On the Mechanisms of Harmful Effects of Certain Medicinal Preparations on the Auditory Organ and Methods for Their Prevention

Various drugs are discussed and many references are mentioned. It was concluded that the development of methods of pharmacological prevention of the harmful effect of drugs on the auditory analyzor is a necessity

Network Friendly P2P-TV: The Napa-Wine Approach

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Localized disorganization of the cochlear inner hair cell synaptic region after noise exposure

The prevalence and importance of hearing damage caused by noise levels not previously thought to cause permanent hearing impairment has become apparent in recent years. The damage to, and loss of, afferent terminals of auditory nerve fibres at the cochlear inner hair cell has been well established, but the effects of noise exposure and terminal loss on the inner hair cell are less known. Using three-dimensional structural studies in mice we have examined the consequences of afferent terminal damage on inner hair cell morphology and intracellular structure. We identified a structural phenotype in the pre-synaptic regions of these damaged hair cells that persists for four weeks after noise exposure, and demonstrates a specific dysregulation of the synaptic vesicle recycling pathway. We show evidence of a failure in regeneration of vesicles from small membrane cisterns in damaged terminals, resulting from a failure of separation of small vesicle buds from the larger cisternal membranes

Infection dynamics of two renal myxozoans in hatchery reared fry and juvenile Atlantic cod Gadus morhua L.

In order to study the infection dynamics of 2 renal myxozoans, Zschokkella hildae Auerbach, 1910 and Gadimyxa atlantica Køie, Karlsbakk and Nylund, 2007 in cultured Atlantic cod, Gadus morhua L. aged 3–19 months, a specific single-round PCR assay and a double-label in situ hybridization protocol were developed. The results demonstrated that the 2 myxozoans show spatial separation of their development with regard to spore formation inside the renal tubules versus the collecting ducts and ureters, as well as temporal separation with Z. hildae proliferating and developing spores only once the G. atlantica infection decreases, despite the presence of both myxozoans in the smallest fry studied. These results strongly suggest within-host competition of the 2 myxozoans with potential suppression of Z. hildae by G. atlantica until G. morhua acquires immunity against G. atlantica. The quantification of the G. atlantica infection inside the renal tubules before and after a 29-day experimental growth performance study using fry from hatcheries with differing filtration systems showed that the intensity of infection with G. atlantica seems to be controlled if prolonged exposure to the myxozoan transmission stages takes place from hatching onwards. Surprisingly, growth rates in the trial were inversely affected suggesting that G. atlantica does not negatively influence cod fry growth performance

A Novel Hypothesis for Thalidomide-Induced Limb Teratogenesis: Redox Misregulation of the NF-κB Pathway

Several hypotheses have been proposed to explain the mechanisms of thalidomide teratogenesis, although none adequately accounts for the observed malformations and explains the basis for species specificity. Recent observations that thalidomide increases the production of free radicals and elicits oxidative stress, coupled with new insights into the redox regulation of nuclear transcription factors, lead to the suggestion that thalidomide may act through redox misregulation of the limb outgrowth pathways. Oxidative stress, as marked by glutathione depletion/oxidation and a shift in intracellular redox potential toward the positive, occurs preferentially in limbs of thalidomide-sensitive rabbits, but not in resistant rats. DNA binding of nuclear factor κ-B (NF-κB), a redox-sensitive transcription factor and key regulator of limb outgrowth, was shown to be significantly attenuated in rabbit limb cells and could be restored following the addition of a free radical spin-trapping agent, phenyl N-tert-butyl nitrone. The inability of NF-κB to bind to its DNA promoter results in the failure of limb cells to express fibroblast growth factor (FGF)-10 and twist in the limb progress zone (PZ) mesenchyme, which in turn attenuates expression of FGF-8 in the apical ectodermal ridge (AER). Failure to establish an FGF-10/FGF-8 feedback loop between the PZ and AER results in the truncation of limb outgrowth. We hypothesize that species-selective alterations in redox microenvironment caused by free radical production from thalidomide results in attenuation of the NF-κB-mediated gene expression that is responsible for limb outgrowth.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63400/1/152308604771978291.pd

The Autoimmune Disorder Susceptibility Gene CLEC16A Restrains NK Cell Function in YTS NK Cell Line and Clec16a Knockout Mice

CLEC16A locus polymorphisms have been associated with several autoimmune diseases. We overexpressed CLEC16A in YTS natural killer (NK) cells and observed reduced NK cell cytotoxicity and IFN-γ release, delayed dendritic cell (DC) maturation, decreased conjugate formation, cell-surface receptor downregulation and increased autophagy. In contrast, siRNA mediated knockdown resulted in increased NK cell cytotoxicity, reversal of receptor expression and disrupted mitophagy. Subcellular localization studies demonstrated that CLEC16A is a cytosolic protein that associates with Vps16A, a subunit of class C Vps-HOPS complex, and modulates receptor expression via autophagy. Clec16a knockout (KO) in mice resulted in altered immune cell populations, increased splenic NK cell cytotoxicity, imbalance of dendritic cell subsets, altered receptor expression, upregulated cytokine and chemokine secretion. Taken together, our findings indicate that CLEC16A restrains secretory functions including cytokine release and cytotoxicity and that a delicate balance of CLEC16A is needed for NK cell function and homeostasis