Intravenous tissue plasminogen activator for an ischemic stroke with occult double primary cancer.

BACKGROUND: In patients with advanced-stage cancer, systemic thrombolysis with tissue plasminogen activator (tPA) for hyperacute ischemic stroke is not strictly off-label, but it is at higher risk of complications (including bleeding). CASE REPORT: A 71-year-old male with unrecognizable malignancy developed a hemispheric ischemic stroke and received intra-venous tPA within 4.5 h of onset, followed by anticoagulation treatment after 24 h of throm-bolysis. Two days later, the patient had tarry stool and progressive anemia, receiving a blood transfusion. The systemic workup documented the presence of double primary cancers with advanced stage gastric and rectal cancers, and the patient subsequently received palliative care. The outcome at 3 months was a modified Rankin Scale of 5, and the patient died 6 months after the stroke. DISCUSSION: Although systemic thrombolysis with tPA for ischemic stroke in patients with advanced-stage cancer may be performed relatively safely, optimal post-thrombolysis management is important to prevent the complications.

Palmitic acid induces osteoblastic differentiation in vascular smooth muscle cells through ACSL3 and NF-κB, novel targets of eicosapentaenoic acid.

Free fatty acids (FFAs), elevated in metabolic syndrome and diabetes, play a crucial role in the development of atherosclerotic cardiovascular disease, and eicosapentaenoic acid (EPA) counteracts many aspects of FFA-induced vascular pathology. Although vascular calcification is invariably associated with atherosclerosis, the mechanisms involved are not completely elucidated. In this study, we tested the hypothesis that EPA prevents the osteoblastic differentiation and mineralization of vascular smooth muscle cells (VSMC) induced by palmitic acid (PA), the most abundant long-chain saturated fatty acid in plasma. PA increased and EPA abolished the expression of the genes for bone-related proteins, including bone morphogenetic protein (BMP)-2, Msx2 and osteopontin in human aortic smooth muscle cells (HASMC). Among the long-chain acyl-CoA synthetase (ACSL) subfamily, ACSL3 expression was predominant in HASMC, and PA robustly increased and EPA efficiently inhibited ACSL3 expression. Importantly, PA-induced osteoblastic differentiation was mediated, at least in part, by ACSL3 activation because acyl-CoA synthetase (ACS) inhibitor or siRNA targeted to ACSL3 completely prevented the PA induction of both BMP-2 and Msx2. Conversely, adenovirus-mediated ACSL3 overexpression enhanced PA-induced BMP-2 and Msx2 expression. In addition, EPA, ACSL3 siRNA and ACS inhibitor attenuated calcium deposition and caspase activation induced by PA. Notably, PA induced activation of NF-κB, and NF-κB inhibitor prevented PA-induction of osteoblastic gene expression and calcium deposition. Immunohistochemistry revealed the prominent expression of ACSL3 in VSMC and macrophages in human non-calcifying and calcifying atherosclerotic plaques from the carotid arteries. These results identify ACSL3 and NF-κB as mediators of PA-induced osteoblastic differentiation and calcium deposition in VSMC and suggest that EPA prevents vascular calcification by inhibiting such a new molecular pathway elicited by PA.

Distinct regulation of plasma LDL cholesterol by eicosapentaenoic acid and docosahexaenoic acid in high fat diet-fed hamsters: participation of cholesterol ester transfer protein and LDL receptor.

Despite established anti-atherogenic action, previous reports have shown that fish oils or n-3 poly-unsaturated fatty acid (PUFA) increase plasma LDL-C in animals and humans. However, which component of n-3 PUFAs and what mechanisms contribute to this increase are unclear. We investigated the effects of the major components of n-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on plasma LDL-C in high fat diet-fed hamsters. While LDL-C increased significantly with n-3 PUFA oil and DHA, EPA had no effect on LDL-C. Interestingly, a positive correlation was found between plasma cholesterol ester transfer protein (CETP) activity and LDL-C. Only DHA increased plasma CETP activity and significantly decreased LDL receptor expression in the liver. Our data suggest that DHA, not EPA, is a major factor in the LDL-C increasing effect of n-3 PUFA oil. These differential effects on LDL-C may arise from differences in plasma CETP activity and LDL receptor expression.

[Endogenous endophthalmitis and meningo-encephalitis in septic bacteremia of Klebsiella pneumoniae].

Endogenous endophthalmitis may be a rare condition in acute meningo-encephalitis. A 69-year-old compromised adult abruptly developed septic bacteremia and meningo-encephalitis by Klebsiella pneumoniae. After an improvement from initial conscious disturbance and systemic inflammatory unstable vital conditions by treatment of intensive antibiotic medications, severe unilateral endogenous endophthalmitis with impaired visual acuity was diagnosed by detailed ophthalmological assessments and it deteriorated rapidly. After early vitreous surgery with anti-biotic direct injection, the patient successfully regained visual acuity of 20/200. Among the organisms of endogenous bacterial endophthalmitis, Klebsiella pneumoniae is the worst pathogen mostly resulting in vision loss or enucleation despite any aggressive treatments. The neuro-physicians should recognize the presence of refractory endophthalmitis by Klebsiella pneumoniae, even if clinically asymptomatic, because prompt ophthalmologic diagnosis and managements may improve the outcome.

Eicosapentaenoic acid attenuates statin-induced ER stress and toxicity in myoblast.

We previously reported that eicosapentaenoic acid (EPA) improved statin-induced rhabdomyolysis in rats (Naba et al. [6]). In this study, we report for the first time direct improvement by EPA of statin-induced toxicity in cultured myoblasts and the mechanistic involvement of endoplasmic reticulum (ER) stress. Differentiated rhabdomyosarcoma cells (RD cells) were treated with statins and EPA for 1-4days. Statins induced various toxic changes in RD cells, and EPA attenuated all of these changes. Interestingly, statins increased mRNA expression of ER stress markers (XBP-1 and CHOP) and EPA attenuated both. Further, in a statin-induced rat model of rhabdomyolysis, these markers in skeletal muscle were significantly correlated with plasma CPK activity. In RD cells, statins also increased p-c-Jun protein content and caspase-3/7 activity, while 4-PBA, an ER stress attenuator, PPAR-δ agonist, and EPA attenuated them. These findings suggest that EPA attenuates statin-induced ER stress, JNK activation and toxicity in cultured myoblast cells, and that PPAR-δ may mechanically involved in the effects of EPA.

Ionic Polymers Act as Polyelectrolytes in Nonpolar Media.

Polyelectrolytes are ubiquitous materials, and their unique properties originate from dissociation of ionic groups to the small number of macromolecular ions and the large number of small counterions. They have been exploited only in water or high-dielectric media and scarcely in nonpolar ones (ε < 10). Herein, we demonstrate that poly(octadecyl acrylate) bearing tetraalkylammonium tetraarylborate as ionic groups behaves as a polyelectrolyte in the common nonpolar organic solvents such as chloroform, THF, and 1,2-dichloroethane. Conductivity measurement, DOSY NMR spectroscopy, and viscosity measurements clearly indicate that they form the extended conformation in them. This result emphasizes that the ionic polymers bearing suitable ion pairs ionizable in the given media act as polyelectrolytes. Various characteristic properties and processes of polyelectrolytes should be realized in nonpolar media by designing ion pairs and polymer chains in the ionic polymers. Moreover, our results imply that electrostatic interaction is readily available as a long-range repulsive force even in the nonpolar media.

Antiobesity effect of eicosapentaenoic acid in high-fat/high-sucrose diet-induced obesity: importance of hepatic lipogenesis.

OBJECTIVE: Given the pleiotropic effect of eicosapentaenoic acid (EPA), it is interesting to know whether EPA is capable of improving obesity. Here we examined the anti-obesity effect of EPA in mice with two distinct models of obesity. RESEARCH DESIGN AND METHODS: Male C57BL/6J mice were fed a high-fat/high-sucrose diet (25.0% [w/w] fat, 32.5% [w/w] sucrose) (HF/HS group) or a high-fat diet (38.1% [w/w] fat, 8.5% [w/w] sucrose) (HF group) for 4-20 weeks. A total of 5% EPA was administered by partially substituting EPA for fat in the HF/HS + EPA and HF + EPA groups. RESULTS: Both the HF/HS and HF groups similarly developed obesity. EPA treatment strongly suppresses body weight gain and obesity-related hyperglycemia and hyperinsulinemia in HF/HS-fed mice (HF/HS + EPA group), where hepatic triglyceride content and lipogenic enzymes are increased. There is no appreciable effect of EPA on body weight in HF-fed mice (HF + EPA group) without enhanced expression of hepatic lipogenic enzymes. Moreover, EPA is capable of reducing hepatic triglyceride secretion and changing VLDL fatty acid composition in the HF/HS group. By indirect calorimetry analysis, we also found that EPA is capable of increasing energy consumption in the HF/HS + EPA group. CONCLUSIONS: This study is the first demonstration that the anti-obesity effect of EPA in HF/HS-induced obesity is associated with the suppression of hepatic lipogenesis and steatosis. Because the metabolic syndrome is often associated with hepatic lipogenesis and steatosis, the data suggest that EPA is suited for treatment of the metabolic syndrome.