Biologic therapy for amyloid A amyloidosis secondary to rheumatoid arthritis treated with interleukin 6 therapy: Case report and review of literature.

INTRODUCTION: Secondary amyloidosis is a rare complication of rheumatoid arthritis (RA) that is histologically characterized by the deposition of amyloid fibrils in target organs, such as the kidneys and gastrointestinal tract. Controlling the inflammatory response is essential to prevent organ dysfunction in amyloid A (AA) amyloidosis secondary to RA, and no clear treatment strategy exists. PATIENT CONCERNS AND DIAGNOSIS: A 66-year-old woman with RA, who had been treated with disease-modifying anti-rheumatic drugs for 1 year, presented with recurrent abdominal pain and prolonged diarrhea. Endoscopy showed chronic inflammation, and colon tissue histology confirmed AA amyloidosis. INTERVENTIONS AND OUTCOMES: After tocilizumab therapy was begun, her diarrhea and abdominal pain subsided, and articular symptoms improved. Biologic drugs for RA have been used in patients with secondary AA amyloidosis, including tumor necrosis factor and Janus kinase inhibitors, interleukin 6 blockers, and a T cell modulator. Here, we systematically review existing case reports and compare the outcomes of RA-related AA amyloidosis after treatment with various drugs. CONCLUSION: The data indicate that biologic drugs like tocilizumab might be treatments of choice for AA amyloidosis secondary to RA.

Collagenous Gastritis in Children: Incidence, Disease Course, and Associations With Autoimmunity and Inflammatory Markers.

INTRODUCTION: Collagenous gastritis (CG), a rare disorder of unknown etiology, has been postulated to have immune-mediated mechanisms. We investigated (i) the incidence and prevalence of CG in a pediatric population; (ii) the clinical, endoscopic, and histologic characteristics of childhood-onset CG; and (iii) the evidence for autoimmunity and/or inflammatory activity in these patients. METHODS: Clinical, endoscopic, and histologic data were reviewed longitudinally in a population-based Swedish cohort of 15 patients with childhood-onset CG diagnosed in the period 2008-2019. A set of 11 autoantibodies, 4 blood inflammatory biomarkers, and the human leukocyte antigen DQ2/DQ8 genotype was analyzed cross-sectionally. RESULTS: The incidence rate of childhood-onset CG was 0.25/100,000 person-years, with an incidence rate ratio of girls to boys of 4.2 (95% confidence interval, 1.2-15). The prevalence of CG was 2.1/100,000 in children aged younger than 18 years. The endoscopic and histologic findings remained pathologic in all the examined patients during a median follow-up of 4.4 years. Many patients had heredity for autoimmune disorders (47%) and/or tested positive for autoantibodies (40%) or human leukocyte antigen DQ2/DQ8 (53%). No associated autoimmune comorbidities were observed. The serum levels of calprotectin and amyloid A were increased in 10/15 (67%) and 5/15 (33%) of the patients, respectively, whereas plasma C-reactive protein levels were normal in all, but 1 patient. DISCUSSION: The results indicate that childhood-onset CG is rare and has a chronic disease course. Although signs of autoimmune predisposition are frequent, early development of autoimmune comorbidities seems seldom. Serum calprotectin and amyloid A represent novel candidate biomarkers of inflammatory activity in CG (see Visual Abstract, Supplementary Digital Content 4, http://links.lww.com/CTG/A349).

Dietary Intake of Rosmarinic Acid Increases Serum Inhibitory Activity in Amyloid A Aggregation and Suppresses Deposition in the Organs of Mice.

Serum amyloid A (SAA) is one of the most important precursor amyloid proteins and plays a vital step in AA amyloidosis, although the underlying aggregation mechanism has not been elucidated. Since SAA aggregation is a key step in this pathogenesis, inhibitors are useful to prevent and treat AA amyloidosis, serving as tools to investigate the pathogenic mechanism. In this study, we showed that rosmarinic acid (RA), which is a well-known inhibitor of the aggregation of amyloid ß (Aß), displayed inhibitory activity against SAA aggregation in vitro using a microliter-scale high-throughput screening (MSHTS) system with quantum-dot nanoprobes. Therefore, we evaluated the amyloid aggregation inhibitory activity of blood and the deposition of SAA in organs by feeding mice with Melissa officinalis extract (ME) containing RA as an active substance. Interestingly, the inhibitory activity of ME-fed mice sera for SAA and Aß aggregation, measured with the MSHTS system, was higher than that of the control group. The amount of amyloid deposition in the organs of ME-fed mice was lower than that in the control group, suggesting that the SAA aggregation inhibitory activity of serum is associated with SAA deposition. These results suggest that dietary intake of RA-containing ME enhanced amyloid aggregation inhibitory activity of blood and suppressed SAA deposition in organs. This study also demonstrated that the MSHTS system could be applied to in vitro screening and to monitor comprehensive activity of metabolized foods adsorbed by blood.

Effects of ß-glucan and Vitamin D Supplementation on Inflammatory Parameters in Patients with Diabetic Retinopathy.

The objective of this article is to evaluate the potential effects of beta-glucan and vitamin D supplementation in patients with diabetic retinopathy. We evaluated the levels of several parameters of inflammatory reactions (C-reactive protein [CRP], serum amyloid A [SAA], and interleukin- [IL-] 6), leptin, and vitamin D. Using a 3-month interval, we divided the patients into three groups: (1) supplemented with beta-glucan and vitamin D, (2) supplemented with vitamin D and placebo, and (3) supplemented with vitamin D alone. By this division, we aim not only to observe whether beta-glucan can increase the effects of vitamin D, but also to eliminate the potential effects of placebo. The doses of vitamin D corresponded to phototype, weight, age, and sex of the individual. Fifty-two diabetic retinopathy patients were selected for our study. We found significant vitamin D deficits in all cases, even after three months of supplementation with vitamin D. Significant changes in levels of CRP were observed in the beta-glucan-supplemented group; levels of SAA and IL-6 were not changed. Leptin levels were significantly lowered in the beta-glucan-supplemented group and increased in the other groups. More detailed studies and/or longer supplementation is necessary.

A comparison of the effects of low- and high-dose atorvastatin on lipoprotein metabolism and inflammatory cytokines in type 2 diabetes: Results from the Protection Against Nephropathy in Diabetes with Atorvastatin (PANDA) randomized trial.

BACKGROUND: Statin therapy is recommended in type 2 diabetes (T2DM) although views on treatment intensity and therapeutic targets remain divided. OBJECTIVES: Our objectives were to compare the effects of high-intensity and moderate-intensity atorvastatin treatment on lipoprotein metabolism and inflammatory markers and how frequently treatment goals are met in high-risk T2DM patients. METHODS: Patients with T2DM and albuminuria (urinary albumin:creatinine ratio >5 mg/mmol, total cholesterol <7 mmol/L, proteinuria <2 g/d, creatinine <200 µmol/L) were randomized to receive atorvastatin 10 mg (n = 59) or 80 mg (n = 60) daily. Baseline and 1-year follow-up data are reported. RESULTS: Patients were at high cardiovascular disease risk (observed combined mortality and nonfatal cardiovascular disease annual event rate 4.8%). The non-high-density lipoprotein cholesterol (HDL-C) goal of <2.6 mmol/L was achieved in 72% of participants receiving high-dose atorvastatin, but only in 40% on low-dose atorvastatin (P < .005). The proportion achieving apolipoprotein B (apoB) <0.8 g/L on high-dose and low-dose atorvastatin was 82% and 70%, respectively (NS). Total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, non-HDL-C, oxidized LDL, apoB, glyc-apoB, apolipoprotein E, and lipoprotein-associated phospholipase A2 decreased significantly, more so in participants on high-dose atorvastatin. Adiponectin increased and serum amyloid A decreased without dose dependency. Neither dose produced significant changes in HDL-C, cholesterol efflux, high-sensitivity C-reactive protein, glycated hemoglobin, serum paraoxonase-1, lecithin:cholesterol acyltransferase, or cholesteryl ester transfer protein. CONCLUSIONS: High-dose atorvastatin is more effective in achieving non-HDL-C therapeutic goals and in modifying LDL-related parameters. Recommended apoB treatment targets may require revision. Despite the increase in adiponectin and the decrease in serum amyloid A, HDL showed no change in functionality.

Haptoglobin and serum amyloid-A concentrations and their relationship with oocyst count in neonatal lambs experimentally infected with Cryptosporidium parvum.

This study aimed to evaluate the acute phase response (APR) through haptoglobin (Hp) and serum amyloid A (SAA) concentrations in serum and to examine the correlation between these acute phase proteins (APPs) and oocyst shedding using experimental Cryptosporidium parvum (C. parvum) infection model in neonatal lambs. Twenty lambs were divided into two equal groups: group CON remained uninfected as negative control and lambs of the group EXP were inoculated orally with 1×106C. parvum oocysts. Blood and faecal samples were obtained from both groups before colostrum intake and prior to inoculation (day-1), and at 2, 6, 13, and 20days post-inoculation (dpi). The serum concentrations of SAA increased following the experimental infection of lambs with C. parvum, the difference being statistically significant from pre-inoculation levels at 2 dpi, while significant increases in serum concentration of Hp were observed at 2 and 6 dpi. At the same occasions, serum concentrations of both APPs were significantly higher in the C. parvum-infected lambs compared to the healthy control lambs. A moderate positive correlation (rho=0.67; p< 0.001) was observed between serum Hp concentration and oocyst count (OPG),whereas the serum SAA concentration didn't significantly correlate with OPG (rho=0.18; p>0.05). In conclusion, the results of the study shed some light on APR due to C. parvum infection in neonatal lambs.

Capsaicin Supplementation Improved Risk Factors of Coronary Heart Disease in Individuals with Low HDL-C Levels.

Low high-density lipoprotein cholesterol (HDL-C) is associated with an increased risk of coronary heart disease (CHD). This study aimed to evaluate the effects of capsaicin intervention on the serum lipid profile in adults with low HDL-C. In a randomized, double-blind, controlled clinical trial, 42 eligible subjects were randomly assigned to the capsaicin (n = 21, 4 mg of capsaicin daily) or to the control group (n = 21, 0.05 mg of capsaicin daily) and consumed two capsaicin or control capsules, which contained the powder of the skin of different peppers, twice daily for three months. Thirty-five subjects completed the trial (18 in the capsaicin group and 17 in the control group). The baseline characteristics were similar between the two groups. Compared with the control group, fasting serum HDL-C levels significantly increased to 1.00 ± 0.13 mmol/L from 0.92 ± 0.13 mmol/L in the capsaicin group (p = 0.030), while levels of triglycerides and C-reactive protein and phospholipid transfer protein activity moderately decreased (all p < 0.05). Other lipids, apolipoproteins, glucose, and other parameters did not significantly change. In conclusion, capsaicin improved risk factors of CHD in individuals with low HDL-C and may contribute to the prevention and treatment of CHD.

Effects of feeding an immunomodulatory supplement to heat-stressed or actively cooled cows during late gestation on postnatal immunity, health, and growth of calves.

Heat stress during late gestation negatively affects the physiology, health, and productivity of dairy cows as well as the calves developing in utero. Providing cows with active cooling devices, such as fans and soakers, and supplementing cows with an immunomodulating feed additive, OmniGen-AF (OG; Phibro Animal Health Corporation), improves immune function and milk yield of cows. It is unknown if maternal supplementation of OG combined with active cooling during late gestation might benefit the developing calf as well. Herein we evaluated markers of innate immune function, including immune cell counts, acute phase proteins, and neutrophil function, of calves born to multiparous dams in a 2 × 2 factorial design. Dams were supplemented with OG or a bentonite control (NO) beginning at 60 d before dry off and exposed to heat stress with cooling (CL) or without active cooling (HT) during the dry period (∼46 d). At birth, calves were separated from their dams and fed 6.6 L of their dams' colostrum in 2 meals. Calf body weight and rectal temperature were recorded, and blood samples were collected at birth (before colostrum feeding) and at 10, 28, and 49 d of age. Calves born to either CL dams or OG dams were heavier at birth than calves born to HT or NO dams, respectively. Concentrations of serum amyloid A were higher in the blood of calves born to OG dams relative to NO and for HT calves relative to CL calves. In addition, calves born to cooled OG dams had greater concentrations of plasma haptoglobin than calves born to cooled control dams. Neutrophil function at 10 d of age was enhanced in calves born to cooled OG dams and lymphocyte counts were higher in calves born to OG dams. Together these results suggest that adding OG to maternal feed in combination with active cooling of cows during late gestation is effective in mitigating the negative effects of in utero heat stress on postnatal calf growth and immune competence.

A combination of baseline plasma immune markers can predict therapeutic response in multidrug resistant tuberculosis.

OBJECTIVE: To identify plasma markers predictive of therapeutic response in patients with multidrug resistant tuberculosis (MDR-TB). METHODS: Fifty HIV-negative patients with active pulmonary MDR-TB were analysed for six soluble analytes in plasma at the time of initiating treatment (baseline) and over six months thereafter. Patients were identified as sputum culture positive or negative at baseline. Culture positive patients were further stratified by the median time to sputum culture conversion (SCC) as fast responders (< 76 days) or slow responders (≥ 76 days). Chest X-ray scores, body mass index, and sputum smear microscopy results were obtained at baseline. RESULTS: Unsupervised hierarchical clustering revealed that baseline plasma levels of IP-10/CXCL10, VEGF-A, SAA and CRP could distinguish sputum culture and cavitation status of patients. Among patients who were culture positive at baseline, there were significant positive correlations between plasma levels of CRP, SAA, VEGF-A, sIL-2Rα/CD40, and IP-10 and delayed SCC. Using linear discriminant analysis (LDA) and Receiver Operating Curves (ROC), we showed that a combination of MCP-1/CCL2, IP-10, sIL-2Rα, SAA, CRP and AFB smear could distinguish fast from slow responders and were predictive of delayed SCC with high sensitivity and specificity. CONCLUSION: Plasma levels of specific chemokines and inflammatory markers measured before MDR-TB treatment are candidate predictive markers of delayed SCC. These findings require validation in a larger study.

A Randomized Controlled Trial to Increase Navy Bean or Rice Bran Consumption in Colorectal Cancer Survivors.

Consumption of navy beans (NB) and rice bran (RB) have been shown to inhibit colon carcinogenesis. Given the overall poor diet quality in colorectal cancer (CRC) survivors and low reported intake of whole grains and legumes, practical strategies to increase consumption merit attention. This study determined feasibility of increasing NB or RB intake in CRC survivors to increase dietary fiber and examined serum inflammatory biomarkers and telomere lengths. Twenty-nine subjects completed a randomized controlled trial with foods that included cooked NB powder (35 g/day), heat-stabilized RB (30 g/day), or no additional ingredient. Fasting blood, food logs, and gastrointestinal health questionnaires were collected. The amount of NB or RB consumed equated to 4-9% of subjects' daily caloric intake and no major gastrointestinal issues were reported with increased consumption. Dietary fiber amounts increased in NB and RB groups at Weeks 2 and 4 compared to baseline and to control (P ≤ 0.01). Telomere length correlated with age and HDL cholesterol at baseline, and with improved serum amyloid A (SAA) levels at Week 4 (P ≤ 0.05). This study concludes feasibility of increased dietary NB and RB consumption to levels associated with CRC chemoprevention and warrants longer-term investigations with both foods in high-risk populations that include cancer prevention and control outcomes.

Growth promotion in pigs by oxytetracycline coincides with down regulation of serum inflammatory parameters and of hibernation-associated protein HP-27.

The growth promoting effect of supplementing animal feed with antibiotics like tetracycline has traditionally been attributed to their antibiotic character. However, more evidence has been accumulated on their direct anti-inflammatory effect during the last two decades. Here we used a pig model to explore the systemic molecular effect of feed supplementation with sub therapeutic levels of oxytetracycline (OTC) by analysis of serum proteome changes. Results showed that OTC promoted growth, coinciding with a significant down regulation of different serum proteins related to inflammation, oxidation and lipid metabolism, confirming the anti-inflammatory mechanism of OTC. Interestingly, apart from the classic acute phase reactants also down regulation was seen of a hibernation associated plasma protein (HP-27), which is to our knowledge the first description in pigs. Although the exact function in non-hibernators is unclear, down regulation of HP-27 could be consistent with increased appetite, which is possibly linked to the anti-inflammatory action of OTC. Given that pigs are good models for human medicine due to their genetic and physiologic resemblance, the present results might also be used for rational intervention in human diseases in which inflammation plays an important role such as obesity, type 2 diabetes and cardiovascular diseases.

The effect of colostrum intake on blood plasma proteome profile in newborn lambs: low abundance proteins.

BACKGROUND: Colostrum intake by newborn lambs plays a fundamental role in the perinatal period, ensuring lamb survival. In this study, blood plasma samples from two groups of newborn lambs (Colostrum group and Delayed Colostrum group) at 2 and 14 h after birth were treated to reduce the content of high abundance proteins and analyzed using Two-Dimensional Differential in Gel Electrophoresis and MALDI MS/MS for protein identification in order to investigate low abundance proteins with immune function in newborn lambs. RESULTS: The results showed that four proteins were increased in the blood plasma of lambs due to colostrum intake. These proteins have not been previously described as increased in blood plasma of newborn ruminants by colostrum intake. Moreover, these proteins have been described as having an immune function in other species, some of which were previously identified in colostrum and milk. CONCLUSIONS: In conclusion, colostrum intake modified the low abundance proteome profile of blood plasma from newborn lambs, increasing the concentration of apolipoprotein A-IV, plasminogen, serum amyloid A and fibrinogen, demonstrating that colostrum is essential, not only for the provision of immunoglobulins, but also because of increases in several low abundance proteins with immune function.

Towards a better understanding of salivary and meat juice acute phase proteins determination in pigs: an expression study.

Acute phase proteins (APPs) determination in different fluids like serum, saliva and meat juice measured with ultrasensitive assays can be used to evaluate the disease status of porcine populations under field conditions. Liver is the main production site of serum APPs, but the origin of APPs that can be determined in body fluids different from blood remains unknown. The objective of this study was to clarify the origin of three APPs: C-reactive protein (CRP), serum amyloid A (SAA) and haptoglobin (Hp) in saliva and meat juice. The mRNA expression of these proteins was measured in liver, salivary gland and diaphragmatic muscle by quantitative PCR and compared with the protein levels in serum, saliva and meat juice, respectively in healthy and naturally diseased animals. As expected, concentrations of all APP were significantly higher in all body fluids from diseased animals. Levels of all APPs mRNA were very low in diaphragmatic muscle tissue, and the expression was independent of the disease status. In contrast, we found higher expression levels of SAA and Hp mRNA in the salivary gland of diseased animals, while CRP mRNA was not detected. Our data indicate that the APP present in meat juice derived predominantly from serum. This assumption is also supported by the good correlation of the levels of both proteins in meat juice with those in serum. Further, the lower variability of the APP levels within the two groups of animals, suggests meat juice as an alternate sampling material. The APP levels that are determined in saliva, however, appear to result from an increased local production except for CRP, indicating that the salivary gland responds to disease. These findings are relevant for the establishment of saliva as the preferred diagnostic sample for health monitoring programmes, due to the technical and ethical advantages of the collection.

Lycopene intervention reduces inflammation and improves HDL functionality in moderately overweight middle-aged individuals.

The management of overweight subjects by interventions aimed at reducing inflammation is highly desirable. To date, observational studies have identified a link between increased dietary antioxidant intake and reduced cardiovascular morbidity. However, direct trial evidence regarding the ability of antioxidants to influence inflammation is lacking. Therefore, this study examined lycopene's ability to lower systemic and high-density lipoprotein (HDL)-associated inflammation in moderately overweight middle-aged subjects. Serum was collected before and after a 12-week intervention from 54 moderately overweight, middle-aged individuals. Subjects were randomised to one of three groups: control diet (<10 mg lycopene/week), lycopene-rich diet (224-350 mg lycopene/week) and lycopene supplement (70 mg lycopene/week). HDL was subfractionated into HDL(2&3) by rapid ultracentrifugation. Compliance was monitored by assessing lycopene concentration in serum and HDL(2&3). Systemic and HDL-associated inflammation was assessed by measuring serum amyloid A (SAA) levels. HDL functionality was determined by monitoring the activities of paraoxonase-1 (PON-1), cholesteryl ester transfer protein (CETP) and lecithin cholesterol acyltransferase (LCAT). Lycopene increased in serum and HDL(2&3) following both lycopene interventions (P<.001, for all), while SAA decreased in serum following the lycopene supplement and in HDL(3) following both lycopene interventions (P<.05 for all). PON-1 activity increased in serum and HDL(2&3) in both lycopene groups (P<.05, for all). Furthermore, the activity of CETP decreased in serum following the lycopene supplement, while the activity of LCAT increased in serum and HDL(3) following both lycopene interventions (P<.05 for all). These results demonstrate that in moderately overweight, middle-aged subjects, increasing lycopene intake leads to changes to HDL(2&3), which we suggest enhanced their antiatherogenic properties. Overall, these results show the heart-protective properties of increased lycopene intake.

Vitamin C supplementation in relation to inflammation in individuals with atrophic gastritis: a randomised controlled trial in Japan.

Evidence has shown that both C-reactive protein (CRP) and serum amyloid component A (SAA) are increased in individuals with gastritis and stomach cancer. Controlling the level of these biomarkers by inhibiting the gastric infection with high doses of ascorbic acid may reduce the risk of carcinogenesis. A population-based double-blind randomised controlled trial in a Japanese population with atrophic gastritis in an area of high stomach cancer incidence was conducted between 1995 and 2000. Daily doses of 50 or 500 mg vitamin C were given, and 120 and 124 participants completed the 5-year study, respectively. Although serum ascorbic acid was higher in the high-dosage group (1.73 (SD 0.46) µg/l) than in the low-dosage group (1.49 (SD 0.29) µg/l, P< 0.001), at the end of the study, no significant difference was observed for CRP between the low- and high-dosage groups (0.39 (95 % CI 0.04, 4.19) mg/l and 0.38 (95 % CI 0.03, 4.31) mg/l, respectively; P= 0.63) or for SAA between the low- and high-dosage groups (3.94 (95 % CI 1.04, 14.84) µg/ml and 3.85 (95 % CI 0.99, 14.92) µg/ml, respectively; P= 0.61). Vitamin C supplementation may not have a strong effect on reducing infections in individuals with atrophic gastritis.

Effect of Chaiqinchengqi decoction on serum amyloid A in severe acute pancreatitis patients.

OBJECTIVE: To investigate the effect of Chaiqinchengqi decoction (CQCQD) on serum amyloid A (SAA) in severe acute pancreatitis (SAP) patients. METHODS: Thirty-five participants enrolled and were randomly assigned into either a treatment condition (n = 17, treated with CQCQD) or a control condition (n = 18, treated with placebo) 24 hours following the onset of the disease. No statistical difference was observed in either group at baseline. Upon admission, the Acute Physiology and Chronic Health Evaluation score II (APACHE II), SAA, serum C-reactive protein (CRP) and interleukin-6 (IL-6) were measured, as well as on the first, 3rd and 7th day and were compared between the two groups. Organ complications, infection, operation rate, mortality and hospital stay were also compared. RESULTS: The duration of acute respiratory distress syndrome, acute hepatitis, acute renal failure, gastrointestinal failure and blood coagulation dysfunction were shorter in the treatment group than in those in the control group (P < 0.05). The secondary infection rates and the hospital fees in the treatment group were lower than those in the control group (P < 0.05) as well as length of hospital stay (P < 0.01). After 3 days of hospitalization, the APACHEII, score SAA levels, serum CRP and IL-6 in the treatment group was lower than those in the control group (P < 0.05). SAA was positively correlated with serum CRP (R = 0.346, P = 0.042), Ranson score (R = 0.442, P = 0.008) and serum IL-6 (R = 0.359, P = 0.034). The area under the receiver operating characteristic curve of admission SAA predict pancreatic necrosis (PN) was 0.815 (95% CI: 0.625-0.954; P = 0.006). The best cut-off value of admission SAA was 7.85 mg/L with the sensitivity 84.6% and specificity 68.2%. CONCLUSIONS: The CQCQD can reduce the duration of organ damage through lowering the SAA in SAP patients and the SAA can early predict the PN and severity of SAP patients.

Spores from two distinct colony types of the strain Bacillus subtilis PB6 substantiate anti-inflammatory probiotic effects in mice.

BACKGROUND & AIMS: Reducing symptoms of inflammatory bowel diseases (IBD) by dietary supplements represents more than ever an attractive clinical approach. Since the use of spore forming bacteria may offer interesting advantages, the aim of the study was to address the anti-inflammatory potential of Bacillus >subtilis strain PB6 (ATCC - PTA 6737) spores, provided as a powder preparation. METHODS: The immunomodulatory potential of strain PB6 was first characterized in vitro on human immunocompetent cells for both the commercial spore powder (Anaban™) and two phenotypic variants of the vegetative form. Assessment of the in vivo anti-inflammatory capacity of the standard spore powder and a variant spore powder preparation was performed using a mouse model of acute, TNBS-induced colitis. Performance was compared with the drug prednisolone, and was based on blinded macroscopic and histological scores, blood inflammatory markers and measurements of infiltration of mucosal neutrophils. RESULTS: Strain PB6 induced substantial levels of IL-10 but very low levels of IL-12, TNFα and IFNγ on human PBMC. Both spore powders prevented colitis as shown by significant reductions of near all inflammatory read-outs. CONCLUSION: B. subtilis strain PB6, provided as a preparation of spores, shows pre-clinical anti-inflammatory effects, suggesting further evaluation in a clinical intervention trial, e.g. with IBD type patients.

Effect of local anaesthesia and/or analgesia on pain responses induced by piglet castration.

BACKGROUND: Surgical castration in male piglets is painful and methods that reduce this pain are requested. This study evaluated the effect of local anaesthesia and analgesia on vocal, physiological and behavioural responses during and after castration. A second purpose was to evaluate if herdsmen can effectively administer anaesthesia. METHODS: Four male piglets in each of 141 litters in five herds were randomly assigned to one of four treatments: castration without local anaesthesia or analgesia (C, controls), analgesia (M, meloxicam), local anaesthesia (L, lidocaine), or both local anaesthesia and analgesia (LM). Lidocaine (L, LM) was injected at least three minutes before castration and meloxicam (M, LM) was injected after castration. During castration, vocalisation was measured and resistance movements judged. Behaviour observations were carried out on the castration day and the following day. The day after castration, castration wounds were ranked, ear and skin temperature was measured, and blood samples were collected for analysis of acute phase protein Serum Amyloid A concentration (SAA). Piglets were weighed on the castration day and at three weeks of age. Sickness treatments and mortality were recorded until three weeks of age. RESULTS: Piglets castrated with lidocaine produced calls with lower intensity (p < 0.001) and less resistance movements (p < 0.001) during castration. Piglets that were given meloxicam displayed less pain-related behaviour (huddled up, spasms, rump-scratching, stiffness and prostrated) on both the castration day (p = 0.06, n.s.) and the following day (p = 0.02). Controls had less swollen wounds compared to piglets assigned to treatments M, L and LM (p < 0.001). The proportion of piglets with high SAA concentration (over threshold values 200, 400 mg/l) was higher (p = 0.005; p = 0.05) for C + L compared to M + LM. Ear temperature was higher (p < 0.01) for controls compared to L and LM. There were no significant treatment effects for skin temperature, weight gain, sickness treatments or mortality. CONCLUSIONS: The study concludes that lidocaine reduced pain during castration and that meloxicam reduced pain after castration. The study also concludes that the herdsmen were able to administer local anaesthesia effectively.