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Biomedical subjects

Michael D Seidman

Publications and source records attributed to Michael D Seidman.

11 recordsLinked to original sources
PubMed2005

Role of Bcl-2 family of proteins in mediating apoptotic death of PC12 cells exposed to oxygen and glucose deprivation.

Apoptotic cell death has been observed in many in vivo and in vitro models of ischemia. However, the molecular pathways involved in ischemia-induced apoptosis remain unclear. We have examined the role of Bcl-2 family of proteins in mediating apoptosis of PC12 cells exposed to the conditions of oxygen and glucose deprivation (OGD) or OGD followed by restoration of oxygen and glucose (OGD-restoration, OGD-R). OGD decreased mitochondrial membrane potential and induced necrosis of PC12 cells, which were both prevented by the overexpression of Bcl-2 proteins. OGD-R caused apoptotic cell death, induced cytochrome C release from mitochondria and caspase-3 activation, decreased mitochondrial membrane potential, and increased levels of pro-apoptotic Bax translocated to the mitochondrial membrane, all of which were reversed by overexpression of Bcl-2. These results demonstrate that the cell death induced by OGD and OGD-R in PC12 cells is potentially mediated through the regulation of mitochondrial membrane potential by the Bcl-2 family of proteins. It also reveals the importance of developing therapeutic strategies for maintaining the mitochondrial membrane potential as a possible way of reducing necrotic and apoptotic cell death that occurs following an ischemic insult.

Animals↗
PubMed2004

Intratympanic treatment of hearing loss with novel and traditional agents.

As knowledge of the cellular and molecular pathophysiology behind otopathologies expands, the possibility exists of preventing sensorineural hearing loss and perhaps reversing the loss. Cellular and molecular mechanisms seem to be similar in hearing loss secondary to aging, drug ototoxicity, noise, or other mechanisms. A final common pathway may hinge upon apoptosis. It is likely that anti-apoptotic factors will increasingly be realized as an important intervention strategy for sensorineural hearing loss. Furthermore, it is also possible that mounting a staged attack at the various regions in the pathway leading to cellular damage using a combination of several protective substances such as steroids, antioxidants, neurotrophic factors, anti-apoptotic compounds, and mitochondrial enhancers may prevent hearing loss and even reverse it in some situations. This article has presented some of the molecular and cellular mechanisms for hearing loss and potential ways of treating them. In theory, the delivery of these medications to the inner ear transtympanically would decrease systemic side effects and be more target specific. Because most of the studies conducted to date have been animal studies, randomized, double-blind, placebo-controlled clinical trials would be necessary before the use of these therapies becomes common practice.

Administration, Topical↗
PubMed2004

Age-related hearing loss and its association with reactive oxygen species and mitochondrial DNA damage.

Age-related hearing loss, known as presbyacusis, is characterized by the progressive deterioration of auditory sensitivity associated with the aging process and is the leading cause of adult auditory deficiency in the USA. Presbyacusis is described as a progressive, bilateral, high-frequency hearing loss that is manifested on audiometric assessment by a moderately sloping pure tone audiogram. Approximately 23% of the population between 65 and 75 years of age, and 40% of the population older than 75 years of age are affected by this condition. It was estimated in 1980 that 11% of the population was 76 years or older and this number is expected to almost double by the year 2030. When one considers that the population over 65 years of age is experiencing the most accelerated development of hearing loss, the potential socioeconomic ramifications are staggering. Curiously, the frequency of presbyacusis varies across different societies. This discrepancy has been attributed to many factors including genetics, diet, socioeconomic factors, and environmental variables. The purpose of this article is to review the various molecular mechanisms underlying presbyacusis and to offer insights into potential methods of mitigating the effects of aging on hearing impairment.

Animals↗
PubMed2004

Ossicular reconstruction using bone cement.

OBJECTIVE: The objective of this study was to describe our results of ossicular reconstruction using bone cement. STUDY DESIGN: We conducted a retrospective review of 264 patients with chronic suppurative otitis media operated on since 1999. SETTING: Academic tertiary referral center. PATIENTS: : Two hundred sixty-four patients with chronic suppurative otitis media underwent mastoidectomy with tympanoplasty. Eighty patients had incudostapedial disarticulation secondary to infection and or cholesteatoma and were reconstructed using an incus interposition graft (n = 31), a partial ossicular prosthesis (POP; n = 31), or more recently, bone source (n = 18). This study evaluates the results of the ossiculoplasties using bone source. INTERVENTION: Ossicular discontinuity was repaired using bone cement. MAIN OUTCOME MEASURE: Audiometric studies pre- and postintervention were compared. One to 3 years of follow up are provided. RESULTS: Preoperative air-bone gaps ranged from 18 dB to 60 dB and averaged 33 dB. Postoperative air-bone gaps ranged from 1 to 24 dB and averaged 10 dB. No patients have experienced any increase in their persistent conductive hearing loss. The pre-/postoperative hearing loss comparisons showed statistically significant hearing improvement. There were no complications. CONCLUSION: The use of POPs and incus interposition grafts is fraught with the possibility of migration and resultant recurrent conductive hearing loss. Using bone cement to reconstruct the ossicular chain restores the integrity of the ossicular chain in the most natural of ways. This reconstruction technique provides an excellent alternative to currently accepted methods and should be considered for incus-stapes disarticulation. There has been no dissolution of the bone source and the results have persisted thus far.

Adolescent↗
PubMed2004

A new approach for malleus/incus fixation: no prosthesis necessary.

OBJECTIVE: To describe a novel approach to manage malleus/incus fixation. STUDY DESIGN: Retrospective review of 363 patients with conductive hearing loss operated on since 1996. SETTING: Academic tertiary referral center. PATIENTS: Three hundred sixty-three patients with conductive hearing loss, an intact tympanic membrane, and without history for chronic infection underwent middle ear exploration. Three hundred forty-three had otosclerosis and underwent laser stapedotomy; the remaining 20 patients had laser release of their malleus/incus fixation. INTERVENTION: Twenty patients are presented in this paper. Nineteen patients were diagnosed with malleus fixation before surgery. One patient had a total perforation and mobility of the ossicular chain was not verified preoperatively. This patient was, intraoperatively, noted to have complete ossicular fixation. Conductive hearing loss was identified using audiometry and tuning forks. Nineteen of the 20 patients had the diagnosis confirmed using micropneumotoscopy and noting immobility of the malleus. A transcanal approach was used, and the malleus/incus fixation was released using a laser. This space was expanded upon using a drill. A 1.5-2.0 mm space was created where the ossicular fixation existed, thereby reducing the likelihood of refixation. MAIN OUTCOME MEASURE: Audiometric studies before and after intervention were compared. One to seven years of follow up are provided. RESULTS: Preoperative air-bone gaps ranged from 18 dB to 51 dB and averaged 33 dB. Postoperative air-bone gaps ranged from 1-36 dB and averaged 13 dB. No patients have experienced refixation. There were two complications: one perforation requiring a tympanoplasty and one patient sustaining a 20 dB high-frequency sensorineural loss, most likely secondary to inadvertent drill contact to the ossicular chain. CONCLUSION: When fixation of the malleus and/or incus is found, treatment options exist. A common technique involves removal of the incus and head of the malleus and reconstruction with an incus interposition or a partial ossicular prosthesis. Another technique proposed by the senior author (M.D.S.) is maintenance of the normal anatomy and use of the potassium-titanyl-phosphate laser and drill to free the ossicles and widen the epitympanum. This series shows successful closure of the air-bone gap with this technique.

Adolescent↗
PubMed2003

Effect of SOD1 overexpression on age- and noise-related hearing loss.

Reactive oxygen species (ROS) have been implicated in hearing loss associated with aging and noise exposure. Superoxide dismutases (SODs) form a first line of defense against damage mediated by the superoxide anion, the most common ROS. Absence of Cu/Zn SOD (SOD1) has been shown to potentiate hearing loss related to noise exposure and age. Conversely, overexpression of SOD1 may be hypothesized to afford a protection from age- and noise-related hearing loss. This hypothesis may be tested using a transgenic mouse model carrying the human SOD1 gene. Contrary to expectations, here, we report that no protection against age-related hearing loss was observed in mice up to 7 months of age or from noise-induced hearing loss when 8 week old mice were exposed to broadband noise (4-45 kHz, 110 dB for 1 h). Mitochondrial DNA deletion, an index of aging, was elevated in the acoustic nerve of transgenic mice compared to nontransgenic littermates. The results indicate the complexity of oxidative metabolism in the cochlea is greater than previously hypothesized.

Age Factors↗
PubMed2003

Alternative medications and other treatments for tinnitus: facts from fiction.

Tinnitus is a significant medical problem affecting approximately 50 million Americans, 12 million of them severely. Once a thorough evaluation has been performed by a qualified otolaryngologist, and no life-threatening pathology has been identified, the opportunity for treatment exists. Treatment options are extensive and range from approved protocols to anecdotal remedies. Although tinnitus may not miraculously disappear, many therapeutic options exist that may help to make the tinnitus more manageable.

Complementary Therapies↗
PubMed2003

Pharmacologic manipulation of the labyrinth with novel and traditional agents delivered to the inner ear.

We describe the methodology and rationale behind the delivery of therapeutic medicines to the inner ear. The inner ear has long been impervious to pharmacologic manipulation. This is most likely the result of a protective mechanism called the blood-labyrinth barrier, whose function closely resembles that of the blood-brain barrier. This protective barrier impedes the clinician's ability to treat inner ear diseases with systemically administered medications. Since 1935, otolaryngologists have attempted to manipulate the inner ear with trans-tympanically injected medicines. Success has varied widely, but medicinal ablation of vestibular function can be achieved in this manner. Unfortunately, the auditory system is also at great risk from any medicine that is delivered to the inner ear via the middle ear. Over the past 10 years, significant improvements in drug delivery have allowed for more "titratable" treatment, which has reduced (but not eliminated) the risk of permanent hearing loss. In this article, we discuss both novel and time-tested methods of delivering medicines to the inner ear. We also review the classes of medications that alter inner ear function and the attendant risks of such treatments.

Aminoglycosides↗
PubMed2002

Molecular mechanisms of age-related hearing loss.

Age-related hearing loss, known as presbyacusis, is characterized by the progressive deterioration of auditory sensitivity associated with aging and is the most common cause of adult auditory deficiency in the United States. Presbyacusis is defined as a progressive, bilateral, high-frequency hearing loss that is manifested on audiometric assessment by a moderately sloping pure tone audiogram. This condition affects approximately 23% of the population between 65 and 75 years of age and 40% of the population older than 75 years of age. In 1980, it was estimated that 11% of the population was 76 years or older and this number is expected to nearly double by the year 2030 [, Otolaryngol. Head Neck Surg. 100, 262]. When coupled with the fact that the population over 65 years of age is experiencing the most rapid progression of hearing loss, the potential socioeconomic ramifications are staggering. Interestingly, presbyacusis varies in its frequency across differing societies. This discrepancy has been attributed to many factors such as genetics, diet, socioeconomic factors, and environmental variables [, Otolaryngol. Head Neck Surg. 100, 266;. Scand. Audiol. 26 (1997) 133]. The purpose of this discussion is to illuminate the various molecular mechanisms underlying this age-related hearing loss and to offer insights into potential ways to mitigate the effects of aging on hearing impairment.

Aging↗
PubMed2002

Influence of lecithin on mitochondrial DNA and age-related hearing loss.

OBJECTIVES: Lecithin is a polyunsaturated phosphatidylcholine (PPC), which are high energy functional and structural elements of all biologic membranes. PPC play a rate-limiting role in the activation of numerous membrane-located enzymes, including superoxide dismutase and glutathione, which are important antioxidants protecting cell membranes from damage by reactive oxygen species (ROS). ROS-induced damage to mitochondrial DNA may lead to reduced mitochondrial function in the cochlea and resultant hearing loss. STUDY DESIGN AND SETTING: The effects of lecithin on aging and age-associated hearing loss were studied in rats by measuring hearing sensitivities using auditory brainstem responses (ABR). In addition, mitochondrial function as a measure of aging was assessed by determining mitochondrial membrane potentials using flow cytometry and by amplifying mitochondrial DNA deletions associated with aging. Harlan-Fischer rats aged 18 to 20 months (n = 14) were divided into 2 groups. The experimental group was supplemented orally for 6 months with lecithin, a purified extract of soybean phospholipid (Nutritional Therapeutics, Allendale, NJ). RESULTS: The data obtained were compared with the control group. ABRs were recorded at 2-month intervals and showed significant preservation of hearing sensitivities in the treated subjects. Flow cytometry revealed significantly higher mitochondrial membrane potentials in the treated subjects, suggesting preserved mitochondrial function. Finally, the common aging mitochondrial DNA deletion (mtDNA(4834)) were amplified from brain and cochlear tissue including stria vascularis and auditory nerve. This specific deletion was found significantly less frequent in all tissues in the treated group compared with the controls. CONCLUSION: These experiments support our hypothesis and provide evidence that lecithin may preserve cochlear mitochondrial function and protect hearing loss associated with aging.

Administration, Oral↗