Benign paroxysmal positional vertigo and asymmetric hearing loss: is the worst hearing ear likely to suffer from otoconial displacement?

PURPOSE: Benign paroxysmal positional vertigo (BPPV) may be found in patients complaining of hearing disorders. The aim of our investigation was to describe audiological findings in BPPV patients, focusing on subjects with asymmetric hearing loss (AHL), to better understand whether otoconial displacement may occur preferentially in the worst hearing ear. METHODS: A prospective study was performed on 112 BPPV patients. We divided the sample into subjects who suffered from AHL (G1) and patients with did not (G2). Data regarding vestibular symptoms, tinnitus, migraine, antivertigo drug therapy, and vascular risk factors were collected. RESULTS: Out of 30 AHL subjects, 83.33% of them were affected by sensorineural hearing loss (SNHL) in at least one ear, with a significant difference in the distribution of hearing loss type between groups (p = 0.0006). In 70% of cases, the ear affected by BPPV was the one with the worst hearing threshold (p = 0.02); threshold asymmetry predicted BPPV in the worst hearing ear (p = 0.03). The predictability depended neither on the hearing threshold gap between ears nor the severity of the hearing threshold in the worst ear (p > 0.05). No differences in vascular risk factors between groups were observed (p > 0.05). We evidenced a moderate correlation between age and hearing threshold (ρ = 0.43). Age did not result a predictive factor for residual dizziness or BPPV in the worst ear (p > 0.05). CONCLUSIONS: Our study supports the likelihood of an otoconial displacement in the worse hearing ear in BPPV patients. Clinicians should start testing the worst hearing ear when managing AHL patients with suspected BPPV.

Guanosine-Mediated Anxiolytic-Like Effect: Interplay with Adenosine A1 and A2A Receptors.

Acute or chronic administration of guanosine (GUO) induces anxiolytic-like effects, for which the adenosine (ADO) system involvement has been postulated yet without a direct experimental evidence. Thus, we aimed to investigate whether adenosine receptors (ARs) are involved in the GUO-mediated anxiolytic-like effect, evaluated by three anxiety-related paradigms in rats. First, we confirmed that acute treatment with GUO exerts an anxiolytic-like effect. Subsequently, we investigated the effects of pretreatment with ADO or A1R (CPA, CCPA) or A2AR (CGS21680) agonists 10 min prior to GUO on a GUO-induced anxiolytic-like effect. All the combined treatments blocked the GUO anxiolytic-like effect, whereas when administered alone, each compound was ineffective as compared to the control group. Interestingly, the pretreatment with nonselective antagonist caffeine or selective A1R (DPCPX) or A2AR (ZM241385) antagonists did not modify the GUO-induced anxiolytic-like effect. Finally, binding assay performed in hippocampal membranes showed that [3H]GUO binding became saturable at 100-300 nM, suggesting the existence of a putative GUO binding site. In competition experiments, ADO showed a potency order similar to GUO in displacing [3H]GUO binding, whereas AR selective agonists, CPA and CGS21680, partially displaced [3H]GUO binding, but the sum of the two effects was able to displace [3H]GUO binding to the same extent of ADO alone. Overall, our results strengthen previous data supporting GUO-mediated anxiolytic-like effects, add new evidence that these effects are blocked by A1R and A2AR agonists and pave, although they do not elucidate the mechanism of GUO and ADO receptor interaction, for a better characterization of GUO binding sites in ARs.

Anti-inflammatory and cognitive effects of interferon-ß1a (IFNß1a) in a rat model of Alzheimer's disease.

BACKGROUND: Aß1-42 peptide abnormal production is associated with the development and maintenance of neuroinflammation and oxidative stress in brains from Alzheimer disease (AD) patients. Suppression of neuroinflammation may then represent a suitable therapeutic target in AD. We evaluated the efficacy of IFNß1a in attenuating cognitive impairment and inflammation in an animal model of AD. METHODS: A rat model of AD was obtained by intra-hippocampal injection of Aß1-42 peptide (23 µg/2 µl). After 6 days, 3.6 µg of IFNß1a was given subcutaneously (s.c.) for 12 days. Using the novel object recognition (NOR) test, we evaluated changes in cognitive function. Measurement of pro-inflammatory or anti-inflammatory cytokines, reactive oxygen species (ROS), and SOD activity levels was performed in the hippocampus. Data were evaluated by one-way ANOVA with Fisher's Protected Least Significant Difference (PLSD) test. RESULTS: We showed that treatment with IFNß1a was able to reverse memory impairment and to counteract microglia activation and upregulation of pro-inflammatory cytokines (IL-6, IL-1ß) in the hippocampus of Aß1-42-injected rats. The anti-inflammatory cytokine IL-10, significantly reduced in the Aß1-42 animals, recovered to control levels following IFNß1a treatment. IFNß1a also reduced ROS and lipids peroxidation and increased SOD1 protein levels in the hippocampus of Aß1-42-injected rats. CONCLUSION: This study shows that IFNß1a is able to reverse the inflammatory and cognitive effects of intra-hippocampal Aß1-42 in the rat. Given the role played by inflammation in AD pathogenesis and the established efficacy of IFNß1a in the treatment of inflammatory diseases of the central nervous system such as multiple sclerosis, its use may be a viable strategy to inhibit the pro-inflammatory cytokine and oxidative stress cascade associated with Aß deposition in the hippocampus of AD patients.

The endocannabinoid-alcohol crosstalk: Recent advances on a bi-faceted target.

Increasing evidence has focusesed on the endocannabinoid system as a relevant player in the induction of aberrant synaptic plasticity and related addictive phenotype following chronic excessive alcohol drinking. In addition, the endocannabinoid system is implicated in the pathogenesis of alcoholic liver disease. Interestingly, whereas the involvement of CB1 receptors in alcohol rewarding properties is established, the central and peripheral action of CB2 signalling is still to be elucidated. This review aims at giving the input to deepen knowledge on the role of the endocannabinoid system, highlighting the advancing evidence that suggests that CB1 and CB2 receptors may play opposite roles in the regulation of both the reinforcing properties of alcohol in the brain and the mechanisms responsible for cell injury and inflammation in the hepatic tissue. The manipulation of the endocannabinoid system could represent a bi-faceted strategy to counteract alcohol-related dysfunction in central transmission and liver structural and functional disarrangement.

Seeding nerve sutures with minced nerve-graft (MINE-G): a simple method to improve nerve regeneration in rats.

BACKGROUND: The aim of this study was to assess the effect of seeding the distal nerve suture with nerve fragments in rats. METHODS: On 20 rats, a 15 mm sciatic nerve defect was reconstructed with a nerve autograft. In the Study Group (10 rats), a minced 1 mm nerve segment was seeded around the nerve suture. In the Control Group (10 rats), a nerve graft alone was used. At 4 and 12 weeks, a walking track analysis with open field test (WTA), hystomorphometry (number of myelinated fibers (n), fiber density (FD) and fiber area (FA) and soleus and gastrocnemius muscle weight ratios (MWR) were evaluated. The Student t-test was used for statistical analysis. RESULTS: At 4 and 12 weeks the Study Group had a significantly higher n and FD (p = .043 and .033). The SMWR was significantly higher in the Study Group at 12 weeks (p = .0207). CONCLUSIONS: Seeding the distal nerve suture with nerve fragments increases the number of myelinated fibers, the FD and the SMWR. The technique seems promising and deserves further investigation to clarify the mechanisms involved and its functional effects.

Clinical observations and risk factors for tinnitus in a Sicilian cohort.

The aims of this study were to determine the distribution of risk factors associated with tinnitus analysing their role in the development of tinnitus and the effects of their interaction; to evidence the importance of a suitable and adequate clinical and audiologic assessment to avoid those modifiable risk factors responsible for cochlear dysfunction and tinnitus onset. 46 subjects with tinnitus and 74 controls were studied according to: age, sex, Body Mass Index (BMI), neck circumference, tobacco smoking, feeling fatigue or headache, self reporting snoring, hypertension, diabetes, coronary heart disease, and/or hyperlipidemia, and laboratory finding as lipid profile and levels of reactive oxygen metabolites (d-ROM). Audiological assessment was performed by multi-frequency audiometry (PTA(0.5-16 kHz)) and transient-evoked otoacoustic emissions (TEOAE diagnostic). Univariate analysis was performed to examine the association between determinants and occurrence of tinnitus; Mantel-Haenszel test (G.or) was used to investigate the joint effect of determinants on tinnitus. Tinnitus was more frequent among males with age >50 years; BMI >30 kg/m(2), neck circumference >40 cm, headache, hypertension, hypercholesterolemia resulted significant risk factors for tinnitus (P < 0.0001). Tinnitus group had more comorbidity (P < 0.0001) and worse audiometric thresholds (60.87 Vs 21.62% hearing loss; P < 0.0001) with respect to control group. The interaction between hypertension-BMI ≥ 30 kg/m(2) (G.or = 8.45) and smoking-hypercholesterolemia (G.or = 5.08) increases the risk of tinnitus (P < 0.0001). Our results underline that several factors either individually or jointly contribute to tinnitus onset; a comprehensive knowledge about tinnitus risk factors and associated clinical conditions could contribute to minimizing this disorder.

The Influence of the COVID-19 Pandemic Emergency on Alcohol Use: A Focus on a Cohort of Sicilian Workers.

The period between the beginning and the end of the COVID-19 pandemic emergency generated a general state of stress, affecting both the mental state and physical well-being of the general population. Stress is the body's reaction to events or stimuli perceived as potentially harmful or distressing. Particularly when prolonged over time, it can promote the consumption of different psychotropic substances such as alcohol, and thus the genesis of various pathologies. Therefore, our research aimed to evaluate the differences in alcohol consumption in a cohort of 640 video workers who carried out activities in smart working, subjects particularly exposed to stressful situations due to the stringent rules of protection and prevention implemented during the pandemic. Furthermore, based on the results obtained from the administration of the AUDIT-C, we wanted to analyse the different modes of alcohol consumption (low, moderate, high, severe) to understand whether there is a difference in the amount of alcohol consumed that could predispose individuals to health problems. To this end, we administered the AUDIT-C questionnaire in two periods (T0 and T1), coinciding with annual occupational health specialist visits. The results of the present research showed an increase in the number of subjects consuming alcohol (p = 0.0005) and in their AUDIT-C scores (p < 0.0001) over the period considered. A significant decrease in subgroups who drink in a low-risk (p = 0.0049) mode and an increase in those with high (p = 0.00012) and severe risk (p = 0.0002) were also detected. In addition, comparing the male and female populations, it emerged that males have drinking patterns that lead to a higher (p = 0.0067) health risk of experiencing alcohol-related diseases than female drinking patterns. Although this study provides further evidence of the negative impact of the stress generated by the pandemic emergency on alcohol consumption, the influence of many other factors cannot be ruled out. Further research is needed to better understand the relationship between the pandemic and alcohol consumption, including the underlying factors and mechanisms driving changes in drinking behaviour, as well as potential interventions and support strategies to address alcohol-related harm during and after the pandemic.

Prenatal Exposure to Δ9-Tetrahydrocannabinol Affects Hippocampus-Related Cognitive Functions in the Adolescent Rat Offspring: Focus on Specific Markers of Neuroplasticity.

Previous evidence suggests that prenatal exposure to THC (pTHC) derails the neurodevelopmental trajectories towards a vulnerable phenotype for impaired emotional regulation and limbic memory. Here we aimed to investigate pTHC effect on hippocampus-related cognitive functions and markers of neuroplasticity in adolescent male offspring. Wistar rats were exposed to THC (2 mg/kg) from gestational day 5 to 20 and tested for spatial memory, object recognition memory and reversal learning in the reinforce-motivated Can test and in the aversion-driven Barnes maze test; locomotor activity and exploration, anxiety-like behaviour, and response to natural reward were assessed in the open field, elevated plus maze, and sucrose preference tests, respectively. The gene expression levels of NMDA NR1-2A subunits, mGluR5, and their respective scaffold proteins PSD95 and Homer1, as well as CB1R and the neuromodulatory protein HINT1, were measured in the hippocampus. pTHC offspring exhibited deficits in spatial and object recognition memory and reversal learning, increased locomotor activity, increased NR1-, decreased NR2A- and PSD95-, increased mGluR5- and Homer1-, and augmented CB1R- and HINT1-hippocampal mRNA levels. Our data shows that pTHC is associated with specific impairment in spatial cognitive processing and effectors of hippocampal neuroplasticity and suggests novel targets for future pharmacological challenges.

Evaluation of Correlation between Sleep and Psychiatric Disorders in a Population of Night Shift Workers: A Pilot Study.

BACKGROUND: Insomnia is the perception of inadequate, insufficient or non-restorative sleep. Of all sleep-related disorders, insomnia is the most common. It is important to remember that the sleep-wake cycle also plays a central role in the genesis of anxiety and depression. The aim of our study is to evaluate the association between sleep disturbances and anxiety and depression in a group of workers of both sexes who perform night shift work. METHODS: Information on sleep disorders was collected by administering the Insomnia Severity Index (ISI) questionnaire. Statistical analysis was conducted using the Chi-square test to assess whether there were any differences between sex for those who were healthy or who were diagnosed with psychiatric disorders. RESULTS: The results showed that there was a good percentage of subjects with insomnia problems, impairing normal daily activities and promoting the onset of fatigue, daytime sleepiness, cognitive performance deficits and mood disorders. CONCLUSION: We highlighted how anxious and depressive anxiety disorders are more pronounced in people who suffer from altered sleep-wake rhythms. Further research in this direction could prove to be fundamental for understanding the genesis of the onset of other disorders as well.

Musculoskeletal disorders and incongruous postures in workers on ropes: A pilot study.

Background: Occupational hazards believed to cause musculoskeletal disorders in rope workers are traditionally associated with maintaining incongruous postures for prolonged periods of time. Design and methods: A cross-sectional survey was conducted on 132 technical operators in the wind energy and acrobatic construction sectors, who work on ropes, analysing the ergonomic characteristics of the environments, the way in which tasks are carried out, the strain perceived by individual workers, and assessing the presence of any musculoskeletal disorders (MSDs) by means of an objective examination focused on the anatomical districts that were the object of our study. Results: Analysis of the data obtained showed that there were differences in the perception of the level of physical intensity and perceived exertion between the groups of workers. Statistical analysis also revealed a significant association between the frequency of MSDs analysed and perceived exertion. Discussion: The most significant finding to emerge from this study is the high prevalence of MSDs of the cervical spine (52.94%), the upper limbs (29.41%), and the dorso-lumbar spine (17.65%). These values differ from those classically found in those exposed to the risk of conventional manual handling of loads. Conclusions: The high prevalence of disorders of the cervical spine, the scapulo-humeral girdle and the upper limbs, indicates the need to consider the forced position to be assumed for a large part of the work activity, staticity, and the inability to move the lower limbs for long periods as the predominant risk in rope work.

Acetaldehyde oral self-administration: evidence from the operant-conflict paradigm.

BACKGROUND: Acetaldehyde (ACD), ethanol's first metabolite, has been reported to interact with the dopaminergic reward system, and with the neural circuits involved in stress response. Rats self-administer ACD directly into cerebral ventricles, and multiple intracerebroventricular infusions of ACD produce conditioned place preference. Self-administration has been largely employed to assess the reinforcing and addictive properties of most drugs of abuse. In particular, operant conditioning is a valid model to investigate drug-seeking and drug-taking behavior in rats. METHODS: This study was aimed at the evaluation of (i) the motivational properties of oral ACD in the induction and maintenance of an operant-drinking behavior; (ii) ACD effect in a conflict situation employing the punishment-based Geller-Seifter procedure; and (iii) the onset of a relapse drinking behavior, following ACD deprivation. The lever-pressing procedure in a sound-attenuated operant-conditioning chamber was scheduled into 3 different periods: (i) training-rewarded responses with a fixed ratio 1; (ii) conflict-rewarded responses periodically associated with a 0.2 mA foot-shock; and (iii) relapse-rewarded lever presses following 1-week ACD abstinence. RESULTS: Our results show that oral self-administrated ACD induced: a higher rate of punished responses in Geller-Seifter procedures; and the establishment of a relapse behavior following ACD deprivation. CONCLUSIONS: In conclusion, our results indicate that ACD is able to induce an operant-drinking behavior, which is also maintained besides the conflict procedure and enhanced by the deprivation effect, supporting the hypothesis that ACD itself possesses motivational properties, such as alcohol and other substances of abuse.

Alcohol binge drinking in adolescence and psychological profile: Can the preclinical model crack the chicken-or-egg question?

During adolescence, internal and external factors contribute to engaging with alcohol binge drinking (ABD), putting at risk the neurodevelopment of brain regions crucial for emotional control and stress coping. This research assessed the prevalence of ABD in late adolescent students of Southern Italy and characterized their psychological profile and drinking motives. Translational effects of alcohol binge drinking in the animal model were also studied. Seven hundred and fifty-nine high school students of both sexes (aged 18-20) were recruited. Alcohol Use Disorder Identification Test-Consumption (AUDIT-C), Drinking Motives Questionnaire-Revised Short Form, Millon Clinical Multiaxial Inventory-Third Ed., State-Trait Anxiety Inventory, Connor-Davidson Resilience Scale, and Basic Self-Esteem Scale identified alcohol habits, drinking motives, and psychopathological profile. Eighty-five percentage of the students drank alcohol and 28% of them engaged in ABD; AUDIT-C correlated with enhancement, coping, and conformity motives. ABD was related to a greater likelihood of presenting clinical syndromes and personality disorders, as well as low resilience and self-esteem. Thereafter, in the pre-clinical model, adolescent male rats were exposed to alcohol (3.5 g/kg) in an intermittent binge-like paradigm and tested during prolonged abstinence. Rats were evaluated for anxiety-like behavior, motivated behaviors, resilience, and stress response following a psychosocial challenge. Binge-like alcohol-exposed adolescent rats displayed high integrated z-score for social- and novelty-induced anxiety, altered motivation-driven output, decreased resilience, and a blunted HPA axis response to psychosocial stress, with respect to respective controls. Our data confirm that ABD is the chosen pattern of drinking in a significant percentage of high school students in Southern Italy, and highlights AUDIT-C score as a relevant parameter able to predict the occurrence of affective disturbances. The evidence from the preclinical model shows that ABD produces detrimental consequences in the adolescent rat brain, resulting in negative affect, emotional dysregulation, and aberrant stress response, pointing to decreasing excessive alcohol drinking as a primary goal for the global act for brain health.

Risk Factors for Sensorineural Hearing Loss and Auditory Maturation in Children Admitted to Neonatal Intensive Care Units: Who Recovered?

Background: Newborns admitted to neonatal intensive care units (NICUs) are at higher risk of developing sensorineural hearing loss (SNHL), which may improve over time. The aim of this study was to describe the prevalence of the main risk factors for SNHL in a NICU cohort, focusing on children who underwent auditory maturation. Methods: An observational study of 378 children admitted to NICUs, who were followed for at least 18 months, with periodic audiologic assessments. Results: Out of 378 patients, 338 had normal hearing and 40 were hearing-impaired; we found a higher percentage of extremely preterm (EPT) and extremely low-birthweight (ELBW) infants in SNHL children (p < 0.05). Seventeen infants presented auditory improvement, with a mean maturation time of 6.17 months. A significant difference emerged between patients with stable SNHL and those who improved only in the case of hyperbilirubinemia (p = 0.005). The initial hearing threshold was a predictor of auditory improvement and moderately correlated to the time of auditory maturation (p = 0.02). Conclusions: Our study supports the trend toward recognizing worse prognoses and slower maturation processes among NICU children who suffer from severe to profound SNHL. Caution must be taken when deciding on earlier cochlear implantation.

Alcohol and Nicotine Use among Adolescents: An Observational Study in a Sicilian Cohort of High School Students.

In recent years, the mode of alcoholic intake known as binge drinking (BD) has become a common practice, especially among adolescents who, due to socio-environmental motives, tend to reach a rapid state of drunkenness. This drunkeness leads to alterations in brain areas responsible for executive functions and cognitive processes, as well as to the genesis of factors that predispose to lasting addiction. Likewise, nicotine leads to a comparable degree of addiction. On this basis, the aim of this research was to evaluate, on a cohort of 349 high school students (15−17 years old) in the province of Palermo, the following: (I) the drinking model of alcoholic beverages; (II) the use of nicotine and the degree of dependence; (III) the correlation between the consumption of alcoholic beverages and the use of nicotine. We employed the AUDIT-C test and the Fagerström test, two valid and standard instruments, in order to assess alcohol and nicotine use, respectively. Statistical analysis of the data showed that male and female students consumed alcohol prominently in a BD mode (77.2%, audit score (AS) 3.497, confidence interval (CI) 3.206−3.788; 69.6%, AS 2.793, CI 2.412−3.274) and nicotine (41.5%, Fagerström score (FS) 3.882, CI 3.519−4.245; 28%, FS 3.286, CI 2.547−4.024). Furthermore, a positive correlation between alcohol consumption and nicotine use was found for male (r = 0.6798, p < 0.0001) and female (r = 0.6572, p < 0.0001) students. This study provided further insights into the use of legal substances of abuse in adolescents, evidencing the obvious need for the promotion of specific school educational programs aimed at the wellbeing of youth populations.

Efficacy and Pharmacological Appropriateness of Cinnarizine and Dimenhydrinate in the Treatment of Vertigo and Related Symptoms.

Vertigo is not itself a disease, but rather a symptom of various syndromes and disorders that jeopardize balance function, which is essential for daily activities. It is an abnormal sensation of motion that usually occurs in the absence of motion, or when a motion is sensed inaccurately. Due to the complexity of the etiopathogenesis of vertigo, many pharmacological treatments have been tested for efficacy on vertigo. Among these drugs, cinnarizine, usually given together with dimenhydrinate, appears to be the first-line pharmacotherapy for the management of vertigo and inner ear disorders. Based on these considerations, the present non-interventional study aimed to investigate the clinical efficacy and tolerability of a fixed combination of cinnarizine (20 mg) and dimenhydrinate (40 mg) in patients suffering from vertigo-related symptoms. To this end, we enrolled 120 adults-70 males, and 50 females-with an average age of 64 years. Before beginning pharmacological treatment, all patients were screened for the intensity of vertigo, dizziness, and concomitant symptoms through the Visual Scale of Dizziness Disorders and Dizziness Handicap Inventory scales. At the end of the anamnestic evaluation, patients received the fixed-dose combination of cinnarizine (20 mg) plus dimenhydrinate (40 mg) 3 times daily, for 60 days. The results of this study provide further insight regarding the efficacy of the fixed combination when used to reduce symptoms of vestibular vertigo of central and/or peripheral origin, after both the 15- and 60-day therapies. Independent of the type of vertigo, the fixed combination was able to reduce dizziness- and vertigo-associated symptoms in more than 75% of all patients treated, starting from 15 days of therapy, and improving 60 days after starting the therapy. Interestingly, we also found differences between male and female patients in the framework of the pharmacological effects of therapy. This study provides further details concerning the therapeutic efficacy of the fixed combination of cinnarizine and dimenhydrinate, and also focuses attention on the possibility that these drugs could act in a gender-specific manner, paving the way for further research.

Alcohol Abuse and Insomnia Disorder: Focus on a Group of Night and Day Workers.

The sleep-wake cycle plays a fundamental role in maintaining the physiological balance of our body. Its alteration favours the genesis of several organic alterations and diseases including sleep disorders and the consumption of several substances of abuse. It has been reported that the work activity, especially that carried out during the night, is able to influence the sleep-wake cycle, promoting the development of insomnia, which, in turn, would subject the worker to a stressful condition such as to encourage adverse behaviour such as the use/abuse of psychotropic substances. Based on the above premises, the aim of our research was to evaluate, in night workers: (i) the pattern of consumption of alcoholic beverages; (ii) the presence of insomnia; and (iii) the possible correlation between alcohol consumption and insomnia disorder. We used the AUDIT-C test (the abbreviated version of the Alcohol Use Disorders Identification Test) and the Insomnia Severity Index to assess alcohol consumption and insomnia disorder, respectively. All questionnaires were completed by workers of both sexes belonging to different types of work activities, exclusively day or night. The results of our research show a higher propensity of night workers to consume alcoholic beverages than those who work during daytime hours, often in binge-drinking mode. In addition, an increase in the amount of alcohol consumed was found to be related to insomnia disorder, especially in night workers. This study provides further awareness of the importance of the negative impact of alcohol consumption on sleep quality in night workers.

Ethanol modulates corticotropin releasing hormone release from the rat hypothalamus: does acetaldehyde play a role?

BACKGROUND AND METHODS: Ethanol (EtOH) activates hypothalamic-pituitary-adrenal (HPA) axis, resulting in adrenocorticotropin hormone, glucocorticoid release, and in modifications of the response of the axis to other stressors. The initial site of EtOH action within the HPA system seems to be the hypothalamus. Thus, to determine the mechanisms responsible for these effects, we investigated: (i) whether EtOH was able to release corticotrophic releasing hormone (CRH) from incubated hypothalamic explants; (ii) whether acetaldehyde (ACD), its first metabolite formed in the brain by catalase activity, might play a role in EtOH activity. To this aim, rat hypothalamic explants were incubated with: (i) medium containing EtOH at 32.6 x 10(3) microM; (ii) different concentration of ACD (1, 3, 10, and 30 microM); (iii) EtOH plus 3amino-1,2,4-triazole (3AT, 32 x 10(3) microM) an inhibitor of cerebral catalase; (iv) ACD plus D-penicillamine (DP, 50.3 x 10(3) microM) an ACD-trapping agent. CRH levels were evaluated by a radioimmunoassay. RESULTS: Incubation with EtOH induced a 7-fold increase in CRH secretion, with respect to basal levels; ACD was able to stimulate CRH release in a dose-dependent manner; the inhibition of cerebral catalase by 3AT blocked EtOH-induced CRH outflow; the inactivation of ACD by DP reverted the ACD-stimulating effect on CRH secretion. CONCLUSIONS: These data show that both EtOH and acetaldehyde are able to increase hypothalamic CRH release from the rat hypothalamus and that acetaldehyde itself appears to be the mediator of EtOH activity.

Pyrazolobenzotriazinone derivatives as COX inhibitors: synthesis, biological activity, and molecular-modeling studies.

Pyrazolylbenzotriazinones are endowed with a structural analogy with the COX-2 selective inhibitor celecoxib. Considering that our research group has long been interested in the 3-pyrazolyl-substituted benzotriazinones as anti-inflammatory agents, six new pyrazolylbenzotriazinone derivatives 16a-c and 18a-c have been prepared by reacting the opportune ethyl 5-(2-aminobenzamido)-1-(pyridin-2-yl)-1H-pyrazole-4-carboxylate or 5-(2-aminobenzamido)-1-(pyridin-2-yl)-1H-pyrazole-4-carboxyic acid with sodium nitrite in glacial acetic acid. The biological studies revealed a good pharmacological profile for some pyrazolylbenzotriazinones and, in the case of the ethyl 5-(4-oxo-1,2,3-benzotriazin-3(4H)-yl)-1-pyridin-2-yl-1H-pyrazole-4-carboxylate, a good COX-1/COX-2 selectivity. Molecular modeling studies confirmed the obtained biological results.

Targeting the Stress System During Gestation: Is Early Handling a Protective Strategy for the Offspring?

The perinatal window is a critical developmental time when abnormal gestational stimuli may alter the development of the stress system that, in turn, influences behavioral and physiological responses in the newborns. Individual differences in stress reactivity are also determined by variations in maternal care, resulting from environmental manipulations. Despite glucocorticoids are the primary programming factor for the offspring's stress response, therapeutic corticosteroids are commonly used during late gestation to prevent preterm negative outcomes, exposing the offspring to potentially aberrant stress reactivity later in life. Thus, in this study, we investigated the consequences of one daily s.c. injection of corticosterone (25 mg/kg), from gestational day (GD) 14-16, and its interaction with offspring early handling, consisting in a brief 15-min maternal separation until weaning, on: (i) maternal behavior; and (ii) behavioral reactivity, emotional state and depressive-like behavior in the adolescent offspring. Corticosterone plasma levels, under non-shock- and shock-induced conditions, were also assessed. Our results show that gestational exposure to corticosterone was associated with diminished maternal care, impaired behavioral reactivity, increased emotional state and depressive-like behavior in the offspring, associated with an aberrant corticosterone response. The early handling procedure, which resulted in increased maternal care, was able to counteract the detrimental effects induced by gestational corticosterone exposure both in the behavioral- and neurochemical parameters examined. These findings highlight the potentially detrimental consequences of targeting the stress system during pregnancy as a vulnerability factor for the occurrence of emotional and affective distress in the adolescent offspring. Maternal extra-care proves to be a protective strategy that confers resiliency and restores homeostasis.

Night-Time Shift Work and Related Stress Responses: A Study on Security Guards.

Work-related stress can induce a break in homeostasis by placing demands on the body that are met by the activation of two different systems, the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Night-shift work alters the body's exposure to the natural light-dark schedule and disrupts circadian (daily) rhythms. The greatest effect of night-shift work is the disruption of circadian rhythms. The impact that these disruptions may have on the pathogenesis of many diseases, including cancer, is unknown. This study aims to discover the relationship among three different job activities of security guards and their stress-related responses by evaluating salivary cortisol levels and blood pressure. METHODS: Ninety security guards, including night-time workers and night-time and daily-shift workers, were recruited for this study. Each security guard provided two saliva samples before and after three scheduled time points: (i) at 22:00, (ii) at 06:30, and (iii) at 14:00. RESULTS: The results of the study showed a significant alteration in cortisol levels. Night-time shift cortisol levels significantly increased before and after the work shifts. A physiological prevalence of the vagal tone on the cardiocirculatory activity was found during night-shift work. CONCLUSIONS: This study indicates that cortisol levels and blood pressure are sensitive markers of biological responses to severe work stress. Shift-change consequences may occur at the end of the night shift when there is a significant increase in the cortisol level and a significant variation in cardiovascular parameters.