Thistedhyde8843

BACKGROUND Chronic midline low back pain is the number one reason for disability in the United States despite the prolific use of medical and surgical interventions. Notwithstanding the widespread use of epidural spinal cord stimulators (SCSs), there remains a large portion of the population with inadequate pain control thought to be because of the limited volume of stimulated neural tissue. Intradural SCSs represent an underexplored alternative strategy with the potential to improve selectivity, power efficiency, and efficacy. We studied and carried out development of an intradural form of an SCS. Herein we present the findings of in vivo testing of a prototype intradural SCS in a porcine model. Selleckchem Salinomycin METHODS Six female juvenile pigs underwent surgical investigation. One control animal underwent a laminectomy only, whereas the 5 other animals had implantation of an intradural SCS prototype. One of the prototypes was fully wired to enable acute stimulation and concurrent electromyographic recordings. All animals underwent terminal surgery 3 months postimplantation, with harvesting of the spinal column. Imaging (microcomputed tomography scan) and histopathologic examinations were subsequently performed. RESULTS All animals survived implantation without evidence of neurologic deficits or infection. Postmortem imaging and histopathologic examination of the spinal column revealed no evidence of spinal cord damage, cerebrospinal fluid fistula formation, abnormal bony overgrowth, or dural defect. Viable dura was present between the intra- and extradural plates of the device. Electromyographic recordings revealed evoked motor units from the stimulator. CONCLUSIONS Chronically implanted intradural device in the porcine model demonstrated safety and feasibility for translation into humans. BACKGROUND Surgical treatment for symptomatic extracranial carotid artery aneurysms should be encouraged because of their high recurrence rates. CASE DESCRIPTION A 55-year-old man presented with progressive right-sided hemiparesis and dysarthria. Computed tomography angiography revealed the cause of his repeated cerebral infarction was due to the distal emboli from an intra-aneurysmal thrombus of a giant thrombosed aneurysm at the origin of left common carotid artery. Right common carotid artery-saphenous vein graft-left common carotid artery bypass followed by left common carotid artery ligation was successfully performed. CONCLUSIONS Carotid-carotid bypass followed by common carotid artery ligation is an optional procedure for symptomatic proximal common carotid artery aneurysm. Conventional ophthalmic eye drops are limited by their rapid elimination rate and short time of action. Ion exchange resin has been used to achieve sustained ocular drug delivery but the high selectivity of drug molecules restricts its broad application. In situ gel system seems to be a good strategy to address these problems but the influence of in situ gel type on the sustained release behavior and tissue distribution after ocular application is unclear. Therefore, in this study, using betaxolol hydrochloride as a model drug, poloxamer 407 and methylcellulose as the carriers, two thermosensitive in situ gel systems were prepared and characterized. Influence of formulation composition type and concentration on in vitro drug release was studied. Tissue distribution after ocular delivery of two different thermosensitive in situ gels was studied and compared with commercial BH eye drop (Betoptic S®). In vitro studies demonstrated that addition of 4% HPMC 606W in 15% P407 solution and 5% PEG4000 in 2% MC solution obtained gels with appropriate gelation temperature and similar sustained drug release rate. In vivo tissue distribution study indicated that they presented similar drug concentration in cornea, iris-ciliary and aqueous humor irrespective of gel type, with higher drug concentration achieved after 4 h compared to the commercial resin suspension eye drops. The AUC and MRT of the two in situ gel eye drops were 2 times higher than that of the commercial resin suspension eye drops in cornea. In conclusion, the two thermosensitive in situ gels have prolonged drug release after ocular drug delivery compared with ion exchange resin eye drops, implying their potential applications in clinic with broad drug adoptability. Finite dose experiments represent clinical use wherein depletion of dose, evaporation of excipients, and gradual change in vehicle composition may occur. In the present study, we attempted a mathematical approach for predicting skin permeation and concentration of a cosmetic active, rhododendrol (RD), from complex vehicle-based formulations applied in finite dose. In vitro skin permeation and concentration studies of RD were conducted from formulations containing water and polyols with concentrations ranging from 10 to 100% under infinite and finite dose conditions using vertical Franz diffusion cells. Observed data for skin permeation and the viable epidermis and dermis (VED) concentration of RD were estimated by the differential equations under Fick's second law of diffusion together with water evaporation kinetics and changes in the partition coefficient from vehicles to the stratum corneum. As a result, a goodness-of-fit was observed allowing accurate estimation of skin permeation and VED concentration of RD. This mathematical approach could become a useful tool to estimate the skin permeation and concentration of actives from topical formulation applied in finite dose conditions likened in actual use. Niosomes are novel carriers that show superior transdermal permeation enhancement but require the addition of charged stabilizers. In this study, niosomes were prepared using Span 40, cholesterol, and sodium dodecyl sulfate (SDS) as stabilizers for transdermal delivery of salidroside. At concentrations of 0.05-0.40% (w/v), SDS significantly increased the zeta potential of the nanovesicles from -18.5 ± 3.2 to -157.0 ± 5.2 mV and improved the stability of the niosomal formulations. Niosomes prepared with a Span 40cholesterol molar ratio of 43 and 0.1% SDS showed good stability and the highest transdermal drug delivery among all tested formulations, with 2.75-fold higher transdermal flux of 20.26 ± 1.05 μg/(cm2·h) than that of aqueous salidroside solution. However, excess SDS increased the negative charge on the vesicle surface and hence repulsion with skin cells, leading to reduced drug entrapment efficiency and cellular uptake of niosomes. Although SDS in the niosomes dose-dependently increased the in vitro cytotoxicity of the formulation in skin cells, HaCaT and CCC-ESF-1 cell viability was ≥ 80% for formulations containing ≤0.