AIDS-related Burkitt's lymphoma versus diffuse large-cell lymphoma in the pre-highly active antiretroviral therapy (HAART) and HAART eras: significant differences in survival with standard chemotherapy.

PURPOSE: To compare outcomes of patients with HIV-Burkitt's lymphoma (HIV-BL) and HIV-diffuse large-cell lymphoma (HIV-DLCL) after treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or M-BACOD (methotrexate, bleomycin, cyclophosphamide, etoposide) in pre-highly active antiretroviral therapy (HAART) versus HAART eras. PATIENTS AND METHODS: Three hundred sixty-three patients with AIDS-related lymphoma diagnosed from 1982 to 2003 were reviewed retrospectively, including 262 in the pre-HAART (HIV-BL, 117; HIV-DLCL, 145) and 101 in the HAART era (HIV-BL, 18; HIV-DLCL, 83). Pre-HAART included those who did not receive HAART, and HAART era included those diagnosed after January 1997 who received HAART. RESULTS: There were no significant differences between groups in terms of age, sex, history of injection drug use, prior AIDS, lactate dehydrogenase level, and disease stage at diagnosis. Compared with HIV-BL, HIV-DLCL was associated with significantly lower CD4 counts in the pre-HAART but not the HAART era. Although the overall median survival was similar for both groups in the pre-HAART era (HIV-BL, 6.4 months v HIV-DLCL, 8.3 months; P = .43), survival was significantly worse in patients with HIV-BL in the HAART era (HIV-BL, 5.7 months v HIV-DLCL, 43.2 months; P = .0003). Failure to attain complete remission and CD4 count less than 100 cells/mm(3) independently predicted for poor survival in the pre-HAART era. In comparison, histology of HIV-BL and no attainment of complete remission were independent poor prognostic factors in the HAART era. CONCLUSION: Survival of patients with HIV-DLCL has improved in the HAART era, along with CD4 count, whereas survival of similarly treated patients with HIV-BL remained poor. The current practice of using the same regimen for both groups of patients should be re-evaluated.     

Inflammatory cytokine network in schizophrenia

Objectives. The purpose of this review is to analyse, sum up and discuss the available literature on the role of inflammation and inflammatory cytokines in the pathogenesis of schizophrenia. Methods. An electronic literature search of peer-reviewed English language articles using Pubmed was undertaken. These articles together with those published by us provided the background for the present review. Results. An overview of the available literature on this issue clearly demonstrated the alterations in mRNA and protein expression levels of several proinflammatory and chemotactic cytokines in patients with schizophrenia. Importantly, some of these changes are genetically determined. It was noteworthy that, depending on the study population, some variations of the data obtained are detected. Conclusions. Altered inflammatory cytokine production, both genetically and environmentally determined, is implicated in schizophrenia and contributes to disease-associated low-grade systemic inflammation. Proinflammatory and chemotactic cytokines and their receptors may represent additional therapeutic targets for treatment of schizophrenia.     

High pressure as a novel tool for the cationic ROP of γ-butyrolactone

In this study, we report the acid-catalyzed and high pressure assisted ring-opening polymerization (ROP) of γ-butyrolactone (GBL). The use of a dually-catalyzed approach combining an external physical factor and internal catalyst (trifluoromethanesulfonic acid (TfOH) or p-toluenesulfonic acid (PTSA)) enforced ROP of GBL, which is considered as hardly polymerizable monomer still remaining a challenge for the modern polymer chemistry. The experiments performed at various thermodynamic conditions (T = 278–323 K and p = 700–1500 MPa) clearly showed that the high pressure supported polymerization process led to obtaining well-defined macromolecules of better parameters (M_n = 2200–9700 g mol⁻¹; Đ = 1.05–1.46) than those previously reported. Furthermore, the parabolic-like dependence of both the molecular weight (M_W) and the yield of obtained polymers on variation in temperature and pressure at either isobaric or isothermal conditions was also noticed, allowing the determination of optimal conditions for the polymerization process. However, most importantly, this strategy allowed to significantly reduce the reaction time (just 3 h at room temperature) and increase the yield of obtained polymers (up to 0.62 g_PGBL/g_GBL). Moreover, despite using a strongly acidic catalyst, synthesized polymers remained non-toxic and biocompatible, as proven by the cytotoxicity test we performed in further analysis. Additional investigation (including MALDI-TOF measurements) showed that the catalyst selection affected not only M_W and yield but also the linear/cyclic form content in obtained macromolecules. These findings show the way to tune the properties of PGBL and obtain polymer suitable for application in the biomedical industry.

Well-defined poly(γ-butyrolactone) was synthesized with great efficiency via high pressure assisted cationic ROP of hardly polimerizable γ-butyrolactone.     

The Effect of BSA-Based Curcumin Nanoparticles on Memory and Hippocampal MMP-2, MMP-9, and MAPKs in Adult Mice

Although high rate of curcumin consumption has been suggested to decrease the prevalence of Alzheimer’s disease (AD), its administration has no effect on the progression of AD in humans and this has been attributed to its poor bioavailability. Using nanotechnology to break down curcumin increases its bioavailability and improves its effect on the brain. BSA, as a non-toxic protein with high binding capacity, was used to break curcumin to nanosize and to explore the effect of nanocurcumin on passive avoidance memory and hippocampal MMP-2 and -9 and MAPKs. BSA-based nanocurcumin was produced by desolvation method. In this study, 15 and 20 mg/kg/p.o. nanocurcumin (based on our preliminary studies) were administered to male NMRI mice weighing 20–25 g for 10 days. Passive avoidance training was performed on day 10 and 24 h after, a retention trial was done. Upon completion of behavioral studies, the hippocampi were isolated and western blot analysis was performed on MMP-2, MMP-9, and MAPKs (JNK, ERK, and p38). The results showed that BSA-based nanocurcumin administered at 15 and 20 mg/kg doses resulted in a significantly improved performance in passive avoidance memory test while its equivalent doses of natural curcumin did not produce a similar effect. In addition, this effect was accompanied with an increase in MMP-2, MMP-9, and p-ERK and a decrease in p-JNK. This study indicates that breaking curcumin to nanosize produces improved effects on passive avoidance memory in adult mice accompanied with MMP-2, MMP-9, p-ERK, and p-JNK changes in the hippocampus.     

Burden of Cervical Cancer in the Eastern Mediterranean Region During the Years 2000 and 2017: Retrospective Data Analysis of the Global Burden of Disease Study

BackgroundCervical cancer is a growing health concern, especially in resource-limited settings.ObjectiveThe objective of this study was to assess the burden of cervical cancer mortality and disability-adjusted life years (DALYs) in the Eastern Mediterranean Region (EMR) and globally between the years 2000 and 2017 by using a pooled data analysis approach.MethodsWe used an ecological approach at the country level. This included extracting data from publicly available databases and linking them together in the following 3 steps: (1) extraction of data from the Global Burden of Disease (GBD) study in the years 2000 and 2017, (2) categorization of EMR countries according to the World Bank gross domestic product per capita, and (3) linking age-specific population data from the Population Statistics Division of the United Nations (20-29 years, 30-49 years, and >50 years) and GBD’s data with gross national income per capita and globally extracted data, including cervical cancer mortality and DALY numbers and rates per country. The cervical cancer mortality rate was provided by the GBD study using the following formula: number of cervical cancer deaths × 100,000/female population in the respective age group.ResultsThe absolute number of deaths due to cervical cancer increased from the year 2000 (n=6326) to the year 2017 (n=8537) in the EMR; however, the mortality rate due to this disease decreased from the year 2000 (2.7 per 100,000) to the year 2017 (2.5 per 100,000). According to age-specific data, the age group ≥50 years showed the highest mortality rate in both EMR countries and globally, and the age group of 20-29 years showed the lowest mortality rate both globally and in the EMR countries. Further, the rates of cervical cancer DALYs in the EMR were lower compared to the global rates (2.7 vs 6.8 in 2000 and 2.5 vs 6.8 in 2017 for mortality rate per 100,000; 95.8 vs 222.2 in 2000 and 86.3 vs 211.8 in 2017 for DALY rate per 100,000; respectively). However, the relative difference in the number of DALYs due to cervical cancer between the year 2000 and year 2017 in the EMR was higher than that reported globally (34.9 vs 24.0 for the number of deaths and 23.5 vs 18.1 for the number of DALYs, respectively).ConclusionsWe found an increase in the burden of cervical cancer in the EMR as per the data on the absolute number of deaths and DALYs. Further, we found that the health care system has an increased number of cases to deal with, despite the decrease in the absolute number of deaths and DALYs. Cervical cancer is preventable if human papilloma vaccination is taken and early screening is performed. Therefore, we recommend identifying effective vaccination programs and interventions to reduce the burden of this disease.     

Multi-stage Differentiation Defines Melanoma Subtypes with Differential Vulnerability to Drug-Induced Iron-Dependent Oxidative Stress

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