Effects of fluvastatin, a new inhibitor of HMG-CoA reductase, and niceritrol on serum lipids, lipoproteins and cholesterol ester transfer activity in primary hypercholesterolemic patients

Effects of a combination therapy of fluvastatin, a new inhibitor of HMG-CoA reductase, and niceritrol on lipid metabolism were investigated measuring a wide range of parameters in 42 patients with primary hypercholesterolemia. After a wash-out period patients were randomly allocated to 1 of the 2 groups, the fluvastatin-preceding group (G-1) and the niceritrol-preceding group (G-2). In G-1 fluvastatin monotherapy (30 mg/day) significantly decreased total cholesterol (TC) and LDL-cholesterol (LDL-C). There was no significant change in HDL-cholesterol (HDL-C), triglyceride (TG) and lipoprotein (a) (Lp(a)). Further effect in HDL-C and TG was observed after the addition of niceritrol (750 mg/day). On the other hand, in G-2, while niceritrol alone (750 mg/day) produced no significant change in TC, LDL-C, HDL-C, TG and Lp(a), the addition of fluvastatin (30 mg/day) reduced TC and LDL-C levels significantly. Cholesterol ester transfer (CET) activity was significantly reduced by niceritrol monotherapy. After the concomitant use of the 2 drugs CET activity was significantly reduced only in G-2. No significant change in lipoprotein lipase and hepatic triglyceride lipase activities were observed in the 2 groups at either point in time. No serious adverse effect was observed in this study. It is concluded that fluvastatin is an effective drug for lowering LDL-cholesterol and causes no adverse alteration in lipid metabolism. Combination with niceritrol at a dose of 750 mg/day dose not appear to augment or attenuate beneficial effects of fluvastatin.     

Monolithic bioreactor immobilizing trypsin for high-throughput analysis

A miniaturized trypsin reactor was prepared by coating a trypsin-containing gel on a porous silica monolith. The trypsin-encapsulated gel was prepared by the sol-gel method. The sol-gel reaction was optimized so that the sol solution containing trypsin forms a thin film on the sol-gel monolith. The trypsin was encapsulated into the gel matrix without losing its activity. The silica monolith was fabricated to fit into a 96-well microtiter plate well and could then be easily removed. The trypsin-immobilized monolith was reacted in the 96-well microtiter plate. After the reaction, the monolith was removed, and the enzymatic activity was measured. The large surface area of the monolith enabled the immobilized trypsin to achieve a high catalytic turnover rate. Furthermore, the kinetic parameter of the immobilized trypsin indicates the absence of diffusional limitations. The durability and repeatability of the fabricated trypsin-coated monolith was tested and found to be satisfactory. The encapsulated trypsin exhibits an increased stability even after continuous use compared with that in free solution. Furthermore, this on-plate bioreactor was applicable to the digestion of protein with multiple cleavage sites.     

Compositional and histological comparison of carbonate apatite fabricated by dissolution–precipitation reaction and Bio-Oss<Superscript>®</Superscript>

Carbonate apatite (CO₃Ap) is an inorganic component of bone. This study aimed to compare the composition and tissue response to of CO₃Ap (CO₃Ap-DP) fabricated by the dissolution–precipitation reaction using calcite as a precursor and Bio-Oss®, which is widely used in orthopedic and dental fields as a synthetic bone substitute. X-ray diffraction and Fourier transform infrared results showed that CO₃Ap-DP and Bio-Oss® were both B-type carbonate apatite with low crystallinity. The average sizes of CO₃Ap-DP and Bio-Oss® granules were 450?±?58 and 667?±?168μ?m, respectively, and their carbonate contents were 12.1?±?0.6 and 5.6?±?0.1?wt%, respectively. CO₃Ap-DP had a larger amount of CO₃ than Bio-Oss® but higher crystallinity than Bio-Oss®. When a bone defect made at the femur of rabbits was reconstructed with CO₃Ap-DP and Bio-Oss®, CO₃Ap-DP granules were partially replaced with bone, whereas Bio-Oss® remained at 8 weeks after implantation. CO₃Ap-DP granules elicited a significantly larger amount of new bone formation at the cortical bone portion than Bio-Oss® at 4 weeks after the implantation. The results obtained in the present study demonstrated that CO₃Ap-DP and Bio-Oss® showed different behavior even though they were both classified as CO₃Ap. The CO₃ content in CO₃Ap played a more important role than the crystallinity of CO₃Ap for replacement to bone and high osteoconductivity.

Open image in new window

     

An Instance vs. The Instance

This article argues how one problem of computing lies in realizing a significant instance given a class or type. Analysis of a case study on digital narrative suggests two general processes for instantiating significant instances: interaction and optimization. The article then explains how the problem of universals needs to be deconstructed when trying to understand what type of entities significant instances are and what the process for obtaining them is.

Flexible humidity sensor in a sandwich configuration with a hydrophilic porous membrane

We constructed a wearable and flexible humidity sensor (thickness: 80 μm) in a sandwich configuration, with a hydrophilic poly-tetrafluoroethylene membrane placed between two gold deposited layers, using soft-MEMS techniques. The device was used to measure humidity level, via its electrical conductivity, using a multi-frequency LCR-meter at frequencies ranging from 100 Hz to 100 kHz. The device was calibrated at 100 Hz against moist air over the range of 30–85% RH, which includes normal humidity levels in the atmosphere and physiological air such as breath and evaporating sweat. The response sensitivity of the humidity device was extremely high, even for recovery to dry air; for example response time was less than 1 s for a conductivity shift between humid air of 80% RH and dry air of −60 °C dew point. The sensor performance was reproducible over multiple measurements, with a coefficient of variation of 1.77% (n = 5). The sensor was appropriate for physiological applications, and was successfully used in two non-invasive approaches: to monitor breath air at the mouth, and to measure sweat moisture from the nostrils.     

Assessment of groundwater pollution in Tokyo using PPCPs as sewage markers

While the occurrence of pharmaceuticals and personal care products (PPCPs) in groundwater has typically been reported in bank filtration sites, irrigated fields, septic tanks, and sewage disposal practices, fewer studies have been conducted in highly urbanized areas, where infiltration of treated or untreated sewage is not supposed to be a source of groundwater recharge. Furthermore, little is known about the occurrence of various kinds of PPCPs in relation to microbial indicators in groundwater from different types of aquifers. Thus, we examined the city-wide occurrence of selected PPCPs (diethyltoluamide, crotamiton, ethenzamide, propyphenazone, carbamazepine, and caffeine) and E. coli in 50 groundwaters from unconfined aquifers (<30 m in depth) and confined aquifers (up to 500 m in depth) in Tokyo, where unintended groundwater contamination could take place due to decrepit sewer networks. PPCPs were detected in unconfined aquifers and springs (23/34 samples, 68%), and in confined aquifers (7/16 samples, 44%). Compared with published results for sewage influents, concentrations of PPCPs, excluding caffeine, were generally 1-2 orders of magnitude lower, while in some samples concentrations were quite comparable. The high occurrence rate of PPCPs, even in confined aquifers, indicated that such aquifers are not always protected from pollution by sewage near the land surface. Among the PPCPs analyzed, carbamazepine and crotamiton were most frequently detected, which would appear to be owing to their high persistence, combined with the high concentration of crotamiton in sewage. Crotamiton was detected in all four E. coli-positive groundwaters, and thus may potentially serve as a precautionary indicator of E. coli contamination. Using carbamazepine as a sewage marker, we estimated that 0.8%-1.7% of the dry-weather flow of sewage was leaking out into the unconfined aquifers.     

Germline Whole-Gene Deletion of FH Diagnosed from Tumor Profiling

Hereditary leiomyomatosis and renal cell carcinoma (HL (RCC)) entails cutaneous and uterine leiomyomatosis with aggressive type 2 papillary RCC-like histology. HLRCC is caused by pathogenic variants in the FH gene, which encodes fumarate hydratase (FH). Here, we describe an episode of young-onset RCC caused by a genomic FH deletion that was diagnosed via clinical sequencing. A 35-year-old woman was diagnosed with RCC and multiple metastases: histopathological analyses supported a diagnosis of FH-deficient RCC. Although the patient had neither skin tumors nor a family history of HLRCC, an aggressive clinical course at her age and pathological diagnosis of FH-deficient RCC suggested a germline FH variant. After counseling, the patient provided written informed consent for germline genetic testing. She was simultaneously subjected to paired tumor profiling tests targeting the exome to identify a therapeutic target. Although conventional germline sequencing did not detect FH variants, exome sequencing revealed a heterozygous germline FH deletion. As such, paired tumor profiling, not conventional sequencing, was required to identify this genetic deletion. RCC caused by a germline FH deletion has hitherto not been described in Japan, and the FH deletion detected in this patient was presumed to be of maternal European origin. Although the genotype-phenotype correlation in HLRCC-related tumors is unclear, the patient’s family was advised to undergo genetic counseling to consider additional RCC screening.     

Extractive components of boiled–dried scallop adductor muscle and effect on the taste of soup after mixing with chicken leg meat

The extractive components of raw and boiled–dried scallop adductor muscle were examined. On a dry weight basis the levels of total free amino acids, total adenosine triphosphate (ATP) and related compounds, and betaines in the boiled–dried sample were lower than those in the raw muscle, which may have been due to the outflow of these compounds during boiling. Soup prepared from the boiled–dried scallop and chicken leg meat was assessed by sensory evaluation. This soup cooked with the scallop and chicken was stronger in sweetness, umami and body and rated higher in overall preference than the soup containing these ingredients after cooking separately. The inosine monophosphate (IMP) level in the former soup was 4.4 times higher than that in the latter. The adenosine monophosphate (AMP) deaminase (EC 3.5.4.6) activity in the crude extract from the chicken meat was 9.16 units l^?1, whereas no activity could be detected in the crude extract from the boiled–dried scallop. It is concluded that AMP, which was mainly derived from the boiled–dried scallop, was converted to IMP by AMP deaminase from the chicken meat during the preparation of the soup, resulting in an improvement in the taste. Copyright © 2004 Society of Chemical Industry