Basic and clinical studies on tazobactam/piperacillin in pediatric field

A drug susceptibility test of the combination drug TAZ/PIPC, which consists of a newly developed beta-lactamase inhibitor, tazobactam (TAZ), and one of penicillin antibiotics, piperacillin (PIPC), with combination ratio of 1:4 in potency, was conducted with stock strains and clinical isolates. The clinical efficacy and safety of its injection was also evaluated in children with a variety of infectious diseases. The results were as follows: 1. In susceptibility test, 114 strains from 4 species of stock strains were treated with 8 drugs, that is, TAZ/PIPC, PIPC, penicillin G (PCG), ampicillin (ABPC), cefotiam (CTM), cefotaxime (CTX), ceftazidime (CAZ), and sulbactam/cefoperazone (SBT/CPZ). Of three clinically isolated species from patients, Staphylococcus aureus (S. aureus) was treated with TAZ/PIPC, PIPC, methicillin (DMPPC), CTM, CTX, and SBT/CPZ, and the others were treated with the same drugs except for DMPPC. The MICs were measured for these bacterial strains inoculated at the concentration of 10(6) CFU/ml. The MIC90 values of TAZ/PIPC against 45 strains of Streptococcus pyogenes (S. pyogenes), one of the stock cultures of Gram-positive cocci, were 0.05 microgram/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ. The MICs of TAZ/PIPC for 28 strains of Streptococcus agalactiae (S. agalactiae) were 0.39 microgram/ml and similar to those of PIPC, CTM, CAZ, and SBT/CPZ. As for Gram-negative bacilli, the MIC90 of TAZ/PIPC against 10 strains of Bordetella pertussis (B. pertussis) were 0.10 microgram/ml and similar to those of PIPC. The MIC90 of TAZ/PIPC against 31 strains of Haemophilus influenzae (H. influenzae) were 0.05 microgram/ml and similar to those of PIPC, CTX, and SBT/CPZ. Regarding Gram-positive cocci isolated from patients received this combination drug, the MIC90 of TAZ/PIPC against 2 strains of S. aureus, a non beta-lactamase producing strain and a low-beta-lactamase producing strain, were 0.78 microgram/ml and 3.1 micrograms/ml, respectively; the former value was similar to those of PIPC, DMPPC, CTM, and CTX, and the latter was similar to those of PIPC, DMPPC, CTX, and SBT/CPZ. Of 4 strains of Streptococcus pneumoniae, 2 strains were inhibited at 0.05 microgram/ml, and the others at 1.56 micrograms/ml; both values were similar to those of PIPC, SBT/CPZ. As for Gram-negative bacilli, 6 of 7 strains of H. influenzae did not produce beta-lactamase and 1 strain was a high producer. The MICs of TAZ/PIPC against beta-lactamase nonproducing strains were < or = 0.025 microgram/ml in 5 strains and 0.39 microgram/ml in 1 strain, and the values were similar to those of PIPC and SBT/CPZ. While the MIC of TAZ/PIPC against the high beta-lactamase producing strain was 0.78 microgram/ml; similar to that of SBT/CPZ and smaller than that of PIPC. 2. The results of clinical effects on 7 diseases in 33 cases were as follows: TAZ/PIPC was clinically judged "excellent" in 17 (51.5%); good in 14 (42.4%); fair in 2 (6.1%). No case with no response was seen in this study, and the total efficacy rate of "excellent" and "good" was 93.9%. 3. Bacteriological effects were evaluated in 17 strains of 4 species, and all of them were eradicated. 4. Adverse reactions were judged in 35, which consisted of 33 in which the clinical effects were evaluated and 2 dropped from this study. Of these cases, diarrhea was observed in 4 (11.4%). 5. Laboratory tests revealed an increase in platelets in 1 of 32 cases (3.1%), and eosinophilia in 2 of 29 cases (6.9%). Biochemical profile showed an increase in GPT alone and abnormal increases in both GOT and GPT in 1 each out of 21 cases.     

Interpretability in symbolic regression: a benchmark of explanatory methods using the Feynman data set

Genetic Programming and Evolvable Machines - In some situations, the interpretability of the machine learning models plays a role as important as the model accuracy. Interpretability comes from the...     

Anionic polymerization using rotating disk reactor (I)

Anionic polymerization of styrene with sodium naphthalene was carried out using the rotating disk reactor. The mode of disintegration of the polymerization mixture changed from dropwise to filamentwise and finally to filmwise within a few minutes of reaction at low speed revolution and a large amount of flow. Under the condition of high speed revolution and a small amount of flow, only dropwise disintegration was observed and a beadlike polymer was obtained having a unimodal molecular weight distribution. The polymer was found to have a bimodal distribution when the polymerization was terminated on the rotating disk. These results are explained by assuming that a highly viscous layer was formed near the disk surface.     

Strain rate sensitivity of a high strain rate superplastic TiNp/2014 Al composite

The effects of deformation temperature and strain in hot rolling deformation on strain rate sensitivity of the TiN_p/2014 Al composite were studied by tensile tests conducted out at 773, 798, 818 and 838 K with the strain rates from 1.7 ×10^?3 to 1.7 × 10⁰ s^?1. It is shown that the curves of m value of the TiN_p/2014Al composite deformed at different temperatures can be divided into two stages with the variation of strain rate, and the critical strain rates are 10^?1 s^?1. The optimum deformation temperature of the TiN_p/2014 Al composite is near incipient melting temperature of 816 K and the optimum strain rate is a little higher than the critical strain rate. The effect of deformation temperature on strain rate sensitivity is relative to liquid phase helper accommodation. The effect of strain in hot rolling deformation on strain rate sensitivity attributes to change of microstructure and deformation mechanism.     

Development of the arbitrarily primed-representational difference analysis method and chromosomal mapping of isolated high throughput rat genetic markers

Linkage mapping of quantitative trait loci requires analysis of a large number of animals. Although genetic markers isolated by representational difference analysis (RDA) and its modifications meet the needs, the number of these markers has been limited. In the present study, we established the arbitrarily primed (AP)-RDA method to isolate virtually an unlimited number of the high throughput genetic markers. A representation of the genome, an AP-amplicon, was prepared by AP-PCR with a single primer or with a combination of primers using genomic DNA of the ACI/N (ACI) or BUF/Nac (BUF) rat as a template. By subtracting the AP-amplicon of ACI from that of BUF, a total of 40 polymorphic and independent markers were isolated in seven series of AP-RDA using a single primer. Two series of AP-RDA with primer combination yielded seven additional independent markers. All of the markers gave clear positive/negative signals by hybridization of a filter where AP-amplicons from F2 rats of ACI and BUF were dot-blotted at a high density without any concentration or purification. All of the 47 independent markers were mapped to unique chromosomal positions by linkage analysis, even though some arbitrary primers had very similar sequences. The markers were also informative between other strains of rats. Simultaneous hybridization of multiple filters made it possible to genotype a large number of rats simultaneously for multiple genetic loci. The AP-RDA method promises isolation of a large number of high throughput genetic markers in any species and is expected to facilitate linkage mapping of subtle quantitative trait loci.     

Oxidation refining of iron using plasma-arc melting

Oxidation refining of Fe using plasma arc melting, by the addition of iron oxide as an oxidizing agent, has been carried out. In this refining process, an impurity element which has higher affinity for oxygen than iron was expected to be eliminated. As the result, decreases in Si, Mn, Al, Ca, Ga, and Zr were observed and 99.996 mass% of iron could be obtained from 99.93 mass% of electrolytic iron by plasma arc melting under oxidizing conditions followed by argon–hydrogen plasma arc melting. Specifically, the removal of Si was found to proceed by the distribution between in the liquid Fe phase and in the oxide phase. In addition, the relation of Si and oxygen concentration in liquid iron was consistent with the data in the literature.     

A novel filtering method to extract three critical yield losscomponents (gross, repeated, and random) FIMER

This paper describes a novel filtering method (FIMER) to extract three critical yield loss components: gross yield loss from parametric problems or from clustering of defects, repeated yield loss from mask defects or from lithography margin, and random yield loss mainly from particles. It is shown by simulation that FIMER is not only superior to the conventional windowing method in extracting repeated yield loss but also accurately extracts gross yield loss and random yield loss. The simulation studies show that the three components are extracted with an error equal to or less than 5% by optimizing threshold and filter weights, which are the major parameters in FIMER     

Up-regulation of nuclear PP1alpha and PP1delta in hepatoma cells

BACKGROUND: Although most previous studies have attempted to correlate plasma concentrations of vitamins with specific cardiovascular end points, metabolic considerations suggest that changes in myocardial tissue and storage organs may be better indicators of myocardial oxidative stress. METHODS AND RESULTS: Rats fed commercial chow or a diet enriched with vitamin E for 2 weeks were subjected to either a surgical myocardial infarction (MI) or a sham procedure. Rats were hemodynamically assessed 16 weeks after surgery, and their heart, liver, kidney, and plasma were analyzed for antioxidant vitamins E (tocopherol) and A (retinol and total retinyl esters). At 16 weeks, MI rats on a control diet showed depressed peak systolic and elevated diastolic pressures in both right and left ventricles compared with their sham controls. Plasma concentrations of vitamins E and A in MI rats were not different from sham controls fed the same diet. However, concentrations of vitamin E in left ventricle and liver and of vitamin A in liver (retinol) and kidney (retinyl esters) were decreased in rats with MI compared with the sham controls. Vitamin E supplementation improved hemodynamic function in rats with MI and increased plasma, myocardial, liver, and kidney concentrations of vitamin E. The vitamin E diet also prevented the loss of total retinyl esters from the kidney but not of retinol from the liver in MI rats. CONCLUSIONS: Dietary supplements of vitamin E can sustain better cardiac function subsequent to MI. Antioxidant vitamin levels in the myocardium or in storage organs and not in plasma may be better indicators of myocardial oxidative stress.     

Localization of a novel tumor suppressor gene associated with human oral cancer on chromosome 4q25

Recent cytogenetic and molecular studies with highly polymorphic microsatellite markers have implicated allele loss involving chromosome 4 in several human cancers, which suggests the presence of multiple tumor suppressor gene (TSG) loci. However, there has been no detailed analysis of loss of heterozygosity (LOH) on chromosome 4 in oral squamous cell carcinoma (OSCC). To determine the location of a putative TSG associated with OSCC on chromosome 4, polymerase chain reaction (PCR) analysis of microsatellite polymorphisms corresponding to 17 loci was performed to screen 32 patients with OSCC. LOH was observed in the majority of the tumors (75%) in at least one of the loci. The loci on the long arm exhibited a significantly higher frequency of deletions (66%) than those of the short arm (25%). Among the loci tested, frequent LOH was centered at D4S1573 on 4q25, which represents a region of about 4 centimorgans (cM). However, no commonly deleted regions were found on the short arm of the chromosome. We detected microsatellite instability (MI) in 31% of the cases. MI was also observed more frequently on the long arm (28%) than the short arm (6%). Thus, our data indicate that alterations of chromosome 4 regions, especially the long arm, are associated with OSCC tumorigenesis and that the 4q25 region may harbor at least one putative TSG.     

Budgets of major ionic species and nutrients on a dam reservoir in forested watershed.

To evaluate the role of a dam reservoir in the runoff of pollutant loadings from a forested watershed, the input-output budgets in the Ikuno dam reservoir had been investigated for eight years since 1996. The T-N, T-P, TOC and major ionic species in the bulk precipitation, stream water, and outflow were measured. The residence time calculated by using the data of the inflow and outflow was 0.3 year. The average precipitation was 1,772 mm during the investigation period (1996-2004). The direct deposition to water surface was less than one percentage to total loadings of nutrients and major ionic species. The ratios of output to input of TOC, TN, and TP were 1.04 to 1.42, and those of major ionic species were from 0.83 to 0.99 except for NO3(-), which was 1.12. However, the ratios of output to input of major ionic species except for NO3(-) at the Ikuno dam reservoir will be larger, and those of NO3(-), TOC, TN, and TP will be smaller, if we also include rain events. These results suggested that the dam reservoir played a role as a sink for pollutants in forested watershed, and that the pollutant loadings to downstream may decrease.