Increased Numbers of Circulating Th22 and Th17 Cells in Patients with Kawasaki Disease

Background T-helper (Th) 22 and Th17 cells are involved in the pathogenesis of Kawasaki Disease (KD). Methods A total of 43 patients with freshly diagnosed KD and 20 age-/gender-matched healthy controls (HC) were examined for the numbers of Th22, Th17 and Th1 cells were quantified by flow cytometry. The concentrations of serum IL-22, IL-17, IFN-γ and TNF-α were examined by enzymelinked immunosorbent assay. Results In comparison with those in the HC, significantly increased numbers of Th22 and Th17 cells, but not Th1 cells, and increased levels of serum IL-22 and IL-17, but not IFN-γ, were detected in KD patients. Stratification analysis indicated the numbers of both Th22 and Th17 cells and the concentrations of serum IL-22 and IL-17 in KD patients with coronary artery lesions (CAL) were significantly greater than that in those with noncoronary artery lesions (NCAL). Treatment with the intravenous immunoglobulin (IVIG) therapy significantly decreased numbers of Th22 and Th17 cells and concentrations of serum IL-22 and IL-17 in KD patients. The concentrations of serum IL-22 and IL-17 were correlated positively with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values as well as N-terminal pro-brain natriuretic peptide (NT-proBNP) in those patients respectively. Conclusions Our study provided direct evidence that Th22 and Th17 cells might contribute to the pathogenesis of KD.

El tratamiento con resiniferatoxina exhibe propiedades antiinflamatorias en un modelo murino de inflamación inducida por lipopolisacárido

Introducción. La inflamación es una respuesta fisiológica protectora del sistema inmunológico frente a diversos estímulos, tales como la infección o daño celular, la cual, al no resolverse de manera adecuada, puede ser perjudicial para le hospedero. En la búsqueda de nuevas lternativas terapéuticas que inhiban la respuesta inflamatoria, diversos estudios han reportado el uso de varias moléculas, tales como la resiniferatoxina (RTX), un potente agonista del receptor de potencial transitorio vanilloide (TRPV)-1. Objetivo. Evaluar si el tratamiento con RTX exhibe propiedades antiinflamatorias, utilizando un modelo murino de inflamación inducida por lipopolisacárido (LPS). Material y métodos. Se estimularon ratones BALB/c con LPS y posteriormente fueron tratados con dexametasona (DEX), capsaicina (CAP), Bay 11-7082, capsazepina (CPZ) y RTX. Además, otros grupos de ratones fueron estimulados con LPS y luego tratados con Bay 11-7082 y CPZ más RTX. Después del tratamiento, se determinaron cuantitativamente los niveles plasmáticos de prostaglandina (PG)-E2, óxido nítrico (NO), interleucina (IL)-1β y factor de necrosis tumoral (TNF)-α utilizando kits de EnzymeLinked ImmunoSorbent Assay ELISA. Resultados. El tratamiento con RTX disminuyó de manera significativa los niveles plasmáticos de PGE2, NO, IL-1β y TNF-α. Así mismo, se observó que los tratamientos con Bay 11-7082 y CPZ más RTX mostraron un efecto antiinflamatorio sinérgico, observándose una disminución significativa más pronunciada en los niveles plasmáticos de TNF-α y PGE2. Conclusión. Estos hallazgos sugieren que el tratamiento con RTX muestra propiedades antiinflamatorias, aparentemente asociadas con la vía de señalización factor nuclear (NF)-κB, independiente de los receptores TRPV1, colocando a la RTX como un fármaco potencial en el tratamiento de enfermedades inflamatorias.

IMPORTANCE OF ANTIBODIES TO 21-HYDROXYLASE FOR THE DIAGNOSIS, DIFFERENTIAL DIAGNOSIS AND PROGNOSIS OF AUTOIMMUNE CHRONIC PRIMARY ADRENAL INSUFFICIENCY

21-hydroxylase (21-OH) is the main antigen of the adrenal cortex, so the determination of antibodies (Ab) to 21-OH can help in the diagnosis and prognosis of chronic primary adrenal insufficiency (CPAI). Purpose of the study: evaluation of the relevance of Ab to 21-OH for the diagnosis and prediction of autoimmune CPAI. Materials and methods of research: the study consisted of three blocks: 1) assessment of the specificity and sensitivity, as well as the prognostic potential of Ab to 21-OH in patients with polyglandular autoimmune syndrome (APS) – individuals with APS type 1 with and without CPAI (n=106); 2) assessment of the dynamics of the level of Ab to 21-OH – patients with autoimmune CPAI were included (n=41); 3) assessment of the significance of Ab data for the differential diagnosis of various forms of CPAI, including patients with CPAI and APS type 1 exclusion (n=30). The study of Ab to 21-hydroxylase was performed using enzymelinked immunosorbent assay (BioVendor kits, Czech Republic). Results: statistically significant differences were obtained in the frequency of detection of Ab to 21-OH in patients with or without PCNI (p<0,001). The sensitivity of the method was 96%, specificity was 75%, a positive predictive value was 90%, and the negative predictive value was 89%. In 83% of patients, the level of Ab decreased with time (median size decreases – 20,4%/year). An inverse relationship was also found between the level of Ab and the duration of the course of CPAI (R=–0,460, p<0,001). In a group of 30 patients with CPAI and with exclusion of APS type 1, 21 were found to have Ab to 21-OH, only one of them had a monogenic non-autoimmune cause of CPAI (a mutation in the MC2R gene). Monogenic forms of CPAI were found in another 7 patients (mutations were found in the DAX1 and ABCD1 genes), among them an increase in Ab to 21-OH was not detected. Conclusion: determination of Ab to 21-OH is a specific and sensitive method for the diagnosis of autoimmune CPAI. An increase in Ab to 21-OH is a risk marker of autoimmune CPAI development.

Prevalence of Cryptosporidium parvum in sheep in Abeokuta, Ogun State, Nigeria

The prevalence of Cryptosporidium parvum infection in sheep was determined in Abeokuta, Ogun state, Nigeria. Faeces from randomly selected sheep were analyzed using the Enzymelinked Immunosorbent assay (ELISA) technique. Cryptosporidium parvum antigens were detected in stools of 174 sheep by the use of a commercial ELISA kit. A total of 28.7% of the stools were positive for the antigens. The infection rates decreased with age, the pre-weaned lambs (51.1%) having a significantly higher (p<0.05) in males (42.9%) and sheep with diarrhoeic stools (41.8%) than in females (17.5%) and sheep with formed stools (17.9%) respectively. This study therefore reveals that the prevalence of Cryptosporidium parvum infection is high in sheep reared in Abeokuta and may serve as a reservoir for human infections.

Investigation of the anti-diabetic nephropathy activity of puerarin

Puerarin has potential therapeutic effects on diabetic nephropathy (DN), but the effectiveness as a treatment for DN and the underlying mechanism remain to be elucidated. The DN-like model induced by high glucose in vitro and the DN model induced by streptozotocin in vivo were used to observe the effect of puerarin. The results showed that puerarin can enhance the activity of HBZY-1 cells and reduce apoptosis. in vivo enzymelinked immunosorbent assay and biochemical assay showed that puerarin can improve DN symptoms. Using hematoxylin and eosin staining to stain kidney tissues confirmed that puerarin has a protective effect on DN. Furthermore, puerarin can reduce the content of collagen type IV, laminin LN, tumor necrosis factor, p38, CREB, Fos, Jun, and MMP9 in HBZY-1 cells and DN rats. In conclusion, puerarin can effectively prevent apoptosis in vitro and improve DN-like symptoms by inhibiting the p38/MAPK signaling pathway in vivo. Therefore, puerarin has the potential to treat DN.

Trifluorobenzamidine prevents allergic rhinitis by regulating IgE, IL-4 and IL-5 in T-cells

Purpose: To investigate the effect of trifluorobenzamidine (TBI) on a mouse model of ovalbumin (OVA)- induced allergic rhinitis. Methods: Allergic rhinitis was established in mice via sensitization on days 1, 5 and 14 through intraperitoneal injection of OVA (100 μg) in PBS. On day 15, the mice were subjected to intranasal exposure to OVA (1.5 mg dissolved in PBS). Prior to 10 days of intranasal exposure to OVA, the micewere treated with TBI at doses of 5, 10 and 20 μg/kg. Cytokine levels were determined using enzymelinked immunosorbent assay (ELISA) kits, while cyclooxygenase (COX)-2 and caspase-1 activity were assayed with western blotting. Results: Treatment with TBI significantly (p < 0.05) reduced OVA-mediated increases in nasal rub scores, and decreased serum levels of IgE, TNF-α, thymic stromal lymphopoietin (TSLP), IL-1β and histamine in mice. It also significantly regulated spleen weight and IL-4 secretion (p < 0.05) in OVAadministered mice. TBI significantly downregulated the expressions of IL-5, IL-13, TNFα, TSLP, IL-1β and IL-6 (p < 0.05). Administration of TBI caused a marked reduction in OVA-mediated increase in caspase-1 activity in mice intranasal tissues, and also significantly reduced OVA-induced excessive production of MIP-2 and ICAM-1 (p < 0.05). Moreover, TBI prevented OVA-induced infiltration of eosinophils and mast cells into intranasal tissues (p < 0.05). Conclusion: TBI reduces levels of IgE and various pro-inflammatory cytokines in OVA-administered mice. It also regulates Th1:Th2 ratio, inhibited activity of caspase-1, suppressed mast cell/eosinophil infiltration and reduced ICAM-1 and MIP-2 levels. Therefore, TBI possesses inhibitory potential against rhinitis allergy, and thus can potentially be developed as a new treatment strategy for asthma. Keywords: Trifluorobenzamidine, Anti-inflammation, Allergic rhinitis, Cytokines, Caspase-1, Itching

The Role of the Hepatic Tissue Remodeling Regulators MMP-9 and TIMP-1 in the Progression of Liver Cirrhosis

Objective: to study the level of the hepatic tissue remodeling regulators MMP-9 and TIMP-1 in the blood of patients with the progression of chronic diffuse liver diseases.Material and methods. The object of the study was 80 patients with chronic diffuse liver diseases (chronic hepatitis and cirrhosis). The concentration of MMP-9 and TIMP-1 in the blood of the patients was determined by enzymelinked immunosorbent assay (ELISA).Results: As chronic diffuse liver diseases progressed, a statistically significant decrease in the level of MMP-9 in the blood of the patients was revealed, which was reflected in the decreased intensity of the extracellular matrix resorption processes and transformation of chronic hepatitis into liver cirrhosis. The activity of TIMP-1 which suppressed the fibrolytic effects of MMP-9, was statistically significantly higher in the viral etiology of liver cirrhosis, which probably led to more rapid progression of liver fibrosis associated with the presence of hepatitis C and В viruses.

Detection of enterotoxigenic strains Staphylococcus aureus, producing SEC and SEI, isolated in patients with pneumonia, sepsis and burns

Aim. To identify the frequency of occurrence of staphylococcal enterotoxins of the SEC and SEI type produced by Staphylococcus aureus strains isolated from patients with different nosology. As you know, the infection process in them proceeds with severe intoxication without vomiting and intestinal disorders.Materials and methods. 79 strains were studied (43 were isolated in case of pneumonia, 13 - in burns, 11 - in sepsis) S. aureus in the presence of SES and SEI using enzymelinked immunosorbent assay (ELISA).Results. It was found that 48.3% of S. aureus strains isolated from patients with pneumonia produced SEC and 72.1% - SEI. The frequency of occurrence of S. aureus strains producing SEC and SEI isolated in patients with burn infections was 23.0 and 15.4%, respectively. 36.4% of staphylococcal strains isolated in patients with sepsis produced SEC, 45.5% - SEI.Discussion. It was found that the proportion of S. aureus cultures producing SEC enterotoxins during sepsis is significantly higher than the strains producing SEB (5.4%) and much smaller than SEA (75.6%). A high percentage of SEI-positive strains was found compared to strains that produce the classic enterotoxins SEA, SEB and SEC isolated from pneumonia. In burn infections, the proportions of strains producing SEC and SEI were 15.4 and 23.0%, respectively, which is significantly lower than SEA (92.9%).Conclusion. The data obtained indicate the need to identify staphylococcus strains that produce both classic and newly discovered enterotoxins, which are crucial virulence factors leading to lethal sepsis, infectious endocarditis and toxic shock syndrome to eliminate them.

Estimation of effi ciency of comprehensive anti-leukemia measures in agricultural enterprises

The analysis of the dynamics of changes in serological and hematological blood parameters of cattle over the period of comprehensive healthrelated measures against Bovine Leukemia Virus (BLV) infection is presented to assess their effectiveness. For analysis of the epizootological situation, veterinary reporting data and the results of serological and hematological diagnostics for cattle leukemia were used. The work was performed in three agricultural enterprises of the Siberian Federal District: Irkutsk Region Altai Territory and Novosibirsk Region. According to the principle of an individual approach, a programme of comprehensive diagnostic and health anti-leukemia measures for each enterprise was developed. The main purpose of these measures was to break the epizootic chain in chronic BLV infection and ultimately change the epizootic situation by reducing the percentage of infection in the livestock population. The positive dynamics of the reduction of infected and leukemiasick cattle was shown as part of a complex of antiepizootic measures, which was made possible by a deviation from the generally accepted regulations for serological diagnostics in agar gel (AGID). During the quarterly diagnosis, the infection rate decreased over 2 years from 72.41 to 1.94% in cows and from 66.6% to negative results in heifers of the breeding age. Using a more sensitive method of enzymelinked immunosorbent assay in the recovery of young and repair livestock, it was possible to reduce infection from 20.9 to 4.0% and from 43.0 to 2.7%, respectively. In this case the epizootic situation for BLV infection may be more stable due to the identifi cation of hidden carriers of the infection.