Effect of Sodium Salicylate on Calcium Currents and Exocytosis in Cochlear Inner Hair Cells: Implications for Tinnitus Generation / 神经科学通报·英文版

Sodium salicylate is an anti-inflammatory medication with a side-effect of tinnitus. Here, we used mouse cochlear cultures to explore the effects of salicylate treatment on cochlear inner hair cells (IHCs). We found that IHCs showed significant damage after exposure to a high concentration of salicylate. Whole-cell patch clamp recordings showed that 1-5 mmol/L salicylate did not affect the exocytosis of IHCs, indicating that IHCs are not involved in tinnitus generation by enhancing their neuronal input. Instead, salicylate induced a larger peak amplitude, a more negative half-activation voltage, and a steeper slope factor of Ca2+ current. Using noise analysis of Ca2+ tail currents and qRT-PCR, we further found that salicylate increased the number of Ca2+ channels along with CaV1.3 expression. All these changes could act synergistically to enhance the Ca2+ influx into IHCs. Inhibition of intracellular Ca2+ overload significantly attenuated IHC death after 10 mmol/L salicylate treatment. These results implicate a cellular mechanism for tinnitus generation in the peripheral auditory system.

Effect of Ginkgo Biloba Extract on N-Methyl-D-Aspartic Acid Receptor Subunit 2B Expression in a Salicylate-Induced Ototoxicity Model

OBJECTIVES.: Sodium salicylate (SS) is well known for its ototoxic properties that induce functional and morphological changes in the cochlea and brain. Ginkgo biloba extract (GBE) has been widely used for treatment of various neurodegenerative diseases; however, its effects on salicylate-induced ototoxicity remain unclear. Herein, we examined the effects of EGb 761 (EGb), a standard form of GBE, on the plasticity of the N-methyl-D-aspartate receptor subunit 2B (GluN2B) in the inferior colliculus (IC) following SS administration. METHODS.: Seven-week-old Sprague Dawley rats (n=24) were randomly allocated to control, SS, EGb, and EGb+SS groups. The SS group received a single intraperitoneal SS injection (350 mg/kg), the EGb group received EGb orally for 5 consecutive days (40 mg/kg), and the EGb+SS group received EGb for 5 consecutive days, followed by an SS injection. The auditory brainstem responses (ABRs) were assessed at baseline and 2 hours after SS administration. GluN2B expression was examined by Western blot and immunohistochemistry. RESULTS.: There were no significant differences in ABR threshold shifts among the groups. The expression of the GluN2B protein normalized by which of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was significantly lower in the EGb+SS group, as compared to the SS group (P=0.012). Weak and diffused GluN2B immunoreactivity was detected in the IC neural cells of the EGb+SS group, while those of the SS group exhibited strong and diffused GluN2B positivity. CONCLUSION.: EGb may play a role in regulating the GluN2B expression in the IC of salicylate-induced ototoxicity model.

A study on toxic effects of sodium salicylate on rat cochlear spiral ganglion neurons: dopamine receptors mediate expressions of NMDA and GABAreceptors / 生理学报

The aim of the present study was to observe whether dopamine receptor (DR) was involved in the effects of sodium salicylate (SS) on the expressions of N-methyl-D-aspartic acid (NMDA) and γ-aminobutyric acid (GABA) receptors in rat cochlear spiral ganglion neurons (SGNs). Forty-eight hours after primary culture of rat SGNs, immunofluorescence technique was applied to detect expressions of DR1 and DR2, the two subtypes of dopamine receptors. Western blot was performed to assess NMDA receptor NR1 subunit and GABAreceptor subunit α2 (GABRα2) protein expressions in the SGNs after the treatments of SS alone or in combination with DR antagonists. The results demonstrated that: (1) The DR1 and DR2 were expressed in the bodies and axons of the SGN; (2) After the treatment with SS, the surface protein expressions of GABRα2 and NR1 were decreased by 44.69% and 21.57%, respectively, while the total protein expressions showed no significant changes; (3) Neither SS + SCH23390 (DR1 antagonist) group nor SS + Eticlopride (DR2 antagonist) group showed significant differences in GABRα2 and NR1 surface protein expressions compared with the control group. These results suggest that SS regulates the surface GABAand NMDA receptors trafficking on SGN, and the mechanism may involve DR mediation.

The effect of sodium salicylate on the expression of GABAa receptor subunits in cochlear spiral ganglion neurons / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate mRNA expression of GABAa receptor(GABAaR) subunits in the rat cochlear spiral ganglion neurons (SGN) and explore the effect of sodium salicylate (SS) on the expression of GABAaR subunits.@*METHOD@#The realtime fluorescent quantitative PCR (FQ-PCR) was used to detect mRNA expression of twelve GABAaR subunits in the newborn rat SGN and then investigate mRNA expression of GABAaR subunits after treatment with 5 mmol/L SS for 15 min, 30 min, 1 h, 3 h and 6 h in the primary culture SGN.@*RESULT@#(1) GABAaR subunits of α1-6, β1-3, and γ1-3 were detected in the SGN, and the expression of GABAaR subunits was lower than those in the cerebral cortex. In the subunit α family of GABAaR, the expression rank was α2>α3/α5>α4>a1>α6, and the expression of α3 and α5 had no difference (P>0. 05). In the subunit β family, the expression rank was β3>β2>β1. In the subunit γ family, the expression rank was γ1>γ2>γ3. (2) The expression of all subunits of GABAa receptor was obviously fluctuated excepting subunit α5 after treatment with SS. At 15 min post-SS, α1, α2 , β1 and γ1-3 were upregulated, and α3 was downregulated; At 30 min post-SS, α3, β1 and β3 were upregulated, and γ1 was downregulated; At 1 h post-SS, β2 was upregulated and γ3 was downregulated; At 3 h post-SS, β1 and β2 were upregulated, and α3 and γ2 were downregulated; At 6 h post-SS, αl, α3 ,β2, β3 and γ1 were upregulated, and α2, α4 and β1 were downregulated.@*CONCLUSION@#The mRNA of GABAaR was expressed in the rat SGN, and the expression of GABAaR subunits was lower in SGN than the cerebral cortex. SS could alter the GABAaR expression quantity in rat SGN; Most of the subunits expression were elevated obviously in the early post SS (15 min), followed by a slight fluctuation.

A Case of Bilateral Sudden Hearing Loss and Tinnitus after Salicylate Intoxication

Salicylate, the active ingredient of aspirin can cause sensorineural hearing loss and tinnitus when plasma concentrations reach a critical level. The ototoxic mechanisms of salicylate remain unclear but hearing and tinnitus usually recovers a few days after intoxication. There have been few reports of salicylate-induced ototoxicity in Korea, and the majority is caused by a low dose of aspirin. Herein, we report a case of sudden hearing loss and tinnitus after acute salicylate intoxication and review recent updates on salicylate ototoxicity.

Effect of sodium para-aminosalicylic on concentrations of amino acid neurotransmitters in basal ganglia of manganese-exposed rats / 中华预防医学杂志

<p><b>OBJECTIVE</b>To probe the effect of sodium para-aminosalicylate (PAS-Na) on concentration of amino acid neurotransmitters including glutamate (Glu), glutamine (Gln), glycine (Gly) and gamma-aminobutyric acid (GABA) in basal ganglia of subacute manganese (Mn)-exposed rats.</p><p><b>METHODS</b>Forty Sprague-Dawley male rats were randomly divided into the control, Mn-exposed, low dose PAS-Na (L-PAS) and high dose PAS-Na (H-PAS) groups. Rats in experiment groups received daily intraperitoneally injections of manganese chloride (MnCl₂ · 4H₂O, 15 mg/kg), while rats in control group received daily intraperitoneally injections of normal saline (NS), all at 5 days/week for 4 weeks. Then the rats in PAS groups followed by a daily subcutaneously dose of PAS-Na (100 and 200 mg/kg as the L-PAS and H-PAS groups, respectively) for another 3 and 6 weeks; while the rats in Mn-exposed and control group received NS. The concentrations of Glu, Gln, Gly and GABA in basal ganglia of rat was detected by the high performance liquid chromatography fluorescence detection technique.</p><p><b>RESULTS</b>After treating with PAS-Na for 3 weeks, the concentration of Gly in the Mn-exposed rats decreased to (0.165 ± 0.022) µmol/L (control = (0.271 ± 0.074) µmol/L, Mn vs control, t = 4.65, P < 0.05). After the further 6-week therapy with PAS-Na, the concentrations of Glu, Gln, Gly in the Mn-exposed rats were lower than those of the control rats ((0.942 ± 0.121), (0.377 ± 0.070), (0.142 ± 0.048), (1.590 ± 0.302), (0.563 ± 0.040), (0.247 ± 0.084) µmol/L; t = 7.72, 5.85, 4.30, P < 0.05); and also lower than in L-PAS and H-PAS groups, whose concentrations were separately (1.268 ± 0.124), (1.465 ± 0.196), (0.497 ± 0.050), (0.514 ± 0.103), (0.219 ± 0.034) µmol/L (L-PAS Glu and Gln vs Mn, t = 3.87, 3.77, P < 0.05; H-PAS Glu, Gln and Gly vs Mn, t = 6.78, 4.70, 3.42, P < 0.05).</p><p><b>CONCLUSION</b>The toxic effect of manganese on Glu, Gln and Gly in basal ganglia of Mn-exposed rats is obvious, especially appears earlier on Gly. The toxic effect still continues to develop when relieved from the exposure. PAS-Na may play an antagonism role in toxic effect of manganese on concentration of Glu, Gln and Gly in basal ganglia of Mn-exposed rats.</p>

A Case of Bilateral Sensorineural Hearing Loss after Salicylate Intoxication / 대한이비인후과학회지

Salicylates, such as aspirin, are considered the most commonly used medicine in Korea for its anti-inflammatory, anti-pyretic, and analgesic properties. In spite of its wide range of benefits, aspirin produces unwanted adverse effects such as mucosal bleeding in the gastrointestinal tract, renal and hepatic dysfunction, Reye's syndrome in children, and hypersensitivity reactions, etc. Aspirin can also induce ototoxicity, such as reversible hearing loss and tinnitus. The pattern of hearing loss is typically mild to moderate and bilaterally flat in the absence of preexisting hearing loss. Hearing usually recovers in 72 hours after medication. However, it's rare that salicylate-induced ototoxicity are encountered. So we present this case of bilateral hearing loss that occurred after salicylate intoxication with a review of relevant literature.

Effect of ketorolac and diclofenac on the impairment of endothelium-dependent relaxation induced by reactive oxygen species in rabbit abdominal aorta / 대한마취과학회지

BACKGROUND: Reactive oxygen species (ROS) induce lipid peroxidation and tissue damage in endothelium. We studied the influences of ketorolac and diclofenac on ROS effects using the endothelium of rabbit abdominal aorta. METHODS: Isolated rabbit aortic rings were suspended in an organ bath filled with Krebs-Henseleit (K-H) solution bubbled with 5% CO2 and 95% O2 at 37.5degrees C. After being stimulated to contract with phenylephrine (PE, 10(-6) M), changes in arterial tension were recorded following the cumulative administration of acetylcholine (ACh, 3 x 10(-8) to 10(-6) M). The percentages of ACh-induced relaxation of aortic rings before and after exposure to ROS, generated by electrolysis of K-H solution, were used as the control and experimental values, respectively. The aortic rings were pretreated with ketorolac or diclofenac at the same concentrations (10(-5) M to 3 x 10(-4) M), and the effects of these agents were compared with the effects of ROS scavengers: catalase, mannitol, sodium salicylate and deferoxamine and the catalase inhibitor, 3-amino-1,2,4-triazole (3AT). RESULTS: Both ketorolac and diclofenac maintained endothlium-dependent relaxation induced by ACh in a dose-related manner inspite of ROS attack (P < 0.05 vs. control value). The 3AT pretreated ketorolac (3 x 10(-3) M) group was decreased more significantly than un-pretreated ketorolac (P < 0.05). CONCLUSIONS: These findings suggest that ketorlac and diclofenac preserve the endothelium-dependent vasorelaxation against the attack of ROS, in a concentration-related manner. One of the endothelial protection mechanisms of ketorolac may be hydrogen peroxide scavenging.

Antioxidant effect of lidocaine and procaine on reactive oxygen species-induced endothelial dysfunction in the rabbit abdominal aorta / 대한마취과학회지

BACKGROUND: Reactive oxygen species (ROS) induce lipid peroxidation and tissue damage in the endothelium. We tested the antioxidant effect of lidocaine and procaine on ROS-induced endothelial damage in the rabbit aorta. METHODS: Aortic rings isolated from rabbits were suspended in an organ bath filled with Krebs-Henseleit (K-H) solution bubbled with 5% CO2 and 95% O2 at 37.5degrees C. After precontraction with phenylephrine (PE, 10(-6) M), changes in tension were recorded following a cumulative administration of acetylcholine (ACh 3 x 10(-8) to 10(-6) M). Differences were measured as percentages of ACh-induced relaxation of aortic rings before and after exposure to ROS as generated by electrolysis of the K-H solution. The aortic rings were pretreated with lidocaine or procaine (10(-5) M to 3 x 10(-3) M) to compare their effects, as well as ROS scavengers, catalase, mannitol, sodium salicylate, and deferoxamine, and a catalase inhibitor, 3-amino-1,2,4-triazole (3AT). RESULTS: Lidocaine and procaine dose-dependently maintained endothelium-dependent relaxation induced by ACh despite ROS activity (P < 0.05 vs control value). The 3AT pretreated procaine (3 x 10(-3) M) group decreased more significantly than the un-pretreated procaine group (P < 0.05). CONCLUSIONS: These findings suggest that lidocaine and procaine dose-dependently preserve endothelium-dependent vasorelaxation against ROS attack, potentially via hydrogen peroxide scavenging.

Inflammation and Insulin Resistance: An Old Story with New Ideas / 당뇨병

Years before insulin was discovered, anti-inflammatory sodium salicylate was used to treat diabetes in 1901. Intriguingly for many years that followed, diabetes was viewed as a disorder of glucose metabolism, and then it was described as a disease of dysregulated lipid metabolism. The diabetes research focused on the causal relationship between obesity and insulin resistance, a major characteristic of type 2 diabetes. It is only within the past 20 years when the notion of inflammation as a cause of insulin resistance began to surface. In obesity, inflammation develops when macrophages infiltrate adipose tissue and stimulate adipocyte secretion of inflammatory cytokines, that in turn affect energy balance, glucose and lipid metabolism, leading to insulin resistance. This report reviews recent discoveries of stress kinase signaling involving molecular scaffolds and endoplasmic reticulum chaperones that regulate energy balance and glucose homeostasis. As we advance from a conceptual understanding to molecular discoveries, a century-old story of inflammation and insulin resistance is re-born with new ideas.

Acute Sensorineural Hearing Loss and Tinnitus with Aspirin: A Case Report / 대한평형의학회지

Salicylate (aspirin) causes ototoxic side effects in some patients, such as bilateral mild to moderate sensorineural hearing loss and tinnitus although its ototoxic mechanisms still remain largely unclear. We report about one case with acute sensorineural hearing loss anf tinnitus after one week of low dose aspirin therapy. Audiogram revealed a mild sensorineural hearing loss at 35.0 dBHL in the right ear. Tinnitus became louder more and more, and sounded like a unilateral or bilateral high-pitch noise with each recurrence persisting for five minutes or longer. Audiologic problem of this case resolve within two or three days after the aspirin is discontinued. Generally, ototoxicity of salicylate manifests as bilateral, flat to high-frequency sensorineural hearing loss, and the risk of ototoxicity increases with higher doses and prolonged treatment course. But our case tend to suggest that symptoms of ototoxicity also might be occur in patients in even low dose salicylate with variable audiologic finding case tend to suggest that symptoms of ototoxicity also can occur in patients in even low dose salicylate use with variable audiologic finding. Further work on the relationships between plasma salicylate concentrations and ototoxicity is required.

Performance of Starch obtained from Dioscorea dumetorium as Disintegrant in Sodium Salicylate Tablets

Starch obtained from Dioscorea dumetorium was employed as a disintegrant in Sodium Salicylate based tablets at concentrations of 5 -15w/w. Properties of the starch evaluated include: bulk and tapped densities; water uptake by capillarity; Hausner's quotient and percent compressibility. Compound tablets were evaluated for hardness; friability; disintegration time and dissolution rate. Batches of tablets containing equivalent concentrations of AC-di-sol or maize starch were employed as standards. Results obtained indicate that Dioscorea dumetorium starch performed as much better as a disintegrant in sodium salicylate tablets as maize starch but less than Ac-di-sol

Effect of sodium salicylate on the auditory brain stem response threshold and expression of glutamic acid decarboxylase in spiral ganglion of juvenile and adult guinea pigs / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the differences of regulation of sodium salicylate on the auditory brain stem response (ABR) threshold and expression of glutamic acid decarboxylase (GAD) protein in spiral ganglion of juvenile and adult guinea pigs.</p><p><b>METHODS</b>Fourty juvenile guinea pigs which were born just four days and fourty adult guinea pigs which were born thirty days were selected. They were divided four groups (group A; group B; group C; group D). ABR threshold was detected before administration, after administration for 15 days and after administration stopped for 30 days. The protein expression of GAD were measured after administration for 15 days and after administration stopped for 30 days by the method of immunohistochemistry.</p><p><b>RESULTS</b>ABR threshold of juvenile sodium salicylate groups (group C) was increased remarkably than that of before administration and the control after administration for 15 days (P < 0.001). ABR threshold of group C was returned to the level of that of before administration and after administration stopped for 30 days. ABR threshold of adult sodium salicylate groups (group D) was increased remarkably than that of before administration and the control after administration for 15 days (P < 0.001). ABR threshold of group D was kept the high level after administration stopped for 30 days. The protein expression of GAD of sodium salicylate groups (group C and D) was decreased than that of the control after administration for 15 days. The protein expression of group C was more visible regression than that of group D (t = 4.7, P < 0.001). The protein expression of group C was returned the level of before administration after administration stopped for 30 days, but the protein expression of group D was kept the high level.</p><p><b>CONCLUSIONS</b>The results suggest that sodium salicylate can regulate differently ABR threshold and expression of GAD protein in spiral ganglion of juvenile and adult guinea pigs. The effects of sodium salicylate on ABR threshold and expression of GAD protein in spiral ganglion of juvenile pigs are more noticeable than that of adult guinea pigs, but these changes are easier to return the normal than that of adult guinea pigs.</p>

Estudo comparativo da regulação da apoptose mediada por agentes pró-E anti inflamatórios em granulócitos humanos / Comparative study of the regulation of apoptosis mediated by agents pro-and anti inflammatory in human granulocytes

A morte celular programada, reconhecida através do quadro morfológico de apoptose, é um mecanismo central de regulação de populações celulares em animais multicelulares, que, no sistema imunológico, permite a resolução dos processos inflamatórios, o controle fino da expansão clonal e a prevenção da auto-imunidade. O presente estudo se ocupa dos mecanismos pelos quais a apoptose é modulada por agentes externos. em dois diferentes tipos de granulócitos humanos, neutrófilos e eosinófilos, que compartilham uma origem comum na medula óssea, assim como muitas características morfológicas e funcionais, mas desempenham papéis diferentes na defesa do hospedeiro... A indometacina revelou-se uma forte indutora de apoptose om neutrófilos humanos, na ausência de outros fatores exógenos, um efeito igualmente ainda não descrito na literatura. Estas observações indicam que: a) embora neutrófilos humanos possam apresentar respostas ao ATRA e à dexametasona semelhantes às observadas durante o desenvolvimento de eosinófilos murinos, mas distintas das de eosinófilos humanos maduros, esta semelhança não se estende aos efeitos de outros agentes; b) as vias de sinalização iniciadas pelo ATRA e pela dexametasona em neutrófilos humanos maduros apresentam forte interação (cross-talk), cujo mecanismo precisa ser estabelecido; c) a indometacina pode apresentar, neste modelo, ações prá-apoptóticas distintas para outros agentes anti-inflamatórios não esteroidais, como a aspirina e o salicilato de sódio.

Inhibition of salicylate on voltage-gated sodium channels in rat inferior colliculus neurons / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the mechanism of the tinnitus inducer, sodium salicylate, on voltage-gated sodium channels.@*METHOD@#The effects of salicylate on voltage-gated sodium channels in freshly dissociated inferior colliculus neurons of rats were studied, using the whole-cell voltage clamp method.@*RESULT@#Salicylate blocked sodium current (INa) in concentration-dependent manner (0.1-10 mmol/L). The IC50 value for the blocking action of salicylate was 1.43 mmol/L. Salicylate did not affect the conductance-voltage curve and the steady-state activation curve of INa. The steady-state INa inactivation curve of INa was shifted by about 9 mV in the hyperpolarizing direction. In addition, salicylate delayed the sodium channel recovery from INa inactivation by increasing the slow time constant.@*CONCLUSION@#Our results suggest that salicylate causes a concentration-dependent blockade of INa and shifts the INa inactivation curve to more hyperpolarized potentials, which could be related to the mechanism of salicylate-induced tinnitus.

Effects of sodium salicylate on the expressions of gamma-aminobutyricacid and glutamate and auditory response properties of the inferior colliculus neurons / 生理学报

The effects of sodium salicylate (NaSA) on the expressions of gamma-aminobutyricacid (GABA) and glutamate (Glu), and auditory response properties of the inferior colliculus neurons in mice were studied. Thirty-six Kunming mice were divided into three groups: control group (saline injection); NaSA group (NaSA 450 mg/kg, i.p., each day for 15 d); NaSA + lidocaine group (NaSA 450 mg/kg + lidocaine 10 mg/kg, i.p., each day for 15 d). The expressions of GABA and Glu were examined with immunohistochemical method. The intensity-rate function, intensity-latency function and frequency-tuning curve were determined with extracellular electrophysiological recording. Results are as follows: (1) The expression of GABA in the NaSA and NaSA + lidocaine groups decreased remarkably compared with that in the control group; there was no noticeable difference between the NaSA and NaSA + lidocaine groups. The expression of Glu in the NaSA group increased significantly compared with that in the control and NaSA + lidocaine groups. No difference in the expression of Glu was found between the control and NaSA + lidocaine groups. (2) In NaSA group, the intensity-rate function displayed a non-monotonic pattern, rising at low intensity and descending at high intensity; the tip of frequency-tuning curves became broad after administration of NaSA. (3) The changes in intensity-rate function and intensity-latency function were not evident and the tips of the frequency-tuning curves sharpened in the NaSA + lidocaine group. These results suggest that administration of NaSA increases the expression of Glu-positive neurons and reduces that of GABA-positive neurons in the inferior colliculus. NaSA changes the auditory response properties of the inferior colliculus and lidocaine can reverse these changes.

The effects of sodium salicylate on the expression of GABAalpha, NR1 and hearing response properties of inferior colliculus neurons in mice / 中国应用生理学杂志

<p><b>AIM</b>To study the effects of sodium salicylate on the expression of GABAalpha NR1 and hearing response properties of inferior colliculus neurons in mice.</p><p><b>METHODS</b>Thirty-six kunming mice were divided into three groups (A, B, C,). The expression of GABAalpha NR1 were measured by using RT-PCR. The intensity-rates functions, intensity-latency functions and frequency-turning curves were recorded by extracellular electrophysiological recording techniques.</p><p><b>RESULTS</b>(1) The expression of GABAalpha mRNA of B group was decreased remarkably than the control group (A group, P < 0.05), there weren't noticeable differences between A group and C group (P > 0.05). The expression of NR1 mRNA of B group was increased remarkably than the control group (A group, P < 0.01), there were noticeable differences between A group and C group P < 0.05). (2) The intensity-rates functions, intensity-latency functions were monotonic while the frequency-turning curves were more broad when sodium salicylate was given. (3) The intensity-rates functions, intensity-latency functions were non-monotonic while the frequency-turning curves were sharpened after lidocaine was given.</p><p><b>CONCLUSIONS</b>(1) The results suggested that administration of sodium salicylate decreased the expression of GABAalpha while increased the expression of NR1mRNA. (2) The intensity-rates functions, intensity-latency functions were monotonic, the frequency-turning curves were more broad when salicylate was given and the changes above could be reversed by given lidocaine.</p>

Differentially expressed gene profiles of cochlea in rats induced by acute and chronic sodium salicylate injection / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the mechanism of electrophysiologic changes caused by different type of sodium salicylate injection.</p><p><b>METHODS</b>Decapitated three group rats ( acute injected, chronic injected and normal rats ) separately, dissected the temporal bones to collect cochlea, and the otic capsules were removed. Then the cochlear materials from each groups were pooled and homogenized respectively, extracted the total RNA, obtained cDNA from purified total RNA by reversed transcription, cDNA were transcripted to cRNA probes in vitro. Hybridized the cRNA probes with tester chip to evaluate the quality of probes, if good, hybridized the probes with real chip. Obtained three gene expression profiles of different groups of cochlea Analyzed the differentially expressed genes among three groups by SOM. Analogized the SOM result to electrophysiologic changes. Then analyzed the genes in clusters of analog results by Gene Ontology. Then the genes in clusters of analog results were analyzed by Gene Ontology. Hsp27 was chosen to validate the result of gene chip using real time quantitative reverse transcription PCR ( RTQ RT-PCR).</p><p><b>RESULTS</b>The probes was good, and the chip hybridization results was credible. We obtained 6 clusters genes by SOM analysis, in which we choose cluster 3 and cluster 4 as candidate cluster. There were 46 genes in cluster 3 and 30 genes in cluster 4 employing GO analysis, which involved in cell communication, cell motility, metabolism, immune response and nerve ensheathment, et al. The result of RTQ RT-PCR showed high concordance with that of gene chip.</p><p><b>CONCLUSION</b>It's a new method to study the mechanism of electrophysiologic changes caused by sodium salicylate by gene chip and SOM analysis.</p>

enhancing effect of sodium glycocholate and sodium salicylate on rats gastro-intestinal permeability to insulin

There have been numerous efforts to formulate insulin into an oral dosage form. The major problems involved with the oral administration of insulin are acidic and enzymatic decomposition by the gastric medium, and poor absorption in the small intestine due to its macromolecular structure. This study attempted to test the enhancing ability of two absorption enhancers, sodium glycocholate [Na-GC] and sodium salicylate [Na-Sal], in different parts of rat's gastrointestinal tract. The amount of insulin in each formulation was 0.6 iu/kg body weight. The concentration of enhancers [Na-Sal or Na-GC] in each formulation was 10 micro g/ml. Formulations made of insulin and enhancers were prepared and injected directly to stomach, duodenum, jejunum and ileum of anesthetized rats through an abdominal incision. Blood samples were taken at 45 and 60 min intervals. The glucose concentration was determined by the o-toluidine method. Injections [IP] of insulin and normal saline were positive and negative controls, respectively. The blood glucose concentrations showed a significant decrease [p<0.05] due to the injection of insulin into duodenum, while the effect noted in jejunum was insignificant [p>0.05]. Also, there was no anti-hyperglycemic effect accompanied by formulations administered into the stomach and ileum. It could be concluded that insulin, if formulated in a protected form to prevent acidic and enzymatic decomposition, in combination with such enhancers may overcome hyperglycemia due to insulin deficiency

Mechanisms of muscovite on gastric mucosal protective effect / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the mechanisms of muscovite gastric mucosal protective effect.</p><p><b>METHOD</b>Rat model of chronic gastritis were used. After gastric mucosal injury was induced, the rats were divided into 6 groups and were treated with different drugs. 2 weeks later, the tissue and blood samples were obtained and measured.</p><p><b>RESULT</b>The general conditions, the observations under macroscopy, microscope and electron microscope of the middle and high dose of muscovite groups resembled those of the normal group. Their PH levels were higher than those of the model group, and the rates of intestinal metaplasia were lower, but the PGE2 level of the middle dose of muscovite group was the highest.</p><p><b>CONCLUSION</b>Muscovite can be adsorbed on the surface of the gastric mucosa. It has gastric mucosal protective effect by improving excretion of mucus and synthesis of PGE2 in gastric mucosa, restraining gastric acid, reversing of intestinal metaplasia and decreasing inflammation cells.</p>