Mesenteric Vascular Dysregulation and Intestinal Inflammation Accompanies Experimental Spinal Cord Injury

Cervical and high thoracic spinal cord injury (SCI) drastically impairs autonomic nervous system function. Individuals with SCI at thoracic spinal-level 5 (T5) or higher often present cardiovascular disorders that include resting systemic arterial hypotension. Gastrointestinal (GI) tissues are critically dependent upon adequate blood flow and even brief periods of visceral hypoxia triggers GI dysmotility. The aim of this study was to test the hypothesis that T3-SCI induces visceral hypoperfusion, diminished postprandial vascular reflexes and concomitant visceral inflammation. We measured in vivo systemic arterial blood pressure and superior mesenteric artery (SMA) and duodenal blood flow in anesthetized T3-SCI rats at 3 days and 3 weeks post-injury either fasted or following enteral feeding of a liquid mixed-nutrient meal (Ensure™). In separate cohorts of fasted T3-SCI rats, markers of intestinal inflammation were assayed by qRT-PCR. Our results show that T3-SCI rats displayed significantly reduced SMA blood flow under all experimental conditions (p\u3c0.05). Specifically, the anticipated elevation of SMA blood flow in response to duodenal nutrient infusion (postprandial hyperemia) was either delayed or absent after T3-SCI. The dysregulated SMA blood flow in acutely-injured T3-SCI rats coincides with abnormal intestinal morphology and elevation of inflammatory markers, all of which resolve after 3 weeks. Specifically, Icam1, Ccl2 (MCP-1) and Ccl3 (MIP-1α) were acutely elevated following T3-SCI. Our data suggest that arterial hypotension diminishes mesenteric blood flow necessary to meet mucosal demands at rest and during digestion. The resulting GI ischemia and low-grade inflammation may be an underlying pathology leading to GI dysfunction seen following acute T3-SCI

Dynamic Passivation with BSA Overcomes LTCC Mediated Inhibition of PCR

The increasing use of low temperature co-fired ceramic (LTCC) for the fabrication of biological microfluidic devices necessitates further research on LTCC biocompatibility. In this study we explore the inhibitory effect of DuPont\u27s 951 LTCC on Polymerase Chain Reaction (PCR), and demonstrate a novel mechanism to increase biocompatibility between LTCC and PCR with the addition of a common passivation substance, bovine serum albumin (BSA). We show that DuPont\u27s 951 LTCC binds negatively charged proteins including BSA and ovalbumin (OVA). This is a significant discovery as proteins (enzymes) are an essential component of most biological reactions, and a frequent addition to microfluidic devices. A proposed model for LTCC inhibition of PCR by enzyme adsorption is presented

An analysis of connected replenishment operational data: the distribution of CONREP service time

http://www.archive.org/details/analysisofconnec00beseLieutenant Commander, United States NavyApproved for public release; distribution is unlimited

Altered Physiology of Gastrointestinal Vagal Afferents Following Neurotrauma

The adaptability of the central nervous system has been revealed in several model systems. Of particular interest to central nervous system-injured individuals is the ability for neural components to be modified for regain of function. In both types of neurotrauma, traumatic brain injury and spinal cord injury, the primary parasympathetic control to the gastrointestinal tract, the vagus nerve, remains anatomically intact. However, individuals with traumatic brain injury or spinal cord injury are highly susceptible to gastrointestinal dysfunctions. Such gastrointestinal dysfunctions attribute to higher morbidity and mortality following traumatic brain injury and spinal cord injury. While the vagal efferent output remains capable of eliciting motor responses following injury, evidence suggests impairment of the vagal afferents. Since sensory input drives motor output, this review will discuss the normal and altered anatomy and physiology of the gastrointestinal vagal afferents to better understand the contributions of vagal afferent plasticity following neurotrauma

Postprandial glycemic response to a high-protein diabetes-specific nutritional shake compared to isocaloric instant oatmeal in people with type 2 diabetes: a randomized, controlled, crossover trial

IntroductionMinimizing postprandial glucose response is an important goal for overall diabetes management. Diabetes-specific nutritional shakes (DSNS) have been clinically shown to minimize postprandial glucose response in people with type 2 diabetes (T2DM) compared to high-glycemic foods. However, it is unknown how a high-protein, low-fat DSNS impacts the GLP-1 response.MethodsWe tested the postprandial glucose, insulin, and GLP-1 response to a high-protein, low-fat diabetes-specific nutritional shake (DSNS-HP) compared to isocaloric instant oatmeal (IOM) in a randomized, controlled, crossover study in adults with T2DM (n = 24). Participants were randomly selected to receive IOM or DSNS-HP on two test days. Glucose, insulin, and total GLP-1 concentration were measured at baseline and 15, 30, 45, 60, 90, 120, 180, and 240 min postprandially.ResultsCompared to IOM, the glucose-positive area under the curve (pAUC) was significantly lower (P = .021). DSNS-HP significantly increased GLP-1 pAUC response by 213% (P <.001) with a corresponding increase in insulin pAUC (P = .033) compared to IOM.DiscussionA high-protein, low-fat DSNS leads to favorable changes in GLP-1 response and is a suitable option to minimize blood glucose response in people with type 2 diabetes

Development of OTM Syngas Process and Testing of Syngas Derived Ultra-clean Fuels in Diesel Engines and Fuel Cells

This topical report summarizes work accomplished for the Program from November 1, 2001 to December 31, 2002 in the following task areas: Task 1: Materials Development; Task 2: Composite Development; Task 4: Reactor Design and Process Optimization; Task 8: Fuels and Engine Testing; 8.1 International Diesel Engine Program; 8.2 Nuvera Fuel Cell Program; and Task 10: Program Management. Major progress has been made towards developing high temperature, high performance, robust, oxygen transport elements. In addition, a novel reactor design has been proposed that co-produces hydrogen, lowers cost and improves system operability. Fuel and engine testing is progressing well, but was delayed somewhat due to the hiatus in program funding in 2002. The Nuvera fuel cell portion of the program was completed on schedule and delivered promising results regarding low emission fuels for transportation fuel cells. The evaluation of ultra-clean diesel fuels continues in single cylinder (SCTE) and multiple cylinder (MCTE) test rigs at International Truck and Engine. FT diesel and a BP oxygenate showed significant emissions reductions in comparison to baseline petroleum diesel fuels. Overall through the end of 2002 the program remains under budget, but behind schedule in some areas

Metal ions in macrophage antimicrobial pathways: emerging roles for zinc and copper

The immunomodulatory and antimicrobial properties of zinc and copper have long been appreciated. In addition, these metal ions are also essential for microbial growth and survival. This presents opportunities for the host to either harness their antimicrobial properties or limit their availability as defence strategies. Recent studies have shed some light on mechanisms by which copper and zinc regulation contribute to host defence, but there remain many unanswered questions at the cellular and molecular levels. Here we review the roles of these two metal ions in providing protection against infectious diseases in vivo, and in regulating innate immune responses. In particular, we focus on studies implicating zinc and copper in macrophage antimicrobial pathways, as well as the specific host genes encoding zinc transporters (SLC30A, SLC39A family members) and CTRs (copper transporters, ATP7 family members) that may contribute to pathogen control by these cells

X-Ray Fluorescence Microscopy Reveals Accumulation and Secretion of Discrete Intracellular Zinc Pools in the Lactating Mouse Mammary Gland

The mammary gland is responsible for the transfer of a tremendous amount of zinc ( approximately 1-3 mg zinc/day) from maternal circulation into milk during lactation to support the growth and development of the offspring. When this process is compromised, severe zinc deficiency compromises neuronal development and immune function and increases infant morbidity and/or mortality. It remains unclear as to how the lactating mammary gland dynamically integrates zinc import from maternal circulation with the enormous amount of zinc that is secreted into milk.Herein we utilized X-ray fluorescence microscopy (XFM) which allowed for the visualization and quantification of the process of zinc transfer through the mammary gland of the lactating mouse. Our data illustrate that a large amount of zinc first accumulates in the mammary gland during lactation. Interestingly, this zinc is not cytosolic, but accumulated in large, discrete sub-cellular compartments. These zinc pools were then redistributed to small intracellular vesicles destined for secretion in a prolactin-responsive manner. Confocal microscopy identified mitochondria and the Golgi apparatus as the sub-cellular compartments which accumulate zinc; however, zinc pools in the Golgi apparatus, but not mitochondria are redistributed to vesicles destined for secretion during lactation.Our data directly implicate the Golgi apparatus in providing a large, mobilizable zinc storage pool to assist in providing for the tremendous amount of zinc that is secreted into milk. Interestingly, our study also provides compelling evidence that mitochondrial zinc pools expand in the mammary gland during lactation which we speculate may play a role in regulating mammary gland function

Pseudorabies Virus Infected Porcine Epithelial Cell Line Generates a Diverse Set of Host MicroRNAs and a Special Cluster of Viral MicroRNAs

Pseudorabies virus (PRV) belongs to Alphaherpesvirinae subfamily that causes huge economic loss in pig industry worldwide. It has been recently demonstrated that many herpesviruses encode microRNAs (miRNAs), which play crucial roles in viral life cycle. However, the knowledge about PRV-encoded miRNAs is still limited. Here, we report a comprehensive analysis of both viral and host miRNA expression profiles in PRV-infected porcine epithelial cell line (PK-15). Deep sequencing data showed that the ∼4.6 kb intron of the large latency transcript (LLT) functions as a primary microRNA precursor (pri-miRNA) that encodes a cluster of 11 distinct miRNAs in the PRV genome, and 209 known and 39 novel porcine miRNAs were detected. Viral miRNAs were further confirmed by stem-loop RT-PCR and northern blot analysis. Intriguingly, all of these viral miRNAs exhibited terminal heterogeneity both at the 5′ and 3′ ends. Seven miRNA genes produced mature miRNAs from both arms and two of the viral miRNA genes showed partially overlapped in their precursor regions. Unexpectedly, a terminal loop-derived small RNA with high abundance and one special miRNA offset RNA (moRNA) were processed from a same viral miRNA precursor. The polymorphisms of viral miRNAs shed light on the complexity of host miRNA-processing machinery and viral miRNA-regulatory mechanism. The swine genes and PRV genes were collected for target prediction of the viral miRNAs, revealing a complex network formed by both host and viral genes. GO enrichment analysis of host target genes suggests that PRV miRNAs are involved in complex cellular pathways including cell death, immune system process, metabolic pathway, indicating that these miRNAs play significant roles in virus-cells interaction of PRV and its hosts. Collectively, these data suggest that PRV infected epithelial cell line generates a diverse set of host miRNAs and a special cluster of viral miRNAs, which might facilitate PRV replication in cells

Genome sequence of a pathogenic isolate of monkey B virus (species Macacine herpesvirus 1)

The only genome sequence for monkey B virus (BV; species Macacine herpesvirus1) is that of an attenuated vaccine strain originally isolated from a rhesus monkey (BVrh). Here we report the genome sequence of a virulent BV strain isolated from a cynomolgus macaque (BVcy). The overall genome organization is the same, although sequence differences exist. The greatest sequence divergence is located in non-coding areas of the long and short repeat regions. Like BVrh, BVcy has duplicated Ori elements and lacks an ORF corresponding to the γ34.5 gene of herpes simplex virus. Nine of ten miRNAs and the majority of ORFs are conserved between BVrh and BVcy. The most divergent genes are several membrane-associated proteins and those encoding immediate early proteins