Endovascular treatment

Acute pulmonary thromboembolism is a common condition with non-specific findings, high mortality, and multiple therapeutic options. Death in patients with acute massive pulmonary thromboembolism is caused by sudden circulatory collapse as a consequence of obstructed pulmonary blood flow. Initial therapy must therefore be directed toward quickly restoring pulmonary circulation. In a number of cases, thrombolytic therapy may fail to achieve this therapeutic goal in time. Percutaneous catheter treatment may represent an additional option for high-risk patients. In this paper, different concepts of such treatment include pigtail catheter thrombectomy and embolus aspiration with PTCA guiding catheter are described.     

A novel neurotrophic agent, T-817MA [1-{3-[2-(1-benzothiophen-5-yl) ethoxy] propyl}-3-azetidinol maleate], attenuates amyloid-beta-induced neurotoxicity and promotes neurite outgrowth in rat cultured central nervous system neurons

Progressive neuronal loss in Alzheimer's disease (AD) is considered to be a consequence of the neurotoxic properties of amyloid-beta peptides (A beta). T-817MA (1-{3-[2-(1-benzothiophen-5-yl) ethoxy] propyl}-3-azetidinol maleate) was screened as a candidate therapeutic agent for the treatment of AD based on its neuroprotective potency against A beta-induced neurotoxicity and its effect of enhancing axonal regeneration in the sciatic nerve axotomy model. The neuroprotective effect of T-817MA against A beta(1-42) or oxidative stress-induced neurotoxicity was assessed using a coculture of rat cortical neurons with glia. T-817MA (0.1 and 1 microM) was strongly protective against A beta(1-42)-induced (10 microM for 48 h) or H2O2-induced (100 microM for 24 h) neuronal death. T-817MA suppressed the decrease of GSH levels induced by H2O2 exposure (30 microM for 4 h) in cortical neuron culture; therefore, T-817MA was likely to alleviate oxidative stress. Besides the neuroprotective effect, T-817MA (0.1 and 1 microM) promoted neurite outgrowth in hippocampal slice cultures and reaggregation culture of rat cortical neurons. T-817MA also increased the growth-associated protein 43 content in the reaggregation culture of cortical neurons. These findings suggest that T-817MA exerts neuroprotective effect and promotes neurite outgrowth in rat primary cultured neurons. Based on these neurotrophic features, T-817MA may have a potential for disease modification and be useful for patients with neurodegenerative diseases, such as AD.     

Relaxant effects of forskolin on guinea pig tracheal smooth muscle

We investigated the relaxant effects of forskolin, a diterpene derivative isolated from the roots ofColeus forskohlii, on guinea pig airway smooth muscle by measuring the isometric tension of tracheal smooth muscle in vitro and transcutaneous Po₂ during the histamine inhalation test (HIT) in vivo. Forskolin (10⁻⁹–10⁻⁵ M) caused dose-dependent relaxant effects on resting tone and on leukotriene C₄ (10⁻⁷ M)-, leukotriene D₄ (10⁻⁷ M)-, and carbachol (3 × 10⁻⁶ M)-induced contraction of tracheal smooth muscle. Moreover, with propranolol pretreatment the relaxant effect of forskolin on tracheal smooth muscle did not change, whereas with the same pretreatment the relaxant effect of isoproterenol diminished. Forskolin (10⁻⁸–10⁻⁶ M) raised tissue cyclic AMP levels dose-dependently in tracheal smooth muscle (6.7–359.9 pmol/mg protein). Forskolin (1 mg/kg) administered subcutaneously raised the respiratory threshold of (RT-histamine in the HIT. The determination of the RT-histamine by measuring tcPo₂ was possible without anesthesia. These results suggest that forskolin relaxes airway smooth muscle in guinea pigs in vitro and in vivo by raising tissue cyclic AMP levels and that its actions are independent ofβ-adrenoceptors.     

Depression, activities of daily living, and quality of life of community-dwelling elderly in three Asian countries: Indonesia, Vietnam, and Japan

The purpose of this study was to examine the prevalence of screening-based depression and the association of depression with activities of daily living (ADL) and quality of life (QOL) of community-dwelling elderly in the developing and developed countries. A total of 2,695 community-dwelling elderly subjects aged 60 years or older living in five rural Asian towns (Indonesia: 411, Vietnam: 379, Japan: 1,905) participated in this cross-sectional study. Depressive symptoms were assessed using a 15-item geriatric depression scale (GDS-15). ADL, higher daily activities, and medical and social history were assessed by interviews or self-report questionnaires. For the assessment of subjective QOL, a 100mm visual analogue scale was used. Using a cut-point of 5/6 for the GDS-15, 782 participants (29.0%) appeared to have depression (Indonesia: 33.8%, Vietnam: 17.2%, Japan: 30.3%). Subjects with depression had significantly lower scores for both ADL and QOL than those without depression in all the three countries. In all the three countries, 17.2-33.8% of community-dwelling elderly subjects had screening-based depression, which was commonly associated with both lower quantitative ADL and lower QOL.     

Impaired consciousness caused by a metastatic adrenal tumor of pulmonary adenocarcinoma

We report a case of pulmonary adenocarcinoma metastasizing to the adrenal glands, which caused adrenal insufficiency leading to impaired consciousness. A 62 year-old man was admitted with impaired consciousness. The patient started chemotherapy from 2004 for pulmonary adenocarcinoma. In August 2004, a metastatic adrenal tumor was detected and chemotherapy was continued thereafter. From July 2005, the patient started to have mild hyperkalemia, anorexia and general malaise, which progressed to disturbance of consciousness. At admission, physical examination showed generalized pigmentation in the skin and mucosa. Blood test revealed hypoglycemia, hyponatremia and hyperkalemia. A dexamethasone suppression test and a rapid ACTH loading test led to a diagnosis of primary hypoadrenalism (Addison's disease). Treatment with hydrocortisone improved the physical status and blood test values. However, the patient subsequently died of disseminated intravascular coagulation due to the tumor.     

Multiple early esophageal cancers arising from Barrett's esophagus, and a review of cases of early adenocarcinoma in Barrett's esophagus in Japan

A case of early esophageal adenocarcinoma arising in Barrett's esophagus is reported. Many cases of Barrett's esophagus, which is considered a premalignant condition, have been reported in Western countries, but few cases have been reported in Japan. The patient, a 53-year-old man with nausea and vomiting, was a drinker (four glasses wine/day for about 30 years), but did not smoke. He had had a hiatal hernia of the esophagus. Since endoscopic biopsies demonstrated an early adenocarcinoma in Barrett's esophagus, subtotal esophagectomy was performed. In the resected esophageal material, Barrett's esophagus was seen to extend for 12 cm. In addition to the cancer detected preoperatively as a 0-IIc lesion (1.5 cm in diameter), a 0-IIb lesion (1.5 cm in diameter) was also detected in the post-operative survey. Both lesions were well differentiated adenocarcinoma that had invaded only into the lamina propria mucosa. The 23 cases of early adenocarcinoma in Barrett's esophagus that have been reported in Japan were reviewed, and it was learned that the present case is the second of multiple early cancer arising in Barrett's esophagus so far reported in Japan.     

The efficacy of a novel collagen–gelatin scaffold with basic fibroblast growth factor for the treatment of vocal fold scar

Vocal fold scar remains a therapeutic challenge. Basic fibroblast growth factor (bFGF) was reported to have regenerative effects for vocal fold scar, although it has the disadvantage of rapid absorption in vivo. A collagen–gelatin sponge (CGS) can compensate for the disadvantage by providing a sustained release system. The current study evaluated the efficacy of CGS combined with bFGF on vocal fold scar, using rat fibroblasts for an in vitro model and a canine in vivo model. We prepared fibroblasts from scarred vocal folds (sVFs) in rats and showed that bFGF accelerated cell proliferation and suppressed expression levels of cleaved caspase 3 and α‐smooth muscle actin. Has 1, Has 3, Fgf2, Hgf and Vegfa mRNA levels were significantly upregulated, while Col1a1 and Col3a1 were dose‐dependently downregulated, with a maximum effect at 100 ng/ml bFGF. In an in vivo assay, 6 weeks after lamina propria stripping, beagles were divided into three groups: CGS alone (CGS group); CGS with bFGF (7 µg/cm²; CGS + bFGF group); or a sham‐treated group. Vibratory examination revealed that the glottal gap was significantly reduced in the bFGF group and the two implanted groups, whereas the CGS + bFGF group showed higher mucosal wave amplitude. Histological examination revealed significantly restored hyaluronic acid and elastin redistribution in the CGS + bFGF group and reductions in dense collagen deposition. These results provide evidence that CGS and bFGF combination therapy may have therapeutic potential and could be a promising tool for treating vocal fold scar. Copyright © 2015 John Wiley & Sons, Ltd.     

Regulation of anaphylactic responses by phosphatidylinositol phosphate kinase type I {alpha}

The membrane phospholipid phosphatidylinositol 4, 5-bisphosphate [PI(4,5)P(2)] is a critical signal transducer in eukaryotic cells. However, the physiological roles of the type I phosphatidylinositol phosphate kinases (PIPKIs) that synthesize PI(4,5)P(2) are largely unknown. Here, we show that the alpha isozyme of PIPKI (PIPKIalpha) negatively regulates mast cell functions and anaphylactic responses. In vitro, PIPKIalpha-deficient mast cells exhibited increased degranulation and cytokine production after Fcepsilon receptor-I cross-linking. In vivo, PIPKIalpha(-/-) mice displayed enhanced passive cutaneous and systemic anaphylaxis. Filamentous actin was diminished in PIPKIalpha(-/-) mast cells, and enhanced degranulation observed in the absence of PIPKIalpha was also seen in wild-type mast cells treated with latrunculin, a pharmacological inhibitor of actin polymerization. Moreover, the association of FcepsilonRI with lipid rafts and FcepsilonRI-mediated activation of signaling proteins was augmented in PIPKIalpha(-/-) mast cells. Thus, PIPKIalpha is a negative regulator of FcepsilonRI-mediated cellular responses and anaphylaxis, which functions by controlling the actin cytoskeleton and dynamics of FcepsilonRI signaling. Our results indicate that the different PIPKI isoforms might be functionally specialized.