Concentration-dependent vascular effects of divalent manganese

Oral Presentation: no. OP9OBJECTIVES: Divalent manganese is a cofactor for soluble guanylyl cyclase (sGC), the enzyme producing cyclic GMP in vascular smooth muscle cells that causes relaxation. Manganese competes with magnesium to activate sGC. These divalent cations can bias the activity of the enzyme to produce cyclic nucleotides other than cyclic GMP, in particular cyclic AMP and cyclic IMP. Cyclic IMP, preferably produced in the presence of magnesium, can cause contraction in ...postprin

Antiretroviral treatment can affect the release of NO and EDCF, but EDH in rat arteries

This journal suppl. entitled: EDHF 2012 - 10th Anniversary MeetingDespite improving clinical outcomes, highly active antiretroviral therapy (HAART) is an independent potential risk factor for cardiovascular diseases. Currently the recommended HAART regimen commonly comprises a protease inhibitor (PI) with ritonavir (RTV)-boosting or a nonnucleoside reverse transcriptase inhibitor (NNRTI), and two nucleoside reverse transcriptase inhibitors. The present study examined whether or not boosted lopin...postprin

Cytotoxic activity of Treponema denticola

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A comparative study of the quality of life of patients with advanced chronic obstructive pulmonary disease and terminal cancer

2005-2006 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Endothelium-dependent vasoconstrictor signals requiring activation of soluble guanylyl cyclase in isolated arteries

Conference Theme: Tomorrow's medicines: pharmacology, patients and populationsINTRODUCTION: Thymoquinone causes an endothelium-dependent augmentation of contraction in isolated arteries, similar to that evoked by hypoxia. AIMS: Ex vivo experiments were designed to study the mechanisms underlying this unexpected response. METHODS: Arterial rings with or without endothelium were suspended in organ chambers for isometric tension recording. Certain rings were incubated with inhibitors of nitric oxide …published_or_final_versio

Analysis of the meaning of negligence of care in the context of ethical responsibility and legal liability

2003-2004 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Chromosome in situ hybridisation, Ki-67, and telomerase immunocytochemistry in liquid based cervical cytology

Aims: To assess the potential value of chromosome in situ hybridisation (CISH), Ki-67, and telomerase immunocytochemistry in liquid based cervical cytology to help detect carcinoma cells and precursors. Method: Sixty ThinPrep processed cervical cytology samples were studied: 23 cases within the normal limit, 13 low grade squamous intraepithelial lesions (LSILs), 10 high grade squamous intraepithelial lesions (HSILs), six squamous cell carcinomas, three endocervical adenocarcinomas, two cervical adenosquamous cell carcinomas, and three endometrial adenocarcinomas. CISH was performed with DNA probes specific for the pericentromeric regions of chromosome 11 and 16. Hybridisation signals were visualised with the streptavidin-biotin peroxidase technique. The monoclonal MIB1 and polyclonal TRT-H231 antibodies were used to detect Ki-67 and telomerase immunoreactivity, respectively. Results: Non-specific background staining was almost absent in CISH slides. Normal squamous and glandular cells showed a diploid chromosomal pattern. A relative gain in chromosomes 11 and 16 (aneusomy) was seen in HSIL and the carcinomas (p<0.0001 ). In MIB1 stained smears, normal cells and koilocytes showed inconspicuous immunoreactivity, whereas strongly immunoreactive nuclei were found in cancer cells and HSIL (p<0.0001). Not only carcinoma and HSIL cells, but also some normal cells, showed cytoplasmic staining for telomerase. Conclusions: These preliminary results indicate that ThinPrep processed cervical smears are suitable for CISH and immunocytochemical studies. The neoplastic squamous and glandular cells were easily identified based on nuclear aneusomy and strong Ki-67 immuoreactivity in the context of abnormal nuclear morphology. This is the first study to apply CISH in cervical cytology using an immunoenzymatic approach.published_or_final_versio

Thymoquinone causes endothelium-dependent augmentation of contraction depending on activation of soluble guanylyl cyclase in isolated arteries

Poster - Vascular Responsiveness: no. 4/7INTRODUCTION: Experiments were designed to determine the effects of thymoquinone, an alkaloid with in vivo vasodilator properties, in isolated arteries. METHODS: Rings, with or without endothelium, of rat mesenteric arteries, rat aorta and porcine coronary arteries were suspended in conventional organ chambers for isometric tension recording. Certain rings were incubated with inhibitors of nitric oxide (NO) synthase inhibitor (L-N^G-nitroarginine methyl ester, L-NAME) or soluble guanylyl cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ). They were contracted with phenylephrine (rat arteries) or prostaglandin F_2alpha (porcine coronary arteries) and exposed to increasing ...postprin

A pilot controlled trial of a combination of dense cranial electroacupuncture stimulation and body acupuncture for post-stroke depression

Our previous studies have demonstrated the treatment benefits of dense cranial electroacupuncture stimulation (DCEAS), a novel brain stimulation therapy in patients with major depression, postpartum depression and obsessive-compulsive disorder. The purpose of the present study was to further evaluate the effectiveness of DCEAS combined with body acupuncture and selective serotonin reuptake inhibitors (SSRIs) in patients with post-stroke depression (PSD).published_or_final_versio

Relaxation effect of abacavir on rat basilar arteries

Background The use of abacavir has been linked with increased cardiovascular risk in patients with human immunodeficiency virus infection; however, the mechanism involved remains unclear. We hypothesize that abacavir may impair endothelial function. In addition, based on the structural similarity between abacavir and adenosine, we propose that abacavir may affect vascular contractility through endogenous adenosine release or adenosine receptors in blood vessels. Methods The relaxation effect of abacavir on rat basilar arteries was studied using the myograph technique. Cyclic GMP and AMP levels were measured by immunoassay. The effects of abacavir on nucleoside transporters were studied using radiolabeled nucleoside uptake experiments. Ecto-5′ nucleotidase activity was determined by measuring the generation of inorganic phosphate using adenosine monophosphate as the substrate. Results Abacavir induced the relaxation of rat basilar arteries in a concentration-dependent manner. This relaxation was abolished when endothelium was removed. In addition, the relaxation was diminished by the nitric oxide synthase inhibitor, L-NAME, the guanylyl cyclase inhibitor, ODQ, and the protein kinase G inhibitor, KT5820. Abacavir also increased the cGMP level in rat basilar arteries. Abacavir-induced relaxation was also abolished by adenosine A2 receptor blockers. However, abacavir had no effect on ecto-5’ nucleotidase and nucleoside transporters. Short-term and long-term treatment of abacavir did not affect acetylcholine-induced relaxation in rat basilar arteries. Conclusion Abacavir induces acute endothelium-dependent relaxation of rat basilar arteries, probably through the activation of adenosine A2 receptors in endothelial cells, which subsequently leads to the release of nitric oxide, resulting in activation of the cyclic guanosine monophosphate/protein kinase G-dependent pathway in vascular smooth muscle cells. It is speculated that abacavir-induced cardiovascular risk may not be related to endothelial dysfunction as abacavir does not impair relaxation of blood vessels. The most likely explanation of increased cardiovascular risk may be increased platelet aggregation as suggested by other studies