Wine. Optical method for quantifying rates of mucus secretion from single submucosal glands. Am J Physiol Lung Cell Mol Physiol 281: L458-L468, 2001.-We describe an optical method to quantify singlegland secretion. Isolated tracheal mucosa were mounted at the air-Krebs interface and coated with oil. Gland secretions formed spherical bubbles that were digitally imaged at intervals, allowing rates of secretion to be calculated. We monitored 340 glands in 54 experiments with 12 sheep. Glands secreted basally at low rates (0.57 Ϯ 0.04 nl ⅐ min Ϫ1 ⅐ gland Ϫ1 , 123 glands) in tissues up to 9 h postharvest and at lower rates for up to 3 days. Carbachol (10 M) stimulated secretion with an early transient and a sustained or oscillating phase. Peak secretion was 15.7 Ϯ 1.2 nl ⅐ min Ϫ1 ⅐ gland Ϫ1 (60 glands); sustained secretion was 4.5 Ϯ 0.5 nl ⅐ min Ϫ1 ⅐ gland Ϫ1(10 glands). Isoproterenol and phenylephrine (10 M each) stimulated only small, transient responses. We confirmed that cats have a large secretory response to phenylephrine (11.6 Ϯ 3.7 nl ⅐ min Ϫ1 ⅐ gland Ϫ1 , 12 glands), but pigs, sheep, and humans all have small responses (Ͻ2 nl⅐ min Ϫ1 ⅐ gland Ϫ1 ). Carbachol-stimulated peak secretion was inhibited 56% by bumetanide, 67% by HCO 3 Ϫ replacement with HEPES, and 92% by both. The distribution of secretion rates was nonnormal, suggesting the existence of subpopulations of glands.

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The detection and analysis of rare blood biomarkers is necessary for early diagnosis of cancer and to facilitate the development of tailored therapies. However, current methods for the isolation of circulating tumour cells (CTCs) or nucleic acids present in a standard clinical sample of only 5–10 ml of blood provide inadequate yields for early cancer detection and comprehensive molecular profiling. Here, we report the development of a flexible magnetic wire that can retrieve rare biomarkers from the subject’s blood in vivo at a much higher yield. The wire is inserted and removed through a standard intravenous catheter and captures biomarkers that have been previously labelled with injected magnetic particles. In a proof-of-concept experiment in a live porcine model, we demonstrate the in vivo labelling and single-pass capture of viable model CTCs in less than 10 s. The wire achieves capture efficiencies that correspond to enrichments of 10–80 times the amount of CTCs in a 5-ml blood draw, and 500–5,000 times the enrichments achieved using the commercially available Gilupi CellCollector.

Background: Neuromodulation by transcranial focused ultrasound (FUS) offers the potential to noninvasively treat specific brain regions, with treatment location verified by magnetic resonance acoustic radiation force imaging (MR-ARFI). Objective: To investigate the safety of these methods prior to widespread clinical use, we report histologic findings in two large animal models following FUS neuromodulation and MR-ARFI. Methods: Two rhesus macaques and thirteen Dorset sheep were studied. FUS neuromodulation was targeted to the primary visual cortex in rhesus macaques and to subcortical locations, verified by MR-ARFI, in eleven sheep. Both rhesus macaques and five sheep received a single FUS session, whereas six sheep received repeated sessions three to six days apart. The remaining two control sheep did not receive ultrasound but otherwise underwent the same anesthetic and MRI procedures as the eleven experimental sheep. Hematoxylin and eosin-stained sections of brain tissue (harvested zero to eleven days following FUS) were evaluated for tissue damage at FUS and control locations as well as tissue within the path of the FUS beam. TUNEL staining was used to evaluate for the presence of apoptosis in sheep receiving high dose FUS. Results: No FUS-related pre-mortem histologic findings were observed in the rhesus macaques or in any of the examined sheep. Extravascular red blood cells (RBCs) were present within the meninges of all sheep, regardless of treatment group. Similarly, small aggregates of perivascular RBCs were rarely noted in non-target regions of neural parenchyma of FUS-treated (8/11) and untreated (2/2) sheep. However, no concurrent histologic abnormalities were observed, consistent with RBC extravasation occurring as postmortem artifact following brain extraction. Sheep within the high dose FUS group were TUNEL-negative at the targeted site of FUS. Conclusions: The absence of FUS-related histologic findings suggests that the neuromodulation and MR-ARFI protocols evaluated do not cause tissue damage.

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