IL16 and IL18 gene polymorphisms in women with gestational diabetes

Objectives: Gestational diabetes mellitus is a carbohydrate intolerance that occurs during pregnancy. Various inflammatory mediators are considered to be risk factors leading to GDM development. Among them are pro-inflammatory cytokines, such as IL16 and IL18. The aim of this study was to examine the association between IL16 and IL18 polymorphisms and GDM. Material and methods: This study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance (NGT). All samples were genotyped in duplicate using allelic discrimination assays with TaqMan® probes. Results: We observed that there was a decreased frequency of IL16 rs4778889 CC genotype carriers among women with GDM (CC vs. CT + TT: OR = 0.14; 95% CI = 0.02–1.15; p = 0.034). However, there was no significant difference in the distri­bution of alleles (C vs. T: OR = 0.81; 95% CI = 0.54–1.21; p = 0.30). There was a decreased frequency of the IL18 rs187238 G allele among GDM women (G vs. C: OR = 0.71; 95% CI = 0.53–0.96; p = 0.027). We also observed a decreased frequency of the IL18 rs1946518 T allele among women with GDM; however, this difference had only borderline statistical significance. We observed an association between IL18 rs187238, rs1946518 and BMI in pregnant women. Conclusions: The results of this study suggest that IL18 rs187238 and rs1946518 polymorphisms may be associated with an increased risk of GDM as well as with BMI in pregnant women

Effects of common functional MMP12 gene polymorphisms on PD in a Polish population

The present study investigated associations of two functional MMP12 polymorphisms with PD risk and cognitive impairment in PD. A total of 478 study subjects (241 PD and 237 age and sex matched controls) were included in the study. UPDRS score, Hoehn–Yahr staging and Schwab–England scale were used to assess motor abilities and activity during daily life. All patients were classified into groups with dementia (PDD, n=72) and without dementia (nPDD, n=159) based on the neuropsychological assessment. The two most common functional single nucleotide polymorphisms (SNPs) in MMP12 gene were determined using TaqMan real-time PCR assays. Frequencies of evaluated MMP12 rs2276109 alleles and genotypes were similar in PD and the controls, whereas rs652438G allele genotypes were significantly more frequent among healthy individuals (p=0.013, OR 0.47 (0.26–0.85). The rs2276109 and rs652438 allele and genotype frequencies were not associated with dementia in PD patients. The current results suggest that MMP12 rs652438 but not MMP12 rs2276109 may affect the risk for PD, as the minor G allele genotypes might be a protective factor

An optimization of protocol for mixed chimerism induction in mice model.

Studies on mixed chimerism are currently focused primarily on obtaining less toxic conditioning protocols. With these issues in mind, we have undertaken the attempt to optimize the procedure of mixed chimerism induction in mice. In order to reduce toxicity, we used decreasing doses of total body irradiation (TBI) together with combination of blocking antibodies. We also tried to eliminate immunosuppression (cyclophosphamide - CP) treatment after bone marrow transplantation. B6.SJL-PtprcaPep3b mice were injected with 20-30 x 106 bone marrow cells from Balb C mice. Mice were treated with TBI (3 - 1.5 - 0 Gy) on "-1" day of the experiment and blocking antibodies against CD40L ("0", and "4" days) and additionally anti-CD8 ("-2" day) and/or anti-NK1.1 ("-3" day). Mice in certain groups also received CP (175 mg/kg) on "2" day. Presence of mixed chimerism was assessed in peripheral blood cells by flow cytometry on the 1st, 2nd, 3rd, 4th, 6th and 8th weeks of the experiment by detecting of CD45.1 (characteristic for B6.SJL-PtprcaPep3b strain) and CD45.2 (characteristic for Balb C strain) antigens expression. We also analyzed the percentage of peripheral blood CD8 T-cells (CD3e/CD8a) and NK cells (Ly-49D/NK1.1). We found that reduction of TBI dose and elimination of CP decrease the rate of mixed chimerism formation. The highest percentage of donor cells was obtained in the group of animals treated with 3 Gy of TBI, CP and combination of anti-CD40L, anti-CD8, and anti-NK1.1 antibodies. The 3 Gy TBI was necessary to induce stable mixed chimerism, but it could be obtained without the CP use. The percentage of CD3e/CD8a and Ly-49D/NK1.1 cells was significantly lower in the groups of mice treated by corresponding antibodies. Moreover, we observed the lowest number of peripheral blood Ly-49D/NK1.1 cells in the group of animals with highest mixed chimerism. Our experiments in mice model can help in better understanding of mixed chimerism phenomenon and in selecting the method of mixed chimerism induction with lowest possible toxicity. This also might improve the protocols of stable mixed chimerism induction in humans, and in the future, the effectiveness of vascularized organ transplantation

An optimization of hematopoietic stem and progenitor cell isolation for scientific and clinical purposes by the application of a new parameter determining the hematopoietic graft efficacy.

The transplantation of hematopoietic stem and progenitor cells (HSPC) is an established lifesaving therapy. Bone marrow (BM), harvested from heparinized cadaveric organ donors, peripheral blood (PB) and cord blood (CB), are important sources of hematopoietic stem cells. HSPCs, which are used for transplantation purposes, are routinely evaluated in terms of number of mononuclear cells (MNCs), CD34+ MNCs count and viability. The efficacy of grafting is determined additionally in clonogenic tests in vitro. These tests deliver important information about the number of HSPCs and their proliferative potential. Unfortunately, they do not give a possibility to evaluate the functional HSPC chemotactic reactivity in the SDF-1 gradient, which is probably the key phenomenon for HSPC homing after transplantation procedure. Thus, the aim of our study was to optimize HSPC isolation according to their chemotactic reactivity in SDF-1 gradient. Using multiparameter cell sorter (FACS Aria, BD) we examined the HSPCs attracted by SDF-1 on a single cell level. The population of cells which participated in the chemotactic process was highly enriched in CXCR4+lin-AC133+CD45+ cells (referred as hematopoietic stem cells) and to our surprise in CXCR4+lin-AC133+CD45- cells (referred as pluripotent stem cells) in quantitative amounts. Since reactivity of HSPCs may depend on various factors involved in the protocol of their isolation and short-term storage, we tested the most commonly used anticoagulants (ACD, CPDA-1, EDTA and Heparin) and culture media (DME, IMDM, RPMI). HSPCs, harvested from CB, PB and BM, were subsequently investigated for clonogenic growth of CFU-GM in methylcellulose cultures and for the level of apoptosis by employing annexin V staining. Evaluating clonogenic potential, ability of chemotactic reactivity in SDF-1 gradient and intensification of apoptosis of HSPC as the most safe anticoagulant and medium were selected. This study has proved that chemotactic reactivity of HSPCs is a new but very important parameter which should be included in the procedure of their isolation

Higher perfusion pressure and pump flow during cardiopulmonary bypass are beneficial for kidney function–a single-centre prospective study

Background: Kidneys play an essential role in the circulatory system, regulating blood pressure and intravascular volume. They are also set on maintaining an adequate filtration pressure in the glomerulus. During the CPB, a decrease in systemic blood pressure and hemoglobin concentration may lead to renal ischemia and subsequent acute kidney injury.Methods: One hundred nine adult patients were prospectively enrolled in this study. The intervention in this study was increasing the flow of the CPB pump to reach the target MAP of > 90 mmHg during the procedure. The control group had a standard pump flow of 2.4 L/min/m2.Results: Standard pump flow of 2.4 L/min/m2 resulted in mean MAP < 90 mmHg during the CPB in most patients in the control group. Maintaining a higher MAP during CPB in this study population did not affect CSA-AKI incidence. However, it increased the intraoperative and postoperative diuresis and decreased renin release associated with CPB. Higher MAP during the CPB did not increase the incidence of cerebrovascular complications after the operation; patients in the highest MAP group had the lowest incidence of postoperative delirium, but the result did not obtain statistical significance.Conclusion: Maintaining MAP > 90 mmHg during the CPB positively impacts intraoperative and postoperative kidney function. It significantly reduces renal hypoperfusion during the procedure compared to MAP < 70 mmHg. MAP > 90 mmHg is safe for the central nervous system, and preliminary results suggest that it may have a beneficial impact on the incidence of postoperative delirium

Genetic data: The new challenge of personalized medicine, insights for rheumatoid arthritis patients

Rapid advances in genotyping technology, analytical methods, and the establishment of large cohorts for population genetic studies have resulted in a large new body of information about the genetic basis of human rheumatoid arthritis (RA). Improved understanding of the root pathogenesis of the disease holds the promise of improved diagnostic and prognostic tools based upon this information. In this review, we summarize the nature of new genetic findings in human RA, including susceptibility loci and gene-gene and gene-environment interactions, as well as genetic loci associated with sub-groups of patients and those associated with response to therapy. Possible uses of these data are discussed, such as prediction of disease risk as well as personalized therapy and prediction of therapeutic response and risk of adverse events. While these applications are largely not refined to the point of clinical utility in RA, it seems likely that multi-parameter datasets including genetic, clinical, and biomarker data will be employed in the future care of RA patients