Bnip3 as a Dual Regulator of Mitochondrial Turnover and Cell Death in the Myocardium

The Bcl-2 adenovirus E1B 19 kDa-interacting protein 3 (Bnip3) is a pro-apoptotic BH3-only protein associated with the pathogenesis of many diseases, including cancer and cardiovascular disease. Studies over the past decade have provided insight into how Bnip3 induces mitochondrial dysfunction and subsequent cell death in cells. More recently, Bnip3 was identified as a potent inducer of autophagy in cells. However, the functional role of Bnip3-mediated autophagy has been difficult to define and remains controversial. New evidence has emerged suggesting that Bnip3 is an important regulator of mitochondrial turnover via autophagy in the myocardium. Also, studies suggest that the induction of Bnip3-dependent mitochondrial autophagy is a separately activated process independent of Bax/Bak and the mitochondrial permeability transition pore (mPTP). This review discusses the current understanding of the functional role that Bnip3 plays in the myocardium. Recent studies suggest that Bnip3 might have a dual function in the myocardium, where it regulates both mitochondrial turnover via autophagy and cell death and that these are two separate processes activated by Bnip3

Nicotine and smoking do not decrease basal gastric mucosal blood flow in anesthetized rats

The literature regarding the effect of nicotine and cigarette smoke on gastric blood flow is conflicting. The hydrogen gas clearance technique was used to measure the effects of nicotine and cigarette smoke on basal gastric mucosal blood flow in anesthetized rats. Blood flow was measured before, during, and after treatment with either intravenous nicotine (4 or 40 μg/kg/min) or inhaled cigarette smoke (nicotine or nicotine free). Neither intravenous nicotine nor cigarette smoke significantly altered gastric mucosal blood flow. On the other hand, hypotension produced by hemorrhage significantly decreased mucosal blood flow ( P <0.05). Thus the technique used could detect a decrease in blood flow. These findings indicate that in the anesthetized rats, hypotension but not intravenous nicotine or cigarette smoke, in the doses given, reduce gastric mucosal blood flow.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44399/1/10620_2005_Article_BF01320320.pd

The desmosome and pemphigus

Desmosomes are patch-like intercellular adhering junctions (“maculae adherentes”), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required

Controversies in the management of advanced prostate cancer

For advanced prostate cancer, the main hormone treatment against which other treatments are assessed is surgical castration. It is simple, safe and effective, however it is not acceptable to all patients. Medical castration by means of luteinizing hormone-releasing hormone (LH-RH) analogues such as goserelin acetate provides an alternative to surgical castration. Diethylstilboestrol, previously the only non-surgical alternative to orchidectomy, is no longer routinely used. Castration reduces serum testosterone by around 90%, but does not affect androgen biosynthesis in the adrenal glands. Addition of an anti-androgen to medical or surgical castration blocks the effect of remaining testosterone on prostate cells and is termed combined androgen blockade (CAB). CAB has now been compared with castration alone (medical and surgical) in numerous clinical trials. Some trials show advantage of CAB over castration, whereas others report no significant difference. The author favours the view that CAB has an advantage over castration. No study has reported that CAB is less effective than castration. Of the anti-androgens which are available for use in CAB, bicalutamide may be associated with a lower incidence of side-effects compared with the other non-steroidal anti-androgens and, in common with nilutamide, has the advantage of once-daily dosing. Only one study has compared anti-androgens within CAB: bicalutamide plus LH-RH analogue and flutamide plus LH-RH analogue. At 160-week follow-up, the groups were equivalent in terms of survival and time to progression. However, bicalutamide caused significantly less diarrhoea than flutamide. Withdrawal and intermittent therapy with anti-androgens extend the range of treatment options. © 1999 Cancer Research Campaig