Characterization of Student Drinking Behaviors at the Beginning of the First Academic Year at One University in Southern Italy.

It is well recognized that both college and noncollege students are at-risk age groups for alcohol consumption. We investigated the alcohol consumption habits of undergraduate students with an emphasis on binge drinking. Participants (N = 809, 61.2% female) were freshmen attending courses at one of the main universities of southern Italy. They were asked to fill out a paper-and-pencil questionnaire that was administered between October 2017 and January 2018. Nearly 90% of the questioned students reported drinking alcohol during the 12 months before the survey. Among them, 31.4% of female students and 41.5% of male students engaged in binge drinking, mainly once a month; binge drinkers preferred highly alcoholic beverages during parties, underestimated the alcoholic content of their drinks, started drinking alcohol at a younger age than nonbinge drinkers, and drank weekly and between meals. Binge drinkers started smoking earlier than their peers, and a great number of them consumed illicit drugs. Moreover, 30.3% of female and 34.8% of male nonbinge drinkers declared that they consumed 6 or more units of alcohol in one occasion, making them unaware binge drinkers. Furthermore, approximately 50% of students recognized that alcohol consumption has effects similar to those induced by illicit drugs but only considered their peers' drinking behavior to be risky.This study highlights that most students involved in this survey expose themselves to a risky lifestyle by heavy drinking and, most alarmingly, that some of them are not even aware of that.

Topical Fisionerv® is effective in treatment of peripheral neuropathic pain.

BACKGROUND: Management of neuropathic pain (Neu P) is complex and difficult. Although there are several therapeutic options, treatment with Neu P is often inadequate, which led to undertreated patients. Thus, it would be desirable, for Neu P treatment, further multimechanistics approaches. OBJECTIVE: The aim of the present study was to evaluate, in Neu P management, the effectiveness of "FISIONERV, a gel for topical use. SETTING: This study was conducted in the "Rehabilitation Unit of N. Melli's Hospital, Brindisi, Italy". PATIENTS AND INTERVENTION: In this study a double- blind randomized controlled clinical trial was conducted over 8-week treatment on 58 outpatients affected by Neu P caused by lumbar sciatica or lumbar disk herniation and/or lumbar canal stenosis (31 subjects), or with carpal tunnel syndrome (27 subjects), randomly assigned to the following two groups: Group A; n=29, received (fisionerv® gel, 3 times/day) added to physiotherapy (forty minutes-daily session). Group B; n=29 received a vehicle gel (placebo, 3 times/day) added to physiotherapy (forty minutes-daily session). MEASUREMENTS: Pain was assessed by a visual analogue scale (VAS). Neuropathic symptoms frequency (pain, burning, paraesthesiae and numbness) were scored at baseline and at the end of the treatment. Treatment compliance and safety were also evaluated. RESULTS: Both groups experienced a significant reduction in VAS and neuropathic symptoms after 8-treatment weeks. However, a significant (p<0.05) improvement was observed in group A (VAS mean 5.3 (1.10) with respect to group B (VAS mean=6.17 (0.80), already after 4 weeks of treatment. A further VAS reduction was recorded at 8 treatment weeks, with significant difference between the treatments (group A: VAS mean=1.89 (0.77); group B: VAS mean=3.79 (1.20) (p<0.001). In addition, more patients of the group A, than in group B, reported an improvement of their neurophatc pain (p<0.01). No adverse drug reaction was observed. CONCLUSION: Use of fisionerv®, in combination with physiotherapy, resulted a useful approach to NP treatment. CLINICAL REHABILITATION IMPACT: These preliminary observations suggest that some interesting goals (better pain control and physical wellbeing) could be achieved by a multimodal therapy in NP patients.

Bedsores successfully treated with topical phenytoin.

Phenytoin is normally used in epilepsy treatment. One of the side effect affecting a significative part of the treated patients is the gingival overgrowth. It could surely be a correlation between this stimulatory effect and the assessment of phenytoin in wound healing. In fact, some studies of the literature have shown that topical phenytoin promotes healing of traumatic wounds, burns and ulcers by decubitus or stasis (diabetic or venous) and we emphasize, in vitiligo, a particular attention into repigmentation. The related mechanism of action seems to be multifactorial. In the present paper topical phenytoin has been used as wound-healing agent in 19 documented cases of bedsores, divided in treated and placebo group. The used concentration of phenytoin was 5 mg/L dissolved in a water solution of 9 g NaCl /L (0.9% P/V of NaCl). Patches soaked with phenytoin solution were applied over the bedsores along 3 hours every 12 hours. Results showed that phenytoin treated patients healed their wounds significantly before (p<0.001) with respect to controls.

Clinical improvement and resorption of calcifications in calcific tendinitis of the shoulder after shock wave therapy at 6 months' follow-up: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the effectiveness of shock wave therapy (SWT) for functional improvement and the reduction of pain in patients with calcific tendinitis of the shoulder, and to determine the rate of disappearance of calcifications after therapy at 6 months' follow-up. DATA SOURCES: Articles were searched from the Cochrane Library, MEDLINE, Embase, CINAHL, and Ovid database. STUDY SELECTION: We included randomized controlled trials from 1992 to 2011, and their quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. DATA EXTRACTION: Studies were evaluated by 2 independent reviewers for their methodologic quality. Disagreements were settled by a third reviewer. Data were then extracted and cross-checked for accuracy. The reviewers were not blinded to the authors of the articles. DATA SYNTHESIS: In 4 of the 6 studies included for review, the resorption of calcifications was evaluated using meta-analysis because the studies had 2 treatment groups, while the other 2 studies were analyzed descriptively because they had 3 treatment groups. Fixed- and random-effects models were used to meta-analyze total and partial resorption ratios, and I(2) statistics were calculated to assess heterogeneity. CONCLUSIONS: We found a clinical improvement with a pooled total resorption ratio of 27.19 (95% confidence interval [CI], 7.20-102.67) and a pooled partial resorption ratio of 16.22 (95% CI, 3.33-79.01). SWT increases shoulder function, reduces pain, and is effective in dissolving calcifications. These results were maintained over the following 6 months.

Extracorporeal shock-wave therapy for supraspinatus calcifying tendinitis: a randomized clinical trial comparing two different energy levels.

BACKGROUND: Extracorporeal shock-wave therapy (ESWT) represents a valid intervention in the treatment of people with supraspinatus calcifying tendinitis (SCT), but there is limited evidence for the useful range of ESWT doses. OBJECTIVE: The aim of this study was to compare 2 different ranges of energy flux density in treatment of SCT with ESWT. DESIGN: This study was designed as a single-blind randomized clinical trial. SETTING: This study was performed in a university hospital. PATIENTS: Forty-six patients with SCT were randomly assigned to 2 groups that received different therapeutic energy doses of ESWT: (1) group A received ESWT at an energy level of 0.20 mJ/mm², and (2) group B received ESWT at an energy level of 0.10 mJ/mm². INTERVENTION: The treatment protocol consisted of 4 sessions performed once a week. MEASUREMENTS: The change in mean Constant Murley Scale (CMS) scores at 3 and 6 months was the primary endpoint. The change in the mean visual analog scale (VAS) scores from baseline to 3 and 6 months after the intervention and radiographic change in size of calcium deposits were evaluated as secondary endpoints. At 12 months, pain relief was assessed using a numeric rating scale. RESULTS: Significant clinical improvement based on mean CMS scores was observed after 6 months in group A (X=79.43, SD=10.33) compared with group B (X=57.91, SD=6.53). Likewise, after 6 months, a significant decrease in VAS scores was found in group A (X=2.09, SD=1.54) compared with group B (X=5.36, SD=0.78). Calcific deposits disappeared in the same percentage of patients in both groups. LIMITATIONS: The small sample size and lack of a control group were limitations of the study. CONCLUSIONS: In ESWT for SCT, an energy level of 0.20 mJ/mm² appears to be more effective than an energy level of 0.10 mJ/mm² in pain relief and functional improvement.

Isolation rearing-induced reduction of brain 5α-reductase expression: relevance to dopaminergic impairments.

Isolation rearing (IR), a well-established rat model of early chronic psychosocial stress, engenders marked behavioral alterations related to changes of dopamine (DA) neurotransmission in cortical and subcortical brain regions. Stress-induced shifts in γ-aminobutyric acid (GABA)-ergic signaling have been implicated in the dysregulation of DA release. The neurosteroid 3α-hydroxy-5α-pregnan-20-one (allopregnanolone/AP), synthesized from progesterone by the action of the rate-limiting enzyme 5α-reductase (5AR), is a potent positive allosteric modulator of GABA(A) receptor function. Thus, alterations of 5AR activity/expression may impact upon DA neurotransmission. We studied the effects of IR on the 5AR expression/function and extracellular concentrations of DA and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the rat nucleus accumbens (NAcc) and medial prefrontal cortex (mPFC). Immediately after weaning, male rats were subjected to either IR or social rearing (SR) conditions for 5-8 weeks. Compared to SR, IR rats exhibited significantly lower protein expression of 5AR isoforms (1 and 2) in both brain regions and reduced brain, but not plasma, content of AP and allotetrahydrodeoxycorticosterone, the 5α-reduced metabolite of deoxycorticosterone. IR-exposed rats also exhibited higher levels of DA and DOPAC in the NAcc shell, but not in mPFC, when compared to SR rats. The 5AR inhibitor finasteride (FIN, 100 mg/kg, i.p.) enhanced DA and DOPAC content in the NAcc shell of SR, but not IR rats. FIN, however, elicited equivalent increases in DA and DOPAC levels in the mPFC of both groups. These results show that IR induces changes in expression/activity of brain 5AR which, in a brain-region specific manner, may partially underlie the alterations in DA signaling induced by this manipulation. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.

Prenatal exposure to carbon monoxide delays postnatal cardiac maturation.

Prenatal exposure to toxicants, such as maternal smoking, may impair cardiovascular autonomic maturation in infants. We recently showed that exposure of pregnant rats to a mild concentration of carbon monoxide (CO), a component of cigarette smoke, delays postnatal electrophysiological maturation of ventricular myocytes from newborns rats, likely predisposing to life-threatening arrhythmias. To get a comprehensive view of developmental molecular abnormalities induced, at cardiac level, by prenatal CO exposure, we used microarray analysis approach on the rat heart at 4, 7 and 20 days postnatal life. The relationship between molecular and functional alterations was investigated by assessing the ventricular expression of f-current, an electrophysiological marker of immature cardiac phenotype. Rats were prenatally exposed to 0 (CTR) or 150 p.p.m. CO and mRNA obtained from ventricular samples. Differential analysis and biological pathway analysis of microarray data were performed by using Newton's approach and the GENMAPP/MAPPFinder, respectively. The real-time RT-PCR reactions were performed by TaqMan probe-based chemistry. Freshly isolated patch-clamped ventricular cardiomyocytes were used to measure I(f). Genes and pathways controlling cell cycle and excitation-contraction coupling were significantly modified in CO-exposed rats. The higher effect was observed in cardiomyocytes harvested from 7-day-old rats, in which mRNA expression for crucial sarcomeric proteins (myosin and actin subunits, troponin I), transporters (Ca(2+) transporting ATPase) and enzymes (aldolase) were significantly downregulated. Accordingly, the molecular and functional expression of f-channels, which represents a marker of fetal ventricular phenotype, was transiently greater in CO-exposed rats (+200%) than in control ones. In conclusion, our study provides new insights into the molecular and functional mechanisms underlying cardiac maturation and its impairment by prenatal exposure to toxic components of smoking, such as CO.

Cognitive impairment and increased brain neurosteroids in adult rats perinatally exposed to low millimolar blood alcohol concentrations.

Epidemiological evidence suggests that adolescents and adults perinatally exposed to alcohol, even at low doses, show high prevalence of cognitive impairment and social behavior deficits, which may be in part related to alcohol-induced changes of the gamma-aminobutyric acid (GABA)ergic neurotransmission. The endogenous neurosteroid 3alpha-hydroxy,5alpha-pregnan-20-one (3alpha,5alpha-tetrahydroprogesterone/3alpha,5alpha-THP), a potent positive allosteric modulator of GABA(A) receptor function, is implicated in the physiological tuning of GABA-mediated fast inhibition and in various alcohol's actions in the brain. This study was undertaken to determine whether perinatal exposure to low millimolar blood alcohol concentrations alters cognitive skills (social discrimination and inhibitory avoidance tests), emotional reactivity (elevated plus maze test), and neurosteroid content in brain cortex and hippocampus of adult male offspring. Dams had access to a 3% alcohol solution or to an equicaloric sucrose solution from gestational day 15 to postnatal day 9. Eighty-day old alcohol-exposed male offspring exhibited impaired social recognition memory, but unchanged inhibitory avoidance performance and normal behavior on the elevated-plus maze. The concentrations of 3alpha,5alpha-THP and its precursor progesterone were more than doubled in brain cortex and hippocampus of alcohol-exposed rats, whereas in plasma only progesterone was increased. Thus, exposure to low millimolar blood alcohol concentrations has a long-lasting impact on the developing brain as it causes an impairment of social recognition as well as an increase of brain neurosteroid content in mature animals. The latter may be consequent to altered expression/activity of brain steroidogenic enzymes, as reflected by the enduring increase of the GABA(A) receptor-active neurosteroid 3alpha,5alpha-THP in brain cortex and hippocampus, but not in plasma. It is speculated that, by inducing a greater amplification of GABA(A) receptor function, the elevation of 3alpha,5alpha-THP brain content contributes to the cognitive impairment exhibited by adult alcohol-exposed offspring.

Prenatal exposure to the CB1 receptor agonist WIN 55,212-2 causes learning disruption associated with impaired cortical NMDA receptor function and emotional reactivity changes in rat offspring.

The aim of this study was to investigate whether prenatal exposure to the cannabinoid CB1 receptor agonist WIN 55,212-2 (WIN) at a daily dose devoid of overt signs of toxicity and/or gross malformations (0.5 mg/kg, gestation days 5-20), influences cortical glutamatergic neurotransmission, learning and emotional reactivity in rat offspring. Basal and K+-evoked extracellular glutamate levels were significantly lower in cortical cell cultures obtained from pups exposed to WIN during gestation with respect to those measured in cultures obtained from neonates born from vehicle-treated dams. The addition of NMDA to cortical cell cultures from neonates born from vehicle-treated dams concentration-dependently increased glutamate levels, and this was absent in cell cultures obtained from WIN-exposed pups. WIN-exposed rats also revealed a poorer performance in homing (10-12 days of age) and active avoidance tests (80 days of age) as well as a decrease in the rate of separation-induced ultrasonic emission (10 days of age). Finally, prenatal exposure to WIN induced a reduction in the number of cortical neuronal population. These findings (i) provide evidence for a deficit in cortical glutamatergic neurotransmission and behaviour in the rat neonate following prenatal exposure to WIN; and (ii) suggest that the reduction in cortical glutamatergic neurotransmission, NMDA receptor activity and alterations in neuronal development might underlie, at least in part, the learning deficit and decreased emotional reactivity observed in the offspring.

Prenatal exposure to carbon monoxide affects postnatal cellular electrophysiological maturation of the rat heart: a potential substrate for arrhythmogenesis in infancy.

BACKGROUND: Maternal smoking is an independent risk factor for sudden infant death syndrome (SIDS). Carbon monoxide (CO) is a major component of smoke. No information is available about the effect of CO and/or smoking on postnatal maturation of the heart. The aim of this study was to investigate the effect of prenatal exposure to CO on cellular electrophysiological maturation in male Wistar rats. METHODS AND RESULTS: The patch-clamp technique was used to measure action potential (AP) and ionic currents (I(to) and I(Ca,L)) from rat ventricular myocytes. During growth, AP duration measured at -20 and -50 mV (APD(-)(20) and APD(-)(50)) decreased progressively in both groups; the process was significantly delayed in rats exposed prenatally to 150 ppm CO: At 4 weeks, APD(-)(20) and APD(-)(50) were 89.5+/-18.2 and 147.7+/-24.5 ms in CO (n=13) and 35.6+/-4.5 and 77.8+/-8.3 ms in control rats (Ctr; n=14; P<0.01 and P<0.05, respectively) and normalized at 8 weeks. At 4 weeks, the density of I(Ca,L) was significantly higher (21.3+/-1.6 pA/pF, n=17, versus 15.9+/-1.6 pA/pF, n=22; P<0.05) and the density of I(to) significantly lower (9.6+/-1.5, n=22, versus 15.2+/-2.2 pA/pF, n=19; P<0.01) in CO than in Ctr and normalized thereafter. CONCLUSIONS: Prenatal CO exposure affects the physiological shortening of APD in neonatal rats. We speculate that a prolonged myocyte repolarization induced by prenatal exposure to smoke may establish a period of vulnerability for life-threatening arrhythmias in infancy.

Prenatal exposure to a cannabinoid agonist produces memory deficits linked to dysfunction in hippocampal long-term potentiation and glutamate release.

To investigate the possible long-term consequences of gestational exposure to cannabinoids on cognitive functions, pregnant rats were administered with the CB1 receptor agonist WIN 55,212-2 (WIN), at a dose (0.5 mgkg) that causes neither malformations nor overt signs of toxicity. Prenatal WIN exposure induced a disruption of memory retention in 40- and 80-day-old offspring subjected to a passive avoidance task. A hyperactive behavior at the ages of 12 and 40 days was also found. The memory impairment caused by the gestational exposure to WIN was correlated with alterations of hippocampal long-term potentiation (LTP) and glutamate release. LTP induced in CA3-CA1 synapses decayed faster in brain slices of rats born from WIN-treated dams, whereas posttetanic and short-term potentiation were similar to the control group. In line with LTP shortening, in vivo microdialysis showed a significant decrease in basal and K(+)-evoked extracellular glutamate levels in the hippocampus of juvenile and adult rats born from WIN-treated dams. A similar reduction in glutamate outflow was also observed in primary cell cultures of hippocampus obtained from pups born from mothers exposed to WIN. The decrease in hippocampal glutamate outflow appears to be the cause of LTP disruption, which in turn might underlie, at least in part, the long-lasting impairment of cognitive functions caused by the gestational exposure to this cannabinoid agonist. These findings could provide an explanation of cognitive alterations observed in children born from women who use marijuana during pregnancy.

Transgenic mice expressing F3/contactin from the TAG-1 promoter exhibit developmentally regulated changes in the differentiation of cerebellar neurons.

F3/contactin (CNTN1) and TAG-1 (CNTN2) are closely related axonal glycoproteins that are differentially regulated during development. In the cerebellar cortex TAG-1 is expressed first as granule cell progenitors differentiate in the premigratory zone of the external germinal layer. However, as these cells begin radial migration, TAG-1 is replaced by F3/contactin. To address the significance of this differential regulation, we have generated transgenic mice in which F3/contactin expression is driven by TAG-1 gene regulatory sequences, which results in premature expression of F3/contactin in granule cells. These animals (TAG/F3 mice) display a developmentally regulated cerebellar phenotype in which the size of the cerebellum is markedly reduced during the first two postnatal weeks but subsequently recovers. This is due in part to a reduction in the number of granule cells, most evident in the external germinal layer at postnatal day 3 and in the inner granular layer between postnatal days 8 and 11. The reduction in granule cell number is accompanied by a decrease in precursor granule cell proliferation at postnatal day 3, followed by an increase in the number of cycling cells at postnatal day 8. In the same developmental window the size of the molecular layer is markedly reduced and Purkinje cell dendrites fail to elaborate normally. These data are consistent with a model in which deployment of F3/contactin on granule cells affects proliferation and differentiation of these neurons as well as the differentiation of their synaptic partners, the Purkinje cells. Together, these findings indicate that precise spatio-temporal regulation of TAG-1 and F3/contactin expression is critical for normal cerebellar morphogenesis.

Modulation of anxiety through blockade of anandamide hydrolysis.

The psychoactive constituent of cannabis, Delta(9)-tetrahydrocannabinol, produces in humans subjective responses mediated by CB1 cannabinoid receptors, indicating that endogenous cannabinoids may contribute to the control of emotion. But the variable effects of Delta(9)-tetrahydrocannabinol obscure the interpretation of these results and limit the therapeutic potential of direct cannabinoid agonists. An alternative approach may be to develop drugs that amplify the effects of endogenous cannabinoids by preventing their inactivation. Here we describe a class of potent, selective and systemically active inhibitors of fatty acid amide hydrolase, the enzyme responsible for the degradation of the endogenous cannabinoid anandamide. Like clinically used anti-anxiety drugs, in rats the inhibitors exhibit benzodiazepine-like properties in the elevated zero-maze test and suppress isolation-induced vocalizations. These effects are accompanied by augmented brain levels of anandamide and are prevented by CB1 receptor blockade. Our results indicate that anandamide participates in the modulation of emotional states and point to fatty acid amide hydrolase inhibition as an innovative approach to anti-anxiety therapy.

Genetic factors involved in the effects of developmental low-level alcohol induced behavioral alterations in rats.

Behavioral and neurochemical effects of perinatal alcohol exposure (3% v/v solution from Day 15 of gestation to Day 7 after parturition) have been investigated in Sardinian alcohol-preferring (sP) and alcohol-nonpreferring (sNP) rat lines, selectively bred for opposite alcohol preference and consumption. In an elevated zero-maze model of anxiety, sucrose-exposed sP rats (sP-S): (i) spent significantly less time on the open arms (TO); (ii) exhibited a significantly lower number of head dips (HDIPS); and (iii) showed a higher number of stretched attend-postures (SAP) than sucrose-exposed sNP rats (sNP-S) at 90 and 180 days of age. The two rat lines displayed different emotional reactivity in response to alcohol exposure. Subtle differences in sexual behavior and ultrasonic emission (latency to the first intromission and to the first 50 kHz call) were observed between sP-S and sNP-S rats. sP-alcohol exposed (sP-A) offspring exhibited a higher latency to the first intromission than sNP-alcohol (sNP-A) treated rats. Moreover, a lower number of sP-A rats exhibited both intromission and ejaculation with respect to sNP-A animals. sP-S rats were significantly slower in recover of the righting reflex than sNP-S animals after a challenge dose of alcohol (3 g/kg, i.p.). Perinatal alcohol did not affect either onset or duration of sleep time in either line. Neurochemical experiments have shown that perinatal alcohol did not influence basal dopamine levels or amphetamine-induced dopamine increase in the prefrontal cortex of either sP or sNP offspring. These results, showing an endpoint-specific differential sensitivity of sP and sNP lines to perinatal low alcohol exposure, indicate that genetic factors could be responsible for selective susceptibility to behavioral alterations induced by developmental treatment with this drug of abuse.