Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/W-v mice

Background and purpose: W/Wv and wild-type murine bladders were studied to determine whether the W/Wv phenotype, which causes a reduction in, but not abolition of, tyrosine kinase activity, is a useful tool to study the function of bladder interstitial cells of Cajal (ICC).

Experimental approach: Immunohistochemistry, tension recordings and microelectrode recordings of membrane potential were performed on wild-type and mutant bladders.

Key results: Wild-type and W/Wv detrusors contained c-Kit- and vimentin-immunopositive cells in comparable quantities, distribution and morphology. Electrical field stimulation evoked tetrodotoxin-sensitive contractions in wild-type and W/Wv detrusor strips. Atropine reduced wild-type responses by 50% whereas a 25% reduction occurred in W/Wv strips. The atropine-insensitive component was blocked by pyridoxal-5-phosphate-6-azophenyl-2',4'-disulphonic acid in both tissue types. Wild-type and W/Wv detrusors had similar resting membrane potentials of -48 mV. Spontaneous electrical activity in both tissue types comprised action potentials and unitary potentials. Action potentials were nifedipine-sensitive whereas unitary potentials were not. Excitatory junction potentials were evoked by single pulses in both tissues. These were reduced by atropine in wild-type tissues but not in W/Wv preparations. The atropine-insensitive component was abolished by pyridoxal-5-phosphate-6-azophenyl-2',4'-disulphonic acid in both preparations.

Conclusions and implications: Bladders from W/Wv mice contain c-Kit- and vimentin-immunopositive ICC. There are similarities in the electrical and contractile properties of W/Wv and wild-type detrusors. However, significant differences were found in the pharmacology of the responses to neurogenic stimulation with an apparent up-regulation of the purinergic component. These findings indicate that the W/Wv strain may not be the best model to study ICC function in the bladder.

V-band 57-65 GHz receiver

A simple V-band radio IQ receiver architecture based around a six-port monolithic microwave integrated circuit (MMIC) is presented. The receiver assembly is designed to cover the 57-65 GHz broadband wireless communication system frequency allocation. The receiver that has an integral 10 dB microstrip antenna consumes 120 mW of dc power and occupies an area of 23 mm x 16 mm. The receiver can be used in heterodyne or in homodyne mode and has the capacity to demodulate quadrature amplitude modulation (QAM), binary phase shift keying (BPSK)/quadrature phase shift keying (QPSK)/offset quadrature phase shift keying (OQPSK). At 60 GHz the receiver can operate over 10 m range for transmitter effective isotropic radiated power (EIRP) of 20 dBm.

Antibody Targeting of Cathepsin S Inhibits Angiogenesis and Synergistically Enhances Anti-VEGF

BACKGROUND: Angiogenesis is a key hallmark of tumourigenesis and its inhibition is a proven strategy for the development of novel anti-cancer therapeutics. An important aspect of early angiogenesis is the co-ordinated migration and invasion of endothelial cells through the hypoxic tumour tissue. Cathepsin S has been shown to play an important role in angiogenesis as has vascular endothelial growth factor (VEGF). We sought to assess the anti-angiogenic effect of Fsn0503, a novel cathepsin S inhibitory antibody, when combined with anti-VEGF on vascular development.

METHODOLOGY/PRINCIPAL FINDINGS: Cathepsin S expression and secretion from endothelial cells was characterised using RT-PCR and western blotting. We further show that cathepsin S promotes pericellular hydrolysis of extracellular matrix components in the tumour microenvironment and facilitates endothelial invasion. The cathepsin S inhibitory antibody, Fsn0503, blocks extracellular proteolysis, inhibiting endothelial invasion and tube formation in cell-based assays. The anti-angiogenic effects of Fsn0503 were also shown in vivo where it significantly retarded the development of vasculature in human xenograft models. Furthermore, when Fsn0503 was combined with an anti-VEGF antibody, a synergistic inhibition of microvascular development was observed.

CONCLUSIONS/SIGNIFICANCE: Taken together, this data demonstrates that the antibody-mediated targeting of cathepsin S represents a novel method of inhibiting angiogenesis. Furthermore, when used in combination with anti-VEGF therapies, Fsn0503 has the potential to significantly enhance current treatments of tumour neovascularisation and may also be of use in the treatment of other conditions associated with inappropriate angiogenesis.

Annotation of Case C-43/93, Raymond Vander Elst v Office des Migrations Internationales, ECR I-3803

Freedom to provide services - Nationals of a non-member country - Posted Workers

Annotation of Case C-353/92, Hellenic Republic v Council, ECR 1994 I-3411, and Case C-358/92, Hellenic Republic v Commission, ECR I-3507

Action for annulment - Council Regulation (EEC) Nº 1765/92 of 30 June 1992 establishing a support system for producers of certain arable crops - Commission Regulation (EEC) Nº 2294/92 of 31 July 1992 on detailed rules for the application of the support system for producers of the oil seeds referred to in Council Regulation (EEC) Nº 1765/92 - Obligation to observe a final date for sowing and for lodging an application for a compensatory payment

Annotation of Case C-375/92, Commission v Kingdom of Spain, ECR 1994 I-923, and Case C-45/93, Commission v Kingdom of Spain, ECR 1994 I-911

Failure to fulfil obligations - Freedom to provide services - Tourist guides - Professional qualification required by national rule - Discrimination - Museum admission

Annotation of Case C-56/91, Hellenic Republic v Commission, ECR 1993 I-3433

Common Agricultural Policy - Clearance of EAGGF accounts - 1988 financial year

Annotation of Case C-183/91, Commission v Hellenic Republic, ECR 1993 I-3131

State aid - Tax exemption on earnings from exports - Recovery

Micronutrients: dietary intake v. supplement use

Whilst clinical deficiency of micronutrients is uncommon in the developed world, a suboptimal intake of certain micronutrients has been linked with an increased risk of chronic diseases such as CVD and cancer. Attention has therefore focused on increasing micronutrient status in order to theoretically reduce chronic disease risk. Increasing micronutrient status can involve a number of approaches: increasing dietary intake of micronutrient-rich foods; food fortification; use of supplements. Observational cohort studies have demonstrated an association between high intakes of micronutrients such as vitamin E, vitamin C, folic acid and beta-carotene, and lower risk of CHD, stroke and cancer at various sites. However, randomised intervention trials of micronutrient supplements have, to date, largely failed to show an improvement in clinical end points. The discordance between data from cohort studies and the results so far available from clinical trials remains to be explained. One reason may be that the complex mixture of micronutrients found, for example, in a diet high in fruit and vegetables may be more effective than large doses of a small number of micronutrients, and therefore that intervention studies that use single micronutrient supplements are unlikely to produce a lowering of disease risk. Studies concentrating on whole foods (e.g. fruit and vegetables) or diet pattern (e.g. Mediterranean diet pattern) may be more effective in demonstrating an effect on clinical end points. The present review will consider the clinical trial evidence for a beneficial effect of micronutrient supplements on health, and review the alternative approaches to the study of dietary intake of micronutrients.