Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034067 (emphysema)
11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Emphysema is a chronic pulmonary disorder characterized by a permanent enlargement of the air spaces distal to the terminal bronchioles consequent to destruction of the alveolar walls, including the epithelial and endothelial cells and the connective tissue matrix. There is increasing evidence that an imbalance of oxidants and antioxidants in the lower respiratory tract contributes to this process. Oxidants such as O2-., H2O2, OH, OCl- are generated in the lower respiratory tract as a result of normal biochemical processes, activation of inflammatory cells and inhaled toxic gases. Under normal circumstances, the parenchymal cells are protected by intracellular antioxidants and membrane radical scavengers. In addition, the fluid lining the epithelial surface contains a catalase-like antioxidant that protects the epithelial cells from oxidants. If the oxidant burden overcomes these defenses, the parenchymal cells may be injured, the connective tissue matrix may be partially degraded, the antiprotease screen that protects the lower respiratory tract from attack by neutrophil elastase may be rendered impotent. The alveolar wall then becomes highly vulnerable to elastolytic attack, with a complete destruction of the interstitial connective tissue matrix. In this regard, it is reasonable to hypothesize that reestablishment of the oxidant-antioxidant balance in favor of the antioxidants would be useful as a therapeutic strategy to suppress the emphysematous process.
...
PMID:Oxidants, antioxidants and the pathogenesis of emphysema. 299 6

Activated granulocytes have been implicated in mediating pulmonary endothelial damage in the Adult Respiratory Distress Syndrome. In another lung disease, emphysema, pulmonary granulocytes (PMNs) are thought to be doubly responsible for lung dissolution: they release potent proteolytic enzymes including elastase, and they generate reactive oxygen species that oxidize a reactive site methionine group in alpha-1-protease inhibitor (alpha-1-PI) rendering it, in turn, impotent as an anti-elastase. This suggested an analogous scenario for pulmonary vascular damage: namely, undefended PMN elastase might also mediate endothelial injury. Our strategy to prove this notion used 51chromium-labeled human endothelial cells exposed to intact PMN or to enucleate "neutroplasts." The latter are elastase-free cytoplasmic blebs derived from PMN. When activated, both PMN and neutroplasts generate similar amounts of toxic oxygen species; yet neutroplasts caused insignificant endothelial damage, measured as 51Cr "lift-off"from anchoring matrix (PMN = 24.3% +/- 1.8% vs neutroplast = 1.2% +/- 0.4%; p less than 0.001). Adding pure elastase back to neutroplasts increased endothelial cell lift-off (7% +/- 0.2%). Although the prototypic serine protease inhibitor phenyl methylsulfonylfluoride (PMSF) protected endothelium from PMNs, pure alpha-1-PI (also a potent anti-elastase) when added in physiologic amounts did not protect endothelial cells from PMN assault, suggesting that PMN oxidants might inactivate it. By adding exogenous myeloperoxidase (MPO) to MPO-deficient neutroplasts, we demonstrated that MPO-dependent oxidants, probably N-chloramines, are critical inactivators of alpha-1-PI. This was further confirmed since added free methionine, a scavenger of chloramine, protected alpha-1-PI from inactivation by reagent chloramine or that produced by rearmed neutroplasts or PMN.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Neutrophil oxidants inactivate alpha-1-protease inhibitor and promote PMN-mediated detachment of cultured endothelium. Protection by free methionine. 348 53

We retrospectively compared 50 patients treated with open retropubic prostatectomy (RRP) with 50 patients treated with laparoscopic extraperitoneal radical prostatectomy (LRP) at our institution, in the same time period, with a follow-up up to 7 years. We focused on operative data, complications, pathological outcome and mid-term outcome and follow-up in terms of oncological results. The same surgeons performed both operations. The 2 groups were similar with respect to mean patient age, mean prostate specific antigen value, median Gleason score. No previous transurethral resection of the prostate nor neoadjuvant treatment, had been undertaken in both groups of pts. Mean operating time was significantly shorter after open surgery (126 minutes, range 90-185 minutes) [p = 0.03] compared to the laparoscopic group (188 minutes, range 130-250) but it did not differ significantly from the last 20 laparoscopic procedures, in which the time of procedure was reduced to a mean of 155 minutes group (range 140-184 minutes) [p = 0.1]. Mean blood loss (1,150 versus 800 cc) and transfusion rates (55.7% versus 19.6%) in the 2 groups significantly favored the laparoscopic group. Number of lymphnodes dissected during the procedures favoured, but not significantly, the RRP group: for RRP a mean 11 lymphnodes right side, 13 left side (ranges 2-20 and 2-19 respectively), while for LRP a mean of 9 lymphnodes right side, 11 left side (ranges 2-15 and 2-13 respectively) were collected. The complication rate was almost the same in both groups, with no major adverse events nor deaths, (19.2% versus 14.7%) but the spectrum differed. The laparoscopic group had a higher incidence of fever (1.8% versus 3.2% respectively) and subcutaneous or scrotal emphysema, whereas more lymphoceles (6.9% versus 0%), wound infection (2.3% versus 0.5%), embolism/pneumonia (2.3% versus 0.5%) and anastomotic strictures (15.9% versus 4%) occurred after open surgery. Median catheter time was longer after open retropubic prostatectomy (22 versus 8.9 days, respectively) but the continence rates (intended as complete continence with no use of pads) were similar in both groups at 12 months (90.3% versus 91.7%). The rate of positive margins did not differ significantly in groups, and was in all cases very low (8.2% versus 7.0%), prostate specific antigen biochemical recurrence was equivalent (10% vs 10%). Data regarding postoperative sexual function favoured the laparoscopic group, even if no statistical significance was recorded (55% vs 67%). No statistical differences were observed in terms of oncological results, with a 24 months mean follow-up. Laparoscopic radical prostatectomy is technically demanding, with an initially longer operative time and learning curve. The overall outcome in our series favours the laparoscopic approach regarding catheterization time, recover of continence and impotence, hospital stay, transfusion rate. The open approach is favoured for the still shorter time necessitating for the procedure. Consequently, at our institution laparoscopic radical prostatectomy is becoming the method of choice.
...
PMID:Laparoscopic versus open radical retropubic prostatectomy: a case-control study at a single institution. 2081 35