Improving ability to identify malaria and correctly use chloroquine in children at household level in Nakonde District, Northern Province of Zambia

BACKGROUND: This study investigated causes of malaria and how cases were managed at household level, in order to improve the ability to identify malaria and ensure correct use of chloroquine. It was conducted in Nakonde District, Northern Province of Zambia, between 2000 and 2001. Nakonde district is in a hyperendemic malaria province, where Plasmodium falciparum is predominant. The district has a total population of 153, 548 people, the majority of whom are peasant farmers. The main aim of the post intervention survey was to establish the proportion of caretakers of children five years and below, who were able to identify simple and severe malaria and treat it correctly using chloroquine in the home. METHODS: A baseline survey was conducted in five wards divided into intervention and control.Intervention and control wards were compared. Village health motivators and vendors were identified and trained in three intervention wards, as a channel through which information on correct chloroquine dose could be transmitted. A total of 575 carers, who were 15 years old and above and had a child who had suffered from malaria 14 days before the survey commenced, were interviewed. The two control wards received no intervention. 345 caretakers were from the intervention wards, while 230 came from the control wards. Identification of malaria and correct use of anti-malarial drugs was assessed in terms of household diagnosis of malaria in children under five years, type and dose of anti-malarial drugs used, self medication and the source of these anti-malarials. RESULTS: The majority of respondents in the study were females (81%). Chloroquine was the most frequently used anti-malarial (48.5%) in both the intervention and control wards. There was no difference between the intervention and control wards at pre-intervention (P = 0.266 and P = 0.956), in the way mothers and other caretakers identified simple and severe malaria. At baseline, knowledge on correct chloroquine dosage in the under five children was comparable between intervention and control wards. Post-intervention revealed that mothers and other caretakers were 32% and 51%, respectively, more likely to identify simple and severe malaria. There was a 60% increase on correct chloroquine dosage in all age groups among carers living in post-intervention wards. CONCLUSION: Compliance with standard therapeutic doses and correct identification of malaria was poorest in control wards, where no motivators and vendors were trained.     

Immunological studies of sheep brain keratan sulphate proteoglycans

Recently, we reported the isolation and partial characterization of keratan sulphate (KS) from sheep brain. In this study, a panel of monoclonal antibodies (Mab) recognizing epitopes within KS chains and core proteins of KS-containing proteoglycans were used to detect, by immunoblotting, antigenically related molecules extracted from cerebrum, cerebellum and brainstem, respectively. Although the intensity of labelling varied with each of the antibodies, the brain KSPGs were recognized by all the monoclonals used, confirming the presence of KS side chains, which react with the Mabs: 5-D-4, EFG-11, EFG-4, I22, as also the presence of KSPGs related to phosphacan-KS (3H1 proteoglycan). Extracts of all the three brain areas could bind both anti-KS and anti-core protein Mabs, as also anti-HNK-1 monoclonal antibody. Binding was sensitive to keratanases degradation in the cerebrum and brainstem except cerebellum where the presence of a large molecular size hybrid CS/KSPG bearing KS chains partially resistant to keratanases was identified. This population reacts only with 5-D-4, EFG-11 and EFG-4 antibodies. Furthermore, the presence of HNK-1 epitope in CSPGs was detected in the cerebellum and brainstem. In contrast, in the cerebrum the coexistence of HNK-1 epitope and KS in KSPGs was identified. These data suggest that the KSs of sheep brain are part of proteoglycans containing protein and KS antigenic sites related to those of corneal and cartilage KSPG, as also of the brain proteoglycan phosphacan-KS.     

IGF-I affects glycosaminoglycan/proteoglycan synthesis in breast cancer cells through tyrosine kinase-dependent and -independent pathways

The insulin-like growth factor I (IGF-I) has been implicated in breast cancer development acting through insulin-like growth factor I receptor (IGF-IR), but also through estrogen receptor (ER). The effect of IGF on proteoglycan (PG) synthesis by two human breast cancer epithelial cell lines, the ER-positive MCF-7 and the ER-negative BT-20, was studied alone and in combination with genistein. Both cell lines synthesise hyaluronan (HA), matrix secreted and cell membrane-associated galactosaminoglycan containing proteoglycans (GalAGPGs) and heparan sulphate proteoglycans (HSPGs) in variable amounts. IGF-I affects the synthesis of PGs by BT-20 cells by decreasing the amounts of HA and secreted GalAGPGs and HSPGs and upregulates the expression of cell membrane-associated GalAGPGs and HSPGs. IGF-I exerts this effect on BT-20 cells acting mainly through receptors with protein tyrosine kinase activity (PTK). In contrast, IGF-I stimulates the synthesis of secreted GalAGPGs and HSPGs by MCF-7 cells, exhibiting only a slight suppression on synthesis of cell-associated GalAGPGs and HSPGs. The regulatory effect of IGF-I on PGs distribution in MCF-7 cells is mediated through a mix of pathways, which involves both receptors with PTK activity and PTK-independent signalling. It is suggested that the effects of IGF-I on the synthesis and distribution of PGs by epithelial breast cancer cells also depend on the presence or the absence of ER. The result of the IGF-I action is the balanced biosynthesis between the matrix and cell-associated PGs in both cell lines, approaching a common biosynthetic phenotype.     

Interferon alpha-induced apoptosis in tumor cells is mediated through the phosphoinositide 3-kinase/mammalian target of rapamycin signaling pathway

Interferon (IFN) alpha induces a caspase-dependent apoptosis that is associated with activation of the proapoptotic Bak and Bax, loss of mitochondrial membrane potential, and release of cytochrome c. In addition to the onset of the classical Jak-STAT pathway, IFNalpha also induced phosphoinositide 3-kinase (PI3K) activity. Pharmacological inhibition of PI3K activity by Ly294002 disrupted IFN-induced apoptosis upstream of mitochondria. Inhibition of mTOR by rapamycin or by overexpression of a kinase dead mutant of mTOR, efficiently blocked IFNalpha-induced apoptosis. A PI3K and mTOR-dependent phosphorylation of p70S6 kinase and 4E-BP1 repressor was induced by IFNalpha treatment of cells and was strongly inhibited by Ly294002 or rapamycin. The activation of Jak-STAT signaling upon IFNalpha stimulation was not affected by abrogating PI3K/mTOR pathway. Neither was the expression of several IFNalpha target genes affected, nor the ability of IFNalpha to protect against virus-induced cell death affected by inhibition of the PI3K/mTOR pathway. These data demonstrate that an intact PI3K/mTOR pathway is necessary for the ability of IFNalpha to induce apoptosis, whereas activation of the Jak-STAT pathway alone appears to be insufficient for this specific IFNalpha-induced effect.     

Identification, quantification and fine structural characterization of glycosaminoglycans from uterine leiomyoma and normal myometrium

The type, amount and fine chemical composition of glycosaminoglycans (GAGs) present both in human normal myometrium and uterine leiomyoma have been studied. GAGs were fractionated by ion-exchange chromatography on DEAE-Sephacel, isolated by gel-permeation chromatography on Sepharose CL-6B and characterized using electrophoresis in cellulose acetate membranes, specific enzymic treatments and analysis by high-performance capillary electrophoresis (HPCE). No statistical intrabatch differences in total GAG content in both tissues were identified, whereas significant interbatch differences between normal myometrium and uterine leiomyoma were recorded. Hyaluronan (HA), chondroitin sulphate (CS), dermatan sulphate (DS), heparan sulphate (HS) and keratan sulphate (KS) were identified in both tissues. Statistically significant (P 相似文献   

Combined prime-boost vaccination against tick-borne encephalitis (TBE) using a recombinant vaccinia virus and a bacterial plasmid both expressing TBE virus non-structural NS1 protein

Background  

Heterologous prime-boost immunization protocols using different gene expression systems have proven to be successful tools in protecting against various diseases in experimental animal models. The main reason for using this approach is to exploit the ability of expression cassettes to prime or boost the immune system in different ways during vaccination procedures. The purpose of the project was to study the ability of recombinant vaccinia virus (VV) and bacterial plasmid, both carrying the NS1 gene from tick-borne encephalitis (TBE) virus under the control of different promoters, to protect mice against lethal challenge using a heterologous prime-boost vaccination protocol.     

Trichoderma spp. and Bacillus spp. as growth promoters in maize (Zea mays L.)

Microbes that are beneficial to plants are used to enhance the crop growth, yield and are alternatives to chemical fertilizers. Trichoderma and Bacillus are the predominant plant growth-promoting fungi and bacteria. The objective of this study was select, characterize, and evaluate isolates of Trichoderma spp. and Bacillus spp. native from the northern region of Sinaloa, Mexico, and assess their effect on growth promotion in maize (Zea mays L.). In greenhouse conditions, four Trichoderma isolates and twenty Bacillus isolates, as well as two controls, were tested in a completely randomized design with three replicates. We selected the two best strains of Trichoderma and Bacillus: TB = Trichoderma asperellum, TF = Trichoderma virens, B14 = Bacillus cereus sensu lato and B17 = Bacillus cereus, which were evaluated in the field in a completely randomized blocks in factorial arrangement design with three replicates applying different rates of nitrogen fertilizer (0, 150 kg N/ha, and 300 kg N/ha). Treatments 5 (B17 = B. cereus) and 11 (TF = T. virens) both fertilized with 150 kg N/ha showed similar yields and they did not reveal significant differences from the treatments fertilized with 300 kg N/ha. This indicated that treatment 5 (B17= B. cereus with 150 kg N/ha) and treatment 11 (TF= T. virens with 150 kg N/ha) were efficient as growth promoters, by not showing significant differences in root volume and dry weight of foliage. The results indicated a reduction of 50% in the rate of nitrogen to fertilizer required for maize (Zea mays L.) crops. These microorganisms Trichoderma and Bacillus could be an alternative to reduce the use of chemical fertilizers in maize.