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Intravenous lipid emulsions (ILEs) are a source of nonprotein calories and fatty acids and help promote growth in preterm infants and infants with intestinal failure. An ILE dose and oil source determines its fatty acid, phytosterol, and vitamin E delivery. These factors play a role in the infant’s risk for essential fatty acid deficiency and cholestasis, and help modulate inflammation, immunity, and organ development. This article reviews different ILEs and their constituents and their relationship with neonatal health.

Children with cholestatic liver diseases are increasingly living into adulthood, thanks to innovations in medical and surgical therapies. The excellent outcomes observed in pediatric liver transplantation for diseases, such as biliary atresia, have transformed the life trajectory of children born with once-fatal liver diseases. The evolution of molecular genetic testing, has helped expedite the diagnosis of other cholestatic disorders, improving the clinical management, disease prognosis, and family planning for inherited disorders, such as progressive familial intrahepatic cholestasis and bile acid synthesis disorders. The expanding list of therapeutics, including bile acids and the newer ileal bile acid transport inhibitors, has also helped slow the progression of disease and improve the quality of life for certain diseases, like Alagille syndrome. More and more children with cholestatic disorders are expected to require care from adult providers familiar with the natural history and potential complications of these childhood diseases. The aim of this review is to bridge the gap between pediatric and adult care in children with cholestatic disorders. The present review addresses the epidemiology, clinical features, diagnostic testing, treatment, prognosis, and transplant outcomes of 4 hallmark childhood cholestatic liver diseases: biliary atresia, Alagille syndrome, progressive familial intrahepatic cholestasis, and bile acid synthesis disorders.

Modern infrared (IR) microscopy, communication, and sensing systems demand control of the spectral characteristics and polarization states of light. Typically, these systems require the cascading of multiple filters, polarization optics, and rotating components to manipulate light, inevitably increasing their sizes and complexities. Here, we report two-terminal mid-infrared (mid-IR) emitters, in which tuning the polarity of the applied bias can switch their emission peak wavelengths and linear polarization states along two orthogonal orientations. Our devices are composed of two back-to-back p–n junctions formed by stacking anisotropic light-emitting materials, black phosphorus and black arsenic–phosphorus with MoS2. By controlling the crystallographic orientations and engineering the band profile of heterostructures, the emissions of two junctions exhibit distinct spectral ranges and polarization directions; more importantly, these two electroluminescence (EL) units can be independently activated, depending on the polarity of the applied bias. Furthermore, we show that when operating our emitter under the polarity-switched pulse mode, the time-averaged EL exhibits the characteristics of broad spectral coverage, encompassing the entire first mid-IR atmospheric window (λ: 3–5 μm), and electrically tunable spectral shapes.

The ability to read, reason, and infer lies at the heart of neural reasoning architectures. After all, the ability to perform logical reasoning over language remains a coveted goal of Artificial Intelligence. To this end, models such as the Turing-complete differentiable neural computer (DNC) boast of real logical reasoning capabilities, along with the ability to reason beyond simple surface-level matching. In this brief, we propose the first probe into DNC’s logical reasoning capabilities with a focus on text-based question answering (QA). More concretely, we propose a conceptually simple but effective adversarial attack based on metamorphic relations. Our proposed adversarial attack reduces DNCs’ state-of-the-art accuracy from 100% to 1.5% in the worst case, exposing weaknesses and susceptibilities in modern neural reasoning architectures. We further empirically explore possibilities to defend against such attacks and demonstrate the utility of our adversarial framework as a simple scalable method to improve model adversarial robustness. [ABSTRACT FROM AUTHOR]

An overview of methods of indexing and searching XML documents is presented. Issues posed by XML, concerning information retrieval and database research, are identified and discussed.

Spondylodiscitis (SD) is an infection of the intervertebral disc with involvement of the adjacent vertebral bodies. Diagnostic tests with CT-guided biopsy only provide a positive yield in 14%–48% of cases. Percutaneous endoscopic debridement and drainage (PEDD) has recently shown promise in the treatment of spondylodiscitis.

Elizabeth Crosby (1888-1983) is a beloved and well-respected titan of neuroanatomy. Her contributions to our understanding of neuroanatomy are rooted in her seminal text, The Comparative Anatomy of the Nervous System of Vertebrates, Including Man, published in 1936, which is a masterful and comprehensive account of comparative neuroanatomy. Her later texts, Correlative Neurosurgeryand Correlative Anatomy of the Nervous System, are standard reference texts to this day. Her mentorship of graduate students, close work with the University of Michigan neurosurgery department, and the quality of her research and scientific publications were recognized with many awards, culminating in the National Medal of Science presented by President Carter in 1980.

Graphical Abstract

Many attempts have been made over the last two decades to computerize the management of patient records using advanced computing and networking facilities across hospitals, clinics, and billing agents. A patient's record represents the key repository for information concerning his or her health care. A truly ubiquitous availability of patient records can greatly improve health care delivery by providing medical personnel with timely access of often critical medical records such as past medical history, blood type, and even next-of-kin information. The emergence of smart card technology is recognized as a potential solution to manage a patient's medical records effectively and accurately. A smart card provides the rich benefits of storing a comprehensive and accurate medical history of a patient while its pocket size offers easy mobility. But, a smart card has yet to gain the mass support critical for wide market acceptance of such technology. A major hindrance of such advancement is attributed to the diverse protocol currently available from various vendors. As such, medical records stored on a smart card from a hospital are not readable by another hospital. In a step toward facilitating a common standard, ISO has standardized the protocol communication between a smart card and a smart card reader based on the ISO 7816 specification family.

Venous malformations (VMs) are slow flowing congenital vascular malformations that demonstrate continuous growth. They are prone to bleeding and frequent invasion of adjacent structures. It is therefore important to differentiate them from schwannomas, which can appear similar on imaging. Currently, the literature demonstrates only a few examples of pathology misdiagnosed as a schwannoma, and of VMs associated with neurological deficits. We will illustrate the characteristics and management of VMs causing compressive neuropathy in the cervical and upper extremity regions and contrast them against the features of peripheral nerve sheath tumors.

Neuroblastoma and other pediatric tumors show a paucity of gene mutations, which has sparked an interest in their epigenetic regulation. Several tumor types include phenotypically divergent cells, resembling cells from different lineage development stages. It has been proposed that super-enhancer-associated transcription factor (TF) networks underlie lineage identity, but the role of these enhancers in intratumoral heterogeneity is unknown. Here we show that most neuroblastomas include two types of tumor cells with divergent gene expression profiles. Undifferentiated mesenchymal cells and committed adrenergic cells can interconvert and resemble cells from different lineage differentiation stages. ChIP–seq analysis of isogenic pairs of mesenchymal and adrenergic cells identified a distinct super-enhancer landscape and super-enhancer-associated TF network for each cell type. Expression of the mesenchymal TF PRRX1 could reprogram the super-enhancer and mRNA landscapes of adrenergic cells toward a mesenchymal state. Mesenchymal cells were more chemoresistant in vitro and were enriched in post-therapy and relapse tumors. Two super-enhancer-associated TF networks, which probably mediate lineage control in normal development, thus dominate epigenetic control of neuroblastoma and shape intratumoral heterogeneity.

Neurons expressing agouti-related protein (AgRP) are essential for feeding. The majority of these neurons are located outside the blood-brain barrier (BBB), allowing them to directly sense circulating metabolic factors. Here, we show that, in adult mice, AgRP neurons outside the BBB (AgRPOBBB) were rapidly ablated by peripheral administration of monosodium glutamate (MSG), whereas AgRP neurons inside the BBB and most proopiomelanocortin (POMC) neurons were spared. MSG treatment induced proliferation of tanycytes, the putative hypothalamic neural progenitor cells, but the newly proliferated tanycytes did not become neurons. Intriguingly, AgRPOBBBneuronal number increased within a week after MSG treatment, and newly emerging AgRP neurons were derived from post-mitotic cells, including some from the Pomc-expressing cell lineage. Our study reveals that the lack of protection by the BBB renders AgRPOBBBvulnerable to lesioning by circulating toxins but that the rapid re-emergence of AgRPOBBBis part of a reparative process to maintain energy balance.

Classically, transoccipital hippocampal depth electrode implantation requires a stereotactic headframe and arc and the patient to be placed in a seated or prone position, which can be cumbersome to position and uncomfortable for the surgeon. Robotic intracranial devices are increasingly being utilized for stereotactic procedures such as stereolectroencephalography (SEEG) but commonly require patients be placed in head-neutral position to perform facial registration.

The Accreditation Council for Graduate Medical Education (ACGME) established duty-hour regulations for accredited residency programs on July 1, 2003. It is unclear what changes occurred in the national incidence of medication errors in surgical patients before and after ACGME regulations.

Surgery can be an effective treatment for epilepsy if the seizure onset is adequately localized. Invasive monitoring is used if noninvasive methods are inconclusive. Initial invasive monitoring may fail if the pre-surgical hypothesis regarding location of epileptic foci is wrong. At this point, a decision must be made whether to remove all electrodes without a clearly defined location of onset or to implant additional electrodes with the aim of achieving localization by expanding coverage.

Adaptivity is the capacity of software to adjust itself to changes in its environment. A common approach to achieving adaptivity is to introduce dedicated code during software development stage. However, since those code fragments are designed a priori, self-adaptive software cannot handle situations adequately when the contextual changes go beyond those that are originally anticipated. In this case, the original builtin adaptivity should be tuned. For example, new code should be added to provide the capacity to sense the unexpected environment or to replace outdated adaptation decision logic. The technical challenges in this process, especially that of tuning software adaptivity at runtime, cannot be understated. In this paper, we propose an architecture-centric application framework for self-adaptive software named Auxo. Similar to existing work, our framework supports the development and running of self-adaptive software. Furthermore, our framework supports the tuning of software adaptivity without requiring the running self-adaptive software to be terminated. In short, the architecture style that we are introducing can encapsulate not only general functional logic but also the concerns in the self-adaptation loop (such as sensing, decision, and execution) as architecture elements. As a result, a third party, potentially the operator or an augmented software entity equipped with explicit domain knowledge, is able to dynamically and flexibly adjust the self-adaptation concerns through modifying the runtime software architecture. To truly exercise, validate, and evaluate our approach, we describe a self-adaptive application that was deployed on the framework, and conducted several experiments involving self-adaptation and the online tuning of software adaptivity.

The contribution of cloud computing and mobile computing technologies lead to the newly emerging mobile cloud computing paradigm. Three major approaches have been proposed for mobile cloud applications: 1) extending the access to cloud services to mobile devices; 2) enabling mobile devices to work collaboratively as cloud resource providers; 3) augmenting the execution of mobile applications on portable devices using cloud resources. In this paper, we focus on the third approach in supporting mobile data stream applications. More specifically, we study how to optimize the computation partitioning of a data stream application between mobile and cloud to achieve maximum speed/throughput in processing the streaming data. To the best of our knowledge, it is the first work to study the partitioning problem for mobile data stream applications, where the optimization is placed on achieving high throughput of processing the streaming data rather than minimizing the makespan of executions as in other applications. We first propose a framework to provide runtime support for the dynamic computation partitioning and execution of the application. Different from existing works, the framework not only allows the dynamic partitioning for a single user but also supports the sharing of computation instances among multiple users in the cloud to achieve efficient utilization of the underlying cloud resources. Meanwhile, the framework has better scalability because it is designed on the elastic cloud fabrics. Based on the framework, we design a genetic algorithm for optimal computation partition. Both numerical evaluation and real world experiment have been performed, and the results show that the partitioned application can achieve at least two times better performance in terms of throughput than the application without partitioning.

Neurosurgeons use Ojemann cortical stimulators to map and localize cortical and subcortical regions of the brain to map functional areas intraoperatively to avoid resecting or damaging functional tissue. Here we describe a technique where, rather than using a separate retracting tool, a handheld Ojemann cortical stimulator was used to retract cerebral parenchyma while simultaneously stimulating descending white matter tracts to prevent accidental damage to white matter tracts involved with motor function.

Application scheduling plays an important role in high-performance cluster computing. Application scheduling can be classified as job scheduling and task scheduling. This paper presents a survey on the software tools for the graph-based scheduling on cluster systems with the focus on task scheduling. The tasks of a parallel or distributed application can be properly scheduled onto multi-processors in order to optimize the performance of the program (e.g., execution time or resource utilization). In general, scheduling algorithms are designed based on the notion of task graph that represents the relationship of parallel tasks. The scheduling algorithms map the nodes of a graph to the processors in order to minimize overall execution time. Although many scheduling algorithms have been proposed in the literature, surprisingly not many practical tools can be found in practical use. After discussing the fundamental scheduling techniques, we propose a framework and taxonomy for the scheduling tools on clusters. Using this framework, the features of existing scheduling tools are analyzed and compared. We also discuss the important issues in improving the usability of the scheduling tools.Application scheduling plays an important role in high-performance cluster computing. Application scheduling can be classified as job scheduling and task scheduling. This paper presents a survey on the software tools for the graph-based scheduling on cluster systems with the focus on task scheduling. The tasks of a parallel or distributed application can be properly scheduled onto multi-processors in order to optimize the performance of the program (e.g., execution time or resource utilization). In general, scheduling algorithms are designed based on the notion of task graph that represents the relationship of parallel tasks. The scheduling algorithms map the nodes of a graph to the processors in order to minimize overall execution time. Although many scheduling algorithms have been proposed in the literature, surprisingly not many practical tools can be found in practical use. After discussing the fundamental scheduling techniques, we propose a framework and taxonomy for the scheduling tools on clusters. Using this framework, the features of existing scheduling tools are analyzed and compared. We also discuss the important issues in improving the usability of the scheduling tools.

The monitor concept provides a structured and flexible high‐level programming construct to control concurrent accesses to shared resources. It has been widely used in a concurrent programming environment for implicitly ensuring mutual exclusion and explicitly achieving process synchronization. This paper proposes an extension to the monitor construct for detecting runtime errors in monitor operations. Monitors are studied and classified according to their functional characteristics. A taxonomy of concurrency control faults over a monitor is then defined. The concepts of a monitor event sequence and a monitor state sequence provide a uniform approach to history information recording and fault detection. Rules for detecting various types of faults are defined. Based on these rules, fault‐detection algorithms are developed. A prototypical implementation of the proposed monitor construct with runtime fault detection mechanisms has been developed in Java. We shall briefly report our experience with and the evaluation of the robust monitor prototype. Copyright © 2005 John Wiley & Sons, Ltd.

Abstract This paper describes a dynamic service reconfiguration model where the proxy is composed of a chain of service objects called mobilets (pronounced as mo-be-lets), which can be actively deployed onto a network. This model offers flexibility because the chain of mobilets can be dynamically reconfigured to adapt to dynamic changes in the wireless environment, without interrupting service provision for other mobile nodes. We have realized the dynamic service reconfiguration model by crafting its design into a programmable infrastructure that forms the baseline architecture of the WebPADS (short for Web Proxy for Actively Deployable Services) system.

This paper discusses the synchronous viewing and editing of object-oriented models based on the Unified Modeling Lan guage (UML) by multiple users on the internet. Each user works on a copy of the model, which is continuously synchronized with the master copy on a central server. A group of users can work together in the common single writer-multiple reader mode, controlled by a token that can be passed from user to user. Alternatively, different users can lock different parts of the model for exclusive editing while the changes are visible to all other users. One can improve on basic granular locking by considering the semantics of the graphical nota tion. A semantics-based locking mechanism has been designed and implemented for UML class diagrams in order to allow users to col laborate more effectively: A prototype collaborative UML (CUML) editing system has been implemented in Java to validate the design.

Serial Analysis of Gene Expression (SAGE) is an efficient method to establish a complete mRNA expression profile of a tissue. We applied SAGE to identify expression of developmental control genes in neuroblastoma. The human homologue of the Drosophila Delta gene Delta like-1 (DLK1) was shown to have an unusually high expression in a SAGE library of the SK-N-FI neuroblastoma cell line. Northern blot analysis confirmed high DLK1 expression in SK-N-FI and several other neuroblastoma cell lines. Signalling between Delta and its receptor Notch controls many differentiation steps in Drosophila and man, including neural crest cell fate decision. Our data therefore suggest a role for the Delta-Notch pathway in neuroblast differentiation. Med. Pediatr. Oncol. 35:554–558, 2000. © 2000 Wiley-Liss, Inc.

The generation of reactive oxygen species (ROS) is a steady-state cellular event in respiring cells. Their production can be grossly amplified in response to a variety of pathophysiological conditions such as inflammation, immunologic disorders, hypoxia, hyperoxia, metabolism of drug or alcohol, exposure to UV or therapeutic radiation, and deficiency in antioxidant vitamins. Uncontrolled production of ROS often leads to damage of cellular macromolecules (DNA, protein, and lipids) and other small antioxidant molecules. A number of major cellular defense mechanisms exist to neutralize and combat the damaging effects of these reactive substances. The enzymic system functions by direct or sequential removal of ROS (superoxide dismutase, catalase, and glutathione peroxidase), thereby terminating their activities. Metal binding proteins, targeted to bind iron and copper ions, ensure that these Fenton metals are cryptic. Nonenzymlc defense consists of scavenging molecules that are endogenously produced (GSH, ubiqulnols, uric acid) or those derived from the diet (vitamins C and E, lipoic acid, selenium, riboflavin, zinc, and the carotenoids). These antioxidant nutrients occupy distinct cellular compartments and among them, there are active recycling. For example, oxidized vitamin E (tocopheroxy radical) has been shown to be regenerated by ascorbate, GSH, lipoic acid, or ubiqulnols. GSH disulfides (GSSG) can be regenerated by GSSG reductase (a riboflavin-dependent protein), and enzymic pathways have been identified for the recycling of ascorbate radical and dehydroascorbate. The electrons that are used to fuel these recycling reactions (NADH and NADPH) are ultimately derived from the oxidation of foods. Sickle cell anemia, thalassemia, and glucose-6-phosphate-dehydrogenase deficiency are all hereditary disorders with higher potential for oxidative damage due to chronic redox imbalance in red cells that often results in clinical manifestation of mild to serve hemolysis in patients with these disorders. The release of hemoglobin during hemolysis and the subsequent therapeutic transfusion in some cases lead to systemic iron overloading that further potentiates the generation of ROS. Antioxidant status in anemia will be examined, and the potential application of antioxidant treatment as an adjunct therapy under these conditions will be discussed.

The release of arachidonic acid is the rate limiting step in eicosanoid synthesis. In mammalian cells, the release of arachidonic acid is catalyzed by several enzymes. The 85 kDa cytosolic phospholipase A2 (cPLA2) is the key enzyme for the release reaction because of its specific acyl selectivity in phospholipid substrates. We have previously reported that vitamin E enrichment potentiates the arachidonic acid release as well as the spontaneous prostacyclin release in human endothelial cells. In contrast, similar enrichment of diets caused a dose-dependent suppression of platelet thromboxane synthesis. Therefore, the present study was undertaken to determine the effect of vitamin E on arachidonate release and phospholipase A2 activity in a platelet precursor cell, the MEG-01 megakaryocyte cell line. When these cells were incubated with different concentrations of vitamin E, cellular incorporation was linear with the dosages of this vitamin. Determination of arachidonate release after labeling cells with [3H]-arachidonate showed that vitamin E enrichment caused a dose-dependent increase in ionophore A23187-induced [3H]-arachidonic acid release. Analysis of PLA2 activity showed that activity was detected in the cytosol and this activity was completely abolished by the addition of anti-cPLA2, antibody. Determination of cPLA2 activity demonstrated that vitamin E enrichment caused an increase in enzyme activity. Analysis of cPLA2 protein by Western blot revealed that vitamin E caused an increase in enzyme protein. These data showed that the potentiation of arachidonic acid release and cPLA2, activity by vitamin E was mediated by the enhanced expression of cPLA2 protein.

Chromosomal region 1p36.2 harbors an intriguing gene cluster of about 1 Mb. In addition to normal high-copy-number repeats, this cluster consists entirely of locally repeated sequences among which there are tRNA and small nuclear RNA (snRNA) genes. In 23 PACs and YACs from the 1p36.2 cluster, we identified eight different copies of a sequence with about 97% homology to the macrophage stimulating protein (MSP) gene located on chromosomal band 3p21. These MSP-like (MSPL) sequences on 1p36.2 are scattered over the repeat region. Nucleotide substitutions and single nucleotide deletions in exons of all identified MSPL genes on 1p36.2 mark them as pseudogenes. We constructed a phylogenetic tree of these sequences with their most likely order of origin in evolution. MSP from 3p21 could be identified as the ancestral sequence, a copy of which was captured into the cluster of tRNA and snRNA genes on 1p36.2 about 6 million years (MY) ago. MSP subsequently coamplified with the other sequences in the cluster. Analysis of the DNA of 18 individuals shows that the MSPL copy number is polymorphic, with a range of four to seven or more copies per haploid genome. Analysis of corresponding clusters in macaque chromosomes indicated an age for the tRNA/snRNA cluster of at least 30 MY. The MSPL sequence thus functions as a probe for the more recent primate evolution of this cluster and suggests a continuation of its unusual activity over the last 6 MY.

The objectives of this study were to determine whether the recycling of tocopherol occurs in elicited rat polymorphonuclear leukocytes and if so, whether the recycling process is anzymic or chemical. When incubated with hemoglobin. tocopherol was oxidized in cell homogenates in a time-and concentration-dependent manner. The oxidized tocopherol could be regenerated by addition of ascorbate, glutathione or nordihydroguaiaretic acid. Time course studies showed a rapid regeneration of tocopherol which peaked at 1 min after the addition of reductants. Determination of the regeneration reaction in the presence of CHCl 3and MeOH indicated that under these enzyme-denaturing conditions, a considerable amount of tocopherol was still regenerated, suggesting that the regeneration reaction is predominantly a chemical reaction. This study provided direct evidence from mass analysis that oxidized vitamin E can be regenerated by cellular water-soluble reductants such as ascorbate and glutathione.

This study was designed to evaluate the effects of different amounts of dietary vitamin E on platelet tocopherol levels and 12-lipoxygenase activity when exogenous arachidonic acid was used as substrate. Weanling male Sprague-Dawley rats were fed diets containing 0, 50, and 5000 ppm of D-α-tocopherol acetate for 4 months. Platelet tocopherol was increased with increasing concentrations of dietary vitamin E; however, the conversion of exogenously added arachidonate by platelet to 12-HETE (12-hydroxyeicosatetraenoic acid) and thromboxane B2 from these three dietary groups was essentially the same. This study provides direct evidence that platelet 12-lipoxygenase activity is independent of its vitamin E content when exogenously added arachidonate was used as substrate.

Cytosolic phospholipase A2 (cPLA2) selectively catalyses the release of arachidonic acid from the sn-2 position of glycerophospholipids to produce prostaglandins and leukotrienes. In this study, vitamin E enrichment of rat heart myoblastic H9c2 cells caused an increase in the release of arachidonate during ionophore (A23187) stimulation. PLA2 activity in the cytosolic fraction was also enhanced but enzyme activity in the particulate fraction was not affected by this treatment. Immunoblotting analysis with a polyclonal anti-cPLA2 antibody showed an increased level of the enzyme in vitamin E-treated cells. Direct incorporation of vitamin E into lipid vesicles in the assay mixture resulted in modulation of enzyme activity in a biphasic manner. Pretreatment of cells with phorbol 12-myristate 13-acetate, a known activator of protein kinase C, synergistically potentiated the ionophore-induced arachidonate release in both the control and vitamin E-treated cells. However, vitamin E treatment by itself did not affect the protein kinase C activity, indicating that the vitamin E-induced activation of cPLA2 was independent of the protein kinase C cascade. Collectively, these results suggest that vitamin E potentiates arachidonate release through the direct and/or indirect modulation of cPLA2 activity.

This study was designed to evaluate the effects of dietary vitamin E and synthetic antioxidants on prostacyclin (PGI2) synthesis in isolated aorta segments and perfused hearts as well as thromboxane (TxA2) synthesis in thrombin-stimulated washed platelets. Weanling male New Zealand rabbits were fed a vitamin E-deficient basal diet or the basal diet supplemented with either all-rac-α-tocopherol acetate or propyl gallate or DPPD (N,N′-diphenyl-p-phenylenediamine). After 30 days on the diet, plasma tocopherol level, pyruvate kinase and liver microsomal NADPH oxidase were determined. DPPD but not propyl gallate prevented the development of myopathy. None of the synthetic antioxidants could substitute for vitamin E in decreasing enzymatic lipid peroxidation. PGI2release by the aorta was lowered in vitamin E deficiency and was highest with DPPD supplementation. In the Langendorff perfused heart, however, PGI2release was highest in the vitamin E-deficient group, possibly due to cardiomyopathy. TxA2synthesis by washed platelets challenged with thrombin was independent of the antioxidant status of the animal. The data showed that dietary antioxidants selectively affect eicosanoid synthesis in different tissues.

The key enzyme controlling prostaglandin (PG) catabolism, 15-hydroxyprostaglandin dehydrogenase (PGDH), was characterized in rabbit tissues. The apparent Michaelis constant (Km) using PGE2as substrate was found to be 5.3, 4.0, 4.0 and 7.1 μM for semitendinosus and soleus muscles, heart and kidney, respectively. The effect of dietary vitamin E depletion and repletion on the PGDH activity in these tissues was studied. Vitamin E deficiency caused an elevation of PGDH activity in rabbit skeletal muscles but not in the heart and kidney. Oral supplementation of tocopherol acetate to the deficient animals did not affect the skeletal muscle PGDH activity. A long period of refeeding (30 days) was required to suppress the elevated PGDH level to the control values. The data indicates a higher turnover of the PGs in the vitamin E-deficient rabbit skeletal muscles. The significance of such a change in connection to prostaglandin metabolism is discussed.

The effects of dietary vitamin E-depletion and repletion on the cyclooxygenase activity was studied in the semitendinosus muscle of rabbits. The prostaglandin (PG) cyclooxygenase system in rabbit semitendinosus muscle was characterized and found to depend on reduced glutathione and 1-epinephrine as cofactors. Skeletal muscle cyclooxygenase generates PGE2and PGF2α at a ratio approximately equal to one. Weanling New Zealand white rabbits were fed a vitamin E-deficient diet for 4 to 5 weeks. Controls received 50 mg dl-α-tocopherol acetate twice weekly. Vitamin E deficiency caused a significant reduction in cyclooxygenase activity but did not change the PGE2/PGF2α ratio. Oral supplementation of tocopherol acetate promptly returned the cyclooxygenase activity back to the control values within 48 hours. The decreased cyclooxygenase activity explains in part the increased level of arachidonic acid in skeletal muscle phospholipid previously reported in this laboratory. The possible involvement of decreased prostaglandin endoperoxides with platelet aggregation in vitamin E deficiency is discussed.