A Possible Relation Between Mechanical, Chemical and Electrical Quantities

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A neutral low-coordinate heterocyclic bismuth-tin species

The reaction of distannadiazane bearing bulky RAr*-groups (RAr* = C6H2{C(H)Ph2}2R-2,6,4; R = iPr, tBu) with ECl3 (E = Sb, Bi) was studied resulting in the isolation of previously unknown N,N-bis(dichloropnictino)amines (3) and a novel heterocyclic carbenoid bismuth species (4) bearing a Bi(III) and a Sn(IV) center. The structure and bonding was investigated by means of X-ray structure elucidations and DFT calculations

Dose-area product measurements during Barium enema radiograph examinations -a Western Cape study

The aim of this study was to obtain a direct measurement of the typical dose delivered to an average adult patient during a barium enema examination. Measurement was done on a sample of 50 patients at three departments, using a dose-area product (DAP) meter. The comparison of the results with UK median levels indicates that the doses measured in South Africa are higher (41 Gy cm2 (dose x area) v. 48 Gy cm2 ). Patient protection can be improved by comparing local practice with national reference levels. The values obtained in this study (first quartile 35 Gy cm2, median 48 Gy cm2, third quartile 84 Gy cm2) are recommended as initial reference dose levels for barium enemas in South Africa

The c- Jun N-terminal kinase JNK participates in cytokine- and isolation stress-induced rat pancreatic islet apoptosis

Aims/hypothesis: The protocols used for the preparation of human pancreatic islets immediately induce a sustained and massive activation of the c-Jun-N-terminal kinase (JNK). JNK, which participates in apoptosis of insulin-secreting cells, is activated by mechanical stresses, as well as by exposure to pro-inflammatory cytokines. Here, we investigated whether the delivery of a protease-resistant JNK inhibitory peptide (D-JNKI) through a protein transduction system during pancreatic digestion might impair JNK signalling throughout the transplantation procedure. Methods: Rat pancreases were treated with D-JNKI through the pancreatic duct and cells then isolated by enzymatic digestion. Protein extracts were prepared to determine JNK activity by kinase assays and total RNA was extracted to measure gene expressions by a Light-Cycler technique. Cell apoptosis rate was determined by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and by scoring cells displaying pycnotic nuclei. Results: Our data establish that the peptide transduction system used here efficiently transfects islets, allowing for stable in vivo (up to 2days) transfection of human islets transplanted under the kidney capsule. Further, D-JNKI decreases intracellular JNK signalling during isolation and following cytokine exposure in both human and rat islets, as measured by kinase assays and reduced c-fos expression; D-JNKI also confers protection against apoptosis induced during the rat islet preparation and subsequent to IL-1β exposure. Conclusions/interpretation: JNK signalling participates in islet isolation- and IL-1β-induced apoptosis in rat islets. Furthermore, the system we used might be more generally applicable for the persistent blockage (several days) of pro-apoptotic pathways in the transplanted islets; this days-long protection might potentially be an absolute prerequisite to help transplanted islets better survive the first wave of the non-specific inflammatory attac

Block-Transitive Designs in Affine Spaces

This paper deals with block-transitive $t$-$(v,k,\lambda)$ designs in affine spaces for large $t$, with a focus on the important index $\lambda=1$ case. We prove that there are no non-trivial 5-$(v,k,1)$ designs admitting a block-transitive group of automorphisms that is of affine type. Moreover, we show that the corresponding non-existence result holds for 4-$(v,k,1)$ designs, except possibly when the group is one-dimensional affine. Our approach involves a consideration of the finite 2-homogeneous affine permutation groups.Comment: 10 pages; to appear in: "Designs, Codes and Cryptography

State dependent dissociation of HERG channel inhibitors

BACKGROUND AND PURPOSE: Inhibition of HERG channels prolongs the ventricular action potential and the QT interval with the risk of torsade de pointes arrhythmias and sudden cardiac death. Many drugs induce greater inhibition of HERG channels when the cell membrane is depolarized frequently. The dependence of inhibition on the pulsing rate may yield different IC(50) values at different frequencies and thus affect the quantification of HERG channel block. We systematically compared the kinetics of HERG channel inhibition and recovery from block by 8 blockers at different frequencies. EXPERIMENTAL APPROACH: HERG channels were expressed heterologously in Xenopus oocytes and currents were measured with the two-electrode voltage clamp technique. KEY RESULTS: Frequency-dependent block was observed for amiodarone, cisapride, droperidol and haloperidol (group 1) whereas bepridil, domperidone, E-4031 and terfenadine (group 2) induced similar pulse-dependent block at all frequencies. With the group 1 compounds, HERG channels recovered from block in the presence of drug (recovery being voltage-dependent). No substantial recovery from block was observed with the second group of compounds. Washing out of bepridil, domperidone, E-4031 and terfenadine was substantially augmented by frequent pulsing. Mutation D540K in the HERG channel (which exhibits reopening at negative voltages) facilitated recovery from block by these compounds at −140 mV. CONCLUSION AND IMPLICATIONS: Drug molecules dissociate at different rates from open and closed HERG channels (‘use-dependent' dissociation). Our data suggest that apparently ‘trapped' drugs (group 2) dissociated from the open channel state whereas group 1 compounds dissociated from open and resting states

Vascular white matter lesions negatively correlate with brain metastases in malignant melanoma - results from a retrospective comparative analysis

Brain metastasis (BM) is a major complication of different cancers. There is increasing evidence for influence of vascular factors on BM in patients with non-small cell lung cancer (NSCLC). It is not known if the same is true for other tumors that might rely on different forms of vasculogenesis. The objective of this retrospective study was to evaluate a possible negative association of vascular white matter lesions and vascular risk factors (vasRF) with brain metastases in patients with melanoma