Omega 3 (n−3) fatty acids down-regulate nuclear factor-kappa B (NF-κB) gene and blood cell adhesion molecule expression in patients with homozygous sickle cell disease

Chronic inflammation and reduced blood levels of omega-3 fatty acids (n − 3) are known characteristics of sickle cell disease (SCD).The anti-inflammatory properties of n − 3 fatty acids are well recognized. Omega-3 treated (n = 24), hydroxyurea (HU) treated (n = 18), and n − 3 untreated (n = 21) homozygous SCD patients (HbSS) and healthy (HbAA) controls (n = 25) matched for age (5–16 years), gender and socioeconomic status were studied. According to age (5–10) or (11–16) years, two or three capsules containing 277.8 mg docosahexaenoic (DHA) and 39.0 mg eicosapentaenoic (EPA) or high oleic acid placebo (41%) were assigned to n − 3 treated and n − 3 untreated groups, respectively. Hydroxyurea treated group was on dosage more than 20 mg/kg/day. The effect of supplementation on systemic and blood cell markers of inflammation was investigated. The n − 3 treated group had higher levels of DHA and EPA (p < 0.001) and lower white blood cell count and monocyte integrin (p < 0.05) compared with the n − 3 untreated. No difference was detected between the two groups regarding C-reactive protein, granulocytes integrin and selectin, plasma tumour necrosis factor-α and interleukin-10. The n − 3 treated group had lowered nuclear factor-kappa B (NF-κB) gene expression compared to n − 3 untreated and HU treated groups (p < 0.05). This study provides evidence that supplementation with n − 3 fatty acids may ameliorate inflammation and blood cell adhesion in patients with SCD

Malaria and pre-eclampsia in an area with unstable malaria transmission in Central Sudan

<p>Abstract</p> <p>Background</p> <p>Placental malaria and pre-eclampsia occur frequently in women in tropics and are leading causes of maternal and perinatal morbidities and mortality. Few data exist concerning the interaction between placental malaria and pre-eclampsia.</p> <p>Methods</p> <p>A case control study was conducted in Medani Hospital, which locates in an area of unstable malaria transmission in Central Sudan. Case (N = 143) were women with pre-eclampsia, which was defined as systolic blood presure≥140 mm Hg or diastolic blood pressure ≥ 90 mm Hg and proteinuria. Controls were parturient women (N = 143) without any blood pressure values > 139/89 mm Hg or proteinuria. Obstetrical and medical characteristics were gathered from both groups through structured questionnaires. Placental histopathology examinations for malaria were performed.</p> <p>Results</p> <p>Twenty-eight (19.6%) vs. 16 (11.2%); <it>P </it>= 0.04 of the cases vs. controls, had placental malaria infections. Five (2%), 1 (2%) and 22 (28.0%) vs. 1, 2 and 13 of the placentae showed acute, chronic and past infection on histopathology examination in the two groups respectively, while 115 (80.4%) vs.127 (88.8%) of them showed no infection, <it>P </it>= 0.04. In multivariate analysis, while there were no associations between age, parity, educational level, lack of antenatal care, blood groups and body mass index and pre-eclampsia; family history of hypertension and placental malaria (OR = 2.3, 95% CI = 1.0-5.2; <it>P </it>= 0.04) were significantly associated with pre-eclampsia.</p> <p>Conclusion</p> <p>Placental malaria was associated with pre-eclampsia. Further research is needed.</p

A nosocomial transmission of crimean-congo hemorrhagic fever to an attending physician in north kordufan, Sudan

<p>Abstract</p> <p>Background</p> <p>Crimean-Congo hemorrhagic fever (CCHF), a tick-borne disease caused by Crimean-Congo hemorrhagic fever virus (CCHFV), is a member of the genus Nairovirus in the family Bunyaviridae. Recently, CCHFV has been reported as an important emerging infectious viral pathogen in Sudan. Sporadic cases and multiple CCHF outbreaks, associated with nosocomial chain of transmission, have been reported in the Kordufan region of Sudan.</p> <p>Aims</p> <p>To confirm CCHF in an index patient and attending physician in North Kordufan region, Sudan, and to provide some information on virus genetic lineages.</p> <p>Methods</p> <p>Antibody captured ELISA, reverse transcription PCR, partial S segment sequences of the virus and subsequent phylogenetic analysis were used to confirm the CCHFV infection and to determine the virus genetic lineages.</p> <p>Results</p> <p>CCHF was confirmed by monitoring specific IgM antibody and by detection of the viral genome using RT-PCR. Treatment with oral ribavirin, replacement with fluid therapy, blood transfusion and administration of platelets concentrate resulted in rapid improvement of the health condition of the female physician. Phylogenetic analysis of the partial S segment sequences of the 2 CCHFV indicates that both strains are identical and belong to Group III virus lineage, which includes viruses from Africa including, Sudan, Mauritania, South Africa and Nigeria.</p> <p>Conclusion</p> <p>Further epidemiologic studies including, CCHFV complete genome analysis and implementation of improved surveillance are urgently needed to better predict and respond to CCHF outbreaks in the Kordufan region, Sudan.</p

RNAi technology and its use in studying the function of nuclear receptors and coregulators

Until just a few years ago, RNA interference (RNAi) technology was restricted to the research fields of plants, C. elegans or Drosophila. The discovery of gene silencing by in vitro synthesized double-stranded RNA (dsRNA) in mammalian cells has made the use of RNAi possible in nearly the entire life science kingdom. DNA vectors delivering small interfering RNA (siRNA) directed by polymerase III or polymerase II promoters to persistently inhibit target genes expression have extended this technology to study in vivo function of these genes. Recently, RNAi has been used as a powerful tool in the functional analysis of nuclear receptors and their coregulators. This short review will cover studies in this area

The differential effects of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on seizure frequency in patients with drug-resistant epilepsy – A Randomized, double-blind, placebo-controlled trial

Abstract The omega-3 (n-3) fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are known to play an important role in maintenance and modulation of neuronal functions. There is evidence that omega-3 fatty acids may have anticonvulsant effects. The effect of DHA and EPA on seizure rate in patients with DRE was investigated. Methods: A double-blind, randomized, placebo-controlled clinical trial included ninety-nine (n=99) DRE patients, aged 5-16 (n=85) and 17-45 (n=14). After randomization, patients were given two, four or six capsules per day of DHA (417.8 mg DHA and 50.8 mg EPA/capsule, n=33), EPA (385.6 mg EPA and 81.2 mg DHA/capsule, n=33) or placebo (high oleic acid sunflower oil, n=33) for one year. The primary endpoint was the effect of treatment on rate of seizure. Random-effects negative binomial regression models were fitted to model the patients’ total count of seizures per month. The treatment effects on seizure incidence rate ratio was tested after controlling for the covariate effects of gender, age, rate of seizure per week at enrollment, type of seizure and number of AEDs combinations used at enrollment. Results: Fifty-nine patients (n=59) completed the study (59.6%).The average number of seizures per month were 9.7 ± 1.2 in the EPA group, 11.7 ± 1.5 in the DHA group, and 16.6 ± 1.5 in the placebo group. Age, gender and seizure type adjusted seizure incidence rate ratios (IRRs) of the EPA and DHA groups compared with the placebo were 0.61 (CI= 0.42-0.88, p=0.008, 42% reduction) and 0.67 (CI = 0.46-1.0, p= 0.04, 39% reduction), respectively. There was no difference in IRR between the EPA and DHA groups (p=0.56). Both treatment groups had a significantly higher number of seizure-free days compared to placebo (p<0.05). Significance: This study demonstrates that EPA and DHA are effective in reducing seizure frequency in patients with DRE

Non-targeting siRNA induces NPGPx expression to cooperate with exoribonuclease XRN2 for releasing the stress

Short interfering RNAs (siRNAs) target specific mRNAs for their degradation mediated by RNA-induced silencing complex (RISC). Persistent activation of siRNA-RISC frequently leads to non-targeting toxicity. However, how cells mediate this stress remains elusive. In this communication, we found that the presence of non-targeting siRNA selectively induced the expression of an endoplasmic reticulum (ER)-resident protein, non-selenocysteine containing phospholipid hydroperoxide glutathione peroxidase (NPGPx), but not other ER-stress proteins including GRP78, Calnexin and XBP1. Cells suffering from constant non-targeting siRNA stress grew slower and prolonged G1 phase, while NPGPx-depleted cells accumulated mature non-targeting siRNA and underwent apoptosis. Upon the stress, NPGPx covalently bound to exoribonuclease XRN2, facilitating XRN2 to remove accumulated non-targeting siRNA. These results suggest that NPGPx serves as a novel responder to non-targeting siRNA-induced stress in facilitating XRN2 to release the non-targeting siRNA accumulation

Severe anaemia is associated with a higher risk for preeclampsia and poor perinatal outcomes in Kassala hospital, eastern Sudan

<p>Abstract</p> <p>Background</p> <p>Anaemia during pregnancy is major health problem. There is conflicting literature regarding the association between anaemia and its severity and maternal and perinatal outcomes.</p> <p>Methods</p> <p>This is a retrospective case-control study conducted at Kassala hospital, eastern Sudan. Medical files of pregnant women with severe anaemia (haemoglobin (Hb) < 7 g/dl, n = 303) who delivered from January 2008 to December 2010 were reviewed. Socio-demographic and obstetric data were analysed and compared with a similar number of women with mild/moderate anaemia (Hb = 7-10.9 g/dl, n = 303) and with no anaemia (Hb > 11 g/dl, n = 303). Logistic regression analysis was performed separately for each of the outcome measures: preeclampsia, eclampsia, preterm birth, low birth weight (LBW) and stillbirth.</p> <p>Results</p> <p>There were 9578 deliveries at Kassala hospital, 4012 (41.8%) women had anaemia and 303 (3.2%) had severe anaemia. The corrected risk for preeclampsia increased only in severe anaemia (OR = 3.6, 95% CI: 1.4-9.1, <it>P </it>= 0.007). Compared with women with no anaemia, the risk of LBW was 2.5 times higher in women with mild/moderate anaemia (95% CI: 1.1-5.7), and 8.0 times higher in women with severe anaemia (95% CI: 3.8-16.0). The risk of preterm delivery increased significantly with the severity of anaemia (OR = 3.2 for women with mild/moderate anaemia and OR = 6.6 for women with severe anaemia, compared with women with no anaemia). The corrected risk for stillbirth increased only in severe anaemia (OR = 4.3, 95% CI: 1.9-9.1, <it>P </it>< 0.001).</p> <p>Conclusions</p> <p>The greater the severity of the anaemia during pregnancy, the greater the risk of preeclampsia, preterm delivery, LBW and stillbirth. Preventive measures should be undertaken to decrease the prevalence of anaemia in pregnancy.</p

Small RNA interference-mediated gene silencing of heparanase abolishes the invasion, metastasis and angiogenesis of gastric cancer cells

<p>Abstract</p> <p>Background</p> <p>Heparanase facilitates the invasion and metastasis of cancer cells, and is over-expressed in many kinds of malignancies. Our studies indicated that heparanase was frequently expressed in advanced gastric cancers. The aim of this study is to determine whether silencing of heparanase expression can abolish the malignant characteristics of gastric cancer cells.</p> <p>Methods</p> <p>Three heparanase-specific small interfering RNA (siRNAs) were designed, synthesized, and transfected into cultured gastric cancer cell line SGC-7901. Heparanase expression was measured by RT-PCR, real-time quantitative PCR and Western blot. Cell proliferation was detected by MTT colorimetry and colony formation assay. The <it>in vitro </it>invasion and metastasis of cancer cells were measured by cell adhesion assay, scratch assay and matrigel invasion assay. The angiogenesis capabilities of cancer cells were measured by tube formation of endothelial cells.</p> <p>Results</p> <p>Transfection of siRNA against 1496-1514 bp of encoding regions resulted in reduced expression of heparanase, which started at 24 hrs and lasted for 120 hrs post-transfection. The siRNA-mediated silencing of heparanase suppressed the cellular proliferation of SGC-7901 cells. In addition, the <it>in vitro </it>invasion and metastasis of cancer cells were attenuated after knock-down of heparanase. Moreover, transfection of heparanase-specific siRNA attenuated the <it>in vitro </it>angiogenesis of cancer cells in a dose-dependent manner.</p> <p>Conclusions</p> <p>These results demonstrated that gene silencing of heparanase can efficiently abolish the proliferation, invasion, metastasis and angiogenesis of human gastric cancer cells <it>in vitro</it>, suggesting that heparanase-specific siRNA is of potential values as a novel therapeutic agent for human gastric cancer.</p