Reproducibility of cardiac 31P MRS at 7 T

Synopsis Cardiac PCr/ATP ratios measured by P MRS change in cardiovascular disease giving them value as a biomarker. We scanned 13 healthy volunteers at 7T, assessing their PCr/ATP with 6 ½ min P CSI scans. These data have better reproducibility than a 30min 3T protocol previously published by our centre. Repeated PCr/ATP measurements from subjects in this study were not significantly (P=0.83) different. Measurements were significantly different (P<0.001) from DCM patient data acquired in a previous 7T study using the same coil and pulse sequence. This data will allow us to plan future 7T P-MRS clinical studies.Funded by a Sir Henry Dale Fellowship from the Wellcome Trust and the Royal Society (Grant No. 098436/Z/12/Z). JE receives a DPhil (PhD) studentship from the Medical Research Council (UK)

Kemijski profil sedimenata Plominskog zaljeva

Granulometric, chemical, and leaching properties of sediments dredged in the Plomin Bay (Northern Adriatic Sea, Croatia) were investigated in order to asses the risk of remobilisation of heavy metals into the water column. In total 65 samples from 65 sampling sites were taken from different sediment depths within the bay. Analysis of variance confirmed the homogeneity of granulometric and elemental composition of the investigated sediment throughout its volume. Granulometric analysis showed that all samples corresponded to a pelitic fraction (<0.063 mm). Bulk elemental mass fractions in the sediments were similar to literature data on relatively unpolluted areas of the Adriatic Sea. High sedimentation rate caused by constant infl ow of material from the Boljunčica River drainage may be responsible for low levels of heavy metals and negligible infl uence of fl y and bottom ash from a nearby disposal site on the chemical composition of the sediments. In contact with sea water only 0.29 mg kg-1 of V, 0.04 mg kg-1 of Cr, 0.07 mg kg-1 of Ni, 0.33 mg kg-1 of Cu, 0.67 mg kg-1 of Zn and 0.06 mg kg-1 of Pb could be remobilised from sediment material into the water column. However, these values increased three to ten times in case of leaching with organic acids.Granulometrijska i kemijska svojstva te mogućnost otpuštanja teških metala ispitivani su u sedimentima Plominskog zaljeva (Sjeverni Jadran, Hrvatska) u svrhu utvrđivanja rizika od remobilizacije teških metala iz sedimenta u stupac vode. Uzeto je 65 uzoraka s različitih točaka i dubina unutar zaljeva. Analizom varijance potvrđena je granulometrijska i kemijska homogenost cijelog volumena sedimenta, što upućuje na jedan prevladavajući izvor tijekom cijeloga sedimentacijskog razdoblja. Granulometrijskom analizom je utvrđeno da u svim uzorcima prevladava sitnozrnata frakcija (<0,063 mm). Koncentracije elemenata u ukupnim uzorcima sedimenata slične su literaturnim vrijednostima objavljenim za relativno onečišćena područja Jadranskog mora. Velika brzina sedimentacije uzrokovana konstantnim donosom materijala iz slijevnog područja Boljunčice vjerojatan je uzrok niskih koncentracija teških metala i slabo vidljivog utjecaja odlagališta šljake i pepela na sastav sedimenata. U kontaktu s morskom vodom moguća je remobilizacija samo 0,29 mg kg-1 V, 0,04 mg kg-1 Cr, 0,07 mg kg-1 Ni, 0,33 mg kg-1 Cu, 0,67 mg kg-1 Zn i 0,06 mg kg-1 Pb iz sedimenta u stupac morske vode. Ipak ove vrijednosti su tri do deset puta povećane u slučaju izluživanja s pomoću organskih kiselina

Monocyte chemoattractant protein-1 serum levels in ovarian cancer patients

The chemokine monocyte chemoattractant protein (MCP)-1 is an important mediator of monocyte infiltration in various solid tumours of epithelial origin. The aim of the present study was to evaluate the role of MCP-1 in the natural history of ovarian cancer and to determine its value as differentiation marker and prognostic marker regarding disease free and overall survival. This retrospective study comprises 86 patients with ovarian cancer, 48 with primary ovarian cancer and 38 with recurrent ovarian cancer, 67 patients with benign ovarian cysts and 42 healthy women. Median serum levels in patients with primary ovarian cancer, recurrent ovarian cancer, benign ovarian cysts and in healthy women were 535.6 (range 129.6–1200) pg ml–1, 427.3 (range 193.4–1101) pg ml–1, 371.2 (range 222–986.8) pg ml–1 and 318.7 (range 241.3–681.4) pg ml–1 respectively (Mann–Whitney U-test, P < 0.001). Univariate logistic regression models revealed a significant influence of MCP-1 serum levels on the odds of presenting with primary ovarian cancer versus benign cysts and versus healthy women respectively (univariate logistic regression, P < 0.001 and P < 0.001 respectively). In a multivariate logistic regression model considering MCP-1 and CA 125 serum levels simultaneously, both MCP-1 and CA 125 revealed statistical significance on the odds of presenting with primary ovarian cancer versus benign cysts (multivariate logistic regression, P = 0.05 and P < 0.001 respectively). In ovarian cancer patients, MCP-1 serum levels showed a statistically significant correlation with histological grade (Mann–Whitney U-test, P = 0.02) and age at the time of diagnosis (Mann–Whitney U-test, P = 0.03). Elevated MCP-1 serum levels prior to therapy were not associated with disease-free and overall survival (log-rank test, P = 0.2 and P = 0.7 respectively). In summary these data indicate that MCP-1 might play a functional role in the natural history of ovarian cancer and might serve as differentiation marker between benign ovarian cysts and ovarian cancer, providing additional information to the established tumour marker CA 125. © 1999 Cancer Research Campaig

Inflammatory mediators in breast cancer: Coordinated expression of TNFα & IL-1β with CCL2 & CCL5 and effects on epithelial-to-mesenchymal transition

<p>Abstract</p> <p>Background</p> <p>The inflammatory chemokines CCL2 (MCP-1) & CCL5 (RANTES) and the inflammatory cytokines TNFα & IL-1β were shown to contribute to breast cancer development and metastasis. In this study, we wished to determine whether there are associations between these factors along stages of breast cancer progression, and to identify the possible implications of these factors to disease course.</p> <p>Methods</p> <p>The expression of CCL2, CCL5, TNFα and IL-1β was determined by immunohistochemistry in patients diagnosed with: (1) Benign breast disorders (=healthy individuals); (2) Ductal Carcinoma <it>In Situ </it>(DCIS); (3) Invasive Ducal Carcinoma without relapse (IDC-no-relapse); (4) IDC-with-relapse. Based on the results obtained, breast tumor cells were stimulated by the inflammatory cytokines, and epithelial-to-mesenchymal transition (EMT) was determined by flow cytometry, confocal analyses and adhesion, migration and invasion experiments.</p> <p>Results</p> <p>CCL2, CCL5, TNFα and IL-1β were expressed at very low incidence in normal breast epithelial cells, but their incidence was significantly elevated in tumor cells of the three groups of cancer patients. Significant associations were found between CCL2 & CCL5 and TNFα & IL-1β in the tumor cells in DCIS and IDC-no-relapse patients. In the IDC-with-relapse group, the expression of CCL2 & CCL5 was accompanied by further elevated incidence of TNFα & IL-1β expression. These results suggest progression-related roles for TNFα and IL-1β in breast cancer, as indeed indicated by the following: (1) Tumors of the IDC-with-relapse group had significantly higher persistence of TNFα and IL-1β compared to tumors of DCIS or IDC-no-relapse; (2) Continuous stimulation of the tumor cells by TNFα (and to some extent IL-1β) has led to EMT in the tumor cells; (3) Combined analyses with relevant clinical parameters suggested that IL-1β acts jointly with other pro-malignancy factors to promote disease relapse.</p> <p>Conclusions</p> <p>Our findings suggest that the coordinated expression of CCL2 & CCL5 and TNFα & IL-1β may be important for disease course, and that TNFα & IL-1β may promote disease relapse. Further <it>in vitro </it>and <it>in vivo </it>studies are needed for determination of the joint powers of the four factors in breast cancer, as well as analyses of their combined targeting in breast cancer.</p

Postsynaptic nigrostriatal dopamine receptors and their role in movement regulation

The article presents the hypothesis that nigrostriatal dopamine may regulate movement by modulation of tone and contraction in skeletal muscles through a concentration-dependent influence on the postsynaptic D1 and D2 receptors on the follow manner: nigrostriatal axons innervate both receptor types within the striatal locus somatotopically responsible for motor control in agonist/antagonist muscle pair around a given joint. D1 receptors interact with lower and D2 receptors with higher dopamine concentrations. Synaptic dopamine concentration increases immediately before movement starts. We hypothesize that increasing dopamine concentrations stimulate first the D1 receptors and reduce muscle tone in the antagonist muscle and than stimulate D2 receptors and induce contraction in the agonist muscle. The preceded muscle tone reduction in the antagonist muscle eases the efficient contraction of the agonist. Our hypothesis is applicable for an explanation of physiological movement regulation, different forms of movement pathology and therapeutic drug effects. Further, this hypothesis provides a theoretical basis for experimental investigation of dopaminergic motor control and development of new strategies for treatment of movement disorders

Tumor-associated macrophages in invasive breast cancer.

ANTICANCER RESEARCH (ATHENS