The effect of palytoxin on neuromuscular junctions in the anococcygeus muscle of the rat

Palytoxin, a highly toxic natural product isolated from zoanthids of the genus Palythoa, is accumulated by a wide range of fishes and marine invertebrates used as food in the Indo-Pacific. It is responsible for many incidents of human morbidity and mortality. The toxin is a potent smooth muscle spasmogen. The cause of the contraction of smooth muscle is unclear, but recent work strongly suggests that it is primarily initiated by the release of neurotransmitters from the motor innervation of the smooth muscle. We show here that palytoxin caused the swelling of the muscle cells and some internal organelles of the anococcygeus muscle of the rat, but no substantial structural damage to the tissue. Axons and Schwann cells were also swollen but the most dramatic feature was the depletion of synaptic vesicles from putative release sites in the axons. Some axons were physically damaged following exposure to the toxin, but this was relatively uncommon (<10% of all axons studied). In the majority of axons there was no damage to nerve terminal membranes, but there was damage to mitochondria. The depletion of vesicles involved all types – clear, dense-cored, large and small. Our observations and pharmacological data gathered elsewhere, provide a neuropathological basis for the spasmogenic activity of palytoxin.     

Cosolvency of Dimethyl Isosorbide for Steroid Solubility

Dimethyl isosorbide (DMI), which is currently under investigation for its potential use as a pharmaceutical vehicle and drug permeation enhancer, is a water-miscible liquid with relatively low viscosity. The solubilization behavior of DMI as a cosolvent for nonpolar drugs was characterized via dielectric constant measurements of binary solvent systems containing DMI and either water, propylene glycol (PG), or polyethylene glycol (PEG). Evidence from the dielectric constant profiles and NMR studies suggest that DMI undergoes complexation with water and PG, but not with PEG, through hydrogen bonding interactions. The solvent complexation exhibited a major effect on the solubilities of prednisone, dexamethasone, and prednisolone in the mixed solvent systems. Maximum solubility of each drug was found to occur near a DMI/water or DMI/PG concentration ratio of 1:2. In the DMI–PEG mixed system, while there is no apparent interaction between DMI and PEG molecules, the solubility of prednisone was found to increase with decreasing dielectric constant.     

Screw angulation affects bone-screw stresses and bone graft load sharing in anterior cervical corpectomy fusion with a rigid screw-plate construct: a finite element model study

Background contextAnterior corpectomy and reconstruction with bone graft and a rigid screw-plate construct is an established procedure for treatment of cervical neural compression. Despite its reliability in relieving symptoms, there is a high rate of construct failure, especially in multilevel cases.PurposeThere has been no study evaluating the biomechanical effects of screw angulation on construct stability; this study investigates the C4–C7 construct stability and load-sharing properties among varying screw angulations in a rigid plate-screw construct.Study designA finite element model of a two-level cervical corpectomy with static anterior cervical plate.MethodsA three-dimensional finite element (FE) model of an intact C3–T1 segment was developed and validated. From this intact model, a fusion model (two-level [C5, C6] anterior corpectomy) was developed and validated. After corpectomy, allograft interbody fusion with a rigid anterior screw-plate construct was created from C4 to C7. Five additional FE models were developed from the fusion model corresponding to five different combinations of screw angulations within the vertebral bodies (C4, C7): (0°, 0°), (5°, 5°), (10°, 10°), (15°, 15°), and (15°, 0°). The fifth fusion model was termed as a hybrid fusion model.ResultsThe stability of a two-level corpectomy reconstruction is not dependent on the position of the screws. Despite the locked screw-plate interface, some degree of load sharing is transmitted to the graft. The load seen by the graft and the shear stress at the bone-screw junction is dependent on the angle of the screws with respect to the end plate. Higher stresses are seen at more divergent angles, particularly at the lower level of the construct.ConclusionThis study suggests that screw divergence from the end plates not only increases load transmission to the graft but also predisposes the screws to higher shear forces after corpectomy reconstruction. In particular, the inferior screw demonstrated larger stress than the upper-level screws. In the proposed hybrid fusion model, lower stresses on the bone graft, end plates, and bone-screw interface were recorded, inferring lower construct failure (end-plate fractures and screw pullout) potential at the inferior construct end.     

Linear and angular measurements of computer-generated models: are they accurate, valid, and reliable?

INTRODUCTION: Traditional advanced imaging modalities such as CT and MRI are limited in their ability to perform accurate linear distance and angular measurements regardless of anatomical orientation. The construction of 3D models has been used to perform anthropometric analyses as well as in the reconstruction of rapid prototypes. We hypothesized that such measurements would be precise to within 2 mm or 2 degrees of measurements performed with a coordinate measurement machine (CMM). We also hypothesized that there would be a high degree of interobserver reliability with these measurements. MATERIALS AND METHODS: Multiple aluminum screws were implanted in various positions in three foam pelvises which were subsequently scanned by CT and rendered as 3D models using a commercially available software package (Mimics). Linear and angular measurements were performed using a CMM machine, the software package, and a dial caliper or goniometer. The deviation of the measurements from the CMM data was compared using ANOVA. The interobserver reliability of both the manual and computer-generated measurements was calculated. RESULTS: The mean difference between the CMM distances and those measured manually and with the software was 2.12 +/- 1.20 mm and 1.57 +/- 1.05 mm, respectively. The mean difference between the CMM angular measurements and the angular measurements performed manually and with the software was 4.07 +/- 4.70 degrees and 1.62 +/- 1.32 degrees, respectively. In all cases, the manual measurements were significantly less accurate (p < 0.0001) and there was a high degree of interobserver reliability. CONCLUSIONS: Computer-generated measurements taken from three-dimensionally reconstructed models are more accurate than manual measurements and are within 2 mm and 2 degrees of measurements performed with a CMM. These measurements have high interobserver reliability.     

Coronary stenting for coronary artery narrowing in a heart transplant recipient

Transplant atherosclerotic coronary disease remains the leading cause of death in heart transplant recipients. We report the first case of coronary stent implantation in a heart graft for epicardial focal stenosis. Due to the lower rate of restenosis after stenting in the native coronary artery, we suggest that coronary stenting be considered an acceptable, first intention therapeutic option instead of angioplasty alone whenever possible.     

Reduction in acute rejections decreases chronic rejection graft failure in children: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

Chronic rejection accounted for 32% of all graft losses in 7123 pediatric transplants. In a previous study acute, multiple acute and late acute rejections were risk factors for the development of chronic rejection. We postulated that the recent decrease in acute rejections would translate into a lower risk for chronic rejection among patients with recent transplants. We reviewed our data on patients transplanted from 1995 to 2000, and using multivariate analysis and a proportional hazards model developed risk factors for patients whose grafts had failed due to chronic rejection. A late initial rejection increased the risk of chronic rejection graft failure 3.6-fold (p < 0.001), while a second rejection resulted in further increase of 4.2-fold (p < 0.001). Recipients who received less than 5 mg/kg of cyclosporine at 30 days post-transplant had a relative risk (RR) of 1.9 (p = 0.02). Patients transplanted from 1995 to 2000 had a significantly lower risk (RR = 0.54, p < 0.001) of graft failure from chronic rejection than those who received their transplants earlier (1987-94). Since we were able to demonstrate that there is a decreased risk of chronic rejection graft failure in our study cohort, we would conclude that the goal of future transplants should be to minimize acute rejections.