Acute production of vascular superoxide by angiotensin II but not by catecholamines

OBJECTIVE: To determine whether vascular superoxide is rapidly released by angiotensin II and is involved in vascular contraction. DESIGN: The effect of superoxide dismutase (SOD) on angiotensin II induced elevation of mean arterial blood pressure was measured. Subsequently, acute production of vascular superoxide by angiotensin II and its effect on isometric tension were measured in rat aortic rings. The effects of catecholamines were concomitantly measured. METHODS AND RESULTS: The acute pressor effects of angiotensin II were significantly reduced when rats were pretreated intravenously with SOD. When angiotensin II was added on aortic segments in the presence of Cypridina luciferin analog, immediate elevations of chemiluminescence were observed which were inhibited by SOD. Furthermore, angiotensin II-induced elevations of isometric tension in aortic rings were significantly reduced by SOD. The effects of epinephrine and norepinephrine were concomitantly measured and were not significant CONCLUSIONS: The acute superoxide producing effect is likely to be specific to angiotensin II, because such a significant modification of the effects was not observed for catecholamines. Our results suggest that angiotensin II causes acute vascular superoxide production, which may be involved in the acute pressor effects.     

Comparison of the newly developed MB redox system with mycobacteria growth indicator tube (MGIT) and 2% Ogawa egg media for recovery of mycobacteria in clinical specimens

The rate of recovery and the mean time to detection of mycobacteria in clinical specimens were determined in a newly-developed MB Redox system based on liquid medium, and the results were compared with those of MGIT and 2% Ogawa egg media. From 587 sputum specimens processed, totally 203 mycobacterial isolates were detected, of which 177 (87.2%) with MB Redox, 185 (91.1%) with MGIT and 133 (65.6%) with 2% Ogawa medium. The difference in the percentages of positive cultures between either of the two liquid media and 2% Ogawa medium was significant (p < 0.0001). The mean time to detection of the Mycobacterium tuberculosis complex was 17.5 days with MB Redox, 18.7 days with MGIT, and 26.2 days with 2% Ogawa medium. The contamination rates were 1.5, 1.7, and 4.1% for MB Redox, MGIT, and 2% Ogawa medium, respectively. In conclusion, both MB Redox and MGIT systems, based on liquid medium, are more efficient than 2% Ogawa medium for the recovery of mycobacteria in clinical specimens.     

Effectiveness of an antiplatelet agent for coronary artery ectasia associated with silent myocardial ischemia

A 74-year-old Japanese male was referred to our hospital because of an abnormal electrocardiogram. The electrocardiogram revealed tall P waves in leads II, III, and aV(F). Echocardiography disclosed hypokinesis extending from the anteroseptal region to the apex. Iodine-123 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (123-BMIPP) scintigraphy revealed reduced uptake from the anteroseptal region to the apex. Coronary arteriography demonstrated diffuse dilatation of the right and left coronary arteries without organic stenosis, and left ventriculography showed hypokinesis at the same area. Furthermore, the coronary flow reserve in the left anterior descending artery was decreased. He was treated with an antiplatelet agent. Ten months later, the left ventriculography, 123I-BMIPP scintigraphy findings and coronary flow reserve were normalized. These findings demonstrate that antiplatelet therapy may be useful in the preservation of left ventricular function in patients with coronary artery ectasia.     

Adrenal pheochromocytoma with multiple neurofibromatosis on the trunk

We report a case of adrenal pheochromocytoma in a patient with neurofibromatosis type 1 (NF1). A 65-year-old female patient was admitted to our hospital for examination of a right adrenal mass. The adrenal tumor was incidentally discovered by abdominal computed tomography during examination for hypertension in another hospital. She had large multiple neurofibromatous lesions and café-au-lait spots on the trunk. We thought that it was difficult to make a skin incision on normal skin. Serum and urinary catecholamines were markedly increased. Magnetic resonance imaging revealed a solid round tumor 3 cm in diameter, located in the right adrenal gland. Laparoscopic right adrenalectomy was performed. Serum and urinary catecholamines returned to the normal range on post-operative day 10. Laparoscopic surgery may be a good option for NF1 patients with pheochromocytoma, especially those who had multiple neurofibromatosis on the trunk.     

Technical options for the surgical management of extracranial carotid artery aneurysms. Three case reports

Three cases of extracranial carotid artery (ECA) aneurysm were treated with various surgical options. Two female patients (74 and 37-year-old women) presented with pulsatile masses in their necks, which were confirmed as ECA aneurysms. Another 65-year-old woman presented with a calcified mass in her neck caused by an ECA aneurysm. The first case was treated with aneurysmorrhaphy with primary closure, the second with replacement of the involved site with vascular prosthesis, and the third with a high flow bypass with proximal ligation of the internal carotid artery. All three different surgical techniques were successful. ECA aneurysms are rare and require careful selection of the surgical method according to etiology, shape, and location of the ECA aneurysm. Proficiency in various vascular reconstruction techniques is a desirable prerequisite for the surgeon in-charge.     

Galectin-9 prolongs the survival of septic mice by expanding tim-3-expressing natural killer T cells and PDCA-1+ CD11c+ macrophages

Introduction

Galectin-9 ameliorates various inflammatory conditions including autoimmune diseases by regulating T cell and macrophage/dendritic cell (DC) functions. However, the effect of galectin-9 on polymicrobial sepsis has not been assessed.

Methods

We induced polymicrobial sepsis by cecal ligation and puncture (CLP) in mice. The survival rate was compared between galectin-9- and PBS-treated CLP mice. An ELISA was used to compare the levels of various cytokines in the plasma and culture supernatants. Fluorescence-activated cell sorting analysis was further performed to compare the frequencies of subpopulations of spleen cells.

Results

Galectin-9 exhibited a protective effect in polymicrobial sepsis as demonstrated in galetin-9 transgenic mice and therapeutic galectin-9 administration. In contrast, such effect was not observed in nude mice, indicating the involvement of T cells in galectin-9-mediated survival prolongation. Galectin-9 decreased TNFα, IL-6, IL-10 and, high mobility group box 1 (HMGB1) and increased IL-15 and IL-17 plasma and spleen levels. Galectin-9 increased the frequencies of natural killer T (NKT) cells and PDCA-1⁺ CD11c⁺ macrophages (pDC-like macrophages) but did not change the frequency of CD4 or CD8 T cells, γδT cells or conventional DC. As expected, galectin-9 decreased the frequency of Tim-3⁺ CD4 T cells, most likely Th1 and Th17 cells. Intriguingly, many spleen NK1.1⁺ NKT cells and pDC-like macrophages expressed Tim-3. Galectin-9 increased the frequency of Tim-3-expressing NK1.1⁺ NKT cells and pDC-like macrophages. Galectin-9 further increased IL-17⁺ NK1.1⁺ NKT cells.

Conclusion

These data suggest that galectin-9 exerts therapeutic effects on polymicrobial sepsis, possibly by expanding NKT cells and pDC-like macrophages and by modulating the production of early and late proinflammatory cytokines.     

Comparison of the effects of the novel vasodilator FK409 with those of nitroglycerin in isolated coronary artery of the dog.

1. The vasorelaxant effects of FK409, a new nitrovasodilator synthesized from a microbial product, were compared with those of nitroglycerin in isolated coronary artery rings of the dog contracted with U46619 (10(-7) M). 2. FK409 (10(-11)-10(-5) M) and nitroglycerin (10(-9)-10(-4) M) each produced a concentration-dependent relaxation. Comparison of EC50 values showed that FK409 was about 25 times more potent than nitroglycerin. 3. Submaximum concentrations of nitroglycerin (10(-6) M) and FK409 (3 x 10(-8) M) elevated guanosine 3':5'-cyclic monophosphate (cyclic GMP) levels, effects associated with vasorelaxation. Adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels were unaffected. 4. The concentration-relaxation curves for nitroglycerin and FK409 were shifted to the right by methylene blue (3 x 10(-6) - 3 x 10(-5) M), an inhibitor of soluble guanylate cyclase, and to the left by M&B22,948 (3 x 10(-6) - 3 x 10(-5) M), an inhibitor of cyclic GMP phosphodiesterase. 5. After exposure of coronary arteries to the maximally-effective concentration of nitroglycerin (10(-4) M), the mean EC50 value of FK409 did not change significantly, although that of nitroglycerin increased about 60 fold. After exposure to the maximally-effective concentration of FK409 (10(-5) M), the mean EC50 value of FK409 increased about 6 fold and that of nitroglycerin about 11 fold. 6. These results suggest that the vasorelaxant effect of FK409, like that of nitroglycerin, is due to activation of soluble guanylate cyclase and a resultant increase in intracellular cyclic GMP. However, compared with nitroglycerin, there was less self-tolerance to the relaxant effects of FK409 and relatively little cross-tolerance between the two agents.