alpha1-Adrenergic receptor antagonists induce production of IL-18 and expression of ICAM-1 and CD40 in human monocytes

The activation of T cells plays a role in antitumor response. Monocytes activate T cells by inducing the cell-to-cell interaction that involves the engagement of adhesion molecules with their ligands, and the production of IL-18. The authors examined the effect of the quinazoline-based alpha1-adrenergic receptor antagonists bunazosin, doxazosin, prazosin, and terazosin on the expression of adhesion molecules such as ICAM-1, B7.1, B7.2, CD40, and CD40L on monocytes isolated from human peripheral blood mononuclear cells. Doxazosin, prazosin, and terazosin induced the expression of ICAM-1 and CD40 but had no effect on the expression of B7.1, B7.2, and CD40L. Moreover, IL-18 was detected in the medium of incubated monocytes treated with doxazosin, prazosin, and terazosin. Bunazosin did not affect adhesion molecule expression and IL-18 production, suggesting that the chemical structure of quinazoline might not be related to the effect of doxazosin, prazosin, and terazosin. Although caspase-1 inhibitor completely abolished the production of IL-18, anti-IL-18 mAb and caspase-1 inhibitor partially inhibited the increase in ICAM-1 and CD40 expression induced by doxazosin, prazosin, and terazosin. Doxazosin, prazosin, and terazosin can induce monocyte activation with a specific pattern of expression of adhesion molecules and IL-18 production, and this may lead to T-cell activation through the cell-to-cell interaction. The activation of T cells induced by the increase of the expression of ICAM-1 and CD40 and the production of IL-18 may be involved in the anti-cancer effects of doxazosin, prazosin, and terazosin.     

Antioxidants and cardiovascular disease

Oxygen-free radical reactions have been implicated in many chronic diseases, including atherosclerotic cardiovascular disease (CVD). Epidemiologic studies have demonstrated an association between increased intake of naturally occurring antioxidant vitamins such as vitamin E and vitamin C and reduced morbidity and mortality from CVD. By contrast, most of the completed randomized trial did not show any clear reduction in CVD. However, the trials were not specifically designed to assess CVD, did not provide data on nonfatal CVD, may have had insufficient treatment durations, and used suboptimal vitamin E doses. Despite the lack of a general consensus, recent data reinforce the concept that the regular intake of antioxidants present in foods limits the progression of atherosclerotic CVD.     

Removal of coronary sinus intima by a guidewire during cardiac resynchronization therapy

Previously, complications associated with the placement of the left ventricular pacing lead were reported in 1.9-6% of cases. We describe a case with a stripping of venous intima from the coronary sinus by a guidewire during a left ventricular lead implantation. Judging from this case, the firm guidewire and coronary catheter should not be used within the coronary sinus.     

Epidural hematoma after epidural anesthesia: a case report of non-surgical management

Neuraxial block with intraoperative intravenous (IV) heparin use is considered to be a safe technique. The risk of epidural hematoma is low as long as concomitant anti-coagulation is not used [ASRA: Neuraxial Anesthesia and Anticoagulation Consensus Statements, 1998]. We describe a patient who developed epidural hematoma under those circumstances and was successfully treated without surgical intervention.

A 75-year-old female underwent aorto-mesenteric arterial bypass for chronic mesenteric ischemia. Combined general and epidural anesthesia was used and IV heparin (total 6000 IU) was given intraoperatively. In the recovery room, aspiration of blood was noted through the epidural catheter. The next day, she developed severe back pain without sensory or motor deficit. Magnetic resonance imaging (MRI) scan revealed an epidural hematoma with spinal cord compression. Neurosurgical consultation resulted in a decision to monitor for neurological changes. She never developed a neurological deficit and was discharged from the hospital on post-operative day 7.

Our case suggests that epidural hematoma may not be uncommon phenomena in patients with neuraxial block and intraoperative IV heparin use. Implications for the decision as to which of these patients should be imaged and which should not are discussed.     

Genetic polymorphism of COX-1 gene and NSAID-induced ulcer

Cyclooxygenase-1(COX-1) has traditionally been regarded as a constitutively expressed enzyme that generates prostaglandins for gastrointestinal integrity. The effects of non-steroidal anti-inflammatory drug(NSAID) on the gastric mucosal damage are caused by the inhibition of this enzyme. Although A-842G in the COX-1 gene promoter was reported as a functional polymorphism, we could not detect this polymorphism in Japanese population. However, T-1676C polymorphism (rs1330344) was significantly associated with the development of peptic ulcer, especially gastric ulcer. In addition, rs1330344 was also significantly associated with the development of NSAID-induced ulcer diseases. In conclusions, the assessment for genotype of COX-1 gene promoter polymorphism, especially rs1330344, may be useful for detecting the high risk group of developing NSAID-induced ulcer diseases.     

Protective effect of N,N’‐dimethylthiourea against stress‐induced gastric mucosal lesions in rats

In the present study, we examined the protective effect of N,N’‐dimethylthiourea (DMTU), a scavenger of hydroxyl radical (), against water‐immersion restraint stress (WIRS)‐induced gastric mucosal lesions in rats. When male Wistar rats fasted for 24 h were exposed to WIRS for 3 h, gastric mucosal lesions occurred with increases in the levels of gastric mucosal myeloperoxidase (MPO), an index of tissue neutrophil infiltration, pro‐inflammatory cytokines (tumor necrosis factor alpha and interleukin 1beta), lipid peroxide (LPO), and nitrite/nitrate (NOx), an index of nitric oxide synthesis, and decreases in the levels of gastric mucosal nonprotein SH and vitamin C and gastric adherent mucus. DMTU (1, 2.5, or 5 mmol/kg) administered orally at 0.5 h before the onset of WIRS reduced the severity of gastric mucosal lesions with attenuation of the changes in the levels of gastric mucosal MPO, pro‐inflammatory cytokines, LPO, NOx, nonprotein SH, and vitamin C and gastric adherent mucus found at 3 h after the onset of WIRS in a dose‐dependent manner. Serum levels of corticosterone and glucose, which are indices of stress responses, increased in rats exposed to WIRS for 3 h, but DMTU pre‐administered at any dose had no effect on these increases. These results indicate that DMTU protects against WIRS‐induced gastric mucosal lesions in rats by exerting its antioxidant action including scavenging and its anti‐inflammatory action without affecting the stress response.