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Long-term outcome of chronic hepatitis C patients with sustained virological response to peginterferon plus ribavirin

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World Journal of gastroenterology 2011年第4期17卷 493-498页

作者： maría Trapero-marugán Jorge Mendoza maría Chaparro Leticia gonzález-Moreno José Andrés Moreno-Monteagudo maría Jesús Borque Ricardo Moreno-Otero gastroenterology-Hepatology Department University Hospital La Princesa and Princesa Research Institute Autonomous University of Madrid and CIBERehd (Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas)

AIM: To assess the clinical, biochemical and virological long-term outcome in chronic hepatitis C (CHC) patients with a sustained virological response (SvR) after peginterferon (PEg-IFN) plus ribavirin combination therapy. METHODS: One hundred and fifty three patients with a SvR after treatment with PEg-IFN plus ribavirin were included in a 5-year follow-up study in a single Spanish center, based on standard clinical practice. Clinical anamnesis, biochemical analysis, hepatitis C virus RNA and alpha-fetoprotein measurement, ultrasonography and transient elastography were performed annually. RESULTS: The mean follow-up period of the 153 patients was 76 ± 13 mo after they obtained a SvR. Five patients (3.26%) presented with cirrhosis before treatment and 116 (75.8%) had genotype 1. No patient showed evidence of hepatic decompensation. One patient (0.65%) developed a hepatocellular carcinoma at month 30 after achieving SvR. There were no virological relapses during this follow-up period. Persistently elevated alanine aminotransferase was found in only one patient (0.65%). At the end of the 5-year follow-up, the mean value of transient elastography was 7 ± 4.3 kPa (F1). There were no deaths and no other tumors. CONCLUSION: The long-term outcome of 153 CHC patients with SvR to PEg-IFN plus ribavirin was good. No evidence of a virological relapse was seen. One patient (0.65%) developed a hepatocellular carcinoma.

关键词： Chronic hepatitis C Peginterferon Ribavirin Sustained virological response Long-term effects

Pathology handling of pancreatoduodenectomy specimens:Approaches and controversies

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World Journal of gastrointestinal Oncology 2014年第9期6卷 351-359页

作者： maría del Carmen gómez-Mateo Luis Sabater-Ortí Antonio Ferrández-Izquierdo Department of Pathology Hospital Universitario Donostia Department of general and gastroenterological Surgery Hospital Clínico ValenciaUniversity of Valencia Department of Pathology Hospital Clínico ValenciaUniversity of Valencia

Pancreatic cancer,with a 5% 5-year survival rate,is the fourth leading cause of cancer death in Western ***,only 20% of all patients benefit from surgical *** need to prolong survival has prompted pathologists to develop improved protocols to evaluate pancreatic specimens and their surgical ***,the new protocols will provide clinicians with more powerful prognostic indicators and accurate information to guide their therapeutic *** the availability of several guidelines for the handling and pathology reporting of duodenopancreatectomy specimens and their continual updating by expert pathologists,there is no consensus on basic issues such as surgical margins or the definition of incomplete excision(R1) of pancreatic ductal *** article reviews the problems and controversies that dealing with duodenopancreatectomy specimens pose to pathologists,the various terms used to define resection margins or infiltration,and *** reviewing the literature,including previous guidelines and based on our own experience,we present our protocol for the pathology handling of duodenopancreatectomy specimens.

关键词： Pancreatic ductal adenocarcinoma Duodenopancreatectomy specimens Resection margins Pathology protocols

Effect of Hardfaced Interlayer Thickness and Low Hydrogen Ferritic Capping on Ballistic Performance of Shielded Metal Arc Welded Armour Steel Joints

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Journal of Iron and Steel Research International 2013年第12期20卷 82-91页

作者： M Balakrishnan v Balasubramanian g Madhusudhan Reddy Center for Materials Joining and Research(CEMAJOR) Department of Manufacturing EngineeringAnnamalai University Solidification Technology Division Metal Joining GroupDefense Metallurgical Research Laboratory(DMRL)

Armour grade quenched and tempered steel closely confirming to AISI 4340 is well known for its superior ballistic performance and hence used in the fabrication of combat vehicles. The traditional fillers like austenitic stain- less steel showed poor ballistic performance of these welded joints as compared to the base metal. Attempts have been made to deposit hardfaced interlayer between austenitic stainless steel weld metals. Though this method, mar-- ginal improvements in ballistic performance can be yielded, and cracks were observed in between base metal and hardfaced layer. Thickness of the hardfaced interlayer plays a vital role for the effective ballistic performance. Thus, an attempt has been made to investigate the effect of hardfaced interlayer thickness on ballistic performance of ar- mour steel welds. The results of effect of buttering, low hydrogen ferritic （LHF） filler and three different hardfaced layer thicknesses （4, 5.5 and 7 ram） on ballistid performance of shielded metal arc welded armour steel joints were g.v.n.

关键词： armour steel low hydrogen ferritic electrode sandwich structure ballistic performance hardfacing metallography

Is interferon-beta an alternative treatment for chronic hepatitis C?

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World Journal of gastroenterology 2006年第17期12卷 2730-2736页

作者： Ricardo Moreno-Otero maría Trapero-marugán Elena gómez-Domínguez Luisa garcía-Buey JoséA Moreno-Monteagudo Unit of Hepatology Hospital Universitario de La Princesa Universidad Autónoma de MadridSpain

The treatment of chronic hepatitis C （CHC） is still far from optimal, particularly for those subpopulations that do not respond to the standard combination therapy with Interferon-α （IFNα） plus ribavirin. Although in some cases the use of higher doses or longer treatment periods may be effective, these approaches are generally associated with a higher incidence of adverse events, which may either lead to a reduction in patient compliance or require drug withdrawal. IFNβ could represent an interesting alternative for treating CHC patients. Controversial data about IFNβ efficacy in CHC exist, the main reason being that many results stem from pilot studies with small cohorts of patients. However, promising results have been obtained in some subgroups of patients that fail to respond to IFNα. Additionally, the good tolerability of IFNβ represents an important advantage of the drug. The rates of dropouts in controlled clinical trials, as well as the need for dose reductions or treatment discontinuation are very low. It might be worth assessing the value of IFNβ plus ribavirin in randomized studies with a larger cohort of patients, not eligible or not tolerating standard therapy, and for non-responders.

关键词： Hepatitis C Hepatitis C virus Interferon beta Ribavirin

Reactivation of hepatitis B virus infection after cytotoxic chemotherapy or immunosuppressive therapy

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World Journal of gastroenterology 2011年第12期17卷 1531-1537页

作者： maría Luisa Manzano-Alonso gregorio Castellano-Tortajada Department of gastroenterology Hospital 12 de OctubreAv Andalucia28041 MadridSpain

Reactivation of hepatitis B is defined as the recurrence or an abrupt rise in hepatitis B virus(HBv) replication,often accompanied by an increase in serum transaminase levels,and both events occurring in a patient with a previous inactive hepatitis B *** reactivation can occur in situations in which the ratio of HBv replication and immune response is *** can happen during the treatment of hemato-oncological malignancies with chemotherapy and in immunosuppression of autoimmune *** manifestations of hepatitis B reactivation are variable and can range from asymptomatic to acute hepatitis,which are sometimes serious and result in acute liver failure with risk of death,and usually occur in the periods between cycles or at the end of *** drugs such as corticosteroids or azathioprine can induce HBv reactivation in patients carrying hepatitis B virus surface antigen(HBsAg) or anti-HBc,but much less frequently than chemotherapy *** tumor necrosis factorαinhibitors infliximab,etanercept and adalimumab may cause reactivation of hepatitis B,and the overall frequency with infliximab may be similar(50%-66%) to that caused by *** HBv serology is recommended for all patients receiving chemotherapy and immunosuppressive drugs,and HBsAg positive patients should receive anti-HBv prophylaxis to decrease virus reactivation and death rates.

关键词： Hepatitis B Immune response Immunosuppression Reactivation

Adalimumab-induced interstitial pneumonia in a patient with Crohn's disease

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World Journal of gastroenterology 2015年第7期21卷 2260-2262页

作者： maría José Casanova maría Chaparro Claudia valenzuela Carolina Cisneros Javier P gisbert gastroenterology Department Hospital Universitario de La Princesa Instituto de Investigación Sanitaria Princesa (IIS-IP) Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) Pneumology Department Hospital Universitario de La Princesa

There are several reports of anti-tumor necrosis factor(TNF)-induced lung disease,especially in patients with rheumatologic *** is an antiTNF drug used to induce and maintain remission in patients with immune-mediated diseases,such as Crohn’s *** pulmonary disorders could be an extra-intestinal manifestation of inflammatory bowel disease,biologic therapy could also be a cause of lung *** few cases of adalimumab-induced lung toxicity have been reported,and the majority of them were in patients with rheumatologic *** injury secondary to anti-TNF therapy should,after ruling out other etiologies,be considered in patients who have a temporal association between the onset of respiratory symptoms and the exposure to these drugs.A compatible pattern in the biopsy and the clinical improvement after discontinuation of the anti-TNF drug would strongly support the diagnosis.

关键词： Adalimumab Anti-tumor necrosis factor Crohn’s dise

Effect of dichloromethylene diphosphonate on liver regeneration following thioacetamide-induced necrosis in rats

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World Journal of Hepatology 2013年第7期5卷 379-386页

作者： Mirandeli Bautista maría ngeles gómez del Rio Juana Benedí maría Isabel Sánchez-Reus José A Morales-gonzález Ana maría Téllez-López maricela López-Orozco rea Académica de Farmacia Instituto de Ciencias de la Salud Universidad Autónoma del Estado de Hidalgo Departamento de Bioquímica y Biología Molecular Facultad de Farmacia Ciudad Universitaria Departamento de Farmacología Facultad de Farmacia Ciudad Universitaria Escuela Superior de Medicina Instituto Politécnico Nacional

AIM: To study the effect of dichloromethylene diphos-phonate (DMDP), a selective kupffer cell toxicant in reference to liver damage and postnecrotic liver regeneration in rats induced by sublethal dose thioacetamide (TA). METHODS: Rats, intravenously (iv ) pre-treated with a single dose of DMDP (10 mg/kg), were intraperitoneally (ip ) injected with TA 6.6 mmol/kg (per 500 mg/kg body weight). Hepatocytes were isolated from rats at 0, 24, 48 and 72 h following TA intoxication and blood and liver samples were obtained. To evaluate the mecha-nisms involved in the postnecrotic regenerative state, DNA distribution and ploidy time course were assayed in isolated hepatocytes. Circulating cytokine tumor necrosis factor-alpha (TNF-α) was assayed in serum and determined by reverse transcriptase-polymerase chain reaction in liver extract. RESULTS: The effect of DMDP induced noticeable changes in postnecrotic regeneration, causing an increased percentage of hepatocytes in the cell cycle S phase. The increase at 24 h in S1 population in rats pretreated with DMDP + TA was significantly (P group (18.07% vs 8.57%). Hepatocytes increased their proliferation as a result of these changes. Also, TNF-α expression and serum level were increased in rats pre-treated with DMDP. Thus, DMDP pre-treatment reduced TA-induced liver injury and accelerated postnecrotic liver regeneration. CONCLUSION: These results demonstrate that kupffer cells are involved in TA-induced liver, as well as in post-necrotic proliferative liver states.

关键词： Dichloromethylene diphosphonate kupffer cells Thioacetamide Hepatotoxicity Cell cycle

MicroRNAs contribute to ATP-binding cassette transporter-and autophagy-mediated chemoresistance in hepatocellular carcinoma

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World Journal of Hepatology 2019年第4期11卷 344-358页

作者： maría v Espelt maría L Bacigalupo Pablo Carabias maría F Troncoso Facultad de Farmacia y Bioquímica Instituto de Química y Fisicoquímica Biológicas Consejo Nacional de Investigaciones Científicas y Técnicas Universidad de Buenos Aires

Hepatocellular carcinoma(HCC) has an elevated mortality rate, largely because of high recurrence and metastasis. Additionally, the main obstacle during treatment of HCC is that patients usually develop resistance to *** drug resistance involves many different mechanisms, including alterations in drug metabolism and processing, impairment of the apoptotic machine, activation of cell survival signaling, decreased drug sensitivity and autophagy, among others. Nowadays, miRNAs are emerging as master regulators of normal physiology-and tumor-related gene expression. In HCC,aberrant expression of many miRNAs leads to chemoresistance. Herein, we particularly analyzed miRNA impact on HCC resistance to drug therapy. Certain miRNAs target ABC(ATP-binding cassette) transporter genes. As most of these miRNAs are downregulated in HCC, transporter levels increase and intracellular drug accumulation decrease, turning cells less sensitive to death. Others miRNAs target autophagy-related gene expression, inhibiting autophagy and acting as tumor suppressors. Nevertheless, due to its downregulation in HCC, these miRNAs do not inhibit autophagy or tumor growth and, resistance is ***, modulation of ABC transporter and/or autophagy-related gene expression or function by miRNAs could be determinant for HCC cell survival under chemotherapeutic drug treatment. Undoubtedly, more insights on the biological processes, signaling pathways and/or molecular mechanisms regulated by miRNAs are needed. Anyway, miRNA-based therapy together with conventional chemotherapeutic drugs has a great future in cancer therapy.

关键词： Hepatocellular carcinoma Chemoresistance ABC transporter Autophagy miRNA

Intestinal Ca2+ absorption revisited: A molecular and clinical approach

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World Journal of gastroenterology 2020年第24期26卷 3344-3364页

作者： vanessa A Areco Romina kohan germán Talamoni Nori g Tolosa de Talamoni maría E Peralta López Laboratorio“Dr.Fernando Canas” Cátedra de Bioquímica y Biología MolecularFacultad de Ciencias MédicasINICSA(CONICET-Universidad Nacional de Córdoba)Córdoba 5000Argentina

Ca2+has an important role in the maintenance of the skeleton and is involved in the main physiological *** homeostasis is controlled by the intestine,kidney,bone and parathyroid *** intestinal Ca2+absorption occurs mainly via the paracellular and the transcellular *** proteins involved in both ways are regulated by calcitriol and other hormones as well as dietary *** growth factor 23(FgF-23)is a strong antagonist of vitamin D *** of the intestinal Ca2+movement seems to be vitamin D *** Ca2+absorption changes according to different physiological *** is promoted under high Ca2+demands such as growth,pregnancy,lactation,dietary Ca2+deficiency and high physical *** contrast,the intestinal Ca2+transport decreases with *** stress inhibits the intestinal Ca2+absorption whereas the antioxidants counteract the effects of prooxidants leading to the normalization of this physiological *** pathologies such as celiac disease,inflammatory bowel diseases,Turner syndrome and others occur with inhibition of intestinal Ca2+absorption,some hypercalciurias show Ca2+hyperabsorption,most of these alterations are related to the vitamin D endocrine *** research work should be accomplished in order not only to know more molecular details but also to detect possible therapeutic targets to ameliorate or avoid the consequences of altered intestinal Ca2+absorption.

关键词： Ca2+absorption Transcellular pathway Paracellular pathway Hormones Dietary calcium Physiological conditions Pathological alterations