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Biomedical subjects

R Steinberg

Publications and source records attributed to R Steinberg.

At least 19 recordsLinked to original sources
PubMed2006

Effects of the vasopressin (V1b) receptor antagonist, SSR149415, and the corticotropin-releasing factor 1 receptor antagonist, SSR125543, on FG 7142-induced increase in acetylcholine and norepinephrine release in the rat.

Arginine vasopressin and corticotropin-releasing factor are two neuroactive peptides that regulate hypothalamic-pituitary-axis and associated stress response. While the potential antidepressant and anxiolytic profiles of corticotropin-releasing factor 1 antagonists have been well studied, the concept of blockade of vasopressin system as another approach for the treatment of emotional processes has only been made available recently by the synthesis of the first non-peptide antagonist at the V1b receptor, SSR149415. In the present study SSR149415 has been compared with the corticotropin-releasing factor 1 antagonist SSR125543 and with anxiolytic and antidepressant drugs on the response of hippocampal cholinergic and cortical noradrenergic systems to the anxiogenic benzodiazepine receptor inverse agonist FG 7142. Acute (0.3-10 mg/kg, i.p.) and long-term administration (10 mg/kg, i.p., 21 days) of SSR149415 and SSR125543 reduced the FG 7142-induced increase in extracellular concentrations of acetylcholine in the hippocampus of anesthetized rats measured by microdialysis. By contrast acute and long-term administration of SSR149415 failed to reduce the FG 7142-induced increase in the release of norepinephrine in the cortex of freely moving rats. The present results demonstrate that the two compounds have similar profiles in a model of activation by an anxiogenic drug of the hippocampal cholinergic system and they suggest that SSR149415 and SSR125543 may have anti-stress anxiolytic and antidepressant effects via a mechanism of action different from classical benzodiazepine ligands and noradrenergic antidepressants.

Acetylcholine↗
PubMed2006

Infectious complications of implantable ports and Hickman catheters in paediatric haematology-oncology patients.

The aim of this study was to define and compare the infectious and non-infectious complications associated with Hickman catheters and implantable ports in children. The study was conducted over a three-year period in the Department of Haematology-Oncology at the Schneider Children's Medical Center of Israel. All patients who required a central venous catheter (CVC) were included in the study. For each episode of catheter-associated bloodstream infection, demographic, clinical and microbiology data were recorded. During the study period, 419 tunnelled CVCs (246 implantable ports and 173 Hickman) were inserted in 281 patients. Compared with implantable ports, Hickman catheters were associated with a significantly higher rate of bloodstream infections (4.656 vs 1.451 episodes per 1000 catheter-days), shorter time to first infection (52.31 vs 108.82 days, P < 0.001), shorter duration of catheterization (140.75 vs 277.28 days, P < 0.001), and higher rate of removal because of mechanical complications (P < 0.005). Gram-positive bacterial infections were more prevalent in the implantable port group (63.6% vs 41.6%), whereas Gram-negative rods, polymicrobial infections and mycobacterial infections were more prevalent in the Hickman group (31.4% vs 50.9%, 17% vs 36% and 0% vs 4.4%, respectively; P < 0.05 for all). Haematopoietic stem cell transplantation was identified as an independent risk factor for infection [odds ratio (OR) -1.68, P = 0.005] and for catheter removal due to complications (OR -2.0, P < 0.001). Implantable ports may be considered the preferred device for most paediatric oncology and stem cell transplantation patients.

Adolescent↗
PubMed2006

Segmental liver transplantation from non-heart beating donors--an early experience with implications for the future.

We report our experience of pediatric liver transplantation with partial grafts from non-heart beating donors (NHBD). Controlled donors less than 40 years of age with a warm ischemia time (WI) of less than 30 min were considered for pediatric recipients. Death was declared 5 min after asystole. A super-rapid recovery technique with aortic and portal perfusion was utilized. Mean donor age was 29 years and WI 14.6 min (range 11-18). Seven children, mean age 4.9 years (0.7-11), median weight 20 kg (8.4-53) received NHBD segmental liver grafts. Diagnoses included seronegative hepatitis, neonatal sclerosing cholangitis, familial intrahepatic cholestasis, hepatoblastoma, primary hyperoxaluria and factor VII deficiency (n=2). The grafts included four reduced and one split left lateral segments, one left lobe and one right auxiliary graft. Mean cold ischemia was 7.3 h (6.2-8.8). Complications included one pleural effusion and one biliary collection drained percutaneously. At 20 months (10-36) follow-up all children are alive and well with functioning grafts. Donation after cardiac death is a significant source of liver grafts for adults and children with careful donor selection and short cold ischemic times.

Adolescent↗
PubMed2005

Ex vivo liver surgery for extraadrenal pheochromocytoma.

A case of a 15-year-old girl with a malignant extraadrenal pheochromocytoma situated between the inferior vena cava and the portal triad is described. Using ex vivo technique, the tumour was successfully resected on the bench, as a previous attempt to remove the tumour in situ had been abandoned. The surgical aspects and implications of ex vivo surgery are discussed, highlighting the increased operative risk, perioperative mortality, and poor long-term results in patients with malignant tumours.

Adolescent↗
PubMed2005

2-Chloro-N-[(S)-phenyl [(2S)-piperidin-2-yl] methyl]-3-trifluoromethyl benzamide, monohydrochloride, an inhibitor of the glycine transporter type 1, increases evoked-dopamine release in the rat nucleus accumbens in vivo via an enhanced glutamatergic neurotransmission.

2-Chloro-N-S-phenyl 2S-piperidin-2-yl methyl]-3-trifluoromethyl benzamide, monohydrochloride (SSR504734) is a potent and selective inhibitor of the glycine transporter type 1, which increases central N-methyl-D aspartate glutamatergic tone. Since glutamate has been shown to play a role in the regulation of the dopaminergic system in dopamine-related disorders, such as schizophrenia, we investigated the possibility that SSR504734 may modify the basolateral amygdala-elicited stimulation of dopamine release in the nucleus accumbens via an augmentation of glutamate receptor-mediated neurotransmission. First, our data confirmed that SSR504734 is an inhibitor of GlytT1. In the nucleus accumbens of anesthetized rat, SSR504734 (10 mg/kg, i.p.) induced an increase of extracellular levels of glycine as measured by microdialysis coupled with capillary electrophoresis with laser-induced fluorescence detection. Second, the data demonstrated that SSR504734 (10 mg/kg, i.p.) enhanced the facilitatory influence of glutamatergic afferents on dopamine neurotransmission in the nucleus accumbens. Using an electrochemical technique, we measured dopamine release in the nucleus accumbens evoked by an electrical stimulation of the basolateral amygdala. SSR504734 facilitated dopamine release evoked by a 20 or a 40 Hz frequency basolateral amygdala stimulation. This facilitatory effect was dependent on glutamatergic tone, as intra-nucleus accumbens application of 6-7-dinitroquinoxaline-2,3-dione (10(-3) M) or DL-2-amino-5-phosphonopentanoic acid (10(-3) M), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and N-methyl-D aspartate receptors antagonists, respectively, inhibited dopamine release evoked by basolateral amygdala stimulation. Furthermore DL-2-amino-5-phosphonopentanoic acid co-administrated with SSR504734 hampered the dopamine-evoked release facilitation. These data underline the in vivo implication of the glycine uptake mechanism in the control of subcortical glutamate/dopamine interactions.

Amygdala↗
PubMed2005

[Differential indications for atypical neuroleptics: Amisulprid, Clozapin, Olanzapin, Quetiapin und Risperidon. Results of a pilot study of prescription habits in psychiatric clinical usage in the BRD].

With the introduction of atypical neuroleptics, the therapy of schizophrenia has been improved by a group of antipsychotic substances characterized by better tolerability concerning extrapyramidal side effects and higher efficiency against negative symptoms. However, these atypical antipsychotics are not a homogeneous class of drugs but rather represent a group of substances with very different neurobiologic, pharmacologic, and clinical features. This fact and the growing variety of available atypical neuroleptics illustrate the difficulty in choosing the "right" antipsychotic drug for each patient. The aim of this investigation was to evaluate preliminary empirical data for possible differential indication of atypical neuroleptics by a questionnaire-based survey of 192 physicians in ten psychiatric hospitals active in the biological psychiatry work group of the German Federal Directors' Conference.

Antipsychotic Agents↗
PubMed2004

Difficulties in making the diagnosis of Hirschsprung disease in early infancy.

This study highlights the less common presentations of Hirschsprung disease (HD) and HD-associated enterocolitis (HAE) in neonates and infants. We present three infants whose diagnosis was delayed because of atypical presenting features, especially with failure to gain weight, decreased appetite, episodes of diarrhoea and vomiting and hypoalbuminaemia. The reported incidence of HAE ranges from 0 to 16.2%. To avoid complications of life-threatening HAE, primary care physicians require a high index of suspicion of the more unusual presentations of HD in neonates and infants.

Colostomy↗
PubMed2003

Unusual intestinal sequelae after operations for Ascaris lumbricoides infestation.

Two children with severe bowel sequelae distal to the site of an Ascaris lumbricoides bowel obstruction are reported. It is postulated that these resulted from inflammatory reaction to toxic decomposition products of disintegrating worms. Surgery should be modified in the presence of bowel-wall injury distal to the site of ascarid worm - bolus obstruction.

Animals↗
PubMed2003

Control by tachykinin NK(2) receptors of CRF(1) receptor-mediated activation of hippocampal acetylcholine release in the rat and guinea-pig.

In vivo microdialysis was employed to explore the effects of different selective non-peptides NK(1),NK(2) and NK(3) receptor antagonists on the corticotropin releasing factor (CRF)-induced release of acetylcholine (ACh) in the hippocampus of rats and guinea-pigs. In both species, the intracerebroventricular (i.c.v.) administration of CRF produced a time- and dose-dependent increase in hippocampal ACh release that was totally suppressed by an intraperitoneally (i.p.) pretreatment with the selective non-peptide CRF(1) receptor antagonist antalarmin (30 mg/kg). Pretreatment with the selective NK(2) receptor antagonist SR48968 (1mg/kg, i.p.) significantly reduced the increase of ACh induced by CRF. In contrast, its low-affinity enantiomer SR48965 (1mg/kg, i.p.) or the NK(1) receptor antagonist, GR205171 (1mg/kg, i.p.) did not exert any antagonist effect. Moreover, administration of the selective NK(3) receptor antagonist SR142801 (1mg/kg, i.p.) did not significantly reduce the CRF-induced hippocampal ACh release in guinea-pigs (the only species studied). The selective activity of SR48968 versus GR205171 or SR142801 indicates that NK(2) receptors play a major role in the control of CRF-induced hippocampal ACh release. Moreover, in freely moving rats, two sessions of stroking of the neck and back of the rat for 30 min, at 90 min intervals, known to be a stressful stimulus, produced a marked and reproducible increase in hippocampal ACh release. This effect was prevented by the administration of the two selective non-peptide CRF1 and NK(2) receptor antagonists antalarmin (30 mg/kg, i.p.) and SR48968 (1mg/kg, i.p.), respectively. This suggests that stress-induced activation of the hippocampal ACh system may be under the control of both endogenously released CRF and NKA, and opens the possibility of the existence of a functional interplay between the pathways containing these peptides as we observed in our experiments on anaesthetized animals.

Acetylcholine↗
PubMed2002

SR141716, a central cannabinoid (CB(1)) receptor antagonist, blocks the motivational and dopamine-releasing effects of nicotine in rats.

The central CB(1) cannabinoid receptor has recently been implicated in brain reward function. In the present study we evaluated first the effects of the selective CB(1) receptor antagonist, SR141716, on the motivational effects of nicotine in the rat. Administration of SR141716 (0.3 and 1 mg/kg) decreased nicotine self-administration (0.03 mg/kg/injection). SR141716 (0.3-3 mg/kg) neither substituted for nicotine nor antagonized the nicotine cue in a nicotine discrimination procedure, but dose-dependently (0.01-1 mg/kg) antagonized the substitution of nicotine for D-amphetamine, in rats trained to discriminate D-amphetamine. Secondly, using brain microdialysis, SR141716 (1-3 mg/kg) blocked nicotine-induced dopamine release in the shell of the nucleus accumbens (NAc) and the bed nucleus of the stria terminalis. To investigate whether SR141716 would block the dopamine-releasing effects of another drug of abuse, we extended the neurochemical study to the effect of ethanol, consumption of which in rodents is reduced by SR141716. Dopamine release induced by ethanol in the NAc was also reduced by SR141716 (3 mg/kg). These results suggest that activation of the endogenous cannabinoid system may participate in the motivational and dopamine-releasing effects of nicotine and ethanol. Thus, SR141716 may be effective in reduction of alcohol consumption, as previously suggested, and as an aid for smoking cessation.

Animals↗
PubMed2002

Mediastinal tumors in children: a single institution experience.

Mediastinal masses in children are a heterogeneous group of asymptomatic or potentially life-threatening congenital, infectious, or neoplastic lesions that present complex diagnostic and therapeutic dilemmas. Some patients are asymptomatic; in others, the mass may compress mediastinal structures and cause sudden asphyxia. In these cases, close cooperation is needed among pediatric surgeons, anesthesiologists, intensivists, oncologists, and radiologists. The files of 45 children with mediastinal masses admitted between 1986 and 1999 to the Pediatric Intensive Care Unit (PICU) of Schneider Children's Medical Center of Israel were reviewed. Twenty-one were admitted for perioperative care, and 21 for emergency care, including 19 with respiratory distress. Five of the emergency care group had asphyxia and 10 needed assisted ventilation. Two children were admitted for evaluation and 1 for leukopheresis. The children admitted on an emergency basis had more clinical findings than the postoperative group: almost 80% had dyspnea and more than 45% had oxygen desaturation; 33% had cough and noisy breathing, and 25%, superior vena cava syndrome or hepatosplenomegaly. Eight patients (17.8%) had benign disease and 37 (82.2%) malignant disease. The patients with a benign mass were significantly younger than the patients with a malignant mass (p<0.005); in 5 cases (12.5%), a congenital anomaly presented as a mediastinal mass. Most of the malignant masses were of hematologic origin (40.5%), followed by neurogenic tumors (27%). Twenty-seven patients underwent surgery, including 6 emergency procedures (3 partial resections, 2 biopsies, 1 lymph node biopsy). There were no intraoperative or postoperative deaths. The present series emphasizes the complex care children with a mediastinal mass require. They should be treated in a tertiary center with a multidisciplinary approach.

Adolescent↗
PubMed2001

VEGF(165) requires extracellular matrix components to induce mitogenic effects and migratory response in breast cancer cells.

The expression of VEGF and the relapse-free survival rate of breast cancer patients are inversely related. While VEGF induces the proliferation and migration of vascular endothelial cells, its function in breast cancer cells is not well studied. We reported previously that fibronectin increased VEGF-dependent migration in breast cancer cells. Since VEGF has an extracellular matrix (ECM)-binding domain and possesses binding affinity for heparin, we sought to determine the effects of VEGF in breast cancer cells and the role of heparin and/or fibronectin in VEGF-induced signaling. Cells grown on plastic were compared to those grown on fibronectin or to those grown on plastic in the presence of heparin, and analysed for intracellular signaling, proliferation and migration in response to VEGF(165). Both heparin and fibronectin enhanced the binding of VEGF to T47D cells. After treatment with VEGF, [(3)H]thymidine incorporation, c-fos induction, and the number of migrating cells were significantly higher ( approximately twofold) in cells grown on fibronectin or in cells grown on plastic in the presence of heparin when compared to those grown on plastic only. Likewise, tyrosine phosphorylation of VEGF receptors, MAPK activity and PI3-kinase activity were all several-fold higher in cells seeded on fibronectin or in the presence of heparin as compared to cells exposed to VEGF alone. VEGF-dependent c-fos induction was found to be regulated through a MAPK-dependent, but PI3-kinase-independent pathway. In contrast, the migration of T47D cells in response to VEGF, in the presence of ECM, was regulated through PI3-kinase. Therefore, VEGF requires ECM components to induce a mitogenic response and cell migration in T47D breast cancer cells.

Breast Neoplasms↗
PubMed2001

Endogenous neurotensin down-regulates dopamine efflux in the nucleus accumbens as revealed by SR-142948A, a selective neurotensin receptor antagonist.

SR-142948A belongs to the second generation of potent, selective, non-peptide antagonists of neurotensin receptors. It was used to investigate the role of endogenous neurotensin in the regulation of dopamine efflux in the nucleus accumbens and striatum of anaesthetized and pargyline-treated rats. All the data were obtained using in vivo electrochemistry. Electrically evoked (20 Hz, 10 s) dopamine efflux was monitored by differential pulse amperometry, whereas variations in basal (tonic) dopamine efflux were monitored by differential normal pulse voltammetry. Like the first-generation compound SR-48692, SR-142948A did not affect the tonic and evoked dopamine efflux, but dose-dependently enhanced haloperidol (50 microg/kg, i.p.) induced facilitation of the electrically evoked dopamine release in the nucleus accumbens. In contrast to SR-48692, SR-142948A dose-dependently potentiated haloperidol (50 microg/kg, i.p.) induced increase in the basal dopamine level in the nucleus accumbens. This potentiating effect did not appear in the striatum. When dopaminergic and/or neurotensinergic transmissions were modified by a higher dose of haloperidol (0.5 mg/kg, i.p.), apomorphine, amphetamine or nomifensine, SR-142948A pre-treatment affected only the effect of apomorphine on the basal dopamine level in the nucleus accumbens. These results strengthen the hypothesis that endogenous neurotensin could exert a negative control on mesolimbic dopamine efflux.

Adamantane↗
PubMed2001

Role of vascular endothelial growth factor in the stimulation of cellular invasion and signaling of breast cancer cells.

The expression of vascular endothelial growth factor (VEGF) by breast tumors has been previously correlated with a poor prognosis in the pathogenesis of breast cancer. Furthermore, VEGF secretion is a prerequisite for tumor development. Although most of the effects of VEGF have been shown to be attributable to the stimulation of endothelial cells, we present evidence here that breast tumor cells are capable of responding to VEGF. We show that VEGF stimulation of T-47D breast cancer cells leads to changes in cellular signaling and invasion. VEGF increases the cellular invasion of T-47D breast cancer cells on Matrigel/ fibronectin-coated transwell membranes by a factor of two. Northern analysis for the expression of the known VEGF receptors shows the presence of moderate levels of Flt-1 and low levels of Flk-1/KDR mRNAs in a variety of breast cancer cell lines. T-47D breast cancer cells bind 125I-labeled VEGF with a Kd of 13 x 10(-9) M. VEGF induces the activation of the extracellular regulated kinases 1,2 as well as activation of phosphatidylinositol 3'-kinase, Akt, and Forkhead receptor L1. These findings in T-47D breast cancer cells strongly suggest an autocrine role for VEGF contributing to the tumorigenic phenotype.

Breast Neoplasms↗
PubMed2001

Selective blockade of neurokinin-2 receptors produces antidepressant-like effects associated with reduced corticotropin-releasing factor function.

The present study investigated the effects of the selective neurokinin-2 (NK2) receptor antagonist SR48968 in behavioral, electrophysiological, and biochemical tests sensitive to the action of prototypical antidepressants (fluoxetine, imipramine) or to corticotropin-releasing factor (CRF) receptor antagonists, which have been proposed recently as potential antidepressants. Results showed that SR48968 (0.3-10 mg/kg i.p.) produced antidepressant-like activity because it reduced immobility in the forced swimming test in both mice and rats, and decreased the amount of maternal separation-induced vocalizations in guinea pig pups. This latter effect appears to involve a reduction of stress-induced substance P release because SR48968 reduced the separation-induced increase in the number of neurons displaying neurokinin-1 receptor internalization in the amygdala. Furthermore, SR48968 increased the expression of the cAMP response-element binding protein mRNA in the rat hippocampus after repeated (1 mg/kg i.p., 21 days), but not acute administration. Finally, neuronal firing of the locus coeruleus (LC) and noradrenergic (NE) release in the prefrontal cortex both elicited by an uncontrollable stressor or an intraventricular administration of CRF were reduced by SR48968 (0.3-1 mg/kg i.p.). The finding that SR48968 (1 mg/kg i.p.) blocked the cortical release of NE induced by an intra-LC infusion of the preferential NK2 receptor agonist neurokinin A suggested the presence of NK2 receptors in this latter region. Importantly, SR48965 (1-10 mg/kg i.p.), the optical antipode of SR48968, which is devoid of affinity for the NK2 receptor, was inactive in all the models used. These data suggest that NK2 receptor blockade may constitute a novel mechanism in the treatment of depression and CRF-related disorders.

Animals↗
PubMed2000

A simple method of intraoperative confirmation of intestinal patency.

Routine intraoperative rectal temperature monitoring may serve in addition as a means of distal intestinal patency confirmation. A simple method, which is of immense importance especially when operating on infants and small children after NEC or intestinal atresia, is described.

Body Temperature↗