Simultaneous Determination of the Flavonoids and Limonoids in Citrus junos Seed Shells Using a UPLC–DAD-ESI/MS

Citrus junos seeds (CS) have been traditionally used for the treatment of cancer and neuralgia. They are also used to manufacture edible oil and cosmetic perfume. A large amount of CS shells without oil (CSS) are discarded after the oil in CS is used as foods or herbal remedy. To efficiently utilize CSS as a by-products, it needs to be studied through chemical analysis. Therefore, we developed an ultra-performance liquid chromatography (UPLC)–diode array detection (DAD) method for simultaneous determination and quantitative analysis of five components (two flavonoids and threes limonoids) in CSS. A Waters Acquity UPLC HSS T3 column C18 (2.1 × 100 mm, 1.8 μm) was used for this separation. It was maintained at 40 oC. The mobile phase used for the analysis was distilled water and acetonitrile with gradient elution. To identify the quantity of the five components, a mass spectrometer (MS) with an electrospray ionization (ESI) source was used. The regression equation showed great linearity, with correlation coefficient ≥ 0.9912. Limits of detection (LOD) and limits of quantification (LOQ) of the five compounds were 0.09 – 0.13 and 0.26 – 0.38 μg/mL, respectively. Recoveries of extraction ranged from 97.45% to 101.91%. Relative standard deviation (RSD) values of intra- and inter-day precision were 0.06 – 1.15% and 0.19 – 0.25%, respectively. This UPLC–DAD method can be validated to simultaneously analyze quantities of marker flavonoids and limonoids in CSS.

Simvastatin Reduces Lipopolysaccharides-Accelerated Cerebral Ischemic Injury via Inhibition of Nuclear Factor-kappa B Activity

Preceding infection or inflammation such as bacterial meningitis has been associated with poor outcomes after stroke. Previously, we reported that intracorpus callosum microinjection of lipopolysaccharides (LPS) strongly accelerated the ischemia/reperfusion-evoked brain tissue damage via recruiting inflammatory cells into the ischemic lesion. Simvastatin, 3-hydroxy-3-methylgultaryl (HMG)-CoA reductase inhibitor, has been shown to reduce inflammatory responses in vascular diseases. Thus, we investigated whether simvastatin could reduce the LPS-accelerated ischemic injury. Simvastatin (20 mg/kg) was orally administered to rats prior to cerebral ischemic insults (4 times at 72, 48, 25, and 1-h pre-ischemia). LPS was microinjected into rat corpus callosum 1 day before the ischemic injury. Treatment of simvastatin reduced the LPS-accelerated infarct size by 73%, and decreased the ischemia/reperfusion-induced expressions of pro-inflammatory mediators such as iNOS, COX-2 and IL-1beta in LPS-injected rat brains. However, simvastatin did not reduce the infiltration of microglial/macrophageal cells into the LPS-pretreated brain lesion. In vitro migration assay also showed that simvastatin did not inhibit the monocyte chemoattractant protein-1-evoked migration of microglial/macrophageal cells. Instead, simvastatin inhibited the nuclear translocation of NF-kappaB, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of IkappaB. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions.

4-hydroxy-2(E)-Nonenal facilitates NMDA-Induced Neurotoxicity via Triggering Mitochondrial Permeability Transition Pore Opening and Mitochondrial Calcium Overload

N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity is one of the major causes for neuronal cell death during cerebral ischemic insult. Previously, we reported that the final product of lipid membrane peroxidation 4-hydroxy-2E-nonenal (HNE) synergistically increased NMDA receptor-mediated excitotoxicity (J Neurochem., 2006). In this study, we investigated the mechanism involved in the synergistic neuronal cell death induced by co-treatment with HNE and NMDA. Although neither HNE (1 microM) nor NMDA (2 microM) alone induced the death of cortical neurons, simultaneous treatment of neuronal cells with HNE and NMDA synergistically evoked the death of the cells. However, the synergistic effect on neuronal death was observed only in the presence of calcium. HNE neither increased the cytosolic calcium level ([Ca2+]i) nor altered the NMDA-induced intracellular calcium influx. However, HNE together with NMDA elevated the mitochondrial calcium level and depolarized the mitochondrial transmembrane potential. Furthermore, HNE evoked damage of isolated mitochondria at the cytosolic calcium level (200 nM), which is maximally induced by 2 microM NMDA. Consistently, ATP was depleted in neurons when treated with both HNE and NMDA together. Ciclopirox, a potent inhibitor of mitochondrial permeability transition pore opening (Br. J. Pharmacol., 2005), largely prevented the synergistic damage of mitochondria and death of cortical neurons. Therefore, although low concentrations of HNE and NMDA cannot individually induce neuronal cell death, they can evoke the neuronal cell death by synergistically accelerating mitochondrial dysfunction.

Risk Factors of Cryptogenic Hepatocellular Carcinoma in Patients with Low Body Mass Index or without Metabolic Syndrome

BACKGROUND/AIMS: Many patients are diagnosed with cryptogenic hepatocellular carcinoma (HCC) without metabolic syndrome (MS). We investigated the risk factors for cryptogenic HCC in patients with a low body mass index (BMI) or without MS. METHODS: Thirty-six patients were diagnosed with cryptogenic HCC over a 10-year period at a tertiary research hospital. Data including BMI score and risk factors for MS were analyzed retrospectively. Patients with fewer than two risk factors for MS (n = 16) were compared with those with two or more risk factors (n = 20). Patients with high BMI (> or = 23 kg/m2, n = 20) were also compared with those with lower BMI (n = 16). RESULTS: Patients with fewer than two risk factors for MS were significantly more likely to smoke and be hepatitis B surface antibodies (anti-HBs)-positive vs. patients with two or more risk factors. However, only smoking was statistically significant on multivariate analysis. Peaks of BMI were observed in two regions. Lower BMI was significantly associated with the presence of anti-HBs compared with high BMI, although this association was not statistically significant on multivariate analysis. CONCLUSIONS: Smoking is a potential risk factor for cryptogenic HCC in patients without MS. Remote hepatitis B virus infection may be a risk factor for cryptogenic HCC in patients without MS or with a low BMI.

Xanthogranulomatous Pancreatitis Presents as a Solid Tumor Mass: A Case Report

Xanthogranulomatous inflammation (XGI) is a rare, idiopathic process in which lipid-laden histiocytes are deposited at various locations in the body. Although XGI has been reported to occur in various organs such as the gallbladder, kidney, bone, stomach, colon, appendix, lymph nodes, urachus, and urinary bladder and in soft tissues, xanthogranulomatous pancreatitis (XGP) is extremely rare. Herein, we report a case of XGP occurring in a 70-yr-old woman, who presented with abdominal pain for several months. On physical examination, mild epigastric tenderness was noted. Abdomen CT scan revealed a low attenuated mass in uncinate process of pancreas, suggesting malignant lesion. Whipple's operation was performed and the final pathologic diagnosis was XGP. The patient's post-operative course was uneventful, and no recurrence was found within 7 months of the operation. When a pancreatic mass does not show clinico-radiological features typical of common pancreatic neoplasms, XGP should be considered for a differential diagnosis.

Risk Factors Associated with Left Ventricular Diastolic Dysfunction in Type 2 Diabetic Patients without Hypertension / 당뇨병

BACKGROUND: Hypertension and age are recognized as important risk factors for left ventricular (LV) diastolic dysfunction. Some studies have shown that diabetes itself may also be an independent risk factor for LV diastolic dysfunction, although this is controversial. The aim of this study was to determine the factors associated with LV diastolic dysfunction in patients with type 2 diabetes in the absence of hypertension or ischemic heart disease (IHD). METHODS: Participants in this study consisted of 65 type 2 diabetes patients (M : F = 45 : 20; mean age 51 [26 to 76] years; mean body mass index [BMI] 25.0 +/- 2.5 kg/m2) without hypertension, heart disease, or renal disease. Individuals with ischemic electrocardiographic changes were excluded. LV diastolic function was evaluated by Doppler echocardiographic studies. RESULTS: Fifteen patients (23.1%) showed LV diastolic dysfunction on Doppler echocardiographic studies. Patients with LV diastolic dysfunction were older than those without diastolic dysfunction (60.0 +/- 2.5 vs. 50.5 +/- 1.9 years; P < 0.01). After adjusting for age and sex, BMI was higher (26.6 +/- 0.7 vs. 24.6 +/- 0.3 kg/m2; P < 0.01) and diabetes duration was longer (9.65 +/- 1.48 vs. 4.71 +/- 0.78 years; P < 0.01) in patients with LV diastolic dysfunction than in those without diastolic dysfunction. There were no differences in sex, smoking, blood pressure, lipid profiles, hemoglobin A1C, fasting glucose, fasting insulin, or diabetic microvascular complications between the LV diastolic dysfunction group and the normal diastolic function group. After adjusting for age, sex, and BMI, diabetes duration was found to be independently associated with LV diastolic dysfunction (odds ratio 1.38; confidence interval 1.12 to 1.72; P = 0.003). CONCLUSION: These results suggest that diabetes duration may be a risk factor for LV diastolic dysfunction in type 2 diabetic patients without hypertension or IHD.

A Case of Primary Biliary Cirrhosis in Association with an Overlap Syndrome of Systemic Sclerosis and Systemic Lupus Erythematosus / 대한류마티스학회지

Primary biliary cirrhosis (PBC) is a slowly progressive autoimmune disease of the liver that is related to anti-mitochondria antibody and the disease is characterized by portal inflammation and immune-mediated destruction of the intrahepatic bile ducts. Several autoimmune diseases, such as hypothyroidism, Sjogren syndrome and systemic sclerosis (SSc), occur with increased frequency in patients with PBC. However, there are a few reports of a possible connection between systemic lupus erythematosus (SLE) or autoimmune hemolytic anemia (AIHA) and PBC. A 52-year-old female was admitted with fatigue and dyspnea that she had suffered with for the past month. She had suffered from jaundice for 2 weeks before admission. Many of the clinical manifestations and laboratory findings suggested the diagnosis of PBC with SSc of the limited type and AIHA. She was treated with methylprednisolone pulse therapy and ursodeoxycholic acid. We consequently diagnosed her as having SLE, as she satisfied the 4 relative diagnostic criteria-arthritis, AIHA, positive antinuclear antibody and positive antiphospholipid antibodies.

A Familial Case of Hereditary Hemorrhagic Telangiectasia / 결핵및호흡기질환

Hereditary hemorrhagic telangiectasia (HHT, also called Osler-Weber-Rendu Disease) is a rare systemic fibrovascular dysplasia characterized by recurrent epistaxis, cutaneous telangiectasia, and visceral arteriovenous malformations (AVMs). HHT is an autosomal dominant disease with a prevalence of 1 in 5,000~8,000. Recurrent epistaxis is often the first and most common manifestation, and about 30% of patients reveal pulmonary AVM. Presently, we report a familial case of HHT. A 61-year-old male with asymptomatic multiple pulmonary AVMs was successfully treated with embolization. His older brother who presented with recurrent epistaxis and multiple telangiectasias was treated with laser ablation. Their pedigree revealed a family history of recurrent epistaxis.

A Case of Native Valve Endocarditis due to Staphylococcus epidermidis / 감염과화학요법

Although Staphylococcus epidermidis is a frequent cause of prosthetic valve endocarditis (PVE), it is regarded as a rare pathogen of native valve endocarditis (NVE). We report a case of NVE caused by methicillin-resistant S. epidermidis in a 62-year-old man. The bacterium was isolated from blood and tissue culture. The patient underwent valve replacement due to heart failure and was successfully treated by surgery and vancomycin administration for 7 weeks.

A Case of Native Valve Endocarditis due to Staphylococcus epidermidis / 감염과화학요법

Although Staphylococcus epidermidis is a frequent cause of prosthetic valve endocarditis (PVE), it is regarded as a rare pathogen of native valve endocarditis (NVE). We report a case of NVE caused by methicillin-resistant S. epidermidis in a 62-year-old man. The bacterium was isolated from blood and tissue culture. The patient underwent valve replacement due to heart failure and was successfully treated by surgery and vancomycin administration for 7 weeks.