Pediatric Antibiotic Prescribing and Utilization Practices for RTIs at Private Urgent Care Centers.

Data on pediatric antibiotic prescribing and utilization practices at urgent care centers (UCC) remain limited. In this study, an electronic medical record-based review of UCC encounters for respiratory tract infections (RTI) of patients belonging to one mid-sized pediatric practice was performed. Antibiotic prescribing and guideline adherence were compared between UCCs that were staffed exclusively by pediatric-trained providers to those staffed otherwise. Of a total of 457 RTI visits, 330 (72%) occurred at the pediatric UCC. Across all bacterial RTIs, 82% of encounters at the pediatric UCC were guideline-adherent versus 59% at nonpediatric UCCs (P < .001). At nonpediatric UCCs, pharyngitis was the most common RTI encounter diagnosis (40%), and full streptococcal management guideline adherence was 41%. While 93% of RTI-UCC encounters for <2 years were at pediatric UCCs, the majority of children >10 presented to nonpediatric UCCs. RTI guideline education to UCCs should be a focus of ambulatory stewardship efforts.

Endothelin-1 increases calcium and attenuates renin gene expression in As4.1 cells.

Endothelin-1 (ET-1) is a potent vasoconstrictor and blood pressure modulator. Renin secretion from juxtaglomerular (JG) cells is crucial for blood pressure and electrolyte homeostasis and has been shown to be modulated by ET-1; however, the cellular and molecular mechanism of this regulation is not clear. The purpose of this study was to gain a better understanding of the cellular and molecular pathways activated by ET-1 by using a renin-producing cell line As4.1. ET-1 caused an increase in As4.1 cell intracelluar Ca(2+) concentration ([Ca(2+)](i)) mediated by the ET(A) receptor as its antagonist, BQ-123, abolished the response. The nitric oxide donor nitroprusside, but not 8-bromo-cGMP, reduced the time necessary for successive ET-1 responses. Endothelin-3 had no effect on [Ca(2+)](i). ET-1 dose dependently increased total inositol phosphates with an EC(50) of 2.1 nM. ET-1 reduced renin mRNA by 68% independently of changes in message decay. With the use of a renin-luciferase reporter system in As4.1 cells, ET-1 reduced luciferase activity by 51%, suggesting that renin gene transcription is directly modified by ET-1.

Evaluating a Model of an NRE Mediated Tissue-Specific Expression of Murine Renin Genes.

-We have used comparative sequence analysis to evaluate a putative silencer element that has been proposed to be involved in the differential tissue-expression of the murine renin genes: Ren-1 and Ren-2. In the mouse, these genes share a similar pattern of tissue-specific renin expression. One significant difference is seen in the submandibular gland (SMG) where renin expression from the Ren-2 locus is 100-fold greater than the expression from the Ren-1 locus. One model proposes that this differential expression arises from the interplay among a negative regulatory element and a cAMP responsive element, their respective binding factors, and the disruption of the negative regulatory element by an insertion (M2) that is found in Ren-2 but not in Ren-1. The abrogation of the negative regulatory element's function as a result of the M2 insertion was proposed to be specifically responsible for the higher level of Ren-2 expression in the SMG as compared with Ren-1. We have assessed this hypothesis by looking at an allelic variant in the closely related mouse species M. hortulanus. This species shares the same high level of Ren-2 expression in the SMG as seen in other Ren-2 positive mouse strains. However, the Ren-2 M. hortulanus allele does not appear to contain the disruptive M2 element according to restriction-enzyme mapping. Our sequence analysis confirms that the M. hortulanus Ren-2 allele contains the same sequence elements present in the DBA/2 Ren-2 allele except for the M2 element. Moreover, the proposed negative regulatory element is intact at the sequence level in Ren-2 M. hortulanus allele. This analysis suggests that any involvement of the negative regulatory element in differential Ren-1 and Ren-2 expression in the SMG is not as straightforward as previously hypothesized.