Haemostatic effect and tissue reactions of methods and agents used for haemorrhage control in apical surgery

To compare the haemostatic effect and tissue reactions of different agents and methods used for haemorrhage control in apical surgery.

The stem cell gene "inhibitor of differentiation 1" (ID1) is frequently expressed in non-small cell lung cancer

Inhibitor of differentiation 1 (ID1) plays a role in cellular differentiation, proliferation, angiogenesis and tumor invasion. As shown recently, ID1 is positively regulated by the tyrosine kinase SRC in lung carcinoma cell lines and with that appears as a potential new therapeutic target in non-small cell carcinoma (NSCLC). To substantiate this hypothesis we examined ID1, SRC and matrix metalloproteinase-9 (MMP-9) immunohistochemically in human NSCLC specimens.

The effects of PTK787/ZK222584, an inhibitor of VEGFR and PDGFR? pathways, on intussusceptive angiogenesis and glomerular recovery from Thy1.1 nephritis

The aim of our study was to investigate the phenomenon of intussusceptive angiogenesis with a focus on its molecular regulation by vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor β (PDGFRβ) pathways and biological significance for glomerular recovery after acute injury. Glomerular healing by intussusception was examined in a particular setting of Thy1.1 nephritis, where the lysis of mesangial cells results in an initial collapse and successive rebuilding of glomerular capillary structure. Restoration of capillary structure after induction of Thy1.1 nephritis occurred by intussusceptive angiogenesis resulting in i) rapid expansion of the capillary plexus with reinstatement of the glomerular filtration surface and ii) restoration of the archetypical glomerular vascular pattern. Glomerular capillaries of nephritic rats after combined VEGFR2 and PDGFRβ inhibition by PTK787/ZK222584 (PTK/ZK) were tortuous and irregular. However, the onset of intussusceptive angiogenesis was influenced only after long-term PTK/ZK treatment, providing an important insight into differential molecular regulation between sprouting and intussusceptive angiogenesis. PTK/ZK treatment abolished α-smooth muscle actin and tensin expression by injured mesangial cells, impaired glomerular filtration of microspheres, and led to the reduction of glomerular volume and the presence of multiple hemorrhages detectable in the tubular system. Collectively, treatment of nephritic patients with PTK/ZK compound is not recommended.

68Ga-DOTATOC PET/CT and somatostatin receptor (sst1-sst5) expression in normal human tissue: correlation of sst2 mRNA and SUVmax

By targeting somatostatin receptors (sst) radiopeptides have been established for both diagnosis and therapy. For physiologically normal human tissues the study provides a normative database of maximum standardized uptake value (SUV(max)) and sst mRNA.

Estimation of the postmortem interval by means of ¹H MRS of decomposing brain tissue: influence of ambient temperature

Standard methods for the estimation of the postmortem interval (PMI, time since death), based on the cooling of the corpse, are limited to about 48 h after death. As an alternative, noninvasive postmortem observation of alterations of brain metabolites by means of (1)H MRS has been suggested for an estimation of the PMI at room temperature, so far without including the effect of other ambient temperatures. In order to study the temperature effect, localized (1)H MRS was used to follow brain decomposition in a sheep brain model at four different temperatures between 4 and 26°C with repeated measurements up to 2100 h postmortem. The simultaneous determination of 25 different biochemical compounds at each measurement allowed the time courses of concentration changes to be followed. A sudden and almost simultaneous change of the concentrations of seven compounds was observed after a time span that decreased exponentially from 700 h at 4°C to 30 h at 26°C ambient temperature. As this represents, most probably, the onset of highly variable bacterial decomposition, and thus defines the upper limit for a reliable PMI estimation, data were analyzed only up to this start of bacterial decomposition. As 13 compounds showed unequivocal, reproducible concentration changes during this period while eight showed a linear increase with a slope that was unambiguously related to ambient temperature. Therefore, a single analytical function with PMI and temperature as variables can describe the time courses of metabolite concentrations. Using the inverse of this function, metabolite concentrations determined from a single MR spectrum can be used, together with known ambient temperatures, to calculate the PMI of a corpse. It is concluded that the effect of ambient temperature can be reliably included in the PMI determination by (1)H MRS.

Long-term tissue coverage of a biodegradable polylactide polymer-coated biolimus-eluting stent: comparative sequential assessment with optical coherence tomography until complete resorption of the polymer

Biolimus-eluting stents (BESs) with a biodegradable polymer in abluminal coating achieve more complete coverage at 9 months compared with sirolimus-eluting stents (SESs) with a durable polymer, as assessed by optical coherence tomography (OCT). Whether this advantage persists or augments after complete resorption of the polymer (>12 months) is unknown.

Tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent vs. a fluoropolymer-coated everolimus-eluting stent at 13-month follow-up: an optical coherence tomography substudy from the RESOLUTE All Comers trial

Aims To compare the tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent (ZES) vs. a fluoropolymer-coated everolimus-eluting stent (EES) at 13 months, using optical coherence tomography (OCT) in an ‘all-comers' population of patients, in order to clarify the mechanism of eventual differences in the biocompatibility and thrombogenicity of the devices. Methods and results Patients randomized to angiographic follow-up in the RESOLUTE All Comers trial (NCT00617084) at pre-specified OCT sites underwent OCT follow-up at 13 months. Tissue coverage and apposition were assessed strut by strut, and the results in both treatment groups were compared using multilevel logistic or linear regression, as appropriate, with clustering at three different levels: patient, lesion, and stent. Fifty-eight patients (30 ZES and 28 EES), 72 lesions, 107 stents, and 23 197 struts were analysed. Eight hundred and eighty-seven and 654 uncovered struts (7.4 and 5.8%, P= 0.378), and 216 and 161 malapposed struts (1.8 and 1.4%, P= 0.569) were found in the ZES and EES groups, respectively. The mean thickness of coverage was 116 ± 99 µm in ZES and 142 ± 113 µm in EES (P= 0.466). No differences in per cent neointimal volume obstruction (12.5 ± 7.9 vs. 15.0 ± 10.7%) or other areas–volumetric parameters were found between ZES and EES, respectively. Conclusion No significant differences in tissue coverage, malapposition, or lumen/stent areas and volumes were detected by OCT between the hydrophilic polymer-coated ZES and the fluoropolymer-coated EES at 13-month follow-up.

Clinical study of mucosa-associated lymphoid tissue lymphomas of the head and neck

Background: Limited information is available on mucosa-associated lymphoid tissue lymphomas arising in the head and neck. Method: A retrospective analysis was conducted of 20 patients who were histologically diagnosed with mucosa-associated lymphoid tissue lymphoma and treated at our institution between January 1990 and December 2009. Results: Treatment consisted of surgical resection alone in two patients (10 per cent), surgical resection with consecutive radiotherapy in one (5 per cent), and radiotherapy alone in eight (40 per cent). Three patients (15 per cent) were treated with systemic chemotherapy, and three (15 per cent) received chemoradiotherapy. Three patients (15 per cent) were informed of the diagnosis but not treated for their condition. Conclusion: All of the 20 patients were still alive after a mean follow-up period of 50.8 months. Local treatment for mucosa-associated lymphoid tissue lymphoma of the head and neck should be the first choice in early-stage disease. However, prolonged follow up is important to determine these patients' long-term response to treatment.

The immunomodulator FTY720 and its phosphorylated derivative activate the Smad signalling cascade and upregulate connective tissue growth factor and collagen type IV expression in renal mesangial cells

1.--The immunomodulating agent FTY720 is a substrate for the sphingosine kinase and the phosphorylated form is able to bind to sphingosine 1-phosphate (S1P) receptors. In this study, we show that exposure of renal mesangial cells to phospho-FTY720 leads to a rapid and transient activation of several protein kinase cascades, including the mitogen- and stress-activated protein kinases. The nonphosphorylated FTY720 also increased MAPK phosphorylation, but with a reduced potency and a more delayed time course. In addition, phospho-FTY720 and FTY720 are able to increase phosphorylation of Smad proteins which are classical members of the transforming growth factor-beta (TGF-beta) signalling device, thus suggesting a crosstalk between FTY720 and TGF-beta signalling. 2.--Pretreatment with the S1P(3) receptor antagonist suramin inhibits FTY720 and phospho-FTY720-induced Smad phosphorylation, whereas pertussis toxin pretreatment, which blocks G(i/0) proteins, has no effect on Smad phosphorylation. 3.--Since TGF-beta is a potent profibrotic cytokine in mesangial cells and upregulates the connective tissue growth factor (CTGF) and collagen as important hallmarks in the fibrotic sequelae, we investigated whether FTY720 and phospho-FTY720 are able to mimic these effects of TGF-beta. Indeed, FTY720 and phospho-FTY720 markedly upregulate CTGF and collagen type IV protein expressions. In addition, the tissue inhibitor of metalloproteinase-1 is transcriptionally activated by FTY720, whereas cytokine-induced matrix metalloproteinase-9 is down-regulated by FTY720. 4.--Depletion of the TGF-beta receptor type II by the siRNA transfection technique blocks not only Smad phosphorylation but also CTGF upregulation. Similarly, Smad-4 depletion by siRNA transfection also abrogates CTGF upregulation induced by FTY720 and phospho-FTY720. 5.--In summary, our data show that FTY720 and phospho-FTY720 not only activate the Smad signalling cascade in mesangial cells, but also upregulate the expression of CTGF and collagen. These findings suggest that FTY720 may have additional effects besides the established immunomodulatory action and, importantly, a profibrotic activity has to be considered in future experimental approaches.

In bacterial meningitis cortical brain damage is associated with changes in parenchymal MMP-9/TIMP-1 ratio and increased collagen type IV degradation

Adverse outcome in bacterial meningitis is associated with the breakdown of the blood-brain barrier (BBB). Matrix-metalloproteinases (MMPs) facilitate this process by degradation of components of the BBB. This in turn results in acute complications of bacterial meningitis including edema formation, increased intracranial pressure and subsequent ischemia. We determined the parenchymal balance of MMP-9 and TIMP-1 (tissue inhibitor of MMP) and the structural integrity of the BBB in relation to cortical damage in an infant rat model of pneumococcal meningitis. The data demonstrate that the extent of cortical damage is significantly associated with parenchymal gelatinolytic activity and collagen type IV degradation. The increased gelatinolysis was found to be associated with a brain parenchymal imbalance of MMP-9/TIMP-1. These findings provide support to the concept that MMPs mediated disruption of the BBB contributes to the pathogenesis of bacterial meningitis and that protection of the vascular unit may have neuroprotective potential.

Metzincins, including matrix metalloproteinases and meprin, in kidney transplantation

Chronic allograft nephropathy, including chronic rejection, remains one of the major causes of renal allograft failure. Amongst other mediators, metzincins, such as matrix metalloproteinases (MMP), direct extracellular matrix metabolism and cell proliferation. Thus, we hypothesized, that these proteolytic enzymes are differentially regulated in chronic renal transplant rejection in rats and in human renal allograft nephropathy. Our studies demonstrated on the experimental level and in humans an overall up-regulation of MMP, tissue inhibitors of metalloproteinases (TIMP) and related enzymes as a result of rejection processes. Thus, metzincins may represent novel markers and therapeutic targets with respect to renal allograft rejection.