Distribution of transient receptor potential cation channel subfamily V member 1-expressing nerve fibers in mouse esophagus.

Transient receptor potential cation channel subfamily V member 1 (TRPV1) plays a role in esophageal function. However, the distribution of TRPV1 nerve fibers in the esophagus is currently not well understood. In the present study, we investigated the distribution of TRPV1 and neurotransmitters released from TRPV1 nerve fibers in the mouse lower esophagus. Furthermore, we investigated changes in the presence of TRPV1 in the mouse model of esophagitis. Numerous TRPV1-immunoreactive nerve fibers were seen in both the submucosal layer and myenteric plexus of the lower esophagus and colocalized with calcitonin gene-related peptide (CGRP). TRPV1 colocalized with substance P in axons in the submucosal layer and myenteric plexus. TRPV1 colocalized with neuronal nitric oxide synthase in the myenteric plexus. We observed some colocalization of CGRP with the vesicular acetylcholine (ACh) transporter, packaging of ACh into synaptic vesicles after its synthesis in terminal cytoplasm, in the submucosal layer and myenteric plexus. In the esophagitis model, the number of the TRPV1 nerve fibers did not change, but their immunoreactive intensity increased compared with sham-operated mice. Inhibitory effect of exogenous capsaicin on electrically stimulated twitch contraction significantly increased in esophagitis model compared with the effect in sham-operated mice. Overall, these results suggest that TRPV1 nerve fibers projecting to both the submucosal and muscle layer of the esophagus are extrinsic spinal and vagal afferent neurons. Furthermore, TRPV1 nerve fibers contain CGRP, substance P, nitric oxide, and ACh. Therefore, acid influx-mediated TRPV1 activation may play a role in regulating esophageal relaxation.

Anti-diabetic drug metformin dilates retinal blood vessels through activation of AMP-activated protein kinase in rats.

The aim of this study was to examine whether metformin, a biguanide anti-hyperglycemic drug, dilates retinal blood vessels in rats. Ocular fundus images were captured with an original high-resolution digital fundus camera in vivo and diameters of retinal blood vessels were measured. Both systemic blood pressure and heart rate were continuously recorded. Metformin (0.01-0.3mg/kg/min) increased diameters of retinal blood vessels in a dose-dependent manner. This retinal vasodilator effect of metformin was abolished by compound C, an inhibitor of AMP-activated protein kinase (AMPK), and NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide (NO) synthase. Similar results were obtained with the AMPK activator 5-aminoimidazole-4-carboxamide-1-ß-D-ribonucleoside (AICAR, 0.01-1mg/kg/min). Neither metformin nor AICAR exerted significant effect on mean blood pressure and heart rate. However, a significant pressor response to AICAR was observed upon inhibition of NO synthase. These results suggest that metformin dilates retinal blood vessels through activation of AMPK, and NO plays an important role in the retinal vasodilator response following AMPK activation.

Closure of tracheoesophageal fistula with prefabricated deltopectoral flap.

Tracheoesophageal fistula (TEF) is a serious complication associated with impaired quality of life. However, a successful TEF closure is difficult owing to the high incidence of recurrence. We utilized a prefabricated deltopectoral (DP) flap for closure of a TEF that occurred after an extended total thyroidectomy. Prefabrication of the inner soft tissue lining the DP flap with a split skin graft was performed prior to surgical closure of a TEF. Esophageal and tracheal mucosa were sutured to the split thickness side and full thickness side of the prefabricated DP flap, respectively. A successful closure of the fistula was achieved with this procedure. Prefabricated DP flap is a useful procedure for the surgical treatment of TEF.

Protective effects of sodium thiosulfate for cisplatin-mediated ototoxicity in patients with head and neck cancer.

CONCLUSIONS: Intra-arterial high-dose cisplatin chemoradiation (CRT-IA) with sodium thiosulfate (STS) causes relatively less severe cisplatin ototoxicity than intravenous cisplatin chemoradiation without STS (CRT-IV). The results of this study also suggest that early detection of ototoxicity is possible by testing the hearing loss at ultra-high frequencies. OBJECTIVES: To investigate protective effects of STS against cisplatin ototoxicity. METHODS: Between 2011 and 2013, 18 patients with head and neck carcinomas were treated with intra-arterial infusions of high-dose cisplatin (range 100-180 mg/body, mean 111 mg/body; range 2-5 courses, mean 3.6 courses) and systemic administration of cisplatin (range 66-185 mg/body, mean 130 mg/body; range 1-3 courses, mean 2.6 courses) and concurrent radiation therapy (range 60-70 Gy, mean 69 Gy). Cisplatin was neutralized by STS in CRT-IA but not in CRT-IV. RESULTS: Intra-arterial infusion in the high-dose cisplatin group caused significant hearing loss at ultra-high frequencies of 10 and 12 kHz (p = 0.028, 0.039, respectively), whereas the group receiving systemic administration of cisplatin had significant hearing loss at high frequencies of 8 and 10 kHz (p = 0.016, 0.027, respectively).

Purification and characterization of a novel secondary fimbrial protein from Porphyromonas gulae.

BACKGROUND: Porphyromonas gulae are black-pigmented anaerobic bacteria isolated from the gingival sulcus of various animal hosts and are distinct from Porphyromonas gingivalis originating in humans. We previously reported the antigenic similarities of 41-kDa fimbriae between P. gulae ATCC 51700 and P. gingivalis ATCC 33277. In this study, to clarify the presence of another type of fimbriae of P. gulae, we have purified and characterized the secondary fimbrial protein from P. gulae ATCC 51700. METHODS: The secondary fimbrial protein was purified from P. gulae ATCC 51700 using an immunoaffinity column coupling with antibodies against the 41-kDa fimbrial protein. The expression of fimbriae on the cell surface of P. gulae ATCC 51700 was investigated by transmission electron microscopy. The N-terminal amino acid sequence was determined by an amino acid sequencer system. RESULTS: The molecular mass of this protein was approximately 53-kDa, as estimated by SDS-PAGE. The polyclonal antibodies against the 53-kDa protein did not react with the 41-kDa fimbrial protein of P. gulae ATCC 51700. Immunogold electron microscopy revealed that anti-53-kDa fimbrial serum bound to fimbria on the cell surface of P. gulae ATCC 51700. The amino acid sequence of the N-terminal 15 residues of the 53-kDa fimbrial protein showed only 1 of 15 residues identical to the 41-kDa fimbrial protein. CONCLUSION: The 53-kDa fimbriae are different in molecular weight and antigenicity from the 41-kDa fimbrial protein of P. gulae ATCC 51700. These results clearly suggest that the 41-kDa and the 53-kDa fimbriae are distinct types of fimbriae expressed simultaneously by this organism.