Understanding and managing fish populations: keeping the toolbox fit for purpose.

Wild fish populations are currently experiencing unprecedented pressures, which are projected to intensify in the coming decades. Developing a thorough understanding of the influences of both biotic and abiotic factors on fish populations is a salient issue in contemporary fish conservation and management. During the 50th Anniversary Symposium of The Fisheries Society of the British Isles at the University of Exeter, UK, in July 2017, scientists from diverse research backgrounds gathered to discuss key topics under the broad umbrella of 'Understanding Fish Populations'. Below, the output of one such discussion group is detailed, focusing on tools used to investigate natural fish populations. Five main groups of approaches were identified: tagging and telemetry; molecular tools; survey tools; statistical and modelling tools; tissue analyses. The appraisal covered current challenges and potential solutions for each of these topics. In addition, three key themes were identified as applicable across all tool-based applications. These included data management, public engagement, and fisheries policy and governance. The continued innovation of tools and capacity to integrate interdisciplinary approaches into the future assessment and management of fish populations is highlighted as an important focus for the next 50 years of fisheries research.

Increased transforming growth factor beta (TGF-beta) immunoreactivity is independently associated with chronic injury in both consequential and primary radiation enteropathy.

PURPOSE: Radiation enteropathy is characterized by sustained increase in transforming growth factor beta (TGF-beta) immunoreactivity and connective tissue mast cell (CTMC) hyperplasia that may be responsible for progressive fibrosis and lead to clinical complications. We examined to what extent these chronic molecular and cellular phenomena are associated with acute mucosal breakdown (consequential injury) and/or direct (primary) radiation injury in late-responding compartments. METHODS AND MATERIALS: Rat small intestine was exposed to 50.4 Gy x-irradiation given either over 18 days (2.8 Gy daily or 5.6 Gy every other day) or 9 days (2.8 Gy twice daily or 5.6 Gy daily). Intestinal complications were recorded and groups of animals were euthanized at 2 and 26 weeks to assess subacute and chronic injury. Histopathologic changes were assessed with a radiation injury scoring system (RIS), total TGF-beta immunoreactivity was quantified with computerized image analysis, and CTMC hyperplasia was assessed in toluidine blue-stained sections. RESULTS: TGF-beta immunoreactivity and CTMC hyperplasia colocalized in areas of injury and were highly significantly correlated. Increased fraction size and decreased overall treatment time were associated with increased RIS (p < 0.01 and p < 0.00001), increased TGF-beta immunoreactivity (p = 0.01 andp < 0.001), and degree of CTMC hyperplasia (p = 0.01 and p < 0.001). Postradiation CTMC numbers increased across treatment groups from 2 to 26 weeks (p < 0.01). TGF-beta immunoreactivity was independently associated with chronic intestinal wall fibrosis (p = 0.003). CONCLUSION: This in vivo study supports in vitro evidence linking increased TGF-beta immunoreactivity and mast cell hyperplasia and strongly suggests their involvement in the molecular pathogenesis of both primary and consequential radiation enteropathy.

Radiation-induced granulocyte transmigration predicts development of delayed structural changes in rat intestine.

We examined whether early radiation-induced granulocyte transmigration (assessed by the fecal transferrin excretion ELISA assay) predicts subsequent development of (consequential) chronic radiation enteropathy. After accounting for the effect of radiation dose, transferrin excretion remained an independent predictor of overall tissue injury, intestinal fibrosis, and mucosal ulcers, but not TGF-beta immunoreactivity.

Upregulation and spatial shift in the localization of the mannose 6-phosphate/insulin-like growth factor II receptor during radiation enteropathy development in the rat.

BACKGROUND AND PURPOSE: Transforming growth factor beta1 (TGF-beta1) appears to play an important role in the pathogenesis of chronic radiation-induced fibrosis in the intestine and several other organs. TGF-beta1 is secreted as a non-biologically active complex and its function depends on activation. In vitro data suggest that the mannose 6-phosphate/insulin-like growth factor-beta (M6P/IGF-II) receptor is involved in the mechanism of TGF-beta1 activation. Thus, we used a rat model of radiation enteropathy to examine the potential role of the M6P/IGF-II receptor in the in vivo regulation of TGF-beta1 activity and localization. MATERIALS AND METHODS: A scrotal hernia containing a loop of small intestine was created in male rats. The intestine in the scrotum was exposed to 0, 12, or 21 Gy single dose X-radiation. Groups of rats were euthanized 1 day and 2, 6 and 26 weeks after irradiation. Histopathologic injury was assessed with a radiation injury score (RIS). Computerized image analysis was used to identify M6P/IGF-II receptor-positive cells and to quantify extracellular matrix-associated TGF-beta1 immunoreactivity. Changes in urokinase plasminogen activator (uPA), tissue-like plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) immunoreactivity were also assessed. RESULTS: In normal (sham-irradiated) intestine, M6P/IGF-II immunoreactivity was confined to relatively weak, but specific epithelial staining. Irradiated intestine exhibited a highly significant time- and dose-dependent increase in the number of M6P/IGF-II receptor-positive cells (P < 0.001). There was a striking spatial shift of M6P/IGF-II receptor immunoreactivity from epithelium during the early post-radiation phase to stromal cells, most notably fibroblasts during the later stages of injury. Irradiated intestine exhibited distinct co-localization of M6P/ IGF-II receptor-positive cells and extracellular matrix-associated TGF-beta1 in areas of histopathologic injury. There were highly significant associations between the number of M6P/IGF-II receptor-positive stromal cells and TGF-beta1 immunoreactivity (P < 0.001), radiation-induced fibrosis (P < 0.001) and RIS (P < 0.001). Endothelial tPA immunoreactivity decreased significantly after irradiation (P < 0.001), whereas uPA and PAI-1 immunoreactivity levels appeared to be unchanged. CONCLUSIONS: M6P/IGF-II receptor upregulation may be a key factor in the in vivo control of TGF-beta1 activity and responsible for the tissue specificity of TGF-beta1 action after irradiation.

Is the loss of endothelial thrombomodulin involved in the mechanism of chronicity in late radiation enteropathy?

BACKGROUND AND PURPOSE: Radiation enteropathy is characterized by locally elevated levels of inflammatory and fibrogenic cytokines. Microvascular injury may sustain these alterations through persistent local hypercoagulopathy, platelet aggregation, leukocyte adhesion and release of biologically active mediators. This study assessed the relationship of endothelial thrombomodulin (TM), a key regulator of the protein C anticoagulant pathway and marker of endothelial function, with transforming growth factor beta (TGF-beta) immunoreactivity and morphologic alterations in radiation enteropathy. MATERIALS AND METHODS: Small bowel resection specimens from 9 patients with radiation enteropathy were analyzed by computerized quantitative immunohistochemistry using antibodies against TM, von Willebrand factor (vWF) and TGF-beta. Identical measurements were performed on intestinal resection specimens from otherwise healthy penetrating trauma victims and on archived small intestines. A previously validated image analysis technique was used to assess submucosal vessels for TM and vWF immunoreactivity, and the intestinal wall for total extracellular matrix-associated TGF-beta immunoreactivity. RESULTS: Specimens from irradiated patients showed prominent submucosal and subserosal thickening and fibrosis, and obliterative vasculopathy. Control specimens were histopathologically normal. Vascular density and vWF immunoreactivity were similar in radiation enteropathy patients and controls. The image-analysis techniques were highly reproducible, with correlation coefficients for repeated measurements ranging from 0.86 to 0.93. Radiation enteropathy specimens exhibited a highly significant reduction in the number and proportion of TM-positive submucosal vessels per unit area (P < 0.0001) and increased intestinal wall TGF-beta immunoreactivity (P = 0.002). CONCLUSIONS: These data support the theory that sustained endothelial dysfunction is involved in the molecular pathogenesis of radiation enteropathy, and point to TM as important in the chronic nature of radiation enteropathy and a potential target for prophylactic and therapeutic interventions.

Association of transforming growth factor beta (TGF-beta) immunoreactivity with specific histopathologic lesions in subacute and chronic experimental radiation enteropathy.

Irradiated intestine consistently exhibits increased immunoreactivity of transforming growth factor beta-1 (TGF-beta 1). It is not known whether this increase occurs secondary to mucosal barrier disruption (consequential injury) or to injury in late-responding tissue compartments (primary radiation enteropathy). This study therefore assessed the association between TGF-beta immunoreactivity and specific consequential and primary histopathologic alterations. A small bowel loop was fixed inside the scrotum in male rats and subsequently exposed to either 18 daily fractions of 2.8 Gy or nine daily fractions of 5.6 Gy orthovoltage X-radiation. Radiation-induced induced intestinal complications were recorded and groups of animals were euthanized 2 and 26 weeks post-irradiation. Radiation injury was assessed with a histopathologic radiation injury score (RIS). Total TGF-beta was detected immunohistochemically and measured with interactive computerized image analysis. The image analysis technique yielded highly reproducible quantitation data. The 2.8-Gy group maintained mucosal integrity and had fewer intestinal complications, lower RIS and lower TGF-beta levels than the 5.6-Gy group. There was highly significant correlation between TGF-beta immunoreactivity and radiation injury at both observation times (P < 0.001 and P < 0.0001). At 2 weeks, TGF-beta immunoreactivity correlated with mucosal ulceration (P = 0.002), epithelial atypia (P = 0.005), and serosal thickening (P = 0.0004). At 26 weeks, TGF-beta levels correlated significantly with six of seven histopathologic parameters, most strikingly with vascular sclerosis (P = 0.0003). We conclude that mucosal barrier breakdown is closely associated with increased TGF-beta immunoreactivity in consequential radiation enteropathy. The highly significant correlation between TGF-beta expression levels and alterations in late-responding tissue compartments also suggest a role for TGF-beta in primary radiation enteropathy.

Association of p53 mutations, microvessel density and neoangiogenesis in pairs of colorectal cancers and corresponding liver metastases.

p53 suppressor gene mutations are a well known step which occurs in the late stages of the complex tumourigenesis of colorectal cancer. A deregulation of p53 protein function may be associated with increased neovascularization and aggressive tumour growth. In vitro studies have shown that these genetic alterations cause a loss of wild-type p53-induced anti-angiogenetic control and could possibly induce expression of the neoangiogenic vascular endothelial growth factor (VEGF). Therefore, this in vivo study was performed to assess p53 mutations, i.e. hot spots in exons 4-9, in primary colorectal cancers and in corresponding liver metastases in order to test whether there is an association between p53 mutated tumours with increased microvessel density (MVD) and VEGF overexpression. Twenty-two tissue samples taken from primary colorectal cancers and the corresponding liver metastases were immediately snap-frozen in liquid nitrogen and fixed in formaldehyde. After DNA extraction exons 4-9 were amplified and directly sequenced. Cryostat sections were stained immunohistochemically using antibodies against VEGF, CD34, and p53 protein. A modified semiquantitative Weidner score and interactive computerized image analysis was used to assess MVD. Overexpression of immunohistochemically detected p53 protein was found in 7 of the 11 primary tumours and liver metastases (64%). Sequencing showed 3 out of 11 primary tumours (27%) and 5 out of 11 liver metastases (46%) to have p53 point or frameshift mutations; these samples tested immunohistochemically positive for p53 protein. Two p53 mutations in samples of liver metastases were not detectable in the corresponding primaries. We detected one frameshift mutation in exon 4 that has not yet been described in the literature. Tumour samples with p53 mutations and increased VEGF immunoreactivity were associated with higher MVD (p<0.01 and p<0.05, respectively). However, there was no association detected immunohistochemically between p53 and MVD as well as p53 mutations and VEGF overexpression. Our data demonstrate specific genetic alterations in the coding regions of p53 suppressor gene in both primary colorectal cancers and corresponding liver metastases, these alterations are associated with an increase in MVD, but not in VEGF overexpression. In addition, a novel frameshift mutation in both colorectal cancer and metastasis is described.

Changes in transforming growth factor beta1 gene expression and immunoreactivity levels during development of chronic radiation enteropathy.

Chronic intestinal radiation injury is associated with locally increased TGF-beta1 immunoreactivity that correlates with morphological alterations. However, the underlying mechanisms are not known. This study examined changes in intestinal TGF-beta1 immunoreactivity, steady-state TGF-beta1 mRNA levels, and cellular localization of TGF-beta1 mRNA during development of chronic radiation enteropathy in a rat model. A loop of small bowel was fixed inside the scrotum of orchiectomized male rats. The intestine was subsequently exposed locally to 0, 12 or 21 Gy X radiation. Intestine was procured at 24 h and 2, 6 and 26 weeks and subjected to histopathological analysis, quantitative immunohistochemistry with computerized image analysis, assessment of steady-state TGF-beta1 mRNA levels with quantitative reverse transcriptase polymerase chain reaction, and identification of cell types expressing TGF-beta1 mRNA with in situ hybridization. Intestine from the 21-Gy group exhibited more histopathological injury and increased TGF-beta immunoreactivity 2-26 weeks after irradiation compared to the 12-Gy group and sham-irradiated controls. TGF-beta1 mRNA in irradiated intestine increased up to six times relative to controls at 24 h and 2 weeks, was less at 6 weeks, and did not differ from controls at 26 weeks. In situ hybridization detected TGF-beta1 mRNA in epithelial and Paneth cells in control intestine. Irradiated intestine exhibited additional TGF-beta1 mRNA in inflammatory and fibroblast-like cells. We conclude that there is a radiation-induced shift in the cellular sources of TGF-beta1, and that Tgfb1 gene expression is increased mainly during the early phases of radiation enteropathy, preceding the increase in immunoreactivity and histopathological injury. Translational or post-translational mechanisms are likely involved in sustaining increased TGF-beta1 immunoreactivity levels during the chronic phase of radiation enteropathy.

Differential effect of radiation on endothelial cell function in rectal cancer and normal rectum.

BACKGROUND: Chronic radiation injury of the intestine is associated with significant underexpression of a potent physiological anticoagulant, endothelial cell thrombomodulin (TM). This study compared early and late radiation-induced changes in endothelial TM, urokinase plasminogen activator (uPA), and transforming growth factor beta (TGF-beta) in normal rectum and tumors. METHODS: Rectal resection specimens from 27 patients were analyzed: Nine patients underwent primary resection of rectal cancer, 11 tumors were resected after neo-adjuvant radiotherapy, and 7 because of local recurrence after prior resection and adjuvant radiotherapy. TM, uPA, and extracellular matrix-associated TGF-beta, immunoreactivity were assessed using computerized image analysis. RESULTS: Multivariate analysis revealed that tumors had more TM-positive vessels (P = 0.003), more uPA-positive cells (P <0.001), and higher TGF-beta immunoreactivity levels (P <0.001) than normal rectum. Preoperative irradiation was associated with decreased proportions of TM-positive vessels in tumors (P = 0.003) and normal rectum (P <0.001). Irradiated tumors had fewer uPA-positive cells (P = 0.003) and less TGF-beta immunoreactivity (P = 0.001) than unirradiated tumors. The proportion of TM-positive vessels in irradiated rectum from patients with recurrence was decreased (P = 0.03), whereas the recurrent (ie, unirradiated) tumors did not differ from primary tumors in terms of TM, TGF-beta, or uPA immunoreactivity. CONCLUSIONS: The results support a role for endothelial dysfunction in the pathogenesis of radiation proctitis. Maintaining endothelial cell anticoagulant function may be a potential method to optimize the therapeutic ratio of adjuvant radiotherapy of rectal cancer.

Association between decreased pulmonary endothelial cell thrombomodulin and local fibrin deposition in pneumonia.

Thrombomodulin (TM) plays an important role in anticoagulation by forming a complex with thrombin, which subsequently activates protein C. TM is inactivated and downregulated by inflammatory cell mediators. This study examined whether bronchopneumonia is associated with changes in TM immunoreactivity, and whether a decrease in TM is accompanied by evidence of hypercoagulability, i.e. local deposition of fibrin. Double antibody staining for TM and fibrin was performed on lung tissue sections from patients who had died of pneumonia and from patients who had died rapidly, secondary to trauma. Inflammatory changes were assessed histologically and immunohistochemically using antibodies against interleukin-1alpha, tumor necrosis factor-alpha, and myeloperoxidase. Areas with bronchopneumonia exhibited markedly decreased endothelial TM staining of alveolar walls and small vessels. These changes were associated with prominent fibrin immunoreactivity. Some areas exhibited mild to moderate inflammation with little fibrin deposition and variable amounts of TM in adjacent vessels. This study is the first to relate changes of TM immunoreactivity levels to fibrin deposition in a human disease process. These data may have implications for pulmonary pathophysiology in patients with bronchopneumonia.

Presarcomatous lesions of experimentally induced sarcomas in rats: morphologic, histochemical, and immunohistochemical features.

Morphological studies have been performed mainly on manifest sarcomas, leading to divergent views of its histogenesis. However, histogenesis requires understanding of the tumor precursor cells and cannot be resolved by static morphologic studies. Defining presarcomatous lesions is made more difficult because they do not possess a basement membrane that serves as biologic and nosologic boundary like in epithelial cancers. The present study, therefore, investigated the early phases of experimentally induced rat sarcoma, which closely resembles human malignant fibrous histiocytoma (MFH). Histological, enzyme- and immunohistochemical methods were used to define the sequential events involved in tumorigenesis. A benzo[a]pyrene-oil mixture was injected intramuscularly into the thighs of rats, producing MFH 120 days later. Groups of animals were sacrificed every 10 days. The injections produced soft tissue lesions characterized by three distinct phases that overlapped or existed simultaneously in one animal: an initial acute inflammatory reaction characterized by an infiltration of lymphocytes, monocytes and macrophages, a second mesenchymal fibromatous phase characterized by the predominance of spindle-shaped, focally atypical fibroblast-like cells and collagen, and a third premalignant neovascularization phase characterized by dominant capillary proliferations. Overt MFH developed 120 days after injection and consisted of spindle-shaped fibroblast- and histiocyte-like cells containing atypical mitoses and arranged in a storiform pattern. Control animals injected with olive oil revealed acute inflammatory reactions after 30 days and no signs of chronic inflammation or malignancy after 60 and 120 days. We concluded that these experimentally-induced rat sarcomas develop in a triphasic pattern that resembles non-healing granulation tissue, with neovascularization preceding the occurrence of overt MFH.

Glycohistochemical monitoring of chemically induced sarcomas at different stages of tumorigenesis.

Malignant soft tissue tumors still represent a source of uncertainty and controversy concerning histogenetic origin and histological behavior. Considering this, chemically induced sarcomas furnish an attractive model for the elucidation of cellular alterations during tumorigenesis. This approach allows us to closely follow cyto- and histological changes within coherent stages of tumor development. The specimen under scrutiny comprised 35 rat tissue samples from day 10 up to day 200 after benzo[a]pyrene injection. Additionally, for comparison and validation two human malignant fibrous histiocytomas (MFH) were investigated. The essential biological significance of protein-carbohydrate interactions warranted the histochemical application of synthetic tools (neo-glycoproteins-NGP) and lectins in order to reveal phenotypical dynamics in this aspect throughout the process of tumor development. Namely, 6 plant lectins (carbohydrate-binding proteins with defined saccharide specificity), 7 custom-made synthetic NGP (as the corresponding ligands visualizing endogenous lectins) and additionally three antibodies were employed. Characteristic cell populations were histochemically demonstrated in four stages of tumor development: exudation (n = 5), mesenchymal proliferation (n = 7), atypical granulation tissue (n = 7) and sarcoma (n = 16). Changes of glycohistochemical binding patterns were in close phenotypic relation to cellular activity, differentiation, local distribution as well as malignant transformation and tumor progression. At present, the new glycobiological features of the malignant phenotype substantiate the assumption that not only glycosylation but also the receptor display is altered upon carcinogenesis. In conclusion, this chronological longitudinal study takes advantage of the combination of a coherent model of tumorigenesis with innovative histochemical tools whose ligands are supposed to act as mediators of cell-cell- and cell-matrix interactions. It clearly demonstrates the suitability of the glycohistochemical method for comparative approaches. The systematic analysis of glycohistochemical determinants will improve our understanding of the early tumor biological processes with potential implications for therapeutic interventions.

[HELLP Syndrome as an indication for liver transplantation]. / HELLP-Syndrom als Indikation für eine Lebertransplantation.

Liver rupture followed by multiorgan failure is perhaps the most catastrophic complication of the HELLP syndrome (hemolysis, elevated liver function, low platelets). Specific treatment options are currently limited and not routinely clarified. Here, we present a patient successfully managed by an innovative surgical approach consisting of combined total hepatectomy, portacaval shunt, and liver transplantation. A 26-year-old primipara (39th week of gestation) who suffered liver rupture as a complication of HELLP syndrome after delivery underwent a portacaval shunt after total hepatectomy. This combination was sufficient until the patient underwent orthotopic liver transplantation. The patient was discharged from the hospital after a dramatic recovery. Bridging portacaval shunt and consecutive orthotopic liver transplantation represented an effective therapy for this patient and should be considered early as a treatment option in patients with liver rupture complicating severe HELLP syndrome.

[Red eye and visual impairment two months after esophageal resection with complicated postoperative course]. / Rotes Auge und Visusstörung zwei Monate nach Osophagusresektion mit kompliziertem postoperativem Verlauf.

A patient with a red, painful eye and gradual visual impairment is examined ophthalmologically. Culture of the vitreal aspirate yields Candida tropicalis. Subsequent medical evaluation reveals that during an acute hospitalization eight weeks prior positive blood cultures for Candida had been reported but not acted on, despite a high risk constellation of operative therapy, intensive care unit treatment, central catheters, parenteral nutrition and broad spectrum antibiotics. Diagnosis and treatment of candidemia with a focus on candida endophthalmitis is discussed.

The database dbEST correctly predicts gene expression in colon cancer patients.

This study aims to test the predictive power of gene expression data derived from NIH's database dbEST, which collects gene expression results from a large number and variety of DNA array experiments. The motivation of this study is to make comparable experimental studies, which are usually performed only for one or a few tissues or organs, with a wide variety of other tissues. Confirmation of a good predictive power of dbEST would put a number of interesting and partially surprising recent findings, solely based on data mining, on a more solid basis than available so far. The expression of nine genes (eIF4E, DDX6, HAT1, USP28, HSP90(beta, PKM2, PLK1, COX2 and OPN) plus two calibration genes in paired normal and cancer colon tissues of eight individual patients was investigated by quantitative RT-PCR and compared with the predictions made by the data-base. GUS and beta-actin reveal only little variation among different patients, making them good internal calibration standards. In normal colon tissue, data mining correctly predicts the expression of all nine genes, which covers two orders of magnitude. In cancer, dbEST is somewhat less precise, but still valuable for the comparison with clinical results.

Cellular sources of transforming growth factor-beta isoforms in early and chronic radiation enteropathy.

The three mammalian transforming growth factor (TGF)-beta isoforms (TGF-beta1, TGF-beta2, and TGF-beta3) differ in their putative roles in radiation-induced fibrosis in intestine and other organs. Furthermore, tissue specificity of TGF-beta action may result from temporal or spatial changes in production and/or activation. The present study examined shifts in the cell types expressing TGF-beta mRNA relative to TGF-beta immunoreactivity and histopathological injury during radiation enteropathy development. A 4-cm loop of rat small intestine was locally exposed to O, 12, or 21-Gy single doses of x-irradiation. Sham-irradiated and irradiated intestine were procured 2 and 26 weeks after irradiation. Cells expressing the TGF-beta1, TGF-beta2, or TGF-beta3 transcripts were identified by in situ hybridization with digoxigenin-labeled riboprobes. Intestinal wall TGF-beta immunoreactivity was measured using computerized image analysis, and structural radiation injury was assessed by quantitative histopathology. Normal intestinal epithelium expressed transcripts for all three TGF-beta isoforms. Two weeks after irradiation, regenerating crypts, inflammatory cells, smooth muscle cells, and mesothelium exhibited increased TGF-beta1 expression and, to a lesser degree, TGF-beta2 and TGF-beta3 expression. Twenty-six weeks after irradiation, TGF-beta2 and TGF-beta3 expression had returned to normal. In contrast, TGF-beta1 expression remained elevated in smooth muscle, mesothelium, endothelium, and fibroblasts in regions of chronic fibrosis. Extracellular matrix-associated TGF-beta1 immunoreactivity was significantly increased at both observation times, whereas, TGF-beta2 and TGF-beta3 immunoreactivity exhibited minimal postradiation changes. Intestinal radiation injury is associated with overexpression of all three TGF-beta isoforms in regenerating epithelium. Radiation enteropathy was also associated with sustained shifts in the cellular sources of TGF-beta1 from epithelial cells to cells involved in the pathogenesis of chronic fibrosis. TGF-beta2 and TGF-beta3 did not exhibit consistent long-term changes. TGF-beta1 appears to be the predominant isoform in radiation enteropathy and may be more important in the mechanisms of chronicity than TGF-beta2 and TGF-beta3.

[Lysis therapy of thrombosis of the superior mesenteric artery]. / Lysetherapie bei arterieller Thrombose der Arteria mesenterica superior.

INTRODUCTION: For surgeons the acute intestinal ischaemia is still a diagnostic and therapeutic challenge. If clinically suspected, the diagnostic procedures such as duplex sonography and arterial angiography should be carried out immediately. Although the diagnosis is often quickly clear, perioperative mortality rate remains high. We report the acute local thrombolytic therapy as an alternative treatment. CASE REPORT: A 80-year-old male patient was referred to our hospital with a complete occlusion of the superior mesenteric artery. Duplex sonography and the arterial angiogram confirmed the clinical diagnosis. Because the patient was assessed to be at high risk we decided to avoid an operation and local thrombolytic therapy using rt-PA and urokinase was carried out. RESULT: The local thrombolytic therapy was successful and led to a complete restoration of the arterial flow within the superior mesenteric artery. The clinical symptoms subsided and no complications were observed. CONCLUSION: Local thrombolytic therapy appears to be a suitable therapeutic option in patients suffering of mesenteric arterial occlusion. Although the duplex sonography often confirms the diagnosis with high accuracy the angiography remains the diagnostic gold standard.

Association of granulocyte transmigration with structural and cellular parameters of injury in experimental radiation enteropathy.

Inflammatory cells are involved in the pathogenesis of tissue injury through release of cytokines and biologically active compounds. This study used a novel, noninvasive method to assess the association between granulocyte transmigration and structural and molecular changes in radiation enteropathy. A 4 cm loop of rat small intestine was exposed to 0, 2.8, 12, or 23 Gy localized irradiation. Feces was collected in metabolic cages before and 3, 7, 14, 28, and 42 days after irradiation. Granulocyte marker protein (GMP) was measured in buffer extracts of feces by enzyme-linked immunosorbent assay (ELISA). Irradiated and shielded intestine were procured at 2 and 26 weeks and assessed for histopathologic injury [radiation injury score (RIS)], ED-2 positive macrophages, and interleukin-1 alpha (IL-1 alpha) positive cells. Irradiated intestine exhibited characteristic histopathologic alterations and increased numbers of macrophages and IL-1 alpha positive cells. There was a highly significant dose-dependent increase in post-radiation GMP (P < 0.0001). Maximal GMP excretion occurred 3-7 days after irradiation. Six weeks after irradiation, GMP excretion had returned to normal in the 2.8 and 12 Gy groups, but was still 3.5 times higher in the 23 Gy group than in controls. The associations between early GMP excretion and RIS and fibrosis at 26 weeks were highly significant (P < 0.001 and P < 0.0001, respectively). Post-radiation granulocyte transmigration is dose-dependent and correlates with structural and molecular changes, as well as with subsequent chronic injury. The GMP assay is a sensitive, non-invasive indicator of acute intestinal radiation injury and a promising biological predictor of chronic toxicity. Our data underscore the importance of consequential mechanisms in radiation enteropathy.