Bufotenine, a tryptophan-derived alkaloid, suppresses the symptoms and increases the survival rate of rabies-infected mice: the development of a pharmacological approach for rabies treatment

Between 40,000-70,000 people die yearly of rabies, an incurable disease. Besides post-bite vaccination, no treatment is available for it. Methods: First, virus dilution for antiviral effects in mice was determined. Then, animals were treated as follows: control (NaCl 250 µL/animal/day); bufotenine (0.63, 1.05 and 2.1 mg in 250 µL of NaCl/animal/day); rabies (10-6,82CVS dilution); and test (10-6,82 CVS dilution and bufotenine, in the above-mentioned doses). Animals were observed daily for 21 days or until the 3rd stage of rabies infection. Twitch-tension and liposome studies were applied to understand the possible interaction of bufotenine with receptors, particularly acetylcholine. Results: Bufotenine was able to increase the survival rate of intracerebrally virus-infected mice from 15 to 40%. Bufotenine did not seem to interfere with the acetylcholine response in the skeletal muscle, indicating that its mechanism of action is not blocking the virus entrance due to nAChR antagonism. By analyzing liposomes, we could observe that bufotenine did not passively penetrates cell membranes, indicating the necessity of complementary structures to cell penetration. Conclusions: Bufotenine is a promising candidate for drug development. After further chemical modification, it might be possible to dissociate minor side effects, increase efficiency, efficacy and pharmacokinetics, yielding a true anti-rabies drug.(AU)

Influence of additional weight on the frequency of kicks in infants with Down syndrome and infants with typical development

BACKGROUND: Infants with Down syndrome present with organic and neurological changes that may lead to a delay in the acquisition of motor skills such as kicking, a fundamental skill that is a precursor of gait and is influenced by intrinsic and extrinsic factors. Therefore, this movement should be taken into account in early physical therapy interventions in infants. OBJECTIVE: To analyze and to compare the effect of additional weight on the frequency of kicks in infants with Down syndrome and infants with typical development at 3 and 4 months of age. METHOD: Five infants with Down syndrome and five with typical development at 3 and 4 months of age were filmed. The experiment was divided into four experimental conditions lasting 1 minute each: training, baseline, weight (addition of ankle weight with 1/3 the weight of the lower limb), and post-weight. RESULTS: There were significant differences between groups for all variables (p<0.05), with lower frequencies observed for infants with Down syndrome in all variables. There were significant differences between the experimental conditions baseline and post-weight (p<0.001) for both groups in the frequency of contact and success, with a higher frequency in the post-weight condition. CONCLUSIONS: The weight acted as an important stimulus for both groups, directing the kicks toward the target and improving the infants' performance in the task through repetition, however, the infants with Down syndrome had lower frequencies of kicks. .

Preferência podal em lactentes com síndrome de Down: fatores extrínsecos e intrínsecos / Foot preference in infants with Down syndrome: extrinsic and intrinsic factors

Durante o processo de aquisição do chute em lactentes, a preferência podal pode ser influenciada de forma diferente pelos fatores extrínsecos e intrínsecos. O objetivo foi comparar a preferência podal e verificar a influência do peso adicional e do Reflexo Tônico Cervical Assimétrico (RTCA) na preferência podal entre lactentes com síndrome de Down e típicos. Participaram do estudo cinco lactentes com síndrome de Down e cinco típicos aos três e quatro meses de idade. O experimento foi subdividido em quatro condições experimentais: Treinamento, Linha de Base, Peso e Pós-Peso. Os lactentes com síndrome de Down apresentaram preferência à esquerda ou indefinida e os típicos, preferência à direita. O RTCA influenciou na preferência podal em ambos os grupos, indicando que o lado de rotação da cabeça orientou o chute do mesmo lado. Nos lactentes com síndrome de Down a correlação entre RTCA e chutes foi positiva, sendo forte aos três meses e moderada aos quatro meses. Para os lactentes típicos foi observada correlação positiva fraca aos três meses, e aos quatro meses a correlação não foi estatisticamente significativa. Lactentes com síndrome de Down apresentam preferência podal contrária aos lactentes típicos. O RTCA exerce influência na preferência podal por um período mais longo em lactentes com síndrome de Down em comparação aos lactentes típicos.

During the acquisition process of the kick in infants, foot preference may be influenced differently by extrinsic and intrinsic factors. The aim was to compare the foot preference and find the influence of additional weight and Asymmetrical Neck Tonic Reflex (ANTR) on the foot preference of infants with Down syndrome and typical ones. Five infants with Down syndrome and five typical infants at three and four months of age participated of the sudy. The experiment was divided into four experimental conditions: Training, Baseline, Weight and After Weight. Infants with Down syndrome showed preference to the left or indefinite, the typical infants showed preference to the right. ANTR influenced the foot preference in both groups, indicanting that the rotation of head side oriented the kicking for the same side. For infants with Down syndrome the correlation between ANTR and kicking was positive, with a strong positive correlation at three months of age and a moderate positive correlation at four months of age observed. For typical infants it was observed weak positive correlation at three months of age and at four months of age, the correlation was not significant. Infants with Down syndrome have foot preference contrary to typical infants. ATNR influences the foot preference for a longer period in infants with Down syndrome compared to typical infants.