Interleukin 2 receptor antagonists for liver transplant recipients: a systematic review and meta-analysis of controlled studies

Interleukin 2 receptor antagonists (IL-2Ra) are frequently used as induction therapy in liver transplant recipients to decrease the risk of acute rejection while allowing the reduction of concomitant immunosuppression. We conducted a systematic review of prospective, controlled studies to test the hypothesis that the use of IL-2Ra is associated with a decrease in acute rejection and/or a decrease in the side effects of concomitant medication. We performed a search of all major databases and secondary sources from inception to December 2010. Random effects models were used to assess the incidence of acute rejection, graft loss, patient death, and adverse side effects, with or without IL-2Ra. Subgroup analysis and meta-regression were used to explore differences in effect and sources of heterogeneity. Eighteen studies (13 randomized and 5 nonrandomized) met the inclusion and exclusion criteria. Acute rejection at 12 months or later favored the use of IL-2Ra (relative risk [RR] 0.83; 95% confidence interval [CI] 0.76-0.94) and steroid-resistant rejection was also less frequent in patients receiving IL-2Ra (RR 0.66; CI 0.48-0.91). Graft loss and patient death did not differ significantly between treatments. Patients who received IL-2Ra in addition to reduced or delayed calcineurin inhibitors had better renal function (mean difference of estimated glomerular filtration rate: 6.29 mL/min; CI 1.66-10.91) and a lower incidence of renal dysfunction (RR 0.46; CI 0.27-0.78). The use of IL-2Ra was also associated with a lower incidence of posttransplant diabetes mellitus, whereas the incidence of other adverse events was similar. CONCLUSION: The use of IL-2Ra is associated with a lower incidence of acute rejection after transplantation. Concomitant immunosuppression can be reduced, avoiding long-term side effects of immunosuppression.     

Molecular cloning,characterization and functional analysis of a novel juvenile-specific cathepsin L of Fasciola gigantica

Cathepsin L proteases are a major class of endopeptidases expressed at a high level in Fasciola parasites. Several isoforms of cathepsin L were detected and they may perform different functions during the parasite development. In this study, a complete cDNA encoding a cathepsin L protease was cloned from a newly excysted juvenile (NEJ) cDNA library of Fasciola gigantica and named FgCatL1H. It encoded a 326 amino acid preproenzyme which shared 62.8–83.1% and 39.5–42.9% identity to Fasciola spp. and mammalian cathepsins L, respectively. All functionally important residues previously described for cathepsin L were conserved in FgCatL1H. Phylogenetic analysis demonstrated that FgCatL1H belonged to a distinct group, clade 4, with respect to adult and other juvenile Fasciola cathepsin L genes. FgCatL1H expression was detected by RT-PCR, using gene specific primers, in metacercariae and NEJ, and the expression gradually decreased in advanced developmental stages. A recombinant proFgCatL1H (rproFgCatL1H) was expressed in the yeast Pichia pastoris, affinity purified, and found to migrate in SDS-PAGE at approximately 47.6 and 38.3 kDa in glycosylated and deglycosylated forms, respectively. The molecular mass of the activated mature rFgCatL1H in glycosylated form was approximately 40.7 kDa. Immunoblotting and immunohistochemistry using rabbit antibodies against rproFgCatL1H showed that FgCatL1H was predominantly expressed in epithelial cells of the digestive tract of metacercariae, NEJs and juveniles of F. gigantica. FgCatL1H could cleave the synthetic fluorogenic substrate Z-Phe-Arg-MCA preferentially over Z-Gly-Pro-Arg-MCA at an optimum pH of 6.5. It also showed hydrolytic activity against native substrates, including type I collagen, laminin, and immunoglobulin G (IgG) in vitro, suggesting possible roles in host tissue migration and immune evasion. Therefore, the FgCatL1H is a possible target for vaccine and chemotherapy for controlling F. gigantica infection.     

Effects of acute and chronic exposure to both 900 MHz and 2100 MHz electromagnetic radiation on glutamate receptor signaling pathway

Purpose: To demonstrate the molecular effects of acute and chronic exposure to both 900 and 2100?MHz radiofrequency electromagnetic radiation (RF-EMR) on the hippocampal level/activity of some of the enzymes – including PKA, CaMKIIα, CREB, and p44/42 MAPK – from N-methyl-D-aspartate receptor (NMDAR)-related signaling pathways.

Materials and methods: Rats were divided into the following groups: sham rats, and rats exposed to 900 and 2100?MHz RF-EMR for 2?h/day for acute (1 week) or chronic (10 weeks), respectively. Western blotting and activity measurement assays were used to assess the level/activity of the selected enzymes.

Results: The obtained results revealed that the hippocampal level/activity of selected enzymes was significantly higher in the chronic groups as compared to the acute groups at both 900 and 2100?MHz RF-EMR exposure. In addition, hippocampal level/activity of selected enzymes was significantly higher at 2100?MHz RF-EMR than 900?MHz RF-EMR in both acute and chronic groups.

Conclusions: The present study provides experimental evidence that both exposure duration (1 week versus 10 weeks) and different carrier frequencies (900 vs. 2100?MHz) had different effects on the protein expression of hippocampus in Wistar rats, which might encourage further research on protection against RF-EMR exposure.     

Central nervous system lymphoma and Epstein-Barr virus in immunocompetent patients in Thailand

A series of 11 apparently immunocompetent patients with primary non-Hodgkin's lymphoma of the central nervous system (NHL-CNS) together with six patients with systemic lymphoma involving the spinal cord and/or brain were studied for immunophenotyping and the presence of Epstein-Barr virus (EBV). Immunohistochemistry and polymerase chain reaction (PCR) were performed on paraffin-embedded tissues. Nine of 11 primary NHL-CNS and all six secondary CNS lesions were of B cell origin. The EBV sequences were detected in six primary tumors and four systemic lesions by PCR while the immuno-histochemical marker for the EBV-latent membrane protein was positive in five primary lesions and three secondary neoplasms. Our results suggest that the association of EBV and NHL-CNS is not only restricted to patients with immunosuppression but that it includes a broad spectrum of conditions in which this relationship occurs in patients without immunodeficiency. The mortality rate is high particularly in patients with EBV-associated NHL-CNS.     

Percutaneous PDA Closure in Extremely Low Birth Weight Babies

Aim

Patent Ductus Arteriosus is an important cause of morbidity and mortality in preterms. As birth weight decrease, risks increase. Main aim of our study is to emphasize the effectiveness and safety of percutaneous PDA closure even in extremely low birth infants.

Materials and Methods

In our center between the dates June 2014–June 2016, PDA of 10 patients less than 1,000 gr were closed percutaneously. To the best of our knowledge this study includes the largest cohort of infants less than 1,000 g in the literature, that PDA of those were percutaneously closed.

Results

Symptomatic patients, less than 1,000 gr having PDA were included in the study. All have 3 times medical therapy for PDA closure but it did not work. PDA was decided to be contributor of this medical state of them. The mean patient age was 19.5 ± 7.2 days. The median weight was 950 (842–983) gr. Mean gestational age was: 26.3 ± 0.63 weeks. Mean PDA diameter was 1.9 ± 0.41 mm. Morphology of PDA:6 of them were conical and 4 of them were tubular. In all patients ADOII‐AS device were used for PDA closure via venous route. No major complications were reported. Left pulmonary arterial stenosis was detected in 1 patient who was resolved in 6 months duration.

Conclusion

We want to emphasize that in experienced centers percutaneous closure of PDA can be an alternative to surgery even in the extremely low birth weight babies.