In vitro evaluation of three-dimensional single-walled carbon nanotube composites for bone tissue engineering.

The purpose of this study was to develop three-dimensional single-walled carbon nanotube composites (SWCNT/PLAGA) using 10-mg single-walled carbon nanotubes (SWCNT) for bone regeneration and to determine the mechanical strength of the composites, and to evaluate the interaction of MC3T3-E1 cells via cell adhesion, growth, survival, proliferation, and gene expression. PLAGA (polylactic-co-glycolic acid) and SWCNT/PLAGA microspheres and composites were fabricated, characterized, and mechanical testing was performed. MC3T3-E1 cells were seeded and cell adhesion/morphology, growth/survival, proliferation, and gene expression analysis were performed to evaluate biocompatibility.

Ginkgo biloba extract (EGb 761) protects against cisplatin-induced ototoxicity in rats.

Hypothesis: A standardized Ginkgo biloba extract, EGb 761, may have protective effect against cisplatin-induced ototoxicity in rats.

Background: Cisplatin-induced ototoxicity is a major dose-limiting side effect in anticancer chemotherapy. Cisplatin-induced ototoxicity has been correlated to depletion of the cochlear antioxidant system and increased lipid peroxidation.

Mechanisms of cisplatin-induced ototoxicity and prevention.

Cisplatin is a widely used chemotherapeutic agent to treat malignant disease. Unfortunately, ototoxicity occurs in a large percentage of patients treated with higher dose regimens. In animal studies and in human temporal bone investigations, several areas of the cochlea are damaged, including outer hair cells in the basal turn, spiral ganglion cells and the stria vascularis, resulting in hearing impairment.

Ototoxicity: therapeutic opportunities.

Two major classes of drugs currently in clinical use can cause permanent hearing loss. Aminoglycoside antibiotics have a major role in the treatment of life-threatening infections and platinum-based chemotherapeutic agents are highly effective in the treatment of malignant disease. Both damage the hair cells of the inner ear, resulting in functional deficits.

Partial protection by lipoic acid against carboplantin-induced ototoxicity in rats.

Objective: To investigate the alterations in auditory brainstem evoked responses (ABRs) and the changes of carboplatin-induced ototoxicity in the cochlear oxidant/antioxidant systems and otoprotection by an antioxidant lipoate.

Methods: Male wistar rats were divided into four groups and treated as follows: 1) vehicle (saline) control, 2) carboplatin (256 mg/kg, i.p.

Time response of carboplatin-induced nephrotoxicity in rats.

Carboplatin, a second-generation platinum-containing anti-cancer drug, is currently being used against human cancers. High-dose carboplatin chemotherapy can cause renal tubular injury in cancer patients. We have shown a dose-dependent nephrotoxicity of carboplatin in a rat model.

Vitamin E reduces cisplatin ototoxicity.

Objectives/hypothesis: Cisplatin ototoxicity is a major dose-limiting factor in the treatment of several neoplasms. Vitamin E, a slow-acting free radical scavenger, has been shown to ameliorate nephrotoxicity and endothelial cell damage in animals receiving cisplatin. The purpose of the study was to determine the effectiveness of vitamin E as an otoprotectant.

Protection against cisplatin ototoxicity by adenosine agonists.

Cisplatin is a commonly used antineoplastic agent that causes ototoxicity through the formation of reactive oxygen species (ROS). Previous studies have shown that cisplatin causes an upregulation of A(1) adenosine receptor (A(1)AR) in the cochlea, and that application of the adenosine agonist, R-phenylisopropyladenosine (R-PIA), to the round window (RW) results in significant increases in cochlear glutathione peroxidase and superoxide dismutase. These data suggest that adenosine receptors (ARs) are an important part of the cytoprotective system of the cochlea in response to oxidative stress.

Noise induces A1 adenosine receptor expression in the chinchilla cochlea.

Adenosine plays a major cytoprotective role during ischemia and conditions of oxidative stress. Previous studies in our laboratory indicate that oxidative stress induces expression of the A1 adenosine receptor (A1AR) via activation of nuclear factor (NF)-kappaB. In this study, we tested whether noise exposure could induce oxidative stress and determine whether this induces expression of the A1AR in the chinchilla cochlea.

Round window pH manipulation alters the ototoxicity of systemic cisplatin.

The effect of manipulation of pH on the ototoxicity of systemic cisplatin was studied in Wistar rats. After control auditory brainstem responses (ABR) were performed, the auditory bullae were opened and acidic (pH 6.0), neutral (pH 7.

Aminoguanidine reduces cisplatin ototoxicity.

Cisplatin is known to cause high-frequency neurosensory hearing loss. While reactive oxygen species have been shown to play a role, reactive nitrogen species have been implicated, but not proven to be involved, in cisplatin ototoxicity. The purpose of the present study was to investigate the role of nitric oxide (*NO) in cisplatin ototoxicity by administering aminoguanidine (AG), a relatively specific inhibitor of inducible nitric oxide synthase (iNOS), in conjunction with cisplatin.

Carboplatin-induced oxidative injury in rat inferior colliculus.

Carboplatin is currently being used as an anticancer drug against human cancers. However, high dose of carboplatin chemotherapy resulted in ototoxicity in cancer patients. Carboplatin-induced ototoxicity was related to oxidative stress to the cochlea and inner hair cell loss in animals.

Influence of pH on the ototoxicity of cisplatin: a round window application study.

Cisplatin is an antineoplastic agent that produces a number of dose-limiting side effects, including ototoxicity. We investigated the effect of pH on cisplatin ototoxicity. Auditory brainstem responses (ABR) were recorded in chinchillas.

Migration of cochlear lateral wall cells.

The role of apoptosis and proliferation in maintenance of cochlear lateral wall cells was examined. The methods employed for detection of apoptosis were the Hoechst fluorescence stain and TUNEL (TdT-mediated dUTP-biotin nick-end-labeling) assay, and proliferations were 5-bromo-2'-deoxyuridine (BrdU) incorporation and presence of the proliferating cell nuclear antigen. The incidence of apoptosis in the strial marginal cell was 50% greater (32.

Round window application of D-methionine provides complete cisplatin otoprotection.

Objective: Cisplatin is a widely used, very effective chemotherapeutic agent that can cause severe ototoxicity. In this study, D-methionine was tested as an otoprotectant via round window membrane (RWM) application in the chinchilla.

Methods: A minute amount of cisplatin alone, or D-methionine followed by cisplatin, was applied topically directly to the intact RWM of anesthetized adult chinchillas.

Cisplatin up-regulates the adenosine A(1) receptor in the rat kidney.

Cisplatin, a widely used anticancer drug, produces significant oto- and nephrotoxicity. Previous data from our laboratory, using cultured cell lines, indicated that cisplatin increases the expression of the adenosine A(1) receptor subtype through generation of reactive oxygen species and activation of nuclear factor-kappa B (NF-kappa B). Since the adenosine A(1) receptor plays an important role in normal renal physiology, this study was performed to determine whether cisplatin modulates adenosine A(1) receptor expression in vivo and whether these receptors play a role in the nephrotoxicity.