Skeletal health consequences associated with inflammatory diseases of the airways significantly contribute to morbidity. Sex differences have been described independently for lung and bone diseases. Repetitive inhalant exposure to lipopolysaccharide (LPS) induces bone loss and deterioration in male mice, but comparison effects in females are unknown. Using an intranasal inhalation exposure model, 8-week-old C57BL/6 male and female mice were treated daily with LPS (100 ng) or saline for 3 weeks. Bronchoalveolar lavage fluids, lung tissues, tibias, bone marrow cells, and blood were collected. LPS-induced airway neutrophil influx, interleukin (IL)-6 and neutrophil chemoattractant levels, and bronchiolar inflammation were exaggerated in male animals as compared to female mice. Trabecular bone micro-CT imaging and analysis of the proximal tibia were conducted. Inhalant LPS exposures lead to deterioration of bone quality only in male mice (not females) marked by decreased bone mineral density, bone volume/tissue volume ratio, trabecular thickness and number, and increased bone surface-to-bone volume ratio. Serum pentraxin-2 levels were modulated by sex differences and LPS exposure. In proof-of-concept studies, ovarectomized female mice demonstrated LPS-induced bone deterioration, and estradiol supplementation of ovarectomized female mice and control male mice protected against LPS-induced bone deterioration findings. Collectively, sex-specific differences exist in LPS-induced airway inflammatory consequences with significant differences found in bone quantity and quality parameters. Male mice demonstrated susceptibility to bone loss and female animals were protected, which was modulated by estrogen. Therefore, sex differences influence the biologic response in the lung-bone inflammatory axis in response to inhalant LPS exposures.
RATIONALE: Nonspecific nasal reactivity characterizes both idiopathic non-allergic rhinitis [''nonallergic rhinopathy''] and a subset of allergic rhinitis patients. This trait involves exaggerated nasal secretion and/or nasal obstruction in response to nonspecific physical and chemical stimuli. Although parasympathetic reflexes are strongly implicated in the secretory response, mechanism(s) underlying the obstructive response are less clearcut, and are explored here. METHODS: A series of experiments was conducted utilizing 15 min. nasal-only exposures to dilute (1.0 ppm) chlorine gas (Cl 2 ) as a provocation agent and active posterior rhinomanometry as the physiologic endpoint. Clean air served as a control exposure on separate days. A subset of subjects also underwent nasal lavage pre-and post-exposure. Subjects included 27 intermittent allergic rhinitis (IAR) patients studied outside of their relevant aeroallergen season, and 25 non-atopic, non-rhinitic controls. RESULTS: Subjective odor and irritation were rated, on average, as ''slight'' (< 1 on a 0-5 scale). Nevertheless, in a stratified sample of 52 subjects, both allergic rhinitis and older age predicted significantly increases in nasal airway resistance in response to Cl 2 provocation. Double-blinded pre-treatment of subjects with a cholinergic blocker did not alter this response. Nasal lavage, performed on a subset of subjects, showed no increases in mast cell tryptase, nor systematic alterations in neuropeptide (SP, CGRP, VIP, NPY) levels. CONCLUSIONS: In this series of experiments, intermittent allergic rhinitis patients showed an augmented obstructive response to irritant provocation relative to controls. Mechanistic studies failed to implicate mast cell degranulation, parasympathetic or neuropeptide-mediated reflexes. Alternative mechanisms (e.g., epithelial cell activation) remain to be explored.
Isolated cecal necrosis (ICN) is a rare form of ischemic colitis that can mimic conditions such as appendicitis, malignancy, or diverticulitis. Most cases of ICN have been identified in patients with significant comorbidities that increase risk of vascular disease. We present a case of ICN mimicking a mass lesion in an elderly patient with few comorbid conditions. Although computed tomography was concerning for colonic mass, diagnostic colonoscopy revealed ischemic colon. The patient underwent right hemicolectomy, and pathology confirmed ICN. It is important to recognize conditions ICN can mimic, understand ICN can present without acute abdomen, and consider ICN in the differential diagnosis even in relatively healthy patients without a history of vascular disease.
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