BACKGROUND AND PURPOSENeurocognitive disorders afflict approximately 20% of HIV-infected patients. HIV-1-infected cells in the brain shed viral proteins such as transactivator of transcription (Tat). Tat elicits cell death and synapse loss via processes initiated by NMDA receptor activation but mediated by separate downstream signalling pathways. Subunit selective NMDA receptor antagonists may differentially modulate survival relative to synaptic changes. EXPERIMENTAL APPROACHTat-evoked cell death was quantified by measuring propidium iodide uptake into rat hippocampal neurons in culture. The effects of Tat on synaptic changes were measured using an imaging-based assay that quantified clusters of the scaffolding protein postsynaptic density 95 fused to green fluorescent protein. KEY RESULTSDizocilpine, a non-competitive NMDA receptor antagonist, inhibited Tat-induced synapse loss, subsequent synapse recovery and Tat-induced cell death with comparable potencies. Memantine (10 mM) and ifenprodil (10 mM), which preferentially inhibit GluN2B-containing NMDA receptors, protected from Tat-induced cell death with no effect on synapse loss. Surprisingly, memantine and ifenprodil induced synapse recovery in the presence of Tat. In contrast, the GluN2A-prefering antagonist TCN201 prevented synapse loss and recovery with no effect on cell death. CONCLUSIONS AND IMPLICATIONSSynapse loss is a protective mechanism that enables the cell to cope with excess excitatory input. Thus, memantine and ifenprodil are promising neuroprotective drugs because they spare synaptic changes and promote survival. These GluN2B-preferring drugs induced recovery from Tat-evoked synapse loss, suggesting that synaptic pharmacology changed during the neurotoxic process. NMDA receptor subtypes differentially participate in the adaptation and death induced by excitotoxic insult. AbbreviationsDMEM, Dulbecco's modified Eagles media; HAND, HIV-associated neurocognitive disorders; HIV-1, human immunodeficiency virus type 1; LRP, low-density lipoprotein receptor-related protein; PI, propidium iodide; PSD95, post-synaptic density protein 95; RAP, receptor-associated protein; Tat, transactivator of transcription; TBS, tris-buffered saline
Recent studies have reported that glial cell line-derived growth factor (GDNF) has neurotrophic effects on the central nervous system, and the neural stem cells (NSCs) engrafted in animal models of stroke survive and ameliorate the neurological deficits. In this study, a stable human NSC line overexpressing GDNF (F3.GDNF) was transplanted next to the intracerebral hemorrhage (ICH) lesion site and a possible therapeutic effect was investigated. F3.GDNF human NSC line was transplanted into the cortex overlying the striatal ICH lesion. ICH was induced in adult mice by the unilateral injection of bacterial collagenase into the striatum. The animals were evaluated for 8 weeks with rotarod and limb placement tests. Transplanted NSCs were detected by b-gal immunostaining with double labeling of neurofilament, microtubule associated protein-2, glial fibrillary acidic protein or human nuclear matrix antigen (HuNuMA). F3.GDNF human NSCs produced a four times higher amount of GDNF over parental F3 cells in vitro, induced behavioral improvement in ICH mice after brain transplantation and two-to threefold increase in cell survival of transplanted NSCs at 2 and 8 weeks post-transplantation. In F3.GDNFgrafted ICH brain, a significant increase in the antiapoptotic protein and cell survival signal molecules, and a marked reduction in proapoptotic proteins were found as compared with control group. Brain transplantation of human NSCs overexpressing GDNF in ICH animals provided functional recovery in ICH animals, and survival and differentiation of grafted human NSCs. These results indicate that the F3.GDNF human NSCs should be of a great value as a cellular source for the cellular therapy in animal models of human neurological disorders including ICH.
A 2 × 2 factorial design Experiment 1 was conducted in order to characterize the effects of soyabean hulls (control or soyabean hulls diet) and metal-amino acid chelated minerals (MAC) (sulphate or MAC) on growth performance and nutrient digestibility in growing pigs. Forty eight pigs with the initial body weight (BW) 18.0 ± 1.1 kg were assigned on the basis of weight and sex to one of four treatments (2 pigs/pen, 6 replication pens/treatment, 6 barrows and 6 gilts/treatment). Throughout the experimental period, growth performance was not shown to be affected by dietary treatments. The coeffi cients of the total tract apparent digestibility of dry matter (DM) and nitrogen (N) remained unaffected by soyabean hulls diets or MAC supplementation. In Experiment 2, four barrows were used in a 4 × 4 Latin square design, to determine the effects of soyabean hulls and mineral types on emission of faeces and slurry noxious gas, including ammonia (NH 3 ), hydrogen sulphide (H 2 S) and mercaptans (R.SH), in growing pigs. Faeces and urine grab samples were collected, and the faeces (300 g) and slurry (faeces + urine = 150 + 150 g) were mixed, stored, and fermented for 5 d in order to evaluate noxious gas emission. Pigs fed diets with soyabean hulls tended to have lower NH 3 emission from faeces (P=0.09) than those fed the control diet, but NH 3 emission from the slurry was not affected by soyabean hulls diet (P=0.12). No signifi cant effects on the faeces or slurry NH 3 emission were exerted in MAC supplementation treatment. A signifi cant level of interaction between soyabean hulls and MAC was observed both in the faeces and slurry NH 3 emission (P=0.05, P=0.01). Pigs fed diets with soyabean hulls tend to exhibit lower H 2 S emission from the slurry (P=0.07), but signifi cantly lower levels of H 2 S emission both from faeces and slurry (P=0.004, P=0.02) was observed when pigs were fed on MAC diets. The emission of R.SH from faeces signifi cantly decreased (P=0.02) in MAC supplementation treatments, but not from slurry, and no soyabean hulls effects or interaction were observed in relation to R.SH emission.* Supported by the Rural Development Administration of Korea 1 Corresponding author: e-mail: inhokim@dankook.ac.kr Journal of Animal and Feed Sciences, 17, 2008, 171-181 SOYABEAN HULLS AND MAC IN GROWING PIGSWe conclude that the interaction between dietary soyabean hulls and MAC may have an effect on noxious gas emission. The emission of NH 3 from pig faeces could be substantially reduced by diets enriched with soyabean hulls and emission of H 2 S both from pig faeces and slurry could be reduced by MAC supplementation.
Emphysematous cystitis is characterized by gas collection within the bladder wall and lumen. We report two cases of emphysematous cystitis of the urinary bladder in a 67-year-old and a 63-year-old women. They presented with bladder irritation symptoms such as dysuria, hematuria and frequency. Urinalysis showed pyuria. Cystoscopic examination revealed that bladder mucosa was studded with vesicles varying in size and arranged in clumps. CT scans of the pelvis showed mottled gas bubbles within the bladder. They were treated with antibiotics. Four days after the treatment, the symptoms subsided and plain abdominal film showed no evidence of gas shadows in the pelvic cavity.
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