New fraternine analogues: Evaluation of the antiparkinsonian effect in the model of Parkinson's disease.

Venom-derived peptides are important sources for the development of new therapeutic molecules, especially due to their broad pharmacological activity. Previously, our research group identified a novel natural peptide, named fraternine, with promising effects for the treatment of Parkinson's disease. In the present paper, we synthesized three peptides bioinspired in fraternine: fra-10, fra-14, and fra-24. They were tested in the 6-OHDA-induced model of parkinsonism, quantifying motor coordination, levels of TH+ neurons in the substantia nigra pars compacta (SN), and inflammation mediators TNF-α, IL-6, and IL-1ß in the cortex. Peptides fra-14 and fra-10 improved the motor coordination in relation to 6-OHDA lesioned animals. However, most of the peptides were toxic in the doses applied. All three peptides reduced the intensity of the lesion induced rotations in the apomorphine test. Fra-24 higher dose increased the number of TH+ neurons in SN and reduced the concentration of TNF-α in the cortex of 6-OHDA lesioned mice. Overall, only the peptide fra-24 presented a neuroprotection effect on dopaminergic neurons of SN and a reduction of cytokine TNF-α levels, making it worthy of consideration for the treatment of PD.

Toxicity and toxin identification in Colomesus asellus, an Amazonian (Brazil) freshwater puffer fish.

Toxicity and toxin identification in Colomesus asellus, an Amazonian (Brazil) freshwater puffer fish. By using four different techniques--mouse bioassay, ELISA, HPLC and mass spectrometry-we evaluated the toxicity in the extracts of C. asellus, a freshwater puffer fish from the rivers of the Amazon, and identified for the first time the components responsible for its toxicity. The T20G10 monoclonal antibody raised against TTX, and employed in an indirect competitive enzyme immunoassay, showed very low affinity for the C. asellus extracts, indicating that TTX and its analogs are not the main toxic components of the extracts. This antibody was efficient in detecting presence of TTX in a total extract of Sphoeroides spengleri, which is one of the most toxic puffer fish found in the Atlantic coast. Extracts of C. asellus were toxic when administered intraperitonially into mice with an average toxicity of 38.6+/-12 mouse unit (MU)/g, while HPLC analysis indicated a lower toxin content (7.6+/-0 5MU/g). The HPLC profile showed no traces of TTX, but only the presence of PSPs (STX, GTX 2 and GTX 3). These toxins were also confirmed by electrospray ionization mass spectrometry.

Síndrome de Mõbius: significados na vida dos portadores / Mõbius syndrome: the meaning in the life of the carriers

JUSTIFICATIVA E OBJETIVO: A síndrome de Mõbius, evento raro, resulta de uma desordem neurológica que se caracteriza por paralisia congênita do sétimo par de nervos cranianos, acompanhada de mal formações límbicas e das demais estruturas orofaciais. Caracteriza-se clinicamente pela ausência de expressão facial e distúrbios da fala, principalmente. Tais alterações influenciam diretamente na vida social do portador. Trata-se de uma síndrome rara, por isso pouco estudada, sendo o aspecto emocional não abordado pela literatura atual. O objetivo deste estudo foi identificar o sentimento e o significado da síndrome na vida de seus portadores. MÉTODOS: Foram entrevistados portadores da síndrome e, por meio do Discurso do Sujeito Coletivo, buscou-se avaliar o significado da síndrome. RESULTADOS: Evidenciou-se que, apesar das malformações e das dificuldades na fala, que impõem dificuldades no dia a dia, há adaptação por parte dos sindrômicos, que vivem normalmente. CONCLUSÃO: Os portadores da síndrome de Mõbius reconhecem as dificuldades impostas por sua condição, mas se adaptam bem a elas vivendo normalmente.

BACKGROUND AND OBJECTIVE: The Moebius syndrome, a rare disorder, results from a neurological disorder that is characterized by congenital paralysis of the seventh cranial nerve accompanied by limbic and other orofacial structures malformations. It is clinically characterized by the absence of facial expression and speech disorders, especially. These changes directly influence the social life of the patient. This is a rare syndrome, so, little studied, and the emotional aspect not addressed by the current literature. The objective of this article was to identify the feeling and the meaning of the syndrome in the lives of their carriers. METHODS: Patients with the syndrome were interviewed and through the Collective Subject Discourse, we seek to assess the significance of this syndrome. RESULTS: The results showed that despite the defects and difficulties in speech, which imposes difficulties in day-to-day, there is adaptation by the syndromic, which normally live. CONCLUSION: Moebius syndrome carriers recognize the difficulties imposed by their condition, but they adapt well to living normally.

Outer membrane vesicles (OMVs) and detoxified lipooligosaccharide (dLOS) obtained from Brazilian prevalent N. meningitidis serogroup B strains protect mice against homologous and heterologous meningococcal infection and septic shock.

Neisseria meningitidis (N. meningitidis) is a serious bacterial pathogen that causes life-threatening invasive bacterial infections especially in children below 2 years of age, teenagers and young adults. We have investigated the protective potential of outer membrane vesicles (OMVs) and detoxified lipooligosaccharide (dLOS) obtained from Brazilian prevalent N. meningitidis serogroup B strains. Swiss mice were immunized with different combinations of OMV and dLOS from N. meningitidis serogroup B strains compared to a reference vaccine (VA-MENGOC-BC), Cuba). The OMVs + dLOS from Brazilian prevalent strains induced higher bactericidal antibody titers against homologous and heterologous target strains and stronger inhibition of thrombocytopenia as compared to the reference vaccine. When the challenge was performed with the B strain, all immunogens tested showed similar survival rates (80%) significantly higher than the control group. Bacterial clearance against the group B strain was comparable for animals immunized with the tested immunogen and the reference vaccine. Inclusion of dLOS from the B strain with the OMV, induced a similar clearance of C strain bacteria as compared to VA-MENGOC-BC. The immunogens, as well as the reference vaccine drastically inhibited increases in TNF-alpha and IL-6 plasma levels after challenge. In conclusion, the OMV/dLOS formulation obtained from Brazilian prevalent strains of N. meningitidis has a remarkable performance protecting mice against the lethal effects of meningococcal challenge showing a good potential as a vaccine and should be considered for clinical evaluation.