Biomedical subjects

M Serra

Publications and source records attributed to M Serra.

At least 91 records · Page 5Linked to original sources

PubMed1998

Neonatal morbidity associated with disproportionate intrauterine growth retardation at term.

We set out to compare neonatal morbidity between disproportionate intrauterine growth retarded newborn infants and proportionate retarded ones at term, based on ponderal index. This is a prospective study of 185 single pregnancies with evidence of intrauterine growth retardation at term. Sixty three cases (34%) were disproportionate and 122 (66%) proportionate in terms of ponderal index. All were born in the University Hospital 'Principe de Asturias' of Alcala de Henares, Madrid, Spain. Proportionate or disproportionate intrauterine growth retardation diagnosis was established using the ponderal index (weight/length3). The following outcomes of neonatal morbidity were investigated: (1) perinatal asphyxia (meconium-stained amniotic fluid, abnormal fetal heart rates, newborn acidosis or low Apgar score 7 at 5 minutes) and/or (2) early neonatal medical complications. Disproportionate intrauterine growth retardated newborn infants presented higher rates of perinatal asphyxia (54% vs. 32%, P 0.01), with higher abnormal fetal heart rates (37% vs. 15%, P 0.01), higher frequency of arterial pH 7.20 (31% vs. 16%, P 0.05); and also higher rates of early neonatal medical complications (40% vs. 11%, P 0.001), mainly hypoglycaemia (25% vs. 4%, P 0.01). Morbidity among disproportionate intrauterine growth retardated Aconates is significantly higher compared with proportionate ones, demonstrating the heterogeneity of the intrauterine growth retardation population. Proportionate and disproportionate intrauterine growth retardation should be diagnosed as early as possible, since the majority of the morbidity is intimately related to this difference.

Journal Article↗

PubMed1998

Predictors of adherence to tuberculosis treatment in a supervised therapy programme for prisoners before and after release. Study Group of Adherence to Tuberculosis Treatment of Prisoners.

The prison population is a high-risk group for tuberculosis (TB). This investigation aimed to study predictive factors of treatment adherence among prisoners involved in a pilot programme of supervised treatment. The study included TB patients from the Men's Penitentiary Center of Barcelona (MPCB) in 1995. Directly observed therapy (DOT) was carried out in the infirmary or in a methadone programme. Released prisoners were referred to the municipal maintenance methadone programmes (MMP) and other social resources. Incentives and enablers were used to improve compliance (economic aid for nutritional and housing needs, methadone programmes and admittance to a sociosanitary centre). The outcome of the patients' adherence was classified as follows: completed, defaulted, dead or transferred out. Factors associated with adherence were investigated through logistic regression. The programme included 62 patients, 43 of whom were intravenous drug users (IVDU) and 46 were infected with the human immunodeficiency virus (HIV). Nineteen had previously had TB and 32 were released from prison during TB treatment. Overall adherence was 89%; 97% among those who completed treatment in prison, and 79% among those who completed treatment outside prison (p=0.05). Ninety-five per cent of IVDU in an MMP completed treatment. Homeless or alcoholic exprisoners completed treatment only if they were admitted to sociosanitary centres. DOT throughout treatment resulted in better adherence (odds ratio (OR)= 16.80; confidence interval (CI): 2.42-116.2)). Those who were incarcerated throughout treatment also showed better adherence (OR= 7.36; CI: 0.79-48.16). Antituberculosis treatment adherence in prisoners was high even after release with adequate co-ordination among intrapenitentiary and extrapenitentiary programmes. Maintenance methadone programmes proved very useful in intravenous drug users, as did admittance to sociosanitary centres for indigent or alcoholic exprisoners undergoing treatment.

AIDS-Related Opportunistic Infections↗

PubMed1998

Early and late results after surgical therapy of postinfarction left ventricular aneurysm.

From 1979 to 1993, 139 patients had reduction of left ventricular aneurysm (LVA) by plication (PL) (25 cases) linear repair (74 cases) or ventricular reconstruction (VR) (40 cases). Coronary bypass grafting was performed in 89 patients. We retrospectively reviewed our experience in order to identify predictore of early and late outcome and determine whether ventricular reconstruction (VR) can improve postoperative and late prognosis. Operative mortality (OM) was 7.2%. Among 129 hospital survivors, 48 died during FU (LM). OM was related to a more recent myocardial infarction (p=0.0001), a higher residual score (RS) (p=0.02), a lower EF (p=0.038), a higher left ventricular score (p=0.059), a three-system disease (TSD) (p=0.09) and a right coronary disease (RCD) (p=0.13). At Multivariate Analysis (Stepwise Logistic Regression) TSD (p=0.001), RCD (p=0.008) and RS (p=0.04) are independent risk factors. Actuarial survival rate at 15 years is 33.5+/-6.9% (OM included). According to the comparison of the Actuarial Curves (Tests of Mantel and Breslow, OM excluded) the most significant risk factors were: non use of left internal mammary artery (LIMA) (p=0.004), VR (p=0.01), TSD (p=0.03) and higher NYHA class (p=0.019). Multivariate Analysis (Co Model) confirms that late prognosis is influenced by non use of LIMA (p=0.03) and TSD (p=0.04); outcome is also affected by preoperative arrhythmias (p=0.022). Five-year survival after VR is 87.5+/-5.7% vs 64.9+/-5.5% after simple linear closure or PL (p=0.1075 and p=0.2252). Our results confirm that OM and LM are influenced by extent of myocardial ischemic damage; in agreement with the majority of Authors we advocate a complete revascularization using IMA, when appropriate, on left anterior descending artery. Our limited experience with VR fails to demonstrate this technique as an independent factor of late survival.

Adult↗

PubMed1998

Expression of functional CD40 on human osteosarcoma and Ewing's sarcoma cells.

CD40, a membrane glycoprotein of the tumor necrosis factor receptor family, is expressed by several tumor types, including B-cell lymphomas, carcinomas, and melanoma, but little is known concerning its expression by sarcoma. We used flow cytometry to analyze the expression of CD40 in human cell lines derived from 12 osteosarcomas, 6 Ewing's sarcomas, and 5 rhabdomyosarcomas. Detectable CD40 levels ranging from low to very high were found in one-third of osteosarcomas, whereas five of six Ewing's sarcomas expressed intermediate levels of CD40; all rhabdomyosarcomas were CD40-negative. At the tissue level, two of eight primary high-grade osteosarcomas showed CD40-positive immunostaining. Osteosarcoma cells and Ewing's sarcoma cells expressing CD40 were treated with recombinant soluble CD40 ligand to analyze CD40 function. Treatment with soluble CD40 ligand increased the level of apoptotic cells and stimulated the transcription of matrix metalloproteinase 9 gene, enhancing matrix metalloproteinase 9 enzyme secretion. The results indicate that in human osteosarcoma and Ewing's sarcoma, CD40 is a functional receptor whose engagement can have opposite effects on tumor cell survival and malignancy.

Apoptosis↗

PubMed1998

Genetic imbalances in 67 synovial sarcomas evaluated by comparative genomic hybridization.

We used comparative genomic hybridization (CGH) to evaluate DNA sequence copy number changes in 67 synovial sarcomas of both monophasic and biphasic histological subtypes. Changes (mean among aberrant cases: 4.7 aberrations/tumor; range: 1-17), affecting most often entire chromosomes or chromosome arms, were detected in 37 sarcomas (55%). Gains and losses were distributed equally, but different chromosomes were affected with variable frequencies. The most frequent aberrations, each detected in 9-11 of 67 tumors, were gain of 8q and gain at 12q (12q14-15 and 12q23-qter), loss of 13q21-31, and loss of 3p. Other frequent changes (in 7 or 8 cases) included gains at 2p, 1q24-31, and 17q22-qter, and losses at 3cen-q23 and 10q21. High-level amplifications were seen in 7 cases. A total of 16 regions were detected. Two of them, 8p12-qter and 21q21-qter, seen in 4 and 2 tumors, respectively, were recurrent. No aberrations specific to histological subtype were identified. However, genetic changes in the monophasic tumors were more complex and numerous (mean among aberrant cases: 5.3 aberrations/tumor; range: 1-17) than in the biphasic tumors (mean: 2.5 aberrations/tumor; range: 1-5), and high-level amplifications occurred more frequently. All but 1 of the sarcomas showing high-level amplification were of the monophasic subtype. These findings may reflect differences in the pathogenesis and biological behavior of both histological subtypes of synovial sarcoma.

Adolescent↗

PubMed1997

Reversal of a selective decrease in hippocampal acetylcholine release, but not of the persistence of kindling, after discontinuation of long-term pentylenetetrazol administration in rats.

The time course of the effect of pentylenetetrazol (PTZ)-induced kindling on acetylcholine release in the hippocampus of freely moving rats was investigated with the transversal microdialysis technique. The basal extracellular concentration of acetylcholine in the hippocampus was reduced significantly (-29%, P < 0.05) after 3 weeks, and the effect was maximal (-52%, P < 0.01) after 4 weeks and remained essentially unchanged during the remaining 4 weeks of PTZ treatment (30 mg/kg, i.p., 3 times/week), relative to vehicle-treated rats. The basal release of acetylcholine in the prefrontal cortex and in the striatum of kindled rats was unchanged compared with that of vehicle-treated rats. The specific binding of [3H]quinuclidinyl benzilate, a non-selective ligand of muscarinic receptors, was significantly increased (+29%, P < 0.01) in hippocampal membrane, but not in membranes prepared from the prefrontal cortex or striatum, of PTZ-kindled rats. Thirty days after discontinuation of PTZ treatment, both hippocampal acetylcholine output and the density of muscarinic receptors had returned to values characteristic of vehicle-treated rats, whereas seizure susceptibility did not differ significantly from that apparent 4 days after PTZ administration. These results suggest that the selective and transient decrease in acetylcholine output and the parallel increase in the density of postsynaptic muscarinic receptors in the hippocampus may play a role in facilitating the development of kindling rather than in the maintenance of the kindled state.

Acetylcholine↗

PubMed1997

Enhancement of basal and pentylenetetrazol (PTZ)-stimulated dopamine release in the brain of freely moving rats by PTZ-induced kindling.

The effects of pentylenetetrazol (PTZ)-induced kindling on the activity of mesocortical, mesoaccumbens, and nigrostriatal dopaminergic neurons was investigated with the transversal microdialysis technique in freely moving rats. Four days after the last chronic administration of PTZ, the basal extracellular concentrations of dopamine in the prefrontal cortex, nucleus accumbens, and striatum of kindled rats were significantly increased (+76, +36, +49%, respectively) relative to those of animals chronically treated with saline. Moreover, dopamine output was markedly more sensitive to the effect of a challenge injection of PTZ (20 mg/kg ip) in the prefrontal cortex (+93 vs. +50%, relative to basal values), the nucleus accumbens (+36 vs. +4%), and the striatum (+50 vs. + 35%) of kindled rats relative to that in the control animals. Because kindled rats and their controls are habituated to handling, the neurochemical mechanisms that underlie the effects of chemical kindling on the sensitivity of dopaminergic neurons to PTZ were investigated by comparing the effects of an acute administration of PTZ (20 mg/kg ip) between naive and handling-habituated animals. The sensitivity of dopamine output to PTZ in naive rats was markedly greater than that in handling-habituated animals for the prefrontal cortex (+83 vs. +50%) and nucleus accumbens (+35 vs. +4%), but not for the striatum (+35 vs. +32%). These results indicate that PTZ kindling enhances the basal activity and the sensitivity to PTZ of dopamine neurons in rat brain and suggest that mesocortical, mesoaccumbens, and nigrostriatal dopaminergic neurons contribute to the central alterations associated with experimental epilepsy.

Animals↗

PubMed1997

Enhancement by flumazenil of dopamine release in the nucleus accumbens of rats repeatedly exposed to diazepam or imidazenil.

The effect of long-term treatment (three times daily for 3 weeks) with a behaviorally relevant dose of the benzodiazepine receptor partial agonist imidazenil (0.5 mg/kg, IP) on basal dopamine release in the nucleus accumbens of freely moving rats was compared with that of diazepam (3 mg/kg, IP), a benzodiazepine receptor full agonist. Challenge doses of imidazenil and diazepam decreased the extracellular dopamine concentration in the nucleus accumbens by approximately the same extent in animals repeatedly exposed to vehicle or to the respective drug. Moreover, the abrupt discontinuation of long-term treatment with diazepam or imidazenil failed to affect basal dopamine release in this brain area during the first 5 days of withdrawal. In contrast, administration of the benzodiazepine receptor antagonist flumazenil (4 mg/kg, IP) elicited a marked increase (95 or 60%) in dopamine release in the nucleus accumbens 6 h after withdrawal of diazepam or imidazenil, respectively. Flumazenil induced a similar but smaller effect (50% increase) 5 days after diazepam withdrawal but had no effect 5 days after discontinuation of imidazenil treatment. The results support an involvement of the mesoaccumbens dopaminergic neurons in the withdrawal syndrome precipitated by flumazenil and allow further differentiation of benzodiazepine receptor partial and full agonists with respect to dependence liability of dopaminergic neurons in the nucleus accumbens.

Animals↗

PubMed1997

Antagonism of convulsions but failure to enhance GABA(A) receptor function by felbamate in mice tolerant to diazepam.

The transfer of tolerance between drugs may indicate a common mode of action. The development of cross-tolerance to the anticonvulsant effect of felbamate after long-term treatment of mice with diazepam, a positive modulator of gamma-aminobutyric acid (GABA)-mediated transmission, was therefore studied in order to clarify the mechanism of this action of felbamate. A challenge injection of felbamate, administered 36 h after the last dose of chronic diazepam treatment, antagonized convulsions elicited by administration of isoniazid. In contrast, felbamate had no effect on the isoniazid-induced increase in t-[35S]butylbicyclophosphorothionate binding to cerebral cortical membranes of diazepam-tolerant mice. These results suggest that the action of felbamate on GABAergic transmission is not required for the anticonvulsant effect of this drug. This conclusion is consistent with studies that have indicated that the antiepileptic activity of felbamate depends on its modulatory activity at excitatory amino acid receptors.

Animals↗

PubMed1997

Effect of pentylenetetrazole-induced kindling on acetylcholine release in the hippocampus of freely moving rats.

The role of gamma-aminobutyric acid (GABA) modulation of septohippocampal cholinergic neurons in kindling was investigated. Hippocampal acetylcholine release was evaluated with the microdialysis technique in freely moving rats either after acute administration of isoniazid (an inhibitor of GABA synthesis) or pentylenetetrazole (PTZ) (a blocker of the GABAA receptor-associated Cl- channel) or after chronic administration of PTZ. Short-term treatment with PTZ (5-50 mg/kg, i.p.) or isoniazid (150-250 mg/kg, s.c.) increased hippocampal acetylcholine release in a dose-dependent manner. In contrast, the basal concentration of acetylcholine in the dialysate from the hippocampus of rats chronically treated with PTZ (kindled animals) was significantly reduced relative to that of vehicle-treated rats (2.39 +/- 0.21 vs. 4.2 +/- 0.31 pmol per 20-min sample; p < 0.01). Moreover, the release of acetylcholine was markedly more sensitive to the effect of a challenge injection of PTZ (10 or 20 mg/kg, i.p.) in kindled rats than in naive rats or rats chronically treated with vehicle. Abecarnil, a selective benzodiazepine receptor agonist with marked anticonvulsant activity, was administered together with chronic PTZ to evaluate whether persistent activation of GABAA receptors and suppression of seizures during kindling might affect the sensitivity of septohippocampal cholinergic neurons to a challenge dose of PTZ. Abecarnil (1 mg/kg, i.p.) administered 40 min before each PTZ injection neither antagonized the decrease in basal acetylcholine release (2.26 +/- 0.19 pmol per 20-min sample) nor prevented the development of kindling. In contrast, abecarnil prevented the chronic PTZ-induced increase in the sensitivity of acetylcholine release to a challenge dose of PTZ. These results provide novel in vivo data concerning the role of hippocampal acetylcholine function in the development of kindling and potentially in the learning and memory deficits associated with this phenomenon.

Acetylcholine↗

PubMed1997

Generation of free radicals during anoxia and reoxygenation in perfused osteoblastlike cells.

Sensitivity to ischemia and reperfusion injury is a main problem afflicting tissues exposed to a prolonged period of oxygen deprivation. The generation of oxygen free radicals, in particular, is considered a major cause of postischemic reperfusion injury. However, studies on the mechanisms of production of free radicals are limited by the difficulty to measure in real time their formation and to discriminate between the different oxyradical species. The aim of this study was to determine whether the formation of oxygen free radicals occurs in murine osteoblastlike cells (MC3T3-E1) exposed to anoxia and reoxygenation and to explore its relation to the reoxygenation injury. Cells were cast in agarose and perfused with oxygenated Krebs-Henseleit bicarbonate buffer. Anoxia was obtained by shifting the gas phase of the media to 95% N2-5% CO2. Oxygen free radicals were detected by enhanced chemiluminescence: anion superoxide or hydrogen peroxide was measured by adding lucigenin or luminol plus horseradish peroxidase to the media, respectively. Cell injury was assessed by the rate of lactate dehydrogenase release. During the control period, lucigenin and luminol plus horseradish chemiluminescences were 15 +/- 1 nA per chamber and 20 +/- 2 nA per chamber, respectively. and lactate dehydrogenase release was 10 +/- 1 mU per minute. During anoxia, both chemiluminescences dropped to background levels, although lactate dehydrogenase release increased progressively to 38 +/- 7 mU per minute. During reoxygenation, O2 formation increased sharply to 45 +/- 6 nA and decreased to control levels; H2O2 production increased slowly, reaching 42 +/- 7 nA at the end of the reoxygenation period; lactate dehydrogenase declined progressively to control values. These results show that osteoblastlike cells produce measurable amounts of superoxide and hydrogen peroxide radicals during reoxygenation. Because lactate dehydrogenase release did not appear to relate to chemiluminescence, oxyradical flux may serve as a signal for other events that eventually lead to cell injury.

Animals↗

PubMed1997

Soluble CD30 antigen in human colostrum.

It is now well established that the CD30 glycoprotein is a surface antigen expressed by activated T cells producing T-helper (Th)-2-type lymphokines. Mounting laboratory evidence, however, suggests that CD30 expression is not confined to a functionally restricted subset of T cells, but also identifies activated cells with a Th-1 and Th-0 pattern of cytokine secretion. CD30-bearing T lymphocytes release a soluble form of the molecule (sCD30), which can be detected both in vitro and in vivo. In the present study, very high levels of sCD30 were found in colostrum from 20 puerperal women, but not in autologous and heterologous (nonpregnant women) blood samples. These data strongly support an involvement of CD30+ T cells in the immune processes which take place at the level of the mammary gland during pregnancy and lactation. Passively transferred immune components such as immunoglobulins, cytokines, macrophages, natural killer cells, granulocytes and memory/activated T cells, all of which may help the baby to fight off infections, have been revealed in human breast milk. However, how Th-2-type cytokine-secreting T cells or other T-cell types help to endow the congenitally immunocompromised newborn infant with extrinsic immunological support remains an open question.

Colostrum↗

PubMed1997

Evaluation of gestrinone after surgery in treatment of endometriosis.

OBJECTIVE: The clinical and histological efficacy of gestrinone in the treatment of endometriosis was evaluated. METHODS: A prospective study was performed with longitudinal follow-up of 4 years duration (minimum) for each patient. Twenty-five cases of endometriosis were treated with gestrinone (as a drug of choice or associated with other local surgical treatment) during 6 months. RESULTS: The total or partial response to pain was induced with treatment in 19 of the 20 cases (95%), and posttreatment pregnancies were induced in 3 of the 9 cases of infertility (33.3%). The global clinical efficacy was as follows: none (n = 5, 20%), poor (n = 2, 8%), moderate (n = 2, 8%), good (n = 3, 12%) and excellent (n = 13, 52%). The pretreatment American Fertility Society score was 23.1 +/- 3.8 points (2-58) and that after treatment (re-examination) 7.8 +/- 3.7 points (0-52), p < 0.01. Global histological efficacy (n = 17) results were as follows: none (23.6%), poor (0%), moderate (5.8%), good (35.3%) and excellent (35.3%). CONCLUSIONS: Gestrinone is presented as a drug with an efficacy comparable to other pharmacological agents currently available in the medical treatment of endometriosis. Adequate posology and acceptable effectiveness were also observed.

Abdominal Pain↗

PubMed1997

Risk of recurrence after reoperation for prosthetic valve endocarditis.

Reoperation after a surgical procedure for prosthetic valve endocarditis (PVE) is often required due to the existence of either septic recurrence or sterile para-prosthetic leak (PL). The aim of this study was to assess the risk to patients of undergoing a second operation after PVE. Thirty-six patients underwent operation for active PVE at our institution. The operative mortality rate was 11.2%. Among the 32 patients discharged, six underwent a second operation (in two cases due to persisting sepsis) and two underwent a third procedure. Multivariate analysis demonstrated increased probability of further operation for: inability to identify the infecting organism (p = 0.005); drug addiction (p = 0.007); existence of annular abscess (p = 0.016); and early occurrence of PVE (p = 0.018). In the case of mechanical prostheses, PVE was not an independent risk factor (p = 0.206). Nonetheless, 58.3% of patients with mechanical prostheses compared with 5.3% of those with bioprostheses showed annular abscesses, while 41.7% of the former versus 5.6% of the latter suffered one or more recurrences.

Abscess↗

PubMed1997

Different postnatal growth between disproportionate and proportionate fetal growth retardation at term.

OBJECTIVE: To evaluate the postnatal growth of full-term infants with fetal growth retardation (FGR) syndrome and their subgroups (disproportionate and proportionate) after six months of delivery. METHODS: This is a prospective follow-up study of 200 full-term gestations. We compare 100 FGRs (34 cases of FGR-disproportionate and 66 FGR-proportionate) infants against 100 normal infants/controls. At the sixth months of postnatal life, the infants were subjected to a standard paediatric evaluation and examination. RESULTS: At the sixth months of postnatal life, the infant weight was 7.183 g +/- 727 in the FGR group vs. 8.019 g +/- 823 in the control group, p < 0.001. 31% of FGR infants were found under the 10th percentile value as read for the 6th months standard, whereas the same value was detected in only 3% of control infants, p < 0.001. Likewise, 38% of FGR cases were under the 10th percentile of height versus 7% of control cases, p < 0.001. Proportionate FGR infants showed a higher increase of height in comparison to those from a disproportionate group (17.3 cm +/- 1.4 vs. 15.5 cm +/- 3.4, p < 0.05). A negative correlation was found between neonatal ponderal index (NPI) and weight gain (R = -0.16, p < 0.05). CONCLUSIONS: Six months after delivery, weight and height were lower in FGR infants than in controls. At that age, disproportionate and proportionate FGR infants had similar weight and height, being the height catch-up more significant in proportionate ones.

Body Height↗

PubMed1997

[Preservation of the muscle in the use of rectus abdominis free flap in breast reconstruction: from TRAM to DIEP (Deep inferior epigastric perforator) flap. Technical notes and results].

The advantages of TRAM (Transverse Rectus Abdominus Muscle) flap for breast reconstruction is now well recognised. This technique allows a cosmetic reconstruction with a more natural shape than with conventional reconstruction with prosthesis. However the disadvantage is the need of removal of part or all rectus abdominis muscle. If the techniques of free flap are now recognised to be more reliable than pedicle TRAM they have not demonstrate a superiority in term of parietal sequellae. To avoid such problem some teams have progressively developed the DIEP (Deep Inferior Epigastric Peforator Flap). This flap is harvested only on the transmuscular perforators. We are presenting here our expertise which progressively has leed us from free partial TRAM to DIEP. From december 1995 to january 1997 we have practice 18 breast reconstructions with free flap. On 13 DIEP we had only one parietal complication due to incomplete closing of the aponeurosis at the lowest part of the surgical approach. This complication was easily corrected as the muscle was still tonic. On 5 TRAM, clinical examination finds parietal weakness on 3 cases. We believe that this technique is full of promises as it brings autologous tissue with no complication on donor site.

Humans↗

PubMed1996

Insulin-like growth factor I receptor-mediated circuit in Ewing's sarcoma/peripheral neuroectodermal tumor: a possible therapeutic target.

The disappointingly low survival rate observed in Ewing's sarcoma (ES)/peripheral neuroectodermal tumor (PNET) despite the adoption of aggressive multimodal treatments prompted us to study the existence of autocrine circuits to be used as innovative therapeutic targets. Of the several circuits analyzed, only the insulin-like growth factor receptor (IGF-IR)-mediated loop was found to be constantly present both in cell lines and clinical samples, suggesting a role for this autocrine circuit in the pathogenesis of ES/PNET. The in vitro inhibition of the IGF-IR-mediated circuit by the specific IGF-IR binding antibody alphaIR3 suppressed the growth of ES/PNET cells by decreasing the proliferative rate and increasing apoptosis. alphaIR3 also significantly inhibited the ability of ES/PNET cells to grow in soft agar and to migrate following a chemotactic stimulus. Inactivation of the IGF-IR signaling pathway may therefore be considered as an effective therapeutic modality for patients with ES/PNET.

Antibodies↗

PubMed1996

Biochemical evaluations of the effects of loreclezole and propofol on the GABAA receptor in rat brain.

The effects of loreclezole on the function of the gamma-aminobutyric acid type A (GABAA) receptor complex in rat cerebral cortical membrane preparations were compared with those of propofol and diazepam. Loreclezole and propofol modulated [3H]muscimol binding and t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to washed and unwashed membranes with potencies and efficacies greater than those of diazepam. Loreclezole and propofol enhanced [3H]flunitrazepam binding to washed membranes with efficacies lower than those of GABA and muscimol. Both loreclezole and propofol showed biphasic effects on [35S]TBPS binding to washed membranes: at low concentrations (5 to 10 microM), both drugs, with different efficacies, enhanced [35S]TBPS binding whereas, at higher concentrations (30 to 100 microM), they inhibited this biochemical parameter. In contrast, diazepam enhanced [35S]TBPS binding to washed membranes at all concentrations tested. The combination of loreclezole with GABA, at a concentration (0.3 microM) that only slightly increased [35S]TBPS binding to washed membranes, reversed the increase in binding elicited by loreclezole (5 to 10 microM) and significantly potentiated the inhibitory effect exerted by higher concentrations (30 to 100 microM) of this drug. Similar effects were observed with the combination of GABA and propofol. However, GABA had no effect on the enhancement of [35S]TBPS binding induced by diazepam. The ability of GABA to reverse and potentiate the effects of loreclezole and propofol on [35S]TBPS binding to washed membranes was shared by pentobarbital (200 microM) and alphaxalone (3 microM). These anesthetics showed greater efficacies in combination with pentobarbital (200 microM) and alphaxalone (3 microM). These anesthetics showed greater efficacies in combination with propofol than with loreclezole. These results suggest that, unlike diazepam, loreclezole and propofol may activate the receptor-associated Cl- channel in the absence of GABA. Furthermore, the difference in the pharmacological profiles of loreclezole and propofol may result from their different effectiveness in activating the receptor Cl- channel directly.

Anesthetics↗