Vascular smooth muscle cell (VSMC) accumulation is a hallmark of atherosclerosis and vascular injury. However, fundamental aspects of proliferation and the phenotypic changes within individual VSMCs, which underlie vascular disease remain unresolved. In particular, it is not known if all VSMCs proliferate and display plasticity, or whether individual cells can switch to multiple phenotypes. To assess whether proliferation and plasticity in disease is a general characteristic of VSMCs or a feature of a subset of cells, multi-colour lineage labelling is used to demonstrate that VSMCs in injury-induced neointimal lesions and in atherosclerotic plaques are oligo-clonal, derived from few expanding cells, within mice. Lineage tracing also revealed that the progeny of individual VSMCs contribute to both alpha Smooth muscle actin (aSma)-positive fibrous cap and Mac-3-expressing macrophage-like plaque core cells. Co-staining for phenotypic markers further identified a double-positive aSma+ Mac3+ cell population, which is specific to VSMC-derived plaque cells. In contrast, VSMC-derived cells generating the neointima after vascular injury generally retained expression of VSMC markers and upregulation of Mac3 was less pronounced. Monochromatic regions in atherosclerotic plaques and injury-induced neointima did not contain VSMC-derived cells expressing a different fluorescent reporter protein, suggesting that proliferation-independent VSMC migration does not make a major contribution to VSMC accumulation in vascular disease. Similarly, VSMC proliferation was examined in an Angiotensin II perfusion model of aortic aneurysm in mice, oligo-clonal proliferation was observed in remodelling regions of the vasculature, however phenotypic changes were observed in a large proportion of VSMCs, suggesting that the majority of VSMCs have some potential to modulate their phenotype. To understand the mechanisms behind the inherent VSMC heterogeneity and observed functionality, the single cell transcriptomic techniques Smart-seq2 and the Chromium 10X system were optimized for use on VSMCs. The work within this thesis suggests that extensive proliferation of a low proportion of highly plastic VSMCs results in the observed VSMC accumulation after injury, and the atherosclerotic and aortic aneurysm models of cardiovascular disease.

Made available in DSpace on 2016-08-17T18:39:45Z (GMT). No. of bitstreams: 1 4725.pdf: 4003213 bytes, checksum: c40eb861711bbe31a91e5b1600b14b63 (MD5) Previous issue date: 2012-09-21 / Universidade Federal de Sao Carlos / Intellectual disability (ID) is manifest sign of more than 2,000 different clinical conditions and is present in 5% of the population. Because it is a heterogeneous group of clinical conditions, with different causal factors and simultaneously involved, about 50% of patients with ID have no defined etiology. Chromosomal microdeletions, situations in which there is loss of a fragment of up to 5Mb of the genome resulting in haploinsufficiency of one or multiple genes, are one of the possible causes of ID. The aim of this study was to standardize genetic testing with the technique of MLPA (Multiplex Ligation Probe Amplification) to investigate the presence of microdeletion syndromes in a sample of patients with idiopathic DI or with diagnosis not yet confirmed by molecular genetic testing. The MLPA kit used (SALSA® MLPA® P064-B2 MR1) detected, at the same time, 11 microdeletion syndromes: 1p36 deletion, Sotos, Miller-Dieker, 22q11.2 deletion, Saethre-Chotzen, Prader-Willi, Angelman, Williams, Alagille, Smith-Magenis and Canavan. We selected 57 patients with idiopathic ID and facial dysmorphias, with normal conventional karyotyping and normal brain imaging studies. The presence of microdeletion was identified in 4 patients (7%), 3 patients had Williams syndrome and 1 had 22q11.2 deletion. The results reinforce the usefulness of MLPA in the etiologic research of ID, helping in the clinical management and familial genetic counseling. / Deficiência intelectual (DI) é sinal manifesto de mais de 2.000 condições clínicas diferentes e está presente em 5% da população. Por se tratar de um grupo heterogêneo de condições clínicas, com fatores causais distintos e simultaneamente envolvidos, cerca de 50% dos pacientes com DI não têm sua etiologia definida. Entre as possíveis causas de DI estão as microdeleções cromossômicas, situações nas quais há perda de um fragmento de até 5Mb do genoma, implicando na haploinsuficiência de um ou múltiplos genes. O objetivo desse trabalho foi padronizar testes genéticos fundamentados na técnica de MLPA (Amplificação de Múltiplas Sondas dependentes de Ligação) para investigar a presença de síndromes de microdeleção em uma amostra de pacientes com DI idiopática ou com hipótese diagnóstica ainda não confirmada por teste genético molecular. O kit de MLPA utilizado (SALSA® MLPA® P064-B2 MR1) detectava, simultaneamente, 11 síndromes de microdeleção: deleção 1p36, Sotos, Miller-Dieker, deleção 22q11.2, Saethre- Chotzen, Prader-Willi, Angelman, Williams, Alagille, Smith-Magenis e Canavan. Foram selecionados clinicamente 57 pacientes com DI e dismorfias faciais, com cariótipo convencional e exame de imagem de encéfalo normais. A presença de microdeleção foi identificada em 4 pacientes (7%), tendo sido detectados 3 pacientes com síndrome de Williams e 1 com deleção 22q11.2. Os resultados reforçam a utilidade da técnica de MLPA na investigação etiológica da DI, ajudando no manejo clínico dos pacientes e no aconselhamento genético familiar.

Submitted by AGDA JESSICA DE FREITAS GALLETTI null (aj.mat@hotmail.com) on 2018-03-23T18:26:29Z No. of bitstreams: 1 Dissertacao Agda.pdf: 8703134 bytes, checksum: 38fab95cf6a37646cb9076182d7acefe (MD5) / Approved for entry into archive by Luciana Pizzani null (luciana@btu.unesp.br) on 2018-03-26T17:31:07Z (GMT) No. of bitstreams: 1 galletti_ajf_me_bot.pdf: 8692893 bytes, checksum: 24ce44d5b41a0465faf8c7d5f279a7bb (MD5) / Made available in DSpace on 2018-03-26T17:31:07Z (GMT). No. of bitstreams: 1 galletti_ajf_me_bot.pdf: 8692893 bytes, checksum: 24ce44d5b41a0465faf8c7d5f279a7bb (MD5) Previous issue date: 2018-02-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A cirrose é uma doença hepática assintomática que, muitas vezes, é descoberta quando o quadro é irreversível. Por isso, o tratamento consiste em uma série de medidas para controlar o avanço da enfermidade, visto que a principal consequência da cirrose é o aumento da pressão na veia portal, que por sua vez, acarreta no surgimento de varizes e no seu respectivo rompimento, podendo ser fatal. Estudos relacionados à esta doença são muito importantes, pois a análise estatística é uma ferramenta que permite auxiliar na tomada de decisões nos procedimentos médicos e acompanhamento de pacientes. Um método estatístico bastante explorado nas ciências biomédicas é a análise de sobrevivência, que consiste em descrever o tempo de um evento inicial até a ocorrência de um outro de interesse. No entanto, existem situações em que uma proporção da amostra não vivencia o desfecho de interesse, mesmo que acompanhado por um período longo de tempo. Nestes casos, tais observações são dita imunes ao desfecho de interesse e as metodologias tradicionais de análise de sobrevivência não são indicadas. Logo, os modelos de fração de cura ou de longa duração, desenvolvido a partir do modelo de mistura, são os utilizados nestas situações. Neste trabalho diverso modelos foram considerados para analisar os tempos de vida de pacientes submetidos à Ligadura Elástica de Varizes Esofágicas, ao qual foram anotados os tempos até o óbito durante o acompanhamento de 129 pacientes do Hospital das Clínicas da Faculdade de Medicina da UNESP, Campus Botucatu (SP), no período de 2006 a 2010. O modelo Weibull Modificado com fração de cura foi considerado adequado, indicando que quanto maior a idade e o grau da doença hepática, se os pacientes não usam o medicamento Beta-Bloqueador e são homens, menor é a chance deles serem sobreviventes de longa duração. / Cirrhosis is an asymptomatic liver disease that is often discovered when the patient's condition is irreversible. Therefore, the treatment consists of a series of measures to control the progression of the disease, since the main consequence of the cirrhosis is the increase of the portal venous pressure, which causes the appearance of varices and their respective rupture may be fatal. Studies related to that disease are very important, so the statistical analysis is a tool that helps to make decisions in medical procedures and patient follow-up. The most applied statistical method in the biomedical sciences is survival analysis, which consists of describing the time of occurrence until the event of interest. However, there are situations in which a proportion of the sample does not experience the interest outcome, even if they are accompanied by a long period of time. In such cases, such observations are said to be immune to the outcome of interest and traditional survival analysis methodologies are not appropriated. Therefore, the care fraction or long duration models can be used in these situations because they incorporate mixtures of models to solve the complexity inherent in the actual study. In this work, some statistical models were considered to analyze the survival times of patients, after surgery of Endoscopic Band Ligation of the Esophageal Varices, such as Exponential, Gamma and Weibull models. The data is related to survival times of 129 patients, who were treated in the Hospital das Clínicas of the Medical School of UNESP, Campus Botucatu (SP), from 2006 to 2010. The Modi ed Weibull distribution with cure rate was considered adequate to the data, indicating that older male patients with higher Child-Pugh score without taking beta blockers medicine are more likely not to be a long-term survivor.

INTRODUÇÃO: O ozônio (O3) é encontrado na natureza e também pode ser produzido no corpo humano através da ativação de anticorpos. Seus efeitos anti-bactericidas são descritos na literatura, mas esses dados são controversos quanto a um potencial efeito benéfico da ozonioterapia no tratamento de certos tipos de infecção. OBJETIVO: Avaliar os efeitos da aplicação intraperitoneal (i.p.) de uma mistura gasosa de ozônio em um modelo de ligadura e punção de ceco (LPC) em ratos, através da dosagem de interleucinas (IL)-6, IL-10 e da quimiocina CINC-1 (cytokine-induced neutrophil chemoattractant), da lesão pulmonar aguda (LPA) e da análise das taxas de sobrevida. MÉTODO: Quatro grupos de ratos Wistar foram utilizados para análise de cada objetivo (CTR, LPC, LPC+O2 e LPC+O3). Os animais do grupo CTR foram submetidos somente a laparotomia. O grupo LPC foi submetido aos procedimentos de LPC. Os outros grupos foram submetidos à LPC e receberam injeção (i.p.) da mistura gasosa correspondente, administrada a cada 12 horas durante o período de observação. Os níveis séricos de IL-6, CINC-1 e IL-10 foram determinados por imuno- ensaio (enzyme linked immunosorbent assay- ELISA). A LPA foi avaliada através da histologia pulmonar e quantificada através do método do extravasamento pulmonar do Azul de Evans. Os animais da análise de sobrevivência foram observados por cinco dias. Os valores obtidos foramexpressos como médias ± erro-padrão da média (EP) ou medianas mais percentis 25 e 75(P25; P75), de acordo com a distribuição dos dados. Considerou-se significante p<0,05. RESULTADOS: Os ratos do grupo CTR exibiram os menores níveis de CINC-1 (p<0,01). O grupo LPC+O3 teve níveis menores de CINC-1 comparado a LPC+O2 e LPC (p<0,05). Os níveis de IL-10 do grupo CTR foram menores do que nos outros 3 grupos(p=0,02) . Não houve diferenças entre os outros 3 grupos (p=0,85). IL-6 foi significativamente menor para o grupo CTR (30,8± 4,8) quando comparado a todos os outros grupos (p<0,001). LPC+O3 e LPC+O2 exibiram níveis menores quando comparados ao grupo LPC (p<0,01). Não houve diferença entre os grupos LPC+O3 e LPC+O2 (p=0,54). O escore de histologia pulmonar foi menor para CTR (p=0,02). Os outros grupos não apresentaram diferenças significantes intergrupos (p=0,3). Os valores dos coeficientes de extravasamento pulmonar do Azul de Evans foram menores para LPC+O3 quando comparado aos grupos LPC+O2 e LPC (p=0,02), porém não houve diferença na comparação com CTR O grupo CTR teve o maior tempo de sobrevida (110±10h) comparado com os outros grupos, ou seja, LPC (57,3± 10,4h), LPC+O2 (71 ± 12,9h) e LPC+O3 (52,1 ± 8), os quais não apresentaram diferenças entre si quanto à sobrevida (p=0,4). CONCLUSÃO: No presente estudo experimental em ratos, a ozonioterapia teve um benefício potencial na modulação da resposta inflamatória e na LPA, mas não influenciou as taxas de sobrevida dos animais. / INTRODUCTION: Ozone (O3) is found in nature and also can be produced in the human body through activation of antibodies. Its antibacterial effect has been described in the literature, but these data are controversial regardi ng a benefic role of O3 therapy in the treatment of certain types of infection. OBJECTIVE: To evaluate the effects of intraperitoneal (i.p.) application of an O3 gas mixture in a rat model of cecal ligation and puncture (CLP), by analyzing interleukin (IL)-6, IL-10 and cytokine-induced neutrophil chemoattractant (CINC)-1 levels, acute lung injury (ALI) and survival rates. METHOD: Four animal groups were used (SHAM, CLP, CLP+O2 and CLP+O3). SHAM animals were submitted solely to laparotomy. CLP group was submitted to cecal ligation and puncture. The other groups were submitted to CLP and received injections (i.p.) of the corresponding gas mixture every 12 hours during the observation period. The serum concentrations of IL-6, CINC-1 and IL-10 were determined by the enzyme-linked immunosorbent assay (ELISA). ALI was evaluated with pulmonary histology and quantitated by means of the Evans blue dye (EBD) lung leakage method. For survival analysis, animals were observed for 5 days. Values were expressed as means ± SEM or medians (P25; P75), according to the data distribution. A p<0,05 was considered significant.RESULTS: SHAM rats had the lowest levels of CINC-1 compared to all other groups (p<0,01). CLP+O3 group had lower levels of CINC-1 compared to CLP+O2 and CLP (p<0,05). SHAM IL-10 levels were the lowest compared to the 3 other groups (p=0,02). There were no differences between the other 3 groups (p=0,85). IL-6 was significantly lower for SHAM compared to all groups (p<0,001). CLP+O3 and CLP+O2 had lower levels when compared to CLP (p<0,01). Comparison between groups CLP+O3 and CLP+O2 showed no significant difference (p=0,54). Pulmonary histology score was lower for SHAM (p=0,02). The other groups presented no statistical difference when compared to each other (p=0,3). EBD lung leakage values were lower to CLP+O3 compared to CLP+O2 and CLP (p=0,02). SHAM group had the longest survival time (110±10h) compared to all other groups (p=0,002). CLP (57,3± 10,4h), CLP+O2 (71 ± 12,9h) and CLP+O3 (52,1 ± 8h), which did not show difference on survival compared to each other (p=0,4). CONCLUSION: In this rat model of sepsis, ozone therapy had a potential benefit in the modulation of inflammatory response and ALI, but no improvement on survival rates was observed.

Submitted by isabela.moljf@hotmail.com (isabela.moljf@hotmail.com) on 2017-05-12T13:37:04Z No. of bitstreams: 1 pedroluizrodriguesguedes.pdf: 3448334 bytes, checksum: 3bac263ee478fd60c02c5d6036a0e81e (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-12T15:44:09Z (GMT) No. of bitstreams: 1 pedroluizrodriguesguedes.pdf: 3448334 bytes, checksum: 3bac263ee478fd60c02c5d6036a0e81e (MD5) / Made available in DSpace on 2017-05-12T15:44:09Z (GMT). No. of bitstreams: 1 pedroluizrodriguesguedes.pdf: 3448334 bytes, checksum: 3bac263ee478fd60c02c5d6036a0e81e (MD5) Previous issue date: 2013-07-30 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Condroitim sulfato (CS) é um glicosaminoglicano (GAG), presente na matriz extracelular (MEC) de vários tecidos de mamíferos, utilizado para o tratamento da osteoartrite e, recentemente, tem despertado grande interesse devido ao seu potencial anti-inflamatório. Vários modelos experimentais in vivo de inflamação são empregados para o estudo da atividade anti-inflamatória, entre eles o modelo de fibrose induzida por colestase extra-hepática. A colestase produz lesão hepatocelular com edema do trato portal, infiltrado leucocitário, proliferação de células epiteliais biliares e fibrose do trato portal. O objetivo deste trabalho foi analisar os efeitos do CS no modelo de colestase extra-hepática emperimental induzido por laqueadura do ducto biliar (BDL) em ratos Wistar. Para isso foram utilizados animais (n = 82) de 6 a 8 semanas de idade eutanasiados 2, 7 ou 14 dias após o procedimento cirúrgico divididos nos grupos: BDL, BDL tratado com CS, Sham e Sham tratado com CS. Foram avaliados peso corporal e do fígado dos animais, concentrações séricas de bilirrubina direta (BD), globulinas, atividades de gama glutamil transpeptidase (Gama GT), fosfatase alcalina (FA), alanina transaminase (ALT) e aspartato transaminase (AST), alterações morfológicas no tecido, atividade de mieloperoxidase (MPO), atividade de metaloproteases (MMP-9, MMP-2 e pró MMP-2) e conteúdo de GAGs no fígado dos animais, além da análise histopatológica do tecido hepático. O CS obtido para a realização do trabalho apresentou teores superiores a 92%, com peso molecular de aproximadamente 40 kDa e um conteúdo dissacarídico com predominância de Δdi4S (65%). BDL gerou vários sintomas relacionados à lesão celular e ao processo inflamatório como aumento dos níveis séricos de BD e globulinas, aumento das atividades de Gama GT, FA, ALT e AST, infiltrado inflamatório e modificação morfométrica, com proliferação ductular, e na MEC do fígado dos animais induzidos. CS levou a redução do aumento inicial das transaminases indicando proteção dos tecidos lesados no procedimento cirúrgico. O tratamento levou à redução do infiltrado inflamatório no tecido, expresso pela diminuição significativa da atividade de MPO no homogenato. A remodelação tecidual também foi reduzida, havendo diminuição da atividade de MMP-9, pró MMP-2 e MMP-2 e ainda dos níveis dos GAGs dermatam sulfato e heparam sulfato presentes, produzidos por células estreladas em resposta ao dano no tecido. Estes resultados mostram que o CS reduziu os efeitos da lesão hepática do modelo e foi capaz de retardar a fibrogênese hepática. / Chondroitin sulfate (CS) is a glycosaminoglycan (GAG) present in the extracellular matrix (ECM) of many mammalian tissue, used for osteoarthritis treatment and, recently, has aroused great interest due to its anti-inflammatory potential. Several in vivo inflammation experimental models are employed to study anti-inflammatory activity, including extra-hepatic cholestasis induced fibrosis. Cholestasis produces hepatocellular injury with portal tract edema, leukocyte infiltration, biliary epithelial cells proliferation and portal tract fibrosis. The aim of this work was to analyze CS effects on an extra-hepatic cholestasis experimental model induced by bile duct ligation (BDL) on Wistar rats. For this purpose 6 to 8 weeks old animals (n = 82) were euthanized 2, 7 or 14 days after surgical procedure, previously divided into groups: BDL, CS treated BDL, Sham, CS treated Sham. To analyze disease evolution body and liver weight, serum concentrations of direct bilirubin (BD), globulins, activities of gamma glutamyl transferase (Gama GT), alkaline phosphatase (FA), alanine and aspartate aminotransferases (ALT and AST), morphological changes on tissue, mieloperoxidase (MPO) activity, matrix metalloproteinases (MMP-9, pró MMP-2 and MMP-2) activities and liver GAGs content, besides histopathological analysis of the tissue. CS acquired presented over 92% tenor, molecular weight of approximately 40 kDa and disaccharide content of Δdi4S predominantly (65%).BDL caused many symptoms related to cellular damage and inflammatory process such as increasing BD and globulins, elevation of Gama GT, FA, ALT and AST activities, inflammatory infiltrate and changes on liver morphometry, with ductular proliferation, and on the ECM. CS reduced initial burst on aminotransferases, indicating protection of tissues injured on surgery procedure. Treatment led to reduction of inflammatory infiltrate, showed by significant decreasing on MPO activity. Tissue remodeling was also reduced, with decrease of MMP-9, pro MMP-2 and MMP-2 activities and also of GAGs dermatam sulfate and heparam sulfate levels, produced by hepatic stellate cells in response of tissue damage. These results show that CS reduced cholestasis hepatic injury effects, being capable to slow down liver fibrogenesis.

L’immunothérapie anti-cancéreuse vise à éliminer les cellules tumorales en stimulant les propres cellules du système immunitaire du patient. Dans ce projet, nous avons développé une nouvelle stratégie d’immunothérapie visant à cibler directement des immunostimulants a la surface des cellules tumorales par ligation bio-orthogonale. Nous utilisons, pour marquer spécifiquement les cellules tumorales, leur métabolisme particulier et très actif qui permet d’intégrer à leur surface, dans leurs glycanes, des azido sucres capables de se lier en grand nombre avec divers immunostimulants portant des groupements réactifs adéquats (= glyco-ingénierie métabolique). Pour la ligation aux glycanes, nous employons la chimie bio-orthogonale qui est basée sur l’utilisation de 2 groupements mutuellement réactifs, tous 2 absents des milieux biologiques et qui peuvent se coupler rapidement très sélectivement et donc pratiquement sans réactions secondaires dans des conditions douces compatibles avec une application in vivo. Notre choix d’immunostimulants s’est porte sur les oligonucléotides de type CpG (puissants immunostimulants) et sur les β-glucanes qui, en combinaison avec des anticorps thérapeutiques, stimulent la phagocytose et n’entrainent pas une secretion importante de cytokines. Ainsi, après avoir determiné les meilleures conditions d’incorporation des azido sucres et mis au point le couplage des immunostimulants à différents groupements bioorthogonaux, nous sommes parvenus à montrer in vitro la fixation des immunostimulants à la surface de différentes lignées tumorales. Des tests immunologiques in vitro et une étude in vivo ont ensuite permis de valider l’effet des immunostimulants fixés à la surface des cellules tumorales. Nous avons ainsi observe sur une série de souris, un ralentissement de développement tumoral en présence d’un puissant immunostimulant fixé sur les cellules tumorales. / Cancer immunotherapy uses the patient's own immune system to fight cancer. In this research project, we propose a new strategy for immunotherapy: binding immunostimulants in situ to the tumor cell surface using bio-orthogonal chemistry. For that purpose we use the particular and active metabolism of tumor cells to introduce by metabolic glycoengineering into their cell surface glycans, azido sugars capable of binding many different immunostimulants carrying adequate reactive groups. The biorthogonal chemistry allowing this specific ligation is based on the use of two mutually reactive groups both naturally absent from biological systems and which can be coupled selectively and very quickly in conditions totally compatible with living organisms. Our choice of immunostimulants consists, on one hand, of CpG oligonucleotides (powerful general immunostimulants) and on the other hand of β-glucans (phagocytosis stimulants used in combination with therapeutic antibodies without causing strong cytokine secretion). We determined the best conditions for the introduction of azido sugars into cell glycans of different tumor models and tried different biorthogonal groups and reaction conditions to obtain the best immunostimulant coupling to the surface of various tumor cell lines. Then, we performed in vitro immunological tests and in vivo studies in mice in order to validate the effect of the association between immunostimulants and tumor cells on the immune response against tumors. Thereby, we observed on a group of mice, reduced tumor growth when the strong immunostimulant CpG was fixed onto tumor cell surface.

Sepsis-induced organ failure is associated with high morbidity and mortality rates. The onset of an exaggerated host response to microbial invasion and/or trauma, is believed to be the primary cause of excessive inflammation and the subsequent tissue hypoperfusion observed in patients with severe sepsis. In our mouse model of sepsis induced by cecal ligation and perforation (CLP), symptoms indicative of the disease, including diarrhea, increased ventilation and persistent hypothermia, are present at six hours after the surgery (T6). In the untreated CLP mice, mortality occurs starting at T15. As induced hypothermia has shown to exert immunomodulatory effects, this study is aimed at assessing its potential in attenuating inflammation and improving survival in experimental sepsis. Our data has shown that deep hypothermia initiated at T6, by means of cold chamber-induced cooling, prolongs survival. Plasma cytokine quantification by enzyme-linked immunosorbent assays (ELISA) also reveals that induced deep hypothermia reduces tumour necrosis factor(TNF)-α and interleukin (IL)-6 production in untreated CLP mice. In contrast, induced moderate hypothermia does not have such effect. Antibiotic (cefotaxime) and saline resuscitation initiated immediately following CLP ensures survival. However, when these supportive treatments are initiated at T6, >50% mortality is observed in the CLP mice with or without induced hypothermia. In summary, this preliminary study provides proof for a downregulated inflammatory response mediated by external cooling. However, to achieve a survival benefit, treatment strategies in addition to cooling and antibiotics may be required.

We demonstrate a novel and ready to prepare thermoreversible hetero Diels–Alder dilinker on the basis of dithiooxalates, enabling the mild, rapid and catalyst-free linkage of diverse diene species under ambient conditions for applications in the fields of, for example, modular ligation, self-healing or recyclable materials and surface modification amongst others. The linker was studied using quantum chemical calculations, and experimentally in small molecular reactions via UV/Vis spectroscopy, mass spectrometry and NMR as well as in step-growth polymerizations with diene-difunctional building blocks – characterized via (temperature dependent) SEC and HT NMR – as an example for efficient polymer ligation.

Background: Endoscopic band ligation (EBL) is generally accepted as the treatment of choice for bleeding from esophageal varices. It is also used for secondary prophylaxis of esophageal variceal hemorrhage. However, there is no data or guidelines concerning endoscopic control of ligation ulcers. We conducted a retrospective study of EBL procedures analyzing bleeding complications after EBL. Methods: We retrospectively analyzed data from patients who underwent EBL. We analyzed several data points, including indication for the procedure, bleeding events and the time interval between EBL and bleeding. Results: 255 patients and 387 ligation sessions were included in the analysis. We observed an overall bleeding rate after EBL of 7.8%. Bleeding events after elective treatment (3.9%) were significantly lower than those after treatment for acute variceal hemorrhage (12.1%). The number of bleeding events from ligation ulcers and variceal rebleeding was 14 and 15, respectively. The bleeding rate from the ligation site in the group who underwent emergency ligation was 7.1% and 0.5% in the group who underwent elective ligation. Incidence of variceal rebleeding did not vary significantly. Seventy-five percent of all bleeding episodes after elective treatment occurred within four days after EBL. 20/22 of bleeding events after emergency ligation occured within 11 days after treatment. Elective EBL has a lower risk of bleeding from treatment-induced ulceration than emergency ligation. Conclusions: Patients who underwent EBL for treatment of acute variceal bleeding should be kept under medical surveillance for 11 days. After elective EBL, it may be reasonable to restrict the period of surveillance to four days or even perform the procedure in an out-patient setting.

No description available.