Expression of V1A and GRP receptors leads to cellular transformation and increased sensitivity to substance-P analogue-induced growth inhibition.

Small-cell lung cancer (SCLC) is a particularly aggressive cancer, which metastasises early. Despite initial sensitivity to radio- and chemo-therapy, it invariably relapses, so that the 2-year survival remains less than 5%. Neuropeptides particularly arginine vasopressin (AVP) and gastrin-releasing peptide (GRP) act as autocrine and paracrine growth factors and the expression of these and their receptors are a hallmark of the disease. Substance-P analogues including [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-substance-P (SP-D) and [Arg6,D-Trp7,9,NmePhe8]-substance-P (6-11) (SP-G) inhibit the growth of SCLC cells by modulating neuropeptide signalling. We show that GRP and V1A receptors expression leads to the development of a transformed phenotype. Addition of neuropeptide provides some protection from etoposide-induced cytotoxicity. Receptor expression also leads to an increased sensitivity to substance-P analogue-induced growth inhibition. We show that SP-D and SP-G act as biased agonists at GRP and V1A receptors causing blockade of Gq-mediated Ca2+ release while directing signalling to activate ERK via a pertussis toxin-sensitive pathway. This is the first description of biased agonism at V1A receptors. This unique pharmacology governs the antiproliferative properties of these agents and highlights their potential therapeutic potential for the treatment of SCLC and particularly in tumours, which have developed resistance to chemotherapy

Bridging the gap between molecular and elemental mass spectrometry: Higher energy collisional dissociation (HCD) revealing elemental information

Molecular mass spectrometry has been applied to simultaneously obtain molecular and elemental information from metal-containing species. Energy tuning of the higher-energy collision dissociation (HCD) fragmentation cell allows the controlled production of typical peptide fragments or elemental reporter ions informing about the metallic content of the analyzed species. Different instrumental configurations and fragmentation techniques have been tested, and the efficiency extracting the elemental information has been compared. HCD fragmentation operating at very high energy led to the best results. Platinum, lanthanides, and iodine reporter ions from peptides interacting with cisplatin, peptides labeled with lanthanides-MeCAT-IA, and iodinated peptides, respectively, were obtained. The possibility to produce abundant molecular and elemental ions in the same analysis simplifies the correlation between both signals and open pathways in metallomics studies enabling the specific tracking of metal-containing species. The proposed approach has been successfully applied to in solution standards and complex samples. Moreover, interesting preliminary MALDI-imaging experiments have been performed showing similar metal distribution compared to laser ablation (LA)-ICPMS

Postmortem health and pollution investigation on harbour seals (Phoca vitulina) of the Islands Helgoland and Sylt

Helgoland and Sylt are important centers of tourism in the North Sea. Harbor and grey seals are one reason for the attraction of these islands. However, little is known about these local seal groups. The present post mortem health and pollution study describes a multiparameter investigation of \ufb01ve ill harbor seals which were shot for animal welfare reasons. Firstly, results of pathology and blood investigations support the bad prognosis of survival made in the \ufb01eld. Signs of in\ufb02ammation in organs, malnutrition, a high-stress level, and reduced thyroid activity were found. Secondly, metal and organic contaminants were investigated. Metal pollutants in blood, liver, muscle, and kidney tissue were not elevated. Lead and mercury concentrations showed a decreased level compared to former studies. Additionally, interesting insights were found for several organic contaminants in comparison with other studies. The Helgoland seals may be in\ufb02uenced by the contaminants of the Elbe plume

Laser-based optical techniques for the detection of chemical agents

Among numerous existing and developing techniques for the detection of air pollution, laser-based optical methods (LBM) are possibly the most promising ones. Unique sensing capabilities of LBM include high speed of analysis, high selectivity, sensitivity and accuracy, low detection limits, and remote detection. This paper gives a brief review of several laser-based systems for optical sensing of gas-phase chemical agents: laser intra-cavity, photoacoustic and laser-induced breakdown spectroscopy, and remote sensing based on differential absorption. For each method, a brief description of the principles of operation is given, and its analytical capabilities are outlined