Acceleration of glycolysis in erythrocytes by the antidiabetic agent M16209

The effects of M16209 (1-(3-bromobenzofuran-2-ylsulfonyl)hydantoin), an antidiabetic agent and aldose reductase inhibitor, on glycolysis were studied in rat and human erythrocytes in vitro. M16209 increased lactate production from glucose when incubated with rat and human erythrocytes, and also increased glucose consumption in rat erythrocytes. The rates of production of lactate in rat erythrocytes treated with M16209 at 10, 25 and 50 microM were 113, 118 and 123%, respectively, of those in vehicle treated cells. Sorbinil (aldose reductase inhibitor), tolbutamide (sulfonylurea), and buformine (biguanide) did not increase lactate production in rat erythrocytes when tested at 50 microM. On the other hand, M16209 did not affect lactate production from D-glyceraldehyde in rat erythrocytes. At 100 microM the agent decreased both glucose-6-phosphate and fructose-6-phosphate in rat erythrocytes, and increased fructose-1,6-bisphosphate; at 10 microM it also increased 6-phosphofructokinase activity in rat hemolysates. These findings suggest that M16209 accelerates glycolysis in erythrocytes via activation of 6-phosphofructokinase.     

Effects of olprinone on IL-6 and IL-10 production during and after cardiac surgery

Phosphodiesterase inhibitor (PDEI) has been accepted as an inodilator with positive inotoropic and vasodilating actions. Recently many new PDEIS have been available for the treatment of heart failure. We investigated the effect of a new PDEI-III agent, olprinone, on IL-6 and IL-10 production during and after coronary bypass graft surgery (CABG). Twelve patients scheduled for CABG were assigned to 2 groups. In 6 patients (Group-O), olprinone was administered continuously for 30 minutes at a rate of 0.3 micrograms.kg-1.min-1 (gamma) after the anesthesia induction. Then, the infusion rate of olprinone was decreased to 0.2 gamma and it was kept until the 3rd post-operative day. In another 6 patients (Group-C), phentolamine was used for vasodilator instead of olprinone. The plasma levels of IL-6 in Group-O did not show any significant change during perioperative period, whereas those in Group-C reached the peak at the end of extracorporeal circulation and did not recover to control level until the 3rd post-operative day. The plasma levels of IL-10 in Group-O increased to the maximum level at the end of extra-corporeal circulation and were significantly higher than those in Group-C. It is suggested that olprinone has not only inodilating action but also anti-inflammatory action at therapeutic concentrations used for heart failure.     

Estimation of adverse drug reactions by the evaluation scores of subjective symptoms (complaints) and background of patients. I. Drug-induced liver disorders

The purpose of this study was to develop, implement, and assess an estimation procedure for preventing drug-induced liver disorders. We have built a database for CARPIS (case reports of adverse drug reaction and poisoning information services) since 1987, and the case reports of adverse drug reaction accumulated in the CARPIS database to be total about 11,000. We studied the estimation procedure by evaluating the subjective symptoms, backgrounds and laboratory data of patients in 199 cases cumulated in the CARPIS database. The evaluation scores were created on the basis of the subjective symptoms and backgrounds of the patients. Then, we re-estimated 199 cases with the evaluation scores, among which were 165 cases (82.9%) in 199 cases drug-induced liver disorders. For the rest of 34 cases (17.1%) drug-induced liver disorders could not be estimated from our evaluation scores. These 34 cases were either those which the subjective symptoms were not described in their reports, because the patients were hospitalized for other diseases and drug-induced liver disorders were discovered by a clinical examination, or cases of infants for whom it was difficult to confirm the subjective symptoms. The validity of this evaluation scores were sensitivity = 82.9%, specificity = 91.0% and predictive value of positive test = 94.8%. To apply this evaluation scores onto the clinical practice, we prepared an evaluation form for the subjective symptoms and backgrounds of the patients with drug suspecting-induced liver disorders.     

Is GBV-C (hepatitis G virus) an innocent bystander?

Kangari, an earthenware brazier containing burning charcoal, is used for personal warming during the winter months by most of the people in Kashmir valley. Kangari is usually held close to the lower abdomen or in between the legs while squatting on the ground. The use of kangari is associated with development of skin cancer at the sites of prolonged exposure. In the present study 43 patients with Kangari cancer were analyzed prospectively with the objective of understanding their clinico-pathological profile and the response to various treatment modalities. Variables such as age, gender, grade, site of lesion etc., were evaluated for their prognostic significance.     

Neural networks in computational mechanics

Summary In this paper, recent neural network applications, epecially to the fields related with the computational mechanics, were surveyed. The most outstanding characteristics of the neural network aided computation is that neither complicated programmings nor rigid algorithms are needed. Another important point is that the neural network's inherent parallelism, that is, concurrent signal transmissions over numerous, information processing elements suits the massively parallel computer architectures. First, we briefly review the neural network applications to the computational mechanics fields from recent publications, and describe the mathematical basis of the neural network. Next, the following topics are detailed: quantitative nondestructive evaluation, structural identification, modeling of viscoplastic material behaviors, crack growth analysis of welded specimens, structural design, parameter estimation for nonlinear finite element analyses, and equation solver.     

High-performance guided-wave multi/demultiplexer based on novel design using embedded gradient-index waveguides in glass

A guided-wave multi/demultiplexer which comprises low-loss gradient-index ion-exchange waveguides embedded in a glass substrate and optimised interference filters was successfully fabricated. Around ? 1dB insertion losses for demultiplexing and less than 2dB insertion losses for multiplexing with sufficient transmission bandwidth as wide as 66 nm were achieved.     

A four-level storage 4-Gb DRAM

A 4-Gb DRAM with multilevel-storage memory cells has been developed. This large memory capacity is achieved by storing data at four levels, each corresponding to two-bit-data storage in a single memory cell. The four-level storage reduces the effective cell size by 50%. A sense amplifier using charge coupling and charge sharing was developed for the four-level sensing and restoring. The sense amplifier uses a hierarchical bit-line scheme and operates in a time-sharing mode, thus reducing the sense amplifier area. A 4-Gb DRAM fabricated using 0.15-μm CMOS technology measures 986 mm². The memory cell is 0.23 μm². Its capacitance of 60 fF is achieved by using a high-dielectric-constant material BST     

A novel glycoprotein obtained from Chlorella vulgaris strain CK22 shows antimetastatic immunopotentiation

A glycoprotein extract (CVS), derived from the unicellular green alga Chlorella vulgaris, strain CK22, exhibited a pronounced antitumor effect against both spontaneous and experimentally induced metastasis in mice. Inhibition of tumor metastasis was enhanced when intratumor administration of CVS was followed by s.c. injection of CVS. Anti-metastatic immunopotentiation was observed in euthymic mice, but not in athymic nude mice. The antitumor activity of CVS was reflected in antigen-specific, T-cell-mediated immunity. Both CD4 and CD8 T cells contributed to the antimetastatic effects, as shown by in vivo depletion experiments with anti-T-cell subset antibodies. Furthermore, CVS caused the recruitment of T cells to the regional lymph nodes and their proliferation in these organs. The CD4-positive population, following CVS injection at the time of tumor rechallenge, displayed a pronounced increase in the proportion of T cells that were CD18 bright, CD44 bright, CD25+, CD54+, CD69+ or CD71+ in the lymph nodes. Thus, CVS induces T cell activation in peripheral lymph nodes in tumor-bearing mice. We conclude that CVS augments antimetastatic immunity through T cell activation in lymphoid organs and enhances recruitment of these cells to the tumor sites. Presurgical treatment with CVS might prevent metastasis or tumor progression.