Pulmonary homograft endocarditis after Ross procedure

We report the case of a 36-year-old patient who experienced an isolated acute pulmonary homograft endocarditis two years after a Ross procedure for aortic valve infective endocarditis.     

Bilateral anterior thalamic nucleus lesions and high-frequency stimulation are protective against pilocarpine-induced seizures and status epilepticus

OBJECTIVE: The thalamus is thought to play an important role in secondary generalization of seizures. The aim of the present study was to investigate the influence of anterior thalamic nucleus lesions and high-frequency stimulation in the pilocarpine model of secondarily generalized seizures in rats. METHODS: Adult Wistar rats underwent unilateral (n = 7) or bilateral anterior nucleus thalamotomies (n = 10), or unilateral (n = 4) or bilateral (n = 9) anterior thalamic nucleus stimulation through implanted electrodes. Control animals (n = 9) received bilateral implants but no stimulation. Seven days after these procedures, animals were provided pilocarpine (320 mg/kg intraperitoneally) to induce seizures and status epilepticus (SE). Electrographic recordings from hippocampal and cortical electrodes were evaluated, and ictal behavior was assessed. RESULTS: In the control group, 67% of the animals developed SE 15.3 +/- 8.8 minutes after pilocarpine administration. Neither unilateral anterior nucleus lesions nor stimulation significantly reduced the propensity or latency for developing seizures and SE. Bilateral thalamic stimulation did not prevent SE (observed in 56% of the animals), but it significantly prolonged the latency to its development (48.4 +/- 17.7 min, P = 0.02). Strikingly, no animal with bilateral anterior nucleus thalamotomies developed seizures or SE with pilocarpine. CONCLUSION: Bilateral anterior thalamic nuclear complex stimulation and thalamotomies were protective against SE induced by pilocarpine.     

Numerical simulation of electroporation in spherical cells

This article presents a numerical study of the electroporation process of spherical cells suspended in an electrolyte solution, using the equivalent circuit method (ECM) for field calculation proposed by Ramos et al. A model for the electric conductance of the cell membrane derived from the analytical and experimental results obtained by Glaser et al. for planar lipidic membranes was applied. The influence of the cell concentration and membrane properties (described in the model) on the membrane current, membrane potential, and dependence of the electrolyte conductivity on the applied electric field was studied. These results clarify the electric events connected with the pore opening process and allow the planning of experimental approaches to study reversible membrane rupture in real cells.     

Evolution of renal interstitial inflammation and NF-kappaB activation in spontaneously hypertensive rats

Lymphocytes and macrophages infiltrate the kidney of spontaneously hypertensive rats (SHR) and interventions leading to their reduction are associated with improvement of the hypertension. The present studies examined the evolution of the interstitial inflammation in the natural course of the SHR to gain insight on the potential role of interstitial immune cell accumulation in the development of hypertension. We studied SHR and control WKY rats at 3 weeks (SHR-3 wk group, n = 11 and WKY-3 wk group, n = 10), 11 weeks (SHR-11 wk group, n = 5 and WKY-11 wk group, n = 5) and 24 weeks (SHR-24 wk group, n = 10 and WKY-24 wk group, n = 10). The SHR-3 wk group was normotensive and older SHR developed hypertension that was severe in the SHR-24 wk group. Tubulointerstitial accumulation of lymphocytes, macrophages, angiotensin II-positive cells, cells expressing the p65 DNA-binding subunit of NF-kappaB and activation of NF-kappaB in the kidney were all significantly increased (p < 0.01) in the prehypertensive SHR-3 wk group and augmented progressively, with the highest values in the SHR-24 wk group. The SHR-24 wk group showed increased (p < 0.001) helper (CD4) T cell infiltration and a high CD4/CD8 ratio. These findings are consistent with the possibility that activation of NF-kappaB and renal interstitial infiltration of immune cells may be part of the pathophysiologic process that drives hypertension in the SHR.     

Pharmacokinetics of controlled-release polymers in the subarachnoid space after subarachnoid hemorrhage in rabbits

OBJECT: Implantation of controlled-release polymers into the subarachnoid space to deliver drugs for treatment of vasospasm after subarachnoid hemorrhage (SAH) is currently of interest. Among the issues regarding local delivery of drugs in the subarachnoid space, however, are the extent of diffusion and the rate of release of the loaded agents. In this study Evans blue dye (EBD) was loaded into controlled-release polymers and its pharmacokinetic properties were determined in vitro and in vivo by using a rabbit model of SAH. METHODS: Ethylene-vinyl acetate copolymer (EVAc) was loaded 40% (w:w) with EBD and its pharmacokinetics were spectrophotometrically determined in vitro by examining three EBD-EVAc polymers. Additional polymers were implanted either into the frontal lobe or into the cisterna magna of 16 New Zealand White rabbits. Subarachnoid hemorrhage was induced in eight of the animals by an injection of 1.5 ml of arterial blood into the cisterna magna. The animals were killed 3 or 14 days postoperatively, their brains and spinal cords were harvested, and samples of each were placed in formamide for dye extraction and quantification. Specimens were examined macroscopically and the concentrations of EBD were determined with the aid of a spectrophotometer. The EBD-EVAc polymers continuously released EBD over a 133-day period. The controlled release of the dye into the subarachnoid space in either location resulted in staining of the entire central nervous system (CNS) in rabbits when the polymers were placed either on the frontal lobe or in the cisterna magna. The EBD diffusion covered a distance of at least 40 cm. The presence of blood in the subarachnoid space did not interfere with the diffusion. CONCLUSIONS: In this study the authors define the rate and extent of diffusion of EBD from controlled-release polymers placed in the subarachnoid space under conditions of SAH. Evans blue dye diffused through the entire rabbit CNS, covering a distance greater than that of the longest dimension of the hemicircumference of the subarachnoid space around the human brain. The pharmacokinetic properties of EBD-EVAc polymers are comparable to those of antivasospasm agents that are successfully used in animal models of SAH.     

Inhibition of cerebral vasospasm by intracranial delivery of ibuprofen from a controlled-release polymer in a rabbit model of subarachnoid hemorrhage

OBJECT: Leukocyte-endothelial cell interactions may play a role in the development of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) because the extravasation of circulating leukocytes into the periadventitial space within 24 hours after the hemorrhage appears to be a critical event in this process. Ibuprofen is an antiinflammatory agent that inhibits the expression of specific cell adhesion molecules and, consequently, disrupts leukocyte-endothelial cell interactions. The authors investigated the efficacy of ibuprofen delivered locally from controlled-release polymers in the rabbit basilar artery (BA) model of cerebral vasospasm. METHODS: Ibuprofen was incorporated into controlled-release ethylene-vinyl acetate copolymer (EVAc) constituting 45% of the resulting polymer by weight. Fifty-four New Zealand White rabbits were randomized to 10 groups: sham operation (seven animals); SAH only (seven animals); and SAH plus either empty EVAc or ibuprofen-EVAc polymer at 30 minutes or 6, 12, or 24 hours (five animals per group; 40 total). The rabbits were killed 72 hours after induction of SAH, at the time of maximal vasospasm. The efficacy of ibuprofen in preventing vasospasm was assessed by measuring lumen patency of the rabbit's BAs. The intracranial controlled release of ibuprofen resulted in a significant inhibition of vasospasm when treatment was initiated at 30 minutes (patency 92.3 +/- 5.1% compared with 52.1 +/- 5.1% in animals given empty EVAc; p < 0.001) and 6 hours (patency 69.5 +/- 3.5% compared with 47.2 +/- 1.5% in animals given empty EVAc; p < 0.03) after blood deposition compared with treatment with empty EVAc. No effect was observed when treatment was begun at either 12 or 24 hours. CONCLUSIONS: Local intracranial delivery of ibuprofen accomplished using controlled-release polymers prevents vasospasm in the rabbit BA model of vasospasm when administered within 6 hours after blood exposure.