Acadesine extends the window of protection afforded by ischaemic preconditioning in conscious rabbits

OBJECTIVE: Ischaemic preconditioning protects myocardium from infarction if the reperfusion interval between the brief and prolonged ischaemic intervals is less than 1 h. In anaesthetised rabbits acadesine (5-amino-4-imidazolecarboxamide riboside, AICAR), an adenosine enhancer which increases tissue adenosine during ischaemia, prolongs the window of protection to 2 h. The aim of this study was to try to determine the maximum extension of this window of protection, using chronically instrumented, unsedated rabbits. METHODS: Rabbits were instrumented with a balloon occluder around a major branch of the left coronary artery for reversible coronary occlusion. Five to seven days after surgery all animals underwent a 30 min coronary occlusion. Animals were randomised to one of seven groups: (1) No additional treatment (control); (2) Ischaemic preconditioning with 5 min regional ischaemia followed by 10 min reperfusion before the 30 min coronary occlusion; (3) and (4) Ischaemic preconditioning followed by 2 or 4 h of reperfusion before the 30 min occlusion, respectively; (5) Treatment with acadesine (2.5 mg.kg-1.min-1 intravenously for 5 min and then 0.5 mg.kg-1.min-1 beginning 45 min before and continuing until 30 min after release of the 30 min occlusion) without ischaemic preconditioning; (6) and (7) Treatment with the higher dose of acadesine for 5 min beginning 35 min before the 5 min ischaemic period, and then the lower dose continuing until 30 min after release of the 30 min coronary occlusion in rabbits with 4 or 6 h reperfusion intervals, respectively. RESULTS: Rabbits with ischaemic preconditioning with 10 min reperfusion preceding the 30 min coronary occlusion (group 2) had only 5.6(SEM 1.1)% infarction of the ischaemic zone. Ischaemic preconditioning followed by 2 h reperfusion (group 3) offered continued protection [18.2(2.2)% infarction] as compared to control animals [37.7(2.6)% infarction]. However, protection waned if ischaemic preconditioning was followed by 4 h reperfusion (group 4) [36.7(3.0)% infarction]. Additionally, treatment with acadesine alone did not modify infarct size (group 7) [39.5(4.0)%], but acadesine largely restored the protection of ischaemic preconditioning despite a 4 h reperfusion interval (group 5) [20.4(3.0)% infarction, P < 0.01 v control]. However, when reperfusion was extended to 6 h (group 6) acadesine could no longer restore protection [36.2(0.9)% infarction]. CONCLUSIONS: The protection afforded by a 5 min ischaemic preconditioning period lasts from 2 to 4 h in the awake, unsedated rabbit, and acadesine can extend the duration of this window of protection to at least 4 h but not to 6 h.     

Detection of skeletal metastases in Nigerian breast cancer patients: evaluation of radioisotope bone scan and radiography

Cerebellar granule cells isolated from postnatal day 7 mice, and cultured in minimal medium containing only insulin-like growth factor-I (IGF-I), both survive and differentiate. This differentiation is marked by neurite growth and expression of genes associated with terminal differentiation, the myocyte-specific enhancer factor 2A (MEF2A) and the alpha 6 subunit of the gamma-aminobutyric acidA receptor (GABAA alpha 6). Percoll gradient purified granule cells maintained without IGF-I, in minimal medium alone or in medium containing the antioxidant N-acetylcysteine (NAC), also express MEF2A and GABAA alpha 6. Thus, cultured granule neurons can differentiate to some extent cell-autonomously and IGF-I may not be a critical factor for this process.     

CHOP vs. ProMACE-CytaBOM in the treatment of aggressive non-Hodgkin's lymphomas: long-term results of a multicenter randomized trial.(PETHEMA: Spanish Cooperative Group for the Study of Hematological Malignancies Treatment, Spanish Society of Hematology)

From May 1985 to May 1989, 175 patients with previously untreated aggressive non-Hodgkin's lymphoma were randomized to receive CHOP or ProMACE-CytaBOM. Eligibility criteria included follicular large-cell diffuse small cleaved-cell, diffuse mixed, diffuse large-cell and immunoblastic lymphoma with an Ann Arbor stage II, III or IV. One hundred and forty-eight patients were evaluable. There were no significant differences between the 2 treatments in response rate (83.5% [57.5% CR] for CHOP vs. 88% [62% CR] for ProMACE-CytaBOM), time to treatment failure (29% vs. 31% at 5 yr), or overall survival (42% in both groups at 5 yr). Furthermore, there were no significant differences between the 2 regimens when response rates and outcome were analyzed for different prognostic subgroups. Toxicity was not significantly different between the 2 regimens, although only 1 patient died as result of treatment-related toxicity in the CHOP arm compared to 6 patient in the ProMACE-CytaBOM group (p = 0.126). In conclusion, in this study ProMACE-CytaBOM has not proved to be superior to CHOP in aggressive lymphomas. This trial gives support to the notion that CHOP still is the standard chemotherapy for aggressive lymphomas, and that new treatment approaches for these lymphomas should be compared to CHOP.     

Cortical variations of the dimension of correlation in children with attention deficit hyperactivity syndrome

INTRODUCTION AND OBJECTIVE: The syndrome of deficient attention and hyperactivity affects approximately 5% of children of school age. Clinically it is characterized by deficient attention, impulsiveness and excessive motor activity. Developments in nonlinear dynamic theory have made it possible to think of modelling cerebral activity as a dynamic system of chaotic type. One the most widely standardized measurements is the dimension of correlation (D2). In this paper we study the electroencephalographic traces of a control group of 9 healthy children and another group of 19 children with the syndrome of deficient attention, at rest and whilst carrying out a visuomotor task (Test of perception of differences). MATERIAL AND METHODS: The dimension of correlation was estimated for both groups. Statistical comparison was made between the cortical distributions of the D2 between both types of recordings and between both groups. RESULTS: The children with lack of attention showed a larger number of activated cortical areas than those of the control group when carrying out the same task. However, during the resting state there were no differences in the D2 between the control children and the children with deficient attention. The indicates that both groups have the same basal level of activation. CONCLUSION: The dimension of correlation is a method which permits the demonstration of an increase in neuronal activity in the stimulated areas, in this case in the occipital region.     

Slow skeletal troponin I gene transfer, expression, and myofilament incorporation enhances adult cardiac myocyte contractile function

The functional significance of the developmental transition from slow skeletal troponin I (ssTnI) to cardiac TnI (cTnI) isoform expression in cardiac myocytes remains unclear. We show here the effects of adenovirus-mediated ssTnI gene transfer on myofilament structure and function in adult cardiac myocytes in primary culture. Gene transfer resulted in the rapid, uniform, and nearly complete replacement of endogenous cTnI with the ssTnI isoform with no detected changes in sarcomeric ultrastructure, or in the isoforms and stoichiometry of other myofilament proteins compared with control myocytes over 7 days in primary culture. In functional studies on permeabilized single cardiac myocytes, the threshold for Ca2+-activated contraction was significantly lowered in adult cardiac myocytes expressing ssTnI relative to control values. The tension-Ca2+ relationship was unchanged from controls in primary cultures of cardiac myocytes treated with adenovirus containing the adult cardiac troponin T (TnT) or cTnI cDNAs. These results indicate that changes in Ca2+ activation of tension in ssTnI-expressing cardiac myocytes were isoform-specific, and not due to nonspecific functional changes resulting from overexpression of a myofilament protein. Further, Ca2+-activated tension development was enhanced in cardiac myocytes expressing ssTnI compared with control values under conditions mimicking the acidosis found during myocardial ischemia. These results show that ssTnI enhances contractile sensitivity to Ca2+ activation under physiological and acidic pH conditions in adult rat cardiac myocytes, and demonstrate the utility of adenovirus vectors for rapid and efficient genetic modification of the cardiac myofilament for structure/function studies in cardiac myocytes.     

Isolation of translactone-containing triterpenes with thrombin inhibitory activities from the leaves of Lantana camara

Methanolic extracts prepared from the leaves of Lantana camara have been found to inhibit human thrombin. An assay, in which thrombin activity is measured as a function of clot formation from fibrinogen, was used to guide the fractionation and purification of five principal active constituents (1-5), which were all characterized as 5,5-trans-fused cyclic lactone-containing euphane triterpenes.     

English teaching in the Italian medical faculties: results of a survey

BACKGROUND: Although a compulsory examination in medical English has been present in the medical degree curriculum in Italy since 1990, guidelines indicating what should be learnt and suggesting some means of overcoming the various problems this entails are still lacking. OBJECTIVE: To investigate the main features of teaching English in the Medical Faculties and enquire into how the various problems are solved in the individual English teaching units. METHOD: A questionnaire addressing the above issues was sent out to all the Italian Universities with a Medical Faculty. RESULTS: The first finding of our survey was that response was very poor: less than 30% of the survey volunteered any reply. Within the very reduced sample which responded, there was a high degree of variation among the solutions adopted, although the underlying problems were perceived to be much the same throughout Italy. CONCLUSIONS: The general objective of the English course for medicine should be more precisely defined, together with a series of specific minimum skills the student should possess to pass the final examination. A closer collaboration among the English teaching units might help to standardize these requirements, improve the quality of the teaching and hence the level of proficiency in English for the specific purpose of medical practice.