Improving glucose metabolism in the auditory cortex delays the aging of auditory function of guinea pig.

The glucose homeostasis is essential for brain function, and energy deficiency is a key feature of brain aging. We investigated whether improving glucose metabolism in the auditory cortex can delay the aging of auditory function of guinea pigs with age-related hearing loss (ARHL) by d-galactose. Auditory function was assessed by auditory brainstem response (ABR), glucose metabolism was detected by micro PET/CT, and the proteome were identified in auditory cortex by two-dimensional electrophoresis and matrix assisted laser desorption/ionization mass spectrometry. Glucose metabolism decreased in the auditory cortex of d-galactose group, and improving glucose metabolism can delay the aging of auditory function by upregulating seven metabolism-related proteins including ATP synthase subunit beta, triosephosphate isomerase, creatine kinase U-type, pyruvate dehydrogenase E1 component subunit beta, alpha-enolase, phosphoglycerate kinase, and tubulin beta-2A chain. These results suggest that the decrease of glucose metabolism in the auditory cortex may be an important role in the aging of auditory function, and improving glucose metabolism in the auditory cortex can delay the aging of auditory function of guinea pig with ARHL induced by d-galactose.

[Effect of Electroacupuncture on Expression of Catechol-O-methyltransferase in the Inferior Colliculus and Auditory Cortex in Age-related Hearing Loss Guinea Pigs].

OBJECTIVE: To observe the expression of catechol-O-methyltransferase (COMT) in inferior colliculus and auditory cortex of guinea pigs with age-related hearing loss(AHL) induced by D-galactose, so as to explore the possible mechanism of electroacupuncture(EA) underlying preventing AHL. METHODS: Thirty 3-month-old guinea pigs were randomly divided into control group, model group and EA group(n=10 in each group), and ten 18-month-old guinea pigs were allocated as elderly group. The AHL model was established by subcutaneous injection of D-galactose. EA was applied to bilateral "Yifeng"(SJ 17) and "Tinggong"(SI 19) for 15 min in the EA group while modeling, once daily for 6 weeks. After treatment, the latency of auditory brainstem response(ABR) Ⅲ wave was measured by a brain-stem evoked potentiometer. The expressions of COMT in the inferior colliculus and auditory cortex were detected by Western blot. RESULTS: Compared with the control group, the latencies of ABR Ⅲ wave were significantly prolonged and the expressions of COMT in the inferior colliculus and auditory cortex were significantly decreased in the model group and the elderly group(P<0.05). After the treatment, the latency of ABR Ⅲ wave was significantly shortened and the expressions of COMT in the inferior colliculus and auditory cortex were significantly increased in the EA group in comparison with the model group (P<0.05). CONCLUSIONS: EA at "Yifeng" (SJ 17) and "Tinggong" (SI 19) can improve the hearing of age-related deafness in guinea pigs, which may contribute to its effect in up-regulating the expression of COMT in the inferior colliculus and auditory cortex.

The role of dendritic cells in immune regulation of nasal polyps.

Nasal polyps (NPs) are caused by a variety of immune cells and inflammatory cells. However, as the most potent antigen-presenting cells in the immune system, the role of dendritic cells (DCs) in NPs is still unclear. In the present research, we studied the role of DCs in immune regulation of NPs. Thirty patients with NPs, who served as the experimental group, received systemic and local glucocorticoids for 4-7 d, and specimens were collected prior to hormone treatment and during surgery. Normal middle turbinate mucosa tissues from 18 patients who underwent nasal septum surgery were collected as controls. The expression levels of CD83, tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4) and eosinophils (EOS) in NP tissues before and after glucocorticoid therapy and in control middle turbinate mucosa tissues were studied. After glucocorticoid therapy, the expression levels of CD83, TNF-α, IL-4 and EOS decreased significantly. In addition, the expression of IL-4 was lower than that of TNF-α, reversing the Th2 cytokine-dominant condition. CD83 and EOS showed a positive correlation. DCs participated in the development and progression of NPs and could promote the generation of Th2 cytokines. After interference by glucocorticoid therapy, DCs could inhibit the expression of Th2 cytokines and induce secretion of Th1 cytokines. DCs and EOS thus might both play roles in promoting the development and progression of NPs, but the underlying mechanism requires further study.

Reversible neurotoxicity of kanamycin on dorsal cochlear nucleus.

The time course of aminoglycoside neurotoxic effect on cochlear nucleus is still obscure. We examined dynamic pathological changes of dorsal cochlear nucleus (DCN) and investigated whether apoptosis or autophagy was upregulated in the neurotoxic course of kanamycin on DCN after kanamycin treatment. Rats were treated with kanamycin sulfate/kg/day at a dose of 500mg by subcutaneous injection for 10 days. Dynamic pathological changes, neuron density and neuron apoptosis of the DCN were examined at 1, 7, 14, 28, 56, 70 and 140 days after kanamycin treatment. The expressions of JNK1, DAPK2, Bcl-2, p-Bcl-2, Caspase-3, LC3B and Beclin-1 were also detected. Under transmission electron microscopy, the mitochondrial swelling and focal vacuoles as well as endoplasmic reticulum dilation were progressively aggravated from 1 day to 14 days, and gradually recovered from 28 days to 140 days. Meanwhile, both autophagosomes and autolysosomes were increased from 1 day to 56 days. Only few neurons were positive to the TUNEL staining. Moreover, neither the expressions of caspase-3 and DAPK2 nor neurons density of DCN changed significantly. LC3-II was drastically increased at 7 days. Beclin-1 was upgraded at 1 and 7 days. P-Bcl-2 increased at 1, 7, 14 and 28 days. JNK1 increased at 7 days, and Bcl-2 was downgraded at 140 days. LC3-B positive neurons were increased at 1, 7 and 14 days. These data demonstrated that the neurons damage of the DCN caused by kanamycin was reversible and autophagy was upregulated in the neurotoxic course of kanamycin on DCN through JNK1-mediated phosphorylation of Bcl-2 pathway.

[Research progress of acute kanamycin sulfate-induced deafness in guinea pig].

To present a summary of current knowledge regarding acute kanamycin sulfate-induced deafness in guinea pig, by reviewing the published literature. Animal model of acute deafness induced by a single dose of kanamycin sulfate in combination with ethacrynic acid or furosemide in guinea pig was usually used to investigate the mechanism of cochlear cell degeneration. There were different time sequences of cell degeneration of spiral ganglion cell and hair cell in different studies. The findings may result from different doses, order of two drugs administration or time point chosen. There remains scope for further research in chronic kanamycin-induced deafness, which more replicates the type of exposure to people than acute deafness.

[The expression of hepatocyte growth factor and heparanase in laryngeal squamous cell carcinoma and its clinical significance].

OBJECTIVE: To explore the discrepancy of HGF and Hpa expressed in laryngeal squamous cell carcinoma of different pathology grades (differentiation of high, moderate or poor), which can provide the new thought and theory evidence for clinical treatment and control metastasis or palindromic. METHOD: Forty paraffin-embedded samples of laryngeal squamous cell carcinoma, forty paraffin-embedded samples of laryngeal papilloma and twelve paraffin-embedded samples of normal tissue adjacent to cancerous location of our department between May 2004 and April 2005, which were analyzed with SP immunohistochemistry staining. RESULT: The positive rate of HGF were 77.5% and that of Hpa were 72.5% in laryngeal squamous cell carcinoma, which have positive correlation and were higher than that in laryngeal papilloma and normal tissue adjacent to cancerous location with significant statistical difference (P<0.01). The expression of HGF and Hpa had no relationship with primary locations (P>0.05), that have positive correlation with clinical stages and have negative correlation with the level of cellular differentiation. The expression of HGF and Hpa in lymph node metastasis group was significantly higher than the non-metastasis group (P<0.05). CONCLUSION: The expression of HGF and Hpa in laryngeal squamous cell carcinoma are higher than that in nonmalignant ones. They correlates with lymph node metastasis, clinical stages and pathological grading, but they has no relationship with the primary locations. The positive correlation relationship of expression between HGF and Hpa might be worthiness to determine the prognosis of laryngeal squamous cell carcinoma.