No abstract available.
Perilymph* ; Sodium Salicylate* ; Sodium*

This study was designed to investigate the mole- cular mechanism of chemokine induction by lipopoly-saccharide(LPS) of E. coli. Chemokine gene expression was evaluated by the reverse transcriptase-polymerase chain reaction(RT-PCR) assay using RNAs isolated either from kidneys of LPS-injected inice or from the mesangial cells stimulated with LPS, IFN-r or TNF-a. LPS was shown to induce interferon gamma(IFN- 7 ) inducible protein 10 (IP-10) and monokine induced by interferon gamma (MIG) in kidney. IP-10 gene expression was induced by LPS and IFN-r, but MIG gene expression was induced by IFN-r in mesangial cell. Chemokines induced by LPS increased splenocyte migration. Sodium salicylate, wortmanin and piperazine blocked LPS mediated chemokine induction suggesting the activation of nuclear factor-a B pathway. It is concluded from this study that mesangial cells are the target of LPS in the renal failure resulting from the systemic infections. LPS induces chemokines directly and/or indirectly in the mesan- gial cells, and these chemokines may associated with renal inflammation.
Chemokines ; Gene Expression* ; Inflammation ; Interferons ; Kidney ; Mesangial Cells* ; Renal Insufficiency ; RNA ; Sodium Salicylate

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.
Aspirin ; Hearing ; Hearing Loss ; Hearing Loss, Sensorineural ; Hearing Loss, Sudden ; Korea ; Plasma ; Sodium Salicylate ; Tinnitus

BACKGROUND AND OBJECTIVES: Salicylates are well-known for producing reversible hearing loss and tinnitus. However, the site and mechanism of salicylate ototoxicity remain unresolved. Recent experiments suggest that reversible biochemical and/or metabolic changes in the cochlea seem to play an important role in salicylate ototoxicity. The purpose of this study was to investigate the site of lesion in salicylate ototoxicity by audiometric study. MATERIALS AND METHOD: ABRs and DPOAEs were observed after intraperitoneal injection of 500 mg/kg of sodium salicylate on 24 ears of guinea pigs. RESULTS: Salicylate produced a significant increase in the ABR threshold. Maximum changes were obtained in 4 hours, and recovered to the baseline in 24 hours after salicylate administration. The pattern of hearing loss shown by latency-intensity function was compatible with the cochlear type of hearing loss. The echo amplitude on DPOAEs at f2=2002, 4004 Hz was significantly decreased at 2, 4, 6, 8 hours, and returned to the baseline in 24 hours after salicylate administration. The time course of the change of DPOAEs was parallel with that of ABRs. CONCLUSION: These results reflect that the cochlear outer hair cells may be the main site of lesion in salicylate ototoxicity.
Animals ; Audiometry ; Cochlea ; Ear ; Guinea Pigs* ; Guinea* ; Hair ; Hearing Loss ; Injections, Intraperitoneal ; Salicylates ; Sodium Salicylate ; Tinnitus

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.
Aspirin ; Atrial Natriuretic Factor ; Ear ; Hearing Loss, Sensorineural ; Humans ; Noise ; Plasma ; Recurrence ; Sodium Salicylate ; Tinnitus

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 Ca_V1.3 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.
Animals ; Calcium ; Exocytosis ; Hair Cells, Auditory, Inner ; Mice ; Sodium Salicylate/pharmacology* ; Tinnitus/chemically induced*

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.
Adipocytes ; Adipose Tissue ; Cytokines ; Endoplasmic Reticulum ; Glucose ; Homeostasis ; Inflammation ; Insulin ; Insulin Resistance ; Lipid Metabolism ; Macrophages ; Obesity ; Phosphotransferases ; Sodium Salicylate

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.
Animals ; Inferior Colliculi ; cytology ; Male ; Neurons ; drug effects ; metabolism ; Patch-Clamp Techniques ; Rats ; Rats, Wistar ; Sodium Channels ; drug effects ; metabolism ; Sodium Salicylate ; pharmacology

BACKGROUND AND OBJECTIVES: Salicylate is one of the most commonly prescribed drugs although it has been recognized that salicylate induces hearing loss and tinnitus reversibly. There are many presumed mechanisms of salicylate ototoxicity including an impairment of the cochlear blood circulation. But the exact mechanism of salicylate ototoxicity is not known clearly. The purpose of this present study was to determine if the decreased blood flow after salicylate injection could be the possible cause of hearing loss. MATERIAL AND METHODS: We used the ventral approach to expose cochlea in 5 guinea pigs showing normal Preyer reflex. We simultaneously measured cochlear blood flow (CBF) by laser doppler and distortion product otoacoustic emission (DPOAE) after a high dose of salicylate injection (300 mg/kg). RESULTS: After salicylate injection, the cochlear blood flow were decreased by 29.1 % in a 3 hour period and the thresholds of DPOAE were elevated by 5 to 25 dB for 3 kHz, 4 kHz, 6 kHz, 8 kHz. CONCLUSION: Sodium salicylate caused a decrease in cochlear blood flow and an increase in the hearing threshold simultaneously after an intraperitoneal injection of sodium salicylate. These findings suggest that the ototoxic mechanism of sodium salicylate could be explained by a certain damage of out hair cell due to decrease in cochlear blood flow.
Animals ; Blood Circulation ; Cochlea ; Guinea Pigs ; Guinea* ; Hair ; Hearing ; Hearing Loss ; Injections, Intraperitoneal ; Reflex ; Regional Blood Flow ; Sodium Salicylate* ; Sodium* ; Tinnitus

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.
Acetylcholine ; Amitrole ; Antioxidants ; Aorta ; Aorta, Abdominal ; Baths ; Catalase ; Deferoxamine ; Electrolysis ; Endothelium ; Hydrogen Peroxide ; Lidocaine ; Lipid Peroxidation ; Mannitol ; Oxygen ; Phenylephrine ; Procaine ; Rabbits ; Reactive Oxygen Species ; Relaxation ; Sodium Salicylate ; Vasodilation