Fucoidan from Ericaria crinita Alleviates Inflammation in Rat Paw Edema, Downregulates Pro-Inflammatory Cytokine Levels, and Shows Antioxidant Activity.

Fucoidans are sulfated polysaccharides detected mainly in the cell walls of brown seaweeds. Here, we examined the effects of single doses of fucoidan derived from Ericaria crinita (formerly Cystoseira crinita) on carrageenan-induced paw inflammation in rats. The serum levels of TNF-α, IL-1ß, IL-6, and IL-10 of rats with LPS-induced systemic inflammation after 14 days of treatment were also evaluated. Subchronic treatment with fucoidan from E. crinita attenuated the inflammation during the late phase of the degraded carrageenan-induced paw edema (3rd to 5th hour after carrageenan injection) with peak activity at the 3rd hour after the application. Both doses of fucoidan from E. crinita (25 and 50 mg/kg bw) significantly decreased the levels of all tested pro-inflammatory cytokines (IL-1ß, TNF-α, and IL-6) in the serum of rats with a model of system inflammation but had no effect on the anti-inflammatory cytokine IL-10. The results showed that the repeated application of fucoidan has a more prominent effect on the levels of some pro-inflammatory cytokines in serum in comparison to a single dose of the sulfated polysaccharide. This reveals the potential of E. crinita fucoidan as an anti-inflammatory agent. Furthermore, E. crinita fucoidan exhibited in vitro antioxidant capacity, determined by 2,2-diphenyl-1-picryl-hydrazyl radical scavenging and ferric reducing antioxidant power assays as follows: IC50 = 412 µg/mL and 118.72 µM Trolox equivalent/g, respectively.

Extraction, Structural Characterization, and In Vivo Anti-Inflammatory Effect of Alginate from Cystoseira crinita (Desf.) Borry Harvested in the Bulgarian Black Sea.

The aim of this study was to identify the chemical composition and sequential structure of alginate isolated from C. crinita harvested in the Bulgarian Black Sea, as well as its effects in histamine-induced paw inflammation in rats. The serum levels of TNF-α, IL-1ß, IL-6, and IL-10 in rats with systemic inflammation, and the levels of TNF-α in a model of acute peritonitis in rats were also investigated. The structural characterization of the polysaccharide was obtained by FTIR, SEC-MALS, and 1H NMR. The extracted alginate had an M/G ratio of 1.018, a molecular weight of 7.31 × 104 g/mol, and a polydispersity index of 1.38. C. crinita alginate in doses of 25 and 100 mg/kg showed well-defined anti-inflammatory activity in the model of paw edema. A significant decrease in serum levels of IL-1ß was observed only in animals treated with C. crinita alginate in a dose of 25 mg/kg bw. The concentrations of TNF-α and IL-6 in serum were significantly reduced in rats treated with both doses of the polysaccharide, but no statistical significance was observed in the levels of the anti-inflammatory cytokine IL-10. A single dose of alginate did not significantly alter the levels of the pro-inflammatory cytokine TNF-α in the peritoneal fluid of rats with a model of peritonitis.

Structural Characterization and In Vivo Anti-Inflammatory Activity of Fucoidan from Cystoseira crinita (Desf.) Borry.

The aim of this study was to evaluate the effects of fucoidan isolated from C. crinita on histamine-induced paw inflammation in rats, and on the serum levels of TNF-α, IL-1ß, IL-6, and IL-10 in rats during systemic inflammation response. The levels of TNF-α in a model of acute peritonitis in rats were also investigated. The isolated crude fucoidan was identified as a sulfated xylogalactofucan with high, medium, and low molecular weight fractions and a content of fucose of 39.74%, xylose of 20.75%, and galactose of 15.51%. Fucoidan from C. crinita showed better anti-inflammatory effects in the rat paw edema model, and this effect was present during all stages of the experiment. When compared to controls, a commercial fucoidan from F. vesiculosus, the results also displayed anti-inflammatory activity on the 60th, 90th, and 120th minute of the experiment. A significant decrease in serum levels of IL-1ß in rats treated with both doses of C. crinita fucoidan was observed in comparison to controls, whereas TNF-α concentrations were reduced only in the group treated with fucoidan from C. crinita at the dose of 25 mg/kg bw. In the model of carrageenan-induced peritonitis, we observed a tendency of decrease in the levels of the pro-inflammatory cytokine TNF-α in peritoneal fluid after a single dose of C. crinita fucoidan, but this did not reach the statistical significance margin. Single doses of C. crinita fucoidan did not alter serum levels of the anti-inflammatory cytokine IL-10 in animals with lipopolysaccharide-induced systemic inflammation.

Dopaminergic agonist pramipexole improves memory and increases IL-10 production in LPS-challenged rats.

OBJECTIVES: A variety of cytokines are involved in cognitive functioning. Balance restoration between protective and degenerative neuro-inflammation is of great interest in newer therapeutic approaches. In the current study, we investigated the effect of pramipexole (PMX) on memory functions, hippocampal amyloid deposition, serum cytokines, and brain-derived neurotrophic factor (BDNF) levels in lipopolysaccharide (LPS) challenged-rats. MATERIALS AND METHODS: Male Wistar rats were divided into 5 groups (n=8): control (saline), lipoppolysacharide (LPS 250 mcg/kg bw), and experimental groups (LPS and PMX 0.5, 1, and 3 mg/kg bw). Learning and memory were assessed by the novel object recognition test (NORT), Y-maze, and step-through test. Immunological and histological assays were performed. RESULTS: In memory tasks, LPS-challenged rats showed reduction in the observed parameters. In NORT, PMX 1 mg/kg increased recognition index compared with controls, whereas the other two doses increased this index only against the LPS-control. In Y-maze, all doses of PMX significantly had increased alternation when compared with LPS. In the step-through test, only the lowest dose of PMX extended the latency compared with LPS. Histological examination revealed that PMX at doses of 0.5 and 1 mg/kg reduced amyloid deposition in the hippocampus. Interleukin (IL)-10 serum levels were elevated by 1 mg/kg PMX. Tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-ß1 serum levels remained under the detectable minimum in all experimental groups. PMX at all doses significantly decreased BDNF serum concentration. CONCLUSION: In rats with LPS-induced neuro-inflammation PMX improved hippocampal-dependent memory and exerted immuno-modulatory effects by increasing IL-10.

Effect of Bulgarian propolis on the oral microflora in adolescents with plaque-induced gingivitis

ABSTRACT We compared the effect of two therapeutic approaches (marketed toothpaste and addition of Bulgarian propolis extract to the toothpaste) on gingival inflammation, plaque formation and oral microbial flora on Bulgarian adolescents with moderate plaque-induced gingivitis. The participants were divided randomly into two groups of 35 students. The first group was instructed to use marketed toothpaste in their routine oral hygiene. The second group was instructed to add 10 drops of Propolin® to the toothpaste before every brushing. The Gingival index and Plaque index were registered and dental plaque samples were collected on the first visit and on the 20th day of the study. After the treatment, the number of students with Gingival index = 1.1-2.0 in the second group was significantly lower than the respective number in the first group. Neisseria spp. and Streptococcus spp. were present in all samples before and after treatment. The addition of propolis resulted in the complete eradication of Streptococcus mutans, Candida albicans, Fusobacterium varium, Gram-negative cocci, Gram-positive rods, Porphyromonas asaccharolyticus, Prevotella bivia, Prevotella intermedia, Prevotella melani and Streptococcus intermedius. The analyses of Propolin® composition revealed it was a black poplar type propolis and is rich in compounds with pronounced antimicrobial activity. In conclusion, the addition of Bulgarian propolis to the toothpaste improved the gingival health in adolescents with moderate plaque-induced gingivitis and resulted in increased activity against potential periodontal and cariogenic pathogens.

Fatal Chemotherapy-induced Combined Infection in a Hodgkin's Disease Patient: a Case Report.

Multimodal therapy, used for the treatment of patients with Hodgkin's disease (HD), makes them prone to life-threatening infections, attributed mainly to febrile neutropenia. Herein, we present a case report of fatal combined bacterial and viral infection in a 49-year-old female patient, subject to polychemotherapy for HD. Rapid microbiological diagnosis performed by multiplex polymerase chain reaction elucidated the causes of the infection within hours. Listeria monocytogenes was detected in both the cerebrospinal fluid and blood samples. Nasopharyngeal swabs returned positive for two swine-derived strains of influenza A virus. We aimed to emphasize the importance of these pathogens and draw attention to their association in the aetiology of infections among patients receiving chemotherapy. In conclusion, better surveillance is needed to improve the early diagnosis of infectious complications in these patients.

Serotype changes and antimicrobial nonsusceptibility rates of invasive and non-invasive Streptococcus pneumoniae isolates after implementation of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Bulgaria

Abstract The 10-valent pneumococcal conjugate vaccine (PCV10) has been included in Bulgarian Childhood Immunization Program since 2010. This study aimed to assess serotype distribution and antimicrobial resistance of 198 invasive and non-invasive Streptococcus pneumoniae strains that had been isolated in Bulgaria during 2011-2016 from patients with invasive (IPD) and non-invasive (NIPD) pneumococcal diseases. The most common invasive serotypes were 3 (10.1%), 19F (4.0%), and 7F (3.0%). A significant decrease in the proportion of invasive vaccine types (VTs) from 64.2% to 35.2% was found in comparison with pre-vaccine era. The most common serotypes among middle ear fluids were 3, 19A and 19F (5.6% each), and VTs fell down from 66.4% to 40.0% in post-PCV10 period. Among respiratory isolates, the most prevalent serotypes were some emergent serotypes such as 15A/B/C (5.0%), 19A, and 6C (4.0% each). VTs decreased significantly (16.3%) among vaccinated children compared to unvaccinated children and adults (44.0%). Two non-VTs (19A and 6C) have increased significantly more (p < 0.05) in vaccinated children than in unvaccinated patients. The rates of antibiotic nonsusceptible S. pneumoniae in Bulgaria remained high in post-PCV10 era. Among all source of isolates, antimicrobial nonsusceptibility rates were: oral penicillin - 46.5%, trimethoprim-sulfamethoxazole - 45.4%, erythromycin - 43.9%, tetracycline - 37.4%, and multidrug-resistance (MDR) was 44%. The most common MDR serotypes were 19F, 19A, 6A/C, 15A/B/C and 23A. Our results proved that PCV10 vaccination substantially reduced VTs pneumococcal IPD and NIPD. There has been a shift in the distribution of S. pneumoniae serotypes mostly in vaccinated children but also in the whole population and strong serotype-specific antibiotic resistance was observed after vaccine implementation. Therefore, it is important to continue monitoring serotype changes and pneumococcal resistance among all patient ages in addition to aid in determining the long-term effectiveness of PCV10 interventions.

Serum levels of interferon-gamma, interleukin-12, tumour necrosis factor-alpha, and interleukin-10, and bacterial clearance in patients with gastroenteric Salmonella infection.

Cytokines as intercellular signal molecules are responsible to a great extent for the pathological processes in Salmonella infection, as well as for the development of protective mechanisms in the disease. The present study aimed to reveal the correlation between serum levels of IFN-gamma, IL-12, TNF-alpha and IL-10, measured by enzyme-immunoassay, and clearance of bacteria in stool of patients with gastroenteric Salmonella infection. The study included 36 patients with culture confirmed gastroenteric Salmonella infection. At discharge from hospital, 20 patients recovered with bacteriological negative stool culture for Salmonella and 16 were Salmonella excretors. Mean serum concentrations of IFN-gamma, IL-12, TNF-alpha and IL-10 in the acute stage were compared between the 2 groups of patients and with those of healthy controls. Serum levels of examined cytokines were increased (p<0.001) in the patients in comparison with the healthy controls. In patients with early bacterial clearance mean serum concentrations of IFN-gamma, IL-12 and TNF-alpha in the acute stage were significantly (p<0.05) higher than in the non-clearance group. IL-10 serum level showed an opposite correlation (p<0.01) and higher values in Salmonella excretors. The accumulated data imply that Th1 type cytokines probably participate in protective immunity and early bacterial clearance in patients with gastroenteric Salmonella infection.

Cytokines in Salmonella infections.

Cytokines are intercellular signal molecules involved in the immune pathogenesis of infectious diseases. Cytokine mediated pathological alterations are mainly attributable to an imbalance in cytokine production. Experimental and clinical studies have documented the fact that Salmonella infections induce a Th1 dependent immune response and interferon-gamma and interleukin-12 are central to its genesis. Salmonella endotoxins, flagellins and porins are among the chief mediators of cytokine release. Lectin binding proteins, Toll-like receptors, transcription factors and various cells also contribute to this process. Serum and local (fecal) cytokine determination in salmonellosis provides evidence on the immune events occurring after antigen challenge. They might also serve as clinical and prognostic markers of disease severity and outcome. Recent studies are focused on the effect and interaction between pro-inflammatory (interleukin-1, interferon-gamma and tumor necrosis factor) and anti-inflammatory cytokines (interleukin-10).