RESUMEN

Background: The management of preoperative anxiety in pediatric patients, as well as its implications, has remained challenging for anesthesiologists. In this study, we compared the safety and efficacy of intranasal dexmedetomidine, midazolam, and ketamine as surgical premedication in children. Methods: This double-blinded randomized clinical trial was conducted at two tertiary hospitals in January 2014, on 90 children aged between 2-7 years old. The participants' American Society of Anesthesiologists (ASA) physical status was I or II, and they were scheduled for elective unilateral inguinal herniorrhaphy. Using the block randomization method, the patients were randomly assigned to three groups, each receiving intranasal dexmedetomidine (2 µg/Kg), midazolam (0.2 mg/Kg), and ketamine (8 mg/Kg) 60 min before induction of anesthesia. Anxiety and sedation state were evaluated before drug administration, and then every 10 min for the next 50 min. Parental separation anxiety, mask acceptance, postoperative agitation, pain, nausea, and vomiting were also recorded and compared between these groups. All the statistical analyses were performed using SPSS software (version 21.0). P<0.05 was considered statistically significant. Results: Ketamine indicated the strongest sedative effect 10, 20, and 30 min after administration of premedication (P<0.001, P=0.03, P=0.01, respectively). However, dexmedetomidine was more effective than other drugs after 40 and 50 min (P<0.001). Other variables indicated no statistically significant difference. Conclusion: In case of emergencies, intranasal ketamine, with the shortest time of action, could be administered. Intranasal dexmedetomidine, which was revealed to be the most potent drug in this study, could be administrated 40-50 min before elective pediatric surgeries.Trial registration number: IRCT2013081614372N1.

Asunto(s)

RESUMEN

BACKGROUND: Aortic coarctation is a potentially fatal condition that is primarily treated surgically. Despite successful procedures, patients frequently experience postoperative anxiety and depression, which can hinder recovery and worsen outcomes. Pharmacological interventions, such as 5-hydroxytryptamine (5-HT) and norepinephrine reuptake inhibitors, are commonly prescribed; however, their efficacy alone or in combination with non-invasive brain stimulation techniques, such as repetitive transcranial magnetic stimulation (TMS), remains unclear. AIM: To assess the effect of medications and TMS on post-aortic surgery anxiety and depression. METHODS: We analyzed the outcomes of 151 patients with anxiety and depression who were hospitalized for aortic dissection between January 2020 and September 2022. Using the random number table method, 75 and 76 patients were allocated to the normal control and study groups, respectively. All the patients were treated using routine procedures. The control group was administered anti-anxiety and anti-depression drugs, whereas the study group was treated with TMS in addition to these medications. The patients in both groups showed improvement after two courses of treatment. The Hamilton Anxiety Scale (HAMA) and the Hamilton Depression Scale (HAMD) were used to assess anxiety and depression, respectively. The serum levels of brain-derived neurotrophic factor (BDNF) and 5-HT were determined using enzyme-linked immunosorbent assay. The Pittsburgh Sleep Quality Index (PSQI) was used to estimate sleep quality, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to assess cognitive function. RESULTS: The HAMD and HAMA scores reduced in 2 groups, with the study group achieving a lower level than control (P < 0.05). In the control group, 43 patients recovered, 17 showed improvement, and 15 were deemed invalid. In the study group, 52 recovered, 20 improved, and four were invalid. The efficacy rate in study group was 94.74% compared to 80.00% in control (P < 0.05). The BDNF and 5-HT levels increased in both groups, with higher levels observed in the experimental group (P < 0.05). Moreover, the PSQI scores decreased in 2 groups, but were lower in the intervention group than control (P < 0.05). The scores of the RBANS items increased, with the study group scoring higher than control (P < 0.05). CONCLUSION: Combining anti-anxiety and anti-depressive drugs with repetitive TMS after aortic surgery may enhance mood and treatment outcomes, offering a promising clinical approach.

RESUMEN

Aim: The aim of this study was to examine the characteristics of habitual hypnotic users in Japan. Methods: This nationwide, cross-sectional survey used self-administered questionnaires. Data were collected from four national surveys conducted every 2 years between 2015 and 2021. The participants were Japanese individuals who had taken prescription hypnotics in the past year or had never taken them. We divided 13,396 participants into three groups to compare the social background and status of taking medication and controlled drugs, drinking, and smoking among the three groups: people who use hypnotics habitually daily (habitual hypnotic users [HUs]), people who use them only occasionally (occasional hypnotic users [OUs]), and people who do not use them (hypnotic non-users [NUs]). We compared the perception of using hypnotics between the HU and OU groups. Results: HUs were more likely to be older, unemployed, and to habitually use anxiolytics and analgesics than NUs. The main reasons for taking anxiolytics in HUs were alleviating insomnia and reducing anxiety, whereas the main reason for taking analgesics was improving joint pain. Additionally, the HU group had a higher proportion of habitual smokers than the OU group. There was no difference in drinking status or taking of controlled drugs among the three groups. HUs were more likely to use hypnotics and to have concerns about their side-effects than OUs. Conclusion: HUs were more likely to be unemployed, habitually use anxiolytics and analgesics, smoke heavily, and take hypnotic drugs with concerns regarding side-effects. These results may help encourage the appropriate use of hypnotics.

RESUMEN

Positive leadership behaviours at work are associated with worker well-being and performance. However there is less knowledge about whether exposure to low levels of positive leadership behaviours increase workers' risk of clinical mental disorders. We investigated whether low levels of positive leadership behaviours are prospectively associated with risk of treatment for depressive and anxiety disorders. In a cohort study, we linked survey data from 59,743 respondents from the Work Environment and Health in Denmark survey with national health register data. Leadership behaviours were measured with an eight-item scale. Treatment was defined as redeemed prescription for antidepressants or anxiolytics or hospital treatment for depression or anxiety. Using Cox proportional hazard regression, adjusting for demographic variables, job type and sector, adverse life events and childhood adversities, we estimated the association between leadership behaviours at baseline and risk of treatment during follow-up. We identified 999 cases of depression and anxiety treatment during follow-up. Compared to high levels of leadership behaviours, exposure to medium low and low levels were associated with an increased risk of treatment after adjustment for covariates. The results suggest that low levels of positive leadership behaviours are associated with an increased risk of treatment for depressive or anxiety disorders.

Asunto(s)

RESUMEN

BACKGROUND: Depression, anxiety and insomnia often co-occur. However, there is a lack of research regarding how they cluster and how this is related to medication used to treat them. AIMS: To describe the frequencies and associations between depression, anxiety and insomnia, and treatment for these conditions in primary care. METHOD: A retrospective cohort study using UK electronic primary care records. We included individuals aged between 18 and 99 years old with one or more records suggesting they had a diagnosis, symptom or drug treatment for anxiety, depression or insomnia between 2015 and 2017. We report the conditional probabilities of having different combinations of diagnoses, symptoms and treatments recorded. RESULTS: There were 1 325 960 records indicative of depression, anxiety or insomnia, for 739 834 individuals. Depression was the most common condition (n = 106 117 records), and SSRIs were the most commonly prescribed medication (n = 347 751 records). Overall, individuals with a record of anxiety were most likely to have co-occurring symptoms and diagnoses of other mental health conditions. For example, of the individuals with a record of generalised anxiety disorder (GAD), 24% also had a diagnosis of depression. In contrast, only 0.6% of those who had a diagnosis of depression had a diagnosis or symptom of GAD. Prescribing of more than one psychotropic medication within the same year was common. For example, of those who were prescribed an SNRI (serotonin-norepinephrine reuptake inhibitor), 40% were also prescribed an SSRI (selective serotonin reuptake inhibitor). CONCLUSIONS: The conditional probabilities of co-occurring anxiety, depression and insomnia symptoms, diagnoses and treatments are high.

RESUMEN

OBJECTIVE: Fasedienol (PH94B) is a pherine compound formulated as a nasal spray that is hypothesized to regulate olfactory-amygdala circuits of fear and anxiety. Fasedienol's effect on the local electrogram of nasal chemosensory neurons (EGNR) and autonomic nervous system (ANS) responses versus steroidal hormones and controls in healthy adults is reported. METHODS: Eight males and 8 females randomly received aerosolized control (propylene glycol) and study drugs (fasedienol, 17ß-estradiol, progesterone, cortisol, and testosterone, 0.4 µg each in propylene glycol) onto the nasal septum mucosal lining at 30-min intervals over 2 sessions. EGNR was continuously monitored; autonomic parameters were recorded before and after administration. RESULTS: Fasedienol significantly increased EGNR amplitude (males: 5.0 vs. 0.6 mV, p < 0.001; females:5.7 vs. 0.6 mV, p < 0.001), and rapidly reduced respiratory rate (p < 0.05), heart rate (p < 0.01), and electrodermal activity (p < 0.05) versus control. EGNR and ANS responses after steroidal hormone administration were similar to control. 81% reported feeling less tense/more relaxed after receiving fasedienol, but not after receiving either control or steroidal hormones. CONCLUSIONS: Intranasal fasedienol, but not control or steroidal hormones, activated EGNR and rapidly reduced ANS responses, consistent with sympatholytic effects. Combined with subjective reports, results suggest fasedienol may provide acute relief in anxiety conditions.

Asunto(s)

RESUMEN

OBJECTIVES: Older adults commonly take benzodiazepines (BZDs) that may have long-term adverse cognitive effects. We investigated whether BZD use was related to developing mild cognitive impairment (MCI) or dementia in cognitively normal older adults in the community. SETTING/PARTICIPANTS: A population-based cohort (n = 1959) of adults aged 65 and over, recruited from communities of low socioeconomic status. MEASUREMENTS: BZD use, Clinical Dementia Rating (CDR), anxiety symptoms, depression symptoms, sleep difficulties, and APOE genotype. DESIGN: We examined time from study entry to MCI (CDR = 0.5) and time from study entry to dementia (CDR ≥ 1) in participants who were cognitively normal at baseline (CDR = 0). We used survival analysis (Cox model), adjusted for age, sex, education, sleep, anxiety, and depression. For all the models, we included an interaction term between BZD use and APOE*4. RESULTS: Taking BZDs was significantly associated with higher risk of developing MCI, but not of developing dementia. The effect was not affected by APOE genotype. CONCLUSIONS: In a population-based sample of cognitively normal older adults, BZD use is associated with developing MCI, but not dementia. BZD use may be a potentially modifiable risk factor for MCI.

Asunto(s)

RESUMEN

Introduction: This comprehensive review delves into the intricate and multifaceted relationship between anesthesia and melatonin, aiming to provide essential insights for perioperative clinical anesthesiologists and stimulate interest in related research. Anesthesia and surgery have the potential to disrupt melatonin secretion, leading to sleep disorders, postoperative neurocognitive dysfunction and other symptoms. In comparison to previous reviews, this review provides a comprehensive summary of the various aspects linking melatonin and anesthesia, going beyond isolated perspectives. It explores the potential benefits of administering melatonin during the perioperative period, including alleviating anxiety, reducing pain, enhancing perioperative sleep quality, as well as demonstrating immunomodulatory and anti-tumor effects, potentially offering significant advantages for cancer surgery patients. Recent Findings: Anesthesia and surgery have a significant impact on melatonin secretion, the hormone crucial for maintaining circadian rhythms. These procedures disrupt the normal secretion of melatonin, leading to various adverse effects such as sleep disturbances, pain, and postoperative neurocognitive dysfunction. However, the administration of exogenous melatonin during the perioperative period has yielded promising results. It has been observed that perioperative melatonin supplementation can effectively reduce anxiety levels, improve pain management, enhance the quality of perioperative sleep, and potentially decrease the occurrence of postoperative delirium. In recent years, studies have found that melatonin has the potential to improve immune function and exhibit anti-cancer effects, further underscoring its potential advantages for patients undergoing cancer surgery. Summary: In summary, melatonin can serve as an adjuvant drug for anesthesia during the perioperative period. Its administration has demonstrated numerous positive effects, including anti-anxiety properties, sedation, analgesia, improved postoperative sleep, and the potential to reduce the incidence of postoperative delirium. Furthermore, its immune-modulating and anti-tumor effects make it particularly valuable for cancer surgery patients. However, further studies are required to determine the optimal dosage, long-term safety, and potential adverse reactions associated with melatonin administration.

RESUMEN

Objective: Echium amoenum and Hypericum perforatum dried flowers have been used for therapy of mental disorders in Iranian traditional medicine. In this study, we assessed the efficacy of the E. amoenum and H. perforatum extracts in patients with mild to moderate depression. Materials and Methods: In an 8-week double-blind, parallel-group trial, 51 patients randomly consumed 20 mg of fluoxetine or 350 mg of herbal medicine twice daily. The Hamilton Rating Scale for Depression (HAM-D) was used to assess depression severity in patients at weeks 0, 4, and 8. Results: According to the Hamilton score, there were no significant differences between the fluoxetine- and herbal medicine-treated groups after 4 and 8 weeks (p>0.05). Dry mouth was the only reported side effect which was significantly lower in the herbal group (p<0.05) in weeks 2 and 4. Conclusion: E. amoenum and H. perforatum have anti-depressant properties similar to fluoxetine and they can be used to treat depression as an alternative to fluoxetine.

RESUMEN

OBJECTIVE: To describe the successful treatment of severe neurological and cardiovascular abnormalities in a dog following ingestion of the neuropsychotropic drug, phenibut. CASE SUMMARY: A 2-year-old neutered male Weimaraner was found unresponsive and laterally recumbent in his urine after ingesting approximately 1600 mg/kg of phenibut. On presentation to an emergency clinic, the dog was neurologically inappropriate, tachycardic, hypertensive, and exhibiting a profoundly decreased respiratory rate. Because of progressive clinical signs, electrolyte abnormalities, increased hepatic enzyme activity and bilirubin concentrations, and the development of pigmenturia, referral to specialist care was sought. On presentation, the dog was intermittently somnolent and then maniacal. Sinus tachycardia persisted, and hyperthermia was documented. Hospitalization for supportive care was undertaken, and the dog was administered IV fluids, flumazenil, antiepileptics, and IV lipid emulsion therapy. The dog developed hypoglycemia and treated with dextrose supplementation. Progressive increases in liver enzyme activities as well as pronounced increase in creatine kinase activity, consistent with rhabdomyolysis, were noted. Over the course of 48 hours, the hypoglycemia resolved, and clinical signs significantly improved. Ultimately, the dog was discharged with improved clinical signs, with the owner reporting that 1 week after discharge, a full recovery had been made, and no residual clinical signs persisted. NEW INFORMATION PROVIDED: To the authors' knowledge, there are no previous reports of phenibut intoxication in small animals. The growing availability and use of this drug by people in the past several years highlight the need for a greater understanding of its effects in companion animals.

Asunto(s)

RESUMEN

Introduction Mental health problems affect millions worldwide, and the prescription of psychotropic drugs is increasing globally. The World Health Organization (WHO) has emphasized the need for proper monitoring of psychotropic drug prescriptions. This study aims to characterize and find trends in the prescription of psychotropics in a Latin American General Hospital. Methods The study analyzed the dispensation of psychotropic prescriptions to outpatients at three pharmacies in the central headquarters of Hospital Clínica Bíblica in San José, Costa Rica, from 2017 to 2021. Psychotropic drugs were classified by the Anatomical Therapeutic Chemical (ATC) code, and the amount of each medication dispensed was standardized using the defined daily dose per 10,000 population per day metric. Patients' ages were categorized into four groups: under 18 years, 18 to 39 years, 40 to 64 years, and 65 years and above. The prescriptions were categorized according to medical specialty. Regression analyses were performed to determine the significance of trends observed in the data Results A total of 5793 psychotropic prescriptions were recorded. The average age of the patients was 58 years. The total consumption of psychotropics decreased by 33.94% from 2017 to 2021, with the most significant decline until 2020. However, there was an increase in consumption in 2021. Clonazepam was the most consumed medication, followed by bromazepam and alprazolam, which was the sole drug to exhibit an escalation in usage between 2017 and 2021. Regression analysis showed that only alprazolam and zopiclone had statistically significant trends. The highest number of prescriptions was dispensed to patients aged between 40 and 64 years, followed by those aged over 65 years. Anxiolytics were also the most commonly prescribed group of drugs. General medicine (20.22%), psychiatry (19.95%), and internal medicine (12.73%) were the primary specialties that prescribed psychotropic; 38.6% of prescriptions were associated with the 10th decile of patients, and 44.9% of prescriptions were issued by the 10th decile of physicians.  Conclusion The consumption of psychotropic drugs decreased from 2017 to 2020 but increased in 2021, with alprazolam being the only drug that showed an increase in consumption throughout the entire period. General practitioners and psychiatrists were found to be the specialties that most commonly prescribe these medications. The study found significant trends only for the consumption of alprazolam and zopiclone and for prescription patterns among psychiatrists and internal medicine physicians.

RESUMEN

The present study assessed the prevalence of the use of anxiolytics/antidepressants and associated factors among university students in the pre-vaccine period of the COVID-19 pandemic. A cross-sectional study was conducted with 983 students of public and private universities in Brazil. Data were collected between September and December 2020 with the aid of a questionnaire available on the Survey Monkey® platform addressing socioeconomic data, self-rated health, the use of anxiolytics/antidepressants, history of depression, psychological/psychiatric treatment and aspects of the undergraduate course. Statistical analysis involved descriptive statistics and Poisson regression with robust variance (α= 5%). The prevalence of anxiolytics/antidepressants use was 15.7%. The use of anxiolytics/antidepressants was associated with the female sex (PR = 1.53; 95% CI: 1.03-2.26), dissatisfaction with one's overall health (PR = 1.40; 95% CI: 1.08-1.82), undergoing psychological/psychiatric treatment (PR = 2.85; 95% CI: 1.91-4.22) and a medical diagnosis of depression (PR = 3.44; 95% CI: 2.52-4.70). The female sex, dissatisfaction with one's own overall health status, undergoing psychological/psychiatric treatment and a medical diagnosis of depression exerted an influence onthe use of anxiolytics/antidepressants by undergraduate university students during the COVID-19 pandemic (AU).

El presente estudio evaluó la prevalencia del uso de ansiolíticos/antidepresivos y factores asociados entre estudiantes universitarios en el período previo a la vacunación de la pandemia COVID-19. Se realizó un estudio transversal con 983 estudiantes de universidades públicas y privadas de Brasil. Los datos fueron recolectados entre septiembre y diciembre de 2020 con la ayuda de un cuestionario disponible en la plataforma Survey Monkey® que aborda datos socioeconómicos, salud autoevaluada, uso de ansiolíticos/antidepresivos, antecedentes de depresión, tratamiento psicológico/psiquiátrico y aspectos de la carrera universitaria. curso. El análisis estadístico implicó estadística descriptiva y regresión de Poisson con varianza robusta (α= 5%). La prevalencia del uso de ansiolíticos/antidepresivos fue del 15,7%. El uso de ansiolíticos/antidepresivos se asoció con el sexo femenino (RP = 1,53; IC 95%: 1,03-2,26), insatisfacción con la salud general (RP = 1,40; IC 95%: 1,08-1,82), estar sometido a tratamiento psicológico/psiquiátrico (RP = 2,85; IC 95%: 1,91-4,22) y diagnóstico médico de depresión (RP = 3,44; IC 95%: 2,52-4,70). El sexo femenino, la insatisfacción con el propio estado de salud general, el tratamiento psicológico/psiquiátrico y el diagnóstico médico de depresión influyeron en el uso de ansiolíticos/antidepresivos por parte de estudiantes universitarios durante la pandemia de COVID-19 (AU).

O presente estudo avaliou a prevalência do uso de ansiolíticos/antidepressivos e fatores associados entre estudantes universitários no período pré-vacinal da pandemia de COVID-19. Foi realizado um estudo transversal com 983 estudantes de universidades públicas e privadas do Brasil. Os dados foram coletados entre setembro e dezembro de 2020 com auxílio de questionário disponível na plataforma Survey Monkey® abordando dados socioeconômicos, autoavaliação de saúde, uso de ansiolíticos/antidepressivos, histórico de depressão, tratamento psicológico/psiquiátrico e aspectos da graduação curso. A análise estatística envolveu estatísticadescritiva e regressão de Poisson com variância robusta (α= 5%). A prevalência de uso de ansiolíticos/antidepressivos foi de 15,7%. O uso de ansiolíticos/antidepressivos esteve associado ao sexo feminino (RP = 1,53; IC 95%: 1,03-2,26), insatisfação com asaúde geral (RP = 1,40; IC 95%: 1,08-1,82), estar em tratamento psicológico/psiquiátrico (RP = 2,85; IC 95%: 1,91-4,22) e diagnóstico médico de depressão (RP = 3,44; IC 95%: 2,52-4,70). O sexo feminino, a insatisfação com o próprio estado geral de saúde, a realização de tratamento psicológico/psiquiátrico e o diagnóstico médico de depressão exerceram influência no uso de ansiolíticos/antidepressivos por estudantes universitários de graduação durante a pandemia de COVID-19 (AU).

Asunto(s)

RESUMEN

AIMS AND METHOD: Rates of prescriptions of antidepressants and suicide are inversely correlated at an epidemiological level. Less attention has been paid to relationships between other drugs used in mental health and suicide rates. Here we tested relationships between prescriptions of anxiolytics and antipsychotics and suicide rates in Scotland. RESULTS: Suicide rates were inversely correlated with prescriptions of antidepressants and antipsychotics over 14 years (2004-2018), and positively with prescriptions of anxiolytics. CLINICAL IMPLICATIONS: This illustrates the role of medications used in mental health in suicide prevention, and highlights the importance of identifying causal mechanisms that link anxiolytics with suicide.

RESUMEN

BACKGROUND: Spain as multiple other countries has been experiencing an increasing and sustained trend in the use of psychotropic medications since the mid 90s. Recent studies show public health measures implemented to control SARS-Cov2, such as mobility restrictions and the shutdown of nonessential activities increased mental suffering, even contributing to a higher number of anxiety, depression and insomnia disorders that could lead to an increase in the consumption of psychotropics. The aims were: 1) Evaluate the temporal trend in psychotropic consumption by pharmacological subgroup, sex, and age group 2) Estimate the effect of the COVID-19 pandemic in the use of psychotropic drugs. METHODS: We conducted a retrospective observational study, retrieving all prescriptions of anxiolytics, hypnotics and sedatives, and antidepressants dispensed in pharmacies of Asturias (Northern Spain) for Primary Care patients for the period 2018-2021. We presented the data expressed in Daily Defined Doses (DDDs) for 1000 persons/day (DHD). To estimate changes in DHDs by year and age group we conducted two multiple linear regressions (one for males and one for females) for every pharmacological subgroup studied. Changes were considered statistically significant when the regression coefficient was p < 0.05. We used the Software R 4.1.0. RESULTS: For the studied period, the highest DHDs are for antidepressants, although all of the subgroups experienced an increase in consumption rates. Women consumed more psychotropic drugs than men. In 2021, 372 out of every 1000 women were taking daily 1 DDD of these drugs versus 184 out of every 1000 men. Consumption rates for all psychotropic drugs progressively increases with age. Conversely, the biggest increases in consumption were among the youngest age groups (0-14 and 15-29 years) for women, while for men there is more variability. The regression models suggest an upward trend in psychotropic consumption during all the period, especially remarkable from 2020, for both genders and all age groups. CONCLUSIONS: - The consumption of psychotropic drugs has gradually increased over the last 4 years, with a significant boost starting in 2020 for both sexes, matching the start of the SARS-COV2 pandemic and the implementation of strict Public Health measures to contain it. - The increase observed on children and adolescents is a matter of concern.

Asunto(s)

RESUMEN

Background and study aims: Functional dyspepsia is a common chronic condition with upper abdominal symptoms in the absence of an organic cause. The first line treatment consists of protonpomp inhibition or Helicobacter pylori eradication. However, this approach often does not provide enough symptom relief. Neuromodulating agents are commonly used in clinical practice but only tricyclic antidepressant (TCAs) are mentioned in European and American and Canadian guidelines. Methods: We performed a comprehensive review of the literature in Pubmed for full-text randomized controlled trials in English with adult participants (>18 years) who met the Rome II, III or IV criteria or were diagnosed by a physician with a negative upper endoscopy and that compared a neuromodulating agent with placebo. Results: The search strategy identified 386 articles of which 14 articles met the eligibility criteria. TCAs like amitriptyline and imipramine have been shown to be effective in the treatment of functional dyspepsia whereas other neuromodulating agents like tetracyclic antidepressants, levosulpiride and anxiolytics might be beneficial but conclusive evidence is lacking. serotonin and noradrenaline reuptake inhibitors (SNRI) and selective serotonin reuptake inhibitors (SSRI) have not shown benefit in patients with functional dyspepsia. Conclusion: Selected neuromodulators have an established efficacy in functional dyspepsia. The best supporting evidence is available for TCAs with a potential role for tetracyclic antidepressants, levosulpiride and anxiolytics.

Asunto(s)

RESUMEN

We examined the role of toll-like receptors (TLRs) and proinflammatory cytokine signaling pathways in the prefrontal cortex (PFC) in anxiety-like behaviors after repeated use of morphine. Morphine (10 mg/kg) was used twice daily for 8 days to induce morphine dependence in male Wistar rats. On day 8, opioid dependence was confirmed by measuring naloxone-precipitated withdrawal signs. On days 1 and 8, anxiety-like behaviors were evaluated using a light/dark box test. Expression of TLR1 and 4, proinflammatory cytokines, and some of the downstream signaling molecules was also evaluated in the bilateral PFC at mRNA and protein levels following morphine dependence. The results revealed that morphine caused anxiolytic-like effects on day 1 while induced anxiety following 8 days of repeated injection. On day 8, a significant decrease in TLR1 expression was detected in the PFC in morphine-dependent rats, but TLR4 remained unaffected. Repeated morphine injection significantly increased IL1-ß, TNFα, and IL6 expression, but decreased IL1R and TNFR at mRNA and protein levels except for IL6R at the protein level in the PFC. The p38α mitogen-activated protein (MAP) kinase expression significantly increased but the JNK3 expression decreased in the PFC in morphine-dependent rats. Repeated injection of morphine also significantly increased the NF-κB expression in the PFC. Further, significant increases in Let-7c, mir-133b, and mir-365 were detected in the PFC in morphine-dependent rats. We conclude that TLR1 and proinflammatory cytokines signaling pathways in the PFC are associated with the anxiogenic-like effects of morphine following its chronic use in rats via a MAP kinase/NF-κB pathway.

Asunto(s)

RESUMEN

The aim of this systematic review and network meta-analysis (NMA) of randomized controlled trials was to evaluate the effectiveness of treatments for pain relief of burning mouth syndrome (BMS). Five databases and gray literature were searched. Independent reviewers selected studies, extracted data, and assessed the risk of bias. The primary outcome was pain relief or burning sensation, and the secondary outcomes were side effects, quality of life, salivary flow, and TNF-α and interleukin 6 levels. Four comparable interventions were grouped into different network geometries to ensure the transitivity assumption for pain: photobiomodulation therapy, alpha-lipoic acid, phytotherapics, and anxiolytics/antidepressants. Mean difference (MD) and 95% CI were calculated for continuous outcomes. The minimal important difference to consider a therapy beneficial against placebo was an MD of at least -1 for relief of pain. To interpret the results, the GRADE approach for NMA was used with a minimally contextualized framework and the magnitude of the effect. Forty-four trials were included (24 in the NMA). The anxiolytic (clonazepam) probably reduces the pain of BMS when compared with placebo (MD, -1.88; 95% CI, -2.61 to -1.16; moderate certainty). Photobiomodulation therapy (MD, -1.90; 95% CI, -3.58 to -0.21) and pregabalin (MD, -2.40; 95% CI, -3.49 to -1.32) achieved the minimal important difference of a beneficial effect with low or very low certainty. Among all tested treatments, only clonazepam is likely to reduce the pain of BMS when compared with placebo. The majority of the other treatments had low and very low certainty, mainly due to imprecision, indirectness, and intransitivity. More randomized controlled trials comparing treatments against placebo are encouraged to confirm the evidence and test possible alternative treatments (PROSPERO CRD42021255039).

Asunto(s)

RESUMEN

Sirtuin 6 (SIRT6) is a nuclear silencing information regulator that is widely expressed in brain. Inhibition of SIRT6 in the brain induced antidepressant effects in rodents. However, SIRT6 knockout in neurons induced developmental retardation and cognitive impairments. In this study, a mouse strain of astrocyte conditional knockout SIRT6 (AKO) was constructed. Unlike whole brain SIRT6 knockout mice, AKO mice did not show growth retardation. We showed that SIRT6 knockout in astrocytes did not impair the learning and memory ability of mice. Chronic unpredictable mild stress (CUMS) was used to evaluate the anti-depression and anti-anxiety effects in mice. In tail suspension test and forced swimming test, AKO mice did not show depression like phenotype induced by CUMS. In addition, knockout of SIRT6 in astrocytes alleviated the high anxiety level induced by CUMS in light and dark box test, open field test and elevated cross maze test. Three box social test showed that the deletion of SIRT6 in astrocytes changed the social preference of mice. Re-expression of SIRT6 in astrocytes mediated by adeno-associated virus reversed the social preference of AKO mice, but the re-expression also eliminated the anti-depression and anti-anxiety effects in AKO mice. Deletion of SIRT6 in astrocytes change the purine metabolic homeostasis of medial prefrontal cortex in mice. The results of transcriptomics and metabolomics analysis showed that the deletion of SIRT6 would change the purine metabolic pathway of cultured astrocytes and increase the contents of inosine and the second messenger cyclic adenosine monophosphate in astrocytes. In conclusion, knockout of SIRT6 in astrocytes induced anti-depression and anti-anxiety effects in mice without impairing the development and cognitive ability of mice.

Asunto(s)

RESUMEN

Baicalein is a flavonoid mainly obtained from plants with wide range of biological activities, including neuroprotection. An acute and unexpected chronic stress (UCS) protocol has recently been adapted to zebrafish, a popular vertebrate model in brain research. The present study was aimed to evaluate baicalein's anti-anxiety potential in a zebrafish model by induction, which included neuropharmacological evaluation to determine behavioural parameters in the novel tank diving test (NTDT) and light-dark preference test (LDPT). The toxicity was also assessed using the brine shrimp lethality assay, and the 50% lethal concentration (LC50) was determined. The animals were then stressed for 7 days before being treated with different doses of baicalein (1 and 2 mg/L) for another 7 days in UCS condition. Due to acute stress and UCS, the frequency of entries and time spent in the 1) top region and 2) light area of the novel tank reduced significantly, indicating the existence of elevated anxiety levels. The biological activity of baicalein was demonstrated by its high LC50 values (1,000 µg/ml). Additionally, baicalein administration increased the frequency of entries and duration spent in the light region, indicating a significant decrease in anxiety levels. Overall, the present results showed that baicalein has a therapeutic advantage in reversing the detrimental consequences of UCS and acute stress, making it is a promising lead molecule for new drug design, development, and therapy for stress.

RESUMEN

Background: At present, people are susceptible to developing depression and anxiety disorders in response to stress. However, there is no specific medicine for anxiety. Os Draconis (OD, named "Long gu" in Chinese) are fossilized bones that have been used in traditional Chinese medicine to treat neurological diseases for thousands of years. Thus, we conducted this study to determine the biological basis for the anxiolytic effect of OD. Methods: In this study, novel carbon dots (OD-CDs) from OD decoctions were discovered and separated. OD-CDs were anatomized using nanomaterials characterization methods to characterize the morphological structure, optical properties, and functional group properties. Four behavioural tests were conducted to observe the behavioural activities of mice, including the open field test (OFT), light/dark box test (LDT), elevated plus maze test (EPMT), and novelty-suppressed feeding test (NSFT), to determine its anxiolytic effects. Moreover, we assessed the possible mechanisms of the OD-CDs by detecting hormones associated with the hypothalamic-pituitary-adrenal (HPA) axis. Results: OD-CDs were spherical and monodispersed with a narrow size distribution between 1 and 5 nm and had a yield of 3.67%. OD-CDs increased the activity time of mice in the central zone in the OFT. The mice in the experimental group showed more frequent activity in the light compartment and the open arms, in LDT and EPMT, respectively. In addition, OD-CDs shortened the feeding latency in the NSFT. Furthermore, the results after OD-CDs intervention showed a significant increase in serum serotonin (5-HT) and norepinephrine (NE). In addition, the concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ATCH), and corticosterone (CORT) were decreased. Conclusion: These results demonstrate a definite anxiolytic effect of OD-CDs and reveal the possible mechanism of action of OD-CDs' anxiolytic effect, which supports the research of OD for neurological disorders and a promising new trend of therapeutic approach and drug development.

Asunto(s)