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Objectives: Laparoscopic adrenalectomy has been the gold standard surgical procedure. However, the adaptation criteria for malignant tumors and predictors of perioperative outcomes are not well defined. Therefore, this study tried to identify valid predictors for perioperative outcomes of laparoscopic adrenalectomy and consider the adaptation criteria. Methods: We retrospectively reviewed the preoperative and perioperative data of 216 patients who underwent transperitoneal laparoscopic adrenalectomy in our hospital. Preoperative factors associated with perioperative outcomes were analyzed using multiple regression analysis. Results: Among 216 patients, 165 (76.4%), 26 (12.0%), and 25 (11.6%) were suspected of having benign tumors, pheochromocytoma, and malignant tumors, respectively. Median tumor size was 25.0 mm (interquartile range 18.0–35.0); median perirenal fat thickness was 9.2 mm (interquartile range 4.9–15.6) on preoperative computed tomography scans. The median operative time was 145.5 min (interquartile range 117.5–184.0) and the median estimated blood loss was 0.0 mL (interquartile range 0.0–27.3). Perirenal fat thickness (p < 0.001), tumor size (p < 0.001), and malignant tumors (p = 0.020) were associated with operative time, and perirenal fat thickness (p = 0.038) and malignant tumors (p = 0.002) were associated with estimated blood loss. Conclusions: Perirenal fat thickness, tumor size, and malignant tumors are valid predictors of the surgical outcomes of transperitoneal laparoscopic adrenalectomy. As only perirenal fat thickness is associated with both surgical outcomes except for malignant tumors, it is a powerful predictor. Transperitoneal laparoscopic adrenalectomy for large malignant adrenal tumors with thick perirenal fat should be performed with caution. [ABSTRACT FROM AUTHOR]

Among the side effects of methimazole (MMI) for the treatment of Graves' disease, MMI-induced acute pancreatitis (MIP) is a rare adverse reaction, with only 7 cases being reported to date. However, 2 large-scale population-based studies recently revealed that the risk of MIP was significantly higher, ranging from 0.02% to 0.56%. Although MIP is common in middle-aged and elderly Asian women, its pathogenesis remains largely unknown. We herein present a case of a 72-year-old Japanese woman with Graves' disease who developed MIP 12 days after the initiation of MMI. The MMI was discontinued, the patient was switched to propylthiouracil (PTU) therapy, and pancreatitis gradually resolved. Serological human leukocyte antigen (HLA) typing identified HLA-DRB1*08:03:02. This HLA allele was previously detected in a patient with MIP and is one of the major risk factors for agranulocytosis induced by antithyroid drugs, including PTU as well as MMI. In cases of MIP, PTU is being considered as an alternative to MMI; however, its safety needs further investigation and patients require close monitoring after the switch to PTU. Further studies are warranted, particularly on the relationship between MIP and the presence of HLA alleles causing antithyroid drug-induced agranulocytosis. [ABSTRACT FROM AUTHOR]

Reduced nitric oxide (NO) in the brain might contribute to enhanced sympathetic drive in heart failure (HF). The aim of this study was to determine whether increased NO production induced by local overexpression of endothelial NO synthase (eNOS) in the nucleus tractus solitarius (NTS) of the brain stem reduces the enhanced sympathetic drive in mice with HF. Myocardial infarction (MI) was induced in mice by ligating the left coronary artery. MI mice exhibited left ventricular dilatation and a reduced left ventricular ejection fraction. Urinary norepinephrine excretion in MI mice was greater than that in sham-operated mice, indicating that sympathetic drive was enhanced in this model. Thus this model has features that are typical of HF. Western blot analysis and immunohistochemical staining for neuronal NOS (nNOS) indicated that nNOS protein expression was significantly reduced in the brain stem of MI mice. MI mice had a significantly smaller increase in blood pressure evoked by intracisternal injection of [N.sup.G]-monomethyl-L-arginine than sham-operated mice. Adenoviral vectors encoding either eNOS (AdeNOS) or [beta]-galactosidase (Ad[beta]gal) were transfected into the NTS to examine the effect of increased NO production in the NTS on the enhanced sympathetic drive in HF. After the gene transfer, urinary norepinephrine excretion was reduced in AdeNOS-transfected MI mice but not in Ad[beta]gal-transfected MI mice. These results indicate that nNOS expression in the brain stem, especially in the NTS, is reduced in the MI mouse model of HF, and increased NO production induced by overexpression of eNOS in the NTS attenuates the enhanced sympathetic drive in this model. nitric oxide; heart failure; brain; sympathetic; genes

Tumor necrosis factor-[alpha] (TNF-[alpha]) plays a pathophysiological role in the development and progression of heart failure. Matrix metalloproteinase (MMP)-2 is involved in extracellular matrix remodeling. Recent evidence suggests a protective role for this protease against tissue inflammation. Although MMP-2 is upregulated in the failing heart, little is known about its pathophysiological role. We thus hypothesized that ablation of the MMP-2 gene could affect cardiac remodeling and failure in TNF-[alpha]-induced cardiomyopathy. We crossed transgenic mice with cardiac-specific overexpression of TNF-[alpha] (TG) with MMP-2 knockout (KO) mice. Four groups of male and female mice were studied: wild-type (WT) with wild MMP-2 (WT/MM[P.sup.+/+]), WT with MMP-2 KO (WT/MM[P.sup.-/-]), TNF-[alpha] TG with wild MMP-2 (TG/MMP+/+), and TG with MMP-2 KO (TG/MM[P.sup.-/-]). The upregulation of MMP-2 zymographic activity in TG/MM[P.sup.+/+] mice was completely abolished in TG/MM[P.sup.-/-] mice, and other MMPs and tissue inhibitors of metalloproteinase were comparable between groups. Survival was shorter for male TG/ MM[P.sup.-/-] than TG/MM[P.sup.+/+] mice. Female TG/MM[P.sup.-/-] mice were more severely affected than TG/MM[P.sup.+/+] mice with diminished cardiac function. Myocardial TNF-[alpha] and other proinflammatory cytokines were increased in TG/MM[P.sup.+/+] mice, and this increase was similarly observed in TG/MMP[P.sup.-/-] mice. The extent of myocardial infiltrating cells including macrophages was greater in TG/MMP[P.sup.-/-] than in TG/MM[P.sup.+/+] mice. Selective ablation of the MMP-2 gene reduces survival and exacerbates cardiac failure in association with the increased level of myocardial inflammation. MMP-2 may play a cardioprotective role in the pathogenesis of cytokine-induced cardiomyopathy. metalloproteinases; heart failure; tumor necrosis factor

Monocyte chemoattractant protein-1 (MCP-1) is a proinflammatory chemokine and may play an important role in the development of pulmonary fibrosis. We examined a new therapeutic strategy that comprises the transfection of the mutant MCP-1 gene into skeletal muscles as a biofactory for anti-MCP-1 therapy against Neomycin-induced pulmonary fibrosis in mice. Overexpression of the mutant MCP-l gene at 10-14 days after intratracheal instillation of Neomycin resulted in decreased DNA damage, apoptosis, and pulmonary fibrosis at 14 days. However, overexpression of the mutant MCP-1 at 0-4 days after bleomycin instillation did not result in decreased pathological grade, DNA damage, or apoptosis at 7 and 14 days. Because, in this model, inflammatory cell infiltration begins at 3 days and is followed by interstitial fibrosis, it is likely that MCP-1 has an important role to play in the development of fibrogenesis but not in the development of early lung inflammation. This method does not require the use of viral vector or neutralizing antibody, and, as such, it is possible to avoid problems regarding the pathogenicity of the viral vector or immunocomplex. This new strategy may be a beneficial method of treating pulmonary fibrosis from the viewpoint of clinical application. apoptosis; electroporation

Amlodipine (a new class of calcium channel antagonist) has been shown to limit the progression of arteriosclerosis and decrease the incidence of cardiovascular events. The mechanisms underlying the beneficial effects of amlodipine, however, remain unclear. Therefore, we hypothesized that amlodipine attenuates the development of arteriosclerosis through the inhibition of inflammation in vivo. Long-term inhibition of nitric oxide (NO) by administration of a NO synthase inhibitor, [N.sup.[omega]]-nitro-L-arginine methyl ester (L-NAME), to rats induces coronary vascular inflammation [monocyte infiltration, monocyte chemoattractant protein-1 (MCP-1) expression, increased activity of angiotensin-converting enzyme (ACE)], and arteriosclerosis. Here, we used the rat model to investigate the anti-inflammatory effects of amlodipine in vivo. Treatment with amlodipine markedly inhibited the L-NAME-induced increase in vascular inflammation, oxidative stress, and local ACE and Rho activity and prevented arteriosclerosis. Interestingly, amlodipine prevented the L-NAME-induced increase in MCP-I receptor CCR2 expression in circulating monocytes. Amlodipine markedly attenuated the high mortality rate at 8 wk of treatment. These data suggest that amlodipine attenuated arteriosclerosis through inhibiting inflammatory disorders in the rat model of long-term inhibition of NO synthesis. The anti-inflammatory effects of amlodipine seem to be mediated not only by the inhibition of local factors such as MCP-I but also by the decrease in CCR2 in circulating monocytes. Inhibition of the MCP-I to CCR2 pathway may represent novel anti-inflammatory actions of amlodipine beyond blood pressure lowering. remodeling; angiotensin; monocytes

Matrix metalloproteinase-2 (MMP-2) is prominently overexpressed both after myocardial infarction (MI) and in heart failure. However, its pathophysiological significance in these conditions is still unclear. We thus examined the effects of targeted deletion of MMP-2 on post-MI left ventricular (LV) remodeling and failure. Anterior MI was produced in 10- to 12-wk-old male MMP-2 knock-out (KO) and sibling wild-type (WT) mice by ligating the left coronary artery. By day 28, MI resulted in a significant increase in mortality in association with LV cavity dilatation and dysfunction. The MMP-2 KO mice had a significantly better survival rate than WT mice (56% vs. 85%, P < 0.05), despite a comparable infarct size (50 [+ or -] 3% vs. 51 [+ or -] 3%, P = not significant), heart rate, and arterial blood pressure. The KO mice had a significantly lower incidence of LV rupture (10% vs. 39%, P < 0.05), which occurred within 7 days of MI. The KO mice exerted less LV cavity dilatation and improved fractional shortening after MI by echocardiography. The LV zymographic MMP-2 level significantly increased in WT mice after coronary artery ligation; however, this was completely prevented in KO mice. In contrast, the increase in the LV zymographic MMP-9 level after MI was similar between KO and WT mice. MMP-2 activation is therefore considered to contribute to an early cardiac rupture as well as late LV remodeling after MI. The inhibition of MMP-2 activation may therefore be a potentially useful therapeutic strategy to manage post-MI hearts. matrix metalloproteinase; cardiac rupture; heart failure; myocyte; extracellular matrix; mouse