Targeting chronic lymphocytic leukemia using CIGB-300, a clinical-stage CK2-specifc cell-permeable peptide inhibitor

Chronic lymphocytic leukemia (CLL) remains an incurable malignancy, urging for the identifcation of new molecular targets for therapeutic intervention. CLL cells rely on overexpression and hyperactivation of the ubiquitous serine/threonine protein kinase CK2 for their viability in vitro. CIGB-300 is a cell-permeable selective CK2 inhibitor peptide undergoing clinical trials for several cancers. Here, we show that CIGB-300 promotes activation of the tumor suppressor PTEN and abrogates PI3K-mediated downstream signaling in CLL cells. In accordance, CIGB-300 decreases the viability and proliferation of CLL cell lines, promotes apoptosis of primary leukemia cells and displays antitumor efcacy in a xenograft mouse model of human CLL. Our studies provide pre-clinical support for the testing and possible inclusion of CK2 inhibitors in the clinical arsenal against CLL.     

Effects of Telestroke on Thrombolysis Times and Outcomes: A Meta-analysis

Objective: Telestroke systems are tools, used to provide an advanced stroke care in regions without sufficient neurologic services. We performed this meta-analysis to assess the effects of telemedicine on treatment times and clinical outcomes of acute stroke care. Methods: A literature search of PubMed, SCOPUS, and Cochrane CENTRAL was conducted for original studies investigating telemedicine applications in acute stroke care. Dichotomous data on treatment outcomes were pooled as odds ratios (ORs), while continuous data on thrombolysis times were pooled as mean differences (MDs) with 95% confidence interval (CI), using RevMan software (version 5.3). Results: Pooling data from 26 studies (6605 thrombolysed patients) showed no significant differences between the telestroke and control groups in terms of in-hospital mortality (OR = 1.21, 95% CI [0.98, 1.49]), 90-day mortality (OR = 1.08, 95% CI [0.85, 1.37]), symptomatic intracranial hemorrhage (sICH) (OR = 1.10, 95% CI [0.79, 1.53]), and favorable clinical outcome at discharge (OR = 1.03, 95% CI [0.69, 1.53]) and 90 days later (OR = 0.99, 95% CI [0.82, 1.18]). The onset-to-door (OTD) duration (MD = ?10.4 minutes, 95% CI [?14.79, ?.01]) and length of hospital stay (MD = ?0.55 days, 95% CI [?1.02, ?0.07]) were significantly shorter in the telestroke group, compared to the control group. Although the overall effect estimate (under the fixed-effect model) showed a significant decrease in the onset-to-treatment (OTT) duration in the telestroke group (MD = ?5.83 minutes, 95% CI [?8.57, ?3.09]), employing the random-effects model for between-study heterogeneity abolished this significance (MD = ?5.90 minutes, 95% CI [?13.23, 1.42]). Conclusion: Telestroke significantly reduced OTD and hospital stay durations in stroke patients without increasing the risk of mortality or sICH. Therefore, telemedicine can improve stroke care in regional areas with minor experience in thrombolysis. Further randomized controlled trials are needed to assess the benefits of telestroke systems, especially in terms of cost-effectiveness and quality of life outcomes.     

N-acetylcysteine protects against star fruit-induced acute kidney injury

Background: Star fruit (SF) is a popular fruit, commonly cultivated in many tropical countries, that contains large amount of oxalate. Acute oxalate nephropathy and direct renal tubular damage through release of free radicals are the main mechanisms involved in SF-induced acute kidney injury (AKI). The aim of this study was to evaluate the protective effect of N-acetylcysteine (NAC) on SF-induced nephrotoxicity due to its potent antioxidant effect.

Materials and methods: Male Wistar rats received SF juice (4?mL/100?g body weight) by gavage after a 12?h fasting and water deprivation. Fasting and water deprivation continued for 6?h thereafter to warrant juice absorption. Thereafter, animals were allocated to three experimental groups: SF (n?=?6): received tap water; SF?+?NAC (n?=?6): received NAC (4.8?g/L) in drinking water for 48?h after gavage; and Sham (n?=?6): no interventions. After 48?h, inulin clearance studies were performed to determine glomerular filtration rate. In a second series of experiment, rats were housed in metabolic cages for additional assessments.

Results: SF rats showed markedly reduced inulin clearance associated with hyperoxaluria, renal tubular damage, increased oxidative stress and inflammation. NAC treatment ameliorated all these alterations. Under polarized light microscopy, SF rats exhibited intense calcium oxalate birefringence crystals deposition, dilation of renal tubules and tubular epithelial degeneration, which were attenuate by NAC therapy.

Conclusions: Our data show that therapeutic NAC attenuates renal dysfunction in a model of acute oxalate nephropathy following SF ingestion by reducing oxidative stress, oxaluria, and inflammation. This might represent a novel indication of NAC for the treatment of SF-induced AKI.     

Clinical and laboratory characteristics in septic arthritis patients with and without isolated germs

Background

The management of septic arthritis without bacteriological evidence is not well codified.