Memory changes in patients with hippocampal sclerosis submitted to surgery to treat mesial temporal lobe epilepsy.

PURPOSE: This study was performed with the purpose of analysing the relationship between epileptological and surgical variables and post-operative memory performance, following surgery for refractory mesial temporal lobe epilepsy (MTLE) due to hippocampal sclerosis (HS). METHODS: Logical memory (LM) and visual memory (VM) scores for immediate and late follow-up of 201 patients operated for MTLE/HS were reviewed. Scores were standardized with a control group of 54 healthy individuals matched for age and education. The Reliable Change Index (RCI) was calculated to verify individual memory changes for late LM and VM scores. A multiple linear regression analysis was carried out with the RCI, using LM and VM scores as well as the clinical variables. RESULTS: A total of 112 (56%) patients had right HS. The RCI of the right HS group demonstrated that 6 (7%) patients showed improvement while 5 (6%) patients showed decreased scores in late LM; for late VM, 7 (8%) patients presented improvement, and 2 (3%) patients showed poorer scores. RCI of the left HS group showed that 3 (3%) individuals showed improved scores, while scores of 5 (4%) patients worsened for late LM; for late VM, 3 (3%) patients presented higher scores and 6 (5%) showed lower scores. Left HS and advanced age at onset of the first epileptic seizure were predictors of late LM loss (p<.05). CONCLUSION: Left MTLE/HS and seizure onset at advanced ages were predictive factors for the worsening of late LM. We observed poorer baseline LM function in the left HS group and improvement of LM in some patients who had resection of the right MTL. Patients in the right HS group showed a higher percentage of reliable post-operative improvement for both VM and LM scores.

Immunostimulating activity of Uncaria tomentosa in RAW 264.7 macrophages.

Uncaria tomentosa is a plant native to the Amazon that has immunomodulatory and antitumor properties due to the alkaloids found in the plant, being able to modify the immune response by potentiating or suspending the action of cytokines secreted by macrophages that induce the immune response, either by the classical route (M1) or through the alternative route (M2). Macrophages activated by M1 convert L-arginine into L-citrulline and nitric oxide (NO), whereas macrophages activated by the M2 pathway use the enzymatic activity of arginase to convert the same substrate into L-ornithine and urea. The aim of this work was to evaluate the immunostimulating activity of the crude hydroalcoholic extract from the bark of the U. tomentosa stem in RAW 264.7 macrophages. Concentrations of 0.2, 0.1 and 0.05 mg/mL of U. tomentosa extract associated with LPS, INF-γ and IL-4 inducers were tested by determining NO production and arginase enzyme activity. Nitric oxide production was enhanced by the extract when associated with LPS and LPS + INF-γ inducers. In the activity of the arginase enzyme, the extract decreased the stimulation of IL-4 on the enzyme, mainly at 0.2 mg/mL concentration. Therefore, it is concluded that the crude hydroalcoholic extract of the stem bark of U. tomentosa in RAW 264.7 cells, at a concentration of 0.2 mg/mL, showed considerable pro-inflammatory activity.

Inhibition of Pro-Inflammatory Microglia with Minocycline Improves Cognitive and Sleep-Wake Dysfunction Under Respiratory Stress in a Sporadic Model for Alzheimer's Disease.

BACKGROUND: Neuroinflammation in Alzheimer's disease (AD) can occur due to excessive activation of microglia in response to the accumulation of amyloid-ß peptide (Aß). Previously, we demonstrated an increased expression of this peptide in the locus coeruleus (LC) in a sporadic model for AD (streptozotocin, STZ; 2 mg/kg, ICV). We hypothesized that the STZ-AD model exhibits neuroinflammation, and treatment with an inhibitor of microglia (minocycline) can reverse the cognitive, respiratory, sleep, and molecular disorders of this model. OBJECTIVE: To evaluate the effect of minocycline treatment in STZ model disorders. METHODS: We treated control and STZ-treated rats for five days with minocycline (30 mg/kg, IP) and evaluated cognitive performance, chemoreflex response to hypercapnia and hypoxia, and total sleep time. Additionally, quantification of Aß, microglia analyses, and relative expression of cytokines in the LC were performed. RESULTS: Minocycline treatment improved learning and memory, which was concomitant with a decrease in microglial cell density and re-establishment of morphological changes induced by STZ in the LC region. Minocycline did not reverse the STZ-induced increase in CO2 sensitivity during wakefulness. However, it restored the daytime sleep-wake cycle in STZ-treated animals to the same levels as those observed in control animals. In the LC, levels of A and expression of Il10, Il1b, and Mcp1 mRNA remained unaffected by minocycline, but we found a strong trend of minocycline effect on Tnf- α. CONCLUSION: Our findings suggest that minocycline effectively reduces microglial recruitment and the inflammatory morphological profile in the LC, while it recovers cognitive performance and restores the sleep-wake pattern impaired by STZ.

Neuron-associated macrophage proliferation in the sensory ganglia is associated with peripheral nerve injury-induced neuropathic pain involving CX3CR1 signaling.

Resident macrophages are distributed across all tissues and are highly heterogeneous due to adaptation to different tissue-specific environments. The resident macrophages of the sensory ganglia (sensory neuron-associated macrophages, sNAMs) are in close contact with the cell body of primary sensory neurons and might play physiological and pathophysiological roles. After peripheral nerve injury, there is an increase in the population of macrophages in the sensory ganglia, which have been implicated in different conditions, including neuropathic pain development. However, it is still under debate whether macrophage accumulation in the sensory ganglia after peripheral nerve injury is due to the local proliferation of resident macrophages or a result of blood monocyte infiltration. Here, we confirmed that the number of macrophages increased in the sensory ganglia after the spared nerve injury (SNI) model in mice. Using different approaches, we found that the increase in the number of macrophages in the sensory ganglia after SNI is a consequence of the proliferation of resident CX3CR1+ macrophages, which participate in the development of neuropathic pain, but not due to infiltration of peripheral blood monocytes. These proliferating macrophages are the source of pro-inflammatory cytokines such as TNF and IL-1b. In addition, we found that CX3CR1 signaling is involved in the sNAMs proliferation and neuropathic pain development after peripheral nerve injury. In summary, these results indicated that peripheral nerve injury leads to sNAMs proliferation in the sensory ganglia in a CX3CR1-dependent manner accounting for neuropathic pain development. In conclusion, sNAMs proliferation could be modulated to change pathophysiological conditions such as chronic neuropathic pain.

An exuberant case of protothecosis: an emergent disease in tropical dermatology.

Protothecosis is a rare condition caused by the aclorophylated algae of the genus Prototheca. We described an exuberant case treated as sporotrichosis with prolonged course which evolved to arm deformation. Itraconazole treatment for 8 months was inefective.

Case report: Biliobronchial fistula after biliary tract stenosis.

Biliobronchial fistula (BBF) is a rare abnormality resulting from congenital or acquired communication between the bile ducts and the bronchial tree. Patients often suffer from chronic cough, dyspnea, and bilioptysis, a pathognomonic symptom of this condition. Conservative methods such as less-invasive procedures are gradually consolidating. Nonetheless, surgery remains the primary treatment, especially in more complex cases. We present the case of a 44-year-old woman with a chronic cough, no verified periods of fever, cyclic jaundice, and episodes of yellowish sputum. She had undergone cholecystectomy in 2018 and had been hospitalized several times since for pneumonia treatment. All consequent investigations for mycobacteriosis were negative. When referred to our hospital, she had cyclic jaundice and parenchymal consolidation in the right lower lobe. Suspected bilioptysis motivated the search for a biliobronchial fistula. Magnetic resonance cholangiography (MRC) confirmed stenosis of the biliary tract and fistulous path, and sputum analysis indicated high bilirubin levels. External biliary bypass was performed as an initial conservative and definitive therapy due to the presence of liver cirrhosis. Although BBF is a rare condition when bilioptysis is suspected, a diagnostic investigation should be initiated. Our case study proposes two criteria for diagnosis: an imaging exam demonstrating the fistulous path and confirmation of bilirubin in the sputum or bronchoalveolar lavage (BAL). When diagnosed, surgical correction should be performed.

Phototherapy

Abstract Of all the therapeutic options available in Dermatology, few of them have the history, effectiveness, and safety of phototherapy. Heliotherapy, NB-UVB, PUVA, and UVA1 are currently the most common types of phototherapy used. Although psoriasis is the most frequent indication, it is used for atopic dermatitis, vitiligo, cutaneous T-cell lymphoma, and cutaneous sclerosis, among others. Before indicating phototherapy, a complete patient assessment should be performed. Possible contraindications should be actively searched for and it is essential to assess whether the patient can come to the treatment center at least twice a week. One of the main method limitations is the difficulty that patients have to attend the sessions. This therapy usually occurs in association with other treatments: topical or systemic medications. Maintaining the regular monitoring of the patient is essential to identify and treat possible adverse effects. Phototherapy is recognized for its benefits and should be considered whenever possible.

Phototherapy.

Of all the therapeutic options available in Dermatology, few of them have the history, effectiveness, and safety of phototherapy. Heliotherapy, NB-UVB, PUVA, and UVA1 are currently the most common types of phototherapy used. Although psoriasis is the most frequent indication, it is used for atopic dermatitis, vitiligo, cutaneous T-cell lymphoma, and cutaneous sclerosis, among others. Before indicating phototherapy, a complete patient assessment should be performed. Possible contraindications should be actively searched for and it is essential to assess whether the patient can come to the treatment center at least twice a week. One of the main method limitations is the difficulty that patients have to attend the sessions. This therapy usually occurs in association with other treatments: topical or systemic medications. Maintaining the regular monitoring of the patient is essential to identify and treat possible adverse effects. Phototherapy is recognized for its benefits and should be considered whenever possible.

Structure and spatial distribution of the rotifer assemblages along a tropical reservoir.

The construction of reservoirs is a common practice in the world. These systems modify the hydric landscape and alter the flow of rivers, becoming lotic environments in lentic. Here we investigated the structure and spatial distribution of rotifers along a tropical reservoir. We sampled four points in the Pedra do Cavalo Reservoir, Bahia, Brazil, bimonthly, between August 2014 and June 2015. We registered more than 70 taxa distributed in 17 families, with the majority of species belonging to the Lecanidae, Brachionidae and Trichocercidae families. The species rarefaction curve did not achieve a total asymptote, indicating that species richness in the reservoir is higher than what was registered. Based in the species frequency of occurrence, we identified 48 rare species, 16 common species, five constant species and one frequent species. The highest beta diversity values were registered in riverine P1 (0.513) and intermediate P2 (0.503), although there were no significant differences between the sampling points. Despite the high abundance values in P1, P2 and P3 no significant differences were found between the studied points. Thus, this study substantially increases the knowledge on the rotifer community in the Paraguaçu River and contributes to future studies that focus on biodiversity, ecology and conservation in the Brazilian reservoir ecosystems.

Structure and spatial distribution of the rotifer assemblages along a tropical reservoir / Estrutura e distribuição espacial da comunidade de rotíferos em um reservatório tropical

The construction of reservoirs is a common practice in the world. These systems modify the hydric landscape and alter the flow of rivers, becoming lotic environments in lentic. Here we investigated the structure and spatial distribution of rotifers along a tropical reservoir. We sampled four points in the Pedra do Cavalo Reservoir, Bahia, Brazil, bimonthly, between August 2014 and June 2015. We registered more than 70 taxa distributed in 17 families, with the majority of species belonging to the Lecanidae, Brachionidae and Trichocercidae families. The species rarefaction curve did not achieve a total asymptote, indicating that species richness in the reservoir is higher than what was registered. Based in the species frequency of occurrence, we identified 48 rare species, 16 common species, five constant species and one frequent species. The highest beta diversity values were registered in riverine P1 (0.513) and intermediate P2 (0.503), although there were no significant differences between the sampling points. Despite the high abundance values in P1, P2 and P3 no significant differences were found between the studied points. Thus, this study substantially increases the knowledge on the rotifer community in the Paraguaçu River and contributes to future studies that focus on biodiversity, ecology and conservation in the Brazilian reservoir ecosystems.

A construção de reservatórios é uma prática comum no mundo. Esses sistemas modificam a paisagem hídrica e alteram o fluxo dos rios, tornando-se ambientes lóticos em lênticos. Aqui investigamos a estrutura e distribuição espacial de rotíferos ao longo de um reservatório tropical. Foram amostrados quatro pontos no Reservatório da Pedra do Cavalo, Bahia, Brasil, bimestralmente, entre agosto de 2014 e junho de 2015. Registramos mais de 70 táxons distribuídos em 17 famílias, com a maioria das espécies pertencentes às famílias Lecanidae, Brachionidae e Trichocercidae. A curva de rarefação das espécies não alcançou uma assíntota total, indicando que a riqueza de espécies no reservatório é superior à registrada. Com base na frequência de ocorrência das espécies, identificamos 48 espécies raras, 16 espécies comuns, cinco espécies constantes e uma espécie frequente. Os maiores valores de diversidade beta foram registrados no ribeirinho P1 (0,513) e no intermediário P2 (0,503), embora não houvesse diferenças significativas entre os pontos de amostragem. Apesar dos altos valores de abundância em P1, P2 e P3, não foram encontradas diferenças significativas entre os pontos estudados. Assim, este estudo aumenta substancialmente o conhecimento sobre a comunidade de rotíferos no rio Paraguaçu e contribui para estudos futuros que enfocam biodiversidade, ecologia e conservação nos ecossistemas de reservatórios brasileiros.

Bidens pilosa L. (Asteraceae) cultivated in Brazil on acute liver disease in dogs / [Bidens pilosa L. (Asteraceae) cultivada no Brasil na doença hepática aguda em cães]

Bidens pilosa L. is a medicinal plant popularly used for treatment of liver diseases. In this study, the dry extract of aerial parts of Bidens pilosa and Silymarin, a phytocomplex obtained from the Silybum marianum fruits and marketed as hepatoprotective, were tested in dogs experimentally acutely intoxicated with carbon tetrachloride. The liver activity was evaluated by hematological and biochemical profiles, and histological and ultrasound analyzes. It was observed that the lowest serum activities of ALT and serum concentrations of total bilirubin occurred in the groups treated with the dry extract of Bidens pilosa, while only decreased serum concentrations of total bilirubin occurred in the group treated with Silymarin. Best liver recovery was also observed for the dry extract of B. pilosa at a 400mg/Kg dose by ultrasonography. This study showed that the dry extract of Bidens pilosa acted more efficiently in the treatment of acute toxic hepatitis induced in dogs than Silymarin.(AU)

Bidens pilosa L. é uma planta medicinal utilizada popularmente para tratamento de doenças hepáticas. Neste trabalho, o extrato seco das partes aéreas da Bidens pilosa e a silimarina, um fitocomplexo obtido dos frutos da Silybum marianum e comercializado como hepatoprotetor, foram testados em cães intoxicados experimentalmente de forma aguda com tetracloreto de carbono. A atividade hepática foi avaliada por meio dos perfis hematológico e bioquímico, análises histológica e ultrassonográfica. Observou-se que, nos grupos tratados com o extrato seco da Bidens pilosa, ocorreram as menores atividades séricas da ALT e de concentrações séricas de bilirrubina total, enquanto no grupo tratado com silimarina, ocorreu apenas diminuição de concentrações séricas de bilirrubina total. Melhor recuperação hepática também foi verificada para o extrato seco de B. pilosa na dose de 400mg/kg por ultrassonografia. Este estudo evidenciou que o extrato seco da Bidens pilosa atuou de forma mais eficiente no tratamento da hepatite aguda tóxica induzida em cães do que a silimarina.(AU)

Selumetinib for plexiform neurofibromas in neurofibromatosis type 1: a single-institution experience.

BACKGROUND: Plexiform neurofibromas (PN) are the most frequent tumors associated with Neurofibromatosis type 1 (NF-1). PN can cause significant complications, including pain, functional impairment, and disfigurement. There is no efficient medical treatment and, surgical resection of large PN is frequently infeasible. Selumetinib (AZD6244/ARRY-142886) is a mitogen-activated protein kinase enzyme (MEK1/2) inhibitor and works by targeting the MAPK pathway. It is an investigational treatment option for inoperable symptomatic PN associated with NF-1. Herein, we describe a single institutional experience with selumetinib for inoperable PN in NF-1. METHODS: Case series study of demographics, clinical, baseline characteristics, treatment effect, and follow-up of consecutive genetically confirmed NF1 patients with inoperable PN associated with significant or potential significant morbidity treated with selumetinib (April 2018 to April 2019). RESULTS: Nineteen patients were treated with selumetinib. Predominant target locations were head and neck (31.6%, 6/19), chest (26.3%, 5/19) and pelvis (21%, 4/19) and the most important comorbidities were disfigurement (47.4%, 9/19) and pain (26.3%, 5/19). The mean follow-up time was 223 days (range 35-420 days). All but one had sustained clinical improvement, mainly in the first 60-90 days of treatment. In one patient, the treatment was suspended after 168 days (lack of clear benefit and left ventricular ejection fraction drop). There were no adverse effects leading to treatment suspension. CONCLUSIONS: In the first observational study of selumetinib for NF-1 associated PN we showed that the drug was associated with clinical and radiological improvement. Our study also confirms the safety described in the clinical trials.