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Years and Volumes

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Articles from this Volume

Mian Zhou, Subir R Maitra, and Ping Wang

Sepsis, septic shock and multiple organ failure continue to be the most common causes of death in noncardiac intensive care units. Despite advances in the management of trauma victims, the incidence of sepsis and septic shock has increased significantly over the past two decades.  Downregulation of vascular endothelial constitutive nitric oxide synthase (ecNOS) contributes to the vascular hyporesponsiveness in sepsis.  Circulating levels of adrenomedullin (AM) increase significantly in patients with septic shock, systemic inflammation response syndrome and after major surgery, but AM binding protein (AMBP-1) was significantly reduced in sepsis.  While co-administration of AM and the AMBP-1 maintains cardiovascular stability and reduces mortality in sepsis, it is unknown whether AM/AMBP-1 prevents endothelial cell dysfunction.  Zhou et al. (488-494) investigated this possibility in an animal model of sepsis.  Their results indicate that that AM/AMBP-1 preserves ecNOS and this mechanism may be responsible for the beneficial effect of AM/AMBP-1 in sepsis.

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Posted by Leah Caracappa on Sep 5, 2007 12:00 AM CDT
Andreas Arkudas, Jimmy Tjiawi, Oliver Bleiziffer, Lucia Grabinger, Elias Polykandriotis, Justus P Beier, Michael Stürzl, Raymund E Horch, and Ulrich Kneser

Cells transplanted in the body require sufficient supplies of oxygen and nutrients for survival.  Suboptimal initial vascularization limits the survival of cells in the center of large cellularized implants, but angigogenic factors may be used to shorten the time period between implantation and vascularization of matrices.  Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are two of the most extensively tested angioinductive growth factors in animal models.  Here, Arkudas et al. (480-487) evaluated the angiogenic effects of VEGF and bFGF immobilized in a fibrin-based drug delivery system in the arteriovenous loop (AVL) model.  VEGF and bFGF both induced absolute and relative vascular density as well as blood vessel sprouting.  Implanting vascular carriers into growth factor-loaded matrix volumes may allow efficient generation of axially vascularized, tissue-engineered composites.

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Posted by Leah Caracappa on Sep 4, 2007 12:00 AM CDT
Ulrich Matzner, Frank Matthes, Eva Herbst, Renate Lüllmann-Rauch, Zsuzsanna Callaerts-Vegh, Rudi D’Hooge, Cecilia Weigelt, Carl Eistrup, Jens Fogh, and Volkmar Gieselmann

Metachromatic Leukodystrophy (MLD) is a member of a family of genetic diseases known as leukodystrophies, which affect the growth, development and maintenance of myelin.  MLD is a lysosomal storage disease caused by a deficiency of arylsulfatase A (ASA), which leads to the accumulation and deposition of sulfatide in oligodendrocytes and Schwann cells.  The result is demyelination of the peripheral and central nervous system, which leads to neurological symptoms and premature death.  Enzyme replacement therapy is a putative treatment for MLD, however, repeated injection of human ASA (hASA) in ASA knock out mice elicits an immune response leading to treatment resistance, anaphylactic reactions and high mortality.  In contrast to ASA knockout mice, the majority of MLD patients is not completely ASA deficient, but expresses a low or normal ASA level with reduced specific activity or stability.  Therefore, knockout ASA animal models, currently the only available model for MLD, may not be truly representative of the patient population.  In this work, Matzner et al. (471-479) transgenically expressed an active site mutant of hASA in the knockout animals, which allowed tolerance to hASA and maintained the MLD-like phenotype.  This novel transgenic strain may be advantageous to assess the benefit and risk of long-term enzyme replacement therapy.

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Posted by Leah Caracappa on Sep 3, 2007 12:00 AM CDT
Jenny Nordquist, Anna-Stina Höglund, Holly Norman, Xiaorui Tang, Barry Dworkin, and Lars Larsson

Muscle wasting associated with long-term intensive care unit treatment has a negative effect on muscle function resulting in prolonged periods of rehabilitation and a decreased quality of life.  Skeletal muscle atrophy is mediated by a shift in the normal balance between protein synthesis and protein breakdown.  While potential molecular switches controlling this balance have been identified, knowledge regarding these signaling pathways is limited.  Here, Nordquist et al. (461-470) investigate the mechanisms involved in muscle wasting using a rat model to mimic conditions in an intensive care unit. While results show that ubiquitin ligases are up-regulated, differences exist between fast- and slow-twitch muscles, suggesting these muscles respond differently to muscle unloading signals. Future work using this model may allow for more detailed studies of muscle wasting, which may advance intensive care intervention for patients kept on a mechanical ventilator.

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Posted by Leah Caracappa on Sep 2, 2007 12:00 AM CDT
Arif Khan, Yogeshwer Shukla, Neetu Kalra, Maroof Alam, Manzoor Gatoo Ahmad, Seema Rashid Hakim, and Mohammad Owais

Throughout history garlic has been shown to possess potential health benefits.  The chemotherapeutic and antitumor activity associated with garlic has been attributed to the presence of various organosulfide based compounds including diallyl sulfide (DAS). This active component of garlic possesses strong anti-neoplastic properties against various forms of cancer.  Topical application is the most promising approach for local treatment of skin tumors.  More efficient delivery methods are necessary to ensure that drugs are effectively carried to their targets because topical delivery of small molecules tend to diffuse across the skin surface.  Topical liposome-based formulations have shown promise in this area and in the present study Arif et al. (443-451) evaluated the effects of liposomised-DAS against dimethyl benz (a) anthracene (DMBA)-induced skin papilloma. Results showed that liposomised-DAS could effectively delay the onset of tumorogenesis and reduce the cumulative numbers and size of tumor papillomas in treated mice. The promising chemo-preventive nature of liposomal DAS may form the basis for establishing effective means of controlling various forms of cancer including skin papilloma.

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Posted by Leah Caracappa on Aug 8, 2007 12:00 AM CDT
Roberto D Fanganiello, Andréa L Sertié, Eduardo M Reis, Erika Yeh, Nélio AJ Oliveira, Daniela F Bueno, Irina Kerkis, Nivaldo Alonso, Sérgio Cavalheiro, Hamilton Matsushita, Renato Freitas, Sergio Verjovski-Almeida, and Maria Rita Passos-Bueno

Craniosynostosis is a common malformation in which the sutures form prematurely. Early corrective surgery is necessary to allow proper brain and skull growth. As a result of continuous bone healing defects, several surgeries are usually necessary during childhood and puberty. Apert syndrome (AS) is a severe form of craniosynostosis caused by mutations in the fibroblast growth factor 2 receptor (FGFR2). The periosteum, a dense fibrous membrane covering bone surfaces may play a role in cranial bone regeneration but the contribution of the periosteum to AS and its cranial pathophysiology is unknown. Here, Fanganiello, Sertié et al. (422-442) observed that AS periosteal cells (harboring the FGFR2 p.Ser252Trp mutation) are more committed towards the osteblast lineage. Additionally, a global gene expression analysis on AS patients periosteal cells showed that several genes involved in cellular proliferation and extracellular matrix formation are differentially expressed when compared with control subjects. While additional studies are needed these results suggest that the periosteum may be involved in the pathophysiology of craniosynostosis.

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Posted by Leah Caracappa on Aug 7, 2007 12:00 AM CDT
Davide Sartini, Andrea Santarelli, Valentina Rossi, Gaia Goteri, Corrado Rubini, Domenico Ciavarella, Lorenzo Lo Muzio, and Monica Emanuelli

Squamous cell carcinoma is the most common type of cancer in the oral cavity, representing 90% of all oral cancers.  Treatment methods for oral squamous cell carcinoma (OSCC) usually include surgery or radiation treatment, with or without chemotherapy.  Despite advances in surgical techniques and therapies, the mortality rate of OSCC has shown little improvement over the last three decades.  The overall five-year survival rate of these patients is less than 50% and diagnostic delay seems to be responsible for this poor prognosis.  Abnormal expression of nicotinamide N-methyltransferase (NNMT), an enzyme involved in the biotransformation and detoxification of many xenobiotics, has been reported in various cancers.  Upregulation of NNMT is inversely related to tumor size, suggesting the enzyme may play a role in an initial step of malignant conversion.  Studying tumor and non-tumor tissues, Sartini et al. (415-421) found a correlation between NNMT enzyme gene upregulation and favorable prognosis in OSCC patients.  While the function of NNMT in cancer cell metabolism is still unclear, these data suggest that NNMT may serve as a therapeutic target and potential biomarker for oral squamous cell carcinoma, which may lead to earlier detection of this disease.

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Posted by Leah Caracappa on Aug 6, 2007 12:00 AM CDT
Birgit H Funke, Todd Lencz, Christine T Finn, Pamela DeRosse, G David Poznik, Alex M Plocik, John Kane, John Rogus, Anil K Malhotra, and Raju Kucherlapati

A significant portion of patients with 22q11 deletion syndrome (22q11DS) develop psychiatric disorders including schizophrenia and and other psychotic and affective symptoms. The gene/s responsible for this syndrome may also play a significant role in the etiology of nonsyndromic psychiatric disease. The primary candidate 22q11DS gene, TBX1, is involved in epithelial and mesenchymal interactions, a mechanism which is crucial for the development of a wide variety of organs including the forebrain, heart, face and limbs. TBX1 may therefore play a role in brain development and thus in 22q11DS-associated as well as nonsyndromic psychiatric disease. Funke et al. (407-414) tested whether variation in the TBX1 gene could be associated with psychotic and affective disorders relevant to 22q11DS in Caucasian patients. Results show that allele and haplotype frequencies were not significantly different between affected cases and controls.  Therefore, it is unlikely that the TBX1 gene plays a major role in the genetic etiology of nonsyndromic schizophrenia and other psychiatric disorders observed in 22q11DS. However, 22q11DS may still represent a genetic subclass of schizophrenia which is very similar but genetically distinct from the nonsyndromic form. In this case TBX1 may still contribute to the risk of developing psychiatric disease in patients with 22q11DS.

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Posted by Leah Caracappa on Aug 5, 2007 12:00 AM CDT
Posted by Leah Caracappa on Aug 4, 2007 12:00 AM CDT
Kathryn M Taylor, Helen E Morgan, Kathryn Smart, Normawati M Zahari, Sara Pumford, Ian O Ellis, John FR Robertson, and Robert I Nicholson

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Posted by Leah Caracappa on Aug 3, 2007 12:00 AM CDT
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