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.

Laparoscopy-assisted radical nephrectomy with inferior vena caval thrombectomy for level II to III tumor thrombus: a single-institution experience and review of the literature.

PURPOSE: Laparoscopy-assisted radical nephrectomy and vena caval thrombectomy (LARN-VCT) is reported to be an alternative to open surgery for renal-cell carcinoma (RCC). We describe our experience and review the current literature evaluating the feasibility and safety of LARN-VCT. PATIENTS AND METHODS: We retrospectively reviewed the medical records of all patients who underwent laparoscopic radical nephrectomy for RCC at our institution between June 2004 and May 2009, and selected those who underwent LARN-VCT. We analyzed patients' clinical, radiographic, intraoperative, pathologic, and postoperative parameters. For the literature review, we performed a MEDLINE search to identify publications that focused on laparoscopic radical nephrectomy with VCT. RESULTS: LARN-VCT was completed in six of seven patients; elective conversion in one patient to open surgery occurred because of disease progression. Five of the six patients with RCC had no evidence of disease recurrence at a median follow-up of 16 months. The literature review revealed case reports and small series demonstrating the technical feasibility and safety of LARN-VCT in selected patients. CONCLUSIONS: LARN-VCT is a technically feasible approach in carefully selected patients with right-sided level II to III tumor thrombus. Optimal patient selection, extensive laparoscopic experience, and multidisciplinary support are critical elements for the safe application of this approach. Fluid and volume resuscitation must be thoughtfully considered given the transition from laparoscopy to open cross clamping of the vena cava. The worldwide literature on LARN-VCT is still limited and additional data are needed.

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).