Lipid extract from completely sporoderm‐broken germinating Ganoderma sinensis spores elicits potent antitumor immune responses in human macrophages

Ganoderma sinensis has been used widely in Oriental countries for the prevention and treatment of various diseases including cancer. Previous studies have shown that the lipid extract from Ganoderma exhibits direct cytotoxicity against tumor cells. Here, it is reported that the lipid extract from germinating G. sinensis spores, at lower concentrations that have no direct tumoricidal activity, induce potent antitumor immune responses in human monocytes/macrophages. Upon stimulation with the lipid extract, monocytes/macrophages exhibited markedly increased production of proinflammatory cytokines and surface expression of costimulatory molecules. Conditioned medium from stimulated cells effectively suppressed the growth of tumor cells. Apparently, the lipid extract triggered macrophage activation via a mechanism different from that associated with LPS. Moreover, it was observed that the lipid extract could partially re‐establish the antitumor activity of the immunosuppressive tumor‐associated macrophages. These results indicated that in addition to its direct tumoricidal activity, the lipid extract from G. sinensis spores could exert antitumor activity by stimulating the activation of human monocytes/macrophages. Copyright © 2008 John Wiley & Sons, Ltd.     

Detection of glaucomatous damage using multifocal ERG

The first‐order kernel analysis in multifocal electroretinogram (mfERG) using low contrast stimulation is suggested as a way to detect the inner retinal responses in animal studies. In this case report, this protocol is applied to human patients with glaucoma to demonstrate the possibility of using mfERG as a tool to detect glaucomatous damage. Two patients with glaucoma were recruited and had mfERG measurements with the 103‐scaled hexagonal stimulus pattern at low (50 per cent) contrast. Their responses were analysed and compared with those from normal subjects with the mfERG measured under the same condition. In the normal subjects, there were obvious oscillatory components on the ascending and descending limbs of the first‐order kernel response to 50 per cent contrast. In the glaucomatous patients, the oscillatory component on the descending limb was obviously diminished. In addition, this component was significantly diminished in the quadrant with a glaucomatous visual field defect. This suggests that the low‐contrast stimulation condition in mERG measurement may provide a good way to detect glaucomatous damage and this may help in clinical diagnosis of glaucoma.     

Novel azapeptide inhibitors of cathepsins B and K. Structural background to increased specificity for cathepsin B

Abstract: We have designed and synthesized a new series of azapeptides which act as potential inhibitors of cathepsin B and/or cathepsin K. Their structures are based upon the inhibitory sites of natural cysteine protease inhibitors, cystatins. For the synthesized azapeptides, the equilibrium constants for dissociation of inhibitor–enzyme complex, K_i, were determined. Comparison of these values indicated that all of the azainhibitors act much stronger toward cathepsin B. Z‐Arg‐Leu‐His‐Agly‐Ile‐Val‐OMe ( 7 ) proved to be approximately 500 times more potent for cathepsin B than for cathepsin K. To be able to explain the obtained experimental values we used the molecular dynamics procedures to analyze the interactions between cathepsin B and compound 7 . We also determined the structure of the most potent and selective cathepsin B azainhibitor by means of NMR studies and theoretical calculations. In this report, we describe SAR studies of azapeptide inhibitors indicating the influence of the conformational flexibility of the examined compounds on inhibition of cathepsins B and K.     

Performance and comparison of the Cockcroft-Gault and simplified Modification of Diet in Renal Disease formulae in estimating glomerular filtration rate in a Chinese Type 2 diabetic population.

AIMS: Our aim was to assess performances of the Cockcroft-Gault and simplified Modification of Diet in Renal Disease (MDRD) formulae in estimating glomerular filtration rate (GFR) in Chinese diabetic populations and their association with vascular risks. METHODS: A total of 1009 patients with Type 2 diabetes were categorized into low estimated GFR groups (GFR < 60 ml/min/1.73 m(2)) and control groups by the two equations. The performances of these formulae were assessed at different stages of kidney function. Carotid artery intima-media thickness (IMT) and the prevalence of diabetic retinopathy or albuminuria were compared among the groups. The ability of these formulae to identify established vascular risk markers using sensitivity, specificity, positive and negative predictive values were also compared. RESULTS: The prevalence of low estimated GFR was 32.7% with the Cockcroft-Gault formula and 5.2% with the MDRD formula, respectively. In low estimated GFR subjects by the MDRD formula, IMT was significantly thicker than those by the Cockcroft-Gault formula (1.2 mm vs. 1.0 mm; P < 0.05), with a higher prevalence of albuminuria (78.4 vs. 52.8%, P < 0.05) and diabetic retinopathy (46.5 vs. 30.5%; P < 0.05). The Cockcroft-Gault formula gave a specificity of 71.7% and a sensitivity of 37.0%, and the MDRD formula gave a specificity of 96.6% and a sensitivity of 7.9% in estimating low GFR relevant for established vascular risks. CONCLUSIONS: These formulae performed differently in Chinese diabetic populations. The simplified MDRD formula is minimally superior to the Cockcroft-Gault formula for its high specificity and positive predictive values in estimating low GFR relevant for vascular risks.