Kynurenic acid and zaprinast diminished CXCL17-evoked pain-related behaviour and enhanced morphine analgesia in a mouse neuropathic pain model

Background

The G protein-coupled receptor 35 (GPR35), is considered important for nociceptive transmission, as suggested by accumulating evidence. This receptor was discovered in 1998; however, a lack of pharmacological tools prevented a complete understanding of its function and how to exploit it therapeutically. We studied the influence of CXCL17, kynurenic acid and zaprinast on nociceptive transmission in naïve and neuropathic mice. Additionally, we investigated the influence of kynurenic acid and zaprinast on morphine effectiveness in neuropathic pain.

Genetic diversity and antimicrobial resistance of Staphylococcus aureus from recurrent tonsillitis in children

The aim of this study was to analyze the prevalence of Staphylococcus aureus in the tonsils of children subjected tonsillectomy due to recurrent tonsilitis and to determine the spa types of the pathogens, carriage of virulence genes and antimicrobial resistance profiles. The study included 73 tonsillectomized children. Bacteria, including S. aureus were isolated from tonsillar surface prior to tonsillectomy, recovered from tonsillar core at the time of the surgery, and from posterior pharynx 2–4 weeks after the procedure. Staphylococcus aureus isolates were compared by spa typing, tested for antimicrobial susceptibility and for the presence of superantigenic toxin genes (sea-seu, eta, etb, tst, lukS/lukF-PV) by multiplex polymerase chain reaction. Seventy-three patients (mean 7.1 ± 4.1 years, 61.6% male) were assessed. The most commonly isolated bacteria were S. aureus. The largest proportion of staphylococcal isolates originated from tonsillar core (63%), followed by tonsillar surface (45.1%) and posterior pharynx in tonsillectomized children (18.2%, p = 0.007). Five (6.3%) isolates were identified as MRSA (mecA-positive). Up to 67.5% of the isolates synthesized penicillinases (blaZ-positive isolates), and 8.8% displayed MLS_B resistance. The superantigenic toxin genes were detected in more than half of examined isolates (56.3%). spa types t091, t084, and t002, and clonal complexes (CCs) CC7, CC45, and CC30 turned out to be most common. Staphylococcus aureus associated with RT in children showed pathogenicity potential and considerable genetic diversity, and no clones were found to be specific for this condition although further studies are needed.     

Serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinases 2 (TIMP-2) in colorectal cancer patients

The objective of the study was the assessment of serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in patients with colorectal cancer (CRC). The study included 72 CRC patients and 68 healthy subjects. The serum levels of MMP-2 and TIMP-2 were measured using enzyme-linked immunosorbent assay (ELISA) method, whereas tissue expression of MMP-2 and TIMP-2 in cancer cells, interstitial inflammatory cells, and adjacent normal colorectal mucosa were examined by immunohistochemical staining of tumor samples. The serum levels of MMP-2 and TIMP-2 in cancer patients were significantly lower than those in control group, but the percentage of positive immunoreactivity of these proteins were higher in malignant and inflammatory cells as compared to normal tissue. There was a significant correlation between MMP-2 immunoreactivity in inflammatory cells and the presence of distant metastases and between TIMP-2 expression in inflammatory cells and tumor size, nodal involvement, and distant metastases. Area under receiver operating characteristic (ROC) curve (AUC) for serum MMP-2 was higher than for serum TIMP-2. Moreover, positive tissue expression of MMP-2 was a significant prognostic factor for CRC patients’ survival. Our findings suggest that MMP-2 and TIMP-2 might play a role in the process of colorectal cancer invasion and metastasis, but the significance of their interactions with tumor stroma and interstitial inflammatory infiltration in colorectal neoplasia require further elucidation.     

Wczesna niehematologiczna toksyczność po chemioterapii w wysokich dawkach i autologicznym przeszczepieniu komórek krwiotwórczych u chorych na nowotwory limfoidalne powyżej 60. roku życia

Early non-haematological toxicity of high dose therapy (HDT) and autologous haematopoietic cell transplantation (autoHCT) can be more hazardous in older patients (pts) with comorbidities. The aim of the study was to analyze incidence and grade of the organ-related early complications up to 30 days post-transplant period in elderly lymphoma patients. Between January 2005 and November 2011, 44 consecutive lymphoma pts underwent HDT followed by autoHCT. Median age of pts was 62 years (range 60–67). Conditioning regimens were: BEAM(carmustine, etoposide, cytarabine, melphalan) in 16, melphalan 200 in 22, cytarabine, melphalan or cyclophosphamide – in 6 pts. 32% pts had comorbidities: in 71% cardiovascular. Early non-haematologic complications within 30 days after autoHCT were reported in 84% of pts. The most common events were gastrointestinal (77%): 55% pts had prolonged (more than 7 days) diarrhoea grade III—IV, nausea and vomiting occurred in 40% of pts, 50% of pts demonstrated mucositis (grade III—IV in 34% of pts). Neutropenic fever was reported in 59% of pts with sepsis in 1.9% of pts. Cardiac events occurred in 9% of pts. Median hospitalization was 21 days (range 16—45). One patient died from transplanted related toxicity. HDT resulted in high incidence of non-hematologic toxicity in elderly patients during early post-transplant period. The toxicity of this procedure is acceptable, with mortality rate of only 2% in the elderly transplanted patients. The most common toxicities were: neutropenic fever, gastrointestinal toxicity and cardiac complications     

Transforming growth factor-beta1 and IL-13 response to allergen predict steroid needs in asthmatic children

BackgroundThe remission of asthma, which is induced during specific immunotherapy (SIT) or appears spontaneously in children is not completely understood and predictors of this phenomenon are still undefined.ObjectiveTo assess CD4⁺CD25⁺Foxp3⁺ Treg cells and cytokine/proliferation response to allergen-specific stimulation of PBMC as predictors of steroid sparing effect of SIT and steroid dosage needs without SIT during 5 years of follow-up in asthmatic children.MethodsThis is a 5-year long study of 32 asthmatic children, sensitive only to house dust mite (HDM). Eighteen children who had completed 5 years of HDM SIT – SIT group, and 14 children without SIT as a control group were studied. All patients had baseline clinical/immunological assessment; before and after observation the minimum effective ICS dose was defined and lung function was measured.ResultsIn children from SIT group minimum effective ICS dose was reduced more than in children from control group (median reduction 65% vs. 0%; p < 0.001). Among patients in control group asthma severity was reduced after 5 years of observation in those who had at baseline higher TGF-beta1 and lower IL-13 answer to allergen stimulation of PBMC. Better response to 5 years immunotherapy was observed in those who had at baseline higher TGF-beta1 and lower proliferation answer to allergen stimulation of PBMC.ConclusionSimilar processes may decide on both, SIT-induced and spontaneously appearing, reduction in asthma severity. Immunotherapy was much more effective than pharmacotherapy in our study. IL-13 overproduction may impede reduction of disease severity in asthmatic children independently from TGF-beta pathway.