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Biomedical subjects

F Soler

Publications and source records attributed to F Soler.

At least 19 recordsLinked to original sources
PubMed2006

Two-stage treatment with preoperative endoscopic retrograde cholangiopancreatography (ERCP) compared with single-stage treatment with intraoperative ERCP for patients with symptomatic cholelithiasis with possible choledocholithiasis.

BACKGROUND AND STUDY AIMS: An ideal treatment for choledocholithiasis in the laparoscopic era has not been established. The objective of this study was to elucidate whether a treatment strategy of performing intraoperative endoscopic retrograde cholangiopancreatography (ERCP) during laparascopic cholecystectomy (when choledocholithiasis is confirmed by intraoperative cholangiography) is better for patients with suspected common bile duct stones than the current strategy (preoperative ERCP followed by laparoscopic cholecystectomy). PATIENTS AND METHODS: This was a prospective randomized study to evaluate which of these two approaches was most benefit- and cost-effective for patients with intermediate risk of choledocholithiasis. Patients underwent either preoperative ERCP followed by a laparoscopic cholecystectomy a few weeks later (the "preoperative ERCP" group) or intraoperative ERCP (the "intraoperative ERCP" group). Intraoperative ERCP was performed using the rendezvous technique. RESULTS: There were 64 patients in the preoperative ERCP group and 59 patients in the intraoperative ERCP group. The demographic and clinical characteristics of the two groups were similar, except that the bilirubin and gamma-glutamyl transferase (GGT) levels and the number of patients treated on an inpatient basis were higher in the preoperative ERCP group. Success rates were similar (96.6 % in the preoperative ERCP group vs. 90.2 % in the intraoperative ERCP group in the per-protocol study). Total morbidity, post-ERCP morbidity, and post-ERCP acute pancreatitis rates were higher in the preoperative ERCP group, but there were no differences between the two groups in the frequency of residual common bile duct stones, the conversion rate to open cholecystectomy, or surgical morbidity. The length of hospital stay and costs were lower in the intraoperative ERCP group despite the longer surgical times in this group. Univariate analysis did not find any relationship between morbidity and total bilirubin or GGT. Logistic regression analysis confirmed that morbidity was related only to the treatment group and the time spent in the operating room: the relative risk (RR) was 4.37 for morbidity and 1.015 for the time spent in the operating room); the RR for papillotomy was 5.49. CONCLUSIONS: Both treatment approaches were equally effective but the intraoperative ERCP group had less morbidity, a shorter hospital stay, and reduced costs. The lower morbidity in the intraoperative ERCP group resulted from the lower rate of papillotomy and lower rates of post-ERCP pancreatitis and cholecystitis. Total morbidity was principally related to the type of treatment approach used.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed2003

Bifid mandibular canal.

PURPOSE: To determine the incidence and characteristics of bifid mandibular canals. METHODS: A retrospective study was performed using panoramic radiographs of 2012 patients subjected to dental treatment in the Dental Clinic of the Valencia University Dental School (Valencia, Spain) between 1996 and 1999. The goal was to investigate the presence of double mandibular canals. RESULTS: The extraoral panoramic radiographs revealed a total of 7 images suggestive of bifid canals. Mandibular computed tomography revealed the existence of this anatomic variant in 2 of 3 patients. An analysis was performed on the incidence of this type of image in extraoral panoramic radiography, its possible interpretations, and the clinical implications of bifid mandibular canals. CONCLUSIONS: In this study, 0.35% of canals were bifid. All cases were in women.

Adolescent↗
PubMed2001

Unravelling the interaction of thapsigargin with the conformational states of Ca(2+)-ATPase from skeletal sarcoplasmic reticulum.

Preincubation of thapsigargin with sarcoplasmic reticulum vesicles in the presence of high Ca(2+) or the addition of high Ca(2+) to microsomal vesicles preincubated with thapsigargin in the absence of Ca(2+) allowed full enzyme phosphorylation by ATP. However, the enzyme activity was not protected by high Ca(2+) even when the samples were subjected to gel filtration before ATP addition. Our data indicate that: (i) the enzyme in the Ca(2+)-bound conformation can be stabilized in the presence of thapsigargin; (ii) the conformational transition from the Ca(2+)-free to the Ca(2+)-bound state can be elicited by Ca(2+) when thapsigargin is present; (iii) thapsigargin binding occurs whether or not the enzyme is in the presence of Ca(2+), and so a ternary complex enzyme-Ca(2+)-thapsigargin may be formed; (iv) thapsigargin can be dissociated from the enzyme with a slow kinetics after dilution under drastic conditions; (v) the kinetics of Ca(2+) binding is clearly slowed down by thapsigargin; and (vi) thapsigargin does not affect the hydrolysis rate of phosphorylating substrates when measured in the absence of Ca(2+), indicating that thapsigargin specifically inhibits the Ca(2+)-dependent activity.

Animals↗
PubMed2001

Sliding osteotomies in mandibular reconstruction.

The aim of this article is to describe a few simple and atraumatic methods for mandibular reconstruction following the ablation of tumors or traumas. These reconstruction techniques are indicated for rebuilding short mandibular defects (less than 4 cm) or for patients in poor general condition with larger defects that cannot be remedied using longer and more complicated procedures. Five types of osteotomies were used: "C," single, double, bilateral sliding, and sagittal sliding. Osteotomies were performed on 14 patients, 13 with malignant tumors and one with a gunshot wound. Good results were obtained in 10 patients, total failure occurred in two, and complications without failure of the reconstruction arose in the other two.

Adult↗
PubMed2000

Testing the versatility of the sarcoplasmic reticulum Ca(2+)-ATPase reaction cycle when p-nitrophenyl phosphate is the substrate.

A detailed characterization of p-nitrophenyl phosphate as energy-donor substrate for the sarcoplasmic reticulum Ca(2+)-ATPase was undertaken in this study. The fact that p-nitrophenyl phosphate can be hydrolyzed in the presence or absence of Ca(2+) by the purified enzyme is consistent with the observed phenomenon of intramolecular uncoupling. Under the most favorable conditions, which include neutral pH, intact microsomal vesicles, and low free Ca(2+) in the lumen, the Ca(2+)/P(i) coupling ratio was 0.6. A rise or decrease in pH, high free Ca(2+) in the lumenal space, or the addition of dimethyl sulfoxide increase the intramolecular uncoupling. Alkaline pH and/or high free Ca(2+) in the lumen potentiate the accumulation of enzyme conformations with high Ca(2+) affinity. Acidic pH and/or dimethyl sulfoxide favor the accumulation of enzyme conformations with low Ca(2+) affinity. Under standard assay conditions, two uncoupled routes, together with a coupled route, are operative during the hydrolysis of p-nitrophenyl phosphate in the presence of Ca(2+). The prevalence of any one of the uncoupled catalytic cycles is dependent on the working conditions. The proposed reaction scheme constitutes a general model for understanding the mechanism of intramolecular energy uncoupling.

Calcium↗
PubMed2000

Insight into the uncoupling mechanism of sarcoplasmic reticulum ATPase using the phosphorylating substrate UTP.

Ca(2+) transport and UTP hydrolysis catalyzed by sarcoplasmic reticulum Ca(2+)-ATPase from skeletal muscle was studied. A passive Ca(2+) load inside microsomal vesicles clearly decreased the net uptake rate and the final accumulation of Ca(2+) but not the UTP hydrolysis rate, causing energy uncoupling. In the absence of passive leak, the Ca(2+)/P(i) coupling ratio was 0.7-0.8. UTP hydrolysis did not maintain a rapid component of Ca(2+) exchange between the cytoplasmic and lumenal compartments as occurs with ATP. The uncoupling process in the presence of UTP is associated with: (i) the absence of a steady state accumulation of ADP-insensitive phosphoenzyme; (ii) the cytoplasmic dissociation of Ca(2+) bound to the ADP-sensitive phosphoenzyme; and (iii) the absence of enzyme inhibition by cyclopiazonic acid. All these characteristics confirm the lack of enzyme conformations with low Ca(2+) affinity and point to the existence of an uncoupling mechanism mediated by a phosphorylated form of the enzyme. Suboptimal coupling values can be explained in molecular terms by the proposed functional model.

Adenosine Triphosphatases↗
PubMed2000

Clomipramine and related structures as inhibitors of the skeletal sarcoplasmic reticulum Ca2+ pump.

The Ca2+-pumping activity of skeletal sarcoplasmic reticulum vesicles is half-maximally inhibited by 120 microM clomipramine, 250 microM desipramine, and 500 microM imipramine or trimipramine. The inhibition is attributed to the dihydrodibenzazepine moiety, since 3-(dimethylamino)propionitrile, reproducing the aliphatic amine chain, has no inhibitory action. The inhibition is shown as a marked decrease of Ca2+ binding at equilibrium in the absence of ATP and as a reduction of phosphorylation of the Ca2+-free conformation by inorganic phosphate. Therefore, the drug effect is consistent with preferential interaction of tricyclic antidepressants with the Ca2+-free conformation of the nonphosphorylated enzyme. An additional decrease in the apparent rate constant of enzyme dephosphorylation, i.e., in the release of phosphate from ATP during enzyme cycling was also noticed.

Adenosine Triphosphate↗
PubMed1999

Overlapping effects of S3 stalk segment mutations on the affinity of Ca2+-ATPase (SERCA) for thapsigargin and cyclopiazonic acid.

Chimeric exchanges and mutations were produced in the Ca(2+)-ATPase (SERCA) to match (in the majority of cases) corresponding sequences of the Na(+),K(+)-ATPase. The effects of these mutations on the concentration dependence of the specific Ca(2+)-ATPase inhibition by thapsigargin (TG) and cyclopiazonic acid (CPA) were then determined. Extensive chimeric mutations on the large cytosolic loop, on the S4 stalk segment, and on the M3 transmembrane segments produced little or no modification of the Ca(2+)-ATPase sensitivity to either inhibitor. On the other hand, the presence of a six amino acid Na(+), K(+)-ATPase sequence within the S3 stalk segment of the Ca(2+)-ATPase raised 60-fold the apparent K(i) for TG and 250-fold the apparent K(i) for CPA. More limited mutations within the same S3 segment, however, affected differently the concentration dependence of the Ca(2+)-ATPase inhibition by TG or CPA. Specifically, single mutation of Phe256 to Val increased 20-fold the apparent K(i) for TG, while having very little effect on the apparent K(i) for CPA. These findings indicate significant overlap of the TG and CPA binding domains within the S3 stalk segment of the Ca(2+)-ATPase, where the contribution of each protein residue is dependent on the structures of the two inhibitors. Saturating concentrations of either or both TG and CPA produce an identical reduction of the affinity of the ATPase for ATP, suggesting that only one inhibitor can bind at any time due to significant overlap of their binding domains. It is suggested that perturbations produced by binding of either inhibitor within the stalk segment interfere with the long-range functional linkage between ATP utilization in the ATPase cytosolic region and Ca(2+) binding in the membrane-bound region.

Adenosine Triphosphate↗
PubMed1999

Tricyclic antidepressants inhibit the Ca(2+)-dependent ATPase activity from plasma membrane.

Tricyclic antidepressants are moderately potent inhibitors of the plasma membrane Ca(2+)-ATPase activity measured in erythrocyte ghosts. For the calmodulin-activated activity, half-maximal inhibition was observed in the presence of 0.25 mM clomipramine. Desipramine, imipramine, and trimipramine show half-maximal inhibition in the range of 0.8 to 1 mM. The inhibition dependence on clomipramine concentration is the same whether the enzyme is activated by exogenous calmodulin or by tryptic digestion. A similar behavior was observed for desipramine. The inhibition mechanisms utilized by clomipramine and desipramine are different. The clomipramine effect is associated with the Ca(2+)-bound enzyme conformation and can be attributed to a decrease in the rate of phosphorylation by ATP. The desipramine effect appears more related to the Ca(2+)-free conformation, since the partial reaction involved in the release of inorganic phosphate is perturbed by this drug. There is also little or no effect of tricyclics on the enzyme's affinity for ligand (Ca(2+) or ATP) binding.

Adenosine Triphosphate↗
PubMed1998

Ritodrine inhibition of the plasma membrane Ca2+-ATPase from human erythrocyte.

The Ca(2+)-ATPase activity of human erythrocyte membrane can be inhibited in vitro by ritodrine, a beta 2-adrenergic agonist. The inhibitory profile shows a low-affinity interaction and no competition with the specific transport and catalytic substrates. The activated conformation of the enzyme (in the presence of calmodulin or after trypsin digestion) facilitates the interaction with ritodrine. This suggests that the C-terminal tail of the enzyme plays a protective role. By studying selected partial reactions of the catalytic and transport cycle we found that the inhibition can be basically assigned to a lower rate of phosphorylation by ATP. A minor effect on the phosphorylation level by Pi in the absence of Ca2+ and no effect on the enzyme affinity for Ca2+ or ATP were also observed. The inhibition of the plasma membrane Ca(2+)-ATPase by ritodrine shows a clear similarity with that of the sarcoplasmic/endoplasmic reticulum membrane. The inhibition under study does not foresee a pharmacological effect of ritodrine on the myometrial plasma membrane Ca(2+)-ATPase when administered for the management of preterm labor.

Adenosine Triphosphate↗
PubMed1998

Cyclopiazonic acid effect on Ca2+-dependent conformational states of the sarcoplasmic reticulum ATPase. Implication for the enzyme turnover.

The affinity of sarcoplasmic reticulum Ca2+-ATPase for cyclopiazonic acid is dependent on the conformational state of the enzyme. It is high in the absence of Ca2+ but low in its presence. When Ca2+ was added to the enzyme in the presence of equimolar toxin, the apparent rate constant for Ca2+ binding was 0.6 min-1 when measured at 37 degrees C. The apparent equilibrium constant for Ca2+ dissociation increased from 0.2 to 0.6 microM at neutral pH, and from 5.9 to 37 microM at pH 6.0. The apparent equilibrium constant for Ca2+ dissociation increased progressively as the amount of toxin increased above an equimolar level. Cyclopiazonic acid decreased phosphorylation by ATP and Ca2+ when the enzyme in the absence of Ca2+ was incubated in the presence of toxin, although no effect was observed after a preliminary incubation with Ca2+ at 37 degrees C. Cyclopiazonic acid incubated with the enzyme in the presence of Ca2+ could be eliminated with a Sephadex column. However, the toxin could not be removed when it was incubated with the enzyme in the absence of Ca2+. In the latter case, cyclopiazonic acid was eliminated when the enzyme in the presence of toxin was incubated with Ca2+ at 37 degrees C. Under turnover conditions and in the presence of 10 microM ATP, the toxin-enzyme interaction can be characterized by an apparent Kd of 7 nM. With an ATP concentration of 1 mM, the enzyme was inhibited completely at a toxin/enzyme molar ratio of approximately 10. Furthermore, enzyme activity was observed to recover at a toxin/enzyme molar ratio of 1 when the Ca2+ concentration was raised, which is consistent with the competitive character of cyclopiazonic acid and Ca2+. It is concluded that ATP and Ca2+ can protect against cyclopiazonic acid inhibition.

Animals↗
PubMed1998

Cytotoxicity of paraquat in freshly isolated rat hepatocytes: effects of L-carnitine.

The effects of L-carnitine, a mitochondrial carrier of fatty acids, on paraquat (PQ) cytotoxicity in freshly isolated rat hepatocytes were studied. Addition of PQ (10 mM) to hepatocytes resulted in a time-dependent depletion of intracellular glutathione (GSH) accompanied by an increase in accumulation of malondialdehyde (MDA) in the incubation medium which proceeded to a loss of cell viability. Pretreatment of hepatocytes with L-carnitine (50-mM) alone did not affect cell viability or intracellular levels of GSH, or accumulation of MDA in the medium during the incubation period; however, pretreatment with L-carnitine 30 min prior to PQ addition did promote the depletion of intracellular GSH and MDA accumulation induced by PQ, and ultimately enhanced the cytotoxicity of PQ.

Animals↗
PubMed1998

Accentuation of paraquat-induced toxicity by L-carnitine in mice.

The effects of L-carnitine on toxicity induced by paraquat (PQ) in mice were investigated. L-carnitine pretreatment surprisingly promoted the toxicity of PQ in a dose-dependent manner shortening the survival time. The maximum effect occurred when L-carnitine, at a dose of 16 mmol/kg, was intraperitoneally administered 30 min before an intraperitoneal injection of PQ (75 mg/kg). Lipid peroxidation in lung significantly increased 6 h after PQ administration. L-carnitine accelerated this effect since L-carnitine-pretreated mice already showed a significant increase of lung malondialdehyde 1 h after PQ administration. In liver, PQ administration did not produce lipid peroxidation; nevertheless L-carnitine-pretreated mice showed a significant increase of malondialdehyde 6 h after PQ administration. Lung and liver glutathione decreased in mice receiving only PQ but this effect was not significantly changed by L-carnitine pretreatment. These results indicate that L-carnitine accelerates PQ-induced mortality rate by facilitating lipid peroxidation.

Analysis of Variance↗
PubMed1998

Acute 2,4-D poisoning in tench (Tinca tinca L.): lesions in the hematopoietic portion of the kidney.

An experimental model was designed to study the acute lesions caused by a continuous exposure to 2,4-dichlorophenoxyacetic acid (2,4-D) disolved in water (400 mg/L) in hematopoietic kidney tissue in tench (Tinca tinca L). Fifty fish were used in this study, 15 for calculating LC50 and 35 were euthanized 1, 2, 5, 8, and 12 days postpoisoning (five treated and two controls each time). Tissue samples, fixed in 5% glutaraldehyde in 0.1 M phosphate buffer (pH 7. 2) for histopathological examination, revealed marked alteration of hematopoietic tissue, characterized by progressive swelling and cell necrosis, activation of the phagocyte system, and subsequent formation of myelin figures. Variations recorded in hematocrit and hemoglobin levels in blood samples indicated changes in membrane permeability, complementing the findings on hematopoietic tissue. The lethal dose (LC50) at 96 h demonstrated the importance of the species and chemical form used as factors in calculating a product's toxicity.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1997

On the inhibition mechanism of sarcoplasmic or endoplasmic reticulum Ca2+-ATPases by cyclopiazonic acid.

Ca2+-ATPase inhibition by stoichiometric and substoichiometric concentrations of cyclopiazonic acid was studied in sarcoplasmic reticulum preparations from rabbit fast-twitch muscle. The apparent affinity of the nonphosphorylated enzyme for ATP showed a Kd of approximately 3 microM in the absence of cyclopiazonic acid and approximately 28 microM in the presence of the drug. Fractional saturation of the enzyme by cyclopiazonic acid was accompanied by the appearance of two ATP-binding populations (enzyme with and without drug) and a progressive increase in the half-maximal concentration for saturating the ATP-binding sites. Enzyme turnover in the presence of stoichiometric concentrations of cyclopiazonic acid displayed lower apparent affinity for ATP and lower maximal hydrolytic activity than in the absence of the drug. When cyclopiazonic acid is in the substoichiometric range, the observed kinetic parameters will correspond to the simultaneous contribution of two different reaction cycles sustained by the enzyme with and without drug. The inhibition could be elicited by adding ATP to allow the enzyme turnover when cyclopiazonic acid was preincubated with the enzyme in the presence of Ca2+. The onset of inhibition during enzyme cycling was observed over a period of seconds, revealing the existence of a low inhibition rate constant. It is concluded that cyclopiazonic acid decreases enzyme affinity for ATP in non-turnover conditions by approximately one order of magnitude. This allows enzyme cycling after drug binding, provided that a high ATP concentration is used. Cyclopiazonic acid and ATP do not compete for the same binding site.

Adenosine Triphosphate↗
PubMed1996

Betulinic acid derivatives: a new class of specific inhibitors of human immunodeficiency virus type 1 entry.

A novel series of omega-aminoalkanoic acid derivatives of betulinic acid were synthesized and evaluated for their activity against human immunodeficiency virus (HIV). The anti-HIV-1 activity of several members of this new series was found to be in the nanomolar range in CEM 4 and MT-4 cell cultures. The optimization of the omega-aminoalkanoic acid side chain is described. The presence of an amide function within the side chain was found important for optimal activity. RPR 103611 (14g), a statine derivative, was found to be inactive against HIV-1 protease, reverse transcriptase, and integrase as well as on gp120/CD4 binding. "Time of addition" experiments suggested interaction with an early step of HIV-1 replication. As syncytium formation, but not virus-cell binding, seems to be affected, betulinic acid derivatives are assumed to interact with the postbinding virus-cell fusion process.

Antiviral Agents↗
PubMed1996

Betulinic acid derivatives: a new class of human immunodeficiency virus type 1 specific inhibitors with a new mode of action.

A series of omega-undecanoic amides of lup-20(29)-en-28-oic acid derivatives were synthesized and evaluated for activity in CEM 4 and MT-4 cell cultures against human immunodeficiency virus type 1 (HIV-1) strain IIIB/LAI. The potent HIV inhibitors which emerged, compounds 5a, 16a, and 17b, were all derivatives of betulinic acid (3beta-hydroxylup-20(29)-en-28-oic acid). No activity was found against HIV-2 strain ROD. Compound 5a showed no inhibition of HIV-1 reverse transcriptase activity with poly(C).oligo(dG) as template/primer, nor did it inhibit HIV-1 protease. Additional mechanistic studies revealed that this class of compounds interfere with HIV-1 entry in the cells at a postbinding step.

Antiviral Agents↗