Cellular Delivery of CNTF but not NT-4/5 Prevents Degeneration of Striatal Neurons in a Rodent Model of Huntington’s Disease

The delivery of neurotrophic factors to the central nervous system (CNS) has gained considerable attention as a potential treatment strategy for neurodegenerative disorders such as Huntington’s disease (HD). In the present study, we directly compared the ability of two neurotrophic factors, ciliary neurotrophic factor (CNTF), and neurotrophin-4/5 (NT-4/5), to prevent the degeneration of striatal neurons following intrastriatal injections of quinolinic acid (QA). Expression vectors containing either the human CNTF or NT-4/5 gene were transfected into a baby hamster kidney fibroblast cell line (BHK). Using a polymeric device, encapsulated BHK-control cells and those secreting either CNTF (BHK-CNTF) or NT-4/5 (BHK-NT-4/5) were transplanted unilaterally into the rat lateral ventricle. Seven days later, the same animals received unilateral injections of QA (225 nmol) into the ipsilateral striatum. Nissl-stained sections demonstrated that the BHK-CNTF cells significantly reduced the volume of striatal damage produced by QA. Quantitative analysis of striatal neurons further demonstrated that both choline acetyltransferase (ChAT)- and glutamic acid decarboxylase (GAD)-immunoreactive neurons were protected by CNTF implants. In contrast, the volume of striatal damage and loss of striatal ChAT and GAD-positive neurons in animals receiving BHK-NT-4/5 implants did not differ from control-implanted animals. These results help better define the scope of neuronal protection that can be afforded following cellular delivery of various neurotrophic factors. Moreover, these data further support the concept that implants of polymer-encapsulated CNTF-releasing cells can be used to protect striatal neurons from excitotoxic damage, and that this strategy may ultimately prove relevant for the treatment of HD.     

Pott's disease of the cervico-occipital junction in an AIDS patient

Pott's disease of the cervical spine is relatively rare despite the fact that tuberculous spondylitis is still the most common manifestation of bone and joint infection. We describe a case, the first to our knowledge, of sub-occipital Pott's disease associated with a retropharyngeal abscess in an acquired immune deficiency syndrome (AIDS) patient. Neurological signs were the main clinical findings. The patient was successfully treated with anti-tuberculosis drugs combined with external stabilization of the spine.     

A review of inhalation toxicology studies with Para-aramid fibrils

The paper summarizes the results of inhalation toxicology studies associated with para-aramid (p-aramid) fibrils. The review is subdivided into two categories: the results of inhalation toxicity studies and mechanistic inhalation studies. Keratin-associated lesions were observed in the lungs of female rats following chronic exposure to high concentrations of p-aramid. These lesions were originally interpreted as cystic keratinizing squamous cell carcinomas (CKSCC). In recent years, this keratinizing lesion has been observed in the lungs of rats with greater regularity in numerous chronic inhalation studies following exposures to a variety of dusts. In an attempt to reach a consensus on an appropriate diagnosis for this lesion, an international panel of pathologists was convened to evaluate the morphological aspects of this lesion. The panel considered that the most appropriate diagnosis for this lesion was ‘proliferative keratin cyst’ (PKC). the biological potential of the PKC remains controversial, but it appears to be unique to the rat species and has little relevance for humans. Mechanistic studies with p-aramid have demonstrated that acute inhalation of high concentrations of fibrils produces a potent but transient pulmonary inflammatory and cell labelling response. The inhaled fibrils have low durability in the lungs of rats as evidenced by a progressive decrease in median fibre lengths with increasing residence time in the lung. In contrast, in a comparative study, size-separated chrysotile asbestos produced a sustained increase over controls in cellular proliferation responses of terminal airways, parenchyma, subpleural and mesothelial regions. In addition, while the short fibres were cleared at a normal or rapid rate, the long (i.e. > 5 μm) chrysotile fibres were retained in the lung or cleared at a slow rate, suggesting that this subpopulation of fibres is durable in the lungs of exposed rats. These results point out the differences in the lung responses between p-aramid fibrils when compared to chrysotile asbestos fibres, namely, that chrysotile produced enhanced and sustained cell proliferation responses, and that the long chrysotile fibres were retained in the lungs of exposed rats.     

Comparative case contamination: Three disinfection systems

This prospective single-masked clinical study analyzes the microbial contamination of the overnight storage solution and biofilm in contact lens cases. Thirty-one masked subjects were divided into three groups and assigned to use either AOSept,® ReNu,™ or OptiFree™ lens care systems for 6 weeks. They followed manufacturers' instructions and returned for microbial sampling at 4- and 6-week visits. The cases were sampled without opening the seal following disinfection the night before. Despite a large variability within the ReNu and OptiFree groups, the level of solution contamination was significantly lower with the AOSept system at the 6-week visit. The incidence of biofilm contamination was significantly worse for the ReNu group at the 4-week visit, and the AOSept group was significantly better than were ReNu and OptiFree at the 6-week visit. There was a trend toward increasing contamination with time in the chemical soaking systems and a strong correlation between solution contamination and biofilm contamination.