Oral 5-aminolevulinic acid combined with sodium ferrous citrate prevents blood-aqueous barrier breakdown after anterior chamber paracentesis in healthy beagle dogs.

This study investigated the preventive effect of 5-aminolevulinic acid combined with sodium ferrous citrate (5-ALA/SFC) on blood-aqueous barrier (BAB) breakdown induced after anterior chamber paracentesis (ACP) in beagles. 5-ALA/SFC (1/0.64 mg/kg or 3/1.92 mg/kg) or carprofen (4.0 mg/kg) was orally administered daily for 7 days prior to ACP. Then, a sample of the aqueous humor (AH) was collected from one eye via ACP (first sample) and again 60 min later (second sample). The protein and prostaglandin E2 (PGE2) concentrations in both samples were measured. Compared with the control group, high-dose 5-ALA/SFC and carprofen significantly reduced the AH protein and PGE2 concentrations in the second sample. Our findings suggest that 5-ALA/SFC suppresses BAB breakdown in dogs.

Sodium Ferrous Citrate and 5-Aminolevulinic Acid Exert a Therapeutic Effect on Endotoxin-Induced Uveitis in Rats.

The metabolism of 5-aminolevulinic acid (ALA) is more efficient when combined with sodium ferrous citrate (SFC). Our previous study revealed that oral administration of ALA, which has anti-inflammatory properties, and SFC (ALA/SFC) immediately before lipopolysaccharide (LPS) inoculation suppressed endotoxin-induced uveitis (EIU) in rats. However, the therapeutic effect of ALA/SFC post-administration remains unexplored. Hence, this study aimed to evaluate the therapeutic efficacy of ALA/SFC on EIU in rats, which were administered with a gastric gavage of ALA/SFC (100/157 mg/kg) or prednisolone (Pred, 10 mg/kg) after 4 h of LPS inoculation. The treatment groups showed ameliorated clinical scores, inflammatory cells, protein levels in the aqueous humor (AqH), and histopathologic evaluation 24 h after LPS inoculation. Furthermore, the treatment groups had reduced tumor necrosis factor-α, nitric oxide, prostaglandin E2, and interleukin-6 levels in the AqH. ALA/SFC demonstrated an anti-inflammatory effect equivalent to that demonstrated by Pred. These findings indicate that ALA/SFC exerts a therapeutic effect on EIU in rats, indicating its clinical usefulness in uveitis treatment.

5-ALA/SFC Ameliorates Endotoxin-Induced Ocular Inflammation in Rats by Inhibiting the NF-κB Signaling Pathway and Activating the HO-1/Nrf2 Signaling Pathway.

Sodium ferrous citrate (SFC) is involved in the metabolism of 5-aminolevulinic acid (5-ALA) and enhances its anti-inflammatory effects. The effects of 5-ALA/SFC on inflammation in rats with endotoxin-induced uveitis (EIU) have yet to be elucidated. In this study, during lipopolysaccharide injection, 5-ALA/SFC (10 mg/kg 5-ALA plus 15.7 mg/kg SFC) or 5-ALA (10 or 100 mg/kg) was administered via gastric gavage, wherein we saw that 5-ALA/SFC ameliorated ocular inflammation in EIU rats by suppressing clinical scores; by infiltrating cell counts, aqueous humor protein, and inflammatory cytokine levels; and by improving histopathological scores to the same extent as 100 mg/kg 5-ALA. Immunohistochemistry showed that 5-ALA/SFC suppressed iNOS and COX-2 expression, NF-κB activation, IκB-α degradation, and p-IKKα/ß expression, and activated HO-1 and Nrf2 expression. Therefore, this study has investigated how 5-ALA/SFC reduces inflammation and revealed the pathways involved in EIU rats. 5-ALA/SFC is shown to inhibit ocular inflammation in EIU rats by inhibiting NF-κB and activating the HO-1/Nrf2 pathways.

Effects of Oral 5-Aminolevulinic Acid on Lipopolysaccharide-Induced Ocular Inflammation in Rats.

This study aimed to investigate the anti-inflammatory effect of 5-aminolevulinic acid (5-ALA) on endotoxin-induced uveitis (EIU) in rats. EIU was induced in male Sprague Dawley rats by the subcutaneous injection of lipopolysaccharide (LPS). During LPS injection, 5-ALA diluted with saline was administered via gastric gavage. After 24 h, clinical scores were assessed after which aqueous humor (AqH) samples were obtained. The number of infiltrating cells, protein concentration, and levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), and prostaglandin E2 (PGE2) in AqH were measured. For histological examination, both eyes of some rats were enucleated. In vitro, a mouse macrophage cell line (RAW264.7 cells) was stimulated by LPS with or without 5-ALA. Western blot was used to analyze the expression of inducible NO synthase (iNOS) and cyclooxygenase-2. 5-ALA suppressed the EIU clinical scores, infiltrating cell number, and protein concentration while improving the histopathologic scores. In particular, 100 mg/kg 5-ALA reduced the concentrations of NO, PGE2, TNF-α, and IL-6 in AqH, similar to 1 mg/kg prednisolone. In addition, 5-ALA suppressed iNOS upregulation in LPS-stimulated RAW264.7 cells. Therefore, 5-ALA has an anti-inflammatory effect on EIU through the inhibition of the upregulation of inflammatory mediators.

Denileukin diftitox-induced systemic capillary leak syndrome with acute kidney injury.

Systemic capillary leak syndrome is a rare and life-threatening disorder, characterized by recurrent episodes of unexplained hypotension, hemoconcentration, and hypoalbuminemia. This condition is caused by leakage of plasma and proteins into the extravascular space and can be classified as either idiopathic or secondary. Secondary systemic capillary leak syndrome can result from cancer, infections, medications, or surgery. Systemic capillary leak syndrome frequently develops as a side effect of denileukin diftitox treatment of refractory cutaneous T-cell lymphoma. However, the pathophysiology of this disease is not well understood. Herein, we report a case of denileukin diftitox-induced systemic capillary leak syndrome.

Novel insights into host specificity of Pyricularia oryzae and Pyricularia grisea in the infection of gramineous plant roots.

Pyricularia oryzae and Pyricularia grisea are pathogens that cause blast disease in various monocots. It has been reported that P. oryzae infects the leaves and roots of rice via different mechanisms. However, it is unclear to what extent the tissue types affect the host specificities of P. oryzae and P. grisea. Here, we evaluated the tissue-specific infection strategies of P. oryzae and P. grisea in various gramineous plants. Generally, mycelial plug inoculation caused root browning but the degree of browning did not simply follow the disease index on leaves. Interestingly, the Triticum and Digitaria pathotypes caused strong root growth inhibition in rice, wheat, and barley. Moreover, the Digitaria pathotype inhibited root branching only in rice. Culture filtrate reproduced these inhibitory effects on root, suggesting that some secreted molecules are responsible for the inhibitions. Observation of root sections revealed that most of the infection hyphae penetrated intercellular spaces and further extended into root cells, regardless of pathotype and host plant. The infection hyphae of Digitaria and Triticum pathotypes tended to localize in the outer layer of rice roots, but not in those of wheat and barley roots. The infection hyphae of the Oryza pathotype were distributed in both the intercellular and intracellular spaces of rice root cells. Pathogenesis-related genes and reactive oxygen species accumulation were induced after root inoculation with all combinations. These results suggest that resistance reactions were induced in the roots of gramineous plants against the infection with Pyricularia isolates but failed to prevent fungal invasion.

Retention, Bacterial Adhesion, and Biofilm Formation between Anionic and Zwitterionic Bandage Contact Lenses in Healthy Dogs: A Pilot Study.

This study aimed to compare the in vitro and in vivo retention, bacterial adhesion, and biofilm formation between anionic and zwitterionic bandage contact lenses (BCLs) in healthy canines. BCL retention and tolerance were evaluated in 10 healthy canines via a single-masked, crossover study for 7 days. To compare in vitro bacterial adhesion and biofilm formation, four Staphylococcus strains were incubated with the BCLs at 37 °C for 2 or 24 h, and the bacterial colony forming units (CFUs) adhering to the BCLs were counted. Next, to compare in vivo bacterial adhesion, the CFUs of bacteria adhering to the BCLs worn by canines for 24 h were counted. Anionic lenses significantly retained and reduced in vitro bacterial adhesion than in the zwitterionic lenses. However, the amount of in vitro biofilm formation was more likely to be higher on anionic lenses than on zwitterionic lenses. In vivo bacterial adhesion was not significantly different between the two types of BCLs. Nevertheless, both BCLs were well-tolerated by the canines; thus, their short-term use in dogs can be recommended as safe.

Accelerating the Smith-Waterman algorithm with interpair pruning and band optimization for the all-pairs comparison of base sequences.

BACKGROUND: The Smith-Waterman algorithm is known to be a more sensitive approach than heuristic algorithms for local sequence alignment algorithms. Despite its sensitivity, a greater time complexity associated with the Smith-Waterman algorithm prevents its application to the all-pairs comparisons of base sequences, which aids in the construction of accurate phylogenetic trees. The aim of this study is to achieve greater acceleration using the Smith-Waterman algorithm (by realizing interpair block pruning and band optimization) compared with that achieved using a previous method that performs intrapair block pruning on graphics processing units (GPUs). RESULTS: We present an interpair optimization method for the Smith-Waterman algorithm with the aim of accelerating the all-pairs comparison of base sequences. Given the results of the pairs of sequences, our method realizes efficient block pruning by computing a lower bound for other pairs that have not yet been processed. This lower bound is further used for band optimization. We integrated our interpair optimization method into SW#, a previous GPU-based implementation that employs variants of a banded Smith-Waterman algorithm and a banded Myers-Miller algorithm. Evaluation using the six genomes of Bacillus anthracis shows that our method pruned 88% of the matrix cells on a single GPU and 73% of the matrix cells on two GPUs. For the genomes of the human chromosome 21, the alignment performance reached 202 giga-cell updates per second (GCUPS) on two Tesla K40 GPUs. CONCLUSIONS: Efficient interpair pruning and band optimization makes it possible to complete the all-pairs comparisons of the sequences of the same species 1.2 times faster than the intrapair pruning method. This acceleration was achieved at the first phase of SW#, where our method significantly improved the initial lower bound. However, our interpair optimization was not effective for the comparison of the sequences of different species such as comparing human, chimpanzee, and gorilla. Consequently, our method is useful in accelerating the applications that require optimal local alignments scores for the same species. The source code is available for download from http://www-hagi.ist.osaka-u.ac.jp/research/code/.