Exploring the safety and effectiveness of subcutaneous autologous serum therapy versus conventional intramuscular autologous serum therapy in chronic urticaria: An observer-blind, randomized, controlled study.

BACKGROUND: Autologous serum therapy aims to supplement the existing pharmacotherapy in chronic urticaria by decreasing the antihistamine pill-burden and maintaining symptom-free interval. Subcutaneous autologous serum therapy further modifies the amount of serum (2 mL to 1 mL) and gauge of a needle (24G to 31G) to improve compliance and facilitate ease of application. OBJECTIVES: To assess clinical effectiveness and safety of subcutaneous autologous serum therapy versus conventional intramuscular autologous serum therapy and to compare the quality of life in the two treatment arms. METHODS: Institution-based, assessor-blind, prospective, randomized, parallel-group, active-controlled trial with 32 patients in each treatment arm and analyzed on a modified intention to treat principle. After baseline autologous serum skin test, autologous serum was injected as per randomization every week for 9 consecutive weeks. RESULTS: Among the study population, conventional intramuscular autologous serum therapy and subcutaneous autologous serum therapy had a comparable duration of disease (P = 0.164, Mann-Whitney U test), autoreactive status (P = 0.796), urticaria total severity score (P = 0.637) and urticaria activity score summed up over 7 days (P = 0.982). Both urticaria activity score summed up over 7 days and total severity score along with antihistamine pill-burden reduced significantly (P < 0.001, Friedman's analysis of variance) in both subcutaneous autologous serum therapy and conventional intramuscular autologous serum therapy from first follow-up onwards (P < 0.05, Post hoc Dunn's test). Significant improvement was noted in patient's as well as physician's global assessment of disease activity improvement scale (P < 0.001, Friedman's analysis of variance). Intergroup analysis showed that there was no significant difference in urticaria activity score summed up over 7 days either at baseline (P = 0.982, Mann-Whitney U test) or at study end (P = 0.398, Mann-Whitney U test). Similar comparable results were found in the total severity score at the end of the study (P = 0.345, Mann-Whitney U test). Dermatology life quality index showed marked improvement with both types of treatment (P < 0.0001, Wilcoxon test), and the intergroup comparison showed comparable dermatology life quality index values (P = 0.994, Mann-Whitney U test). The pain score at the injection site was more with conventional intramuscular autologous serum therapy than subcutaneous autologous serum therapy (P = 0.0115, Mann-Whitney test). Younger age and lower baseline total severity scores were associated with a better therapeutic response. Baseline urticaria activity score added up over a period of 7 days and total severity scores and the diameter of lesions showed a positive correlation with response pattern. LIMITATION: Basophil histamine release assay not done. Logistics could not support follow-up beyond the end of treatment. CONCLUSION: Subcutaneous autologous serum therapy is not inferior to conventional intramuscular autologous serum therapy with the additional advantage of less pain and operational feasibility.

Effects of dietary yeast cell wall on biochemical indices, serum and skin mucus immune responses, oxidative status and resistance against Aeromonas hydrophila in juvenile Persian sturgeon (Acipenser persicus).

The present study aims to shed light on the effects of yeast cell wall (ImmunoWall®) supplementation on biochemical indices, oxidative status, serum and mucus immune responses as well as disease resistance of juvenile Persian sturgeon (Acipenser persicus). For this purpose, one hundred fifty three juvenile Persian sturgeons (47.78 ± 0.39 g) were distributed into nine tanks (500 L) and fed with basal diets containing two levels of yeast cell wall (YCW) 0.5% (T1) and 1% (T2) and a diet without YCW as control (0%). As shown by the results obtained at the end of 56-day feeding trial, YCW had no significant effect on glucose, cortisol, SGOT, lysozyme and IgM in serum (P > 0.05) albeit an enhancement of cholesterol, LDH, ALP and SOD and ACH50 was observed in fish fed YCW supplemented diets. However, plasma triglyceride levels were lower in fish fed YCW compared with the control group. Also, total protein content, lysozyme and protease activities in skin mucus were unaffected by the supplemented diets (P > 0.05) and only total immunoglobulin and ALP enzyme activity were significantly increased in T1 and T2 groups (P > 0.05). The cumulative mortality of the fish fed supplemented diets at the end of disease challenge was 100% where cumulative mortality of those fed the control diet was 75% (P < 0.05). The present study shows that increasing immune parameters in serum and mucus of juvenile Persian sturgeon by YCW dietary supplementation did not improve resistance against Aeromonas hydrophila. According to the obtained results, the YCW supplementation at 0.5 and 1% in the juvenile Persian sturgeon diet is not recommended.

Analyzing weight evolution in mice infected by Trypanosoma cruzi

Concerning the specificities of a longitudinal study, the trajectories of a subject's mean responses not always present a linear behavior, which calls for tools that take into account the non-linearity of individual trajectories and that describe them towards associating possible random effects with each individual. Generalized additive mixed models (GAMMs) have come to solve this problem, since, in this class of models, it is possible to assign specific random effects to individuals, in addition to rewriting the linear term by summing unknown smooth functions, not parametrically specified, then using the P-splines smoothing technique. Thus, this article aims to introduce this methodology applied to a dataset referring to an experiment involving 57 Swiss mice infected by Trypanosoma cruzi, which had their weights monitored for 12 weeks. The analyses showed significant differences in the weight trajectory of the individuals by treatment group; besides, the assumptions required to validate the model were met. Therefore, it is possible to conclude that this methodology is satisfactory in modeling data of longitudinal sort, because, with this approach, in addition to the possibility of including fixed and random effects, these models allow adding complex correlation structures to residuals.

Does Neospora caninum cause reproductive problems in pigs?

Neospora caninum is known to cause reproductive disturbances in several animal species, such as cattle, sheep, and goats. However, research on the effects of N. caninum on reproduction in pigs is limited. The objective of this study was to verify the transplacental transmission of N. caninum in pigs during several gestational stages. Twelve healthy Toxoplasma gondii and N. caninum seronegative female pigs were selected and separated into four groups of three animals each. Group A was maintained as a control group. Groups B, C, and D were inoculated intravenously with 2.9 × 107 tachyzoites of the N. caninum strain Nc1, 30 days before conception and at 45 and 90 days of gestation, respectively. Blood samples were collected from females periodically through IFAT for IgG and IgM screening to confirm the infection. At birth, after blood samples were collected from the piglets, they were then euthanized for the collection of the brain, heart, lung, liver, and diaphragm, which were then subjected to PCR. All inoculated gilts seroconverted (IgG) from the seventh day after inoculation. Nine of the 12 females expelled 24 mummified fetuses at the time of delivery, two in group A (eight), two in group B (four), three in group C (nine), and two in group D (three). Of the 24 mummified fetuses, nine were positive for N. caninum (one (25%) fetus of group B, seven (77.8%) of group C, and one (33.3%) of group D). A total of 126 live piglets were born. When the organs of the piglets from the inoculated females were analyzed by PCR for N. caninum, 88 (93.61%) were positive. All gilts inoculated produced at least one positive piglet. This demonstrates that there is transplacental transmission of N. caninum in all phases of gestation, regardless of the time of infection.

Antibacterial activity of Oliveria decumbens against Streptococcus iniae in Nile tilapia (Oreochromis niloticus) and its effects on serum and mucosal immunity and antioxidant status.

The aims of this study were to investigate the antibacterial, immunostimulatory and antioxidant properties of different derivatives of Oliveria decumbens, in vitro and in vivo. The GC-MS spectrometry analysis showed γ-terpinene as the most frequent compound in essential oil, whereas carvacrol and thymol were the most common ones in aromatic water. Plant essential oil and hydroethanolic extract showed a positive in vitro bactericidal activity against Streptococcus iniae as evaluated by disc diffusion, minimum inhibitory concentration and minimum bactericidal concentration methods. Also, in vivo resistance against S. iniae and immune and antioxidant responses of Nile tilapia (Oreochromis niloticus) were assayed after 60 days treatment with O. decumbens derivatives. Plant hydroethanolic extract and essential oil and their 1:1 combination were added to diet at 0 (negative control), 0.01, 0.1 and 1% (w:w). The plant aromatic water at doses of 0.0312, 0.0625 and 0.1250% were also used as bath treatment. The results showed that aromatic water at lowest dose was more effective than other treatments in increment of fish resistance against S. iniae (7.14% mortality in comparison with 50% mortalities in control fish) and modulation of post-challenge respiratory burst activity. The bactericidal activity and biochemical contents of skin mucus did not change significantly among treatments. The levels of superoxide dismutase and catalase antioxidant enzymes activities in spleen tissue were significantly higher in treatments received extract, essential oils and their combination in comparison to other groups, while treatments did not affect peroxidase level. In conclusion, administration of different derivatives of Oliveria decumbens showed remarkable antibacterial activity against streptococcosis and enhanced antioxidant status and post-challenge immunity in Nile tilapia.

Using serum and plasma samples to assess failure of transfer of passive immunity in dairy calves.

The objectives of this study were (1) to determine the differences in IgG and total protein (TP) content of serum and plasma samples collected from the same calves; (2) to evaluate the correlation between calf serum and plasma IgG levels, Brix scores, and TP concentrations; (3) to determine whether different cut-off values should be used for plasma and serum to assess failure of transfer of passive immunity (FTPI) in dairy calves; and (4) to evaluate the level of agreement between results obtained from using serum and plasma samples of the same calves to assess FTPI using optimal cut-off values. Blood samples (n = 217) were collected from Holstein calves at 3 to 10 d of age on 30 commercial dairy farms in Nova Scotia and Newfoundland, Canada. Paired serum and plasma samples were analyzed for IgG concentration by the reference radial immunodiffusion assay, transmission infrared (TIR) spectroscopy, digital and optical Brix refractometers, and optical TP refractometer. The IgG concentrations measured by RID and TIR spectroscopy in serum were similar to those in plasma. However, the Brix and TP refractometer readings were significantly higher in plasma than in serum. The prevalence of FTPI in serum and plasma samples based on a RID-IgG concentration <10 g/L was 43.3 and 46.5%, respectively. The RID-IgG concentration was correlated with TIR-IgG (r = 0.92 and 0.89), digital Brix (r = 0.80 and 0.80), optical Brix (r = 0.77 and 0.77), and optical TP (r = 0.75 and 0.77) refractometers in serum and plasma, respectively. The correlations between paired serum and plasma IgG content were 0.85 by TIR spectroscopy, 0.80 by digital Brix, 0.77 by optical Brix, and 0.79 by optical TP refractometer. The optimal cut-off values for TIR spectroscopy, digital Brix, optical Brix, and TP refractometers to assess FTPI using serum were 13.1 g/L, 8.7% Brix, 8.4% Brix and 5.1 g/dL, respectively; and the optimal cut-off values with plasma were 13.4 g/L, 9.4% Brix, 9.3% Brix and 5.8 g/dL, respectively. When using these optimal cut-off values, the level of agreement (88.1%) between results derived from testing serum and plasma by TIR spectroscopy was substantial, with a kappa (κ) value of 0.76. The results derived from testing serum and plasma by digital Brix refractometer showed substantial agreement (83.4%), with a κ value of 0.65, which is higher than the agreement and κ value (74.7% and 0.51) reported for the optical Brix refractometer. Substantial agreement (81.6%) between serum and plasma TP was also obtained when using the optical TP refractometer, with a κ value of 0.63. In conclusion, serum or plasma samples can be used interchangeably for measuring IgG concentrations and assessing FTPI in dairy calves. However, different cut-offs must be used to assess FTPI depending on the sample matrix. Furthermore, results obtained from serum samples showed higher agreement with the reference RID assay than those obtained from plasma samples.

Effects of dietary threonine and immune stress on growth performance, carcass trait, serum immune parameters, and intestinal muc2 and NF-κb gene expression in Pekin ducks from hatch to 21 days.

An experiment was conducted to investigate the effects of different dietary threonine (Thr) levels and immune stress on Pekin ducklings' growth performance, carcass traits, serum immune parameters, and intestinal mucin 2 (MUC2) and nuclear factor kB (NF-κB) gene expressions. A total of 320 Pekin ducklings was randomly assigned to a 5 × 2 factorial arrangement of treatments. Each treatment group consisted of 4 replicate pens with 8 ducks per pen. Ducklings were fed 5 graded levels of Thr: 0.49, 0.56, 0.60, 0.65, and 0.76% from hatch to 21 d of age. At 11 d of age, ducks in the stressed groups were challenged with bovine serum albumin (BSA), and ducks in the unstressed groups were injected with normal saline water. The results showed that increasing Thr supplementation from 0.49 to 0.56% in the diet can improve BWG; feed consumption; weight and relative weight of breast and leg; weight of liver, bursa of Fabricius, spleen, and thymus; serum natural immune globulin A (IgA) concentration; and MUC2 gene expression in the ileum of 21-day-old Pekin ducks, significantly (P < 0.05). Immune stress with BSA had a significant effect on 21-day-old Pekin ducklings' BWG, feed consumption, and weight and relative weight of breast and thymus (P < 0.05), but no interaction between BSA and dietary Thr content was noticed in our experiment in 21-day-old Pekin ducks (P < 0.05). Dietary Thr requirements of the unstressed groups and stressed groups based on broken-line model analyses for ducks' BWG were 0.705 and 0.603%, respectively, and for ducks' feed consumption were 0.724 and 0.705%, respectively.

Protective effect of glutamine and arginine against soybean meal-induced enteritis in the juvenile turbot (Scophthalmus maximus).

Soybean meal can induce enteritis in the distal intestine (DI) and decrease the immunity of several cultured fish species, including turbot Scophthalmus maximus. Glutamine and arginine supplementation have been used to improve immunity and intestinal morphology in fish. This study was conducted to investigate the effects of these two amino acids on the immunity and intestinal health of turbot suffering from soybean meal-induced enteritis. Turbots (initial weight 7.6 g) were fed one of three isonitrogenous and isolipidic diets for 8 weeks: SBM (control diet), with 40% soybean meal; GLN, SBM diet plus 1.5% glutamine; ARG, the SBM diet plus 1.5% arginine. Symptoms that are typical of soybean meal-induced enteritis, including swelling of the lamina propria and subepithelial mucosa and a strong infiltration of various inflammatory cells was observed in fish that fed the SBM diet. Glutamine and arginine supplementation significantly increased (1) the weight gain and feed efficiency ratio; (2) the height and vacuolization of villi and the integrity of microvilli in DI; (3) serum lysozyme activity, and the concentrations of C3, C4, and IgM. These two amino acids also significantly decreased the infiltration of leucocytes in the lamina propria and submucosa and the expression of inflammatory cytokines including il-8, tnf-α, and tgf-ß. For the mucosal microbiota, arginine supplementation significantly increased microbiota community richness and diversity, and glutamine supplementation significantly increased the relative abundance of Lactobacillus and Bacillus. These results indicate that dietary glutamine and arginine improved the growth performance, feed utilization, and distal intestinal morphology, activated the innate and adaptive immune systems, changed the intestinal mucosal microbiota community, and relieved SBMIE possibly by suppression of the inflammation response.

Autologous Conditioned Serum.

Autologous conditioned serum was developed in the mid 1990s as an expeditious, practical, and relatively inexpensive means of generating the interleukin-1 receptor antagonist, a naturally occurring inhibitor of the cytokine interleukin-1. The latter is thought to be an important mediator of inflammation, pain, and tissue destruction in musculoskeletal conditions. ACS has been widely and successfully used in the local treatment of human and equine osteoarthritis and radicular compression; it has also shown promise in treating tendinopathies, muscle injuries, and tunnel widening after reconstruction of the anterior cruciate ligament. Experience suggests that autologous conditioned serum is safe and effective.

S1 domain of the porcine epidemic diarrhea virus spike protein as a vaccine antigen.

BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is a highly contagious virus infecting pigs of all ages with high morbidity and mortality among newborn piglets. Currently, there is no effective vaccine available to protect the pigs from PEDV. The N-terminal subunit of spike protein (S1) is responsible for virus binding to the cellular receptor and contains a number of neutralizing antibody epitopes. Thus, we expressed and produced recombinant S1 protein to protect newborn piglets by immunization of sows. METHODS: Affinity tagged PEDV S1 protein was expressed in a secretory form in yeast, insect and mammalian cells to identify the most suitable production system. Purified recombinant protein was analysed by SDS-PAGE, Western blot and deglycosylation assay. A pregnant sow was intramuscularly immunized three times with adjuvanted recombinant protein prior to farrowing. PEDV-specific immune responses in sera and colostrum of the sow and piglets were assayed by ELISA and virus neutralization assays. Piglets were challenged orally with PEDV, and clinical parameters were monitored for 6 days post-challenge. RESULTS AND CONCLUSION: Of three eukaryotic expression systems tested (yeast, insect-cell, and mammalian), expression by HEK-293 T cells gave the highest yield of protein that was N-glycosylated and was the most appropriate candidate for vaccination. Administration of the subunit vaccine in a sow resulted in induction of S1-specific IgG and IgA that were passively transferred to the suckling piglets. Also, high virus neutralization titres were observed in the serum of the vaccinated sow and its piglets. After PEDV challenge, piglets born to the vaccinated sow exhibited less severe signs of disease and significantly lower mortality compared to the piglets of a control sow. However, there were no significant differences in diarrhea, body weight and virus shedding. Thus, vaccination with S1 subunit vaccine failed to provide complete protection to suckling piglets after challenge exposure, and further improvements are needed for the development of a subunit vaccine that fully protects against PEDV infection.

Oral rice-based vaccine induces passive and active immunity against enterotoxigenic E. coli-mediated diarrhea in pigs.

Enterotoxigenic Escherichia coli (ETEC) causes severe diarrhea in both neonatal and weaned pigs. Because the cholera toxin B subunit (CTB) has a high level of amino acid identity to the ETEC heat-labile toxin (LT) B-subunit (LTB), we selected MucoRice-CTB as a vaccine candidate against ETEC-induced pig diarrhea. When pregnant sows were orally immunized with MucoRice-CTB, increased amounts of antigen-specific IgG and IgA were produced in their sera. CTB-specific IgG was secreted in the colostrum and transferred passively to the sera of suckling piglets. IgA antibodies in the colostrum and milk remained high with a booster dose after farrowing. Additionally, when weaned minipigs were orally immunized with MucoRice-CTB, production of CTB-specific intestinal SIgA, as well as systemic IgG and IgA, was induced. To evaluate the cross-protective effect of MucoRice-CTB against ETEC diarrhea, intestinal loop assay with ETEC was conducted. The fluid volume accumulated in the loops of minipigs immunized with MucoRice-CTB was significantly lower than that in control minipigs, indicating that MucoRice-CTB-induced cross-reactive immunity could protect weaned pigs from diarrhea caused by ETEC. MucoRice-CTB could be a candidate oral vaccine for inducing both passive and active immunity to protect both suckling and weaned piglets from ETEC diarrhea.

Effects of Lactobacillus acidophilus dietary supplementation on the performance, intestinal barrier function, rectal microflora and serum immune function in weaned piglets challenged with Escherichia coli lipopolysaccharide.

This study was conducted with a lipopolysaccharide (LPS)-challenged piglet model to determine the effects of diets containing Lactobacillus acidophilus on the performance, intestinal barrier function, rectal microflora and serum immune function. A total of 150 piglets (initial body weight (BW) 7.53 ± 0.21 kg) were allotted to one of the following diets, including a basal diet, a basal diet supplemented with 250 mg/kg Flavomycin, or basal diet plus 0.05, 0.1 or 0.2 % L. acidophilus. On day 28 of the trial, the pigs were given an intraperitoneal injection of LPS (200 µg/kg body weight) followed by blood collection 3 h later. Diets with either antibiotics, 0.1 or 0.2 % Lactobacillus increased (P < 0.05) the final BW and decreased (P < 0.05) feed gain ratio (F/G) compared with the control group. Pigs fed diets containing antibiotic or Lactobacillus had greater average daily gain (ADG) (P < 0.05) than pigs fed the control diet. The rectal content Lactobacillus counts for pigs fed diet containing Lactobacillus were significant higher (P < 0.01) than those fed antibiotic or control diet. Feeding the Lactobacillus diets decreased the Escherichia coli counts of rectal content (P < 0.01). Pigs fed diets containing 0.1 or 0.2 % Lactobacillus decreased serum DAO activity (P < 0.05) compared with pigs fed the control diet. Serum IL-10 concentration was enhanced in pigs fed the diet with Lactobacillus compared to pigs fed the control diet and antibiotic diet. Feeding a diet with Lactobacillus reduced (P < 0.05) IFN-γ concentration compared to the control diet. Inclusion of Lactobacillus in diets fed to pigs reduced TNF-α concentration compared with pigs fed no Lactobacillus (P < 0.05). These results indicate that feeding with L. acidophilus improved growth performance and protected against LPS-induced inflammatory status.

Age and psychological influences on immune responses to trivalent inactivated influenza vaccine in the meditation or exercise for preventing acute respiratory infection (MEPARI) trial.

BACKGROUND: Strategies to improve influenza vaccine protection among elderly individuals are an important research priority. Mindfulness-based stress reduction (MBSR) and exercise have been shown to affect aspects of immune function in some populations. We hypothesized that influenza vaccine responses may be enhanced with meditation or exercise training as compared with controls. RESULTS: No differences in vaccine responses were found comparing control to MBSR or exercise. Individuals achieving seroprotective levels of influenza antibody ≥160 units had higher optimism, less anxiety, and lower perceived stress than the nonresponders. Age correlated with influenza antibody responses, but not with IFNγ or IL-10 production. CONCLUSION: The MBSR and exercise training evaluated in this study failed to enhance immune responses to influenza vaccine. However, optimism, perceived stress, and anxiety were correlated in the expected directions with antibody responses to influenza vaccine. METHODS: Healthy individuals≥50 y were randomly assigned to exercise (n=47) or MBSR (n=51) training or a waitlist control condition (n=51). Each participant received trivalent inactivated influenza vaccine after 6 weeks, and had blood draws prior to and 3 and 12 weeks after immunization. Serum influenza antibody, nasal immunoglobulin A, and peripheral blood mononuclear cell interferon-γ (IFNγ) and interleukin-10 (IL-10) concentrations were measured. Measures of optimism, perceived stress, and anxiety were obtained over the course of the study. Seroprotection was defined as an influenza antibody concentration≥160 units. Vaccine responses were compared using ANOVA, t tests, and Kruskal-Wallis tests. The correlation between vaccine responses and age was examined with the Pearson test.

[Effect of yangyin yiqi huoxue recipe on immune balance of Th1/Th2 in serum and submaxillary glands of NOD mice with Sjogren's syndrome].

OBJECTIVE: To observe the effect of Yangyin Yiqi Huoxue Recipe (YYHR) on expression of interferon-gamma (IFN-gamma), IL-2, IL-4, IL-10, and immune balance of Th1/Th2 in serum and submaxillary glands of non-obese diabetic (NOD) mice with Sjogren's syndrome (SS), and to explore its mechanisms. METHODS: Totally 32 NOD mice were randomly into 4 groups, i.e., the model group, the Chinese medicine group [CM, administered with YYHR at the dose of 0.4 mL by gavage (100 g/kg)], the Western medicine group [WM group, administered with hydroxychloroquine 0.4 mL by gavage (60 mg/kg)], and the combined group [administered with YYHR (50 g/kg) and hydroxychloroquine (60 mg/kg) 0.4 mL by gavage], 8 mice in each group. Eight Balb/C mice were recruited as the normal control group. Mice were sacrificed to withdraw blood after 8 weeks. The submaxillary gland was excised. Serum levels of IFN-gamma, IL-2, IL-4, and IL-10 were detected by ELISA. Protein expression of IFN-gamma, IL-2, IL-4, and IL-10 in submaxillary glands was detected by SP method. RESULTS: Compared with the normal group, levels of IFN-gamma, IL-2, IL-4, and IL-10 in serum and submaxillary glands all increased in the model group (P < 0.05). Levels of IFN-gamma and IL-10 in serum in the CM group and the combined group were lower than those of the WM group (P < 0.05). Serum levels of IFN-gamma and IL-2 in submaxillary glands in combined group were lower than those of the WM group (P < 0.05). The ratio of IFN-gamma/IL-4 in serum and submaxillary glands in the model group were higher than that of the rest groups (P < 0.05). Besides, it was the nearest to that of the normal group. CONCLUSIONS: YYHR could decrease the levels of Th1 and Th2 related cytokines and the ratio of IFN-gamma/IL-4 in serum and submaxillary glands of NOD mice with SS. It could achieve therapeutic effects through adjusting immune balance of Th1/Th2 in SS mice.

Autologous conditioned serum for the treatment of osteoarthritis and other possible applications in musculoskeletal disorders.

INTRODUCTION: The therapeutic use of interleukin 1 (IL-1) cytokine receptor antagonists (IL-1RA) has promoted the development of new biological therapies for osteoarthritis (OA). Autologous conditioned serum (ACS) is an alternative, safe and well-tolerated treatment in OA. Sources of data We performed a comprehensive search of PubMed, Medline, Cochrane, CINAHL, Embase, SportDiscus, Pedro and Google scholar databases using keywords such as 'interleukin 1', 'osteoarthritis' and 'autologous conditioned serum'. AREAS OF AGREEMENT: ACS, containing endogenous anti-inflammatory cytokines including IL-1RA and several growth factors, could reduce pain and increase function and mobility in mild to moderate knee OA. AREA OF CONTROVERSY: Given the limited data available on the composition of ACS, the mechanisms through which ACS produces clinical improvement, the duration of its effect and the changes in cytokine levels after repeated injections are still unknown. Growing points Although previous clinical data are encouraging and confirm the safety of this modality, given the limitations of current studies, there should be additional, controlled trials to further confirm efficacy for the use of ACS in OA treatment. AREA TIMELY FOR DEVELOPING RESEARCH: ACS can lead to enhancement of tissue regeneration and to reduction of degenerative mechanisms.

6b,11b-Dihydroxy-6b,11b-dihydro-7H-indeno[1,2-b]naphtho[2,1-d]furan-7-one (DHFO), a small molecule targeting NF-κB, demonstrates therapeutic potential in immunopathogenic chronic inflammatory conditions.

6b,11b-Dihydroxy-6b,11b-dihydro-7H-indeno[1,2-b]naphtho[2,1-d]furan-7-one (DHFO), an easily synthesisable, orally bioavailable and relatively non-toxic small molecule synthesised in our lab, was previously reported to possess anti-oxidant, 5-lipoxygenase inhibitory, anti-inflammatory and peripheral analgesic activities. The present work deals with exploration of DHFO's efficacy in immunopathogenic chronic inflammatory conditions - arthritis and allergy. In carrageenan-induced inflammatory air pouch, which resembles the arthritic synovium, DHFO effectively reduced inflammatory redness and swelling and neutrophil infiltration. In complete Freund's adjuvant-induced arthritis, DHFO significantly decreased paw oedema and nitrite levels with efficacy comparable to diclofenac. DHFO inhibited neutrophil activation (observed as decreased myeloperoxidase levels), in both the in vivo models of inflammation. Interestingly, DHFO did not ulcerate the gastrointestinal tract, while diclofenac was observed to be extremely ulcerogenic. In antigen-induced active and passive anaphylaxis (allergy) models, DHFO dose-dependently prevented mesenteric mast cell (MC) degranulation with efficacy comparable to ketotifen. DHFO also inhibited compound 48/80 (C48/80)-induced paw oedema and peritoneal MC degranulation. DHFO stabilised p815 murine MCs stimulated by C48/80 and calcium ionophore-A23187, indicating an action downstream of calcium mobilisation. DHFO's anti-allergic mechanism could be two-pronged involving (1) inhibition of IgE production and/or (2) MC stabilisation. DHFO inhibited lipopolysaccharide (LPS)-induced pro-inflammatory mediator release (ROS, NO, IL-6 levels) and COX2 expression in RAW264.7 murine macrophages. Protein expression studies confirmed DHFO's ability to reduce nuclear levels of NF-κB in LPS-stimulated macrophages. Thus, DHFO is a promising non-ulcerogenic synthetic small molecule lead for immunopathogenic chronic inflammatory conditions.

Total flavonoids of Bidens bipinnata L. a traditional Chinese medicine inhibits the production of inflammatory cytokines of vessel endothelial cells stimulated by sera from Henoch-Schönlein purpura patients.

OBJECTIVES: Bidens bipinnata L. is well known as a traditional antipyretic, anti-inflammatory and anti-rheumatic medicine in China. This study was designed to evaluate the role of total extracted flavonoids from B. bipinnata (TFB) in inhibiting the production of inflammatory cytokines. METHODS: Human umbilical vein endothelial cells (HUVEC) were used to examine the effect of TFB on the production of inflammatory cytokines. The supernatant interleukin (IL)-8, tumour necrosis factor (TNF)-α and nitric oxide (NO) levels of HUVEC were measured with ELISA methods. Nuclear factor-kappaB (NF-κB) and fractalkine expression was evaluated by RT-PCR and Western blot methods, respectively. KEY FINDINGS: We observed that IL-8, TNF-α and NO release of HUVEC incubated with sera from active Henoch-Schönlein purpura (HSP) was significantly increased. TFB intervention may significantly suppressed the supernatant IL-8, TNF-α and NO levels of HUVEC. Similarly, TFB obviously suppressed the NF-κB and fractalkine mRNA and protein expression. CONCLUSIONS: These results suggested that TFB may be useful for improving microvascular inflammation in HSP patients.

Autologous whole blood and autologous serum injections are equally effective as placebo injections in reducing disease activity in patients with chronic spontaneous urticaria: a placebo controlled, randomized, single-blind study.

BACKGROUND: Recent demonstration of circulating anti-IgG antibodies towards IgE and its receptor (FcϵRI) has led to an interest in inducing tolerance to circulating histamine-releasing factors with autologous blood injections as a treatment option in chronic spontaneous urticaria (CU). The aim of the study was to assess the efficacy of autologous whole blood (AWB) and autologous serum (AS) injections in patients with CU compared to placebo. METHODS: A total of 88 CU patients with (+) autologous serum skin test (ASST) (59) and (-) ASST (29) were randomized into three parallel subgroups and were treated with weekly injections of AWB, AS or placebo for 10 weeks. Clinical assessments included urticaria activity score (UAS) and dermatology life quality index. RESULTS: In ASST (+) patients, the percentages of patients with >30% improvement in UAS and DLQI were 85% and 90% in AWB group, 65% and 65% in AS group and 79% and 90% in placebo group, respectively. In ASST (-) patients, these figures were 67% and 89% in the AWB group, 80% and 80% in the AS group and 60% and 70% in the placebo group. The intergroup difference for complete subsidence was not statistically significant. CONCLUSIONS: Even though we could not show a better efficacy than placebo, autohemotherapy resulted in a marked decrease in disease activity and improvement in quality of life scores in CU patients.

Correlation analysis of two serum-specific immunoglobulin E test systems and skin-prick test in allergic rhinitis patients from northeast China.

BACKGROUND: Skin-prick testing (SPT) is the most common screening method for allergy evaluation. The detection of serum-specific immunoglobulin E (sIgE) is also commonly used. The sensitivity and specificity of these testing methods may vary due to type of causative allergen and type of allergic manifestation. The purpose of this study was to evaluate the correlation between two methods of measuring sIgE (AllergyScreen [Mediwiss Analytic GmbH, Moers, Germany] and ImmunoCAP [Pharmacia, Uppsala, Sweden]) and SPT for the diagnosis of allergic rhinitis (AR). METHODS: All 216 patients who were referred to the allergist for suspected AR from June to October 2009 had SPT and the two serological tests. One hundred fifty-eight patients had a positive clinical history and a related positive SPT. The SPT was used as reference standard, and we selected three allergens (Dermatophagoides pteronyssinus, mugwort, and ragweed), which were common in fall in northeast China, to analyze the correlation of the two serum tests and SPT. RESULTS: Compared with the SPT, the diagnostic indexes (accuracy, sensitivity and specificity) of the AllergyScreen system and the ImmunoCAP system were 0.819 versus 0.810, 0.780 versus 0.872, and 0.862 versus 0.741, respectively. The accuracy was similar between the two systems (p > 0.05). The ImmunoCAP system method had a higher sensitivity (p < 0.01). The AllergyScreen system had a higher specificity (p < 0.01). CONCLUSION: These data support that the AllergyScreen system and ImmunoCAP system can identify potentially significant allergens in the diagnosis of AR in patients from northeastern China.

Contributions of conventional and heavy-chain IgG to immunity in fetal, neonatal, and adult alpacas.

In addition to conventional immunoglobulins, camelids produce antibodies that do not incorporate light chains into their structures. These so-called heavy-chain (HC) antibodies have incited great interest in the biomedical community, as they have considerable potential for biotechnological and therapeutic application. Recently, we have begun to elucidate the immunological functions of HC antibodies, yet little is known about their significance in maternal immunity or about the B lymphocytes that produce them. This study describes the application of isotype-specific reagents toward physiological assessments of camelid IgGs and the B cells that produce them. We document the specificities of monoclonal antibodies that distinguish two conventional IgG1 isotypes and two HC IgG3 variants produced by alpacas. Next, we report that the relative concentrations of five isotypes are similar in serum, milk, and colostrum; however, following passive transfer, the concentrations of HC IgG2 and IgG3 declined more rapidly than the concentration of conventional IgG1 in the sera of neonates. Finally, we assessed the distribution of B cells of distinct isotypes within lymphoid tissues during fetal and adult life. We detected IgG1, IgG2, and IgG3 in lymphocytes located in lymph node follicles, suggesting that HC B cells affinity mature and/or class switch. One IgG3 isotype was present in B cells located in ileal Peyer's patches, and one conventional IgG1 isotype was detected in splenic marginal zone B cells. Our findings contribute to the growing body of knowledge pertaining to HC antibodies and are compatible with functional specialization among conventional and HC IgGs in the alpaca.