Chronic deep brain stimulation in an Alzheimer's disease mouse model enhances memory and reduces pathological hallmarks.

BACKGROUND: Alzheimer's disease (AD) is a progressive degenerative disorder that currently remains extremely disabling. Recent work has shown that deep brain stimulation (DBS) has promising effects in AD patients. In parallel to the clinical trials, we investigated the impact of chronic DBS in 3xTg mice, a well-established animal model of AD. METHODS: AD mice were assigned to control (Cont), non-stimulation (NS) and stimulation (DBS) groups, along with age matched wild type controls (WT-Cont). Bilateral electrodes were implanted in the entorhinal cortex to deliver chronic high frequency stimulation for 25 days. Animals were tested in memory behavioral tasks, with post-mortem measurements of pathological markers. RESULTS: We found that chronic DBS in AD mice normalized their impaired performance in the Morris water maze task to that of the WT group in the probe test. In the novel object and novel place preference tasks, AD-DBS mice spent more time at the novel object and novice location compared to AD-NS mice. These cognitive improvements in AD-DBS mice were associated with DBS induced increased neurogenesis in the dentate gyrus, a significant reduction in ß-amyloid plaques, a reduction in CA-1 cellular ß-amyloid-42 levels, decreased cortical total-tau and phosphorylated-tau, along with decreased hippocampal total-tau. CONCLUSION: Overall, we show that chronic DBS of the entorhinal cortex in AD mice improves both memory and AD specific pathological markers. These results support further testing of DBS as a potential treatment in AD patients.

Laryngeal Rhabdomyosarcoma in a dog: case report / Rabdomiossarcoma na laringe em cão: relato de caso

The larynx is part of the upper respiratory tract and is responsible for phonation. It allows air to pass between the pharynx and the trachea, but prevents food from entering the airways. Laryngeal neoplasms, including rhabdomyosarcomas, are uncommon in dogs. However, these tumors can trigger numerous progressive clinical signs related to respiratory difficulty and altered phonation. The diagnosis of laryngeal cancer should be made based on the history and symptoms of the patient, combined with complementary tests. The treatment of choice is surgical excision, combined or not with chemotherapy. In view of the low incidence of laryngeal cancer, the objective of the present work was to describe a case of laryngeal rhabdomyosarcoma detected during necropsy of an adult dog and diagnosed by histopathology, in addition to raising awareness about the importance of the diagnosis and early therapy for the quality of life and survival of affected patients. The results showed that the location of the tumor impaired its early diagnosis. Although malignant, the animal did not develop metastases as has been described in the literature.(AU)

A laringe é um dos órgãos que compõem o trato respiratório superior, sendo também responsável pela fonação. Permite a passagem do ar entre a faringe e traqueia, mas impede que alimentos adentrem as vias aéreas. As neoplasias laringeanas, incluindo os rabdomiossarcomas, são incomuns em cães, porém, quando presentes, desencadeiam inúmeros sinais clínicos progressivos relacionados à dificuldade respiratória e à alteração na fonação. O diagnóstico das neoplasias na laringe deve ser baseado no histórico e na sintomatologia do paciente, associado a exames complementares. O tratamento de eleição é a exérese cirúrgica, concomitante ou não com a quimioterapia. Desse modo, diante da baixa incidência desse tipo neoplásico, inclusive na laringe, o objetivo do atual trabalho é descrever o caso de rabdomiossarcoma em laringe, detectado durante o exame de necropsia de um cão adulto e diagnosticado por histopatologia, bem como conscientizar sobre a importância do diagnóstico e da terapêutica precoce na qualidade de vida e sobrevida dos afetados. De acordo com a descrição do caso, pode-se admitir que a localização da neoplasia prejudicou o diagnóstico precoce e que, apesar de esta ser maligna, não houve metástases conforme descrição na literatura.(AU)

Retrospective study of ocular complication following phacoemulsification with intraocular acrylic lens implantation in dogs / Estudo retrospectivo das complicações oculares em cães submetidos à facoemulsificação com implantação de lente acrílica

The aim of this study was to analyze for 120 days, post-operative complications following bimanual phacoemulsification with implantation of hydrophilic or hydrophobic intraocular acrylic lens. The hospital records of 15 dogs were analyzed, and distributed in two groups, being Gfi and Gfo the hydrophilic intraocular lens and hydrophobic intraocular lens group, respectively. On the first day, both groups presented blepharospasm, conjunctival hyperemia and flare. On day 1, fibrin was slightly apparent in two and three eyes of Gfi and Gfo, and on day 7, present in one and two patients from Gfi and Gfo. Synechia was observed on day 1 in one eye from Gfi and Gfo. Two eyes from Gfi developed from 7 to 120 days, and in Gfo, one eye developed from 7 to 90 days, on day 120, two eyes formed them. The presence of posterior capsule opacity of the lens in all periods, there was no statistical significant between the groups. Only one eye, in Gfo, that had no opacity formation. The intraocular pressure of both groups remained within normal range. There was no statistical significance between hydrophilic and hydrophobic intraocular lens, the use of intraocular lens has led to satisfactory results in visual ability.(AU)

Objetivou-se com o presente estudo avaliar por 120 dias as complicações após a facoemulsificação bimanual com implantação de lentes acrílicas hidrofílicas ou hidrofóbicas. Os prontuários de 15 cães foram avaliados, sendo distribuídos em dois grupos, Gfi e Gfo, grupos com lentes intraoculares hidrofílicas e com lentes hidrofóbicas, respectivamente. No primeiro dia, ambos os grupos apresentaram blefarospasmo, hiperemia conjuntiva e flare. No dia 1, fibrina foi discretamente observada em dois e três olhos do Gfi e Gfo; no dia 7, observou-se em um e três olhos nos pacientes do Gfi e Gfo. Foi observada sinéquia no dia 1 em um olho do Gfi e do Gfo; em dois olhos do Gfi ocorreu do dia 7 ao dia 120. No Gfo apenas um olho teve sinéquia do dia 7 ao dia 90, contudo aos 120 dias, dois olhos formaram-na. A opacidade de cápsula posterior da lente esteve presente em todos os períodos, não havendo diferença estatística entre os grupos. Somente um olho, do Gfo, não teve formação de opacidade. A pressão intraocular foi normal em ambos os grupos. Não houve diferença estatística entre as lentes hidrofílicas e hidrofóbicas. O uso de lentes intraoculares apresentaram resultados satisfatórios na acuidade visual.(AU)

Schinus terebinthifolius Raddi extract and linoleic acid from Passiflora edulis synergistically decrease melanin synthesis in B16 cells and reconstituted epidermis.

Several treatments for skin whitening are available today, but few of them are completely adequate, especially owing to the carcinogenic potential attributed to classical drugs like hydroquinone, arbutin and kojic acid. To provide an alternative and safer technology for whitening, we developed two botanical compounds originated from Brazilian biodiversity, an extract of Schinus terebinthifolius Raddi and a linoleic acid fraction isolated from Passiflora edulis oil. The whitening effect of these compounds was assessed using biochemical assays and in vitro models including cellular assays and equivalent skin. The results showed that S. terebinthifolius Raddi extract is able to reduce the tyrosinase activity in vitro, and the combination of this extract with linoleic acid is able to decrease the level of melanin produced by B16 cells cultured with melanocyte-stimulating hormone. Furthermore, melanin was also reduced in human reconstituted epidermis (containing melanocytes) treated with the compounds. The combination of the compounds may provide a synergistic positive whitening effect rather than their isolated use. Finally, we demonstrated that the performance of these mixed compounds is comparable to classical molecules used for skin whitening, as kojic acid. This new natural mixture could be considered an alternative therapeutic agent for treating hyperpigmentation and an effective component in whitening cosmetics.

A new potent natural antioxidant mixture provides global protection against oxidative skin cell damage.

Oxidative stress occurs when there is an over production of free radicals and cells are not able to neutralize them by their own antioxidant mechanisms. These excess of free radicals will attack cellular macromolecules leading to cell damage, function impairment or death. Because of that, antioxidant substances have been largely used in products to offer complementary protection. In this study a new mixture of three known antioxidants (cocoa, green tea and alpha-tocopherol) was evaluated and its antioxidant protection was assessed focusing on its capacity to protect main cell macromolecules. Results have shown that it has a high antioxidant capacity by protecting lipids, DNA and proteins against oxidative damage. The antioxidant effect of the mixture on cells was also investigated and it was able to reduce oxidative stress generated by lipopolisacharide in human fibroblasts. Finally, as the mixture has proved to be highly antioxidant, its effect on cell senescence was evaluated, and it was demonstrated that fibroblasts in culture had delayed senescence when treated with these actives on a mixture. All results together provide important data about a new antioxidant mixture that uses a small amount of actives and is able to protect cell against oxidative damages in a global way.

Post-secretory events alter the peptide content of the skin secretion of Hypsiboas raniceps.

A novel family of antimicrobial peptides, named raniseptins, has been characterized from the skin secretion of the anuran Hypsiboas raniceps. Nine cDNA molecules have been successfully cloned, sequenced, and their respective polypeptides were characterized by mass spectrometry and Edman degradation. The encoded precursors share structural similarities with the dermaseptin prepropeptides from the Phyllomedusinae subfamily and the mature 28-29 residue long peptides undergo further proteolytic cleavage in the crude secretion yielding consistent fragments of 14-15 residues. The biological assays performed demonstrated that the Rsp-1 peptide has antimicrobial activity against different bacterial strains without significant lytic effect against human erythrocytes, whereas the peptide fragments generated by endoproteolysis show limited antibiotic potency. MALDI imaging mass spectrometry in situ studies have demonstrated that the mature raniseptin peptides are in fact secreted as intact molecules within a defined glandular domain of the dorsal skin, challenging the physiological role of the observed raniseptin fragments, identified only as part of the crude secretion. In this sense, stored and secreted antimicrobial peptides may confer distinct protective roles to the frog.

Molecular identification of four different alpha-amylase inhibitors from baru (Dipteryx alata) seeds with activity toward insect enzymes.

The endophytic bruchid pest Callosobruchus maculatus causes severe damage to storage cowpea seeds, leading to economical losses. For this reason the use of alpha-amylase inhibitors to interfere with the pest digestion process has been an interesting alternative to control bruchids. With this aim, alpha-amylase inhibitors from baru seeds (Dipteryx alata) were isolated by affinity chromatographic procedures, causing enhanced inhibition of C. maculatus and Anthonomus grandis alpha-amylases. To attempt further purification, this fraction was applied onto a reversed-phase HPLC column, generating four peaks with remarkable inhibition toward C. maculatus alpha-amylases. SDS-PAGE and MALDI-ToF analysis identified major proteins of approximately 5.0, 11.0, 20.0 and 55 kDa that showed alpha-amylase inhibition. Results of in vivo bioassays using artificial seeds containing 1.0% (w/w) of baru crude extract revealed 40% cowpea weevil larvae mortality. These results provide evidence that several alpha-amylase inhibitors classes, with biotechnological potential, can be isolated from a single plant species.

Antimicrobial peptide from the skin secretion of the frog Leptodactylus syphax.

Antimicrobial peptides are considered part of the innate immune system of the majority of living organisms. Most of these molecules are small, cationic and show amphiphilic nature. The skin secretions of Leptodactylus syphax were extracted by mild electrical stimulation and its semipreparative reverse-phase chromatography was resolved in more than 40 fractions. Among these fractions, an antimicrobial peptide was isolated and its amino acid sequence determined by de novo sequencing. Six other truncated forms were characterized in skin secretion. The longest one (25 amino acid residues), named syphaxin (SPX), is amidated at the C-terminal, and shares strong sequence similarity with antimicrobial peptides found in the skin secretion of leptodactylid frogs. Two of the truncated peptides (SPX(1-22) and SPX(1-16)) were tested against Escherichia coli and Staphylococcus aureus, showing low minimal inhibitory concentration (MIC) and no significant toxicity towards blood cells, including both leukocytes and erythrocytes, based on their direct incubation in whole blood at the highest MIC concentration (64 microg/mL).

Reação farmacodérmica decorrente do uso do levamisol: relato de caso / Pharmacodermic adverse reaction due to levamisole: a case report

Relata-se a ocorrência de um caso de farmacodérmica pelo levamisol e discute-se sobre a manifestação clínica e o estabelecimento do diagnóstico dessa reação cutânea adversa. O animal desenvolveu lesões exsudativas na face, com resolução espontânea após a suspensão do fármaco.

Effects of low-intensity pulsed ultrasound on wound healing in corneas of dogs following keratoplasty.

The effects of low-intensity pulsed ultrasound on wound healing were evaluated at the graft-cornea transition in dogs following lamellar keratoplasty using tunica vaginalis preserved in 98% glycerin. Twenty-one dogs were subdivided into three groups of seven animals. The first group (W/US) received daily treatment of low-intensity pulsed ultrasound (20 mW/cm2) for 15 min for the first 10 days post surgery. The second group (N/US) was submitted to the same procedure but with the ultrasound apparatus turned off. The third group, the control (CO), underwent the surgical procedure only. The animals were clinically evaluated during the initial (1-15 days), intermediate (16-30 days) and late (31-120 days) postoperative period. The corneas were evaluated by light microscopy at 1, 3, 7, 15, 30, 60 and 120 days after surgery. Clinically, there were no differences which would promote an advantage to any of the treatments. Light microscopy, however, revealed more extensive vascularization and more advanced wound healing in the W/US group, as well as a tendency towards early graft incorporation. Based on the present results, low-intensity pulsed ultrasound shows advantages, especially in situations where trophic support is a mandatory condition, facilitating better graft incorporation and rapid recovery of stromal organization.