Relevance of CT for the detection of septic foci: diagnostic performance in a retrospective cohort of medical intensive care patients.

AIM: To analyse the diagnostic yield of computed tomography (CT) in septic patients from a medical intensive care unit (ICU). MATERIALS AND METHODS: A full-text search of the department's radiological information system (RIS) retrieved 227 body CT examinations undertaken to search for a septic focus in 2018 from medical ICU patients. CT reports were categorised according to the identified foci. Clinical and laboratory information was gathered. Data were analysed statistically using descriptive statistics, diagnostic test quality criteria, binomial tests and chi-square test. RESULTS: A total of 227 CT examinations from 165 septic patients detected 264 foci, which were distributed as follows: 58.3% (n=154/264) chest, 26.5% (n=70/264) abdomen, 5.3% (n=14/264) genitourinary system, and 9.8% (n=26/264) other body regions. In 15.9% (n=36/227) no focus was identified on CT. Based on CT reports, 37.5% (n=99/264) of foci were graded as certain, 18.9% (n=50/264) as likely, and 15.9% (n=42/264) as possible infectious sources. Septic foci were detected using CT with 75.8% sensitivity (95% confidence interval [CI] 69.6-81.9%) and 59.46% specificity (95% CI 42.9-76.1%). The positive predictive value was 90.6% (95% CI 86-95.2%), with a negative predictive value of 32.4% (95% CI 21-43.8%). CONCLUSION: The present results confirm that body CT is a suitable rule-in test for septic patients in medical intensive care, although it cannot reliably rule out a septic focus. Follow-up CT examinations may reveal a septic source in the further course of a patient's hospital stay.

Immuno-modulating properties of Tulathromycin in porcine monocyte-derived macrophages infected with porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive-stranded RNA virus that grows in macrophages and causes acute pneumonia in pigs. PRRSV causes devastating losses to the porcine industry. However, due to its high antigenic variability and poorly understood immunopathogenesis, there is currently no effective vaccine or treatment to control PRRSV infection. The common occurrence of PRRSV infection with bacterial infections as well as its inflammatory-driven pathobiology raises the question of the value of antibiotics with immunomodulating properties for the treatment of the disease it causes. The macrolide antibiotic Tulathromycin (TUL) has been found to exhibit potent anti-inflammatory and immunomodulating properties in cattle and pigs. The aim of this study was to characterize the anti-viral and immunomodulating properties of TUL in PRRSV-infected porcine macrophages. Our findings indicate that blood monocyte-derived macrophages are readily infected by PRRSV and can be used as an effective cellular model to study PRRSV pathogenesis. TUL did not change intracellular or extracellular viral titers, not did it alter viral receptors (CD163 and CD169) expression on porcine macrophages. In contrast, TUL exhibited potent immunomodulating properties, which therefore occurred in the absence of any direct antiviral effects against PRRSV. TUL had an additive effect with PRRSV on the induction of macrophage apoptosis, and inhibited virus-induced necrosis. TUL significantly attenuated PRRSV-induced macrophage pro-inflammatory signaling (CXCL-8 and mitochondrial ROS production) and prevented PRRSV inhibition of non-opsonized and opsonized phagocytic function. Together, these data demonstrate that TUL inhibits PRRSV-induced inflammatory responses in porcine macrophages and protects against the phagocytic impairment caused by the virus. Research in live pigs is warranted to assess the potential clinical benefits of this antibiotic in the context of virally induced inflammation and tissue injury.

Toll-like receptor 2 ligand, lipoteichoic acid is inhibitory against infectious laryngotracheitis virus infection in vitro and in vivo.

Lipoteichoic acid (LTA) is one of the pathogen associated molecular patterns (PAMPs) that activates toll-like receptor (TLR)2-cluster of differentiation (CD)14 signalling pathway. This recognition elicits antiviral responses that have been recorded against viruses of mammals although such responses have not been characterized adequately against avian viruses. In this investigation, we characterized the LTA induced antiviral responses against infectious laryntotracheitis virus (ILTV) infection in vitro and in vivo. We found that LTA is capable of up regulating mRNA expression of innate proteins in macrophages such as MyD88, iNOS and IL-1ß and reduces the ILTV plaques in vitro. Similarly, we found that LTA treatment of embryonic day 18 (ED18) eggs can lead to the antiviral response against pre-hatch ILTV infection in vivo and is associated with expansion of macrophage populations and expression of IL-1ß and MyD88 in the lung. The data highlight that LTA can be a potential innate immune stimulant that can be used against ILTV infection in chickens.

Short communication: expression of peptide YY, proglucagon, neuropeptide Y receptor Y2, and glucagon-like peptide-1 receptor in bovine peripheral tissues.

The role of distal gut signals in control of feed intake and metabolism in cattle has received scant attention. Peptide YY (PYY) and glucagon-like peptide-1, which are secreted from enteroendocrine cells of the distal gut in monogastrics have several functions, including regulation of energy balance. However, little is known of the tissue expression of these peptides and their receptors in cattle. The aim of the current study was to characterize the tissue distribution of PYY, neuropeptide Y receptor Y2 (Y2), proglucagon (GCG), and glucagon-like peptide-1 receptor (GLP1R) in various peripheral tissues of cattle. Four male 7-wk-old dairy calves were euthanized and 16 peripheral tissues were collected. Conventional PCR and quantitative real-time PCR were performed to confirm tissue expression and quantify the transcript abundance in various tissues. The results of conventional PCR revealed that mRNA for both PYY and Y2 was detectable in the rumen, abomasum, duodenum, jejunum, ileum, and colon but not in other tissues. Quantitative real-time PCR data demonstrated that PYY mRNA was 2- to 3-fold greater in the pancreas, kidney, and heart relative to the liver. By conventional PCR, GCG mRNA was detected in the abomasum, duodenum, jejunum, ileum, and colon and GLP1R mRNA was expressed in all gut segments, pancreas, spleen, and kidney. Quantitative real-time PCR data demonstrated that, relative to transcript abundance in the liver, GCG mRNA was 4- to 40-fold higher from abomasum to colon, and GLP1R mRNA was 50- to 300-fold higher from the rumen to colon, 14-fold greater in the pancreas, 18-fold higher in the spleen, and 166-fold greater in the kidney. The tissue distribution of PYY, GCG, and their receptors observed in the current study is, in general, consistent with expression patterns in monogastrics. The predominant expression of PYY, Y2, and GCG in the gut, and the presence of GLP1R in multiple peripheral tissues suggest a role for PYY in controlling gut functions and for GLP-1 in regulating multiple physiological functions in cattle.

When versatility matters: activins/inhibins as key regulators of immunity.

Activins and inhibins are members of the transforming growth factor-ß superfamily that have been considered crucial regulators of cell processes, such as differentiation, proliferation and apoptosis, in different cell types. Initial studies about the function of activin A in the immune system focused on the regulation of hematopoiesis in the bone marrow under homeostatic and inflammatory conditions. Recent data provide a more comprehensive understanding about the role of activins/inhibins in the immune system. Novel findings included in this review point out the important requirement of activin/inhibin signaling to maintain the balance between homeostatic and inflammatory signals that are required for the optimal development and function of immune cells. The purpose of this review is to highlight the versatile nature of activins/inhibins as key regulators of both the innate and adaptive immune responses.

Design, implementation and testing of an implantable impedance-based feedback-controlled neural gastric stimulator.

Functional neural gastrointestinal electrical stimulation (NGES) is a methodology of gastric electrical stimulation that can be applied as a possible treatment for disorders such as obesity and gastroparesis. NGES is capable of generating strong lumen-occluding local contractions that can produce retrograde or antegrade movement of gastric content. A feedback-controlled implantable NGES system has been designed, implemented and tested both in laboratory conditions and in an acute animal setting. The feedback system, based on gastric tissue impedance change, is aimed at reducing battery energy requirements and managing the phenomenon of gastric tissue accommodation. Acute animal testing was undertaken in four mongrel dogs (2 M, 2 F, weight 25.53 ± 7.3 kg) that underwent subserosal two-channel electrode implantation. Three force transducers sutured serosally along the gastric axis and a wireless signal acquisition system were utilized to record stimulation-generated contractions and tissue impedance variations respectively. Mechanically induced contractions in the stomach were utilized to indirectly generate a tissue impedance change that was detected by the feedback system. Results showed that increasing or decreasing impedance changes were detected by the implantable stimulator and that therapy can be triggered as a result. The implantable feedback system brings NGES one step closer to long term treatment of burdening gastric motility disorders in humans.

Comparative gastric motility study of Enterra ™ Therapy and neural gastric electrical stimulation in an acute canine model.

BACKGROUND: Gastric electrical stimulation (GES) is an avenue for treating gastroparesis and obesity by controlling gastric motility using electrically mediated gastric contractions. Neural gastrointestinal electrical stimulation (NGES) is a GES modality capable of producing strong lumen-occluding local gastric contractions. Conversely, Enterra ™ Therapy, a commercial implantable gastric electrical stimulator, has been utilized to treat symptoms of gastroparesis, but its nominal electrical parameters are not capable of generating lumen-occluding contractions. However, comparative studies between these two stimulation modalities are lacking. METHODS: Strain gauge transducers complemented by endoscopic monitoring have been utilized to register gastric contractions invoked with NGES and Enterra neurostimulators in four acute dogs. Mucosal and serosal electrode implantations, 'nominal' and 'maximum' electrical parameters, and longitudinal and transverse electrode placements have been tested with each neurostimulator type. KEY RESULTS: Strong lumen-occluding, circumferential contractions were induced with a wide variety of NGES parameters utilizing both transverse and longitudinal electrode configurations from the serosal side of the stomach. Similarly, local gastric contractions were observed with the Enterra neurostimulator programmed at its 'maximum' electrical parameters but only when utilizing transverse serosal electrode implantation. Under 'maximum' electrical parameters Enterra was not capable of producing registerable gastric contractions with longitudinally implanted serosal electrodes. Mucosal electrode implantations did not result in GES-invoked gastric contractions in both stimulation modalities. CONCLUSIONS & INFERENCES: Enterra Therapy is capable of producing gastric contractions under 'maximum' parameters and transverse electrode configuration. Neural gastrointestinal electrical stimulation produces stronger, lumen-occluding contractions under a wider range of electrode configurations and parameters.

Early biochemical and histological alterations in rat corticoencephalic cell cultures following metabolic damage and treatment with modulators of mitochondrial ATP-sensitive potassium channels.

The present study was aimed at characterizing alterations of the nucleotide content and morphological state of rat corticoencephalic cell cultures subjected to metabolic damage and treatment with modulators of mitochondrial ATP-dependent potassium channels (mitoK(ATP)). In a first series of experiments, in vitro ischemic changes of the contents of purine and pyrimidine nucleoside diphosphates and triphosphates were measured by high performance liquid chromatography (HPLC) and the corresponding histological alterations were determined by celestine blue/acid fuchsin staining. As an ischemic stimulus, incubation with a glucose-free medium saturated with argon was used. Ischemia decreased the levels of adenosine, guanine and uridine triphosphate (ATP, GTP, UTP) and increased the levels of the respective dinucleotides ADP and UDP, whereas the GDP content was not changed. Both 5-hydroxydecanoate (5-HD) and diazoxide failed to alter the contents of nucleoside diphosphates and triphosphates, when applied under normoxic conditions. 5-HD (30 microM) prevented the ischemia-induced changes of nucleotide and nucleoside levels. Diazoxide (300 microM), either alone or in combination with 5-hydroxydecanoate (30 microM) was ineffective. Pyruvate (5 mM) partially reversed the effects of ischemia or ischemia plus 2-deoxyglucose (20mM) in the incubation medium. Diazoxide (300 microM) and 5-HD (30 microM) had no effect in the presence of pyruvate (5mM) and 2-deoxyglucose (20mM). Staining the cells with celestine blue/acid fuchsin in order to classify them as intact, reversibly or profoundly injured, revealed a protective effect of 5-HD. When compared with 5-HD, diazoxide, pyruvate and 2-deoxyglucose had similar but less pronounced effects. In conclusion, these results suggest a protective role of 5-hydroxydecanoate on early corticoencephalic nucleotide and cell viability alterations during ischemia.

A novel technique for the isolation of Lewy bodies in brain.

Previously, immunohistochemical methods were primarily used to detect and provide indirect evidence on the composition of Lewy bodies, the pathological hallmark of Parkinson's disease. This was chiefly because there are very few procedures that describe the isolation of these structures. We report here a relatively simple method that we have developed for the exclusive isolation of Lewy bodies from brain tissue. The isolation of the Lewy bodies and subsequent evaluation of their components may furnish an insight into their role in the neurodegenerative mechanism(s) operating in the spectrum of Lewy body disorders.