3-Alkyl-3-hydroxyglutaric acids: a new class of hypocholesterolemic HMG CoA reductase inhibitors. 1.

Derivatives of 3-hydroxy-3-methylglutaric acid (HMG), a portion of the substrate for HMG CoA reductase, were prepared and tested for their inhibitory action against rat liver HMG CoA reductase and for their hypocholesterolemic activity. Structure-dependent competitive inhibition was observed. Optimal structures had a free dicarboxylic acid with an alkyl group of 13-16 carbons at position 3. 3-n-Pentadecyl-3-hydroxyglutaric acid (3j) (IC50 = 50 microM) reduced serum cholesterol in the Triton-treated rat and HMG CoA reductase activity in the 20,25-diazacholesterol-treated rat.

Metal/cement interface strength in cemented stem fixation.

To characterize the strength of the interface between stem-type metal implants and bone cements, a fracture mechanics parameter was used. This parameter, the critical strain energy release rate (Gc), was determined from "push-out" tests of cylindrical specimens. The specimens, formed using molds of bone, were maintained and tested at body temperature. The strength of interfaces formed with cancellous bone surrounding the cement mantle was significantly less than the strength of those formed in apposition to cortical bone. A marked degradation of strength was found with saline immersion for SS316LVM/cement interfaces formed with Zimmer regular, Simplex-P, and Zimmer LVC cements. After 60 days of immersion the interface Gc was only 10-20% of the value for bulk cement. Interfaces formed with thin-film polymethylmethacrylate-precoated metals (SS316LVM, Co-Cr-Mo, and Ti-6A1-4V) yielded "dry" Gc values one order of magnitude greater than those measured with interfaces formed with uncoated metals. Moreover, the strength of precoated SS316LVM/cement interfaces formed with all three brands of cement did not change after saline immersion for 60 days.

Mandible height and syllable-final tenseness.

Mandible movements in the vowel-to-consonant transition manifest consistent differences between /t/ and /d/ in syllable final position. Both mandible position at its peak value near the articulatory release of the stop and velocity of its ascending movement in the transition are found to be apparently relevant to the tense/lax distinction, even though the reliability of these criteria for categorizing t/d data somewhat varies depending on the speaker. Some related characteristics of lingual movements and similar mandible characteristics for the k/g distinction are mentioned. The data were obtained by the computer-controlled X-ray microbeam system in cooperation with the University of Tokyo group.

Mechanical compatibility of noncemented hip prostheses with the human femur.

It is generally accepted that more flexible implants are needed to reduce stress shielding and postoperative thigh pain. However, there is no detailed information on the stiffness of currently used implants relative to the human femur. The purpose of this study was to determine the stiffness characteristics (bending, torsional, and axial) of human femora relative to commercially available prostheses as a first step in assessing the mechanical compatibility of the implants. This was achieved by computerized tomography scanning of a collection of human femora from proximal to distal at 10 mm intervals, digitizing the cross-sectional contours, and calculating the stiffness characteristics of each section using standard beam theory. The results show that significant stiffness mismatches exist, especially for larger stem sizes and for stems fabricated from cobalt-chrome alloy. Interestingly, certain implant stiffness values are lower than those of the femur for stems up to 15 mm in diameter, substantially so if the implant is made from titanium alloy and incorporates design features that reduce area and moments of inertia. The data suggest that only larger implant sizes need to be adjusted for increased flexibility compared with current stands.