Autophagy is increased in prostate cancer cells overexpressing acid ceramidase and enhances resistance to C6 ceramide.

Acid ceramidase (AC) overexpression has been observed in prostate cancer cell lines and primary tumors, and contributes to resistance to chemotherapy and radiation. The consequence of AC overexpression is the ability to convert ceramide, which is often produced as a proapoptotic response to stress, to sphingosine, which can then be converted to the prosurvival molecule sphingosine-1-phosphate. In addition to their ability to metabolize ceramide produced in response to stress, we show here that prostate cancer cell lines overexpressing AC also have increased lysosomal density and increased levels of autophagy. Furthermore, pretreatment with 3-methyladenine restores sensitivity of these cells to treatment with C(6) ceramide. We also observed increased expression of the lysosomal stabilizing protein KIF5B and increased sensitivity to the lysosomotropic agent LCL385. Thus, we conclude that AC overexpression increases autophagy in prostate cancer cells, and that increased autophagy enhances resistance to ceramide.

Succinylcholine increases intraocular pressure in the human eye with the extraocular muscles detached.

BACKGROUND: The increase in intraocular pressure in the human eye that is associated with the use of intravenous succinylcholine has long been ascribed to contraction of the extraocular muscles leading to compression of the globe. This created concern that such contraction would extrude global contents in the patient with an open globe, and led clinicians to avoid the use of succinylcholine in these patients. METHODS: The authors studied 15 patients undergoing elective enucleation, and compared the intraocular pressure change after the administration of succinylcholine in the diseased eye after all the extraocular muscles had been detached to that of the normal eye that had the extraocular muscles attached. RESULTS: The authors found no difference in baseline intraocular pressure (mmHg) between eyes (15.1 vs. 16.1) or at peak intraocular pressure (25.2 vs. 24.7), but did observe a significant difference in pressure in both eyes when baseline was compared with peak pressure. CONCLUSIONS: The authors concluded that extraocular muscle contraction does not contribute to the increase in intraocular pressure after succinylcholine.

Cataract surgery in anticoagulated patients.

A prospective study was performed on 31 patients having planned extracapsular cataract extraction with posterior chamber intraocular lens implantation. The patients were considered to be anticoagulated because of the medications they were taking. The patients were instructed to continue their usual medications throughout the perioperative period including the day of surgery. All patients had routine narcoleptic sedation and retrobulbar anesthesia. The surgical technique was altered to use an inferior corneal traction suture and a single planed clear corneal incision. No intraoperative or postoperative anterior chamber bleeding was seen. The observed complications were increased awareness of corneal sutures, increased endothelial cell loss, delayed visual rehabilitation from with-the-rule astigmatism, and transient corneal edema. All patients achieved 20/40 or better visual acuity without corneal edema by three months post-surgery.

The effects of caffeine on caffeine users and non-users.

This work examined the effects of consuming relatively small amounts of caffeine, from 20 to 160 mg, on performance and self-reports of mood in a group of caffeine users. A group of non-caffeine users were studied after ingesting 160 mg of caffeine. At regular intervals after consumption subjects were tested on several behavioral measures and blood samples were taken for caffeine analysis. Results showed caffeine users had higher blood caffeine levels and lower blood pressure at some doses than did non-users. Regular caffeine users showed a tendency toward better performance on a rotary pursuit task than non-caffeine users given a placebo treatment. They also experienced a performance decrement, relative to users given placebo, when blood caffeine levels were relatively high. Caffeine users showed no sign of caffeine withdrawal when compared to non-users before caffeine treatment. Performance of non-users given caffeine was poorer than control performance, and they tended not to report altering effects of caffeine. However, in caffeine users, the ratio of alertness:tension self-ratings tended to roughly track plasma caffeine with the lowest ratios occurring when plasma caffeine peaked after 160 mg dose. Low ratios were also found after 0, 20, and 40 mg caffeine treatments. The ratio was highest after 80 mg caffeine, suggesting that an optimum caffeine dose might exist for peak alertness:tension, with higher or lower doses resulting in a decrease of that ratio. These data suggest that real or expected mood and perhaps performance benefits experienced by caffeine users contribute to the motivation for consumption.