An l-RNA-based aquaretic agent that inhibits vasopressin in vivo

A class of diuretic/aquaretic agents based on mirror-image oligonucleotides (so-called Spiegelmers) has been identified. These molecules directly bind and inhibit the neuropeptide vasopressin (AVP). AVP is the major regulatory component of body fluid homeostasis mediated through binding to the renal V(2) receptor. Elevated plasma levels of AVP are implicated in several pathological conditions, mainly cardiovascular diseases. In congestive heart failure, AVP is part of a neuroendocrine imbalance that is responsible for progressive worsening of the disease. Employing in vitro selection techniques, RNA aptamers that bind to the unnatural d-configuration of AVP were isolated. The best aptamer displayed an affinity to d-AVP of ≈560 pM at 37°C. The corresponding Spiegelmer, a 38-mer mirror-image oligonucleotide (l-RNA) termed NOX-F37, inhibits vasopressin-dependent activation of V(1a) as well as V(2) receptors with IC(50) values of 6.1 nM and 1 nM, respectively. NOX-F37 administered to healthy rats effectively neutralized AVP and increased diuresis dose-dependently for 24 h. The mode of action was strictly aquaretic, i.e., the increase in urine volume was not accompanied by an increase in electrolytes. These results clearly prove the in vivo efficacy of NOX-F37 and points out its potential as a drug in the treatment of diseases that are associated with body fluid overload

Caregiver and Youth Agreement Regarding Youth\u27s Trauma Histories: Implications for Youth\u27s Functioning After Exposure to Trauma

Epidemiological research has demonstrated that youth are exposed to potentially traumatic events at high rates. Caregivers play an important role in youths’ successful recovery following exposures to potentially traumatic events. However, past research has documented poor caregiver–youth agreement regarding youths’ exposures to potentially traumatic events, indicating a potential lack of support for many youth exposed to such events. This study examined caregiver–youth discrepancies in the reports of youths’ lifetime exposures to potentially traumatic events, and the relationship between these reporting discrepancies and youths’ post-traumatic stress disorder (PTSD) symptoms, mood symptoms, and functional impairment following disclosures of sexual abuse. Participants included 114 caregiver–youth dyads participating in a family-based intervention at four Child Advocacy Centers in New York City. Standardized measures of trauma history, youth PTSD symptoms, youth mood symptoms, youth functional impairment, and caregiver PTSD symptoms were given in interview format to caregivers and youth at the time of intake into the intervention. The demographic composition of the youth sample was 86.8 % female, 13.2 % male, 32.5 % African American, 54.4 % Latino/a, 2.6 % Caucasian, 0.9 % Asian American, 8.8 % other race/ethnicity. Youth ranged in age from 7 to 16. Results demonstrated poor agreement between youth and caregivers regarding youths’ exposure to a range of potentially traumatic events and regarding youths’ PTSD symptoms, mood symptoms and functional impairment. Both caregiver–youth discrepancies regarding youths’ histories of exposures to potentially traumatic events and caregiver PTSD symptoms were significantly associated with youths’ self-reported symptoms and functional impairment. Only caregiver PTSD symptoms were related to caregivers’ reports of youths’ symptoms and functional impairment. Findings underscore the importance of family support and communication regarding exposures to potentially traumatic events and the detrimental associations of caregiver–youth disagreement about youths’ exposures to potentially traumatic events. Recommendations are provided for the assessment and treatment of families presenting in the aftermath of traumatic exposures