Pharmakologische Effekte von Sinupret<Superscript>®</Superscript>

The herbal medicinal product Sinupret has been successfully used for the treatment of sinusitis for 70 years. In Germany the product is established as a standard in the therapy of sinusitis. The most recent pharmacodynamic findings resulted from close scientific cooperation with Pontus Stierna and co-workers from the Karolinska Institute in Stockholm:Mice were infected intranasally with Streptococcus pneumoniae to induce bacterial rhinosinusitis. Animals were randomized to treatment with ampicillin, dexamethasone, Sinupret, or sham treatment. All groups receiving active treatment showed a reduction in bacterial growth after 4 days and a significant reduction of bacterial growth after 8 days. Similar results were observed regarding histopathology. Initial findings in a sinusitis model in the New Zealand White rabbit confirmed the results observed in the aforementioned studies in mice.Understanding of the pharmacological profile of Sinupret supports the knowledge about the clinical efficacy of this herbal medicinal product.     

Null Mutation of α<Subscript>1D</Subscript> Ca<Superscript>2+</Superscript> Channel Gene Results in Deafness but No Vestibular Defect in Mice

Multiple Ca²⁺ channels confer diverse functions to hair cells of the auditory and vestibular organs in the mammalian inner ear. We used gene-targeting technology to generate _1D Ca²⁺ channel-deficient mice to determine the physiological role of these Ca²⁺ channels in hearing and balance. Analyses of auditory-evoked brainstem recordings confirmed that _1D^–/– mice were deaf and revealed that heterozygous (_1D^+/–) mice have increased hearing thresholds. However, hearing deficits in _1D^+/– mice were manifested mainly by the increase in threshold of low-frequency sounds. In contrast to impaired hearing, _1D^–/– mice have balance performances equivalent to their wild-type littermates. Light and electron microscope analyses of the inner ear revealed outer hair cell loss at the apical cochlea, but no apparent abnormality at the basal cochlea and the vestibule. We determined the mechanisms underlying the auditory function defects and the normal vestibular functions by examining the Ba²⁺ currents in cochlear inner and outer hair cells versus utricular hair cells in _1D^+/– mice. Whereas the whole-cell Ba²⁺ currents in inner hair cells consist mainly of the nimodipine-sensitive current (~85%), the utricular hair cells express only ~50% of this channel subtype. Thus, differential expression of _1D channels in the cochlear and utricular hair cells confers the phenotype of the _1D null mutant mice. Because vestibular and cochlear hair cells share common features and null deletion of several genes have yielded both deafness and imbalance in mice, _1D null mutant mice may serve as a model to disentangle vestibular from auditory-specific functions.     

Suitability of Auditory Speech Sound Evaluation (A§E<Superscript>®</Superscript>) in German cochlear implant patients

A§E^® is an audiological evaluation tool based on speech sounds as stimuli and was developed by The Eargroup, Antwerp. It consists of three levels: detection, discrimination and identification of phonemes and is a sufficient tool to measure supraliminal auditory capacities in Flemish language of children 10 months and older as well as adults. The aim of this study was to test the suitability of patients for cochlear implant in Germany, using 245 consecutive measurements (141 adults, 79 children, 25 controls) in a standard test protocol for phoneme detection and discrimination, Mainzer and Göttinger in children and Freiburger in adults pre-, 3 and 6 months and 1 year after implantation. Results in detection and discrimination regarding frequency spectrum and fitting parameters were evaluated using the following statistical methods: t test and correlation analysis. Detection improves first, followed by numbers, phoneme discrimination and monosyllables. Test results compared pre- to 3, 6 months and later, postoperatively, differ significantly (p < 0.05). A “ceiling-effect” is obtained between 6 months and 1 year (reproduction in A§E^® >90%). Development of detection and discrimination correlates directly with results in numbers and monosyllables (r = 0.92). Non-German speaking patients cope better with A§E^® than with numbers and monosyllables. Evaluation of phoneme discrimination enables better frequency specific fitting. Results indicated that A§E^® is a valuable diagnostic supplement in fitting and therapy of cochlear implant patients regardless of cognitive level, age and language. Important information on frequency-resolving power of cochlear nerve after implantation is gained. Use of A§E^® enables comparability and evaluation of study results in different countries.     

Nasal congestion after visual sexual stimulation with and without sildenafil (Viagra<Superscript>®</Superscript>): a randomized placebo-controlled study

Sildenafil (Viagra^®) is a selective phosphodiesterase type 5 inhibitor (PDE5-I) approved for treatment of erectile dysfunction. Although relatively well-tolerated, sildenafil is associated with undesired effects including headache, flushing, dyspepsia, nasal congestion, and visual disturbances. In the present study we explored the impact of sildenafil on nasal airway parameters in young potent men. Eleven men (age 26.0 ± 1.8 years) with normal BMI (25.7 ± 0.5) and without nasal respiratory disorders were enrolled in a double-blind, crossover study. All men underwent evaluation of systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), SpO₂%, acoustic rhinometry, and nasal endoscopy before and after placebo or sildenafil (50 mg) plus visual sexual stimulation (VSS). Nasal examination was performed using 0° rigid telescopes, 4 mm in diameter. A Student’s t test was used for direct comparisons, while the Kruskal–Wallis test (K–W) was utilized for multiple comparisons. After administration of sildenafil plus VSS, the minimum cross sectional area (MCA) was significantly lower that observed with either placebo (P = 0.03) or sildenafil alone (P = 0.003). However, the post-stimulation values did not demonstrate any significant differences among the different treatment arms (P = 0.48; DF = 2; K–W test). In contrast, endonasal volume (VOL) was significantly lower after sildenafil + VSS (P = 0.01), but not after placebo + VSS (P = 0.18). None of the other parameters monitored showed any significant variations. Rhinoscopy showed a characteristic increase of the volume of the inferior turbinates, with subjective differences between placebo and sildenafil. These preliminary results suggest that sildenafil reduces nasal volume, and that sexual stimulation may decrease nasal airflow by itself.     

Randomised,multi-centre study of the usefulness of the heat and moisture exchanger (Provox HME<Superscript>®</Superscript>) in laryngectomised patients

This study included 60 patients (30 in Nice and 30 in Reims), who were randomised between a control group that used no device of this type and a group equipped with the Provox HME^®. After 3 months of using the device, a notable improvement was found which was statistically significant with regard to cough (P = 0.00174) and to bronchorrhoea (P = 0.0031), and very close to achieving significance with regard to breathing effort. An overall improvement in the prosthetic (tracheo-oesophageal) voice was found in the 21 patients using the HME^® and a voice prosthesis for all of the parameters studied. The device was used daily by 80% of the patients of whom 42% used it day and night at the end of the 3 months. Seven patients suffered from minor cutaneous intolerance (of whom 6 had received radiation therapy), which did not require the use of the HME^® to be abandoned (PC). After 3 months, patients were asked the following questions: “Do you feel any improvement?”: 92% of affirmative answers; “Are you breathing better?”: 88% of affirmative answers; “Are you speaking more easily?”: 81% had experienced speech improvement. The general adaptation to the device was judged to be satisfactory for 95% of the patients after 3 months. The results of this randomised study show an improvement in the pulmonary symptoms and in the prosthetic voice after 3 months of using Provox HME^®. This light and easy-to-use device appears to us to afford a significantly improved quality of life for laryngectomees and should be offered systematically during functional rehabilitation of these patients.     

Elevated levels of interleukins IL-1<Emphasis Type="Italic">β</Emphasis>, IL-6 and IL-8 in naturally acquired viral rhinitis

We studied the cytokines IL(interleukin)-1β, IL-4, IL-6 and IL-8 in nasal lavage samples from 20 patients with naturally acquired viral rhinitis and 5 healthy controls without nasal complaints. IL-1β, IL-6 and IL-8 levels in lavage fluid from the viral rhinitis patients were significantly elevated when compared to control subjects. IL-4 was not measurable in any of the samples. The cytokine levels in secretions from the healthy controls remained stable intraindividually on 5 consecutive sampling days. We suggest that cytokines such as IL-1β, IL-6 and IL-8, but not IL-4, are involved in the pathophysiology of the common cold.     

Natural Compounds as Occult Ototoxins? <Emphasis Type="Italic">Ginkgo biloba</Emphasis> Flavonoids Moderately Damage Lateral Line Hair Cells

Several drugs, including aminoglycosides and platinum-based chemotherapy agents, are well known for their ototoxic properties. However, FDA-approved drugs are not routinely tested for ototoxicity, so their potential to affect hearing often goes unrecognized. This issue is further compounded for natural products, where there is a lack of FDA oversight and the manufacturer is solely responsible for ensuring the safety of their products. Natural products such as herbal supplements are easily accessible and commonly used in the practice of traditional eastern and alternative medicine. Using the zebrafish lateral line, we screened a natural products library to identify potential ototoxins. We found that the flavonoids quercetin and kaempferol, both from the Gingko biloba plant, demonstrated significant ototoxicity, killing up to 30 % of lateral line hair cells. We then examined a third Ginkgo flavonoid, isorhamnetin, and found similar levels of ototoxicity. After flavonoid treatment, surviving hair cells demonstrated reduced uptake of the vital dye FM 1-43FX, suggesting that the health of the remaining hair cells was compromised. We then asked if these flavonoids enter hair cells through the mechanotransduction channel, which is the site of entry for many known ototoxins. High extracellular calcium or the quinoline derivative E6 berbamine significantly protected hair cells from flavonoid damage, implicating the transduction channel as a site of flavonoid uptake. Since known ototoxins activate cellular stress responses, we asked if reactive oxygen species were necessary for flavonoid ototoxicity. Co-treatment with the antioxidant D-methionine significantly protected hair cells from each flavonoid, suggesting that antioxidant therapy could prevent hair cell loss. How these products affect mammalian hair cells is still an open question and will be the target of future experiments. However, this research demonstrates the potential for ototoxic damage caused by unregulated herbal supplements and suggests that further supplement characterization is warranted.     

"中耳微型肺"理论

“中耳微型肺”理论是关于中耳炎发生机制的重要理论，有助于深入理解中耳正常的生理功能，将对指导临床诊断和治疗有重要意义。