Inhibition of malaria parasite Plasmodium falciparum development by crotamine, a cell penetrating peptide from the snake venom.

We show here that crotamine, a polypeptide from the South American rattlesnake venom with cell penetrating and selective anti-fungal and anti-tumoral properties, presents a potent anti-plasmodial activity in culture. Crotamine inhibits the development of the Plasmodium falciparum parasites in a dose-dependent manner [IC50 value of 1.87 µM], and confocal microscopy analysis showed a selective internalization of fluorescent-labeled crotamine into P. falciparum infected erythrocytes, with no detectable fluorescence in uninfected healthy erythrocytes. In addition, similarly to the crotamine cytotoxic effects, the mechanism underlying the anti-plasmodial activity may involve the disruption of parasite acidic compartments H(+) homeostasis. In fact, crotamine promoted a reduction of parasites organelle fluorescence loaded with the lysosomotropic fluorochrome acridine orange, in the same way as previously observed mammalian tumoral cells. Taken together, we show for the first time crotamine not only compromised the metabolism of the P. falciparum, but this toxin also inhibited the parasite growth. Therefore, we suggest this snake polypeptide as a promising lead molecule for the development of potential new molecules, namely peptidomimetics, with selectivity for infected erythrocytes and ability to inhibit the malaria infection by its natural affinity for acid vesicles.

Feasibility of an endoscopic approach to the axillary nerve and the nerve to the long head of the triceps brachii with the help of the Da Vinci Robot.

Surgery to transfer the axillary nerve and the nerve of the long head of the triceps presents two obstacles: 1) the access portals are not standardized and 2) the nerves are for their larger part approached through large incisions. The goal of this study was to explore the feasibility of an endoscopic microsurgical approach. The posterior aspect of a cadaver shoulder was approached through three communicating mini-incisions. The Da Vinci robot camera was installed on a central trocart, and the instrument arms on the adjacent trocarts. A gas insufflation distended the soft tissues up to the lateral axillary space. The branches of the axillary nerve and the nerve to the long head of the triceps brachii muscle were identified. The dissection of the axillary nerve trunk and its branches was easy. The posterior humeral circumflex veins and artery were dissected as well without any difficulty. Finding the nerve to the long head of the triceps brachii was found to be more challenging because of its deeper location. Robots properties allow performing conventional microsurgery: elimination of the physiologic tremor and multiplication of the movements. They also facilitate the endoscopic approach of the peripheral nerves, as seen in our results on the terminal branches of the axillary nerve and the nerve to the long head of the triceps brachii.

[Study of apoptosis and mitosis mechanisms in the eye. Experimental model of gestational toxic syndrome]. / Estudio de los mecanismos de apoptosis y mitosis en el globo ocular. Modelo experimental del síndrome tóxico gestacional.

OBJECTIVE: To improve knowledge of the mechanisms of cellular differentiation and proliferation during retinal development, by studying cellular and molecular damage in a rat model of prenatal ethanol exposure. METHODS: Female, juvenile Wistar rats (200g body weight) and their offspring were divided into two groups, which were fed a liquid diet: 1) ethanol-exposed group (5% ethanol weight/vol as 35% of daily total calories) and 2) isocaloric control group (maltose/dextrin as 35% of daily total calories). Eyeballs were obtained at 21 days of gestation, embedded in paraffin, and immunodetection procedures performed on apoptotic (TUNEL) and mitotic profiles, which were observed and photographed using a confocal microscope. RESULTS: Analysis of the microphotographs revealed a statistically significant increase of apoptotic profiles and a decrease in mitotic profiles in the ethanol exposed group compared to controls (p<0.05). Ganglion cells and photoreceptors showed more changes than other retinal cell phenotypes. These findings suggest that abnormalities in the differentiation and proliferation processes of the retina were caused by the alcohol exposure. CONCLUSIONS: Alcohol abuse during pregnancy alters development of the visual system by inducing developmental changes in the mitotic and apoptotic processes of the retina. These latter changes may be the result of changes in the expression of regulatory genes as well as the result of alteration in signalling pathways for both differentiation-proliferation and apoptotic events.