Ex Vivo Application of Carbon Monoxide in University of Wisconsin Solution to Prevent Intestinal Cold Ischemia/Reperfusion Injury

Carbon monoxide (CO), a byproduct of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. In vivo recipient CO inhalation at low concentrations prevented ischemia/reperfusion (I/R) injury associated with small intestinal transplantation (SITx). This study examined whether ex vivo delivery of CO in University of Wisconsin (UW) solution could ameliorate intestinal I/R injury. Orthotopic syngenic SITx was performed in Lewis rats after 6 h cold preservation in control UW or UW that was bubbled with CO gas (0.1-5%) (CO-UW). Recipient survival with intestinal grafts preserved in 5%, but not 0.1%, CO-UW improved to 86.7% (13/15) from 53% (9/17) with control UW. At 3 h after SITx, grafts stored in 5% CO-UW showed improved intestinal barrier function, less mucosal denudation and reduced inflammatory mediator upregulation compared to those in control UW. Preservation in CO-UW associated with reduced vascular resistance (end preservation), increased graft cyclic guanosine monophosphate levels (1 h), and improved graft blood flow (1 h). Protective effects of CO-UW were reversed by ODQ, an inhibitor of soluble guanylyl cyclase. In vitro culture experiment also showed better preservation of vascular endothelial cells with CO-UW. The study suggests that ex vivo CO delivery into UW solution would be a simple and innovative therapeutic strategy to prevent transplant-induced I/R injury.     

Pancreatic metastasis of malignant melanoma diagnosed by EUS-guided fine needle aspiration (EUS-FNA)]

Pancreatic metastasis of malignant melanoma is rarely diagnosed while the patient is alive. We report a case of metastatic melanoma of the pancreas in a 35-year-old woman presenting with a solid mass of the pancreas. Her past medical history included a radical hysterectomy 2 years previously for malignant melanoma of the vagina. Twelve months later, lung metastasis was also resected. EUS-guided fine needle aspiration (EUS-FNA) identified that the pancreatic tumor was histologically and immunohistochemically identical to the surgical specimen of her lung neoplasm. Imaging studies including US, CT, and MRI have limited value to distinguish the tumors from primary ductal adenocarcinoma. EUS-FNA can provide tissue diagnosis from pancreatic masses, specifically when other modalities have failed.     

Effectiveness of short-contact topical tretinoin in promoting wound healing in db/db mice.

We have investigated the effects of short-contact topical application of tretinoin using 16 male db/db mice by creating two full-thickness wounds on the skin of the back. A 0.1% tretinoin aqueous gel was applied to one wound for five minutes daily for five successive days while only aqueous gel was applied to the other (control). The mean (SD) percentage surface area unhealed before and after treatment were 0.88 (0.3) and 0.64 (0.15). In tretinoin-treated mice and non-treated mice (controls), the mean (SD) thicknesses of granulation were 1.383 (697) micro m and 683 (413) micro m, the density of capillary vessels in granulation was 12.2 (5.5)% and 5.7 (3.9)%, respectively. Differences between the two groups were significant for each variable. Wound healing was accelerated with short-contact topical application of tretinoin in db/db mice.     

Changes in the distribution of filipin-sterol complexes in the boar sperm head plasma membrane during epididymal maturation and in the uterus.

The distribution of filipin-sterol complexes (FSCs) and intramembranous particles (IMPs) in the plasma membrane of the late spermatid of the boar and of the sperm obtained from the epididymides, ejaculates, and uterus 2 hours after mating was examined by a freeze-fracture replica technique. In the late spermatid, the FSC density was found to be very low. A majority of the FSCs in the acrosomal plasma membrane (APM) appeared as protuberances on the E face in the epididymal, ejaculate, and uterine sperm. The density of the FSCs in the principal segment (PS) of the APM was 291 +/- 44 FSC/microns2 (mean +/- standard deviation, S.D.), 322 +/- 41 FSC/microns2 and 355 +/- 31 FSC/microns2 in the caput, corpus, and cauda epididymidis, respectively. In comparison with the cauda epididymal sperm, the FSC density gradually decreased in the PS of the ejaculated (277 +/- 39 FSC/microns2) and uterine sperm (243 +/- 50 FSC/microns2). The reduction was especially remarkable in the equatorial segment (ES), where the density of FSCs in ejaculated and uterine sperm decreased to about half and less than half of that in the cauda epididymal sperm, respectively. Large (13 nm) and small (8 nm) IMPs were distributed evenly and densely in the P face of the APM in the late spermatid, epididymal, and ejaculated sperm. In the uterine sperm, IMP-free areas were observed in the P face of the plasma membrane, a feature thought to represent one of the capacitation changes of the boar sperm.     

Block of cardiac sodium channels by antiarrhythmic drugs

The effects of seven Class-I antiarrhythmic drugs on the maximum upstroke velocity (Vmax) of action potential were examined in isolated guinea pig ventricular muscles in order to characterize their use- and state-dependent sodium channel blocking action. From the onset and offset kinetics of the use-dependent Vmax inhibition during stimulation trains, the seven drugs were subdivided into two groups; fast drugs (lidocaine, mexiletine, and tocainide), and slow drugs (quinidine, aprindine, disopyramide and flecainide). In experiments to assess the state-dependent sodium channel block, a conditioning clamp pulse to 0 mV was applied by using the single sucrose-gap voltage-clamp technique, and the Vmax of test action potential 100 msec after the clamp pulse was measured. The decrease in Vmax by 10 msec clamp pulse was defined as the activated channel block (ACB), and the decrease in Vmax as the clamp pulse duration was prolonged from 10 to 500 msec was defined as the inactivated channel block (ICB). The ratio of ICB to ACB was less than 1.0 for quinidine, disopyramide and flecainide, and much greater than 1.0 for aprindine, lidocaine, mexiletine, and tocainide. These characteristics may contribute to the differences in efficacy of each drug in treating various types of arrhythmias.     

Interhemispheric epithelial cyst. Case report

We report a rare case of a 54-year-old woman with an interhemispheric epithelial cyst. This will be the first report of an interhemispheric epithelial cyst without callosal agenesis. A partial excision of the cyst wall has led to her recovery with no evidence of recurrence. Ultrastructural studies suggest that the cyst was derived from the primitive neuroepithelium. We discuss the pathogenesis of the interhemispheric epithelial cyst.