Mechanism of olfactory masking in the sensory cilia

Olfactory masking has been used to erase the unpleasant sensation in human cultures for a long period of history. Here, we show a positive correlation between the human masking and the odorant suppression of the transduction current through the cyclic nucleotide–gated (CNG) and Ca2+-activated Cl− (Cl(Ca)) channels. Channels in the olfactory cilia were activated with the cytoplasmic photolysis of caged compounds, and their sensitiveness to odorant suppression was measured with the whole cell patch clamp. When 16 different types of chemicals were applied to cells, cyclic AMP (cAMP)-induced responses (a mixture of CNG and Cl(Ca) currents) were suppressed widely with these substances, but with different sensitivities. Using the same chemicals, in parallel, we measured human olfactory masking with 6-rate scoring tests and saw a correlation coefficient of 0.81 with the channel block. Ringer's solution that was just preexposed to the odorant-containing air affected the cAMP-induced current of the single cell, suggesting that odorant suppression occurs after the evaporation and air/water partition of the odorant chemicals at the olfactory mucus. To investigate the contribution of Cl(Ca), the current was exclusively activated by using the ultraviolet photolysis of caged Ca, DM-nitrophen. With chemical stimuli, it was confirmed that Cl(Ca) channels were less sensitive to the odorant suppression. It is interpreted, however, that in the natural odorant response the Cl(Ca) is affected by the reduction of Ca2+ influx through the CNG channels as a secondary effect. Because the signal transmission between CNG and Cl(Ca) channels includes nonlinear signal-boosting process, CNG channel blockage leads to an amplified reduction in the net current. In addition, we mapped the distribution of the Cl(Ca) channel in living olfactory single cilium using a submicron local [Ca2+]i elevation with the laser photolysis. Cl(Ca) channels are expressed broadly along the cilia. We conclude that odorants regulate CNG level to express masking, and Cl(Ca) in the cilia carries out the signal amplification and reduction evenly spanning the entire cilia. The present findings may serve possible molecular architectures to design effective masking agents, targeting olfactory manipulation at the nano-scale ciliary membrane

Accidental Ingestion of Nasal Packing Gauze during Endonasal Endoscopic Dacryocystorhinostomy under Local Anesthesia: A Case Report

Purpose: To report a case of accidental ingestion of a nasal packing gauze during endonasal endoscopic dacryocystorhinostomy (en-DCR) under local anesthesia. Case Report: A 66-year-old female patient underwent an en-DCR for a right acquired nasolacrimal duct obstruction. The surgery was performed in a supine position under local anesthesia. An X-ray detectable ribbon gauze soaked in 0.02% epinephrine was placed in the middle meatus to prevent blood and liquid from flowing into the pharynx. The same packing gauze was also used for hemostasis during the surgery. At the end of the surgery, 1 piece of gauze was missing and could not be detected by the endonasal endoscopic exploration. An abdominal X-ray image performed on the same day demonstrated the presence of the gauze in the stomach although the patient did not notice swallowing the gauze. The gauze was not there on the X-ray 1 week later. Conclusion: Surgeons need to be aware of accidental ingestion of a nasal packing gauze in en-DCR under local anesthesia. Keeping the gauze end out of the nostril is likely preventive for this complication. The use of X-ray detectable gauze was helpful to detect its location

Thioredoxin deficiency increases oxidative stress and causes bilateral symmetrical degeneration in rat midbrain

Thioredoxin, encoded by Txn1, acts as a critical antioxidant in the defense against oxidative stress by regulating the dithiol/disulfide balance of interacting proteins. The role of thioredoxin in the central nervous system (CNS) is largely unknown. A phenotype-driven study of N-ethyl-N-nitrosourea-mutated rats with wild-running seizures revealed the importance of Txn1 mutations in CNS degeneration. Genetic mapping identified Txn1-F54L in the epileptic rats. The insulin-reducing activity of Txn1-F54L was approximately one-third of that of the wild-type (WT). Bilateral symmetrical vacuolar degeneration in the midbrain, mainly in the thalamus and the inferior colliculus, was observed in the Txn1-F54L rats. The lesions displayed neuronal and oligodendrocytic cell death. Neurons in Txn1-F54L rats showed morphological changes in the mitochondria. Vacuolar degeneration peaked at five weeks of age, and spontaneous repair began at seven weeks. The TUNEL assay showed that fibroblasts derived from homozygotes were susceptible to cell death under oxidative stress. In five-week-old WT rats, energy metabolism in the thalamus was significantly higher than that in the cerebral cortex. In conclusion, in juvenile rats, Txn1 seems to play an essential role in reducing oxidative stress in the midbrains with high energy metabolism

Assessment of Arterial Transit Time and Cerebrovascular Reactivity in Moyamoya Disease by Simultaneous PET/MRI

We investigated the relationship between MRI-arterial spin labeling (ASL) parameters and PET-cerebral blood flow (CBF)/cerebrovascular reactivity (CVR) simultaneously obtained by PET/MRI in Moyamoya disease. Twelve patients underwent 15O-water PET/MRI with the acetazolamide (ACZ) challenge test. PET-CBF and PET-CVR were measured using 15O-water PET. Pseudo-continuous ASL obtained the robust arterial transit time (ATT) and ASL-CBF estimation. ASL parameters were compared with PET-CBF and PET-CVR. Before ACZ loading, absolute and relative ASL-CBF were significantly correlated with absolute and relative PET-CBF (r = 0.44, p p p p p p p 30% (898 ± 197 ms). ASL-ATT ratio of MCA territories with CVR 30% (81.4 ± 11.3%). ATT correction using multiple postlabeling delays increased the accuracy of ASL-CBF quantitation. Baseline ASL-ATT is a hemodynamic parameter and may represent an efficient alternative to PET-CVR