A comparison of two clinical scores for bronchiolitis. A multicentre and prospective study conducted in hospitalised infants.

BACKGROUND: There are a number of clinical scores for bronchiolitis but none of them are firmly recommended in the guidelines. METHOD: We designed a study to compare two scales of bronchiolitis (ESBA and Wood Downes Ferres) and determine which of them better predicts the severity. A multicentre prospective study with patients <12 months with acute bronchiolitis was conducted. Each patient was assessed with the two scales when admission was decided. We created a new variable "severe condition" to determine whether one scale afforded better discrimination of severity. A diagnostic test analysis of sensitivity and specificity was made, with a comparison of the AUC. Based on the optimum cut-off points of the ROC curves for classifying bronchiolitis as severe we calculated new Se, Sp, LR+ and LR- for each scale in our sample. RESULTS: 201 patients were included, 66.7% males and median age 2.3 months (IQR=1.3-4.4). Thirteen patients suffered bronchiolitis considered to be severe, according to the variable severe condition. ESBA showed a Se=3.6%, Sp=98.1%, and WDF showed Se=46.2% and Sp=91.5%. The difference between the two AUC for each scale was 0.02 (95%CI: 0.01-0.15), p=0.72. With new cut-off points we could increase Se and Sp for ESBA: Se=84.6%, Sp=78.7%, and WDF showed Se=92.3% and Sp=54.8%; with higher LR. CONCLUSIONS: None of the scales studied was considered optimum for assessing our patients. With new cut-off points, the scales increased the ability to classify severe infants. New validation studies are needed to prove these new cut-off points.

Systemic oxytocin increases glutamate efflux in the nucleus accumbens core of cocaine-experienced male and female rats but only increases dopamine efflux in males.

Oxytocin attenuates cocaine-seeking when administered both systemically and directly into the nucleus accumbens core. This effect is blocked by intra-accumbens antagonism of mGlu2/3 and, together with our finding that intra-accumbens oxytocin increases glutamate concentrations in this brain region, indicates that pre-synaptic regulation of glutamate release by oxytocin influences cocaine relapse. However, mGlu2/3 receptors also regulate dopamine release in the nucleus accumbens. Here we aimed to determine whether systemic oxytocin increases glutamate and dopamine concentrations in the nucleus accumbens core of cocaine-experienced and cocaine-naïve male and female rats. A subset of rats self-administered cocaine (0.5 mg/kg/infusion) and then underwent extinction training for 2-3 weeks. Rats were implanted with microdialysis probes in the accumbens core and samples were collected for a baseline period, and following saline (1 mL/kg), and oxytocin (1 mg/kg, IP) injections. Locomotion was assessed during microdialysis. In cocaine-experienced rats, oxytocin increased glutamate concentrations in the accumbens core to the same extent in males and females but only increased dopamine concentrations in male rats. Oxytocin did not alter glutamate levels in cocaine-naïve rats. Oxytocin did not produce sedation. These results extend previous findings that systemic oxytocin increases nucleus accumbens dopamine in a sex-specific manner in cocaine-experienced rats. These data are the first to find that systemic oxytocin increases nucleus accumbens glutamate after cocaine experience, providing a mechanism of action by which oxytocin attenuates the reinstatement of cocaine seeking in both male and female rats.

Incidence and Severity of Community- and Hospital-Acquired Hyponatremia in Pediatrics.

Hyponatremia is the most common electrolyte disturbance in hospitalized children, with a reported incidence of 15-30%, but its overall incidence and severity are not well known. The objective of our study was to determine the incidence, severity, and associated risk factors of community- and hospital-acquired hyponatremia on a general pediatric ward. Data of 5550 children admitted from June 2012 to December 2019 on plasma sodium and discharge diagnosis were analyzed by logistic regression model. Clinically relevant diagnostic groups were created. Hyponatremia was classified as mild, moderate, and severe. The incidence of community- and hospital-acquired hyponatremia was 15.8% and 1.4%, respectively. Most of the cases were mild (90.8%) to moderate (8.6%), with only two cases of severe community-acquired hyponatremia. There were no clinical complications in any of the hyponatremic children. Age and diagnosis at discharge were principal factors significantly correlated with hyponatremia. Community-acquired hyponatremia is more common than hospital-acquired hyponatremia in clinical practice. Severe cases of both types are rare. Children from 2 to 11 years of age presenting with infections, cardiovascular disorders, and gastrointestinal disorders are at risk of developing hyponatremia.

Mortality predictors in patients with COVID-19 pneumonia: a machine learning approach using eXtreme Gradient Boosting model.

Recently, global health has seen an increase in demand for assistance as a result of the COVID-19 pandemic. This has prompted many researchers to conduct different studies looking for variables that are associated with increased clinical risk, and find effective and safe treatments. Many of these studies have been limited by presenting small samples and a large data set. Using machine learning (ML) techniques we can detect parameters that help us to improve clinical diagnosis, since they are a system for the detection, prediction and treatment of complex data. ML techniques can be valuable for the study of COVID-19, especially because they can uncover complex patterns in large data sets. This retrospective study of 150 hospitalized adult COVID-19 patients, of which we established two groups, those who died were called Case group (n = 53) while the survivors were Control group (n = 98). For analysis, a supervised learning algorithm eXtreme Gradient Boosting (XGBoost) has been used due to its good response compared to other methods because it is highly efficient, flexible and portable. In this study, the response to different treatments has been evaluated and has made it possible to accurately predict which patients have higher mortality using artificial intelligence, obtaining better results compared to other ML methods.

Atypical eye lesion in a human immunodeficiency virus-positive patient.

AIDS-related Kaposi sarcoma (KS), nowadays known to be an angioproliferative disease, occurs in several clinical-epidemiological forms, all of which are associated with infection by human herpesvirus-8. KS can affect the eye, with the bulbar conjunctiva and lacrimal gland being rare sites of occurrence. We present a case of AIDS-related KS of the conjunctiva and also discuss recent literature.

Bemiparin as a long-term treatment for venous thrombosis in cancer patients: the ELEBAMA study.

INTRODUCTION: Low-molecular-weight heparin (LMWH) is the standard treatment for cancer-associated venous thromboembolism (VTE). There have been no specific studies evaluating bemiparin for VTE in people with cancer. The aim of this study is to evaluate the effects of bemiparin for long-term treatment of VTE in routine clinical practice. METHODS/PATIENTS: Prospective observational study. Consecutive patients with active cancer and VTE, under treatment with bemiparin for at least 6 months, were recruited. RESULTS: We included 89 patients. The 6- and 9-month cumulative VTE recurrence rates were 2.4% and 5.9%, respectively. The 6-month cumulative rate of major bleeding was 1.3%, and of clinically relevant non-major bleeding, 8%. CONCLUSIONS: The incidence of events in this study is lower than that reported in randomized trials. Bemiparin is effective and safe for the long-term treatment of cancer-associated VTE in routine clinical practice.

Pharmacokinetic interaction between efavirenz and ketoconazole in rats.

1. It is well known that efavirenz and ketoconazole act as an inducer and inhibitor of CYP3A4, respectively. As a result of these actions, co-administration of these drugs may result in changes in the pharmacokinetic parameters of one or both of them. 2. Duodenum-cannulated rats have been used to compare the effect of intraduodenal (KC(i.d.)) and intravenous administration of ketoconazole (KC(i.v.)) on the pharmacokinetics of efavirenz after intraduodenal administration, as well as the potential effect of efavirenz as a CYP450 inducer on ketoconazole pharmacokinetic profile. 3. While KC(i.v.) did not show any significant effect on efavirenz pharmacokinetic profile, KC(i.d.) increased significantly (p < 0.05) the peak concentration (C(max)) and the area under the plasma concentration-time curve (AUC) of efavirenz by 25.5% and 44.5%, respectively. In addition, the time necessary to reach peak concentration (T(max)) increased markedly by 71%. However, the mean total clearance (CL/F) of efavirenz was significantly decreased by 45%. Efavirenz did not produce any alteration in ketoconazole pharmacokinetics. 4. These findings suggest that when the treatment starts with enteral administration of ketoconazole, the inhibitor effect on CYP450 prevails over the inducer effect of efavirenz.

In vivo evaluation of a new sustained-release formulation of morphine.

The pharmacokinetics of a novel sustained-release oral formulation of morphine have been evaluated. The formulation consisted of tablets containing a morphine-EudragitL complex (MEC) which had shown good sustained-release properties in previous in vitro dissolution studies. MEC tablets were administered orally to beagle dogs and the morphine plasma levels and pharmacokinetic parameters obtained were compared with those obtained with MST Continus, a commercially available sustained release form of morphine. Blood samples were withdrawn up to 12 h after dosing and plasma morphine concentrations were determined by HPLC with electrochemical detection. Both formulations presented a relatively rapid absorption of morphine with similar values of Cmax (MST: 53 ng/ml; MEC: 50 ng/ml) and Tmax (MST: 86 min; MEC: 88 min), and prolonged morphine plasma levels. Mean plasma morphine concentrations were higher for the MEC tablets than for MST tablets during the terminal phase of the corresponding curves and the mean AUC(0-12h) for MEC tablets was 138% of that obtained with MST tablets. Our findings indicate that MEC tablets can produce prolonged plasma levels of morphine and could be an alternative to commercially available morphine sustained-release forms.

Similarity and discrimination learning in humans.

In an experiment involving a new behavioural preparation the role played by similarity in discrimination learning was examined using visual patterns (i.e., paintings) that might share common elements (specifically, A, BC, and ABC). A-C were small stars of three specific colours (target colours), which were intermixed with other stars of two different colours (distracting colours). The target colours were balanced through A-C. Students received discrimination training in which a fictitious painter was the author of paintings A and BC, while paintings ABC were assigned to a second fictitious painter. During training, the students had to make a choice, in the presence of each pattern, between two response keys, each of them indicating one of the painters. The time taken to respond was also measured. Feedback was always given after each key-press. The results showed that while at times the A+ ABC- discrimination was acquired more readily than was the BC+ ABC- discrimination, on other occasions the reverse was also true, the critical factor being the way in which the colours were combined.

[Complete isosexual precocious puberty: clinical, pelvic ultrasound and laboratory features]. / Pubertad precoz completa isosexual: hallazgos clínicos, de laboratorio y ecografía pélvica.

OBJECTIVE: To determine whether initial presentation varies according to aetiology, whether such differences allow differential diagnosis between idiopathic and organic forms, and whether CNS imaging can be avoided in some patients with central precocious puberty (CPP). PATIENTS AND METHODS: Children referred for evaluation of precocious puberty were evaluated, and the subpopulation of children with CPP was enrolled in this prospective observational study. Clinical, laboratory and ultrasound features of 62 consecutive patients with CPP (5 boys and 57 girls) were recorded. We compared the characteristics of idiopathic (3 boys, 49 girls) and organic (2 boys, 8 girls) CPP. RESULTS: There were no differences in pubertal staging, age at puberty onset (7.0 [5.8-7.5] vs. 7.3 [5.1-8.3] years), bone age/chronological age ratio (1.26 [1.2-1.3] vs. 1.23 [1.1-1.3]), maternal menarche (11.7+/-0.2 vs. 11.7+/-0.6 years) between idiopathic and organic CPP, respectively. Organic CPP patients had a poorer height SD (0.35+/-0.4 vs. 1.6+/-0.1; p<0.01), predicted adult height, growth rate and growth rate SD (0.8+/-0.9 vs. 3.7+/-0.7). Girls with organic CPP had significantly higher oestradiol levels (47.5 [25-68] vs. 27 [14-43] pg/ml) than girls with idiopathic CPP. Pelvic ultrasound at the time of diagnosis revealed the presence of pubertal changes in internal genitalia in 43.9% of girls (37.2% idiopathic versus 62.5% organic CPP subpopulation; p=0.18). CONCLUSIONS: There is a clinical-ultrasound overlap between idiopathic and organic CPP. Imaging remains necessary in all cases of central precocious puberty, and ultrasound data should not be replaced by other diagnostic investigations.

Diseño y validación de una escala observacional sobre el estilo motivador docente / Desenho e validação de uma escala observacional sobre o estilo de ensino motivador / Design and validation of a scale for measuring motivational teaching style

La metodología observacional permite analizar el estilo motivacional que despliega el docente en clase y proporciona una nueva perspectiva para interpretar la influencia de las interacciones docentes en el proceso de instrucción. El objetivo de este trabajo fue diseñar una escala de estimación ad hoc para la Medida del Estilo Interpersonal Docente (MEID) y validarla Participaron 30 docentes universitarios (16 mujeres y 14 hombres) con una edad media de 46.1 años (DT = 5.8) y con una experiencia docente de 15.71 años (DT = 6.9). La calidad del dato fue alcanzada a través de la técnica de validez de contenido y el aspecto cuantitativo fue tratado por medio del análisis del W de Kendall, ajustando un modelo final de 60 ítems agrupados en 4 dimensiones exhaustivas y mutuamente excluyentes: apoyo a la autonomía, apoyo a la estructura antes de la tarea, apoyo a la estructura durante la tarea y apoyo a la relación. Las evidencias iniciales de la escala MEID lo presentan como un instrumento psicométrico robusto y fiable para poder ser empleado como técnica observacional del estilo interpersonal docente. Los resultados obtenidos abren nuevas líneas de estudio en las que la escala MEID podría ser empleada en programas formativos encaminados a la optimización de patrones motivacionales docentes adaptativos. (AU)

The observational methodology allows the analysis of the motivational style displayed by the teacher in class and provides a new perspective to interpret the influence of teacher interactions in the instructional process. The aim of this work was to design an ad hoc estimation scale for the Measure of Interpersonal Teaching Style (MEID) and to validate it. 30 university teachers (16 women and 14 men) with a mean age of 46.1 years (SD = 5.8) and with a teaching experience of 15.71 years (SD = 6.9) participated. Data quality was achieved through the content validity technique by expert judgment and the quantitative aspect was treated through Kendall's W analysis, fitting a final model of 60 items grouped into 4 exhaustive and mutually exclusive dimensions: autonomy support, pre-task structure support, on-task structure support, and relationship support. The initial evidence of the MEID scale presents it as a robust and reliable psychometric instrument to be used as an observational technique of interpersonal teaching style. The results obtained open new lines of study in which the MEID scale could be used in training programs aimed at optimizing adaptive motivational teaching patterns. (AU)

A metodologia observacional permite-nos analisar o estilo motivacional que os professores exibem na aula e fornece uma nova perspectiva para interpretar a influência das interacções dos professores no processo instrucional. O objectivo deste trabalho era conceber uma escala de estimativa ad hoc para a Medida de Estilo de Ensino Interpessoal (MEID) e validá-la. Trinta professores universitários (16 mulheres e 14 homens) com uma idade média de 46,1 anos (SD = 5,8) e com uma experiência de ensino de 15,71 anos (SD = 6,9) participaram no estudo. A qualidade dos dados foi conseguida através da técnica de validade do conteúdo através do julgamento de peritos e o aspecto quantitativo foi tratado através da análise W de Kendall, encaixando um modelo final de 60 itens agrupados em 4 dimensões exaustivas e mutuamente exclusivas: suporte de autonomia, suporte de estrutura pré-tarefa, suporte de estrutura na tarefa, e suporte de relacionamento. A evidência inicial da escala MEID apresenta-a como um instrumento psicométrico robusto e fiável para ser utilizado como uma técnica de observação do estilo de ensino interpessoal. Os resultados obtidos abrem novas linhas de estudo nas quais a escala MEID poderia ser utilizada em programas de formação destinados a optimizar os padrões motivacionais adaptativos nos profesores. (AU)

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

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

Brain ethanol levels in rats after voluntary ethanol consumption using a sweetened gelatin vehicle.

A novel procedure for initiation of voluntary ethanol consumption in the rat was evaluated in terms of ease of initiation, consistency, and resulting brain ethanol levels. The "jello shot" consists of 10% ethanol in gelatin along with a caloric source (Polycose). Initiation of "jello shot" consumption in Sprague-Dawley rats required no food or water restriction and resulted in initial daily (8.4+/-0.6 g/kg body weight) and eventual hourly (1.1+/-0.1 g/kg body weight) intake of ethanol comparable to other procedures using either alcohol-preferring or non-genetically selected rats. Rat intake of ethanol via "jello shots" recovered quickly from environmental alterations and surgical implantation of a guide cannula. During 1-h free access sessions, consumption of the "jello shot" occurred during the initial 10 min and resulted in a dose-related increase in ethanol levels in nucleus accumbens measured using microdialysis. These brain ethanol levels were comparable to those achieved using other self-administration methods. However, when 0.5 g/kg ethanol was gavaged either in "jello shot" or saline, there was about a 20% decrease in brain ethanol concentrations after gavage of the "jello shot" compared to saline. Even so, lack of a need for initial food or water deprivation and the rapidity with which stable self-administration can be achieved both suggest utility of the "jello shot" as a completely voluntary ethanol procedure.

Neurochemical basis of disruption of hippocampal long term potentiation by chronic alcohol exposure.

The aim of this review is to summarize the possible mechanisms underlying the long-term impairment of learning and memory resulting from chronic ethanol treatment (CET) especially that involving decrements in long-term potentiation (LTP) in hippocampus. CET for a 28-week duration affects the rat hippocampal formation in such a way as to decrease the magnitude of LTP; an effect that can last as long as 7 months after ethanol withdrawal. It appears that NMDA receptor number in hippocampus is unchanged after CET whereas the data suggest a more pronounced role for changes in GABAergic and cholinergic synaptic transmission in determining how CET influences the induction of LTP in hippocampus. In particular, changes in presynaptic modulation of neurotransmitter release in hippocampus may be one mechanism by which CET inhibits LTP. Thus, the mechanisms underlying the effect of CET on LTP are a result of changes in a number of neurotransmitter systems in hippocampus (GABAergic and cholinergic) rather than based solely on changes in glutamate transmission.

Antisense inhibition of striatal GABAA receptor proteins decreases GABA-stimulated chloride uptake and increases cocaine sensitivity in rats.

The functional status of striatal GABAA receptors appears to be inversely related to the magnitude of cocaine-induced behaviors. Exposure of striatum to antisense oligodeoxynucleotides (ASODNs) targeted to the mRNAs for the alpha 2 and the beta 3 subunits of the GABAA receptor should decrease expression of receptor proteins and therefore might be expected to increase cocaine sensitivity. ASODNs, scrambled ODNs or saline were injected into right lateral ventricle of rats and behavioral responses to cocaine were tested 18-20 h after treatment. Animals injected separately with alpha 2 or beta 3 ASODNs exhibited increased behavioral sensitivity to cocaine compared to rats injected with saline or scrambled ODNs including performing more 360 degrees turns to the left than to the right. There was significantly less GABA-stimulated Cl uptake in right striatum compared to left striatum of ASODN-treated rats with no significant difference between sides in control animals. Specific binding to benzodiazepine and convulsant sites on the GABAA receptor was not selectively altered by ASODN treatment. Combined alpha 2 beta 3 ASODN treatment did not affect either cocaine sensitivity or GABAA receptor function. There was no difference between the density of Nissl stained cells in the left and right edges of striatum in control or ASODN-treated rats indicating the absence of significant neurotoxic effects of the ASODN treatment. Injection of fluorescein-conjugated ASODNs indicated that ASODN is present in striatum at times during which behavioral and neurochemical indices of GABA receptor function are decreased. Thus, the functional status of GABAA receptors in striatum may be involved in determining cocaine sensitivity.

The influence of alumina and ultra-high molecular weight polyethylene particles on osteoblast-osteoclast cooperation.

Particle-induced macrophage activation, mainly by UHMWPE wear, has been recognized as the biological mechanism leading to periprosthetic bone resorption, which is responsible for the loosening of the total hip replacements (THR). Ceramic-on-ceramic implants have been advocated as a means of reducing wear products. Many studies investigated the effect of alumina (Al(2)O(3)) particles on monocytes/macrophages, but only limited information are available on their participation to bone turnover. An in vitro model was performed to investigate how Al(2)O(3) and UHMWPE particles may influence the osteoblast-osteoclast interaction: human osteoblasts (HOB) were obtained from trabecular bone, while osteoclasts were derived from peripheral blood mononuclear cells (PBMC) of healthy donors. The amount of IL6, TNF alpha, GM-CSF, and other factors acting on the bone turnover, i.e. the 'receptor activator of NF kappa B' ligand (RANKL) and osteoprotegerin (OPG), was detected in culture medium of particle-challenged HOB (HOB-CM). The Al(2)O(3) and UHMWPE particles did not affect either cell viability or TNF and GM-CSF release, while the increase in IL6 release seemed to be dependent on the particle concentration. UHMWPE increased the release of RANKL from HOB, while OPG and OPG-to-RANKL ratio were significantly inhibited. The ability of HOB-CM to promote osteoclastogenesis was tested via osteoblast/monocyte cooperation: after seven days of culture UHMWPE HOB-CM induced a large amount of multinucleated TRAP-positive giant cells, as well as significantly reduced the amount of IL6, GM-CSF and RANKL in the supernatant. With regard to the inductive effect on the osteoclastogenesis, our results show that the Al(2)O(3) wear debris are less active.

Do corticosteroids add any benefit to standard GVHD prophylaxis in allogeneic BMT?

In a retrospective study, we compared 15 patients who received cyclosporine (CsA), methotrexate (MTX) and prednisone (PDN) and 15 patients who received CsA-MTX for GVHD prophylaxis after allogeneic BMT (HLA-identical sibling (n = 22), related one HLA mismatch (n = 1), unrelated matched donors (n = 6), unrelated one HLA mismatch (n = 1)). The primary objectives of this study were to compare the incidence of GVHD and post-transplantation complications. Secondary objectives were to compare relapse rate, transplant-related mortality and overall survival. The incidence of acute GVHD grade III-IV was similar between the two groups (P = 0.66), as was the incidence of chronic GVHD (P = 0.67). Incidence of arterial hypertension was significantly higher in patients who received prophylactic PDN, (P = 0.03) and more insulin treatment was required in this group (P = 0.003). We observed no differences in the incidence of infections or upper digestive tract bleeding. Musculoskeletal complications appeared earlier in the group which received PDN. With a median follow-up of 4.4 years, patients in the CsA-MTX group had better overall survival, 46.7% vs 13.3% (P = 0.026). Relapse was a more frequent cause of death in the CsA-MTX group, whereas procedure-related mortality was more frequent in the CsA-MTX-PDN group (P = 0.013). These results suggest that prophylactic prednisone when combined with cyclosporine and methotrexate adds no benefit in acute or chronic GVHD prevention and may increase the morbidity of allogeneic transplantation. Corticosteroids may be reserved for GVHD treatment.

Individually adjusted prophylactic donor lymphocyte infusions after CD34-selected allogeneic peripheral blood stem cell transplantation.

T cell depletion of the graft increases graft failure and relapse rate in allogeneic PBSC transplantation. Delayed lymphocyte add-back after T cell-depleted transplants might prevent these complications. We present 22 consecutive allogeneic PBSC transplants from related histocompatible donors with positive selection of CD34+ cells. Recipients received prophylactic donor lymphocyte infusions (DLI) depending on their risk of relapse and of developing GVHD. Patients were considered at high risk of relapse with AML > first CR, ALL > second CR, and CML in accelerated or blastic phase. Patients were considered at high risk of developing GVHD if older than 35 years, or with a donor sensitized through previous pregnancy or blood transfusion. Patients at high risk of relapse and low risk of GVHD were scheduled to receive three DLI. Patients at low risk of relapse and high risk of GVHD did not receive DLI. The remaining patients were scheduled to receive two DLI. The DLI were administered on days +28 (2 x 10(5)/kg), +60 (2 x 10(5)/kg) and +90 (2 x 10(6)/kg) after transplant. G-CSF mobilized peripheral stem cells from healthy donors were positively selected by an immunomagnetic method. The mean CD34+ cells and CD3+ cells infused were 4.4 x 10(6)(range 1.9-10.6) and 0.085 x 10(5) (range 0.01-0.67). Cyclosporin A was given to prevent GVHD. All the patients engrafted. Twenty-two prophylactic DLI were performed in 12 patients: seven developed acute GVHD (one case grade III-IV) and none presented pancytopenia. At a mean follow-up of 585 days (range 89-1103), 14 patients were alive in CR, one patient was alive in relapse, four patients had died of relapse and three had died of transplant-related complication. Individually adjusted prophylactic DLI at the doses we used with an escalating schedule allowed an acceptable GVHD rate and a good engraftment of donor hematopoiesis.

Behavioral and neurochemical changes caused by repeated ethanol and cocaine administration.

Combined cocaine and ethanol abuse has become increasingly popular, yet research on the behavioral and neurochemical interactions of these two substances is limited. Four groups of male rats received either daily cocaine (10 mg/kg, IP) or saline injections with either water (groups C and S) or only 15% ethanol to drink (groups CE and E). Initially, locomotor activity was increased equally by ethanol or cocaine and to the greatest extent by both. After 2 weeks of drug treatment, group C exhibited behavioral sensitization to cocaine, group E exhibited ethanol tolerance and group CE exhibited greater cocaine sensitization with no indication of ethanol tolerance. In support of enhanced sensitization to cocaine, amphetamine-stimulated 3H-dopamine (DA) release in striatum and D2 DA receptor binding in the nucleus accumbens (NAC) were increased in group CE compared to group C. In support of a loss of ethanol tolerance, increases in striatal D2 DA and 35S-TBPS binding seen in group E (which exhibited ethanol tolerance) were absent in group CE (which did not exhibit tolerance). Thus, the synergistic effect of ethanol and cocaine on behavior may be due to complex interactions of these two drugs both on DA and GABA transmission in mesolimbic and nigrostriatal areas.

Presynaptic dopaminergic properties of differentiated mouse embryonic stem cells.

This study characterized the presynaptic dopaminergic properties of neuronally differentiated mouse embryonic stem (ES) cells. Approximately 30% of the ES cells expressed tyrosine hydroxylase (TH) immunoreactivity when co-cultured with PA6 cells. These cultures expressed high affinity, sodium-dependent dopamine uptake as well as depolarization-induced and calcium-dependent dopamine release of this transmitter. These and other important dopaminergic genes found expressed in these cultures by RT-PCR included Nurr1, vesicular monoamine transporter 2 (VMAT2), TH, dopamine transporter (DAT), and glial cell line-derived neurotrophic factor (GDNF) receptors c-Ret and GFRalpha1. These results demonstrate that differentiated ES cells have the presynaptic functions for maintaining dopaminergic homeostasis, which may be essential for their long-term use in restoring CNS levels of this transmitter.