Encapsulation of Neurotoxins, Blockers of Nicotinic Acetylcholine Receptors, in Nanomaterials Based on Sulfated Polysaccharides.

Three-finger snake neurotoxins are selective antagonists of some nicotinic acetylcholine receptor subtypes and are widely used to study these receptors. The peptide neurotoxin azemiopsin, recently isolated from the venom of Azemipos feae, is a selective blocker of muscle-type nicotinic acetylcholine receptor. In order to reduce their toxicity and increase resistance under physiological conditions, we have encapsulated these toxins into nanomaterials. The study of nanomaterials after interaction with neurotoxins by the methods of transmission electron microscopy and dynamic light scattering revealed an increase in the size of nanoparticles, which indicates the inclusion of neurotoxins in nanomaterials.

Compression injury in the mouse spinal cord elicits a specific proliferative response and distinct cell fate acquisition along rostro-caudal and dorso-ventral axes.

Harnessing the regenerative capabilities of endogenous precursor cells in the spinal cord may be a useful tool for clinical treatments aimed at replacing cells lost as a consequence of disease or trauma. To better understand the proliferative properties and differentiation potential of the adult spinal cord after injury, we used a mouse model of compression spinal cord injury (SCI). After injury, adult mice were administered BrdU to label mitotic cells and sacrificed at different time-points for immunohistochemical analysis. Our data show that the rate of proliferation increased in all regions of the spinal cord 1day after injury, peaked after 3days, and remained elevated for at least 14days after injury. Proliferation was greater at the injury epicenter than in rostral and caudal adjacent spinal segments. The number of proliferative cells and rate of proliferation varied between dorsal and ventral regions of the spinal cord and between the gray and white matter. Newly generated cells expressed markers for progenitor cells (Nestin and Olig2), oligodendrocytes (Sox10), astrocytes (S100b and glial fibrillary acidic protein), and microglia (Iba1), but not neuronal markers (Map2 and NeuN). Marker expression varied with regard to the dorso-ventral region, rostro-caudal proximity to the injury epicenter, and time after injury. At early time-points after injury, BrdU(+) cells mainly expressed microglial/macrophage and astrocytic markers, while at these same time-points in the control spinal cord the mitotic cells predominately expressed oligodendrocyte and oligodendrocyte progenitor cell markers. The profile of proliferation and cell fate marker expression indicates that after moderate compression, the spinal cord has the capacity to generate a variety of glial cells but not neurons, and that this pattern is space and time specific. Future studies should focus on ways to control proliferation and cell fate after injury to aid the development of cell replacement treatments for SCI.

Vacuum therapy in erectile dysfunction--science and clinical evidence.

Vacuum therapy (VT) utilizes negative pressure to distend the corporal sinusoids and to increase the blood inflow to the penis. Depending on its purpose, VT could be used as vacuum constriction device (VCD), with the aid of an external constricting ring which is placed at the base of penis to prevent blood outflow, maintaining the erection for sexual intercourse. Also, as a vacuum erectile device (VED), without the application of a constriction ring, just increases blood oxygenation to the corpora cavernosa and for other purposes. The emerging of phosphodiesterase 5 inhibitors (PDE(5)I) for the treatment of erectile dysfunction (ED) eclipsed VCD as therapeutic choice for ED; however, widespread usage of VED as part of penile rehabilitation after radical prostatectomy and other purposes rekindle the interest for VT. The underlying hypothesis is that the artificial induction of erections shortly after surgery facilitates tissue oxygenation, reducing cavernosal fibrosis in the absence of nocturnal erections, and potentially increases the likelihood of preserving erectile function. Due to its ability to draw blood into the penis regardless of nerve disturbance, VED has become the centerpiece of penile rehabilitation protocols. Herein, we reviewed the history, mechanism, application, side effects and future direction of VT in ED.

Solution spatial structure of 'long' neurotoxin M9 from the scorpion Buthus eupeus by 1H-NMR spectroscopy.

1H-NMR spectra of Buthus eupeus neurotoxin M9 (66 amino acid residues, four disulfide bonds) reveal two slowly exchangeable conformations at acidic pH. The spatial structure of the conformer prevailing under physiologically relevant conditions has been determined from two-dimensional 1H-NMR data treated by means of a distance geometry algorithm and refined by molecular modelling. Interrelation between the structure and function of mammalian neurotoxin M9 is discussed by comparing its conformation with those of the scorpion insectotoxins which exhibit different biological specificity (insectotoxins v-2, v-3 and I5A).