Dysregulation of murine immune functions on inhalational exposure to ammonia, dimethyl disulfide, 3-methylindole, or propionic acid.

Animal husbandry workers are exposed to various malodorous compounds in the workplace. Although these compounds cause severe nuisance, no systemic investigation of their effects on the immune system has been conducted. To address this issue, we evaluated the effects of inhalational exposure to ammonia, dimethyl disulfide, 3-methylindole (3-MI), and propionic acid (PA), representing four major groups of malodorous compounds, on humoral and cellular immunity in mice. Mice were exposed to the substances (low dose: 10 µL and high dose: 200 µL) for 10 min/day for 4 weeks in a modified standard mouse cage. Neutrophil% and splenic cytotoxic T cell% were significantly lower in the high-dose ammonia group than in the vehicle control. Exposure to ammonia and 3-MI increased immature thymic T lymphocyte% relative to control and concomitantly decreased both mature helper and cytotoxic T-cell populations in the thymus. In the ammonia exposure group, levels of serum immunoglobulin E and immunoglobulin A were elevated, and the IgG2a:IgG1 ratio in the serum was reduced in a dose-dependent manner. Splenic natural killer cell activity was significantly less in the PA exposure group than in the control. Overall, our findings suggest that inhalational exposure to these malodorous substances disturbs immune homeostasis in vivo.

Non-invasive quantification of immunoglobulin A in chimpanzees (Pan troglodytes schweinfurthii) at Gombe National Park, Tanzania.

Immunoglobulin A (IgA) is the primary antibody responsible for mucosal defense in mammals and has been used as a marker for chronic stress and immune status. Therefore, this antibody may provide a more reliable indicator of an individual's immunocompetence than is currently available through other methods. Immunoglobulin A has never before been quantified in a wild population of non-human primates using non-invasive sample collection techniques. In this study, we present methodology for non-invasive IgA extraction in the field and provide quantification of mean fecal IgA concentrations in wild chimpanzees (Pan troglodytes schweinfurthii). During the study period (November 2009-October 2010), we collected fecal samples (N = 1463) from 59 individuals at Gombe National Park, Tanzania. We modified a field extraction technique for steroidal hormones to extract IgA from the fecal samples and then quantified mean IgA concentrations (ng/g) using a commercial human IgA enzyme immunoassay. Mean IgA concentration varied among individuals but not by sex or reproductive status. Mature animals tended toward higher mean IgA concentration than immature. Mean IgA concentration differed by quartile season, following a similar pattern previously observed for respiratory illness rates in this population, with the late dry season having significantly higher averages than the late wet. A circadian rhythm was also evident with mean IgA concentrations higher in samples collected in the latter half of the day. These demographic and temporal patterns of IgA concentration provide baseline values necessary to interpret future results, which may be combined with other health values to better understand the role of health and long-term stress in wild great ape populations. Am. J. Primatol. 80:e22558, 2018. © 2016 Wiley Periodicals, Inc.

IgA1 Protease Treatment Reverses Mesangial Deposits and Hematuria in a Model of IgA Nephropathy.

IgA nephropathy (IgAN), characterized by mesangial IgA1 deposits, is a leading cause of renal failure worldwide. IgAN pathogenesis involves circulating hypogalactosylated IgA1 complexed with soluble IgA Fc receptor I (sCD89) and/or anti-hypogalactosylated-IgA1 autoantibodies, but no specific treatment is available for IgAN. The absence of IgA1 and CD89 homologs in the mouse has precluded in vivo proof-of-concept studies of specific therapies targeting IgA1. However, the α1KI­CD89Tg mouse model of IgAN, which expresses human IgA1 and human CD89, allows in vivo testing of recombinant IgA1 protease (IgA1­P), a bacterial protein that selectively cleaves human IgA1. Mice injected with IgA1­P (1-10 mg/kg) had Fc fragments of IgA1 in both serum and urine, associated with a decrease in IgA1-sCD89 complexes. Levels of mesangial IgA1 deposits and the binding partners of these deposits (sCD89, transferrin receptor, and transglutaminase 2) decreased markedly 1 week after treatment, as did the levels of C3 deposition, CD11b(+) infiltrating cells, and fibronectin. Antiprotease antibodies did not significantly alter IgA1­P activity. Moreover, hematuria consistently decreased after treatment. In conclusion, IgA1­P strongly diminishes human IgA1 mesangial deposits and reduces inflammation, fibrosis, and hematuria in a mouse IgAN model, and therefore may be a plausible treatment for patients with IgAN.

Uteroglobin is essential in preventing immunoglobulin A nephropathy in mice.

The molecular mechanism(s) of immunoglobulin A (IgA) nephropathy, the most common primary renal glomerular disease worldwide, is unknown. Its pathologic features include hematuria, high levels of circulating IgA-fibronectin (Fn) complexes, and glomerular deposition of IgA, complement C3, Fn and collagen. We report here that two independent mouse models (gene knockout and antisense transgenic), both manifesting deficiency of an anti-inflammatory protein, uteroglobin (UG), develop almost all of the pathologic features of human IgA nephropathy. We further demonstrate that Fn-UG heteromerization, reported to prevent abnormal glomerular deposition of Fn and collagen, also abrogates both the formation of IgA-Fn complexes and their binding to glomerular cells. Moreover, UG prevents glomerular accumulation of exogenous IgA in UG-null mice. These results define an essential role for UG in preventing mouse IgA nephropathy and warrant further studies to determine if a similar mechanism(s) underlies the human disease.

Enzymatically synthesized exopolysaccharide of a probiotic strain Leuconostoc mesenteroides NTM048 shows adjuvant activity to promote IgA antibody responses.

Leuconostoc mesenteroides strain NTM048 produces an exopolysaccharide (EPS; glucose polymers 94% and fructose polymers 6%) with adjuvanticity for mucosal vaccination. Strain NTM048 includes three putative EPS-synthesizing genes, gtf1 and gtf2 for synthesizing glucose polymers, and lvnS for synthesizing fructose polymer. To elucidate the key polymer structure for adjuvanticity, two genes, gtf1 and gtf2, which were annotated as glycoside hydrolase family 70 enzyme genes, were expressed in Escherichia coli. Glycosyl-linkage composition analysis and NMR analysis showed that the recombinant enzyme Gtf1 produced a soluble form of α-1,6-glucan, whereas the recombinant enzyme Gtf2 produced glucans with approximately equal percentages of α-1,6- and α-1,3-glucose residues both in the supernatant (S-glucan) and as a precipitate (P-glucan). Comparison of polysaccharides synthesized by Gtf1, Gtf2, and LvnS revealed that Gtf2-S-glucan, which was produced in the supernatant by Gtf2 and formed particles of 7.8 µm, possessed 1.8-fold higher ability to stimulate IgA production from murine Peyer's patch cells than native NTM048 EPS. Evaluation of adjuvanticity by intranasal administration of mice with an antigen (ovalbumin) and Gtf2-S-glucan or NTM048 EPS showed that Gtf2-S-glucan induced the production of higher antigen-specific antibodies in the airway mucosa and plasma, suggesting a pivotal role of Gtf2-S-glucan in the adjuvanticity of NTM048 EPS.

Propensity of IgA to self-aggregate via tailpiece cysteine-471 and treatment of IgA nephropathy using cysteamine.

IgA nephropathy is caused by deposition of circulatory IgA1 in the kidney. Hypogalactosylated IgA1 has the propensity to form poly-IgA aggregates that are prone to deposition. Herein, we purified poly-IgA from the plasma of patients with IgA nephropathy and showed that the complex is susceptible to reducing conditions, suggesting intermolecular disulfide connections between IgA units. We sought to find the cysteine residue(s) that form intermolecular disulfide. Naturally assembled dimeric IgA, also known as secretory IgA, involves a J chain subunit connected with 2 IgA1 molecules via their penultimate cysteine-471 residue on a "tailpiece" segment of IgA heavy chain. It is plausible that, with the absence of J chain, the cysteine residue of mono-IgA1 might aberrantly form a disulfide bond in poly-IgA formation. Mutagenesis confirmed that cysteine-471 is capable of promoting IgA aggregation. These discoveries prompted us to test thiol-based drugs for stabilizing cysteine. Specifically, the cystine-reducing drug cysteamine used for treatment of cystinosis showed a remarkable potency in preventing self-aggregation of IgA. When administrated to rat and mouse models of IgA nephropathy, cysteamine significantly reduced glomerular IgA deposition. Collectively, our results reveal a potentially novel molecular mechanism for aberrant formation of IgA aggregates, to which the repurposed cystinosis drug cysteamine was efficacious in preventing renal IgA deposition.

Clinical and microbiological efficacy of prulifloxacin for the treatment of chronic bacterial prostatitis due to Chlamydia trachomatis infection: results from a prospective, randomized and open-label study.

The purpose of this study was to compare the efficacy of a 14-day course of prulifloxacin 600 mg with standard antibiotic therapy for the treatment of chronic prostatitis due to Chlamydia trachomatis (Ct) infection. All patients with clinical and instrumental diagnosis of bacterial chronic prostatitis (CP) due to Ct infection were enrolled. After randomization, all patients were administered oral prulifloxacin 600 mg once daily for 14 days or doxycycline 100 mg orally twice daily for 21 days. At enrollment and 30 days after beginning treatment, all patients underwent microbiological cultures for uropathogens bacteria and yeasts, DNA extraction and mucosal IgA evaluation for Ct diagnosis, seminal plasma IL-8 evaluation and serum IgA and IgG anti-Ct analysis. The National Institutes of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) was given to each patient. A total of 109 patients received prulifloxacin and 102 received standard therapy. Prulifloxacin had clinical efficacy rates equivalent to standard therapy (82.5% vs. 79.9%) (P = 0.08) and showed superior microbiological efficacy rates compared to standard therapy, in terms of decreasing mucosal IgA (P < 0.001) and IL-8 levels (P < 0.001). Prulifloxacin was also equivalent to standard therapy for clinical success, as demonstrated by a decrease in the number of patients affected by CP due to Ct infection.

Alemtuzumab therapy changes immunoglobulin levels in peripheral blood and CSF.

OBJECTIVE: The use of alemtuzumab, a humanized monoclonal anti-CD52 antibody has changed the therapy of highly active relapsing-remitting MS (RRMS). Alemtuzumab infusion depletes most lymphocytes in peripheral blood, whereas differential recovery of immune cells, probably those with a less CNS-autoreactive phenotype, is supposed to underlie its long-lasting effects. To determine whether alemtuzumab significantly reduces immunoglobulin levels in blood and CSF of treated patients, we analyzed blood and CSF samples of 38 patients with MS treated with alemtuzumab regarding changes in immunoglobulin levels. METHODS: Blood and CSF samples of patients were collected at the beginning of alemtuzumab treatment and at 12, 24, and 36 months after the first administration of the drug. Specimens were analyzed regarding immunoglobulin concentrations in blood and CSF. RESULTS: We observed significant and dose-dependent reductions of immunoglobulin levels (IgG, IgM, and IgA) in serum and CSF 12 and 24 months following 2 courses of alemtuzumab. Patients with persistent or returning disease activity who were treated with a third course of alemtuzumab exhibited even further decrease in IgG levels compared with matched controls treated twice. Here, alemtuzumab-treated patients with IgG levels below the lower limits of normal were more susceptible to pneumonia, sinusitis, and otitis, whereas upper respiratory tract and urinary tract infections were not associated therewith. CONCLUSIONS: Our results suggest to monitor IgG levels for safety reasons in patients treated with alemtuzumab-in particular when additional treatment courses are required-and to consider preventive action in critical cases. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with RRMS alemtuzumab reduces immunoglobulin levels.

Immunomodulatory Effect of a Salvia plebeia R. Aqueous Extract in Forced Swimming Exercise-induced Mice.

This study investigated the immunomodulatory effect of Salvia plebeia R. aqueous extract (FIE-SP, SPW) in forced swimming exercise-induced mice and the immunostimulatory effects on Raw264.7 cells. Mice were randomly assigned to four groups: the control group (CON), the forced swimming test group (FST), and two FIE-SP groups (low and high dose of FIE-SP). Compared with the control group, the FIE-SP groups showed significantly increased ratios of T lymphocyte surface markers CD4+/CD8+ and major histocompatibility complex (MHC)I/MHCII, as well as increased concentrations of immunoglobulin (Ig)A and IgG. FIE-SP groups significantly increased Th1 cytokines and decreased Th2 cytokines compared with negative control exercise-induced mice. Conversely, the immunostimulatory effects of FIE-SP significantly increased phagocytic activities, nitric oxide (NO) production, and pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1ß in Raw264.7 cells. Furthermore, FIE-SP increased natural killer (NK) cell activities and cytokines (IL-12) in splenocytes compared with the CON group. These results indicated that FIE-SP supplementation could prevent imbalanced immune states and produce immunostimulatory effects to support innate immunity.

A case of proliferative glomerulonephritis with immunoglobulin A1-lambda deposits successfully treated by chemotherapy.

A 74-year-old man presented with nephrotic syndrome and kidney insufficiency. Laboratory tests revealed monoclonal gammopathy of immunoglobulin A-lambda. Renal biopsy revealed diffuse mesangial proliferation and double-contoured basement membranes. Immunofluorescent analyses showed granular deposition of immunoglobulin A and C3 at the capillary walls and mesangial regions. Immunohistochemistry suggested monoclonal deposition of immunoglobulin A1-lambda. Electron microscopic analyses showed finely granular electron-dense deposits at mesangial and subendothelial areas. These findings suggested immunoglobulin A-type proliferative glomerulonephritis with monoclonal immunoglobulin deposits. Based on the results of bone marrow aspiration, multiple myeloma was diagnosed. Because the renal manifestation was considered to be affected by monoclonal gammopathy, chemotherapy was initiated rather than immunomodulatory therapy. Although bortezomib and dexamethasone proved ineffective, second chemotherapy with elotuzumab, lenalidomide, and dexamethasone was successful, and kidney function recovered. Effective treatments for proliferative glomerulonephritis with monoclonal immunoglobulin deposits have not been established. This represents the first description of a patient successfully treated for proliferative glomerulonephritis with monoclonal immunoglobulin deposits by chemotherapy using elotuzumab.

Triptolide inhibits tonsillar IgA production by upregulating FDC-SP in IgA nephropathy.

IgA nephropathy (IgAN) is primarily resulted of qualitative abnormality of IgA. The occurrence of IgAN is associated with affected tonsils which enhances the IgA production via IgA class switching and immuno-activation. Follicular dendritic cell-secreted protein (FDC-SP) was found to be a negative effect for IgA production in tonsil. The previous studies suggested that Triptolide might reduce IgA production by its immunosuppression role. Given this background, this study investigated the mechanisms underlying the role of Triptolide and FDC-SP in the generation of IgA and IgA class switching in tonsil of IgAN patients. Immunohistochemistry and reverse transcription-polymerase chain reaction revealed that the expression of FDC-SP was increased in the tonsils of IgAN patients with Triptolide treatment compared with those without treatment. Meanwhile, the expression of FDC-SP was negatively correlated with IgA inducing cytokines in the tonsils of IgAN patients treated with Triptolide, due to the significant decreased IgA-bearing cells. The expression of FDC-SP in tonsillar tissue was confirmed by double immunofluorescence. Importantly, Triptolide promoted FDC-SP secretion, and correlated negatively with decreased IgA production in isolated FDC-associated clusters, which had been isolated from patients without TW treatment previously. Our study demonstrated that Triptolide might have an impact on FDC-SP production and downregulation of IgA synthesis in the tonsils of IgAN patients, which could be a promising strategy for therapeutic intervention in IgAN patients.

Single dose of rituximab for refractory steroid-dependent nephrotic syndrome in children.

We conducted a multicenter prospective trial to evaluate the efficacy, safety and pharmacokinetics of a single dose of rituximab (375 mg/m(2) body surface area) for the treatment of children with refractory steroid-dependent nephrotic syndrome (SDNS). All patients (n = 12) were able to discontinue steroids at a median of 74 days after treatment. The frequency of relapses per 6 months was significantly reduced and the steroid-free period per 6 months was significantly increased after treatment compared with those before treatment. The condition in nine of the patients (75%) relapsed at a median of 129 days after treatment, and seven patients were given additional rituximab due to steroid dependency. Most of the relapses developed simultaneously with recovery of B-cells. However, three patients (25%) did not have a relapse with B-cell recovery and the disease was kept in remission for more than 1 year. None of the patients developed life-threatening adverse events. This is the first report of a prospective study of a single dose of rituximab for refractory SDNS. Treatment with a single dose of rituximab may be effective for refractory SDNS, but its efficacy to prevent relapses was transient in most of the patients.

Efficacy of methylprednisolone, cyclophosphamide in pediatric IgA nephropathy assessed by renal biopsy.

AIMS: IgA nephropathy is one of the most common glomerular diseases in children. The aim of this study was to investigate the clinical and pathologic efficacy of methylprednisolone and cyclophosphamide in the treatment of primary pediatric IgA nephropathy. METHODS: 11 patients with renal-biopsy-diagnosed Grade IV IgA nephropathy were treated with methylprednisolone and cyclophosphamide. Pathological changes were evaluated by post-treatment renal biopsies. RESULTS: At follow-up (18 - 60 months post-treatment), 6 patients were in complete remission. For the remaining 5, treatment was rated "markedly effective." Renal biopsies showed less mesangial proliferation, significantly decreased crescent formation, reduced segmental sclerosis, and significantly reduced mesangial IgA deposition. CONCLUSIONS: Methylprednisolone and cyclophosphamide in children with Grade IV IgA nephropathy stabilized renal function and significantly reduced hematuria, proteinuria, mesangial IgA deposition, and the renal pathological activity index.

Bevacizumab-induced immunoglobulin A vasculitis with nephritis: A case report.

RATIONALE: Bevacizumab-an inhibitor of vascular endothelial growth factor-is effective against various advanced cancers. However, it is associated with the development of hypertension and high-grade proteinuria during thrombotic microangiopathy of the kidney. In addition, there are several reports of immunoglobulin A deposition in the glomeruli, but the etiology is unclear. PATIENT CONCERNS: A 67-year-old Japanese man with metastatic rectal cancer underwent low anterior rectal resection, followed by treatment with bevacizumab and SOX (S-1 plus oxaliplatin). Six months later, the patient developed hematuria, nephrotic syndrome, and purpura. DIAGNOSES: Renal biopsy revealed endocapillary proliferative glomerulonephritis. Immunofluorescence analyses showed granular mesangial deposition of galactose-deficient immunoglobulin A1. Skin biopsy revealed leukocytoclastic vasculitis. INTERVENTIONS: We ceased bevacizumab treatment, while continuing the remaining chemotherapy regimen, as we suspected bevacizumab-induced nephropathy. OUTCOMES: Proteinuria and purpura improved immediately after cessation of bevacizumab. We identified this as a case of bevacizumab-induced immunoglobulin A vasculitis with nephritis. LESSONS: To our knowledge, this is the first case of bevacizumab-related immunoglobulin A vasculitis with nephritis, as evidenced by galactose-deficient immunoglobulin A1. When a patient's urine tests are abnormal during bevacizumab treatment, clinicians should consider not only thrombotic microangiopathy but also vasculitis.

Immune modulating therapy for IgA nephropathy: rationale and evidence.

Our current understanding of the initial pathogenetic steps in IgA nephropathy (IgAN) provides relatively limited rationale for immunosuppressive therapy. However, it is conceivable that immunosuppressive drugs might affect secondary inflammatory events triggered by glomerular immune deposits or even proteinuria per se. Some, but not all, randomized clinical trials on either corticosteroid monotherapy, mycophenolate mofetil monotherapy, or immunosuppressive combination therapy have provided evidence for a benefit on either surrogate parameters such as proteinuria or hard end points such as renal failure. The central problem of these studies is that most were designed in the 1980s or 1990s, when recommendations for supportive therapy were strikingly different from those of today. In the meantime an equal number of randomized clinical studies reporting a benefit of supportive therapy has been published only regarding patients with IgAN and, unfortunately, no head-to-head comparisons of these 2 approaches currently are available. Several ongoing clinical trials may help to resolve this dilemma. Until the data of such studies become available, a pragmatic approach is to first optimize supportive therapy and reserve immunosuppressive medication for those patients failing a supportive approach and remaining at risk for progressive loss of renal function.

3,3'-Diindolylmethane stimulates murine immune function in vitro and in vivo.

3,3'-Diindolylmethane (DIM), a major condensation product of indole-3-carbinol, exhibits chemopreventive properties in animal models of cancer. Recent studies have shown that DIM stimulates interferon-gamma (IFN-gamma) production and potentiates the IFN-gamma signaling pathway in human breast cancer cells via a mechanism that includes increased expression of the IFN-gamma receptor. The goal of this study was to test the hypothesis that DIM modulates the murine immune function. Specifically, the effects of DIM were evaluated in a panel of murine immune function tests that included splenocyte proliferation, reactive oxygen species (ROS) generation, cytokine production and resistance to viral infection. DIM was found to induce proliferation of splenocytes as well as augment mitogen- and interleukin (IL)-2-induced splenocyte proliferation. DIM also stimulated the production of ROS by murine peritoneal macrophage cultures. Oral administration of DIM, but not intraperitoneal injection, induced elevation of serum cytokines in mice, including IL-6, granulocyte colony-stimulating factor (G-CSF), IL-12 and IFN-gamma. Finally, in a model of enteric virus infection, oral DIM administration to mice enhanced both clearance of reovirus from the GI tract and the subsequent mucosal IgA response. Thus, DIM is a potent stimulator of immune function. This property might contribute to the cancer inhibitory effects of this indole.

Dietary sphingomyelin alleviates experimental inflammatory bowel disease in mice.

The effect of dietary sphingomyelin (SM) on inflammatory bowel disease (IBD) induced with dextran sodium sulfate (DSS) was examined in mice. Although the severity of IBD as expressed by the disease activity index (DAI) markedly increased with DSS administration, feeding a diet containing SM lowered the DAI value significantly. Myeloperoxidase (MPO) activity in colonic tissue also increased with DSS administration, suggesting the development of inflammation. Because simultaneous administration of SM with DSS prevented the MPO activity increase, we concluded that SM could suppress the development of inflammation. These results provide novel evidence that dietary supplementation with SM can alleviate the symptoms of IBD in mice. Dietary SM also increased the amount of IgA in the large intestine, suggesting that SM promotes IgA secretion into the large intestine. These results suggest that the mechanism of IBD mitigation by SM is complex and involves the immune system.

Autonomic neurotransmitters modulate immunoglobulin A secretion in porcine colonic mucosa.

Secretory immunoglobulin A (sIgA) plays a crucial role in mucosal surface defense. We tested the hypothesis that colonic sIgA secretion is under enteric neural control. Immunohistochemistry of the porcine distal colonic mucosa revealed presumptive cholinergic and adrenergic nerve fibers apposed to secretory component (SC)-positive crypt epithelial cells and neighboring IgA(+) plasmacytes. The cholinomimetic drug carbamylcholine elicited rapid, atropine-sensitive IgA secretion into the luminal fluid bathing mucosal explants mounted in Ussing chambers. The adrenergic receptor agonist norepinephrine also increased IgA secretion, an action inhibited by phentolamine. These effects were independent of agonist-induced anion secretion. In Western blots of luminal fluid, both agonists increased the density of protein bands co-immunoreactive for IgA and SC. Mucosal exposure to enterohemorrhagic Escherichia coli did not affect IgA secretion, and carbamylcholine treatment did not affect mucosal adherence of this enteropathogen. Acetylcholine and norepinephrine, acting respectively through muscarinic cholinergic and alpha-adrenergic receptors in the colonic mucosa, stimulate sIgA secretion and may enhance mucosal defense in vivo.

Effects of bovine colostrum supplementation on immune variables in highly trained cyclists.

The aim of this study was to investigate the influence of low-dose bovine colostrum protein concentrate (CPC) supplementation on selected immune variables in cyclists. Twenty-nine highly trained male road cyclists completed an initial 40-km time trial (TT(40)) and were then randomly assigned to either a supplement (n = 14, 10 g bovine CPC/day) or placebo group (n = 15, 10 g whey protein concentrate/day). After 5 wk of supplementation, the cyclists completed a second TT(40). They then completed 5 consecutive days of high-intensity training (HIT) that included a TT(40), followed by a final TT(40) in the following week. Venous blood and saliva samples were collected immediately before and after each TT(40), and upper respiratory illness symptoms were recorded over the experimental period. Compared with the placebo group, bovine CPC supplementation significantly increased preexercise serum soluble TNF receptor 1 during the HIT period (bovine CPC = 882 +/- 233 pg/ml, placebo = 468 +/- 139 pg/ml; P = 0.039). Supplementation also suppressed the postexercise decrease in cytotoxic/suppressor T cells during the HIT period (bovine CPC = -1.0 +/- 2.7%, placebo = -9.2 +/- 2.8%; P = 0.017) and during the following week (bovine CPC = 1.4 +/- 2.9%, placebo = -8.2 +/- 2.8%; P = 0.004). Bovine CPC supplementation prevented a postexercise decrease in serum IgG(2) concentration at the end of the HIT period (bovine CPC = 4.8 +/- 6.8%, P = 0.88; placebo = -9.7 +/- 6.9%, P = 0.013). There was a trend toward reduced incidence of upper respiratory illness symptoms in the bovine CPC group (P = 0.055). In summary, low-dose bovine CPC supplementation modulates immune parameters during normal training and after an acute period of intense exercise, which may have contributed to the trend toward reduced upper respiratory illness in the bovine CPC group.

[Immunological and pathogenetic aspects of imunofan administration in aged patients with duodenal ulcer].

AIM: To specify immunological and pathogenetic aspects of imunophan use in aged patients with duodenal ulcer (DU). MATERIAL AND METHODS: Imunophan was given to 24 DU patients (mean age 62.0 +/- 1.5 years), in whom the size of ulcer varied from 0.6 to 2.1 cm. RESULTS: The patients on anti-ulcer therapy plus imunophan had a pain relief median 6.2 +/- 0.2 days (p < 0.001), control ones--11.8 +/- 0.1 days. The median of scarring duration in the test group was 16.2 +/- 0.2 days (p < 0.001), in the controls--23.8 +/- 0.3 days. In 3 (30.0%) cases the scars were rough. The count of T-lymphocytes in the study group increased from 53.1 +/- 0.6 to 65.1 +/- 0.2% (p < 0.001), of T-helpers/inductors--from 27.8 +/- 0.2 to 38.5 +/- 0.3% (p < 0.001), of cytotoxic T-lymphocytes--from 18.5 +/- 0.5 to 27.3 +/- 0.3 (p < 0.001), of B-lymphocytes--from 12.3 +/- 0.2 to 19.1 +/- 0.1% (p < 0.001). The therapy including imunophan reduced concentration of malonic dialdehide by 23.5%, trienic conjugates by 61.6%; raised the level of superoxide dismutase 1.6-fold, catalase 1.4-fold, glutathione reductase by 41.9% (p < 0.001). Neither immune status nor LPO-AOD changed significantly in patients on the basic therapy alone. CONCLUSION: The results obtained evidence for a positive action of imunophan on inflammation, immune status and antioxidant defense. Therefore, imunophan can be recommended as an adjuvant of basic anti-ulcer therapy in elderly and senile patients.