Santos Barrigón

Measuring interdisciplinary collaboration within a university: The effects of the multidisciplinary research programme

A Multidisciplinary Research Programme (MRP) is being developed since 1989 in the Universidad Complutense de Madrid (UCM), Spain, to support cross-disciplinary research projects. This paper analyses the incidence of interdisciplinarity in the UCM scientific publications over the period 1990–96 and tries to determine the success of the Programme at fostering cross-disciplinary research. Interdisciplinary in the UCM is measured through the collaboration of authors from different institutional addresses within the UCM, both in scientific publications and in research projects. Publications jointly signed by the different teams that collaborate in the projects were identified as an indicator of the success of the Programme in integrating disciplines. Interdisciplinary collaboration within the UCM showed an upward trend over time. Publications of MRP groups showed a higher interdisciplinary collaboration rate than the rest of the UCM (17% vs. 9%). Dramatic repercussions of the Programme were not expected due to its limited magnitude, but it worked as a catalyst, enhancing interdisciplinary relations within the UCM. The interest of such a programme is supported by its effects, both direct effects on granted teams and indirect on the whole UCM community.

Bibliometric analysis of publications of Spanish pharmacologists in the SCI (1984-89). I: Contribution to the pharmacology & pharmacy subfield (ISI)

The present study is a bibliometric analysis, of publications of Spanish pharmacologists, referenced in the journals of the Pharmacology & Pharmacy subfield of the Science Citation Index- CD Edition from 1984 to 1989. During this time the scientific output of Spanish pharmacologists has been growing at an impressive rate being almost doubled. This rate being notably greater than that corresponding to publications of Spain in all science fields. This increase in scientific output was accompanied by a time-dependent decrease on year by year step basis in the expected impact factor (EIF) of publications (Articles plus Notes), from 1.71 in 1984 to 1.28 in 1989, in close correlation with an increase of mean number of authors per paper, from 3.67 to 4.16 authors/paper, respectively. Moreover, the larger the number of authors/paper, the smaller the EIF. Only 8 journals cumulated more than 50% of the papers. The scientific production was geographically localized at a high extent (Barcelona, Madrid, Valencia accounted for the 63.7% of all the papers) in governmental institutions (University, 75.2%, Hospitals, 14.1%; CSIC, 10.5%) with one large geographical area lacking any productivity.

Electrophysiological effects of platelet-activating factor (PAF-acether) in guinea-pig papillary muscles.

The effects of PAF-acether (10(-11) to 10(-7) M) were studied on the electrical and mechanical activity of guinea-pig papillary muscles. At 10(-11) M PAF-acether did not modify the amplitude and Vmax of the upstroke or the resting membrane potential. At higher concentrations PAF-acether produced a dose-dependent increase in the amplitude and Vmax of the upstroke, shortened the action potential duration and hyperpolarized the resting membrane potential. These effects were accompanied by a biphasic effect on ventricular contractile force. The shortening of the APD was inhibited in muscles pretreated with tetraethylammonium or verapamil. In papillary muscles depolarized by 27 mM K Tyrode solution PAF-acether induced slow action potentials which were blocked by verapamil. PAF-acether produced a dose-dependent increase in amplitude and Vmax of the upstroke on the slow action potentials elicited by isoproterenol, prolonged the action potential duration and hyperpolarized the resting membrane potential. These results suggest that in guinea-pig papillary muscles PAF-acether increased Ca influx via the slow inward current.

BIBLIOMETRIC ANALYSIS OF PUBLICATIONS OF SPANISH PHARMACOLOGISTS IN THE SCI (1984-89). PART II. CONTRIBUTION TO SUBFIELDS OTHER THAN "PHARMACOLOGY & PHARMACY" (ISI)

During the period 1984–89 Spanish pharmacologists published 344 papers (44.3% of their total scientific production) (Science Citation Index, CD-Edition) in journals classified by theSCI in subfields different from Pharmacology & Pharmacy. Distribution by institutions, geographical regions, journals, subfields and research levels are presented. The Normalized Journal Position (NJP) is introduced as indicator of the expected impact in each subfield. Results are compared with those of the analysis of the production of Spanish pharmacologists in the Pharmacology & Pharmacy subfield, presented in a previous paper. Some of the features detected are common to both areas, such as: increasing trend in the productivity over years, irregular geographical distribution with three regions as major producers, or university as main producer institution. Special features of the extra-Pharmacology area are also pointed out: irregular growth of publication number over years, high dispersion of publications in journals and subfields, high collaboration rate, and low percentage of authors with at least 1 paper/year, among others. Attending to journal of publication, cross-disciplinarity research of Spanish pharmacologists is analysed, being Neurosciences, Biochemistry & Molecular Biology and Physiology, the main border fields involved.

Effects of chlorbutol on 45 Ca movements and contractile responses of rat aorta and its relevance to the actions of Syntocinon

The effects of chlorbutol (0.7, 1.4 and 2.8 mM) on the contractile responses induced by KCl and noradrenaline (NA) and on 45Ca movements have been studied on rat isolated thoracic aorta. Chlorbutol decreased, in a dose-dependent manner, contractions induced by KCl and NA and this effect was observed whether it was added before or after the induced contractions. Preincubation with chlorbutol inhibited the contractile responses elicited by addition of Ca (1-5 mM) to Ca-free high-potassium solution. It also inhibited in a dose-dependent manner the 45Ca influx but increased 45Ca efflux in rat aortic strips. These results suggest that chlorbutol decreases peripheral resistance by reducing the availability of intracellular Ca to the contractile machinery in vascular smooth muscle cells. The effects of synthetic oxytocin (Syntocinon) at concentrations containing the same chlorbutol concentration were quantitatively similar from those produced by chlorbutol alone. Therefore, the inhibitory cardiovascular effects ascribed previously to synthetic oxytocin may be attributed to its preservative, chlorbutol, and not to oxytocin itself.

THE MECHANISM OF THE POSITIVE INOTROPIC ACTION OF KETAMINE ON ISOLATED ATRIA OF THE RAT

1 The effect of ketamine (10−7 m‐5 × 10−4 m) on electrical and mechanical properties of isolated atria of the rat was investigated. 2 On spontaneously beating right atria, ketamine produced a dose‐dependent positive inotropic effect which was accompanied by a progressive reduction in atrial rate. 3 In electrically driven left atria, ketamine produced a dose‐dependent positive inotropic effect which was accompanied by a parallel increase in df/dtmax and by a prolongation in the time to peak tension and in the time for total contraction. The positive inotropic effect occurred concomitantly with an increase in the height and duration of the plateau phase of the action potential of atrial fibres. 4 The positive inotropic effect of ketamine varied with the concentration of Ca and Na in the bathing media and the rate of stimulation. 5 Ketamine decreased post‐extrasystolic potentiation and the amplitude‐interval relationship. 6 The positive inotropic effect of ketamine was inhibited by verapamil (10−6 m) and by caffeine (4 × 10−3 m). 7 Ketamine, 5 × 10−5 m and 10−4 m, increased 45Ca uptake in electrically driven left atria. At 10−4 m and 5 × 10−4 m, ketamine also increased 45Ca efflux. 8 These results suggest that ketamine produces its positive inotropic effect by two possible mechanisms. One of these is presumed to be an effect on the cell membrane which leads to an increased Ca influx into atrial fibres; the other is probably related to the inhibition of Ca sequestration by the sarcoplasmic reticulum.

Protective effects of cyclopiazonic acid on ischemia-reperfusion injury in rabbit hearts.

The cardioprotective effects on myocardial ischemia of the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA) inhibitor, cyclopiazonic acid (CPA), were studied. We used the isolated arterially perfused interventricular septum of the rabbit heart submitted to 30-min global ischemia/30-min reperfusion. Mechanical [maximal increase in resting tension (MIRT), and the recovery of developed tension (RDT)], and biochemical parameters [creatine phosphokinase activity (CPK) in the effluent] were analyzed. CPA, 1 microM, perfused 30 min before the ischemia intervention significantly increased RDT by 54% and lessened MIRT by 66%. CPA also decreased CPK in the perfusate by 67.7 and 71.4% at 0-2 and 5-7 min of reperfusion, respectively. No additional benefits were shown either when the drug was perfused, both during ischemia and reperfusion, or with higher CPA concentrations (10-30 microM). The CPA cardioprotection was lost when the drug was present only during the reperfusion period. CPA exhibits functional and biochemical cardioprotective effects on myocardial ischemia. We postulated a decreased SR calcium contribution to the initial cytoplasmic calcium overload as the most probable mechanism involved.

Time-tracking of the research profile of a drug using bibliometric tools

This study explores the usefulness of bibliometric analyses to detect trends in the research profile of a therapeutic drug, for which Aspirin was selected. A total of 22,144 documents dealing with Aspirin and published in journals covered by MEDLINE during the years 1965-2001 are studied. The research profile of Aspirin over the 37-year period is analyzed through Aspirin subheadings and MeSH indexing terms. Half of the documents had Aspirin as a major indexing term, being the main aspects studied therapeutic uses (28% of the documents), pharmacodynamics (26%), adverse effects (18%), and administration and dosage (10%). A frequency data table crossing indexing terms × years is examined by correspondence analysis to obtain time trends, which are shown graphically in a map. Four time periods with a different distribution of indexing terms are identified through cluster analysis. The indexing term profile of every period is obtained by comparison of the distribution of indexing terms of each cluster with that of the whole period by means of the Chi-2 test. The research profile of the drug tends to change faster with time. The most relevant finding is the expanding therapeutic profile of Aspirin over the period. The main advantages and limitations of the methodology are pointed out.

Presence of a nitric oxide synthase inhibitor in the graft efflux during reperfusion in human liver transplantation

Involvement of the nitric oxide (NO) system in complications following human orthotopic liver transplants (OLT) has been reported, but the contribution of the graft to the modulation of the NO system during reperfusion in normal OLT has not been characterized. We have studied the contribution of the graft efflux to the modulation of the NO system in 20 consecutive OLT. We evaluated its effects on isolated vascular reactivity of the rabbit and on rat cultured macrophages stimulated with lipopolysaccharide (LPS).In none of the donor liver biopsies was expression of inducible NO synthase (iNOS) activity by Northern or Western blot analysis found. Graft efflux after the onset of liver reperfusion, but not pre‐transplant patient plasma, reversibly inhibited the acetylcholine‐induced relaxation of norepinephrine‐contracted rabbit aortic rings. Moreover, graft efflux reversibly inhibited NO production in rat macrophages treated with LPS, as evidenced by both a decrease in nitrite plus nitrate formation and a decrease in the production of [ C]citrulline from [ C]arginine. Addition of a 10% dilution of graft efflux to cultured rat macrophages incubated with LPS increased iNOS mRNA levels, suggesting direct inhibition of the enzyme but not of its expression. These results cannot be ascribed to the depletion of arginine – the iNOS substrate – since they can be reproduced even in the presence of an excess (10 mM) of exogenously added arginine. No correlation was found between the iNOS inhibitory activity in each sample and the corresponding clinical parameters related to either the graft function after the OLT or the existence of post‐reperfusion syndrome.Our results indicate the existence of a soluble factor in the graft efflux from human OLT that reversibly and unspecifically inhibits NOS activity. Its involvement in the physiology and/or pathology of human liver diseases deserves further study.

The effect of oxytocin on contractile responses and 45Ca movements in rat isolated aortic strips

1 The effects of oxytocin (Oxt) on contractile responses and transmembrane Ca fluxes were studied in rat isolated aortic strips. 2 Oxt (50–1000 mu ml−1) induced a dose‐dependent contractile response and spontaneous myogenic activity. 3 The Oxt‐induced contractile response was not inhibited by pretreatment of aortic strips with phentolamine plus practolol, atropine, diphenhydramine plus cimetidine or indomethacin, but was significantly reduced by verapamil or deamino‐ethyl‐Oxt. 4 The dose‐response curve for Oxt was shifted upwards and to the left by increasing the Ca concentration of the medium from 1.8 to 4 mm. 5 Oxt also shifted upwards the dose‐response curve to Ca (1 to 5 mm) in aortic strips incubated in K depolarizing Ca‐free media. 6 Oxt increased the La3+‐resistant 45Ca content without altering 45Ca efflux. 7 The present results suggest that in rat isolated aortic strips Oxt produces a contractile response which, as previously found with other neurotransmitters, can be partly attributed to an increase of Ca influx through receptor‐operated channels and to the release of Ca from intracellular stores.