Introduction: Illicit drugs abuse is associated with several clinical life-threatening consequences that are primarily mediated by oxidative damage to multiple cellular components with a subsequent cellular dysfunction and death. Primarily, this study aimed to investigate oxidative stress to protein and lipid components of circulatory platelets among chronic heroin and hashish addicts. Methods: Platelet lysates were prepared from 20 chronic intravenously administrated heroin addicts and 20 chronic smoked hashish addicts. For comparative purposes, two control groups of 20 cigarette smokers and 20 nonsmokers were included in the study. Oxidative stress to platelet’s proteins and lipids was investigated using carbonyl group contents assay and thiobarbituric acid reactive substances (TBARS) assay, respectively. Results: In comparison to control groups, carbonyl group contents and TBARS concentration were significantly higher among heroin addicts but not among hashish addicts. Both of these markers were significantly correlated to the duration of addiction but not to the daily administrated dose. While in regard of the timing of the latest administrated dose (TLAD), only carbonyl group contents were significantly correlated to the TLAD. Conclusions: Considering the contribution of drug’s route of administration, drug’s pharmacokinetics, and kinetics of circulatory platelet, we concluded that chronic heroin addiction is associated with significant levels of oxidative stress to platelet’s proteins and lipids. Due to the high proteomic contents of platelets, protein’s oxidative stress is more prominent compared to lipids. Chronic hashish smoking is not associated with significant levels of oxidative stress in platelet’s proteins and lipids.

Background: Wilms tumor (WT1) and p53 proteins were identified in the pathogenesis of several malignancies, including hematological malignancies. As a result of their interaction and diverse context-specific functions, this study aimed to emphasize the diagnostic and prognostic impacts of WT1 and p53 expression in acute myeloid leukemia (AML). Methods: Twelve bone marrow (BM) biopsies were obtained from AML patients who were diagnosed in accordance with the French-American-British diagnostic criteria. For comparative purposes, nine normal BM biopsies were included. The expression rate of WT1 and p53 were determined by an immunohistochemistry assay. Results: A significantly higher (p < 0.005) and strongly correlated (p = 0.855, p = 0.001) expression rates of WT1 and p53 were observed in the BM of AML patients in comparison to control BM. Furthermore, relapsed AML patients had significantly higher expression of WT1, but not p53, when compared to newly diagnosed patients. In regard of patient's responsiveness to chemotherapy, no significant difference was reported between good and poor responders. However, the relative ratio of p53 to WT1 expression was evidently correlated to the responsiveness groups (p < 0.05), where the ratio was observed to be significantly higher among poor responders. Poor responders were characterized by a statistically significant and dominant p53 expression (p53/WT1 > 1.0) while both good responding patients and control subjects had a dominant WT1 expression (p53/WT1 < 1.0). Conclusions: The enhanced expression levels of WT1 and p53 proteins in the BM of AML patients is supportive of their intermediate role in the pathogenesis of the disease. WT1 expression rate may encompass a negative prognostic value of the disease. Furthermore, the ratio of p53/WT expression may serve as a hallmark of the patient's responsiveness to chemotherapy, where a dominant WT1 expression may reveal good responsiveness to chemotherapy. Herein, we are proposing a kinetic model where the p53/WT1 ratio might be useful as a laboratory approach to evaluate the prognostic value of AML including the patient's responsiveness to chemotherapeutic regimen.

In the context of iron deficiency anemia, central dopamine, serotonin, and brain-derived neurotrophic factor (BDNF) are intensively investigated. However, peripheral isoforms are poorly investigated. This study aimed to investigate the modulation of plasma levels of dopamine, serotonin, and BDNF among children with iron deficiency anemia. A total of seventy-three iron-deficient (n=38) and iron-sufficient (n=35) children were included in the study. Twenty-nine subjects were showing clinical presentations and were diagnosed with iron deficiency anemia and forty-four were asymptomatic normal children. Plasma levels of dopamine, serotonin, and brain-derived neurotrophic factor were determined by enzyme-linked immunosorbent assay. As compared to corresponding levels among control subjects, Anemic subjects were having significantly higher plasma dopamine and lower plasma brain-derived neurotrophic factor levels. A significant linear and monotonic association of plasma dopamine and brain-derived neurotrophic factor with hemoglobin concentration (r=-0.520, P < 0.001 and ρ = 0.411, P = 0.001), respectively. Furthermore, there were significantly higher plasma serotonin levels among iron-deficient subjects with a significant inverse linear association with serum ferritin levels (r = -0.337, P = 0.005). Iron deficiency anemia is associated with the modulation of peripheral dopamine, serotonin, and brain-derived neurotrophic factor. Upregulation of dopamine and downregulation of brain-derived neurotrophic factor are correlated to the anemic status. The upregulation of plasma serotonin levels is iron-dependent and, probably, is attributed to the impairment of its metabolic fate. Further investigation is required to explore the pathophysiological and clinical association of these peripheral biomolecules in the context of iron deficiency anemia. (www.actabiomedica.it)

A wide variety of the host immune elements play an influential role in the defence against cytomegalovirus (CMV) infection. However, the role of complement in the clearance of CMV infection is less well studied. Decay accelerating factor (DAF/CD55) is a membrane-bound complement regulatory protein that inhibits the formation and accelerates the decay of C3-convertase. Here we hypothesize that murine CMV (MCMV) utilizes DAF as an immunoevasive strategy through down-regulation of host adaptive responses against the virus. To test our hypothesis, DAF knock-out (DAF KO) C57BL/6 mice and wild-type (WT) littermates were infected with a sublethal dose of MCMV, and their immune responses were compared. WT mice lost 7·8% of their initial weight within the first 4 days after infection and quickly began to recover. This is in contrast to the DAF KO mice, that lost a total of 19·4% of their initial weight and did not start recovery until 6 days post-infection. Flow cytometric analysis of lung digests revealed that infected DAF KO mice had a significantly increased infiltration of inflammatory cells, the majority being CD8⁺ T lymphocytes. Serum levels of tumour necrosis factor (TNF)-α and interferon (IFN)-γ were also increased markedly in the DAF KO mice compared to the infected WT mice. More interestingly, increased viral genome copies (DNA) in the splenocytes of DAF KO mice was accompanied with mRNA transcripts in the DAF KO mice, an indication of active viral replication. These data suggest an intriguing effect of reduced DAF expression on host responses following in vivo MCMV infection.