Factors responsible for neurofibrillary tangles and neuronal cell losses in tauopathy

TgTauP301L mice that overexpress the mutant human tauP301L present in FTDP-17 reproduce neurofibrillary tangles (NFTs), neuronal cell losses, memory disturbance, and substantial phenotypic variation. To demonstrate factors responsible for NFT formation and neuronal cell losses, sets of TgTauP301L for comparison with or without NFTs and neuronal cell losses were studied with oligonucleotide microarrays. Gene expressions were altered in biological pathways, including oxidative stress, apoptosis, mitochondrial fatty acid betaoxidation, inflammatory response pathway, and complement and coagulation cascade pathways. Among 24 altered genes, increased levels of apolipoprotein D (ApoD) and neuronal PAS domain protein 4 (Npas4) and decreased levels of doublecortin (DCX) and potassium channel, voltage-gated, shaker-related subfamily, β member 1 (Kcnab1) were found in the TgTauP301L with NFTs and neuronal cell losses, Alzheimer's brains, and tauopathy brains. Thus, many biological pathways and novel molecules are associated with NFT formation and neuronal cell losses in tauopathy brains.     

Intraocular penetration of itraconazole in patient with fungal endophthalmitis

The purpose of this study was to determine the penetration of itraconazole, a type of azole antifungal agent, into the aqueous humor and vitreous after repeated oral administrations. Fungal endophthalmitis developed bilaterally in a 21-year-old man who had a history of intravenous hyperalimentation following abdominal surgery. Itraconazole capsules (200 mg/day) were taken orally for 12 consecutive days. Vitrectomy was performed on the left eye 30 h after the last oral itraconazole. Samples of blood, aqueous, and vitreous were collected during the vitrectomy. The concentration of itraconazole was determined by high performance liquid chromatography. The concentration of itraconazole was 0.492 μg/mL in the plasma, 0.020 μg/mL in the vitreous, and none in the aqueous of the left eye. Although no fungal organisms were isolated from the plasma and vitreous samples from both eyes, fungal DNA was detected in the vitreous from the left eye. Our findings indicate that oral itraconazole has limited penetration in eyes with fungal endophthalmitis.