Aducio Thiesen - Academia.edu (original) (raw)

Papers by Aducio Thiesen

ACG Case Reports Journal, 2021

Plasminogen deficiency (PD) is a rare autosomal recessive disease that results in the formation o... more Plasminogen deficiency (PD) is a rare autosomal recessive disease that results in the formation of fibrin-rich pseudomembranes, which impair wound-healing capacity. We report a 21-year-old man with congenital PD-associated inflammatory bowel disease. After an episode of Clostridioides difficile infection, he developed chronic diarrhea. Colonoscopy revealed moderate friability and erythema of the colon. Histology showed fibrin deposits in the lamina propria of the colonic mucosa with surrounding inflammation and focal ulceration. He was treated with infliximab and achieved clinical remission. To our knowledge, this is the first reported case of colonic involvement of PD.

Liver Transplantation, Feb 1, 2010

Epithelioid hemangioendothelioma (EHE) is a low-grade, malignant vascular tumor that most commonl... more Epithelioid hemangioendothelioma (EHE) is a low-grade, malignant vascular tumor that most commonly presents within the liver. Patients with hepatic EHE are often candidates for liver transplantation as the disease is usually multifocal at diagnosis. Although these patients achieve excellent early outcomes post-transplant, there are very few data regarding tumor markers that can further direct chemotherapy in hepatic EHE to prevent recurrent disease. The purpose of this study was to analyze the expression of the angiogenic factor vascular endothelial growth factor (VEGF) and its receptors in hepatic EHE. Six patients with hepatic EHE were assessed for liver transplantation at our center. Pathology specimens of primary and recurrent EHE were analyzed by hematoxylin and eosin staining and by immunofluorescence for VEGF, fetal liver kinase 1 (Flk-1), and fms-related tyrosine kinase 1 (Flt-1) expression. Five patients underwent liver transplantation, and 1 patient underwent liver resection. Biopsy-proven recurrent EHE occurred in 3 patients. VEGF expression was present in 100% of the EHE specimens examined, whereas Flt-1 expression was present in only 1 sample, and Flk-1 was not observed in any of the specimens. In 1 patient with recurrent hepatic EHE post-liver transplantation, a progressive increase in the VEGF fluorescence intensity and distribution was observed. In conclusion, in this series, VEGF expression was observed in all hepatic EHE specimens analyzed. These data suggest that anti-VEGF chemotherapeutic agents will be of use in patients with hepatic EHE, particularly as a means of reducing the tumor volume prior to resection, as a means of treating unresectable or metastatic disease, or as an adjuvant therapy in the setting of liver transplantation.

ACG Case Reports Journal, May 1, 2021

ABSTRACT Plasminogen deficiency (PD) is a rare autosomal recessive disease that results in the fo... more ABSTRACT Plasminogen deficiency (PD) is a rare autosomal recessive disease that results in the formation of fibrin-rich pseudomembranes, which impair wound-healing capacity. We report a 21-year-old man with congenital PD-associated inflammatory bowel disease. After an episode of Clostridioides difficile infection, he developed chronic diarrhea. Colonoscopy revealed moderate friability and erythema of the colon. Histology showed fibrin deposits in the lamina propria of the colonic mucosa with surrounding inflammation and focal ulceration. He was treated with infliximab and achieved clinical remission. To our knowledge, this is the first reported case of colonic involvement of PD.

The Canadian journal of gastroenterology, 2000

The topic of the biology of gut cholecystokinin (CCK) and gastrin receptors has been reviewed (1)... more The topic of the biology of gut cholecystokinin (CCK) and gastrin receptors has been reviewed (1). Hyperinsulinemia increases plasma noradrenaline concentrations as well as muscle sympathetic nerve activity, even in the absence of hypoglycemia. In guinea pig-isolated ileal synaptosomes, insulin stimulates in a concentration-dependent manner the secretion of noradrenaline. This is mediated by signalling that involves insulin receptors through downstream activation of calcium influx (2). The luminal CCK-releasing factor is present throughout the gastrointestinal tract. Immunohistochemical analysis shows diffuse CCK immunoreactivity throughout the gastrointestinal tract and the pancreas (3). Luminal nutrients and neuroendocrine peptides exert differential effects on somatostatin-28 release from the rat intestine compared with those of somatostatin-14 (4). The somatostatin analogue octreotide is effective in the treatment of the diarrhea and flushing that occur in patients with carcinoid syndrome. Octreotide retards colonic and small bowel transit. This action may be mediated by the associated reduction in circulating levels of peptide Y (PYY), neurotensin, vasoactive intestinal polypeptide (VIP) and substance P (SP); however, octreotide has no effect on plasma motilin concentrations (5). The topics of VIP and secretin receptors, and the G protein-coupled receptors have been reviewed (6). The inactive proforms of gastrointestinal peptide hormones and neuropeptides (such as VIP, PYY and glucagonlike peptides) are processed in part by specific endoproteases through selective cleavage at the C-terminal side of paired basic amino acid sites. Prohormone convertase (PC)-6A mRNA is expressed throughout the entire gastrointestinal tract, with the highest levels in the small intestine (7). Ileal PC-6A mRNA expression increases with fasting and declines with refeeding, whereas dietary fat increases PC-6A mRNA levels in the ileum. Neuropeptide Y (NPY) and PYY are structurally related peptides that mediate inhibitory activity in terms of gastro

International Journal of Molecular Sciences, Mar 22, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Journal of Applied Physiology, Feb 1, 2003

cocorticosteroids enhance digestive and absorptive functions of the intestine of weaning and adul... more cocorticosteroids enhance digestive and absorptive functions of the intestine of weaning and adult rats. This study was undertaken to assess the influence of treatment of weaning male rats with budesonide (Bud), prednisone (Pred), or control vehicle on the in vitro jejunal and ileal uptake of glucose and fructose. Bud and Pred had no effect on the uptake of D-glucose by sodium glucose transporter-1. In contrast, the uptake of D-fructose by GLUT-5 was similarly increased with Bud and with Pred. The increases in the uptake of fructose were not due to variations in the weight of the intestinal mucosa, food intake, or in GLUT-5 protein or mRNA expression. There were no steroid-associated changes in mRNA expression of c-myc, c-jun, c-fos, proglucagon, or selected cytokines. However, the abundance of ileal ornithine decarboxylase mRNA was increased with Pred. Giving postweaning rats 4 wk of Bud or Pred in doses equivalent to those used in clinical practice increases fructose but not glucose uptake. This enhanced uptake of fructose was likely regulated by posttranslational processes.

BackgroundFollowing viral infection, genetically manipulated mice lacking immunoregulatory functi... more BackgroundFollowing viral infection, genetically manipulated mice lacking immunoregulatory function may develop colitis and dysbiosis in a strain specific fashion that serves as a model for inflammatory bowel disease (IBD). We found that one such model of spontaneous colitis, the interleukin (IL)-10 knockout (IL-I0-/-) model derived from the SvEv mouse, had evidence of increased mouse mammary tumor virus (MMTV) viral RNA expression compared to the SvEv wildtype. MMTV is endemic in several mouse strains as an endogenously encoded betaretrovirus that is passaged as an exogenous agent in breast milk. As MMTV requires a viral superantigen to replicate in the gut associated lymphoid tissue prior to the development of systemic infection, we evaluated whether MMTV may contribute to the development of colitis in the IL-10-/-model.ResultsViral preparations extracted from IL-10-/-weanling stomachs revealed augmented MMTV load compared to the SvEv wildtype. Illumina sequencing of the viral gen...

Journal of Pediatric Surgery, Feb 1, 2003

Glucocorticosteroids alter the function of the intestine. This study was undertaken to assess the... more Glucocorticosteroids alter the function of the intestine. This study was undertaken to assess the effect on D-glucose uptake of budesonide (Bud), prednisone (Pred), or dexamethasone (Dex) in animals with a 50% intestinal resection and fed chow or a diet enriched with saturated (SFA) or polyunsaturated fatty acids (PUFA). In vitro ring uptake technique, Western blots, and Northern blots were performed. Bud increased the jejunal D-glucose uptake, and this effect was prevented by feeding PUFA. SGLT1 and Na+/K+ ATPase protein and mRNA abundance did not correlate with the change in the rate of uptake of glucose. (1) Bud increased the jejunal glucose uptake, (2) the activity of the sugar transporter does not correlate with the abundance of protein or their respective mRNAs, (3) th Bud effect on glucose uptake is prevented by feeding PUFA. Thus, the desired intestinal adaptive response after intestinal resection may be enhanced further by the administration of the locally acting steroid budesonide and by feeding a saturated compared with a polyunsaturated fatty acid diet.

Gastroenterology, 2018

using MEDLINE, EMBASE, Scopus, CENTRAL and ISI Web of knowledge. Citation selection utilized a hi... more using MEDLINE, EMBASE, Scopus, CENTRAL and ISI Web of knowledge. Citation selection utilized a highly sensitive search strategy identifying studies with MeSH headings relating to: (i) ulcerative colitis (ii) severity of illness index, (iii) invasive and non-invasive scoring systems. Recursive searches, cross-referencing, and subsequent hand-searches were completed. All fully published trials in French or English comparing patients reported outcomes with endoscopy were included. Trials comprising only pediatric or inpatients were excluded. Two investigators (S.R and C-Y C.) assessed citation eligibility with discrepancies resolved by an independent reviewer (P.L.L). The quality of trials was graded using the Quadas-2 tool. All data abstraction and entries were validated independently by two authors and a third authors re-validated few studies afterwards. Results: Out of 3163 citations, 21 trials (1 RCT and 20 observational studies) fulfilled our inclusion criteria (n = 3172 patients, weighted average of mean age 41.3 +/-13.4, indication of endoscopy was an active disease in 18 trials). Clinical scales for UC severity assessment included SCCAI, pMAYO, Rachmilevich, Seo index and patient reported outcomes (diarrhea and bleeding). Endoscopic scales as comparators encompassed UCCIS, MAYO, Rachmilevich, St Mark, Baron and UCEIS. Comparison methods between clinical and endoscopic scores were conducted using correlation coefficient in 17 trials, while agreement coefficient and AUC in 1 and 2 trials respectively. Dramatic heterogeneity precludes valid meta-analysis. Overall, mean correlation coefficients were very high when comparing clinical and endoscopic scores (partial Mayo 0.71+/-0.14, range 0.49-0.97; Seo index 0.68+/-0.06, range 0.64-0.72; SCCAI 0.67+/-0.15 range 0.44-0.87; Rachmilevich 0.67+/-0.11 range 0.52-0.79; patient reported outcomes 0.8+/-0.12 range 0.71-0.88). AUC for the presence or absence of rectal bleeding was as high as 0.78. Conclusion: Mucosal healing can be predicted reliably by clinical symptoms, especially by the presence or absence of rectal bleeding. This is the first narrative review suggesting that assessing and treating patients based on reported symptoms seems to be appropriate.

American Journal of Gastroenterology, 2015

PLOS ONE, 2019

Background Normothermic machine perfusion (NMP) of liver grafts donated after circulatory death (... more Background Normothermic machine perfusion (NMP) of liver grafts donated after circulatory death (DCD) has shown promise in large animal and clinical trials. Following procurement, initial flush with a cold preservation solution is the standard of care. There is concern that initial cooling followed by warming may exacerbate liver injury, and the optimal initial flush temperature has yet to be identified. We hypothesize that avoidance of the initial cold flush will yield better quality liver grafts. Methods Twenty-four anaesthetized pigs were withdrawn from mechanical ventilation and allowed to arrest. After 60-minutes of warm ischemia to simulate a DCD procurement, livers were flushed with histidine-tryptophan-ketoglutarate (HTK) at 4˚C, 25˚C or 35˚C (n = 4 per group). For comparison, an adenosine-lidocaine crystalloid solution (AD), shown to have benefit at warm temperatures in heart perfusions, was also used (n = 4 per group). During 12-hours of NMP, adenosine triphosphate (ATP), lactate, transaminase levels, and histological injury were determined. Bile production and hemodynamics were monitored continuously. Results ATP levels recovered substantially following 1-hour of NMP reaching pre-ischemic levels by the end of NMP with no difference between groups. There was no difference in peak aspartate aminotransferase (AST) or in lactate dehydrogenase (LDH). Portal vein resistance was PLOS ONE |

Transplantation, 2018

Background. In current studies of ex situ liver perfusion there exists considerable variability i... more Background. In current studies of ex situ liver perfusion there exists considerable variability in perfusate composition, including the type of oxygen carrier. Herein, we aim to clarify the minimal hemoglobin level necessary during normothermic porcine ex situ liver perfusion. Methods. Livers procured from 35 to 45 kg domestic pigs were connected to our experimental ex situ circuit (n = 10). In the treatment group, perfusate was sequentially diluted hourly to predetermined hemoglobin levels. At the end of each hemoglobin dilution, perfusate samples were analyzed for liver transaminases, lactate dehydrogenase (LD), total bilirubin, and lactate levels. Liver oxygen consumption was measured. In the control group, livers were perfused continually for a duration of 24 hours at target hemoglobin levels of 30 and 20 g/L. Results. Rising liver transaminases, significantly higher lactate (P < 0.001), and LD levels (P < 0.001) were noted at lower perfusate hemoglobin levels in the treatment group. Liver oxygen utilization (P < 0.001) and hepatic artery oxygen delivery (P < 0.001) were significantly lower at lower hemoglobin levels, whereas liver vessel resistance remained relatively constant. Histology demonstrated increasing parenchymal damage at lower hemoglobin levels. In control livers, higher perfusate transaminases, higher lactate, and LD levels were noted at a perfusion hemoglobin level of 20 g/L. Conclusions. Ex situ liver function decompensated during perfusion between a mean hemoglobin level of 30 to 20 g/L, as evidenced by notably rising lactate and LD levels. This study demonstrates optimal hemoglobin concentration during normothermic ex situ liver perfusion to ensure a fully metabolically functioning graft.

Best Practice & Research Clinical Gastroenterology, 2003

The intestine has an inherent ability to adapt morphologically and functionally in response to in... more The intestine has an inherent ability to adapt morphologically and functionally in response to internal and external environmental changes. The functional adaptations encompass modifications of the brush border membrane fluidity and permeability, as well as up-or down-regulation of carrier-mediated transport. Intestinal adaptation improves the nutritional status following the loss of a major portion of the small intestine, following chronic ingestion of ethanol, following sublethal doses of abdominal irradiation, in diabetes, in pregnancy and lactation, with ageing, and with fasting and malnutrition. Following intestinal resection, morphological and functional changes occur depending upon the extent of the intestine removed, the site studied, and the lipid content of the diet. Therefore, intestinal adaptation has important implications in the survival potential and welfare of the host. An understanding of the mechanisms of, and signals for, intestinal adaptation in the experimental setting forms the basis for the use of management strategies in humans with the short-bowel syndrome.

PLOS ONE

Background Liver ischemia reperfusion injury (IRI) remains a challenge in liver transplantation. ... more Background Liver ischemia reperfusion injury (IRI) remains a challenge in liver transplantation. A number of compounds have previously demonstrated efficacy in mitigating IRI. Herein, we applied three specific additive strategies to a mouse IRI screening model to determine their relative potencies in reducing such injury, with a view to future testing in a large animal and clinical ex situ normothermic perfusion setting: 1) F573, a pan-caspase inhibitor, 2) anti-inflammatory anakinra and etanrecept and 3) BMX-001, a mimetic of superoxide dismutase. Methods A non-lethal liver ischemia model in mice was used. Additives in the treatment groups were given at fixed time points before induction of injury, compared to a vehicle group that received no therapeutic treatment. Mice were recovered for 6 hours following the ischemic insult, at which point blood and tissue samples were obtained. Plasma was processed for transaminase levels. Whole liver tissue samples were processed for histology, markers of apoptosis, oxidative stress, and cytokine levels. Results In an in vivo murine IRI model, the F573 treatment group demonstrated statistically lower alanine aminotransferase (ALT) levels (p = 0.01), less evidence of apoptosis (p = 0.03), and lower cytokine levels compared to vehicle. The etanercept with anakinra treatment group demonstrated significantly lower cytokine levels. The BMX-001 group demonstrated significantly decreased apoptosis (p = 0.01) evident on TUNEL staining. Conclusions The administration of pan-caspase inhibitor F573 in a murine in vivo model likely mitigates liver IRI based on decreased markers of cellular injury, decreased evidence of apoptosis, and improved cytokine profiles. Anakinra with etanercept, and BMX-001 did not demonstrate convincing efficacy at reducing IRI in this model, and likely need further optimization.

Biomedicines

Acute liver failure (ALF) is a rare but devastating disease associated with substantial morbidity... more Acute liver failure (ALF) is a rare but devastating disease associated with substantial morbidity and a mortality rate of almost 45%. Medical treatments, apart from supportive care, are limited and liver transplantation may be the only rescue option. Large animal models, which most closely represent human disease, can be logistically and technically cumbersome, expensive and pose ethical challenges. The development of isolated organ perfusion technologies, originally intended for preservation before transplantation, offers a new platform for experimental models of liver disease, such as ALF. In this study, female domestic swine underwent hepatectomy, followed by perfusion of the isolated liver on a normothermic machine perfusion device. Five control livers were perfused for 24 h at 37 °C, while receiving supplemental oxygen and nutrition. Six livers received toxic doses of acetaminophen given over 12 h, titrated to methemoglobin levels. Perfusate was sampled every 4 h for measuremen...

Arteriosclerosis, Thrombosis, and Vascular Biology, 2009

Objective— Impaired hepatic phosphatidylcholine (PC) synthesis lowers plasma lipids. We, therefor... more Objective— Impaired hepatic phosphatidylcholine (PC) synthesis lowers plasma lipids. We, therefore, tested the hypothesis that lack of phosphatidylethanolamine N-methyltransferase (PEMT), a hepatic enzyme catalyzing PC biosynthesis, attenuates the development of atherosclerosis. Methods and Results— Mice deficient in both PEMT and low-density lipoprotein receptors ( Pemt −/− /Ldlr −/− mice) were fed a high-fat/high-cholesterol diet for 16 weeks. Atherosclerotic lesion area was ≈80% lower ( P <0.01) in Pemt −/− /Ldlr −/− mice than in Pemt +/+ /Ldlr −/− mice, consistent with the atheroprotective plasma lipoprotein profile (ie, significant reduction in very low–density lipoprotein [VLDL]/intermediate-density lipoprotein/low-density lipoprotein–associated phospholipids [≈45%], triacylglycerols [≈65%], cholesterol [≈58%], and cholesteryl esters [≈68%]). Plasma apoB was decreased by 40% to 60%, whereas high-density lipoprotein levels were not altered. In addition, PEMT deficiency reduc...

Gene, 2022

●Background: Zinc finger C3H1 domain-containing protein (ZFC3H1) is differentially expressed betw... more ●Background: Zinc finger C3H1 domain-containing protein (ZFC3H1) is differentially expressed between primary tumor and the normal in most cancers. Additionally, a recent study has suggested that ZFC3H1 could serve as a novel marker for the prognosis of prostate adenocarcinoma (PRAD). However, the relationship between ZFC3H1 expression and the prognostic values in most tumors remains unclear. Our study is mainly for exploring the prognosis of ZFC3H1 in pan-cancer and for further discovering a potential therapeutics target. ●Methods: Based on the clinical big data, we performed a pan-cancer analysis of ZFC3H1, including gene expression, survival prognosis, genetic alteration, protein phosphorylation, immune infiltration and enrichment analysis. In addition, Real-Time PCR and Western Blot were used to further confirm the role of ZFC3H1 in the colorectal cancer. ●Results: We found that ZFC3H1 expression was connected with the prognosis of multiple malignant tumors. Furthermore, we also observed that ZFC3H1 was highly expressed in colorectal cancer through Real-Time PCR and Western Blot. The primary tumors presented higher phosphorylation level of the S655 site in lung adenocarcinoma, colon adenocarcinoma and uterine corpus endometrial carcinoma. ZFC3H1 expression was positively correlated with the immune infiltration of Cancer-associated fibroblasts (CAFs) in some tumors, such as liver hepatocellular carcinoma. And RNA surveillance pathways may be closely associated with the occurrence of tumors. ●Conclusions: Our study first reveals that ZFC3H1 could serve as a novel prognostic biomarker of pan-cancer, especially colorectal cancer.