Intensity of Nematode Infection in Children Aged 3 to 5 Years Living in Mukuru Kwa Njenga Slum Settlement, Nairobi, Kenya.

BACKGROUND: The burden of nematode infections is high mostly in children below 5 years old, with clinical manifestations ranging from mild to painful symptoms due to severe infections that end up suppressing the immune system of the infected children. The occurrence of these infections is highest in areas of extreme poverty. This study evaluated the intensity of nematode infections and assessed the status of deworming in children aged 3 to 5 years living in Mukuru slum settlement, Nairobi County, Kenya. Methodology. A total of 172 children aged between 3 and 5 years were sampled across the 5 major villages of Mukuru Slum settlement: Kwa Njenga, Vietnum, Wapewape, Kwa Reuben, and Motomoto. Community health workers administered questionnaires on the deworming history of children. Stool samples were collected, macroscopically examined, and microscopically analysed using Kato-Katz technique to assess the intensity of infection. The intensities of nematode infections were expressed as eggs per gram (epg) of faeces. RESULTS: The point prevalence of nematode infection among the 98 children in the 1st sampling was 25.5% with a mean infection intensity of 5424 epg, whereas among the 74 children sampled in 2nd sampling, 47.3% had nematode infection with a mean infection intensity of 12384 epg. The average nematode infection for the 172 participants was 34.9% with a mean intensity of 17808 epg. The highest number of children infected with nematodes was in the village of Wapewape where 34 participants were examined and 36.3% were infected with a mean intensity of 3216 epg. Kwa Reuben and Vietnum villages had the same prevalence values of 32.4% where 34 participants in each village had a mean intensity of 3624 epg and 4512 epg, respectively. In both samplings, more than 80% of children had been dewormed more than 6 months prior to the study. Ascaris lumbricoides was the only species of intestinal nematodes identified to be present in the stool samples of children in this study, whereas Trichuris trichiura and hookworm infections were found to be absent. The intensity of infection was not dependent on age or gender.

Rapid activation of nuclear factor κB by 17ß-estradiol and selective estrogen receptor modulators: pathways mediating cellular protection.

17ß-Estradiol (E2) treatment activates a set of protective response that has been found to protect cells from injury and more importantly to significantly abate the injuries associated with trauma-hemorrhage in vivo. Rapid NF-κB activation has been found to be an important signaling step in E2-mediated protection in cell culture, in vivo ischemia, and trauma-hemorrhage. In the current study, we investigated the signaling cascades linking E2 signaling with NF-κB activation and the protective response and compared them with the effects of two selective estrogen receptor modulators (SERMs), raloxifene and tamoxifen. Two candidate pathways, mitogen-activated protein kinases and phosphatidylinositol-3-kinase (PI3K) were studied. Selective inhibitors were used to identify each pathway's contribution to NF-κB activation. Treatment of human coronary artery endothelial cells with E2 activated PI3K/Akt, p38, and JNK, all of which activated ERK1/2 followed by NF-κB activation. The combined activation of Akt, p38, and JNK was essential to activate NF-κB. The two SERMs activated PI3K and p38, which then phosphorylated ERK1/2 and activated NF-κB independent of the JNK pathway. Nuclear factor κB activation by these compounds protected cells from hypoxia/reoxygenation injury. However, E2, unlike either SERM, led to modest increases in apoptosis through the JNK pathway. Selective estrogen receptor modulator treatment led to increased expression of the protective proteins, Mn superoxide dismutase, and endothelial nitric oxide synthase, which was not seen with E2. These results provide new insight into the pathways activating NF-κB by E2 and SERMs and demonstrate that SERMs may have greater protective benefits than E2 in adult endothelial cells and potentially in vivo, as well.

Changes in genotypes of Plasmodium falciparum human malaria parasite following withdrawal of chloroquine in Tiwi, Kenya.

Chloroquine (CQ) drug was withdrawn in 1998 as a first-line treatment of uncomplicated malaria in Kenya. This was in response to resistance to the drug in Plasmodium falciparum malaria parasite. Investigations were conducted to determine prevalence of CQ resistance genotypes in the parasites in Tiwi, a malaria endemic town in Kenya, before and about a decade after the withdrawal of the drug. Blood samples were collected and spotted on filter papers in 1999 and 2008 from 75 and 77 out-patients respectively with uncomplicated malaria. The sampling was conducted using finger pricking technique. DNA was extracted from individual spots in the papers and screened for the presence of P. falciparum chloroquine resistance transporter (Pfcrt) and multi drug resistance (Pfmdr-1) markers using nested PCR. Nature of mutations (haplotypes) in the Pfcrt and Pfmdr-1 markers in the samples were confirmed using dot blot hybridization technique. Changes in pattern of CQ resistance in the parasite samples in 1999 and 2008 were assessed by Chi Square test. There was a significant (P<0.05) reduction in CQ resistant genotypes of the parasite between 1999 and 2008. Pfmdr and Pfcrt CQ resistant genotypes in 2008 reduced to 54.10 and 63.64% respectively, from 75.39 and 88.0% respectively in 1999. This reduction was accompanied by emergence of Pfcrt specific CQ sensitive (IEK) and intermediate/partially CQ resistant (MET) haplotypes. Results suggest significant reversal of the phenotype of the parasite from chloroquine resistant to wild/sensitive type. The novel haplotypes indicates transitional phase of the parasite to the wild type. Current prevalence of chloroquine resistant genotype is definitely above the threshold for efficacious re-introduction of chloroquine for treatment of malaria in Tiwi.

Impact of aging vs. estrogen loss on cardiac gene expression: estrogen replacement and inflammation.

Despite an abundance of evidence to the contrary from animal studies, large clinical trials on humans have shown that estrogen administered to postmenopausal women increases the risk of cardiovascular disease. However, timing may be everything, as estrogen is often administered immediately after ovariectomy (Ovx) in animal studies, while estrogen administration in human studies occurred many years postmenopause. This study investigates the discrepancy by administering 17ß-estradiol (E2) in a slow-release capsule to Norway Brown rats both immediately following Ovx and 9 wk post-Ovx (Late), and studying differences in gene expression between these two groups compared with age-matched Ovx and sham-operated animals. Two different types of microarray were used to analyze the left ventricles from these groups: an Affymetrix array (n = 3/group) and an inflammatory cytokines and receptors PCR array (n = 4/group). Key genes were analyzed by Western blotting. Ovx without replacement led to an increase in caspase 3, caspase 9, calpain 2, matrix metalloproteinase (MMP)9, and TNF-α. Caspase 6, STAT3, and CD11b increased in the Late group, while tissue inhibitor of metalloproteinase 2, MMP14, and collagen I α1 were decreased. MADD and fibronectin were increased in both Ovx and Late. TNF-α and inducible nitric oxide synthase (iNOS) protein levels increased with Late replacement. Many of these changes were prevented by early E2 replacement. These findings suggest that increased expression of inflammatory genes, such as TNF-α and iNOS, may be involved in some of the deleterious effects of delayed E2 administration seen in human studies.

Effects of dietary decosahexaenoic acid (DHA) on eNOS in human coronary artery endothelial cells.

Endothelial dysfunction occurs in heart disease and may reduce functional capacity via attenuations in peripheral blood flow. Dietary decosahexaenoic acid (DHA) may improve this dysfunction, but the mechanism is unknown. This study determined if DHA enhances expression and activity of eNOS in cultured human coronary artery endothelial cells (HCAEC). HCAEC from 4 donors were treated with 5 nM, 50 nM, or 1 microM DHA for 7 days to model chronic DHA exposure. A trend for increased expression of endothelial nitric oxide synthase (eNOS) and phospho-eNOS was observed with 5 and 50 nM DHA. DHA also enhanced expression of 2 proteins instrumental in activation of eNOS: phospho-Akt (5 and 50 nM) and HSP90 (50 nM and 1 microM). Vascular endothelial growth factor-induced activation of Akt increased NOx in treated (50 nM DHA) versus untreated HCAEC (9.2 +/- 1.0 vs 3.3 +/- 1.1 micromol/microg protein/microL). Findings suggest that DHA enhances eNOS and Akt activity, augments HSP90 expression, and increases NO bioavailability in response to Akt kinase activation.