New treatment strategies for Alzheimer's disease: is there a hope?

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease, and corresponds to the most common cause of dementia worldwide. Although not fully understood, the pathophysiology of AD is largely represented by the neurotoxic events triggered by the beta-amyloid cascade and by cytoskeletal abnormalities subsequent to the hyperphosphorylation of microtubule-associated Tau protein in neurons. These processes lead respectively to the formation of neuritic plaques and neurofibrillary tangles, which are the pathological hallmarks of the disease. Clinical benefits of the available pharmacological treatment for AD with antidementia drugs (namely cholinesterase inhibitors and memantine) are unquestionable, although limited to a temporary, symptomatic support to cognitive and related functions. Over the past decade, substantial funding and research have been dedicated to the search and development of new pharmaceutical compounds with disease-modifying properties. The rationale of such approach is that by tackling key pathological processes in AD it may be possible to attenuate or even change its natural history. In the present review, we summarize the available evidence on the new therapeutic approaches that target amyloid and Tau pathology in AD, focusing on pharmaceutical compounds undergoing phase 2 and phase 3 randomized controlled trials.

Evaluation of clinical and inflammatory markers of subclinical carotid atherosclerosis in postmenopausal women

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Rastreamento e detecção precose de doença aterosclerítica em pacientes com HIV positivo

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Síntese, caracterização e avaliação farmacológica de derivados N-acilhidrazônicos para a prevenção de aterotrombose

Atherosclerosis is a chronic inflammatory disease characterized by accumulation of lipid and fibrous components in arterial vessels, giving rise to atheromas. Development of Atheromatou plaques leads to arterial steatosis, triggering ischemic events. Atherotrombosis has a strong correlation with atherosclerosis, where rupture of atheromatous plaques cause release of vessel wall's pro-thrombotic components, activating platelet aggregation and thromosis. Due to the major role played by platelets on thrombus-embolic conditions, drugs that inhibit platelet aggregation demonstrate great relevance for atherothrombosis prevention, reducing patient mortality. Currently, there are a variety of drugs acting on several different targets, preventing platelet activation. However, these therapies demosntrate side effects such as thrombocytopenia, neutropenia, hemorrhage and low oral availability. Thus, the application of molecular modifications such as hybridization can produce novel, more efficient antiplatelet aggregation inhibitors. In this project we describe the synthesis and characterization of novel N-acilhydrazone compounds, acting through multiple mechanisms such as platelet calcium chelation and nitric oxide donation by furoxanic subunits. Furthermore, we demonstrate that such compounds exhibit biological activity in in vivo bleeding time, in vitro antiplatelet aggregation and in vivo antinociceptive assays. Therefore, novel N-acilhydrazone compounds demonstrate potential as antiplatelet drugs for atherothrombosis prevention.

Avaliação do perfil de risco de cárie dentária em gestantes de Araraquara, Brasil

The knowledge of risk of carried during pregnant is essential for an appropriate treatment using educational and preventives actions to mother for a good care of their oral health and that of children. The main objective of present retrospective study was to identify the risk of caries of pregnants (aged 15-44, mean= 25 years) came to clinic of Preventive Odontology of Araraquara-UNSEP from 1999 to 2007, using 166 medical records obtained by the third pregraduate year students, following the pre-established guidelines. The information collected includes: classification of caries risk diagnosis, pregnancy trimester, carbohydrates ingestion (between or during foods), dental plaques (O'Leary's plaque control registry) and the number of teeth with caries. The statistical analysis used the Chi2 and ANOVA tests. Most of patients showed a 25 % or more of teeth surfaces with dental plaques (92.1 %) and carbohydrates consumption among foods (89.2 %). The mean (SD) of carried and restores teeth was of 7.9 (5.1) and 4.0 (3.4), respectively and the posterior teeth were the more involved by caries/restorations. As regards the diagnosis of caries risk, classification of high risk was observed in the 38.5 % of pregnants, moderate in the 47.6 %) and low in the 13.9 %. There was a statistically significant association (p= 0.001) between the carbohydrates consumption and the diagnosis of caries risk. The plaque's rate was similar in the different trimesters of pregnancy (f= 0.223; p= 0.803). The caries risk of most pregnant women was high or moderate and it was associated with the consumption of carbohydrates.

Epitheliotropic cutaneous T-cell lymphoma associated with melanoma in a dog: case report

Several types of tumors affect dogs' skin. Simultaneously occurring neoplasms with different histological patterns might be rarely present in the same animal. This paper describes the occurrence of epitheliotropic cutaneous T-cell lymphoma and melanoma in a dog. The animal had nodular lesions in the abdominal region and serpiginous plaques on the dorsal region of the trunk. Cytology evidenced malignant fusiform cells from the abdominal lesions as well as few round cells from the dorsal. The histopathological examination of the abdominal lesions showed dermis with polygonal to spindle-shaped neoplastic cells. The lesion of the dorsal region evidenced neoplastic round cells with generally distinct cell borders and a moderate amount of eosinophilic cytoplasm. Abdominal lesions were positive for Melan A. Dorsal and forelimb lesions were positive for CD3. This study reports the occurrence of epitheliotropic cutaneous T-cell lymphoma and malignant melanoma in a crossbred Boxer dog and discusses the importance of performing immunohistochemical profile to confirm the phenotype of the tumor.

Sign of the kiss in dermatitis caused by vesicant beetles (potós or Paederus sp.)

The cosmopolitan beetles of the Paederus genus (potos) cause a severe dermatitis when the insect is crushed against the skin of exposed areas (the cervical region is the most affected). Toxins (pederin and others) from the hemolymph of the insect cause plaques and/or bizarre, linear lesions with erythema, edema, blisters, pustules, crusts and exulcerations. There may be a burning sensation and severe conjunctivitis. Lesions disappear after 10 days and may leave hyperchromic macules. Treatment is made with topical corticosteroids and intensive washing.

Lichenoid reaction: case report

Lichenoid lesions are mucocutaneous disease of chronic inflammatory origin. Can produce side effects to drugs, dental materials, affecting 0.5 to 1% of the world population mainly in women in the fourth decade of life. The history and meticulous clinical servation may clarify the reactive nature, but the clinical diagnosis will only be conclusive when associated with tests such as histopathology. Therefore the objective of the study is to report a case of a woman of 55 years old, complaining of "white spots sore". Reported being allergic to metals, chocolate, acidic foods and certain types of clothes. From accurate intraoral clinical examination, white plaques were found in the dorsum of the tongue, hard palate and buccal mucosa, inaccurate and rough limits, and ulcerations throughout the labial edge and upper palate. Histopathology revealed a lichenoid reaction. Was instituted as pharmacological treatment, the use of systemic corticosteroids. Clinical follow-up of one year showed reduction of clinical symptoms, allowing to conclude that the clinical follow-up of this disease is necessary since its dubious malignant potential and diagnostic difficulty. Thus, early recognition of this disease allows instituting appropriate treatment with relief of anxiety of the patient and their family.

Impacto de andrógenos na diferenciação e atividade de osteoclastos em cultura celular

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)