Butylidenephthalide blocks potassium channels and enhances basal tension in isolated guinea-pig trachea.

Butylidenephthalide (Bdph, 30~300 µM), a constituent of Ligusticum chuanxiong Hort., significantly enhanced tension in isolated guinea-pig trachea. In this study, we investigate the mechanism(s) of Bdph-induced contraction in the tissue. Isolated trachea was bathed in 5 mL of Krebs solution containing indomethacin (3 µM), and its tension changes were isometrically recorded. Cromakalim (3 µM), an ATP-dependent K+ channel opener, significantly antagonized the Bdph-induced enhancement of baseline tension. Bdph (300 µM) also significantly antagonized cromakalim-induced relaxation. Bdph (300 µM) did not significantly influence the antagonistic effects of glibenclamide (GBC, 1 µM) and tetraethylammonium (TEA, 8 mM) against the cromakalim-induced relaxation. However, Bdph (300 µM) and 4-aminopiridine (4-AP, 5 mM), a blocker of K v 1 family of K+ channels, in combination significantly rightward shifted the log concentration-relaxation curve of cromakalim. The antagonistic effect of the combination almost equals the sum of the individual effects of Bdph and 4-AP, suggesting that the antagonistic mechanism of Bdph may be similar to that of 4-AP. All calcium channel blockers influenced neither the baseline tension nor antagonistic effect of Bdph against cromakalim. In conclusion, Bdph may be similar to 4-AP, a blocker of K v 1 family of K+ channels, to enhance the baseline tension of guinea-pig trachea.

Salivary gland tumors: A 20-year review of clinical diagnostic accuracy at a single center.

Obtaining reliable pre-operative diagnosis is crucial in planning treatment for patients with salivary gland tumors. The purpose of this study was to evaluate the accuracy of pre-operative clinical diagnosis of salivary gland tumors managed at a single tertiary university hospital over a period of 20 years. A retrospective analysis of the period between 1992 and 2011 was carried out to review the cases of patients with salivary gland tumors. A total of 101 patients were enrolled and general data were described. Clinical diagnosis was compared with the final pathological diagnosis to reveal the clinical diagnostic accuracy. Of the parotid and submandibular gland tumors, 86 and 67% were benign, respectively. The clinical diagnostic accuracies for diagnosis of parotid tumors as benign or malignant were 100 and 57%, respectively. The clinical diagnostic accuracies for diagnosis of submandibular tumors as benign or malignant were 67%. Therefore, the overall clinical judgment of benign and malignant tumors in the submandibular gland is unreliable. The accuracy for a parotid tumor to be clinically interpreted as benign was 100%. While it is difficult to draw any conclusion for non-parotid gland tumors, surgical intervention should be recommended in patients with parotid tumors clinically suspected to be malignant, and all submandibular, sublingual and minor salivary gland tumors.

Adhesive strength of ethyl-2-cyanoacrylate tissue adhesive: how strong is it?

PURPOSE: We evaluated the adhesive strength of ethyl-2-cyanoacrylate and compared the findings with those of traditional monofilament synthetic sutures. We also investigated the factors that could affect the effectiveness of cyanoacrylate bonding by skin surface modifications at the adhesion site. METHODS: Using a porcine skin model, we measured the maximum load for ethyl-2-cyanoacrylate adhesive under various application conditions. RESULTS: When the application width was 5 mm, no differences were found in the maximum force load for one layer or two layers of ethyl-2-cyanoacrylate adhesive (3.3 ± 1.7 and 4.8 ± 1.5 N, p = 0.176). When the application width was extended to 10 mm, the maximum force load for one layer was 8.2 ± 0.6 N, which was significantly higher than for 5 mm (p < 0.002). The force fell to within the loads generated by 6-0 to 5-0 ETHILON™ monofilament non-absorbable synthetic sutures. Roughening of the application surface had little effect on adhesion; however, smoothing resulted in a decrease in overall adhesive strength. CONCLUSIONS: The width of the application of ethyl-2-cyanoacrylate adhesive over the skin defect was important for achieving good and stable adhesive strength. Increasing the number of layers of adhesive through repeated applications of the cyanoacrylate did not increase overall adhesive strength. Skin surface modifications other than regular cleaning should be avoided.

Impact of head and neck malignancies on risk factors and survival in systemic lupus erythematosus.

CONCLUSIONS: Systemic lupus erythematosus (SLE) is associated with an increased risk of developing a head and neck malignancy (HNM). A history of SLE did not significantly impact the survival of our study cohort after cancer developed. OBJECTIVES: To examine the risk and survival rates of HNM in patients with SLE. METHODS: This was a population-based, retrospective cohort study. We compared patients newly diagnosed with SLE between 2001 and 2008 (n = 8751) with age-matched controls (1:10) (n = 87 510). The incidence of HNMs at the end of 2009 was then determined. RESULTS: We found a 2.16-fold higher risk of HNMs in patients diagnosed with SLE compared with the risk of first malignancy in the age-matched controls (incidence rate ratio, IRR = 2.16, p < 0.05). The site with the highest incidence of HNMs in SLE patients was the oral cavity (5/11, 45.45%), followed by the nasopharynx (4/11, 36.36%). SLE displayed no synergic effect on the survival of SLE patients with an HNM compared with age-matched controls with a new HNM (p = 0.2446).

Increased risk of erectile dysfunction in patients with sudden sensorineural hearing loss: a nationwide, population-based cohort study.

OBJECTIVES: Previous studies have proposed that impaired cochlear blood perfusion and microvascular damage are important etiopathogenetic events in the development of sudden sensorineural hearing loss (SSHL). The purpose of this study was to test the hypothesis that SSHL is a risk factor for the development of erectile dysfunction (ED). STUDY DESIGN: A retrospective cohort study. SETTING: Population-based study of Taiwan National Health Insurance Research Database. METHODS: We compared male patients newly diagnosed with SSHL between January 1, 2001, and December 31, 2006 (N = 23,212), with age-matched controls (1:2) (N = 46,424). MAIN OUTCOME MEASURES: The incidence of ED at the end of 2009 was determined. RESULTS: After adjusting for potential confounding factors, we found an adjusted hazard ratio (HR) of 1.942 (95% confidence interval, 1.688-2.233, p < 0.05), showing that patients with SSHL were more likely to experience ED than the control population. When stratified by patients' age, the incidence of ED was 1.90-, 2.25-, and 1.84-fold higher for SSHL-diagnosed patients 16 to 34 years old (p = 0.0408), 35 to 49 years old (p < 0.0001), and 50 to 64 years old (p < 0.0001), respectively, than in the non-SSHL group. Hypertension and chronic renal disease comorbidities in patients with SSHL seemed to be associated with an increased risk of developing ED. CONCLUSION: SSHL may confer an independent risk of ED. This observation supports the assumption of the underlying vascular mechanism regarding the development of SSHL. Thus, clinicians managing SSHL patients should be aware of the potential of the development of ED. EVIDENCE LEVEL: 2B.

Inhibitory effects of hesperetin derivatives on guinea pig phosphodiesterases and their ratios between high- and low-affinity rolipram binding.

The phosphodiesterase (PDE)4 molecule exists as two distinct conformers, PDE4H and PDE4L , which have high and low affinities, respectively, for the selective PDE4 inhibitor, rolipram. The inhibition of PDE4H and PDE4L is associated with adverse responses, such as nausea, vomiting, and gastric hypersecretion, and with anti-inflammatory and bronchodilator effects, respectively. We determined the therapeutic (PDE4H/PDE4L) ratios of hesperetin-7-O-methylether, hesperetin-5,7,3'-O-trimethylether (HTME), hesperetin-7-O-acetate, hesperetin-7,3'-O-diacetate, hesperetin-5,7,3'-O-triacetate (HTA), hesperetin-5,7,3'-O-tripropionate, hesperetin-5,7,3'-O-tributyrate, hesperetin-5,7,3'-O-triisobutyrate, and hesperetin-5,7,3'-O-tripivatate, and compared these ratios to those of hesperetin, hesperetin-7,3'-O-dimethylether, hesperidin, and hesperidin-3'-O-methylether to identify derivatives with therapeutic ratios and to characterize the structure-activity relationships among these compounds. The activities of PDE isozymes 1 through 5 were measured using a two-step procedure using [(3)H]adenosine 3',5'-cyclic monophosphate or [(3)H]guanosine 3',5'-cyclic monophosphate as substrates. The inhibitory concentration (IC50) for 50% of PDE4 inhibition and effective concentration (EC50) for replacing 50% of [(3)H]rolipram binding on high-affinity rolipram-binding sites was taken as the PDE4L and PDE4H value, respectively. The HTME and the HTA dually inhibited PDE3 and PDE4, and displayed PDE4H/PDE4L ratios of 18.3 and 20.8, respectively, suggesting that they may be candidate drugs for treating asthma and chronic obstructive pulmonary disease (COPD) because the combined inhibition of PDE3 and PDE4 has synergistically anti-inflammatory and bronchodilator effects in COPD patients.

Increased risk of getting sudden sensorineural hearing loss in patients with chronic kidney disease: a population-based cohort study.

OBJECTIVES/HYPOTHESIS: To examine the risk of getting Sudden Sensorineural Hearing Loss (SSHL) among patients with chronic kidney disease (CKD). STUDY DESIGN: A retrospective cohort study. METHODS: Population-based representative insurance claims data were used to examine the risk of getting SSHL among patients with chronic kidney disease. Data extracted from the Taiwan National Health Insurance Research Database yielded 37,421 patients with newly diagnosed renal insufficiency and 37,421 subjects without renal insufficiency from between 2000 and 2004. RESULTS: The incidence of SSHL at the end of 2009 was determined. The incidence of SSHL was 1.57 times higher in the CKD-carrying group compared to the incidence in the non-CKD group (10.24 vs. 6.52 per 10,000 person-years), with adjusted hazard ratio (HR) of 1.46 (95% CI = 1.194-1.787) using Cox proportional hazard regressions. Age was an independent risk factor of getting SSHL, with adjusted HRs of 2.01, 3.178, and 2.285 for age ranges of 35 ≈ 49, 50 ≈ 64 and ≥ 65 compared with age range of 0 ≈ 35. Diabetes Mellitus was another independent risk factor with HR of 1.31 (95% CI = 1.003-1.711). CONCLUSIONS: Present results suggested a significant association between CKD and increased risk of getting SSHL. Comorbidity of diabetes in patients with CKD appeared to be associated with increased risk of getting SSHL, especially for the patients who are 35 years of age and older.

Cryptococcal infection of the vocal folds.

Cryptococcosis of the larynx is rare. In this manuscript we present a case of laryngeal cryptococcosis with a clear history of pigeon exposure. Cryptococcal laryngitis may present as hoarseness without other typical symptoms, even in immunocompetent individuals.

Hesperidin-3'-o-methylether is more potent than hesperidin in phosphodiesterase inhibition and suppression of ovalbumin-induced airway hyperresponsiveness.

Hesperidin is present in the traditional Chinese medicine, "Chen Pi," and recently was reported to have anti-inflammatory effects. Therefore, we were interested in comparing the effects of hesperidin and hesperidin-3'-O-methylether on phosphodiesterase inhibition and airway hyperresponsiveness (AHR) in a murine model of asthma. In the present results, hesperidin-3'-O-methylether, but not hesperidin, at 30 µmol/kg (p.o.) significantly attenuated the enhanced pause (P(enh)) value, suppressed the increases in numbers of total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, suppressed total and OVA-specific immunoglobulin (Ig)E levels in the serum and BALF, and enhanced the level of total IgG(2a) in the serum of sensitized and challenged mice, suggesting that hesperidin-3'-O-methylether is more potent than hesperidin in suppression of AHR and immunoregulation. The different potency between them may be due to their aglycons, because these two flavanone glycosides should be hydrolyzed by ß-glucosidase after oral administration. Neither influenced xylazine/ketamine-induced anesthesia, suggesting that they may have few or no adverse effects, such as nausea, vomiting, and gastric hypersecretion. In conclusion, hesperidin-3'-O-methylether is more potent in phosphodiesterase inhibition and suppression of AHR and has higher therapeutic (PDE4(H)/PDE4(L)) ratio than hesperidin. Thus, hesperidin-3'-O-methylether may have more potential for use in treating allergic asthma and chronic obstructive pulmonary disease.

Effects of the electrode location on tonal discrimination and speech perception of Mandarin-speaking patients with a cochlear implant.

OBJECTIVES/HYPOTHESIS: This study assessed the effects of varying the electrode location on tonal discrimination and speech perception in Mandarin Chinese-speaking patients. STUDY DESIGN: A controlled study with six experimental conditions. METHODS: Seven Mandarin-speaking listeners who received a MED-EL cochlear implant (CI), ranging in age from 12.88 to 36.43 years (mean, 25.51 years), with an average of 5.28 years of device experience, participated this study. To evaluate the effects of electrode location, six experimental conditions each with the switch off at six different electrodes were designed. Identification tests of Mandarin lexical tones and words were performed. RESULTS: Among experimental conditions with electrode lengths of 31, 23.8, and 16.6 mm, the CI subjects exhibited improved vowel and consonant identification in the condition of 31 mm, reflecting the apical location of electrodes. Specifically, the improvement was observed in the identification score for the vowel backness and height, as well as for the consonant place of articulation. Comparison among three settings with a same electrode length of 12.6 mm and the setting with stimulation to the midregion of the cochlea produces better words as well as the vowel and consonant identification compared with stimulation to basal and apical regions. However, no significant difference was observed for the lexical tone identification among conditions with different electrode location and stimulating region. CONCLUSIONS: Less mismatch of the frequency-to-place alignment may account for the improvement of word identification in conditions with electrodes coverage to more apical location; and in conditions where the mid-region of the cochlea were stimulated.

Hesperetin, a Selective Phosphodiesterase 4 Inhibitor, Effectively Suppresses Ovalbumin-Induced Airway Hyperresponsiveness without Influencing Xylazine/Ketamine-Induced Anesthesia.

Hesperetin, a selective phosphodiesterase (PDE)4 inhibitor, is present in the traditional Chinese medicine, "Chen Pi." Therefore, we were interested in investigating its effects on ovalbumin- (OVA-) induced airway hyperresponsiveness, and clarifying its rationale for ameliorating asthma and chronic obstructive pulmonary disease (COPD). Hesperetin was revealed to have a therapeutic (PDE4(H)/PDE4(L)) ratio of >11. Hesperetin (10 ~ 30 µmol/kg, intraperitoneally (i.p.)) dose-dependently and significantly attenuated the airway hyperresponsiveness induced by methacholine. It also significantly suppressed the increases in total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, interferon-γ, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF). It dose-dependently and significantly suppressed total and OVA-specific immunoglobulin E levels in the BALF and serum. However, hesperetin did not influence xylazine/ketamine-induced anesthesia, suggesting that hesperetin has few or no emetic effects. In conclusion, the rationales for ameliorating allergic asthma and COPD by hesperetin are anti-inflammation, immunoregulation, and bronchodilation.

Hesperetin-7,3'-O-dimethylether selectively inhibits phosphodiesterase 4 and effectively suppresses ovalbumin-induced airway hyperresponsiveness with a high therapeutic ratio.

BACKGROUND: Hesperetin was reported to selectively inhibit phosphodiesterase 4 (PDE4). While hesperetin-7,3'-O-dimethylether (HDME) is a synthetic liposoluble hesperetin. Therefore, we were interested in investigating its selectivity on PDE4 and binding ability on high-affinity rolipram-binding sites (HARBs) in vitro, and its effects on ovalbumin-induced airway hyperresponsiveness in vivo, and clarifying its potential for treating asthma and chronic obstructive pulmonary disease (COPD). METHODS: PDE1~5 activities were measured using a two-step procedure. The binding of HDME on high-affinity rolipram-binding sites was determined by replacing 2 nM [3H]-rolipram. AHR was assessed using the FlexiVent system and barometric plethysmography. Inflammatory cells were counted using a hemocytometer. Cytokines were determined using mouse T helper (Th)1/Th2 cytokine CBA kits, and total immunoglobulin (Ig)E or IgG2a levels were done using ELISA method. Xylazine (10 mg/kg)/ketamine (70 mg/kg)-induced anesthesia was performed. RESULTS: HDME revealed selective phosphodiesterase 4 (PDE4) inhibition with a therapeutic (PDE4H/PDE4L) ratio of 35.5 in vitro. In vivo, HDME (3~30 µmol/kg, orally (p.o.)) dose-dependently and significantly attenuated the airway resistance (RL) and increased lung dynamic compliance (Cdyn), and decreased enhanced pause (Penh) values induced by methacholine in sensitized and challenged mice. It also significantly suppressed the increases in the numbers of total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, interferon-γ, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF) of these mice. In addition, HDME (3~30 µmol/kg, p.o.) dose-dependently and significantly suppressed total and ovalbumin-specific immunoglobulin (Ig)E levels in the BALF and serum, and enhanced IgG2a level in the serum of these mice. CONCLUSIONS: HDME exerted anti-inflammatory effects, including suppression of AHR, and reduced expressions of inflammatory cells and cytokines in this murine model, which appears to be suitable for studying the effects of drugs on atypical asthma and COPD, and for screening those on typical asthma. However, HDME did not influnce xylazine/ketamine-induced anesthesia. Thus HDME may have the potential for use in treating typical and atypical asthma, and COPD.

Calcium channel subtypes for cholinergic and nonadrenergic noncholinergic neurotransmission in isolated guinea pig trachea.

The Ca(2+) channel subtypes in the neurotransmission of isolated guinea pig trachea were elucidated by monitoring the effects of specific Ca(2+) channel blockers on cholinergic contractions and nonadrenergic noncholinergic (NANC) relaxation elicited by electrical field stimulation (EFS). In isolated guinea pig trachea, cholinergic contractile responses to low- and high-frequency EFS were inhibited by the selective N-type calcium channel blocker, ω-conotoxin MVIIA. ω-Agatoxin IVA (a selective P-type blocker), ω-conotoxin MVIIC (a nonselective N-, Q-, and P-type blocker), and nifedipine (a selective L-type blocker) were ineffective, whereas Ni(2+) (a T- and R-type blocker) facilitated cholinergic contractions and produced a late contracture when its concentration exceeded 30 µM. The more the concentration of Ni(2+) increased, the greater the number of incidences and the late contracture areas which occurred. Late contracture did not seem to be due to the effects of acetylcholine, tachykinins, or other polypeptides, but disappeared in the absence of indomethacin. The NANC relaxant responses elicited by the low- and high-frequency EFS were inhibited by ω-conotoxin MVIIA or Ni(2+), but unaffected by ω-Agatoxin IVA, ω-conotoxin MVIIC, and nifedipine. In the absence of indomethacin, Ni(2+) did not alter the ω-conotoxin MVIIA (100 nM)-resistant component of cholinergic contraction, but significantly further inhibited that of NANC relaxation. These results suggest that in isolated guinea pig trachea, cholinergic contraction is regulated by N-type calcium channels which may mask T- and R-type calcium channels and may be co-modulated by both, while NANC relaxation is mainly and independently controlled by N-, T-, and R-type calcium channels.

Parotid neoplasms: diagnosis, treatment, and intraparotid facial nerve anatomy.

The demographics of parotid neoplasms in different populations have been reported by various centres. In this investigation, we reviewed retrospectively all the in-patient and out-patient charts and records of 108 patients who were diagnosed with parotid neoplasms and received parotidectomies in our department from 1 January 1993 to 15 April 2000. Patient age, gender, tumour pathology, fine-needle aspiration cytology results, and the intraparotid anatomy of the facial nerve were noted. We showed that despite the difference between our Taiwanese and previously studied patient populations, both populations had a similar distribution, diagnosis and treatment of parotid neoplasms, although the incidence of parotid tuberculosis was higher in our patient group. In addition, the facial nerve anatomy within the parotid gland had three main branching patterns in the upper and lower division.