A substance P (neurokinin-1) receptor mutant carboxyl-terminally truncated to resemble a naturally occurring receptor isoform displays enhanced responsiveness and resistance to desensitization

Two isoforms of the substance P (SP) receptor, differing in the length of the cytoplasmic carboxyl-terminus by ≈8 kDa, have been detected previously in rat salivary glands and other tissues. The binding and functional properties of these two isoforms have been investigated using full-length (407 amino acids) and carboxyl-terminally truncated (324 amino acids) rat SP receptors transfected stably into Chinese hamster ovary cells. Both the full-length and the truncated receptor bound radiolabeled SP with a similar K_d (≈0.1 nM). The average number of high affinity SP binding sites per cell was 1.0 × 10⁵ and 0.3 × 10⁵ for the full-length and the truncated SP receptor, respectively. In both cell lines, SP induced a rapid but transient increase in cytosolic calcium concentration ([Ca²⁺]_i), which consisted of the release of Ca²⁺ from intracellular stores and the influx of extracellular Ca²⁺. Both components are dependent on phospholipase C activation. Although the full-length and the truncated receptor utilize the same calcium pathways, they differ in their EC₅₀ values (0.28 nM for the full-length; 0.07 nM for the truncated). These differences in responsiveness may be related to the observed differences in receptor desensitization. The truncated receptor, in contrast to the full-length receptor, does not undergo rapid and long-lasting desensitization. Cells possessing the short isoform of the SP receptor would thus be expected to exhibit a prolonged responsiveness.     

Impact of early abciximab administration on myocardial reperfusion in patients with ST-segment elevation myocardial infarction pretreated with 600 mg of clopidogrel before percutaneous coronary intervention

Early rapid platelet inhibition with abciximab before primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) is suggested as beneficial. In previous studies on early abciximab administration clopidogrel was administered in cathlab in low loading dose. We investigated the role of early abciximab administration on top of early clopidogrel 600 mg loading dose in patients with STEMI treated with PPCI. A total of 73 non-shock STEMI < 6 h patients admitted to remote hospitals with anticipated delay to PPCI < 90 min were randomly assigned to three study groups—24 pts received abciximab before transfer to cathlab (early = group EA), 27 in cathlab during PPCI (late = group LA) and in 22 abciximab administration was left to operator’s discretion during PPCI (selective = SA; given in 22.7% of patients). All patients received clopidogrel (600 mg), aspirin and heparin (70 U/kg) before transfer to cathlab. Angiography revealed more frequent infarct-related artery patency (TIMI 2 + 3: EA vs LA vs SA: 45.8 vs 18.5 vs 13.6%, P = 0.024), better myocardial tissue perfusion (MBG 2 + 3: EA vs LA vs SA: 45.8 vs 14.8 vs 13.6%, P = 0.02) in EA group in baseline angiography. There was no difference in these angiographic parameters and ECG ST-segment resolution after PPCI. In multivariate analysis early abciximab administration was an independent predictor of infarct-related artery patency in baseline angiography (OR 6.5; 95% CI 1.83–23.1; P = 0.004). Early abciximab administration before transfer for PPCI in patients with STEMI pretreated with 600 mg of clopidogrel results in more frequent infarct-related artery patency and better myocardial tissue perfusion before PPCI.     

Coxiella burnetii seroprevalence of shepherds and their flocks in the lower Saint-Lawrence River region of Quebec, Canada.

OBJECTIVE: To determine the seroprevalence of Coxiella burnetii among the shepherds and their sheep in the lower Saint-Lawrence River region (LSLRR) of Quebec, Canada. DESIGN: A prospective human-animal comparative study was conducted with 81 shepherds from 46 farms and a control group matched for sex and age. All participants answered a standardized questionnaire to evaluate their risk factors for Q fever, including a specific section on the work practices of the shepherds. All human subjects had a blood sample taken for serology to phase I and phase II antigens of C burnetii performed by indirect immunofluorescence assay. At each participating farm, seven to nine sheep had blood samples taken for C burnetii serology to be assessed by the complement fixation test. RESULTS: The seroprevalence to C burnetii was higher in the group of shepherds (28.4%) than the control group (1.2%) (P<0.005). Among the group of shepherds, spending more than 5 h/week in the sheep barn (P=0.06) and buying and/or trading sheep within the past six months (P=0.004) were associated with positive C burnetii serology. A total of 137 of 334 sheep (41%) were seropositive for C burnetii. These positive sheep were distributed in 41 of the 46 flocks (89%). No correlation could be demonstrated between a serology for C burnetii in the herds and the shepherds. CONCLUSION: Q fever is highly prevalent in the LSLRR of Quebec, affecting 89% of the flocks and 28% of the shepherds. Shepherds in this region are at increased risk for C burnetii infection in comparison to the general population.     

Primary Angioplasty in Patient with St-Segment Elevation Myocardial Infarction in the Setting of Intentional Carbon Monoxide Poisoning

Background

ST-segment elevation myocardial infarction (STEMI) due to coronary artery occlusion in the setting of acute carbon monoxide (CO) poisoning is a very rare presentation.

Objective

Our aim was to report on the use of primary angioplasty in a patient with STEMI in the setting of CO poisoning.

Case Report

A 36-year-old man with retrosternal chest pain was admitted after exposure to CO. The initial electrocardiogram (ECG) showed ST depression in I, aVL, and V3−V4 with slight ST elevation in II, III, aVF leads. Toxic carboxyhemoglobin level of 22% and troponin I of 2.19 μg/L were confirmed. After oxygen therapy the chest pain diminished, but after about 15 h it returned. The repeat ECG revealed normalization of previous ST depression with persistent ST elevation in II, III, aVF leads. The troponin I concentration was 5.94 μg/L. An echocardiogram demonstrated an apex hypokinesia involving the adjacent segments of the anterior and lateral wall. On the coronary angiogram, an acute occlusion of the distal left anterior descending coronary artery was confirmed. Primary percutaneous coronary intervention (PCI) of the infarct-related artery was performed. After PCI, the patient was symptom free and had partial ST-segment elevation resolution. The patient was discharged home after 7 days, with persistent ST-T changes and mild hypokinesia of the apex suggesting myocardial injury.

Conclusions

Patients with toxic CO exposure who have symptoms of STEMI should be carefully evaluated with serial ECG, cardiac necrosis marker measurements, and an echocardiogram. When there is evidence of myocardial injury, a wider use of coronary angiography can identify patients who could benefit from PCI.     

In Situ Regeneration of Copper-Coated Gas Diffusion Electrodes for Electroreduction of CO2 to Ethylene

A key challenge for carbon dioxide reduction on Cu-based catalysts is its low faradic efficiency (FE) and selectivity towards higher-value products, e.g., ethylene. The main factor limiting the possibilities of long-term applications of Cu-based gas diffusion electrodes (GDE) is a relatively fast drop in the catalytic activity of copper layers. One of the solutions to the catalyst stability problem may be an in situ reconstruction of the catalyst during the process. It was observed that the addition of a small amount of copper lactate to the electrolyte results in increased Faradaic efficiency for ethylene formation. Moreover, the addition of copper lactate increases the lifetime of the catalytic layer ca. two times and stabilizes the Faradaic efficiency of the electroreduction of CO₂ to ethylene at ca. 30%. It can be concluded that in situ deposition of copper through reduction of copper lactate complexes present in the electrolyte provides new, stable, and selective active sites, promoting the reduction of CO₂ to ethylene.     

Genetic susceptibility to pancreatic cancer and its functional characterisation: The PANcreatic Disease ReseArch (PANDoRA) consortium

Pancreatic cancer is the fourth leading cause of cancer deaths in the European Union and in the USA, but little is known about its genetic susceptibility. The PANcreatic Disease ReseArch (PANDoRA) consortium was established to unite the efforts of different research groups; its aim is to create a large bio-database to uncover new genetic factors for pancreatic cancer risk, response to treatment, and patient survival. So far 2220 cases of pancreatic adenocarcinoma, a smaller number of cases of endocrine pancreatic tumours (n = 86), chronic pancreatitis (n = 272) and 3847 healthy controls have been collected. As a collective effort of the consortium, SNPs associated with pancreatic adenocarcinoma risk from a genome-wide association study performed in Caucasians were replicated. The possibility that the same genetic polymorphisms may influence patient survival as well was also addressed. This collective effort is particularly important for pancreatic cancer because it is a relatively rare disease for which little is known about aetiopathogenesis and risk factors. The recruitment of additional collaborators and partner institutions is continuously on-going.     

Synthesis and structural studies of new copolyimides 2. Influence of pyromellitimide rings on copolymer structure

The reaction of pyromellitic dianhydride (1,2 : 4,5-benzenetetracarboxylic dianhydride) ( 1 ) with L - and D -alanine ( 2 L ) and ( 2 D ) leads to new monomers which were used to synthesize new copolymers. These copolymers were obtained as a product of the condensation of optical isomers of bis[N-(1-chloroformylethyl)]pyromellitimides (CFEP) with poly(ethylene glycol) PEG-2000 ( 5 ). The effect of monomer structure on the structure and thermal properties of the polymers was studied using X-ray diffraction, differential scanning calorimetry and thermogravimetry. The copolymers were compared with similar copolyimides obtained previously from bis(N-chloroformylmethyl)pyromellitimide and poly(ethylene glycol), PEG 2000. The dominating effect of poly(ethylene glycol) comonomer on the crystallinity, structure and thermal stability of these new copolymers is proven.