Background: Hypocholesterolemia is the most frequently encountered lipid abnormality in sickle cell disease (SCD). We enrolled pediatric patients to determine the relationships between lipid profile and parameters of hemolysis, oxidative stress and chronic inflammation in SCD. Methods: The study involved 35 pediatric SCD patients and 19 healthy controls. Patients were crisis-free and had not received transfusions for the last 3 months. Total cholesterol, triglyceride, HDL-C, LDL-C, VLDL-C, apolipoprotein A1, apolipoprotein B, LCAT, LDH, bilirubin, haptoglobin, iron, ferritin, hemin, serum amyloid A (SAA), myeloperoxidase (MPO), uric acid, ALT and GGT levels were evaluated in patients’ blood. Results: Patients had hypocholesterolemia depicted by lower levels of total cholesterol, HDL-C, LDL-C, as well as Apolipoprotein A1 and Apolipoprotein B compared to controls. The chronic hemolysis of SCD was evident in patients by higher LDH and bilirubin and almost undetectable haptoglobin levels. Hemin levels (as a measure of oxidized heme) were significantly increased in patients with SCD. Inflammation markers, SAA and MPO, were significantly increased in the patients as well. There were negative correlations between HDL-C and LDH, and Apo A1 and SAA. Hemin was positively correlated to MPO. Conclusion: Hemolysis was associated with decreased HDL –C, and Inflammation was linked to decreased apolipoprotein A1 levels in our SCD patients. Therefore, we suggest that the HDL particle is altered during the course of the disease. The altered HDL in SCD may become dysfunctional and result with a slowing down of the reverse cholesterol transport.

Various therapeutic protocols were used for the management of sepsis including hyperbaric oxygen (HBO) therapy. It has been shown that ozone therapy (OT) reduced inflammation in several entities and exhibits some similarity with HBO in regard to mechanisms of action. We designed a study to evaluate the efficacy of OT in an experimental rat model of sepsis to compare with HBO. Male Wistar rats were divided into sham, sepsis+cefepime, sepsis+cefepime+HBO, and sepsis+cefepime+OT groups. Sepsis was induced by an intraperitoneal injection of Escherichia coli; HBO was administered twice daily; OT was set as intraperitoneal injections once a day. The treatments were continued for 5 days after the induction of sepsis. At the end of experiment, the lung tissues and blood samples were harvested for biochemical and histological analysis. Myeloperoxidase activities and oxidative stress parameters, and serum proinflammatory cytokine levels, IL-1β and TNF-α, were found to be ameliorated by the adjuvant use of HBO and OT in the lung tissue when compared with the antibiotherapy only group. Histologic evaluation of the lung tissue samples confirmed the biochemical outcome. Our data presented that both HBO and OT reduced inflammation and injury in the septic rats' lungs; a greater benefit was obtained for OT. The current study demonstrated that the administration of OT as well as HBO as adjuvant therapy may support antibiotherapy in protecting the lung against septic injury. HBO and OT reduced tissue oxidative stress, regulated the systemic inflammatory response, and abated cellular infiltration to the lung demonstrated by findings of MPO activity and histopathologic examination. These findings indicated that OT tended to be more effective than HBO, in particular regarding serum IL-1β, lung GSH-Px and histologic outcome.

Human milk samples contain microvesicles similar to the retroviruses. These microvesicles contain mRNA transcripts and possess reverse transcriptase activity. They contain about 14,000 transcripts representing the milk transcriptome. Microvesicles are also enriched with proteins related to “caveolar-mediated endocytosis signaling” pathway. It has recently been reported that microvesicles could be transferred to other cells by endocytosis and their RNA content can be translated and be functional in their new location. A significant percentage of the mammalian genome appears to be the product of reverse transcription, containing sequences whose characteristics point to RNA as a template precursor. These are mobile elements that move by way of transposition and are called retrotransposons. We thought that retrotransposons may stem from about 14,000 transcriptome of breast milk microvesicles, and reviewed the literature.

Sickle cell disease (SCD) causes anemia, oxidative stress, chronic inflammation, and lipid abnormalities. Oxysterols are oxidized derivatives of cholesterol and affect cholesterol metabolism and eryptosis. Our aim was to determine whether the plasma concentrations of 7-ketocholesterol (7-KC) and cholestane-3β,5α,6β-triol (C-triol) were associated with hemolysis and lipid profile in patients with SCD. A total of 32 steady-state pediatric patients with SCD (22 HbSS and 10 HbSß⁺) and 25 healthy controls were included in the study. Hemolysis parameters, ferritin, serum iron, lipids, 7-KC and C-triol concentrations of all subjects were measured. Oxysterols were quantified with N,N-dimethylglycine derivatization via LC-MS/MS. 7-KC and C-triol concentrations were found to be increased in SCD patients, while there was no difference between the HbSS and HbSß⁺ subgroups. 7-KC concentrations s were correlated negatively with hemoglobin and positively with lactate dehydrogenase concentrations, while C-triol concentrations were negatively correlated with HDL cholesterol. Furthermore, while 7-KC and C-triol concentrations were highly correlated among controls, there was no correlation in patients. The findings of our study suggest that 7-KC and C-triol may have a role in SCD pathophysiology. The lack of correlation in patients’ 7-KC and C-triol concentrations suggest alterations in oxysterol production in patients with SCD.