Pravastatin attenuates tourniquet-induced skeletal muscle ischemia reperfusion injury

Background Revascularization of a limb following prolonged ischemia results in substantial skeletal muscle injury. Statins play a well-understood role in the treatment of hypercholesterolemia but are also known to have anti-inflammatory properties. The purpose of this study was to examine the effects of pravastatin pre-treatment in the setting of skeletal muscle ischemia reperfusion injury (IRI).

Methods Adult male Sprague Dawley rats (n = 27) were randomized into 3 groups: control group, I/R group, IR group pre-treated with pravastatin. Bilateral hind-limb ischemia was induced by rubber band application proximal to the level of the greater trochanters for 2.5 h. Treatment groups received normal saline in equal volumes prior to tourniquet release. Following 12 h reperfusion, the tibialis anterior muscle was dissected and muscle function assessed electrophysiologically by electrical field stimulation. The animals were then killed and skeletal muscle harvested for evaluation.

Results We found that pre-treatment with pravastatin reduces the tissue oxidative damage and edema associated with skeletal muscle reperfusion injury. Skeletal muscle injury, measured by edema, leucose-questration and electrical properties were significantly lower with pravastatin pre-treatment compared to the non-treated group.

Interpretation We feel that pravastatin pre-treatment may be a potential therapeutic intervention for skeletal muscle ischemia reperfusion injury in the clinical setting. ▪     

Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes

AIMS/HYPOTHESIS: Although ischaemic heart disease is the predominant cause of mortality in older people with diabetes, age-specific mortality rates have not been published for patients with Type 1 diabetes. The Diabetes UK cohort, essentially one of patients with Type 1 diabetes, now has sufficient follow-up to report all heart disease, and specifically ischaemic heart disease, mortality rates by age. METHODS: A cohort of 23,751 patients with insulin-treated diabetes, diagnosed under the age of 30 years and from throughout the United Kingdom, was identified during the period 1972 to 1993 and followed for mortality until December 2000. Age- and sex-specific heart disease mortality rates and standardised mortality ratios were calculated. RESULTS: There were 1437 deaths during the follow-up, 536 from cardiovascular disease, and of those, 369 from ischaemic heart disease. At all ages the ischaemic heart disease mortality rates in the cohort were higher than in the general population. Mortality rates within the cohort were similar for men and women under the age of 40. The standardised mortality ratios were higher in women than men at all ages, and in women were 44.8 (95%CI 20.5-85.0) at ages 20-29 and 41.6 (26.7-61.9) at ages 30-39. CONCLUSIONS/INTERPRETATION: The risk of mortality from ischaemic heart disease is exceptionally high in young adult women with Type 1 diabetes, with rates similar to those in men with Type 1 diabetes under the age of 40. These observations emphasise the need to identify and treat coronary risk factors in these young patients.     

对发展中国家改善用药的10点建议

WHO建议改善药品管理的工作要在国家药物政策保障之下.在许多国家,执行国家药物政策的机制是实施国家基本药物计划,其要点是强调公共领域的药品选择、采购、流通与使用的合理性.不适当的处方使医疗质量降低并导致资源浪费.本文以探讨在国家药物政策范畴内鼓励更合理地使用药品的问题为重点,在已有证据的基础上,详细阐明基本药物计划内容中的合理用药问题.本文评述了在发展中国家改善用药状况的有效策略及最新知识,并为决策者与管理者提出达到改善用药目标的建议.     

A highly specific L-galactose-1-phosphate phosphatase on the path to ascorbate biosynthesis

Ascorbate is a critical compound in plants and animals. Humans are unable to synthesize ascorbate, and their main source of this essential vitamin are plants. However, the pathway of synthesis in plants is yet to be established, and several unknown enzymes are only postulated to exist. We describe a specific L-galactose-1-phosphate (L-gal-1-P) phosphatase that we partially purified from young kiwifruit (Actinidia deliciosa) berries. The enzyme had a native molecular mass of approximately 65 kDa, was completely dependent on Mg2+ for activity and was very specific in its ability to hydrolyze L-gal-1-P. The activity had a pH optimum of 7.0, a K(-M(L-gal-1-P) of 20-40 microM and a Ka(Mg2+) of 0.2 mM. The activity was inhibited by Mg2+ at concentrations >2 mM. The enzyme from Arabidopsis thaliana shoots showed similar properties to the kiwifruit enzyme. The Arabidopsis thaliana enzyme preparation was digested with trypsin, and proteins present were identified by using liquid chromatography-MS. One of 24 proteins present in our preparation was an Arabidopsis thaliana protein, At3g02870, annotated myo-inositol-1-phosphate phosphatase in GenBank, that matched the characteristics of the purified l-gal-1-phosphate phosphatase. We then expressed a kiwifruit homologue of this gene in Escherichia coli and found that it showed 14-fold higher maximum velocity for l-gal-1-P than myo-inositol-1-P. The expressed enzyme showed very similar properties to the enzyme purified from kiwifruit and Arabidopsis, except that its KM(L-gal-1-P) and Ka(Mg2+) were higher in the expressed enzyme. The data are discussed in terms of the pathway to ascorbate biosynthesis in plants.     

Gap junction proteins exhibit early and specific expression during intramembranous bone formation in the developing chick mandible

The spatial and temporal expression of three closely related members of the connexin family of gap junction proteins (connexin42, Cx42; connexin43, Cx43; and connexin45, Cx45) was evaluated during bone formation in the mandibular process of the chick embryo. Mandibles of chick embryos from Hamburger and Hamilton stage 25 (approximately 5 days) through 19 days of development were dissected, serially sectioned and processed for immunocytochemical localization, employing site-specific anti-connexin antibodies. Our data revealed that (1) Cx43 was present throughout mandibular bone formation; (2) although it appeared to be associated with all bone cell types, Cx43 was concentrated in mesenchymal cells during the earliest stages in the osteogenic lineage; (3) most importantly, the localization of Cx43 at sites of bone formation appeared to precede the overt expression of the osteogenic phenotype; (4) by contrast, Cx45 was more restricted, spatially and temporally, in its distribution; (5) Cx42 expression was not detected in osteogenic tissue during mandibular bone formation. From all of the data obtained, Cx45 appeared to be associated with stages of bone formation characterized by the elaboration of matrix and the progressive expression of the differentiated osteogenic phenotype. Cx43 appeared to be associated with condensation of mesenchyme and the earliest stages of osteogenesis. Because of these associations, we propose that connexin expression may be necessary for the initiation of bone formation and the full expression of the osteogenic phenotype.     

A calibration service for biomedical instrumentation maintenance laboratories

An in-house calibration laboratory for the Biomedical Instrumentation Maintenance Services of the hospitals in the West of Scotland was established in 1993. This paper describes the development of this calibration service in the context of an overall quality system and also estimates its costs. Not only does the in-house service have many advantages but it is shown to be cost effective for workloads exceeding 260 items per annum.     

Expression of an inducible nitric oxide synthase gene in rainbow trout Oncorhynchus mykiss

Using oligonucleotide primers based on mammalian nitric oxide synthases (NOS), expression of an inducible NOS (iNOS) gene was detected in head kidney and gill tissue of bacterially-challenged rainbow trout. Three overlapping fragments were amplified by RT-PCR and used to construct a contiguous sequence of 1410bp, with high nucleotide homology to iNOS in birds (61%) and mammals (57-59%). The nucleotide sequence translated in one reading frame to produce a partial peptide containing 470 amino acids, with 69-71% amino acid homology with mammalian iNOS, 81% homology with chicken iNOS and 85% homology with a partial (492bp) goldfish iNOS sequence. In vitro stimulation of head kidney macrophages with LPS also induced expression of the trout iNOS RNA, with optimal expression seen using 20-50 microg/ml LPS at 2h to 6h post-stimulation. The evolutionary and functional significance of the trout iNOS sequence are discussed.