Occult malignancy presenting as constrictive pericarditis

Metastatic tumour progression to the pericardium is generally characterised by an effusional pericarditis. It is extremely rare for tumour to metastasise to the pericardium and cause constrictive pericarditis in the absence of a pericardial effusion. We report the recent case of a patient who was referred to our centre with constrictive pericarditis. Following pericardectomy and histopathological analysis this was found to be secondary to an occult metastatic adenocarcinoma.     

Tumor necrosis factor alpha (TNF-α) autoregulates its expression and induces adhesion molecule expression in asthma

Subjects with mild asthma underwent repeated low-dose allergen exposure and bronchial biopsies were examined for the expression of TNF-α and adhesion molecules. Bronchial biopsies from moderately severe asthmatics were then tested in an explant culture system to assess the effect of Der p and CDP-870, a TNF-α blocking pegylated-antibody Fab, on expression of TNF-α and adhesion molecules. Low-dose allergen challenge significantly upregulated sub-mucosal mast cells, TNF-α(+) cells, and VCAM. When bronchial explants were exposed to Der p and CDP 870 for 24h, CDP 870 caused a significant reduction in TNF-α release both at baseline and following stimulation with Der p allergen. The bronchial biopsies showed significant upregulation of TNF-α positive cells and ICAM-1 following exposure to Der p (p=0.03) and this was reduced in the presence of CDP-870. So, allergen exposure up-regulates TNF-α expression in asthma and down-stream targets, including adhesion molecules that contribute to airway inflammation.     

Distinct cellular and therapeutic effects of obatoclax in rituximab-sensitive and -resistant lymphomas

Bcl-2 proteins represent a rheostat that controls cellular viability. Obatoclax, a BH3-mimetic, has been designed to specifically target and counteract anti-apoptotic Bcl-2 proteins. We evaluated the biological effects of obatoclax on the anti-tumour activity of rituximab and chemotherapy agents. Obatoclax induced cell death of rituximab/chemotherapy-sensitive (RSCL), -resistant cell lines (RRCL) and primary tumour-cells derived from patients with B-cell lymphomas (N=39). Obatoclax also enhanced the activity of rituximab and had synergistic activity when combined with chemotherapy agents. The ability of Obatoclax to induce PARP cleavage varied between patient samples and was not observed in some RRCL. Inhibition of caspase activity did not affect obatoclax activity, suggesting the existence of caspase-independent death pathways. Autophagy was detected by LC3 conversion and/or electron microscopy in RRCL and in patient-derived tumour cells. Moreover, obatoclax activity was inhibited by Beclin-1 knockdown. In summary, obatoclax is an active Bcl-2 inhibitor that potentiates the activity of chemotherapy agents and, to a lesser degree, rituximab. Defining the molecular events triggered by obatoclax is necessary to further its clinical development and identify potential biomarkers that are predictive of response.     

Comparison of two methods using plasma triglyceride concentration as a surrogate estimate of insulin action in nondiabetic subjects: triglycerides × glucose versus triglyceride/high-density lipoprotein cholesterol

The objective was to compare relationships between insulin-mediated glucose uptake and surrogate estimates of insulin action, particularly those using fasting triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations. Insulin-mediated glucose uptake was quantified by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test in 455 nondiabetic subjects. Fasting TG, HDL-C, glucose, and insulin concentrations were measured; and calculations were made of the following: (1) plasma concentration ratio of TG/HDL-C, (2) TG × fasting glucose (TyG index), (3) homeostasis model assessment of insulin resistance, and (4) insulin area under the curve (insulin-AUC) during a glucose tolerance test. Insulin-AUC correlated most closely with SSPG (r ∼ 0.75, P < .001), with lesser but comparable correlations between SSPG and TG/HDL-C ratio, TyG index, homeostasis model assessment of insulin resistance, and fasting TG and insulin (r ∼ 0.60, P < .001). Calculations of TG/HDL-C ratio and TyG index correlated with SSPG concentration to a similar degree, and the relationships were comparable to estimates using fasting insulin. The strongest relationship was between SSPG and insulin-AUC.     

Neuroprotective effects of vitexin, a flavonoid, on pentylenetetrazole-induced seizure in rats

Flavonoids are important constituents of food and beverages and have several neuropharmacological activities. Many of these compounds are ligands for γ-aminobutyric acid type A receptors in the central nervous system. This study aimed to investigate the anticonvulsant effects of intracerebroventricularly administered vitexin (5, 7, 4-trihydroxyflavone-8-glucoside), a flavonoid found in plants, in rats treated with pentylenetetrazole (90 mg/kg, intraperitoneally) and to clarify the underlying mechanism. Vitexin (100 and 200 μm, i.c.v) affected minimal clonic seizures and generalized tonic-clonic seizures induced by pentylenetetrazole by increasing the seizure onset time. Pretreatment with flumazenil suppressed the anticonvulsant effects of vitexin during the onset of both the seizures. These results indicate that vitexin has anticonvulsant effects in the brain, possibly through interaction at the benzodiazepine site of the γ-aminobutyric acid type A receptor complex.     

Quantification of sub-nanomolar levels of Penicillin G by differential pulse adsorptive stripping voltammetry

A novel selective and sensitive method is developed for determination of Penicillin G by Differential Pulse Adsorptive Stripping Voltammetry (DPAdSV). Penicillin G gave well-resolved diffusion-controlled cathodic peaks at -0.42 and -0.584 V, respectively (vs Ag/AgCl) in pH 7.50 of borate buffer. Optimal conditions were obtained as pH 7.50, accumulation potential of -0.2 V (vs Ag/AgCl), accumulation time of 120 s, and scan rate of 100 mV/s. Under the optimized conditions, a linear calibration curve was established for the concentration of Penicillin G in the range of 0.007-2.13 μg/ml with a detection limit of 0.000717 μg/ml. The procedure was successfully applied to the determination of Penicillin G in various medicine and biological samples. The relative standard deviation of the method at 0.05 and 0.5 μg/ml Penicillin G, for 10 runs, was 2.55% and 2.06%, respectively.     

Vicarin, a new isoflavone from Eremostachys vicaryi

Vicarin (1), a new isoflavone, has been isolated from the ethyl acetate-soluble fraction of the ethanolic extract of Eremostachys vicaryi, along with soforanarin B (2), luteolin 7-O-β-D-glucopyranoside (3), and hamighriprasin (4). Their structures were elucidated on the basis of their spectral data including MS and 2D NMR.