Moscatilin,a bibenzyl derivative from the India orchid Dendrobrium loddigesii, suppresses tumor angiogenesis and growth in vitro and in vivo

Attacking angiogenesis is considered an effective strategy for controls the expansion and metastasis of tumors and other related-diseases. The aim of this study was to assess the effects of moscatilin, a bibenzyl derivative, on VEGF and bFGF-induced angiogenesis in cultured human umbilical vein endothelial cells (HUVECs) in vitro and in vivo. Moscatilin significantly inhibited growth of lung cancer cell line A549 (NSCLC) and suppressed growth factor-induced neovascularization. In addition, VEGF- and bFGF-induced cell proliferation, migration, and tube formation of HUVECs was markedly inhibited by moscatilin. Western blotting analysis of cell signaling molecules indicated that moscatilin inhibited ERK1/2, Akt, and eNOS signaling pathways in HUVECs. These results suggest that inhibition of angiogenesis by moscatilin may be a major mechanism in cancer therapy.     

The quality of eight health status measures were compared for chronic opioid dependence

ObjectiveTo provide a comparative analysis of the psychometric properties of eight measures of health status among chronic opioid-dependent patients.Study Design and SettingLongitudinal data were analyzed for 251 patients enrolled in the North American Opiate Medication Initiative randomized controlled trial, conducted in Vancouver, British Columbia and Montreal, Quebec, Canada. Content validity, evidence of floor and ceiling effects, internal consistency, construct validity, and responsiveness were assessed for the Addiction Severity Index (ASI) medical and psychiatric (ASImed and ASIpsych) composite scores, the Maudesley Addiction Profile (MAP) physical and mental health scores (MAP-physical health score [MAP-PHS], MAP-mental health score [MAP-MHS]), the World Health Organization Disability Assessment Schedule-II, the EuroQol Group's EQ-5D index score and visual analog scale, EuroQol visual analog scale (EQ-VAS), and the Short Form SF-6D index score.ResultsASImed was best able to discriminate among patients with and without chronic conditions. The MAP-PHS and MAP-MHS were not unidimensional. ASImed and ASIpsych had prominent ceiling effects. ASImed, MAP-MHS, MAP–PHS, EQ-VAS, and EQ-5D were all responsive to decreases in illicit drug use.ConclusionNone of the instruments performed uniformly as “best” or “worst.” The EQ-5D appeared to be the preferable generic, indirect utility measure. Our results provide an evidence base to inform selection and further development of health status measures in opioid-dependent populations.     

Characterization of alpha 1-adrenoceptor subtypes in tension response of human prostate to electrical field stimulation.

1. The effects of various alpha 1-adrenoceptor antagonists and nifedipine on tension responses of human prostate to electrical field stimulation were evaluated in this study. 2. Prazosin (3 x 10(-10) to 10(-8) M) and 5-methyl-urapidil (10(-9) to 3 x 10(-8) M) blocked concentration-dependently the tension responses to electrical field stimulation and completely abolished them in the maximal concentrations (10(-8) M and 3 x 10(-8) M, respectively); in contrast, chloroethylclonidine (CEC), in the maximal concentration of 100 microM, blocked these effects by only 50%. 3. The contractile responses of rat vas deferens and spleen to exogenously-applied alpha 1-adrenoceptor agonists were competitively inhibited by prazosin and 5-methyl-urapidil; in addition, the pA2 values were calculated and the relative potencies with reference to prazosin were obtained. The relative potency of 5-methyl-urapidil in human prostate (0.105) was close to that in rat vas deferens (0.257), which contains primarily putative alpha 1A-adrenoceptors. However, it was much more than that in rat spleen (0.011), which contains primarily putative alpha 1B-adrenoceptors. 4. Nifedipine (10(-8) to 10(-6) M) inhibited concentration-dependently the contractile responses to electrical field stimulation in human prostate; in addition, the inhibition percentages were similar to those to exogenously-applied noradrenaline in rat vas deferens. In contrast, CEC (10 microM), which almost flattened the concentration-response curve of the rat spleen to phenylephrine, only partially inhibited (by 33.1%) the nerve-mediated contraction of human prostate. 5. The involvement of prejunctional alpha 2-adrenoceptors situated on the sympathetic nerve terminals of human prostate was also examined.(ABSTRACT TRUNCATED AT 250 WORDS)     

(-)-Discretamine, a selective alpha 1D-adrenoceptor antagonist, isolated from Fissistigma glaucescens.

1. The selectivity of (-)-discretamine for alpha 1-adrenoceptor subtypes was investigated by use of functional and binding studies in rat vas deferens, spleen and aorta, and in cultured DDT1MF-2 and A10 cells. 2. In prostatic portions of rat vas deferens, the competitive antagonists (-)-discretamine, 5-methylurapidil (5-MU) and prazosin inhibited contractions to noradrenaline (NA) with pA2 values of 6.21, 8.71 and 9.27, respectively. The irreversible antagonist, chloroethylclonidine (CEC, 100 microM) failed to affect contractions to NA while nifedipine (1 microM) blocked them almost completely. 3. In rat spleen, the competitive antagonists (-)-discretamine, 5-MU and prazosin inhibited contractions to phenylephrine with pA2 values of 6.44, 7.19 and 9.45, respectively. CEC (100 microM) significantly reduced the maximum contraction to phenylephrine while nifedipine (1 microM) did not affect it. 4. In rat aorta, the competitive antagonists (-)-discretamine, 5-MU and prazosin inhibited contractions to NA with pA2 values of 7.60, 8.00 and 9.40, respectively. CEC also antagonized the contractions to NA in a competitive manner with a pA2 value of 6.10. 5. The specific binding of [3H]-prazosin to DDT1MF-2 and A10 cells was concentration-dependent and saturated at 3-5 nM with KD values of 0.24 +/- 0.02 and 0.20 +/- 0.02 nM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alterations of glomerular and extracellular levels of glutathione peroxidase in patients and experimental rats with diabetic nephropathy

To investigate the status and role of glutathione peroxidase (GPX) in diabetic nephropathy, we measured GPX in the plasma and urine of 14 patients with diabetic glomerulosclerosis (DGS) and measured glomerular GPX immunostaining in these patients and in rats with streptozotocin-induced diabetes of varying duration. Plasma GPX levels were significantly lower in DGS patients than in diabetic patients without nephropathy (P < .05) or normal controls (P < .01). Urinary GPX concentrations were also significantly lower in DGS patients than in diabetic patients without nephropathy or normal controls (both P < .05). Immunostaining of glomerular GPX was significantly less in DGS patients than in normal controls (P < .05) and was negatively correlated with the glomerular sclerosis score and the index of mesangial expansion. Serial examination of glomerular GPX in diabetic rats showed that immunostaining scores for glomerular GPX in rats were significantly lower than those in normal control rats after 1 and 3 months' duration of diabetes, and staining scores were also significantly lower in rats killed after 3 months of diabetes than in those killed after 1 week. In conclusion, our study demonstrates that GPX concentrations in plasma, urine, and glomeruli are decreased in individuals with DGS and that the immunostaining of glomerular GPX decreases progressively.     

Role of lipid control in diabetic nephropathy

Patients with diabetic nephropathy are known to be associated with many lipoprotein abnormalities, including higher plasma levels of very low-density lipoprotein, low-density lipoprotein and triglycerides, and lower levels of high-density lipoprotein. Many studies have reported that lipids may induce both glomerular and tubulointerstitial injury through mediators such as cytokines, reactive oxygen species, chemokines, and through hemodynamic changes. Clinical studies in patients with diabetic nephropathy showed that lipid control can be associated with an additional effect of reduction in proteinuria. Experimental studies demonstrated that lipid-lowering agents exerted a certain degree of renoprotection, through both indirect effects from lipid lowering and a direct effect on cell protection. Therefore, lipid control appears to be important in the prevention and treatment of diabetic nephropathy. Diabetic nephropathy has become the leading cause of end-stage renal failure in many countries, including Taiwan. One of the major risk factors for the development and progression of diabetic nephropathy is dyslipidemia. In this paper we will review the role of lipid in mediating renal injury and the beneficial effects of lipid control in diabetic nephropathy.     

Differential effects of circulating IgA isolated from patients with IgA nephropathy on superoxide and fibronectin production of mesangial cells.

BACKGROUND: IgA nephropathy (IgAN) is characterized by predominant deposition of IgA in the glomerular mesangium. Serum IgA is often elevated in patients with IgAN, and it has been postulated that it is responsible for the mesangial lesions. However, the direct effect of circulating IgA on mesangial cells is not clear. METHODS: We investigated the effects of sera and IgA which were isolated from patients with IgAN on thymidine uptake, superoxide and fibronectin production and fibronectin mRNA expression of cultured rat mesangial cells, and we compared the findings to the effects of IgA isolated from patients with non-IgA mesangial proliferative glomerulonephritis (MsPGN) and normal controls. IgA was isolated with affinity chromatography using cyanogen bromide activated Sepharose 4B coupled to sheep antihuman IgA antiserum. RESULTS: Our results demonstrated that both sera and IgA from patients with IgAN dose-dependently increased mitogenesis of mesangial cells as measured by (3)H-labeled thymidine uptake. The thymidine uptake by sera and IgA isolated from patients with IgAN was significantly higher than that of sera and IgA isolated from patients with MsPGN and normal controls. Sera and IgA from patients with IgAN significantly enhanced superoxide and fibronectin production and fibronectin mRNA expression of mesangial cells. The superoxide and fibronectin production was also significantly higher as compared with patients with MsPGN and normal controls. CONCLUSIONS: Our results indicate that circulating IgA isolated from patients with IgAN is different from that of patients with MsPGN and normal controls and may potentially induce oxidative injury and production of extracellular matrix of glomerular mesangial cells in IgAN.     

Frequency of panton-valentine leukocidin-producing methicillin-sensitive Staphylococcus strains in patients with complicated skin and soft tissue infection in bronx, new york

lukF-PV was present in 36% of skin and soft tissue infection (SSTI)-derived methicillin-susceptible Staphylococcus aureus (MSSA) strains and comprised six distinct clones, which contained fewer enterotoxin genes than strains without lukF-PV. Clinical presentations and outcomes of lukF-PV(+) methicillin-resistant S. aureus (MRSA) and MSSA SSTIs were comparable. In multivariable analysis, the presence of lukF-PV remained a significant predictor for incision and drainage among MSSA strains.     

Castleman’s disease of the mesorectum: Report of a case

Castleman’s disease is a benign lymphoid proliferative disorder, which most commonly presents as a solitary mass in the mediastinum, although extrathoracic sites have been reported in the neck, axilla, pelvis, mesentery, pancreas, and retroperitoneum. We report a case of asymptomatic, isolated Castleman’s disease in the mesorectum, which is extremely rare. The patient was a 34-year-old woman who underwent investigations for vaginal spotting. A presacral mass was located on the left side of the rectum, 10 cm from the anal verge. Contrast-enhanced computed tomography showed a large, well-demarcated, strongly enhancing mass with internal radiating septa in the mesorectum. The mass was well circumscribed and isointense to muscle on T1-weighted magnetic resonance imaging, appearing as a slightly hyperintense mass on T2-weighted imaging. We performed laparoscopic mesorectal mass excision, and histological examination revealed features typical of the hyaline-vascular type of Castleman’s disease. Thus, when a mesorectal mass is being investigated, Castleman’s disease should be considered in the differential diagnosis.