Anthropogenic noise and biological sounds in a heavily industrialized coastal area (Gulf of Naples, Mediterranean Sea).

Underwater noise is one of the most widespread threats to the world oceans. Its negative impact on fauna is nowadays well established, but baseline data to be used in management and monitoring programs are still largely lacking. In particular, the acoustic assessment of human-impacted marine coastal areas provides complementary information on the health status of marine ecosystems. The objective of our study was to provide a baseline of underwater noise levels and biological sounds at two sites within the Gulf of Naples (Italy), one of which is located in Bagnoli-Coroglio, a Site of National Interest (SIN) for its high contamination levels. Within the SIN, sounds were recorded both before and during sediment coring activities (vibrocorer sampling), in order to investigate the potential acoustic impact due to such operations. Acoustic recordings were analyzed following the European Marine Strategy Framework Directive indications as defined in the frame of the Descriptor 11. Results reported here show that the investigated area is characterized by a high anthropogenic noise pressure. Ambient noise levels were principally driven by shipping noise and biological sounds of invertebrates (e.g., snapping shrimps). Sounds referable to other biological activity were difficult to detect because heavily masked by shipping noise. Coring activity determined a substantial introduction of additional noise at a local spatial scale. This study expands underwater noise baseline data to be further implemented in future monitoring programs of coastal areas affected by anthropogenic impacts. In addition, it proposes new cues for using underwater acoustic monitoring tools to complement traditional methodologies for evaluating health status of ecosystems and for investigating recovery rates after restoration/reclamation programs.

Impact of historical contamination on meiofaunal assemblages: The case study of the Bagnoli-Coroglio Bay (southern Tyrrhenian Sea).

The effects of contaminants on marine organisms have been documented since decades, but the long-term responses and recovery rates of benthic communities to mixtures of contaminants, several years after the cessation of industrial activities, need to be further investigated. Bagnoli-Coroglio Bay (Gulf of Naples, Tyrrhenian Sea) is a typical example of historically contaminated coastal area due to industrial activities stopped at the beginning of nineties. In the present study we carried out a fine spatial scale analysis of the distribution of meiofaunal (and nematodes) assemblages along five bathymetric transects located at increasing distance from the historical source of contamination in relation with the polycyclic aromatic hydrocarbon and heavy metal concentrations present in the sediment. Meiofaunal abundance and biomass changed widely along transects but independent from the distance from the source of contamination. Even when the contamination levels were expected to induce significant detrimental biological consequences, meiofaunal abundance and biomass were similar to those reported in unpolluted benthic coastal areas worldwide. Conversely, biodiversity in terms of meiofaunal taxa richness was generally low (range: 5-8 taxa in 12 of the overall 15 stations investigated). This was explained by the lack of sensitive groups such as ostracods, gastrotrichs and tardigrades commonly encountered in benthic coastal ecosystems, thus reflecting an overall poor/moderate environmental quality of the investigated area. Nematode (structural and functional) diversity was also low, particularly at stations characterized by higher contamination levels. At the same time, nematode species composition did not change significantly among stations suggesting a widespread effect of contaminants able to reduce the variability (i.e., turnover diversity) within the assemblages of the whole study area. Overall, our results indicate that even decades after the cessation of contaminant emissions, benthic biodiversity was affected in terms of both meiofaunal taxa and nematode species. These findings strongly reinforce the call for reducing sources of chronic pollution in marine ecosystems and provide new insights for a better understanding of the ecological recovery of historically contaminated marine environments.

Multiple human pressures in coastal habitats: variation of meiofaunal assemblages associated with sewage discharge in a post-industrial area.

Marine ecosystems are globally threatened by human activities, but some areas, such as those affected by abandoned industrial plants, show an overlap of acute and chronic impacts, which determine a considerable deterioration of their health status. Here we report the results of a research conducted on coastal sewers that discharge their loads in the highly contaminated area of Bagnoli-Coroglio (Tyrrhenian Sea, Western Mediterranean). The sampling area is characterized by heavy industrial activities (a steel plant using coal, iron and limestone) started in 1905 and ceased in 1990, which left widespread heavy metals and hydrocarbon contamination. After taking into account the potential influence of sediment grain size ranges through their inclusion as covariates in the analysis, we tested the potential impact of sewage discharge on the total abundance and multivariate structure of meiofaunal assemblages, as well as on the abundance of single taxa. The organic matter was analysed in terms of total phytopigment and biopolymeric carbon concentrations. Nematoda, Copepoda (including their nauplii), and Tardigrada were the most abundant meiofaunal taxa at all sites, but nematodes did not show a consistent pattern relative to the sewage outfalls. However, the sewer located in the historically most contaminated area showed a minimal abundance of all taxa, including nematodes, while copepods were relatively less abundant at the two southernmost sewers. Comparing the north vs. south site of the sewers, higher meiofaunal abundances were observed in the southward part, likely as a result of the local circulation. The results of this study indicate the general adaptation of meiofauna to multiple stressors (sewage discharge, superimposed to chronic industrial contamination) and its likely modulation by other local processes. They also provide relevant baseline information for future restoration interventions that would take into account the spatial variation of target organisms as needed.

Tratamiento de la artritis psoriásica con ustekinumab en diferentes escenarios clínicos. Casos reales y revisión de la literatura / Treatment of psoriatic arthritis with ustekinumab in different clinical scenarios. Real cases anda literature review

El tratamiento de la Artritis Psoriásica (APs) se basa en suprimir los signos y síntomas en todos los componentes de la enfermedad (articular, piel, entesis, compromiso axial). Dentro de las opciones terapéuticas contamos con los antinflamatorios no esteroideos (AI-NEs), corticoides, drogas modificadoras de la enfermedad (DMARs) entre ellas el metotrexato y leflunomida, y los anti-TNF. Estas últimas han demostrado actualmente amplia eficacia a largo plazo y buen perfil de seguridad. Fueron el único mecanismo de acción para el tratamiento de la APs; sin embargo en el último año fue aprobado en varios países, ustekinumab, un inhibidor de la subunidad p40 de la IL12 y 23. Esta revisión presenta una serie de 6 casos clínicos donde hemos utilizado esta opción terapéutica en diferentes escenarios

Estrategia para la derivación oportuna: experiencia en un centro de referencia en reumatología / Strategy for temely referral: experience in a reference center in rheumatology

Introducción: En los últimos años se ha reconocido la importancia del diagnóstico precoz de la artritis reumatoidea y las espondiloartritis. Aún existen barreras que impiden la derivación precoz de estos pacientes. Objetivo: Evaluar si existe un aumento significativo en el número de derivaciones al Servicio de Reumatología luego de implementar una estrategia de concientización a otros especialistas. Material y métodos: Estudio observacional, retrospectivo. Resultados: Durante el primer período, el servicio realizó un total de 1027 consultas, de las cuales 130 fueron derivaciones. Las consultas efectuadas luego de la implementación del plan de derivación fueron 1199 con 202 derivaciones (17% IC 95 14,7-19); la diferencia entre ambos períodos fue estadísticamente significativa (p 0,003). Conclusión: La implementación de estrategias de derivación fue valiosa, puesto que encontramos un incremento en el número de derivaciones realizadas. Consideramos que estas intervenciones deben perdurar en el tiempo para mejorar el diagnóstico precoz.

Introduction: In recent years, the importance of early diagnosisof rheumatoid arthritis and spondyloarthritis has been recognized. However, there are still barriers that obstruct the early referral ofthese patients. Objective: To evaluate whether there is a significant increase in thenumber of referrals to the department of Rheumatology after implementinga strategy of awareness to other specialists. Material and methods: Observational and retrospective study. Results: During the first period, the service conducted a total of1027 consultations, of which 130 were referrals. Consultations made after the implementation of the derivation strategy were 1199 of which 202 were referrals (17% CI 95 14.7-19); the difference between the two periods was statistically significant (p 0.003). Conclusion: The implementation of this strategy was valuable, since we found an increase in the number of referrals made. Weconsider that these interventions should last over time to improveearly diagnosis.

Molecular and pharmacological evidence for a facilitatory functional role of pre-synaptic GLUK2/3 kainate receptors on GABA release in rat trigeminal caudal nucleus.

BACKGROUND: Gamma-aminobutyric acid (GABA) and glutamate (GLU) are involved in nociceptive signals processing in the trigeminal system. In this study, we investigated the influence of excitatory transmission on GABA release in nerve terminals isolated from the rat trigeminal caudal nucleus (TCN). METHODS: We utilize biochemical (superfused synaptosomes loaded with [(3) H]GABA) and morphological (immunofluorescence experiments with specific antibody) techniques. RESULTS: Our results show that GLU potentiates the release of [(3) H]GABA evoked by 9, 15 and 30 mM [K(+)](e); 15 mM [K(+)](e)-evoked [(3) H]GABA release was also reinforced by domoate and kainate (KA), two naturally occurring GLU-receptor agonists. The enhancement of 15 mM [K(+)](e)-evoked [(3) H]GABA release produced by 100 µM KA was abolished by NBQX, a mixed AMPA/KA receptor antagonist, but was not affected by GYKI52466, a selective AMPA receptor antagonist. ATPA, a selective agonist for KA receptors containing the GLUK1 subunit, had no effect on depolarization-induced [(3) H]GABA release, and UBP310, which selectively antagonizes these same receptors, failed to reverse the KA-induced potentiation of 15 mM [K(+)](e)-evoked [(3) H]GABA release. The KA-induced potentiation was also unaffected by concanavalin A (10 µM), a positive allosteric modulator of GLUK1- and GLUK2-containing KA receptors. Immunofluorescence experiments revealed that GABAergic nerve terminals in the TCN differentially expressed GLUK subunits, with GLUK2/3-positive terminals being twice more abundant than GLUK1-containing synaptosomes. CONCLUSIONS: These findings indicate that pre-synaptic KA receptors facilitating GABA release from TCN nerve terminals mainly express GLUK2/GLUK3 subunits, supporting the notion that different types of KA receptors are involved in the various stages of pain transmission.

KV7 channels regulate muscle tone and nonadrenergic noncholinergic relaxation of the rat gastric fundus.

Voltage-dependent type 7 K+ (KV7) channels play important physiological roles in neurons and muscle cells. The aims of the present study were to investigate the motor effects of KV7 channel modulators in the rat gastric fundus and the expression of KV7 channels in this tissue. Muscle tone and electrical field stimulation (EFS)-evoked relaxations of precontracted longitudinal muscle strips of the rat gastric fundus were investigated under nonadrenergic noncholinergic conditions by organ bath studies. Gene expression was studied by real-time PCR and tissue localization of channels was investigated by immunohistochemistry. The KV7 channel blocker XE-991 induced concentration-dependent contractions, with mean pD2 and Emax of 5.4 and 48% of the maximal U46619-induced contraction, respectively. The KV7 channel activators retigabine and flupirtine concentration-dependently relaxed U46619-precontracted strips, with pD2s of 4.7 and 4.4 and Emax of 93% and 91% of the maximal relaxation induced by papaverine, respectively. XE-991 concentration-dependently inhibited retigabine-induced relaxation with a pIC50 of 6.2. XE-991 and DMP-543, another KV7 channel blocker, increased by 13-25% or reduced by 11-21% the relaxations evoked by low- or high-frequency EFS, respectively. XE-991 also reduced the relaxation induced by vasoactive intestinal polypeptide (VIP) by 33% of controls. Transcripts encoded by all KV7 genes were detected in the fundus, with 7.4 and 7.5 showing the highest expression levels. KV7.4 and 7.5 channels were visualized by confocal immunofluorescence in both circular and longitudinal muscle layers. In conclusion, in the rat proximal stomach, KV7 channels appear to contribute to the resting muscle tone and to VIP- and high-frequency EFS-induced relaxation. KV7 channel activators could be useful relaxant agents of the gastric smooth muscle.

Impacts of marine aquaculture at large spatial scales: evidences from N and P catchment loading and phytoplankton biomass.

While several studies point at off-shore aquaculture as a possible source of impacts on the local marine environment, very few have analysed its effects at large scales such as at the bay, gulf or basin levels. Similar analyses are hampered by the multiple sources of disturbance that may concomitantly affect a given area. The present paper addresses these issues taking the Gulf of Castellammare (Southern Tyrrhenian Sea) as an example. Nitrogen (N) and phosphorous (P) loads were calculated for the period 1970-2007, and compared to chlorophyll-a concentration as measured inside and outside the Gulf over the same period. Results indicate that N and P catchment loading has constantly decreased because of improved environmental management. Nevertheless, nutrient concentration in the Gulf has steadily increased since the establishment of aquaculture facilities in 1999. Chlorophyll-a concentration followed this trend, showing a marked increase from 2001 onwards. In the same period, chlorophyll-a concentrations measured inside and outside the Gulf have significantly diverged. As all the other possible causes can be ruled out, aquaculture remains the sole explanation for the observed situation. This paper demonstrates for the first time ever that off-shore aquaculture may affect the marine ecosystem well beyond the local scale and provides an additional element of concern to be kept into consideration when allocating oceans' space for new fish-farming activities.

Technology-assisted programs for promoting leisure or communication engagement in two persons with pervasive motor or multiple disabilities.

OBJECTIVE: To evaluate technology-assisted programs to help a man with pervasive motor disabilities and an adolescent with multiple disabilities manage the use of a radio and a special messaging system, respectively. METHOD: The technology for the man (Study I) involved a modified radio device, an electronic control unit, an amplified MP3 player with verbal questions about radio operations (changes), and an optic microswitch. This allowed the man to respond to the questions and carry out operations through minimal chin movement. The technology for the adolescent (Study II) involved a net-book computer fitted with specifically designed software, a global system for mobile communication (GSM) modem, and an optic microswitch. This allowed the adolescent to select the persons to whom he wanted to send messages and the messages to send them, and to listen to messages sent to him. RESULTS: The data showed that both programs were effective, with the two participants learning to use the radio and the messaging system, respectively. CONCLUSION: Technology-assisted programs may represent useful tools for providing persons with pervasive and multiple disabilities leisure and communication opportunities.

AMPA- and P2X7-receptor-mediated facilitation of [3H]D-aspartate release from nerve terminals isolated from the rat caudal brainstem.

Glutamate (GLU) plays a key role in the transmission and modulation of sensory input to the trigeminal caudal nuclei (TCN). In the present study, we investigated the regulation of previously taken-up [3H]D-aspartate ([3H]D-ASP) release from nerve terminals isolated from rat caudal brainstem, in particular from the zone containing the TCN. TCN neurons can be considered integrative relay neurons linking peripheral and central pain mechanisms. Understanding the mechanisms that control the release of GLU in this area could lead to more effective treatment of migraines and other types of pain associated with the trigeminal nerve. In isolated rat caudal brainstem synaptosomes, exposure to AMPA dose-dependently potentiated [K+](e)-stimulated release of [3H]D-ASP (maximum increase: 218±13.08%; EC(50): 1.60±0.08 µM). This effect was inhibited by selective AMPA-receptor antagonists (competitive [NBQX] and non-competitive [GYKI52466]) but not by the kainate receptor subunit antagonists NS102 and ACET. AMPA-evoked responses were significantly enhanced by preventing AMPA receptor desensitization with cyclothiazide (10 µM). Basal release of [3H]D-ASP was stimulated by millimolar concentrations of ATP (maximum increase: 197.80±11.85%; EC(50): 545±3.15 µM) and by the selective P2X7-receptor agonist benzoylbenzoyl-ATP. ATP also potentiated the release of [3H]D-ASP induced by depolarization. Its effect on basal [3H]D-ASP release was inhibited by the selective P2X7-receptor antagonist A-438079 and by the non-selective antagonist PPADS, but it was only partially suppressed by the ionotropic purinergic receptor antagonist TNP-ATP. Our findings demonstrate that glutamatergic nerve terminals in rat caudal brainstem express AMPA receptors that can facilitate [3H]D-ASP during terminal depolarization and P2X7 receptors that can also enhance this release under basal conditions.

Small hand-closure movements used as a response through microswitch technology by persons with multiple disabilities and minimal motor behavior.

This study assessed small hand-closure movements as a potential response for microswitch activation with two participants with profound multiple disabilities of 5.2 and 20.6 yr. of age. The microswitch consisted of a two-membrane thin pad fixed to the palm of the hand and a control system. The outer membrane (the one facing the fingers) was a touch-sensitive layer; the inner membrane was activated if the participant applied a pressure of over 20 gm. The activation of either membrane triggered an electronic control system, which in turn activated one or more preferred stimuli for 6 sec. except in baseline phases. Each participant received an ABAB sequence, in which A represented baseline and B intervention phases, and a 1-mo. postintervention check. Analysis showed both participants increased their responding during the intervention phases and maintained that responding at the postintervention check. Implications of the findings are discussed.

[Organization of work, hardship at work, mobbing: new problem areas that must be considered by the competent doctor in formulating fitness evaluation]. / L'organizzazione del lavoro, il disagio lavorativo, il mobbing: le nuove problematiche all'attenzione del medico competente per la formulazione del giudizio di idoneità.

In recent years, in addition to the more common occupational-health risks (chemical, physical, biological), increasing importance is given to psychological and psychosomatic illness as a result of malfunction in the organization of work: burn-out, mobbing, maladjustment at work. In order to be able to evaluate the influence of such phenomenon whilst judging fitness in some working realities in Sicily, 18 small, medium and large dimension companies with a total of 1413 employees were examined. The typology of the work embraced the industrial, health, information-technology, construction and telephony sectors. The research involved analyzing, with the respective competent physicians, (in a few cases the same physician dealt with more than one company) the Risk Evaluation document, the clinical and risk records and the fitness evaluations. The analysis of the data obtained pointed out that of the 1413 employees observed, 87% was judged fit, 2% fit with limitation and/or prescription, almost 1% not fit. Notwithstanding the type of judgment, it was ascertained how in the above evaluation, only classical "physical" risks were evaluated (noise, MMC, VDT, etc.). The worker is judged as an individual removed from the general context of the company, of it's organization, or, as one who participates only by means of his various organs and apparatus, and who can singularly become ill because of exposure to some occupational risk. As a matter of fact, in none of the DVR's of the 18 companies object of the research, was an element of evaluation of the working organization found. Nor on the communication means, on the transparency of the procedures, on the quality of relations, lack of instruments or physical sites fit to working activity, nor to emotionally extreme working activities. It must therefore be emphasized that the competent physician only possesses the individual pathologies encountered in the various working situations. He lacks elements of evaluation that would supply useful information on the working organization, and on the effects the latter can have on the health of the employees, and, therefore on their fitness to work. The latter; in our opinion, is data that cannot be disregarded in the correct judgment of psycho-physical fitness, as foreseen by the regulations in force.

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.

[Work organization and mobbing: application of cognitive methodology in medical circle]. / L'organizzazione del lavoro e mobbing: applicazione di una procedura conoscitiva in ambito sanitario.

Mobbing is a phenomenon produced for the most part by factors related to work organization. During the medical control of workers in Universitary Policlinico Hospital of Palermo, we used a methodology (in advance applied with effectiveness by ISPESL in other institutions) that is able to evidence factors of work organization causing Mobbing. 338 out 2060 workers (total staff) with different professional figures were recruited. We evidenced the working classes that had more troubles about communications of business information, about interpersonal relationships at work with top manager, with other members of team and with colleagues. Particularly doctors and OTA, in worrying percentage, stated that they suffered psychological molestations. Aim of our study was to assay a procedure that, even if it doesn't identify proclaimed mobbing phenomenon, enables us to acquire information about relationships between business management and workers and organizational aspects perceiving by subordinates. A I level study about a phenomenon in expansion is very useful to recognize preventively intentionally made mobbing actions.

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.

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.

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.

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.

Long-lasting handling affects behavioural reactivity in adult rats of both sexes prenatally exposed to diazepam.

Environmental stressors can substantially affect the adaptive response of rats to novelty in a sexually dimorphic manner. Gender-related differences are also observed in neurochemical and behavioural patterns of adult rats following prenatal exposure to diazepam (DZ). In the present study the behavioural reactivity to novelty is investigated in open field (OF) and in acoustic startle reflex (ASR) tests, in non handled (NH), short-lasting handled (SLH) and long-lasting handled (LLH) adult male and female rats prenatally exposed to DZ. A single daily s.c. injection of DZ (1.5 mg/kg) over gestation days 14-20 decreases GABA/BDZ receptor function in both sexes, as shown by the decreased electrographic hippocampal response to DZ and the increased response to picrotoxin, after intra-locus coeruleus injection of the two compounds. In OF NH DZ-exposed males display a lower total distance travelled (TDT), a higher rearing frequency (RF) and a greater number of transitions in the centre of the arena (CNT) compared to NH rats prenatally exposed to vehicle. Conversely, NH DZ-exposed females show slight changes in TDT and RF and a greater reduction in CNT and in the amount of time spent in the centre of the arena (CAT). These effects are associated with an increase in the peak amplitude of the ASR in both sexes. Short-lasting handling slightly influences DZ-evoked effects in animals of both sexes. In DZ-exposed males long-lasting handling attenuates the reduction in TDT and the enhancement in RF, prevents the increase in CNT and reduces the peak amplitude of ASR. In DZ-exposed females, long-lasting handling increases TDT and RF, induces a lower avoidance of the centre of the arena, and does not modify the peak amplitude of ASR, when compared to controls. These findings indicate that prenatal exposure to DZ differently affects behavioural reactivity in adult male and female rats, and suggest that a long-lasting handling is able to attenuate some behavioural deficits induced by prenatal DZ exposure.

Interaction of formamidine pesticides with the presynaptic alpha(2)-adrenoceptor regulating.

The effects of the formamidine pesticides amitraz and chlordimeform on the alpha(2)-adrenergic receptor subtype that mediates the release of [(3)H]noradrenaline by synaptosomes from rat hypothalami were studied. We initially characterized the presynaptic autoreceptor on noradrenergic nerve endings using selective antagonists. Yohimbine (a nonselective alpha(2) antagonist) and BRL 44408 (selective for subtypes alpha(2A)/alpha(2D)) diminished the inhibitory effect of xylazine on K(+)-evoked release of [(3)H]noradrenaline; the K(B) values were 481 and 154 nM, respectively. In contrast, prazosin (a selective alpha(2B)/alpha(2C) antagonist) did not modify the inhibitory effect of xylazine. These results indicate that the release of noradrenaline by noradrenergic nerve endings in the rat hypothalamus is regulated by alpha(2D)-adrenoceptors, a species variation of the human alpha(2A) subtype. We then assessed the effects of the two pesticides on the K(+)-evoked release of [(3)H]noradrenaline. Amitraz reduced release in a dose-dependent manner; the effect observed at the maximal concentration tested (10 microM) was 13.0 +/- 2.0% and it was reversed by yohimbine. Amitraz also diminished the inhibitory effects of the alpha(2)-adrenergic agonists clonidine and xylazine. Chlordimeform displayed no effects, possibly because the true active compound of this insecticide is its demethylated metabolite. Based on these findings we conclude that the formamidine pesticides act as partial agonists of presynaptic alpha(2D)-adrenergic receptors in the rat hypothalamus. This interaction may be responsible for the in vivo alterations in catecholaminergic regulation of cyclic variations in gonadotropin-releasing hormone (GnRH) secretion, which can have grave functional repercussions on the reproductive system of mammals exposed to these xenobiotics.