On the prediction of cytotoxicity of diverse chemicals for topminnow (Poeciliopsis lucida) hepatoma cell line, PLHC-1$.

Two data sets on the cytotoxicity of diverse chemicals to topminnow (Poeciliopsis lucida) hepatoma cell line (PLHC-1) were modelled with quantitative structure-toxicity relationship (QSTR). The data sets are based on 3-amino-7-dimethylamino-2-methylphenazine hydrochloride (NR) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays representing lysosomal damage and metabolic impairment, respectively. The descriptors were calculated with DRAGON 6 and SPARTAN 10 software packages. Descriptor selection was made by 'all subset' and genetic algorithm-based features implemented in QSARINS software. The proposed QSTR models were validated both internally and externally. For both endpoints, statistically satisfactory QSTR models were generated with nTr = 39; r2Tr = 0.782; RMSETr = 0.466; nTest = 18; r2Test = 0.799; RMSETest = 0.360 for NR-based model and nTr = 32; r2Tr = 0.775; RMSETr = 0.460; nTest = 10; r2Test = 0.864; RMSETest = 0.290 for MTT-based model. Additionally, the QSTR models generated for NR and MTT endpoints were used to predict the cytotoxicity of an external set of 657 and 652 diverse chemicals with structural coverage of 98.6% and 98.3%, respectively. A moderate correlation was observed between the experimental in vivo and predicted in vitro values for external set chemicals. The QSTR models may provide an initial, rapid screening and prioritization of these diverse chemicals for the acute fish toxicity assessment and reduce the need for extensive in vivo toxicity testing.

Time-course changes of nLDL-induced erectile dysfunction.

Hyperlipidemia is an important risk factor for atherosclerosis and is frequently seen in patients with erectile dysfunction (ED). This study was designed to evaluate whether the acute effect of native low-density lipoprotein (nLDL) on intracavernosal pressure (ICP) is reversible and related to plasma asymmetrical dimethylarginine (ADMA), endogenous inhibition of endothelial nitric oxide synthase (eNOS) levels and eNOS expression in cavernous tissues. Hyperlipidemia was induced by a single dose of intravenous 4 mg kg-1 nLDL. Experiments were performed 72 h (72H), 2 weeks (2W) and 8 weeks (8W) after nLDL injection. Endothelium-dependent relaxations, the ratio of ICP to mean arterial pressure (MAP; ICP/MAP), plasma ADMA levels and eNOS mRNA and protein levels were evaluated. The ICP/MAP ratio decreased in both the 2W and 8W groups. Endothelium-dependent relaxation responses to acetylcholine in the rat thoracic aorta were damaged in the 8W group. Plasma ADMA levels increased in the 8W group. mRNA expression of eNOS decreased in a time-dependent manner, whereas the protein expression increased. These results suggest that acute nLDL injection-induced impairments in erectile functions during an 8-week period are irreversible and might be related to an increase in ADMA levels and changes in the regulation of the eNOS/NO pathway.

Polyurethane/hydroxypropyl cellulose electrospun nanofiber mats as potential transdermal drug delivery system: characterization studies and in vitro assays.

Donepezil hydrochloride containing polyurethane/hydroxypropyl cellulose (PU/HPC) nanofibers were prepared by the electrospinning for transdermal drug delivery. PU/HPC nanofibers were characterized with SEM, DSC, and Pascal mercury porosimetry. Drug-excipient interaction was studied by ATR-FTIR. In vitro release of PU/HPC nanofiber mat (10:2:1) exhibited Korsmeyer-Peppas release kinetics controlled by the diffusion of drug. In vitro permeation studies across skin resembling synthetic membrane demonstrated the flux of model drug. The in vitro cytotoxicity data obtained via MTT assay indicated that PU/HPC nanofiber mat could be well tolerated by the skin and the components was not irritant for the skin.

Profound sensorineural hearing loss: analysis of 310 adult cases.

OBJECTIVES: Sensorineural hearing loss is caused by problems in the inner ear, vestibulocochlear nerve, or brain central processing centers. This study aimed to analyze the patient-reported etiology, clinical aspects, and hearing evolution of patients with profound sensorineural hearing loss (PSNHL). STUDY DESIGN: Retrospective. METHODS: A total of 310 adult patients diagnosed with PSNHL in one or both ears between January 2002 and January 2008 were studied at a secondary center. Most subjects were military-aged males who were diagnosed with PSNHL during routine examinations prior to recruitment. A pure-tone audiometry test was performed in all patients. Auditory brainstem response was recorded in 142 (45.8%) patients. RESULTS: A total of 310 adult patients (276 males [89%] and 34 females [11%]) with a mean age of 23.1 (range 20-81) years comprising 486 ears consisting of 176 (56.8%) bilateral and 134 (43.2%) unilateral PSNHL cases were evaluated. Etiology was based on patient self reporting. The disease was congenital in 93 (30%) patients and acquired in 217 (70%). Etiology was unknown in 35 (11.3%) patients. Acquired hearing losses were rapid in 188 (86.6%) and progressive in 29 (13.4%) patients. Articulation was impaired (no understandable speech) in a total of 146 patients (47.1%), including all patients with congenital PSNHL. CONCLUSION: The cause of hearing loss is often understood from medical history. Taking measures for the most common causes (congenital hearing loss and childhood infectious diseases) may reduce occurrences of PSNHL cases. Auditory screening and beginning hearing rehabilitation as soon as possible in newborns is vital.