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D Cycle (d + cycle)
Selected AbstractsComparison of the effects of early handling and early deprivation on maternal care in the ratDEVELOPMENTAL PSYCHOBIOLOGY, Issue 4 2001Christopher R. Pryce Abstract It has been reported in the rat that postnatal manipulations can induce robust and persistent effects on offspring neurobiology and behavior, mediated in part via effects on maternal care. There have, however, been few studies of the effects of postnatal manipulations on maternal care. Here, we describe and compare the effects on maternal behavior on postnatal days 1,12 of two manipulations, early handling (EH, 15-min isolation per day) and early deprivation (ED, 4-hr isolation per day), relative to our normal postnatal husbandry procedure. Maternal behavior was measured at five time points across the dark phase of the reversed L:D cycle. EH yielded an increase in arched-back nursing across several time points but did not affect any other behavior. ED stimulated a bout of maternal behavior such that licking and arched-back nursing were increased at the time of dam,litter reunion, although not at any other time point. Neither EH nor ED affected weaning weight significantly. Importantly, within-treatment variation was high relative to these between-treatment effects. © 2001 John Wiley & Sons, Inc. Dev Psychobiol 38: 239,251, 2001 [source] DIEL VARIATIONS IN OPTICAL PROPERTIES OF IMANTONIA ROTUNDA (HAPTOPHYCEAE) AND THALASSIOSIRA PSEUDONANA (BACILLARIOPHYCEAE) EXPOSED TO DIFFERENT IRRADIANCE LEVELS,JOURNAL OF PHYCOLOGY, Issue 3 2008Sébastien Mas Diel variations of cellular optical properties were examined for cultures of the haptophyte Imantonia rotunda N. Reynolds and the diatom Thalassiosira pseudonana (Hust.) Hasle et Heimdal grown under a 14:10 light:dark (L:D) cycle and transferred from 100 ,mol photons · m,2 · s,1 to higher irradiances of 250 and 500 ,mol photons · m,2 · s,1. Cell volume and abundance, phytoplankton absorption coefficients, flow-cytometric light scattering and chl fluorescence, and pigment composition were measured every 2 h over a 24 h period. Results showed that cell division was more synchronous for I. rotunda than for T. pseudonana. Several variables exhibited diel variability with an amplitude >100%, notably mean cell volume for the haptophyte and photoprotective carotenoids for both species, while optical properties such as flow-cytometric scattering and chl a,specific phytoplankton absorption generally showed <50% diel variability. Increased irradiance induced changes in pigments (both species) and mean cell volume (for the diatom) and amplified diel variability for most variables. This increase in amplitude is larger for pigments (factor of 2 or more, notably for cellular photoprotective carotenoid content in I. rotunda and for photosynthetic pigments in T. pseudonana) than for optical properties (a factor of 1.5 for chl a,specific absorption, at 440 nm, in I. rotunda and a factor of 2 for the absorption cross-section and the chl a,specific scattering in T. pseudonana). Consequently, diel changes in optical properties and pigmentation associated with the L:D cycle and amplified by concurrent changes in irradiance likely contribute significantly to the variability in optical properties observed in biooptical field studies. [source] Acute sleep-promoting action of the melatonin agonist, ramelteon, in the ratJOURNAL OF PINEAL RESEARCH, Issue 2 2008Simon P. Fisher Abstract:, Insomnia, which is severe enough to warrant treatment, occurs in ,10% of the general population. It is associated with a range of adverse consequences for human health, economic productivity and quality of life. In animal and human studies, administration of melatonin has been reported to promote sleep, although there has been controversy regarding its effectiveness. The present study used a chronically implanted radiotelemetry transmitter to record electroencephalogram (EEG) and electromyogram (EMG) to enable discrimination of wake (W), nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep in un-restrained rats. The acute action of melatonin and ramelteon, a melatonin agonist recently approved for long-term treatment of insomnia in the USA, was examined. Radioligand binding assays on recombinant human MT1/MT2 receptors showed that both the melatonin and ramelteon were both high affinity, nonsubtype selective ligands. Both compounds acted as potent full agonists on a cellular model of melatonin action, the pigment aggregation response in Xenopus laevis melanophores. Both melatonin and ramelteon (10 mg/kg, i/p), administered close to the mid-point of the dark phase of the L:D cycle, significantly reduced NREM sleep latency (time from injection to the appearance of NREM sleep). Both the drugs also produced a short-lasting increase in NREM sleep duration, but the NREM power spectrum was unaltered. Neither drug altered REM latency, REM sleep duration nor power spectrum during REM sleep. In conclusion, ramelteon administration, like melatonin, exerted an acute, short-lasting sleep-promoting effect in the rat, the model most commonly used to evaluate the activity of novel hypnotic drugs. [source] Photic and non-photic entrainment on daily rhythm of locomotor activity in goatsANIMAL SCIENCE JOURNAL, Issue 1 2010Claudia GIANNETTO ABSTRACT We studied the photic (L/D cycle) and non-photic (restricted feeding) entrainment on the patterns of daily rhythm of total locomotor activity in goats. Six female Maltese goats were subjected to three different artificial L/D cycles: 12/12 L/D, 12/12 D/L and constant light. During the 12/12 L/D and 12/12 D/L, food and water were available ad libitum. During constant light, animals were subjected to a restricted feeding treatment. Total activity was recorded by means of an actigraphy-based data logger (Actiwatch-Mini®). Our results showed that goats exhibited clear daily rhythms of activity in 12/12 L/D cycle, 12/12 D/L cycle and constant light, although they showed FAA prior the feeding time during the restricted feeding treatment. Goats were diurnal, with activity consistently beginning promptly following the onset of light. Even when the L/D cycle was delayed by 12 h on some days, to the daily rhythm was re-established. During the constant light period, the onset of activity was linked to the time of food administration. Our study evidences two factors for the rhythm of total locomotor activity in goats: light stimuli (photic) and food access (non photic), strongly coupled to permit organisms the adaptive temporal coordination of behaviour with stable and unstable environmental periodicities. [source] A phase I clinical trial of the histone deacetylase inhibitor belinostat in patients with advanced hematological neoplasiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2008Peter Gimsing Abstract Purpose:, To determine the safety, dose-limiting toxicity and maximum tolerated dose (MTD) of the novel hydroxamate histone deacetylase inhibitor belinostat (PXD101) in patients with advanced hematological neoplasms. Patients and methods:, Sequential dose-escalating cohorts of three to six patients with hematological malignancies received belinostat administered as a 30-min i.v. infusion on days 1,5 of a 21-d cycle. Experience from a parallel dose-finding study in patients with solid tumors influenced the selection of the final dose. Results:, Sixteen patients received belinostat at one of three dose levels: 600 mg/m2/d (three patients), 900 mg/m2/d (three patients) and 1000 mg/m2/d (10 patients), the dose determined to be the MTD in a phase I solid tumor study [Steele et al. (2008) Clin Cancer Res, 14, 804,10]. The most common treatment-related adverse events (all grades) were nausea (50%), vomiting (31%), fatigue (31%) and flushing (31%). No grade 3 or 4 hematological toxicity compared with baseline occurred except one case of grade 3 lymphopenia. There were two related grade 4 adverse events of renal failure observed. Both events occurred in patients with multiple myeloma and had similar characteristics, i.e. an acute episode of decrease in renal function (pre-existing nephropathy in one patient), with a metabolic profile and decrease in tumor burden consistent with tumor lysis syndrome. No other related grade 4 events were noted. The only related grade 3 events noticed in more than one patient were fatigue and neurological symptoms (one patient had status epilepticus in association with uremia and one patient had paresthesia), all other related grade 3 events occurred in single patients. No cardiac events were noted. No complete or partial remissions were noted in these heavily pre-treated (median of four prior regimens) patients. However, five patients, including two patients with diffuse large-cell lymphoma [including one patient with transformed chronic myelomcytic leukaemia (CLL)], two patients with CLL and one patient with multiple myeloma, achieved disease stabilization in of two to nine treatment cycles. Conclusions:, Intravenous belinostat at 600, 900 and 1000 mg/m2/d is well tolerated by patients with hematological malignancies. The study was carried out in parallel to a similar dose-finding study in patients with solid tumors, in which the MTD was determined to be 1000 mg/m2/d days 1,5 in a 21-d cycle. This dose can also be recommended for phase II studies in patients with hematological neoplasms. [source] Lenalidomide and dexamethasone for the treatment of refractory/relapsed multiple myeloma: dosing of lenalidomide according to renal function and effect on renal impairmentEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2010Meletios A. Dimopoulos Abstract Objectives:, Lenalidomide and dexamethasone (LenDex) is an active regimen for relapsed/refractory multiple myeloma (MM). However, there is limited data for the effect of LenDex on renal impairment (RI) and on renal reversibility. Patients & Methods:, Fifty consecutive patients with relapsed/refractory MM received LenDex in 28-d cycles. Median lines of previous therapies were 2 (range: 1,6). Lenalidomide was administered on days 1,21 according to creatinine clearance (CrCl), while dexamethasone was given at a dose of 40 mg on days 1,4 and 15,18 for the first four cycles and only on days 1,4 thereafter. Results:, Twelve patients (24%) had RI at baseline, defined as CrCl < 50 mL/min. Most patients were pretreated with either thalidomide or bortezomib and > 50% of them were refractory to both drugs. At least partial response was documented in 60.5% and 58% of patients with and without RI. Median progression-free survival (PFS) and overall survival (OS) for all patients was 9 and 16 months, respectively. RI was not associated with an inferior PFS or OS. There were no differences in the incidence of adverse events among patients with and without RI. Three of 12 patients with RI (25%) achieved complete renal response and two (16%) achieved minor renal response with LenDex. Conclusions:, We conclude that LenDex is an active treatment even in heavily pretreated MM. With dosing of lenalidomide according to renal function, LenDex can be administered to patients with RI (who may not have other treatment options) without excessive toxicity. Furthermore, LenDex may improve the renal function in approximately 40% of patients with RI. [source] PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myelomaBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2005Heather E. Oakervee Summary Bortezomib (formerly PS-341) has significant activity in patients with relapsed multiple myeloma (MM), its efficacy is increased with the addition of dexamethasone and it demonstrates synergy with doxorubicin, thus providing the rationale for combination therapy with bortezomib, doxorubicin and dexamethasone (PAD). Patients with untreated MM received four 21-d cycles of PAD, comprising bortezomib 1·3 mg/m2 on days 1, 4, 8 and 11, along with dexamethasone 40 mg on days 1,4, 8,11 and 15,18 during cycle 1 and days 1,4 during cycles 2,4. During days 1,4, patients also received 0, 4·5 or 9 mg/m2 of doxorubicin at dose levels 1, 2, and 3 respectively. Following peripheral blood stem cell (PBSC) collection, patients received high-dose melphalan (MEL200) with PBSC transplantation (PBSCT). After PAD induction alone, 20 of 21 patients (95%) achieved at least a partial response (PR), including complete response (CR) in five patients (24%). Twenty of 21 had PBSC mobilized, and 18 of 20 received MEL200/PBSCT. In an intention-to-treat analysis, response rates were: CR 43%, near CR 14%, very good PR 24%, PR 14% and stable disease 5%. PAD was effective, did not prejudice subsequent PBSC collection, and should be further evaluated in prospective randomized trials. [source] | |||||||||||||