CMV reactivation is associated with a lower incidence of relapse after allo-SCT for CML.

Preemptive therapy at CMV reactivation has diminished post-transplant CMV mortality. Furthermore, recent studies suggest a favorable 'virus-versus-leukemia' effect from reactivating CMV, reducing relapse of AML after SCT. We studied the relationship of CMV reactivation with leukemic relapse in 110 patients with CML receiving HLA-identical sibling SCT between 1993 and 2008. Of these, 79 (72%) were in chronic phase, 5 in second chronic phase, 17 in accelerated phase and 9 in blast phase. A total of 97 patients (88%) received a myeloablative conditioning regimen, 97 received 4-log ex vivo T cell-depleted grafts and 13 received T-replete grafts. CMV reactivation before day 100 was observed in 72 patients (65.5%). At a median follow-up of 6.2 years, CMV reactivation < day 100 as a time-dependent covariate was an independent factor associated with decreased relapse. We conclude that CMV reactivation may contribute to a beneficial GVL effect in CML transplant recipients.

Beta-adrenergic receptors in corpora lutea from different stages of the estrous cycle in conscious and slaughtered cattle.

The overall objective of this study was to determine the pattern of beta-adrenergic receptors in bovine luteal membranes obtained from slaughtered and from conscious cattle on different days of the estrous cycle. Two approaches were used with respect to the CL collection. In the first approach, CL (n = 20) were obtained from animals slaughtered in a local abattoir. The day of the estrous cycle was estimated based on the morphology of luteal tissue and follicles present. Using 3H-dihydroalprenolol (3H-DHA) as a ligand, we were unable to find specific binding in any of the tissues examined. Therefore, for the second approach we decided to collect CL from mature heifers or cows under local anesthesia on Days 4 (n = 15), 8 (n = 7), 12 (n = 6), and 16 (n = 3) of the estrous cycle by means of colpotomy or by lumbar incision. This procedure was chosen to reduce the influence of stress factors before CL collection. In these samples, specific beta-adrenergic binding sites were found and they varied during the estrous cycle. Maximal binding (Bmax; fmol/mg of protein) was highest on Day 4 (178.3 +/- 15.2); it then decreased significantly (73.2 +/- 14.7, 40.1 +/- 5.5, 10.8 +/- 0.8) on Days 8, 12, and 16, respectively. The dissociation constant (Kd; nM), which followed the same pattern, was 52.0 +/- 14.4, 16.3 +/- 3.9, 14.9 +/- 3.2, and 7.6 +/- 4.0) on the same days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of dopaminergic neurons in denervation-induced alpha 1-adrenergic up-regulation in the rat cerebral cortex.

The density of [3H]prazosin binding to alpha 1-adrenoceptors in the rat cortex was measured after selective and mixed noradrenergic or dopaminergic lesions. DSP-4 produced a selective noradrenergic lesion and increased the density of alpha 1-adrenoceptors. 6-Hydroxydopamine produced a selective dopaminergic lesion (after desipramine protection of noradrenergic neurons) and a mixed noradrenergic and dopaminergic lesion that did not change the cortical alpha 1-adrenoceptor binding. On the basis of the results obtained, a hypothesis is put forward that the central dopaminergic system controls the denervation-induced cortical alpha 1-adrenoceptor up-regulation.

Behavioural and neurochemical effects of Ro 40-7592, a new COMT inhibitor with a potential therapeutic activity in Parkinson's disease.

Behavioural and some neurochemical effects of Ro 40-7592 (3,4-dihydroxy-4'-methyl-5-nitrobenzophenone), a new COMT inhibitor, were studied in rats and mice. Ro 40-7592 increased the effect of L-DOPA (plus benserazide) on locomotor activity, reserpine-induced hypothermia, and catalepsy induced by pimozide, haloperidol and fluphenazine. Locomotor hyperactivity induced by amphetamine or nomifensine, as well as stereotypy induced by amphetamine (but not apomorphine), were also increased by Ro 40-7592. The drug stimulated exploratory activity in the open field test. It decreased the levels of HVA and 3-MT, increased the level of DOPAC but did not change the levels of dopamine in the striatum, nucleus accumbens and frontal cortex. These results indicate that Ro 40-7592 may improve the therapy with L-DOPA (plus decarboxylase inhibitor) of Parkinson's disease.