A Salivary Gland Resident Macrophage Subset Regulating Radiation Responses.

Radiotherapy of head and neck cancers frequently leads to irreversible hypofunction of salivary glands, which severely compromises the quality of life and is extremely difficult to treat. We found recently that salivary gland resident macrophages are sensitive to radiation and interact with epithelial progenitors and endothelial cells through homeostatic paracrine factors. Heterogeneous subpopulations of resident macrophages are present in other organs with distinct functions, whereas subpopulations of salivary gland resident macrophages with distinct functions or transcriptional profiles have not been reported yet. Using single-cell RNA sequencing, we found that mouse submandibular glands (SMGs) contain 2 distinct self-renewing resident macrophage subsets, an MHC-IIhi subset present in many other organs and an uncommon Csf2r+ subset. The main source of Csf2 in SMGs are innate lymphoid cells (ILCs) that rely on IL15 for maintenance, while the main source of IL15 protein is Csf2r+ resident macrophages, indicating a homeostatic paracrine interaction between these cells. Csf2r+ resident macrophages are the major source of hepatocyte growth factor (Hgf) that regulates homeostasis of SMG epithelial progenitors. Meanwhile, Csf2r+ resident macrophages are responsive to Hedgehog signaling that can rescue salivary function impaired by radiation. Consistently, irradiation persistently decreased numbers of ILCs and levels of IL15 and Csf2 in SMGs, which were all recovered by transient activation of Hedgehog signaling after radiation. Csf2r+ resident macrophages and MHC-IIhi resident macrophages share transcriptome profiles of perivascular macrophages and macrophages associated with nerves and/or epithelial cells in other organs, respectively, and such niche preferences were supported by lineage tracing and immunofluorescent staining. These findings reveal an uncommon resident macrophage subset that regulates the homeostasis of the salivary gland and is promising as the target to restore salivary gland function impaired by radiation.

The Global Landscape of Occupational Exposure Limits--Implementation of Harmonization Principles to Guide Limit Selection.

Occupational exposure limits (OELs) serve as health-based benchmarks against which measured or estimated workplace exposures can be compared. In the years since the introduction of OELs to public health practice, both developed and developing countries have established processes for deriving, setting, and using OELs to protect workers exposed to hazardous chemicals. These processes vary widely, however, and have thus resulted in a confusing international landscape for identifying and applying such limits in workplaces. The occupational hygienist will encounter significant overlap in coverage among organizations for many chemicals, while other important chemicals have OELs developed by few, if any, organizations. Where multiple organizations have published an OEL, the derived value often varies considerably-reflecting differences in both risk policy and risk assessment methodology as well as access to available pertinent data. This article explores the underlying reasons for variability in OELs, and recommends the harmonization of risk-based methods used by OEL-deriving organizations. A framework is also proposed for the identification and systematic evaluation of OEL resources, which occupational hygienists can use to support risk characterization and risk management decisions in situations where multiple potentially relevant OELs exist.

Biomonitoring Equivalents for interpretation of urinary fluoride.

Exposure to fluoride is widespread due to its natural occurrence in the environment and addition to drinking water and dental products for the prevention of dental caries. The potential health risks of excess fluoride exposure include aesthetically unacceptable dental fluorosis (tooth mottling) and increased skeletal fragility. Numerous organizations have conducted risk assessments and set guidance values to represent maximum recommended exposure levels as well as recommended adequate intake levels based on potential public health benefits of fluoride exposure. Biomonitoring Equivalents (BEs) are estimates of the average biomarker concentrations corresponding to such exposure guidance values. The literature on daily urinary fluoride excretion rates as a function of daily fluoride exposure was reviewed and BE values corresponding to the available US and Canadian exposure guidance values were derived for fluoride in urine. The derived BE values range from 1.1 to 2.1mg/L (1.2-2.5µg/g creatinine). Concentrations of fluoride in single urinary spot samples from individuals, even under exposure conditions consistent with the exposure guidance values, may vary from the predicted average concentrations by several-fold due to within- and across-individual variation in urinary flow and creatinine excretion rates and due to the rapid elimination kinetics of fluoride. Thus, the BE values are most appropriately applied to screen population central tendency estimates for biomarker concentrations rather than interpretation of individual spot sample concentrations.

High-performance liquid chromatographic method to screen and quantitate seven selective serotonin reuptake inhibitors in human serum.

A high-performance liquid chromatographic screening method (HPLC) is described for the determination of seven selective serotonin reuptake inhibitors (SSRIs) (fluvoxamine, milnacipran, paroxetine, sertraline, fluoxetine, citalopram, venlafaxine) and for three pharmacologically active N-demethylated metabolites (desmethylcitalopram, didesmethylcitalopram and norfluoxetine). A tricyclic antidepressant, clomipramine, was used as an internal standard. The method consists of liquid extraction of serum after alcalinisation at pH 9.50, followed by chromatography on a Beckman C18 reversed-phase column. Compounds were detected at 200.4 nm. The standard curves were linear over a working range of 50-1,000 ng/ml for fluvoxamine, 15-1,000 ng/ml for fluoxetine, 25-500 ng/ml for norfluoxetine, 50-500 ng/ml for sertraline, 20-500 ng/ml for paroxetine, 25-550 ng/ml for citalopram, 25-750 ng/ml for desmethylcitalopram, 25-800 ng/ml for didesmethylcitalopram, 25-650 ng/ml for milnacipran, and 25-500 ng/ml for venlafaxine. The quantitation limits of the method were 15 ng/ml for fluoxetine, 20 ng/ml for paroxetine, 25 ng/ml for venlafaxine, norfluoxetine and citalopram, and its metabolites, 40 ng/ml for sertraline and 50 ng/ml for fluvoxamine. No interferences were noted with this sensitive and specific method which can be used for therapeutic drug monitoring.