Whole-brain 320-detector row dynamic volume CT perfusion detected crossed cerebellar diaschisis after spontaneous intracerebral hemorrhage.

INTRODUCTION: The purpose of this study was to evaluate the value of 320-detector row CT used to detect crossed cerebellar diaschisis (CCD) in patients with unilateral supratentorial spontaneous intracerebral hemorrhage (SICH). METHODS: We investigated 62 of 156 patients with unilateral supratentorial SICH using 320-detector row CT scanning. Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), mean transit time (rMTT), and time to peak (rTTP) levels were measured in different regions of interest (ROIs) that were manually outlined on computed tomography perfusion (CTP) for the cerebrum, including normal-appearing brain tissue that surrounded the perilesional low-density area (NA) and the perihematomal low-density area (PA) in all patients and the cerebellum (ipsilateral and contralateral) in CCD-positive patients. RESULTS: Of 62 cases, a total of 14 met the criteria for CCD due to cerebellar perfusion asymmetry on CTP maps. In the quantitative analysis, significant differences were found in the perfusion parameters between the contralateral and ipsilateral cerebellum in CCD-positive cases. No significant differences were found between the CCD-positive group and the CCD-negative group according to the hematoma volume, NIHSS scores, and cerebral perfusion abnormality (each P > 0.05). The correlation analysis of the degree of NA, PA perfusion abnormality, and the degree of CCD severity showed negative and significant linear correlations (R, -0.66∼-0.56; P < 0.05). CONCLUSION: 320-detector row CT is a robust and practicable method for the comprehensive primary imaging work-up of CCD in unilateral supratentorial SICH patients.

Intestinal ischemia/reperfusion enhances microglial activation and induces cerebral injury and memory dysfunction in rats.

OBJECTIVE: The mortality of critically ill patients associated with intestinal ischemia/reperfusion remains very high, which results from multiorgan dysfunction or failure due to intestinal injury induced by intestinal ischemia/reperfusion. This study was carried out to investigate whether intestinal ischemia/reperfusion can cause cerebral injury and concomitant memory dysfunction, and explore the potential mechanisms. DESIGN: Prospective, controlled, and randomized animal study. SETTING: University research laboratory. SUBJECTS: Male, adult Sprague-Dawley rats (weighing 250-300 g). INTERVENTIONS: Intestinal ischemia/reperfusion was established by clamping the superior mesenteric artery for 90 mins followed by different reperfusion durations (2, 6, 12, 24, or 48 hrs). The sham surgical preparation including isolation of the superior mesenteric artery without occlusion was performed as control. MEASUREMENTS AND MAIN RESULTS: In comparison with sham control, intestinal ischemia/reperfusion caused severe intestinal injury, accompanied by notable cerebral damage evidenced by increased wet-to-dry brain weight ratio reflecting brain edema and neuronal cell apoptosis manifested by increased apoptotic cell number and cleaved caspase-3 protein expressions. All these changes were concomitant with reduced survival rates as well as impaired memory function determined by Morris water maze test at 24 and 48 hrs after reperfusion. In addition, intestinal ischemia/reperfusion resulted in significant increases in the levels of tumor necrosis factor-α and interleukin-6 both in the serum and in cortices and hippocampal Cornu Ammonis area 1 regions, concomitant with the activation of microglia, a key cellular mediator involved in neuroinflammation and neurodegeneration, which was evidenced by increased protein expressions of ionized calcium binding adaptor molecule 1. Furthermore, the releases of reactive oxygen species evidenced by increased malondialdehyde levels and decreased superoxide dismutase activities in cortices and hippocampal Cornu Ammonis area 1 regions were found after reperfusion. CONCLUSIONS: These findings indicate that intestinal ischemia/reperfusion-induced intestinal injury can lead to cerebral damage and memory dysfunction partly via microglia activation which further facilitates oxidative injury, inflammatory response, and neuronal cell apoptosis.

Chemical constituents from the Streptomyces morookaensis strain Sm4-1986.

Three new compounds, including 6-methoxy-3,4,5,7-tetramethylisochromane-3,8-diol (1), 3,4,5,7-tetramethylisochromane-3,6,8-triol (2), streptimidone derivative (3), along with ten known compounds (4-13) were isolated from the Streptomyces morookaensis strain Sm4-1986. Their chemical structures were established based on the information from UV, IR, NMR (1H NMR, 13C NMR, 1H-1H COSY, HSQC, HMBC, NOESY), and mass spectroscopic. Moreover, all the isolated new compounds were evaluated for antibacterial activities (S. aureus, B. cereus, S. epidermids and methicillin-resistant S. aureus) and their cytotoxicities against MCF-7, A549, Hela tumor cell lines and Marc-145 normal cell line.

An ester derivative of tenacigenin B from Marsdenia tenacissima (Roxb.) Wight et Arn reversed paclitaxel-induced MDR in vitro and in vivo by inhibiting both P-gp and MRP2.

ETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia tenacissima is a medicinal plant, used as a raw material for cancer treatment in China. In our previous studies, 11α-O-2-methylbutanoyl-12ß-O-tigloyl-tenacigenin B (MT2), the main steroid aglycone isolated from M. tenacissima, was found to significantly enhance the antitumor activity of paclitaxel (PTX) in vivo. However, it is unclear whether MT2 reverses multidrug resistance (MDR) in tumors. AIM OF THE STUDY: To determine the role and mechanism of MT2 in reversing tumor MDR. MATERIALS AND METHODS: MDR cell line HeLa/Tax was established from the human cervical carcinoma cell line HeLa by long-term exposure to subtoxic concentrations of PTX and was used to evaluate the ability of MT2 to restore chemosensitivity of cells both in vitro and in a nude mouse model. The expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2) was determined using western blotting and immunohistochemistry. The substrate transport function was assessed using an MDR function assay kit. The binding modes of MT2 and P-gp were determined using the conformation-sensitive anti-P-gp antibodies. The permeability and transport properties of MT2 were analyzed in Caco-2 cell monolayers. RESULTS: Compared to parental cells, HeLa/Tax cells overexpress P-gp and MRP2 and are approximately 100-360 fold more resistant to the anticancer drugs PTX, docetaxel, and vinblastine. MT2 at 5 or 10 µmol/L significantly increased the sensitivity of HeLa/Tax to these three anticancer drugs (18-56-fold decrease in IC50 value) and suppressed the expression of P-gp and MRP2. Knockdown of P-gp with small interfering RNA partially reversed MT2-induced sensitivity to PTX in HeLa/Tax cells. Moreover, MT2 directly inhibited P-gp-mediated substrate transport while interacting with membrane P-gp in non-substrate ways. MT2 was highly permeable and could not be transported in the Caco-2 cell monolayers. In nude mice bearing HeLa/Tax xenografts, the combination treatment with MT2 and PTX exerted a synergistic inhibitory effect on the growth of tumors and the expression of P-gp and MRP2 without increasing toxicity. CONCLUSION: MT2 is a potential agent for reversing MDR. It impedes membrane drug efflux pumps by suppressing P-gp and MRP2 expression, and directly inhibiting the transport function of P-gp.

Prenylated stilbenes and flavonoids from the leaves of Cajanus cajan.

Three new prenylated stilbenes, named as cajanusins A-C (1-3), and one new natural product cajanusin D (4), along with six known derivatives (5-10) were isolated from the leaves of Cajanus cajan. Their structures were fully elucidated by means of extensive spectroscopic methods and comparison with data in the reported literatures. The new compounds of 1 and 2 were evaluated for in vitro cytotoxic activities against a panel of human cancer cell lines.

Association of alcohol consumption and components of metabolic syndrome among people in rural China.

BACKGROUND: Accumulative evidence in the literature suggests alcohol consumption is a protective factor of the metabolic syndrome (MS). However, few studies investigated the relationship between alcohol consumption and components of MS. We examined association of several types of alcoholic beverage with components of MS among people in rural China. METHODS: In the Nantong Metabolic Syndrome Study (NMSS), a cross-sectional study, a total of 20,502 participants, including 13,505 women and 6,997 men aged 18-74 years, were recruited between 2007 and 2008 in Nantong, China. Socio-economic status, dietary intake, physical exercise, alcoholic beverage consumption, and smoking status information were obtained, and triglycerides (TG), high-density lipoprtein cholesterol (HDL-c), blood pressure (BP) and blood glucose level were examined for all participants. Logistic regression model and the restricted cubic spline approach were used to analyze the associations between alcoholic beverage consumption and MS components. RESULTS: The MS prevalence was 21.1% in the whole population, which was significantly low among drinkers (20.6%), compared with non-drinkers (23.6%) in women, and was comparable in men (16.4% versus 17.1%). High HDL-c level was observed among drinkers, compared with non-drinkers in both men and women. Low TG level and Systolic BP (SBP) were found only among rice wine drinkers in women, and high waist circumference, high TG and BP were found among beer and liquor drinkers in men. Furthermore, we found that the highest quartile of rice wine drink in women may decrease 24% risk of high TG, 30% risk of low HDL-c and 43% risk of high glucose among MS components cases respectively, compared with non-drinkers (p for trend <0.01 for those three components). While compared non-drinkers among men, the highest quartile of liquor drink may increase 32% risk of high SBP, 55% risk of high Diastolic BP (DBP) and 34% risk of abdominal obesity among MS components cases respectively, but decrease 45% risk of low HDL-c (p for trend <0.05 for those four components). CONCLUSION: Our data suggested that all alcoholic beverages increased HDL-c level. Rice wine decreased both TG level and blood glucose in women only and it could be one of healthy alcoholic beverages in MS prevention in Chinese women. While excessive liquor consumption increased BP and waist circumference level and it may lead to hypertension and central obesity in Chinese men.