Markers of systemic inflammation in delayed pressure urticaria

Background We have previously reported, increased plasma IL‐6 concentration in chronic urticaria. In addition, it has been suggested that IL‐6 and C‐reactive protein (CRP) may be useful markers of the disease activity. Aim The aim of this study was to evaluate whether a systemic inflammation is present in delayed pressure urticaria (DPU). Methods Plasma IL‐6 and serum CRP concentrations, biomarkers of acute phase response, were measured in DPU, and the healthy subjects matched by age, gender, and BMI using ELISA method. Results DPU patients showed significantly higher plasma IL‐6 and serum CRP concentrations than the healthy subjects. Conclusions Similarly to the known locally increased IL‐6 activity in DPU lesions, the elevated circulating levels of IL‐6 and CRP have been currently found in DPU. This indicates that the disease induces a systemic inflammatory process, termed the acute phase response.     

Influences of polymorphic variants of DRD2 and SLC6A3 genes, and their combinations on smoking in Polish population

Background  

Polymorphisms in dopaminergic genes may influence cigarette smoking by their potential impact on dopamine reward pathway function. A1 allele of DRD2 gene is associated with a reduced dopamine D2 receptor density, and it has been hypothesised that A1 carriers are more vulnerable to smoking. In turn, the 9-repeat allele of dopamine transporter gene (SLC6A3) has been associated with a substantial reduction in dopamine transporter, what might result in the higher level of dopamine in the synaptic cleft, and thereby protective role of this allele from smoking. In the present study we investigated whether polymorphic variants of DRD2 and SLC6A3 genes and their combinations are associated with the smoking habit in the Polish population.     

Immunosenescence increases the rate of acceptance of kidney allotransplants in elderly recipients through exhaustion of CD4 T-cells

Compromised immunity is the hallmark of ageing. Paradoxically, it may be “an ally” in facilitating acceptance of allogeneic grafts in the elderly. In this retrospective study we looked for biomarkers of immunosenescence that distinguish elderly recipients less prone to reject kidney allografts.Recruited kidney recipients aged ≥60 or <60 were designated ‘elderly’ and ‘young’, respectively. Both age-groups were divided according to the history of acute rejection. The phenotype, length of telomeres, expression of FoxP3 and proliferative responses were assessed in CD4⁺ and CD8⁺ T-cell subsets. In addition, IL6, IL10 and TGFβ were measured on the level of mRNA and serum protein.Acute-rejection-free history in elderly transplant recipients was associated with short telomeres, a decreased proportion of CD28⁺ T-cells associated with CMV-seropositivity and low proliferation of CD4⁺ T-cells. In contrast, elderly recipients who experienced acute rejection kept preserved telomere length, had a higher number of functional CD4⁺CD28⁺ cells and exhibited vigorous proliferation in vitro. These differences were not found in the young group.The major conclusion of this study is that the impaired condition of CD4⁺ T-cells, so-called immunosenescence, renders transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients of >60 years of age.     

Putative Biological Mechanisms of Efficiency of Substrate Reduction Therapies for Mucopolysaccharidoses

Mucopolysaccharidoses (MPS) are inherited metabolic diseases caused by mutations in genes coding for lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). Dysfunction of any of these enzymes results in the accumulation of GAGs, which leads to severe clinical symptoms and significantly shortened life span. Several kinds of therapies have been proposed to treat MPS, including bone marrow or stem cell transplantation, enzyme replacement therapy, and gene therapy. Another option is substrate reduction therapy (SRT), in which synthesis of GAGs is inhibited. Recent studies employing in vitro and animal models suggested that this therapy may be efficient in decreasing levels of GAGs in MPS cells, including those bearing two null alleles of the affected gene. Results of behavioral tests in animals as well as some preliminary clinical observations with pediatric patients corroborated the suggestions about possible efficacy of SRT in MPS treatment, including brain functions. Efficient reduction of GAG levels in MPS cells homozygous for null mutations may be intriguing in the commonly accepted scheme of SRT mode of action. In this paper, we propose an explanation of this phenomenon, based on already known facts. Thus, we suggest that SRT may lead to reduction of GAG levels in MPS cells due to inhibition of efficiency of GAG synthesis combined with (a) any readthrough of the stop codon, (b) dilution of already accumulated GAGs due to cell growth followed by cell divisions, and (c) action of endoglycosidases degrading GAGs, e.g., heparanase, in combination with functional GAG-specific hydrolases.     

Estimating age-specific breast cancer risks: a descriptive tool to identify age interactions

OBJECTIVE: Clarifying age-specific female breast cancer risks and interactions may provide important etiologic clues. METHOD: Using a population-based case-control study in Poland (2000-2003) of 2,386 incident breast cancer cases and 2,502 control subjects aged 25-74 years, we estimated age-specific breast cancer incidence rates according to risk factors. RESULTS: Breast cancer risks were elevated among women with positive family history (FH), younger age at menarche, older age at first full-term birth, nulliparity, exogenous hormonal usage, and reduced physical activity (PA). Notwithstanding overall risks, we observed statistically significant quantitative (non-crossover) and qualitative (crossover) age interactions for all risk factors except for FH and PA. For example, nulliparity compared to parity reduced breast cancer risk among women ages 25-39 years then rates crossed or reversed, after which nulliparity increased relative risks among women ages 40-74 years. CONCLUSION: Though quantitative age interactions could be expected, qualitative interactions were somewhat counterintuitive. If confirmed in other populations, qualitative interactions for a continuous covariate such as age will be difficult to reconcile in a sequential (multistep or monolithic) 'stochastic' breast cancer model. Alternatively, the reversal of relative risks among younger and older women suggests subgroup heterogeneity with different etiologic mechanisms for early-onset and late-onset breast cancer types.     

Occurrence of Pneumocystis carinii DNA and anti-Pneumocystis antibodies in the sera of infants during a period of of physiologic decreased immune response

The polymerase chain reaction (PCR) and indirect immunofluorescent test (IF) were used for examination of serum samples obtained from infants with respiratory tract infections. Sixty (11.9%) out of the 503 examined infant samples were positive for anti-P. carinii IgM and 354 (70.4%) contained anti-Pneumocystis IgG. P. carinii DNA was found in 6 (6.7%) sera from 90 of infected infants. Five out these 6 samples were for anti-Pneumocystis antibodies positive; 4 contained both IgG and IgM classes and one had only IgG. The sixth sample had neither IgG nor IgM, despite of P. carinii DNA presence. The results of the studies indicated that for diagnosis Pneumocystis carinii pneumonia (PCP) in infants on serum specimens detection of antibodies by IF test is of greater value than Pneumocystis DNA amplification by PCR method.     

Relationship between activity of hydrolases in fungi isolated from vagina of pregnant women and selected symptoms

Pregnancy is considered a factor of vulvovaginal mycosis. Secretion of hydrolases is an important determinant of Candida virulence. Thus, the aim of the study was to found the relationship between activity of 19 hydrolases in fungi isolated from vagina of pregnant women and symptoms of mycosis. 251 pregnant women were examined. Samples were collected from vagina and cultured on Sabouraud media. Activity of hydrolytic enzymes was evaluated using API ZYM (bioMerieux) test Fungi were found in 20.1% of vaginal samples. Symptoms were detected in 45.8% of women. Only 32.1% of women with discharge and 26.4% with pruritus had mycosis. Out of the 19 examined hydrolazes, 13 active enzymes were detected in fungal strains. We found for the first time the relationship between activity of fungal esterase lipase and the presence of vaginal discharge in pregnant women.