Renan Antonio Ceretta

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.

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.

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 × 109 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.

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.

Meta-analysis of magnetic resonance imaging accuracy for diagnosis of oral cancer

Objective To establish the diagnostic accuracy of magnetic resonance imaging (MRI) as an auxiliary means for the diagnosis of oral cancer through a systematic review and meta-analysis. Methods An exhaustive search of publications from 1986 to 2016 was performed of Medline, Embase and Cochrane (and related databases), including grey literature. Primary diagnostic accuracy studies that assessed oral cancer (target condition) using MRI (index test) were included. Diagnostic threshold, sensitivity and meta-regression analyses were performed. A meta-analysis was performed using Meta-DiSc® v. 1.4 software. Results A total of 24 primary studies were assessed, comprising 1,403 oral cancer lesions. Nine studies used diffusion-weighted MRI, with a diagnostic odds ratio (DOR) of 30.7 (95% confidence interval [CI]: 12.7–74.3) and area under the curve (AUC) of 0.917 (95% CI: 0.915–0.918); seven studies used dynamic contrast-enhanced MRI, with a DOR of 48.1 (95%CI: 22.4–103.2) and AUC of 0.936 (95% CI: 0.934–0.937); and 13 studies used traditional MRI, with a DOR of 23.9 (95%CI: 13.2–43.3) and AUC of 0.894 (95% CI: 0.894–0.895). Meta-regression analysis indicated that the magnetic field strength may have influenced the heterogeneity of the results obtained (p = 0.0233) using traditional MRI. Sensitivity analysis revealed a discrete reduction of inconsistency in some subgroups. Conclusion The three types of MRI assessed exhibited satisfactory accuracy compared to biopsy. Considering the relevance of early treatment and screening and that better health care results in improved survival rates and quality of life for oral cancer patients, we suggest the use of MRI as a part of the pre-treatment and monitoring protocol at public health services.

Association between experimental bacterial meningitis and periapical lesion

INTRODUCTION Mortality and morbidity from bacterial meningitis in African adults is significantly higher than those in better resourced settings. At the same time, the periodontal diseases are highly prevalent and can affect up to 90% of the population. Dental caries in Uganda was recorded in 40% and 62.5% of the children and adults, respectively. We hypothesize that pneumococcal meningitis could interfere in the development of periapical lesion. The aim of this study was to evaluate periapical lesion in Wistar rats subjected to pneumococcal meningitis. MATERIALS AND METHODS The animals were divided in control, control/periapical lesion, meningitis, and meningitis/periapical lesion groups. The surgical exposure of molars and the infection of the dental pulp were from the oral environment. Pulp necrosis was induced on the left mandibular first molars during adulthood. Dental pulps were exposed by drilling cavities on the central portion of the occlusal surface with a 1011 HL round bur in high speed to a depth nearly equal to the bur diameter. Animals were subjected to behavioral task and evaluation of the size of periodontal ligament. Data from periodontal ligament space and open field task were reported as mean ± SEM and analysed by Two-way ANOVA and paired Students t-test, respectively. RESULTS AND CONCLUSION Meningitis/periapical increased the periodontal ligament space by 61% when compared with control/periapical. In the open-field task, there were no differences in the number of crossings and rearing movements between training and test session in meningitis and periapical lesion groups demonstrating habituation memory impairment. Bacterial meningitis and periapical lesion may play an important role in development of cognitive impairment.

Imipramine treatment reverses depressive- and anxiety-like behaviors, normalize adrenocorticotropic hormone, and reduces interleukin-1β 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-1β (IL-1β), IL-6, and serum adrenocorticotropic hormone (ACTH) levels were higher in the periapical lesion group. However, rats treated with imipramine had lower IL-1β 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

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.

Meta-Analysis of Prevalence of Xerostomia in Diabetes Mellitus

Background: As with other complications of diabetes mellitus, the occurrence of dry mouth can lead to a poor quality of life. Therefore, this study aimed to identify the prevalence of xerostomia in patients with diabetes mellitus through a systematic review and meta-analysis. Method: Systematic review and meta-analysis. Results: After the screening process, 23 studies were included in the meta-analysis. Overall, the incidence of dry mouth was investigated in 1979 people with diabetes (cases) and 1225 controls. The global prevalence of diabetes in xerostomia was 42.22% (95% CI: 33.97%-50.92%). In the analysis by specific subtype, the overall prevalence was 37.42% (95% CI: 22.33%-55.44%) among individuals with Type 1 diabetes and 46.09% (95% CI: 23.99%-69.85%) among those with type 2 diabetes. The prevalence of xerostomia found in Asia (49.01%; 95% CI: 32.08%-66.16%) was higher than that found in Europe (40.04%; 95% CI: 29.58%-51.50%) and America (38.39%; 95% CI: 23.63%-55.65%). Analysis of the case-control studies showed a statistically significant association between xerostomia and diabetes mellitus (OR=3.15; 95% CI: 2.11-4.70; p<0.001). Conclusion: Through the data collected, we can infer that the prevalence of xerostomia in individuals affected by diabetes mellitus types 1 and 2 was high and independent of geographic location.