Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes.

Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of γ-glutamylcysteine synthetase (γ-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine in vivo. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH

Endoscopic Thyroidectomy via an Axillo-Breast Approach without Gas Insufflation for Benign Thyroid Nodules and Micropapillary Carcinomas: Preliminary Results

PURPOSE: To examine the feasibility of endoscopic thyroidectomy (ET) via an axillo- breast approach without gas insufflation for large thyroid tumors and micropapillary carcinomas. MATERIALS AND METHODS: The patients in the benign group were separated into groups 1 (n=95, <4 cm in tumor diameter) and 2 (n=37, ≥4 cm in tumor diameter). Also, 57 patients in the micropapillary carcinoma group underwent an endoscopic hemithyroidectomy (HT) (group 3) and were compared with 60 patients who received conventional open HT (group 4). Postoperative functional outcome, local complications, surgical outcomes, and pathological outcomes were compared between the groups. RESULTS: In the benign group, there was no significant difference in mean operating time, hospital stay, or overall perioperative complications between the two groups. In the micropapillary carcinoma group, mean operating time and hospital stay in group 3 were significantly longer than in group 4 (p=0.015 and p≤0.001). The overall perioperative complications did not differ significantly between the groups. The postoperative cosmetic result was better in groups 1-3 (endo group) than in group 4 (open group). CONCLUSION: ET via a gasless axillo-breast approach seems to be a safe procedure even for benign thyroid lesions ≥4 cm and micropapillary carcinomas. Although it has the advantage of better cosmetic results over open thyroidectomy, there is room for improvement in terms of lessening its invasiveness and shortening the operative time.ope

Rubi Fructus ( Rubus coreanus

Rubi Fructus (RF) is known to exert several pharmacological effects including antitumor, antioxidant, and anti-inflammatory activities. However, its antiobesity effect has not been reported yet. This study was focused on the antidifferentiation effect of RF extract on 3T3-L1 preadipocytes. When 3T3-L1 preadipocytes were differentiating into adipocytes, 10–100 μg/mL of RF was added. Next, the lipid contents were quantified by Oil Red O staining. RF significantly reduced lipid accumulation and downregulated the expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT0-enhancer-binding proteins α (C/EBPα), adipocyte fatty acid-binding protein 2 (aP2), resistin, and adiponectin in ways that were concentration dependent. Moreover, RF markedly upregulated liver kinase B1 and AMP-activated protein kinase (AMPK). Interestingly, pretreatment with AMPKα siRNA and RF downregulated the expression of PPARγ and C/EBPα protein as well as the adipocyte differentiation. Our study shows that RF is capable of inhibiting the differentiation of 3T3-L1 adipocytes through the modulation of PPARγ, C/EBPα, and AMPK, suggesting that it has a potential for therapeutic application in the treatment or prevention of obesity

Introduction of Transmembrane Inner Ear (tmie) Gene Can Recover the Hearing Impairment and Abnormal Behavior in the Circling Mouse

The spontaneous mutant circling mouse (cir/cir) shows a circling behavior and hearing loss. We produced transgenic mice overexpressing the causative gene, transmembrane inner ear (tmie), for the phenotypic rescue of the circling mouse. Through the continuous breeding with circling mice, the cir/cir homozygous mice carrying the transgene (cir/cir-tg) were produced. The rescued cir/cir -tg mice were able to swim in the water with proper orientation and did not show any circling behavior like wild type mice. Western blot and immunohistochemical analysis exhibited that the transgenic tmie was expressed in the inner ear. Inner and outer hair cells were recovered in the cochlea and spiral ganglion neurons were also recovered in the rescued mice. Auditory brainstem response (ABR) test demonstrated that the cir/cir -tg mice are able to respond to sound. This study demonstrates that tmie transgene can recover the hearing impairment and abnormal behavior in the circling mouse

Crotonis Fructus

Introduction. Crotonis fructus (CF) is the mature fruit of Croton tiglium L. and has been used for the treatment of gastrointestinal disturbance in Asia. It is well known that the main component of CF is croton oil (CO). The present study is to investigate the effects of CF extracts (CFE) and CO on lipolysis in OP9 adipocytes. Methods. Glycerol release to the culture supernatants was used as a marker of adipocyte lipolysis. Results. Treatment with various concentrations of CFE and CO stimulates glycerol release in a dose-dependent manner. The increase in glycerol release by CFE is more potent than isoproterenol, which is a β-adrenergic agonist as a positive control in our system. The increased lipolysis by CFE and CO was accompanied by an increase of phosphorylated hormone sensitive lipase (pHSL) but not nonphosphorylated HSL protein and mRNA. Pretreatment with H89, which is a protein kinase A inhibitor, significantly abolished the CFE- and CO-induced glycerol release in OP9 adipocytes. These results suggest that CFE and CO may be a candidate for the development of a lipolysis-stimulating agent in adipocytes

Dry mouth among the elderly in Korea: a survey of prevalence, severity, and associated factors

Objectives. The aim of this study was to investigate the prevalence and severity of dry mouth among elderly population of Korea and to evaluate associate factors and their impact. Study Design. Telephone interviews were conducted on a stratified random sample of 1,012 subjects aged >= 55 years. Prevalence of dry mouth symptoms, severity of overall oral dryness, and associated factors were assessed using a structured questionnaire. Results. Among the subjects, 70.1% reported to have at least one dry mouth-related symptom and 25.8% were classified with considerable dry mouth. Overall oral dryness severity of each of these groups was 4.30 +/- 2.67 and 6.09 +/- 2.25, respectively, on a 0-10 scale. Odds ratio of dry mouth increased in women, in smokers, and with increased age and number of medications taken. Women and number of medications taken were significantly associated with overall oral dryness severity. Conclusion. A major portion of the Korean elderly reported various dry mouth symptoms, and a wide range of severity and discomfort was caused by these symptoms. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:475-483)

Dry mouth among the elderly in Korea: A survey of prevalence, severity, and associated factors

Objectives: The aim of this study was to investigate the prevalence and severity of dry mouth among elderly population of Korea and to evaluate associate factors and their impact. Study Design: Telephone interviews were conducted on a stratified random sample of 1,012 subjects aged <55 years. Prevalence of dry mouth symptoms, severity of overall oral dryness, and associated factors were assessed using a structured questionnaire. Results: Among the subjects, 70.1% reported to have at least one dry mouthrelated symptom and 25.8% were classified with considerable dry mouth. Overall oral dryness severity of each of these groups was 4.30 ± 2.67 and 6.09 ± 2.25, respectively, on a 0-10 scale. Odds ratio of dry mouth increased in women, in smokers, and with increased age and number of medications taken. Women and number of medications taken were significantly associated with overall oral dryness severity. Conclusion: A major portion of the Korean elderly reported various dry mouth symptoms, and a wide range of severity and discomfort was caused by these symptoms.Supported by a grant of the Korean Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (01-PJ5-PG1-01CH12-0002)

(-)-Epigallocatechin-3-gallate protects against NO-induced ototoxicity through the regulation of caspase- 1, caspase-3, and NF-κB activation.

Excessive nitric oxide (NO) production is toxic to the cochlea and induces hearing loss. However, the mechanism through which NO induces ototoxicity has not been completely understood. The aim of this study was to gain further insight into the mechanism mediating NO-induced toxicity in auditory HEI-OC1 cells and in ex vivo analysis. We also elucidated whether and how epigallocatechin-3-gallate (EGCG), the main component of green tea polyphenols, regulates NO-induced auditory cell damage. To investigate NO-mediated ototoxicity, S-nitroso-N-acetylpenicillamine (SNAP) was used as an NO donor. SNAP was cytotoxic, generating reactive oxygen species, releasing cytochrome c, and activating caspase-3 in auditory cells. NO-induced ototoxicity also mediated the nuclear factor (NF)-κB/caspase-1 pathway. Furthermore, SNAP destroyed the orderly arrangement of the 3 outer rows of hair cells in the basal, middle, and apical turns of the organ of Corti from the cochlea of Sprague-Dawley rats at postnatal day 2. However, EGCG counteracted this ototoxicity by suppressing the activation of caspase-3/NF-κB and preventing the destruction of hair cell arrays in the organ of Corti. These findings may lead to the development of a model for pharmacological mechanism of EGCG and potential therapies against ototoxicity