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M Grau

Publications and source records attributed to M Grau.

At least 19 recordsLinked to original sources

The influence of landmark salience in a navigation task: an additive effect between its components.

In 2 experiments, rats were trained in a Morris pool to find a hidden platform in the presence of 1 landmark. After acquisition, the rats were tested without the platform. Experiment 1 tested whether the size of a landmark and its relative distance from the platform are additive effects. On test, the rats' best performance was with a near and big landmark; intermediate performance was with either a near and small landmark or a far and big one; and the worst performance was with a far and small landmark. The results of Experiment 2 suggested that the different distances from the goal of the 2 landmarks might not be sufficient to explain the previous results.

Analysis of Variance↗

Persistent effects of cognitive-behavioral stress management on cortisol responses to acute stress in healthy subjects--a randomized controlled trial.

Psychosocial stress leads to a release of cortisol. While this psychoneuroendocrine response helps to maintain physiological as well as psychological equilibrium under stress, exaggerated secretion of cortisol has been shown to have negative effects on somatic health and cognitive functioning. The study set out to examine the long-term effects of cognitive-behavioral stress management training on cortisol stress responses in healthy men and women. Eighty-three healthy subjects were randomly assigned to cognitive-behavioral stress management (CBSM) training or a control condition. Four months after the CBSM, 76 subjects underwent a standardized psychosocial stress test. Salivary cortisol responses were assessed repeatedly before and after the stress test. Subjects in the CBSM group showed significantly reduced cortisol stress responses. With regard to gender, this effect was observed in both men and women. However, the magnitude of the CBSM effect on cortisol responses was smaller in women than in men. Use of oral contraceptives in women influenced the cortisol response, but did not have an impact on the CBSM effect on cortisol. The results show that the previously reported attenuation of cortisol stress responses through CBSM persists and are observable in both men and women. Since stress-induced alterations of hypothalamus pituitary adrenal axis functioning are discussed to be involved in the onset and maintenance of both somatic and psychiatric conditions, similar interventions could be used for prevention and therapy of these detrimental stress effects.

Acute Disease↗

Modulation of hepatocyte growth factor plasma levels in relation to the dose of exogenous heparin administered: an experimental study in rats.

INTRODUCTION: Partial liver transplantation has been consolidated to be a valid treatment option. We sought to understand the factors that modulate and may be harnessed to accelerate hepatocyte regeneration. We sought to determine the impact of heparin on m-hepatocyte growth factor (HGF) plasma concentrations. MATERIALS AND METHODS: Sixteen rats were assigned to four groups of four animals each: group A, without heparin; group B, 600 IU/kg; group C, 1000 IU/kg, group D, 1400 IU/kg. Blood samples (0.5 mL) were obtained from each rat at baseline and at 30, 60, 120, and 240 minutes. After the samples were centrifuged to separate supernates from the cell phase they were stored at -20 degrees C in the m-HGF reagent and subsequently tested using enzyme-linked immunosorbent assay. Results were analyzed using SPSS 11.5 statistical software. RESULTS: Among the 16 rats, one died at 110 minutes, just prior to the last extraction. The remaining rats were sacrificed. Mean weight was: 466 +/- 64.24 g with no intergroup differences (P = .149). The comparative results (using Student t test) were: baseline A(1-4) versus A(1-4) 30 minutes: P < .05; baseline A(1-4) versus A(1-4) 60 minutes: P < .05; baseline A(1-4) versus A(1-4) 120 minutes: P = .10 (NS); baseline A(1-4) versus A(1-4) 240 minutes: P = .15 (NS). No significant differences were found among group B: baseline C(1-4) versus C(1-4) 30 minutes and 60 minutes: NS; baseline C(1-4) versus C(1-4) 120 minutes: P < .001; baseline C(1-4) versus C(1-4) 240 minutes: P < .10 (NS). Finally, the results in group D were: baseline D(1-4) versus D(1-4) 30 minutes: NS; baseline D(1-4) versus D(1-4) 60 minutes and 120 minutes: P < .05; baseline D(1-4) versus D(1-4) 240 minutes: P < .0005. When we compared group A to C and D, we detected differences (albeit not when compared to B) with P values = .01. Peak values were obtained at 120 and 240 minutes (225.21 pg/mL and 221.78 pg/mL) among groups C and D. CONCLUSION: Heparin has a positive effect to increase serum HGF concentrations among rats. The effect was dependent on the administered dose and the time elapsed.

Animals↗

Opiate maintenance with buprenorphine in ambulatory care: a 24-week follow-up study of new users.

BACKGROUND: Many studies suggest that buprenorphine, a long acting partial opioid agonist, may be comparable to methadone in efficacy, with fewer withdrawal symptoms and a lower risk of overdose. The aim of this study was to assess the patterns of buprenorphine prescription use in ambulatory care and retention rate under treatment during a 24-week follow-up period. METHODS: This observational cohort study included buprenorphine users identified from the French Health System prescription database in an area of 1 million inhabitants and followed for 24 weeks. RESULTS: We selected 282 users of buprenorphine defined as "new users" (74% male, mean age 32.4+/-6.2 years). Three groups were defined: 50% of "rational users" (141 subjects, no more than 2 prescribers), 24% of "occasional users" (67 subjects, less than 2 buprenorphine prescriptions) and 26% of "non-rational users" (74 subjects, 3 or more prescribers). The overall 24-week treatment retention rate was 37%. Misuse of buprenorphine or benzodiazepines was significantly more frequent in "non-rational" than "rational users". CONCLUSION: The retention rate with buprenorphine estimated in this observational study was very similar to that obtained in controlled trials. A majority of regular users of buprenorphine could be regarded as "rational users" in this area of France.

Adolescent↗

[Breast feeding and birth of twins].

OBJECTIVES: To investigate the breast-feeding (BF) situation after birth of twins and find what factors affect the decision to breast-feed, its length and the reasons for stopping it. DESIGN: Retrospective, observational study. SETTING: Sabadell Hospital, Barcelona. PARTICIPANTS: All the women who gave birth to twins between January 1994 and June 1997 (n = 72). MAIN RESULTS: 64 women (88.9%) began BF. It was exclusive in 37 cases (57.8%) and mixed in the other 27 (42.2%). The main reason for choice was "better feeding" (100% of cases). The age of mothers, the type of birth, the weight of the children, admissions to the New-born Baby Department, work situation, mother's educational qualifications and the existence of domestic help affected neither initial breast-feeding nor its length. Women with prior counselling started BF in greater numbers than those not counselled (p = 0.026). Almost half of them received the information through the matron or nurse. Mean length of BF was 102 days. After two months, half of those who began BF were still breast-feeding; and at four months, 26.5%. CONCLUSIONS: We observed a high level of starting breast-feeding after twin births, almost the same as for single births. Women with previous knowledge of the question are more likely to breast-feed. The length of BF is slightly greater in the studies reviewed. Adequate prenatal, postnatal and puerperal support from health-workers can have a positive effect on the success of BF after twin births.

Adult↗

[Chronic low back pain: multispecialty assessment of 100 patients].

OBJECTIVES: Chronic lower-back pain (CLP) is a common pathology and has a high social and economic impact, especially in primary care where its treatment is changing at present. The results of the multi-disciplinary assessment of 100 patients with chronic lower-back pain are given. DESIGN: Cross-sectional, observational and prospective study. SETTING: Out-patient clinics of the rheumatology service of a tertiary-level hospital (referral from base districts where there is no primary care rheumatologist). PATIENTS: 100 consecutive patients seen for back pain lasting for more than 6 months were analysed. INTERVENTIONS: There was no therapeutic intervention. MEASUREMENTS AND MAIN RESULTS: The personal, work, clinical, examination, x-ray, functional and psychological features of 100 patients with CLP were analysed. There were 38 men and 62 women, with average age of 45 +/- 10 years and low social, cultural and job levels. Pain had lasted 82 +/- 7 months and 52% had had time off work. Mean intensity of pain was 6.5 +/- 2.3 (scale of zero to 10). There was vertebral restriction in 16%, and conduct expressing pain on examination in 47%. The x-ray showed disorder in 51%. Functional incapacity was nil or light in 46% and severe in 16%. 74.5% of the patients were depressed; 57% had features of anxiety; and 44% were anxious at the time of the interview. CONCLUSIONS: Patients with CLP are middle-aged, with long-standing pain and frequent time off work. Pain intensity is high, but vertebral restriction, disorders on x-rays and functional incapacity are scant. However, anxiety and depression levels are high. This could suggest a change in how we treat CLP towards a multi-disciplinary approach and psycho-affective, social and labour assessment, both at the time of assessment and in later treatment of patients.

Adult↗

Time window for clinical effectiveness of mass evacuation in a rat balloon model mimicking an intraparenchymatous hematoma.

The purpose of this study is to evaluate in a rat model if the early removal of an experimental intracerebral mass mimicking an extensive subcortical hematoma improves neurological outcome. Fifty six male Wistar rats were studied. A balloon was placed sterotactically at the level of the striatum. The balloon was inflated to 100 microl for periods of 10, 60 or 120 min (with 10 animals in each group). In 10 animals the balloon was not deflated and there were four sham operated cases. Neurological deficit was evaluated by a blinded observer by means of a clinical scale from 0 to 8 points at 24 and 72 h after inflation. Three additional animals at each inflation period were sacrificed after 6 h for pathological study with hematoxylin-eosin staining. Death rate was 9/10 animals who had permanent inflation, 4/10 in those with 2 h inflation, 2/10 for 1 h inflation and 0/10 for 10 min inflation (P<0.01 in chi square test). Many animals developed a particular clinical syndrome not previously described. Mean 72 h clinical scores (0-8 points) were 7.6 (S.D.: 1. 2) for the permanent inflation group, 4.4 (S.D.: 3.2) for 2 h of inflation, 2.3 (S.D.: 3.2) for 1 h and 0.4 (0.9) for 10 min of inflation (P<0.01 in Kruskal Wallis test). In the pathological study the rate of damaged neurons was significantly higher in the permanent than in transient inflation groups. In conclusion, in this balloon model evacuation of an extensive acute expanding subcortical (hematoma-like) mass must be performed within a limited time window to prevent the development of irreversible neurological deficits or death.

Animals↗

Isolation and partial characterization of dengue virus type 2 and 4 strains from dengue fever and dengue haemorrhagic fever patients from Mindanao, Republic of the Philippines.

OBJECTIVE: Isolation of dengue virus from dengue fever and dengue haemorrhagic fever cases from Mindanao, Republic of the Philippines. METHODS: 12 patients with clinically suspected dengue fever (DF) or dengue haemorrhagic fever (DHF) presenting in four regional hospitals between August and September 1995 on Minadano were enrolled in the study. Dengue virus was isolated by inoculation of Vero/E6 or C6/36 cells with patient serum. IgM antibodies were measured using a commercial test system. Up to 454 bp of the capsid region and 240 bp of the E/NS1 gene junction of different viral isolates were sequenced and phylogenetically analyzed. RESULTS: Virus could be isolated from seven patients, five isolates were typed as dengue virus type 2 and two as dengue virus type 4 by immunostaining with monoclonal antibodies or by RT/PCR. Phylogenetic analysis confirmed a close relationship of the dengue virus type 2 isolates with viruses isolated in the Philippines in 1983 and 1988. CONCLUSION: As observed in studies from other parts of South East Asia, dengue virus type 2 was readily isolated from dengue haemorrhagic fever cases. Dengue virus type 2 and 4 circulate in Mindanao, Philippines, with dengue type 2 being responsible for most of our severe DF or DHF cases.

Child↗

Tirant is a new member of the gypsy family of retrotransposons in Drosophila melanogaster.

In this paper, we propose a consensus sequence for a putative complete Tirant retrotransposon. Several defective copies, as well as relevant sequences available in databases have been analyzed. The putative complete Tirant element is 8533 bp long, and presents all the structural features of a retrovirus-like transposable element of the gypsy family. It contains three ORFs (open reading frames) that encode putative products resembling the retroviral Gag, Pol, and Env proteins. Southern blot analyses show that complete and defective Tirant elements are widespread in Drosophila melanogaster. The different hybridization patterns observed in several natural populations of this species suggest that Tirant is an active element.

Animals↗

Epidermal growth factor secreted from submandibular salivary glands interferes with the lipolytic effect of adrenaline in mice.

We had described that epidermal growth factor (EGF) interfered with the lipolytic effect of catecholamines in isolated adipocytes. Since catecholamines stimulate the release of EGF from submandibular salivary glands to blood plasma in male mice, we studied whether EGF affected also the lipolytic response to adrenaline in whole animals. We studied the effect of adrenaline in sialoadenectomized and sham-operated mice receiving or not a high dose of EGF following adrenaline injection. There was no difference in plasma EGF concentration between sham-operated and sialoadenectomized animals receiving saline. After adrenaline administration plasma EGF increased by 20-fold in sham-operated but did not increase in sialoadenectomized mice. Indeed, the increase was much higher (more than 100-fold) in mice receiving exogenous EGF. The effect of adrenaline on plasma concentration of both glycerol and nonesterified fatty acids was higher as lower was plasma EGF concentration. Isolated adipocytes obtained from sham-operated or sialoadenectomized mice had identical lipolytic response to adrenaline. The lipolytic response of adipocytes to isoproterenol was decreased by addition of EGF. To study whether the interference with the in vivo lipolytic effect of adrenaline had further metabolic consequences, we measured plasma beta-hydroxybutyrate concentration in plasma. There was no difference in the response to adrenaline between sham-operated and sialoadenectomized mice in spite of the difference in plasma nonsterified fatty acid concentration. Studies in isolated hepatocytes indicated that ketogenesis run at near maximal rate in this range of substrate concentration. These results suggest that EGF in the physiological range decreases the lipolytic effect of adrenaline but does not compromise further metabolic events like the enhancement of ketogenesis.

3-Hydroxybutyric Acid↗

Novel arylpyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxides as inhibitors of platelet aggregation. 1. Synthesis and pharmacological evaluation.

A series of N-1-substituted derivatives of pyrazino[2,3-c][1,2, 6]thiadiazine 2,2-dioxides bearing aryl groups at the pyrazino moiety have been prepared. The synthesis involves ring formation between the diaminothiadiazine and suitable dicarbonyl compounds and subsequent introduction of the substituent at N-1. The compounds have been tested in vitro, as inhibitors of rabbit and human platelet aggregation, and ex vivo against rat platelet aggregation induced by arachidonic acid, ADP, collagen, U46619, and I-BOP. The results obtained indicate that some pyrazino[2,3-c][1,2, 6]thiadiazine derivatives show significant platelet aggregation inhibition similar to other antithrombotic agents and that the antiplatelet properties may be mediated by interference with the arachidonic acid pathway.

Animals↗

PF9404C, a new slow NO donor with beta receptor blocking properties.

1. PF9404C is the S-S diesteroisomer of a novel blocker of beta adrenergic receptors with vasodilatory properties. It causes a concentration-dependent relaxation of rat aorta helical strips pre-contracted with 10(-6) M noradrenaline (NA; IC(50) 33 nM). It was equipotent to nitroglycerin (NTG; IC(50) 49 nM), but much more potent than isosorbide dinitrate (ISD; IC(50) 15,000 nM). 2. Oxyhaemoglobin (10 microM) shifted to the right the concentration-response curve for the relaxation induced by PF9404C (IC(50) 530 nM) or NTG (IC(50) 61 nM). 3. Either methylene blue (MB) or ODQ (1 microM each) largely prevented the vasorelaxing responses to increasing concentrations of PF9404C or NTG. 4. In rat aorta smooth muscle cells, PF9404C increased the formation of cyclic GMP from 3 pmol mg(-1) protein in basal conditions, to 53 pmol mg(-1) protein in 10 microM PF9404C. Neither metoprolol nor carvedilol enhanced cyclic GMP. 5. In the electrically driven guinea-pig left atrium, PF9404C blocked the inotropic effects of isoprenaline in a concentration-dependent manner. Its IC(50) (30 nM) was similar to that for S-propranolol (22.4 nM) and lower than the IC(50)s for metoprolol (120 nM) and atenolol (192 nM). The beta-adrenergic ligand (-)-[(3)H]-CGP12177 (0.2 nM) was displaced from its binding to rat brain membranes with K(i) of 7 nM, 17 nM, 170 nM and 1.2 microM respectively for PF9404C, S-(-)propranolol, metoprolol, and atenolol. 6. The data are consistent with the idea that the S-S diesteroisomer PF9404C, is a potent vasorelaxing agent, as well as a blocker of cardiac beta adrenergic receptors. The mechanism of its vasorelaxing effects involves the slow generation of NO. This molecule can, therefore, exhibit antihypertensive and cardioprotective actions through a double mechanism, NO donation and beta blockade.

Adrenergic beta-Antagonists↗

Early complete recanalization in internal carotid artery embolism treated with high-dose t-PA: a sequential angiographic study in a novel model of embolism in rats.

Complete early recanalization rate of human internal carotid artery embolic occlusion treated with thrombolytic drugs is low. To study factors related with this difficulty to recanalize we have developed a novel model of rat ica embolism using a fragment of human embolus. In 50 male Wistar rats the ica was embolized through the external carotid artery with a fragment of an embolus obtained from a human embolectomy passed through a catheter of 0.8 mm diameter. Recanalization was assessed by sequential angiograms from 15 to 120 min after embolization. Reperfusion was classified according to TIMI grades. Emboli of either 1 (group 1) or 2 mm (group 2) in length were cut. In group 1, four groups of nine animals each were treated, 15 min after embolization, with i.v. t-PA at doses of 1 mg/kg, 10 mg/kg and 20 mg/kg or saline. In group 2 there was one control group of seven animals treated with saline and another of seven animals treated with 10 mg/kg t-PA. Complete recanalization (TIMI grade 3) within the first 30 min was present in two animals treated with 10 and 20 mg/kg. Complete recanalization within the first 60 min was present in 0% of controls and animals treated with 1 mg/kg and in 44% of the 10 and 20 mg/kg groups (P<0.05 in chi-square test). Incomplete recanalization (TIMI grades 0, 1 and 2) occurred in 33%. In group 2 total recanalization occurred in 1/7 controls and in 3/7 animals receiving 10 mg/kg of t-PA. Early (60 min) complete i.v. t-PA induced internal carotid artery embolic recanalization is low with standard doses and increases moderately when high doses are used. Further increases in the dose do not improve recanalization rate, which is not clearly influenced by embolus size. Complete recanalization within 30 min, the period after which infarction develops in the rat, is uncommon in our model.

Angiography↗

[Transient radicular nerve conduction block in patients with intermittent neurogenic claudication].

Patients with neurogenic claudication do not usually exhibit symptoms at rest. The diagnosis is uncertain when there are no signs of lumbar radiculopathy. However, the functional deficiary could show up during a brief time at presentation of the symptoms if appropriate electrophysiological techniques are used to measure nerve conduction at the radicular segment. In 8 patients with neurogenic claudication, we examined the curve of recruitment of the soleus H reflex and in four of them the chronodispersion of the F wave of the posterior tibial nerve, before and after walking was also examined. Both studies showed normal results before walking in all patients. The H wave showed a transient diminution of excitability in 6 patients after walking, which lasted for a mean period of 7 min. Only one of these patients also showed an increase in the chronodispersion of the F wave. Our data suggest that conduction is transiently blocked in large myelinated fibers at a radicular level in patients with neurogenic claudication after walking. This could partially explain the symptoms of neurogenic claudication.

Adult↗

Pharmacological activity of PF-904 in guinea pig in vivo, and on human bronchus and neutrophils in vitro.

The effects of PF-904 (4-amino-1-ethyl-6-methylpyrazino[2,3-c][1,2,6]thiadiazine 2,2-dioxide), a pyrazinothiadiazine derivative, were examined in guinea-pig airways in vivo, in human isolated bronchus and human polymorphonuclear leukocytes. PF-904 (12.5-200 mg/kg, intraduodenal) reduced bronchoconstriction in response to histamine, arachidonic acid, platelet-activating factor (PAF) and methacholine. PF-904 (50-200 mg/kg) prevented PAF-induced airways hyperreactivity and inhibited antigen-induced bronchoconstriction, airway microvascular leakage and eosinophil lung accumulation, but antigen-induced airways hyperresponsiveness was not reduced. PF-904 (1 microM-1 mM) produced complete inhibition of spontaneous (-logEC50 = 3.57+/-0.04; n = 10) and histamine-stimulated tone (-logEC50 = 3.66+/-0.07; n = 10) of human isolated bronchus. Glibenclamide (10 microM) or precontraction with KCl (80 mM) did not impede PF-904-induced bronchial relaxation. PF-904 inhibited cyclic AMP (-logIC50 = 2.83+/-0.25; n = 8) and cyclic GMP (-logIC50 = 2.90+/-0.21; n = 8) phosphodiesterase activity in human bronchus. The activity of type IV phosphodiesterase was inhibited by PF-904 (-logIC50 = 3.43+/-0.11; n= 3). PF-904 also inhibited superoxide release by N-formylmethionyl-leucyl-phenylalanine-stimulated human polymorphonuclear leukocytes, but the maximal effect was approx. 50% of that produced by rolipram (10 microM). This profile of activities of PF-904 suggests that this compound has potential therapeutic value as an anti-asthma drug.

Animals↗

Interaction between adrenaline and epidermal growth factor in the control of liver glycogenolysis in mouse.

Epidermal growth factor (EGF) stimulates glycogenolysis in mouse liver, but the effect requires concentrations that are only achieved in plasma upon adrenergic stimulation of EGF release from submandibular salivary glands. Thus, we studied the interaction between adrenaline and EGF in liver glycogen metabolism, both in whole animals and in isolated hepatocytes. Adrenaline administered to anesthetized mice stimulated both the endocrine secretion of EGF from submandibular salivary glands and the degradation of glycogen in the liver. In sialoadenalectomized mice, adrenaline administration did not increase plasma EGF concentration. In these animals, the glycogenolytic response to adrenaline was enhanced. The sensitivity of hepatocytes to adrenaline was similar in cells from sialoadenalectomized and sham-operated mice. EGF, added to isolated hepatocytes, reduced the glycogenolytic effect of adrenaline (the maximal effect but not the ED50). Adrenaline stimulated glycogen degradation through both an alpha1-adrenergic mediated Ca2+ increase and a beta-adrenergic-mediated cAMP increase. EGF did not interfere with the rise of cytosolic Ca2+ but decreased the cAMP signal. EGF did not decrease the glycogenolytic effect of phenylephrine or VP (which increased cytosolic Ca2+ but not cAMP), but EGF decreased both the glycogenolytic effect and the cAMP signal generated by glucagon or forskolin. EGF did not interfere with the glycogenolytic effect of CPT-cAMP or bt2-cAMP. The effect of EGF on cAMP was blocked by 3-isobutyl-1-methylxanthine. These results demonstrate that the effect of EGF on the glycogenolytic action of adrenaline involves interference with the generation of the cAMP signal. We suggest that EGF induces such an effect through the activation of a phosphodiesterase.

Animals↗

Epidermal growth factor administration decreases liver glycogen and causes mild hyperglycaemia in mice.

Several laboratories report different effects of epidermal growth factor (EGF) on glycogen metabolism in hepatocytes. The discrepancies may be attributed to differences in the experimental conditions. It is therefore important to establish the actual effect of EGF in vivo. Because large physiological variations of EGF concentration in plasma occur in mice, we used this species to address this question. In freshly isolated mouse hepatocytes, EGF increased glycogen degradation in a dose-dependent manner. The maximal effect (36% increase over basal glycogenolysis) was smaller than maximal effects of classical glycogenolytic hormones like adrenaline or glucagon (more than 150% increase over basal). This is in keeping with the smaller effect of EGF on phosphorylase a activity. In contrast with these hormones, EGF did not inhibit glycolysis. Thus these effects of EGF in mouse hepatocytes are similar to those recently described by us in rat hepatocytes [Quintana, Grau, Moreno, Soler, Ramirez and Soley (1995) Biochem J 308, 889-894]. When administered to whole animals, EGF increased phosphorylase a activity, decreased the glycogen content in the liver and caused mild hyperglycaemia. Taking together the results obtained for isolated cells and for whole animals, we suggest that the glucosyl residues released from glycogen are used mostly by the liver rather than released to the circulation. This would be different from the action of the classical glycogenolytic hormones, adrenaline and glucagon.

Animals↗