Nonspecific Immune Stimulation Research Articles

NETs production and citrullinated histone H3 level in children with tuberculosis

Aim. To characterize parameters of neutrophil extracellular trap (NET) production in the leukocyte culture and citrullinated histone H3 (citH3) level in peripheral blood to assess the features of NETosis in children with tuberculosis.Materials and methods. The study included 20 children with active pulmonary tuberculosis (TB group) and 20 clinically healthy children without signs of sensitization to Mycobacterium tuberculosis antigens (control group). The ability of neutrophils to form NETs under ex vivo exposure to a non-specific immune stimulant and the concentration of citH3 in peripheral blood were investigated.Results. Neutrophils in children with tuberculosis formed filamentous NETs (Me = 21.0 and Me = 16.0, respectively; p = 0.0474) and cloud-like NETs (Me = 10.5 and Me = 4.0, respectively; p = 0.0068) more frequently than the controls. Filamentous NETs prevailed in both groups. However, cloud-like NETs were registered in all patients in the TB group (100%) and only in 15 of 20 children in the control group (χ2 = 16.01; p < 0.0068). The concentration of citH3 in the blood was 18.9 times higher in the TB group than in the control group (Me = 26.5 and Me = 1.4, respectively; p = 0.0041). A strong positive correlation was found between the citH3 concentration and the generation of filamentous (r = 0.86; p = 0.0137), but not cloud-like NETs (r = 0.95; p = 0.0008) in both groups.Conclusion. The high level of citH3 in the TB group can reflect its NETosis-induced release and be caused by increased NETosis in vivo. This may be due to the previously formed potential of neutrophils to generate NETs (a proNETotic phenotype), which is consistent with our observation of an increased ability of isolated neutrophils to form extracellular traps ex vivo in children of the TB group.

Critical analysis of Echinacea preparations marketed in Germany.

Colds are the most common cause of incapacity to work in 2023 and therefore have a significant impact on the German economy. Echinacea preparations are considered a non-specific immune stimulant that is used as a phytotherapeutic agent for the treatment and prevention of colds. In the 2021 ZEIT ranking of the best-selling pharmacy-only medicines in Germany, four Echinacea preparations were among the top ten, and they experienced a new hype during the SARS-CoV-2 pandemic. In this study, 22 Echinacea monopreparations, which are approved as herbal medicinal products, were analyzed based on their package inserts. The preparations used in clinical studies were compared with the preparations available on the market with regard to the criteria of plant species used, plant part used, preparation (extract or pressed juice), drug-extract ratio, single dose administered, standardization of the preparations, prior performance of an ingredient analysis, galenics, dosage, duration of administration, and daily dose administered. The analysis revealed that the preparations available on the market are very heterogeneous. The composition can vary considerably in terms of ingredients. For customers, these products appear homogeneous in terms of their presentation on the market. The legal framework conditions promote this situation. The clinical studies are also unable to adequately reflect the market situation. New studies based on market reality, with an analysis of ingredients in the preparations used, a standardized study design, and the inclusion of hematological and biochemical parameters in the evaluation should improve this situation. Days of incapacity for work as an outcome parameter could be well suited.

33 Beyond bacteria: Impact of live yeast as a probiotic on the intestinal health of dogs

Abstract Inactivated yeast and yeast-based products are commonly used in pet food to improve palatability, contribute to dietary protein content, and improve gastrointestinal functionality. However, the use of viable yeast Saccharomyces as a probiotic may contribute to additional beneficial effects on dogs and cats. Considering that, in this presentation, we will focus on the use of viable yeast as a probiotic for dogs. A study conducted at the Federal University of Parana, Brazil, observed that Beagle dogs supplemented with a probiotic yeast presented reduced fecal concentrations of total biogenic amines, ammonia, and aromatic compounds and greater fecal concentrations of butyrate. The supplemented dogs also presented an improvement in dysbiosis index, a greater abundance of Bifidobacterium and Turicibacter, and a reduced abundance of Escherichia coli in feces. In addition, control group dogs presented upregulation in microbial genes related to virulence factors (such as lipopolysaccharide export system), antibiotic resistance, and osmotic stress, compared with the probiotic group. These results may indicate a possible protective effect of the yeast probiotic against potential pathogenic bacteria in the gut. The mechanisms by which yeast probiotics may contribute to gastrointestinal functionality in dogs and cats are not fully elucidated. However, they are usually attributed to the stimulation of brush edge disaccharidases; competition for adhesion sites against potential pathogens; stimulation of nonspecific immunity; neutralization of toxins; and direct effect against potentially pathogenic microorganisms. Many of these mechanisms are influenced directly by yeast cell wall components, such as mannans and beta-glucans. One of the main mechanisms of action of mannans is the elimination of bacteria with pathogenic potential that present type-1 fimbriae, such as some strains of E. coli and Salmonella, preventing their adhesion and colonization to the host mucosa. This may also contribute to the establishment of beneficial bacteria in the gut. We can conclude that viable yeast Saccharomyces as a probiotic may have promising beneficial effects on intestinal functionality of dogs.

Egg-sensitised infants have elevated CD4+ effector memory T regulatory cells from birth.

IgE-mediated sensitisation to egg is common in infants. In some cases, the processes leading to egg sensitisation are established in early life, even before introduction to solid foods. The underlying mechanisms remain poorly understood. We performed detailed immune cell phenotyping of peripheral blood mononuclear cells and determined invitro cytokine responses following allergen specific and non-specific immune stimulation. To determine if unique immune profiles were linked to early-life egg sensitisation, we compared 92 infants at 4-6 months of age, with (EggCAP+, n = 41) and without (EggCAP-, n = 51) early egg sensitisation. Additionally, 47 cord blood samples were analysed. For a subset of participants (n = 39), matching cord blood mononuclear cells were assessed by flow cytometry to establish the impact of IgE sensitisation on immune developmental trajectories. EggCAP+ infants were found to exhibit a unique immune phenotype characterised by increased levels of circulating CD4+ T regulatory cells (Treg), CD4+ effector memory (EM) Treg and increased expression of the IgE receptor, FcεR1, on basophils. The increased CD4+ EM Treg profiles were already present in cord blood samples from EggCAP+ infants. A general Th2-skewing of the immune system was observed based on increased IL-13 production following phytohemagglutinin stimulation and by comparing immune developmental trajectories, EggCAP+ infants displayed an expansion of basophils and reduced levels of CD4- T cells compared to EggCAP- infants. Immunological profiles associated with egg sensitisation are detectable in infant circulation at 4-6 months of age and at birth. Understanding the immune mechanisms underlying early-life sensitisation could provide important insights for future food allergy prevention strategies.

ANALYSIS OF T-CELL IMMUNITY IN WOMEN WITH VAGINAL MICROBIOTA DISORDERS UNDER COMPLEX TREATMENT

Introduction. Immunological aspects of vaginal microbiota encompass the state of humoral and cellular immunity, which serves the primary function of nonspecific immune system stimulation. Therefore, alterations in its species composition lead to numerous disruptions in both cellular and humoral immune responses. The aim of the study – to investigate the parameters of T-cell immunity in women of reproductive age with vaginal microbiota disorders. Research Methods. We examined 115 women of reproductive age with vaginal microbiota disorders. To treat bacterial vaginosis in the third group of women according to the “Anomalous Vulvovaginal Discharge” treatment protocol, we selected the antibiotic metronidazole. In the second group with an intermediate type of vaginal microbiota, probiotics containing live Lactobacillus casei IMB B-7280 strains in the form of capsules and suppositories were used to normalize the species composition. After applying comprehensive therapy, we assessed the indicators of T-cell immunity in the study groups before treatment and one month after treatment. Results and Discussion. When studying T-cell immunity in women of reproductive age with vaginal microbiota disorders, no statistically significant changes in the levels of T-cells (CD3+, CD19-), T-helpers (CD4+, CD8-), and T-suppressors/T-cytotoxic cells (CD4-, CD8+) were found within the reference norms. However, statistically significant differences in T-suppressors/T-cytotoxic cells (CD4-, CD8+) were observed before treatment depending on the study groups. The lowest statistically significant level of these cells was found in the group of women with bacterial vaginosis, but the indicators of this immune branch tended to increase compared to the control group after complex treatment. After probiotic therapy, there was a tendency to increase T-helpers (CD4+, CD8-) in women with an intermediate type of vaginal microbiota. Conclusions. In conclusion, the analysis of the studied parameters of cellular immunity in women with vaginal microbiota disorders revealed a statistically significant decrease in T-suppressors/T-cytotoxic cells (CD4-, CD8+), which deepened as the vaginal microbiota disorder progressed. This indicates the influence of the species composition of vaginal microbiota on the T-suppressor/T-cytotoxic cellular immune branch.

RIG-I-Mediated Innate Immune Stimulation by Chemically Synthesized Long Double-Stranded RNAs Is Structure and Sequence Dependent.

Double-stranded RNAs (dsRNAs) longer than 30 bp have not been considered desirable RNA interference (RNAi) triggering structures in mammalian cells as they nonspecifically activate innate immune response. However, in earlier studies, not only dsRNA length but also 5'-triphosphate moiety produced by in vitro transcription might have affected the stimulation of innate immune system. Herein, using chemically synthesized long dsRNAs without 5'-triphosphate, we elucidated direct relationship between length of dsRNAs and innate immune stimulation. First, we found that blunt-ended, chemically synthesized 38/40-60 bp-long dsRNAs induced retinoic acid-inducible gene I (RIG-I)-mediated innate immune response, which was suppressed by the introduction of the 2-nt 3' overhang structure. Surprisingly, we discovered that RIG-I activation by these long dsRNAs is also sequence dependent, and the sequence composition at dsRNA termini is important for RIG-I activation. In addition, we identified that long dsRNAs over 38 bp could elicit single- or dual-target gene silencing in a Dicer-independent manner. Taken together, our findings may serve as guidelines to develop an immunostimulatory RNAi trigger to exploit host's innate immune system, as well as a specific dual-gene targeting RNAi therapeutics platform without nonspecific innate immune stimulation by RIG-I.

Application of a multiplex urinalysis test for the prediction of intravesical BCG treatment response: A pilot study.

BACKGROUND: Intravesical Bacillus Calmette-Guerin (BCG), a live attenuated tuberculosis vaccine that acts as a non-specific immune system stimulant, is the most effective adjuvant treatment for patients with intermediate or high-risk non-muscle-invasive bladder cancer (NMIBC). However, to date, there are no reliable tests that are predictive of BCG treatment response. In this study, we evaluated the performance of Oncuria, a bladder cancer detection test, to predict response to intravesical BCG.METHODS: Oncuria data was evaluated in voided urine samples obtained from a prospectively collected cohort of 64 subjects with intermediate or high risk NMIBC prior to treatment with intravesical BCG. The Oncuria test, which measures 10 cancer-associated biomarkers was performed in an independent clinical laboratory. The ability of the test to identify those patients in whom BCG is ineffective against tumor recurrence was tested. Predictive models were derived using supervised learning and cross-validation analyses. Model performance was assessed using ROC curves.RESULTS: Pre-treatment urinary concentrations of MMP9, VEGFA, CA9, SDC1, PAI1, APOE, A1AT, ANG and MMP10 were increased in patients who developed disease recurrence. A combinatorial predictive model of treatment outcome achieved an AUROC 0.89 [95% CI: 0.80–0.99], outperforming any single biomarker, with a test sensitivity of 81.8% and a specificity of 84.9%. Hazard ratio analysis revealed that patients with higher urinary levels of ANG, CA9 and MMP10 had a significantly higher risk of disease recurrence.CONCLUSIONS: Monitoring the urinary levels of a cancer-associated biomarker panel enabled the discrimination of patients who did not respond to intravesical BCG therapy. With further study, the multiplex Oncuria test may be applicable for the clinical evaluation of bladder cancer patients considering intravesical BCG treatment.

Immunomodulatory therapy for bacterial infections in pregnant sows

The paper presents data reflecting the titers of agglutinins to specific antigens in the blood of pregnant sows and the dynamics of T and B lymphocytes, with specific immunocorrection of general intestinal diseases with the OKZ vaccine containing the antigens of colibacillosis, salmonellosis, Klebsiellosis and Proteus infection, and PPS containing Sal.cholerae suis , Sal.typhimurium, Pasteurella multocida (serovars A, B, D) and streptococci (serogroups C and R) in combination with the immunomodulator metallosuccinate. It is known that the most common pathogens are opportunistic bacteria of the Enterobacteriaceae family: Escherichia coli, Proteus vulgaris, Klebsiella pneumonia, Morganella morgani, which are widely represented in the environment, and are also resident representatives of the normal microflora of animals. In this regard, the specific prevention of bacterial infections with the simultaneous stimulation of nonspecific immunity in pregnant sows is of scientific and practical importance. Specific prophylaxis of sows, in combination with metallosuccinate, increases agglutinin titers, respectively, to pasteurellosis antigen within 19.8% - 24.7%, salmonella antigens (S. cholerae suis 2.2 times, S. typhimurium 2.9 times) and by 77.9% after the second injection, to the Escherichiosis antigen by 9.2% -67.3% and to the streptococcal antigen by 2.8 times compared with the animals of the control group. An increase in agglutinin titers was found without the use of specific drugs, which characterizes metallosuccinate as a drug with antigenicity. The use of metallosuccinate in sows using specific biological products made it possible to activate the synthesis of B-lymphocytes within 47.7% after the first injection, by 50.7% 10 days after the second injection and by 42.6% 20 days after the second injection. Thus, in the studies carried out, a strategy and basic principles of simultaneous immune and metabolic correction of the body of pregnant sows have been proposed.

Innate Immune Stimulation Should not be Overlooked in Post-exposure Prophylaxis and Early Therapy for Coronavirus Infections.

We discuss the suitability of innate immune stimulation in acute respiratory infection post-exposure prophylaxis. The induction of innate immunity can be used to reduce susceptibility to immune-evasive pathogens (coronavirus, influenza virus, respiratory syncytial virus and rhinovirus). After the emergence of multiple SARS-CoV-2 variants, scientists are debating whether new variants could affect vaccine efficacy and how antigens could be redesigned to compensate. In addition, there is insufficient vaccine production to cover universal demand, and equitable vaccine distribution is a global challenge. Given these factors, non-specific immune stimulators may be suitable for a quick first response in the case of a suspected or early respiratory infection. Our group completed several HeberNasvac studies in healthy volunteers and patients with respiratory infections, and is currently starting large clinical trials in patients with early SARS-CoV-2 infections. This nasal formulation of hepatitis B vaccine has demonstrated its capacity to stimulate innate immunity markers (TLR3, TLR7 and TLR8 in tonsils) at the virus' entry site, in systemic compartments (HLA class II in monocytes and lymphocytes) and in the activation of dendritic cells, lymphocytes and other cell lines in vitro and ex vivo. In addition, research generated by the current pandemic may obtain results useful for treating other acute respiratory infections, which have long been main drivers of mortality among older adults and in early childhood.

S3 guideline Allergy Prevention.

S3 guideline Allergy Prevention.

Effect of peripartal administration of mycobacterium cell wall fraction on health and fertility of Holstein cows under organic-certified management.

The main objective of this study was to evaluate the effect of peripartal administration of a commercially available nonspecific immune stimulant (mycobacterium cell wall fraction; MCWF [Amplimune, NovaVive Inc., Napanee, ON, Canada]) on the incidence of disease during early lactation and subsequent fertility of dairy cows. A second objective was to characterize the dynamics of circulating white blood cells (WBC) and metabolic markers following treatment administration. Cows in an United States Department of Agriculture (USDA) organic-certified dairy herd were blocked by parity and, based on sequential calving dates, randomly assigned to receive two injections (5 mL s.c.) of either a placebo (saline solution) as a control (CON; n = 71) or MCWF (n = 65) at enrollment (7 d before expected calving) and within 24 h after calving. Blood samples were collected from a subsample of the study population (MCWF = 16; CON = 18) for WBC count at enrollment, at day 2 post enrollment, and at days 1, 3, 7, and 14 after calving. Serum fatty acids, beta-hydroxybutyrate, and Ca concentrations were determined at days 1 and 7 postpartum (MCWF = 21; CON = 21). Main outcome variables included incidence risk of peripartal and early lactation health disorders and pregnancy at first artificial insemination (AI), at 100, and at 150 days in milk (DIM). In addition, the average daily milk yield up to 90 DIM and death and live culling before 305 DIM were compared. Treatment effects were assessed using multivariable logistic regression, time-to-event analyses, and repeated measures analysis of variance (ANOVA). A treatment effect on the incidence risk of some of the health disorders in the study was established. Incidence risk of metritis and clinical mastitis <28 DIM was smaller in MCWF than in CON cows (36.9% vs. 50.7% and 6.3% vs. 19.7%, respectively). On the contrary, the incidence risk of respiratory disease <28 DIM was smaller in CON (0%) than in MCWF (7.7%). Reproductive performance of multiparous cows was affected by MCWF administration: pregnancy at first AI and pregnancy at 100 and 150 DIM were greater in MCWF than in CON (35.6% vs. 19.2%; 51.1% vs. 25.0%; and 64.4% vs. 40.4%, respectively). Overall, median intervals from calving to pregnancy were 90 vs. 121 d in MCWF and CON cows, respectively. No treatment effects on the dynamics of circulating WBC or in postpartum metabolic status were established. No differences for milk yield or for the proportion of cows that survived up to 305 DIM were determined, although cows in MCWF left the herd earlier than cows in CON. In conclusion, incidence risks of metritis and mastitis in early lactation were smaller in cows receiving MCWF, whereas the incidence risk of respiratory disease was smaller in CON. Fertility significantly improved in MCWF compared with CON cows. As this study was performed in an organic-certified dairy, specific health and reproductive management practices may affect the external validity of the current findings.

What's New in Shock, February 2021?

What's New in Shock, February 2021?

Case Report: An EGFR-Targeted 4-1BB-agonistic Trimerbody Does Not Induce Hepatotoxicity in Transgenic Mice With Liver Expression of Human EGFR.

Agonistic monoclonal antibodies (mAbs) targeting the co-stimulatory receptor 4-1BB are among the most effective immunotherapeutic agents across pre-clinical cancer models. However, clinical development of full-length 4-1BB agonistic mAbs, has been hampered by dose-limiting liver toxicity. We have previously developed an EGFR-targeted 4-1BB-agonistic trimerbody (1D8N/CEGa1) that induces potent anti-tumor immunity without systemic toxicity, in immunocompetent mice bearing murine colorectal carcinoma cells expressing human EGFR. Here, we study the impact of human EGFR expression on mouse liver in the toxicity profile of 1D8N/CEGa1. Systemic administration of IgG-based anti-4-1BB agonist resulted in nonspecific immune stimulation and hepatotoxicity in a liver-specific human EGFR-transgenic immunocompetent mouse, whereas in 1D8N/CEGa1-treated mice no such immune-related adverse effects were observed. Collectively, these data support the role of FcγR interactions in the major off-tumor toxicities associated with IgG-based 4-1BB agonists and further validate the safety profile of EGFR-targeted Fc-less 4-1BB-agonistic trimerbodies in systemic cancer immunotherapy protocols.

ПРОБИОТИЧЕСКИЙ ШТАММ LACTOBACILLUS REUTERI И ЕГО ВЛИЯНИЕ НА ПРОДУКТИВНОСТЬ ПОРОСЯТ В ПОСЛЕОТЬЕМНЫЙ ПЕРИОД

The article presents data on the study of the effectiveness of a probiotic based on two strains of Lactobacillus reuteri on the indicators of nonspecific resistance and productivity of weaned piglets. The normalization of the digestive tract microflora under the action of probiotics, manifested in an increase in the number of lactobacilli and bifidobacteria, with a simultaneous decrease in the number of salmonella, as well as the stimulation of non-specific immunity, together led to an increase in the growth rate of piglets. At the end of the experiment, the live weight of piglets treated with Lactobacillus reuteri was 9.3% higher and the average daily gains were 15.8% higher than the control group. At the same time, feed costs per 1 kg of growth decreased by 13.6%. This allows the use of probiotic strains of Lactobacillus reuteri in the diet of piglets to increase non-specific resistance and growth indicators in the post-weaning period.

Effects of the Administration of a Non-specific Immune Stimulant Around Transportation on Health and Performance of Jersey and Jersey-Cross Heifer Calves During the Rearing Period: Randomized Clinical Trial.

Our objective was to evaluate the effects of a non-specific immune stimulant (IS) administered around transportation on health scores (HS), average daily gain (ADG), disease treatment and mortality of Jersey and Jersey-cross calves during the rearing period. Newborn calves (4 d ± 1) were randomly allocated to receive either 1 mL of saline (CON; n = 438), 1 mL of IS before transport (BTIS; n = 431), or 1 mL of IS immediately after transport (ATIS; n = 436). Calves were health scored weekly for 3 weeks after transport. The data were analyzed using multivariable linear mixed models and multivariable logistic regression models. Kaplan-Meier survival analysis was performed for time to event analysis. Treatment, birth weight, breed, site of birth, serum total solids, dam parity, season of enrollment, and metaphylaxis were offered to models. Differences in respiratory and fecal HS, and ADG between treatment groups were not statistically significant. A total of 196 (15.0%) calves were treated at least once for any disease and 52 calves were treated multiple times. The proportion of calves treated for respiratory disease and/or diarrhea were 14.4, 14.4, and 16.2% for BTIS, ATIS and CON groups, respectively. Although the differences in the likelihood of treatment for both respiratory disease and/or diarrhea during the first 9 weeks of life was not statistically different between groups, we observed that more calves in the control group received disease treatments around 15 days of age compared with calves that received IS. The likelihood of treatment for respiratory diseases alone during the first 30 days of life was smaller in the calves that received IS before transportation when compared to the control group. Only 18 (1.4%) calves died within the study period. The calf mortality likelihood was not statistically different between study groups; however, fewer calves in the IS groups died when compared to CON. In conclusion, the use of IS around transportation did not influence weekly HS, ADG, and the number of disease treatments during the rearing period, but administering IS before transportation resulted in fewer treatments of respiratory diseases during the first 30 days post-transport and marginally lower mortality rates during the rearing period.

Non-specific protection from respiratory tract infections in cattle generated by intranasal administration of an innate immune stimulant.

Alternatives to antibiotics for prevention of respiratory tract infections in cattle are urgently needed given the increasing public and regulatory pressure to reduce overall antibiotic usage. Activation of local innate immune defenses in the upper respiratory tract is one strategy to induce non-specific protection against infection with the diverse array of viral and bacterial pathogens associated with bovine respiratory disease complex (BRDC), while avoiding the use of antibiotics. Our prior studies in rodent models demonstrated that intranasal administration of liposome-TLR complexes (LTC) as a non-specific immune stimulant generated high levels of protection against lethal bacterial and viral pathogens. Therefore, we conducted studies to assess LTC induction of local immune responses and protective immunity to BRDC in cattle. In vitro, LTC were shown to activate peripheral blood mononuclear cells in cattle, which was associated with secretion of INFγ and IL-6. Macrophage activation with LTC triggered intracellular killing of Mannheimia hemolytica and several other bacterial pathogens. In studies in cattle, intranasal administration of LTC demonstrated dose-dependent activation of local innate immune responses in the nasopharynx, including recruitment of monocytes and prolonged upregulation (at least 2 weeks) of innate immune cytokine gene expression by nasopharyngeal mucosal cells. In a BRDC challenge study, intranasal administration of LTC prior to pathogen exposure resulted in significant reduction in both clinical signs of infection and disease-associated euthanasia rates. These findings indicate that intranasal administration of a non-specific innate immune stimulant can be an effective method of rapidly generating generalized protection from mixed viral and bacterial respiratory tract infections in cattle.

Effects of the administration of a bovine non-specific immune stimulant around transportation on health and performance of Jersey and Jerseycross heifer calves in the first 60 days of life

Health and performance of pre-weaned dairy calves have great influence on adult life performance. Amongst the diseases that affect young dairy calves, diarrhea and pneumonia are the most prevalent and economically important. The main objective of this study was to evaluate the effects of a non-specific immune stimulant (IS; Amplimune, NovaVive, Inc., Canada), administered around transportation, on the health and performance of Jersey and Jersey-cross heifer calves during the first 60 days of life. We hypothesized that calves receiving IS would have decreased disease treatment hazard, lower weekly health scores (HS), decreased mortality, and superior performance.

Reaction of the Palatine Tonsillar Immunocompetent Cells to Irrigation of Crypts by Suspension of Silica Nanoparticles under Conditions of Chronic Tonsillitis.

We studied the response of neutrophils, macrophages, and mast cells to local application of silica nanoparticles (10-20 nm). Histological examination of tonsillar postoperative material from 6 patients aged 24-44 years with recurrent tonsillitis was carried out. Irrigation of the tonsillar lacunae was carried out over 5 days before bilateral tonsillectomy: on the right by Polysorb MP suspension (1 g/liter), on the left by saline. The contact of nanoparticles with the mucosa led to a decrease in the number of cells expressing myeloperoxidase (p=0.02) and an increase in the count of CD68+ cells (p=0.04); the count of mast cells remained unchanged. Local use of medical adsorbent based on silica nanoparticles induced changes in cells due to their resorption by the tissue. Positive chemotaxis of CD68+ macrophages revealed in the tonsillar lymphoid tissue attested to stimulation of non-specific immunity and inductive phase of specific immunity. The authors hypothesized that internalization of medical nanoparticles by resident phagocytes of the mucosa could support targeted biodistribution of drugs in the palatine tonsils.

Chelonid Alphaherpesvirus 5 DNA in Fibropapillomatosis-Affected Chelonia mydas.

Fibropapillomatosis is a panzootic and chronic disease among Chelonia mydas-usually associated with anthropogenic impacts. This study contributes towards understanding fibropapillomatosis implications for C. mydas populations as a reflector of environmental quality, via prevalence and histological, molecular and blood analyses at a World Heritage site in southern Brazil. Sixty-three juvenile C. mydas (31.3-54.5cm curved carapace length-CCL) were sampled during two years. Eighteen specimens (~ 29%) had tumours (which were biopsied), while 45 had none. Degenerative changes in the epidermis and Chelonid alphaherpesvirus 5 DNA detection with three variants support a herpesvirus infection. Phylogenetic analysis indicated that variants A and B were similar to a herpesvirus lineage from the Atlantic group, but variant C was similar to a herpesvirus from the eastern Pacific lineage and represents the first published case for marine turtles off Brazil. Significantly lower levels of seven blood parameters, but greater numbers of eosinophils, were observed in tumour-afflicted animals. These observations were attributed to metabolism efficiencies and/or differences in diet associated with temporal-recruitment bias and disease development, and greater non-specific immune stimulation. While most animals had adequate body condition independent of disease, longer-term studies are required to elucidate any protracted population effects.

Stimulation of non-specific immunity, gene expression, and disease resistance in Nile Tilapia, Oreochromis niloticus (Linnaeus, 1758), by the methanolic extract of the marine macroalga, Caulerpa scalpelliformis.

Aim:The objective of the present study was to test the immunostimulating potential of marine macroalga, Caulerpa scalpelliformis, in terms of non-specific immune responses, gene expression, and disease resistance of Nile tilapia, Oreochromis niloticus (Linnaeus, 1758).Materials and Methods:O. niloticus was injected intraperitoneally with three different doses of methanol extract of C. scalpelliformis (CSME) (2 mg/kg, 20 mg/kg, or 200 mg/kg body weight), or MacroGard™ (commercial immunostimulant, positive control, and 20 mg/kg body weight), or distilled water (untreated control). In one set of fish, 5 days post-injection, serum lysozyme, myeloperoxidase, and antiprotease activities were assayed. 24 h after injection, gene expression was analyzed in a separate set of fish. To another set of fish, 1 week post-administration of the products, fish were challenged with lethal dose 50 (LD50) dose of a live virulent pathogen, Aeromonas hydrophila and subsequent resistance to it was noted in terms of cumulative percent mortality.Results:CSME increased serum lysozyme, myeloperoxidase, and antiprotease activities. There was an increase in the expression of lysozyme gene in the spleen of treated fish. Mid dose of CSME caused the minimum mortality of 10% (consequent relative percentage survival = 73) which is comparable to that of the positive control.Conclusion:CSME is considered to have the potential to be developed into an immunostimulant for finfish aquaculture.