Histamine release inhibition in anti-inflammatory mechanism

Rats were depleted of skin histamine by more than 80 % by intraperitoneal injections of sinomenine with daily increasing doses for 6 days. In these rats, egg-white edema induced in the hind paws was inhibited by 68 % of control. The weight of the wall of granuloma pouch made by croton oil was also evidently smaller in the rat treated similarly with sinomenine than that of control. This suggests an important role of histamine participating in the inflammation. It has been observed that a variety of non-steroidal anti-inflammatory drugs inhibited both degranulation and histamine release induced by compound 48/80 of mast cells isolated from rat peritoneal fluid. The degranulation inhibiting actions of anti-inflammatory drugs were markedly decreased in the presence of glucose as in cases of dinitrophenol, dicumarol and warfarin which are known uncouplers of oxidative phosphorylation. Also, prevention of edema provoked by anti-rat serum is roughly correlated to a potency of degranulation inhibiting effect of anti-inflammatory agents. These observations suggest that there is a common mechanism between these two phenomena, and the prevention of mast cell degranulation by the anti-inflammatory agents is, at least, partially due to their uncoupling effects. A working hypothesis explaining the process of edema formation at the inflammatory site has. been made based on the data of the present experiment and other ob3ervations: a leakage of plasma into the tissue space from the gap between two adjacent endothelial cells which are contracted by released histamine may activate a kinin-forming system in the plasma, and kinin(s) may further aggravate a leakage. The mechanism of action of anti-inflammatory agents, which interfere with the histamine effect in inflammation, should be understood in twofold: one is prevention of histamine release from the tissue, mainly by inhibiting mast-cell degranulation, and the other is prevention of the contraction of endothial cells by their uncoupling activities.</p

Novel scotoma detection method using time required for fixation to the random targets

We developed a novel scotoma detection system using time required for fixation to the random targets, or the” eye-guided scotoma detection method “. In order to verify the” eye-guided scotoma detection method “, we measured 78 eyes of 40 subjects, and examined the measurement results in comparison with the results of measurement by Humphrey perimetry. The results were as follows: (1) Mariotte scotomas were detected in 100% of the eyes tested; (2) The false-negative rate (the percentage of cases where a scotoma was evaluated as a non-scotoma) was less than 10%; (3) The positive point distribution in the low-sensitivity eyes was well matched. These findings suggested that the novel scotoma detection method in the current study will pave the way for the realization of mass screening to detect pathological scotoma earlier.[Author summary] Conventional perimeters, such as the Goldmann perimeter and Humphrey perimeter, require experienced examiners and space occupying. With either perimeter, subjects’ eye movements need to be strictly fixed to the fixation target of the device. Other perimeters can monitor fixation and automatically measure the visual field. With the eye-guided scotoma detection method proposed in the current study, subjects feel less burdened since they do not have to fixate on the fixation target of the device and can move their eyes freely. Subjects simply respond to visual targets on the display; then, scotomas can be automatically detected. The novel method yields highly accurate scotoma detection through an algorithm that separates scotomas from non-scotomas

Efficacy and Tolerability of Weekly Paclitaxel in Combination with High-dose Toremifene Citrate in Patients with Metastatic Breast Cancer

Toremifene citrate is expected to prevent drug resistance in cancer patients by inhibiting p-glycoprotein activity. The safety and efficacy of combination therapy with high-dose toremifene citrate and paclitaxel were investigated. Between December 2003 and June 2004, 15 women with a mean age of 53 years old with metastatic breast cancer were enrolled. The administration schedule was 80mg/m2 of paclitaxel given on Days 1, 8, and 15, and 120mg/day of toremifene citrate orally administered starting on Day 18. On Days 32 and 39, paclitaxel was concurrently administered again. Toxicities, response rate, and time to treatment failure were assessed. All patients had been treated with endocrine or chemotherapy. Grade 3 leukopenia occurred in 2 patients on the administration of paclitaxel alone, and grade 3 febrile neutropenia occurred in 1 patient given the combination therapy. There was no grade 3 or greater non-hematological toxicity. There was no complete response and 1 partial response, producing a response rate of 6.7%. Median time to treatment failure was 2.7 months. Combination therapy of paclitaxel and toremifene was safe and well tolerated with minimal toxicity. Further clinical trials targeting patients with functional p-glycoprotein are warranted.</p

Multi Proxy Anchor Loss and Effectiveness of Deep Metric Learning Performance Metrics

Deep metric learning (DML) learns the mapping, which maps into embedding space in which similar data is near and dissimilar data is far. However, conventional proxy-based losses for DML have two problems: gradient problems and applying the real-world dataset with multiple local centers. Besides, DML performance metrics also have some issues have stability and flexibility. This paper proposes multi-proxies anchor (MPA) loss and normalized discounted cumulative gain (nDCG@k) metric. This study contributes three following: (1) MPA loss is able to learn the real-world dataset with multi-local centers. (2) MPA loss improves the training capacity of a neural network owing to solving the gradient issues. (3) nDCG@k metric encourages complete evaluation for various datasets. Finally, we demonstrate MPA loss's effectiveness, and MPA loss achieves higher accuracy on two datasets for fine-grained images

The Effect of Bovine Brain Gangliosides on Essential Tremor

We reported the case of a 74-year-old woman suffering from essential tremor for 20 years which was treated effectively with purified bovine brain gangliosides containing GM1, GD1a, GD1b and GT1b gangliosides. The trials of the treatment were conducted twice, 40 mg and 20 mg gangliosides per day respectively administered intramuscularly. Essential tremor dramatically improved with gangliosides on the second day of treatment, suggesting that the effect of gangliosides was not induced by neuronal sprouting or regeneration. It is speculated that a certain type of essential tremor is a reversible disease of membrane disorder