Metalloproteinase inhibitors from bovine cartilage and body fluids

Inhibitors of the mammalian metalloproteinases, collagenase, proteoglycanase and gelatinase were isolated from bovine cartilage (extracts and culture medium) and bovine amniotic fluid and serum. These inhibitors either bind or do not bind to concanavalin-A--Sepharose, with Mr (gel filtration) of about 30 000 and 20 000, respectively. Cartilage and chondrocyte culture media contained only concanavalin-A-binding inhibitors whereas cartilage extracts contained only a non-binding inhibitor: serum and amniotic fluid contained both forms of inhibitory activities. In moist biochemical respects, particularly in their abilities to inhibit metalloproteinases, all of the inhibitors were found to be similar. It is concluded that the forms of the inhibitors that differ in Mr may be closely related to the tissue inhibitor of metalloproteinases (TIMP) previously purified from rabbit and human sources. These findings help to clarify other studies on collagenase inhibitors and support the concept that TIMP-like inhibitors may be important in the control of connective tissue degradation.     

Protamines in plant sperm

Sperm protamines have been isolated from representatives of three major plant groups: algae (Chara corallina ), bryophytes ( Marchantia polymorpha), and ferns ( Marsilea vestitia ). We previously reported the complete displacement of histones by protamines in Marchantia (Reynolds W F & Wolfe, S L, Exp cell res 116 (1978) 269 [8] ). Marchantia protamines appear as four components on acid-urea gels, whereas Chara and Marsilea protamines comigrate as a single band with a mobility comparable to salmon protamine. The amino acid compositions of the plant protamines show these to be arginine-rich, highly basic (35-42%) proteins which display overall similarity in amino acid composition (84-91%). The molecular weights of Chara and Marsilea protamines are approx. 4700-5300 D.     

N-dealkylation of chlorimipramine and chlorpromazine in patients undergoing chronic treatment with both drugs: preliminary results

Data obtained in this preliminary study show that in patients chronically treated either with Chlorimipramine (n = 6) or with Chlorpromazine (n = 2), significant amounts of the corresponding Nor1- and Nor2-metabolites were detected in plasma. The role of these metabolites in the overall therapeutic effect is under investigation.     

Nodulation studies on legumes exotic to Australia: Hedysarum coronarium

Abstract Symbiotic experiments in glasshouse, controlled environment cabinet, and field were conducted with four lines of sulla ( Hedysarum coronarium ) and 15 strains of Rhizobium spp. This plant is highly Rhizobium -specific and appropriate strains are most unlikely to occur naturally in Australia. Under several sets of experimental conditions, H. coronarium nodulated abundantly and effectively with homologous rhizobia introduced from Spain and Italy. The optimum temperature for nitrogen fixation was relatively low (approx. 21°C) but significant interactions between line of host, strain of rhizobia, and growth temperature were frequent. The rhizobia were persistent in soil.     

Bahavioral fever in crayfish

Crayfish (Cambarus bartoni) were tested individually in an electronic shuttlebox thermoregulatory device which allowed them to control water temperature, and thereby their body temperature, by their movements.Crayfish which initially selected 22.1°C water increased their preferred temperature by 1.8°C following injection of killed bacteria (Aeromonas hydrophila) into the gill cavity.This behavioral fever appears similar to that of vertebrates, and may enhance host defense reactions against pathogens.     

Ultra-short acting beta-blockers: a proposal for the treatment of the critically ill patient

Beta-blockade is of proven value in the therapy of acute myocardial infarction but, unfortunately, may produce cardiac failure by removal of needed sympathetic support. The long duration of action of available blockers (hours) makes reversal of failure a complicated problem and precludes rapid modification of therapy to match changing autonomic conditions. To improve the safety and efficacy of beta-blockade in this setting we have developed the concept of ultra-short beta-blockade and have identified a novel beta-blocker (ASL-8052) which possesses a duration of action less than 15 minutes. This compound is cardioselective and possesses efficacy in an animal model of acute myocardial infarction. It, therefore, appears to be suitable for rapid attainment of controlled levels of beta-blockade via intravenous infusion and rapid recovery from beta-blockade if required by the clinical situation. The compound should, therefore, be useful for safe therapy in critically ill cardiac patients.     

Isopropanol enhancement of carbon tetrachloride metabolism in vivo

We examined the effects of isopropanol (ISOP) pretreatment on the metabolism of ¹⁴CCl₄ to ¹⁴CO₂ and CHCl₃ exhaled in the breath, to ¹⁴C metabolite excreted in 24 hr urine and feces from 0 to 24 hr, and to ¹⁴C metabolite bound to liver at 24 hr. Fasted male rats were given 0.1 or 2.0 mmoles ¹⁴CCl₄/kg. ISOP pretreatment, which markedly enhanced the hepatotoxicity of CCl₄, selectively enhanced the rate and total extent of ¹⁴CO₂ and CHCl₃ metabolite exhalation. The pathways of CCl₄ metabolism leading to CO₂ and CHCl₃ metabolite formation may be more relevant to the hepatotoxicity of CCl₄ than the pathways leading to urinarym fecal or covalently bound metabolites.