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L Aguirre

Publications and source records attributed to L Aguirre.

At least 19 recordsLinked to original sources
PubMed2003

[Isolated non-compaction of the left ventricle].

Isolated non compaction of the left ventricle is a rare congenital cardiomyopathy linked to an arrest of normal myocardial embryogenesis. We report two cases of isolated non compaction of the left ventricle discovered by echocardiography in 2 males of 30 and 55 years. The first had progressively worsening cardiac insufficiency, the second was being followed for an unexplained cardiomyopathy. In both cases, the diagnosis was able to be confirmed by transthoracic echocardiography, supported by MRI data. Although present from birth, this condition can become apparent at various ages and is complicated by sudden death (principal cause of mortality), severe cardiac insufficiency, or thrombo-embolic accidents. The diagnosis of left ventricular non compaction should be considered when faced with unexplained cardiac insufficiency in the adult.

Adult↗
PubMed2001

The cytoskeletal/non-muscle isoform of alpha-actinin is phosphorylated on its actin-binding domain by the focal adhesion kinase.

alpha-Actinin is tyrosine-phosphorylated in activated human platelets (Izaguirre, G., Aguirre, L., Ji, P., Aneskievich, B., and Haimovich, B. (1999) J. Biol. Chem. 274, 37012--37020). Analysis of platelet RNA by reverse transcription-polymerase chain reaction revealed that alpha-actinin expressed in platelets is identical to the cytoskeletal/non-muscle isoform. A construct of this isoform containing a His(6) tag at the amino terminus was generated. Robust tyrosine phosphorylation of the recombinant protein was detected in cells treated with the tyrosine phosphatase inhibitor vanadate. The tyrosine phosphorylation site was localized to the amino-terminal domain by proteolytic digestion. A recombinant alpha-actinin protein containing a Tyr --> Phe mutation at position 12 (Y12F) was no longer phosphorylated when expressed in vanadate-treated cells, indicating that tyrosine 12 is the site of phosphorylation. The wild type recombinant protein was not phosphorylated in cells lacking the focal adhesion kinase (FAK). Re-expression of FAK in these cells restored alpha-actinin phosphorylation. Purified wild type alpha-actinin, but not the Y12F mutant, was phosphorylated in vitro by wild type as well as a Phe-397 mutant of FAK. In contrast, no phosphorylation was detected in the presence of a kinase-dead FAK. Tyrosine phosphorylation reduced the amount of alpha-actinin that cosedimented with actin filaments. These results establish that alpha-actinin is a direct substrate for FAK and suggest that alpha-actinin mediates FAK-dependent signals that could impact the physical properties of the cytoskeleton.

Actinin↗
PubMed2001

Effects of supplemental oxygen during activity in patients with advanced COPD without severe resting hypoxemia.

STUDY OBJECTIVES: To assess oxygen desaturation during activities and to evaluate the short-term effects of supplemental O(2) use in patients with severe COPD who do not qualify for long-term O(2) therapy. DESIGN: A double-blind, randomized, placebo-controlled trial. SETTING: Outpatients from the pulmonary diseases division of a tertiary-care university hospital. PATIENTS: Twenty patients with stable COPD with FEV(1)/FVC ratios of < 50%, FEV(1) levels < 55% of the predicted normal value, and PaO(2) levels of > 60 mm Hg when resting. INTERVENTIONS: Patients were initially evaluated with pulmonary function tests, blood gas analysis, and Doppler echocardiography, and they underwent the following three 6-min walking tests (WTs) in a random sequence: basal WT (BWT); WT while breathing compressed air (CAWT); and WT while breathing O(2) (O(2)WT). MEASUREMENTS AND RESULTS: The distance walked was recorded in meters. Dyspnea was measured by Borg scale measurement before and after the tests, and arterial oxygen saturation measured by pulse oximetry (SpO(2)) was continuously monitored. Results were analyzed by grouping patients in the following manner: desaturators (DSs) (ie, patients with a drop in SpO(2) of at least 5% and < 90% during the WT) vs nondesaturators (NDSs); and O(2) responders (ie, patients with an increase of at least 10% in the distance walked and/or a decrease of at least 3 points in Borg index score) vs nonresponders. During the BWT, 11 of 20 patients (55%) were defined as desaturators. During the O(2)WT, the SpO(2) remained at > 90% in every patient. The distance walked increased by 22% (p < 0.02), and dyspnea decreased 36% (p < 0.01) in DS patients. In NDS patients, O(2) administration reduced dyspnea by 47% (p < 0.001), but the distance walked did not improve. Responses were markedly different from one patient to another. No significant differences were noticed between the results of the BWT and CAWT in any of the groups. Thirteen O(2) responders did not differ from 7 nonresponders either in basal data or in desaturation measure during the BWT, except that all walking responders (five patients) were above the median of basal left ventricle performance. CONCLUSIONS: Most of the studied COPD patients desaturated during the BWT. O(2) administration avoided desaturation and could increase the distance walked and reduce dyspnea, but these effects were not related to walking desaturation in individual cases. Improvements were not a placebo effect. The therapeutic role of O(2) during activities in some patients with severe COPD needs to be individually assessed.

Aged↗
PubMed2000

Interleukin-10 inhibits intimal hyperplasia after angioplasty or stent implantation in hypercholesterolemic rabbits.

BACKGROUND: Intimal hyperplasia after stent implantation is the main cause of in-stent restenosis. Activated monocytes play a key role in intimal growth. The anti-inflammatory cytokine interleukin-10 (IL-10) is a potent monocyte deactivator, endogenously produced in the atherosclerotic plaque. We tested the hypothesis that exogenous IL-10 may limit postangioplasty intimal hyperplasia after balloon angioplasty or stenting. METHODS AND RESULTS: Hypercholesterolemic rabbits were treated with recombinant human IL-10 (rhuIL-10) for 3 days after balloon angioplasty or 28 days after stent implantation. High IL-10 serum levels and intense deactivation of circulating monocytic cells, assessed by inhibition of IL-1beta release by lipopolysaccharide-stimulated whole blood, were detected for at least 8 hours after rhuIL-10 intravenous injection (ELISA). Morphometric analyses, performed 28 days after injury, indicated that rhuIL-10 reduced intimal growth by approximately 50% after balloon angioplasty or stenting, resulting in more preserved lumen in stented arteries. Moreover, rhuIL-10 reduced macrophage infiltration by 67% and proliferative activity by 81% in the intima and the media. No toxic effect was detected except minor changes in blood cell count. CONCLUSIONS: The anti-inflammatory cytokine rhuIL-10 reduces postinjury intimal hyperplasia. The potent attenuation of in-stent intimal growth by rhuIL-10 and its favorable toxicity profile suggest that rhuIL-10 may be useful in the prevention of in-stent restenosis.

Animals↗
PubMed1999

Tyrosine phosphorylation of alpha-actinin in activated platelets.

The integrin alpha(IIb)beta(3) mediates tyrosine phosphorylation of a 105-kDa protein (pp105) in activated platelets. We have partially purified a 105-kDa tyrosine-phosphorylated protein from platelets stimulated with phorbol 12-myristate 13-acetate and obtained the sequence of an internal 12-mer peptide derived from this protein. The sequence was identical to human alpha-actinin sequences deposited in the Swiss Protein Database. alpha-Actinin, a 105-kDa protein in platelets, was subsequently purified from activated platelets by four sequential chromatographic steps. Fractions were analyzed by Western blotting and probed with alpha-actinin and anti-phosphotyrosine antibodies. The distribution of alpha-actinin and pp105 overlapped throughout the purification. Furthermore, in the course of this purification, a 105-kDa tyrosine-phosphorylated protein was only detected in fractions that contained alpha-actinin. The purified alpha-actinin protein was immunoprecipitated with antibodies to phosphotyrosine in the absence but not in the presence of phenyl phosphate. alpha-Actinin resolved by two-dimensional gel electrophoresis of activated platelet lysates was recognized by the antibodies to phosphotyrosine, whereas pretreatment of the platelets with bisindolylmaleimide, a protein kinase C inhibitor that prevents tyrosine phosphorylation of pp105, inhibited the reactivity of the antibodies to phosphotyrosine with alpha-actinin. Taken together, these data demonstrate that a fraction of alpha-actinin is tyrosine-phosphorylated in activated platelets.

Actinin↗
PubMed1998

Flow cytometric study of mitochondrial dysfunction after AMPA receptor activation.

The effect of AMPA-receptor stimulation on MMP and on the concentration of intracellular calcium ([Ca2+]i) was studied in dissociated CGC from rat pups, by flow cytometry. In the presence of cyclothiazide, AMPA induced a sodium-independent decrease in MMP up to 30.7+/-2.5%. This effect was antagonized by CNQX and NBQX. Mepacrine and dibucaine reversed the effect of AMPA on MMP, suggesting that it is mediated by a release of arachidonic acid. AMPA alone induced a slight (about 7%) increase in [Ca2+]i. In the presence of cyclothiazide, AMPA induced a concentration-dependent [Ca2+]i increase up to 29.10+/-2.10% that was not reversed by flunarizine. This increase was similar to that observed in a Na+-free medium, and was antagonized by CNQX and NBQX, but not by MK-801. Mitochondria play a key role in the modulation of [Ca2+]i since a significant [Ca2+]i increase was found in the presence of FCCP. On the other hand, the dantrolene-sensitive calcium pools do not participate in the [Ca2+]i increase induced by stimulation of AMPA receptors. It is concluded that when AMPA-receptor desensitization is blocked, a decrease in MMP and an increase in [Ca2+]i occurs, which could be additional events to potentiate neuronal cell death induced by glutamate.

Animals↗
PubMed1998

U-83836E prevents kainic acid-induced neuronal damage.

The effect of kainic acid (KA) on mitochondrial membrane potential (MMP) and reactive-oxygen species (ROS) production was studied in dissociated cerebellar granule cells from rat pups. KA induced a maximum increase of 361%+/-35% in ROS production. The lazaroid compound U-83836E (at concentrations ranging from 10(-9) to 5x10(-6) M) completely inhibited this increase, with an IC50 value of 3.02+/-1.08x10(-7) M. KA also decreased the mitochondrial membrane potential (MMP), with a maximum decrease of about 30%. Absence of Na+ in the incubation medium did not significantly alter the effect of KA on MMP. As expected, the AMPA/kainate receptor antagonist NBQX inhibited the effects of KA on MMP with an IC50 value of 1.1+/-0.8 microM. However, the lazaroid U-83836E, indomethacin, nor-dihydroguaiaretic acid and L-nitroarginine all failed to inhibit the KA-induced decrease in the MMP. Finally, to assess the neuroprotective effect of U-83836E on KA-induced neurotoxicity in vivo, the increase in the peripheral-type benzodiazepine receptor density in rat hippocampus was measured. Treatment with KA increased the Bmax to 1341+/-192 fmol mg(-1). When U-83836E was coadministered with KA, the Bmax was reduced to 765+/-122 fmol mg(-1), which was not significantly different from the Bmax obtained from untreated rats (Bmax: 518+/-33 fmol mg(-1)). We conclude that treatment with the lazaroid U-83836E might be a suitable therapeutic strategy in neurodegenerative disorders.

Animals↗
PubMed1996

Effects of short-term zinc supplementation on cellular immunity, respiratory symptoms, and growth of malnourished Equadorian children.

OBJECTIVE: To assess the effect of zinc supplementation on respiratory tract disease, immunity and growth in malnourished children. DESIGN: A randomized double-blind placebo-controlled trial. SETTING: A day-care center in Quito, Ecuador. SUBJECTS: Fifty children (12-59 months old) recruited by height-for-age and weight-for-age deficit. INTERVENTIONS: Twenty-five children (supplemented, S group) received 10 mg/day of zinc as zinc sulfate, and 25 (nonsupplemented, NS group) received a placebo during 60 days. All were also observed during a 60-day postsupplementation period. Two children of the S group dropped out. Daily the clinical presence of cough, respiratory tract secretions, and fever, was recorded. On days 0,60 and 120, the cutaneous delayed-type hypersensitivity (DTH) to multiple antigens, and anthropometric parameters were assessed. On days 0 and 60 serum zinc levels were also measured. RESULTS: On day 60, DTH was significantly larger (20.8 +/- 7.1 vs 16.1 +/- 9.7 mm), and serum zinc levels were significantly higher (118.6 +/- 47.1 vs 83.1 +/- 24.5 micrograms/dl) in the S group than in the NS group (P <0.05 for each). The incidence of fever [relative risk (RR): 0.30, c.i. = 0.08- 0.95, P =0.02], cough (RR): 0.52, c.i. = 0.32-0.84, P = 0.004) and upper respiratory tract secretions (RR):0.72, c.i. = 0.59-0.88, P = 0.001) was lower in the S group than in the NS group at day 60. At the end of the postsupplementation observation period (day 120), the incidence of fever and upper respiratory tract secretions was the same in both the S and NS groups. The incidence of cough was higher at day 120 in the S group than in the NS group (RR): 2.28, c.i. = 1.37-3.83, P = 0.001). CONCLUSIONS: This study supports a role for zinc in immunity, and immunity to respiratory infections, while pointing out the need for larger studies.

Adjuvants, Immunologic↗
PubMed1996

[Acute effect of lorazepam on respiratory muscles in stable patients with chronic obstructive pulmonary disease].

Benzodiazepines are known to cause muscle hypotonia, but their effects on respiratory muscle function, particularly on diaphragm, have not yet been studied. Our aim was to look for any effect of lorazepam on respiratory muscle function in patients with chronic obstructive pulmonary disease (COPD). Nine stable COPD patients (mean +/- SD forced expiratory volume in one second (FEV1) 0.91 +/- 0.31 l) were included in the study. The following measurements were performed before and 1 hour after lorazepam administration (doses: 1.5 to 2 mg) by sublingual route: forced vital capacity (FVC), FEV1, maximal voluntary ventilation (MVV), arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), minute ventilation (Ve), tidal volume (Vt), respiratory rate (f), inspiratory time/inspiratory plus expiratory time (Ti/Ttot)-, mean inspiratory flow (Vi), maximal inspiratory (MIP) and expiratory (MEP) pressures, maximal pleural pressure (Pplmax), transdiaphragmatic pressures (Pdi) and skeletal muscle strength and endurance. As expected, no change was noted in FVC, FEV1, FEV1/FVC (Table-1). Besides stability of expiratory flows, this denotes no change in collaboration in spite of the sedative effects of lorazepam. There was a 20% decrease in Ve, due to a Vt reduction and a small increase in PaCO2. These could be explained by the central effects of benzodiazepines. Skeletal muscle strength and endurance decreased significantly (22 and 50% respectively-Table 2), in accordance with the previously reported muscular actions of this pharmacological group. Respiratory muscle function parameters, MIP, MEP, MVV and Ppl showed significant reductions (10 to 20 per cent), as was the case with diaphragmatic function measured by Pdi (Muller maneuver with abdominal protrussion and maximal open-glottis expulsive maneuver) (Table 3). This study demonstrates that a single lorazepam dose reduces strength and endurance of respiratory muscle in chronic stable COPD patients.

Female↗
PubMed1982

The influence of indomethacin and possible role of prostaglandins on calcium renal excretion.

Our aim was to evaluate the possible role of prostaglandins (PG) on renal calcium excretion in humans through the PG inhibitory effects of indomethacin. Renal calcium excretion was evaluated by a technique of impulse analysis which gives a function W(t) specific of the tubular calcium transport. Several parameters were derived from this function: (1) the fractional excretion of filtered calcium as % of total dose (FECa % TD); (2) the peak excretion rate, and (3) the mean transit time (MTT, min). The aforementioned parameters were determined in 7 healthy subjects in basal conditions and again after 10 days of treatment with 100 mg indomethacin daily. FECa was significantly (p less than 0.02) higher with indomethacin (8.18 +/- 0.97) than under basal conditions (5.02 +/- 0.57). The peak excretion rate and MTT remained unchanged after indomethacin. These results indicate that indomethacin increases renal calcium excretion. As indomethacin did not produce any significant change in glomerular filtration rate (125 +/- 7 ml/min before vs. 129 +/- 9 ml/min after) one can assume that PG play a role in tubular calcium reabsorption. However, the mechanism remains to be elucidated: direct action or mediated through the cyclic AMP system.

Adolescent↗
PubMed1982

Restored synergistic entero-hormonal response after addition of dietary fibre to patients with impaired glucose tolerance and reactive hypoglycaemia.

Although some dietary fibres (DF) improve glucose tolerance by slowing carbohydrate absorption, other mechanisms are certainly involved. Some of the entero-hormonal responses after DF were investigated in six patients with impaired glucose tolerance and reactive hypoglycaemia. All patients received two different breakfasts, each containing 25 g of starch supplied either as white bread (WB) or a fibre-enriched bread preparation (FB): 4 g hemicellulose and 4 g guar. Metabolic and hormonal responses were evaluated over 5 hours. Compared to WB, the FB had a blunting effect on the resulting blood glucose peak (116 +/- 9 mg/100 ml with FB vs. 148 +/- 15 with WB P less than 0.025) or trough (88 +/- 3 mg/100 ml with FB vs. 79 +/- 5 with WB), and upon the insulin response at 60 min (20 +/- 4 micro U/ml with FB vs. 70 +/- 20 with WB). Gut glucagon immunoreactivity was diminished with FB at 90 min (185 +/- 39 vs. 242 +/- 42 P less than 0.05) and 150 min (180 +/- 39 vs. 242 +/- 40). Pancreatic glucagon was initially similar after FB and WB, but a significant rise was observed with FB at 180 min (116 +/- 17 pg/ml vs. 67 +/- 18 P less than 0.05). The improvement of the blood glucose pattern with DF, especially the suppression of reactive hypoglycaemia, seems to depend partly on reduced and delayed response of the entero-hormonal axis. This in turn results in a better synergistic secretion of insulin and glucagon in the late post-prandial period.

Adult↗
PubMed1982

[The influence of indomethacin and possible role of prostaglandin on renal calcium excretion (author's transl)].

Our aim was to evaluate the possible role of prostaglandins (PG) on renal calcium excretion in humans through the PG inhibitory effects of indomethacin. Renal calcium excretion was evaluated by a technique of impulse analysis which gives a specific index of tubular calcium transport. Several parameters were derived from this specific transport function W(t): 1) the fractional excretion of filtered calcium as % of total dose (FECa % TD); 2) the peak excretion rate; 3) the mean transit time (MTT, min). The aforementioned parameters were determined in 7 healthy subjects in basal conditions and again after 10 days of treatment with 100 mg indomethacin daily. FECa was significantly (P less than 0.02) higher with indomethacin (8.18 +/- 0.97) than under basal conditions : (5.02 +/- 0.57). The peak excretion rate and MTT remained unchanged after indomethacin. These results indicate that indomethacin increases renal calcium excretion. As indomethacin did not produce any significant change in glomerular filtration rate (125 +/- 7 ml/min before v.s. 129 +/- 9 after) one can assume that PG play a role in tubular calcium reabsorption. However the mechanism remains to be elucidated : direct action of mediated through the cyclic AMP system.

Adolescent↗
PubMed1980

Evidence and mechanism for pectin-reduced intestinal inorganic iron absorption in idiopathic hemochromatosis.

The intestinal absorption of iron was measured in 13 patients suffering from idiopathic hemochromatosis by using a double radiotracer technique. For each patient, iron absorption was determined in the fasting state, i.e., under basal conditions, and after an oral indigestible fiber load (9 g/m2 of body surface) with either pectin (group I: eight patients) or cellulose (group II: five patients). The results were compared with those from a group of seven normal control subjects investigated under basal conditions. The patients with haemochromatosis (groups I and II) had a significant increase in the basal value of fractional iron absorption as compared with controls. In the patients of group I, the pectin induced a significant fall in fractional iron absorption (P less than 0.02). In group II, iron absorption rates remained unchanged whether or not cellulose was given. Furthermore, we found in vitro that pectin had a high iron binding activity, while cellulose bound none. From the present study, we conclude that pectin but not cellulose reduces iron absorption by forming unabsorbable complexes with dietary iron. Thus, enrichment of the diet with foods providing significant amounts of noncellulosic dietary fibers, such as pectin, may be useful in the management of hemochromatosis patients.

Adult↗
PubMed1978

Intestinal and renal handling of calcium in human diabetes mellitus: influence of acute oral glucose loading and diabetic control.

The intestinal absorption and the urinary excretion of calcium were compared in two groups of diabetic patients during periods of satisfactory and poor control. In a first group of ten patients, periods of isolated high glycosuria were obtained by giving an oral glucose load. The second group consisted of ten patients with a severe endogenous insulin deficiency. The subjects of this latter group were investigated before and after a few days of insulin therapy. In group I, the oral glucose load induced a significant increase in the intestinal calcium absorption and had a tendency to lower the urinary calcium excretion. Furthermore, an inverse relationship was found between the changes in the intestinal calcium absorption and the variations of the urinary calcium excretion. In group II, both intestinal absorption and urinary excretion of calcium fell significantly after recovery of satisfactory metabolic control by insulin therapy. From the results as obtained in group I one can conclude that glucose enhances the calcium transfer from the luminal to the serosal pole of both intestinal and renal tubular cells. During severe ketosis as observed in group II, calcium metabolism is considerably accelerated and the increase in the intestinal calcium absorption rate may be interpreted as compensatory mechanism for the high urinary loss of calcium.

Adolescent↗
PubMed1976

Simultaneous vaccination of cattle with foot-and-mouth disease and vesicular stomatitis live virus vaccines.

Four- to six- month-old cattle were simultaneously vaccinated with foot-and-mouth disease (FMD) and vesicular stomatitis (VS) live virus vaccines by injection of FMD vaccine in one side of the body and VS vaccine in the other side. These cattle were again vaccinated with FMD and VS vaccines given simultaneously three and nine months after the first vaccination. The antibody levels of the vaccinated animals were studied by serum protection test in suckling mice and results were compared with those obtained when cattle are vaccinated either with FMD alone or with VS vaccine alone. It appears that an interference mechanism is responsible for the lack or the low levels of antibody formation observed in the animals simultaneoulsy vaccinated with the two vaccines.

Animals↗