Real-world healthcare costs and resource utilization in patients with von Willebrand disease and angiodysplasia.

OBJECTIVE: To describe the economic burden among VWD patients with angiodysplasia compared to VWD patients without angiodysplasia and the general population. METHODS: This was a retrospective analysis using the Merative MarketScan Commercial and Medicare Databases® (January 2011-September 2020). Selected patients had ≥1 medical claim for VWD or low VWF, ≥1 medical claim for AGD, and ≥3 GI-related bleeding episodes within a year. HCRU and all-cause costs were compared with the VWD (only) and the general cohorts. RESULTS: The mean total all-cause costs were $150,101 among patients with VWD and angiodysplasia (n = 34), higher compared to $48,249 among matched VWD patients without angiodysplasia (n = 136) and $31,029 among matched individuals of the general population [n = 136; p-value < 0.0001]. The differences in costs between groups were primarily due to inpatient care. During the 12-month follow-up, VWD patients with symptomatic (n = 35), asymptomatic (n = 81), and suspected (n = 378) angiodysplasia had an average of 4.1, 0.6, and 3.8 gastrointestinal (GI) bleeds, respectively. Desmopressin, VWF concentrates, and aminocaproic acid were the most frequent treatments used. The most frequent procedures to treat GI-related bleeding and underlying lesions were blood transfusion and laser therapy. CONCLUSIONS: Despite recent therapeutic advances, there is room for considerable reduction of the disease burden in patients with VWD and angiodysplasia.

Primary central nervous system vasculitis: A diagnostic and therapeutic challenge. A series of 7 patients.

INTRODUCTION: Primary central nervous system vasculitis (PCNSV) is a rare disease affecting medium- and small-calibre blood vessels of the central nervous system. OBJECTIVE: The aim of this study was to analyse clinical findings and diagnostic aspects, with special attention to histopathological findings, as well as the treatments used and treatment response in patients diagnosed with PCNSV at our hospital. PATIENTS AND METHODS: We conducted a retrospective descriptive analysis of patients with a diagnosis of PCNSV at discharge from our centre and meeting the 1988 Calabrese criteria. To this end, we analysed the hospital discharge records of Hospital General Universitario de Castellón between January 2000 and May 2020. RESULTS: We analysed a series of 7 patients who were admitted with transient focal alterations and other less specific symptoms such as headache or dizziness; diagnosis was based on histological findings in 5 cases and on suggestive arteriographic findings in the remaining 2. Neuroimaging results were pathological in all cases, and CSF analysis detected alterations in 3 of the 5 patients who underwent lumbar puncture. All patients received initial treatment with megadoses of corticosteroids followed by immunosuppressive treatment. Progression was unfavourable in 6 cases, with fatal outcomes in 4. CONCLUSIONS: Despite the diagnostic challenge of PCNSV, it is essential to attempt to reach a definitive diagnosis using such tools as histopathology and/or arteriography studies, in order to promptly establish appropriate treatment and thus reduce the morbidity and mortality of this condition.

In-house 3D treatment planning for mandibular reconstruction by free fibula flap in cancer: Our technique.

Planning of free fibula flaps for mandibular reconstruction improves the quality of conformation and reduces the operating time. Many methods based on modeling and 3D printing have been described with excellent results, but planning and production of custom-made guides and/or plates are often time-consuming and expensive. In this article, we describe our 3D printing-assisted free fibula flap planning method, routinely performed exclusively by the surgical team in less than 72hours, compatible with urgent cancer management. Fibula and mandible models were printed by using preoperative CT data. The mandibular resection, the length of fibula and the number of osteotomies and their angles were planned on the printed models. Titanium fixation plates were then conformed on the printed model and sterilized prior to surgery and templates were made to guide fibula osteotomies. Preliminary analysis based on 7 cases shows a reduction of conformation time with good clinical and radiological results. This 3D printing-assisted planning technique is simple, cost-effective and readily reproducible, allowing mandibular reconstruction with good cosmetic and functional results.

Use of omental free flap for craniofacial reconstruction in unfavorable wound bed: A case report.

INTRODUCTION: The omental free flap is an effective tool for craniofacial reconstruction. However it is generally under-utilised by a large number of practitioners. This paper's goal is to increase awareness of this free flap's accessibility and to demonstrate that it can be an attractive option for reconstructive surgery. CLINICAL REPORT: This article outlines the details of a 57-year-old patient who required coverage of a fronto-parietal wound with dura mater exposure. After previous failed conventional free flap attempts, a procedure using the omental free flap was finally performed on this severe wound. The omentum was harvested via a 8cm laparotomy and anastomosed to the temporal vessels. The final result was successful, with a favorable aesthetic result. DISCUSSION: The omental free flap has many advantages: the pedicle length is long, it allows coverage of a large wound, it can be applied to a wound bed previously irradiated and infected, it has a low morbidity rate to the donor site, the surgical technique of harvesting is easy, the aesthetic result is satisfactory. However, the absence of skin slice is a disadvantage of the omental free flap because it makes monitoring difficult and it requires a skin graft in a second procedure. Laparoscopic harvest of omentum free flaps is a safe and effective tool in the reconstructive armamentarium. Every maxillofacial and plastic surgeon should aim to master and use this method as a legitimate option in some infrequent but appropriated cases.

Analysis of PTPN22, ZFAT and MYO9B polymorphisms in Turner Syndrome and risk of autoimmune disease.

Turner syndrome (TS) is one of the most common sexual chromosome abnormalities and is clearly associated with an increased risk of autoimmune diseases, particularly thyroid disease and coeliac disease (CD). Single-nucleotide polymorphism analyses have been shown to provide correlative evidence that specific genes are associated with autoimmune disease. Our aim was to study the functional polymorphic variants of PTPN22 and ZFAT in relation to thyroid disease and those of MYO9B in relation to CD. A cross-sectional comparative analysis was performed on Mexican mestizo patients with TS and age-matched healthy females. Our data showed that PTPN22 C1858T (considered a risk variant) is not associated with TS (X2  = 3.50, p = .61, and OR = 0.33 [95% CI = 0.10-1.10]). Also, ZFAT was not associated with TS (X2  = 1.2, p = .28, and OR = 1.22 [95% CI = 0.84-1.79]). However, for the first time, rs2305767 MYO9B was revealed to have a strong association with TS (X2  = 58.6, p = .0001, and OR = 10.44 [95% C = 5.51-19.80]), supporting a high level of predisposition to CD among TS patients. This report addresses additional data regarding the polymorphic variants associated with autoimmune disease, one of the most common complications in TS.

DIAGNOSTIC PERFORMANCE OF WAIST CIRCUMFERENCE MEASUREMENTS FOR PREDICTING CARDIOMETABOLIC RISK IN MEXICAN CHILDREN.

OBJECTIVE: The accumulation of abdominal fat is associated with cardiometabolic abnormalities. Waist circumference (WC) measurements allow an indirect evaluation of abdominal adiposity. However, controversy exists over which WC reference values are the most suitable for identifying the pediatric population at risk. The aim of the study was to evaluate the ability of various WC indices to identify abdominal obesity as diagnostic tools for predicting cardiometabolic risk in Mexican children and adolescents. METHODS: Anthropometric measurements were performed and biochemical profiles determined in a crosssectional study that included 366 children and adolescents. Four parameters were used to evaluate abdominal obesity in our study group: (1) WC >90th percentile, according to the Fernández reference in a Mexican-American population measured by the National Center for Health Statistics (NCHS) technique; (2) WC >90th percentile, according to the Klünder reference in a Mexican population (measured by the World Health Organization [WHO] technique); (3) waist-to-height ratio (WHtR) >0.5 according to WHO; and (4) WHtR >0.5 according to NCHS. The ability of each of the indices to discriminate cardiometabolic abnormalities (fasting plasma glucose, dyslipidemia, and hypertension) was assessed. RESULTS: WHtR >0.5 according to WHO or NCHS references showed greater sensitivity to detect metabolic abnormalities compared to percentile reference parameters (74.3 to 100% vs. 59.0 to 88.9%; P<.05). However, the percentiles displayed more specificity to identify these alterations (46.2 to 62.2 vs. 21.3 to 46.9; P<.05). Area under the curve analysis showed that WHtR >0.5 can more readily detect hypertriglyceridemia (0.642), hypoalphalipoproteinemia (0.700), and a combination of two or more metabolic abnormalities (0.661), whereas WC >90th percentile, according to Klünder, better detected hyperglycemia (0.555). CONCLUSION: WHtR >0.5 is a sensitive measure to identify pediatric patients with cardiometabolic alterations, despite its low specificity, and is a useful diagnostic tool to detect populations at risk. Based on the results of this study, we recommend preferential use of the Klünder waist circumference references over the Fernández method in Mexican pediatric populations. ABBREVIATIONS: AUC = area under the curve BMI = body mass index HDL = high-density lipoprotein IDF = International Diabetes Federation LDL = low-density lipoprotein MS = metabolic syndrome NCHS = National Center for Health Statistics ROC = receiver operating characteristic WC = waist circumference WHO = World Health Organization WHtR = waist-to-height ratio.

Co-infection of Ornithodoros coriaceus with the relapsing fever spirochete, Borrelia coriaceae, and the agent of epizootic bovine abortion.

The soft tick, Ornithodoros coriaceus (Koch) (Acari: Argasidae), is a common mammalian parasite of livestock in many arid regions of the western U.S.A. The tick is a known vector of the undescribed bacterial pathogen that causes epizootic bovine abortion (EBA), which results in late-term abortions in beef cattle and subsequent economic loss, which can be considerable, to producers. A second reported bacterial pathogen, Borrelia coriaceae, a member of the relapsing fever complex, has also been identified in this tick and was at one time hypothesized to be the aetiological agent of EBA. In order to test whether bacterial infections in ticks overlapped geographically and to determine the prevalence of co-infection in O. coriaceus populations, we used molecular methods to detect bacterial DNA from ticks collected from a wide variety of habitats in California, Nevada and Oregon. Of the 15 sites at which ticks tested positive for the agent of EBA (aoEBA), eight also contained ticks positive for Borrelia spp. by polymerase chain reaction assay. Additionally, two ticks were co-infected; both of these were collected from the same location. Univariate risk analysis indicated the presence of juniper-dominated habitat at the collection site and geographic location to be significantly associated with infection of the tick vector by either pathogen.

Supramolecular-directed chiral induction in biaryl derivatives.

A thermodynamically controlled resolution has allowed for the generation of diastereomerically enriched complexes, by chirality transfer from an enantiopure building block to a dynamically racemic biaryl derivative. A switchable sense of induction could be achieved depending on the substituents of the chiral block.

Oxidative and nitrosative stress and fibrogenic response.

Uncontrolled production of collagen I is the main feature of liver fibrosis. Following a fibrogenic stimulus such as alcohol, hepatic stellate cells (HSC) transform into an activated collagen-producing cell. In alcoholic liver disease, numerous changes in gene expression are associated with HSC activation, including the induction of several intracellular signaling cascades, which help maintain the activated phenotype and control the fibrogenic and proliferative state of the cell. Detailed analyses for understanding the molecular basis of the collagen I gene regulation have revealed a complex process involving reactive oxygen species (ROS) as key mediators. Less is known, however, about the contribution of reactive nitrogen species (RNS). In addition, a series of cytokines, growth factors, and chemokines, which activate extracellular matrix (ECM)-producing cells through paracrine and autocrine loops, contribute to the fibrogenic response.

[Hepatocyte oxidant stress and alcoholic liver disease]. / Estrés oxidativo hepatocitario y hepatopatía alcohólica.

Acute and chronic alcohol consumption increases the production of reactive oxygen species (ROS), and enhances lipid peroxidation of lipids, proteins, and DNA. The mechanism by which alcohol causes cell injury is still not clear but a major role for ROS and lipid peroxidation-end products is considered. Many pathways have been suggested to play a role on how ethanol induces a state of "oxidative stress", including redox-state changes, acetaldehyde production, damage to the mitochondria, membrane injury, apoptosis, ethanol-induced hypoxia, effects on the immune system and altered cytokine production, increased endotoxin levels and activation of Kupffer cells, mobilization of iron, changes in the antioxidant defense, particularly mitochondrial glutathione (GSH), one electron oxidation of ethanol to 1-hydroxy-ethyl radical, and induction of CYP2E1. These pathways are not exclusive of one another and it is likely that several, indeed many systems contribute to the ability of ethanol to induce a state of oxidative stress.

Estrés oxidativo hepatocitario y hepatopatía alcohólica / No disponible

El consumo agudo y crónico de alcohol aumenta la producciónde especies de oxígeno reactivas (EOR) y potencia la peroxidaciónde los lípidos, las proteínas y el ADN. El mecanismo por el que elalcohol produce lesión celular sigue sin estar claro, pero se piensaque las EOR y los productos de la peroxidación lipídica intervienende forma decisiva. Se ha señalado la intervención de muchasvías en la manera que tiene el etanol de inducir un estado de “estrésoxidativo”, incluidos los cambios de estado redox, la producciónde acetaldehído, el daño mitocondrial, las lesiones membranosas,la apoptosis, la hipoxia inducida por etanol, los efectossobre el sistema inmunitario y la producción alterada de citocinas,el aumento de los niveles de endotoxinas y de activación de las célulasde Kupffer, la movilización del hierro, la modulación de ladefensa antioxidante, especialmente del glutatión mitocondrial(GSH), la oxidación monoelectrónica del etanol a un radical 1-hidroxi-etilo y la inducción de la CYP2E1. Estas vías no son excluyentesentre sí y es probable que sean varios, ciertamente muchos,los sistemas que contribuyan a la capacidad que posee eletanol de inducir un estado de estrés oxidativo

Acute and chronic alcohol consumption increases the productionof reactive oxygen species (ROS), and enhances lipid peroxidationof lipids, proteins, and DNA. The mechanism by which alcoholcauses cell injury is still not clear but a major role for ROSand lipid peroxidation-end products is considered. Many pathwayshave been suggested to play a role on how ethanol induces a stateof “oxidative stress”, including redox-state changes, acetaldehydeproduction, damage to mitochondria, membrane injury, apoptosis,ethanol-induced hypoxia, effects on the immune system andaltered cytokine production, increased endotoxin levels and activationof Kupffer cells, mobilization of iron, modulation of the antioxidantdefense, particularly mitochondrial glutathione (GSH),one electron oxidation of ethanol to 1-hydroxy-ethyl radical, andinduction of CYP2E1. These pathways are not exclusive of oneanother and it is likely that several, indeed many, systems contributeto the ability of ethanol to induce a state of oxidative stress

[Hepatic stellate cells and oxidative stress]. / Células estrelladas hepáticas y estrés oxidativo.

Hepatic fibrosis is a wound-healing response that takes place during chronic liver injury and is characterized by excessive production and deposition of extracellular matrix (ECM) components, mainly collagen type I. Hepatic stellate cells (HSC) are responsible for the excessive production of scar tissue during liver fibrosis. Activation of HSC, the main step in the development of hepatic fibrosis, is mediated by cytokines and reactive oxygen species (ROS) released by damaged hepatocytes and/or activated Kupffer cells and even HSC themselves. While HSC usually remain quiescent, in response to factors promoting liver injury they undergo activation and become highly proliferative and fibrogenic. Indeed a key feature of HSC activation is uncontrolled production of collagen type I. Collagen is a heterotrimeric protein composed of two a1 chains and one a2 chain forming a triple helix structure. Initiation of HSC activation is largely due to paracrine stimulation, whereas the perpetuation of such activated state involves autocrine as well as paracrine loops. This review focuses on the role of oxidant stress on the activation of stellate cells.

Células estrelladas hepáticas y estrés oxidativo / Hepatic stellate cells and oxidative stress

La fibrosis hepática ocurre en la lesión hepática crónica y se caracteriza por la producción excesiva y el depósito de componentes de la matriz extracelular (MEC), fundamentalmente de colágeno de tipo I. Las células estralladas hepáticas (CEH) son las responsables de la producción excesiva de matriz extracelular durante la fibrosis. La activación de las CEH, constituye el paso fundamental del desarrollo de la fibrosis hepática y está mediada por citoquinas específicas y especies reactivas de oxígeno (ERO) que liberan los hepatocitos dañados, las células de Kupffer y las CEH activadas. Aunque las CEH permanecen normalmente en estado quiescente, se activan en respuesta a los factores que promueven la lesión hepática y proliferan y generan matriz. Un rasgo fundamental de la activación de las CEH es la producción incontrolada de colágeno de tipo I con una escasa degradación. El colágeno es una proteína heterotrimérica que se compone de dos cadenas α1 y una cadena α2, formando una triple hélice. El inicio de la activación de las células estrelladas se debe en gran medida a una estimulación paracrina, mientras que la perpetuación de dicho estado activado implica regulación tanto autocrina como paracrina. Esta revisión trata del papel del estrés oxidativo sobre la activación de las CEH

Hepatic fibrosis is a wound-healing response that takes place during chronic liver injury and is characterized by excessive production and deposition of extracellular matrix (ECM) components, mainly collagen type I. Hepatic stellate cells (HSC) are responsible for the excessive production of scar tissue during liver fibrosis. Activation of HSC, the main step in the development of hepatic fibrosis, is mediated by specific cytokines and reactive oxygen species (ROS) released by damaged hepatocytes and/or activated Kupffer cells and HSC. While HSC usually remain quiescent, in response to factors promoting liver injury they undergo activation and become highly proliferative and fibrogenic. Indeed a key feature of HSC activation is uncontrolled production of collagen type I with very little degradation. Collagen is a heterotrimeric protein composed of two α1 chains and one α2 chain forming a triple helix structure. Initiation of stellate cell activation is largely due to paracrine stimulation, whereas the perpetuation of such activated state involves autocrine as well as paracrine loops. This review focuses on the role of oxidant stress on the activation of stellate cells

Hepatic stellate cells and alcoholic liver disease.

Liver fibrosis represents a significant health problem worldwide for which no effective therapy exists. A great deal of research has been carried out to understand the molecular mechanisms responsible for the development of liver fibrosis. Activated stellate cells are the primary cell type responsible for the production of collagen I, the key protein involved in the development of liver fibrosis. Excessive deposition of collagen I occurs along with impaired extracellular matrix remodeling. Following a fibrogenic stimulus stellate cells transform into an activated collagen type I-producing cell. Numerous changes in gene expression are associated with stellate cell activation, including the induction of several intracellular signaling cascades, which help maintain the activated phenotype and control the fibrogenic and proliferative state of the cell. Activation of stellate cells is mediated by factors released from hepatocytes and Kupffer cells as they produce reactive oxygen species, nitric oxide, cytokines, growth factors, and cyclooxygenase and lipoxygenase metabolites, which provide pivotal paracrine effects in the liver milieu. Inhibition of stellate cell activation, proliferation, and the increased production of extracellular matrix (i.e. collagen type I) are therefore crucial steps for intervention in hepatic fibrogenesis.

Kupffer cells and alcoholic liver disease.

Liver disease is a major cause of illness and death worldwide. A central component in the complex network leading to the development of alcoholic liver disease is the activation of Kupffer cells by endotoxin and other soluble mediators. Alcohol consumption induces a state of "leaky gut increasing plasma and liver endotoxin levels. When Kupffer cells become activated, they interact with a complex of proteins located on the extracellular membrane signaling to produce a wide array of soluble factors, including cytokines, chemokines, growth factors, cyclooxygenase and lipoxygenase metabolites, and reactive oxygen species such as superoxide anion, hydrogen peroxide, and nitric oxide, all of which provide physiologically diverse and pivotal paracrine effects on all other liver cell types and, ultimately, liver injury. Kupffer cells are also central to the liver homeostatic response to injury as upon cellular degenerative changes, they immediately respond to the insult and release mediators to orchestrate inflammatory and reparative responses. Thus, the homeostatic responses are initiated by Kupffer cell-derived mediators at the cellular level and underlie the liver s defense and reparative mechanisms against injury. In order to understand better the role of Kupffer cells in the onset of liver injury, animal models in which Kupffer cells are inactivated, and cell culture settings (e.g. co-cultures) are being used with promising results that advance our understanding of alcoholic liver disease.

Células estrelladas hepáticas y hepatopatía alcohólica / Hepatic stellate cells and alcoholic liver disease

La fibrosis hepática es un importante problema de salud entodo el mundo para el que no hay tratamiento efectivo. Se hanrealizado muchas investigaciones para comprender los mecanismosmoleculares que son responsables del desarrollo de la fibrosishepática. Las células estrelladas activadas son el principaltipo celular responsable de la producción de colágeno I, la proteínaclave implicada en el desarrollo de la fibrosis hepática. Sedesarrolla en excesivos depósitos de colágeno I junto con un deteriorodel remodelado de la matriz extracelular. Tras un estímulofibrogénico, las células estrelladas se transforman en célulasactivadas productoras de colágeno de tipo I. Son numerosos loscambios de expresión génica que se asocian a la activación delas células estrelladas, incluida la inducción de varias cascadas deseñalización celular, lo que ayuda a conservar el fenotipo activadoy a controlar el estado fibrogénico y proliferativo de la célula.La activación de las células estrelladas está mediada por factoresque liberan los hepatocitos y las células de Kupffer al producirespecies de oxígeno reactivas, óxido nítrico, citoquinas, factoresde crecimiento y metabolitos de la ciclooxigenasa y la lipooxigenasa,que inducen efectos paracrinos esenciales en el medio hepático.Inhibir la activación y proliferación de las células estrelladas,y la producción de matriz extracelular (es decir, de colágenode tipo I) es un paso crucial para poder prevenir en la fibrogénesishepática

Liver fibrosis represents a significant health problem worldwidefor which no effective therapy exists. A great deal of research hasbeen carried out to understand the molecular mechanisms responsiblefor the development of liver fibrosis. Activated stellate cellsare the primary cell type responsible for the production of collagenI, the key protein involved in the development of liver fibrosis.Excessive deposition of collagen I occurs along with impaired extracellularmatrix remodeling. Following a fibrogenic stimulus stellatecells transform into an activated collagen type I-producingcell. Numerous changes in gene expression are associated withstellate cell activation, including the induction of several intracellularsignaling cascades, which help maintain the activated phenotypeand control the fibrogenic and proliferative state of the cell.Activation of stellate cells is mediated by factors released from hepatocytesand Kupffer cells as they produce reactive oxygenspecies, nitric oxide, cytokines, growth factors, and cyclooxygenaseand lipoxygenase metabolites, which provide pivotalparacrine effects in the liver milieu. Inhibition of stellate cell activation,proliferation, and the increased production of extracellularmatrix (i.e. collagen type I) are therefore crucial steps for interventionin hepatic fibrogenesis

Células de Kupffer y hepatopatía alcohólica / Kupffer cells and alcoholic liver disease

Las hepatopatías son una de las principales causas de morbilidady mortalidad en todo el mundo. Uno de los componentesesenciales de la compleja red que lleva al desarrollo de la hepatopatíaalcohólica es la activación de las células de Kupffer por endotoxinasy otros mediadores solubles. El consumo de alcohol induceun estado de "escapes digestivos" que aumenta los niveles deendotoxinas en plasma e hígado. Cuando las células de Kupffer seactivan, interactúan con un complejo de proteínas situado en lavía de señalización de las membranas extracelulares para producirtoda una serie de factores solubles, como citocinas, quimiocinas,factores de crecimiento, metabolitos de la ciclooxigenasa y la lipooxigenasay especies reactivas del oxígeno como el anión superóxido,el peróxido de hidrógeno y el óxido nítrico, todos los cualesejercen efectos paracrinos fisiológicamente diversos y fundamentalessobre todos los demás tipos de células del hígado, produciendoen última instancia la lesión hepática. Las células de Kupfferson también esenciales para la respuesta homeostática del hígadoa las lesiones, ya que, al presentarse cambios celulares degenerativos,responden de inmediato a la agresión y liberan mediadoresque orquestan las reacciones inflamatorias y reparadoras. Así, lasrespuestas homeostáticas comienzan por los mediadores que procedende las células de Kupffer, que, a nivel celular, se encuentranen la base de los mecanismos de defensa y reparadores del hígadofrente a las lesiones. Para poder comprender mejor el papel de lascélulas de Kupffer en el inicio de la lesión hepática, se están empleandocultivos celulares (p. ej., co-cultivos) y modelos animalesen los que dichas células de Kupffer se encuentran inactivadas. Estosestudios están proporcionando resultados prometedores, yaque están contribuyendo a progresar en nuestros conocimientossobre la hepatopatía alcohólica

Liver disease is a major cause of illness and death worldwide. Acentral component in the complex network leading to the developmentof alcoholic liver disease is the activation of Kupffer cellsby endotoxin and other soluble mediators. Alcohol consumptioninduces a state of ‘leaky gut’ increasing plasma and liver endotoxinlevels. When Kupffer cells become activated, they interact witha complex of proteins located on the extracellular membrane signalingto produce a wide array of soluble factors, including cytokines,chemokines, growth factors, cyclooxygenase and lipoxygenasemetabolites, and reactive oxygen species such assuperoxide anion, hydrogen peroxide, and nitric oxide, all ofwhich provide physiologically diverse and pivotal paracrine effectson all other liver cell types and, ultimately, liver injury. Kupffercells are also central to the liver homeostatic response to injury asupon cellular degenerative changes, they immediately respond tothe insult and release mediators to orchestrate inflammatory andreparative responses. Thus, the homeostatic responses are initiatedby Kupffer cell-derived mediators at the cellular level and underliethe liver’s defense and reparative mechanisms against injury.In order to understand better the role of Kupffer cells in theonset of liver injury, animal models in which Kupffer cells are inactivated,and cell culture settings (e.g. co-cultures) are being usedwith promising results that advance our understanding of alcoholicliver disease

Practical synthesis of Shi's diester fructose derivative for catalytic asymmetric epoxidation of alkenes.

[reaction: see text] A practical synthesis of Shi's diester 3 for catalytic asymmetric epoxidations has been developed. The catalyst has been prepared in multigram quantities from D-fructose in four steps with a 66% overall yield. Efficiency, cost, and selectivity aspects of the reagents involved for its preparation have been taken care of during its preparation. The workup procedures have been simplified to the bare minimum, rendering a very practical preparation method. The well-known high efficiency of this catalyst 3 in the epoxidation of alpha,beta-unsaturated carbonyl compounds has also proved to be high in unfunctionalized alkenes.

Role of hydrogen peroxide and oxidative stress in healing responses.

Oxidative stress is a host defense mechanism whose involvement in maintaining homeostasis and/or inducing disease has been widely investigated over the past decade. Various reactive oxygen species (ROS) have been defined and the enzymes involved in generating and/or eliminating them have been widely studied. In this review we briefly discuss general mechanisms of oxidative stress and the oxidative stress response of the host. We focus primarily on hydrogen peroxide and summarize the systems involved in its formation and elimination. We describe mechanisms whereby hydrogen peroxide and other ROS can modify protein conformation and, thus, alter protein function, and describe a group of transcription factors whose biological activity is modulated by the redox state of cells. These basic aspects of oxidative stress are followed by a discussion of mechanisms whereby hydrogen peroxide and other ROS can modulate some physiological and pathological processes, with special emphasis on wound healing and scarring of the liver.

Use of cultured cells in assessing ethanol toxicity and ethanol-related metabolism.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Terrence M. Donohue, Jr, and Dahn L. Clemens. The presentations were (1) Characterization of single and double recombinant hepatoma cells that express ethanol-metabolizing enzymes, by Terrence M. Donohue, Jr; (2) Inhibition of cell growth by ethanol metabolism, by Dahn L. Clemens; (3) Use of transfected HeLa cells to study the genesis of alcoholic fatty liver, by Andrea Galli and David Crabb; (4) CYP2E1-mediated oxidative stress induces COL1A2 mRNA in hepatic stellate cells and in a coculture system of HepG2 and stellate cells, by Natalia Nieto; (5) Transforming growth factor-alpha secreted from ethanol-exposed hepatocytes contributes to development of alcoholic hepatic fibrosis, by Junji Kato; and (6) Effect of ethanol on Fas-dependent caspase-3 activation and apoptosis in CD4+ T cells, by Shirish S. Barve.