Acute liver failure: Management update and prognosis.

Acute liver failure is a rare but serious syndrome, with an incidence of approximately 2,000 to 3,000 cases per year in North America. Its pathophysiology and clinical course vary, depending on the cause of the primary liver injury, and can lead to high morbidity and mortality or the need for liver transplantation, despite available therapies. This syndrome involves excessive activation of the immune system, with damage in other organs, contributing to its high mortality rate. The most accepted definition includes liver injury with hepatic encephalopathy and coagulopathy within the past 26 weeks in a patient with no previous liver disease. The main causes are paracetamol poisoning, viral hepatitis, and drug-induced liver injury, among others. Identifying the cause is crucial, given that it influences prognosis and treatment. Survival has improved with supportive measures, intensive therapy, complication prevention, and the use of medications, such as N-acetylcysteine. Liver transplantation is a curative option for nonresponders to medical treatment, but adequate evaluation of transplantation timing is vital for improving results. Factors such as patient age, underlying cause, and severity of organ failure influence the post-transplant outcomes and survival.

Hepatitis C virus-positive donors in HCV-negative recipients in liver transplantation: Is it possible in Mexico?

Hepatitis C virus (HCV) infection is a worldwide public health problem associated with significant morbidity and mortality. In the context of liver transplantation, the demand for organs continues to exceed the supply, prompting the consideration of using organs from HCV-positive donors in HCV-negative recipients. The introduction of direct-acting antivirals (DAAs), which have demonstrated great efficacy in eradicating the virus, has made transplantation of organs from donors with HCV infection possible. The present article provides a brief review of the current evidence on the use of organs from HCV-infected patients.

The dynamics of arsenic and copper in solid and aqueous phases in reactive confluences receiving acid drainage: The role of turbidity and particle size.

The fate of suspended solids in aqueous systems enriched with copper (Cu) and arsenic (As) is still poorly understood, especially in mildly acidic streams with natural turbidity. This study integrated field, laboratory, and modeling to determine how turbidity, particle size distribution, and the partition of Cu and As interact in two model river confluences in an Andean watershed (upper Elqui, North-Central Chile). The mildly acidic Toro River (40.4 mgL-1; CuTOTAL>8 mgL-1) was diluted and neutralized at two consecutive confluences, resulting in dissolved As and Cu lower than 0.04 and 0.1 mgL-1, respectively. On-site laser scattering measurements showed that the size of suspended sediments was dominated by ultrafine (d<6 µm) and fine (6200 µm) were not observed, contrasting with other reactive Andean confluences that work as natural coagulation-flocculation reactors. Laboratory mixing experiments with filtered endmembers followed closely the trends observed in the field measurements. SEM observations and thermodynamic calculations, suggested that As-rich amorphous Fe minerals dominated the fine suspended solid inflow (d<15 µm) from the Toro River, while XRD did not reveal significant amounts of crystalline forms of Fe, As, or Cu minerals. Despite fresh precipitates that further associated dissolved As and Cu, the particles from the Toro River grew only slightly after the confluences, thus limiting particle settling potential and a significant metal-(loid)s removal. Consequently, the seasonal variation in the size and chemical nature of suspended solids in acid drainage inflows control the distinct physical and chemical fates of As and Cu after neutralization, as well as hydrodynamic or hydraulic conditions likely also constrain sediment deposition. The combined monitoring of chemical parameters and particle size distributions is a simple and cost-effective method to obtain information about the behavior of metal(loid)s and sediments.

Guillain-Barré syndrome associated with SARS-CoV-2 infection: A case series from 4 Colombian cities during the pandemic.

SARS-CoV-2 infection has been associated with multiple neurological manifestations. One such manifestation, which has been described since the early stages of the COVID-19 pandemic and is relevant for current neurological practice, is Guillain-Barré syndrome (GBS). The literature describes neurotoxic mechanisms of the virus itself and the possible pathways by which it may affect the peripheral nerves in experimental studies; however, we still lack information on the mechanisms causing the immune response that gives rise to GBS in the context of SARS-CoV-2 infection. Colombia is one of the Latin American countries worst affected by the pandemic, with the third-highest number of cases in the region; thus, it is essential to recognise GBS, as this potential postinfectious complication may severely compromise the patient's functional status in the absence of timely diagnosis and treatment. We present a series of 12 cases of GBS associated with SARS-CoV-2 infection from hospitals in 4 different Colombian cities and describe the clinical presentation, laboratory and electrophysiological study findings, and treatment.

En el año 2020 se declaro la pandemia ocasionada por la infección por el virus SARSCoV-2, virus de la familia del coronavirus, adoptándose el nombre de COVID-19 a la enfermedad 1. En Bogotá, Colombia, se confirmó el primer caso de COVID-19 el 6 de marzo de 2020 (2). Los principales síntomas reportados en la infección por SARSCoV-2 son fiebre (43.8% en la admisión y 88.7% durante la hospitalización) y tos (67.8%) (3). Otros síntomas encontrados son fatiga (38.1%), producción de esputo (33.7%) y cefalea (13.6%). Los principales signos neurológicos reportados en los pacientes con infección severa por SARS-Cov-2 son agitación (69%), compromiso en tracto corticoespinal (67%) y delirium (65%) (4). Las principales complicaciones neurológicas descritas asociadas a Covid 19 son: anosmia, disgeusia, encefalopatia, Síndrome de Guillain Barre, complicaciones cerebrovasculares y daño en musculo esquelético (5­8).En el presente articulo se presenta una serie de casos de pacientes con síndrome de Guillain-Barré asociado a infección por SARS-CoV-2. Se recolectaron casos de diferentes instituciones medicas de Colombia.

Use of healthcare REsources and associated COsts in controlled versus uncontrolled carcinoid SYndrome in patients with neuroendocrine tumours: the RECOSY study.

PURPOSE: To report healthcare resource use and associated costs in controlled versus uncontrolled carcinoid syndrome (CS) in patients with neuroendocrine tumours. METHODS: A cross-sectional, non-interventional multicentre study was conducted with retrospective data analysis. Resource use was compared between two patient groups: those with controlled CS (> 12 months with no uncontrolled CS episodes) and uncontrolled CS (< 12 months since last uncontrolled episode). Patients were matched for age, sex, and origin and grade of tumour. When no matching patients were available, data from deceased patients were used. Information on healthcare resource use came from review of medical records, patient history and physician reports. Working capacity was assessed using the Work Productivity and Activity Impairment General Health questionnaire. RESULTS: Twenty-six university hospitals in Spain participated, between July 2017 and April 2018. 137 patients were enrolled; 104 were analysed (2 groups of 52). Patients with uncontrolled CS had 10 times more emergency department (ED) visits (mean 1.0 vs 0.10 visits; P = 0.0167), were more likely to have a hospital admission (40.4% vs 19.2%; P = 0.0116) and had longer hospital stays (mean 7.87 vs 2.10 days; P = 0.0178) than those with controlled CS. This corresponded to higher annual hospitalisation costs (mean €5511.59 vs €1457.22; P = 0.028) and ED costs (€161.25 vs €14.85; P = 0.0236). The mean annual total healthcare costs were 60.0% higher in patients with uncontrolled than controlled CS (P = NS). CONCLUSION: This study quantifies higher health resource use, and higher hospitalisation and ED costs in patients with uncontrolled CS. Better control of CS may result 3in lower medical costs.

Medical education from the point of view of medical students: Results from four participatory Delphi panels in Quito, Ecuador.

BACKGROUND: Medical curricula have historically been designed in a top-down approach, usually excluding students. While Delphi panels have been used as a tool for medical education curricula design, none have been conducted in Ecuador. In addition, no such approach has ever included students both as panelists and researchers. MATERIAL AND METHODS: Four Delphi panels were developed and conducted using a participatory approach that allowed medical students to take part both as expert panelists and researchers: specifically, students developed the questionnaire and conducted a qualitative synthesis. Questionnaire responses were anonymized and dispatched online to panelists. The information was organized and collected to develop the qualitative syntheses and prepare the final statements. RESULTS: Thirty-two medical students participated between February and May 2018. A total of 32 questions were developed, corresponding to five different categories. For some questions, consensus was reached; for other questions, general statements were obtained.Discussion and conclusion: Developing the questionnaire, responding to it and analyzing the answers allowed students to raise significant concerns regarding medical education topics proposing relevant policy and curricula change. Participatory Delphi panels can be an efficient tool to obtain organized feedback, improve student class involvement, and promote research skills.

NaStEP, an essential protein for self-incompatibility in Nicotiana, performs a dual activity as a proteinase inhibitor and as a voltage-dependent channel blocker.

The S-specific pollen rejection response in Nicotiana depends on the interaction between S-RNase and a suite of SLF proteins. However, the biochemical pathway requires other essential proteins. One of them is the stigmatic protein NaStEP, which belongs to the Kunitz-type protease inhibitor family. Within the pollen tubes, NaStEP is a positive regulator of HT-B stability, likely inhibiting its degradation and, additionally, interacts with NaSIPP, a mitochondrial phosphate carrier. To gain a deeper understanding of the biochemical role of NaStEP in pollen rejection, we evaluated whether the activity of NaStEP as protease inhibitor is specific to a particular type of protease and whether it has the function of a voltage-dependent channel (VDC) blocker. Our findings indicate that, in vitro, NaStEP inhibits a subtilisin-like protease in an irreversible manner, but not other proteases, such as thermolysin and papain. Furthermore, we found that subtilisin processes the native NaStEP (24 kDa) into two lower molecular weight peptides of 21 and 14 kDa. Moreover, when we incubated NaStEP along with Xenopus leavis oocytes expressing the voltage-dependent potassium channel Kv 1.3, the current was blocked, indicating that NaStEP acts as a VDC blocker. These data allow us to propose NaStEP acts as a key molecule with two functions, one protecting HT-B from degradation by inhibiting a subtilisin-like protease and the second one by forming a complex with a mitochondrial VDC that could destabilize the mitochondria to trigger cell death, which would reinforce S-specific pollen rejection in Nicotiana.

[Neuroethics of body transplantation]. / Neuroetica del trasplante de cuerpo.

INTRODUCTION: Recent contributions to the specialised literature address the topic of body transplantation, mostly produced by Sergio Canavero and a group of researchers from China. For several years they have been announcing that they will carry out the procedure, but it has still not been performed. AIMS: The aim of this study is to perform a neuroethical analysis of body transplantation, based on the methodology of Diego Gracia on ethics and bioethics and an analysis of facts, values and duties. Furthermore, we also propose that, with the knowledge available today, body transplantation must be addressed from the perspective of research ethics. DEVELOPMENT: As regards the facts, it can be said that, although the history of attempts to perform a body transplant dates back almost a century, there are many limitations preventing it from being performed with our current knowledge. This is due to the fact that no serious and rigorous preclinical research has been conducted (at most some anecdotal data can be found). With the data that is available, it does not even seem possible to think of designing a protocol to include human beings for body transplantation. In terms of values, according to the model developed by Emanuel, who proposes eight requirements that must be met to comply with the ethics of clinical research, it is not even possible to comply with one of them. Regarding duties, it would be wise to recommend that such a procedure should not be carried out on humans. CONCLUSIONS: Considering the scientific knowledge currently available and the values of research ethics, a body transplantation should not be performed in human beings either as clinical research or as clinical practice.

TITLE: Neuroetica del trasplante de cuerpo.Introduccion. Existe bibliografia reciente en revistas especializadas acerca del trasplante de cuerpo, generada fundamentalmente por Sergio Canavero y un grupo chino. Desde hace un par de años vienen anunciando que realizaran el procedimiento, pero aun no ha ocurrido. Objetivo. Realizar un analisis neuroetico sobre el trasplante de cuerpo, proponiendo la metodologia de Diego Gracia en etica y bioetica analizando hechos, valores y deberes. Se propone ademas que, con el conocimiento actual, el trasplante de cuerpo debe tratarse desde la etica de la investigacion. Desarrollo. Aunque desde hace casi un siglo hay antecedentes de intentar conseguir un trasplante de cuerpo, existen numerosas limitaciones para poder realizarlo con el conocimiento actual porque no hay investigacion preclinica seria y rigurosa (se encuentran a lo sumo datos anecdoticos). Con los datos disponibles, ni siquiera parece que pueda pensarse en el diseño de un protocolo de inclusion de seres humanos para el trasplante de cuerpo. En cuanto a valores, atendiendo al modelo de Emanuel, quien propone ocho requisitos para cumplir con la etica de la investigacion clinica, no es posible siquiera cumplir uno cabalmente. Lo mas prudente es recomendar que no debe realizarse un procedimiento asi en seres humanos. Conclusiones. Considerando el conocimiento cientifico disponible y los valores de la etica de la investigacion, no debe realizarse un trasplante de cuerpo en seres humanos, ni como investigacion clinica ni mucho menos como practica clinica.

Hyperglycemia exacerbates colon cancer malignancy through hexosamine biosynthetic pathway.

Hyperglycemia is a common feature of diabetes mellitus, considered as a risk factor for cancer. However, its direct effects in cancer cell behavior are relatively unexplored. Herein we show that high glucose concentration induces aberrant glycosylation, increased cell proliferation, invasion and tumor progression of colon cancer. By modulating the activity of the rate-limiting enzyme, glutamine-fructose-6-phosphate amidotransferase (GFAT), we demonstrate that hexosamine biosynthetic pathway (HBP) is involved in those processes. Biopsies from patients with colon carcinoma show increased levels of GFAT and consequently aberrant glycans' expression suggesting an increase of HBP flow in human colon cancer. All together, our results open the possibility that HBP links hyperglycemia, aberrant glycosylation and tumor malignancy, and suggest this pathway as a potential therapeutic target for colorectal cancer.

Uncommon disturbance of root development after tooth replantation: five-year follow-up period case report / Trastorno del desarrollo radicular poco frecuente posterior a reimplante dentario: reporte de caso con 5 años de seguimiento

To present an uncommon disturbance of root development with ingrowth of bone and periodontal tissue into the pulp space in a delayed replanted immature permanent incisor at five years of follow-up. Severe arrest of root formation with uncommon healing of an immature permanent maxillary incisor after delayed replantation is reported. Continued development of a tooth root separate from the body of the tooth was not observed. A 6-year-old girl sustained an avulsion injury to her upper left central permanent incisor. The tooth was replanted and splinted 2 hours after the accident. Patient has been monitored clinically and with radiography for 5 years. The periodontal tissues presented good healing without replacement resorption. However, severe arrest of root formation with development of hard-like tissue and internal periodontal ligament inside the pulp canal have been observed. Despite being a delayed tooth replantation, the patient has been asymptomatic, and has maintained alveolar bone volume. Clinicians must be vigilant and monitor traumatized immature teeth closely.

El objetivo de este trabajo fue presentar una alteración poco frecuente del desarrollo de la raíz con el crecimiento del tejido óseo y periodontal en el espacio pulpar en un incisivo permanente inmaduro reimplantado de manera tardía, a los cinco años de seguimiento.Se observó una suspensión severa de la formación de raíces con cicatrización poco común, de un incisivo maxilar permanente inmaduro después de una reimplantación tardía. No se observó el desarrollo continuo de la raíz dentaria separada del diente. Una niña de 6 años de edad sufrió una lesión por avulsión en su incisivo central superior izquierdo. El diente fue replantado dos horas después del accidente. La paciente ha sido monitoreada clínicamente y con exámenes radiológicos durante 5 años. Los tejidos periodontales presentaron buena cicatrización sin reabsorción de reemplazo. Sin embargo, se ha observado una detención severa de la formación de las raíces, con desarrollo de tejido duro y ligamento periodontal interno dentro del canal pulpar. A pesar de ser una reimplantación tardía del diente, la paciente presenta asintomática, y ha mantenido el volumen del hueso alveolar. Los médicos deben estar atentos y mantener en observación los dientes inmaduros traumatizados.

Long-term evaluation and clinical outcomes of children with dental transplants in Temuco city, Chile.

AIM: To assess the clinical and radiographic outcomes of 36 transplanted teeth and the possible factors affecting the results. MATERIALS AND METHODS: In 26 children, 36 teeth transplants were performed. The main reason for transplantations was the loss of anterior teeth due to trauma; 80.5% of transplanted teeth were immature bicuspids. The transplants were clinically and radiolographycally monitored in respect of pulp vitality, root canal obliteration, periradicular changes and root formation. Fisher Exact Test and Kaplan-Meier analyses were performed to determine the association between the variables and estimation of survival rates, respectively. RESULTS: Thirty (83.3%) of the transplantations were recorded as successful and six as unsuccessful (16.7%). The survival rate was 97.2% during average time of 47.5 months ± 27.8 SD. Only one tooth had been extracted and 5 had survived in not ideal conditions. The majority of immature transplanted teeth developed pulp canal obliteration. CONCLUSION: Factors associated to successful outcome were immature root formation of donor tooth and short flexible splinting period. The main factor associated to failure was replacement resorption. The surgical technique did not present statistical significance in the clinical outcome. Tooth transplantation has shown high success and survival rates, and should be considered as a real option in growing patients.

Antimicrobial activity of synthetic bornyl benzoates against Trypanosoma cruzi.

We report here for the first time the in vitro effects of (1S,2R,4S)-1,7,7-trimethyl-bicyclo[2·2·1]heptan-2-yl-3',4',5'-trimethoxy benzoate (1) and (1S,2R,4S)-1,7,7-trimethyl-bicyclo[2·2·1]heptan-2-yl benzoate (2) on the growth and ultrastructure of Trypanosoma cruzi. These two synthetic compounds exerted an antiproliferative effect on the epimastigote forms of the parasite. The ICs(50/72h) of two synthetic L-bornyl benzoates, 1 and 2, was 10·1 and 12·8 µg/ml, respectively. Both compounds were more selective against epimastigotes than HEp-2 cells. Ultrastructural analysis revealed intense cytoplasmic vacuolization and the appearance of cytoplasmic materials surrounded by membranes. The treatment of peritoneal macrophages with compounds 1 and 2 caused a significant decrease in the number of T. cruzi-infected cells. L-Bornyl benzoate derivatives may serve as a potential source for the development of more effective and safer chemotherapeutic agents against T. cruzi infections.

Effects of (-) mammea A/BB isolated from Calophyllum brasiliense leaves and derivatives on mitochondrial membrane of Leishmania amazonensis.

We have previously demonstrated antileishmanial activity on Leishmania amazonensis of the natural (1-2), synthetic (7) and derivatives of coumarin (-) mammea A/BB (3-6) isolated from the dichloromethane extract of Calophyllum brasiliense leaves. The aim of the present study was to evaluate morphological and ultrastructural alterations in Leishmania amazonensis induced by these compounds. In promastigote forms, all seven compounds produced significant morphological and ultrastructural alterations, as revealed by scanning and transmission electron microscopy. The compound 5,7-dihydroxy-8-(2-methylbutanoyl)-6-(3-methylbutyl)-4-phenyl-chroman-2-one (3), the most active antileishmanial with LD50 of 0.9 µM), induced cell shrinkage and a rounded appearance of the cells. Parasites incubated in the presence of compound (3) showed ultrastructural changes, such as the appearance of mitochondrial swelling with a reduction in the density of the mitochondrial matrix and the presence of vesicles inside the mitochondrion, indicating damage and significant change in this organelle; abnormal chromatin condensation, alterations in the nuclear envelope, intense atypical cytoplasmic vacuolization, and the appearance of autophagic vacuoles were also observed. In addition, the compound (3) may be acting to depolarize the mitochondrial membrane potential of the cells, leading to death of the parasite.

Giardia disrupts the arrangement of tight, adherens and desmosomal junction proteins of intestinal cells.

Giardia duodenalis is a parasitic protozoan that causes diarrhea and other symptoms which together constitute a disease known as giardiasis. Although the disease has been well defined, the mechanisms involving the establishment of the infection have not yet been fully elucidated. In this study, we show that after 24h of interaction between parasites and intestinal Caco-2 cells, there was an alteration of the paracellular permeability, as observed by an approximate 42% of reduction in the transepithelial electrical resistance and permeation to ruthenium red, which was concomitant with ultrastructural changes. Nevertheless, epithelium viability was not affected. We also demonstrate that there was no change in expression of junctional proteins (tight and adherens) but that the distribution of these proteins in Caco-2 cells after parasite adhesion was significantly altered, as observed via laser scanning confocal microscopy 3D reconstruction. The present work shows that adhesion of Giardia duodenalis trophozoites to intestinal cells in vitro induces disturbances of the tight, adherens and desmosomal junctions.

Effects of serine protease inhibitors on viability and morphology of Leishmania (Leishmania) amazonensis promastigotes.

To investigate the importance of serine proteases in Leishmania amazonensis promastigotes, we analyzed the effects of classical serine protease inhibitors and a Kunitz-type inhibitor, obtained from sea anemone Stichodactyla helianthus (ShPI-I), on the viability and morphology of parasites in culture. Classical inhibitors were selected on the basis of their ability to inhibit L. amazonensis serine proteases, previously described. The N-tosyl-L: -phenylalanine chloromethyl ketone (TPCK) and benzamidine (Bza) inhibitors, which are potential Leishmania proteases inhibitors, in all experimental conditions reduced the parasite viability, with regard to time dependence. On the other hand, N-tosyl-lysine chloromethyl ketone (TLCK) did not significantly affect the parasite viability, as it was poor Leishmania enzymes inhibitor. Ultrastructural analysis demonstrated that both Bza and TPCK induced changes in the flagellar pocket region with membrane alteration, including bleb formation. However, TPCK effects were more pronounced than those of Bza in Leishmania flagellar pocket in plasma membrane, and intracellular vesicular bodies was visualized. ShPI-I proved to be a powerful inhibitor of L. amazonensis serine proteases and the parasite viability. The ultrastructural alterations caused by ShPI-I were more dramatic than those induced by the classical inhibitors. Vesiculation of the flagellar pocket membrane, the appearance of a cytoplasmic vesicle that resembles an autophagic vacuole, and alterations of promastigotes shape resulted.

Golgi complex disassembly caused by light-activated calphostin C involves MAPK and PKA.

We examined the participation of MAPK and PKA in the Golgi complex disassembly caused by light-activated Calphostin C in HT-29 cells. When these cells were incubated with Calphostin C, fragmentation and dispersal of the Golgi complex was observed as assessed by immunofluorescence microscopy. Electron microscopy analysis showed that clusters of vesicles and large tubule-vesicular membrane structures, resembling the Golgi remnants present in mitotic cells, substituted the Golgi stacks. In addition, Calphostin C treatment caused inhibition of the endocytic route. We confirmed that the Golgi disassembly was not due to PKC inhibition, and suggested, based on the use of specific inhibitors, that other kinases are involved. It was shown that pretreatment with PD98059 and H-89, both inhibitors of MAPK and PKA, respectively, prior to incubation with Calphostin C, caused blockade of the Golgi disassembly, as well as the inhibition of the endocytic pathway caused by this drug. This finding supports the existence of a novel mechanism by which MAPK and PKA may regulate the Golgi breakdown caused by Calphostin C in HT-29 cells.

[An exploratory study regarding the hypothetical human embryo donation in Chile]. / Un estudio exploratorio sobre la donación hipotética de embriones humanos en Chile.

OBJECTIVE: To explore opinions of patients who undergone to complex ART towards gamete and embryo donation, as well as the reasons to do it or not. PATIENTS AND METHODS: The seat was the Hospital Clínico de la Universidad de Chile. There were interviewed ten participants (seven women, three men), who had undergone at least to one ART, without comprising of donation programs. It was a cross-sectional study of descriptive bioethics, done with ethnographic qualitative methodology with a semistructured interview applying speech analysis to the resulting text. RESULTS: Regarding embryo donation, six participants would accept to donate them, five to fertility therapy and one to research. Regarding the cryopreservation, three participants would always accept it, and three with some restrictions, just one on them would rather to discard instead of donating a cryopreserved embryo. DISCUSSION: It could be suggested: gamete donation is more commented and generally accepted; embryo donation is a more conflicting and less discussed subject, as much to donate as to accept; cryopreservation is a complex subject, commented but also conflicting, whose acceptance or not, as well as the destiny of the probably cryopreserved embryos, depends on the believes that participants have about the origin of the life, personal ethics, and the religion. It could be possible to say that a hypothesis constructed in this study (to be verified in future quantitative researches) is that embryo donation could take place, for therapy of fertility, and exceptionally to research.

Claudins: multifunctional players in epithelial tight junctions and their role in cancer.

The molecular architecture of tight junctions has been a subject of extensive studies that have shown tight junctions to be composed of many peripheral and integral membrane proteins. Claudins have been considered the main tight junction-forming proteins; however, the role they play in a series of pathophysiological events, including human carcinoma development, is only now beginning to be understood. Increasing evidence from in vitro and in vivo studies have identified the influence of claudins on tight junction structure and function, although claudins also participate in cellular contexts other than tight junctions. The aim of this review is to summarize and discuss the conceptual framework concerning claudins, focusing on the involvement of these proteins in epithelial cell polarity establishment, paracellular transport control, signal transduction and tumorigenesis.

Valdecoxib provides effective pain relief following acute ankle sprain.

We sought to determine whether valdecoxib is as effective as diclofenac in treating acute ankle sprain. Patients (n=202) with acute first- and second-degree ankle sprain were randomized to valdecoxib (40 mg twice daily on day 1 followed by 40 mg once daily on days 2-7) or diclofenac (75 mg twice daily). The primary efficacy end-point was the Patient's Assessment of Ankle Pain visual analogue scale (VAS, 0-100 mm) value on day 4. Valdecoxib was as efficacious as diclofenac in treating the signs and symptoms of acute ankle sprain. The mean VAS reduction in ankle pain on day 4 was not different between groups; the two-sided 95% confidence interval for the between-group difference was within the prespecified limit for non-inferiority (10 mm). There were no significant differences between groups for all secondary efficacy end-points. The two treatments were similarly effective and well tolerated for treatment of acute ankle sprain.

Morphological and molecular alterations at the junctional complex in irradiated human colon adenocarcinoma cells, Caco-2.

PURPOSE: Ionizing radiation is one of the main modalities used in the treatment of colorectal cancer. Despite a number of epigenetic or non-targeted effects of radiation exposure that have been described, the effect of radiation on cell-cell adhesion in the epithelium has been less studied. We report morphological and molecular alterations induced by ionizing radiation at the junctional complex level of human colon cancer Caco-2 cells. MATERIALS AND METHODS: Cells were irradiated with doses of 2, 5 or 10 Gy and the effects on the junctional complex were monitored for different times after irradiation. Alterations of tight and adherens junction components were observed by measuring the transepithelial electrical resistance, by immunofluorescence and immunoblotting and electron microscopy analyses. RESULTS: Ionizing radiation caused alterations in the junctional complex, as evidenced by: (a) a decrease in the transepithelial electrical resistance, (b) alterations in the pattern of the distribution of junctional proteins as observed for E-cadherin, occludin, and zonula occludens 1 (ZO-1), but with minor changes in claudin-1 localization, and (c) wide spaces between opposed cells. These effects were dose and time-dependent since minor doses of irradiation caused a reversible effect on E-cadherin distribution and transepithelial electrical resistance. CONCLUSIONS: The results obtained show that ionizing radiation caused redistribution of the main junctional proteins E-cadherin, occludin and ZO-1 with minor changes for claudin-1, leading to disassembly of the junctional complex and loss of its functionality in Caco-2 cells. The molecular mechanisms responsible for these events need further elucidation.