Comparison of the Effects of ?-Adrenergic Agents on Pineal Serotonin N-Acetyltransferase Activity and Melatonin Content in Two Species of Hamsters

The nighttime rise in pineal melatonin levels can be blocked by administration of the β‐adrenergic receptor antagonist, propranolol, in both Syrian hamsters and rats. Although the administration of β‐adrenergic receptor agonists such as norepinephrine or isoproterenol stimulates pineal melatonin production in the rat, these drugs are without apparent effect on indole production in the Syrian hamster. To determine whether this lack of stimulatory effect in the Syrian hamster is characteristic of this species, a comparison of the effects of norepinephrine and isoproterenol on pineal serotonin N‐acetyltransferase activity and melatonin content was conducted. In contrast to their lack of effect in the Syrian hamster, norepinephrine and isoproterenol stimulated pineal serotonin N‐acetyltransferase activity and melatonin content in the Djungarian hamster. Hourly injection of norepinephrine during a continuation of light into the normal dark period stimulated increases in the activity of serotonin N‐acetyltransferase and melatonin content in the Djungarian hamster but was without effect on these pineal parameters in the Syrian hamster

Melanopsin (Opn4) requirement for normal light-induced circadian phase shifting.

The master circadian oscillator in the hypothalamic suprachiasmatic nucleus is entrained to the day/night cycle by retinal photoreceptors. Melanopsin (Opn4), an opsin-based photopigment, is a primary candidate for photoreceptor-mediated entrainment. To investigate the functional role of melanopsin in light resetting of the oscillator, we generated melanopsin-null mice (Opn4-/-). These mice entrain to a light/dark cycle and do not exhibit any overt defect in circadian activity rhythms under constant darkness. However, they display severely attenuated phase resetting in response to brief pulses of monochromatic light, highlighting the critical role of melanopsin in circadian photoentrainment in mammals

Treatment of cytomegalovirus disease in solid organ transplant recipients

Background: Treatment failure or relapse is common in solid organ transplant recipients treated for cytomegalovirus (CMV) disease. Because CMV infections induce a vigorous inflammatory response, we investigated whether pretreatment levels of inflammatory markers were associated with virologic and clinical outcomes. Methods: Solid organ transplant recipients enrolled in an international multicenter trial of CMV disease treatment (the VICTOR study) were studied (n=248). Plasma levels of markers of inflammation and endothelial cell activation were assessed at baseline and during follow-up by enzyme immunoassays. Results: Baseline values for the chemokine CXCL16 was an independent predictor of clinical outcome (P=0.003) and was a weak independent predictor of suppression of viral load below level of detection (LOD) (P=0.013) at day 21 after initiation of treatment. Baseline levels of the long pentraxin 3 (PTX3) was an independent predictor of suppression of viral load below LOD at day 21 (P=0.002), whereas baseline levels of von Willebrand factor (vWF) was an independent predictor of clinical outcome at day 21 (P=0.008), and vWF levels at day 21 was a weak independent inflammatory predictor of viral recurrence (P=0.018). Conclusions: The present study shows that the plasma levels of CXCL16, PTX3 and vWF at the start of treatment are independently associated with virologic and clinical treatment failure during anti-CMV therapy in solid organ transplant recipients. These findings suggest a link between CMV infection and inflammation that also may influence the outcome of anti-CMV therapy

The Clinical Utility of Whole Blood Versus Plasma Cytomegalovirus Viral Load Assays for Monitoring Therapeutic Response

Background. In patients with cytomegalovirus (CMV) disease, regular monitoring of viral loads and treatment until negative are recommended. However, with more sensitive polymerase chain reaction (PCR) assays and cellular peripheral sample types, detection of low-level viremia is achievable. We compared a whole blood real-time PCR with a plasma PCR assay for monitoring therapeutic response. Methods. Patients enrolled in a trial to treat CMV disease for 21 days had regular viral load monitoring. The results of a plasma-based PCR assay were compared with a real-time PCR assay of whole blood and assessed for their ability to predict recurrence. Results. In 219 evaluable patients, viral loads in plasma versus whole blood demonstrated good correlation but significant difference in absolute value and clearance kinetics. Virus was still detectable by day 21 in 154 of 219 (70.3%) patients with the whole blood versus 105 of 219 (52.1%; P<0.001) patients with the plasma assay. The positive predictive value of persistent plasma viremia at day 21 for virologic recurrence was 41.9% vs. 36.3% for the whole blood assay. In the subset of patients with a negative plasma but positive whole blood at day 21 (n=49), the incidence of virologic recurrence was similar to that of all patients with a negative plasma assay (23.1% vs. 23.6%). Conclusions. When treating CMV disease, enhanced detection of residual viremia using a whole blood real-time PCR does not seem to offer significant clinical advantages nor allows for better prediction of recurrence of CMV viremia or disease. The treat-to-negative paradigm may not hold true when such assays are used