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11.
R Hashim AM Khatib G Enwere JK Park R Reyburn M Ali NY Chang DR Kim B Ley K Thriemer AL Lopez JD Clemens JL Deen S Shin C Schaetti R Hutubessy MT Aguado MP Kieny D Sack S Obaro AJ Shaame SM Ali AA Saleh L von Seidlein MS Jiddawi 《PLoS neglected tropical diseases》2012,6(7):e1743
Introduction
Mass vaccinations are a main strategy in the deployment of oral cholera vaccines. Campaigns avoid giving vaccine to pregnant women because of the absence of safety data of the killed whole-cell oral cholera (rBS-WC) vaccine. Balancing this concern is the known higher risk of cholera and of complications of pregnancy should cholera occur in these women, as well as the lack of expected adverse events from a killed oral bacterial vaccine.Methodology/Principal Findings
From January to February 2009, a mass rBS-WC vaccination campaign of persons over two years of age was conducted in an urban and a rural area (population 51,151) in Zanzibar. Pregnant women were advised not to participate in the campaign. More than nine months after the last dose of the vaccine was administered, we visited all women between 15 and 50 years of age living in the study area. The outcome of pregnancies that were inadvertently exposed to at least one oral cholera vaccine dose and those that were not exposed was evaluated. 13,736 (94%) of the target women in the study site were interviewed. 1,151 (79%) of the 1,453 deliveries in 2009 occurred during the period when foetal exposure to the vaccine could have occurred. 955 (83%) out of these 1,151 mothers had not been vaccinated; the remaining 196 (17%) mothers had received at least one dose of the oral cholera vaccine. There were no statistically significant differences in the odds ratios for birth outcomes among the exposed and unexposed pregnancies.Conclusions/Significance
We found no statistically significant evidence of a harmful effect of gestational exposure to the rBS-WC vaccine. These findings, along with the absence of a rational basis for expecting a risk from this killed oral bacterial vaccine, are reassuring but the study had insufficient power to detect infrequent events.Trial Registration
ClinicalTrials.gov NCT00709410相似文献12.
Christian Schaetti Mitchell G. Weiss Said M. Ali Claire-Lise Chaignat Ahmed M. Khatib Rita Reyburn Radboud J. Duintjer Tebbens Raymond Hutubessy 《PLoS neglected tropical diseases》2012,6(10)
Background
The World Health Organization (WHO) recommends oral cholera vaccines (OCVs) as a supplementary tool to conventional prevention of cholera. Dukoral, a killed whole-cell two-dose OCV, was used in a mass vaccination campaign in 2009 in Zanzibar. Public and private costs of illness (COI) due to endemic cholera and costs of the mass vaccination campaign were estimated to assess the cost-effectiveness of OCV for this particular campaign from both the health care provider and the societal perspective.Methodology/Principal Findings
Public and private COI were obtained from interviews with local experts, with patients from three outbreaks and from reports and record review. Cost data for the vaccination campaign were collected based on actual expenditure and planned budget data. A static cohort of 50,000 individuals was examined, including herd protection. Primary outcome measures were incremental cost-effectiveness ratios (ICER) per death, per case and per disability-adjusted life-year (DALY) averted. One-way sensitivity and threshold analyses were conducted. The ICER was evaluated with regard to WHO criteria for cost-effectiveness. Base-case ICERs were USD 750,000 per death averted, USD 6,000 per case averted and USD 30,000 per DALY averted, without differences between the health care provider and the societal perspective. Threshold analyses using Shanchol and assuming high incidence and case-fatality rate indicated that the purchase price per course would have to be as low as USD 1.2 to render the mass vaccination campaign cost-effective from a health care provider perspective (societal perspective: USD 1.3).Conclusions/Significance
Based on empirical and site-specific cost and effectiveness data from Zanzibar, the 2009 mass vaccination campaign was cost-ineffective mainly due to the relatively high OCV purchase price and a relatively low incidence. However, mass vaccination campaigns in Zanzibar to control endemic cholera may meet criteria for cost-effectiveness under certain circumstances, especially in high-incidence areas and at OCV prices below USD 1.3. 相似文献13.
P Brodt L Fallavollita A M Khatib A A Samani D Zhang 《The Journal of biological chemistry》2001,276(36):33608-33615
The receptor for the type 1 insulin-like growth factor (IGF-I) regulates multiple cellular functions impacting on the metastatic phenotype of tumor cells, including cellular proliferation, anchorage-independent growth, survival, migration, synthesis of the 72-kDa type IV collagenase and invasion. We have used site-directed mutagenesis to generate domain-specific mutants of the receptor beta subunit to analyze the role of specific tyrosines in the regulation of the invasive/metastatic phenotype. Poorly invasive M-27 carcinoma cells expressing low receptor numbers were transfected with a plasmid vector expressing IGF-I receptor cDNA in which single or multiple tyrosine codons in the kinase domain, namely Tyr-1131, Tyr-1135, and Tyr-1136 or the C-terminal tyrosines 1250 and 1251 were substituted with phenylalanine. Changes in the invasive and metastatic properties were analyzed relative to M-27 cells expressing the wild type receptor. We found that cells expressing the Y1131F,Y1135F,Y1136F or Y1135F receptor mutants lost all IGF-IR-dependent functions and their phenotypes were indistinguishable from, or suppressed relative to, the parent line. The Y1250F,Y1251F substitution abolished anchorage-independent growth, cell spreading, and the anti-apoptotic effect of IGF-I whereas all other IGF-IR-dependent phenotypes were either unperturbed (i.e. mitogenicity) or only partially reduced (migration and invasion). The results identify three types of receptor-dependent functions in this model: those dependent only on an intact kinase domain (DNA synthesis), those dependent equally on kinase domain and Tyr-1250/1251 signaling (e.g. apoptosis, soft agar cloning) and those dependent on kinase domain and enhanced through Tyr-1250/1251 signaling (migration, invasion). They suggest that signals derived from both regions of the receptor cooperate to enhance tumor metastasis. 相似文献
14.
An endogenous virus, denoted ev A, is present at high frequency in all brown egg layer lines. Using inverse polymerase chain reaction (PCR) based on the viral LTR regions, products were obtained containing cellular sequences 5' and 3' to the viral insertion point. PCR of chicken genomic DNA was carried out, using primers chosen from the 5' and 3' cellular sequences and a primer chosen from either the U3 or U5 portions of the viral LTR. Amplification of DNA from birds that did not carry ev A with the primer triplets always gave a single 364bp reaction product, interpreted as representing the flank-to-flank amplification product. Amplification of DNA from known homozygous or heterozygous ev A carriers, with the same primer triplets, always gave both the expected junction product and 364bp product. Therefore, these primer sequences can be used to distinguish ev A carriers from non-carriers but cannot distinguish between homozygous and heterozygous ev A carriers. 相似文献
15.
16.
Wei Ge Shan-He Wang Bing Sun Yue-Lang Zhang Wei Shen Hasan Khatib 《Cell cycle (Georgetown, Tex.)》2018,17(10):1255-1267
The role of melatonin in promoting the yield of Cashmere goat wool has been demonstrated for decades though there remains a lack of knowledge regarding melatonin mediated hair follicle growth. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are widely transcribed in the genome and play ubiquitous roles in regulating biological processes. However, the role of lncRNAs in regulating melatonin mediated hair follicle growth remains unclear. In this study, we established an in vitro Cashmere goat secondary hair follicle culture system, and demonstrated that 500 ng/L melatonin exposure promoted hair follicle fiber growth. Based on long intergenic RNA sequencing, we demonstrated that melatonin promoted hair follicle elongation via regulating genes involved in focal adhesion and extracellular matrix receptor pathways and further cis predicting of lncRNAs targeted genes indicated that melatonin mediated lncRNAs mainly targeted vascular smooth muscle contraction and signaling pathways regulating the pluripotency of stem cells. We proposed that melatonin exposure not only perturbed key signals secreted from hair follicle stem cells to regulate hair follicle development, but also mediated lncRNAs mainly targeted to pathways involved in the microvascular system and extracellular matrix, which constitute the highly orchestrated microenvironment for hair follicle stem cell. Taken together, our findings here provide a profound view of lncRNAs in regulating Cashmere goat hair follicle circadian rhythms and broaden our knowledge on melatonin mediated hair follicle morphological changes. 相似文献
17.
Elena Frati Abdel-Majid Khatib Philippe Front Andrej Panasyuk France Aprile Dragoslav R. Mitrovic 《Free radical biology & medicine》1997,22(7):1139-1144
The effect of photoexcited riboflavin (RF) on the viscosity of hyaluronic acid (HA) solutions has been investigated. UV irradiation of RF causes under aerobic conditions fragmentation of HA and a decrease in the viscosity of its solutions. A decrease of HA viscosity occurs in PO4-buffered solutions and is accelerated by high pH, Fe2+ (but much less so by Fe3+), certain metal chelators, and horseradish peroxidase (HRP); it is partially inhibited by catalase and less so by superoxide dismutase (SOD). The reactivity of the system was completely blocked by Tris, ethanol, aspirin, d-manitol, dimethylthiourea (DMTU), dimethylsulfoxide (DMSO), and sodium azide. These results indicate that the most likely chemical species involved in the reaction is the hydroxyl radical. Singlet oxygen (102) generation is suggested by the ability of NaN3 and DMSO to completely inhibit the reactivity of the system. These two agents, however, may also interact with OH√ radical, as well and suppress the reactivity of the system. H2O2 and
seem also to be produced in significant amounts, because catalase and SOD partially block the reactivity of the system. The effect of HRP may be due to hydrogen subtraction from HA and H2O2 reduction to water. Photoexcitation of RF may potentially occur in vitro and in vivo in the organs and tissues that are permeable to light, such as the eye or skin, and damage HA and other cell-matrix components causing inflammation and accelerating aging. © 1997 Elsevier Science Inc. 相似文献
18.
Andrea Szuchman Michael Aviram Ramadan Musa Soliman Khatib Professor Jacob Vaya 《Biomarkers》2013,18(1):119-131
In the present study, we extend our novel concept of designing and using exogenous markers for the characterization of oxidative stress (OS) and OS-associated diseases. The aim was to use such a synthetic compound as a tool for studying OS in blood from diabetic and hypercholesterolaemic (Hc) patients. The marker used N-linoleoyl tyrosine (LT) was constructed from tyrosine and linoleic acid (LA); both components are known to be easily oxidized upon exposure to different types of reactive oxygen/nitrogen species (ROS/RNS), and to generate specific oxidized products, depending on the type of oxidants present in vivo. Using the LT probe, we showed that the ratios of oxidized LT to total LT (Ox-LT/LT) is significantly higher in blood samples obtained from diabetic patients, than in Hc patients or healthy control subjects. LC/MS analysis revealed that blood from diabetic patients oxidizes the marker with predominant formation of Ox-LT hydroperoxide (LT-OOH) and epoxide (epoxy-LT), where the LA moiety is oxidized to hydroperoxide and to epoxide, respectively. Analysis of oxysterol levels in these samples (GC/MS) revealed that the blood of both diabetic and Hc patients contained significantly more oxysterols than blood of control subjects. Consumption of pomegranate juice by diabetic patients for 3 months suppressed their blood capacity to oxidize the LT and similarly also reduced their blood oxysterol/total cholesterol ratio by 93%. The use of an exogenous marker to characterize OS in blood samples yields important information on the extent of OS, and can provide a fingerprint for the early identification of different pathological conditions associated with OS. 相似文献
19.
Fibroblast growth factor 2 ( FGF2 ) plays an important role in fertility and early embryo development. The objectives of this study were to test the association of FGF2 polymorphisms with fertilization success in cattle using an in vitro fertilization experimental system and to investigate the mechanisms leading to the presence of rare alleles of FGF2 in the Holstein population. A total of 7502 fertilizations were performed and a total of 5049 embryos were produced to collect fertilization and embryo survival records. A total of 444 ovaries, from which oocytes were aspirated and fertilized, were genotyped for two single nucleotide polymorphisms (SNPs) previously identified in FGF2 (g.23G>T and g.11646A>G). Frequency of the TT genotype of the g.23G>T SNP was low in the ovary population (5.4%) and in a different Holstein cattle population (6.6%) examined in this study. Single SNP analysis showed that both SNPs were associated with early embryonic survival rate. Two-way interaction analysis revealed significant association of epistatic interaction between the SNPs with fertilization rate. To test whether or not low frequency of allele T for the g.23G>T SNP in the population is a result of a fertilization failure of T oocytes, semen from six GG bulls was used to fertilize a total of 458 oocytes obtained from 19 GT ovaries. A significant segregation distortion was observed for 169 embryos genotyped for the g.23G>T SNP. We conclude that oocytes carrying the T allele show a reduced fertilization rate and that segregation distortion leads to rarity of the TT genotype in the population. 相似文献