Clinical outcome of HCV-positive patients with diffuse large B-cell lymphoma treated with rituximab-based chemotherapy

The influence of rituximab therapy on prognosis and hepatic toxicity (HT) in patients with hepatitis C virus (HCV)-positive diffuse large B-cell lymphoma (DLBCL) is unclear. Thus, we assessed HT and clinical outcome in patients with DLBCL and HCV infection who received rituximab-containing immunochemotherapy. We carried out a prospective analysis on a total of 280 HCV-positive patients with DLBCL, 200 of whom received chemotherapy plus rituximab (R-CHT), 80 received chemotherapy (CHT)-only. Survival outcomes and HT were compared according to rituximab administration. The median follow-up was 41 months. Addition of rituximab did not significantly affect prognosis (median progression-free survival, 40 vs 35 months, P?=?0.26; median overall survival, 51 vs 43 months P?=?0.09). Of 200 patients who received rituximab, 53 (26.5 %) had severe HT (grade 3–4), compared with 11 of 80 (13.75 %) patients who received rituximab-free regimens (P?=?0.033). Among patients treated with rituximab, 50 patients (25 %) did not complete planned course of therapy, 14 patients because of hepatic toxicity and 36 patients because of progressive disease. Pretreatment liver function impairment was predictive of severe HT. These results raise concerns regarding the routine use of rituximab with chemotherapy in individuals with HCV-positive DLBCL. However, more studies are warranted before a definitive conclusion can be made.     

Nanoparticles in orthodontics,a review of antimicrobial and anti-caries applications

Nanoparticles (NPs) are insoluble particles smaller than 100 nm in size. In order to prevent microbial adhesion or enamel demineralization in orthodontic therapy, two broad strategies have been used. These are incorporating certain NPs into orthodontic adhesives/cements or acrylic resins (nanofillers, silver, TiO₂, SiO₂, hydroxyapatite, fluorapatite, fluorohydroxyapatite) and coating surfaces of orthodontic appliances with NPs (i.e. coating bracket surfaces with a thin film of nitrogen-doped TiO₂). Although the use of NPs in orthodontics can offer new possibilities, previous studies investigated the antimicrobial or physical characteristic over a short time span, i.e. 24 hours to a few weeks, and the limitations of in vitro studies should be recognized. Information on the long-term performance of orthodontic material using nanotechnology is lacking and necessitates further investigation and so do possible safety issues (toxicity), which can be related to the NP sizes.     

Stressors experienced by the family members of brain-dead people during the process of organ donation: A qualitative study

Abstract

More is known about organ donor recipients than donor families. We explored the stressors experienced by family members of brain-dead people during the process of organ donation. Seventeen family members and five organ procurers were interviewed and the data analyzed through conventional qualitative content analysis. Stressors experienced by family members fell into six themes—perceived threat of loss, decision making under conflict, painful corrosive farewell, feeling of insecurity, complexity of grief, and seeking relief. Findings highlight the necessity of developing and using standard protocols for supporting brain-dead people’s family members throughout the process of organ donation and following bereavement.     

The protective impact of adapted trimebutine maleate-loaded nanostructured lipid carriers for alleviating the severity of acute colitis

Nanoparticles for colon-drug delivery were designed and evaluated to solve many discrepancy issues such as high adverse effects of released drugs, insufficient drug amount at diseased areas, and unintentionally premature drug release to noninflamed GIT regions. Herein, the goal of this work was to convert trimebutine maleate (TMB) into nanostructured lipid carriers (NLC) in order to improve its protective effects in ulcerative colitis. NLC of TMB was prepared by the hot homogenization followed by ultra-sonication method. A full 4²-factorial design was used to estimate the produced TMB-NLC. The study design included the exploration of the impact of two independent variables namely lipid mix amount and ratio (glyceryl mono stearate and capryol 90), surfactant concentration (0.5, 1, 1.5, and 2%), on the particle size, polydispersity index, and the entrapment efficiency (EE%). The protective activity of F9 was examined through macroscopical scores, histopathological changes, immunohistochemical localization of tumor necrosis factor-α (TNF-α) and examination of oxidative stress such as reduced glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) against acetic acid-induced colitis in rats. Consistent with our expectations, the orally administered optimized formula (F9) alleviated the severity of colitis in acetic acid-induced rat model of colitis likely owing to the controlled release compared to free TMB. We aimed to develop TMB-loaded NLC for the treatment of acute colitis with the goal of providing a superior drug safety profile over long-term remission and maintenance therapy.     

The Effect of ß-Glucan Prebiotic on Kidney Function,Uremic Toxins and Gut Microbiome in Stage 3 to 5 Chronic Kidney Disease (CKD) Predialysis Participants: A Randomized Controlled Trial

There is growing evidence that gut dysbiosis contributes to the progression of chronic kidney disease (CKD) owing to several mechanisms, including microbiota-derived uremic toxins, diet and immune-mediated factors. The aim of this study was to investigate the effect of a ß-glucan prebiotic on kidney function, uremic toxins and the gut microbiome in stage 3 to 5 CKD participants. Fifty-nine participants were randomized to either the ß-glucan prebiotic intervention group (n = 30) or the control group (n = 29). The primary outcomes were to assess kidney function (urea, creatinine and glomerular filtration rate), plasma levels of total and free levels of uremic toxins (p-cresyl sulfate (pCS), indoxyl-sulfate (IxS), p-cresyl glucuronide (pCG) and indoxyl 3-acetic acid (IAA) and gut microbiota using 16S rRNA sequencing at baseline, week 8 and week 14. The intervention group (age 40.6 ± 11.4 y) and the control group (age 41.3 ± 12.0 y) did not differ in age or any other socio-demographic variables at baseline. There were no significant changes in kidney function over 14 weeks. There was a significant reduction in uremic toxin levels at different time points, in free IxS at 8 weeks (p = 0.003) and 14 weeks (p < 0.001), free pCS (p = 0.006) at 14 weeks and total and free pCG (p < 0.001, p < 0.001, respectively) and at 14 weeks. There were no differences in relative abundances of genera between groups. Enterotyping revealed that the population consisted of only two of the four enterotypes: Bacteroides 2 and Prevotella. The redundancy analysis showed a few factors significantly affected the gut microbiome: these included triglyceride levels (p < 0.001), body mass index (p = 0.002), high- density lipoprotein (p < 0.001) and the prebiotic intervention (p = 0.002). The ß-glucan prebiotic significantly altered uremic toxin levels of intestinal origin and favorably affected the gut microbiome.     

Oxidative stress parameters and keap 1 variants in T2DM: Association with T2DM,diabetic neuropathy,diabetic retinopathy,and obesity

IntroductionChronic hyperglycemia activates the inflammatory pathways and oxidative stress mechanisms with consequent damage to nerve tissue and retina. The Keap1‐Nrf2 pathway acts as one of the most important antioxidant pathways of the organism. Variants of Keap1 could affect susceptibility to diabetes and its complications.MethodsIn a case‐control study, 400 individuals included type 2 diabetes mellitus (T2DM) patients without complication, with neuropathy, with retinopathy, and healthy individuals were investigated. The levels of glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured using chemical methods. Using the PCR‐RFLP method, the Keap1 (rs11085735) variants were identified.ResultsNeuropathic patients had significantly lower levels of GSH, GPx, and TAC and higher levels of total oxidative status (TOS), MDA, and oxidative stress index (OSI) compared to T2DM patients without complication and controls. Lower levels of GSH and GPx and a higher level of MDA were observed in patients with retinopathy compared with controls. Obesity was associated with significantly lower GPx activity and higher TOS. A significantly higher Keap1 AA genotype was found in patients with neuropathy than T2DM without complication and controls. The presence of Keap1 AA genotype correlated with lower GPx activity compared to CC genotype.ConclusionsOur study suggests the role of reduced antioxidant system and Keap1 variants in the pathogenesis of T2DM and its complications of neuropathy and retinopathy and also obesity in enhanced oxidative stress. Monitoring oxidative stress parameters in diabetic patients, especially those with complication and their treatment with antioxidants is suggested.     

Liver kinase B1 depletion from astrocytes worsens disease in a mouse model of multiple sclerosis

Liver kinase B1 (LKB1) is a ubiquitously expressed kinase involved in the regulation of cell metabolism, growth, and inflammatory activation. We previously reported that a single nucleotide polymorphism in the gene encoding LKB1 is a risk factor for multiple sclerosis (MS). Since astrocyte activation and metabolic function have important roles in regulating neuroinflammation and neuropathology, we examined the serine/threonine kinase LKB1 in astrocytes in a chronic experimental autoimmune encephalomyelitis mouse model of MS. To reduce LKB1, a heterozygous astrocyte-selective conditional knockout (het-cKO) model was used. While disease incidence was similar, disease severity was worsened in het-cKO mice. RNAseq analysis identified Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched in het-cKO mice relating to mitochondrial function, confirmed by alterations in mitochondrial complex proteins and reductions in mRNAs related to astrocyte metabolism. Enriched pathways included major histocompatibility class II genes, confirmed by increases in MHCII protein in spinal cord and cerebellum of het-cKO mice. We observed increased numbers of CD4+ Th17 cells and increased neuronal damage in spinal cords of het-cKO mice, associated with reduced expression of choline acetyltransferase, accumulation of immunoglobulin-γ, and reduced expression of factors involved in motor neuron survival. In vitro, LKB1-deficient astrocytes showed reduced metabolic function and increased inflammatory activation. These data suggest that metabolic dysfunction in astrocytes, in this case due to LKB1 deficiency, can exacerbate demyelinating disease by loss of metabolic support and increase in the inflammatory environment.