At least 55 records · Page 3Linked to original sources

Haloperidol disrupts, clozapine reinstates the circadian rest-activity cycle in a patient with early-onset Alzheimer disease.

Measurement of the circadian rest-activity cycle in a patient with early-onset Alzheimer disease for 555 days revealed marked changes in the timing and amount of nocturnal activity. After neuroleptic medication was changed to haloperidol, the rest-activity cycle became completely arrhythmic for two months, concomitant with a marked worsening of cognitive state. Circadian integrity returned together with clinical improvement when the patient was subsequently treated with clozapine. This observation suggests that the known tendency for patients with Alzheimer disease to develop sleep-wake cycle disturbances may be aggravated by a classic neuroleptic; in contrast, the atypical neuroleptic clozapine may consolidate it. Similar observations in schizophrenic patients indicate that this chronobiological finding is drug- and not illness-related.

Age of Onset↗

BCNU with and without cyclophosphamide, vincristine, and prednisone (COP) and cycle-active therapy in non-Hodgkin's lymphoma.

Two hundred and ninety-eight evaluable patients with non-Hodgkin's lymphoma were stratified according to histology, treated with either BCNU, cyclophosphamide, Oncovin (vincristine), and prednisone (BCOP) or cyclophosphamide, Oncovin (vincristine), and prednisone (COP), and evaluated at 3 months. Those with a good partial (PR) or complete response (CR) were then separated and randomized to be treated with either cycle-active therapy (methotrexate, cytosine arabinoside, and 6-thioguanine) or more induction therapy with COP or BCOP. Patients not achieving a good PR at 3 months received cycle-active therapy. The results indicate (a) that there is a significant advantage for good over poor histologies with regard to good PRs at 3 months; (b) that the addition of cycle-active therapy (as administered in this study) is of advantage when the tumor has been significantly reduced only for patients receiving COP induction; and (c) that BCOP has an advantage over COP in diffuse histiocytic lymphoma where the percentage of CRs, their durability, and subsequent survival are superior for patients treated with BCOP. Since this lymphoma accounts for about 25% of all non-Hodgkin's lymphoma patients, this regimen represents a useful tool for the chemotherapist.

Carmustine↗

Mouse strain-dependent changes in frequency and proliferation of hematopoietic stem cells during aging: correlation between lifespan and cycling activity.

We have quantified the frequency and proliferation of five subsets of primitive hematopoietic cells, using the cobblestone area forming cell (CAFC) assay, in marrow of five strains of mice with lifespans ranging from about 500 to 800 days. Stem cell characteristics were determined in young (6 weeks) and old (12 months) mice. We report striking effects of both intrinsic strain lifespan and individual mouse age on stem cell populations. First, the relative and absolute numbers of the most primitive stem cell subsets was threefold to fourfold higher in old than in young mice. Second, a considerable strain-to-strain variation in the number of primitive cells was observed: when absolute frequencies were calculated, there was a trend for longer lifespan to be correlated with a larger stem cell pool. Third, stem cells from old mice had a far lower cycling activity than cells from young mice. However, this was highly strain dependent: short-lived C3H/He and CBA/J mice showed a stronger reduction in cycling activity during aging than long-lived C57BL/6 mice. Finally, a significant negative correlation was demonstrated in young mice between maximal lifespan and proliferative activity. These data show that aging has a major impact on the frequency and cell-cycle kinetics of primitive hematopoietic cell compartments. In addition, the observation that cycling activity of stem cells is related to the maximal lifespan of the mouse strain may open ways to identify the genetic mechanisms of both strain- and age-dependent variation in the structure of primitive hematopoietic cell compartments.

Aging↗

Disturbed circadian rest-activity cycles in schizophrenia patients: an effect of drugs?

The circadian rest-activity cycle of schizophrenia patients stabilized for more than a year on monotherapy with a "classical" neuroleptic (haloperidol, flupentixol) or with the atypical neuroleptic clozapine was documented by continuous activity monitoring for 3-7 weeks. In this pilot study, the three patients treated with clozapine had remarkably highly ordered restactivity cycles, whereas the four patients on classical neuroleptics had minor to major circadian rhythm abnormalities. This is the first documentation of circadian rest-activity cycle disturbances in schizophrenia related to class of drug.

Antipsychotic Agents↗

A new method to analyze basic rest-activity cycle.

A new method was proposed to analyze a basic rest-activity cycle (BRAC), termed BRAC-A. This method calculates a significant cycle length by chi-squared method and the starting points of a resting phase and an active one by analysis of the array consisting of the segmented time series in the same length. Using 20 3-day computer-simulated time series of standard deviation in fetal heart rate fluctuation with known periodicity of the BRAC, we demonstrated that the BRAC-A was a useful tool to reveal the characteristics of the BRAC.

Activity Cycles↗

Airway physiology, autogenic drainage, and active cycle of breathing.

Airway clearance techniques are used to aid in mucus clearance in a variety of disease states. Autogenic drainage and active-cycle-of-breathing technique are 2 such modalities that rely heavily on basic airway physiology to enhance clearance. In this review I discuss the equal pressure point, huffing, and asynchronous and collateral ventilation, and review the literature and theory regarding autogenic drainage and active cycle of breathing. Selection of airway clearance techniques is discussed in the light of evidence-based medicine.

Breathing Exercises↗

Antisense myb inhibition of purified erythroid progenitors in development and differentiation is linked to cycling activity and expression of DNA polymerase alpha.

These studies aimed to determine the expression and functional role of c-myb in erythroid progenitors with different cycling activities. In the first series of experiments the erythroid burst-forming unit (BFU-E) and colony-forming unit (CFU-E) populations from adult peripheral blood (PB), bone marrow (BM), and embryonic-fetal liver (FL) were treated with either c-myb antisense oligomers or 3H-thymidine (3H-TdR). A direct correlation was always observed between the inhibitory effect of anti-myb oligomers and the level of cycling activity. Thus, the inhibitory effect of antisense c-myb on the number of BFU-E colonies was 28.3% +/- 15.8% in PB, 53.4% +/- 9.3% in BM, and 68.2% +/- 24.5% in FL. Both adult and embryonic CFU-E were markedly inhibited (73.2% +/- 10.4% and 74.2% +/- 12.7%). Using highly purified PB progenitors, we observed a similar pattern, although with slightly lower inhibitory effects. In the 3H-TdR suicide assay the killing index of BFU-E was 8.9% +/- 4.2% in PB, 29.4% +/- 6.5% in BM, and 40.1% +/- 9.6% in FL. The values for adult and embryonic CFU-E were 55.7% +/- 7.9% and 60.98% +/- 6.6%, respectively. We then investigated the kinetics of c-myb mRNA level during the erythroid differentiation of highly purified adult PB and FL BFU-E, as evaluated in liquid-phase culture by reverse transcription-polymerase chain reaction. Adult erythroid precursors showed a gradual increase of c-myb mRNA from day 4 through day 8 of culture and a sharp decrease at later times, whereas the expression of c-myb mRNA and protein in differentiation embryonic precursors peaked 2 days earlier. In both cases, c-myb mRNA level peaked at the CFU-E stage of differentiation. Finally, highly purified adult PB BFU-E were stimulated into cycling by a 3-day treatment with interleukin-3 in liquid phase: both the sensitivity to c-myb antisense oligomers and the 3H-TdR suicide index showed a gradual, strictly parallel increase. Under the same experimental conditions a progressive increase of the mRNA level of DNA polymerase alpha was observed. These observations suggest that in early erythroid differentiation c-myb activation is associated with the progression of progenitors into the S phase of the cell cycle, as well as to the synthesis of DNA polymerase alpha.

Antisense Elements (Genetics)↗

Temporal coordination of rest-activity cycle, body temperature, urinary free cortisol, and mood in a patient with 48-hour unipolar-depressive cycles in clinical and time-cue-free environments.

During medication-free observation a 66-year-old male patient showed an almost strict alternation of days with depressed mood and days with normal mood. The experiment consisted of two parts; the first was 4 weeks' observation in the psychiatric ward, while the second was 2 weeks' observation in an experimental unit where the patient was deprived of all known information on local time. In the psychiatric ward the observed circadian rhythms, i.e., the rest-activity cycle, the body temperature, the urinary free cortisol, and the mood rhythm, were all synchronized with the geophysical day. Under isolation from time cues the average rest-activity cycle duration was reduced to about 19.5 hr, whereas the body temperature and the urinary free cortisol continued to show rhythms with near-24-hr periods. The main finding of the study is the persistence of a near-48-hr periodicity in the mood fluctuation under isolation from time cues. Besides this, in the time course of body temperature and urinary free cortisol evoked components correlating with the mood cycles were found.

Activity Cycles↗

Prenatal administration of buprenorphine in the rat: effects on the rest-activity cycle at 22 and 30 days of age.

Three doses of buprenorphine (BUP) were administered by osmotic minipump from day 8 of gestation through parturition. In addition to 0.3, 1.0, and 3.0 mg/kg/day of BUP, a vehicle control group received sterile water via minipump and a nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. BUP produced a dose response reduction in maternal water intake and reduced maternal weight gain among the two high dose groups; resorptions and birthweight were unaffected. BUP increased perinatal mortality in the two high dose groups compared with the vehicle controls and produced inconsistent effects on postnatal growth. To examine the effects of BUP on the rest-activity cycle of the offspring, groups of 3 littermates from each of the treated and control groups were tested for an 8 h observation period on electronic activity monitors at 22 and 30 days of age. Unlike previous effects described for prenatally administered methadone, a disruption in the rest-activity cycle was not observed for any of the BUP treated groups.

Activity Cycles↗

Phase II study of alternating cytoreductive and cycle-active combination chemotherapy for metastatic breast cancer.

Nineteen females with metastatic breast cancer (73% with visceral disease) treated with cyclophosphamide, Adriamycin, and 5-fluorouracil (CAF) cytoreduction followed by, and then alternated with, an intensive "cycle-active" regimen were evaluable. Sixteen of the 19 (84%) patients responded to CAF prior to initiation of the cycle-active regimen, and median remission duration for CAF responders was 50 weeks. The regimen was tolerable and the remission rates and durations were at least as good as those seen with CAF alone. This regimen is now being compared with CAF in a randomized trial of the Southeastern Cancer Study Group.

Adult↗

Prenatal administration of methadone in the rat: acoustic startle amplitude and the rest-activity cycle at 30 days of age.

Two doses of methadone were administered by osmotic minipump from Day 8 of gestation through parturition, a dosing technique previously shown to produce physical dependence in the dams. A pair-fed control group received sterile water via minipump and was allowed to eat and drink only the amount consumed by the high-dose group on the same gestation days. A nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. The effects of methadone on maternal and offspring toxicity replicated our previous findings. At 29-31 days of age each treated and control animal was tested either for changes in acoustic startle amplitude or the rest-activity cycle. Methadone treated offspring were no different from the controls on either measure. These findings support the hypothesis derived from our earlier research that prenatal exposure to methadone produces a prolonged but transitory opioid abstinence. This is evidenced by increased startle amplitude and a disturbed rest-activity cycle that peaks at approximately 3 weeks of age. We demonstrate that these effects are no longer evident at 4 weeks of age. Together, these findings define a state of hyperexcitability in the young rat that resolves by 1 month of age. This transitory state parallels clinical descriptions of human infants undergoing opiate abstinence.

Acoustic Stimulation↗

Treatment of behavioural, cognitive and circadian rest-activity cycle disturbances in Alzheimer's disease: haloperidol vs. quetiapine.

This 5-wk, open-label, comparative study investigated the effects of quetiapine and haloperidol on behavioural, cognitive and circadian rest-activity cycle disturbances in patients with Alzheimer's disease (AD). Out of a total of 30 patients enrolled in the study, there were 22 completers, 11 in the quetiapine group (mean age 81.9+/-1.8 yr, mean baseline MMSE 19.9+/-1.3, mean dose 125 mg) and 11 in the haloperidol group (mean age 82.3+/-2.5 yr, mean baseline MMSE 18.1+/-1.3, mean dose 1.9 mg). As shown in the Neuropsychiatric Inventory, both medications reduced delusion and agitation, whereas quetiapine additionally improved depression and anxiety. Haloperidol worsened aberrant motor behaviour and caused extrapyramidal symptoms. In the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological test battery which assessed cognitive parameters, quetiapine improved word recall; significant interaction terms revealed differences between quetiapine and haloperidol in word-list memory and constructional praxis. According to the Nurses' Observation Scale for Geriatric Patients (NOSGER) quetiapine improved instrumental activities of daily living. Actimetry documented the circadian rest-activity cycle before and after treatment. Sleep analysis revealed that patients receiving quetiapine had shorter wake bouts during the night, whereas patients receiving haloperidol had fewer though longer immobile phases. The study provides evidence that quetiapine at a moderate dose may be efficacious in treating behavioural disturbances in AD, with better tolerability than haloperidol.

Activities of Daily Living↗

Dawn-dusk simulation light therapy of disturbed circadian rest-activity cycles in demented elderly.

We investigated whether low intensity dawn-dusk simulation (DDS), a 'naturalistic' form of light therapy designed to embed sleep in its accustomed phase, could improve the disturbed circadian rest-activity cycle, nocturnal sleep and and/or cognitive functions in dementia. A protocol of 3 weeks each of baseline, treatment and follow-up was completed by 13 patients (85yr old+/-5yr, MMSE 14+/-5; n=9 DDS versus n=4 'placebo' dim red light) who wore an activity/lux monitor throughout. There were no significant changes in clinical or cognitive status, nor modification of circadian stability or amplitude characteristics of the rest-activity cycle. However, two aspects of sleep responded to DDS but not to dim red light. The main sleep episode was 1:14h earlier during treatment (p=0.03) compared with before and after DDS. With respect to actimetry-determined sleep variables, the DDS group tended to have shortened 'sleep latency', longer 'sleep duration', more nocturnal immobility and less nocturnal activity than the dim red group (p<0.1). In parallel, nighttime light exposure tended to be reduced (p=0.07). These promising findings-after only 3 weeks of light treatment in elderly patients with advanced dementia-suggest that the circadian timing system remains functionally responsive even to low intensity DDS light. Increasing zeitgeber strength is an important strategy for improving sleep quality and timing in dementia, and DDS light therapy may provide one of the appropriate means to do so.

Aged↗

TCA cycle activity in Saccharomyces cerevisiae is a function of the environmentally determined specific growth and glucose uptake rates.

Metabolic responses of Saccharomyces cerevisiae to different physical and chemical environmental conditions were investigated in glucose batch culture by GC-MS-detected mass isotopomer distributions in proteinogenic amino acids from (13)C-labelling experiments. For this purpose, GC-MS-based metabolic flux ratio analysis was extended from bacteria to the compartmentalized metabolism of S. cerevisiae. Generally, S. cerevisiae was shown to have low catabolic fluxes through the pentose phosphate pathway and the tricarboxylic acid (TCA) cycle. Notably, respiratory TCA cycle fluxes exhibited a strong correlation with the maximum specific growth rate that was attained under different environmental conditions, including a wide range of pH, osmolarity, decoupler and salt concentrations, but not temperature. At pH values of 4.0 to 6.0 with near-maximum growth rates, the TCA cycle operated as a bifurcated pathway to fulfil exclusively biosynthetic functions. Increasing or decreasing the pH beyond this physiologically optimal range, however, reduced growth and glucose uptake rates but increased the 'cyclic' respiratory mode of TCA cycle operation for catabolism. Thus, the results indicate that glucose repression of the TCA cycle is regulated by the rates of growth or glucose uptake, or signals derived from these. While sensing of extracellular glucose concentrations has a general influence on the in vivo TCA cycle activity, the growth-rate-dependent increase in respiratory TCA cycle activity was independent of glucose sensing.

Biomass↗

[Suppression of cycling activity in sheep using parenteral progestagen treatment].

The objective of this study was to evaluate the effect of two synthetic progestagen preparations Chlormadinone acetate (CAP, Chronosyn, Veterinaria AG Zürich) and Medroxyprogesterone acetate (MPA, Nadigest, G Streuli & Co. Uznach) on cycling activity and fertility in sheep. A flock of 28 non pregnant white alpine sheep was randomly divided into three groups, A (n = 10), B (n = 9) and C (n = 9). During a period of 4 weeks the cycling activity was confirmed by blood progesterone analysis. Thereafter, the animals of group A were treated with 50 mg CAP, those of group B with 140 mg MPA and those of group C with physiological saline solution. All injections were given intramuscularly. Suppression of endogenous progesterone secretion lasted from 28 to 49 days (mean = 39 days) in group A and from 42 to 70 days (mean = 50 days) in group B. The synchronization effect of both preparations was unsatisfactory as the occurrence of first estrus was distributed over a period of 3 weeks in group A and 4 weeks in group B. These findings could also be confirmed by the lambing period which lasted 52 days in group A and 36 days in group B. Control animals lambed within 9 days due to the synchronizing effect of the ram. The first fertile estrus was observed 36 days (group A) and 45 days (group B) after the treatment. In group A all 10 animals and in groups B and C 8 of 9 ewes each became pregnant. Parenteral progestagen application with CAP and MPA is a simple, safe and reversible method of estrus suppression in the sheep. The minimal suppressive duration of 4 (CAP) and 5 weeks (MPA) is not sufficient when a period of 3 months (alpine pasture period) is desired.

Animals↗

Flux control exerted by mitochondrial outer membrane carnitine palmitoyltransferase over beta-oxidation, ketogenesis and tricarboxylic acid cycle activity in hepatocytes isolated from rats in different metabolic states.

The Flux Control Coefficients of mitochondrial outer membrane carnitine palmitoyltransferase (CPT I) with respect to the overall rates of beta-oxidation, ketogenesis and tricarboxylic acid cycle activity were measured in hepatocytes isolated from rats in different metabolic states (fed, 24 h-starved, starved-refed and starved/insulin-treated). These conditions were chosen because there is controversy as to whether, when significant control ceases to be exerted by CPT I over the rate of fatty oxidation [Moir and Zammit (1994) Trends Biochem. Sci. 19, 313-317], this is transferred to one or more steps proximal to acylcarnitine synthesis (e.g. decreased delivery of fatty acids to the liver) or to the reaction catalysed by mitochondrial 3-hydroxy-3-methyl-glutaryl-CoA synthase [Hegardt (1995) Biochem. Soc. Trans. 23, 486-490]. Therefore isolated hepatocytes were used in the present study to exclude the involvement of changes in the rate of delivery of non-esterified fatty acids (NEFA) to the liver, such as occur in vivo, and to ascertain whether, under conditions of constant supply of NEFA, CPT I retains control over the relevant fluxes of fatty acid oxidation to ketones and carbon dioxide, or whether control is transferred to another (intrahepatocytic) site. The results clearly show that the Flux Control Coefficients of CPT I with respect to overall beta-oxidation and ketogenesis are very high under all conditions investigated, indicating that control is not lost to another intrahepatic site during the metabolic transitions studied. The control of CPT I over tricarboxylic acid cycle activity was always very low. The significance of these findings for the integration of fatty acid and carbohydrate metabolism in the liver is discussed.

Animals↗

The role of cell cycle activity in the generation of morphologic heterogeneity in non-Hodgkin's lymphoma.

Cellular and nuclear size heterogeneity are frequently observed in non-Hodgkin's lymphomas, yet the biological basis of this morphologic variability is not well understood. The possible relationship between cell size and cell cycle activity in malignant lymphomas was investigated using multiparameter flow cytometry and digital image analysis. Flow cytometric analysis of ten cases of B cell lymphoma revealed that, regardless of the diagnosis or the proportion of large cells present, large neoplastic cells showed a much greater proportion of S + G2/M phase activity (mean, 35.2%; range, 14.6% to 70.5%) than did small cells (mean, 4.4%; range, 0.5% to 18.4%). Further studies aimed at distinguishing the features of cycling and noncycling cells were performed using quantitative image analysis of nuclear staining by Ki-67 antibody. In both benign and malignant lymphoid infiltrates, resting (Ki-67-negative) nuclei were uniformly smaller than Ki-67-positive nuclei and exhibited a restricted size distribution, whereas the Ki-67-positive nuclei had a broad size distribution and included the vast majority of large forms. Thus, the actively cycling component of the tumor consisted of cells with large nuclei. These studies support the hypothesis that cellular and nuclear size heterogeneity in malignant lymphomas is related to cell cycle phase. The combined influences of cell differentiation and proliferation on cellular morphology can explain many of the histologic features observed in non-Hodgkin's lymphomas.

Antibodies, Monoclonal↗