Medicinal plants in Pujehun District of Sierra Leone

A study was carried out in the Pujehun District of Sierra Leone, West Africa, on the traditional use of plants for curing human diseases. The use of medicinal plants is still widespread especially in the villages and is usually the first treatment utilised. Fifty nine local plant species used for treating various illnesses were collected, identified and deposited in the Fourah Bay College Herbarium. Their medicinal uses and methods of preparing the drug are described.     

Clinical study of multiple breath biomarkers of asthma and COPD (NO, CO(2), CO and N(2)O) by infrared laser spectroscopy

Breath analysis is a powerful non-invasive technique for the diagnosis and monitoring of respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD). Exhaled nitric oxide (NO) and carbon monoxide (CO) are markers of airway inflammation and can indicate the extent of respiratory diseases. We have developed a compact fast response quantum cascade laser system for analysis of multiple gases by tunable infrared absorption spectroscopy. The ARI breath analysis instrument has been deployed in a study of exhaled breath from patients with asthma or COPD. A total of 173 subjects participated, including both adult and pediatric patients. Patients in asthma or COPD exacerbations were evaluated twice-during the exacerbation and at a follow-up visit-to compare variations in breath biomarkers during these events. The change in exhaled NO levels between exacerbation and 'well' visits is consistent with spirometry data collected. Respiratory models are important for understanding the exchange dynamics of nitric oxide and other species in the lungs and airways. At each patient's visit, tests were conducted at four expiratory flow rates. We have applied a trumpet model with axial diffusion to the multi-flow exhaled nitric oxide data, obtaining NO alveolar concentrations and airway fluxes. We found higher airway fluxes for those with more severe asthma and during exacerbation events. The alveolar concentrations from the model were higher in adults with asthma and COPD, but this trend was less clear among the pediatric subjects.     

Meta-analysis: the efficacy of proton pump inhibitors for laryngeal symptoms attributed to gastro-oesophageal reflux disease

BACKGROUND: Many investigators have proposed an association between gastro-oesophageal reflux disease and laryngo-pharyngeal symptoms, suggesting that medical or surgical therapy for reflux may be useful. AIM: To perform a meta-analysis assessing the effectiveness of medical or surgical therapy for reflux disease in adult patients with laryngeal or pharyngeal symptoms presumed to be due to gastro-oesophageal reflux disease. METHODS: Randomized controlled trials comparing medical or surgical treatments for gastro-oesophageal reflux disease against placebo were identified by searching MEDLINE (1966-September 2005), EMBASE (1974-September 2005), the CCRCT (until September 2005) and abstracts from gastroenterology and ENT meetings. The relative risks of reporting symptomatic improvement or resolution of symptoms was evaluated using a random-effects model. RESULTS: Five studies using high-dose proton pump inhibitor as intervention met the inclusion criteria and were included in the meta-analysis. No surgical studies met inclusion criteria. The pooled relative risk was 1.18 (95% confidence interval: 0.81-1.74). There was no heterogeneity between studies but evidence of significant publication bias. Sub-group analysis performed evaluating Jadad scores and symptom type, did not change the relative risk. CONCLUSIONS: Therapy with a high-dose proton pump inhibitor is no more effective than placebo in producing symptomatic improvement or resolution of laryngo-pharyngeal symptoms. Further studies are necessary to identify the characteristics of patients that may respond to proton pump inhibitor therapy.     

Potential role of high mobility group box 1 in viral infectious diseases

A nuclear protein, high mobility group box 1 (HMGB1), is released passively by necrotic cells and actively by macrophages/monocytes in response to exogenous and endogenous inflammatory stimuli. After binding to the receptor for advanced glycation end products (RAGE), or Toll-like receptor 4 (TLR4), HMGB1 activates macrophages/monocytes to express proinflammatory cytokines, chemokines, and adhesion molecules. Pharmacological suppression of its activities or release is protective against lethal endotoxemia and sepsis, establishing HMGB1 as a critical mediator of lethal systemic inflammation. In light of observations that many viruses (e.g., West Nile virus, Salmon anemia virus) can induce passive HMGB1 release, we propose a potential pathogenic role of HMGB1 in viral infectious diseases.     

Comparison of PCR-RFLP and Genescan-based genotyping for analyzing infection dynamics of Plasmodium falciparum

Parameters describing the infection dynamics of Plasmodium falciparum are important determinants of the potential impact of interventions and are potential outcome measurements for malaria intervention trials. Low parasite densities, periodic sequestration of parasites, and the presence of multiple concurrent infections make it essential to use molecular techniques to estimate the force of infection and duration of infections in endemic areas. We now compare two approaches for tracking individual genotypes of the highly polymorphic merozoite surface protein 2: 1) fluorescence-labeled polymerase chain reaction (PCR) and GeneScan-sizing and 2) restriction fragment length polymorphism (RFLP). We analyze samples from a longitudinal field study in Ghana and use statistical approaches that allow for imperfect detectability. The two methods gave broadly similar estimates of parasite dynamics, but GeneScan is more precise and can achieve a higher throughput. The analysis of parasite dynamics indicated an average duration of infection of 210 days by GeneScan versus 152 days by PCR-RFLP in the study population in Kassena-Nankana, Northern Ghana. This reflects the good performance of GeneScan-based genotyping for studies of parasite infection dynamics.     

Nef interference with HIV-1-specific CTL antiviral activity is epitope specific

HIV-1 Nef and HIV-1-specific cytotoxic T lymphocytes (CTLs) have important and opposing roles in the immunopathogenesis of HIV-1 infection. Nef-mediated down-modulation of HLA class I on infected cells can confer resistance to CTL clearance, but the factors determining the efficiency of this process are unknown. This study examines the impact of Nef on the antiviral activity of several CTL clones recognizing epitopes from early and late HIV-1 proteins, restricted by HLA-A, -B, and -C molecules. CTL-targeting epitopes in early proteins remained susceptible to the effects of Nef, although possibly to a lesser degree than CTL-targeting late protein epitopes, indicating that significant Nef-mediated HLA down-regulation can precede even the presentation of early protein-derived epitopes. However, HLA-C-restricted CTLs were unaffected by Nef, consistent with down-regulation of cell-surface HLA-A and -B but not HLA-C molecules. Thus, CTLs vary dramatically in their susceptibility to Nef interference, suggesting differences in the relative importance of HLA-A- and HLA-B- versus HLA-C-restricted CTLs in vivo. The data thus indicate that HLA-C-restricted CTLs may have an under-appreciated antiviral role in the setting of Nef in vivo and suggest a benefit of promoting HLA-C-restricted CTLs for immunotherapy or vaccine development.     

The Cellular and Genomic Response of an Immortalized Microglia Cell Line (BV2) to Concentrated Ambient Particulate Matter

Ambient particulate matter (PM) damages pulmonary tissue through oxidative stress (OS) pathways. Several reports indicate that the brain is another affected target of PM exposure. Since microglia (brain macrophages) are critical to OS-mediated neurodegeneration, the cellular and genomic response of immortalized mouse microglia (BV2) was examined in response to fine (≤ 2.5 μ m) concentrated ambient particles (CAPs) collected from Tuxedo, NY. Samples of CAPs were labeled as high potency (HP) or low potency (LP) depending on their stimulation of nuclear factor (NF)-κ B activity in human bronchial epithelial cells. Compositional analysis of these samples, performed during their original collection, indicated a strong correlation between HP CAPs and and the presence of nickel and vanadium (). Exposure of the BV2 microglia to LP CAPs reduced intracellular levels of ATP (≥ 250 μ g/ml) and depolarized mitochondrial membranes (≥ 6 μ g/ml) within 15 min of exposure. HP and LP CAPs (≥ 25 μ g/ml) differentially affected the endogenous scavengers, glutathione and nonprotein sulfhydryl in BV2 microglia after 1.5 h of exposure. Both HP and LP CAPs stimulated the release of proinflammatory cytokines tumor necrosis factor (TNF) α and interleukin (IL)-6 after 6 h of exposures. Microarray analysis of BV2 microglia exposed to either HP or LP CAPs (75 μ g/ml, 4 h) identified 3200 (HP CAPs) and 160 (LP CAPs) differentially expressed (up- and downregulated) genes relative to media controls. Of the 3200 genes significantly affected by HP CAPs, the most prominent upregulated gene probes related to inflammatory pathways associated with Toll-like receptor signaling, MAPK signaling, T- and B-cell receptor signaling, apoptosis, and various proinflammatory cytokines and their receptors. LP CAPs significantly affected 160 genes that related to pathways associated with cellular maintenance and division, cell cycling and nuclear events. These data suggest that HP CAPs, which contained higher levels of nickel and vanadium than LP CAPs, appear to be more inflammatory and selectively upregulated the expression of inflammatory and innate immunity pathways in BV2 microglia.     

Immunogenicity of novel nanoparticle-coated MSP-1 C-terminus malaria DNA vaccine using different routes of administration

An important aspect in optimizing DNA vaccination is antigen delivery to the site of action. In this way, any alternative delivery system having higher transfection efficiency and eventual superior antibody production needs to be further explored. The novel nanoparticle, pDNA/PEI/γ-PGA complex, is one of a promising delivery system, which is taken up by cells and is shown to have high transfection efficiency. The immunostimulatory effect of this novel nanoparticle (NP) coated plasmid encoding Plasmodium yoelii MSP1-C-terminus was examined. Groups of C57BL/6 mice were immunized either with NP-coated MSP-1 plasmid, naked plasmid or NP-coated blank plasmid, by three different routes of administration; intravenous (i.v.), intraperitoneal (i.p.) and subcutaneous (s.c). Mice were primed and boosted twice at 3-week intervals, then challenged 2 weeks after; and 100%, 100% and 50% mean of survival was observed in immunized mice with coated DNA vaccine by i.p., i.v. and s.c., respectively. Coated DNA vaccine showed significant immunogenicity and elicited protective levels of antigen specific IgG and its subclass antibody, an increased proportion of CD4⁺ and CD8⁺ T cells and INF-γ and IL-12 levels in the serum and cultured splenocyte supernatant, as well as INF-γ producing cells in the spleen. We demonstrate that, NP-coated MSP-1 DNA-based vaccine confers protection against lethal P. yoelii challenge in murine model across the various route of administration and may therefore, be considered a promising delivery system for vaccination.