Interleukin-8 and nuclear factor kappa B are increased and positively correlated in myelodysplastic syndrome

The pathogenesis of myelodysplastic syndromes (MDS) is complex and depends on the interaction between aberrant hematopoietic cells and their microenvironment, probably including aberrations in cytokines and their signaling pathways. To evaluate interleukin-8 (IL-8) plasma levels and nuclear factor kappa B (NF-kB) in patients with MDS and to test possible correlation between IL-8 and NF-Kb, a total of 45 individuals were analyzed: 25 consecutive adult de novo MDS patients and 20 sex and age-matched healthy elderly volunteers. IL-8 analysis was performed by ELISA and activity of NF-kB by chemiluminescent assay. MDS patients showed higher level of IL-8 when compared to controls (p = 0.006). Patients aged 75 and above showed even higher levels (p = 0.035). NF-kB activity was significantly elevated in MDS patients when compared to controls (p < 0.0001) and higher in patients older than 75 years (p = 0.047). NF-kB activity was associated with higher serum ferritin (p = 0.042) and higher percentage of blasts (p = 0.028). A significant positive correlation between IL-8 and NF-kB was demonstrated (r = 0.480; p = 0.015). Many pathways involved in pathophysiology of MDS have been recently described, suggesting that an inflammatory process may act as a pathogenic driver. In this study, significantly elevated levels of IL-8 and NF-kB were demonstrated in MDS patients, with positive association of NF-kB with some markers of poor prognosis. A positive correlation between IL-8 and NF-kB suggests they cooperate as part of a complex networking of immune and inflammatory factors involved in MDS.     

Sécurité de l’attachement des jeunes enfants dans une population française vulnérable

Introduction

Attachment is a long lasting emotional link established between infants and their caregivers. The quality of early relationships allows infants to safely explore their environment and contribute to the establishment of a broad range of social skills. Several intervention programs targeting infant attachment have been implemented in different contexts, showing diverse degrees of efficacy.

Role of sex hormones in gastrointestinal motility in pregnant and non-pregnant rats

AIM: To correlate gastric contractility, gastrointestinal transit, and hormone levels in non-pregnant(estrous cycle) and pregnant rats using noninvasive techniques. METHODS: Female rats(n = 23) were randomly divided into(1) non-pregnant,(contractility, n =6; transit, n = 6); and(2) pregnant(contractility, n = 5; transit, n = 6). In each estrous cycle phase or at 0, 7, 14, and 20 d after the confirmation of pregnancy, gastrointestinal transit was recorded by AC biosusceptometry(ACB), and gastric contractility was recorded by ACB and electromyography. After each recording, blood samples were obtained for progesterone and estradiol determination. RESULTS: In the estrous cycle, despite fluctuations of sex hormone levels, no significant changes in gastrointestinal motility were observed. Days 7 and 14 of pregnancy were characterized by significant changes in the frequency of contractions(3.90 ± 0.42 cpm and 3.60 ± 0.36 cpm vs 4.33 ± 0.25 cpm) and gastric emptying(168 ± 17 min and 165 ± 15 min vs 113 ± 15 min) compared with day 0. On these same days, progesterone levels significantly increased compared with control(54.23 ± 15.14 ng/m L and 129.96 ± 30.52 ng/mL vs 13.25 ± 6.31 ng/mL). On day 14, we observed the highest level of progesterone and the lowest level of estradiol compared with day 0(44.3 ± 15.18 pg/mL vs 24.96 ± 5.96 pg/mL). CONCLUSION: Gastrointestinal motility was unaffected by the estrous cycle. In our data, high progesterone and low estradiol levels can be associated with decreased contraction frequency and slow gastric emptying.     

Focal liver lesions: Practical magnetic resonance imaging approach

With the widespread of cross-sectional imaging, a growth of incidentally detected focal liver lesions (FLL) has been observed. A reliable detection and characterization of FLL is critical for optimal patient management. Maximizing accuracy of imaging in the context of FLL is paramount in avoiding unnecessary biopsies, which may result in post-procedural complications. A tremendous development of new imaging techniques has taken place during these last years. Nowadays, Magnetic resonance imaging (MRI) plays a key role in management of liver lesions, using a radiation-free technique and a safe contrast agent profile. MRI plays a key role in the non-invasive correct characterization of FLL. MRI is capable of providing comprehensive and highly accurate diagnostic information, with the additional advantage of lack of harmful ionizing radiation. These properties make MRI the mainstay for the noninvasive evaluation of focal liver lesions. In this paper we review the state-of-the-art MRI liver protocol, briefly discussing different sequence types, the unique characteristics of imaging non-cooperative patients and discuss the role of hepatocyte-specific contrast agents. A review of the imaging features of the most common benign and malignant FLL is presented, supplemented by a schematic representation of a simplistic practical approach on MRI.     

Genetic characterization of the dihydrofolate reductase gene of Pneumocystis jirovecii isolates from Portugal

OBJECTIVES: The aim of the present study was to evaluate the genetic variation of Pneumocystis jirovecii dihydrofolate reductase (DHFR) gene in an immunocompromised Portuguese population and to investigate the possible association between DHFR genotypes and P. jirovecii pneumonia (PcP) prophylaxis with co-trimoxazole. METHODS: One hundred and thirty-eight P. jirovecii isolates were submitted to DHFR genetic characterization by PCR and sequencing. RESULTS: In the studied population, 72.7% of the patients presented sequences identical to the wild-type sequence of the P. jirovecii DHFR gene and 27.3% presented point substitutions. A total of nine substitution sites were identified; four synonymous substitutions at nucleotide positions 201, 272, 312 and 381 were detected in 31 patients. Five non-synonymous substitutions were observed, leading to the DHFR mutations Leu-13-->Ser, Asn-23-->Ser, Ser-31-->Phe, Met-52-->Leu and Ala-67-->Val. With the exception of the polymorphism at position 312 and the mutation at codon 52, all polymorphisms were reported in this study for the first time. CONCLUSIONS: Our results suggest that DHFR gene polymorphisms are frequent in the Portuguese immunocompromised population but do not seem to be associated with PcP prophylaxis failure (P = 0.748 and P = 0.730).     

Mechanism of Holliday junction resolution by the human GEN1 protein

Holliday junction (HJ) resolution is essential for chromosome segregation at meiosis and the repair of stalled/collapsed replication forks in mitotic cells. All organisms possess nucleases that promote HJ resolution by the introduction of symmetrically related nicks in two strands at, or close to, the junction point. GEN1, a member of the Rad2/XPG nuclease family, was isolated recently from human cells and shown to promote HJ resolution in vitro and in vivo. Here, we provide the first biochemical/structural characterization of GEN1, showing that, like the Escherichia coli HJ resolvase RuvC, it binds specifically to HJs and resolves them by a dual incision mechanism in which nicks are introduced in the pair of continuous (noncrossing) strands within the lifetime of the GEN1–HJ complex. In contrast to RuvC, but like other Rad2/XPG family members such as FEN1, GEN1 is a monomeric 5′-flap endonuclease. However, the unique feature of GEN1 that distinguishes it from other Rad2/XPG nucleases is its ability to dimerize on HJs. This functional adaptation provides the two symmetrically aligned active sites required for HJ resolution.