Exposure to cigarette smoke is a major cause of olfactory dysfunction. However, the underlying mechanisms by which cigarette smoke interferes with the highly regenerative olfactory nerve system remain unclear. To investigate whether cigarette smoke induces olfactory dysfunction by disrupting cell proliferation and cell survival in the olfactory epithelium (OE), we developed a mouse model of smoking that involved intranasal administration of a cigarette smoke solution (CSS). Immunohistological analyses and behavioral testing showed that CSS administration during a period of 24 days reduced the number of olfactory marker protein-positive mature olfactory receptor neurons (ORNs) in the OE and induced olfactory dysfunction. These changes coincided with a reduction in the number of SOX2(+) ORN progenitors and Ki-67(+) proliferating cells in the basal layer of the OE, an increase in the number of caspase-3(+) apoptotic cells, and an increase in the expression of mRNA for the inflammatory cytokines IL-1β and IL-6. Notably, the proliferating ORN progenitor population recovered after cessation of treatment with CSS, resulting in the subsequent restoration of mature ORN numbers and olfaction. These results suggest that SOX2(+) ORN progenitors are targets of CSS-induced impairment of the OE, and that by damaging the ORN progenitor population and increasing ORN death, CSS exposure eventually overwhelms the regenerative capacity of the epithelium, resulting in reduced numbers of mature ORNs and olfactory dysfunction.

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Background: It remains unclear whether the metabolic activity of nasal mucus in the olfactory and respiratory areas is different. Moreover, age-and olfactionrelated changes may affect metabolism.Methods: Hexanal, octanal, and 2-methylbutanal were selected for in vitro metabolism analysis and compared between the olfactory cleft and respiratory mucus of participants < 50-year-old with normal olfaction using gas chromatography mass spectrometry. The metabolic activity of hexanal in the olfactory cleft mucus was further compared between three groups, (1) normal olfaction, age < 50 years old, (2) normal olfaction, age ≥50 years old, and (3) idiopathic olfactory impairment. To characterize the enzyme(s) responsible for aldehyde reduction, we also tested if epalr22897estat and 3,5-dichlorosalicylic acid, types of reductase inhibitors, affect metabolism.Results: Conversion of aldehydes to their corresponding alcohols was observed in the olfactory cleft and respiratory mucus. The metabolic production of hexanol, octanol, and 2-methybutanol was significantly higher in the olfactory cleft mucus than in the respiratory mucus (p < 0.01). The metabolic conversion of hexanal to hexanol in the mucus of the idiopathic olfactory impairment group was significantly lower than that in the age-matched normal olfaction group. Excluding the nicotinamide adenine dinucleotide phosphate (NADPH) regenerating system from the reaction mixture inhibited metabolism. The addition of either epalr22897estat or 3,5-dichlorosalicylic acid did not inhibit this metabolic conversion. Conclusions:The enzymatic metabolism of odorants in the olfactory cleft mucus is markedly higher than in the respiratory mucus and decreases in patients with idiopathic olfactory impairment.

Background: The incidence of olfactory impairment increases with age; however, the detailed molecular and cellular mechanisms underlying this increase are yet to be determined.Methods: We examined the influence of aging on olfactory receptor neurons (ORNs), which are maintained by a unique stem cell system, from olfactory progenitor cells to mature ORNs, by histological comparisons of the physiological status of the olfactory epithelium between young adult and aged mice. Furthermore, we clarified the expression of genes encoding inflammatory cytokines, neurotrophins, growth factors, and extracellular matrix proteins to reveal the molecular mechanisms underlying olfactory impairment caused by aging.Results: The numbers of mature and immature ORNs, but not olfactory progenitors, decreased in the aged olfactory epithelium, with a concurrent reduction in Ki-67-positive proliferating cells. Transcriptome analyses revealed an increase in Il6, encoding a component of senescence-associated secretary phenotypes (SASP), and a decrease in Igf1, encoding a growth factor for ORNs, in the aged nasal mucosa. Interestingly, expression levels of several extracellular matrix genes, including Col1a2, decreased in the aged nasal mucosa. Consistent with the transcriptional changes, the number of Col1a2-GFP-positive cells decreased in the aged lamina propria.Conclusions: Our data suggest that reduction in ORN number and cell proliferation, reduced extracellular matrix gene expression, and increased SASP contribute to olfactory impairment during aging.

Carotid body tumors (CBTs) are rare neoplasms of the carotid body. Most CBTs are benign; however, some can show malignant behavior. Malignant CBTs have an unpredictable history; often, there is no correlation between the histologic findings and the clinical behavior. They are usually diagnosed by the development of local recurrence or lymph node metastasis following total resection of the primary mass, or by the detection of distant metastasis. There are few reports of histopathologic confirmation of malignant CBTs. We report a rare case of malignant CBT with distant metastases, in which the diagnosis was confirmed by histopathology, and present a review of the literature.

Methods. The expression of ABH blood group carbohydrate antigens was examined histochemically in tumors and adjacent nontumorous tissues of 89 cases of human lung carcinoma in which nontumorous tissues expressed blood group carbohydrate antigens compatible with the erythrocyte blood group types. Results and Conclusions. Loss of ABH blood group antigens in lung carcinomas correlated with their metastatic potential, especially with the recurrence of hematogenous metastasis. Consequently, patients with tumors that retained compatible ABH blood group antigens showed a better prognosis than patients with tumors of altered antigenic profiles. The loss of blood group B antigen more significantly affected both the hematogenous metastasis and prognosis than that of A and H antigens. Cancer 1993; 72:75–81.

The posterior nasal nerve is the dominant source of the parasympathetic, sympathetic, and sensory fibers that innervate the nasal respiratory mucosa. Therefore, a posterior nasal neurectomy (PNN) is thought to induce denervation of the nasal mucosa and relieve the nasal symptoms of allergic rhinitis. However, the underlying mechanisms and therapeutic action of PNN remain unknown. To investigate the impact of PNN-induced denervation of the nasal mucosa on allergic rhinitis, we developed a rat model of PNN and examined the effects of PNN on allergic rhinitis in ovalbumin-sensitized rats. This rat model of PNN was characterized by the depletion of nerve fibers, choline acetyltransferase, and neuropeptides (eg, substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, and neuropeptide Y) in the nasal respiratory mucosa. These animals exhibited nasal gland and goblet cell hypertrophy in the septal mucosa and atrophy of the submucosal gland in the lateral nasal wall, as well as reduced nasal secretion due to deficient acetylcholine synthesis. In an ovalbumin-sensitized model of allergic rhinitis, PNN also induced the depletion of nerve fibers, choline acetyltransferase, and neuropeptides in the nasal mucosa and suppressed nasal secretion. However, PNN did not affect mucosal thickening, eosinophil and mast cell infiltration, interleukin-4 and interferon-γ mRNA expression, and allergic symptoms (ie, sneezing and nasal scratching). These results suggest that the peripheral nerves and corresponding neuropeptides regulate nasal secretion, but not hypersensitivity, in allergic rhinitis, and that allergic rhinitis-related mucosal reactions occur in a highly denervated mucosa after PNN. Posterior nasal neurectomy may be a therapeutic option for the treatment of hyperrhinorrhea, but not allergic rhinitis hypersensitivity. Allergic rhinitis is among the most common diseases; affecting 10-30% of people in industrialized countries. [1][2][3] This condition presents with symptoms that reduce the quality of life such as rhinorrhea, sneezing, nasal obstruction, and nasal itching. 4 Medical allergic rhinitis treatment is approached in a stepwise manner and includes agents such as antihistamines and nasal topical steroids. 1,2,5 However, for patients with allergic rhinitis refractory to medication therapy; surgical interventions such as endoscopic posterior nasal neurectomy (PNN) have been attempted.Endoscopic PNN, which involves the intranasal severing of the posterior nasal nerve, is a common surgical treatment for allergic rhinitis in Asia. 2,6,7 The posterior nasal nerve, which is a peripheral branch of the vidian nerve, innervates the nasal cavity via the pterygopalatine ganglion, which comprises parasympathetic and sympathetic vidian nerve fibers and sensory nerve fibers from the trigeminal nerve. Therefore, PNN is expected to suppress nasal hypersecretion by blocking autonomic vidian nerve fibers, similar to vidian neurectomy (VN), as well as hypersensitivity by simultaneously blocking sensory nerve fibers. 6...

The olfactory system is a unique part of the mammalian nervous system due to its capacity for neurogenesis and the replacement of degenerating receptor neurons. Cigarette smoking is a major cause of olfactory dysfunction. However, the mechanisms by which cigarette smoke impairs the regenerative olfactory receptor neurons (ORNs) remain unclear. Here, we investigated the influence of cigarette smoke on ORN regeneration following methimazole-induced ORN injury. Administration of methimazole caused detachment of the olfactory epithelium from the basement membrane and induced olfactory dysfunction, thus enabling us to analyze the process of ORN regeneration. We found that intranasal administration of cigarette smoke solution (CSS) suppressed the recovery of ORNs and olfaction following ORN injury. Defective ORN recovery in CSS-treated mice was not associated with any change in the number of SOX2(+) ORN progenitor cells in the basal layer of the OE, but was associated with impaired recovery of GAP43(+) immature ORNs. In the nasal mucosa, mRNA expression levels of neurotrophic factors such as brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-5, glial cell-derived neurotrophic factor, and insulin-like growth factor-1 (IGF-1) were increased following OE injury, whereas CSS administration decreased the ORN injury-induced IGF-1 expression. Administration of recombinant human IGF-1 prevented the CSS-induced suppression of ORN recovery following injury. These results suggest that CSS impairs regeneration of ORNs by suppressing the development of immature ORNs from ORN progenitors, at least partly by reducing IGF-1 in the nasal mucosa.