Granzyme B as a novel factor involved in cardiovascular diseases

SummaryApoptosis plays an important role in cardiovascular diseases such as atherosclerosis, ischemic heart disease, and congestive heart failure. Previous studies have demonstrated that oxidative stress, physiological stress, and inflammatory cytokines such as tumor necrosis factor and Fas ligand are involved in apoptosis of cardiovascular system. We demonstrate that another apoptosis-related pathway, i.e. granzyme B/perforin system is involved in cardiovascular diseases. Expression of granzyme B, a member of serine protease family is increased in acute coronary syndrome, coronary artery disease with end-stage renal disease, and subacute stage of acute myocardial infarction. Although granzyme B is extensively researched in immunological disorders, the role of granzyme B/perforin system was not clear in the cardiovascular field. In addition, little is known regarding the inhibition of granzyme B system in the clinical situation. In this review we demonstrate recent findings of granzyme B in cardiovascular diseases and possible therapeutic applications of inhibiting the granzyme B/perforin system

High-field magnetization and magnetic phase transition in CeOs2Al10

We have studied the magnetization of CeOs2Al10 in high magnetic fields up to 55 T for H // a and constructed the magnetic phase diagram for H // a. The magnetization curve shows a concave H dependence below T_max \sim40 K which is higher than the transition temperature T_0 \sim29 K. The magnetic susceptibility along the a-axis shows a smooth and continuous decrease down to \sim20 K below T_max \sim40 K without showing an anomaly at T_0. From these two results, a Kondo singlet is formed below T_max and coexists with the antiferro magnetic order below T_0. We also propose that the larger suppression of the spin degrees of freedom along the a-axis than along the c-axis below T_max is associated with the origin of the antiferro magnetic component.Comment: 4 pages, 4 figures, to appear in Phys. Rev. B, Rapid Commu

High-field magnetization and magnetic phase transition in CeOs2Al10

We have studied the magnetization of CeOs2Al10 in high magnetic fields up to 55 T for H // a and constructed the magnetic phase diagram for H // a. The magnetization curve shows a concave H dependence below T_max \sim40 K which is higher than the transition temperature T_0 \sim29 K. The magnetic susceptibility along the a-axis shows a smooth and continuous decrease down to \sim20 K below T_max \sim40 K without showing an anomaly at T_0. From these two results, a Kondo singlet is formed below T_max and coexists with the antiferro magnetic order below T_0. We also propose that the larger suppression of the spin degrees of freedom along the a-axis than along the c-axis below T_max is associated with the origin of the antiferro magnetic component.Comment: 4 pages, 4 figures, to appear in Phys. Rev. B, Rapid Commu

The impact of uncertainty in society on the use of traditional, complementary and alternative medicine: a comparative study on visits to alternative/traditional/folk health care practitioners

Background: While traditional, complementary and alternative medicine (TCAM) is gaining increased interest worldwide, the structural factors associated with the usage of TCAM at the social level have not been sufficiently explored. We aim to understand the social structure of uncertainty in society that affects the TCAM usage for men and women. Methods: We studied 32 countries using data from the International Social Survey Programme and the World Bank. In this study, we defined TCAM usage as visits to an alternative/traditional/folk health care practitioner during the past 12 months. We performed a correlation analysis and used a generalized linear model . Results: The prevalence of TCAM usage in terms of visits to practitioners was 26.1% globally, while usage varied across the 32 countries. Generalized linear models showed that unemployment rate was associated with the prevalence of TCAM usage in terms of visits to practitioners. Conclusions: At the social-structural level TCAM usage involving visits to practitioners was related to job insecurity. Job insecurity led to a decrease in TCAM usage regarding visits to practitioners. These findings suggest that it is necessary to consider the social-structural factors of uncertainty in society when designing health policies related to TCAM

Failure of Hem-o-lok clips

Hem-o-lok clips are commonly used for renal artery ligation in laparoscopic renal surgery. However, failure of the renal artery ligation clips is potentially fatal. A 61-year-old man underwent hand-assisted laparoscopic nephroureterectomy using a retroperitoneal approach for left ureteral carcinoma. One hour postoperatively, he was diagnosed with hemorrhagic shock. An immediate laparotomy revealed two closed, undamaged Hem-o-lok clips around the left renal artery. Pulsatile bleeding was observed, and the renal artery was immediately ligated with non-absorbable thread. We determined that the failure of the Hem-o-lok clips on the renal artery was caused by the lack of space between the two Hem-o-lok clips and the distal renal artery cuff beyond the distal clip. To prevent a potentially fatal failure of the renal artery ligation clips, one should maintain a sufficient space between the Hem-o-lok clips and an adequate distal renal artery cuff beyond the distal clip

Pemafibrate Prevents Rupture of Angiotensin II-Induced Abdominal Aortic Aneurysms

Background: Abdominal aortic aneurysm (AAA) is a life-threatening disease that lacks effective preventive therapies. This study aimed to evaluate the effect of pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist, on AAA formation and rupture. Methods: Experimental AAA was induced by subcutaneous angiotensin II (AngII) infusion in ApoE(-)(/)(-) mice for 4 weeks. Pemafibrate (0.1 mg/kg/day) was administered orally. Dihydroethidium staining was used to evaluate the reactive oxygen species (ROS). Results: The size of the AngII-induced AAA did not differ between pemafibrate- and vehicle-treated groups. However, a decreased mortality rate due to AAA rupture was observed in pemafibrate-treated mice. Pemafibrate ameliorated AngII-induced ROS and reduced the mRNA expression of interleukin-6 and tumor necrosis factor-alpha in the aortic wall. Gelatin zymography analysis demonstrated significant inhibition of matrix metalloproteinase-2 activity by pemafibrate. AngII-induced ROS production in human vascular smooth muscle cells was inhibited by pre-treatment with pemafibrate and was accompanied by an increase in catalase activity. Small interfering RNA-mediated knockdown of catalase or PPAR alpha significantly attenuated the anti-oxidative effect of pemafibrate. Conclusion: Pemafibrate prevented AAA rupture in a murine model, concomitant with reduced ROS, inflammation, and extracellular matrix degradation in the aortic wall. The protective effect against AAA rupture was partly mediated by the anti-oxidative effect of catalase induced by pemafibrate in the smooth muscle cells