Imipramine treatment reverses depressive- and anxiety-like behaviors, normalize adrenocorticotropic hormone, and reduces interleukin-1ß in the brain of rats subjected to experimental periapical lesion.

BACKGROUND: A periodontal lesion is a consequence of chronic inflammatory processes, itself triggered by a bacterial infection of the pulpal and endodontic microenvironment. Evidence suggests that periodontal lesion induction could alter inflammatory cytokines leading to behavior changes. These effects in the context of anxiety and depressive behavior have been not full investigated. We aimed to observe anxiety- and depressive-like behavioral in rodent subjected to periapical dental lesions. METHODS: Pro-inflammatory cytokines levels also were investigated in the frontal cortex and hippocampus. Parameters related to hypothalamic-pituitary-adrenal (HPA) axis activation also were evaluated. Wistar rats were divided in groups: control/saline; control/imipramine; periapical lesion/saline; and periapical lesion/imipramine. Three weeks after induction of the periapical dental lesion, they were subjected to behavioral tests. RESULTS: In the periapical lesion group was demonstrated anhedonic behavior and depressive-like behavior. In the elevated plus-maze test the periapical lesion group had an increase in the number of entries and spent more time in the closed arms. Imipramine treatment was able to reverse depressive- and anxiety-like behaviors. In the hippocampus and frontal cortex tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, and serum adrenocorticotropic hormone (ACTH) levels were higher in the periapical lesion group. However, rats treated with imipramine had lower IL-1ß and ACTH levels. CONCLUSIONS: Our results revealed depressive- and anxiety-like behaviors following induction of a specific dental lesion. These effects could be associated to higher levels of brain pro-inflammatory cytokines and HPA axis changes. Antidepressants treatments could be an alternative to treat comorbidities associated to periodontal lesions.

Prevalência de transtornos ansiosos e algumas comorbidades em idosos: um estudo de base populacional / Prevalence of anxiety disorders and some comorbidities in elderly: a population-based study

RESUMO Objetivo Avaliar a prevalência de transtornos ansiosos e fatores associados em uma amostra populacional de idosos do Sul de Santa Catarina. Métodos Estudo transversal com base em dados populacionais, que avaliou 1.021 indivíduos idosos entre 60 e 79 anos. Foram realizadas entrevistas domiciliares para aferição de variáveis sobre transtornos ansiosos, por meio do questionário MINI, dados sociodemográficos, hipertensão arterial sistêmica (HAS), infarto agudo do miocárdio (IAM) e dosagem de colesterol. Resultados As prevalências entre os transtornos ansiosos foram de 22,0% para o transtorno de ansiedade generalizada (TAG); 14,8% para fobia social (FS); 10,5% para transtorno do pânico (TP); e 8,5% para o transtorno obsessivo-compulsivo (TOC). Além disso, 40,5% dos indivíduos apresentaram pelo menos um transtorno de ansiedade. A distribuição dos transtornos foi semelhante nos dois gêneros; TAG foi mais prevalente nos indivíduos de menor escolaridade; TOC foi mais presente em indivíduos casados ou em união estável. Em relação às variáveis clínicas, HAS foi associada à presença de TOC; FS foi associada com IAM; TOC e FS foram associados com HDL > 40 mg/dL. Conclusão Os dados demonstram que os quadros de ansiedade são muito frequentes em idosos da comunidade, se sobrepõem de forma significativa e estão associados a algumas variáveis clínicas cardiovasculares.

ABSTRACT Objective This study evaluated the prevalence of anxiety disorders and associated factors in a population sample of elderly from South of Santa Catarina. Methods Cross-sectional study based on population data, which evaluated 1,021 elderly individuals, between 60 and 79 years. Home interviews were conducted to measure the variables of anxiety disorders, through of the MINI questionnaire, sociodemographic data, systemic arterial hypertension (SAH), acute myocardial infarction (AMI) and serum cholesterol measurements. Results The prevalence among anxiety disorders were 22.0% for generalized anxiety disorder (GAD), 14.8% for social phobia (FS); 10.5% for panic disorder (PD); 8.5% for obsessive-compulsive disorder (OCD), and with only, at least one disorder 40.5%. The distribution of the disorders were similar in both genders, GAD was more prevalent among those with lower education; OCD was more prevalent in individuals who were married or in union stable. In relation to clinical variables, SAH was associated with the presence of OCD; FS was associated with AMI; FS and OCD were associated with HDL > 40 mg/dL. Conclusion The data demonstrate that anxiety conditions are very common in older adults, significantly overlap and are associated with cardiovascular clinical variables.

Interleukin-1ß Receptor Antagonism Prevents Cognitive Impairment Following Experimental Bacterial Meningitis.

Pneumococcal meningitis is characterized by high rates of mortality and long-term cognitive impairment. In this study, we evaluated the effects of interleukin (IL)-1ß receptor antagonist (IL-1Ra) on memory, cytokine, and brain-derived neurotrophic factor (BDNF) levels in hippocampus after experimental pneumococcal meningitis. In a first experiment the animals were divided into four groups: control/saline, control treated with IL-1Ra, meningitis/saline, and meningitis treated with IL-1Ra. In the meningitis/saline group IL-1ß and cytokine-induced neutrophil chemoattractant-1 (CINC-1) levels increased at 24 h post-infection; adjuvant treatment with IL-1Ra reversed the increased levels in the hippocampus. The levels of tumour necrosis factor-alpha (TNF-α), IL-4, IL-6, IL-10, and BDNF did not change in all groups at 24 h post-infection. In a second experiment, the animals were subjected to behavioural tasks (open field, step-down inhibitory avoidance task, and object recognition task), cytokine, and BDNF levels analysis 10 days after experimental meningitis induction. In the open-field task, the meningitis/saline group did not exhibit difference between the training and test sessions, in the motor and exploratory activity indicating memory injury. The meningitis/IL-1Ra group presented difference between training and test session indicating habituation memory. The meningitis/saline group showed impairment in long-term memory for novel object recognition and in aversive memory. The adjuvant treatment with IL-1Ra prevented memory impairment. After behavioural tasks the hippocampus was evaluated. The levels of IL-4, IL-6, IL-10, and BDNF were maintained elevated 10 days post-infection. CINC-1 levels were elevated only in meningitis/saline group and IL-1ß decreased in meningitis/IL-Ra group. The levels of TNF-α did not change at 10 days post-infection. These findings illustrate the anti-inflammatory activity of IL-1Ra inhibitor in the first hours after meningitis induction. Adjuvant treatment with IL-1ß receptor antagonist could be a new avenue as therapeutic target during bacterial meningitis.

Sodium Butyrate Prevents Memory Impairment by Re-establishing BDNF and GDNF Expression in Experimental Pneumococcal Meningitis.

Pneumococcal meningitis is a serious infection of the central nervous system (CNS) with high fatality rates that causes reduced psychomotor performance, slight mental slowness, impairments in attention executive functions and learning and memory deficiencies. Previously, we demonstrated a correlation between memory impairment and decreased levels of brain-derived neurotropic factor (BDNF) in the hippocampi of rats subjected to pneumococcal meningitis. Emerging evidence demonstrates that histone acetylation regulates neurotrophins; therefore, a potential molecular intervention against cognitive impairment in bacterial meningitis may be the histone deacetylase (HDAC) inhibitor, sodium butyrate, which stimulates the acetylation of histones and increases BDNF expression. In this study, animals received either artificial cerebrospinal fluid as a placebo or a Streptococcus pneumoniae suspension at a concentration of 5 × 10(9) colony-forming units (CFU/mL). The animals received antibiotic treatment as usual and received saline or sodium butyrate as an adjuvant treatment. Ten days after, meningitis was induced; the animals were subjected to open-field habituation and the step-down inhibitory avoidance task. Immediately after these behavioural tasks, the animals were killed, and their hippocampi were removed to evaluate the expression of BDNF, nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). In the meningitis group that received saline, the animals presented memory impairment in both behavioural tasks, and hippocampal BDNF and GDNF expression was decreased. Sodium butyrate was able to prevent memory impairment and re-establish hippocampal neurotrophin expression in experimental pneumococcal meningitis.

Targets for adjunctive therapy in pneumococcal meningitis.

Pneumococcal meningitis is a severe infectious disease of the central nervous system (CNS) and a significant cause of morbidity and mortality worldwide. The inflammatory reaction to the disease contributes to neuronal injury and involves the meninges, the subarachnoid space and the brain parenchymal vessels. Bacterial pathogens may reach the blood-brain barrier and be recognized by antigen-presenting cells through the binding of Toll-like receptors, triggering an inflammatory cascade. This in turn produces cytokines and chemokines, increases adhesion molecule expression and attracts leukocytes from the blood. This cascade leads to lipid peroxidation, mitochondrial damage and blood-brain barrier permeability. In spite of effective antibacterial treatments, approximately one third of survivors suffer from long-term sequelae, such as hearing loss, cerebral palsy, seizures, hydrocephaly or cognitive impairment. This review summarizes the information on targets of adjuvant treatments of acute pneumococcal meningitis.

Anxiety disorders are associated with quality of life impairment in patients with insulin-dependent type 2 diabetes: a case-control study

Objective: To assess the presence of anxiety disorders and quality of life in patients with insulin-dependent type 2 diabetes. Methods: Case-control study of 996 patients with type 2 diabetes and 2,145 individuals without diabetes. The sole inclusion criterion for the case group was insulin-dependent type 2 diabetes. We compared the case and control groups for sociodemographic variables, laboratory and clinical data, and presence of anxiety disorders. Quality of life was evaluated using the WHOQOL-BREF instrument, and the prevalence of anxiety disorder was evaluated by the Mini International Neuropsychiatric Interview (MINI). Results: Patients with diabetes had a higher prevalence of generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder. The presence of these disorders in combination with type 2 diabetes was associated with worse quality of life in the physical, social, psychological, and environmental domains. Conclusions: This study demonstrates the importance of diagnosing and treating anxiety disorders in patients with diabetes, so as to prevent more serious complications associated with these comorbidities. .

Anxiety disorders are associated with quality of life impairment in patients with insulin-dependent type 2 diabetes: a case-control study.

OBJECTIVE: To assess the presence of anxiety disorders and quality of life in patients with insulin-dependent type 2 diabetes. METHODS: Case-control study of 996 patients with type 2 diabetes and 2,145 individuals without diabetes. The sole inclusion criterion for the case group was insulin-dependent type 2 diabetes. We compared the case and control groups for sociodemographic variables, laboratory and clinical data, and presence of anxiety disorders. Quality of life was evaluated using the WHOQOL-BREF instrument, and the prevalence of anxiety disorder was evaluated by the Mini International Neuropsychiatric Interview (MINI). RESULTS: Patients with diabetes had a higher prevalence of generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder. The presence of these disorders in combination with type 2 diabetes was associated with worse quality of life in the physical, social, psychological, and environmental domains. CONCLUSIONS: This study demonstrates the importance of diagnosing and treating anxiety disorders in patients with diabetes, so as to prevent more serious complications associated with these comorbidities.

Vitamin B6 prevents cognitive impairment in experimental pneumococcal meningitis.

Streptococcus pneumoniae is the relevant cause of bacterial meningitis, with a high-mortality rate and long-term neurological sequelae, affecting up to 50% of survivors. Pneumococcal compounds are pro-inflammatory mediators that induce an innate immune response and tryptophan degradation through the kynurenine pathway. Vitamin B6 acts as a cofactor at the active sites of enzymes that catalyze a great number of reactions involved in the metabolism of tryptophan, preventing the accumulation of neurotoxic intermediates. In the present study, we evaluated the effects of vitamin B6 on memory and on brain-derived neurotrophic factor (BDNF) expression in the brain of adult Wistar rats subjected to pneumococcal meningitis. The animals received either 10 µL of artificial cerebral spinal fluid (CSF) or an equivalent volume of S. pneumoniae suspension. The animals were divided into four groups: control, control treated with vitamin B6, meningitis, and meningitis treated with vitamin B6. Ten days after induction, the animals were subjected to behavioral tests: open-field task and step-down inhibitory avoidance task. In the open-field task, there was a significant reduction in both crossing and rearing in the control group, control/B6 group, and meningitis/B6 group compared with the training session, demonstrating habituation memory. However, the meningitis group showed no difference in motor and exploratory activity between training and test sessions, demonstrating memory impairment. In the step-down inhibitory avoidance task, there was a difference between training and test sessions in the control group, control/B6 group, and meningitis/B6 group, demonstrating aversive memory. In the meningitis group, there was no difference between training and test sessions, demonstrating impairment of aversive memory. In the hippocampus, BDNF expression decreased in the meningitis group when compared to the control group; however, adjuvant treatment with vitamin B6 increased BDNF expression in the meningitis group. Thus, vitamin B6 attenuated the memory impairment in animals subjected to pneumococcal meningitis.

Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats submitted to pneumococcal meningitis.

Pneumococcal meningitis is a life-threatening disease characterized by an acute infection affecting the pia matter, arachnoid and subarachnoid space. The intense inflammatory response is associated with a significant mortality rate and neurologic sequelae, such as, seizures, sensory-motor deficits and impairment of learning and memory. The aim of this study was to evaluate the effects of acute and extended administration of cannabidiol on pro-inflammatory cytokines and behavioral parameters in adult Wistar rats submitted to pneumococcal meningitis. Male Wistar rats underwent a cisterna magna tap and received either 10µl of sterile saline as a placebo or an equivalent volume of S. pneumoniae suspension. Rats subjected to meningitis were treated by intraperitoneal injection with cannabidiol (2.5, 5, or 10mg/kg once or daily for 9 days after meningitis induction) or a placebo. Six hours after meningitis induction, the rats that received one dose were killed and the hippocampus and frontal cortex were obtained to assess cytokines/chemokine and brain-derived neurotrophic factor levels. On the 10th day, the rats were submitted to the inhibitory avoidance task. After the task, the animals were killed and samples from the hippocampus and frontal cortex were obtained. The extended administration of cannabidiol at different doses reduced the TNF-α level in frontal cortex. Prolonged treatment with canabidiol, 10mg/kg, prevented memory impairment in rats with pneumococcal meningitis. Although descriptive, our results demonstrate that cannabidiol has anti-inflammatory effects in pneumococcal meningitis and prevents cognitive sequel.

Increased prevalence of mood disorders and suicidal ideation in type 2 diabetic patients.

This study evaluated the association of mood disorders, suicidal ideation and the quality of life in patients with type 2 diabetes. We used a case-control study employing 996 patients suffering with type 2 diabetes (using insulin for over 1 year), and 2.145 individuals without diabetes. The groups were then used to evaluate the presence of different mood disorders and suicidal ideation, beyond quality of life. In addition to this, fasting glucose and glycosylated hemoglobin (Hb1C) were also evaluated. The data were analyzed using the Pearson chi-squared test, logistic regression, ANCOVA and Student's t-tests. We showed an association between type 2 diabetes and depressive episodes (adjusted OR = 1.8, CI 95 % 1.7-2.0, p < 0.001), recurrent depressive episodes (adjusted OR = 2.4, CI 95 % 2.2-2.6, p < 0.001), dysthymia (adjusted OR = 5.2, CI 95 % 4.9-5.5, p < 0.001), mood disorder with psychotic symptoms (adjusted OR = 2.5, CI 95 % 1.5-3.4, p < 0.001) and suicidal ideation (adjusted OR = 3.6, CI 95 % 2.5-4.8, p < 0.001, light; adjusted OR = 4.6, CI 95 % 1.5-7.7, p < 0.01, moderate and severe). The recurrent depression (OR = 1.3, CI 95 % 1.1-1.7, p < 0.05) and psychotic symptoms (OR = 4.1, CI 95 % 1.1-15.1, p < 0.05) were associated with higher levels of Hb1C. Dysthymia was associated with high blood glucose (OR = 1.6, CI 95 % 1.1-2.5, p < 0.05). Patients had lower mean scores in the following domains: physical [36.5 (13.6) × 56.0 (4.9), p < 0.001)], psychological [42.6 (8.6) × 47.9 (8.6), p < 0.001] and environmental [40.0 (8.6) × 49.3 (8.3), p < 0.001], but had higher scores in the area of social relations [50.2 (16.9) × 35.7 (27.9), p < 0.001]. The data demonstrated a worse quality of life, a high comorbidity of type 2 DM with depressive disorders and suicidal ideation. In addition, the poor control of DM is associated with the severity of mood disorders.