Blood Cell Membrane Omega-3 (n-3) Fatty Acid Abnormality and Supplementation in Patients with Sickle Cell Anemia

Sickle cell disease (SCD) is a group of autosomal recessive genetic blood disorders caused by a mutation in the sixth codon of the β goblin gene that results in abnormal hemoglobin (Hemoglobin S, HbS) (Knight-Perry et al., 2009; Rees et al., 2010; Serjeant and Serjeant, 2001). The principal phenotypes are homozygous sickle cell (HbSS) disease, sickle cell-hemoglobin C , sickle cell-β0 thalassemia, sickle cell-β1 thalassemia, HbSOArab and HbSDPunjab and HbSLepore Boston SCD (Nagel et al., 2003; Serjeant and Serjeant, 2001). Deoxygenated HbS forms insoluble rigid polymers (sickle) under hypoxic conditions and reverts back to normal on re-oxygenation. However, with repeated cycles of sickling and unsickling, erythrocytes become irreversibly sickled and lose their biconcave shape and fluidity. The primary pathological process in SCD, namely vasoocclusive crisis is a recurrent occlusion of blood vessels which causes ischemia, severe pain episodes (painful crisis), and damage to the brain, eyes, lungs, spleen, liver, and other vital organs (Ballas et al., 2010; Serjeant and Serjeant, 2001). Despite the apparent genetic simplicity, patients with SCD display a remarkable diversity in clinical manifestations and disease severity (Chui and Dover, 2001; Fertrin and Costa, 2010). The Cooperative Study of Sickle Cell Disease (Platt et al., 1991) found that 39% of 3578 patients with SCD did not have painful episodes, whereas 1% had more than six per year. It appears that type and severity of the complication of the disease are modulated by genetic, environmental, and other factors (Sebastiani et al., 2005; Steinberg, 2005)

Phosphorylation of protein kinase B, the key enzyme in insulin signalling cascade, is enhanced in linoleic and arachidonic acid treated HT29 and HepG2 cells

Objective: Defects in insulin signalling pathway have been implicated in the pathogenesis of impaired glucose uptake, insulin resistance and type II diabetes. However, the specific defects that precipitate these abnormalities are yet to be fully elucidated. The plasma membrane embedded insulin receptor transmembrane protein, after binding to insulin, initiates a cascade of phosphorylation which leads to the activation of protein kinase B (AKT) and subsequently to initiation of some metabolic actions of insulin. The activities of this receptor, insulin binding and tyrosine kinase activation, is dependent on its plasma lipid environment. There are scarcity of published data on the influence of omega-3 and -6 polyunsaturated fatty acids on insulin response. Moreover, the findings of the published investigations, most of which have used omega-3 and -6 PUFA blend, have been inconclusive. Hence, a need for well- thought-out further research. The aim was to elucidate the effect of treatments with LNA, ARA, ALA, DHA, and EPA on cell membrane composition and consequently on insulin signalling pathway, specifically AKT phosphorylation. Research Methods and Procedures: Human colon adenocarcinoma (HT29) and liver hepatocellular (HepG2) cells were treated with or without 40 µM of linoleic (LNA), arachidonic (ARA), alpha-linolenic (ALA), eicosapentaenoic (EPA) or docosahexaenoic (DHA) for 48 hours. Fatty acids composition of phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) from the treated cells by capillary gas liquid chromatograph. Cells were incubated for 30 minutes with or without human insulin (50ng/ml) and the phosphorylation of AKT assessed with the use of western blotting. Results: The fatty acids were incorporated in PtdCho and PtdEtn of both cell lines; but, the level of incorporation was higher in HT29. Phosphorylation of AKT increased when HT29 was treated with LNA (P<0.05) and ARA (P<0.01), but not with ALA, EPA or DHA. A similar but non-significant increase in AKT phosphorylation was observed in LNA and ARA treated HepG2 cells. Conclusion: The finding of this investigation demonstrates, plasma membrane lipid bilayer enrichment with LNA or ARA treatment enhances insulin action by AKT activation

Omega- 3 fatty acids are potential therapy for patients with sickle cell disease

A correspondence letter to “Nature Reviews Disease Primers” about the therapeutic potential of omega 3 fatty acids for patients with sickle cell disease

Knowledge, attitudes and practices (KAP) about malaria among people visiting referral hospitals of Eritrea in 2008

Background: Knowledge, attitudes, awareness, practices and beliefs of communities contribute immensely to sustainable control of endemic diseases such as malaria. Strategic malaria control involves primary prevention which focuses on vector elimination and personal behavior change specifically through the consistent use of insecticide-treated nets (ITNs) and prompt and effective case management. This health facility based study was conducted to investigate the knowledge, attitudes and practices toward malaria among people visiting referral Hospitals of Eritrea, so as to develop a cost effective behavioral change communication strategy for community based malaria control. Methods: The study was conducted in the Referral Hospitals of the four Zobas as well as Teseney Hospital where there was the highest malaria morbidity and mortality. A total of 250 people with 50 people from each hospital were randomly selected. A structured questionnaire covering information on respondent demographics, knowledge, attitudes and practices was administered upon receipt of an informed consent for participation. Results: All the study subjects knew at least one of the symptoms of malaria with nearly three quarters mentioning three or more of the classical symptoms including fever. More than 80% knew that mosquitoes were the vector for the disease with a similar proportion having participated in environmental preventive control measures. Nearly half (44.6%) of the respondents gave priority for usage of ITNs to children under 5 years, to both children and pregnant mother and 11.2% to pregnant mothers. Conclusion: The majority of the respondents in this study knew enough information about malaria, and had participated in environmental preventive measures. The primary prevention of malaria through uninterrupted use of ITNs and transformation of knowledge into practices requires emphasis on the development of a community based behavioral change communication strategy. Key words: KAP, malaria, Behavioral change communication strategy, Eritrea, ITN

Formulation and Characterization of Phytostanol Ester Solid Lipid Nanoparticles for the Management of Hypercholesterolemia: An ex vivo Study.

Background: Phytostanols are naturally occurring compounds that reduce blood cholesterol levels significantly. However, their aqueous insolubility poses formulation challenges. Aim: To formulate and characterize solid lipid nanoparticle carriers for phytostanol esters to enhance the bioavailability of phytostanols. Methods: Phytostanol ester solid lipid nanoparticles were formulated by the microemulsion method. They were characterized for particle size distribution, polydispersity index, shape, surface charge, entrapment efficiency, stability, chemical structure, and thermal properties. The uptake of the formulation by cell lines, HepG2 and HT-29, and its effect on cell viability were evaluated. Results: The formulation of solid lipid nanoparticles was successfully optimised by varying the type of lipids and their concentration relative to that of surfactants in the present study. The optimised formulation had an average diameter of (171 ± 9) nm, a negative surface charge of (− 23.0 ± 0.8) mV and was generally spherical in shape. We report high levels of drug entrapment at (89 ± 5)% in amorphous form, drug loading of (9.1 ± 0.5)%, nanoparticle yield of (67 ± 4)% and drug excipient compatibility. The biological safety and uptake of the formulations were demonstrated on hepatic and intestinal cell lines. Conclusion: Phytostanol ester solid lipid nanoparticles were successfully formulated and characterized. The formulation has the potential to provide an innovative drug delivery system for phytostanols which reduce cholesterol and have a potentially ideal safety profile. This can contribute to better management of one of the main risk factors of cardiovascular disease

Coagulation profile of Sudanese children with homozygous sickle cell disease and the effect of treatment with omega-3 fatty acid on the coagulation parameters

Background: It has been reported that patients with SCD do have an abnormal coagulation profile. Coagulopathy is thought to be one of the key factors that contribute to the vaso-occlusive crisis that characterises sickle cell disease (SCD). In this study, we investigated whether Sudanese sickle cell patients have an abnormal coagulation profile. In addition, the effect of treatment with either omega-3 fatty acids or hydroxyurea on coagulation profile was assessed. Methods: Homozygous SCD patients untreated (n = 52), omega-3 treated (n = 44), hydroxyurea (HU) treated (n = 8) and healthy (HbAA) controls (n = 52) matched for age (4–20 years), gender and socioeconomic status were enrolled. Patients on omega-3 fatty acids, according to age, received one to four capsules containing 277.8 mg DHA and 39.0 mg eicosapentnoic. Patients on Hydroxyurea were in on dosage more than 20 mg/kg/day. The steady state levels of the coagulation parameters and the effect of the treatments with either HU or omega-3 fatty acids on markers of coagulation were investigated. Results: Compared to the healthy controls, treated and untreated HbSS patients had lower hemoglobin, plasma Protein C, proteins S and higher white blood cell count (WBC), platelets count (PLTs) and plasma D-dimer levels,(p 0.05). HU treated group had a lower PLTs count compared to HbSS untreated group (p < 0.5). The prothrombin and activated partial thromboplastin times and international normalized ratio (INR) of untreated patients are significantly higher than n-3 treated, HU-treated patients and health controls, (p < 0.05). Patients treated with omega-3 had lowered D-dimer levels in comparison to HU-treated and untreated HbSS patients, (p < 0.001). Conclusion: This study provides evidence that Sudanese patients have abnormal coagulation profile and treatment with either HU or omega-3 fatty acids might partially ameliorate SCD-associated chronic coagulopathic state. Keywords: Sickle cell disease, Coagulation, Omega-3 fatty acids, D-dimer, Protein C, Protein

Capture of toxic metals by vaious sorbents during fluidized bed coal combustion

This study investigated the potential of employing suitable sorbents to capture trace metallic substances during fluidized bed coal combustion. The objectives of the study were to demonstrate the capture process, identify effective sorbents, and characterize the capture efficiency. Experiments were carried out in a 25.4 mm (1 ``) quartz fluidized bed coal combustor enclosed in an electric furnace. In an experiment, a coal sample from the DOE Coal Sample Bank or the Illinois Basin Coal Sample Bank was burned in the bed with a sorbent under various combustion conditions and the amount of metal capture by the sorbent was determined. The metals involved in the study were arsenic, cadmium, lead, mercury and selenium, and the sorbents tested included bauxite, zeolite and lime. The combustion conditions examined included bed temperature, particle size, fluidization velocity (percent excess air), and sorbent bed height. In addition to the experimental investigations, potential metal-sorbent reactions were also identified through performing chemical equilibrium analyses based on the minimization of system free energy

An Empirical Investigation of the Factors Influencing Formal and Informal Employment in the City of Asmara

This study investigates the factors influencing formal and informal labour market in Asmara, the capital city of Eritrea. The findings reveal that variables such as age, gender, education and birth place influence formal and informal labor market of the city. The chances for young people getting jobs in formal are low relative to older people. Higher educational level is related to securing jobs in the formal sector. Regarding gender males have more chances in the formal sector than females. People from Maekel/Central Region (townships surrounding Asmara) have higher chances to engage in self-employment. Generally, the results reveal that the labor market in Asmara show varied characteristics

Efficacy of docosahexaenoic acid-enriched formula to enhance maternal and fetal blood docosahexaenoic acid levels: randomized double-blinded placebo-controlled trial of pregnant women with gestational diabetes mellitus

BACKGROUND & AIMS Gestational diabetes mellitus (GDM) compromises the level of docosahexaenoic acid (DHA) in phospholipids of maternal and fetal red blood cells and fetal plasma. This is of some concern because of the importance of DHA for fetal neuro-visual development. We have investigated whether this abnormality could be rectified by supplementation with DHA-enriched formula. METHODS Women with GDM (n = 138) recruited from Newham University Hospital, London received two capsules of DHA-enriched formula (active-group) or high oleic acid sunflower seed oil (placebo-group) from diagnosis until delivery. Maternal (baseline and delivery) and fetal (cord blood) red blood cell and plasma phospholipid fatty acid composition, and neonatal anthropometry were assessed. RESULTS One hundred and fourteen women (58 active, 56 placebo) completed the trial. The active-group compared with the placebo-group had significantly enhanced level of DHA in plasma phosphatidylcholine (4.5% vs 3.8%, P = 0.011), red blood cell phosphatidylcholine (2.7% vs 2.2%, P = 0.022) and phosphatidylethoanolamine (9.5% vs 7.6%, P = 0.002). There was no difference in cord plasma and red blood cell phospholipid DHA between the two groups. The neonates of the two groups of women had comparable anthropometric measurements at birth. CONCLUSION Daily supplementation of 600 mg DHA enhances maternal but not fetal DHA status in pregnancy complicated by GDM. The inefficacy of the supplement to improve fetal status suggests that the transfer of DHA across the placenta maybe impaired in women with the condition. Regardless of the mechanisms responsible for the impairment of the transfer, the finding has implications for the management of neonates of women with GDM because they are born with a reduced level of DHA and the condition is thought to be associated with a risk of neuro-developmental deficits. We suggest that babies of women with GDM, particularly those not suckling, similar to the babies born prematurely require formula milk fortified with a higher level of DHA

Trace metal capture by various sorbents during fluidized bed coal combustion

Experiments were conducted in a 1-in. quartz fluidized bed combustor enclosed in an electric furnace. Coal samples were burned in the bed with a sorbent under specific combustion conditions and the amount of metal capture by the sorbent determined. Three different cao samples from the Illinois Basin Coal Sample Bank were tested. Metals involved were Cd, Pb, and Cr; the sorbents included bauxite, zeolite, and lime. Potential metal-sorbent reactions were identified. Results indicated that metal capture by sorbent can be as high as 96%, depending on the metal species and sorbent. All 3 sorbents were capable of capturing Pb, zeolite and lime were able to capture Cr, and bauxite was the only sorbent capable of capturing Cd. Thermodynamic equilibrium calculations suggested the formation of metal-sorbent compounds such as Pb{sub 2}SiO{sub 4}, CdAl{sub 2}O{sub 4}, and CdSiO{sub 3} solids under the combustion conditions