Acute adenoviral infection of a graft by serotype 35 following renal transplantation

Adenoviral infections of immunocompetent patients usually present as self-limiting pharyngitis, gastroenteritis, urocystitis, or conjunctivitis. In immunosuppressed patients, development of the illness can be severe, even life-threatening or fatal, and therapeutical intervention is difficult. Previous case reports of adenoviral infections after kidney transplantation have described a symptomatology of hemorrhagic cystitis, fever, renal dysfunction, and rarely fatal systemic dissemination. Here we report on a 46-year-old female renal transplant recipient suffering from adenoviral serotype 35 nephritis of the donor organ 29 days after transplantation. In this case, the main symptoms of the adenoviral infection were high fever and progressive renal failure of the transplanted organ. At the peak of the clinical symptoms, owing to histological and immunohistochemical evaluations of a kidney biopsy, we were able to establish the diagnosis in time so that adequate therapy could be employed. Immunosuppression was reduced and modified, and a self-limiting course of the infection was observed, followed by significant improvement of graft function. Subsequent to histological diagnosis, adenoviral particles were isolated from urine and identified as adenovirus serotype 35. Adenoviral nephritis of the transplanted organ should be considered in the differential diagnosis of persistent anuria after kidney transplantation. Our case highlights the importance of applying all possible diagnostic techniques, including histological evaluation of renal biopsies.     

Synthesis and characterization of guanidinylated poly(propylene imine) dendrimers as gene transfection agents.

Fourth generation poly(propylene imine) dendrimer has been completely or partially functionalized with guanidinium groups. In the second case, the remaining toxic primary amino groups of the dendrimers were reacted with propylene oxide affording the corresponding hydroxylated derivatives. Five derivatives have been prepared bearing 0, 6, 12, 24 or 32 guanidinium groups. These guanidinylated dendrimers were interacted with plasmid DNA affording the corresponding dendriplexes. The complexes were physicochemically characterized by dynamic light scattering, zeta-potential measurements and AFM, while the extent of complexation was evaluated by agarose gel electrophoresis. Furthermore, their transfection efficiency was assessed employing HEK 293 and COS-7 cell lines, while the serum effect was studied in HEK 293 cells. It was found that complete replacement of primary amino groups with the hydroxylated moieties resulted in complete loss of transfection efficiency. On the contrary, guanidinylation of the parent dendrimer resulted to significant enhancement of its transfection efficiency, this enhancement being dependent on the number of guanidinium groups per dendrimer, the cell line used and the presence or absence of FBS. The fully guanidinylated dendrimer exhibited the best transfection efficiency under all the conditions studied. This efficiency has been attributed to the enhanced penetrating ability of the guanidinylated dendrimers due to the accumulation of the guanidinium group at the dendrimeric surface. It was also found that the derivative with 12 guanidinium groups exhibited the lowest toxicity. The reduction of toxicity was apparently attributed to the decrease of the external primary amino groups coupled with the presence of hydroxylated moieties located at the dendrimeric surface. The functionalization strategy employed leads to dendrimeric derivatives that combine satisfactory transfection efficiency and cytotoxicity.     

Handedness in preterm born children: a systematic review and a meta-analysis

It has been proposed that left and/or non-right handedness (NRH) is over-represented in children with a history of preterm birth because such births are associated with a greater incidence of insult to the brain. We report an approximate two-fold increase in left and/or non-right handedness based on a systematic search of the literature from 1980 to September 2010 for English-language articles reporting handedness status in preterm children compared with fullterm controls either as a main focus of the study or as a secondary finding. In total, thirty articles met the inclusion criteria. However, there was a great variation between the included studies in terms of objectives, population characteristics, sample size and methodologies used. While the majority of studies reported a higher incidence of NRH in preterm than fullterm children, this was not a consistent finding. A quality assessment was made to explore the differences in overall study quality and handedness assessment methodology between studies. A random-effects model meta-analysis was then performed to estimate the accumulated effect of preterm birth on handedness (18 studies; 1947 cases and 8170 controls). Preterm children displayed a significantly higher occurrence of NRH than fullterm children (odds ratio [OR]: 2.12; 95% confidence interval [CI]: 1.59-2.78). Sources of heterogeneity were investigated by supplementary meta-analyses considering studies with high or low overall and handedness assessment quality. Publication bias was assessed by Egger's test of the intercept and Duvall and Tweedie's trim-and-fill method. The outcomes of these procedures did not jeopardize the overall finding of reliably increased OR for NRH in preterm children. The present review suggests that a preterm birth is indeed associated with a greater than two-fold likelihood of NRH. Several studies also explored the relationship between handedness and neuropsychological functioning (cognition mainly) with an array of methods. Although not without disagreement, this association was found to be concordant. Studying handedness in preterm children, therefore, is a potentially important index of hemispheric organization and cognitive and sensory-motor functions following neurodevelopmental disturbance.     

Novel agents targeting nitric oxide

Nitric oxide (NO) is a soluble gas continuously synthesized from the amino acid L-arginine in endothelial cells by the constitutive calcium-calmodulin-dependent enzyme nitric oxide synthase (NOS). Endothelial dysfunction has been identified as a major mechanism involved in all the stages of atherogenesis. Evaluation of endothelial function seems to have a predictive role in humans, and therapeutic interventions improving nitric oxide bioavailability in the vasculature, may improve the long-term outcome in healthy individuals, high-risk subjects or patients with advanced atherosclerosis. Several therapeutic strategies (including statins, angiotensin converting enzyme inhibitors/angiotensin receptors blockers, insulin sensitizers, antioxidant compounds) are now available, targeting both the synthesis and oxidative inactivation of NO in human vasculature, reversing in that way endothelial dysfunction which is enhanced by the release of nitric oxide from the endothelium.     

Administration of a vaccine composed of dendritic cells pulsed with premalignant oral lesion lysate to mice bearing carcinogen-induced premalignant oral lesions stimulates a protective immune response

The use of dendritic cell (DC) vaccines as treatment for malignancy is complicated by immune evasion tactics often employed by carcinomas such as head and neck squamous cell carcinoma (HNSCC). The present study aims to determine if an immune response can be elicited by administering a DC vaccine during the premalignant stages of HNSCC, prior to development of immune escape. Mice treated with the carcinogen 4-nitroquinoline 1-oxide (4NQO) in drinking water develop premalignant oral lesions that progress to HNSCC. As previous studies demonstrated that premalignant lesions and HNSCC overexpress common tumor antigens, bone marrow-derived DCs were pulsed with premalignant lesion lysate (DCpm) and administered to 4NQO-treated mice exhibiting premalignant lesions. Lesion progression was tracked through endoscopy, which revealed that DCpm vaccination and control vaccination with dendritic cells pulsed with normal tongue epithelium lysate (DCnt) significantly decreased lesion burden at 8weeks. Analysis of lymph node cells revealed that while DCnt vaccination resulted in a rapid increase in total lymphocyte count, levels of activated conventional CD4(+) T cells and Th1, Tc1, Th17, Tc17, and Th2 cells, DCpm vaccination results in a delayed, yet substantial, increase in these immune effector mechanisms. This suggests that dendritic cell vaccination may have a beneficial effect on clinical outcome regardless of type of antigenic stimulation. Also, pulsing DCs with premalignant lysate rather than normal tongue epithelium lysate affects the dendritic cells in a way that delays the immune effector response upon vaccination of premalignant lesion-bearing mice.