Overexpression of the gene encoding the 70-kDa heat shock protein (hsp70) has previously been shown to protect neuronal cells against subsequent thermal or ischemic stress. It has no protective effect, however, against stimuli that induce apoptosis, although a mild heat shock (sufficient to induce hsp synthesis) does have a protective effect against apoptosis. We have prepared disabled herpes simplex virus-based vectors that are able to produce high level expression of individual hsps in infected neuronal cells without damaging effects. We have used these vectors to show that hsp27 and hsp56 (which have never previously been overexpressed in neuronal cells) as well as hsp70 can protect dorsal root ganglion neurons from thermal or ischemic stress. In contrast, only hsp27 can protect dorsal root ganglion neurons from apoptosis induced by nerve growth factor withdrawal, and hsp27 also protects the ND7 neuronal cell line from retinoic acid-induced apoptosis. However, hsp70 showed no protective effect against apoptosis in contrast to its anti-apoptotic effect in non-neuronal cell types. These results thus identify hsp27 as a novel neuroprotective factor and show that it can mediate this effect when delivered via a high efficiency viral vector.The heat shock proteins (hsps) 1 were originally identified on the basis of their increased synthesis following exposure to elevated temperature. Subsequently, however, they were shown to be induced by a wide variety of other stresses in many different cell types (for review see Refs. 1-3) including neuronal cells exposed to ischemia (4), amphetamine treatment (5), or to sodium arsenite (6). Such induction of the hsps has been shown to have a protective effect against exposure to a subsequent stress in a variety of cell types. Thus, for example, exposure of primary neuronal cultures to a mild heat stress or ischemic stress sufficient to induce the hsps has been shown to be protective against subsequent exposure to the excitotoxin glutamate or to severe heat or ischemic stress (6 -8), whereas similar exposure in vivo can protect against damaging effects caused by subsequent exposure to light (9) or ischemia (10, 11).In a number of cases the protective effect of a mild hspinducing stress can be reproduced by the artificial overexpression of a single hsp. Thus, for example, dorsal root ganglion (DRG) neurons can be protected against thermal or ischemic stress by overexpression of either the 70-kDa hsp (hsp70) or the 90-kDa hsp (hsp90) (12-14), and a similar protective effect of hsp70 and hsp90 has also been observed in the ND7 immortalized cell line derived from sensory neurons (15). Interestingly, Fink et al. (16) were able to protect cultured hippocampal neurons against subsequent heat shock using a herpes simplex virus (HSV)-derived amplicon vector expressing hsp70 indicating that this effect applies to neurons derived from both the central and peripheral nervous systems. Moreover, the use of an HSV-based vector opens up the possibility of testing the protective effect of the h...
Perineal and posterior vaginal wall reconstruction following abdominoperineal and local cancer resection entails replacement of volume between the perineum and sacrum and restoration of a functional vagina. Ideal local reconstructive options include those which avoid functional muscle sacrifice, do not interfere with colostomy formation, and avoid the use of irradiated tissue. In avoiding the donor site morbidity of other options, we describe a fasciocutaneous option for the reconstruction of the perineum and posterior vaginal wall. We present our technique of superior and inferior gluteal artery perforator (SGAP or IGAP) flaps to reconstruct such defects. Fourteen patients between 2004 and 2008 underwent 11 SGAP and three IGAP flaps. There were no flap failures or partial flap losses and no postoperative hernias. All female patients reported resumption of sexual intercourse following this procedure. Our experience in both the immediate and delayed setting is that this technique produces a good functional outcome with low donor-site morbidity.
In a decade of burn care at the Royal Adelaide Hospital in South Australia, there have been only two patients (of over 3000) who have displayed clinical evidence of upper gastrointestinal bleeding, with ulceration identified at endoscopy. During this time, all patients admitted to the burns unit with burn injury requiring fluid resuscitation (>15% total body surface area, [TBSA]) routinely received stress ulcer prophylaxis with ranitidine 150 mg, twice daily, from admission to discharge. One of the two patients mentioned had the ranitidine replaced with pantoprazole by our gastroenterological colleagues, who after endoscopic confirmation of ulceration advised us that our prophylaxis regimen was outdated and that proton pump inhibitors (PPI) should replace histamine-2 receptor antagonists (H2RA). With our own intensive care unit (ICU) ceasing pharmacological stress ulcer prophylaxis two years ago (relying on enteral feeding alone to prevent such complications), we searched for burn injuryspecific guidance in the literature.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.