Response of hypertrophied myocardium to ischemia: correlation with biochemical and physiological parameters

The increased susceptibility of hypertrophied hearts to ischemic injury during cardiac operations has long been recognized. Although the imbalances in oxygen supply and demand which may occur with hypertrophy during hypotension, ventricular fibrillation, or reperfusion have been extensively studied, the biochemical response of hypertrophied myocardium to ischemia has not been fully elucidated. In the present investigation, rat hearts in which hypertrophy was induced by chronic pressure overload were used to examine the relationship of the physiological parameter, ischemic contracture, to high-energy phosphate content and mitochondrial function during global ischemia. Hypertrophied hearts developed ischemic contracture after significantly shorter duration of ischemia than did normal hearts (5.8 +/- 0.3 minutes versus 10.1 +/- 0.7 minutes). High-energy phosphate content was lower in hypertrophied hearts at control and at ischemic contracture initiation and completion than in normal hearts, whereas mitochondrial function was consistently greater in the hypertrophy group. This investigation demonstrates that the hypertrophied myocardium, independent of flow-related events, is more vulnerable to ischemic injury than normal myocardium and suggests that the increased susceptibility may result from lower high-energy phosphate stores present at the onset of ischemia. The results emphasize the need for rapid cardiac arrest with the induction of ischemia in hypertrophied myocardium and suggest the potential for increasing myocardial high-energy phosphate content in the hypertrophied ventricle by interventions such as arrested perfusion with substrate containing oxygenated cardioplegic solutions prior to the onset of planned ischemia.     

Acoustic properties of normal and cancerous human liver—I. Dependence on pathological condition

Ultrasonic speed, attenuation and backscattering were measured as functions of frequency and orientation in specimens of exercised human liver, with a view to establishing the usefulness of such measurements to characterize the pathology and structure of the tissue. It is observed that acoustic speed is superior to any attenuation or backscattering characteristics for distinguishing in vitro between specimens of tumours and normal human liver selected at random. However, when the data are corrected for variations between one subject and another, sound speed, attenuation and the mean back-scattering coefficient at a given frequency show a comparable degree of usefulness in this respect. Analysis of the periodicities present in the backscattering diffraction patterns did not contribute any improvement in the ability to distinguish between tissue states. On average, by comparison with normal liver, ultrasound travels about 1.5% (± 1%) slower, is attenuated by about 20% (± 30%) less at 3 MHz and is backscattered by about 80% (±115%) less at 3 MHz in the tumor specimens that were measured. Livers infiltrated by diffuse malignant disease appear to possess quite different ultrasonic propagation properties to normal liver although insufficient data are yet available for firm conclusions to be drawn.     

5,6-Diaryl-2,3-dihydroimidazo[2,1-b]thiazoles: a new class of immunoregulatory antiinflammatory agents

A series of substituted 5,6-diaryl-2,3-dihydroimidazo[2,1-b]thiazoles were synthesized and evaluated in the rat adjuvant-induced arthritis and mouse oxazolone-induced contact sensitivity assays to determine the potential of these compounds for use as immunoregulatory antiinflammatory agents. This class of compounds was derived by combining salient structural features of the antiinflammatory agent flumizole and the immunoregulatory drug levamisole. Unlike the latter two, a number of compounds in the target series were found to possess the desired combination of activities. Exploration of structure-activity relationships in the adjuvant-induced arthritic rat assay revealed that optimal potency was exhibited by symmetrically substituted 5,6-diaryl compounds having one of the following alkyl heteroatom or halogen functions at the para position: methoxy, ethoxy, methylthio, N-ethyl-N-methylamino, fluoro, or chloro. Scrambling of these two substituent classes to yield the asymmetrically substituted 5,6-diaryl compounds resulted in potent activity only with the 5-alkyl heteroatom, 6-halo-substituted regioisomers. However in the oxazolone-induced contact sensitivity assay, no consistent relationship of variation in activity with structural change was apparent. The initial target compound 5,6-bis(4-methoxyphenyl)-2,3-dihydroimidazo[2,1-b]thiazole (1) was compared with its progenitors in additional models of inflammation and immunoregulation.     

EFFECTS OF THE INHALATION OF ENFLURANE ON HEPATIC MICROSOMAL ENZYMATIC ACTIVITIES IN THE RAT

We have investigated the possible hepatic microsomal enzymeinduction effect of enflurane, administered by inhalation inanaesthetic doses for periods of 1 h a day. In 15 experimentalgroups, differing from one another in anaesthetic concentration(1,2 and 3% enflurane) and in the number of days of treatment(3,7, 10,14,21 and 24) we found (1) no alteration either inthe ratio of liver to body weight or in the microsomal proteincontent; (2) no modifications in aniline hydroxylase activity;(3) a decrease in the aminopynne demethylase activity aftera number of exposures, varying with the dose.     

The enzymes of pyrimidine biosynthesis in a range of parasitic protozoa and helminths

The activities of carbamoylphosphate synthase, aspartate transcarbamoylase, dihydroorotase, orotate phosphoribosyl transferase and orotidine-5'-phosphate decarboxylase, five of the six enzymes of pyrimidine biosynthesis, have been measured in Crithidia fasciculata, Trypanosoma cruzi, Leishmania major, Trichomonas vaginalis, Eimeria tenella, Toxoplasma gondii, Plasmodium berghei, Fasciola gigantica, Schistosoma mansoni, Hymenolepis diminuta, Nippostrongylus brasiliensis and Trichuris muris. The majority of organisms contained all five enzyme activities. However, in T. vaginalis only carbamoylphosphate synthetase activity and in E. tenella only orotate phosphoribosyl transferase and orotidine-5'-phosphate decarboxylase activities could be detected. It appears therefore that the ability to synthesise pyrimidines by the de novo route is probably both common and widespread amongst parasitic organisms.     

Combined radionuclide and radiocontrast arthrography for evaluating hip arthroplasty

Twenty-two patients had combined radiographic and radiocolloid arthrography. The two procedures were in agreement in 86% of the patients as to whether the femoral component was loose or not. Fourteen patients has surgical revision of the prosthesis and in 3 (23%) radiographic arthrography was falsely negative. No false negative results were obtained with radiocolloid arthrography thus far. The radionuclide method cannot be used to assess the acetabular component.