Impulsivity and Stress Response in Pathological Gamblers During the Trier Social Stress Test.

Gambling has been associated with increased sympathetic nervous system output and stimulation of the hypothalamic-pituitary-adrenal axis. However it is unclear how these systems are affected in pathological gambling. This study aimed to investigate the effect of the Trier Social Stress Test (TSST) on cortisol and on cardiac interbeat intervals in relation to impulsivity, in a sample of male pathological gamblers compared to healthy controls. In addition, we investigated the correlation between the TSST, duration of the disorder and impulsivity. A total of 35 pathological gamblers and 30 healthy controls, ranging from 19 to 58 years old and all male, participated in this study. Stress response was measured during and after the TSST by salivary cortisol and cardiac interbeat intervals; impulsivity was assessed with the Barratt Impulsiveness Scale (BIS-11). Exposure to the TSST produced a significant increase in salivary cortisol and interbeat intervals in both groups, without differences between groups. We found a negative correlation between baseline cortisol and duration of pathological gambling indicating that the longer the duration of the disorder the lower the baseline cortisol levels. Additionally, we found a main effect of impulsivity across groups on interbeat interval during the TSST, indicating an association between impulsivity and the intensity of the neurovegetative stress response during the TSST. Involvement of the hypothalamic-pituitary-adrenal axis in pathological gambling was confirmed together with evidence of a correlation between length of the disorder and diminished baseline cortisol levels. Impulsivity emerged as a personality trait expressed by pathological gamblers; however the neurovegetative response to the TSST, although associated with impulsivity, appeared to be independent of the presence of pathological gambling.

Predictors of early dropout in treatment for gambling disorder: The role of personality disorders and clinical syndromes.

Several treatment options for gambling disorder (GD) have been tested in recent years; however dropout levels still remain high. This study aims to evaluate whether the presence of psychiatric comorbidities predicts treatment outcome according to Millon's evolutionary theory, following a six-month therapy for GD. The role of severity, duration of the disorder, typology of gambling (mainly online or offline) and pharmacological treatment were also analysed. The recruitment included 194 pathological gamblers (PGs) to be compared with 78 healthy controls (HCs). Psychological assessment included the South Oaks Gambling Screen and the Millon Clinical Multiaxial Inventory-III. The "treatment failure" group (n = 70) comprised PGs who prematurely dropped out of the treatment whereas the "abstinent group" (n = 124) included PGs who completed the treatment regardless of whether the outcome was successful or not. As expected, the presence of psychiatric comorbidities was highlighted as a significant predictor in dropping out of the therapy. Specifically negativistic personality disorder, antisocial personality disorder, drug dependence and PTSD were associated with early dropout. These variables were predictive of treatment outcome independently from the typology of gambling, severity, duration of the disorder and pharmacological treatment. Implications for psychological and psychiatric care are discussed.

Primer caso de tratamiento ex utero intraparto realizado por vía vaginal en un feto con síndrome de obstrucción congénita de la vía aérea superior / The first case of exutero intrapartum treatment performed using the vaginal route in a fetus with congenital high airway obstruction syndrome

El síndrome de obstrucción congénita de la vía aérea superior (CHAOS), es una condición infrecuente que causa asfixia o muerte perinatal inmediata, de no mediar una estrategia terapéutica que permita permeabilizar la vía aérea del paciente durante el nacimiento. El diagnóstico prenatal, es fundamental para delinear estrategias de tratamiento perinatal con el fin de minimizar la morbimortalidad de niños con anomalías congénitas. El tratamiento ex-útero intraparto (EXIT) es el procedimiento de elección. Clásicamente se realiza mediante una cesárea programada, manteniendo el soporte fetal a través de la circulación útero-placentaria. Se requiere un equipo altamente calificado y un trabajo coordinado para concretar el procedimiento en estas condiciones. Objetivo: El objetivo es reportar un caso de Síndrome de CHAOS, en el que se realizó un procedimiento EXIT en un niño nacido por parto vaginal, con la participación de un equipo multidisciplinario de profesionales de dos Instituciones Públicas de la Ciudad de Buenos Aires, en el marco de un Programa Conjunto de Diagnóstico y Tratamiento Fetal (AU)

Congenital high airway obstruction syndrome (CHAOS) is a rare entity causing perinatal asphyxia or immediate death if no therapeutic strategy is undertaken to correct airway patency at birth. Prenatal diagnosis is essential to plan perinatal strategies to decrease morbidity and mortality in children with congenital anomalies. The exutero intrapartum treatment (EXIT) is the procedure of choice. Classically, a programmed cesarean section is performed while the fetus is maintained on uteroplacental circulation. A highly trained team is required in the coordinated effort to perform the procedure. Aim: The aim of this study was to report on a case of CHAOS managed with an EXIT procedure in a child born through vaginal delivery performed by a multidisciplinary team of professionals belonging to two public institutions of the city of Buenos Aires in the framework of the Joint Program of Fetal Diagnosis and Treatment (AU)

Programa de diagnóstico y tratamiento fetal. Estudio de cohorte sobre su efectividad en la evolución de neonatos con patologías quirúrgicas / Program for prenatal diagnosis and treatment: A cohort study on effectivity on the outcome of newborns with surgical pathologies

Introducción. El diagnóstico prenatal de las malformaciones congénitas (MC) permite optimizar el cuidado perinatal. Al Hospital Garrahan (HG) ingresan recién nacidos (RN) con MC para tratamiento quirúrgico. Desde el año 2008 funciona el programa de diagnostico y tratamiento fetal (PDTF) para optimizar el cuidado prenatal y perinatal de RN con MC. El objetivo del estudio es evaluar el impacto de la derivación prenatal en RN que ingresan a la unidad de cuidados intensivos neonatales (UCIN) del HG por MC seleccionadas. Población y Métodos: estudio observacional analítico y comparativo entre grupos, sobre condición de ingreso y evolución de RN con gastrosquisis (GTQ), mielomeningocele (MMC) y hernia diafragmática (HD) y grado de stress parental, según ingreso a UCIN por derivación prenatal o postnatal. Se realizó análisis bivariado, descriptivo y comparativo de indicadores generales y especiales de cuidado. Resultados: Se incluyeron 164 RN (44 con derivación prenatal a través del PDTF). Este grupo presentó: mejor control del embarazo (93% vs 66%, p: 0.04), menor edad gestacional al diagnóstico (24s vs 33s p=0.0006) y mayor tasa de cesárea electiva (95 vs 47%, p=0.0001). Los RN tuvieron menor necesidad de reanimación e ingresaron más tempranamente a la Unidad (mediana 4hs vs 10hs, p=0,004). Hubo menor stress parental en relación al hijo (17 vs 40%). Los RN con GTQ ingresaron mejor curados y se alimentaron por vía enteral más rápidamente. Conclusión: Los RN con MC derivados prenatalmente a través del PDTF, ingresan precozmente y presentaron mejores estrategias de cuidado que los ingresados por derivación habitual (AU)

Introduction. Prenatal diagnosis of congenital malformations (CM) improve perinatal care. At the Garrahan Hospital (GH) newborns (NB) with CM are admitted for surgical treatment. Since 2008 a program for prenatal diagnosis and treatment (PDT) has been in place to optimize prenatal and perinatal care of NB with CM. The aim of this study was to assess the impact of prenatal referral of NB that are admitted to the GH for selected CM. Population and Methods: An observational, analytical, and between-group comparative study was conducted on the status on admission and outcome in NB with gastroschisis (GS), myelomeningocele (MMC), and diaphragmatic hernia (DH) and degree of parental stress, according to NICU admission after prenatal or postnatal referral. Bivariate, descriptive and comparative analysis of general and specific markers of care was performed. Results: 164 NB were included (44 were prenatally referred through the PDT program). The latter group presented with better pregnancy control (93% vs 66%, p: 0.04), younger gestational age at diagnosis (24w vs 33w p=0.0006), and higher rate of elective cesarean section (95 vs 47%, p=0.0001). This group of NB needed less reanimation and were admitted to the NICU earlier (∑4hs vs 10hs, p=0.004). Parental child-related stress was less (17 vs 40%). NB with GS had a better surgical outcome and were started on enteral feeding earlier. Conclusion: NB with CM that were prenatally referred through the PDT program, were admitted earlier and could be managed with better strategies than those who were conventionally referred (AU)

Análisis de la evolución clínico-quirúrgica de neonatoscon atresia de esófago con cabos distantes (Long Gap)durante el crecimiento espontáneo de los mismos / Analysis of clinical-surgical course of neonates with long-gap esophageal atresia during their spontaneous growth

Introducción. La atresia de esófago (AE) es una de las patologías quirúrgicas de mayor prevalencia en la etapa neonatal. La corrección quirúrgica es posible despues del nacimiento, pero en ocasiones la distancia entre los cabos esofágicos (CE) imposibilita la anastomosistérmino-terminal (ATT) inicial. La definición de Long Gap (LG) oCE distantes es imprecisa y, si bien hay consenso en que la conservación del esófago propio es la mejor opción terapéutica, existen controversias sobre la oportunidad e impacto clínico que ocasiona la espera del crecimiento de los cabos esofágicos en forma espontánea tal como lo ha propuesto P. Puri. Objetivos. Evaluar la evolución clínico-quirúrgica de los recién nacidos (RN) con AELG durante el ingres en la unidad de cuidados intensivos neonatales (UCIN) de un hospital pediátrico. Material y métodos. Estudio descriptivo, retrospectivo. Se incluyeron todos los RN con AELG ingresados en la UCIN desde enero de2002 a diciembre de 2006. Se analizó sexo, edad gestacional, peso al nacer (PN), tipo de AE, distancia entre CE, complicaciones respiratorias y quirúrgicas, edad al alta y mortalidad. Resultados. En 5 años ingresaron a la UCIN 64 RN con AE; 21(33%) fueron LG (población de estudio). En 8 RN (38%), se logró realizar una ATT (80 ± 40 días); todos tuvieron reflujo gastroesofágico(RGE), el 50% presentó complicaciones: dehiscencia o estenosis de la (..) (AU)

Introduction. Esophageal atresia (EA) is one of the most prevalent surgical conditions in the newborn. Sometimes early oesophagealanastomosis can’t be done due to the esophageal gap. Long gap (LG)definition is not precise. Although consensus exist about conservation of owns esophagus is the best therapeutic option, literature is not clear about how long and under what circunstances is advisable to wait for the spontaneous esophageal pouches to growth (P. Puri approach). Furthermore at present we don’t even know the real repercussion that this waiting can implicate. Objective. The aim of the study was to evaluate the clinical and (..) (AU)

[Analysis of clinical-surgical course of neonates with long-gap esophageal atresia during their spontaneous growth]. / Análisis de la evolución clinico-quirúrgica de neonatos con atresia de esófago con cabos distantes (Long Gap) durante el crecimiento espontáneo de los mismos.

INTRODUCTION: Esophageal atresia (EA) is one of the most prevalent surgical conditions in the newborn. Sometimes early oesophageal anastomosis can't be done due to the esophageal gap. Long gap (LG) definition is not precise. Although consensus exist about conservation of owns esophagus is the best therapeutic option, literature is not clear about how long and under what circunstances is advisable to wait for the spontaneous esophageal pouches to growth (P. Puri approach). Furthermore at present we don't even know the real repercussion that this waiting can implicate. OBJECTIVE: The aim of the study was to evaluate the clinical and surgical outcome of newborns with EALG during their stay in a neonatal intensive care unit (NICU) at a third level children's hospital. MATERIALS AND METHODS: We retrospectively reviewed the charts of all newborn with EA admitted in the NICU from January 2002 to December 2006 in order to analyze sex, gestacional age, weight, type of EA, LG, respiratory and surgical complications, length of stay and mortality. RESULTS: During the study time period 64 newborns with EAwere admitted, 21 (33%) had EALG (our population). We underwent primary repair with esophageal anastomosis in 8 newborns at 80 +/- 40 days. All of them had gastroesophageal reflux, 50% presented different complications such as anastomotic leak, stricture and mediastinal infections. 13 patients required an esophagostomy at a mean age of 46 +/- 34 days due to a lack of growth of esophageal's pouches and/or serious respiratory complications. There were no deaths. CONCLUSIONS: There were high percentages of esophagostomized patients. The result of waiting for the primary repair was a high number of children with chronic lung disease and a high rate of serious complications. Esophageal anastomosis were accompanied by long hospital stays and no clear benefits. The early application of dynamic esophageal lengthening should be explored as an alternative strategy for newborns with EALG.

Design of electrical stimulation bioreactors for cardiac tissue engineering.

Electrical stimulation has been shown to improve functional assembly of cardiomyocytes in vitro for cardiac tissue engineering. Carbon electrodes were found in past studies to have the best current injection characteristics. The goal of this study was to develop rational experimental design principles for the electrodes and stimulation regime, in particular electrode configuration, electrode ageing, and stimulation amplitude. Carbon rod electrodes were compared via electrochemical impedance spectroscopy (EIS) and we identified a safety range of 0 to 8 V/cm by comparing excitation thresholds and maximum capture rates for neonatal rat cardiomyocytes cultured with electrical stimulation. We conclude with recommendations for studies involving carbon electrodes for cardiac tissue engineering.

Perinatal exposure to 5-methoxytryptamine, behavioural-stress reactivity and functional response of 5-HT1A receptors in the adolescent rat.

Serotonin is involved in a wide range of physiological and patho-physiological mechanisms. In particular, 5-HT1A receptors are proposed to mediate stress-adaptation. The aim of this research was to investigate in adolescent rats: first, the consequences of perinatal exposure to 5-metoxytryptamine (5MT), a 5-HT1/5-HT2 serotonergic agonist, on behavioural-stress reactivity in elevated plus maze, open field and forced swim tests; secondly, whether the behavioural effects induced by perinatal exposure to 5MT on open field and forced swim tests were affected by the selective 5-HT1A receptor agonist LY 228729, a compound able to elicit a characteristic set of motor behaviours on these experimental models, and by the co-administration of the selective and silent 5-HT1A antagonist WAY 100635. Results indicate that a single daily injection of 5MT to, pregnant dams from gestational days 12 to 21 (1mg/kg s.c.), and to the pups from postnatal days 2 to 18 (0.5mg kg s.c.), induce in the adolescent rat offspring: an increase in the percentage of entries and time spent on the open arms in the elevated plus maze; a reduction in locomotor activity and rearing frequency, and an increase in the time spent on the central areas in the open field test; a decrease in immobility and an increase in swimming in the forced swim test. Acute administration of LY 228729 (1.5mg/kg s.c.) strongly decreases rearing frequency and increases peripheral activity in the open field test, and decreases immobility and increases swimming in the forced swim test both in perinatally vehicle and 5MT-exposed offspring. Co-administration of WAY 100635 (0.25mg/kg s.c.) abolishes the effects exerted by LY 228729. These results suggest that, in the adolescent rat, perinatal exposure to 5MT enhances the stress-related adaptive behavioural responses, presumably through a predominant action on presynaptic 5-HT1A receptors and does not deteriorate the functional response of 5-HT1A receptors to selective agonist and antagonist compounds.

Biomimetic approach to cardiac tissue engineering.

Here, we review an approach to tissue engineering of functional myocardium that is biomimetic in nature, as it involves the use of culture systems designed to recapitulate some aspects of the actual in vivo environment. To mimic the capillary network, subpopulations of neonatal rat heart cells were cultured on a highly porous elastomer scaffold with a parallel array of channels perfused with culture medium. To mimic oxygen supply by haemoglobin, the culture medium was supplemented with a perfluorocarbon (PFC) emulsion. Constructs cultivated in the presence of PFC contained higher amounts of DNA and cardiac markers and had significantly better contractile properties than control constructs cultured without PFC. To induce synchronous contractions of cultured constructs, electrical signals mimicking those in native heart were applied. Over only 8 days of cultivation, electrical stimulation induced cell alignment and coupling, markedly increased the amplitude of synchronous construct contractions and resulted in a remarkable level of ultrastructural organization. The biomimetic approach is discussed in the overall context of cardiac tissue engineering, and the possibility to engineer functional human cardiac grafts based on human stem cells.

Presynaptic effects of anandamide and WIN55,212-2 on glutamatergic nerve endings isolated from rat hippocampus.

We examined the effects of the endocannabinoide-anandamide (AEA), the synthetic cannabinoid, WIN55,212-2, and the active phorbol ester, 4-beta-phorbol 12-myristate 13-acetate (4-beta-PMA), on the release of [(3)H]d-Aspartate ([(3)H]d-ASP) from rat hippocampal synaptosomes. Release was evoked with three different stimuli: (1) KCl-induced membrane depolarization, which activates voltage-dependent Ca(2+) channels and causes limited neurotransmitter exocytosis, presumably from ready-releasable vesicles docked in the active zone; (2) exposure to the Ca(2+) ionophore-A23187, which causes more extensive transmitter release, presumably from intracellular reserve vesicles; and (3) K(+) channel blockade by 4-aminopyridine (4-AP), which generates repetitive depolarization that stimulates release from both ready-releasable and reserve vesicles. AEA produced concentration-dependent inhibition of [(3)H]d-ASP release stimulated with 15 mM KCl (E(max)=47.4+/-2.8; EC(50)=0.8 microM) but potentiated the release induced by 4-AP (1mM) (+22.0+/-1.3% at 1 microM) and by A23187 (1 microM) (+98.0+/-5.9% at 1 microM). AEA's enhancement of the [(3)H]d-ASP release induced by the Ca(2+) ionophore was mimicked by 4-beta-PMA, which is known to activate protein kinase C (PKC), and the increases produced by both compounds were completely reversed by synaptosome treatment with staurosporine (1 microM), a potent PKC blocker. In contrast, WIN55,212-2 inhibited the release of [(3)H]d-ASP evoked by KCl (E(max)=47.1+/-2.8; EC(50)=0.9 microM) and that produced by 4-AP (-26.0+/-1.5% at 1 microM) and had no significant effect of the release induced by Ca(2+) ionophore treatment. AEA thus appears to exert a dual effect on hippocampal glutamatergic nerve terminals. It inhibits release from ready-releasable vesicles and potentiates the release observed during high-frequency stimulation, which also involves the reserve vesicles. The latter effect is mediated by PKC. These findings reveal novel effects of AEA on glutamatergic nerve terminals and demonstrate that the effects of endogenous and synthetic cannabinoids are not always identical.

Reversal of prenatal diazepam-induced deficit in a spatial-object learning task by brief, periodic maternal separation in adult rats.

In the rat, prenatal exposure to diazepam (DZ) induces a permanent reduction in GABA/BZ receptor (R) function and behavioural abnormalities. Environmental modifications during early stages of life can influence brain development and induce neurobiological and behavioural changes throughout adulthood. Indeed, a subtle, periodic, postnatal manipulation increases GABA/BZ R activity and produces facilitatory effects on neuroendocrine and behavioural responses. We here investigated the impact of prenatal treatment with DZ on learning performance in adult 3- and 8-month-old male rats and the influence of a brief, periodic maternal separation on the effects exerted by prenatal DZ exposure. Learning performance was examined employing a non-aversive spatial, visual and/or tactile task, the "Can test". Behavioural reactivity, emotional state and fear/anxiety-driven behaviour were also examined using open field (OF), acoustic startle reflex (ASR) and elevated plus-maze (EPM) tests. A single daily injection of DZ (1.5mg/kg, s.c.), over gestational days (GD) 14-20, induced, in an age-independent manner, a severe deficit in learning performance, a decrease in locomotor and explorative activity and an increase in peak amplitude in the ASR. Furthermore, anxiety-driven behaviour in EPM was disrupted. Daily maternal separation for 15 min over postnatal days 2-21 exerted opposite effects in all the paradigms examined. Prenatally DZ-exposed maternal separated rats, in contrast to respective non-separated rats, showed an improvement in learning performance, a decrease in emotionality and a normalization of the exploratory behaviour in EPM. These results suggest that a greater maternal care, induced by separation, can serve as a source for the developing brain to enhance neuronal plasticity and to prevent the behavioural abnormalities induced by prenatal DZ exposure.

Fascitis necrotizante en recien nacidos / Necrotizing fascitis in newborns

La fascitis Necrotizante (FN) es una emergencia quirúrgica, resultado de la infección de los tejidos subcutáneos y de la fascia superficial, por una gran variedad de bacterias. En esta etapa neonatal, esta afección puede alcanzar una mortalidad mayor al 70 por ciento. El éxito del tratamiento requiere un preciso diagnóstico y precoz y agresivo desbridamiento de los tejidos afectados, la cobertura por vía parenteral de antibióticos de amplio espectro y un soporte adecuado en cuidados intensivos. Reportamos un caso de FN en recién nacidos de sexo masculino, en quien la enfermedad se desencadenó probablemente luego de una onfalitis. Este reporte ilustra la naturaleza devastadora de este tipo de infección, sin embargo, con tratamiento agresivo y precoz es posible lograr resultados satisfactorios.

Inhibition by anandamide and synthetic cannabimimetics of the release of [3H]D-aspartate and [3H]GABA from synaptosomes isolated from the rat hippocampus.

Cannabinoids (CB) can act as retrograde synaptic mediators of depolarization-induced suppression of inhibition or excitation in hippocampus. This mechanism may underlie the impairment of some cognitive processes produced by these compounds, including short-term memory formation in the hippocampus. In this study, we investigated several compounds known to interact with CB receptors, evaluating their effects on K(+)-evoked release of [3H]D-aspartate ([3H]D-ASP) and [3H]GABA from superfused synaptosomes isolated from the rat hippocampus. [3H]D-ASP and [3H]GABA release were inhibited to different degrees by the synthetic cannabinoids WIN 55,212-2; CP 55,940, and arachidonyl-2'-chloroethylamide/N-(2-chloroethyl)-5Z,8Z,11Z,14Z-eicosatetraenamide (ACEA), as well as by the endocannabinoids, anandamide (AEA), and 2-arachidonoylglycerol (2-AG). Both types of release were also inhibited by capsaicin. The inhibition produced by each of the cannabinoid compounds and capsaicin was unaffected by capsazepine or by the CB1-receptor antagonists AM-251 and SR141716A. The mechanism underlying AEA- and synthetic CB-induced inhibition of the release of [3H]GABA and [3H]D-ASP from rat hippocampal synaptosomes might not involve activation of presynaptic CB1 receptors.

Know-how and know-why in biochemical engineering.

This contribution analyzes the position of biochemical engineering in general and bioprocess engineering particularly in the force fields between fundamental science and applications, and between academia and industry. By using culture technology as an example, it can be shown that bioprocess engineering has moved slowly but steadily from an empirical art concerned with mainly know-how to a science elucidating the know-why of culture behavior. Highly powerful monitoring tools enable biochemical engineers to understand and explain quantitatively the activity of cellular culture on a metabolic basis. Among these monitoring tools are not just semi-online analyses of culture broth by HPLC, GC and FIA, but, increasingly, also noninvasive methods such as midrange IR, Raman and capacitance spectroscopy, as well as online calorimetry. The detailed and quantitative insight into the metabolome and the fluxome that bioprocess engineers are establishing offers an unprecedented opportunity for building bridges between molecular biology and engineering biosciences. Thus, one of the major tasks of biochemical engineering sciences is not developing new know-how for industrial applications, but elucidating the know-why in biochemical engineering by conducting research on the underlying scientific fundamentals.

Effects of 8-OH-DPAT on open field performance of young and aged rats prenatally exposed to diazepam: a tool to reveal 5-HT1A receptor function.

Central GABAergic and serotoninergic systems interact with one another and are implicated in controlling different behaviours. A gentle early long-lasting handling can prevent the deficits in locomotion and exploration in open field (O.F.) in 3-month-old male rats prenatally exposed to diazepam (DZ). Purpose of this study was to extend the research to older handled rats prenatally exposed to DZ and to assess the activity of 5-HT1A receptors (Rs), evaluating the performance in O.F. at 3 and 18 months of age following 8-OH-DPAT administration. A single daily s.c. injection of DZ (1.5 mg/kg) from gestation day 14 to gestation day 20 induced in aged, but not in young rats, a decrease in total distance travelled (TDT) and in rearing frequency (RF) and an increase of transitions from the periphery to the centre of the arena (CNT) and in the time spent in the centre of the arena (CAT), compared to controls. 8-OH-DPAT (0.150 mg/kg s.c.), given 1 h before testing, increased TDT and decreased RF, CNT and CAT in both vehicle- and DZ-exposed young rats. In aged rats prenatally exposed to DZ, 8-OH-DPAT induced an increase in TDT and a slight decrease in RF, CNT and CAT. These findings indicate that the effects of handling and of 8-OH-DPAT in prenatally DZ-exposed rats are age-dependent and suggest that O.F. test can represent a valid tool to identify the changes in 5-HT1A Rs activity following drug treatment.

Prevalence of headache in patients with Behçet's disease without overt neurological involvement.

The aims of the present study were to evaluate the prevalence of headache and the frequency of different headache syndromes in patients with Behçet's Disease (BD) without neurological involvement and to investigate the relationship with other clinical, and behavioural variables. Twenty-seven BD patients and 27 control subjects underwent a validated semistructured questionnaire based on the International Headache Society criteria. Levels of anxiety and depression, disease activity, and current medication were collected. Headache occurred in 88.9% of BD patients. There was no difference in the prevalence of the different headache syndromes between BD patients and controls. Only migraine without aura (MwA) was significantly more frequent in BD patients than controls (44.4% vs. 11.1%, respectively, P= 0.013). No relationship was found between MwA and clinical, and behavioural variables. Among headache syndromes, MwA showed the highest frequency in BD. A vascular or neuronal subclinical dysfunction could justify this association. A careful interview for migraine might be included in the diagnostic work-up of BD.

Alterations in striatal neuropeptide mRNA produced by repeated administration of L-DOPA, ropinirole or bromocriptine correlate with dyskinesia induction in MPTP-treated common marmosets.

Chronic administration of L-DOPA to MPTP-treated common marmosets induces marked dyskinesia while repeated administration of equivalent antiparkisonian doses of ropinirole and bromocriptine produces only mild involuntary movements. The occurrence of dyskinesia has been associated with an altered balance between the direct and indirect striatal output pathways. Using in situ hybridisation histochemistry, we now compare the effects of these drug treatments on striatal preproenkephalin-A (PPE-A) and adenosine A(2a) receptor mRNA expression as markers of the indirect pathway and striatal preprotachykinin (PPT) mRNA and preproenkephalin-B (PPE-B, prodynorphin) mRNA expression as markers of the direct pathway.The equivalent marked losses of specific [3H]mazindol binding in the striatum of all drug treatment groups confirmed the identical nature of the nigral cell loss produced by MPTP treatment. MPTP-induced destruction of the nigro-striatal pathway markedly increased the level of PPE-A mRNA in the caudate nucleus and putamen and decreased the levels of PPT and PPE-B mRNA relative to normal animals. Repeated treatment with L-DOPA for 30 days produced marked dyskinesia but had no effect on the MPTP-induced increase in PPE-A mRNA in the caudate nucleus and putamen. In contrast, L-DOPA treatment normalised the MPTP-induced decrease in the level of PPT and PPE-B mRNA. Repeated treatment with ropinirole produced little or no dyskinesia but markedly reversed the MPTP-induced elevation in PPE-A mRNA in the caudate nucleus and putamen. However, it had no effect on the decrease in PPT or PPE-B mRNA. Similarly, bromocriptine treatment which induced only mild dyskinesia attenuated the MPTP-induced elevation in PPE-A mRNA in the caudate nucleus and putamen with no effect on reduced striatal PPT or PPE-B mRNA. Neither MPTP treatment nor treatment with L-DOPA, bromocriptine or ropinirole had any effect on adenosine A(2a) receptor mRNA in the striatum. These patterns of alteration in striatal PPE-A and PPT and PPE-B mRNA produced by L-DOPA, bromocriptine and ropinirole show differential involvement of markers of the direct and indirect striatal output pathways related to improvement of locomotor activity and mirror the relative abilities of the drugs to induce dyskinesia.

Benign prostatic hyperplasia: correlations between receptor density and binding affinity of alpha(1)-adrenoceptors and several clinical parameters.

The aim of the study was to determine whether relations do exist between the concentration and activity of alpha(1)-adrenoceptors, both inside the prostatic adenoma and the periurethral zone corresponding to the bladder neck, and clinical and biological parameters such as symptoms, evaluated by the American Urological Association (AUA) score, age, weight of the prostate, PSA, and the flow rate. Twenty patients with symptomatic benign prostatic hyperplasia were selected for an open prostatectomy. One gram of tissue was dissected from inside the adenoma and 1 g from the periurethral zone corresponding to the bladder neck. The alpha(1)-adrenoceptors were evaluated for the apparent dissociation constant (K(d)) and the maximal number of binding sites (B(max)). A correlation seems to exist between receptor density inside the adenoma and the bladder neck and an inverse correlation between receptor density and the AUA total symptoms score. Finally, a highly significant difference was found in patients with an AUA score of <15 or >15. No relationship was found between receptor binding affinity and the considered clinical parameters.

6-Hydroxydopamine lesioning differentially affects alpha-synuclein mRNA expression in the nucleus accumbens, striatum and substantia nigra of adult rats.

The effect of a unilateral 6-hydroxydopamine (6-OHDA) lesion and/or repeated administration of levodopa (L-DOPA) to normal and 6-OHDA-lesioned rats on alpha-synuclein mRNA expression was investigated by in situ hybridization histochemistry. A 6-OHDA lesion of the nigro-striatal pathway alone, confirmed by the loss of nigral tyrosine hydroxylase mRNA expression, markedly decreased alpha-synuclein mRNA in the lesioned substantia nigra (SN). In contrast, the levels of alpha-synuclein mRNA in the denervated striatum and nucleus accumbens were not altered. Chronic administration of L-DOPA to normal or 6-OHDA-lesioned rats had no effect on alpha-synuclein mRNA expression in the SN, striatum or nucleus accumbens. These data confirm that alpha-synuclein is localized in the nigro-striatal tract but that its gene expression is not regulated by dopamine.