Lumbar puncture in infants with urinary tract infection: Assessment of infant management in the emergency department.

BACKGROUND: Neonatal bacterial infections must be bacteriologically confirmed from laboratory samples to best adjust antibiotic therapy. Lumbar puncture (LP) has been recommended for infants younger than 1 month with suspected serious bacterial infection (SBI) to manage possible meningitis. However, the incidence of bacterial meningitis associated with other infections and particularly with urinary tract infections (UTIs) is low. Recourse to systematic LP may be less essential if infants have a UTI. We aimed (a) to determine the management and frequency of bacterial meningitis coexisting with a documented diagnosis of UTI in infants aged < 1 month who had an LP, and (b) to evaluate the management of infants in emergency admissions with suspected SBI while assessing antibiotic treatment. METHODS: We conducted a retrospective single-center study from January 2010 to April 2019 including all cases of neonatal bacterial infections, and collected data on the clinical, laboratory, and radiological features. RESULTS: In all, 409 infants were included in the study. Of these, 162 (39.6%) presented with a UTI and eight (2%) had bacterial meningitis. Of the infants diagnosed with UTI, 74.7% had an LP, of whom 34.7% experienced LP complications. No coexistence of UTI and bacterial meningitis was found among infants who had an LP and a documented UTI. CONCLUSION: Although not all infants had an LP and a urine culture at the same time, these results show that bacterial meningitis coexisting with a confirmed UTI diagnosis in infants is rare. Furthermore, LP can be traumatic in some cases and therefore its utility should be assessed according to the clinical context.

Glucocorticoid receptor-interacting protein-1 and receptor-associated coactivator-3 differentially interact with the vitamin D receptor (VDR) and regulate VDR-retinoid X receptor transcriptional cross-talk.

The vitamin D(3) receptor (VDR) is a ubiquitously expressed nuclear hormone receptor, and its ligand, calcitriol, has diverse biological effects. The extent to which transcriptional coactivators are involved in modulating tissue-specific functions of the VDR is unclear. Hence, the current studies investigated the role of p160 coactivators in regulating VDR function and interaction with RXR. Two p160 coactivators, glucocorticoid receptor-interacting protein-1 (GRIP1) and receptor-associated coactivator-3 (RAC3), which are expressed in an inverse fashion in cell lines representative of calcitriol target tissues, interacted directly with the VDR, both in vitro and in yeast cells, but only in the presence of calcitriol. Deletional analyses of VDR indicated that GRIP1 and RAC3 required an intact VDR activation function (AF-2) domain for efficient interaction as well as additional but distinct regions of the VDR. Coexpression experiments in yeast cells indicated that both GRIP1 and RAC3 coassemble with the VDR to form an active transcriptional complex. They also form ternary complexes with VDR homodimers and VDR:RXRalpha heterodimers. In mammalian cells, GRIP1 augmented VDR activation of the osteocalcin promoter, whereas RAC3 enhanced VDR activation indirectly through RXR. These data suggest different coactivators regulate VDR function via distinct mechanisms and support the hypothesis that the VDR recruits different coactivators depending on specific gene and cellular contexts.

Molecular mechanism of vitamin D receptor action.

The vitamin D system is unique in that distinct calcium homeostatic functions and cell growth regulatory activities are mediated through a single ligand, calcitriol, acting through a specific receptor exhibiting ubiquitous tissue expression, the vitamin D receptor (VDR). The VDR is a member of a superfamily of nuclear steroid hormone receptors which regulate gene transcription by interacting with response elements in gene promoters. Structure-function analysis of the VDR protein has defined distinct domains involved in DNA binding, ligand binding, receptor dimerisation and gene transactivation, including a C-terminal activation function domain (AF-2) that is important for cofactor interaction. A model for regulation of gene transcription by the VDR is evolving and proposes VDR interaction with various components of the basal transcriptional machinery, including newly defined coactivators and corepressors, which may act to regulate gene transcription by altering histone acetylation and chromatin structure. This review describes the vitamin D endocrine system and the role of the VDR in regulating this system, including the molecular basis for the diverse actions of synthetic calcitriol analogues in the treatment of autoimmune disease and cancer.

Feasibility of continuous glutamate monitoring in perfused retinal tissue with a potentiometric biosensing probe.

A potentiometric biosensing probe for glutamate has been evaluated as a possible tool to measure the release of glutamate from the isolated retina of Bufo marinus. This probe is based on carbon dioxide detection, following enzymatic conversion of glutamate to gamma-aminobutyric acid (GABA) via glutamic acid decarboxylase (GAD). Probe response characteristics of dynamic range, limit of detection, pH dependency, and selectivity are described. Probe modifications were required for sensor operation in an upside down configuration which was demanded by the need to mount and perfuse the retinal tissue directly at the sensor tip. Overall, these results indicate that this particular potentiometric biosensor is not well suited for direct glutamate measurements in retinal tissue because of pH incompatibility between the sensor and the tissue, and because of high background carbon dioxide levels released from the retina at the pH optimum of the probe. Despite this drawback, the sensor could be utilized to provide a continuous "downstream" monitor of glutamate levels during the course of an experiment, after pH buffering of tissue perfusate. Alternative approaches to probes more compatible with direct tissue measurements are discussed.