Tumor suppressive effects of tocotrienol in vivo and in vitro

Tocotrienols have been reported to have higher biological activities than tocopherols. We investigated the antitumor effect of tocotrienols both in vivo and in vitro. Oral administration of tocotrienols resulted in significant suppression of liver and lung carcinogenesis in mice. In human hepatocellular carcinoma HepG2 cells, delta-tocotrienol exerted more significant antiproliferative effect than alpha-, beta-, and gamma-tocotrienols. delta-Tocotrienol induced apoptosis, and also tended to induce S phase arrest. On the other hand, gene expression analysis showed that delta-tocotrienol increased CYP1A1 gene, a phase I enzyme. Although further study will be necessary to investigate possible adverse effect, the data obtained in present study suggest that tocotrienols could be promising agents for cancer prevention.     

Prolonged nitric oxide inhalation fails to regress hypoxic vascular remodeling in rat lung

STUDY OBJECTIVE: The purpose of present study was to investigate whether long-term nitric oxide (NO) inhalation during the recovery in air might improve the regression of chronic hypoxic pulmonary hypertension (PH) and vascular changes. MATERIALS AND METHODS: The rats were exposed to 10 ppm of NO in air for 10 days (n = 12) and 30 days (n = 4), or 40 ppm of NO in air for 10 days (n = 6) and 30 days (n = 12) following 10 days of hypobaric hypoxia (380 mm Hg, 10% oxygen). For each NO group, air control rats following hypoxic exposure were studied at the same time (n = 13, 11, 9, and 11, respectively). Normal air rats (n = 6) without hypoxic exposure and rats (n = 7) following 10 days of hypoxic exposure were used as normal and chronic hypoxic control groups, respectively. Muscularization of normally nonmuscular peripheral arteries and medial hypertrophy of normally muscular arteries were assessed by light microscopy. An additional 16 rats were used to investigate the recovery of pulmonary artery pressure with (n = 8) and without NO inhalation (n = 8) after 10 days of hypobaric hypoxia. RESULTS: Long-term hypoxia-induced PH, right ventricular hypertrophy (RVH), and hypertensive pulmonary vascular changes, each of which regressed partly after recovery in room air. There were no differences among rats with and without NO during each recovery period in RVH, medial wall thickness of muscular artery, and the percentages of muscularized arteries at the alveolar wall and duct levels. Continuous inhaled 40 ppm NO decreased pulmonary artery pressure from 40.1 +/- 1.1 to 29.9 +/- 3.8 mm Hg (mean +/- SE) [n = 8], which was not different in the rats without NO inhalation (n = 8). Urine nitrate level was higher in rats that had inhaled NO. CONCLUSION: Continuous NO inhalation showed no effect on regression of pulmonary vascular remodeling in chronic hypoxic PH after returning to room air.     

Successful early resection of cardiac papillary fibroelastomas

Two adult patients with previous transient cerebral ischemic attacks (TIAs) or chest oppression were referred for further investigation. A swaying pedicled tumor was detected in the left atrium of the former patient and in the left coronary cusp of the latter by echocardiography. The TIA, or angina-like attack, was anticipated to be caused by thromboembolism of the tumor. Both patients underwent tumor extirpation. The histological findings demonstrated that both tumors were benign papillary fibroelastoma limited to the endocardium/endothelium layer. In conclusion, early surgical resection of a cardiac papillary fibroelastoma should be performed.     

Clinical and procedural characteristics of acute hemodynamic responders undergoing triple-site ventricular pacing for advanced heart failure

The advantages of triple-site ventricular pacing (Tri-V) compared to conventional biventricular site pacing (Bi-V) have been reported. We sought to identify the predictors of acute hemodynamic Tri-V responders. Acute hemodynamic studies were performed in 32 patients with advanced heart failure during Tri-V implantation. After the right ventricular (RV) and left ventricular (LV) leads were implanted for a conventional Bi-V system, an additional pacing lead was implanted in the RV outflow tract for Tri-V. The LV peak +dP/dt and tau were measured during AAI, Bi-V, and Tri-V pacing. A Tri-V responder was defined as a patient whose percentage of increase in the peak +dP/dt during Tri-V was >10% compared to of that during Bi-V. The baseline clinical variables and RV outflow tract lead location were analyzed to identify the characteristics of the Tri-V responders. Of the 32 patients, 10 (31%) were classified as Tri-V responders. The LV end-diastolic volume was greater (246 ± 48 vs 173 ± 53 ml, p <0.01), and the RV outflow tract lead was implanted at a greater outflow tract portion (p <0.05) in the Tri-V responders. Multivariate analysis revealed that only the baseline LV end-diastolic volume (per 50-ml greater) predicted the Tri-V response (odds ratio 2.87, 95% confidence interval 1.03 to 8.00, p <0.05). The area under the receiver operating characteristic curve for the LV end-diastolic volume was 0.84 (p <0.01) and an LV end-diastolic volume of >212 ml had a sensitivity of 80% and specificity of 77% to distinguish Tri-V responders. In conclusion, Tri-V provides greater hemodynamic effect for patients with a larger LV end-diastolic volume owing to its resynchronization effects on the LV anterior wall.     

Serum TNF-related and weak inducer of apoptosis levels in septic shock patients

Capillary permeability is a tightly regulated feature of microcirculation in all organ beds. In sepsis, this feature is fundamentally altered. We have previously reported elevated levels of angiopoietin-2 in patients with septic shock, and have investigated tumor necrosis factor (TNF)-related and weak inducer of apoptosis (TWEAK), which mediates both angiogenesis and inflammation, in those patients. Enzyme-linked immunoassay was used to measure serum TWEAK levels in 20 patients with septic shock, all of whom were treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX), and in 20 non-septic controls. The TWEAK levels were higher in patients with septic shock (192.8 ± 230.5 pg/mL) than in controls (84.1 ± 28.7 pg/mL, P = 0.043). Between 11 survivors and 10 non-survivors, there was no significant difference in the serum TWEAK levels before the DHP-PMX therapy. During DHP-PMX therapy, however, the serum TWEAK levels were significantly increased in non-survivors (142.2 ± 88.1 pg/mL to 399.0 ± 307.1 pg/mL, P = 0.022). There was a significant correlation between the serum TWEAK levels and white blood cell counts (r = 0.393, P < 0.001), platelet counts (r = 0.418, P < 0.001), or serum CRP levels (r = 0.259, P = 0.029), but there was no correlation between the serum TWEAK levels and blood pressure. The serum TWEAK levels were also correlated with the ratio of angiopoietin-2 to -1 (r = 0.464, P < 0.001). TWEAK may be a suitable marker of disease severity and mortality in septic patients, and TWEAK levels may be associated with vascular permeability via angiopoietin balance.     

IgG4-related inflammatory abdominal aortic aneurysm associated with autoimmune pancreatitis

An association between autoimmune pancreatitis (AIP) and inflammatory abdominal aortic aneurysm (AAA) has never been reported. Reported herein is a case of IgG4-related inflammatory AAA accompanying metachronous AIP. A 77-year-old man presented with malaise and intermittent lower abdominal pain. Radiological examination showed inflammatory AAA and right hydronephrosis caused by retroperitoneal fibrosis. Surgical correction of the AAA was performed, but high levels of systemic inflammatory markers persisted. Four months after surgery, the patient presented with epigastric pain, backache, and jaundice. His serum IgG4 concentration was high (571 mg/mL), and he was diagnosed with AIP, based on clinical and radiological findings. Corticosteroid therapy resulted in improvement of the clinical findings and lowered his serum IgG4 levels. Subsequent histological examination of a specimen from the aortic wall showed irregular proliferation of fibroblastic and myofibroblastic cells, severe lymphoplasmacytic infiltration, and obliterative phlebitis in the adventitia. Furthermore, on immunohistochemistry many plasma cells within the lesion were found to be positive for IgG4. These findings suggest that inflammatory AAA has a pathological process similar to that of AIP, and that some cases of inflammatory AAA and retroperitoneal fibrosis may be aortic and periaortic lesions of an IgG4-related sclerosing disease.     

Measures by local government--actions to take in dealing with heat stroke for firefighters

This paper expresses educational viewpoints on preventing "heat stroke (hyperthermia)" for firefighters who are in charge of pre-hospital care such as "life saving and relieving the sick/wounded" considering how firefighters are liable to heat stroke and knowledge that is needed, based on example cases. It is essential to have knowledge and measures to prevent heat stroke considering its particularity not only to firefighters engaged in disaster relief activities but also to people with other occupation and sports.     

Influence of adding pyrroloquinoline quinone to parenteral nutrition on gut-associated lymphoid tissue

Background: Experimental intravenous (IV) parenteral nutrition (PN) diminishes gut‐associated lymphoid tissue (GALT) cell number and function. PN solution cannot maintain GALT at the same level as a normal diet, even when delivered intragastrically (IG). Previous studies demonstrated pyrroloquinoline quinone (PQQ)–deficient mice to be less immunologically responsive. Because standard (STD) PN solution lacks PQQ, PQQ supplementation may prevent PN‐induced GALT changes. This study was designed to determine the influence of adding PQQ to PN on GALT. Methods: In experiment 1, mice (n = 32) were randomized to chow, IV‐STD‐PN, and IV‐PQQ‐PN groups. The chow group was fed chow with the same caloric content as PN. The IV‐STD‐PN group received STD‐PN solution, whereas the IV‐PQQ‐PN group was given PQQ (3 mcg/d)–enriched PN by the IV route. After 5 days of feeding, lymphocytes were isolated from the Peyer's patch (PPs), intraepithelial space (IE), and lamina propria (LP) of the small intestine. GALT lymphocyte number and phenotype (αβTCR+, γδTCR+, CD4+, CD8+, B220+ cells) and intestinal immunoglobulin A (IgA) level were determined. In experiment 2, mice (n = 28) were randomized to IG‐STD‐PN or IG‐PQQ‐PN group. After IG nutrition supports, GALT mass and function were determined as in experiment 1. Results: The IV‐PQQ‐PN group showed increased PP lymphocyte number and PP CD8+ cell number compared with the IV‐STD PN group. The IG‐PQQ‐PN group had significantly greater PP lymphocyte number and PP CD4+ cell numbers than the IG‐STD‐PN group. Neither IV nor IG PQQ treatment raised IgA level. Conclusions: PQQ added to PN partly restores GALT mass, although its effects on GALT function remain unclear.