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1.
Braz Oral Res ; 37: e063, 2023.
Article in English | MEDLINE | ID: mdl-37341234

ABSTRACT

This study aimed to analyze the molecular characteristics of oral epithelial dysplasia (OED), highlighting the pathways and variants of genes that are frequently mutated in oral squamous cell carcinoma (OSCC) and other cancers. Ten archival OED cases were retrieved for retrospective clinicopathological analysis and exome sequencing. Comparative genomic analysis was performed between high-grade dysplasia (HGD) and low-grade dysplasia (LGD), focusing on 57 well-known cancer genes, of which 10 were previously described as the most mutated in OSCC. HGD cases had significantly more variants; however, a similar mutational landscape to OSCC was observed in both groups. CASP8+FAT1/HRAS, TP53, and miscellaneous molecular signatures were also present. FAT1 is the gene that is most affected by pathogenic variants. Hierarchical divisive clustering showed division between the two groups: "HGD-like cluster" with 4HGD and 2LGD and "LGD-like cluster" with 4 LGD. MLL4 pathogenic variants were exclusively in the "LGD-like cluster". TP53 was affected in one case of HGD; however, its pathway was usually altered. We describe new insights into the genetic basis of epithelial malignant transformation by genomic analysis, highlighting those associated with FAT1 and TP53. Some LGDs presented a similar mutational landscape to HGD after cluster analysis. Perhaps molecular alterations have not yet been reflected in histomorphology. The relative risk of malignant transformation in this molecular subgroup should be addressed in future studies.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Carcinoma, Squamous Cell/genetics , Retrospective Studies , Mouth Neoplasms/genetics , Chromosome Mapping , Squamous Cell Carcinoma of Head and Neck
2.
Neurohospitalist ; 13(2): 121-129, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37064927

ABSTRACT

Background and Purpose: Acute ischemic stroke (AIS) and depression are the major causes of disability and decreased quality of life worldwide. Psychiatric disorders are common after stroke, especially post-stroke depression (PSD), which affects one-third of survivors. Although frequent, little is known about the real complexity of the pathophysiology and the factors associated with PSD. Methods: This research aimed to provide data about risk factors and predictors of PSD 90 days after AIS. A cohort study was conducted in a tertiary stroke center located in southern Brazil. We interviewed 148 patients with AIS who were consecutively hospitalized between January 2020 and January 2021. The Hospital Anxiety and Depression Scale (HADS) was applied during hospitalization and at follow-up 90 days after AIS. Furthermore, sociodemographic, clinical, and radiological variables were investigated. Predictive factors were assessed using univariate and multivariate linear regression. The impact of the COVID-19 pandemic on the data was also evaluated. Results: The frequency of PSD 90 days after AIS was 33.9%. In-hospital symptoms of depression and anxiety each represented a 2-fold risk for PSD at follow-up. Furthermore, the HADS - anxiety score 90 days after AIS was strongly associated with the HADS - depression value 90 days after stroke (R: .71; B: .56; P < .01). Conclusions: The present study highlighted a noteworthy frequency of PSD 90 days after AIS. Psychiatric variables during hospitalization and in the follow-up appeared to be the leading associated factors with PSD. These data might support the determination of which patients require more psychiatric management.

3.
Braz. oral res. (Online) ; 37: e063, 2023. tab, graf
Article in English | LILACS-Express | LILACS, BBO - Dentistry | ID: biblio-1439735

ABSTRACT

Abstract This study aimed to analyze the molecular characteristics of oral epithelial dysplasia (OED), highlighting the pathways and variants of genes that are frequently mutated in oral squamous cell carcinoma (OSCC) and other cancers. Ten archival OED cases were retrieved for retrospective clinicopathological analysis and exome sequencing. Comparative genomic analysis was performed between high-grade dysplasia (HGD) and low-grade dysplasia (LGD), focusing on 57 well-known cancer genes, of which 10 were previously described as the most mutated in OSCC. HGD cases had significantly more variants; however, a similar mutational landscape to OSCC was observed in both groups. CASP8+FAT1/HRAS, TP53, and miscellaneous molecular signatures were also present. FAT1 is the gene that is most affected by pathogenic variants. Hierarchical divisive clustering showed division between the two groups: "HGD-like cluster" with 4HGD and 2LGD and "LGD-like cluster" with 4 LGD. MLL4 pathogenic variants were exclusively in the "LGD-like cluster". TP53 was affected in one case of HGD; however, its pathway was usually altered. We describe new insights into the genetic basis of epithelial malignant transformation by genomic analysis, highlighting those associated with FAT1 and TP53. Some LGDs presented a similar mutational landscape to HGD after cluster analysis. Perhaps molecular alterations have not yet been reflected in histomorphology. The relative risk of malignant transformation in this molecular subgroup should be addressed in future studies.

4.
J. inborn errors metab. screen ; 11: e20230001, 2023. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1448571

ABSTRACT

Abstract Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by reduced or absent activity of the enzyme α-galactosidase A. Due to systemic accumulation of glycolipids, FD phenotype is diverse, and diagnosis may be challenging. Clinical manifestations include small fiber neuropathy, renal dysfunction, cardiac involvement, cerebrovascular disease, among others. In the present study, we describe biopsy proven small fiber neuropathy and subclinical cardiac involvement in two cousins diagnosed with FD secondary to a recently described pathogenic variant, highlighting the importance of diagnostic tools to document organ damage and allow early treatment.

5.
Neurohospitalist ; 12(3): 524-528, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35747764

ABSTRACT

Background: This study represents an additional case of a rare entity and complication of COVID-19. Purpose: To further describe COVID's association with acute hemorrhagic leukoencephalopathy (AHL), a variant of acute disseminated encephalomyelitis. Besides, subsequent neuropsychological evaluation is described. Methods: The present case report describes clinical, laboratory, radiological, and electroencephalographic characteristics of AHL triggered by COVID-19, in addition to outcomes in the neuropsychological findings. Results: Radiologic findings of demyelinating lesions in supratentorial white matter permeated by multiple hemorrhagic foci supported the diagnostic of AHL, reinforced by clinical improvement after corticosteroid therapy. Conclusions: There are few similar cases previously reported, and this case highlights the early diagnosis and prompt treatment looking forward to better outcomes in AHL. Further studies are needed to elucidate the involved pathophysiological mechanisms.

6.
Neurol Sci ; 43(8): 4611-4617, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35141804

ABSTRACT

BACKGROUND: COVID-19 pandemic directly impacted the request for hospital care and medical assistance for several diseases worldwide, as occurred with acute ischemic stroke. The present study sought to compare the incidence and severity of acute ischemic stroke (AIS), in addition to sociodemographic, clinical, and radiological characteristics of patients hospitalized in the prepandemic (2018-2019) and pandemic (2020-2021) eras. METHODS: An incidence case-control, observational, and analytical research was carried out in the Stroke Unit of Hospital Governador Celso Ramos, Florianopolis, Santa Catarina, Brazil, including 171 patients admitted with acute ischemic stroke from April 2018 to April 2019 (prepandemic era) and 148 patients between January 2020 and January 2021 (during pandemic). RESULTS: The mean incidence of AIS hospital admissions was significantly lower in the pandemic period (CI 95%, 0.2 to 5.6; p = 0.04), being lower in the lockdown periods and when the incidence of new COVID-19 cases increased. Besides, referring to AIS severity, the mean areas of AIS were larger during the pandemic period (p < 0.01), especially in August, September, December, and January (p < 0.05). Sociodemographic and clinical variables did not show any difference between the two periods of the study. CONCLUSIONS: Hospital admissions for AIS decreased in the COVID-19 pandemic, mostly during months of higher incidences of new COVID-19 cases. When the incidence of admissions diminished, an increase in the severity of AIS was observed, characterized by larger areas. These findings might contribute to other similar referral centers in managing public policies related to stroke.


Subject(s)
COVID-19 , Ischemic Stroke , Stroke , Brazil/epidemiology , Communicable Disease Control , Humans , Ischemic Stroke/epidemiology , Pandemics , Retrospective Studies , Risk Factors , SARS-CoV-2 , Stroke/epidemiology
8.
Acta Myol ; 40(2): 93-100, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34355126

ABSTRACT

Pathogenic germline variants in DMD gene, which encodes the well-known cytoskeletal protein named dystrophin, are associated with a wide range of dystrophinopathies disorders, such as Duchenne muscular dystrophy (DMD, severe form), Becker muscular dystrophy (BMD, mild form) and intermediate muscular dystrophy (IMD). Muscle biopsy, immunohistochemistry, molecular (multiplex ligation-dependent probe amplification (MLPA)/next-generation sequencing (NGS) and Sanger methods) and in silico analyses were performed in order to identify alterations in DMD gene and protein in a patient with a clinical manifestation and with high creatine kinase levels. Herein, we described a previously unreported intronic variant in DMD and reduced dystrophin staining in the muscle biopsy. This novel DMD variant allele, c.9649+4A>T that was located in a splice donor site within intron 66. Sanger sequencing analysis from maternal DNA showed the presence of both variant c.9649+4A>T and wild-type (WT) DMD alleles. Different computational tools suggested that this nucleotide change might affect splicing through a WT donor site disruption, occurring in an evolutionarily conserved region. Indeed, we observed that this novel variant, could explain the reduced dystrophin protein levels and discontinuous sarcolemmal staining in muscle biopsy, which suggests that c.9649+4A>T allele may be re-classified as pathogenic in the future. Our data show that the c.9649+4A>T intronic sequence variant in the DMD gene may be associated with an IMD phenotype and our findings reinforce the importance of a more precise diagnosis combining muscle biopsy, molecular techniques and comprehensive in silico approaches in the clinical cases with negative results for conventional genetic analysis.


Subject(s)
Dystrophin , Muscular Dystrophy, Duchenne , Dystrophin/genetics , Genetic Testing , Humans , Introns/genetics , Muscular Dystrophy, Duchenne/genetics , Mutation , Phenotype
9.
Acta Neurol Scand ; 143(6): 629-636, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33751549

ABSTRACT

OBJECTIVES: To identify variables independently associated with a meaningful improvement in QOL long after surgical treatment of drug-resistant MTLE-HS patients. MATERIAL & METHODS: We prospectively evaluated 72 consecutive MTLE-HS surgically treated patients and analyzed pre and post-surgical variables independently associated with a meaningful improvement in QOL evaluated by the Quality of Life in Epilepsy-31 (QOLIE-31) overall score, and its domain scores determined at follow-up after 36 to 131 months (mean 93 months) after surgery. RESULTS: The mean overall QOLIE-31 score and its subdomain scores improved significantly after surgery (p < 0.01), and 55 patients (76.4%) had a meaningful QOL improvement. Being seizure-free (Engel IA) after surgery showed a non-significant association (OR 2.63, CI 95% 0.53 to 13.05, p = 0.23) and lower depressive symptoms a significant association (OR 4.15, CI 95% 1.19 to 14.53, p = 0.03) with meaningful improvement of QOL. CONCLUSIONS: Patients with MTLE-HS who underwent epilepsy surgery show a sustained, meaningful improvement in their QOL. Pre-surgical variables do not predict long-term QOL improvement after surgery. Lower levels of depressive symptoms at postoperative evaluation are associated with meaningful QOL improvement.


Subject(s)
Epilepsy, Temporal Lobe/surgery , Quality of Life , Treatment Outcome , Adult , Female , Follow-Up Studies , Humans , Male , Middle Aged , Time
10.
Neurol Sci ; 42(5): 1853-1860, 2021 May.
Article in English | MEDLINE | ID: mdl-32929628

ABSTRACT

BACKGROUND: Neurocognitive disorders remain frequent despite highly active antiretroviral treatment (HAART). The CNS is known as the sanctuary of HIV infection, where persistent neuroinflammation occurs regardless of viral suppression. Moreover, opportunistic infections, neurovascular damage and HAART neurotoxicity contribute to neurocognitive impairment. Therefore, detailed epidemiological studies might help to elucidate those complex mechanisms. OBJECTIVE: To investigate the prevalence of cognitive impairment and the associated sociodemographic, clinical and neuropsychological variables among HIV-infected patients admitted to a tertiary centre, in southern Brazil. METHODS: An observational, cross-sectional and analytic study was conducted between February 2019 and March 2020, in Hospital Nereu Ramos (HNR), with148 HIV-infected patients. They were interviewed, submitted to the International HIV Dementia Scale (IHDS) and had their medical data analysed. RESULTS: The prevalence of cognitive impairment was 69.6%. It was higher among women (OR = 3.5; 95% CI 1.5-8; p < 0.01), independently of depression, educational status and age. Full years of schooling were strongly associated with IHDS scores (p < 0.01). Patient Health Questionnaire-9 (PHQ-9) scores for depression (p = 0.8), time since HIV diagnosis (p = 0.2), CD4+ cell counts (p = 0.8) and viral load (p = 0.8) were not associated with IHDS scale. CONCLUSION: A high prevalence of cognitive impairment in HIV-infected patients was identified, independently associated with the female sex and fewer years of schooling. Further studies are needed to clarify the differences in the pathophysiology between sexes and the role of cognitive reserve in prevention of cognitive impairment in HIV infection.


Subject(s)
Cognitive Dysfunction , HIV Infections , Antiretroviral Therapy, Highly Active , Brazil/epidemiology , Cognitive Dysfunction/epidemiology , Cognitive Dysfunction/etiology , Cross-Sectional Studies , Female , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Neuropsychological Tests
11.
Epilepsy Behav ; 112: 107453, 2020 11.
Article in English | MEDLINE | ID: mdl-33181899

ABSTRACT

OBJECTIVE: The objective of the study was to investigate the independent association between clinical, demographic, psychiatric, radiologic, electrophysiological, and pharmacologic variables and cognitive performance of Brazilian patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE). METHODS: Ninety-three patients with pharmacoresistant MTLE related to hippocampal sclerosis (HS) were included in the study. Multiple linear regressions were done to identify predictor variables for 24 cognitive tests. Independent variables analyzed were sex, hand dominance, age, years of education, marital status, work activity, history for an initial precipitant injury (IPI), family history of epilepsy, lesion side, antiseizure medication (ASM) treatment type, ASM serum levels, benzodiazepine (BDZ) treatment, age at epilepsy onset, disease duration, monthly frequency of seizures, and Hospital Anxiety and Depression Scale (HADS) scores. RESULTS: Years of education was an independent and positive predictor in 22 of the 24 cognitive tests evaluated. Male sex was also a positive predictor of one cognitive test. Variables negatively associated with cognitive performance were left side lesion (10 tests), disease duration (5 tests), polytherapy (3 tests), ASM serum levels (3 tests), and BDZ treatment or not working (1 test each). The regression model explained between 6% and 44% of the cognitive test scores variation. SIGNIFICANCE: In Brazilian patients with pharmacoresistant MTLE-HS, up to 44% of cognitive test scores variation is predictable by clinical, demographic, psychiatric, radiologic, electrophysiology, and pharmacological variables. The identification of predictors of cognitive performance may be helpful for better planning of patient care.


Subject(s)
Epilepsy, Temporal Lobe , Brazil , Cognition , Epilepsy, Temporal Lobe/complications , Epilepsy, Temporal Lobe/drug therapy , Epilepsy, Temporal Lobe/pathology , Hippocampus/pathology , Humans , Male , Sclerosis/pathology
12.
Epilepsia ; 58(5): 755-763, 2017 05.
Article in English | MEDLINE | ID: mdl-28332703

ABSTRACT

OBJECTIVES: To investigate prospectively the independent predictors of a minimum clinically important change (MCIC) in quality of life (QOL) after anterior temporal lobectomy (ATL) for drug-resistant mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) in Brazilian patients. METHODS: Multiple binary logistic regression analysis was performed to identify the clinical, demographic, radiologic, and electrophysiologic variables independently associated with MCIC in the Quality of Life in Epilepsy-31 Inventory (QOLIE-31) overall score 1 year after ATL in 77 consecutive patients with unilateral MTLE-HS. RESULTS: The overall QOLIE-31 score and all its subscale scores increased significantly (p < 0.0001) 1 year after ATL. In the final logistic regression model, absence of presurgical diagnosis of depression (adjusted odds ratio [OR] 4.4, 95% confidence interval [CI] 1.1-16.1, p = 0.02) and a complete postoperative seizure control (adjusted OR 4.1, 95% CI 1.2-14.5, p = 0.03) were independently associated with improvement equal to or greater than the MCIC in QOL after ATL. The overall model accuracy for MCIC improvement in the QOL was 85.6%, with a 95.2% of sensitivity and 46.7% of specificity. SIGNIFICANCE: These results in Brazilian patients reinforce the external validation of previous findings in Canadian patients showing that presurgical depression and complete seizure control after surgery are independent predictors for meaningful improvement in QOL after ATL, and have implications for the surgical management of MTLE patients.


Subject(s)
Anterior Temporal Lobectomy/psychology , Drug Resistant Epilepsy/psychology , Drug Resistant Epilepsy/surgery , Epilepsy, Temporal Lobe/psychology , Epilepsy, Temporal Lobe/surgery , Outcome Assessment, Health Care , Quality of Life/psychology , Adult , Depressive Disorder/diagnosis , Depressive Disorder/psychology , Drug Resistant Epilepsy/diagnosis , Epilepsy, Temporal Lobe/diagnosis , Female , Follow-Up Studies , Hippocampus/pathology , Humans , Male , Outcome Assessment, Health Care/statistics & numerical data , Postoperative Complications/diagnosis , Postoperative Complications/psychology , Prospective Studies , Psychometrics , Sclerosis , Young Adult
13.
J Neurol Sci ; 375: 316-320, 2017 Apr 15.
Article in English | MEDLINE | ID: mdl-28320159

ABSTRACT

The progress on HIV infection treatment has allowed a longer survival for HIV-infected patients. However, chronic comorbidities are emerging. Peripheral Neuropathy (PN) represents one of the most prevalent neurologic disorders among these patients, and comprehensive studies may contribute to a reduction in the morbidity of this condition. This is a cross-sectional analytic study conducted in a tertiary referral hospital in southern Brazil. This study investigates the prevalence of PN among HIV-infected patients and associated demographic, clinical and laboratory variables. A number of 150 HIV-infected patients admitted between January and May 2016 were interviewed, submitted to physical and neurological examination, and data from their medical records were obtained. The prevalence of PN was 31.3%. It was increased among older patients (p=0.02), patients with higher CD4 lymphocytes levels (p=0.02), and smokers (OR=3.4; 95% CI 1.6-6.9; p<0.01). The research identified a high prevalence of PN in HIV-infected patients. Older age and higher CD4 levels have been associated with PN. To the best of our knowledge, this was one of the first studies reporting an association between tobacco use and PN among HIV-infected patients. Further studies are necessary to elucidate the pathological mechanisms linking PN and tobacco.


Subject(s)
CD4-Positive T-Lymphocytes/pathology , HIV Infections/complications , HIV Infections/epidemiology , Peripheral Nervous System Diseases , Adult , Brazil/epidemiology , Female , HIV Infections/pathology , Humans , Male , Middle Aged , Peripheral Nervous System Diseases/epidemiology , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/virology , Prevalence
14.
Neurol Sci ; 37(11): 1831-1837, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27457654

ABSTRACT

Deep brain stimulation (DBS) benefits Parkinson's disease (PD) patient's quality of life specially in domains as mobility, activities of daily living (ADL) and bodily discomfort (BD), but little is known about the variables associated with these HRQOL domains in patients presenting for DBS. The objective is to evaluate variables associated with of HRQOL in a Brazilian sample of PD patients presenting for DBS treatment, specifically in the domains related with motor symptoms. In a cross-sectional study of 59 PD patients evaluated at outpatient Unit for Movement Disorders, multiple linear regression analysis was performed to identify independent variables associated with mobility, ADL and BD domains of the 39-item Parkinson's disease questionnaire (PDQ-39). UPDRS III "on" scores, duration of the disease, age, presence of comorbidities and anxiety and depressive symptoms quantified by hospital anxiety and depression scale (HADS), were the independent variables. In our results, HADS scores were independently associated to mobility domain: ß coefficient 1.36 (95 % CI 0.55-2.15) and BD domain: ß coefficient 1.57 (95 % CI 0.67-2.48). UPDRS III "on" scores were independently associated to mobility domain: 0.42 (95 % CI 0.03-0.81). The model of each multiple linear regression analysis explains 25 % of the mobility domain variability (p < 0.01) and 24 % of the BD domain variability (p < 0.01). Psychiatric symptoms were at least as relevant to quality of life as motor symptoms in PD patients presenting for DBS treatment. The effect of treating these psychiatric symptoms on patients' HRQOL deserves further investigation.


Subject(s)
Activities of Daily Living , Parkinson Disease/physiopathology , Quality of Life , Aged , Brazil , Cross-Sectional Studies , Deep Brain Stimulation , Female , Humans , Male , Middle Aged , Parkinson Disease/psychology
15.
Neurochem Res ; 41(4): 880-91, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26586405

ABSTRACT

Mitochondrial respiratory chain complexes enzymatic (MRCCE) activities were successfully evaluated in frozen brain samples. Epilepsy surgery offers an ethical opportunity to study human brain tissue surgically removed to treat drug resistant epilepsies. Epilepsy surgeries are done with hemodynamic and laboratory parameters to maintain physiology, but there are no studies analyzing the association among these parameters and MRCCE activities in the human brain tissue. We determined the intra-operative parameters independently associated with MRCCE activities in middle temporal neocortex (Cx), amygdala (AMY) and head of hippocampus (HIP) samples of patients (n = 23) who underwent temporal lobectomy using multiple linear regressions. MRCCE activities in Cx, AMY and HIP are differentially associated to trans-operative mean arterial blood pressure, O2 saturation, hemoglobin, and anesthesia duration to time of tissue sampling. The time-course between the last seizure occurrence and tissue sampling as well as the sample storage to biochemical assessments were also associated with enzyme activities. Linear regression models including these variables explain 13-17 % of MRCCE activities and show a moderate to strong effect (r = 0.37-0.82). Intraoperative hemodynamic and laboratory parameters as well as the time from last seizure to tissue sampling and storage time are associated with MRCCE activities in human samples from the Cx, AMYG and HIP. Careful control of these parameters is required to minimize confounding biases in studies using human brain samples collected from elective neurosurgery.


Subject(s)
Brain/enzymology , Electron Transport Complex II/metabolism , Electron Transport Complex IV/metabolism , Electron Transport Complex I/metabolism , Epilepsy/enzymology , Adult , Anterior Temporal Lobectomy , Brain/pathology , Brain/surgery , Epilepsy/pathology , Epilepsy/surgery , Female , Freezing , Humans , Male , Specimen Handling/methods , Succinate Dehydrogenase/metabolism
16.
Epilepsy Behav ; 47: 61-5, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26043165

ABSTRACT

INTRODUCTION: Erectile dysfunction (ED) is often reported by patients with epilepsy and may be related to endocrine system abnormalities, side effects of antiepileptic drugs, psychiatric comorbidities, and family or social difficulties. AIMS: This study aimed to identify independent predictor factors for ED in patients with epilepsy. MAIN OUTCOME MEASURES: the five-question form of the International Index of Erectile Function (IIEF-5). METHODS: Independent predictive factors for ED evaluated by the IIEF-5 questionnaire in 36 patients (mean age: 39 years) with focal epilepsy (mean: 6 seizures/month) were identified by multiple linear regression analysis. RESULTS: Eight (21.1%) patients were asymptomatic. Among the symptomatic patients, 11 (28.9%) had mild dysfunction, 10 (26.3%) had moderate dysfunction, and 9 (23.7%) showed severe ED. The multiple linear regression model including family income (B=0.005; p=0.05), education levels in years (B=0.54; p=0.03), depressive symptoms determined by HADS depression subscale (B=-0.49; p=0.03), and prolactin levels (B=-0.45; p=0.07) showed a moderate association (r=0.64) with the IIEF questionnaire and explained 41% (r(2)=0.41) of its variation. CONCLUSIONS: Erectile dysfunction is highly prevalent in patients with focal epilepsies. Education, depressive symptoms, and prolactin levels can predict erectile dysfunction in up to 41% of patients with epilepsy. This preliminary report justifies further efforts to make a large sample size study to identify independent biomarkers and therapeutic targets for ED treatment in patients with epilepsy.


Subject(s)
Anticonvulsants/adverse effects , Epilepsies, Partial/epidemiology , Erectile Dysfunction/etiology , Penile Erection/physiology , Adult , Anticonvulsants/administration & dosage , Comorbidity , Depression/diagnosis , Depression/epidemiology , Erectile Dysfunction/drug therapy , Erectile Dysfunction/epidemiology , Humans , Linear Models , Male , Middle Aged , Predictive Value of Tests , Prevalence , Prolactin/blood , Severity of Illness Index , Surveys and Questionnaires
17.
Neurochem Int ; 87: 22-33, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25983036

ABSTRACT

Disturbances in glutamatergic transmission and signaling pathways have been associated with temporal lobe epilepsy (TLE) in humans. However, the profile of these alterations within specific regions of the hippocampus and cerebral cortex has not yet been examined. The pilocarpine model in rodents reproduces the main features of TLE in humans. The present study aims to characterize specific alterations of the glutamatergic transmission and signaling pathways in the dorsal (DH) and ventral hippocampus (VH) and temporal cortex (Ctx) of male adult Wistar rats 60 days after pilocarpine treatment (chronic period). The western blotting analyzes show a decrease of AMPA glutamate receptor subunit (GluA1)-Ser(845) phosphorylation; reduction of ERK1 and PKA activity; up-regulation of GFAP and down-regulation of the glutamate transporter EAAT2 expression in the DH. In contrast, in the VH it was observed a decrease of GluA1-Ser(831) phosphorylation and JNKp54 and PKC activity. In the Ctx, only ERK1 phosphorylation/activity decreased. The level of GluA1-Ser(845) phosphorylation and PKA activity (DH) and the level of GluA1-Ser(831) phosphorylation and PKC activity (VH) appear to be correlated, respectively. These findings suggest a differential imbalance of the signaling pathways involved in the site-specific phosphorylation of AMPA receptor in the hippocampus. Furthermore, we suggest that dorsal hippocampus is probably more susceptible to the impairment of glutamate uptake and gliose, since only this area displayed a significant decrease of EAAT2 and increment of GFAP. Taken together, our study suggests that specific neurochemical alterations take place in hippocampal sub regions. This approach may be valuable for understanding the onset of seizures and the alterations of neuronal excitability in specific regions and may help to establish therapeutic targets for treatment of this neuropathology.


Subject(s)
Epilepsy/chemically induced , Pilocarpine/toxicity , Receptors, AMPA/metabolism , Signal Transduction , Animals , Disease Models, Animal , Epilepsy/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Male , Phosphorylation , Pilocarpine/administration & dosage , Rats , Rats, Wistar
18.
J Matern Fetal Neonatal Med ; 28(4): 426-30, 2015 Mar.
Article in English | MEDLINE | ID: mdl-24824102

ABSTRACT

OBJECTIVE: Clinical and experimental evidences indicate that intrauterine inflammation during pregnancy is associated to brain damage. The objective of this study is to determine the effects of lipopolysaccharide in temperature, cytokine production and sickness behavior of pregnant dams. METHODS: A single i.p. injection of lipopolysaccharide (LPS) (50, 150 or 300 µg/kg) was administered on E18. Controls received isotonic saline. Body temperature was controlled before and 3 h after injections. Animals' behavior was assessed by the OF test 3 h following treatment. Animals were sacrificed for leukocyte, IL-1ß and TNF-α determination. Placental tissue and abortion were also examined. RESULTS: LPS administration elicited hypothermia. Abortion was observed in LPS 150 and 300 µg/kg. Leukocyte levels were significantly lower with LPS 300 µg/kg than in controls. LPS induced dose-dependent impairment in animals' locomotion. IL-1ß serum and amniotic fluid were higher than the saline, and TNF-α serum and amniotic fluid increased when compared to controls. Placental histopathologic abnormality was not found. CONCLUSION: LPS induces dose-dependent sickness behavior and hypothermia in pregnant mice. Our findings suggest that the presence of inflammation may be a causative factor for premature labor and that Escherichia coli antigens modify the concentration of pro-inflammatory agents in circulatory system and intra-uterine environment.


Subject(s)
Abortion, Spontaneous/chemically induced , Illness Behavior/drug effects , Inflammation/chemically induced , Lipopolysaccharides/administration & dosage , Abortion, Spontaneous/immunology , Animals , Body Temperature , Dose-Response Relationship, Drug , Female , Inflammation/immunology , Injections, Intravenous , Male , Mice , Motor Activity , Pregnancy , Pregnancy Complications/chemically induced , Pregnancy Complications/immunology
19.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; Braz. J. Psychiatry (São Paulo, 1999, Impr.);36(3): 206-212, Jul-Sep/2014. tab, graf
Article in English | LILACS | ID: lil-718440

ABSTRACT

Objective: To evaluate the validity and utility of the Hamilton Rating Scale for Depression (HAM-D), Beck Depression Inventory (BDI), and Hospital Anxiety and Depression Scale (HADS) as screening tools for depression after severe traumatic brain injury (TBI). Methods: Forty-six consecutive survivors of severe TBI were evaluated at a median of 15 months after injury. Receiver operating characteristic (ROC) analysis was performed using HAM-D, BDI, and HADS as predictors, and the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) as gold standard. Results: The area under the curve (AUC) for HAM-D was 0.89, and the optimal cutoff point was 7 (sensitivity 92.9%, specificity 78.1%); for the BDI, the AUC was 0.946 and the optimal cutoff point was 14 (sensitivity 92.3%, specificity 96.7%); for the HADS, the AUC was 0.947 and the optimal cutoff point was 9 (sensitivity 100%, specificity 80.7%); and for the HADS depression subscale, the AUC was 0.937 and the optimal cutoff point was 6 (sensitivity 92.9%, specificity 83.9%). There were no statistically significant differences among the AUCs. Conclusion: Our findings support a high validity and utility for the HAM-D, BDI, and HADS as screening tools for depression in patients with severe TBI, without major changes in standard cutoff points. .


Subject(s)
Adult , Female , Humans , Male , Young Adult , Brain Injuries/psychology , Depressive Disorder/diagnosis , Depressive Disorder/etiology , Psychiatric Status Rating Scales/standards , Age Factors , Area Under Curve , Confidence Intervals , Mass Screening/methods , Prospective Studies , Psychometrics , Surveys and Questionnaires/standards , Reference Values , Reproducibility of Results , Sensitivity and Specificity , Sex Factors
20.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; Braz. J. Psychiatry (São Paulo, 1999, Impr.);36(3): 213-219, Jul-Sep/2014. tab, graf
Article in English | LILACS | ID: lil-718445

ABSTRACT

Objective: To evaluate predictors of non-return to work (nRTW) among social, demographic, clinical, and psychiatric variables after severe traumatic brain injury (TBI) in a cohort of Brazilian patients. Methods: Prospective study. Forty-three community-dwelling individuals treated at a Level I trauma center at the time of TBI were evaluated 18 months after trauma. Measures included DSM-IV-TR criteria for personality changes after TBI and Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) to assess psychiatric diagnosis. Hospitalization variables included Glasgow Coma Scale scores, pupil examination findings, associated limb trauma, Marshall computed tomography classification, and blood glucose levels. Results: After multiple logistic regression analysis, only the diagnosis of personality changes was found to be independently associated with nRTW, with an adjusted odds ratio of 10.92 (p = 0.02, 95% confidence interval 1.41-84.28). Conclusions: In this study, personality changes were an independent predictor of nRTW after severe TBI. Ways to predict risk factors associated with personality changes after severe brain injury could aid in identification of early and effective interventions that might ease the burden associated with this condition. .


Subject(s)
Adolescent , Adult , Female , Humans , Male , Young Adult , Brain Injuries/complications , Personality Disorders/etiology , Return to Work/statistics & numerical data , Brazil , Glasgow Coma Scale , Odds Ratio , Predictive Value of Tests , Prospective Studies , Psychiatric Status Rating Scales , Psychotropic Drugs/therapeutic use , Return to Work/psychology , Risk Factors , Socioeconomic Factors , Statistics, Nonparametric
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