The multifaceted role of mast cells in joint inflammation and arthritis.

OBJECTIVE: To review current knowledge surrounding the role of mast cells in joint inflammation and arthritis. METHOD: Narrative review. RESULTS: Mast cells (MCs) are commonly observed in the synovium of the joint, particularly surrounding blood vessels and nerve endings. Some studies have reported increased MC number and degranulation in patients with osteoarthritis (OA). In two studies, MCs were the only immune cell type found in higher concentrations in synovium of OA patients compared to rheumatoid arthritis patients. Activation of MCs in OA includes signaling pathways such as immunoglobulin E/Fc epsilon Receptor 1 (IgE/FcεR1), immunoglobulin G/Fc gamma receptor (IgG/FcγR), complement, and toll-like cell surface receptor-mediated signaling, resulting in context-dependent release of either pro-inflammatory and/or anti-inflammatory mediators within the joint. Activation of MCs results in the release of pro-inflammatory mediators that ultimately contribute to inflammation of the synovium, bone remodeling, and cartilage damage. However, some studies have proposed that MCs can also exhibit anti-inflammatory effects by secreting mediators that inactivate pro-inflammatory cytokines such as interleukin 6 (IL-6). CONCLUSIONS: MCs may play a role in mediating synovial inflammation and OA progression. However, the mechanisms governing MC activation, the downstream pro- and/or anti-inflammatory effects, and their impact on osteoarthritis pathogenesis remains to be elucidated and requires extensive further study. Furthermore, it is important to establish the pathways of MC activation in OA to determine whether MCs exhibit varying phenotypes as a function of disease stage. Ultimately, such research is needed before understanding whether MCs could be targeted in OA treatments.

Transition milk stimulates intestinal development of neonatal Holstein calves.

Colostrum stimulates gastrointestinal development. Similar to colostrum, transition milk (TM; the first few milkings after colostrum) contains elevated nutrient levels and bioactive components not found in milk replacer (MR), albeit at lower levels than the first colostrum. We hypothesized that feeding neonatal calves TM, compared with MR, for 4 d following colostrum at birth would further stimulate intestinal development. Holstein bull calves were fed 2.8 L of colostrum within 20 min of birth, allocated to 1 of 11 blocks based on birth date and body weight (BW), randomly assigned to MR (n = 12) or TM (n = 11) treatments within block, and fed treatments 3 times per day. Milk from milkings 2, 3, and 4 (TM) of cows milked 2 times daily was pooled by milking number and fed at 1.89 L per feeding; milking 2 was fed at feedings 2 through 5, milking 3 at feedings 6 through 8, and milking 4 at feedings 9 through 12. TM was not pasteurized and contained 17% solids, 5% fat, 7% protein, 4% lactose, and 20 g of IgG per liter on average, whereas MR (as fed) contained 15% solids, 4% protein, 3% fat, 6% carbohydrate, and no IgG. Refusals were similar, so calves fed TM consumed 1.0 Mcal of metabolizable energy per day more than those fed MR. On the morning of d 5, calves were injected i.v. with 5 mg of bromodeoxyuridine per kg of BW and slaughtered 130 min later; then, intestinal sections were excised. Feeding TM, instead of MR, doubled villus length, villus width, villus to crypt ratio, and mucosal length in all intestinal sections, increased submucosal thickness 70% in the proximal and mid jejunum, and tended to increase submucosal thickness in duodenum and ileum. Mucosal surface area was also increased in both the ileum and mid jejunum when feeding TM by 19 and 36%, respectively. Treatment did not alter crypt depth. Bromodeoxyuridine labeling was increased 50% by TM compared with MR in the cells along the epithelium of the crypts and within the villi of all sections, indicating that TM increased cell proliferation compared with MR. Calves fed TM gained more BW than calves fed MR and had improved cough, fecal, nose, and ear scores. We conclude that feeding TM for 4 d following an initial feeding of colostrum stimulates villus, mucosal, and submucosal development in all sections of the small intestine in the first few days of life and improves health and growth.

Review: innovation through research in the North American pork industry.

This article involved a broad search of applied sciences for milestone technologies we deem to be the most significant innovations applied by the North American pork industry, during the past 10 to 12 years. Several innovations shifted the trajectory of improvement or resolved significant production limitations. Each is being integrated into practice, with the exception being gene editing technology, which is undergoing the federal approval process. Advances in molecular genomics have been applied to gene editing for control of porcine reproductive and respiratory syndrome and to identify piglet genome contributions from each parent. Post-cervical artificial insemination technology is not novel, but this technology is now used extensively to accelerate the rate of genetic progress. A milestone was achieved with the discovery that dietary essential fatty acids, during lactation, were limiting reproduction. Their provision resulted in a dose-related response for pregnancy, pregnancy maintenance and litter size, especially in maturing sows and ultimately resolved seasonal infertility. The benefit of segregated early weaning (12 to 14 days of age) was realized for specific pathogen removal for genetic nucleus and multiplication. Application was premature for commercial practice, as piglet mortality and morbidity increased. Early weaning impairs intestinal barrier and mucosal innate immune development, which coincides with diminished resilience to pathogens and viability later in life. Two important milestones were achieved to improve precision nutrition for growing pigs. The first involved the updated publication of the National Research Council nutrient requirements for pigs, a collaboration between scientists from America and Canada. Precision nutrition advanced further when ingredient description, for metabolically available amino acids and net energy (by source plant), became a private sector nutrition product. The past decade also led to fortuitous discoveries of health-improving components in ingredients (xylanase, soybeans). Finally, two technologies converged to facilitate timely detection of multiple pathogens in a population: oral fluids sampling and polymerase chain reaction (PCR) for pathogen analysis. Most critical diseases in North America are now routinely monitored by oral fluid sampling and prepared for analysis using PCR methods.

Effectiveness of a hospital-wide infection control programme on the incidence of healthcare-associated infections and associated severe sepsis and septic shock: a prospective interventional study.

OBJECTIVES: To evaluate whether a hospital-wide infection control programme (ICP) is effective at reducing the burden of healthcare-associated infections (HAIs) and associated severe sepsis/septic shock or death (severe HAIs). METHODS: Prospective, quasi-experimental study with two surveillance periods (September 2011 to August 2012; May 2013 to August 2014). Starting October 2012, the ICP included hand hygiene promotion and bundle implementation for common HAIs. We applied segmented mixed-effects Poisson regression and multi-state models. We reported adjusted incidence rate ratios (aIRR) and adjusted hazard ratios (aHR) with 95% confidence intervals (CI). RESULTS: Overall, 62 154 patients were under surveillance, with 1568 HAIs identified in 1170 patients (4.3 per 100 admissions) in the first and 2336 HAIs identified in 1711 patients (4.9 per 100 admissions) in the second surveillance period. No differences were found in the overall HAI incidence rates between the periods in the general wards (aIRR 1.29, 95% CI 0.78-2.15) and intensive care units (ICUs) (aIRR 0.59, 95% CI 0.27-1.31). However, the HAI incidence rate was declining in the ICUs after starting the ICP (aIRR 0.98, 95% CI 0.97-1.00 per 1-week increment), in contrast to general wards (aIRR 1.01, 95% CI 1.00-1.02). A reduction in severe HAIs (aIRR 0.13, 95% CI 0.05-0.32) and a lower probability of HAI-associated in-hospital deaths (aHR 0.56, 95% CI 0.31-0.99) were observed in the second period in the ICUs. CONCLUSIONS: There was no overall reduction in HAIs after implementation of the ICP. However, there was a significant reduction in severe HAIs in ICUs. Whether this difference was a consequence of the ICP or improvement in HAI case management is not clear.

[Aspects of pulmonary involvement in inflammatory bowel disease]. / Lungenbeteiligung bei chronisch-entzündlichen Darmerkrankungen.

The incidence of pulmonary manifestations of inflammatory bowel disease (IBD) appears to be much higher than previously assumed. In prospective studies, subclinical pulmonary interstitial infiltrates or pathological lung function were found in 40%-60% of IBD patients, both in children and adults. Pulmonary disorders can affect any part of the respiratory system, the most frequent pattern being inflammation of the large airways often associated with bronchiectasis. The differential diagnosis should include drug-related pulmonary disease and infectious causes when receiving immunosuppressive therapy. The diagnostic approach consists of a thorough history and clinical status as well as lung function tests including body plethysmography and high-resolution computed tomography of the thorax. Bronchoscopy with broncheoalveolar lavage and sample collection for histology as well as exclusion of pulmonary embolism may be indicated. Pulmonary disease in association with IBD can develop at any time during the course of IBD: in rare cases, symptoms can evolve even before gastrointestinal symptoms appear. On the other hand, there are frequent reports on the occurrence of pulmonary inflammation after proctocolectomy in patients with ulcerative colitis. The pathophysiologic background is largely unknown, but there seems to be an interaction between gastrointestinal and pulmonary inflammation. The mainstay of therapy are inhaled or systemic corticosteroids. Most patterns of pulmonary involvement in IBD respond well to corticosteroid therapy. Rarely, serious and persisting complications occur, such as strictures or stenosis of the large airways.

Mast Cells Exert Anti-Inflammatory Effects in an IL10-/- Model of Spontaneous Colitis.

Mast cells are well established as divergent modulators of inflammation and immunosuppression, but their role in inflammatory bowel disease (IBD) remains to be fully defined. While previous studies have demonstrated a proinflammatory role for mast cells in acute models of chemical colitis, more recent investigations have shown that mast cell deficiency can exacerbate inflammation in spontaneous colitis models, thus suggesting a potential anti-inflammatory role of mast cells in IBD. Here, we tested the hypothesis that in chronic, spontaneous colitis, mast cells are protective. We compared colitis and intestinal barrier function in IL10-/- mice to mast cell deficient/IL10-/- (double knockout (DKO): KitWsh/Wsh × IL10-/-) mice. Compared with IL10-/- mice, DKO mice exhibited more severe colitis as assessed by increased colitis scores, mucosal hypertrophy, intestinal permeability, and colonic cytokine production. PCR array analyses demonstrated enhanced expression of numerous cytokine and chemokine genes and downregulation of anti-inflammatory genes (e.g., Tgfb2, Bmp2, Bmp4, Bmp6, and Bmp7) in the colonic mucosa of DKO mice. Systemic reconstitution of DKO mice with bone marrow-derived mast cells resulted in significant amelioration of IL10-/--mediated colitis and intestinal barrier injury. Together, the results presented here demonstrate that mast cells exert anti-inflammatory properties in an established model of chronic, spontaneous IBD. Given the previously established proinflammatory role of mast cells in acute chemical colitis models, the present findings provide new insight into the divergent roles of mast cells in modulating inflammation during different stages of colitis. Further investigation of the mechanism of the anti-inflammatory role of the mast cells may elucidate novel therapies.

[Pneumonia in immunocompromised patients]. / Pneumonien bei immunsupprimierten Patienten.

Pneumonia occurs frequently in immunocompromised patients and often shows a complicated course of disease when compared to immunocompetent persons. The type of pathogen involved is directly associated with the type of immunosuppression and includes a wide variety of pathogens. Congenital and primary immunodeficiencies often appear during childhood. Acquired immunodeficiencies are most commonly caused by immunosuppressive medication. The concept of immunosuppression can be extended to patients with COPD or elderly patients because the variety of pathogens and specific features regarding frequency and course of the disease are similar to immunosuppressed patients. Computed tomography can provide an indication of the pathogen and is superior to the chest x­ray in this respect. Blood cultures, antigen and PCR tests are non-invasive diagnostic tools for pathogen diagnostics. Invasive tests include fiberoptic bronchoscopy and complete the diagnostic methods of identifying the causative pathogen.

[Eosinophilia in pulmonary infections]. / Eosinophilie bei pulmonalen Infektionen.

Eosinophilia can be caused by a variety of diseases including allergies, autoimmune diseases, vasculitides, dermatoses, malignancies and drug-induced side effects as well as parasitic and non-parasitic infections. In patients returning from the tropics parasitic infections are the most frequent cause of eosinophilia. The extent of eosinophilia can provide information about the type of pathogen. The diagnostic approach to eosinophilia in travelers returning from the tropics primarily includes three stool examinations for worm eggs and, if necessary, serological tests for helminths. Additionally, a chest x­ray, an ultrasound of the abdomen and an electrocardiogram (ECG) provide information about organ involvement. Recently, specialized laboratories use molecular techniques (multiplex PCR) to detect worm eggs and intestinal parasites in the stool, which provide a significantly higher sensitivity than traditional stool examination techniques. Cryptococcosis, endemic systemic mycoses (coccidioidomycosis, very rarely histoplasmosis) and invasive mould infections (Aspergillus fumigatus, Mucor spp.) are non-parasitic causes of eosinophilia in blood and bronchoalveolar lavage (BAL).

Early weaning stress induces chronic functional diarrhea, intestinal barrier defects, and increased mast cell activity in a porcine model of early life adversity.

BACKGROUND: Early life adversity (ELA) is a risk factor for development of gastrointestinal disorders later in life. The underlying mechanisms through which ELA and sex interact to influence disease susceptibility remains poorly understood. METHODS: Utilizing a porcine early weaning stress (EWS) model to mimic ELA, we investigated the long-term effects of EWS on functional diarrhea, ileal permeability, mast cell activity and mast cell relationship with enteric ganglia. KEY RESULTS: Juvenile and adult EWS pigs exhibited chronic, functional diarrhea (EWS 43.6% vs late wean control(LWC) 4.8%, P<.0001), increased intestinal permeability (2 fold increase EWS vs LWC, P<.0001), and mast cell numbers (at 7 weeks and 20 weeks ~1.6 fold increase EWS vs LWC, P<.05). Compared with EWS male castrates (Male-C), females EWS pigs exhibited more frequent diarrhea (58.8% vs 29.9%, P=.0016), and increased intestinal permeability (1-2 fold higher in EWS females, P<.001). Increased mast cell numbers and their enhanced co-localization with neuronal ganglia were observed in both Male-C and female EWS pigs; however, female pigs exhibited greater release of mast cell tryptase upon activation with c48/80 (~1.5 fold increase, P<.05), compared with Male-C pigs. CONCLUSIONS AND INFERENCES: These data demonstrate that pigs exposed to ELA exhibit increased vulnerability to functional diarrhea, intestinal permeability and mast cell activity. Further, these studies also showed that EWS female and Male-C pigs exhibited dimorphic responses to EWS with female piglets exhibited greater susceptibility and severity of diarrhea, intestinal permeability and mast cell tryptase release. Together, these findings mimic some of the key pathophysiologic findings in human functional GI disorders functional gastrointestinal disorders (FGIDs) suggesting that the EWS porcine model could be a valuable preclinical translational model for FGID research associated with ELA.

Early life adversity in piglets induces long-term upregulation of the enteric cholinergic nervous system and heightened, sex-specific secretomotor neuron responses.

BACKGROUND: Early life adversity (ELA) is a risk factor for the later-life onset of gastrointestinal (GI) diseases such as irritable bowel syndrome (IBS); however, the mechanisms are poorly understood. Here, we utilized a porcine model of ELA, early weaning stress (EWS), to investigate the influence of ELA on the development and function of the enteric nervous system (ENS). METHODS: Female and castrated male (Male-C) piglets were weaned from their sow either at 15 days of age (EWS) or 28 days of age (late weaning control, LWC). At 60 and 170 days of age, ileal mucosa-submucosa preparations were mounted in Ussing chambers and veratridine- and corticotropin releasing factor (CRF)-releasing factor-evoked short circuit current (Isc ) responses were recorded as indices of secretomotor neuron function. Enteric neuron numbers and the expression of select neurotransmitters and their receptors were also measured. KEY RESULTS: Compared with LWC pigs, female, but not Male-C EWS, pigs exhibited heightened veratridine-induced Isc responses at 60 and 170 days of age that were inhibited with tetrodotoxin and atropine. Ileum from EWS pigs had higher numbers of enteric neurons that were choline acetyltransferase positive. Markers of increased cholinergic signaling (increased acetylcholinesterase) and downregulated mucosal muscarinic receptor 3 gene expression were also observed in EWS pigs. CONCLUSIONS & INFERENCES: This study demonstrated that EWS in pigs induces lasting and sex-specific hypersensitivity of secretomotor neuron function and upregulation of the cholinergic ENS. These findings may represent a mechanistic link between ELA and lifelong susceptibility to GI diseases such as IBS.

Lung disease and ulcerative colitis--mesalazine-induced bronchiolitis obliterans with organizing pneumonia or pulmonary manifestation of inflammatory bowel disease?

Ulcerative colitis can be associated with numerous extraintestinal organ manifestations. Pulmonary disease in inflammatory bowel disease (IBD) is supposed to be a rare entity and has to be distinguished from infectious complications and side-effects of medications used in the treatment of IBD. We present the case of a 20-year-old male patient with ulcerative colitis and a 4-week history of respiratory symptoms, malaise, fever and respiratory insufficiency under a medication with mesalazine. Computed tomography showed bilateral subpleural consolidations, bronchoscopy revealed signs of acute bronchitis. The diagnostic work-up ruled out an infectious cause. Under the tentative diagnosis of a mesalazine-induced bronchiolitis obliterans with organizing pneumonia (BOOP) the medication with mesalazine was withdrawn and the patient received a corticosteroid trial. The symptoms quickly improved and prednisone was tapered and stopped after 6 months. Unexpectedly, lung function after complete resolution of respiratory symptoms revealed a residual obstructive ventilatory defect that might be due to an asymptomatic pulmonary manifestation of ulcerative colitis. A review of the literature shows that pulmonary manifestations in IBD as well as pulmonary toxicity of mesalazine might not be as rare as expected and should be included as differential diagnoses in the work-up of respiratory symptoms in patients with IBD. A pragmatic therapeutic approach is reasonable in critically ill patients as it is not always easy to distinguish both entities.

Early-life dietary spray-dried plasma influences immunological and intestinal injury responses to later-life Salmonella typhimurium challenge.

Increasing evidence supports the concept that early-life environmental influences, including nutrition and stress, have an impact on long-term health outcomes and disease susceptibility. The objective of the present study was to determine whether dietary spray-dried plasma (SDP), fed during the first 2 weeks post-weaning (PW), influences subsequent immunological and intestinal injury responses to Salmonella typhimurium challenge. A total of thirty-two piglets (age 16-17 d) were weaned onto nursery diets containing 0, 2·5 % SDP (fed for 7 d PW) or 5 % SDP (fed for 14 d PW), and were then fed control diets (without SDP), for the remainder of the experiment. At 34 d PW (age 50 d), pigs were challenged with 3 × 109 colony-forming units of S. typhimurium. A control group (non-challenged) that was fed 0 % SDP in the nursery was included. At 2 d post-challenge, the distal ileum was harvested for the measurement of inflammatory, histological and intestinal physiological parameters. S. typhimurium challenge induced elevated ileal histological scores, myeloperoxidase (MPO), IL-8 and TNF, and increased intestinal permeability (indicated by reduced transepithelial voltage (potential difference) and elevated 4 kDa fluorescein isothiocyanate dextran (FD4) flux rates). Compared with S. typhimurium-challenged controls (0 % SDP), pigs fed the 5 % SDP-14 d diet exhibited reduced ileal histological scores, MPO levels, IL-8 levels and FD4 flux rates. Pigs fed the 5 % SDP-14 d nursery diet exhibited increased levels of plasma and ileal TNF-α in response to the challenge, compared with the other treatments. These results indicate that inclusion of SDP in PW diets can have an influence on subsequent immunological and intestinal injury responses induced by later-life S. typhimurium challenge.

Interferon-α induced remission in three patients with eosinophilic granulomatosis and polyangiitis. A case study.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic small vessel vasculitis associated with asthma and eosinophilia. Optimal therapy for maintenance of remission is yet to be defined. We present a case-series of three patients with EGPA in whom IFN-α, an immunomodulatory cytokine induced remission, which was maintained even after discontinuation of the drug. In all patients (ages 60, 51, and 50 years), remission was associated with normalisation of eosinophil counts and IgE-levels. Moreover, the patients remained in remission for one to four years. Two patients did not need further immunosuppression, one patient required low dose maintenance therapy. Although reversible side effects occur, IFN-α-therapy induces long-term remission of EGPA even after discontinuation of treatment.

Early postnatal kinetics of colostral immunoglobulin G absorption in fed and fasted piglets and developmental expression of the intestinal immunoglobulin G receptor.

The transport of IgG across the epithelial barrier and into the circulation is achieved in part by the neonatal Fc receptor (FcRn), and this provides passive immunity to the neonate. The objective of this study was to determine the effect of time and feeding state on IgG absorption, intestinal morphology, and expression of IgG receptors in the first 24 h postbirth. Twenty newborn pigs were obtained immediately after birth and fitted with umbilical arterial catheters. Colostrum was manually collected from 12 lactating sows and centrifuged to produce defatted colostrum. Piglets were orally gavaged with 32 mL defatted colostrum per kilogram of BW (given in 2 doses 1 h apart) either at birth (0 h) or at 12 h postbirth under either fed (milk replacer) or fasted (saline solution) condition (n=5 per treatment). A fifth reference group (n=5) was euthanized at birth. Blood was collected every hour for the first 2 h immediately after the catheter was inserted and then every 4 h until 12 h (i.e., 0, 1, 2, 4, 8, and 12 h) for the treatment in which the defatted colostrum was given right after birth. For the treatment gavaged at 12 h postbirth, the sampling schedule was at 12, 13, 14, 16, 20, and 24 h. At 12 h postgavage, pigs were euthanized and jejunum tissues were collected for measurement of villi height, width, crypt depth, and gene expression of FcRn and ß2-microglobulin (ß2M) via reverse transcription PCR. Pig serum IgG concentration was determined by radial immunodiffusion. Data were analyzed according to a 2×2 factorial arrangement of treatments (0 h-fed, 0 h-fasted, 12 h-fed, and 12 h-fasted). There was no interaction between the time (age) of offering defatted colostrum (0 vs. 12 h) and nutritional state (fed vs. fasted) for any of the measurements, and there were no differences between fed and fasted pigs. Serum IgG concentrations increased progressively with time. Piglets offered defatted colostrum at 0 h had greater (P<0.05) overall IgG absorption and greater (P<0.05) villi height than those offered defatted colostrum at 12 h postbirth. Abundance of mRNA of FcRn and ß2M were normalized to glyceraldehyde-3-phosphate dehydrogenase. Abundance of FcRn transcript was lower (P=0.006) in pigs euthanized at birth compared with those euthanized at 12 h of age. In conclusion, the effects of delayed offering of defatted colostrum and age-dependent changes in IgG receptor were modest over the first 24 h of life.

High dietary iron reduces transporters involved in iron and manganese metabolism and increases intestinal permeability in calves.

A 56-d experiment was designed to examine the effect of high dietary Fe on metal transporters involved in Fe and Mn metabolism. Fourteen weaned Holstein calves were stratified by weight and randomly assigned to 1 of 2 treatments: 1) no supplemental Fe (normal Fe) or 2) 750mg of supplemental Fe/kg of dry matter (high Fe). Jugular blood was collected on d 0, 35, and 56. At the end of the trial, 6 calves per treatment were humanely killed and duodenal scrapings, liver, and heart were collected for analysis. Additionally, proximal duodenum was mounted on Ussing chambers to assess intestinal barrier integrity. Calves receiving high dietary Fe displayed decreased transepithelial resistance and increased apical-to-basolateral flux of radiolabeled mannitol, suggesting that high Fe created increased intestinal permeability. Feeding calves a diet high in Fe decreased average daily gain, dry matter intake, and feed efficiency. Hemoglobin and serum Fe concentrations did not differ due to dietary treatment. High dietary Fe increased concentrations of Fe in the liver, but did not affect heart or duodenal Fe concentrations. Duodenal Mn concentrations were lowered by feeding a high Fe diet, but liver and heart Mn concentrations were not affected. As determined by real-time reverse transcription PCR, relative hepatic expression of the gene that encodes the Fe regulatory hormone hepcidin was 5-fold greater in calves fed high dietary Fe. Hepcidin is released in response to increased Fe status and binds to the Fe export protein ferroportin causing ferroportin to be degraded, thereby reducing dietary Fe absorption. Confirmation of this result was achieved through Western blotting of duodenal protein, which revealed that ferroportin was decreased in calves fed high dietary Fe. Duodenal protein expression of divalent metal transporter 1 (DMT1), a Fe import protein that can also transport Mn, tended to be reduced by high dietary Fe. Transcript levels of several genes involved in Fe metabolism in liver and duodenum were unchanged by treatment. In summary, feeding calves a diet high in Fe induced a signal cascade (hepcidin) designed to reduce absorption of Fe (via reduced protein expression of ferroportin and DMT1) in a manner similar to that reported in rodents. Additionally, reduced levels of DMT1 protein appeared to decrease duodenal Mn, suggesting that Mn may also be a substrate for DMT1 in cattle.

[Interferon-alpha as treatment option in severe persistent uncontrolled bronchial asthma: an open label study]. / Interferon-alpha als Therapieoption bei der Behandlung des schwergradig persistierenden, unkontrollierten Asthma bronchiale: Eine offene Studie.

BACKGROUND: The purpose of this study was to evaluate the long-term safety and therapeutic effects of IFN-alpha in patients with severe persistent uncontrolled asthma on long-term oral glucocorticoid (GC) treatment. PATIENTS AND METHODS: The study included 16 patients (2 male, 14 female; age 39 years [range: 24 - 63]) with severe persistent asthma. Diagnosis and severity classification of asthma were established according to the guidelines of the "Deutsche Atemwegsliga". Eight patients stopped the therapy within 7 months due to side effects (n = 3), costs not covered by health insurance (n = 2), non-compliance (n = 2), and change of residence (n = 1). 8 patients (8 female, age 49 years [range: 35 - 68], duration of disease 16 years [range: 5 - 24]) were treated for at least 12 months with IFN-alpha (9 microg) 3 times/week. All patients were on oral glucocorticoids (GCs) for more than 5 years (average dose 17.5 [range: 5.0 - 64.0] mg/d). Clinical signs, lung function, need for reliever medication, number of emergency visits and hospitalisations and diary were assessed prior to and after 12 months of treatment. Data are given as percent of normal or median [range]. RESULTS: IFN-alpha improved lung function after 12 months: FEV1 64 vs. 75 %; FEV1/IVC 76 vs. 89 %; RV 153 % vs. 129 %; Rtot 193 vs. 111 % and morning PEF by 50 - 190 L/min. IFN-alpha also significantly reduced the use of reliever medication (10 [2 - 20] vs. 1 [0 - 3] puffs/d), nocturnal awakening (11 [4 - 30] vs. 1 [0 - 5]/month), emergency visits (7 [2 - 15] vs. 0 [0 - 5]/month) and hospitalisations (4 [1 - 8] vs. 0 [0 - 5]/year). In 5 patients the asthma attacks and nightly disturbances disappeared completely. The improvements were achieved despite a tapering of the oral GCs in all patients from 17.5 (5.0 - 64.0) to 2 (0 - 16) mg/d. In 5 patients GC treatment could be discontinued. The number of blood eosinophils decreased from 0.46 to 0.28 Gpt/L. Adverse events were transient and usually decreased within 3 to 4 weeks. Two patients developed an autoimmune thyreoiditis. CONCLUSION: In severe persistent, uncontrolled, and GC-dependent asthma, treatment with IFN-alpha leads to sustained clinical improvement and allows the reduction or discontinuation of oral GCs. Severe side effects may occur in isolated cases.

Nutritional value for swine of extruded corn and corn fractions obtained after dry milling.

The experiment was designed to assess whether corn fractions or extrusion of corn can result in feed ingredients with a greater nutritional value than corn. Corn grain (8.0% CP, 0.21% P, 9.8% NDF) was processed by extrusion (82.8 degrees C, 345 kPa steam pressure for 12 s) or by dry milling to derive fractions rich in germ (13.1% CP, 1.19% P, 17.2% NDF), hulls (8.1% CP, 0.27% P, 32.6% NDF), and endosperm, namely tails (6.6% CP, 0.07% P, 3.6% NDF) and throughs (7.4% CP, 0.15% P, 4.5% NDF). Relative recovery in each fraction was 16, 20, 44, and 20%, respectively. Ileal digestibility of DM, P, and amino acids was determined using diets containing 7.0% CP from soybean meal and 5.3% CP from one of the test products. To allow for determination of standardized ingredient, ileal digestibility, basal endogenous AA losses were determined using a protein-free diet (74.6% cornstarch and 18.7% sucrose). Soybean meal ileal digestibility was determined using a diet (12.3% CP) based on soybean meal (23.3%). Eight barrows (27 +/- 2 kg) fitted with T-cannulas were fed 8 experimental diets (5-d adaptation and 2-d collection period) such that each diet was evaluated in at least 5 barrows. Relative to corn (77.9 +/- 1.2%), ileal digestibility of DM was greater for extruded corn (82.5%; P = 0.02), tails (85.9%; P < 0.01), and throughs (85.0%; P < 0.01), but it was lower for hulls (62.2%; P < 0.01) and germ (51.1%; P < 0.01). For P, corn (41.6 +/- 9.5%), throughs (47.2%), and hulls (57.3%) had similar ileal digestibility, but germ (7.9%) had lower ileal digestibility (P = 0.02) than corn; tails (27.6%) and extruded corn (23.5%) were not different from corn or germ but were lower than throughs and hulls. For total AA, corn (84.7 +/- 2.4%), throughs (84.3%), and hulls (85.8%) had similar ileal digestibility, but germ (76.6%) had lower ileal digestibility (P < 0.01) than corn; tails (82.0%) and extruded corn (81.7%) were intermediate. In conclusion, germ and hulls have a low ileal DM digestibility; germ also has low AA and P digestibility. Extrusion improved the ileal DM digestibility of corn. To maximize the ileal digestibility, removal of germ and hull from corn or extrusion of corn may thus be of interest.

Selecting soybean meal characteristics preferred for swine nutrition.

As environmental constraints become more important issues for the animal industry, selecting feed ingredients that yield good animal performance but also minimize environmental impact of animal production becomes critical. The objective of this research was to identify which compositional features would be desirable for soybean meal to maximize nutritional value and minimize animal waste. Eight soybean samples were selected from a database of 72, such that maximal variability for CP, NDF, and ADF content was obtained. Samples were subsequently processed into meal using standardized procedures. In Experiment 1, 8 cannulated pigs were used to determine ileal digestibility following a Latin square design. In Experiment 2, 5 of the samples were used in complete feeds and 10 pigs were used in a crossover Latin square design to determine the total tract digestibility, odorants in fresh and 5-d-old manure, and ammonia emission from manure. Differences up to 6% in ileal DM digestibility and 8% in ileal CP digestibility were observed. This difference was reduced to 1.1% for total tract DM digestibility and 4% for total tract CP digestibility. Differences in odorant concentration were 3-fold and for in vitro ammonia emission were 42%. The only compositional variable with a significant effect on digestibility was stachyose, which negatively affected ileal digestibility of DM (r = -0.80, P = 0.02) and energy (r = -0.73, P = 0.04). None of the compositional variables measured affected ileal CP digestibility. Ileal CP digestibility, however, was correlated with estimated CP fermentation in the large intestine (r = -0.86, P = 0.06) and with in vitro ammonia emission after 48 h (r = -0.81, P = 0.09). In conclusion, nutritionally relevant variability exists in soy varieties. Low stachyose content is important for maximizing ileal energy digestibility of soybean meal. Although no compositional variable was identified that explained differences in ileal CP digestibility, maximizing ileal CP digestibility is of interest for maximizing the nutritional value of soybean meal and possibly for reducing ammonia and odor emissions.

Diet and evaluators affect perception of swine waste odor: an educational demonstration.

An educational program was developed for extension agents, faculty, and graduate students to illustrate the effect of diet composition on odor from swine manure. Participants in this program first received a 2-h detailed review on odorous compounds in manure and the effect of diet on odor. For the second portion of the training, nine manure samples were used from pigs fed diets formulated with feed ingredients predicted to have different effects on odor emission or a nutritionally adequate corn-soybean meal diet. Participants were instructed to rate the odor from these samples for pleasantness, irritation, and intensity on a scale of 0 (best) to 8 (worst), using manure from the corn-soybean meal fed pig as the reference with a score defined as 4 for each variable. Results obtained were summarized and discussed before concluding the program. Participants were Cooperative Extension Agents (n = 13) with swine responsibilities and graduate students and faculty (n = 8). The manure from the diet with the worst odor scores (1% garlic) was rated at 70% more odorous across the three odor variables (P < 0.05) than the diet with the least odorous manure (purified diet). Even though a reference sample was used, individual participants differed in their perception of irritation across samples (P < 0.05), ranging in average score across diets from 2.4 (moderately better than reference) to 5.0 (slightly worse than reference). With extension agents, a 1 to 7 scale (very interesting to not at all interesting) was used for evaluation of the training session. Participants found the material to be interesting (mean = 1.7, SD = 0.7) and the training exercise to be well organized and coherent in its presentation (mean = 1.8, SD = 0.7). Participants enjoyed this training and learned that differences in odor are achievable through altering diet composition, and that the response to swine odor depends on individual odor perception.

The nutritional value of degermed, dehulled corn for pigs and its impact on the gastrointestinal tract and nutrient excretion.

Three experiments were designed to assess the feeding value and potential environmental benefits of feeding degermed, dehulled corn, a low fiber by-product originating from the corn dry milling process, to pigs. Twelve 27-kg (SE = 0.8) barrows were used in Exp. 1 to measure the apparent fecal digestibility of DM, GE and N of degermed, dehulled corn compared with corn grain. Two diets were formulated to contain either 96.4% of degermed, dehulled corn or corn grain plus supplemental vitamins and minerals. Digestibilities of DM, GE, and N were greater in degermed, dehulled corn (96.2, 96.0, and 93.6%, respectively) compared with corn grain (89.0, 89.0, and 78.4%, respectively) (P < 0.01). Overall, a 67 and 29% reduction in DM and N excretion, respectively, was observed. In Exp. 2, eight 70-kg (SE =1.8) barrows were surgically fitted with ileal cannulae and fed the same diets as in Exp. 1, to measure the ileal digestibility of nutrients in degermed, dehulled corn. Ileal digestibility of DM, energy, and N was 13, 15, and 7% greater in degermed, dehulled corn (P < 0.05). Apparent ileal digestibility coefficients of leucine, methionine, and phenylalanine were greater in degermed, dehulled corn compared with corn grain (P < 0.05) while a trend for a lower tryptophan digestibility in degermed, dehulled corn was observed (P = 0.067). In Experiment 3, 96 nursery pigs with an initial average BW of 8.8 kg (SE = 0.08), fed a starter diet formulated with degermed, dehulled corn or corn grain as the major grain source, were used in a 28-d growth performance study. At the end of the study, 24 pigs (1 pig per pen) were sacrificed and gastrointestinal tract measurements were taken. Daily growth rates of pigs were the same between diets (0.64 kg/d). A trend for reduced feed intake (P = 0.073) in pigs fed degermed, dehulled corn led to a 4% improvement in gain to feed (P < 0.05). Feeding degermed, dehulled corn had no effect on gut fill, gastrointestinal tract weight, or liver weight (P > 0.05). Ileal villus lengths and crypt depths were not affected by feeding degermed, dehulled corn although ileal villus widths were greater in pigs fed corn grain. Results from these trials suggest that corn processed to remove poorly digestible fiber fractions provides more digestible nutrients than corn grain. As a result, degermed, dehulled corn reduces fecal and N excretion, thus providing a means to reduce nutrient excretion.