Dopamine in the nucleus accumbens core, but not shell, increases during signaled food reward and decreases during delayed extinction.

UNLABELLED: Microdialysis studies in rat have generally shown that appetitive stimuli release dopamine (DA) in the nucleus accumbens (NAc) shell and core. Here we examined the release of DA in the NAc during delivery of reward (food) and during extinction of food reward in the freely moving animal by use of in vivo microdialysis and HPLC. Fifty-two male Wistar rats were trained to receive food reward associated with appearance of cue-lights in a Skinner-box during in vivo microdialysis. Different behavioral protocols were used to assess the effects of extinction on DA and its metabolites. Results Exp. 1: (a) During a 20-min period of cued reward delivery, DA increased significantly in the NAc core, but not shell subregion; (b) for the next 60min period half of the rats underwent immediate extinction (with the CS light presented during non-reward) and the other half did not undergo extinction to the cue lights (CS was not presented during non-reward). DA remained significantly increased in both groups, providing no evidence for a decrease in DA during extinction in either NAc core or shell regions. (c) In half of the animals of the group that was not subjected to extinction, the cue lights were turned on for 30min, thus, initiating extinction to cue CS at a 1h delay from the period of reward. In this group DA in the NAc core, but not shell, significantly decreased. Behavioral analysis showed that while grooming is an indicator of extinction-induced behavior, glances toward the cue-lights (sign tracking) are an index of resistance to extinction. Results Exp. 2: (a) As in Exp. 1, during a 30-min period of cued reward delivery, DA levels again increased significantly in the NAc core but not in the NAc shell. (b) When extinction (the absence of reward with the cue lights presented) was administered 24h after the last reward session, DA again significantly decreased in the NAc core, but not in the NAc shell. CONCLUSIONS: (a) These results confirm the importance of DA release in the NAc for reward-related states, with DA increasing in the core, but not shell subregion. (b) They provide first evidence that during the withholding of expected reward, DA decreases in the NAc core, but not shell region. (c) This decrease in DA appears only after a delay between delivery of reward and extinction likely due to it being masked by persisting DA release. We hypothesize the decrease in extinction-induced release of DA in the NAc core to be a marker for the despair/depression that is known to accompany the failure to obtain expected rewards/reinforcers.

Assessing vaccine hesitancy and vaccine literacy among the European prison population and staff: A multicentre observational study.

Vaccination is the most efficient and cost-effective public health intervention. Prison population, for its low social distancing, constant turnover, and high percentage of migrants, should be an important target of vaccination campaign. However, vaccination coverage in prison is low. In this study we estimated vaccine hesitancy and vaccine literacy among the prison population and staff and assessed their correlation. We conducted a cross-sectional study in 13 prisons of 4 European countries. The sample included 847 people living in prison and 755 staff members. Through a structured questionnaire we assessed vaccine hesitancy, vaccine literacy, general health literacy, previous vaccine refusal and socio-demographic characteristics of participants. Exploratory factor analysis was used to extract three components of vaccine hesitancy. Logistic regression was applied to assess the association between previous vaccine refusal and vaccine hesitancy; linear regression was applied to assess the association between vaccine hesitancy and vaccine and general health literacy. All analyses were adjusted for socio-demographic variables. We identified three components of vaccine hesitancy explaining 49% of the total variance: Mistrust, Concern and Conspiracy. In both people living in prison and staff, all the components were associated to previous vaccine refusal (p-value < 0.001) and presented good internal consistency (Cronbach's alpha = 0.90, 0.73 and 0.78). Young participants presented the highest levels of vaccine hesitancy; migrant people living in prison had the lower levels of Mistrust and the higher level of Concern; all three factors were lower among participants with the highest degree of education. Mistrust and Concern were inversely associated with vaccine literacy while all three subscales were inversely associated with general health literacy (all p-values < 0.001). This study suggests that educational interventions aimed at increasing vaccine literacy in people living and working in prison could decrease vaccine hesitation and consequently increase vaccination uptake among the prison population and staff.

Hydroxypropyl methylcellulose: Physicochemical properties and ocular drug delivery formulations.

Hydroxypropyl methylcellulose (HPMC) is a cellulose ether widely used in drug formulations due to its biocompatibility, uncharged nature, solubility in water and thermoplastic behavior. Particularly for ocular and ophthalmic formulations, HPMC is applied as viscosity enhancer agent in eye drops, gelling agent in injections, and polymeric matrix in films, filaments and inserts. The different therapeutic approaches are necessary due to the complex anatomic structure of the eye. The natural ocular barriers and the low drug permeation into the circulatory system make the drug administration challenging. This review presents the eye anatomy and the usual local routes of drugs administration, which are facilitated by the physicochemical properties of HPMC. The relationship between chemical structure and physicochemical properties of HPMC is displayed. The different types of formulations (local application) including HPMC for ocular drug delivery are discussed with basis on recent literature reports and patents.

Dewetting and surface properties of ultrathin films of cellulose esters.

Surface properties of ultrathin films of cellulose esters deposited onto silicon wafers have been investigated by means of contact angle measurements and atomic force microscopy (AFM). Cellulose acetate (CA), cellulose acetate propionate (CAP), and cellulose acetate butyrate (CAB) films adsorbed or spin-coated onto Si wafers were annealed up to one week. Film stability was monitored by AFM. Dewetting has been observed for CA and CAP. Only CAB films with lower degree of esterification presented dewetting, CAB films with high degree of butyrate were stable even after one week annealing. Surface energy of CA, CAP, and CAB was indirectly determined by contact angle measurements using drops of water, formamide and diiodomethane. The surface energy decreased as the size of alkyl ester group or the degree of esterification increased because van der Waals interactions became weaker. Effective Hamaker constant A(eff) was calculated for CA, CAP, and CAB onto Si wafers in air. Negative values of A(eff) were found for CA, CAP, and lower butyrate content CAB, which are related to instability and agree with dewetting phenomena observed by AFM. In contrast, a positive A(eff) was determined for higher butyrate content CAB, corroborating with experimental observations.

Adsorption behavior and activity of hexokinase.

The study on the adsorption of hexokinase (HK) onto silicon wafers was carried out by means of in situ ellipsometry and atomic force microscopy in the liquid. The thickness values of the adsorbed HK layer determined by both techniques were in excellent agreement and evidenced HK monolayer formation. The adsorption of HK onto Si wafers was favored at low ionic strength, indicating that the adsorption is mainly driven by electrostatic forces, since salt screens not only the segment-segment repulsion but also the segment-surface attraction when the salt concentration increases. The enzymatic activity of free HK and of adsorbed HK was measured as a function of time. Free HK in solution lost activity upon storage. Contrarily, adsorbed HK kept its activity level even after 48 h storage at room temperature. This outstanding behavior was attributed to specific orientation of the HK active site to the solution.

Serotonergic interaction between medial prefrontal cortex and mesotelencephalic DA system underlies cognitive and affective deficits in hemiparkinsonian rats.

Parkinson's disease (PD) patients not only exhibit motor impairments, but also characteristic deficits in cognitive and affective functions. Such functions have consistently been associated with the medial prefrontal cortex (mPFC). To determine whether there is an interaction between the midbrain dopamine system (MDS) and the mPFC underlying the cognitive and emotional deficits seen in rats, we administered a disconnection procedure of these structures by applying lesions to the mPFC (N-methyl-d-aspartic acid (NMDA)) and the medial forebrain bundle (6-hydroxydopamine (6-OHDA)) either in the same or opposite hemispheres. The results indicate a functional interaction of the MDS and the mPFC: Disconnection effects on behavior were observed with respect to memory-, anxiety- and depression-related behaviors. A disconnection of the mPFC and MDS had promnestic, antidepressant- and anxiolytic-like effects. In order to determine whether this circuit between the mPFC and MDS involves serotonergic mechanisms, we also utilized serotonin-specific disconnections of the mPFC by applying the 5-HT-specific agent 5,7-dihydroxytryptamine (5,7-DHT) into the mPFC and 6-OHDA into the medial forebrain bundle, again either in the same or opposite hemispheres. The behavioral effects observed here resembled those incurred by the unspecific disconnection of the mPFC, demonstrating a significant contribution of serotonergic mechanisms to the interplay between the MDS and the mPFC. Taken together, these experiments provide evidence for an interaction of the MDS and the mPFC in the control of cognitive and affective processes known to be impaired in PD and point toward a prominent involvement of the serotonergic system. A disconnection of the mPFC and the MDS had promnestic, antidepressant- and anxiolytic-like behavioral effects. These findings may impact therapeutic approaches in the treatment of cognitive and neuropsychiatric symptoms seen in PD.

Frequency of occurrence of the Gm(21) factor in the Polish population.

In a sample of the Polish population of 610 subjects, frequency of the Gm(21) factor was determined and compared with the frequency of Gm(1). The Gm(21) factor was found with a frequency of 0.359, and Gm(1) with 0.370. Both factors were present in 35.7% of sera examined. Factor Gm(1) alone, unaccompanied by Gm(21), was encountered in 8 sera, and factor Gm(21) without Gm(1) only in one serum.

Neurokinin3-R agonism in aged rats has anxiolytic-, antidepressant-, and promnestic-like effects and stimulates ACh release in frontal cortex, amygdala and hippocampus.

Neurokinin-3 receptors (NK(3)-R) are localized in brain regions which have been implicated in processes governing learning and memory as well as emotionality. The effects of acute subcutaneous (s.c.) senktide (0.2 and 0.4 mg/kg), a NK(3)-R agonist, were tested in aged (23-25 month old) Wistar rats: (a) in an episodic-like memory test, using an object discrimination task (this is the first study to test for deficits in episodic-like memory in aged rats, since appropriate tests have only recently became available); (b) on parameters of anxiety in an open field test, (c) on indices of depression in the forced swimming test and (d) on the activity of cholinergic neurons of the basal forebrain, using in vivo microdialysis and HPLC. Neither the saline-, nor senktide-treated aged animals, exhibited episodic-like memory. However, the senktide-, but not the vehicle-treated group, exhibited object memory for spatial displacement, a component of episodic memory. Senktide injection also had anxiolytic- and antidepressant-like effects. Furthermore, the active doses of senktide on behavior increased ACh levels in the frontal cortex, amygdala and hippocampus, suggesting a relationship between its cholinergic and behavioral actions. The results indicate cholinergic modulation by the NK(3)-R in conjunction with a role in the processing of memory and emotional responses in the aged rat.

Catalytic activity of lipase immobilized onto ultrathin films of cellulose esters.

Ultrathin (approximately 2.0 nm) films of cellulose acetate (CA), cellulose acetate propionate (CAP), and cellulose acetate butyrate (CAB) supported on Si wafers have been prepared by adsorption and characterized by means of ellipsometry, atomic force microscopy (AFM), and contact angle measurements. CA, CAP, and CAB ultrathin films were characterized in air just after their formation and after annealing under reduced pressure at temperature higher than the corresponding melt temperature. Upon annealing, CA, CAP, and CAB ultrathin films became smoother and more hydrophobic, evidencing molecular reorientation at the solid-air interface. CA, CAP, and CAB films were used as supports for the immobilization of lipase. The adsorption of lipase onto annealed films was more pronounced than that onto untreated films, showing the strong affinity of lipase for the more hydrophobic substrates. Enzymatic activity was evaluated by a standard procedure, namely, (spectrophotometric) measurement of p-nitrophenol, the product formed from the hydrolysis of p-nitrophenyl dodecanoate (p-NPD). Lipase immobilized onto hydrophobic films exhibited higher activity than that of free lipase and could be recycled three times while retaining relatively high activity (loss of ca. 30% of original enzymatic activity). The effect of storing time on the activity of immobilized lipase was studied. Compared with free lipase, that immobilized onto more hydrophobic films retained 70% activity after 1 month. More importantly, the latter level of activity is similar to that of free lipase. However, lipase immobilized onto more hydrophilic films retained 50% and 30% activity after 20 and 30 days, respectively. These results are explained in terms of surface wettability and the contribution of the interactions between the polar residues of lipase and the glucopyranosyl moieties of cellulose ester to maintain the natural conformation of immobilized enzyme.

Hemodynamic instability after extracranial carotid stenting.

OBJECTIVE: Hemodynamic instability (hypertension, hypotension and bradycardia) is a well-known complication of carotid endarterectomy. Carotid angioplasty and stenting (CAS) is becoming a valuable alternative treatment for patients with severe carotid stenosis and increased surgical risk. CAS implies instrumentation of the carotid bulb, so baroceptor dysfunction may provoke hemodynamic instability. The aim of this work was to calculate the incidence of this complication and to detect factors to predict it. METHODS: Medical records and angiograms of 51 consecutive patients submitted to CAS for severe atherosclerotic stenosis (40 cases) or postsurgical restenosis (11 cases) were retrospectively reviewed in order to detect the occurrence of intra- and post-procedural hypertension (systolic blood pressure >160 mmHg), hypotension (systolic blood pressure <90 mmHg) and bradycardia (heart rate <60 beats/min). The relationship between clinical, procedural and angiographic factors and the occurrence of hemodynamic instability was assessed with univariate and multivariate analysis (logistic regression). RESULTS: Transient mild systolic post-procedural hypertension occurred in five cases (10%); preprocedural hypertension, asymptomatic stenosis and ipsilateral post-surgical restenosis predicted this. Hypotension with bradycardia also occurred in five cases (10%), one with neurological sequelae. Transient periprocedural bradycardia occurred in 19 cases (37%). Severe bradycardia without hypotension arose in one case only. Factors predicting post-procedural hypotension included the presence of a fibrous plaque and the ratio between the pre- and post-stenting diameter of the internal carotid artery. Peri-procedural bradycardia predicted post-procedural bradycardia. None of these factors were confirmed by multivariate analysis as a significant prognostic predictor. CONCLUSION: Mild systolic hypertension may occur after CAS, but is resolved by medical treatment. Prolonged hypotension and bradycardia may also arise and this can be dangerous because it may cause neurological deterioration due to hypoperfusion. These complications cannot be predicted by clinical, procedural, and angiographic factors.

Hybrid particles of polystyrene and carboxymethyl cellulose as substrates for copper ions.

The synthesis of hybrid particles was carried out by emulsion polymerization of styrene in complexes formed by carboxymethyl cellulose (CMC), a polyanion, and a cationic surfactant, cetyltrimethylammonium bromide (CTAB). CMC chains with variable molecular weights and degrees of substitution were tested. The polymerization condition chosen was that corresponding to CMC chains fully saturated with CTAB and to the onset of pure surfactant micelle formation, namely, at the critical aggregation concentration. The hybrid particles were characterized by zeta potential and light scattering measurements. The period of colloidal stability in the ionic strength of 2.0 mol L(-)(1) NaCl was observed visually. Upon increasing the CMC chain length, the particle characteristics remained practically unchanged, but the colloid stability was increased. The increase in the CMC degree of substitution led to particles with more negative zeta potential values. The adsorption of copper ions (Cu(2+)) on the surface of hybrid particles could be described by the Langmuir model, as determined by potentiometric measurements. The increase in the mean zeta potential values and X-ray absorption near-edge spectra evidenced the immobilization of Cu(2+) ions on the hybrid particles.

Composite graft (Medtronic-Hall) replacement of the ascending aorta and aortic valve in aortic aneurysms: what is adequate follow-up?

Between 1987 and 1994, 39 patients underwent 41 replacements (2 reoperations) of the aortic valve and ascending aorta by composite grafts with mechanical valves. One patient had annuloaortic ectasia, one had a sinus of valsalva aneurysm, 13 patients had a Debakey type I acute dissection, 10 had a Debakey type II acute dissection including two Marfan patients, and 14 had atherosclerotic aneurysms. 6 patients (15%) died within a postoperative period of 30 days. The mean follow-up time was 40 months (1-82 months). Twenty-six patients were restudied by clinical examinations and computed tomography of the chest (CT). Two patients required emergency reoperation due to disruption of the proximal aortic anastomosis and right coronary anastomosis. Both patients had been diagnosed to have Marfan disease. Anastomotic dehiscence of composite grafts has a potentially high risk of lethal complications. In follow-up examination computed tomography was performed as a simple and accurate method to detect complications such as pseudoaneurysms, but up to now did not give the indications for reoperation. We suggest that complications may occur not only in the early postoperative period so that regular CT-scan control studies (every 6 to 12 months) should be performed in all patients who undergo composite graft replacement.

The effect of water or salt solution on thin hydrophobic films.

Hydrophobic films of polystyrene synthesized in bulk (PS) and by emulsion polymerization in the presence of the cationic surfactant cetyltrimethylammonium bromide (PS-CTAB) or the anionic surfactant sodium dodecyl sulfate (PS-SDS) were characterized by means of ellipsometry, contact angle measurements, and atomic force microscopy. Thin (approximately 65 nm) and thick (approximately 300 nm) films were spin-coated on hydrophilic silicon wafers. PS films presented scarcely tiny holes, while PS-CTAB and PS-SDS films presented holes and protuberances. The former were attributed to dewetting effects and the latter to surfactant clusters. The films were exposed to water or to a 0.1 mol/L NaCl solution for 24 h. Ex situ measurements evidenced strong topographic alterations after the exposure to the fluid. A model based on the diffusion of water (or electrolyte) molecules to the polymer/silcon dioxide interface through holes or defects on the film edges was proposed to explain the appearance of wrinkles and protuberances. In situ ellipsometric measurements were performed and compared with simulations, which considered either a water layer between a polymer and a silcon dioxide layer or an air layer between a polymer and water (medium). In the case of thin PS films, the ellipsometric angles evidenced a very thin (0.5-1.0 nm) air layer between water and the PS films. Upon increasing the PS film thickness, no air layer could be observed by ellipsometry. Regardless of the thickness, the ellipsometric data obtained for PS-CTAB and PS-SDS films did not indicate the presence of an air layer between them and the aqueous media. The dramatic changes in the topography of PS, PS-CTAB, and PS-SDS after immersion in salt solution were explained with proposed models. From a practical point of view, this study is particularly relevant because many hydrophobic polymers are used as substrates for biomedical purposes, where the physiological ionic strength is 0.15 mol/L NaCl.

Surgery and stenting As combined treatment of a symptomatic tandem stenosis of the carotid artery.

International co-operative studies have demonstrated a benefit from surgery for symptomatic and asymptomatic patients affected by internal carotid artery stenosis of 60-70%. The presence of a tandem lesion, intracranial or extracranial, may annul the benefit of surgery. Such patients may thus represent a challenging problem for management if age, good general conditions and a normal neurological status favour a therapy. A 54-year-old man developed transient ischaemic attacks of the left hemisphere; his general condition was good, and neurological status was normal. Angiography showed a tight stenosis at the left common carotid artery near the ostium and at the homolateral carotid bifurcation. At first, a self-expanding wall stent was placed at the level of the common carotid artery stenosis, and immediately after a standard endarterectomy under general anaesthesia was performed. The postoperative course was normal and was complicated only by the presence of a mild deficit of the hypoglossal nerve due to the presence of a high bifurcation. The early and late outcome of our case suggests that stenosis of the proximal common carotid artery may be successfully treated by stenting. While awaiting additional data about this new technology, endovascular techniques and surgery may be complementary in the management of patients suffering from such tandem lesions.