A biaryl xanthone derivative having axial chirality from Penicillium vinaceum

A new xanthone derivative having axial chirality was isolated from Penicillium vinaceum. Owing to the axial chirality, its structure, including absolute configuration, was determined by means of extensive spectroscopic data, such as UV, IR, MS, and 1D and 2D NMR spectra, and computational chiroptical methods. The new compound, (a R)-2'-methoxyvinaxanthone, has a structure containing two aromatic moieties with substituents hindering rotation about the biaryl axis. The compound gave positive results in a sea urchin egg test ( Paracentrotus lividus) and a crown gall tumor on potato disks test (Agrobacterium tumefaciens).     

Aluminum Melt Degassing Process Evaluation Depending on the Design and the Degree of the FDU Unit Graphite Rotor Wear

One of the most important indicators of casting quality is porosity. The formation of pores is largely conditioned by the presence of hydrogen in the batch and subsequently in the melt. The gasification of the melt is the primary factor increasing the porosity of casts. This paper addresses the issue of reducing the melt gasification by using FDU (Foundry Degassing Unit) unit. The gas content in the melt is evaluated by determining the Dichte Index depending on the geometry and the degree of the FDU unit rotor wear. For experiments performed under the operating conditions, three types of graphite rotors with different geometries are used. The extent of melt gasification and the Dichte Index are monitored during the rotor wear, at a rate of 0%, 25%, 50%, 75% and 100% rotor wear. Secondly, the chemical composition of the melt is monitored depending on the design and wear of the rotor. It is proven that the design and the degree of rotor wear do not have significant effect on the chemical composition of the melt and all evaluated samples fell within the prescribed quality in accordance with EN 1706. With regard to the overall comparison of the geometry and wear of individual rotor types, it has been proven that, in terms of efficiency, the individual rotors are mutually equivalent and meet the requirements for melt degassing throughout the service life.     

Estimating the mediating effect of different biomarkers on the relation of alcohol consumption with the risk of type 2 diabetes

PurposeModerate alcohol consumption is associated with a reduced type 2 diabetes risk, but the biomarkers that explain this relation are unknown. The most commonly used method to estimate the proportion explained by a biomarker is the difference method. However, influence of alcohol–biomarker interaction on its results is unclear. G-estimation method is proposed to accurately assess proportion explained, but how this method compares with the difference method is unknown.MethodsIn a case–cohort study of 2498 controls and 919 incident diabetes cases, we estimated the proportion explained by different biomarkers on the relation between alcohol consumption and diabetes using the difference method and sequential G-estimation method.ResultsUsing the difference method, high-density lipoprotein cholesterol explained the relation between alcohol and diabetes by 78% (95% confidence interval [CI], 41–243), whereas high-sensitivity C-reactive protein (?7.5%; ?36.4 to 1.8) or blood pressure (?6.9; ?26.3 to ?0.6) did not explain the relation. Interaction between alcohol and liver enzymes led to bias in proportion explained with different outcomes for different levels of liver enzymes. G-estimation method showed comparable results, but proportions explained were lower.ConclusionsThe relation between alcohol consumption and diabetes may be largely explained by increased high-density lipoprotein cholesterol but not by other biomarkers. Ignoring exposure–mediator interactions may result in bias. The difference and G-estimation methods provide similar results.     

IgA1-containing immune complexes in IgA nephropathy differentially affect proliferation of mesangial cells

BACKGROUND: Sera of patients with IgA nephropathy (IgAN) contain circulating immune complexes (CIC) composed of galactose-deficient IgA1 complexed with antiglycan antibodies. The role of these CIC in the pathogenesis of IgAN is not known. METHODS: We studied how proliferation of cultured mesangial cells (MC) is affected by CIC prepared from sera of IgAN patients and healthy control subjects using size-exclusion chromatography. CIC-containing fractions were added to serum-starved MC in culture, and cell proliferation was measured using (3)H-thymidine incorporation. The results were confirmed by staining MC using an antibody against proliferating cell nuclear antigen. RESULTS: The incubation of starved MC with serum fractions with M(r) 800 to 900 kD, rich with galactose-deficient IgA1, stimulated proliferation, while fractions with smaller complexes were inhibitory. Furthermore, CIC-containing larger molecular mass fractions isolated from serum of an IgAN patient collected during an episode of macroscopic hematuria stimulated MC proliferation more than CIC obtained during a subsequent quiescent phase. To examine the role of IgA, we removed IgA1 from serum before fractionation. The resultant IgA1-depleted fractions were devoid of stimulatory IgA-CIC. Sera of IgAN patients were also fractionated after addition of desialylated galactose-deficient polymeric IgA1 to form additional immune complexes. Supplementation with a small quantity of this IgA1 increased cellular proliferation in assays using serum fractions of M(r)>/=800 to 900 kD; uncomplexed IgA1 did not affect MC proliferation significantly. In contrast, supplementation with a larger quantity of this IgA1 inhibited cellular proliferation in assays using serum fractions of M(r) 700 to 800 kD. CONCLUSION: Overall, these findings suggest that CIC containing aberrantly glycosylated IgA1 affect proliferation of MC in vitro and, thus, likely play a role in the pathogenesis of IgAN.     

Cytochrome P450 3A4 and P-glycoprotein Activity and Assimilation of Tacrolimus in Transplant Patients with Persistent Diarrhea

Renal transplant recipients suffering from persistent diarrhea have been repeatedly reported to have increased tacrolimus (Tac) trough levels. This study aimed to explore this phenomenon in detail in 15 renal transplant recipients with diarrhea, whose immunosuppression consisted of corticosteroids, mofetil mycophenolate and Tac. Both hepatic and intestinal CYP3A4 and PGP activity, important determinants of Tac bioavailability, were assessed, together with global CYP activity and investigations for gastrointestinal infection, function and morphology. Global CYP, CYP3A4, PGP and trough/dose levels of Tac were compared with diarrhea-free controls. In addition, a pharmacokinetic study of Tac was performed in 11 patients affected by diarrhea versus 9 controls. As expected, diarrhea was associated with increased Tac trough levels. An even stronger, significant increase of dose-normalized Tac levels was observed between 90 and 360 min after Tac intake. Time to peak concentration and drug half-life, however, were not altered. In addition, a concomitant decrease (+/-50%) of intestinal PGP activity was noticed in patients with diarrhea. For global CYP, CYP3A4 and hepatic PGP activity no such differences were noted. This pattern was not influenced by the specific cause of diarrhea. These data strongly suggest that persistent diarrhea is associated with an increased oral bioavailability of Tac.     

Behaviour of nonresorbable bioactive glass–ceramic implanted into long bone defects: comparison with cancellous allografts

Introduction  The goal of this retrospective study was to compare the long-term results after implantation of the nonresorbable glass–ceramic material and transplantation of the cancellous allografts into the defects of long bones. Method  The bone cysts were excochleated and filled using granules of glass–ceramic material or cancellous allografts. Clinical, radiographic and scintigraphic examinations of 30 patients were carried out 2–14 years after their surgery. Results  Though signs of complete incorporation allowing full weight-bearing capacity were observed on plain radiographs, we detected pain in six out of nine patients after diaphyseal implantation of nonresorbable glass–ceramic. We found an increase in ^99 mTc-methylene diphosphonate uptake on the delayed images in the area of glass–ceramic implantation, mainly in its diaphyseal location. In patients after bone transplantation, the cancellous allografts were completely integrated and the scintigraphic findings were physiological. Conclusion  The implantation of the nonresorbable glass–ceramic material into the diaphyseal defects of long bones is not suitable based on our study.