Diagnostic utility of a single-epitope sandwich B-type natriuretic peptide assay in stable coronary artery disease: Data from the Akershus Cardiac Examination (ACE) 1 Study

ObjectivesTo assess the merit of a novel single-epitope sandwich (SES) assay specific to the stable part of BNP in patients with reversible myocardial ischemia as post-translational modifications of BNP may influence assay performance.Design and methodsWe measured BNP concentration by a conventional assay and the SES-BNP assay in 198 patients referred for myocardial perfusion imaging (MPI). BNP concentration was determined before and immediately after exercise stress testing, and 1.5 and 4.5 h later. Patients were categorized according to MPI results.ResultsBNP concentration was higher with both assays at all time points in patients with reversible myocardial ischemia (n = 19) compared to the other patients (n = 179). Measuring BNP after stress testing or calculating the changes in BNP concentration did not improve diagnostic accuracy compared to baseline measurements: SES-BNP: AUC 0.71 (95% CI 0.58–0.84) vs. conventional BNP: 0.71 (0.59–0.83), p = 0.96. By linear regression analysis, reversible myocardial ischemia was significantly associated with baseline SES-BNP concentration (p = 0.043), but not with measurements by the conventional assay (p = 0.089). In multivariate logistic regression models, only baseline measurement with the SES-BNP assay was significantly associated with reversible myocardial ischemia: odds ratio [logarithmical transformed BNP] 2.00 (95% CI 1.16–3.47), p = 0.013. The SES-BNP assay, but not the conventional BNP assay, reclassified a significant proportion of the patients towards their correct category on top of the best clinical model of our data set: NRI = 0.47, p = 0.04.ConclusionsThe SES-BNP assay was significantly associated with reversible myocardial ischemia as assessed by several statistical indices, while a conventional BNP assay was not.     

Enhancement of rostral ventrolateral medulla neuronal nitric-oxide synthase-nitric-oxide signaling mediates the central cannabinoid receptor 1-evoked pressor response in conscious rats

Our recent studies implicated brainstem GABAergic signaling in the central cannabinoid receptor 1 (CB(1)R)-mediated pressor response in conscious rats. Given the well established link between neuronal nitric-oxide synthase (nNOS)/nitric oxide (NO) signaling and GABAergic transmission in brainstem cardiovascular regulating areas, we elucidated the role of nNOS-generated NO in the central CB(1)R-elicited pressor response. Compared with vehicle, intracisternal (i.c.) microinjection of the CB(1)R agonist (R)-(+)-[2,3-dihydro-5-methyl-3[(4-morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate (WIN55212-2) (15 μg/rat) significantly enhanced nNOS phosphorylation as well as the total nitrate and nitrite content in the rostral ventrolateral medulla (RVLM) at 5, 10, and 30 min, which paralleled the elicited pressor response. These findings were corroborated by: 1) the parallel dose-related increases in blood pressure and RVLM-NO levels, measured in real time by in vivo electrochemistry, elicited by intra-RVLM WIN55212-2 (100, 200, or 300 pmol /80 nl; n = 5) in conscious rats; and 2) the significantly higher phosphorylated nNOS (p-nNOS) levels in the WIN55212-2-injected RVLM compared with the contralateral RVLM. Subsequent neurochemical studies showed that WIN55212-2 (15 μg/rat i.c.) significantly increased the number and percentage of neurons immunostained for nNOS (nitroxidergic neurons) and c-Fos (marker of neuronal activity) within the RVLM. The increases in blood pressure and the neurochemical responses elicited by intracisternal WIN55212-2 were attenuated by prior central CB(1)R blockade by N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251; 30 μg/rat i.c.) or selective nNOS inhibition by N(ω)-propyl-(L)-arginine (1 μg/rat i.c.). These findings implicate RVLM p-nNOS/NO signaling as a molecular mechanism in the central CB(1)R-evoked pressor effect in conscious rats.     

Cardiac troponin T levels and exercise stress testing in patients with suspected coronary artery disease: the Akershus Cardiac Examination (ACE) 1 study

Whether reversible ischaemia in patients referred for exercise stress testing and MPI (myocardial perfusion imaging) is associated with changes in circulating cTn (cardiac troponin) levels is controversial. We measured cTnT with a sensitive assay before, immediately after peak exercise and 1.5 and 4.5 h after exercise stress testing in 198 patients referred for MPI. In total, 19 patients were classified as having reversible myocardial ischaemia. cTnT levels were significantly higher in patients with reversible myocardial ischaemia on MPI at baseline, at peak exercise and after 1.5 h, but not at 4.5 h post-exercise. In patients with reversible ischaemia on MPI, cTnT levels did not change significantly after exercise stress testing [11.1 (5.2-14.9) ng/l at baseline compared with 10.5 (7.2-16.3) ng/l at 4.5 h post-exercise, P=0.27; values are medians (interquartile range)]. Conversely, cTnT levels increased significantly during testing in patients without reversible myocardial ischaemia [5.4 (3.0-9.0) ng/l at baseline compared with 7.5 (4.6-12.4) ng/l, P<0.001]. In conclusion, baseline cTnT levels are higher in patients with MPI evidence of reversible myocardial ischaemia than those without reversible ischaemia. However, although cTnT levels increase during exercise stress testing in patients without evidence of reversible ischaemia, this response appears to be blunted in patients with evidence of reversible ischaemia. Mechanisms other than reversible myocardial ischaemia may play a role for acute exercise-induced increases in circulating cTnT levels.     

A novel hydrogen bonded bimetallic supramolecular coordination polymer {[SnMe3(bpe)][Ag(CN)2] · 2H2O} as anticancer drug

The reaction of Me₃SnCl, K₃[Ag(CN)₄] and 1,2-bis(4-pyridyl)ethane (bpe) in water/CH₃CN solution at room temperature affords the novel bimetallic supramolecular coordination polymer (SCP) {[SnMe₃(bpe)] [Ag(CN)₂]·2H₂O}_n, 1. The structure of 1 consists of cationic {–Sn(Me₃)–bpe–}⁺ chains that are neutralized by [Ag(CN)₂]⁻ anions. The dicyanoargentate(I) anions present discrete uncoordinated fragments between the cationic chains. The water molecules bind the cationic chains and the anions forming 3D-supramolecular structure through hydrogen bonds. 1 exhibits strong fluorescence in the solid state at room temperature. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the in vitro antitumor effects of the SCP 1 on human breast cancer cell line, T-47D. Cell cycle analysis revealed that the SCP 1 induced apoptosis in T-47D breast cancer cell line. Moreover, in vivo, the SCP 1 showed tumor growth inhibition in rat model that developed mammary carcinoma by 44.8% compared to the vehicle treated control. Thus, the SCP 1 exhibits specific in vivo and in vitro antitumor effects.     

Assessment of nutrition knowledge and related aspects among first-year Kuwait University students

Assessing nutrition knowledge of populations assists in drawing strategies for education programs. Nutrition-related problems are common in Kuwait, thus data on nutrition knowledge are needed. This study involved administration of a questionnaire to 1,037 first-year Kuwait University students. The overall nutrition knowledge score was rated as fair, with deficiency in specific areas of knowledge. Students' dietary habits, attitudes, and interest in nutrition information were assessed as fair. Our findings will aid in building a nutrition knowledge database in Kuwait. A simplified course on aspects of healthy nutrition and lifestyle to all Kuwait University students is highly recommended.     

Retrospective observational study of HER2 immunohistochemistry in borderline breast cancer patients undergoing neoadjuvant therapy,with an emphasis on Group 2 (HER2/CEP17 ratio ≥2.0, HER2 copy number <4.0 signals/cell) cases

Background The ASCO/CAP guidance on HER2 testing in breast cancer (BC) has recently changed. Group 2 tumours with immunohistochemistry score 2+ and HER2/CEP17 ratio ≥2.0 and HER2 copy number <4.0 signals/cell were re-classified as HER2 negative. This study aims to examine the response of Group 2 tumours to neoadjuvant chemotherapy (NACT).Methods 749 BC cases were identified from 11 institutions. The association between HER2 groups and pathological complete response (pCR) was assessed.Results 54% of immunohistochemistry HER2 positive (score 3+) BCs showed pCR, compared to 19% of immunohistochemistry 2+ FISH amplified cases. 27% of Group 2 treated with HER2 targeted therapy achieved pCR, compared to 19 and 11% in the combined Groups 1 + 3 and Groups 4 + 5, respectively. No difference in pCR rates was identified between Group 2 and Group 1 or combined Groups 1 + 3. However, Group 2 response rate was higher than Groups 4 + 5 (p = 0.017).Conclusion No difference in pCR was detected in tumours with a HER2/CEP17 ratio ≥2.0 and a HER2 score 2+ by IHC when stratified by HER2 gene copy number. Our data suggest that ASCO/CAP HER2 Group 2 carcinomas should be evaluated further with respect to eligibility for HER2 targeted therapy.Subject terms: Breast cancer, Breast cancer